WO2021122645A1 - Pesticidally active azole-amide compounds - Google Patents

Pesticidally active azole-amide compounds Download PDF

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WO2021122645A1
WO2021122645A1 PCT/EP2020/086285 EP2020086285W WO2021122645A1 WO 2021122645 A1 WO2021122645 A1 WO 2021122645A1 EP 2020086285 W EP2020086285 W EP 2020086285W WO 2021122645 A1 WO2021122645 A1 WO 2021122645A1
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spp
c3alkyl
c3alkoxy
formula
cycloalkyl
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PCT/EP2020/086285
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French (fr)
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André Jeanguenat
Daniel EMERY
Roger Graham Hall
Viorel Andrei IOSUB
Camille LE CHAPELAIN
Julien Daniel Henri GAGNEPAIN
Jagadeesh Prathap KILARU
Mangala Phadte
Thomas Pitterna
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Syngenta Crop Protection Ag
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Publication of WO2021122645A1 publication Critical patent/WO2021122645A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N2300/00—Combinations or mixtures of active ingredients covered by classes A01N27/00 - A01N65/48 with other active or formulation relevant ingredients, e.g. specific carrier materials or surfactants, covered by classes A01N25/00 - A01N65/48

Definitions

  • the present invention relates to pesticidally active, in particular insecticidally active quinazoline compounds, to processes for their preparation, to compositions comprising those compounds, and to their use for controlling animal pests, including arthropods and in particular insects or representatives of the order Acarina.
  • WO2017192385 describes certain heteroaryl-1 ,2,4-triazole and heteroaryl-tetrazole compounds for use for controlling ectoparasites in animals (such as a mammal and a non-mammal animal).
  • the present invention accordingly relates, in a first aspect, to a compound of the formula I wherein:
  • R 1 is hydrogen; Ci-C6alkyl, Ci-C6alkyl substituted with one substituent selected from CN, C(0)NH 2 , C(0)0H, NO2, and -Si(CH3)3, Ci-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C3- C 4 cycloalkyl- Ci-C2alkyl, C3-C 4 cycloalkyl- Ci-C2alkyl substituted with 1 or 2 halo atoms; oxetan-3-yl- CH2-, benzyl, or benzyl substituted with halo or Ci-C3haloalkyl;
  • R 2a is Ci-C3alkyl, Ci-C3haloalkyl, Ci- Cshaloalkylthio, Ci- Csalkoxy, Ci- Cshaloalkoxy, halo, NO2, SFs, CN, C(0)NH 2 , C(0)0H, C(S)NH 2 ;
  • R 3 is Ci-C3alkyl or Ci-C3haloalkyl
  • R 4 is pyridine, pyrimidine, pyrazine or pyridazine; or
  • R 4 is pyridine, pyrimidine, pyrazine or pyridazine each of which, independently of each other, is substituted with one to two substituents independently selected from Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C3-C 4 cycloalkyl, halo, hydroxyl, CN, Ci-C6haloalkoxy, C2-C6haloalkenyloxy, C2- Cehaloalkynyloxy, and C3-C 4 halocycloalkoxy;
  • R 4a is pyridine, pyrimidine, pyrazine, pyridazine; or
  • R 4a is pyridine, pyrimidine, pyrazine or pyridazine each of which, independently of each other, is substituted with one to three substituents independently selected from Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C3-C 4 cycloalkyl, halogen, hydroxyl, cyano, and Ci-C3haloalkoxy; or R 4a is Y1 , Y2, Y3, and Y4 wherein, R a, R b, and R c, independently of each other and independently of Y1 to Y4, are selected from hydrogen, halogen, CN, Ci-C3alkyl, Ci-C3haloalkyl, C3-C 4 cycloalkyl, Ci-C3alkoxy, and Ci- C3haloalkoxy;
  • R 5 is hydrogen, Ci-C3alkyl, Ci-C3haloalkyl, C3-C 4 cycloalkyl, Ci-C3alkoxy, C3-C 4 alkoxyC(0)-, (Ci- C3alkoxy) 2 CH-, halogen, CN, NH 2 C(0), amino (i.e NH2), (Ci-C3alkyl)amino, di(Ci-C3alkyl)amino, hydroxy, C3-C 4 halocycloalkyl, C3-C 4 cyanocycloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2- Cehaloalkynyl, Ci-C 4 haloalkylsulfanyl, Ci-C 4 haloalkylsulfinyl, Ci-C 4 haloalkylsulfonyl, Ci- C 4 alkylsulfanyl
  • R 5 is a 5-membered heteroaromatic ring substituted with one to three substituents selected from Ci- C3alkyl, Ci-C3haloalkyl, Ci-C3alkoxy, C3-C 4 cycloalkyl, halogen, CN and hydroxyl;
  • R5 3 and Rsb are, independently of each other, selected from hydrogen, halogen, CN, Ci-C3alkyl, Ci- C3haloalkyl, C3-C 4 cycloalkyl, Ci-C3alkoxy, and Ci-C3haloalkoxy; and RY is independently selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, CN and cyclopropyl; or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer and N-oxide of the compound of formula I; provided in the instance there are two fluorine substituents on R 2b , R 2b is not cyclopropyl-CF2-.
  • Compounds of formula I which have at least one basic centre can form, for example, acid addition salts, for example with strong inorganic acids such as mineral acids, for example perchloric acid, sulfuric acid, nitric acid, nitrous acid, a phosphorus acid or a hydrohalic acid, with strong organic carboxylic acids, such as Ci-C 4 alkanecarboxylic acids which are unsubstituted or substituted, for example by halogen, for example acetic acid, such as saturated or unsaturated dicarboxylic acids, for example oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid or phthalic acid, such as hydroxycarboxylic acids, for example ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid, or such as benzoic acid, or with organic sulfonic acids, such as Ci-C 4 alkane- or arylsulfonic acids which are unsubstituted or substituted, for example by
  • Compounds of formula I which have at least one acidic group can form, for example, salts with bases, for example mineral salts such as alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts, or salts with ammonia or an organic amine, such as morpholine, piperidine, pyrrolidine, a mono-, di- ortri-lower-alkylamine, for example ethyl-, diethyl-, triethyl- or dimethylpropylamine, or a mono-, di- or trihydroxy-lower-alkylamine, for example mono-, di- or triethanolamine.
  • bases for example mineral salts such as alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts
  • salts with ammonia or an organic amine such as morpholine, piperidine, pyrrolidine, a mono-, di- ortri-lower-alkylamine, for example ethyl-, diethy
  • the compounds of formula I according to the invention are in free form, in oxidized form as a N-oxide or in salt form, e.g. an agronomically usable salt form.
  • N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen containing heteroaromatic compounds. They are described for instance in the book “Heterocyclic N-oxides” by A. Albini and S. Pietra, CRC Press, Boca Raton 1991.
  • the compounds of formula I according to the invention also include hydrates which may be formed during the salt formation.
  • Ci-C n alkyl refers to a saturated straight-chain or branched hydrocarbon radical attached via any of the carbon atoms having 1 to n carbon atoms, for example, any one of the radicals methyl, ethyl, n-propyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2, 2-dimethylpropyl, 1- ethylpropyl, n-hexyl, n-pentyl, 1 ,1-dimethylpropyl, 1 , 2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1 ,1-dimethylbutyl, 1 ,2-dimethylbutyl, 1 ,3-dimethylbutyl, 2,2- dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-e
  • Ci-C n haloalkyl refers to a straight-chain or branched saturated alkyl radical attached via any of the carbon atoms having 1 to n carbon atoms (as mentioned above), where some or all of the hydrogen atoms in these radicals may be replaced by fluorine, chlorine, bromine and/or iodine, i.e., for example, any one of chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 2- fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2,
  • Ci-C2fluoroalkyl would refer to a Ci-C2alkyl radical which carries 1 , 2, 3, 4, or 5 fluorine atoms, for example, any one of difluoromethyl, trifluoromethyl, 1 -fluoroethyl, 2-fluoroethyl, 2,2- difluoroethyl, 2,2,2-trifluoroethyl, 1 ,1 ,2,2-tetrafluoroethyl or pentafluoroethyl.
  • Ci-C n alkoxy refers to a straight-chain or branched saturated alkyl radical having 1 to n carbon atoms (as mentioned above) which is attached via an oxygen atom, i.e., for example, any one of the radicals methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1- methylpropoxy, 2-methylpropoxy or 1 ,1-dimethylethoxy.
  • haloCi-C n alkoxy refers to a Ci-C n alkoxy radical where one or more hydrogen atoms on the alkyl radical is replaced by the same or different halo atom(s) - examples include trifluoromethoxy, 2-fiuoroethoxy, 3- fluoropropoxy, 3,3,3-trifluoropropoxy, 4-chlorobutoxy.
  • C3-C n cycloalkyl refers to 3-n membered cycloalkyl groups such as cyclopropane, cyclobutane, cyclopentane and cyclohexane.
  • C3-C6cycloalkyl-Ci-C6alkyl“ as used herein refers to 3 to 6 membered cycloalkyl group with a Ci to C6 alkylene group, such as methylene or ethylene, which alkylene group is connected to the rest of the molecule. Examples are cyclopropylmethylene, cyclopropylethylene, and cyclobutylmethylene.
  • the C3-C6cycloalkyl-Ci-C6alkyl- group is substituted, the substituent(s) can be on the cycloalkyl group and/or on the alkyl group. In an embodiment, at least one substitutent is on the alkyl group.
  • the C3-C6- cycloalkylidenemethyl group is substituted, the substituent(s) such as bromine, iodine, chlorine, fluorine, cyano, Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy can, depending on the substituent, be on the cycloalkyl group and/or on the unsaturated carbon atom.
  • C3-C6cycloalkylCi-C 4 haloalkoxy refers to a 3 to 6 membered cycloalkyl group connected to a 1 to 4 membered haloalkoxy, which haloalkoxy group is connected to the rest of the molecule.
  • aminocarbonylCi-C n alkyl“ as used herein refers to an alkyl radical where one of the hydrogen atoms in the radical is replaced by a CONH2 group.
  • hydroxycarbonylCi-C n alkyl“ as used herein refers to an alkyl radical where one of the hydrogen atoms in the radical is replaced by a COOH group.
  • Ci-C n alkylsulfanyl“ as used herein refers to a Ci-C n alkyl moiety linked through a sulfur atom.
  • Ci-C n haloalkylthio“ or “Ci-C n haloalkylsulfanyl“ as used herein refers to a Ci- Cnhaloalkyl moiety linked through a sulfur atom.
  • C3-C n cycloalkylsulfanyl refers to 3-n membered cycloalkyl moiety linked through a sulfur atom.
  • trimethylsilaneCi-C n alkyl“ as used herein refers to an alkyl radical where one of the hydrogen atoms in the radical is replaced by a -Si(CH3)3 group.
  • C2-C n alkenyl refers to a straight or branched alkenyl chain having from two to n carbon atoms and one or two double bonds, for example, ethenyl, prop-l -enyl, but-2-enyl.
  • C2-C n haloalkenyl refers to a C2-C n alkenyl moiety substituted with one or more halo atoms which may be the same or different.
  • C2-C n alkynyl refers to a straight or branched alkynyl chain having from two to n carbon atoms and one triple bond, for example, ethynyl, prop-2-ynyl, but-3-ynyl
  • C2-C n haloalkynyl refers to a C2-C n alkynyl moiety substituted with one or more halo atoms which may be the same or different.
  • the configuration at the double bond can be E or Z or a mixture of diastereoisomers.
  • Halogen or “halo” is generally fluorine, chlorine, bromine or iodine. This also applies, correspondingly, to halogen in combination with other meanings, such as haloalkyl
  • heteroaryl or “heteroaromatic” ring as used herein refers to a 5-membered aromatic monocyclic ring having 1 to 3 heteroatoms independently selected from N, O and S. Specific examples are heteroaryls J-1 to J-35 shown in Scheme A below. Preferred heteroaryls are J-18, J-25, and J-30.
  • the pyridine, pyrimidine, pyrazine and pyridazine groups (unsubstituted or substituted) for R4 and R4a are each connected via a carbon atom on the respective ring to the rest of the compound.
  • controlling refers to reducing the number of pests, eliminating pests and/or preventing further pest damage such that damage to a plant or to a plant derived product is reduced.
  • the staggered line as used herein, for example, in R2t > -1, Q a and Y-1, represent the point of connection/ attachment to the rest of the compound.
  • pest refers to insects, acarines, nematodes and molluscs that are found in agriculture, horticulture, forestry, the storage of products of vegetable origin (such as fruit, grain and timber); and those pests associated with the damage of man-made structures.
  • the term pest encompasses all stages in the life cycle of the pest.
  • the term "effective amount” refers to the amount of the compound, or a salt thereof, which, upon single or multiple applications provides the desired effect.
  • An effective amount is readily determined by the skilled person in the art, by the use of known techniques and by observing results obtained under analogous circumstances. In determining the effective amount a number of factors are considered including, but not limited to: the type of plant or derived product to be applied; the pest to be controlled & its lifecycle; the particular compound applied; the type of application; and other relevant circumstances.
  • compounds of formula I contain a stereogenic centre which is indicated with an asterisk in the structure below: where Ri, R2a, R ⁇ b, R3, Q, and A are as defined in the first aspect.
  • the present invention contemplates both racemates and individual enantiomers.
  • Compounds having preferred stereochemistry are set out below.
  • Particularly preferred compounds of the present invention are compounds of formula I’a: where Ri, R2a, R2t > , R3, Q, and A are as defined in the first aspect, and stereoisomers, enantiomers, tautomers and N-oxides of the compounds of formula (I’a), and agrochemically acceptable salts thereof.
  • C3-C6cycloalkyl-Ci-C6 alkyl is optionally substituted with 1 or 2 fluoro atoms
  • C3-C 4 cycloalkyl, C3-C 4 cycloalkyl substituted with 1 fluoro atom and C3-C 4 cycloalkyl substituted with 2 fluoro atoms means C3-C 4 cycloalkyl, C3-C 4 cycloalkyl substituted with 1 fluoro atom and C3-C 4 cycloalkyl substituted with 2 fluoro atoms.
  • Rr is C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, CN or cyclopropyl; or
  • Ci-C6alkyl optionally substituted with one substituent selected from CN, CONH 2 , COOH, NO 2 , and -Si(CH3)3, Ci-C6haloalkyl, C 2 -C6alkenyl, C 2 -C6alkynyl, C 2 -C6haloalkynyl, C3- C4cycloalkyl-Ci-C2alkyl, wherein the C3-C4cycloalkyl is optionally substituted with 1 or 2 halo atoms, oxetan-3-yl-CH2-, or benzyl optionally substituted with halo or Ci-C3haloalkyl; or
  • Ci-C6alkyl optionally substituted with one substituent selected from CN, CONH 2 , COOH, NO 2 , and -Si(CH3)3, Ci-C6haloalkyl, C 2 -C6alkenyl, C 2 -C6alkynyl, C 2 -C6haloalkynyl, C3- C4cycloalkyl- Ci-C 2 alkyl, or benzyl optionally substituted with halo or Ci-C3haloalkyl; or
  • Ci-C6alkyl optionally substituted with one substituent selected from CN, CONH 2 and COOH, Ci-C6haloalkyl, C 2 -C6alkenyl, C 2 -C6alkynyl, C 2 -C6haloalkynyl, C3-C4cycloalkyl-Ci- C 2 alkyl, or benzyl; or
  • Ci-C3alkyl optionally substituted with CN, Ci-C6haloalkyl, C 2 -C 4 alkenyl, C2- C 4 alkynyl, C 2 -C 4 haloalkynyl, C3-C 4 cycloalkyl-Ci-C 2 alkyl or benzyl; or
  • F hydrogen, Ci-C3alkyl, or C3-C 4 cycloalkyl-Ci-C 2 alkyl; or
  • G hydrogen, methyl, or C3-C 4 cyclopropylmethyl
  • R2a is
  • Ci-C3haloalkyl Ci-C3haloalkylthio, Ci-C3alkoxy, Ci-C3haloalkoxy, or CN; or
  • F3 ⁇ 4b is
  • G selected from R 2b -i to R 2b-2i ; or H. selected from R2t > -4, R2t > -6, R2t > -8, R2b-9, R2b-n, and R2b-12.
  • R3 is
  • Ci-C3alkyl or Ci-C3haloalkyl are independently selected from
  • Q a is
  • Q b is
  • R4 is
  • pyridine wherein the pyridine is optionally substituted with one substituent selected from Ci- C3alkyl, Ci-C3haloalkyl, Ci-C3alkoxy, C3-C 4 cycloalkyl, halo, hydroxyl, CN, Ci-C6haloalkoxy, C2- Cehaloalkenyloxy, C 2 -C6haloalkynyloxy, C3-C4halocycloalkoxy, and C3-C6cycloalkylCi- C4haloalkoxy; or
  • C. pyrimidine wherein the pyrimidine is optionally substituted with one substituent selected from Ci-C3alkyl, Ci-C3haloalkyl, Ci-C3alkoxy, C3-C 4 cycloalkyl, halo, hydroxyl, CN, Ci-C6haloalkoxy, C2-C6haloalkenyloxy, C2-C6haloalkynyloxy, C3-C 4 halocycloalkoxy, and C3-C6cycloalkylCi- C4haloalkoxy; or
  • pyridine, pyrimidine, pyrazine or pyridazine wherein the pyridine, pyrimidine, pyrazine or pyridazine is optionally substituted with one substituent selected from Ci-C3alkyl, C3- C 4 cycloalkyl, F, Cl, Br, CN, and Ci-C6haloalkoxy; or
  • pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2- difluoroethoxy and 2,2,2-trifluoroethoxy; or
  • 5-cylopropylpyridine 5-fluoropyridine, 5-chloropyridine, 5-bromopyridine, 5- difluoromethoxypyridine, 5-trifluoromethoxypyridine, 5-cyanopyridine, 5-(2,2-difluoroethoxy)- pyridine, 5-(2,2,2-trifluoroethoxy)-pyridine, pyridine, 5-cylopropylpyrimidine, 5-fluoropyrimidine, 5-chloropyrimidine, 5-bromopyrimidine, 5-difluoromethoxypyrimidine, 5- trifluoromethoxypyrimidine, 5-cyanopyrimidine, 5-(2,2-difluoroethoxy)-pyrimidine, 5-(2,2,2- trifluoroethoxy)-pyrimidine, or pyrimidine; or
  • R 4a is
  • pyridine, pyrimidine, pyrazine or pyridazine wherein the pyridine, pyrimidine, pyrazine or pyridazine, independent of each other, is optionally substituted with one substituent selected from F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and 2,2,2- trifluoroethoxy and selected from Y-1 to Y-4; or
  • R 4a when Y-1 is selected as R 4a , R a and R c, independently of each other, are
  • R’ 4b and R independently of each other, are hydrogen, halogen, CN, Ci-C3alkyl, Ci- C3haloalkyl, C3-C 4 cycloalkyl, Ci-C3alkoxy, and Ci-C3haloalkoxy; or
  • R’ 4b and R independently of each other, are from hydrogen, F, Cl, Br, CN, methyl, CF3, cyclopropyl, methoxy and difluoromethoxy; or
  • R’4b and R c are both hydrogen; or
  • R’ 4b is hydrogen and R is cyclopropyl.
  • R a and R b independently of each other, are A. hydrogen, halogen, CN, Ci-C3alkyl, Ci-C3haloalkyl, C3-C 4 cycloalkyl, Ci-C3alkoxy, and Ci- C3haloalkoxy; or
  • R a, R’ 4b , and R c are, independently of each other, selected from hydrogen, halogen, CN, Ci- C3alkyl, Ci-C3haloalkyl, C3-C 4 cycloalkyl, Ci-C3alkoxy, and Ci-C3haloalkoxy; or
  • R a, R b, and R are, independently of each other, selected from hydrogen, F, Cl, Br, CN, methyl, CF3, cyclopropyl, methoxy and difluoromethoxy; or
  • R a, R b, and R are all hydrogen; or
  • R a and R are hydrogen and R b is CN.
  • Ci-C3alkyl Ci-C3haloalkyl, C3-C 4 cycloalkyl, Ci-C3alkoxy, halogen, Cl, Br, Ci- C3alkoxy-Ci-C3alkyl, Ci-C3alkoxy-Ci-C3alkoxy-Ci-C3alkyl, (Ci-C3alkyl)C(0), (Ci- C3alkoxy)C(0), or Ci-C2haloalkoxy; or
  • Ci-C2alkyl Ci-C2alkoxy, C3-C 4 cycloalkyl, Ci-C2haloalkoxy, halogen, Ci-C2alkoxy- Ci-C2alkyl, Ci-C2alkoxy-Ci-C2alkoxy-Ci-C2alkyl, (Ci-C 2 alkyl)C(0), HC(O), or (Ci- C 2 alkoxy)C(0); or
  • F hydrogen, methyl, trifluoromethoxy, methoxy, cyclopropyl, 2,2-difluroroethoxy, 2,2,2- trifluroroethoxy, difluoromethoxy, 2,2,2-trifluroroethyl, chloro, bromo, methoxyethoxy, methylcarbonyl, or methoxycarbonyl.
  • B hydrogen, halogen, CN, Ci-C3alkyl, Ci-C3haloalkyl, C3-C 4 cycloalkyl or Ci-C3alkoxy; or C. hydrogen, halogen, CN, Ci-C3alkyl, Ci-C3haloalkyl or Ci-C3alkoxy; or
  • RY is independently selected from
  • the compound of formula I can be represented by formula laa with the asterisk indicating a stereogenic centre), wherein A, Ri, R2a, R2t > , and R3, are as defined in the first aspect and Qi corresponds to Q as defined in the first aspect, each with the corresponding embodiments as described above.
  • Particularly preferred compounds of the present invention are compounds of formula I’aa: where A, Ri, R2a, R ⁇ b , and R3, are as defined in the first aspect and Qi corresponds to Q as defined in the first aspect, and stereoisomers, enantiomers, tautomers and N-oxides of the compounds of formula (I’aa), and agrochemically acceptable salts thereof.
  • Qi is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl
  • the present invention accordingly, makes available a compound of formula I having the substituents Ri, R2a, R ⁇ b , R3, Q, and A as defined above in all combinations / each permutation.
  • a compound of formula I with A being of embodiment A (i.e. A is N, CH, or CRr, where Rr is C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, CN or cyclopropyl);
  • Ri being embodiment B (i.e.
  • Ci-C6alkyl optionally substituted with one substituent selected from CN, CONH2, COOH, NO2, and -Si(CH3)3, Ci-C6haloalkyl, C2-C6alkenyl, C2- Cealkynyl, C2-C6haloalkynyl, C3-C 4 cycloalkyl- Ci-C2alkyl, or benzyl optionally substituted with halo or Ci-C3haloalkyl); R ⁇ a being an embodiment L (i.e. halogen or Ci-C3haloalkyl); R ⁇ b being embodiment G (i.e. selected from R ⁇ b -i to R2b-2i); R3 being embodiment B (i.e.
  • Q being embodiment A (i.e. Q is Q a , wherein Q a is embodiment A (i.e. Q a is selected from Q a -1 to Q a -16; and R 4 is embodiment G (i.e. pyridine, or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and 2,2,2-trifluoroethoxy).
  • the compound of formula I has as A N or CH; as Ri hydrogen, methyl, or cyclopropylmethyl; as R ⁇ a halogen or Ci-C3haloalkyl; as R ⁇ b selected from R ⁇ b -i to R2b-2i; as R3 methyl; and as Q selected from Q a -1 to Q a -16 and Q b -1 to Q b -13, where as R4 (for Q a -1 to Q a -16) is pyridine, or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2- difluoroethoxy and 2,2,2-trifluoroethoxy; and R 4a (for Q b -1 to Q b -13) is pyridine or, pyrimidine, wherein the pyridine or pyrimidine, wherein the pyridine or
  • R’ 4b , and R c independently of each other and independently of Y1 to Y4, are selected from hydrogen, halogen, CN, Ci-C3alkyl, Ci-C3haloalkyl, C3-C 4 cycloalkyl, Ci-C3alkoxy, and Ci- C3haloalkoxy).
  • the compound of formula I has as A N or CH; as Ri hydrogen, methyl, or cyclopropylmethyl; as R2a halogen or Ci-C3haloalkyl; as R ⁇ b selected from R2t>-1 to R2b-2i; as R3 methyl; and as Q selected from Q a -1 to Q a -16 and Q b -1 to Q b -13, where as R4 (for Q a -1 to Q a -16) is pyridine, or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2- difluoroethoxy and 2,2,2-trifluoroethoxy; and R4a (for Q b -1 to Q b -13) is pyridine or, pyrimidine, wherein the pyridine or pyrimidine is optionally
  • R b, and R are each hydrogen).
  • the compound of formula I is represented by formula laa, which has as A N or CH; as Ri hydrogen, methyl, or cyclopropylmethyl; as R ⁇ a halogen or Ci-C3haloalkyl; as R ⁇ b selected from R ⁇ b -i to R2b-2i; as R3 methyl; and as Qi selected from Q aa to Q ag and Q ba to Q bf .
  • the present invention makes available a composition
  • a composition comprising a compound of formula I as defined in the first aspect, one or more auxiliaries and diluent, and optionally one or more other active ingredient.
  • the present invention makes available a method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound as defined in the first aspect or a composition as defined in the second aspect.
  • the present invention makes available a method for the protection of plant propagation material from the attack by insects, acarines, nematodes or molluscs, which comprises treating the propagation material or the site, where the propagation material is planted, with an effective amount of a compound of formula I as defined in the first aspect or a composition as defined in the second aspect.
  • the present invention makes available a plant propagation material, such as a seed, comprising, or treated with or adhered thereto, a compound of formula I as defined in the first aspect or a composition as defined in the second aspect.
  • the present invention in a further aspect provides a method of controlling parasites in or on an animal in need thereof comprising administering an effective amount of a compound of the first aspect.
  • the present invention further provides a method of controlling ectoparasites on an animal in need thereof comprising administering an effective amount of a compound of formula I as defined in the first aspect.
  • the present invention further provides a method for preventing and/or treating diseases transmitted by ectoparasites comprising administering an effective amount of a compound of formula I as defined in the first aspect, to an animal in need thereof.
  • compounds of formula II are treated with iPrMgCI/LiCI-complex; subsequent reaction with CuCN and quenching with a compound of formula III, wherein Z and t are as defined above, provides compounds of formula IV (analog to PCT Int. Appl. W02006/067445, page 148).
  • a compound of formula IV, prepared according to methods described in scheme 1 is reacted with a reductant such as NaBhU or Na(CN)BH3 to a compound of formula VIII, as described for example in ACS Medicinal Chemistry Letters, 2011, 2, 238.
  • R3 solvent optional in the presence of a base R2a e.g. Et j N, pyridine Id
  • Z H, halogen, cyano, C,-C, alkyl
  • a compound of formula VIII is alkylated with a compound of formula R 30 -LG, whereas R 30 is a Ci- C3alkyl group and LG is a leaving group such as halogen, O-mesylate, O-triflate, O-tosylate in the presence of a base such as NaH, NEt3, NaOH, K2CO3. Hydrolysis with a base such as LiOH, NaOH or KOH gives a carboxylic acid of formula XI. Subsequent activation of the carboxylic acid of formula XI and final amide coupling with amines of formula VII delivers compounds of formula Id according to methods known to the person skill in the art, as illustrated in Scheme 3.
  • a compound of formula IV is reacted with compound R 31 MgCI, wherein R 31 is Ci-C3alkyl, Ci- C3haloalkyl, C2-C6alkynyl, to a compound of formula XIII, at temperatures between -78°C and 70°C, preferably between -78°C and RT.
  • R 31 MgCI can be reacted directly with a compound of formula V, prepared according to methods described in Scheme 1.
  • Hydrolysis with a base such as LiOH, NaOH or KOH gives a carboxylic acid of formula XIV.
  • Subsequent activation of the carboxylic acid of formula XIV and final amide coupling with amines of formula VII delivers compounds of formula le according to methods known to the person skill in the art, as illustrated in Scheme 4.
  • a compound of formula VIII, prepared according to methods described in scheme 2 is reacted with a reductant such as Et3SiH in the presence of an acid such as trifluoroacetic acid to a compound of formula XVI, as described for example in PCT Int. Appl. W02009/045830 (2009).
  • Carboxylic acids of formula XXXIX can also be treated by a catalyst, for instance a palladium or an iridium catalyst, eventually in the presence of a ligand, and placed under a hydrogen atmosphere at a pressure from 1 bar to 50 bars in a suitable solvent, e.g. ethanol or dichioromethane, at a temperature between room temperature and 150 °C to provide compounds of the formula XVII (Scheme 5).
  • a catalyst for instance a palladium or an iridium catalyst, eventually in the presence of a ligand, and placed under a hydrogen atmosphere at a pressure from 1 bar to 50 bars in a suitable solvent, e.g. ethanol or dichioromethane, at a temperature between room temperature and 150 °C to provide compounds of the formula XVII (Scheme 5).
  • a catalyst for instance a palladium or an iridium catalyst, eventually in the presence of a ligand, and placed under a hydrogen atmosphere at a pressure from
  • a compound of formula Ih wherein t is 1, 23 or 4, R 1 , R 2a , R 3 and Q are defined as above can be prepared according to reaction Scheme 7.
  • compounds of formula XLI wherein R2a is defined as above are treated with tris(dimethylamino)phosphine and dibromodifluoromethane in a solvent such as tetrahydrofuran, at a temperature of minus 78°C up to room temperature, as described for example in Angew. Chem. Int. Ed., 2019, 58, 3918. Hydrolysis with LiOH as already described gives carboxylic acids of formula XLII.
  • Subsequent activation of the carboxylic acid of formula XLI I and final amide coupling with amines of formula VII delivers compounds of formula Ih as illustrated in Scheme 7.
  • Scheme 10 According to scheme I0, compound of formula LI II wherein t is 1 , 23 or 4, A, R 2a are as described above, can be prepared by treatment of compound of formula LI I with a cyanide source such as potassium thiocyanate, copper iodide, p-toluene sulfonyl hydrazide in presence of a suitable base such as DBU and a suitable solvent such as acetonitrile and NMP at temperature between 60 °C- 120 °C preferably 80 °C (see JOC, 2017 (82) 7621).
  • a cyanide source such as potassium thiocyanate, copper iodide, p-toluene sulfonyl hydrazide
  • a suitable base such as DBU
  • a suitable solvent such as acetonitrile and NMP
  • Intermediate of formula Lll can be prepared by treatment of compound of formula XLV with p-toluene sulfonyl hydrazide in presence of a suitable solvent such as methanol at temperature between 60 °C- 120 °C preferably 70 °C.
  • a suitable solvent such as methanol
  • compound of formula LV wherein A, R 2a are as described above, can be prepared by treatment of compound of formula LIV with methyl magnesium bromide and DMMN in presence of a suitable solvent such as diethyl ether at temperature between 60 °C- 100 °C preferably 80 °C and trapped with a suitable electrophile such as dibromoethane as described in Tetrahedron, 2019 (75), 4298.
  • a suitable solvent such as diethyl ether at temperature between 60 °C- 100 °C preferably 80 °C and trapped with a suitable electrophile such as dibromoethane as described in Tetrahedron, 2019 (75), 4298.
  • compound of formula LVII wherein A, R 2a are as described above can be prepared by treatment of compound of formula LVI with 1 -cyanocyclopropane in presence of a suitable base, preferably isopropyl magnesium chloride, and a suitable solvent such as tetrahydrofuran at temperature between -100 °C- 25 °C as described in W09932448.
  • a suitable base preferably isopropyl magnesium chloride
  • a suitable solvent such as tetrahydrofuran at temperature between -100 °C- 25 °C as described in W09932448.
  • compound of formula LX wherein A, R 2a are as described above, can be prepared by treatment of compound of formula LVII with 3-chloro-2-methyl propene with magnesium in presence of a suitable solvent such as diethyl ether at temperature between -100 °C- 25 °C as described in W02005100587 followed by cyclopropanation under Simmons-Smith conditions as described for example in JOC, 2004, 69, 327.
  • a suitable solvent such as diethyl ether
  • Esters of general formula LXIII, wherein Fka is defined as above and A is C or N, could be prepared following the synthesis described in detail in scheme 14.
  • Esters of general formula LXIII can be synthesized by hydrogenation of esters of formula LXII, wherein R2a is defined as above and A is CH or N.
  • Esters of formula LXII can be treated by a catalyst, for instance a palladium or an iridium catalyst, eventually in the presence of a ligand, and placed under a hydrogen atmosphere at a pressure from 1 bar to 50 bars in a suitable solvent, e.g. ethanol or dichloromethane, at a temperature between room temperature and 150 °C.
  • a catalyst for instance a palladium or an iridium catalyst, eventually in the presence of a ligand, and placed under a hydrogen atmosphere at a pressure from 1 bar to 50 bars in a suitable solvent, e.g. ethanol or dichloromethane, at a temperature between room temperature and 150 °C.
  • the reduction can be carried out by a silane such as triethylsilane or polymethylhydrosiloxane in the presence of an acid such as trifluoroacetic acid in a suitable solvent, e.g. dichloromethane.
  • a silane such as triethylsilane or polymethylhydrosiloxane
  • an acid such as trifluoroacetic acid
  • a suitable solvent e.g. dichloromethane.
  • Alkenes of general formula LXII may be synthesized from ketone of general formula LXI, wherein F3 ⁇ 4a is defined as above and A is C or N, by a Wittig reaction.
  • Wittig reactions involve treating ketones of formula LXI with a phosphonium reagent such as methyltriphenylphosphonium bromide in the presence of a base, e.g. potassium tert-butoxide or n-butyllithium in a suitable solvent such as THF at a temperature between -78 °C and the boiling point of the solvent.
  • a base e.g. potassium tert-butoxide or n-butyllithium
  • suitable solvent such as THF
  • Compounds of formula LXII can be prepared by a Suzuki-Miyaura reaction between compounds of formula LXV wherein W can be a boron-derived functional group, as for example B(OH)2 or a pinacol boron ic ester and compounds of formula LXIV, wherein X is a leaving group like, for example, chlorine, bromine, iodine, arylsulfonate, alkylsulfonate or trifluoromethanesulfonate, A is C or N and F3 ⁇ 4a is as defined above.
  • Compounds of formula LXV are generally commercially available.
  • the reaction can be catalyzed by a palladium based catalyst, for example fefrak/s(triphenylphosphine)-palladium or (1,1 'bis(diphenylphosphino)-ferrocene)dichloropalladium-dichloromethane (1 :1 complex), in presence of a base, like sodium carbonate or cesium fluoride, in a solvent or a solvent mixture, like, for example a mixture of 1 ,2-dimethoxyethane and water, dioxane and water, or DMF and water preferably under inert atmosphere.
  • the reaction temperature can preferentially range from room temperature to the boiling point of the reaction mixture.
  • Alkenes of formula LXIII can be synthesized from compounds of formula LXIV by a Suzuki reaction, which entails treating compounds of formula LXIV by compounds of formula LXVII, wherein W can be a boron-derived functional group as described in scheme 15, in the presence of a palladium catalyst, as described for instance in Chem. Comm. 2017, 53, 6440.
  • Compounds of formula LXVII are generally commercially available. Detailed conditions can be found in scheme 15.
  • compounds of formula LXVIII can be synthesized by treating compounds of formula LXIV with a stannane of formula LXVI in presence of a palladium catalyst (Stille reaction).
  • Compounds of formula LXXI I can be prepared by reaction between a halogenated compound of formula LXIX, wherein Z1 is a C1-C4 alkyl, l3 ⁇ 4a is as described above and A is C or N, and X is a leaving group such as a halogen, a mesylate, a tosylate or a triflate, and compounds of formula LXXI, wherein Z2 is a C1-C4 alkyl, or zincate reagents of formula LXX, wherein Z2 is a C1-C4 alkyl (Reformatsky reagents).
  • a catalyst e.g. a palladium catalyst, eventually in the presence of a base, e.g. tripotassium phosphate, and are described in the literature for instance in J. Org. Chem. 2013, 78, 8250 or W02008/055842.
  • compounds of formula LXXI 11 may be prepared by cyciopropanation of enol ether derivatives of formula LXXV, wherein Zi is a C1-C4 alkyl, R2a is as described above and A is C or N.
  • the conditions for the cyciopropanation reaction have been described in detail in scheme 16.
  • An example of such cyciopropanation can be found for example in Org. Biomol. Chem. 2015, 13, 5105.
  • Enol ether of formula LXXV can be prepared by treating ketones of formula LXXIV, wherein Zi is a C1- C4 alkyl, R2a is as described above and A is C or N, with a base, e.g.
  • Ketones of formula LXXIV can be prepared by mono arylation of acetone with aryls of formula LXIX.
  • Arylation of this type are usually carried out in the presence of a catalyst, e.g. a palladium or a copper catalyst, in the presence of acetone or an acetone equivalent such as preformed stannyl or silyl acetone enolate, and a base, e.g. cesium carbonate or tripotassium phosphate, in a suitable solvent at a temperature between room temperature and 150 °C.
  • a catalyst e.g. a palladium or a copper catalyst
  • acetone or an acetone equivalent such as preformed stannyl or silyl acetone enolate
  • a base e.g. cesium carbonate or tripotassium phosphate
  • Compounds of general formula LXXX can be prepared by treating compounds of formula LXXXI with a deoxyfluorination reagent such as Deoxo-Fluor® or diethy!aminosulfur trifluoride in a suitable solvent such as dichloromethane or toluene. Such a transformation has already been exemplified, for instance in W02004/024720 (p.77).
  • compounds of formula LXXX can be obtained by the reduction of compounds of formula LXXIX, wherein F3 ⁇ 4a is as described above, A is C or N, and X01 is a leaving group, such as Cl, Br, I, OMe, OTs or OTf.
  • Such reductions can be done using hydride donor reagents such as sodium borohydride in a solvent, e.g. methanol or ethanol.
  • Compounds of formula LXXIX can be prepared from alcohols of formula LXXVIII, wherein Fka is as described above and A is C or N.
  • alcohols of formula LXXVIII can be treated with triphenylphosphine in the presence of a halogenating reagent such as CCL, CB ⁇ or h.
  • these compounds can be prepared by treating alcohols of formula LXXVIII with a base, such as triethylamine or pyridine, and a compound of formula XOI-SO2CI, such as mesyl chloride.
  • a base such as triethylamine or pyridine
  • a compound of formula XOI-SO2CI such as mesyl chloride.
  • Alcohols of formula LXXVIII may be synthesized by coupling between a haloaryl of formula LXIX and 1- fluorocyclopropylcarboxaldehyde (CAS 134645-39-9).
  • a haloaryl of formula LXIX and 1- fluorocyclopropylcarboxaldehyde (CAS 134645-39-9).
  • compounds of formula LXIX are treated with a Grignard reagent e.g. iPrMgCI and a copper salt before quenching the intermediate by addition of 1-Fluorocyciopropylcarboxaldehyde.
  • This reaction may take place in a solvent such as THF or toluene at a temperature from -78 °C to room temperature.
  • alcohols of formula LXXVIII may be prepared by cyclopropanation of alcohols of formula LXXVII, wherein l3 ⁇ 4a is as described above and A is C or N. Such a process has been described in detail in scheme 16 and has been described for instance in W02005/030213 (p.200-201).
  • Alcohols of formula LXXVII, wherein R2a is as described above and A is C or N may be prepared by coupling of aldehydes of formula LXXVI, wherein R2a is as described above and A is C or N, with 1- fluoroethenyl-methyl-diphenylsilane (CAS 257610-49-4). This reaction is done in the usual way in the presence of a fluoride source such as tetra-n-butylammonium fluoride in a solvent such as THF. Such as reaction has been described in the literature for instance in Chem. Commun., 1999, 2397 or in W02005/030213 (p.200-201).
  • Aldehydes of formula LXXVI may be prepared byformylation of aryl halides of formula XLIV.
  • Formylation can be done by treatment of compounds of formula XLIV with a Grignard reagent such as iPrMgCI in a solvent such as THF, followed by quenching with a formylation reagent such as N , N-d imethylformamide.
  • a formylation reagent such as N , N-d imethylformamide.
  • the formylation can be carried out by treating the aryl halides of formula LXIX with a catalyst, e.g.
  • Compounds of formula LXXXIV may be prepared by hydrobromination or hydrochlorination of alkenes of formula LXXXIII, wherein F3 ⁇ 4a is as described above and A is C or N. This transformation involves treating alkenes of formula LXXXIII with a halogenating reagent such as bromine, chlorine, N-chlorosuccinimide or N- bromosuccinimide in the presence of a solvent, e.g. acetone and water. This has been described in the literature for instance in J. Org. Chem. 2008, 73, 4702 or Synlett 1998, 5, 491.
  • Compounds of formula LXXXIII may be prepared from compounds of formula LXXII by a Wittig reaction.
  • This reaction may take place using a phosphonium reagent, e.g. triphenyI(3-bromopropyI)phosphonium bromide or cyclopropyltriphenylphosphonium bromide, in the presence of a base, such as potassium tert-butoxide or sodium hydride.
  • a phosphonium reagent e.g. triphenyI(3-bromopropyI)phosphonium bromide or cyclopropyltriphenylphosphonium bromide
  • a base such as potassium tert-butoxide or sodium hydride.
  • Compounds of formula I, wherein A, R 1 , R 2a , R 2b and R 3 are as described above may be formed by condensing an acid of formula XC with a compound of formula XCII in the presence of an activating agent such as DCC, EDD or T3P or by condensing an acid chloride of formula XCI with a compound of formula XCII in the presence of a base according to methods known to the person skill in the art, as illustrated in Scheme 21.
  • A, R 1 , R 2a , R 2b and R 3 are as described above.
  • the reactants can be reacted in the presence of a base.
  • suitable bases are alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal hydrides, alkali metal or alkaline earth metal amides, alkali metal or alkaline earth metal alkoxides, alkali metal or alkaline earth metal acetates, alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal dialkylamides or alkali metal or alkaline earth metal alkylsily!amides, alkylamines, alkylenediamines, free or N-alkylated saturated or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxides and carbocyclic amines.
  • Examples which may be mentioned are sodium hydroxide, sodium hydride, sodium amide, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N,N- dimethylamine, N,N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinuclidine, N- methylmorpholine, benzyltrimethylammonium hydroxide and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).
  • DBU 1,8-diazabicyclo[5.4.0]undec-7-ene
  • the reactants can be reacted with each other as such, i.e. without adding a solvent or diluent. In most cases, however, it is advantageous to add an inert solvent or diluent or a mixture of these. If the reaction is carried out in the presence of a base, bases which are employed in excess, such as triethylamine, pyridine, N-methylmorpholine or N,N-diethylaniline, may also act as solvents or diluents.
  • bases which are employed in excess such as triethylamine, pyridine, N-methylmorpholine or N,N-diethylaniline, may also act as solvents or diluents.
  • the reactions are advantageously carried out in a temperature range from approximately -80°C to approximately +140°C, preferably from approximately -30°C to approximately +100°C, in many cases in the range between ambient temperature and approximately +80°C.
  • Salts of compounds of formula I can be prepared in a manner known perse.
  • acid addition salts of compounds of formula I are obtained by treatment with a suitable acid or a suitable ion exchanger reagent and salts with bases are obtained by treatment with a suitable base or with a suitable ion exchanger reagent.
  • Salts of compounds of formula I can be converted in the customary manner into the free compounds I, acid addition salts, for example, by treatment with a suitable basic compound or with a suitable ion exchanger reagent and salts with bases, for example, by treatment with a suitable acid or with a suitable ion exchanger reagent.
  • Salts of compounds of formula I can be converted in a manner known per se into other salts of compounds of formula I, acid addition salts, for example, into other acid addition salts, for example by treatment of a salt of inorganic acid such as hydrochloride with a suitable metal salt such as a sodium, barium or silver salt, of an acid, for example with silver acetate, in a suitable solvent in which an inorganic salt which forms, for example silver chloride, is insoluble and thus precipitates from the reaction mixture.
  • a salt of inorganic acid such as hydrochloride
  • a suitable metal salt such as a sodium, barium or silver salt
  • the compounds of formula I which have saltforming properties can be obtained in free form or in the form of salts.
  • the compounds of formula I and, where appropriate, the tautomers thereof, in each case in free form or in salt form, can be present in the form of one of the isomers which are possible or as a mixture of these, for example in the form of pure isomers, such as antipodes and/or diastereomers, or as isomer mixtures, such as enantiomer mixtures, for example racemates, diastereomer mixtures or racemate mixtures, depending on the number, absolute and relative configuration of asymmetric carbon atoms which occur in the molecule and/or depending on the configuration of non-aromatic double bonds which occur in the molecule; the invention relates to the pure isomers and also to all isomer mixtures which are possible and is to be understood in each case in this sense hereinabove and hereinbelow, even when stereochemical details are not mentioned specifically in each case.
  • Diastereomer mixtures or racemate mixtures of compounds of formula I, in free form or in salt form, which can be obtained depending on which starting materials and procedures have been chosen can be separated in a known manner into the pure diasteromers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and/or chromatography.
  • Enantiomer mixtures such as racemates, which can be obtained in a similar manner can be resolved into the optical antipodes by known methods, for example by recrystallization from an optically active solvent, by chromatography on chiral adsorbents, for example high-performance liquid chromatography (HPLC) on acetyl celulose, with the aid of suitable microorganisms, by cleavage with specific, immobilized enzymes, via the formation of inclusion compounds, for example using chiral crown ethers, where only one enantiomer is complexed, or by conversion into diastereomeric salts, for example by reacting a basic end-product racemate with an optically active acid, such as a carboxylic acid, for example camphor, tartaric or malic acid, or sulfonic acid, for example camphorsulfonic acid, and separating the diastereomer mixture which can be obtained in this manner, for example by fractional crystallization based on their differing solubilities, to give the
  • Pure diastereomers or enantiomers can be obtained according to the invention not only by separating suitable isomer mixtures, but also by generally known methods of diastereoselective or enantioselective synthesis, for example by carrying out the process according to the invention with starting materials of a suitable stereochemistry.
  • N-oxides can be prepared by reacting a compound of the formula I with a suitable oxidizing agent, for example the H2C>2/urea adduct in the presence of an acid anhydride, e.g. trifluoroacetic anhydride.
  • a suitable oxidizing agent for example the H2C>2/urea adduct
  • an acid anhydride e.g. trifluoroacetic anhydride.
  • the compounds of formula I and, where appropriate, the tautomers thereof, in each case in free form or in salt form, can, if appropriate, also be obtained in the form of hydrates and/or include other solvents, for example those which may have been used for the crystallization of compounds which are present in solid form.
  • the compounds of formula I according to the following Tables A-1 to A-18 can be prepared according to the methods described above. The examples which follow are intended to illustrate the invention and show preferred compounds of formula I, in the form of a compound of formula IA.
  • Table A-1 provides 216 compounds A-1 .001 to A-1 .216 of formula IA wherein A is CH, Ri is H, R ⁇ a is CF3, and R ⁇ b and Q are as defined in table T.
  • A-1001 is
  • Table A-2 provides 216 compounds A-2.001 to A-2.216 of formula IA wherein A is CH, Ri is H, R ⁇ a is Cl, and R ⁇ b and Q are as defined in table T.
  • Table A-3 provides 216 compounds A-3.001 to A-3.216 of formula IA wherein A is CH, Ri is H, R2a is Br, and R ⁇ b and Q are as defined in table T.
  • Table A-4 provides 216 compounds A-4.001 to A-4.216 of formula IA wherein A is CH, Ri is Me, R2a is CF3, and R ⁇ b and Q are as defined in table T.
  • Table A-5 provides 216 compounds A-5.001 to A-5.216 of formula IA wherein A is CH, Ri is Me, R2a is Cl, and R ⁇ b and Q are as defined in table T.
  • Table A-6 provides 216 compounds A-6.001 to A-6.216 of formula IA wherein A is CH, Ri is Me, R2a is Br, and R ⁇ b and Q are as defined in table T.
  • Table A-7 provides 216 compounds A-7.001 to A-7.216 of formula IA wherein A is CH, Ri is CH 2 - cyclopropyl, R 2a is CF3, and R ⁇ b and Q are as defined in table T.
  • Table A-8 provides 216 compounds A-8.001 to A-8.216 of formula IA wherein A is CH, Ri is CH2- cyclopropyl, R2a is Cl, and R ⁇ b and Q are as defined in table T.
  • Table A-9 provides 216 compounds A-9.001 to A-9.216 of formula IA wherein A is CH, Ri is CH2- cyclopropyl, R2a is Br, and R ⁇ b and Q are as defined in table T.
  • Table A-10 provides 216 compounds A-10.001 to A-10.216 of formula IA wherein A is N, Ri is H, R2a is CF3, and R ⁇ b and Q are as defined in table T.
  • Table A-11 provides 216 compounds A-11 .001 to A-11 .216 of formula IA wherein A is N, Ri is H, R2a is Cl, and R ⁇ b and Q are as defined in table T.
  • Table A-12 provides 216 compounds A-12.001 to A-12.216 of formula IA wherein A is N, Ri is H, R ⁇ a is Br, and R ⁇ b and Q are as defined in table T.
  • Table A-13 provides 216 compounds A-13.001 to A-13.216 of formula IA wherein A is N, Ri is Me, R ⁇ a is CF3, and R ⁇ b and Q are as defined in table T.
  • Table A-14 provides 216 compounds A-14.001 to A-14.216 of formula IA wherein A is N, Ri is Me, R ⁇ a is Cl, and R ⁇ b and Q are as defined in table T.
  • Table A-15 provides 216 compounds A-15.001 to A-15.216 of formula IA wherein A is N, Ri is Me, R ⁇ a is Br, and R ⁇ b and Q are as defined in table T.
  • Table A-16 provides 216 compounds A-16.001 to A-16.216 of formula IA wherein A is N, Ri is CH2- cyclopropyl, R ⁇ a is CF3, and R ⁇ b and Q are as defined in table T.
  • Table A-17 provides 216 compounds A-17.001 to A-17.216 of formula IA wherein A is N, Ri is CH2- cyclopropyl, R ⁇ a is Cl, and R ⁇ b and Q are as defined in table T.
  • Table A-18 provides 216 compounds A-18.001 to A-18.216 of formula IA wherein A is N, Ri is CH2- cyclopropyl, R ⁇ a is Br, and R ⁇ b and Q are as defined in table T.
  • the present invention accordingly makes available compounds of formula K wherein A, R ⁇ a and R ⁇ b are as defined for formula I in the first aspect. Furthermore, the corresponding embodiments illustrated for formula I in respect of A, R ⁇ a and R ⁇ b also apply to the compounds of formula K.
  • the compounds of formula I according to the invention are preventively and/or curatively valuable active ingredients in the field of pest control, even at low rates of application, which have a very favorable biocidal spectrum and are well tolerated by warm-blooded species, fish and plants.
  • the active ingredients according to the invention act against all or individual developmental stages of normally sensitive, but also resistant, animal pests, such as insects or representatives of the order Acarina.
  • the insecticidal or acaricidal activity of the active ingredients according to the invention can manifest itself directly, i. e. in destruction of the pests, which takes place either immediately or only after some time has elapsed, for example during ecdysis, or indirectly, for example in a reduced oviposition and/or hatching rate.
  • Examples of the above mentioned animal pests are: from the order Acarina, for example,
  • Hyalomma spp. Ixodes spp., Olygonychus spp, Ornithodoros spp., Polyphagotarsone latus, Panonychus spp., Phyllocoptruta oleivora, Phytonemus spp, Polyphagotarsonemus spp, Psoroptes spp., Rhipicephalus spp., Rhizoglyphus spp., Sarcoptes spp., Steneotarsonemus spp, Tarsonemus spp. and Tetranychus spp.; from the order Anoplura, for example,
  • Haematopinus spp. Linognathus spp., Pediculus spp., Pemphigus spp. and Phylloxera spp.; from the order Coleoptera, for example,
  • Agriotes spp. Amphimallon majale, Anomala orientalis, Anthonomus spp., Aphodius spp, Astylus atromaculatus, Ataenius spp, Atomaria linearis, Chaetocnema tibialis, Cerotoma spp, Conoderus spp, Cosmopolites spp., Cotinis nitida, Curculio spp., Cyclocephala spp, Dermestes spp., Diabrotica spp., Diloboderus abderus, Epilachna spp., Eremnus spp., Heteronychus arator, Hypothenemus hampei, Lagria vilosa, Leptinotarsa decemlineata, Lissorhoptrus spp., Liogenys spp, Maecolaspis spp, Maladera castanea, Megas
  • Acyrthosium pisum Adalges spp, Agalliana ensigera, Agonoscena targionii, Aleurodicus spp, Aleurocanthus spp, Aleurolobus barodensis, Aleurothrixus floccosus, Aleyrodes brassicae, Amarasca biguttula, Amritodus atkinsoni, Aonidiella spp., Aphididae, Aphis spp., Aspidiotus spp., Aulacorthum solani, Bactericera cockerelli, Bemisia spp, Brachycaudus spp, Brevicoryne brassicae, Cacopsylla spp, Cavariella aegopodii Scop., Ceroplaster spp., Chrysomphalus aonidium, Chrysomphalus dictyospermi, Cicadella spp, Cofana spec
  • Coptotermes spp Corniternes cumulans, Incisitermes spp, Macrotermes spp, Mastotermes spp, Microtermes spp, Reticulitermes spp.; Solenopsis geminate from the order Lepidoptera, for example,
  • Blatta spp. Blattella spp., Gryllotalpa spp., Leucophaea maderae, Locusta spp., Neocurtilla hexadactyla, Periplaneta spp. , Scapteriscus spp, and Schistocerca spp.; from the order Psocoptera, for example,
  • Liposcelis spp. from the order Siphonaptera, for example,
  • Calliothrips phaseoli Frankliniella spp., Heliothrips spp, Hercinothrips spp., Parthenothrips spp, Scirtothrips aurantii, Sericothrips variabilis, Taeniothrips spp., Thrips spp; from the order Thysanura, for example, Lepisma saccharina.
  • the invention may also relate to a method of controlling damage to plant and parts thereof by plant parasitic nematodes (Endoparasitic-, Semiendoparasitic- and Ectoparasitic nematodes), especially plant parasitic nematodes such as root knot nematodes, Meloidogyne hapla, Meloidogyne incognita, Meloidogyne javanica, Meloidogyne arenaria and other Meloidogyne species; cyst-forming nematodes, Globodera rostochiensis and other Globodera species; Heterodera avenae, Heterodera glycines, Heterodera schachtii, Heterodera trifolii, and other Heterodera species; Seed gall nematodes, Anguina species; Stem and foliar nematodes, Aphelenchoides species; Sting nematodes, Belonolai
  • Needle nematodes Longidorus elongatus and other Longidorus species; Pin nematodes,
  • Pratylenchus species Lesion nematodes, Pratylenchus neglectus, Pratylenchus penetrans, Pratylenchus curvitatus, Pratylenchus goodeyi and other Pratylenchus species; Burrowing nematodes, Radopholus similis and other Radopholus species; Reniform nematodes, Rotylenchus robustus, Rotylenchus reniformis and other Rotylenchus species; Scutellonema species; Stubby root nematodes, Trichodorus primitivus and other Trichodorus species, Paratrichodorus species; Stunt nematodes, Tylenchorhynchus claytoni, Tylenchorhynchus dubius and other Tylenchorhynchus species; Citrus nematodes, Tylenchulus species; Dagger nematodes, Xiphinema species; and other plant parasitic nematode species, such
  • the compounds of the invention may also have activity against the molluscs.
  • Examples of which include, for example, Ampullariidae; Arion (A. ater, A. circumscriptus, A. hortensis, A. rufus); Bradybaenidae (Bradybaena fruticum); Cepaea (C. hortensis, C. Nemoralis); ochlodina; Deroceras (D. agrestis, D. empiricorum, D. laeve, D. reticulatum); Discus (D. rotundatus); Euomphalia; Galba (G. trunculata); Helicelia (H. itala, H.
  • H. aperta Limax (L. cinereoniger, L. flavus, L. marginatus, L. maximus, L. tenellus); Lymnaea; Milax (M. gagates, M. marginatus, M. sowerbyi); Opeas; Pomacea (P. canaticulata); Vallonia and Zanitoides.
  • the active ingredients according to the invention can be used for controlling, i. e. containing or destroying, pests of the abovementioned type which occur in particular on plants, especially on useful plants and ornamentals in agriculture, in horticulture and in forests, or on organs, such as fruits, flowers, foliage, stalks, tubers or roots, of such plants, and in some cases even plant organs which are formed at a later point in time remain protected against these pests.
  • Suitable target crops are, in particular, cereals, such as wheat, barley, rye, oats, rice, maize or sorghum; beet, such as sugar or fodder beet; fruit, for example pomaceous fruit, stone fruit or soft fruit, such as apples, pears, plums, peaches, almonds, cherries or berries, for example strawberries, raspberries or blackberries; leguminous crops, such as beans, lentils, peas or soya; oil crops, such as oilseed rape, mustard, poppies, olives, sunflowers, coconut, castor, cocoa or ground nuts; cucurbits, such as pumpkins, cucumbers or melons; fibre plants, such as cotton, flax, hemp or jute; citrus fruit, such as oranges, lemons, grapefruit or tangerines; vegetables, such as spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes or bell peppers; Lauraceae, such as avocado, Cinnamonium or camphor; and also tobacco, nuts,
  • compositions and/or methods of the present invention may be also used on any ornamental and/or vegetable crops, including flowers, shrubs, broad-leaved trees and evergreens.
  • the invention may be used on any of the following ornamental species: Ageratum spp., Alonsoa spp., Anemone spp., Anisodontea capsenisis, Anthemis spp., Antirrhinum spp., Aster spp., Begonia spp. (e.g. B. elatior, B. semperflorens, B. tubereux), Bougainvillea spp., Brachycome spp., Brassica spp.
  • Ageratum spp. Ageratum spp., Alonsoa spp., Anemone spp., Anisodontea capsenisis, Anthemis spp., Antirrhinum spp., Aster spp., Begonia spp. (e.g. B. elatior, B. semperflorens, B. tubereux), Bougainvillea spp., Brachycome spp.
  • Calceolaria spp. (ornamental), Calceolaria spp., Capsicum annuum, Catharanthus roseus, Canna spp., Centaurea spp., Chrysanthemum spp., Cineraria spp. (C. maritime), Coreopsis spp., Crassula coccinea, Cuphea ignea, Dahlia spp., Delphinium spp., Dicentra spectabilis, Dorotheantus spp., Eustoma grandiflorum, Forsythia spp., Fuchsia spp., Geranium gnaphalium, Gerbera spp.,
  • Gomphrena globosa Heliotropium spp., Helianthus spp., Hibiscus spp., Hortensia spp., Hydrangea spp., Hypoestes phyllostachya, Impatiens spp. (/. Walleriana), Iresines spp., Kalanchoe spp., Lantana camara, Lavatera trimestris, Leonotis leonurus, Lilium spp., Mesembryanthemum spp., Mimulus spp., Monarda spp., Nemesia spp., Tagetes spp., Dianthus spp.
  • Salvia spp. Scaevola aemola, Schizanthus wisetonensis, Sedum spp., Solanum spp., Surfmia spp., Tagetes spp., Nicotinia spp., Verbena spp., Zinnia spp. and other bedding plants.
  • the invention may be used on any of the following vegetable species: Allium spp. (A. sativum, A. cepa, A. oschaninii, A. Porrum, A. ascalonicum, A. fistulosum), Anthriscus cerefolium, Apium graveolus, Asparagus officinalis, Beta vulgarus, Brassica spp. (B. Oleracea, B. Pekinensis, B. rapa), Capsicum annuum, Cicer arietinum, Cichorium endivia, Cichorum spp. (C. intybus, C. endivia), Citrillus lanatus, Cucumis spp. (C. sativus, C.
  • Preferred ornamental species include African violet, Begonia, Dahlia, Gerbera, Hydrangea, Verbena, Rosa, Kalanchoe, Poinsettia, Aster, Centaurea, Coreopsis, Delphinium, Monarda, Phlox, Rudbeckia, Sedum, Petunia, Viola, Impatiens, Geranium, Chrysanthemum, Ranunculus, Fuchsia, Salvia, Hortensia, rosemary, sage, St. Johnswort, mint, sweet pepper, tomato and cucumber.
  • the active ingredients according to the invention are especially suitable for controlling Aphis craccivora, Diabrotica balteata, Heliothis virescens, Myzus persicae, Plutella xylostella and Spodoptera littoralis in cotton, vegetable, maize, rice and soya crops.
  • the active ingredients according to the invention are further especially suitable for controlling Mamestra (preferably in vegetables), Cydia pomonella (preferably in apples), Empoasca (preferably in vegetables, vineyards), Leptinotarsa (preferably in potatos) and Chilo supressalis (preferably in rice).
  • the compounds of formula I are particularly suitable for control of
  • a pest of the order Hemiptera for example, one or more of the species Bemisia tabaci , Aphis craccivora, Myzus persicae, Rhopalosiphum Padi, Nilaparvata lugens, and Euschistus heros (preferably in vegetables, soybeans, and sugarcane);
  • a pest of the order Lepidoptera for example, one or more of the species Spodoptera littoralis, Spodoptera frugiperda, Plutella xylostella, Cnaphalocrocis medinalis, Cydia pomonella, Chrysodeixis includens, Chilo suppressalis, Elasmopalpus lignosellus, Pseudoplusia includens, and Tuta absoluta (preferably in vegetables and corn);
  • Thysanoptera such as the family Thripidae, for example, one or more of Thrips tabaci and Frankliniella occidentalis (preferably in vegetables);
  • soil pests such as of the order Coleoptera
  • the species Diabrotica balteata, Agriotes spp. and Leptinotarsa decemlineata preferably in vegetables and corn.
  • crops is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
  • Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins, for example insecticidal proteins from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as d-endotoxins, e.g. CrylAb, CrylAc, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vip1 , Vip2, Vip3 orVip3A; or insecticidal proteins of bacteria colonising nematodes, for example Photorhabdus spp.
  • insecticidal proteins for example insecticidal proteins from Bacillus cereus or Bacillus popilliae
  • Bacillus thuringiensis such as d-endotoxins, e.g. CrylAb, CrylAc, Cry1F, Cry1Fa2,
  • Xenorhabdus spp. such as Photorhabdus luminescens, Xenorhabdus nematophilus
  • toxins produced by animals such as scorpion toxins, arachnid toxins, wasp toxins and other insect-specific neurotoxins
  • toxins produced by fungi such as Streptomycetes toxins, plant lectins, such as pea lectins, barley lectins or snowdrop lectins
  • agglutinins proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors
  • steroid metabolism enzymes such as 3-hydroxysteroidoxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidases, ecd
  • 5-endotoxins for example CrylAb, CrylAc, Cry1 F, Cry1 Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), for example Vip1 , Vip2, Vip3 or Vip3A
  • Vip vegetative insecticidal proteins
  • Hybrid toxins are produced recombinantly by a new combination of different domains of those proteins (see, for example, WO 02/15701).
  • Truncated toxins for example a truncated CrylAb, are known.
  • modified toxins one or more amino acids of the naturally occurring toxin are replaced.
  • amino acid replacements preferably non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G-recognition sequence is inserted into a Cry3A toxin (see WO 03/018810).
  • Examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0 374 753, WO 93/07278, WO 95/34656, EP-A-0 427 529, EP-A-451 878 and WO 03/052073.
  • Cryl-type deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP-A-0 367 474, EP-A-0 401 979 and WO 90/13651.
  • the toxin contained in the transgenic plants imparts to the plants tolerance to harmful insects.
  • insects can occur in any taxonomic group of insects, but are especially commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and moths (Lepidoptera).
  • Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available. Examples of such plants are: YieldGard® (maize variety that expresses a CrylAb toxin); YieldGard Rootworm® (maize variety that expresses a Cry3Bb1 toxin); YieldGard Plus® (maize variety that expresses a CrylAb and a Cry3Bb1 toxin); Starlink® (maize variety that expresses a Cry9C toxin); Herculex I® (maize variety that expresses a Cry1 Fa2 toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a Cry1 Ac toxin); Bollgard I® (cotton variety that expresses a
  • transgenic crops are:
  • MIR604 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Maize which has been rendered insect-resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G- protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810.
  • MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/DE/02/9. MON 863 expresses a Cry3Bb1 toxin and has resistance to certain Coleoptera insects.
  • NK603 x MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/GB/02/M3/03. Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810.
  • NK603 c MON 810 Maize transgenically expresses the protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, which imparts tolerance to the herbicide Roundup® (contains glyphosate), and also a CrylAb toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer.
  • crops is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-0 392 225).
  • PRPs pathogenesis-related proteins
  • Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818 and EP-A-0 353 191 .
  • the methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
  • Crops may also be modified for enhanced resistance to fungal (for example Fusarium, Anthracnose, or Phytophthora), bacterial (for example Pseudomonas) or viral (for example potato leafroll virus, tomato spotted wilt virus, cucumber mosaic virus) pathogens.
  • fungal for example Fusarium, Anthracnose, or Phytophthora
  • bacterial for example Pseudomonas
  • viral for example potato leafroll virus, tomato spotted wilt virus, cucumber mosaic virus
  • Crops also include those that have enhanced resistance to nematodes, such as the soybean cyst nematode.
  • Crops that are tolerance to abiotic stress include those that have enhanced tolerance to drought, high salt, high temperature, chill, frost, or light radiation, for example through expression of NF-YB or other proteins known in the art.
  • Antipathogenic substances which can be expressed by such transgenic plants include, for example, ion channel blockers, such as blockers for sodium and calcium channels, for example the viral KP1 , KP4 or KP6 toxins; stilbene synthases; bibenzyl synthases; chitinases; glucanases; the so-called "pathogenesis-related proteins" (PRPs; see e.g. EP-A-0 392 225); antipathogenic substances produced by microorganisms, for example peptide antibiotics or heterocyclic antibiotics (see e.g.
  • compositions according to the invention are the protection of stored goods and store rooms and the protection of raw materials, such as wood, textiles, floor coverings or buildings, and also in the hygiene sector, especially the protection of humans, domestic animals and productive livestock against pests of the mentioned type.
  • the present invention provides a compound of the first aspect for use in therapy.
  • the present invention provides a compound of the first aspect, for use in controlling parasites in or on an animal.
  • the present invention further provides a compound of the first aspect, for use in controlling ectoparasites on an animal.
  • present invention further provides a compound of the first aspect, for use in preventing and/or treating diseases transmitted by ectoparasites.
  • the present invention provides the use of a compound of the first aspect, for the manufacture of a medicament for controlling parasites in or on an animal.
  • the present invention further provides the use of a compound of the first aspect, for the manufacture of a medicament for controlling ectoparasites on an animal.
  • the present invention further provides the use of a compound of the first aspect, for the manufacture of a medicament for preventing and/or treating diseases transmitted by ectoparasites.
  • the present invention provides the use of a compound of the first aspect, in controlling parasites in or on an animal.
  • the present invention further provides the use of a compound of the first aspect , in controlling ectoparasites on an animal.
  • controlling when used in context of parasites in or on an animal refers to reducing the number of pests or parasites, eliminating pests or parasites and/or preventing further pest or parasite infestation.
  • treating when used in context of parasites in or on an animal refers to restraining, slowing, stopping or reversing the progression or severity of an existing symptom or disease.
  • preventing when used used in context of parasites in or on an animal refers to the avoidance of a symptom or disease developing in the animal.
  • animal when used in context of parasites in or on an animal may refer to a mammal and a non-mammal, such as a bird or fish. In the case of a mammal, it may be a human or non-human mammal.
  • Non-human mammals include, but are not limited to, livestock animals and companion animals.
  • Livestock animals include, but are not limited to, cattle, camellids, pigs, sheep, goats and horses.
  • Companion animals include, but are not limited to, dogs, cats and rabbits.
  • a “parasite” is a pest which lives in or on the host animal and benefits by deriving nutrients at the host animal's expense.
  • An “endoparasite” is a parasite which lives in the host animal.
  • An “ectoparasite” is a parasite which lives on the host animal. Ectoparasites include, but are not limited to, acari, insects and crustaceans (e.g. sea lice).
  • the Acari (or Acarina) sub-class comprises ticks and mites.
  • Ticks include, but are not limited to, members of the following genera: Rhipicaphalus, for example, Rhipicaphalus (, Boophilus ) microplus and Rhipicephalus sanguineus ; Amblyomrna Dermacentor, Haemaphysalis ; Hyalomma ; Ixodes ; Rhipicentor, Margaropus ; Argas Otobius ; and Ornithodoros.
  • Mites include, but are not limited to, members of the following genera: Chorioptes, for example Chorioptes bovis ; Psoroptes, for example Psoroptes ovis] Cheyletiella] Dermanyssus] for example Dermanyssus gallinae] Ortnithonyssus ; Demodex, for example Demodex canis ; Sarcoptes, for example Sarcoptes scabiei] and Psorergates. Insects include, but are not limited to, members of the orders: Siphonaptera, Diptera, Phthiraptera, Lepidoptera, Coleoptera and Homoptera.
  • Members of the Siphonaptera order include, but are not limited to, Ctenocephalides felis and Ctenocephatides canis.
  • Members of the Diptera order include, but are not limited to, Musca spp .; bot fly, for example Gasterophilus intestinalis and Oestrus ovis ; biting flies; horse flies, for example Haematopota spp. and Tabunus spp.] haematobia, for example haematobia irritans] Stomoxys] Lucilia] midges; and mosquitoes.
  • Members of the Phthiraptera class include, but are not limited to, blood sucking lice and chewing lice, for example Bovicola Ovis and Bovicola Bovis.
  • effective amount when used in context of parasites in or on an animal refers to the amount or dose of the compound of the invention, or a salt thereof, which, upon single or multiple dose administration to the animal, provides the desired effect in or on the animal.
  • the effective amount can be readily determined by the attending diagnostician, as one skilled in the art, by the use of known techniques and by observing results obtained under analogous circumstances.
  • a number of factors are considered by the attending diagnostician, including, but not limited to: the species of mammal; its size, age, and general health; the parasite to be controlled and the degree of infestation; the specific disease or disorder involved; the degree of involvement or the severity of the disease or disorder; the response of the individual; the particular compound administered; the mode of administration; the bioavailability characteristics of the preparation administered; the dose regimen selected; the use of concomitant medication; and other relevant circumstances.
  • the compounds of the invention may be administered to the animal by any route which has the desired effect including, but not limited to topically, orally, parenterally ' and subcutaneously.
  • Topical administration is preferred.
  • Formulations suitable for topical administration include, for example, solutions, emulsions and suspensions and may take the form of a pour-on, spot-on, spray-on, spray race or dip.
  • the compounds of the invention may be administered by means of an ear tag or collar.
  • Salt forms of the compounds of the invention include both pharmaceutically acceptable salts and veterinary acceptable salts, which can be different to agrochemically acceptable salts.
  • Pharmaceutically and veterinary acceptable salts and common methodology for preparing them are well known in the art. See, for example, Gould, P.L., "Salt selection for basic drugs", International Journal of Pharmaceutics, 33: 201 -217 (1986); Bastin, R.J., et al. "Salt Selection and Optimization Procedures for Pharmaceutical New Chemical Entities", Organic Process Research and Development, 4: 427-435 (2000); and Berge, S.M., et al., “Pharmaceutical Salts", Journal of Pharmaceutical Sciences, 66: 1-19, (1977).
  • the present invention also provides a method for controlling pests (such as mosquitoes and other disease vectors; see also http://www.who.int/malaria/vector_control/irs/en/).
  • the method for controlling pests comprises applying the compositions of the invention to the target pests, to their locus or to a surface or substrate by brushing, rolling, spraying, spreading or dipping.
  • an IRS (indoor residual spraying) application of a surface such as a wall, ceiling or floor surface is contemplated by the method of the invention.
  • the method for controlling such pests comprises applying a pesticidally effective amount of the compositions of the invention to the target pests, to their locus, or to a surface or substrate so as to provide effective residual pesticidal activity on the surface or substrate.
  • a pesticidally effective amount of the compositions of the invention to the target pests, to their locus, or to a surface or substrate so as to provide effective residual pesticidal activity on the surface or substrate.
  • Such application may be made by brushing, rolling, spraying, spreading or dipping the pesticidal composition of the invention.
  • an IRS application of a surface such as a wall, ceiling or floor surface is contemplated by the method of the invention so as to provide effective residual pesticidal activity on the surface.
  • it is contemplated to apply such compositions for residual control of pests on a substrate such as a fabric material in the form of (or which can be used in the manufacture of) netting, clothing, bedding, curtains and tents.
  • Substrates including non-woven, fabrics or netting to be treated may be made of natural fibres such as cotton, raffia, jute, flax, sisal, hessian, or wool, or synthetic fibres such as polyamide, polyester, polypropylene, polyacrylonitrile or the like.
  • the polyesters are particularly suitable.
  • the methods of textile treatment are known, e.g. WO 2008/151984, WO 2003/034823, US 5631072, WO 2005/64072, W02006/128870, EP 1724392, WO 2005113886 or WO 2007/090739.
  • compositions according to the invention are the field of tree injection/trunk treatment for all ornamental trees as well all sort of fruit and nut trees.
  • the compounds according to the present invention are especially suitable against wood-boring insects from the order Lepidoptera as mentioned above and from the order Coleoptera, especially against woodborers listed in the following tables A and B:
  • the present invention may be also used to control any insect pests that may be present in turfgrass, including for example beetles, caterpillars, fire ants, ground pearls, millipedes, sow bugs, mites, mole crickets, scales, mealybugs, ticks, spittlebugs, southern chinch bugs and white grubs.
  • the present invention may be used to control insect pests at various stages of their life cycle, including eggs, larvae, nymphs and adults.
  • the present invention may be used to control insect pests that feed on the roots of turfgrass including white grubs (such as Cyclocephala spp. (e.g. masked chafer, C. lurida), Rhizotrogus spp. (e.g. European chafer, R. majalis), Cotinus spp. (e.g. Green June beetle, C. nitida), Popillia spp. (e.g. Japanese beetle, P. japonica), Phyllophaga spp. (e.g. May/June beetle), Ataenius spp. (e.g. Black turfgrass ataenius, A.
  • white grubs such as Cyclocephala spp. (e.g. masked chafer, C. lurida), Rhizotrogus spp. (e.g. European chafer, R. majalis), Cotinus spp
  • Maladera spp. e.g. Asiatic garden beetle, M. castanea
  • Tomarus spp. ground pearls
  • mole crickets tawny, southern, and short-winged; Scapteriscus spp., Gryllotalpa africana
  • leatherjackets European crane fly, Tipula spp.
  • the present invention may also be used to control insect pests of turfgrass that are thatch dwelling, including armyworms (such as fall armyworm Spodoptera frugiperda, and common armyworm Pseudaletia unipuncta), cutworms, billbugs ( Sphenophorus spp., such as S. venatus verstitus and S. parvulus), and sod webworms (such as Crambus spp. and the tropical sod webworm, Herpetogramma phaeopteralis).
  • armyworms such as fall armyworm Spodoptera frugiperda, and common armyworm Pseudaletia unipuncta
  • cutworms such as S. venatus verstitus and S. parvulus
  • sod webworms such as Crambus spp. and the tropical sod webworm, Herpetogramma phaeopteralis.
  • the present invention may also be used to control insect pests of turfgrass that live above the ground and feed on the turfgrass leaves, including chinch bugs (such as southern chinch bugs, Blissus insularis), Bermudagrass mite (Eriophyes cynodoniensis), rhodesgrass mealybug (Antonina graminis), two-lined spittlebug ( Propsapia bicincta), leafhoppers, cutworms ( Noctuidae family), and greenbugs.
  • chinch bugs such as southern chinch bugs, Blissus insularis
  • Bermudagrass mite Eriophyes cynodoniensis
  • rhodesgrass mealybug Antonina graminis
  • two-lined spittlebug Propsapia bicincta
  • leafhoppers Tricotuidae family
  • cutworms Noctuidae family
  • the present invention may also be used to control other pests of turfgrass such as red imported fire ants ( Solenopsis invicta) that create ant mounds in turf.
  • the compositions according to the invention are active against ectoparasites such as hard ticks, soft ticks, mange mites, harvest mites, flies (biting and licking), parasitic fly larvae, lice, hair lice, bird lice and fleas.
  • Anoplurida Haematopinus spp., Linognathus spp., Pediculus spp. and Phtirus spp., Solenopotes spp..
  • Nematocerina and Brachycerina for example Aedes spp., Anopheles spp., Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Chrysops spp., Hybomitra spp., Atylotus spp., Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Glossina spp., Calliphora spp., Glossina spp., Call
  • Siphonaptrida for example Pulex spp., Ctenocephalides spp., Xenopsylla spp., Ceratophyllus spp..
  • Heteropterida for example Cimex spp., Triatoma spp., Rhodnius spp., Panstrongylus spp..
  • Actinedida Prostigmata
  • Acaridida Acaridida
  • Acarapis spp. Cheyletiella spp., Ornitrocheyletia spp., Myobia spp., Psorergatesspp., Demodex spp., Trombicula spp., Listrophorus spp., Acarus spp., Tyrophagus spp., Caloglyphus spp., Hypodectes spp., Pterolichus spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp.
  • compositions according to the invention are also suitable for protecting against insect infestation in the case of materials such as wood, textiles, plastics, adhesives, glues, paints, paper and card, leather, floor coverings and buildings.
  • compositions according to the invention can be used, for example, against the following pests: beetles such as Hylotrupes bajulus, Chlorophorus pilosis, Anobium punctatum, Xestobium rufovillosum, Ptilinuspecticornis, Dendrobium pertinex, Ernobius mollis, Priobium carpini, Lyctus brunneus, Lyctus africanus, Lyctus planicollis, Lyctus linearis, Lyctus pubescens, Trogoxylon aequale, Minthesrugicollis, Xyleborus spec.,Tryptodendron spec., Apate monachus, Bostrychus capucins, Heterobostrychus brunneus, Sinoxylon spec and Dinoderus minutus, and also hymenopterans such as Sirex juvencus, Urocerus gigas, Urocerus gigas taignus
  • a compound TX controls one or more of pests selected from the family: Noctuidae, Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae, Meloidogynidae, and Heteroderidae.
  • the compounds of formulae I, and I’a, or salts thereof, are especially suitable for controlling one or more of pests selected from the genus: Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp. .
  • a compound TX controls one or more of pests selected from the genus: Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp.
  • pests selected from the genus: Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp.
  • the compounds of formulae I, and I’a, or salts thereof, are especially suitable for controlling one or more of Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus herns, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis includens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum padi, and Chilo suppressalis.
  • a compound TX controls one or more of Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus herns, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis includens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum Padia, and Chilo Suppressalis, such as Spodoptera littoralis + TX, Plutella xylostella + TX; Frankliniella occidentalis + TX, Thrips tabaci + TX, Euschistus herns + TX, Cydia pomonella + TX, Nilaparvata lugens + TX, Myzus persicae
  • one compound from Tables A-1 to A-18 and Table P is suitable for controlling Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus herns, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis includens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum Padia, and Chilo Suppressalis in cotton, vegetable, maize, cereal, rice and soya crops.
  • one compound from from Tables A-1 to A-18 and Table P is suitable for controlling Mamestra (preferably in vegetables), Cydia pomonella (preferably in apples), Empoasca (preferably in vegetables, vineyards), Leptinotarsa (preferably in potatos) and Chilo supressalis (preferably in rice).
  • Compounds according to the invention may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against insects or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (against non-target organisms above and below ground (such as fish, birds and bees), improved physico-chemical properties, or increased biodegradability).
  • advantageous levels of biological activity for protecting plants against insects or superior properties for use as agrochemical active ingredients for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (against non-target organisms above and below ground (such as fish, birds and bees), improved physico-chemical properties, or increased biodegradability).
  • certain compounds of formula I may show an advantageous safety profile with respect to non-target arthropods, in particular pollinators such as honey bees, solitary bees, and bumble bees.
  • Apis mellifera is particularly, for example, Apis mellifera.
  • the compounds according to the invention can be used as pesticidal agents in unmodified form, but they are generally formulated into compositions in various ways using formulation adjuvants, such as carriers, solvents and surface-active substances.
  • formulation adjuvants such as carriers, solvents and surface-active substances.
  • the formulations can be in various physical forms, e.g.
  • Such formulations can either be used directly or diluted prior to use.
  • the dilutions can be made, for example, with water, liquid fertilisers, micronutrients, biological organisms, oil or solvents.
  • the formulations can be prepared e.g. by mixing the active ingredient with the formulation adjuvants in order to obtain compositions in the form of finely divided solids, granules, solutions, dispersions or emulsions.
  • the active ingredients can also be formulated with other adjuvants, such as finely divided solids, mineral oils, oils of vegetable or animal origin, modified oils of vegetable or animal origin, organic solvents, water, surface-active substances or combinations thereof.
  • the active ingredients can also be contained in very fine microcapsules.
  • Microcapsules contain the active ingredients in a porous carrier. This enables the active ingredients to be released into the environment in controlled amounts (e.g. slow-release).
  • Microcapsules usually have a diameter of from 0.1 to 500 microns. They contain active ingredients in an amount of about from 25 to 95 % by weight of the capsule weight.
  • the active ingredients can be in the form of a monolithic solid, in the form of fine particles in solid or liquid dispersion or in the form of a suitable solution.
  • the encapsulating membranes can comprise, for example, natural or synthetic rubbers, cellulose, styrene/butadiene copolymers, polyacrylonitrile, polyacrylate, polyesters, polyamides, polyureas, polyurethane or chemically modified polymers and starch xanthates or other polymers that are known to the person skilled in the art.
  • very fine microcapsules can be formed in which the active ingredient is contained in the form of finely divided particles in a solid matrix of base substance, but the microcapsules are not themselves encapsulated.
  • the formulation adjuvants that are suitable for the preparation of the compositions according to the invention are known perse.
  • liquid carriers there may be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1 ,2-dichloropropane, diethanolamine, p- diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, A/,A/-dimethylformamide, dimethyl sulfoxide, 1 ,4- dioxan
  • Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed husks, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar substances.
  • a large number of surface-active substances can advantageously be used in both solid and liquid formulations, especially in those formulations which can be diluted with a carrier prior to use.
  • Surface- active substances may be anionic, cationic, non-ionic or polymeric and they can be used as emulsifiers, wetting agents or suspending agents or for other purposes.
  • Typical surface-active substances include, for example, salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; salts of alkylarylsulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol/alkylene oxide addition products, such as nonylphenol ethoxylate; alcohol/alkylene oxide addition products, such as tridecylalcohol ethoxylate; soaps, such as sodium stearate; salts of alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2- ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryltrimethylammonium chloride, polyethylene glycol esters of
  • Further adjuvants that can be used in pesticidal formulations include crystallisation inhibitors, viscosity modifiers, suspending agents, dyes, anti-oxidants, foaming agents, light absorbers, mixing auxiliaries, antifoams, complexing agents, neutralising or pH-modifying substances and buffers, corrosion inhibitors, fragrances, wetting agents, take-up enhancers, micronutrients, plasticisers, glidants, lubricants, dispersants, thickeners, antifreezes, microbicides, and liquid and solid fertilisers.
  • compositions according to the invention can include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl esters of such oils or mixtures of such oils and oil derivatives.
  • the amount of oil additive in the composition according to the invention is generally from 0.01 to 10 %, based on the mixture to be applied.
  • the oil additive can be added to a spray tank in the desired concentration after a spray mixture has been prepared.
  • Preferred oil additives comprise mineral oils or an oil of vegetable origin, for example rapeseed oil, olive oil or sunflower oil, emulsified vegetable oil, alkyl esters of oils of vegetable origin, for example the methyl derivatives, or an oil of animal origin, such as fish oil or beef tallow.
  • Preferred oil additives comprise alkyl esters of C8-C22 fatty acids, especially the methyl derivatives of C12-C18 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid (methyl laurate, methyl palmitate and methyl oleate, respectively).
  • Many oil derivatives are known from the Compendium of Herbicide Adjuvants, 10 th Edition, Southern Illinois University, 2010.
  • inventive compositions generally comprise from 0.1 to 99 % by weight, especially from 0.1 to 95 % by weight, of compounds of the present invention and from 1 to 99.9 % by weight of a formulation adjuvant which preferably includes from 0 to 25 % by weight of a surface-active substance.
  • a formulation adjuvant which preferably includes from 0 to 25 % by weight of a surface-active substance.
  • commercial products may preferably be formulated as concentrates, the end user will normally employ dilute formulations.
  • the rates of application vary within wide limits and depend on the nature of the soil, the method of application, the crop plant, the pest to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop.
  • a general guideline compounds may be applied at a rate of from 1 to 2000 l/ha, especially from 10 to 1000 l/ha.
  • Preferred formulations can have the following compositions (weight %):
  • Emulsifiable concentrates active ingredient: 1 to 95 %, preferably 60 to 90 % surface-active agent: 1 to 30 %, preferably 5 to 20 % liquid carrier: 1 to 80 %, preferably 1 to 35 %
  • Dusts active ingredient: 0.1 to 10 %, preferably 0.1 to 5 % solid carrier: 99.9 to 90 %, preferably 99.9 to 99 %
  • Suspension concentrates active ingredient: 5 to 75 %, preferably 10 to 50 % water: 94 to 24 %, preferably 88 to 30 % surface-active agent: 1 to 40 %, preferably 2 to 30 %
  • Wettable powders active ingredient: 0.5 to 90 %, preferably 1 to 80 % surface-active agent: 0.5 to 20 %, preferably 1 to 15 % solid carrier: 5 to 95 %, preferably 15 to 90 %
  • Granules active ingredient: 0.1 to 30 %, preferably 0.1 to 15 % solid carrier: 99.5 to 70 %, preferably 97 to 85 %
  • active ingredient 0.1 to 30 %, preferably 0.1 to 15 % solid carrier: 99.5 to 70 %, preferably 97 to 85 %
  • the combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.
  • the combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment.
  • Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.
  • Ready-for-use dusts are obtained by mixing the combination with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed.
  • the combination is mixed and ground with the adjuvants, and the mixture is moistened with water.
  • the mixture is extruded and then dried in a stream of air.
  • the finely ground combination is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol.
  • Non-dusty coated granules are obtained in this manner.
  • the finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
  • the finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
  • 28 parts of the combination are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1).
  • This mixture is emulsified in a mixture of 1 .2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51 .6 parts of water until the desired particle size is achieved.
  • To this emulsion a mixture of 2.8 parts 1 ,6-diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed.
  • the obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent.
  • the capsule suspension formulation contains 28% of the active ingredients.
  • the medium capsule diameter is 8-15 microns.
  • the resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.
  • Formulation types include an emulsion concentrate (EC), a suspension concentrate (SC), a suspo- emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK), a dispersible concentrate (DC), a wettable powder (WP), a soluble granule (SG) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.
  • EC emulsion concentrate
  • SC suspension concentrate
  • SE suspo- emulsion
  • CS capsule suspension
  • WG water dispersible granule
  • Capillary 3.00 kV, Cone range: 30 V, Extractor: 2.00 V, Source Temperature: 150°C, Desolvation Temperature: 350°C, Cone Gas Flow: 50 l/h, Desolvation Gas Flow: 650 l/h, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment , diode-array detector and ELSD detector.
  • reaction mixture was diluted with water and acidified with 1 N hydrochloric acid until pH reached 2.
  • the aqueous layer was extracted three times with ethyl acetate.
  • the combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 3- (cyclopropanecarbonyl)-5-(trifluoromethyl)benzoic acid (60%, 0.152 g) as a white solid.
  • Step B Preparation of 3-(cyclopropanecarbonyl)-N-(cyclopropylmethyl)-N-[1-(2-pyrimidin-2-yl-1 ,2,4- triazol-3-yl)ethyl1-5-(trifluoromethyl)benzamide (Compound P1) (Compound P1)
  • Step A Preparation of methyl 3-[cvclopropyl(hvdroxy)methyl1-5-(trifluoromethyl)benzoate
  • Step B Preparation of 3-[cvclopropyl(hvdroxy)methyl1-5-(trifluoromethyl)benzoic acid
  • Step _ C _ Preparation _ of _ N-[1-[2-(5-cvano-2-pyridyl)-1 ,2.4-triazol-3-yl1ethyl1-3-
  • Step A Preparation of 3-(1-cvclopropyl-1-hvdroxy-ethyl)-5-(trifluoromethyl)benzoic acid
  • Reaction was cooled to 0 °C and more methylmagnesium bromide (1.4 M solution in tetrahydrofura toluene 1 :3, 0.5 ml, 0.71 mmol, 0.48 equiv.) was added. Reaction was further stirred for 30 minutes at room temperature. Saturated aqueous ammonium chloride solution was added to the reaction mixture and the resulting separated organic layer was concentrated under reduced pressure.
  • Step B Preparation of N-[1-[2-(5-cvano-2-pyridyl)-1 .2.4-triazol-3-yl1ethyl1-3-(1-cvclopropyl-1-hvdroxy- ethyl)-5-(trifluoromethyl)benzamide (Compound P4)
  • Step A Preparation of methyl 3-[cvclopropyl(methoxy)methyl1-5-(trifluoromethyl)benzoate
  • Step B Preparation of 3-[cvclooropyl(methoxy)methyl1-5-(trifluoromethyl)benzoic acid
  • Step _ C _ Preparation _ of _ N-[1-[2-(5-cvano-2-pyridyl)-1 ,2.4-triazol-3-yl1ethyl1-3-
  • Step A Preparation of methyl 3-(cvcloprOPylidenemethvD-5-(trifluoiOmethvDbenzoate
  • Step B Preparation of 3-(cvclopropylidenemethvD-5-(trifluoromethvDbenzoic acid
  • Step D Preparation of N-[1-[2-(5-cvano-2-pyridvD-1 .2.4-triazol-3-yl1ethyl1-3-(cvclopropylmethyl)-5- (trifluoromethyl)benzamide (Compound P6)
  • Methyl 3- (cyclopropanecarbonyl)-5-(trifluoromethyl)benzoate (0.5 g, 1.84 mmol, 1 equiv., prepared analog to W02006/067445, page 148) was dissolved in tetrahydrofuran (3 mL) and added dropwise to the reaction mixture and the reaction was stirred at 40 °C for 17 hours.
  • methyltriphenylphosphonium bromide (1.34 g, 3.67 mmol, 2 equiv.) was dissolved in tetrahydrofuran (9 mL), cooled to 0 °C and n-butyllithium (1.6 M in hexane) ( 2.31 mL, 3.67 mmol, 2 equiv.) was added.
  • the mixture was warmed to room temperature and stirred for 1 hour and added to the above reaction and stirred at 40 °C for an additional 72 hours.
  • the reaction was cooled and quenched with 1 M HCI (10 mL).
  • the mixture was diluted with water (50 mL) and extracted with ethyl acetate (50 mL).
  • Step _ B _ Preparation _ of _ N-[1-[2-(5-cvano-2-pyridyl)-1 ,2.4-triazol-3-yl1ethyl1-3-
  • Step A Preparation of 3-(1-cvcloprOPylethvD-5-(trifluoiOmethvDbenzoic acid
  • Step B Preparation of N-[1-[2-(5-cvano-2-pyridyl)-1 .2.4-triazol-3-yl1ethyl1-3-(1-cvclopropylethyl)-5- (trifluoromethyl)benzamide (Compound P9)
  • Step A Preparation of methyl 3-(1-cvclopropyl-2.2-difluoro-vinyl)-5-(trifluoromethyl)benzoate
  • the crude product was purified by column chromatography (silica, gradient of 0 - 20% ethyl acetate in cyclohexane) to produce methyl 3-(1 -cyclopropyl-2, 2-difluoro-vinyl)-5- (trifluoromethyl)benzoate (49%, 55 mg) as a colorless oil.
  • Step B Preparation of 3-(1-cvclopropyl-2,2-difluoro-vinyl)-5-(trifluoromethyl)benzoic acid
  • the reaction mixture was stirred at room temperature for 2 hours, at which point more sodium hydroxide solution (2M) (0.18 ml_, 0.36 mmol, 2.00 equiv.)
  • the reaction was acidified with HCI (2M), diluted with ethyl acetate (30 ml_) and the aqueous layer washed once with ethyl acetate.
  • the combined organic phases were washed with brine (10 ml_), dried with magnesium sulfate, filtered and concentrated under reduced pressure to afford 3-(1 -cyclopropyl-2, 2-difluoro-vinyl)-5- (trifluoromethyl)benzoic acid (86%, 45 mg) as a white solid.
  • Step C Preparation of N-[1-[2-(5-cvano-2-pyridyl)-1 .2.4-triazol-3-yl1ethyl1-3-(1-cvclopropyl-2.2-difluoro- vinyl)-5-(trifluoromethyl)benzamide (Compound P10)
  • Step A Preparation of methyl 3-(C-cvclopropyl-N-methoxy-carbonimidoyl)-5-(trifluoromethyl)benzoate
  • Step B Preparation of 3-(C-cvclopropyl-N-methoxy-carbonimidoyl)-5-(trifluoromethyl)benzoic acid
  • ⁇ 5 -62.75 (s, 0.5 F) and -62.78 (s, 0.5 F).
  • Step B Preparation of 3-(C-cvclopropyl-N-methoxy-carbonimidoyl)-5-(trifluoromethyl)benzoic acid
  • a solution of methyl 3-(C-cyclopropyl-N-methoxy-carbonimidoyl)-5-(trifluoromethyl)benzoate 101 mg, 0.34 mmol, 1 equiv.
  • tetrahydrofuran (1 ml_
  • water 0.5 ml_
  • reaction mixture was stirred at room temperature for 2 hours.
  • the reaction was acidified with 1 N aqueous hydrochloric acid until pH reached 2 and extracted three times with ethyl acetate.
  • the combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 3-(C-cyclopropyl-N-methoxy- carbonimidoyl)-5-(trifluoromethyl)benzoic acid (93%, 89.2 mg), white solid, as a 1 :1 mixture of E and Z isomers.
  • Step C Preparation of 3-[C-cvclopropyl-N-methoxy-carbonimidoyl1-N-(cvclopropylmethvD-N-[1-(2- pyrimidin-2-yl-1 ,2.4-triazol-3-yl)ethyl1-5-(trifluoromethyl)benzamide (Compound P11)
  • Step A Preparation of methyl 2-[3-bromo-5-(trifluoromethvDphenyl1acetate
  • 2-[3-bromo-5-(trifluoromethyl)phenyl]acetic acid (7 g, 24.73 mmol, 1 equiv.) was dissolved in methanol (50 ml_) and concentrated sulfuric acid (0.014 ml_, 0.25 mmol, 0.01 equiv.) was added and the reaction was stirred at room temperature overnight.
  • the reaction mixture was concentrated under reduced pressure and re-dissolved in ethyl acetate, then washed with saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate and filtered. Solvent was removed under reduced pressure to furnish methyl 2-[3-bromo-5-(trifluoromethyl)phenyl]acetate (95%, 6.95 g).
  • Methyl 2-[3-bromo-5-(trifluoromethyl)phenyl]acetate (6.95 g, 23.4 mmol, 1 equiv.) was dissolved in tetrahydrofuran (23.4 mL) and the solution was cooled to 0 °C. Titanium isopropoxide (1.4 mL, 4.68 mmol, 0.20 equiv.) was added and the reaction was stirred for 10 minutes. Next, bromo(ethyl)magnesium solution (3M in diethylether) (16 mL, 49.1 mmol, 2.10 equiv.) was added via syringe pump over 2 hours with constant gas evolution.
  • Step C Preparation of methyl 3-[(1-hvdroxycvclopropyr)methyl1-5-(trifluoromethvDbenzoate
  • Step D Preparation of 3-[(1-hvdroxycvclopropyr)methyl1-5-(trifluoromethvDbenzoic acid
  • Step E _ Preparation _ of _ N-[1-[2-(5-cvano-2-pyridvD-1 .2.4-triazol-3-yl1ethyl1-3-[(1- hvdroxycvclopropyr)methyl1-5-(trifluoromethyr)benzamide (Compound P12)
  • compositions according to the invention can be broadened considerably, and adapted to prevailing circumstances, by adding other insecticidally, acaricidally and/or fungicidally active ingredients.
  • mixtures of the compounds of formula I with other insecticidally, acaricidally and/or fungicidally active ingredients may also have further surprising advantages which can also be described, in a wider sense, as synergistic activity. For example, better tolerance by plants, reduced phytotoxicity, insects can be controlled in their different development stages or better behaviour during their production, for example during grinding or mixing, during their storage or during their use.
  • Suitable additions to active ingredients here are, for example, representatives of the following classes of active ingredients: organophosphorus compounds, nitrophenol derivatives, thioureas, juvenile hormones, formamidines, benzophenone derivatives, ureas, pyrrole derivatives, carbamates, pyrethroids, chlorinated hydrocarbons, acylureas, pyridylmethyleneamino derivatives, macrolides, neonicotinoids and Bacillus thuringiensis preparations.
  • TX means “one compound selected from the compounds defined in Tables A-1 to A-18 and Table P”
  • an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628) + TX
  • an insect control active substance selected from Abamectin + TX, Acequinocyl + TX, Acetamiprid + TX, Acetoprole + TX, Acrinathrin + TX, Acynonapyr + TX, Afidopyropen + TX, Afoxolaner + TX, Alanycarb + TX, Allethrin + TX, Alpha-Cypermethrin + TX, Alphamethrin + TX, Amidoflumet + TX, Aminocarb + TX, Azocyclotin + TX, Bensultap + TX, Benzoximate + TX, Benzpyrimoxan + TX, Bet
  • Isothioate + TX Ivermectin + TX, Kappa-bifenthrin + TX, Kappa-tefluthrin + TX, Lambda-Cyhalothrin + TX, Lepimectin + TX, Lufenuron + TX, Metaflumizone + TX, Metaldehyde + TX, Metam + TX, Methomyl + TX, Methoxyfenozide + TX, Metofluthrin + TX, Metolcarb + TX, Mexacarbate + TX, Milbemectin + TX, Momfluorothrin + TX, Niclosamide + TX, Nicofluprole + TX; Nitenpyram + TX, Nithiazine + TX, Omethoate + TX, Oxamyl + TX, Oxazosulfyl + TX, Parathion-ethyl + TX, Permethrin + T
  • TX Bacillus sp. AQ177 (ATCC Accession No. 55609) + TX, Bacillus subtilis unspecified + TX, Bacillus subtilis AQ153 (ATCC Accession No. 55614) + TX, Bacillus subtilis AQ30002 (NRRL Accession No. B-50421) + TX, Bacillus subtilis AQ30004 (NRRL Accession No. B- 50455) + TX, Bacillus subtilis AQ713 (NRRL Accession No. B-21661) + TX, Bacillus subtilis AQ743 (NRRL Accession No. B-21665) + TX, Bacillus thuringiensis AQ52 (NRRL Accession No.
  • TX Bacillus thuringiensis BD#32 (NRRL Accession No B-21530) + TX, Bacillus thuringiensis subspec. kurstaki BMP 123 + TX, Beauveria bassiana + TX, D-limonene + TX, Granulovirus + TX, Harpin + TX, Helicoverpa armigera Nucleopolyhedrovirus + TX, Helicoverpa zea Nucleopolyhedrovirus + TX, Heliothis virescens Nucleopolyhedrovirus + TX, Heliothis punctigera Nucleopolyhedrovirus + TX, Metarhizium spp.
  • TX Streptomyces sp. (NRRL Accession No. B-30145) + TX, Terpenoid blend + TX, and Verticillium spp.; an algicide selected from the group of substances consisting of bethoxazin [CCN] + TX, copper dioctanoate (IUPAC name) (170) + TX, copper sulfate (172) + TX, cybutryne [CCN] + TX, dichlone (1052) + TX, dichlorophen (232) + TX, endothal (295) + TX, fentin (347) + TX, hydrated lime [CCN] + TX, nabam (566) + TX, quinoclamine (714) + TX, quinonamid (1379) + TX, simazine (730) + TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347
  • an anthelmintic selected from the group of substances consisting of abamectin (1) + TX, crufomate (1011) + TX, Cyclobutrifluram + TX, doramectin (alternative name) [CCN] + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, eprinomectin (alternative name) [CCN] + TX, ivermectin (alternative name) [CCN] + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, piperazine [CCN] + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) and thiophanate (1435) + TX; an avicide selected from the group of substances consisting of chlora
  • Bacillus thuringiensis subsp. tenebrionis (scientific name) (51) + TX, Beauveria bassiana (alternative name) (53) + TX, Beauveria brongniartii (alternative name) (54) + TX, Chrysoperla carnea (alternative name) (151) + TX, Cryptolaemus montrouzieri (alternative name) (178) + TX, Cydia pomonella GV (alternative name) (191) + TX, Dacnusa sibirica (alternative name) (212) + TX, Diglyphus isaea (alternative name) (254) + TX, Encarsia formosa (scientific name) (293) + TX, Eretmocerus eremicus (alternative name) (300) + TX, Helicoverpa zea NPV (alternative name) (431) + TX, Heterorhabditis bacteriophora and H
  • TX 6-isopentenylaminopurine (alternative name) (210) + TX, abamectin (1) + TX, acetoprole [CCN] + TX, alanycarb (15) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, AZ 60541 (compound code) + TX, benclothiaz [CCN] + TX, benomyl (62) + TX, butylpyridaben (alternative name) + TX, cadusafos (109) + TX, carbofuran (118) + TX, carbon disulfide (945) + TX, carbosulfan (119) + TX, chloropicrin (141) + TX, chlorpyrifos (145) + TX, cloethocarb (999) + TX, Cyclobutrifluram + TX, cytokinins (alternative name) (210) + TX, dazomet (
  • TX Paecilomyces fumosoroseus + TX, Phytoseiulus persimilis + TX, Steinernema bibionis + TX, Steinernema carpocapsae + TX, Steinernema feltiae + TX, Steinernema glaseri + TX, Steinernema riobrave + TX, Steinernema riobravis + TX, Steinernema scapterisci + TX, Steinernema spp. + TX, Trichogramma spp.
  • the compounds in this paragraph may be prepared from the methods described in WO 2017/055473, WO 2017/055469, WO 2017/093348 and WO 2017/118689; 2-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3- pyridyl]-1-(1 ,2,4-triazol-1-yl)propan-2-ol + TX (this compound may be prepared from the methods described in WO 2017/029179); 2-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1 ,2,4-triazol-1- yl)propan-2-ol + TX (this compound may be prepared from the methods described in WO 2017/029179); 3-[2-(1 -chlorocyclopropyl)-3-(2-fluorophenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile + TX (this compound may be prepared from the methods described in
  • Bacillus subtilis strain AQ178 + TX Bacillus subtilis strain QST 713 (CEASE® + TX, Serenade® + TX, Rhapsody®) + TX, Bacillus subtilis strain QST 714 (JAZZ®) + TX, Bacillus subtilis strain AQ153 + TX, Bacillus subtilis strain AQ743 + TX, Bacillus subtilis strain QST3002 + TX, Bacillus subtilis strain QST3004 + TX, Bacillus subtilis var.
  • amyloliquefaciens strain FZB24 (Taegro® + TX, Rhizopro®) + TX, Bacillus thuringiensis Cry 2Ae + TX, Bacillus thuringiensis Cry1 Ab + TX, Bacillus thuringiensis aizawai GC 91 (Agree®) + TX, Bacillus thuringiensis israelensis (BMP123® + TX, Aquabac® + TX, VectoBac®) + TX, Bacillus thuringiensis kurstaki (Javelin® + TX, Deliver® + TX, CryMax® + TX, Bonide® + TX, Scutella WP® + TX, Turilav WP ® + TX, Astuto® + TX, Dipel WP® + TX, Biobit® + TX, Foray®) + TX, Bacillus thuringiensis kurstaki BMP 123 (Baritone
  • aizawai (XenTari® + TX, DiPel®) + TX, bacteria spp. (GROWMEND® + TX, GROWSWEET® + TX, Shootup®) + TX, bacteriophage of Clavipacter michiganensis (AgriPhage®) + TX, Bakflor® + TX, Beauveria bassiana (Beaugenic® + TX, Brocaril WP®) + TX, Beauveria bassiana GHA (Mycotrol ES® + TX, Mycotrol O® + TX, BotaniGuard®) + TX, Beauveria brongniartii (Engerlingspilz® + TX, Schweizer Beauveria® + TX, Melocont®) + TX, Beauveria spp.
  • TX Botrytis cineria + TX, Bradyrhizobium japonicum (TerraMax®) + TX, Brevibacillus brevis + TX, Bacillus thuringiensis tenebrionis (Novodor®) + TX, BtBooster + TX, Burkholderia cepacia (Deny® + TX, Intercept® + TX, Blue Circle®) + TX, Burkholderia gladii + TX, Burkholderia gladioli + TX, Burkholderia spp.
  • TX Canadian thistle fungus (CBH Canadian Bioherbicide®) + TX, Candida butyri + TX, Candida famata + TX, Candida fructus + TX, Candida glabrata + TX, Candida guilliermondii + TX, Candida melibiosica + TX, Candida oleophila strain O + TX, Candida parapsilosis + TX, Candida pelliculosa + TX, Candida pulcherrima + TX, Candida reuêtii + TX, Candida saitoana (Bio-Coat® + TX, Biocure®) + TX, Candida sake + TX, Candida spp.
  • TX Cladosporium tenuissimum + TX, Clonostachys rosea (EndoFine®) + TX, Colletotrichum acutatum + TX, Coniothyrium minitans (Cotans WG®) + TX, Coniothyrium spp.
  • TX Filobasidium floriforme + TX, Fusarium acuminatum + TX, Fusarium chlamydosporum + TX, Fusarium oxysporum (Fusaclean® / Biofox C®) + TX, Fusarium proliferatum + TX, Fusarium spp. + TX, Galactomyces geotrichum + TX, Gliocladium catenulatum (Primastop® + TX, Prestop®) + TX, Gliocladium roseum + TX, Gliocladium spp.
  • TX Halomonas subglaciescola + TX, Halovibrio variabilis + TX, Hanseniaspora uvarum + TX, Helicoverpa armigera nucleopolyhedrovirus (Helicovex®) + TX, Helicoverpa zea nuclear polyhedrosis virus (Gemstar®) + TX, Isoflavone - formononetin (Myconate®) + TX, Kioeckera apiculata + TX, Kioeckera spp.
  • Pasteuria spp. Econem® + TX, Pasteuria nishizawae + TX, Penicillium aurantiogriseum + TX, Penicillium billai (Jumpstart® + TX, TagTeam®) + TX, Penicillium brevicompactum + TX, Penicillium frequentans + TX, Penicillium griseofulvum + TX, Penicillium purpurogenum + TX, Penicillium spp.
  • TX Penicillium viridicatum + TX, Phlebiopsis gigantean (Rotstop®) + TX, phosphate solubilizing bacteria (Phosphomeal®) + TX, Phytophthora cryptogea + TX, Phytophthora palmivora (Devine®) + TX, Pichia anomala + TX, Pichia guilermondii + TX, Pichia membranaefaciens + TX, Pichia onychis + TX, Pichia stipites + TX, Pseudomonas aeruginosa + TX, Pseudomonas aureofasciens (Spot-Less Biofungicide®) + TX, Pseudomonas cepacia + TX, Pseudomonas chlororaphis (AtEze®) + TX, Pseudomonas corrugate + TX, Ps
  • TX Pseudomonas syringae (Bio-Save®) + TX, Pseudomonas viridiflava + TX, Pseudomons fluorescens (Zequanox®) + TX, Pseudozyma fioccuiosa strain PF-A22 UL (Sporodex L®) + TX, Puccinia canaliculate + TX, Puccinia thlaspeos (Wood Warrior®) + TX, Pythium paroecandrum + TX, Pythium oligandrum (Polygandron® + TX, Polyversum®) + TX, Pythium periplocum + TX, Rhanella aquatilis + TX, Rhanella spp.
  • Rhodosporidium diobovatum + TX Rhodosporidium toruloides + TX, Rhodotorula spp.
  • Trichoderma asperellum T34 Biocontrol®
  • Trichoderma gamsii TX
  • Trichoderma atroviride Plantmate®
  • Trichoderma harzianum rifai Mycostar®
  • Trichoderma harzianum T-22 Trianum-P® + TX, PlantShield HC® + TX, RootShield® + TX, Trianum-G®) + TX, Trichoderma harzianum T-39 (Trichodex®) + TX, Trichoderma inhamatum + TX, Trichoderma koningii + TX, Trichoderma spp.
  • LC 52 (Sentinel®) + TX, Trichoderma lignorum + TX, Trichoderma longibrachiatum + TX, Trichoderma polysporum (Binab T®) + TX, Trichoderma taxi + TX, Trichoderma virens + TX, Trichoderma virens (formerly Gliocladium virens GL-21) (SoilGuard®) + TX, Trichoderma viride + TX, Trichoderma viride strain ICC 080 (Remedier®) + TX, Trichosporon pullulans + TX, Trichosporon spp. + TX, Trichothecium spp.
  • TX Trichothecium roseum + TX, Typhula phacorrhiza strain 94670 + TX, Typhula phacorrhiza strain 94671 + TX, Ulocladium atrum + TX, Ulocladium oudemansii (Botry-Zen®) + TX, Ustilago maydis + TX, various bacteria and supplementary micronutrients (Natural II®) + TX, various fungi (Millennium Microbes®) + TX, Verticillium chlamydosporium + TX, Verticillium lecanii (Mycotal® + TX, Vertalec®) + TX, Vip3Aa20 (VIPtera®) + TX, Virgibaclillus marismortui + TX, Xanthomonas campestris pv. Poae (Camperico®) + TX, Xenorhabdus bovienii + TX, Xenorhab
  • Plant extracts including: pine oil (Retenol®) + TX, azadirachtin (Plasma Neem Oil® + TX, AzaGuard®
  • TX Chilocorus nigritus + TX, Chrysoperla carnea (Chrysoline®) + TX, Chrysoperla carnea (Chrysopa®) + TX, Chrysoperla rufilabris + TX, Cirrospilus ingenuus + TX, Cirrospilus quadristriatus + TX, Citrostichus phyllocnistoides + TX, Closterocerus chamaeleon + TX, Closterocerus spp.
  • TX Coccidoxenoides perminutus (Planopar®) + TX, Coccophagus cowperi + TX, Coccophagus lycimnia + TX, Cotesia fiavipes + TX, Cotesia plutellae + TX, Cryptolaemus montrouzieri (Cryptobug® + TX, Cryptoline®) + TX, Cybocephalus nipponicus + TX, Dacnusa sibirica + TX, Dacnusa sibirica (Minusa®) + TX, Diglyphus isaea (Diminex®) + TX, Delphastus catalinae (Delphastus®) + TX, Delphastus pusillus + TX, Diachasmimorpha krausii + TX, Diachasmimorpha longicaudata + TX, Diaparsis jucunda + TX, Diaphorencyrtus aligarhensis
  • TX Eretmocerus siphonini + TX, Exochomus quadripustulatus + TX, Feltiella acarisuga (Spidend®) + TX, Feltiella acarisuga (Feltiline®) + TX, Fopius arisanus + TX, Fopius ceratitivorus + TX, Formononetin (Wirless Beehome®) + TX, Franklinothrips vespiformis (Vespop®) + TX, Galendromus occidentalis + TX, Goniozus legneri + TX, Flabrobracon hebetor + TX, Harmonia axyridis (HarmoBeetle®) + TX, Heterorhabditis spp.
  • TX Psyttalia concolor (complex) + TX, Quadrastichus spp. + TX, Rhyzobius lophanthae + TX, Rodolia cardinalis + TX, Rumina decollate + TX, Semielacher petiolatus + TX, Sitobion avenae (Ervibank®) + TX, Steinernema carpocapsae (Nematac C® + TX, Millenium® + TX, BioNem C® + TX, NemAttack®
  • TX Steinernematid spp. (Guardian Nematodes®) + TX, Stethorus punctillum (Stethorus®) + TX, Tamarixia radiate + TX, Tetrastichus setifer + TX, Thripobius semiluteus + TX, Torymus sinensis + TX, Trichogramma brassicae (Tricholine b®) + TX, Trichogramma brassicae (Tricho-Strip®) + TX, Trichogramma evanescens + TX, Trichogramma minutum + TX, Thchogramma ostriniae + TX, Trichogramma platneh + TX, Trichogramma pretiosum + TX, Xanthopimpla stemmator, other biologicals including: abscisic acid + TX, bioSea® + TX, Chondrostereum purpureum (Chontrol Paste®) + TX, Colletotrichum gloeosporio
  • the active ingredient mixture of the compounds of formula I selected from the compounds defined in the Tables A-1 to A-18 and Table P with active ingredients described above comprises a compound selected from Tables A-1 to A-18 and Table P and an active ingredient as described above preferably in a mixing ratio of from 100:1 to 1 :6000, especially from 50:1 to 1 :50, more especially in a ratio of from 20:1 to 1 :20, even more especially from 10:1 to 1 :10, very especially from 5:1 and 1 :5, special preference being given to a ratio of from 2:1 to 1 :2, and a ratio of from 4:1 to 2:1 being likewise preferred, above all in a ratio of 1 :1 , or 5:1 , or 5:2, or 5:3, or 5:4, or 4:1 , or 4:2, or 4:3, or 3:1 , or 3:2, or 2:1 , or 1 :5, or 2:5, or 3:5, or 4:5, or 1 :4, or 2:4, or 3:4, or 1 :3, or 2:3, or 1 :2,
  • the compounds and mixtures as described above can be used in a method for controlling pests, which comprises applying a composition comprising a compound or mixture as described above to the pests or their environment, with the exception of a method for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body.
  • the mixtures comprising a compound of formula I selected from the compounds defined in the Tables A-1 to A-18 and Table P and one or more active ingredients as described above can be applied, for example, in a single “ready-mix” form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a “tank-mix”, and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days.
  • the order of applying the compounds of formula I and the active ingredients as described above is not essential for working the present invention.
  • compositions according to the invention can also comprise further solid or liquid auxiliaries, such as stabilizers, for example unepoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soya oil), antifoams, for example silicone oil, preservatives, viscosity regulators, binders and/or tackifiers, fertilizers or other active ingredients for achieving specific effects, for example bactericides, fungicides, nematocides, plant activators, molluscicides or herbicides.
  • auxiliaries such as stabilizers, for example unepoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soya oil), antifoams, for example silicone oil, preservatives, viscosity regulators, binders and/or tackifiers, fertilizers or other active ingredients for achieving specific effects, for example bactericides, fungicides, nematocides
  • compositions according to the invention are prepared in a manner known per se, in the absence of auxiliaries for example by grinding, screening and/or compressing a solid active ingredient and in the presence of at least one auxiliary for example by intimately mixing and/or grinding the active ingredient with the auxiliary (auxiliaries).
  • auxiliaries for example by grinding, screening and/or compressing a solid active ingredient and in the presence of at least one auxiliary for example by intimately mixing and/or grinding the active ingredient with the auxiliary (auxiliaries).
  • compositions that is the methods of controlling pests of the abovementioned type, such as spraying, atomizing, dusting, brushing on, dressing, scattering or pouring - which are to be selected to suit the intended aims of the prevailing circumstances - and the use of the compositions for controlling pests of the abovementioned type are other subjects of the invention.
  • Typical rates of concentration are between 0.1 and 1000 ppm, preferably between 0.1 and 500 ppm, of active ingredient.
  • the rate of application per hectare is generally 1 to 2000 g of active ingredient per hectare, in particular 10 to 1000 g/ha, preferably 10 to 600 g/ha.
  • a preferred method of application in the field of crop protection is application to the foliage of the plants (foliar application), it being possible to select frequency and rate of application to match the danger of infestation with the pest in question.
  • the active ingredient can reach the plants via the root system (systemic action), by drenching the locus of the plants with a liquid composition or by incorporating the active ingredient in solid form into the locus of the plants, for example into the soil, for example in the form of granules (soil application). In the case of paddy rice crops, such granules can be metered into the flooded paddy-field.
  • the compounds of formula I of the invention and compositions thereof are also be suitable for the protection of plant propagation material, for example seeds, such as fruit, tubers or kernels, or nursery plants, against pests of the abovementioned type.
  • the propagation material can be treated with the compound prior to planting, for example seed can be treated prior to sowing.
  • the compound can be applied to seed kernels (coating), either by soaking the kernels in a liquid composition or by applying a layer of a solid composition. It is also possible to apply the compositions when the propagation material is planted to the site of application, for example into the seed furrow during drilling.
  • These treatment methods for plant propagation material and the plant propagation material thus treated are further subjects of the invention.
  • Typical treatment rates would depend on the plant and pest/fungi to be controlled and are generally between 1 to 200 grams per 100 kg of seeds, preferably between 5 to 150 grams per 100 kg of seeds, such as between 10 to 100 grams per 100 kg of seeds.
  • seed embraces seeds and plant propagules of all kinds including but not limited to true seeds, seed pieces, suckers, corns, bulbs, fruit, tubers, grains, rhizomes, cuttings, cut shoots and the like and means in a preferred embodiment true seeds.
  • the present invention also comprises seeds coated or treated with or containing a compound of formula I.
  • coated or treated with and/or containing generally signifies that the active ingredient is for the most part on the surface of the seed at the time of application, although a greater or lesser part of the ingredient may penetrate into the seed material, depending on the method of application.
  • the present invention makes available a plant propagation material adhered thereto with a compound of formula I.
  • a composition comprising a plant propagation material treated with a compound of formula I.
  • Seed treatment comprises all suitable seed treatment techniques known in the art, such as seed dressing, seed coating, seed dusting, seed soaking and seed pelleting.
  • the seed treatment application of the compound formula I can be carried out by any known methods, such as spraying or by dusting the seeds before sowing or during the sowing/planting of the seeds.
  • the compounds of the invention can be distinguished from other similar compounds by virtue of greater efficacy at low application rates and/or different pest control, which can be verified by the person skilled in the art using the experimental procedures, using lower concentrations if necessary, for example 10 ppm, 5 ppm, 2 ppm, 1 ppm or 0.2 ppm; or lower application rates, such as 300, 200 or 100, mg of Al per m 2 .
  • the greater efficacy can be observed by an increased safety profile (against non-target organisms above and below ground (such as fish, birds and bees), improved physicochemical properties, or increased biodegradability).
  • Example B1 Diabrotica balteata (Corn root worm)
  • Maize sprouts placed onto an agar layer in 24-well microtiter plates were treated with aqueous test solutions prepared from 10 ⁇ 00 ppm DMSO stock solutions by spraying. After drying, the plates were infested with L2 larvae (6 to 10 per well). The samples were assessed for mortality and growth inhibition in comparison to untreated samples 4 days after infestation.
  • Example B2 Euschistus herns (Neotropical Brown Stink Bug)
  • Soybean leaves on agar in 24-well microtiter plates were sprayed with aqueous test solutions prepared from 10 ⁇ 00 ppm DMSO stock solutions. After drying the leaves were infested with N2 nymphs. The samples were assessed for mortality and growth inhibition in comparison to untreated samples 5 days after infestation.
  • Example B3 Chilo suppressalis (Striped rice stemborer)
  • 24-well microtiter plates with artificial diet were treated with aqueous test solutions prepared from 10 ⁇ 00 ppm DMSO stock solutions by pipetting. After drying, the plates were infested with L2 larvae (6-8 per well). The samples were assessed for mortality, anti-feeding effect, and growth inhibition in comparison to untreated samples 6 days after infestation. Control of Chilo suppressalis by a test sample is given when at least one of the categories mortality, anti-feedant effect, and growth inhibition is higher than the untreated sample.
  • Example B4 Plutella xylostella (Diamond back moth)
  • 24-well microtiter plates with artificial diet were treated with aqueous test solutions prepared from 10 ⁇ 00 ppm DMSO stock solutions by pipetting. After drying, Plutella eggs were pipetted through a plastic stencil onto a gel blotting paper and the plate was closed with it. The samples were assessed for mortality and growth inhibition in comparison to untreated samples 8 days after infestation.
  • Example B5 Spodoptera littoralis (Egyptian cotton leaf worm)
  • Cotton leaf discs were placed onto agar in 24-well microtiter plates and sprayed with aqueous test solutions prepared from 10 ⁇ 00 ppm DMSO stock solutions. After drying the leaf discs were infested with five L1 larvae. The samples were assessed for mortality, anti-feeding effect, and growth inhibition in comparison to untreated samples 3 days after infestation. Control of Spodoptera littoralis by a test sample is given when at least one of the categories mortality, anti-feedant effect, and growth inhibition is higher than the untreated sample.
  • Example B6 Plutella xylostella (Diamondback Moth)
  • 96-well microtiter plates containing artificial diet were treated with aqueous test solutions, prepared from 10 ⁇ 00 ppm DMSO stock solutions, by a liquid handling robot. After drying, eggs ( ⁇ 30 per well) were infested onto a netted lid which was suspended above the diet. The eggs hatch and L1 larvae move down to the diet. The samples were assessed for mortality 9 days after infestation.
  • Example 7 Mvzus persicae (Green peach aphid). Intrinsic activity
  • Test compounds prepared from 10 ⁇ 00 ppm DMSO stock solutions were applied by pipette into 24- well microtiter plates and mixed with sucrose solution. The plates were closed with a stretched Parafilm. A plastic stencil with 24 holes was placed onto the plate and infested pea seedlings were placed directly on the Parafilm. The infested plate was closed with a gel blotting paper and another plastic stencil and then turned upside down. The samples were assessed for mortality 5 days after infestation.
  • Example 8 Thrips tabaci (Onion thrips) Feedinq/Contact activity
  • Sunflower leaf discs were placed on agar in 24-well microtiter plates and sprayed with aqueous test solutions prepared from 10 ⁇ 00 ppm DMSO stock solutions. After drying the leaf discs were infested with a thrips population of mixed ages. The samples were assessed for mortality 6 days after infestation.

Abstract

Compounds of formula (I) wherein the substituents are as defined in claim 1, and the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds, can be used as insecticides.

Description

PESTICIDALLY ACTIVE AZOLE-AMIDE COMPOUNDS
The present invention relates to pesticidally active, in particular insecticidally active quinazoline compounds, to processes for their preparation, to compositions comprising those compounds, and to their use for controlling animal pests, including arthropods and in particular insects or representatives of the order Acarina.
WO2017192385 describes certain heteroaryl-1 ,2,4-triazole and heteroaryl-tetrazole compounds for use for controlling ectoparasites in animals (such as a mammal and a non-mammal animal).
There have now been found novel pesticidally active azole-amide compounds.
The present invention accordingly relates, in a first aspect, to a compound of the formula I
Figure imgf000002_0001
wherein:
A is N or CRY; Q is
Figure imgf000002_0002
Q or Qb
R1 is hydrogen; Ci-C6alkyl, Ci-C6alkyl substituted with one substituent selected from CN, C(0)NH2, C(0)0H, NO2, and -Si(CH3)3, Ci-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C3- C4cycloalkyl- Ci-C2alkyl, C3-C4cycloalkyl- Ci-C2alkyl substituted with 1 or 2 halo atoms; oxetan-3-yl- CH2-, benzyl, or benzyl substituted with halo or Ci-C3haloalkyl;
R2a is Ci-C3alkyl, Ci-C3haloalkyl, Ci- Cshaloalkylthio, Ci- Csalkoxy, Ci- Cshaloalkoxy, halo, NO2, SFs, CN, C(0)NH2, C(0)0H, C(S)NH2;
R2b is C3-C6-cycloalkyl-Ci-C6alkyl optionally substituted with one to three substituents independently selected from bromine, iodine, chlorine, fluorine, OH, cyano, Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C2-C6alkynyl, =0, =CH2, =CF2, =CCl2, =N-Ci-C3alkoxy, and =CMe2; or C3-C6-cycloalkylidenemethyl optionally substituted with one to three substituents independently selected from halo, cyano, Ci- C3alkyl, Ci-C3haloalkyl, and Ci- Csalkoxy;
R3 is Ci-C3alkyl or Ci-C3haloalkyl;
R4 is pyridine, pyrimidine, pyrazine or pyridazine; or
R4 is pyridine, pyrimidine, pyrazine or pyridazine each of which, independently of each other, is substituted with one to two substituents independently selected from Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C3-C4cycloalkyl, halo, hydroxyl, CN, Ci-C6haloalkoxy, C2-C6haloalkenyloxy, C2- Cehaloalkynyloxy, and C3-C4halocycloalkoxy;
R4a is pyridine, pyrimidine, pyrazine, pyridazine; or
R4a is pyridine, pyrimidine, pyrazine or pyridazine each of which, independently of each other, is substituted with one to three substituents independently selected from Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C3-C4cycloalkyl, halogen, hydroxyl, cyano, and Ci-C3haloalkoxy; or R4a is Y1 , Y2, Y3, and Y4
Figure imgf000003_0001
wherein, R a, R b, and R c, independently of each other and independently of Y1 to Y4, are selected from hydrogen, halogen, CN, Ci-C3alkyl, Ci-C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy, and Ci- C3haloalkoxy;
R5 is hydrogen, Ci-C3alkyl, Ci-C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy, C3-C4alkoxyC(0)-, (Ci- C3alkoxy)2CH-, halogen, CN, NH2C(0), amino (i.e NH2), (Ci-C3alkyl)amino, di(Ci-C3alkyl)amino, hydroxy, C3-C4halocycloalkyl, C3-C4cyanocycloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2- Cehaloalkynyl, Ci-C4haloalkylsulfanyl, Ci-C4haloalkylsulfinyl, Ci-C4haloalkylsulfonyl, Ci- C4alkylsulfanyl, Ci-C4alkylsulfinyl, Ci-C4alkylsulfonyl, Ci-C3alkoxy-Ci-C3alkyl, Ci-C3alkoxy-Ci- C3alkoxy-Ci-C3alkyl, (Ci-C3alkyl)sulfonylamino, (Ci-C3alkyl)sulfonyl(Ci-C3alkyl)amino, (Ci- C3alkyl)NHC(0), (Ci-C3alkyl)2NC(0), (Ci-C3cycloalkyl)NHC(0), (Ci-C3cycloalkyl)(Ci-C3alkyl)NC(0), (Ci-C3alkyl)C(0)(Ci-C3alkyl)N, (Ci-C3alkyi)C(0)NH, (Ci-C3alkyi)C(0), (Ci-C3aikoxy)C(0), HC(O), diphenylmethanimine, Ci-C3haloalkoxy, phenyl, or a 5-membered heteroaromatic ring; or R5 is phenyl substituted with one to three substituents selected from Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C3-C4cycloalkyl, halogen, CN and hydroxyl; or
R5 is a 5-membered heteroaromatic ring substituted with one to three substituents selected from Ci- C3alkyl, Ci-C3haloalkyl, Ci-C3alkoxy, C3-C4cycloalkyl, halogen, CN and hydroxyl;
R53 and Rsb are, independently of each other, selected from hydrogen, halogen, CN, Ci-C3alkyl, Ci- C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy, and Ci-C3haloalkoxy; and RY is independently selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, CN and cyclopropyl; or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer and N-oxide of the compound of formula I; provided in the instance there are two fluorine substituents on R2b, R2b is not cyclopropyl-CF2-.
Compounds of formula I which have at least one basic centre can form, for example, acid addition salts, for example with strong inorganic acids such as mineral acids, for example perchloric acid, sulfuric acid, nitric acid, nitrous acid, a phosphorus acid or a hydrohalic acid, with strong organic carboxylic acids, such as Ci-C4alkanecarboxylic acids which are unsubstituted or substituted, for example by halogen, for example acetic acid, such as saturated or unsaturated dicarboxylic acids, for example oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid or phthalic acid, such as hydroxycarboxylic acids, for example ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid, or such as benzoic acid, or with organic sulfonic acids, such as Ci-C4alkane- or arylsulfonic acids which are unsubstituted or substituted, for example by halogen, for example methane- or p-toluenesulfonic acid. Compounds of formula I which have at least one acidic group can form, for example, salts with bases, for example mineral salts such as alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts, or salts with ammonia or an organic amine, such as morpholine, piperidine, pyrrolidine, a mono-, di- ortri-lower-alkylamine, for example ethyl-, diethyl-, triethyl- or dimethylpropylamine, or a mono-, di- or trihydroxy-lower-alkylamine, for example mono-, di- or triethanolamine.
In each case, the compounds of formula I according to the invention are in free form, in oxidized form as a N-oxide or in salt form, e.g. an agronomically usable salt form.
N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen containing heteroaromatic compounds. They are described for instance in the book “Heterocyclic N-oxides” by A. Albini and S. Pietra, CRC Press, Boca Raton 1991.
The compounds of formula I according to the invention also include hydrates which may be formed during the salt formation.
The term "Ci-Cnalkyl” as used herein refers to a saturated straight-chain or branched hydrocarbon radical attached via any of the carbon atoms having 1 to n carbon atoms, for example, any one of the radicals methyl, ethyl, n-propyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2, 2-dimethylpropyl, 1- ethylpropyl, n-hexyl, n-pentyl, 1 ,1-dimethylpropyl, 1 , 2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1 ,1-dimethylbutyl, 1 ,2-dimethylbutyl, 1 ,3-dimethylbutyl, 2,2- dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1 ,1 ,2-trimethylpropyl,
1 ,2,2-trimethylpropyl, 1 -ethyl-1 -methylpropyl, or 1-ethyl-2-methylpropyl. The term "Ci-Cnhaloalkyl" as used herein refers to a straight-chain or branched saturated alkyl radical attached via any of the carbon atoms having 1 to n carbon atoms (as mentioned above), where some or all of the hydrogen atoms in these radicals may be replaced by fluorine, chlorine, bromine and/or iodine, i.e., for example, any one of chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 2- fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2- fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl, 2,2-difluoropropyl, 2,3-difluoropropyl, 2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl, 3,3,3-trichloropropyl, 2, 2, 3,3,3- pentafluoropropyl, heptafluoropropyl, 1-(fluoromethyl)-2-fluoroethyl, 1-(chloromethyl)-2-chloroethyl, 1- (bromomethyl)-2-bromoethyl, 4-fluorobutyl, 4-ch loro butyl, 4-bromobutyl or nonafluorobutyl. According a term "Ci-C2fluoroalkyl" would refer to a Ci-C2alkyl radical which carries 1 , 2, 3, 4, or 5 fluorine atoms, for example, any one of difluoromethyl, trifluoromethyl, 1 -fluoroethyl, 2-fluoroethyl, 2,2- difluoroethyl, 2,2,2-trifluoroethyl, 1 ,1 ,2,2-tetrafluoroethyl or pentafluoroethyl.
The term "Ci-Cnalkoxy" as used herein refers to a straight-chain or branched saturated alkyl radical having 1 to n carbon atoms (as mentioned above) which is attached via an oxygen atom, i.e., for example, any one of the radicals methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1- methylpropoxy, 2-methylpropoxy or 1 ,1-dimethylethoxy. The term “haloCi-Cnalkoxy" as used herein refers to a Ci-Cnalkoxy radical where one or more hydrogen atoms on the alkyl radical is replaced by the same or different halo atom(s) - examples include trifluoromethoxy, 2-fiuoroethoxy, 3- fluoropropoxy, 3,3,3-trifluoropropoxy, 4-chlorobutoxy.
The term “C3-Cncycloalkyl” as used herein refers to 3-n membered cycloalkyl groups such as cyclopropane, cyclobutane, cyclopentane and cyclohexane.
The term “C3-C6cycloalkyl-Ci-C6alkyl“ as used herein refers to 3 to 6 membered cycloalkyl group with a Ci to C6 alkylene group, such as methylene or ethylene, which alkylene group is connected to the rest of the molecule. Examples are cyclopropylmethylene, cyclopropylethylene, and cyclobutylmethylene. In the instance, the C3-C6cycloalkyl-Ci-C6alkyl- group is substituted, the substituent(s) can be on the cycloalkyl group and/or on the alkyl group. In an embodiment, at least one substitutent is on the alkyl group.
The term “C3-C6-cycloalkylidenemethyl“ as used herein refers to 3 to 6 membered cycloalkyl group with the =CH group, to which carbon is connected the rest of the molecule. In the instance, the C3-C6- cycloalkylidenemethyl group is substituted, the substituent(s) such as bromine, iodine, chlorine, fluorine, cyano, Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy can, depending on the substituent, be on the cycloalkyl group and/or on the unsaturated carbon atom. The term “C3-C6cycloalkylCi-C4haloalkoxy” as used herein refers to a 3 to 6 membered cycloalkyl group connected to a 1 to 4 membered haloalkoxy, which haloalkoxy group is connected to the rest of the molecule.
The term “aminocarbonylCi-Cnalkyl“ as used herein refers to an alkyl radical where one of the hydrogen atoms in the radical is replaced by a CONH2 group.
The term “hydroxycarbonylCi-Cnalkyl“ as used herein refers to an alkyl radical where one of the hydrogen atoms in the radical is replaced by a COOH group.
The term “Ci-Cnalkylsulfanyl“ as used herein refers to a Ci-Cnalkyl moiety linked through a sulfur atom. Similarly, the term “Ci-Cnhaloalkylthio“ or “Ci-Cnhaloalkylsulfanyl“ as used herein refers to a Ci- Cnhaloalkyl moiety linked through a sulfur atom. Similarly, the term “C3-Cncycloalkylsulfanyl” refers to 3-n membered cycloalkyl moiety linked through a sulfur atom.
The term “Ci-Cnalkylsulfinyl“ as used herein refers to a Ci-Cnalkyl moiety linked through the sulfur atom of the S(=0) group. Similarly, the term “Ci-Cnhaloalkylsulfinyl “ or “Ci-Cnhaloalkylsulfinyl“ as used herein refers to a Ci-Cnhaloalkyl moiety linked through the sulfur atom of the S(=0) group. Similarly, the term “C3-Cncycloalkylsulfinyl” refers to 3-n membered cycloalkyl moiety linked through the sulfur atom of the S(=0) group.
The term “Ci-Cnalkylsulfonyl“ as used herein refers to a Ci-Cnalkyl moiety linked through the sulfur atom of the S(=0)2 group. Similarly, the term “Ci-Cnhaloalkylsulfonyl “ or “Ci-Cnhaloalkylsulfonyl“ as used herein refers to a Ci-Cnhaloalkyl moiety linked through the sulfur atom of the S(=0)2 group. Similarly, the term “C3-Cncycloalkylsulfonyl” refers to 3-n membered cycloalkyl moiety linked through the sulfur atom of the S(=0)2 group
The term “trimethylsilaneCi-Cnalkyl“ as used herein refers to an alkyl radical where one of the hydrogen atoms in the radical is replaced by a -Si(CH3)3 group.
The term “C2-Cnalkenyl” as used herein refers to a straight or branched alkenyl chain having from two to n carbon atoms and one or two double bonds, for example, ethenyl, prop-l -enyl, but-2-enyl.
The term “C2-Cnhaloalkenyl” as used herein refers to a C2-Cnalkenyl moiety substituted with one or more halo atoms which may be the same or different.
The term “C2-Cnalkynyl” as used herein refers to a straight or branched alkynyl chain having from two to n carbon atoms and one triple bond, for example, ethynyl, prop-2-ynyl, but-3-ynyl, The term “C2-Cnhaloalkynyl” as used herein refers to a C2-Cnalkynyl moiety substituted with one or more halo atoms which may be the same or different.
The term “=N-Ci-Cnalkoxy” as used herein refers to an alkoxy moiety linked through a nitrogen atom, which nitrogen atom is linked to the rest of the compound via a double bond; example include =N(OMe). The configuration at the double bond can be E or Z or a mixture of diastereoisomers.
Halogen or “halo” is generally fluorine, chlorine, bromine or iodine. This also applies, correspondingly, to halogen in combination with other meanings, such as haloalkyl
The term “heteroaryl” or “heteroaromatic” ring as used herein refers to a 5-membered aromatic monocyclic ring having 1 to 3 heteroatoms independently selected from N, O and S. Specific examples are heteroaryls J-1 to J-35 shown in Scheme A below. Preferred heteroaryls are J-18, J-25, and J-30.
Scheme A: Examples of 5-membered heteroarmatic rings J-1 to J-35:
Figure imgf000008_0001
The pyridine, pyrimidine, pyrazine and pyridazine groups (unsubstituted or substituted) for R4 and R4a are each connected via a carbon atom on the respective ring to the rest of the compound. As used herein, the term "controlling" refers to reducing the number of pests, eliminating pests and/or preventing further pest damage such that damage to a plant or to a plant derived product is reduced.
The staggered line as used herein, for example, in R2t>-1, Qa and Y-1, represent the point of connection/ attachment to the rest of the compound.
As used herein, the term "pest" refers to insects, acarines, nematodes and molluscs that are found in agriculture, horticulture, forestry, the storage of products of vegetable origin (such as fruit, grain and timber); and those pests associated with the damage of man-made structures. The term pest encompasses all stages in the life cycle of the pest.
As used herein, the term "effective amount" refers to the amount of the compound, or a salt thereof, which, upon single or multiple applications provides the desired effect. An effective amount is readily determined by the skilled person in the art, by the use of known techniques and by observing results obtained under analogous circumstances. In determining the effective amount a number of factors are considered including, but not limited to: the type of plant or derived product to be applied; the pest to be controlled & its lifecycle; the particular compound applied; the type of application; and other relevant circumstances.
As one of ordinary skill in the art will appreciate, compounds of formula I contain a stereogenic centre which is indicated with an asterisk in the structure below:
Figure imgf000009_0001
where Ri, R2a, Råb, R3, Q, and A are as defined in the first aspect.
The present invention contemplates both racemates and individual enantiomers. Compounds having preferred stereochemistry are set out below.
Figure imgf000009_0002
I’a
Particularly preferred compounds of the present invention are compounds of formula I’a: where Ri, R2a, R2t>, R3, Q, and A are as defined in the first aspect, and stereoisomers, enantiomers, tautomers and N-oxides of the compounds of formula (I’a), and agrochemically acceptable salts thereof.
The term “optionally substituted” as used herein means that the group referenced is either unsubstituted or is substituted by a designated substituent, for example, “C3-C6cycloalkyl-Ci-C6 alkyl is optionally substituted with 1 or 2 fluoro atoms” means C3-C4cycloalkyl, C3-C4cycloalkyl substituted with 1 fluoro atom and C3-C4cycloalkyl substituted with 2 fluoro atoms.
Embodiments according to the invention are provided as set out below. In an embodiment of each aspect of the invention, A is
A. N, CH, or CRr, where Rr is C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, CN or cyclopropyl; or
B. N, CH, C-CH3, C-CF3, C-O-CH3; or
C. N or CH; or
D. N; or
E. CH.
In an embodiment of each aspect of the invention, Ri is
A. hydrogen, Ci-C6alkyl optionally substituted with one substituent selected from CN, CONH2, COOH, NO2, and -Si(CH3)3, Ci-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C3- C4cycloalkyl-Ci-C2alkyl, wherein the C3-C4cycloalkyl is optionally substituted with 1 or 2 halo atoms, oxetan-3-yl-CH2-, or benzyl optionally substituted with halo or Ci-C3haloalkyl; or
B. hydrogen, Ci-C6alkyl optionally substituted with one substituent selected from CN, CONH2, COOH, NO2, and -Si(CH3)3, Ci-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C3- C4cycloalkyl- Ci-C2alkyl, or benzyl optionally substituted with halo or Ci-C3haloalkyl; or
C. hydrogen, Ci-C6alkyl optionally substituted with one substituent selected from CN, CONH2 and COOH, Ci-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C3-C4cycloalkyl-Ci- C2alkyl, or benzyl; or
D. hydrogen, Ci-C3alkyl optionally substituted with CN, Ci-C6haloalkyl, C2-C4alkenyl, C2- C4alkynyl, C2-C4haloalkynyl, C3-C4cycloalkyl-Ci-C2alkyl or benzyl; or
E. hydrogen, methyl, methyl substituted with CN, C2-C4alkenyl, C2-C4alkynyl, C3-C4cycloalkyl-Ci- C2alkyl, or benzyl; or
F. hydrogen, Ci-C3alkyl, or C3-C4cycloalkyl-Ci-C2alkyl; or
G. hydrogen, methyl, or C3-C4cyclopropylmethyl; or
H. hydrogen; or
I. methyl; or
J. methyl substituted with CN; or
K. allyl; or
L. propargyl; or
M. cyclopropylmethyl; or
N. benzyl.
In an embodiment of each aspect of the invention, R2a is
A. halogen, Ci-C3haloalkyl, Ci-C3haloalkylthio, Ci-C3alkoxy, Ci-C3haloalkoxy, or CN; or
B. halogen, Ci-C3haloalkyl, or Ci-C3haloalkoxy; or
C. halogen or Ci-C3haloalkyl; or
D. fluorine, chlorine, bromine, ortrifluoromethyl. In an embodiment of each aspect of the invention, F¾b is
A. C3-C6-cycloalkyl-Ci-C6alkyl; C3-C6-cycloalkyl-Ci-C6alkyl substituted with one to three substituents independently selected from bromine, iodine, chlorine, fluorine, OH, cyano, Ci- C3alkyl, Ci-C3haloalkyl, Ci- Csalkoxy, C2-C6alkynyl, =0, =CH2, =CF2, =CCI2, =N-Ci-C3alkoxy, and =CMe2; C3-C6-cycloalkylidenemethyl; or C3-C6-cycloalkylidenemethyl substituted with one to three substituents independently selected from halo, cyano, Ci-C3alkyl, Ci-C3haloalkyl, and Ci- C3alkoxy; or
B. C3-C6-cycloalkyl-Ci-C6alkyl; C3-C6-cycloalkyl-Ci-C6alkyl substituted on the Ci-C6alkyl with one to three substituents independently selected from bromine, iodine, chlorine, fluorine, OH, cyano, Ci-C3alkyl, Ci-C3haloalkyl, Ci- Csalkoxy, C2-C6alkynyl, =0, =CH2, =CF2, =CCI2, =N-Ci- C3alkoxy, and =CMe2; C3-C6-cycloalkylidenemethyl; or C3-C6-cycloalkylidenemethyl substituted with one to three substituents independently selected from halo, cyano, Ci-C3alkyl, Ci-C3haloalkyl, and Ci- C3alkoxy; or
C. C3-C4-cycloalkyl-Ci-C2alkyl; C3-C4-cycloalkyl-Ci-C2alkyl substituted with one to three substituents independently selected from bromine, iodine, chlorine, fluorine, OH, cyano, Ci- C3alkyl, Ci-C3haloalkyl, Ci- Csalkoxy, C2-C6alkynyl, =0, =CH2, =CF2, =CCI2, =N-Ci-C3alkoxy, and =CMe2; C3-C4-cycloalkylidenemethyl; or C3-C4-cycloalkylidenemethyl substituted with one to three substituents independently selected from halo, cyano, Ci-C3alkyl, Ci-C3haloalkyl, and Ci- C3alkoxy; or
D. C3-C4-cycloalkyl-Ci-C2alkyl; C3-C4-cycloalkyl-Ci-C2alkyl substituted on the Ci-C2alkyl with one to three substituents independently selected from bromine, iodine, chlorine, fluorine, OH, cyano, Ci-C3alkyl, Ci-C3haloalkyl, Ci- Csalkoxy, C2-C6alkynyl, =0, =CH2, =CF2, =CCI2, =N-Ci- C3alkoxy, and =CMe2; C3-C4-cycloalkylidenemethyl; or C3-C4-cycloalkylidenemethyl substituted with one to three substituents independently selected from halo, cyano, Ci-C3alkyl, Ci-C3haloalkyl, and Ci- C3alkoxy; or
E. C3-C4-cycloalkyl-Ci-C2alkyl; C3-C4-cycloalkyl-Ci-C2alkyl substituted with one to three substituents independently selected from bromine, iodine, chlorine, fluorine, OH, cyano, methyl, trifluoromethyl, difluoromethyl, methoxy, =0, =CH2, =CF2, =CCI2, and =CMe2; C3-C4- cycloalkylidenemethyl; or C3-C4-cycloalkylidenemethyl substituted with one to three substituents independently selected from bromine, iodine, chlorine, fluorine, cyano, methyl, trifluoromethyl, difluoromethyl, and methoxy; or
F. C3-C4-cycloalkyl-Ci-C2alkyl; C3-C4-cycloalkyl-Ci-C2alkyl substituted on the Ci-C2alkyl with one to three substituents independently selected from bromine, iodine, chlorine, fluorine, OH, cyano, methyl, trifluoromethyl, difluoromethyl, methoxy, =0, =CH2, =CF2, =CCI2, and =CMe2; C3-C4-cycloalkylidenemethyl; or C3-C4-cycloalkylidenemethyl substituted with one to three substituents independently selected from bromine, iodine, chlorine, fluorine, cyano, methyl, trifluoromethyl, difluoromethyl, and methoxy;
G. selected from R2b-i to R2b-2i; or H. selected from R2t>-4, R2t>-6, R2t>-8, R2b-9, R2b-n, and R2b-12.
Table R: preferred examples of substituent Råb
Figure imgf000012_0001
Figure imgf000013_0001
In an embodiment of each aspect of the invention, R3 is
A. Ci-C3alkyl or Ci-C3haloalkyl; or
B. methyl or trifluromethyl; or C. methyl.
In an embodiment of each aspect of the invention, Q is
A. Qa; or
B. Qb.
In an embodiment of each aspect of the invention, Qa is
A. selected from Qa-1 to Qa-16; or
B. selected from Qa-1 , Qa-6, Qa-7, Qa-10, and Qa-15; or
C. Qa-1 or Qa-15.
Figure imgf000013_0002
Figure imgf000014_0001
In an embodiment of each aspect of the invention, Qb is
A. selected from Qb-1 to Qb-13; or
B. Qb-1 .
Figure imgf000015_0001
In an embodiment of each aspect of the invention, R4 is
A. pyridine, or pyrimidine; wherein the pyridine or pyrimidine, independently of each other, is optionally substituted with one substituent selected from Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C3-C4cycloalkyl, halo, hydroxyl, CN, Ci-C6haloalkoxy, C2-C6haloalkenyloxy, C2-
Cehaloalkynyloxy, C3-C4halocycloalkoxy, and C3-C6cycloalkylCi-C4haloalkoxy; or
B. pyridine, wherein the pyridine is optionally substituted with one substituent selected from Ci- C3alkyl, Ci-C3haloalkyl, Ci-C3alkoxy, C3-C4cycloalkyl, halo, hydroxyl, CN, Ci-C6haloalkoxy, C2- Cehaloalkenyloxy, C2-C6haloalkynyloxy, C3-C4halocycloalkoxy, and C3-C6cycloalkylCi- C4haloalkoxy; or
C. pyrimidine; wherein the pyrimidine is optionally substituted with one substituent selected from Ci-C3alkyl, Ci-C3haloalkyl, Ci-C3alkoxy, C3-C4cycloalkyl, halo, hydroxyl, CN, Ci-C6haloalkoxy, C2-C6haloalkenyloxy, C2-C6haloalkynyloxy, C3-C4halocycloalkoxy, and C3-C6cycloalkylCi- C4haloalkoxy; or
D. pyridine, pyrimidine, pyrazine or pyridazine, wherein the pyridine, pyrimidine, pyrazine or pyridazine is optionally substituted with one substituent selected from Ci-C3alkyl, Ci- C3haloalkyl, Ci-C3alkoxy, C3-C4cycloalkyl, F, Cl, Br, CN, and Ci-C6haloalkoxy; or
E. pyridine, pyrimidine, pyrazine or pyridazine, wherein the pyridine, pyrimidine, pyrazine or pyridazine is optionally substituted with one substituent selected from Ci-C3alkyl, C3- C4cycloalkyl, F, Cl, Br, CN, and Ci-C6haloalkoxy; or
F. pyridine, pyrimidine, pyrazine or pyridazine, wherein the pyridine, pyrimidine, pyrazine or pyridazine is optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and 2,2,2-trifluoroethoxy;
G. pyridine, or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2- difluoroethoxy and 2,2,2-trifluoroethoxy; or
H. 5-cylopropylpyridine, 5-fluoropyridine, 5-chloropyridine, 5-bromopyridine, 5- difluoromethoxypyridine, 5-trifluoromethoxypyridine, 5-cyanopyridine, 5-(2,2-difluoroethoxy)- pyridine, 5-(2,2,2-trifluoroethoxy)-pyridine, pyridine, 5-cylopropylpyrimidine, 5-fluoropyrimidine, 5-chloropyrimidine, 5-bromopyrimidine, 5-difluoromethoxypyrimidine, 5- trifluoromethoxypyrimidine, 5-cyanopyrimidine, 5-(2,2-difluoroethoxy)-pyrimidine, 5-(2,2,2- trifluoroethoxy)-pyrimidine, or pyrimidine; or
I. 5-cylopropylpyridin-2-yl, 5-fluoropyrid in-2-yl , 5-chloropyridin-2-yl, 5-bromopyridin-2-yl, 5- difluoromethoxypyridin-2-yl, 5-trifluoromethoxypyridin-2-yl, 5-cyanopyridin-2-yl, 5-(2,2- difluoroethoxy-pyridin-2-yl, 5-(2,2,2-trifluoroethoxy)-pyridin-2-yl, pyridin-2-yl, 5- cylopropylpyrimidin-2-yl, 5-fluoropyrimidin-2-yl, 5-chloropyrimidin-2-yl, 5-bromopyrimidin-2-yl, 5-difluoromethoxypyrimidin-2-yl, 5-trifluoromethoxypyrimidin-2-yl, 5-cyanopyrimidin-2-yl, 5- (2,2-difluoroethoxy)-pyrimidin-2-yl, 5-(2,2,2-trifluoroethoxy)-pyrimidin-2-yl, or pyrimidin-2-yl.
In an embodiment of each aspect of the invention, R4a is
A. pyridine, pyrimidine, pyrazine or pyridazine, wherein the pyridine, pyrimidine, pyrazine or pyridazine, independent of each other, is optionally substituted with one substituent selected from Ci-C3haloalkyl, C3-C4cycloalkyl, halogen, cyano, and Ci-C3haloalkoxy or selected from Y-1 to Y-4; or
B. pyridine, pyrimidine, pyrazine or pyridazine, wherein the pyridine, pyrimidine, pyrazine or pyridazine, independent of each other, is optionally substituted with one substituent selected from F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and 2,2,2- trifluoroethoxy and selected from Y-1 to Y-4; or
C. pyridine or, pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from Ci-C3haloalkyl, C3-C4cycloalkyl, halogen, cyano, and Ci- C3haloalkoxy or selected from Y-1 to Y-4; or
D. pyridine or, pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2- difluoroethoxy and 2,2,2-trifluoroethoxy or selected from Y-1 to Y-4; or
E. 5-cylopropylpyridine, 5-fluoropyridine, 5-chloropyridine, 5-bromopyridine, 5- difluoromethoxypyridine, 5-trifluoromethoxypyridine, 5-cyanopyridine, 5-(2,2-difluoroethoxy)- pyridine, 5-(2,2,2-trifluoroethoxy)-pyridine, pyridine, 5-cylopropylpyrimidine, 5-fluoropyrimidine, 5-chloropyrimidine, 5-bromopyrimidine, 5-difluoromethoxypyrimidine, 5- trifluoromethoxypyrimidine, 5-cyanopyrimidine, 5-(2,2-difluoroethoxy)-pyrimidine, 5-(2,2,2- trifluoroethoxy)-pyrimidine, pyrimidine, or 1 ,2,3-triazole; or
F. 5-cylopropylpyrid in-2-yl , 5-fluoropyrid in-2-yl , 5-chloropyridin-2-yl, 5-bromopyridin-2-yl, 5- difluoromethoxypyridin-2-yl, 5-trifluoromethoxypyridin-2-yl, 5-cyanopyridin-2-yl, 5-(2,2- difluoroethoxy)-pyridin-2-yl, 5-(2,2,2-trifluoroethoxy)-pyridin-2-yl, pyridin-2-yl, 5- cylopropylpyrimidin-2-yl, 5-fluoropyrimidin-2-yl, 5-chloropyrimidin-2-yl, 5-bromopyrimidin-2-yl, 5-difluoromethoxypyrimidin-2-yl, 5-trifluoromethoxypyrimidin-2-yl, 5-cyanopyrimidin-2-yl, 5- (2,2-difluoroethoxy)-pyrimidin-2-yl, 5-(2,2,2-trifluoroethoxy)-pyrimidin-2-yl, pyrimidin-2-yl, or
1 ,2,3-triazol-2-yl.
In an embodiment of each aspect of the invention, when Y-1 is selected as R4a, R a and R c, independently of each other, are
A. hydrogen, halogen, CN, Ci-C3alkyl, Ci-C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy, and Ci- C3haloalkoxy; or
B. from hydrogen, F, Cl, Br, CN, methyl, CF3, cyclopropyl, methoxy and difluoromethoxy; or
C. both hydrogen.
In an embodiment of each aspect of the invention, when Y-2 is selected as R4a,
A. R’4b and R , independently of each other, are hydrogen, halogen, CN, Ci-C3alkyl, Ci- C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy, and Ci-C3haloalkoxy; or
B. R’4b and R , independently of each other, are from hydrogen, F, Cl, Br, CN, methyl, CF3, cyclopropyl, methoxy and difluoromethoxy; or
C. R’4b and R c are both hydrogen; or
D. R’4b is hydrogen and R is cyclopropyl.
In an embodiment of each aspect of the invention, when Y-3 is selected as R4a, R a and R b, independently of each other, are A. hydrogen, halogen, CN, Ci-C3alkyl, Ci-C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy, and Ci- C3haloalkoxy; or
B. hydrogen, F, Cl, Br, CN, methyl, CF3, cyclopropyl, methoxy and difluoromethoxy; or
C. both hydrogen.
In an embodiment of each aspect of the invention, when Y-4 is selected as R4a,
A. R a, R’4b, and R c are, independently of each other, selected from hydrogen, halogen, CN, Ci- C3alkyl, Ci-C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy, and Ci-C3haloalkoxy; or
B. R a, R b, and R are, independently of each other, selected from hydrogen, F, Cl, Br, CN, methyl, CF3, cyclopropyl, methoxy and difluoromethoxy; or
C. R a, R b, and R are all hydrogen; or
D. R a and R are hydrogen and R b is CN.
In an embodiment of each aspect of the invention, Rs is
A. hydrogen, Ci-C3alkyl, Ci-C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy, halogen, Ci-C3alkoxy-Ci- C3alkyl, Ci-C3alkoxy-Ci-C3alkoxy-Ci-C3alkyl, (Ci-C3alkyl)C(0), (Ci-C3alkoxy)C(0), HC(O), Ci- C3haloalkoxy or a 5-membered heteroaromatic ring wherein the 5-membered heteroaromatic ring can be optionally substituted with one to three substituents selected from Ci-C3alkyl, Ci- C3haloalkyl, Ci-C3alkoxy, C3-C4cycloalkyl, halogen, CN or hydroxy; or
B. hydrogen, Ci-C3alkyl, Ci-C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy, halogen, Ci-C3alkoxy-Ci- C3alkyl, Ci-C3alkoxy-Ci-C3alkoxy-Ci-C3alkyl, (Ci-C3alkyl)C(0), (Ci-C3alkoxy)C(0), HC(O) or Ci-C3haloalkoxy; or
C. hydrogen, Ci-C3alkyl, Ci-C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy, halogen, Cl, Br, Ci- C3alkoxy-Ci-C3alkyl, Ci-C3alkoxy-Ci-C3alkoxy-Ci-C3alkyl, (Ci-C3alkyl)C(0), (Ci- C3alkoxy)C(0), or Ci-C2haloalkoxy; or
D. hydrogen, Ci-C3alkyl, Ci-C3alkoxy, C3-C4cycloalkyl, Ci-C3haloalkoxy, halogen, Ci-C3alkoxy- Ci-C3alkyl, Ci-C3alkoxy-Ci-C3alkoxy-Ci-C3alkyl, (Ci-C3alkyl)C(0), HC(O), or (Ci- C3alkoxy)C(0); or
E. hydrogen, Ci-C2alkyl, Ci-C2alkoxy, C3-C4cycloalkyl, Ci-C2haloalkoxy, halogen, Ci-C2alkoxy- Ci-C2alkyl, Ci-C2alkoxy-Ci-C2alkoxy-Ci-C2alkyl, (Ci-C2alkyl)C(0), HC(O), or (Ci- C2alkoxy)C(0); or
F. hydrogen, methyl, trifluoromethoxy, methoxy, cyclopropyl, 2,2-difluroroethoxy, 2,2,2- trifluroroethoxy, difluoromethoxy, 2,2,2-trifluroroethyl, chloro, bromo, methoxyethoxy, methylcarbonyl, or methoxycarbonyl.
In an embodiment of each aspect of the invention, Rsa is
A. hydrogen, halogen, CN, Ci-C3alkyl, Ci-C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy or Ci- C3haloalkoxy; or
B. hydrogen, halogen, CN, Ci-C3alkyl, Ci-C3haloalkyl, C3-C4cycloalkyl or Ci-C3alkoxy; or C. hydrogen, halogen, CN, Ci-C3alkyl, Ci-C3haloalkyl or Ci-C3alkoxy; or
D. hydrogen, halogen, CN, Ci-C3alkyl or Ci-C3alkoxy; or
E. hydrogen or halogen; or
F. hydrogen.
In an embodiment of each aspect of the invention, Rsb is
A. hydrogen, halogen, CN, Ci-C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy, or Ci-C3haloalkoxy; or
B. hydrogen, halogen or Ci-C3alkoxy; or
C. hydrogen.
In an embodiment of each aspect of the invention, RY is independently selected from
A. hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, CN and cyclopropyl; or
B. hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, and cyclopropyl; or
C. hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; or
D. hydrogen, methyl, trifluoromethyl, and methoxy; or
E. hydrogen.
In an embodiment, the compound of formula I can be represented by formula laa with the asterisk indicating a stereogenic centre), wherein A, Ri, R2a, R2t>, and R3, are as defined in the first aspect and Qi corresponds to Q as defined in the first aspect, each with the corresponding embodiments as described above.
Figure imgf000019_0001
laa
The present invention contemplates both racemates and individual enantiomers. Compounds having preferred stereochemistry are set out below. I’aa
Particularly preferred compounds of the present invention are compounds of formula I’aa: where A, Ri, R2a, Råb, and R3, are as defined in the first aspect and Qi corresponds to Q as defined in the first aspect, and stereoisomers, enantiomers, tautomers and N-oxides of the compounds of formula (I’aa), and agrochemically acceptable salts thereof.
In an embodiment, Qi is
A. selected from Qaa to Qag and Qba to Qbf; or
B. selected from Qaa to Qag; or C. selected from Qba to Qbf; or
D. selected from Qaa, Qab , Qaf, Qag, Qba, Qbb, Qbc, Qbd, Qbe and Qbf; or
E. selected from Qaa, Qab , Qaf, Qba, Qbb and Qbf.
Figure imgf000020_0001
Figure imgf000021_0001
The present invention, accordingly, makes available a compound of formula I having the substituents Ri, R2a, Råb, R3, Q, and A as defined above in all combinations / each permutation. Accordingly, made available, for example, is a compound of formula I with A being of embodiment A (i.e. A is N, CH, or CRr, where Rr is C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, CN or cyclopropyl); Ri being embodiment B (i.e. hydrogen, Ci-C6alkyl optionally substituted with one substituent selected from CN, CONH2, COOH, NO2, and -Si(CH3)3, Ci-C6haloalkyl, C2-C6alkenyl, C2- Cealkynyl, C2-C6haloalkynyl, C3-C4cycloalkyl- Ci-C2alkyl, or benzyl optionally substituted with halo or Ci-C3haloalkyl); Råa being an embodiment L (i.e. halogen or Ci-C3haloalkyl); Råb being embodiment G (i.e. selected from Råb-i to R2b-2i); R3 being embodiment B (i.e. methyl ortrifluromethyl); Q being embodiment A (i.e. Q is Qa, wherein Qa is embodiment A (i.e. Qa is selected from Qa-1 to Qa-16; and R4 is embodiment G (i.e. pyridine, or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and 2,2,2-trifluoroethoxy).
In an embodiment of each aspect of the invention, the compound of formula I has as A N or CH; as Ri hydrogen, methyl, or cyclopropylmethyl; as Råa halogen or Ci-C3haloalkyl; as Råb selected from Råb-i to R2b-2i; as R3 methyl; and as Q selected from Qa-1 to Qa-16 and Qb-1 to Qb-13, where as R4 (for Qa-1 to Qa-16) is pyridine, or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2- difluoroethoxy and 2,2,2-trifluoroethoxy; and R4a (for Qb-1 to Qb-13) is pyridine or, pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from cyclopropyl, F,
Cl, Br, CN, -O-CF3, -O-CF2H, -O-CH2CF2H, -O-CH2CF3 and selected from Y-1 to Y-4 (where R’4a,
R’4b, and R c, independently of each other and independently of Y1 to Y4, are selected from hydrogen, halogen, CN, Ci-C3alkyl, Ci-C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy, and Ci- C3haloalkoxy).
In an embodiment of each aspect of the invention, the compound of formula I has as A N or CH; as Ri hydrogen, methyl, or cyclopropylmethyl; as R2a halogen or Ci-C3haloalkyl; as Råb selected from R2t>-1 to R2b-2i; as R3 methyl; and as Q selected from Qa-1 to Qa-16 and Qb-1 to Qb-13, where as R4 (for Qa-1 to Qa-16) is pyridine, or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2- difluoroethoxy and 2,2,2-trifluoroethoxy; and R4a (for Qb-1 to Qb-13) is pyridine or, pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with one substituent selected from cyclopropyl, F,
Cl, Br, CN, -0-CF3, -O-CF2H, -O-CH2CF2H, -O-CH2CF3 and selected from Y-1 to Y-4 (where R’4a,
R b, and R are each hydrogen).
In an embodiment of each aspect of the invention, the compound of formula I is represented by formula laa, which has as A N or CH; as Ri hydrogen, methyl, or cyclopropylmethyl; as Råa halogen or Ci-C3haloalkyl; as Råb selected from Råb-i to R2b-2i; as R3 methyl; and as Qi selected from Qaa to Qag and Qba to Qbf.
In a second aspect, the present invention makes available a composition comprising a compound of formula I as defined in the first aspect, one or more auxiliaries and diluent, and optionally one or more other active ingredient.
In a third aspect, the present invention makes available a method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound as defined in the first aspect or a composition as defined in the second aspect.
In a fourth aspect, the present invention makes available a method for the protection of plant propagation material from the attack by insects, acarines, nematodes or molluscs, which comprises treating the propagation material or the site, where the propagation material is planted, with an effective amount of a compound of formula I as defined in the first aspect or a composition as defined in the second aspect.
In a fifth aspect, the present invention makes available a plant propagation material, such as a seed, comprising, or treated with or adhered thereto, a compound of formula I as defined in the first aspect or a composition as defined in the second aspect.
The present invention in a further aspect provides a method of controlling parasites in or on an animal in need thereof comprising administering an effective amount of a compound of the first aspect. The present invention further provides a method of controlling ectoparasites on an animal in need thereof comprising administering an effective amount of a compound of formula I as defined in the first aspect. The present invention further provides a method for preventing and/or treating diseases transmitted by ectoparasites comprising administering an effective amount of a compound of formula I as defined in the first aspect, to an animal in need thereof.
Compounds of formula I can be prepared by those skilled in the art following known methods. More specifically compounds of formulae I, and I’a, and intermediates therefor can be prepared as described below in the schemes and examples. Certain stereogenic centers have been left unspecified for the clarity and are not intended to limit the teaching of the schemes in any way.
The process according to the invention for preparing compounds of formula I is carried out by methods known to those skilled in the art. Compounds of formula I can be made, for example, as shown in schemes 1 - 20.
Scheme 1 .
A compound of formula lb wherein Z is H, halo, cyano, Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C2- Cealkynyl, =0, =CH, =CF2, =CCb, =CMe2, t is 1 , 23 or 4, R1 R2a, R3 and Q are as described above, can be prepared according to reaction scheme 1. Thus, compounds of formula II are treated with iPrMgCI/LiCI-complex; subsequent reaction with CuCN and quenching with a compound of formula III, wherein Z and t are as defined above, provides compounds of formula IV (analog to PCT Int. Appl. W02006/067445, page 148). Hydrolysis with a base such as LiOH, NaOH or KOH gives a carboxylic acid of formula V. Subsequent activation of the carboxylic acid of formula V and final amide coupling with amines of formula VII delivers compounds of formula lb according to methods known to the person skill in the art, as illustrated in Scheme 1.
Scheme 2. A compound of formula lc wherein Z is H, halo, cyano, Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C2- Cealkynyl, =0, =CH, =CF2, =CCh, =CMe2, t is 1 , 23 or 4, R1, R2a, R3 and Q are as described above, can be prepared according to reaction scheme 2. A compound of formula IV, prepared according to methods described in scheme 1 , is reacted with a reductant such as NaBhU or Na(CN)BH3 to a compound of formula VIII, as described for example in ACS Medicinal Chemistry Letters, 2011, 2, 238. Hydrolysis with a base such as LiOH, NaOH or KOH gives a carboxylic acid of formula IX. Subsequent activation of the carboxylic acid of formula IX and final amide coupling with amines of formula VII delivers compounds of formula lc according to methods known to the person skill in the art, as illustrated in Scheme 2.
Scheme 3
DCC, EDO, THF or pyridine
\ or T3P, base
R3
Figure imgf000026_0001
solvent, optional in the presence of a base R2a e.g. EtjN, pyridine Id
Z = H, halogen, cyano, C,-C, alkyl
C Cahaloalkyl t = 1 to 4
A compound of formula Id wherein Z is H, halo, cyano, Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C2- Cealkynyl, =0, =CH, =CF2, =CCl2, =CMe2, t is 1 , 2 3 or 4, R1, R2a, R3 and Q are as described above, can be prepared according to reaction scheme 3. A compound of formula VIII, prepared according to methods described in scheme 2, is alkylated with a compound of formula R30-LG, whereas R30 is a Ci- C3alkyl group and LG is a leaving group such as halogen, O-mesylate, O-triflate, O-tosylate in the presence of a base such as NaH, NEt3, NaOH, K2CO3. Hydrolysis with a base such as LiOH, NaOH or KOH gives a carboxylic acid of formula XI. Subsequent activation of the carboxylic acid of formula XI and final amide coupling with amines of formula VII delivers compounds of formula Id according to methods known to the person skill in the art, as illustrated in Scheme 3.
Scheme 4 A compound of formula le wherein Z is H, halo, cyano, Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C2- Cealkynyl, =0, =CH, =CF2, =CCl2, =CMe2, t is 1 , 2 3 or 4, R1, R2a, R3 and Q are as described above, can be prepared according to reaction scheme 4. A compound of formula IV, prepared according to methods described in scheme 1 , is reacted with compound R31MgCI, wherein R31 is Ci-C3alkyl, Ci- C3haloalkyl, C2-C6alkynyl, to a compound of formula XIII, at temperatures between -78°C and 70°C, preferably between -78°C and RT. Alternatively, the same compound R31MgCI can be reacted directly with a compound of formula V, prepared according to methods described in Scheme 1. Hydrolysis with a base such as LiOH, NaOH or KOH gives a carboxylic acid of formula XIV. Subsequent activation of the carboxylic acid of formula XIV and final amide coupling with amines of formula VII delivers compounds of formula le according to methods known to the person skill in the art, as illustrated in Scheme 4.
Scheme 5 ft, VI! X
Figure imgf000028_0001
A compound of formula If wherein Z is H, halo, cyano, Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C2- Cealkynyl, =0, =CH, =CF2, =CCl2, =CMe2, t is 1 , 2 3 or 4, R1, R2a, R3 and Q are as described above, can be prepared according to reaction scheme 5. A compound of formula VIII, prepared according to methods described in scheme 2, is reacted with a reductant such as Et3SiH in the presence of an acid such as trifluoroacetic acid to a compound of formula XVI, as described for example in PCT Int. Appl. W02009/045830 (2009). Hydrolysis with a base such as LiOH, NaOH or KOH gives a carboxylic acid of formula XVII. Subsequent activation of the carboxylic acid of formula XVII and final amide coupling with amines of formula Vll delivers compounds of formula if according to methods known to the person skill in the art, as illustrated in Scheme 5.
Scheme 6 A compound of formula XXXIX wherein Z is H, halogen, cyano, Ci-Csalkyl and Ci-C3haloalkyl, t is 1 , 2 3 or 4, R1, R2a, R3 and Q are is defined as above can be prepared according to reaction Scheme 6. Thus, compounds of formula XXXV wherein R2a is defined as above are treated with a Wittig reagent (3-bromopropyl) triphenyiphosphosphonium bromide, or with cyclopropyl triphenylphosphonuim bromide, under basic conditions, for example as described in Organic Letters, 2018, 20, 409, or Tetrahedron Letters, 1988, 29, 2531, provides compounds of formula XXXVII. Hydrolysis with LiOH as already described gives carboxylic acids of formula XXXIX. Subsequent activation of the carboxylic acid of formula XXXIX and final amide coupling with amines of formula VII delivers compounds of formula Ih as illustrated in Scheme 6. Carboxylic acids of formula XXXIX can also be treated by a catalyst, for instance a palladium or an iridium catalyst, eventually in the presence of a ligand, and placed under a hydrogen atmosphere at a pressure from 1 bar to 50 bars in a suitable solvent, e.g. ethanol or dichioromethane, at a temperature between room temperature and 150 °C to provide compounds of the formula XVII (Scheme 5). Such processes have been described for instance in WO2009/58298 or WO2015/175171.
Scheme 7 in the presence
XLIV of a base e g Et3N, pyridine
Ih
A compound of formula Ih wherein t is 1, 23 or 4, R1, R2a, R3 and Q are defined as above can be prepared according to reaction Scheme 7. Thus, compounds of formula XLI wherein R2a is defined as above are treated with tris(dimethylamino)phosphine and dibromodifluoromethane in a solvent such as tetrahydrofuran, at a temperature of minus 78°C up to room temperature, as described for example in Angew. Chem. Int. Ed., 2019, 58, 3918. Hydrolysis with LiOH as already described gives carboxylic acids of formula XLII. Subsequent activation of the carboxylic acid of formula XLI I and final amide coupling with amines of formula VII delivers compounds of formula Ih as illustrated in Scheme 7.
Scheme 8
Figure imgf000030_0001
(COCI) inert solvent e g
Figure imgf000030_0002
optionaly in the presence of a base e g Et3N, pyridine A compound of formula li wherein t is 1, 23 or 4, R1, R2a, R3 and Q are defined as above can be prepared according to reaction Scheme 8. Thus, compounds of formula XLV wherein are treated with a Wittig reagent methyl triphenylphosphonium bromide together with a base, such as butyl lithium in a solvent such as tetrahydrofuran, at a temperature of minus 78°C up to room temperature, as described for example in Angew. Chem. Int. Ed. 2015, 54, 5443, leading to compounds of formula XL VI. Hydrolysis with LiOH as already described gives carboxylic acids of formula XLVII. Alternatively, treatment of compounds of formula XLV with the same Wittig reagent together with a base, such as butyl lithium in a solvent such as tetrahydrofuran, at a temperature of minus 78°C up to room temperature can lead directly to carboxylic acids of formula XLVII. Subsequent activation of the carboxylic acid of formula XLVII and final amide coupling with amines of formula VII delivers compounds of formula li as illustrated in Scheme 8.
Scheme 9
Figure imgf000031_0001
Compounds of formula Ij, wherein t is 1, 2 3 or 4, A, R1, R2a, R3 and Q are defined as above, can be prepared according to reaction Scheme 9. Thus, compounds of formula XLV are treated with a Wittig- Homer reagent diethyl methylphosphonate together with a source of chloride ions, such as benzene sulfonylchloride, with a base, such as butyl lithium in a solvent such as tetrahydrofuran, at a temperature of minus 78°C up to room temperature, as described for example in Synthetic Communications, 1991 , 21, 1657. Hydrolysis with LiOH as already described gives carboxylic acids of formula L. Subsequent activation of the carboxylic acid of formula L and final amide coupling with amines of formula VII delivers compounds of formula Ij as illustrated in Scheme 9.
Scheme 10 According to scheme I0, compound of formula LI II wherein t is 1 , 23 or 4, A, R2a are as described above, can be prepared by treatment of compound of formula LI I with a cyanide source such as potassium thiocyanate, copper iodide, p-toluene sulfonyl hydrazide in presence of a suitable base such as DBU and a suitable solvent such as acetonitrile and NMP at temperature between 60 °C- 120 °C preferably 80 °C (see JOC, 2017 (82) 7621). Intermediate of formula Lll can be prepared by treatment of compound of formula XLV with p-toluene sulfonyl hydrazide in presence of a suitable solvent such as methanol at temperature between 60 °C- 120 °C preferably 70 °C.
Scheme 11
Figure imgf000032_0001
According to scheme 11, compound of formula LV wherein A, R2a are as described above, can be prepared by treatment of compound of formula LIV with methyl magnesium bromide and DMMN in presence of a suitable solvent such as diethyl ether at temperature between 60 °C- 100 °C preferably 80 °C and trapped with a suitable electrophile such as dibromoethane as described in Tetrahedron, 2019 (75), 4298.
Scheme 12
Figure imgf000032_0002
According to scheme 12, compound of formula LVII wherein A, R2a are as described above, can be prepared by treatment of compound of formula LVI with 1 -cyanocyclopropane in presence of a suitable base, preferably isopropyl magnesium chloride, and a suitable solvent such as tetrahydrofuran at temperature between -100 °C- 25 °C as described in W09932448.
Scheme 13
Figure imgf000033_0001
According to scheme 13, compound of formula LX wherein A, R2a are as described above, can be prepared by treatment of compound of formula LVII with 3-chloro-2-methyl propene with magnesium in presence of a suitable solvent such as diethyl ether at temperature between -100 °C- 25 °C as described in W02005100587 followed by cyclopropanation under Simmons-Smith conditions as described for example in JOC, 2004, 69, 327.
Esters of general formula LXIII, wherein Fka is defined as above and A is C or N, could be prepared following the synthesis described in detail in scheme 14.
Scheme 14
Figure imgf000033_0002
Esters of general formula LXIII can be synthesized by hydrogenation of esters of formula LXII, wherein R2a is defined as above and A is CH or N. Esters of formula LXII can be treated by a catalyst, for instance a palladium or an iridium catalyst, eventually in the presence of a ligand, and placed under a hydrogen atmosphere at a pressure from 1 bar to 50 bars in a suitable solvent, e.g. ethanol or dichloromethane, at a temperature between room temperature and 150 °C. Alternatively the reduction can be carried out by a silane such as triethylsilane or polymethylhydrosiloxane in the presence of an acid such as trifluoroacetic acid in a suitable solvent, e.g. dichloromethane. Such processes have been described for instance in WO2017/211307 or WO2016/119758.
Alkenes of general formula LXII may be synthesized from ketone of general formula LXI, wherein F¾a is defined as above and A is C or N, by a Wittig reaction. Wittig reactions involve treating ketones of formula LXI with a phosphonium reagent such as methyltriphenylphosphonium bromide in the presence of a base, e.g. potassium tert-butoxide or n-butyllithium in a suitable solvent such as THF at a temperature between -78 °C and the boiling point of the solvent. Such processes have been described in the literature for instance in J. Am. Chem. Soc. 2014, 136, 17926. Alternatively, alkenes of formula LXII can be prepared by a Suzuki-Miyaura reaction as described in scheme 15. Scheme 15
Figure imgf000034_0001
Compounds of formula LXII can be prepared by a Suzuki-Miyaura reaction between compounds of formula LXV wherein W can be a boron-derived functional group, as for example B(OH)2 or a pinacol boron ic ester and compounds of formula LXIV, wherein X is a leaving group like, for example, chlorine, bromine, iodine, arylsulfonate, alkylsulfonate or trifluoromethanesulfonate, A is C or N and F¾a is as defined above. Compounds of formula LXV are generally commercially available. The reaction can be catalyzed by a palladium based catalyst, for example fefrak/s(triphenylphosphine)-palladium or (1,1 'bis(diphenylphosphino)-ferrocene)dichloropalladium-dichloromethane (1 :1 complex), in presence of a base, like sodium carbonate or cesium fluoride, in a solvent or a solvent mixture, like, for example a mixture of 1 ,2-dimethoxyethane and water, dioxane and water, or DMF and water preferably under inert atmosphere. The reaction temperature can preferentially range from room temperature to the boiling point of the reaction mixture. Such Suzuki reactions are well known to those skilled in the art and have been reported, for example in J. Organomet. Chem. 576, 1999, 147-168, Science of Synthesis 2010, 45b, 547, Eur. J. Org. Chem. 2012, (31), 6248 and Synthesis 2017, 49, 4372.
Alternatively compounds of formula LXII I can be prepared following the synthesis described in scheme 16.
Scheme 16 Compounds of formula LXIII can be prepared by cyclopropanation of alkene compounds of formula LXVIII, wherein l¾a is defined as above and A is C or N. They can be obtained by treating alkenes of formula LXVIII with a metal reagent such as diethylzinc or triethy!aluminum in the presence of a dihalogen reagent, e.g. diodomethane or chloroiodomethane, eventually in the presence of a ligand that can coordinate the metal species, such as a trifluoroacetate. This reaction has been described in the literature for similar substrates for instance in J. Med. Chem. 2017, 60, 3606. Alkenes of formula LXIII can be synthesized from compounds of formula LXIV by a Suzuki reaction, which entails treating compounds of formula LXIV by compounds of formula LXVII, wherein W can be a boron-derived functional group as described in scheme 15, in the presence of a palladium catalyst, as described for instance in Chem. Comm. 2017, 53, 6440. Compounds of formula LXVII are generally commercially available. Detailed conditions can be found in scheme 15. Alternatively, compounds of formula LXVIII can be synthesized by treating compounds of formula LXIV with a stannane of formula LXVI in presence of a palladium catalyst (Stille reaction). Such Stille coupling reactions are well known to those skilled in the art, and have been described in for example J. Org. Chem., 2005, 70, 8601 , J. Org. Chem., 2009, 74, 5599, Angew. Chem. Int. Ed., 2004, 43, 1132, Heterocycles 2010, 80, 1215 and J. Am. Chem. Soc. 2004, 126, 16433.
Compounds of formula LXXIII, wherein Z1 is a C1-C4 alkyl, l¾a is as described above and A is C or N, can be prepared as described in scheme 17.
Scheme 17 Compounds of formula LXXI 11 may be synthesized by treating compounds of formula LXXI I, wherein Zi is a Ci-C4alkyl, Z2 is a Ci-C4alkyl, F¾a is as described above and A is C or N, with a Grignard reagent such as ethylmagnesium bromide in presence of an organometaliic reagent such as titanium isopropropoxide or bis(cyclopentadienyl)zirconium(IV) dichloride. This reaction can take place in a solvent such as toluene or THF at temperatures from -78 °C to the boiling point of the solvent. Such reactions have been described in the literature for instance in Org. Lett. 2015, 17, 6074 or Synthesis, 1991, 234. Compounds of formula LXXI I can be prepared by reaction between a halogenated compound of formula LXIX, wherein Z1 is a C1-C4 alkyl, l¾a is as described above and A is C or N, and X is a leaving group such as a halogen, a mesylate, a tosylate or a triflate, and compounds of formula LXXI, wherein Z2 is a C1-C4 alkyl, or zincate reagents of formula LXX, wherein Z2 is a C1-C4 alkyl (Reformatsky reagents). Such reactions are usually done in the presence of a catalyst e.g. a palladium catalyst, eventually in the presence of a base, e.g. tripotassium phosphate, and are described in the literature for instance in J. Org. Chem. 2013, 78, 8250 or W02008/055842.
Alternatively, compounds of formula LXXI 11 may be prepared by cyciopropanation of enol ether derivatives of formula LXXV, wherein Zi is a C1-C4 alkyl, R2a is as described above and A is C or N. The conditions for the cyciopropanation reaction have been described in detail in scheme 16. An example of such cyciopropanation can be found for example in Org. Biomol. Chem. 2015, 13, 5105. Enol ether of formula LXXV can be prepared by treating ketones of formula LXXIV, wherein Zi is a C1- C4 alkyl, R2a is as described above and A is C or N, with a base, e.g. lithium diisopropylamine or triethylamine, and a silyiation reagent such as trimethylsiiyichloride or trimethylsilyl trifluoro- methanesulfonate in a suitable solvent such as dichloromethane or tetrahydrofuran at a temperature from -78 °C to room temperature. Formation of such kinetic silyl enol ethers have been described in the literature for instance in Tetrahedron Letters 1999, 40, 4037-4040 or J. Org. Chem. 1996, 61, 5532- 5536. Ketones of formula LXXIV can be prepared by mono arylation of acetone with aryls of formula LXIX. Arylation of this type are usually carried out in the presence of a catalyst, e.g. a palladium or a copper catalyst, in the presence of acetone or an acetone equivalent such as preformed stannyl or silyl acetone enolate, and a base, e.g. cesium carbonate or tripotassium phosphate, in a suitable solvent at a temperature between room temperature and 150 °C. Examples of such processes can be found in the literature for instance in J. Am. Chem. Soc. 2010, 132, 8273 or J. Am. Chem. Soc. 2011, 133, 5194. The synthesis of compounds of general formula LXXX, wherein Ria is as described above and A is C or N, is described in scheme 18.
Scheme 18
Figure imgf000037_0001
Compounds of general formula LXXX can be prepared by treating compounds of formula LXXXI with a deoxyfluorination reagent such as Deoxo-Fluor® or diethy!aminosulfur trifluoride in a suitable solvent such as dichloromethane or toluene. Such a transformation has already been exemplified, for instance in W02004/024720 (p.77). Alternatively, compounds of formula LXXX can be obtained by the reduction of compounds of formula LXXIX, wherein F¾a is as described above, A is C or N, and X01 is a leaving group, such as Cl, Br, I, OMe, OTs or OTf. Such reductions can be done using hydride donor reagents such as sodium borohydride in a solvent, e.g. methanol or ethanol. Compounds of formula LXXIX can be prepared from alcohols of formula LXXVIII, wherein Fka is as described above and A is C or N. For compounds of formula LXXIX wherein X01 is a halogen, alcohols of formula LXXVIII can be treated with triphenylphosphine in the presence of a halogenating reagent such as CCL, CB^ or h. For compounds of formula LXXIX wherein X01 is a mesylate, a tosylate or a triflate, these compounds can be prepared by treating alcohols of formula LXXVIII with a base, such as triethylamine or pyridine, and a compound of formula XOI-SO2CI, such as mesyl chloride. Such a process has been described for instance in W02005/030213 (p.200).
Alcohols of formula LXXVIII may be synthesized by coupling between a haloaryl of formula LXIX and 1- fluorocyclopropylcarboxaldehyde (CAS 134645-39-9). Usually compounds of formula LXIX are treated with a Grignard reagent e.g. iPrMgCI and a copper salt before quenching the intermediate by addition of 1-Fluorocyciopropylcarboxaldehyde. This reaction may take place in a solvent such as THF or toluene at a temperature from -78 °C to room temperature.
Alternatively, alcohols of formula LXXVIII may be prepared by cyclopropanation of alcohols of formula LXXVII, wherein l¾a is as described above and A is C or N. Such a process has been described in detail in scheme 16 and has been described for instance in W02005/030213 (p.200-201).
Alcohols of formula LXXVII, wherein R2a is as described above and A is C or N, may be prepared by coupling of aldehydes of formula LXXVI, wherein R2a is as described above and A is C or N, with 1- fluoroethenyl-methyl-diphenylsilane (CAS 257610-49-4). This reaction is done in the usual way in the presence of a fluoride source such as tetra-n-butylammonium fluoride in a solvent such as THF. Such as reaction has been described in the literature for instance in Chem. Commun., 1999, 2397 or in W02005/030213 (p.200-201).
Aldehydes of formula LXXVI may be prepared byformylation of aryl halides of formula XLIV. Formylation can be done by treatment of compounds of formula XLIV with a Grignard reagent such as iPrMgCI in a solvent such as THF, followed by quenching with a formylation reagent such as N , N-d imethylformamide. Such a transformation has been described for instance in Bioorg. Med. Chem. Leters 2009, 19, 5004. Alternatively, the formylation can be carried out by treating the aryl halides of formula LXIX with a catalyst, e.g. a palladium catalyst under an atmosphere of carbon monoxide/hydrogen (SynGas®) at a pressure between 1 bar and 20 bars in a solvent such as toluene at a temperature between room temperature and 150 °C. Such a transformation has been described for instance in W02007/140183 (P-58)
The synthesis of compounds of general formula LXXXVI, wherein R2a is as described above, A is C or N and X02 is Br or Cl, is described in scheme 19.
Scheme 19
Figure imgf000038_0001
Compounds of formula LXXXVI may be formed by reduction of compounds of formula LXXXV, wherein R2a is as described above, A is C or N, X01 is Br, Cl, I, OMs, OTs or OTf, and X02 is Br or Cl, following the conditions described in scheme 18. Compounds of general formula LXXXV may be synthesized from alcohols of formula LXXXIV, wherein F¾a is as described above, A is C or N and X02 is Br or Cl. The preparation is the same as described above for the synthesis of LXXIX. Compounds of formula LXXXIV may be prepared by hydrobromination or hydrochlorination of alkenes of formula LXXXIII, wherein F¾a is as described above and A is C or N. This transformation involves treating alkenes of formula LXXXIII with a halogenating reagent such as bromine, chlorine, N-chlorosuccinimide or N- bromosuccinimide in the presence of a solvent, e.g. acetone and water. This has been described in the literature for instance in J. Org. Chem. 2008, 73, 4702 or Synlett 1998, 5, 491. Compounds of formula LXXXIII may be prepared from compounds of formula LXXXII by a Wittig reaction. This reaction may take place using a phosphonium reagent, e.g. triphenyI(3-bromopropyI)phosphonium bromide or cyclopropyltriphenylphosphonium bromide, in the presence of a base, such as potassium tert-butoxide or sodium hydride. These conditions have been described in more detail in Scheme 14 and has been exemplified in the literature for instance in Chem. Comm. 2015, 51, 7493. Alternatively, compounds of formula LXXXII can be treated with dicyclopropyltitanocene, as described for instance in Tetrahedron Letters, 1993, 34,943.
The synthesis of compounds of general formula LXXXVI I, wherein F¾a is as described above, A is C or N and t = 2 to 4, is described in Scheme 20.
Scheme 20
Figure imgf000039_0001
Compounds of formula LXXXVI I, wherein l¾a is as described above, A is C or N, and t = 2 to 4, may be formed following the conditions described in Scheme 20. Thus, compounds of formula XLV are treated with a fluorinating reagent, such as Deoxofluor® or 2,2-difluoro-1 ,3-dimethyiimidazolidine (DFI) to provide compounds of formula LXXXVI I. This has been described in the literature for instance in WO2005/32465, page 25, or Chem. Commun. 2002, 1618.
Scheme 21
Figure imgf000040_0001
Compounds of formula I, wherein A, R1, R2a, R2b and R3 are as described above may be formed by condensing an acid of formula XC with a compound of formula XCII in the presence of an activating agent such as DCC, EDD or T3P or by condensing an acid chloride of formula XCI with a compound of formula XCII in the presence of a base according to methods known to the person skill in the art, as illustrated in Scheme 21. A, R1, R2a, R2b and R3 are as described above.
Depending on the procedure or the reaction conditions, the reactants can be reacted in the presence of a base. Examples of suitable bases are alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal hydrides, alkali metal or alkaline earth metal amides, alkali metal or alkaline earth metal alkoxides, alkali metal or alkaline earth metal acetates, alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal dialkylamides or alkali metal or alkaline earth metal alkylsily!amides, alkylamines, alkylenediamines, free or N-alkylated saturated or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxides and carbocyclic amines. Examples which may be mentioned are sodium hydroxide, sodium hydride, sodium amide, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N,N- dimethylamine, N,N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinuclidine, N- methylmorpholine, benzyltrimethylammonium hydroxide and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).
The reactants can be reacted with each other as such, i.e. without adding a solvent or diluent. In most cases, however, it is advantageous to add an inert solvent or diluent or a mixture of these. If the reaction is carried out in the presence of a base, bases which are employed in excess, such as triethylamine, pyridine, N-methylmorpholine or N,N-diethylaniline, may also act as solvents or diluents. The reactions are advantageously carried out in a temperature range from approximately -80°C to approximately +140°C, preferably from approximately -30°C to approximately +100°C, in many cases in the range between ambient temperature and approximately +80°C.
Depending on the choice of the reaction conditions and starting materials which are suitable in each case, it is possible, for example, in one reaction step only to replace one substituent by another substituent according to the invention, or a plurality of substituents can be replaced by other substituents according to the invention in the same reaction step.
Salts of compounds of formula I can be prepared in a manner known perse. Thus, for example, acid addition salts of compounds of formula I are obtained by treatment with a suitable acid or a suitable ion exchanger reagent and salts with bases are obtained by treatment with a suitable base or with a suitable ion exchanger reagent.
Salts of compounds of formula I can be converted in the customary manner into the free compounds I, acid addition salts, for example, by treatment with a suitable basic compound or with a suitable ion exchanger reagent and salts with bases, for example, by treatment with a suitable acid or with a suitable ion exchanger reagent.
Salts of compounds of formula I can be converted in a manner known per se into other salts of compounds of formula I, acid addition salts, for example, into other acid addition salts, for example by treatment of a salt of inorganic acid such as hydrochloride with a suitable metal salt such as a sodium, barium or silver salt, of an acid, for example with silver acetate, in a suitable solvent in which an inorganic salt which forms, for example silver chloride, is insoluble and thus precipitates from the reaction mixture.
Depending on the procedure or the reaction conditions, the compounds of formula I, which have saltforming properties can be obtained in free form or in the form of salts.
The compounds of formula I and, where appropriate, the tautomers thereof, in each case in free form or in salt form, can be present in the form of one of the isomers which are possible or as a mixture of these, for example in the form of pure isomers, such as antipodes and/or diastereomers, or as isomer mixtures, such as enantiomer mixtures, for example racemates, diastereomer mixtures or racemate mixtures, depending on the number, absolute and relative configuration of asymmetric carbon atoms which occur in the molecule and/or depending on the configuration of non-aromatic double bonds which occur in the molecule; the invention relates to the pure isomers and also to all isomer mixtures which are possible and is to be understood in each case in this sense hereinabove and hereinbelow, even when stereochemical details are not mentioned specifically in each case. Diastereomer mixtures or racemate mixtures of compounds of formula I, in free form or in salt form, which can be obtained depending on which starting materials and procedures have been chosen can be separated in a known manner into the pure diasteromers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and/or chromatography.
Enantiomer mixtures, such as racemates, which can be obtained in a similar manner can be resolved into the optical antipodes by known methods, for example by recrystallization from an optically active solvent, by chromatography on chiral adsorbents, for example high-performance liquid chromatography (HPLC) on acetyl celulose, with the aid of suitable microorganisms, by cleavage with specific, immobilized enzymes, via the formation of inclusion compounds, for example using chiral crown ethers, where only one enantiomer is complexed, or by conversion into diastereomeric salts, for example by reacting a basic end-product racemate with an optically active acid, such as a carboxylic acid, for example camphor, tartaric or malic acid, or sulfonic acid, for example camphorsulfonic acid, and separating the diastereomer mixture which can be obtained in this manner, for example by fractional crystallization based on their differing solubilities, to give the diastereomers, from which the desired enantiomer can be set free by the action of suitable agents, for example basic agents.
Pure diastereomers or enantiomers can be obtained according to the invention not only by separating suitable isomer mixtures, but also by generally known methods of diastereoselective or enantioselective synthesis, for example by carrying out the process according to the invention with starting materials of a suitable stereochemistry.
N-oxides can be prepared by reacting a compound of the formula I with a suitable oxidizing agent, for example the H2C>2/urea adduct in the presence of an acid anhydride, e.g. trifluoroacetic anhydride. Such oxidations are known from the literature, for example from J. Med. Chem., 32 (12), 2561-73,
1989 or WO 2000/15615.
It is advantageous to isolate or synthesize in each case the biologically more effective isomer, for example enantiomer or diastereomer, or isomer mixture, for example enantiomer mixture or diastereomer mixture, if the individual components have a different biological activity.
The compounds of formula I and, where appropriate, the tautomers thereof, in each case in free form or in salt form, can, if appropriate, also be obtained in the form of hydrates and/or include other solvents, for example those which may have been used for the crystallization of compounds which are present in solid form. The compounds of formula I according to the following Tables A-1 to A-18 can be prepared according to the methods described above. The examples which follow are intended to illustrate the invention and show preferred compounds of formula I, in the form of a compound of formula IA.
Figure imgf000043_0001
Table A-1 provides 216 compounds A-1 .001 to A-1 .216 of formula IA wherein A is CH, Ri is H, Råa is CF3, and Råb and Q are as defined in table T. For example A-1001 is
Figure imgf000043_0002
Table A-2 provides 216 compounds A-2.001 to A-2.216 of formula IA wherein A is CH, Ri is H, Råa is Cl, and Råb and Q are as defined in table T.
Table A-3 provides 216 compounds A-3.001 to A-3.216 of formula IA wherein A is CH, Ri is H, R2a is Br, and Råb and Q are as defined in table T.
Table A-4 provides 216 compounds A-4.001 to A-4.216 of formula IA wherein A is CH, Ri is Me, R2a is CF3, and Råb and Q are as defined in table T.
Table A-5 provides 216 compounds A-5.001 to A-5.216 of formula IA wherein A is CH, Ri is Me, R2a is Cl, and Råb and Q are as defined in table T.
Table A-6 provides 216 compounds A-6.001 to A-6.216 of formula IA wherein A is CH, Ri is Me, R2a is Br, and Råb and Q are as defined in table T.
Table A-7 provides 216 compounds A-7.001 to A-7.216 of formula IA wherein A is CH, Ri is CH2- cyclopropyl, R2a is CF3, and Råb and Q are as defined in table T.
Table A-8 provides 216 compounds A-8.001 to A-8.216 of formula IA wherein A is CH, Ri is CH2- cyclopropyl, R2a is Cl, and Råb and Q are as defined in table T.
Table A-9 provides 216 compounds A-9.001 to A-9.216 of formula IA wherein A is CH, Ri is CH2- cyclopropyl, R2a is Br, and Råb and Q are as defined in table T.
Table A-10 provides 216 compounds A-10.001 to A-10.216 of formula IA wherein A is N, Ri is H, R2a is CF3, and Råb and Q are as defined in table T.
Table A-11 provides 216 compounds A-11 .001 to A-11 .216 of formula IA wherein A is N, Ri is H, R2a is Cl, and Råb and Q are as defined in table T. Table A-12 provides 216 compounds A-12.001 to A-12.216 of formula IA wherein A is N, Ri is H, Råa is Br, and Råb and Q are as defined in table T.
Table A-13 provides 216 compounds A-13.001 to A-13.216 of formula IA wherein A is N, Ri is Me, Råa is CF3, and Råb and Q are as defined in table T. Table A-14 provides 216 compounds A-14.001 to A-14.216 of formula IA wherein A is N, Ri is Me, Råa is Cl, and Råb and Q are as defined in table T.
Table A-15 provides 216 compounds A-15.001 to A-15.216 of formula IA wherein A is N, Ri is Me, Råa is Br, and Råb and Q are as defined in table T.
Table A-16 provides 216 compounds A-16.001 to A-16.216 of formula IA wherein A is N, Ri is CH2- cyclopropyl, Råa is CF3, and Råb and Q are as defined in table T.
Table A-17 provides 216 compounds A-17.001 to A-17.216 of formula IA wherein A is N, Ri is CH2- cyclopropyl, Råa is Cl, and Råb and Q are as defined in table T.
Table A-18 provides 216 compounds A-18.001 to A-18.216 of formula IA wherein A is N, Ri is CH2- cyclopropyl, Råa is Br, and Råb and Q are as defined in table T.
Table T: Substituent definitions of Råb and Q:
Figure imgf000044_0001
Figure imgf000045_0004
33 Q-9
Figure imgf000045_0002
105
Figure imgf000045_0003
R2b-9 I 177
Figure imgf000045_0001
Figure imgf000045_0005
j
Figure imgf000045_0007
j
Figure imgf000045_0006
Figure imgf000046_0001
Footnote: see Table Q for the group Q referenced in table T; and see Table R for the group R2b referenced in table T;
Table Q: Substituent definitions of Q:
Figure imgf000046_0002
Figure imgf000047_0002
Also made available are certain intermediate compounds of formula K some of which are novel.
Figure imgf000047_0001
For example, made available are a compound of formula K, wherein (i) A is CH, Råa is Cl and Råb is as defined in table R; and (ii) A is CH, Råa is trifluoromethyl and Råb is as defined in table R. Table K lists specific examples of compound of formula K. Table K of Intermediates
Figure imgf000048_0001
Figure imgf000049_0001
Figure imgf000050_0001
Figure imgf000051_0001
In further aspect, the present invention accordingly makes available compounds of formula K wherein A, Råa and Råb are as defined for formula I in the first aspect. Furthermore, the corresponding embodiments illustrated for formula I in respect of A, Råa and Råb also apply to the compounds of formula K.
The compounds of formula I according to the invention are preventively and/or curatively valuable active ingredients in the field of pest control, even at low rates of application, which have a very favorable biocidal spectrum and are well tolerated by warm-blooded species, fish and plants. The active ingredients according to the invention act against all or individual developmental stages of normally sensitive, but also resistant, animal pests, such as insects or representatives of the order Acarina. The insecticidal or acaricidal activity of the active ingredients according to the invention can manifest itself directly, i. e. in destruction of the pests, which takes place either immediately or only after some time has elapsed, for example during ecdysis, or indirectly, for example in a reduced oviposition and/or hatching rate.
Examples of the above mentioned animal pests are: from the order Acarina, for example,
Acalitus spp, Aculus spp, Acaricalus spp, Aceria spp, Acarus siro, Amblyomma spp., Argas spp., Boophilus spp., Brevipalpus spp., Bryobia spp, Calipitrimerus spp., Chorioptes spp., Dermanyssus gallinae, Dermatophagoides spp, Eotetranychus spp, Eriophyes spp., Hemitarsonemus spp,
Hyalomma spp., Ixodes spp., Olygonychus spp, Ornithodoros spp., Polyphagotarsone latus, Panonychus spp., Phyllocoptruta oleivora, Phytonemus spp, Polyphagotarsonemus spp, Psoroptes spp., Rhipicephalus spp., Rhizoglyphus spp., Sarcoptes spp., Steneotarsonemus spp, Tarsonemus spp. and Tetranychus spp.; from the order Anoplura, for example,
Haematopinus spp., Linognathus spp., Pediculus spp., Pemphigus spp. and Phylloxera spp.; from the order Coleoptera, for example,
Agriotes spp., Amphimallon majale, Anomala orientalis, Anthonomus spp., Aphodius spp, Astylus atromaculatus, Ataenius spp, Atomaria linearis, Chaetocnema tibialis, Cerotoma spp, Conoderus spp, Cosmopolites spp., Cotinis nitida, Curculio spp., Cyclocephala spp, Dermestes spp., Diabrotica spp., Diloboderus abderus, Epilachna spp., Eremnus spp., Heteronychus arator, Hypothenemus hampei, Lagria vilosa, Leptinotarsa decemlineata, Lissorhoptrus spp., Liogenys spp, Maecolaspis spp, Maladera castanea, Megascelis spp, Melighetes aeneus, Melolontha spp., Myochrous armatus, Orycaephilus spp., Otiorhynchus spp., Phyllophaga spp, Phlyctinus spp., Popillia spp., Psylliodes spp., Rhyssomatus aubtilis, Rhizopertha spp., Scarabeidae, Sitophilus spp., Sitotroga spp., Somaticus spp, Sphenophorus spp, Sternechus subsignatus, Tenebrio spp., Tribolium spp. and Trogoderma spp.; from the order Diptera, for example,
Aedes spp., Anopheles spp, Antherigona soccata.Bactrocea oleae, Bibio hortulanus, Bradysia spp, Calliphora erythrocephala, Ceratitis spp., Chrysomyia spp., Culex spp., Cuterebra spp., Dacus spp., Delia spp, Drosophila melanogaster, Fannia spp., Gastrophilus spp., Geomyza tripunctata, Glossina spp., Hypoderma spp., Hyppobosca spp., Liriomyza spp., Lucilia spp., Melanagromyza spp., Musca spp., Oestrus spp., Orseolia spp., Oscinella frit, Pegomyia hyoscyami, Phorbia spp., Rhagoletis spp, Rivelia quadrifasciata, Scatella spp, Sciara spp., Stomoxys spp., Tabanus spp., Tannia spp. and Tipula spp.; from the order Hemiptera, for example,
Acanthocoris scabrator, Acrosternum spp, Adelphocoris lineolatus, Aleurodes spp., Amblypelta nitida, Bathycoelia thalassina, Blissus spp, Cimex spp., Clavigralla tomentosicollis, Creontiades spp, Distantiella theobroma, Dichelops furcatus, Dysdercus spp., Edessa spp, Euchistus spp., Eurydema pulchrum, Eurygaster spp., Halyomorpha halys, Horcias nobilellus, Leptocorisa spp., Lygus spp, Margarodes spp, Murgantia histrionic, Neomegalotomus spp, Nesidiocoris tenuis, Nezara spp., Nysius simulans, Oebalus insularis, Piesma spp., Piezodorus spp, Rhodnius spp., Sahlbergella singularis, Scaptocoris castanea, Scotinophara spp. , Thyanta spp , Triatoma spp., Vatiga illudens;
Acyrthosium pisum, Adalges spp, Agalliana ensigera, Agonoscena targionii, Aleurodicus spp, Aleurocanthus spp, Aleurolobus barodensis, Aleurothrixus floccosus, Aleyrodes brassicae, Amarasca biguttula, Amritodus atkinsoni, Aonidiella spp., Aphididae, Aphis spp., Aspidiotus spp., Aulacorthum solani, Bactericera cockerelli, Bemisia spp, Brachycaudus spp, Brevicoryne brassicae, Cacopsylla spp, Cavariella aegopodii Scop., Ceroplaster spp., Chrysomphalus aonidium, Chrysomphalus dictyospermi, Cicadella spp, Cofana spectra, Cryptomyzus spp, Cicadulina spp, Coccus hesperidum, Dalbulus maidis, Dialeurodes spp, Diaphorina citri, Diuraphis noxia, Dysaphis spp, Empoasca spp., Eriosoma larigerum, Erythroneura spp., Gascardia spp., Glycaspis brimblecombei, Hyadaphis pseudobrassicae, Hyalopterus spp, Hyperomyzus pallidus, Idioscopus clypealis, Jacobiasca lybica, Laodelphax spp., Lecanium corni, Lepidosaphes spp., Lopaphis erysimi, Lyogenys maidis, Macrosiphum spp., Mahanarva spp, Metcalfa pruinosa, Metopolophium dirhodum, Myndus crudus, Myzus spp., Neotoxoptera sp, Nephotettix spp., Nilaparvata spp., Nippolachnus piri Mats, Odonaspis ruthae, Oregma lanigera Zehnter, Parabemisia myricae, Paratrioza cockerelli, Parlatoria spp., Pemphigus spp., Peregrinus maidis, Perkinsiella spp, Phorodon humuli, Phylloxera spp, Planococcus spp., Pseudaulacaspis spp., Pseudococcus spp., Pseudatomoscelis seriatus, Psylla spp., Pulvinaria aethiopica, Quadraspidiotus spp., Quesada gigas, Recilia dorsalis, Rhopalosiphum spp., Saissetia spp., Scaphoideus spp., Schizaphis spp., Sitobion spp., Sogatella furcifera, Spissistilus festinus, Tarophagus Proserpina, Toxoptera spp, Trialeurodes spp, Tridiscus sporoboli, Trionymus spp, Trioza erytreae , Unaspis citri, Zygina flammigera, Zyginidia scutellaris, ; from the order Hymenoptera, for example,
Acromyrmex, Arge spp, Atta spp., Cephus spp., Diprion spp., Diprionidae, Gilpinia polytoma, Hoplo- campa spp., Lasius spp., Monomorium pharaonis, Neodiprion spp., Pogonomyrmex spp, Slenopsis invicta, Solenopsis spp. and Vespa spp.; from the order Isoptera, for example,
Coptotermes spp, Corniternes cumulans, Incisitermes spp, Macrotermes spp, Mastotermes spp, Microtermes spp, Reticulitermes spp.; Solenopsis geminate from the order Lepidoptera, for example,
Acleris spp., Adoxophyes spp., Aegeria spp., Agrotis spp., Alabama argillaceae, Amylois spp., Anticarsia gemmatalis, Archips spp., Argyresthia spp, Argyrotaenia spp., Autographa spp., Bucculatrix thurberiella, Busseola fusca, Cadra cautella, Carposina nipponensis, Chilo spp., Choristoneura spp., Chrysoteuchia topiaria, Clysia ambiguella, Cnaphalocrocis spp., Cnephasia spp., Cochylis spp., Coleophora spp., Colias lesbia, Cosmophila flava, Crambus spp, Crocidolomia binotalis, Cryptophlebia leucotreta, Cydalima perspectalis, Cydia spp., Diaphania perspectalis, Diatraea spp., Diparopsis castanea, Earias spp., Elasmopalpus lignosellus, Eldana saccharina, Ephestia spp., Epinotia spp, Estigmene acrea, Etiella zinckinella, Eucosma spp., Eupoecilia ambiguella, Euproctis spp., Euxoa spp., Feltia jaculiferia, Grapholita spp., Hedya nubiferana, Heliothis spp., Hellula undalis, Herpetogramma spp, Hyphantria cunea, Keiferia lycopersicella, Lasmopalpus lignosellus, Leucoptera scitella, Lithocollethis spp., Lobesia botrana, Loxostege bifidalis, Lymantria spp., Lyonetia spp., Malacosoma spp., Mamestra brassicae, Manduca sexta, Mythimna spp, Noctua spp, Operophtera spp., Orniodes indica, Ostrinia nubilalis, Pammene spp., Pandemis spp., Panolis flammea, Papaipema nebris, Pectinophora gossypiela, Perileucoptera coffeella, Pseudaletia unipuncta, Phthorimaea operculella, Pieris rapae, Pieris spp., Plutella xylostella, Prays spp., Pseudoplusia spp, Rachiplusia nu, Richia albicosta, Scirpophaga spp., Sesamia spp., Sparganothis spp., Spodoptera spp., Sylepta derogate, Synanthedon spp., Thaumetopoea spp., Tortrix spp., Trichoplusia ni, Tufa absoluta, and Yponomeuta spp.; from the order Mallophaga, for example,
Damalinea spp. and Trichodectes spp.; from the order Orthoptera, for example,
Blatta spp., Blattella spp., Gryllotalpa spp., Leucophaea maderae, Locusta spp., Neocurtilla hexadactyla, Periplaneta spp. , Scapteriscus spp, and Schistocerca spp.; from the order Psocoptera, for example,
Liposcelis spp.; from the order Siphonaptera, for example,
Ceratophyllus spp., Ctenocephalides spp. and Xenopsylla cheopis; from the order Thysanoptera, for example,
Calliothrips phaseoli, Frankliniella spp., Heliothrips spp, Hercinothrips spp., Parthenothrips spp, Scirtothrips aurantii, Sericothrips variabilis, Taeniothrips spp., Thrips spp; from the order Thysanura, for example, Lepisma saccharina. In a further aspect, the invention may also relate to a method of controlling damage to plant and parts thereof by plant parasitic nematodes (Endoparasitic-, Semiendoparasitic- and Ectoparasitic nematodes), especially plant parasitic nematodes such as root knot nematodes, Meloidogyne hapla, Meloidogyne incognita, Meloidogyne javanica, Meloidogyne arenaria and other Meloidogyne species; cyst-forming nematodes, Globodera rostochiensis and other Globodera species; Heterodera avenae, Heterodera glycines, Heterodera schachtii, Heterodera trifolii, and other Heterodera species; Seed gall nematodes, Anguina species; Stem and foliar nematodes, Aphelenchoides species; Sting nematodes, Belonolaimus longicaudatus and other Belonolaimus species; Pine nematodes, Bursaphelenchus xylophilus and other Bursaphelenchus species; Ring nematodes, Criconema species, Criconemella species, Criconemoides species, Mesocriconema species; Stem and bulb nematodes, Ditylenchus destructor, Ditylenchus dipsaci and other Ditylenchus species; Awl nematodes, Dolichodorus species; Spiral nematodes, Heliocotylenchus multicinctus and other Helicotylenchus species; Sheath and sheathoid nematodes, Hemicycliophora species and Hemicriconemoides species; Hirshmanniella species; Lance nematodes, Hoploaimus species; false rootknot nematodes, Nacobbus species;
Needle nematodes, Longidorus elongatus and other Longidorus species; Pin nematodes,
Pratylenchus species; Lesion nematodes, Pratylenchus neglectus, Pratylenchus penetrans, Pratylenchus curvitatus, Pratylenchus goodeyi and other Pratylenchus species; Burrowing nematodes, Radopholus similis and other Radopholus species; Reniform nematodes, Rotylenchus robustus, Rotylenchus reniformis and other Rotylenchus species; Scutellonema species; Stubby root nematodes, Trichodorus primitivus and other Trichodorus species, Paratrichodorus species; Stunt nematodes, Tylenchorhynchus claytoni, Tylenchorhynchus dubius and other Tylenchorhynchus species; Citrus nematodes, Tylenchulus species; Dagger nematodes, Xiphinema species; and other plant parasitic nematode species, such as Subanguina spp., Hypsoperine spp., Macroposthonia spp., Melinius spp., Punctodera spp., and Quinisulcius spp..
The compounds of the invention may also have activity against the molluscs. Examples of which include, for example, Ampullariidae; Arion (A. ater, A. circumscriptus, A. hortensis, A. rufus); Bradybaenidae (Bradybaena fruticum); Cepaea (C. hortensis, C. Nemoralis); ochlodina; Deroceras (D. agrestis, D. empiricorum, D. laeve, D. reticulatum); Discus (D. rotundatus); Euomphalia; Galba (G. trunculata); Helicelia (H. itala, H. obvia); Helicidae Helicigona arbustorum); Helicodiscus; Helix (H. aperta); Limax (L. cinereoniger, L. flavus, L. marginatus, L. maximus, L. tenellus); Lymnaea; Milax (M. gagates, M. marginatus, M. sowerbyi); Opeas; Pomacea (P. canaticulata); Vallonia and Zanitoides.
The active ingredients according to the invention can be used for controlling, i. e. containing or destroying, pests of the abovementioned type which occur in particular on plants, especially on useful plants and ornamentals in agriculture, in horticulture and in forests, or on organs, such as fruits, flowers, foliage, stalks, tubers or roots, of such plants, and in some cases even plant organs which are formed at a later point in time remain protected against these pests. Suitable target crops are, in particular, cereals, such as wheat, barley, rye, oats, rice, maize or sorghum; beet, such as sugar or fodder beet; fruit, for example pomaceous fruit, stone fruit or soft fruit, such as apples, pears, plums, peaches, almonds, cherries or berries, for example strawberries, raspberries or blackberries; leguminous crops, such as beans, lentils, peas or soya; oil crops, such as oilseed rape, mustard, poppies, olives, sunflowers, coconut, castor, cocoa or ground nuts; cucurbits, such as pumpkins, cucumbers or melons; fibre plants, such as cotton, flax, hemp or jute; citrus fruit, such as oranges, lemons, grapefruit or tangerines; vegetables, such as spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes or bell peppers; Lauraceae, such as avocado, Cinnamonium or camphor; and also tobacco, nuts, coffee, eggplants, sugarcane, tea, pepper, grapevines, hops, the plantain family and latex plants.
The compositions and/or methods of the present invention may be also used on any ornamental and/or vegetable crops, including flowers, shrubs, broad-leaved trees and evergreens.
For example the invention may be used on any of the following ornamental species: Ageratum spp., Alonsoa spp., Anemone spp., Anisodontea capsenisis, Anthemis spp., Antirrhinum spp., Aster spp., Begonia spp. (e.g. B. elatior, B. semperflorens, B. tubereux), Bougainvillea spp., Brachycome spp., Brassica spp. (ornamental), Calceolaria spp., Capsicum annuum, Catharanthus roseus, Canna spp., Centaurea spp., Chrysanthemum spp., Cineraria spp. (C. maritime), Coreopsis spp., Crassula coccinea, Cuphea ignea, Dahlia spp., Delphinium spp., Dicentra spectabilis, Dorotheantus spp., Eustoma grandiflorum, Forsythia spp., Fuchsia spp., Geranium gnaphalium, Gerbera spp.,
Gomphrena globosa, Heliotropium spp., Helianthus spp., Hibiscus spp., Hortensia spp., Hydrangea spp., Hypoestes phyllostachya, Impatiens spp. (/. Walleriana), Iresines spp., Kalanchoe spp., Lantana camara, Lavatera trimestris, Leonotis leonurus, Lilium spp., Mesembryanthemum spp., Mimulus spp., Monarda spp., Nemesia spp., Tagetes spp., Dianthus spp. (carnation), Canna spp., Oxalis spp., Beilis spp., Pelargonium spp. (P. peltatum, P. Zonale), Viola spp. (pansy), Petunia spp., Phlox spp., Plecthranthus spp., Poinsettia spp., Parthenocissus spp. (P. quinquefolia, P. tricuspidata), Primula spp., Ranunculus spp., Rhododendron spp., Rosa spp. (rose), Rudbeckia spp., Saintpaulia spp.,
Salvia spp., Scaevola aemola, Schizanthus wisetonensis, Sedum spp., Solanum spp., Surfmia spp., Tagetes spp., Nicotinia spp., Verbena spp., Zinnia spp. and other bedding plants.
For example the invention may be used on any of the following vegetable species: Allium spp. (A. sativum, A. cepa, A. oschaninii, A. Porrum, A. ascalonicum, A. fistulosum), Anthriscus cerefolium, Apium graveolus, Asparagus officinalis, Beta vulgarus, Brassica spp. (B. Oleracea, B. Pekinensis, B. rapa), Capsicum annuum, Cicer arietinum, Cichorium endivia, Cichorum spp. (C. intybus, C. endivia), Citrillus lanatus, Cucumis spp. (C. sativus, C. meld), Cucurbita spp. (C. pepo, C. maxima), Cyanara spp. (C. scolymus, C. cardunculus), Daucus carota, Foeniculum vulgare, Hypericum spp., Lactuca sativa, Lycopersicon spp. (L esculentum, L lycopersicum), Mentha spp., Ocimum basilicum, Petroselinum crispum, Phaseolus spp. ( P . vulgaris, P. coccineus), Pisum sativum, Raphanus sativus, Rheum rhaponticum, Rosemarinus spp., Salvia spp., Scorzonera hispanica, Solarium melongena, Spinacea oleracea, Valerianella spp. ( V . locusta, V. eriocarpa) and Vicia faba.
Preferred ornamental species include African violet, Begonia, Dahlia, Gerbera, Hydrangea, Verbena, Rosa, Kalanchoe, Poinsettia, Aster, Centaurea, Coreopsis, Delphinium, Monarda, Phlox, Rudbeckia, Sedum, Petunia, Viola, Impatiens, Geranium, Chrysanthemum, Ranunculus, Fuchsia, Salvia, Hortensia, rosemary, sage, St. Johnswort, mint, sweet pepper, tomato and cucumber.
The active ingredients according to the invention are especially suitable for controlling Aphis craccivora, Diabrotica balteata, Heliothis virescens, Myzus persicae, Plutella xylostella and Spodoptera littoralis in cotton, vegetable, maize, rice and soya crops. The active ingredients according to the invention are further especially suitable for controlling Mamestra (preferably in vegetables), Cydia pomonella (preferably in apples), Empoasca (preferably in vegetables, vineyards), Leptinotarsa (preferably in potatos) and Chilo supressalis (preferably in rice).
The compounds of formula I are particularly suitable for control of
• a pest of the order Hemiptera, for example, one or more of the species Bemisia tabaci , Aphis craccivora, Myzus persicae, Rhopalosiphum Padi, Nilaparvata lugens, and Euschistus heros (preferably in vegetables, soybeans, and sugarcane);
• a pest of the order Lepidoptera, for example, one or more of the species Spodoptera littoralis, Spodoptera frugiperda, Plutella xylostella, Cnaphalocrocis medinalis, Cydia pomonella, Chrysodeixis includens, Chilo suppressalis, Elasmopalpus lignosellus, Pseudoplusia includens, and Tuta absoluta (preferably in vegetables and corn);
• a pest of the order Thysanoptera, such as the family Thripidae, for example, one or more of Thrips tabaci and Frankliniella occidentalis (preferably in vegetables); and
• soil pests (such as of the order Coleoptera), for example, the species Diabrotica balteata, Agriotes spp. and Leptinotarsa decemlineata (preferably in vegetables and corn).
The term "crops" is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins, for example insecticidal proteins from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as d-endotoxins, e.g. CrylAb, CrylAc, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vip1 , Vip2, Vip3 orVip3A; or insecticidal proteins of bacteria colonising nematodes, for example Photorhabdus spp. or Xenorhabdus spp., such as Photorhabdus luminescens, Xenorhabdus nematophilus; toxins produced by animals, such as scorpion toxins, arachnid toxins, wasp toxins and other insect-specific neurotoxins; toxins produced by fungi, such as Streptomycetes toxins, plant lectins, such as pea lectins, barley lectins or snowdrop lectins; agglutinins; proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors; ribosome-inactivating proteins (RIP), such as ricin, maize-RIP, abrin, luffin, saporin or bryodin; steroid metabolism enzymes, such as 3-hydroxysteroidoxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidases, ecdysone inhibitors, HMG-COA-reductase, ion channel blockers, such as blockers of sodium or calcium channels, juvenile hormone esterase, diuretic hormone receptors, stilbene synthase, bibenzyl synthase, chitinases and glucanases.
In the context of the present invention there are to be understood by 5-endotoxins, for example CrylAb, CrylAc, Cry1 F, Cry1 Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), for example Vip1 , Vip2, Vip3 or Vip3A, expressly also hybrid toxins, truncated toxins and modified toxins. Hybrid toxins are produced recombinantly by a new combination of different domains of those proteins (see, for example, WO 02/15701). Truncated toxins, for example a truncated CrylAb, are known. In the case of modified toxins, one or more amino acids of the naturally occurring toxin are replaced. In such amino acid replacements, preferably non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G-recognition sequence is inserted into a Cry3A toxin (see WO 03/018810).
Examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0 374 753, WO 93/07278, WO 95/34656, EP-A-0 427 529, EP-A-451 878 and WO 03/052073.
The processes for the preparation of such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. Cryl-type deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP-A-0 367 474, EP-A-0 401 979 and WO 90/13651.
The toxin contained in the transgenic plants imparts to the plants tolerance to harmful insects. Such insects can occur in any taxonomic group of insects, but are especially commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and moths (Lepidoptera).
Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available. Examples of such plants are: YieldGard® (maize variety that expresses a CrylAb toxin); YieldGard Rootworm® (maize variety that expresses a Cry3Bb1 toxin); YieldGard Plus® (maize variety that expresses a CrylAb and a Cry3Bb1 toxin); Starlink® (maize variety that expresses a Cry9C toxin); Herculex I® (maize variety that expresses a Cry1 Fa2 toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a Cry1 Ac toxin); Bollgard I® (cotton variety that expresses a Cry1 Ac toxin); Bollgard II® (cotton variety that expresses a Cry1 Ac and a Cry2Ab toxin); VipCot® (cotton variety that expresses a Vip3A and a Cry1 Ab toxin); NewLeaf® (potato variety that expresses a Cry3A toxin); NatureGard®, Agrisure® GT Advantage (GA21 glyphosate-tolerant trait), Agrisure® CB Advantage (Bt11 corn borer (CB) trait) and Protecta®.
Further examples of such transgenic crops are:
1 . Bt11 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer ( Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a truncated Cry1 Ab toxin. Bt11 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
2. Bt176 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer ( Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a CrylAb toxin. Bt176 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
3. MIR604 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Maize which has been rendered insect-resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G- protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810.
4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/DE/02/9. MON 863 expresses a Cry3Bb1 toxin and has resistance to certain Coleoptera insects.
5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/ES/96/02.
6. 1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7 B-1160 Brussels, Belgium, registration number C/NL/00/10. Genetically modified maize for the expression of the protein Cry1 F for achieving resistance to certain Lepidoptera insects and of the PAT protein for achieving tolerance to the herbicide glufosinate ammonium.
7. NK603 x MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/GB/02/M3/03. Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810. NK603 c MON 810 Maize transgenically expresses the protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, which imparts tolerance to the herbicide Roundup® (contains glyphosate), and also a CrylAb toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer.
Transgenic crops of insect-resistant plants are also described in BATS (Zentrum fiir Biosicherheit und Nachhaltigkeit, Zentrum BATS, Clarastrasse 13, 4058 Basel, Switzerland) Report 2003,
(http://bats.ch).
The term "crops" is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818 and EP-A-0 353 191 . The methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
Crops may also be modified for enhanced resistance to fungal (for example Fusarium, Anthracnose, or Phytophthora), bacterial (for example Pseudomonas) or viral (for example potato leafroll virus, tomato spotted wilt virus, cucumber mosaic virus) pathogens.
Crops also include those that have enhanced resistance to nematodes, such as the soybean cyst nematode.
Crops that are tolerance to abiotic stress include those that have enhanced tolerance to drought, high salt, high temperature, chill, frost, or light radiation, for example through expression of NF-YB or other proteins known in the art.
Antipathogenic substances which can be expressed by such transgenic plants include, for example, ion channel blockers, such as blockers for sodium and calcium channels, for example the viral KP1 , KP4 or KP6 toxins; stilbene synthases; bibenzyl synthases; chitinases; glucanases; the so-called "pathogenesis-related proteins" (PRPs; see e.g. EP-A-0 392 225); antipathogenic substances produced by microorganisms, for example peptide antibiotics or heterocyclic antibiotics (see e.g.
WO 95/33818) or protein or polypeptide factors involved in plant pathogen defence (so-called "plant disease resistance genes", as described in WO 03/000906).
Further areas of use of the compositions according to the invention are the protection of stored goods and store rooms and the protection of raw materials, such as wood, textiles, floor coverings or buildings, and also in the hygiene sector, especially the protection of humans, domestic animals and productive livestock against pests of the mentioned type. The present invention provides a compound of the first aspect for use in therapy. The present invention provides a compound of the first aspect, for use in controlling parasites in or on an animal. The present invention further provides a compound of the first aspect, for use in controlling ectoparasites on an animal. The present invention further provides a compound of the first aspect, for use in preventing and/or treating diseases transmitted by ectoparasites.
The present invention provides the use of a compound of the first aspect, for the manufacture of a medicament for controlling parasites in or on an animal. The present invention further provides the use of a compound of the first aspect, for the manufacture of a medicament for controlling ectoparasites on an animal. The present invention further provides the use of a compound of the first aspect, for the manufacture of a medicament for preventing and/or treating diseases transmitted by ectoparasites.
The present invention provides the use of a compound of the first aspect, in controlling parasites in or on an animal. The present invention further provides the use of a compound of the first aspect , in controlling ectoparasites on an animal.
The term "controlling" when used in context of parasites in or on an animal refers to reducing the number of pests or parasites, eliminating pests or parasites and/or preventing further pest or parasite infestation.
The term "treating" when used used in context of parasites in or on an animal refers to restraining, slowing, stopping or reversing the progression or severity of an existing symptom or disease.
The term "preventing" when used used in context of parasites in or on an animal refers to the avoidance of a symptom or disease developing in the animal.
The term "animal" when used used in context of parasites in or on an animal may refer to a mammal and a non-mammal, such as a bird or fish. In the case of a mammal, it may be a human or non-human mammal. Non-human mammals include, but are not limited to, livestock animals and companion animals. Livestock animals include, but are not limited to, cattle, camellids, pigs, sheep, goats and horses. Companion animals include, but are not limited to, dogs, cats and rabbits.
A "parasite" is a pest which lives in or on the host animal and benefits by deriving nutrients at the host animal's expense. An "endoparasite" is a parasite which lives in the host animal. An "ectoparasite" is a parasite which lives on the host animal. Ectoparasites include, but are not limited to, acari, insects and crustaceans (e.g. sea lice). The Acari (or Acarina) sub-class comprises ticks and mites. Ticks include, but are not limited to, members of the following genera: Rhipicaphalus, for example, Rhipicaphalus (, Boophilus ) microplus and Rhipicephalus sanguineus ; Amblyomrna Dermacentor, Haemaphysalis ; Hyalomma ; Ixodes ; Rhipicentor, Margaropus ; Argas Otobius ; and Ornithodoros. Mites include, but are not limited to, members of the following genera: Chorioptes, for example Chorioptes bovis ; Psoroptes, for example Psoroptes ovis] Cheyletiella] Dermanyssus] for example Dermanyssus gallinae] Ortnithonyssus ; Demodex, for example Demodex canis ; Sarcoptes, for example Sarcoptes scabiei] and Psorergates. Insects include, but are not limited to, members of the orders: Siphonaptera, Diptera, Phthiraptera, Lepidoptera, Coleoptera and Homoptera. Members of the Siphonaptera order include, but are not limited to, Ctenocephalides felis and Ctenocephatides canis. Members of the Diptera order include, but are not limited to, Musca spp .; bot fly, for example Gasterophilus intestinalis and Oestrus ovis ; biting flies; horse flies, for example Haematopota spp. and Tabunus spp.] haematobia, for example haematobia irritans] Stomoxys] Lucilia] midges; and mosquitoes. Members of the Phthiraptera class include, but are not limited to, blood sucking lice and chewing lice, for example Bovicola Ovis and Bovicola Bovis.
The term "effective amount" when used used in context of parasites in or on an animal refers to the amount or dose of the compound of the invention, or a salt thereof, which, upon single or multiple dose administration to the animal, provides the desired effect in or on the animal. The effective amount can be readily determined by the attending diagnostician, as one skilled in the art, by the use of known techniques and by observing results obtained under analogous circumstances. In determining the effective amount a number of factors are considered by the attending diagnostician, including, but not limited to: the species of mammal; its size, age, and general health; the parasite to be controlled and the degree of infestation; the specific disease or disorder involved; the degree of involvement or the severity of the disease or disorder; the response of the individual; the particular compound administered; the mode of administration; the bioavailability characteristics of the preparation administered; the dose regimen selected; the use of concomitant medication; and other relevant circumstances.
The compounds of the invention may be administered to the animal by any route which has the desired effect including, but not limited to topically, orally, parenterally' and subcutaneously. Topical administration is preferred. Formulations suitable for topical administration include, for example, solutions, emulsions and suspensions and may take the form of a pour-on, spot-on, spray-on, spray race or dip. In the alternative, the compounds of the invention may be administered by means of an ear tag or collar.
Salt forms of the compounds of the invention include both pharmaceutically acceptable salts and veterinary acceptable salts, which can be different to agrochemically acceptable salts. Pharmaceutically and veterinary acceptable salts and common methodology for preparing them are well known in the art. See, for example, Gould, P.L., "Salt selection for basic drugs", International Journal of Pharmaceutics, 33: 201 -217 (1986); Bastin, R.J., et al. "Salt Selection and Optimization Procedures for Pharmaceutical New Chemical Entities", Organic Process Research and Development, 4: 427-435 (2000); and Berge, S.M., et al., "Pharmaceutical Salts", Journal of Pharmaceutical Sciences, 66: 1-19, (1977). One skilled in the art of synthesis will appreciate that the compounds of the invention are readily converted to and may be isolated as a salt, such as a hydrochloride salt, using techniques and conditions well known to one of ordinary skill in the art. In addition, one skilled in the art of synthesis will appreciate that the compounds of the invention are readily converted to and may be isolated as the corresponding free base from the corresponding salt.
The present invention also provides a method for controlling pests (such as mosquitoes and other disease vectors; see also http://www.who.int/malaria/vector_control/irs/en/). In one embodiment, the method for controlling pests comprises applying the compositions of the invention to the target pests, to their locus or to a surface or substrate by brushing, rolling, spraying, spreading or dipping. By way of example, an IRS (indoor residual spraying) application of a surface such as a wall, ceiling or floor surface is contemplated by the method of the invention. In another embodiment, it is contemplated to apply such compositions to a substrate such as non-woven or a fabric material in the form of (or which can be used in the manufacture of) netting, clothing, bedding, curtains and tents.
In one embodiment, the method for controlling such pests comprises applying a pesticidally effective amount of the compositions of the invention to the target pests, to their locus, or to a surface or substrate so as to provide effective residual pesticidal activity on the surface or substrate. Such application may be made by brushing, rolling, spraying, spreading or dipping the pesticidal composition of the invention. By way of example, an IRS application of a surface such as a wall, ceiling or floor surface is contemplated by the method of the invention so as to provide effective residual pesticidal activity on the surface. In another embodiment, it is contemplated to apply such compositions for residual control of pests on a substrate such as a fabric material in the form of (or which can be used in the manufacture of) netting, clothing, bedding, curtains and tents.
Substrates including non-woven, fabrics or netting to be treated may be made of natural fibres such as cotton, raffia, jute, flax, sisal, hessian, or wool, or synthetic fibres such as polyamide, polyester, polypropylene, polyacrylonitrile or the like. The polyesters are particularly suitable. The methods of textile treatment are known, e.g. WO 2008/151984, WO 2003/034823, US 5631072, WO 2005/64072, W02006/128870, EP 1724392, WO 2005113886 or WO 2007/090739.
Further areas of use of the compositions according to the invention are the field of tree injection/trunk treatment for all ornamental trees as well all sort of fruit and nut trees.
In the field of tree injection/trunk treatment, the compounds according to the present invention are especially suitable against wood-boring insects from the order Lepidoptera as mentioned above and from the order Coleoptera, especially against woodborers listed in the following tables A and B:
Table A. Examples of exotic woodborers of economic importance.
Family Species Host or Crop Infested
Figure imgf000063_0001
Table B. Examples of native woodborers of economic importance.
Figure imgf000063_0002
Figure imgf000064_0001
Figure imgf000065_0001
The present invention may be also used to control any insect pests that may be present in turfgrass, including for example beetles, caterpillars, fire ants, ground pearls, millipedes, sow bugs, mites, mole crickets, scales, mealybugs, ticks, spittlebugs, southern chinch bugs and white grubs. The present invention may be used to control insect pests at various stages of their life cycle, including eggs, larvae, nymphs and adults.
In particular, the present invention may be used to control insect pests that feed on the roots of turfgrass including white grubs (such as Cyclocephala spp. (e.g. masked chafer, C. lurida), Rhizotrogus spp. (e.g. European chafer, R. majalis), Cotinus spp. (e.g. Green June beetle, C. nitida), Popillia spp. (e.g. Japanese beetle, P. japonica), Phyllophaga spp. (e.g. May/June beetle), Ataenius spp. (e.g. Black turfgrass ataenius, A. spretulus), Maladera spp. (e.g. Asiatic garden beetle, M. castanea) and Tomarus spp.), ground pearls ( Margarodes spp.), mole crickets (tawny, southern, and short-winged; Scapteriscus spp., Gryllotalpa africana ) and leatherjackets (European crane fly, Tipula spp.).
The present invention may also be used to control insect pests of turfgrass that are thatch dwelling, including armyworms (such as fall armyworm Spodoptera frugiperda, and common armyworm Pseudaletia unipuncta), cutworms, billbugs ( Sphenophorus spp., such as S. venatus verstitus and S. parvulus), and sod webworms (such as Crambus spp. and the tropical sod webworm, Herpetogramma phaeopteralis).
The present invention may also be used to control insect pests of turfgrass that live above the ground and feed on the turfgrass leaves, including chinch bugs (such as southern chinch bugs, Blissus insularis), Bermudagrass mite (Eriophyes cynodoniensis), rhodesgrass mealybug (Antonina graminis), two-lined spittlebug ( Propsapia bicincta), leafhoppers, cutworms ( Noctuidae family), and greenbugs.
The present invention may also be used to control other pests of turfgrass such as red imported fire ants ( Solenopsis invicta) that create ant mounds in turf. In the hygiene sector, the compositions according to the invention are active against ectoparasites such as hard ticks, soft ticks, mange mites, harvest mites, flies (biting and licking), parasitic fly larvae, lice, hair lice, bird lice and fleas.
Examples of such parasites are:
Of the order Anoplurida: Haematopinus spp., Linognathus spp., Pediculus spp. and Phtirus spp., Solenopotes spp..
Of the order Mallophagida: Trimenopon spp., Menopon spp., Trinoton spp., Bovicola spp., Werneckiella spp., Lepikentron spp., Damalina spp., Trichodectes spp. and Felicola spp..
Of the order Diptera and the suborders Nematocerina and Brachycerina, for example Aedes spp., Anopheles spp., Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Chrysops spp., Hybomitra spp., Atylotus spp., Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp., Oestrus spp., Hypoderma spp., Gasterophilus spp., Hippobosca spp., Lipoptena spp. and Melophagus spp..
Of the order Siphonapterida, for example Pulex spp., Ctenocephalides spp., Xenopsylla spp., Ceratophyllus spp..
Of the order Heteropterida, for example Cimex spp., Triatoma spp., Rhodnius spp., Panstrongylus spp..
Of the order Blattarida, for example Blatta orientalis, Periplaneta americana, Blattelagermanica and Supella spp..
Of the subclass Acaria (Acarida) and the orders Meta- and Meso-stigmata, for example Argas spp., Ornithodorus spp., Otobius spp., Ixodes spp., Amblyomma spp., Boophilus spp., Dermacentor spp., Haemophysalis spp., Hyalomma spp., Rhipicephalus spp., Dermanyssus spp., Raillietia spp., Pneumonyssus spp., Sternostoma spp. and Varroa spp..
Of the orders Actinedida (Prostigmata) and Acaridida (Astigmata), for example Acarapis spp., Cheyletiella spp., Ornithocheyletia spp., Myobia spp., Psorergatesspp., Demodex spp., Trombicula spp., Listrophorus spp., Acarus spp., Tyrophagus spp., Caloglyphus spp., Hypodectes spp., Pterolichus spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp. and Laminosioptes spp.. The compositions according to the invention are also suitable for protecting against insect infestation in the case of materials such as wood, textiles, plastics, adhesives, glues, paints, paper and card, leather, floor coverings and buildings.
The compositions according to the invention can be used, for example, against the following pests: beetles such as Hylotrupes bajulus, Chlorophorus pilosis, Anobium punctatum, Xestobium rufovillosum, Ptilinuspecticornis, Dendrobium pertinex, Ernobius mollis, Priobium carpini, Lyctus brunneus, Lyctus africanus, Lyctus planicollis, Lyctus linearis, Lyctus pubescens, Trogoxylon aequale, Minthesrugicollis, Xyleborus spec.,Tryptodendron spec., Apate monachus, Bostrychus capucins, Heterobostrychus brunneus, Sinoxylon spec and Dinoderus minutus, and also hymenopterans such as Sirex juvencus, Urocerus gigas, Urocerus gigas taignus and Urocerus augur, and termites such as Kalotermes flavicollis, Cryptotermes brevis, Heterotermes indicola, Reticulitermes flavipes, Reticulitermes santonensis, Reticulitermes lucifugus, Mastotermes darwiniensis, Zootermopsis nevadensis and Coptotermes formosanus, and bristletails such as Lepisma saccharina.The compounds of formulae I, and I’a, or salts thereof, are especially suitable for controlling one or more pests selected from the family: Noctuidae, Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae, Meloidogynidae, and Heteroderidae. In a preferred embodiment of each aspect, a compound TX (where the abbreviation “TX” means “one compound selected from the compounds defined in Tables A-1 to A-18 and Table P”) controls one or more of pests selected from the family: Noctuidae, Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae, Meloidogynidae, and Heteroderidae.
The compounds of formulae I, and I’a, or salts thereof, are especially suitable for controlling one or more of pests selected from the genus: Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp. . In a preferred embodiment of each aspect, a compound TX (where the abbreviation “TX” means “one compound selected from the compounds defined in Tables A-1 to A-18 and Table P”) controls one or more of pests selected from the genus: Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp.
The compounds of formulae I, and I’a, or salts thereof, are especially suitable for controlling one or more of Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus herns, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis includens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum padi, and Chilo suppressalis.
In a preferred embodiment of each aspect, a compound TX (where the abbreviation “TX” means “one compound selected from the compounds defined in Tables A-1 to A-18 and Table P”) controls one or more of Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus herns, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis includens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum Padia, and Chilo Suppressalis, such as Spodoptera littoralis + TX, Plutella xylostella + TX; Frankliniella occidentalis + TX, Thrips tabaci + TX, Euschistus herns + TX, Cydia pomonella + TX, Nilaparvata lugens + TX, Myzus persicae + TX, Chrysodeixis includens + TX, Aphis craccivora + TX, Diabrotica balteata + TX, Rhopalosiphum Padi + TX, and Chilo suppressalis + TX.
In an embodiment, of each aspect, one compound from Tables A-1 to A-18 and Table P is suitable for controlling Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus herns, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis includens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum Padia, and Chilo Suppressalis in cotton, vegetable, maize, cereal, rice and soya crops.
In an embodiment, one compound from from Tables A-1 to A-18 and Table P is suitable for controlling Mamestra (preferably in vegetables), Cydia pomonella (preferably in apples), Empoasca (preferably in vegetables, vineyards), Leptinotarsa (preferably in potatos) and Chilo supressalis (preferably in rice).
Compounds according to the invention may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against insects or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (against non-target organisms above and below ground (such as fish, birds and bees), improved physico-chemical properties, or increased biodegradability). In particular, it has been surprisingly found that certain compounds of formula I may show an advantageous safety profile with respect to non-target arthropods, in particular pollinators such as honey bees, solitary bees, and bumble bees. Most particularly, Apis mellifera.
The compounds according to the invention can be used as pesticidal agents in unmodified form, but they are generally formulated into compositions in various ways using formulation adjuvants, such as carriers, solvents and surface-active substances. The formulations can be in various physical forms, e.g. in the form of dusting powders, gels, wettable powders, water-dispersible granules, water- dispersible tablets, effervescent pellets, emulsifiable concentrates, microemulsifiable concentrates, oil- in-water emulsions, oil-flowables, aqueous dispersions, oily dispersions, suspo-emulsions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (with water or a water- miscible organic solvent as carrier), impregnated polymer films or in other forms known e.g. from the Manual on Development and Use of FAO and WHO Specifications for Pesticides, United Nations, First Edition, Second Revision (2010). Such formulations can either be used directly or diluted prior to use. The dilutions can be made, for example, with water, liquid fertilisers, micronutrients, biological organisms, oil or solvents. The formulations can be prepared e.g. by mixing the active ingredient with the formulation adjuvants in order to obtain compositions in the form of finely divided solids, granules, solutions, dispersions or emulsions. The active ingredients can also be formulated with other adjuvants, such as finely divided solids, mineral oils, oils of vegetable or animal origin, modified oils of vegetable or animal origin, organic solvents, water, surface-active substances or combinations thereof.
The active ingredients can also be contained in very fine microcapsules. Microcapsules contain the active ingredients in a porous carrier. This enables the active ingredients to be released into the environment in controlled amounts (e.g. slow-release). Microcapsules usually have a diameter of from 0.1 to 500 microns. They contain active ingredients in an amount of about from 25 to 95 % by weight of the capsule weight. The active ingredients can be in the form of a monolithic solid, in the form of fine particles in solid or liquid dispersion or in the form of a suitable solution. The encapsulating membranes can comprise, for example, natural or synthetic rubbers, cellulose, styrene/butadiene copolymers, polyacrylonitrile, polyacrylate, polyesters, polyamides, polyureas, polyurethane or chemically modified polymers and starch xanthates or other polymers that are known to the person skilled in the art. Alternatively, very fine microcapsules can be formed in which the active ingredient is contained in the form of finely divided particles in a solid matrix of base substance, but the microcapsules are not themselves encapsulated.
The formulation adjuvants that are suitable for the preparation of the compositions according to the invention are known perse. As liquid carriers there may be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1 ,2-dichloropropane, diethanolamine, p- diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, A/,A/-dimethylformamide, dimethyl sulfoxide, 1 ,4- dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1 ,1 ,1 -trichloroethane, 2- heptanone, alpha-pinene, d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropylbenzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxy- propanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol, propionic acid, propyl lactate, propylene carbonate, propylene glycol, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylenesulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol, and alcohols of higher molecular weight, such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, /V-methyl-2- pyrrolidone and the like.
Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed husks, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar substances.
A large number of surface-active substances can advantageously be used in both solid and liquid formulations, especially in those formulations which can be diluted with a carrier prior to use. Surface- active substances may be anionic, cationic, non-ionic or polymeric and they can be used as emulsifiers, wetting agents or suspending agents or for other purposes. Typical surface-active substances include, for example, salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; salts of alkylarylsulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol/alkylene oxide addition products, such as nonylphenol ethoxylate; alcohol/alkylene oxide addition products, such as tridecylalcohol ethoxylate; soaps, such as sodium stearate; salts of alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2- ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryltrimethylammonium chloride, polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and di- alkylphosphate esters; and also further substances described e.g. in McCutcheon's Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood New Jersey (1981).
Further adjuvants that can be used in pesticidal formulations include crystallisation inhibitors, viscosity modifiers, suspending agents, dyes, anti-oxidants, foaming agents, light absorbers, mixing auxiliaries, antifoams, complexing agents, neutralising or pH-modifying substances and buffers, corrosion inhibitors, fragrances, wetting agents, take-up enhancers, micronutrients, plasticisers, glidants, lubricants, dispersants, thickeners, antifreezes, microbicides, and liquid and solid fertilisers.
The compositions according to the invention can include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl esters of such oils or mixtures of such oils and oil derivatives. The amount of oil additive in the composition according to the invention is generally from 0.01 to 10 %, based on the mixture to be applied. For example, the oil additive can be added to a spray tank in the desired concentration after a spray mixture has been prepared. Preferred oil additives comprise mineral oils or an oil of vegetable origin, for example rapeseed oil, olive oil or sunflower oil, emulsified vegetable oil, alkyl esters of oils of vegetable origin, for example the methyl derivatives, or an oil of animal origin, such as fish oil or beef tallow. Preferred oil additives comprise alkyl esters of C8-C22 fatty acids, especially the methyl derivatives of C12-C18 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid (methyl laurate, methyl palmitate and methyl oleate, respectively). Many oil derivatives are known from the Compendium of Herbicide Adjuvants, 10th Edition, Southern Illinois University, 2010.
The inventive compositions generally comprise from 0.1 to 99 % by weight, especially from 0.1 to 95 % by weight, of compounds of the present invention and from 1 to 99.9 % by weight of a formulation adjuvant which preferably includes from 0 to 25 % by weight of a surface-active substance. Whereas commercial products may preferably be formulated as concentrates, the end user will normally employ dilute formulations.
The rates of application vary within wide limits and depend on the nature of the soil, the method of application, the crop plant, the pest to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. As a general guideline compounds may be applied at a rate of from 1 to 2000 l/ha, especially from 10 to 1000 l/ha.
Preferred formulations can have the following compositions (weight %):
Emulsifiable concentrates: active ingredient: 1 to 95 %, preferably 60 to 90 % surface-active agent: 1 to 30 %, preferably 5 to 20 % liquid carrier: 1 to 80 %, preferably 1 to 35 %
Dusts: active ingredient: 0.1 to 10 %, preferably 0.1 to 5 % solid carrier: 99.9 to 90 %, preferably 99.9 to 99 %
Suspension concentrates: active ingredient: 5 to 75 %, preferably 10 to 50 % water: 94 to 24 %, preferably 88 to 30 % surface-active agent: 1 to 40 %, preferably 2 to 30 %
Wettable powders: active ingredient: 0.5 to 90 %, preferably 1 to 80 % surface-active agent: 0.5 to 20 %, preferably 1 to 15 % solid carrier: 5 to 95 %, preferably 15 to 90 %
Granules: active ingredient: 0.1 to 30 %, preferably 0.1 to 15 % solid carrier: 99.5 to 70 %, preferably 97 to 85 % The following Examples further illustrate, but do not limit, the invention.
Figure imgf000072_0001
The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.
Figure imgf000072_0002
The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment.
Figure imgf000072_0003
Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.
Figure imgf000073_0001
Ready-for-use dusts are obtained by mixing the combination with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed.
Figure imgf000073_0002
The combination is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.
Figure imgf000073_0003
The finely ground combination is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.
Suspension concentrate
Figure imgf000073_0004
The finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
Flowable concentrate for seed treatment active ingredients 40 %
Figure imgf000074_0001
The finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
Slow Release Capsule Suspension
28 parts of the combination are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1). This mixture is emulsified in a mixture of 1 .2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51 .6 parts of water until the desired particle size is achieved. To this emulsion a mixture of 2.8 parts 1 ,6-diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed. The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% of the active ingredients. The medium capsule diameter is 8-15 microns. The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.
Formulation types include an emulsion concentrate (EC), a suspension concentrate (SC), a suspo- emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK), a dispersible concentrate (DC), a wettable powder (WP), a soluble granule (SG) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.
Preparatory Examples:
LCMS Methods:
Method 1 :
Spectra were recorded on a Mass Spectrometer from Waters (SQD, SQDII Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions,
Capillary: 3.00 kV, Cone range: 30 V, Extractor: 2.00 V, Source Temperature: 150°C, Desolvation Temperature: 350°C, Cone Gas Flow: 50 l/h, Desolvation Gas Flow: 650 l/h, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment , diode-array detector and ELSD detector. Column: Waters UPLC HSS T3, 1.8 mhi, 30 x 2.1 mm, Temp: 60 °C, DAD Wavelength range (nm): 210 to 500, Solvent Gradient: A = water + 5% MeOH + 0.05 % HCOOH, B = Acetonitrile + 0.05 % HCOOH, gradient: 10-100% B in 1 .2 min; Flow (ml/min) 0.85.
Example 1: Preparation of 3-(cvclopropanecarbonyl)-N-(cvclopropylmethyl)-N-ri-(2-pyrimidin-2- yl-1.2.4-triazol-3-yl)ethvH-5-(trifluoromethyl)benzamide (Compound P1 )
Figure imgf000075_0001
(Compound P1)
Step A: Preparation of 3-(cvclopropanecarbonyr)-5-(trifluoromethyr)benzoic acid
Figure imgf000075_0002
To a solution of methyl 3-(cyclopropanecarbonyl)-5-(trifluoromethyl)benzoate (0.160 g, 0.588 mmol, prepared analog to W02006/067445, page 148) in a mixture of tetrahydrofuran (1.76 ml_) and water (0.882 mL) was added lithium hydroxide monohydrate (24.9 mg, 0.588 mmol, 1.00 equiv.). The reaction mixture was stirred at room temperature for 17 hours. Additional lithium hydroxide monohydrate (24.9 mg, 0.588 mmol, 1 .00 equiv.) was added and it was stirred at room temperature for 1 .5 hours. The reaction mixture was diluted with water and acidified with 1 N hydrochloric acid until pH reached 2. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 3- (cyclopropanecarbonyl)-5-(trifluoromethyl)benzoic acid (60%, 0.152 g) as a white solid.
LC-MS (method 1): Rt 0.90, m/z = 257 (M-H) .
Ή-NMR (400 MHz, CDCI3, ppm) <5 = 8.91 (1 H, s), 8.55 (1 H, s), 8.49 (1 H, s), 2.74 (1 H, tt, J=7.75, 4.54 Hz), 1.34 - 1.38 (2 H, m), 1.16 - 1.22 (2 H, m).
Step B: Preparation of 3-(cyclopropanecarbonyl)-N-(cyclopropylmethyl)-N-[1-(2-pyrimidin-2-yl-1 ,2,4- triazol-3-yl)ethyl1-5-(trifluoromethyl)benzamide (Compound P1) (Compound P1)
A 10 mL round-bottom flask was charged with N-(cyclopropylmethyl)-1-(2-pyrimidin-2-yl-1 ,2,4-triazol-3- yl)ethanamine (65 mg, 0.27 mmol, 1 equiv., prepared analog to W02020/002563, page 72), acetonitrile (0.80 mL), N-ethyl-N-isopropyl-propan-2-amine (94 pL, 0.53 mmol, 2.0 equiv.), 3- (cyclopropanecarbonyl)-5-(trifluoromethyl)benzoic acid (72 mg, 0.28 mmol, 1.05 equiv.) and 1- [bis(dimethylamino)methylene]-1 H-1 ,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (0.156 g, 0.399 mmol, 1 .50 equiv.). The resulting solution was stirred at room temperature for 3 hours. It was then concentrated under reduced pressure. Purification of the crude product by reverse-phase chromatography (gradient of 20 - 100% acetonitrile in water) gave 3-(cyclopropanecarbonyl)-N- (cyclopropylmethyl)-N-[1-(2-pyrimidin-2-yl-1 ,2,4-triazol-3-yl)ethyl]-5-(trifluoromethyl)benzamide (95%, 39 mg) as an orange-brown gum.
LC-MS (method 1): Rt 0.98, m/z = 485 (M+H)+.
Example 2: Preparation of N-ri-r2-(5-cvano-2-pyridyl)-1.2.4-triazol-3-yllethyll-3-
(cvclopropanecarbonyl)-5-(trifluoromethyl)benzamide (Compound P2)
Figure imgf000076_0001
(Compound P2)
A 100 mL round bottom flask was charged with 1-[2-(5-cyano-2-pyridyl)-1 ,2,4-triazol-3- yl]ethylammonium chloride (265 mg, 1.06 mmol, 1.25 equiv., see WO2019/206799 for preparation), tetrahydrofuran (12.7 mL), triethylamine (0.475 mL, 3.39 mmol, 4 equiv.), 3-hydroxytriazolo[4,5- b] pyridine (144 mg, 1.06 mmol, 1.25 equiv.) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (205 mg, 1.06 mmol, 1.25 equiv.). Next, 3-(cyclopropanecarbonyl)-5- (trifluoromethyl)benzoic acid (219 mg, 0.85 mmol, 1.00 equiv. , prepared in Example 1) was dissolved in tetrahydrofuran (2 mL) and added to the mixture above. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was poured in water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude product by column chromatography (silica, gradient of 5 - 55% ethyl acetate in cyclohexane) provided N-[1-[2-(5-cyano-2-pyridyl)-1 ,2,4-triazol-3-yl]ethyl]-3- (cyclopropanecarbonyl)-5-(trifluoromethyl)benzamide (54%, 207 mg) as a solid.
LC-MS (method 1): Rt 0.99, m/z = 455 (M+H)+.
Ή-NMR (400 MHz, CDCb, ppm) <5 = 8.87 - 8.85(m, 1 H), 8.57 (s, 1 H), 8.31 (s, 1 H), 8.26 (s, 1 H), 8.14 - 8.22 (m, 2 H), 8.02 - 8.10 (m, 1 H), 8.02 (s, 1 H), 6.45 (quin, J=7.06 Hz, 1 H), 2.60 - 2.68 (m, 1 H), 1 .74 (d, J=6.97 Hz, 3 H), 1.22 - 1.30 (m, 2 H), 1.10 - 1.14 (m, 2 H).
19F-NMR (376 MHz, CDCb, ppm) <5 = -126.76 (s, 3 F).
Example 3: Preparation of N-ri-r2-(5-cvano-2-pyridyl)-1.2.4-triazol-3-yllethyll-3- rcvclopropyl(hvdroxy)methvH-5-(trifluoromethyl)benzamide (Compound P3)
Figure imgf000077_0001
(Compound P3)
Step A: Preparation of methyl 3-[cvclopropyl(hvdroxy)methyl1-5-(trifluoromethyl)benzoate
Figure imgf000077_0002
To a solution of methyl 3-(cyclopropanecarbonyl)-5-(trifluoromethyl)benzoate (1 g, 3.67 mmol, 1 equiv., prepared analog to W02006/067445, page 148) in methanol (20 ml_) was added sodium borohydride (556 mg, 14.7 mmol, 4 equiv.) portionwise. The mixture was stirred at room temperature for 3 hours. Then, additional sodium borohydride (417 mg, 11 mmol, 3 equiv.) was added and the mixture stirred for another 1 .5 hours. The reaction mixture was evaporated and then extracted with ethyl acetate from water. The organic layer was dried over sodium sulfate, filtered and evaporated under reduced pressure. The crude product was purified by column chromatography (silica, gradient of 0 - 20% ethyl acetate in cyclohexane) to produce methyl 3-[cyclopropyl(hydroxy)methyl]-5-(trifluoromethyl)benzoate (83%, 865 mg) as an oil.
1H-NMR (400 MHz, CDCb, ppm) d 8.29 (s, 1 H), 8.24 (s, 1 H), 7.94 (s, 1 H), 4.11 - 4.17 (m, 1 H), 3.98 (s, 3 H), 2.18 (d, J=2.57 Hz, 1 H), 1.17 - 1.31 (m, 1 H), 0.64 - 0.74 (m, 2 H), 0.46 - 0.58 (m, 2 H). 19F-NMR (376 MHz, CDCb, ppm) <5 = -62.67 (s, 3 F).
Step B: Preparation of 3-[cvclopropyl(hvdroxy)methyl1-5-(trifluoromethyl)benzoic acid
Figure imgf000078_0001
To a solution of methyl 3-[cyclopropyl(hydroxy)methyl]-5-(trifluoromethyl)benzoate (300 mg, 1.09 mmol) in a mixture of tetrahydrofuran (2 ml_) and water (0.5 ml_) was added lithium hydroxide (66.8 mg, 2.74 mmol, 2.50 equiv.). The reaction mixture was stirred at room temperature for 2 hours. The reaction was concentrated under reduced pressure, and the resulting mixture was acidified with 32% aqueous hydrochloric acid until pH reached 2 and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 3- [cyclopropyl(hydroxy)methyl]-5-(trifluoromethyl)benzoic acid (quantitative, 304 mg) as a solid.
LC-MS (method 1): Rt 0.84, m/z = 259 (M-H) .
1H-NMR (400 MHz, CDCI3, ppm) <5 = 8.37 (s, 1 H), 8.31 (s, 1 H), 8.00 (s, 1 H), 4.12 - 4.19 (m, 1 H), 1.19 - 1 .34 (m, 3 H), 0.66 - 0.77 (m, 2 H), 0.48 - 0.60 (m, 2 H).
19F-NMR (376 MHz, CDCI3, ppm) <5 = -62.71 (s, 3 F).
Step _ C: _ Preparation _ of _ N-[1-[2-(5-cvano-2-pyridyl)-1 ,2.4-triazol-3-yl1ethyl1-3-
[cvclopropyl(hvdroxy)methyl1-5-(trifluoromethyl)benzamide (Compound P3)
Figure imgf000078_0002
(Compound P3)
A 30 mL vial was charged with 1-[2-(5-cyano-2-pyridyl)-1 ,2,4-triazol-3-yl]ethylammonium chloride (342 mg, 1.36 mmol, 1.25 equiv.), tetrahydrofuran (16.4 mL), triethylamine (0.612 mL, 4.36 mmol, 4 equiv.), 3-hydroxytriazolo[4,5-b]pyridine (186 mg, 1.36 mmol, 1.25 equiv.) and 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride (264 mg, 1.36 mmol, 1.25 equiv.). Next, 3- [cyclopropyl(hydroxy)methyl]-5-(trifluoromethyl)benzoic acid (284 mg, 1.09 mmol, 1.00 equiv.) was dissolved in tetrahydrofuran (2 mL) and added to the mixture above. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was poured in water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude product by column chromatography (silica, gradient of 0 - 60% ethyl acetate in cyclohexane) provided N-[1-[2-(5-cyano-2-pyridyl)-1 ,2,4-triazol-3-yl]ethyl]-3- [cyclopropyl(hydroxy)methyl]-5-(trifluoromethyl)benzamide (60%, 300 mg) as a solid mixture of diastereomers. LC-MS (method 1): Rt 0.94, /z = 457 (M+H)+.
19F-NMR (376 MHz, CDC , ppm) d = -62.62 (s, 3 F) and -62.65 (s, 3 F) - mixture of two diastereomers.
Example 4: Preparation of N-ri-r2-(5-cvano-2-pyridyl)-1.2.4-triazol-3-yllethyll-3-(1-cvclopropyl-1- hvdroxy-ethyl)-5-(trifluoromethyl)benzamide (Compound P4)
Figure imgf000079_0001
(Compound P4)
Step A: Preparation of 3-(1-cvclopropyl-1-hvdroxy-ethyl)-5-(trifluoromethyl)benzoic acid
Figure imgf000079_0002
A solution of 3-(cyclopropanecarbonyl)-5-(trifluoromethyl)benzoic acid (379 mg, 1.47 mmol, 1 equiv., prepared in Example 1) dissolved in tetrahydrofuran (10 ml_) was cooled to 0 °C. Methylmagnesium bromide (1 .4 M solution in toluene, 2.6 ml, 3.67 mmol, 2.5 equiv.) was added dropwise over 5 minutes. Reaction was warmed to room temperature and stirred for 1 .5 hours. Reaction was cooled to 0 °C and more methylmagnesium bromide (1.4 M solution in tetrahydrofura toluene 1 :3, 0.5 ml, 0.71 mmol, 0.48 equiv.) was added. Reaction was further stirred for 30 minutes at room temperature. Saturated aqueous ammonium chloride solution was added to the reaction mixture and the resulting separated organic layer was concentrated under reduced pressure. The residue was extracted with ethyl acetate from water, and the organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to produce 3-(1 -cyclopropyl-1 -hydroxy-ethyl)-5-(trifluoromethyl)benzoic acid (98%, 408 mg) as an oil. LC-MS (method 1): Rt 0.88, m/z = 273 (M-H) .
19F-NMR (376 MHz, CDCb, ppm) <5 = -62.79 (s, 3 F).
Step B: Preparation of N-[1-[2-(5-cvano-2-pyridyl)-1 .2.4-triazol-3-yl1ethyl1-3-(1-cvclopropyl-1-hvdroxy- ethyl)-5-(trifluoromethyl)benzamide (Compound P4)
Figure imgf000080_0001
(Compound P4)
A 30 mL vial was charged with 1 -[2-(5-cyano-2-pyridyl)-1 ,2,4-triazol-3-yl]ethylammonium chloride (466.3 mg, 1.86 mmol, 1.25 equiv.), tetrahydrofuran (22.3 mL), triethylamine (0.834 mL, 5.95 mmol, 4 equiv.), 3-hydroxytriazolo[4,5-b]pyridine (253.2 mg, 1.86 mmol, 1.25 equiv.) and 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride (360.2 mg, 1.86 mmol, 1.25 equiv.). Next, 3-(1 -cyclopropyl-1 -hydroxy- ethyl)-5-(trifluoromethyl)benzoic acid (408 mg, 1 .49 mmol, 1 .00 equiv.) was dissolved in tetrahydrofuran (2 mL) and added to the mixture above. The reaction mixture was stirred at room temperature overnight. The reaction mixture was poured in water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude product by column chromatography (silica, gradient of 5 - 60% ethyl acetate in cyclohexane) provided N-[1 -[2-(5-cyano-2-pyridyl)-1 ,2,4-triazol-3-yl]ethyl]-3-(1 -cyclopropyl-1 -hydroxy- ethyl)-5-(trifluoromethyl)benzamide (29%, 202 mg) as a solid mixture of diastereomers.
LC-MS (method 1): Rt 0.99, m/z = 471 (M+H)+.
19F-NMR (376 MHz, CDCI3, ppm) d = -62.64 (s, 3 F) and -62.73 (s, 3 F) - mixture of two diastereomers.
Example 5: Preparation of N-ri-r2-(5-cvano-2-pyridyl)-1.2.4-triazol-3-yllethyll-3- rcvclopropyl(methoxy)methvH-5-(trifluoromethyl)benzamide (Compound P5)
Figure imgf000080_0002
(Compound P5)
Step A: Preparation of methyl 3-[cvclopropyl(methoxy)methyl1-5-(trifluoromethyl)benzoate
Figure imgf000080_0003
To a solution of methyl 3-[cyclopropyl(hydroxy)methyl]-5-(trifluoromethyl)benzoate (261 mg, 0.95 mmol, 1 equiv., prepared in Example 3) in tetrahydrofuran (9.5 ml_) was added sodium hydride (60 wt%, 76 mg, 1.94 mmol, 2 equiv.). The mixture was stirred for 20 minutes lodomethane (0.89 ml_, 14.3 mmol, 15 equiv.) was next added and the mixture was stirred at 50 °C for 30 minutes. Additional iodomethane (0.89 ml_, 14.3 mmol, 15 equiv.) was added and the reaction stirred for an additional 30 minutes. The reaction mixture was cooled down, diluted with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and evaporated under reduced pressure. The crude product was purified by column chromatography (silica, gradient of 0 - 10% ethyl acetate in cyclohexane) to produce methyl 3-[cyclopropyl(methoxy)methyl]-5-(trifluoromethyl)benzoate (48%, 137 mg) as an oil.
Ή-NMR (400 MHz, CDCI3, ppm) <5 = 8.25 (s, 1 H), 8.20 (s, 1 H), 7.82 (s, 1 H), 3.99 (s, 3 H), 3.68 (d, J=8.07 Hz, 1 H), 3.32 (s, 3 H), 1 .10 - 1 .19 (m, 1 H), 0.69 - 0.76 (m, 1 H), 0.48 - 0.59 (m, 2 H), 0.27 - 0.36 (m, 1 H).
Step B: Preparation of 3-[cvclooropyl(methoxy)methyl1-5-(trifluoromethyl)benzoic acid
Figure imgf000081_0001
To a solution of methyl 3-[cyclopropyl(methoxy)methyl]-5-(trifluoromethyl)benzoate (209 mg, 0.72 mmol) in a mixture of tetrahydrofuran (4 ml_) and water (1 ml_) was added lithium hydroxide (46.6 mg, 1.09 mmol, 1 .50 equiv.). The reaction mixture was stirred at room temperature for 2 hours. The reaction was concentrated under reduced pressure, and the resulting mixture was acidified with 32% aqueous hydrochloric acid until pH reached 2 and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 3- [cyclopropyl(methoxy)methyl]-5-(trifluoromethyl)benzoic acid (quantitative, 225 mg) as a solid.
1H-NMR (400 MHz, CDCI3, ppm) <5 = 8.33 (s, 1 H), 8.27 (s, 1 H), 7.88 (s, 1 H), 3.71 (d, J=7.70 Hz, 1 H), 3.34 (s, 3 H), 1 .09 - 1 .23 (m, 1 H), 0.70 - 0.78 (m, 1 H), 0.50 - 0.61 (m, 2 H), 0.28 - 0.38 (m, 1 H). 19F-NMR (376 MHz, CDCI3, ppm) <5 = -62.70 (s, 3 F).
Step _ C: _ Preparation _ of _ N-[1-[2-(5-cvano-2-pyridyl)-1 ,2.4-triazol-3-yl1ethyl1-3-
[cvclopropyl(methoxy)methyl1-5-(trifluoromethyl)benzamide (Compound P5)
Figure imgf000081_0002
(Compound P5) A 30 mL vial was charged with 1-[2-(5-cyano-2-pyridyl)-1 ,2,4-triazol-3-yl]ethylammonium chloride (192 mg, 0.77 mmol, 1.25 equiv.), tetrahydrofuran (9.2 mL), triethylamine (0.343 mL, 2.45 mmol, 4 equiv.), 3-hydroxytriazolo[4,5-b]pyridine (104.2 mg, 0.77 mmol, 1.25 equiv.) and 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride (148.3 mg, 0.77 mmol, 1.25 equiv.). Next, 3- [cyclopropyl(methoxy)methyl]-5-(trifluoromethyl)benzoic acid (168 mg, 0.61 mmol, 1.00 equiv.) was dissolved in tetrahydrofuran (2 mL) and added to the mixture above. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was poured in water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the crude product by column chromatography (silica, gradient of 5 - 50% ethyl acetate in cyclohexane) provided N-[1-[2-(5-cyano-2-pyridyl)-1 ,2,4-triazol-3-yl]ethyl]-3- [cyclopropyl(methoxy)methyl]-5-(trifluoromethyl)benzamide (87%, 250 mg) as a solid mixture of two diastereomers.
LC-MS (method 1): Rt 1 .06, m/z = 471 (M+H)+.
Ή-NMR (400 MHz, CDCI3, ppm) <5 = 8.89 (s, 1 H), 8.15 - 8.24 (m, 2 H), 8.02 - 8.06 (m, 1 H), 8.00 (s, 1 H), 7.97 (s, 1 H), 7.76 (s, 1 H), 7.42 (br d, J=7.70 Hz, 1 H), 6.39 - 6.52 (m, 1 H), 3.68 (d, J=8.07 Hz, 1 H), 3.32 (s, 3 H, diastereomer 1), 3.32 (s, 3 H, diastereomer 2), 1 .75 (d, J=6.60 Hz, 3 H), 1 .73 - 1 .75 (m, 2 H), 1 .08 - 1 .20 (m, 1 H), 0.69 - 0.78 (m, 1 H), 0.47 - 0.60 (m, 2 H), 0.26 - 0.35 (m, 1 H).
19F-NMR (376 MHz, CDCI3, ppm) <5 = -62.56 (s, 3 F).
Example 6: Preparation of N-ri-r2-(5-cvano-2-pyridyl)-1.2.4-triazol-3-yllethyll-3-
(cvclopropylmethyl)-5-(trifluoromethyl)benzamide (Compound P6)
Figure imgf000082_0001
(Compound P6)
Step A: Preparation of methyl 3-(cvcloprOPylidenemethvD-5-(trifluoiOmethvDbenzoate
Figure imgf000082_0002
A solution of 3-bromopropyl(triphenyl)phosphonium;bromide (0.96 g, 2.07 mmol, 1.2 equiv.) in tetrahydrofuran (10.1 ml_) was cooled to 0 °C and potassium tert-butoxide (1 M in tetrahydrofuran, 4 mL, 4.14 mmol, 2.4 equiv.) was added. The mixture was stirred at reflux for 10 minutes, and methyl 3-formyl- 5-(trifluoromethyl)benzoate (0.40 g, 1.72 mmol, 1 equiv.) in tetrahydrofuran (3 mL) was added and the reaction was stirred at reflux for an additional 15 minutes. The reaction was cooled to room temperature, poured into a mixture of ethyl acetate (50 ml), brine (50 ml) and 2M HCI (10 ml). The organic layer was washed with brine (10 ml), dried over magnesium sulfate, filtered and concentrated. The crude residue was purified by column chromatography (silica, gradient of 0 - 10% ethyl acetate in cyclohexane) providing methyl 3-(cyclopropylidenemethyl)-5-(trifluoromethyl)benzoate (77%, 0.34 g).
Ή-NMR (400 MHz, CDCb, ppm) <5 = 8.33 (s, 1 H), 8.13 (s, 1 H), 7.95 (s, 1 H), 6.75 - 6.88 (m, 1 H), 3.97 (s, 3H), 1 .47 - 1 .56 (m, 2H), 1 .22 - 1 .30 (m, 2H).
Step B: Preparation of 3-(cvclopropylidenemethvD-5-(trifluoromethvDbenzoic acid
Figure imgf000083_0001
Sodium hydroxide (2M aqueous solution, 1.29 ml_, 2.58 mmol, 2 equiv.) was added to a solution of methyl 3-(cyclopropylidenemethyl)-5-(trifluoromethyl)benzoate (0.33 g, 1.29 mmol, 1 equiv.) in tetrahydrofuran (8 ml_). The reaction was stirred for 2 hours. Next, additional sodium hydroxide (2M aqueous solution, 1 .29 ml_, 2.58 mmol, 2 equiv.) and water (20 ml_) were added. After another 2.5 hours, the reaction was acidified with 2M HCI (5 ml_), diluted with ethyl acetate (30 ml_) and brine (30 ml_). The organic phase was washed with brine (10 ml_), dried over magnesium sulfate, filtered and concentrated to provide 3-(cyclopropylidenemethyl)-5-(trifluoromethyl)benzoic acid (quantitative, 0.33 g).
LC-MS (method 1): Rt 1 .03, m/z = 241 (M-H) .
1H-NMR (400 MHz, CDCIs, ppm) <5 = 8.43 (s, 1 H), 8.22 (s, 1 H), 8.01 (s, 1 H), 6.85 - 6.89 (m, 1 H), 1 .49 - 1 .59 (m, 2H), 1 .24 - 1 .34 (m, 2H).
Step C: Preparation of 3-(cvclopropylmethyr)-5-(trifluoromethyr)benzoic acid
Figure imgf000083_0002
3-(Cyclopropylidenemethyl)-5-(trifluoromethyl)benzoic acid (0.23 g, 0.95 mmol, 1 equiv.) was dissolved in methanol (10 ml_) and water (1 ml_). Saturated aqueous sodium bicarbonate (0.76 ml_) and palladium on charcoal (10 wt%)(50 mg, 0.047 mmol, 0.05 equiv.) were added and the mixture hydrogenated under ambient pressure for 5 hours. The reaction mixture was filtered, acidified with dilute aqueous HCI, diluted with water (20 ml_) and extracted with ethyl acetate (20 ml_). The organic phase was washed with brine (10 ml_), dried over magnesium sulfate, filtered and concentrated. The crude residue was purified by reverse-phase chromatography (gradient of 10 - 100% acetonitrile in water) providing 3- (cyclopropylmethyl)-5-(trifluoromethyl)benzoic acid (38%. 87 mg).
LC-MS (method 1): Rt 1 .04, m/z = 243 (M-H)-. Ή-NMR (400 MHz, CDCI3, ppm) <5 = 8.23 (s, 1 H), 8.21 (s, 1 H), 7.78 (s, 1 H), 2.71 (d, J=6.97 Hz, 2 H), 0.98 - 1 .12 (m, 1 H), 0.60 - 0.68 (m, 2 H), 0.25 - 0.32 (m, 2 H).
Step D: Preparation of N-[1-[2-(5-cvano-2-pyridvD-1 .2.4-triazol-3-yl1ethyl1-3-(cvclopropylmethyl)-5- (trifluoromethyl)benzamide (Compound P6)
Figure imgf000084_0001
(Compound P6)
3-(cyclopropylmethyl)-5-(trifluoromethyl)benzoic acid (87 mg, 0.36 mmol, 1 equiv.) and 1-[2-(5-cyano-2- pyridyl)-1 ,2,4-triazol-3-yl]ethylammonium chloride (89 mg, 0.36 mmol, 1 equiv.) were dissolved in ethyl acetate (4.8 ml_) and 1-propanephosphonic anhydride (50 wt% solution in ethyl acetate) (0.38 ml_, 0.64 mmol, 1.8 equiv.) and N,N-diisopropylethylamine (0.19 ml_, 1.07 mmol, 3 equiv.) were added. The reaction was stirred for 30 minutes, concentrated and the crude residue was purified by column chromatography (silica, gradient of 0 - 100% ethyl acetate in cyclohexane). The product was triturated in cyclohexane and the solid was filtered and dried providing N-[1-[2-(5-cyano-2-pyridyl)-1 ,2,4-triazol-3- yl]ethyl]-3-(cyclopropylmethyl)-5-(trifluoromethyl)benzamide (64%, 100 mg). LC-MS (method 1): Rt 1.10, m/z = 441 (M+H)+.
1H-NMR (400 MHz, CDCI3, ppm) <5 = 8.85 - 8.90 (m, 1 H), 8.14 - 8.21 (m, 2 H), 8.02 (s, 1 H), 7.89 (d, J=4.77 Hz, 2 H), 7.68 (s, 1 H), 7.36 (br d, J=8.07 Hz, 1 H), 6.38 - 6.49 (m, 1 H), 2.67 (d, J=6.97 Hz, 2 H), 1 .73 (d, J=6.97 Hz, 3 H), 0.97 - 1 .08 (m, 1 H), 0.56 - 0.64 (m, 2 H), 0.21 - 0.29 (m, 2 H).
Example 7: Preparation of N-ri-r2-(5-cvano-2-pyridyl)-1,2,4-triazol-3-yllethyll-3-(1- cvclopropylvinyl)-5-(trifluoromethyl)benzamide (Compound P7)
Figure imgf000084_0002
(Compound P7) Step A: Preparation of 3-(1-cvclopropylvinyl)-5-(trifluoromethyl)benzoic acid Methyltriphenylphosphonium bromide (1 .34 g, 3.67 mmol, 2 equiv.) was dissolved in tetrahydrofuran (9 ml_). The mixture was cooled to 0 °C and n-butyllithium (1 .6 M in hexane) (2.31 mL, 3.67 mmol, 2 equiv.) was added. The mixture was warmed to room temperature and stirred for 1 hour. Methyl 3- (cyclopropanecarbonyl)-5-(trifluoromethyl)benzoate (0.5 g, 1.84 mmol, 1 equiv., prepared analog to W02006/067445, page 148) was dissolved in tetrahydrofuran (3 mL) and added dropwise to the reaction mixture and the reaction was stirred at 40 °C for 17 hours. In a separate flask, methyltriphenylphosphonium bromide (1.34 g, 3.67 mmol, 2 equiv.) was dissolved in tetrahydrofuran (9 mL), cooled to 0 °C and n-butyllithium (1.6 M in hexane) ( 2.31 mL, 3.67 mmol, 2 equiv.) was added. The mixture was warmed to room temperature and stirred for 1 hour and added to the above reaction and stirred at 40 °C for an additional 72 hours. The reaction was cooled and quenched with 1 M HCI (10 mL). The mixture was diluted with water (50 mL) and extracted with ethyl acetate (50 mL). The organic layer was washed with brine (10 mL), dried over magnesium sulfate, filtered and concentrated. The crude residue was purified by column chromatography (silica, gradient of 0 - 100% ethyl acetate in cyclohexane) providing 3-(1-cyclopropylvinyl)-5-(trifluoromethyl)benzoic acid (156 mg).
LC-MS (method 1): Rt 1 .07, m/z = 255 (M-H) .
Ή-NMR (400 MHz, CDCI3, ppm) <5 = 10.71 (br s, 1 H), 8.54 (s, 1 H), 8.31 (s, 1 H), 8.10 (s, 1 H), 5.47 (s, 1 H), 5.15 (d, J=1 .10 Hz, 1 H), 1.64 - 1.74 (m, 1 H), 0.92 - 0.99 (m, 2 H), 0.63 - 0.70 (m, 2 H).
Step _ B: _ Preparation _ of _ N-[1-[2-(5-cvano-2-pyridyl)-1 ,2.4-triazol-3-yl1ethyl1-3-
[cvclopropyl(methoxy)methyl1-5-(trifluoromethyl)benzamide (Compound P7)
Figure imgf000085_0001
(Compound P7)
3-(1-cyclopropylvinyl)-5-(trifluoromethyl)benzoic acid (46 mg. 0.18 mmol, 1 equiv.) and 1-[2-(5-cyano-2- pyridyl)-1 ,2,4-triazol-3-yl]ethylammonium chloride (45 mg, 0.18 mmol, 1 equiv.) were dissolved in ethyl acetate (2.7 mL) and 1-propanephosphonic anhydride (50 wt% in ethylacetate) (0.19 mL, 0.32 mmol, 1.8 equiv.) and N,N-diisopropylethylamine (0.095 mL, 0.54 mmol, 3 equiv.) were added. The reaction was stirred for 30 minutes, concentrated and the crude residue was purified by column chromatography (silica, gradient of 0 - 85% ethyl acetate in cyclohexane) providing N-[1-[2-(5-cyano-2-pyridyl)-1 ,2,4- triazol-3-yl]ethyl]-3-(1-cyclopropylvinyl)-5-(trifluoromethyl)benzamide (59%, 48 mg).
LC-MS (method 1): Rt 1.12, m/z = 454 (M+H)+.
Ή-NMR (400 MHz, CDCIs, ppm) <5 = 8.85 - 8.91 (m, 1 H), 8.14 - 8.23 (m, 3 H), 8.02 (s, 1 H), 7.96 (d, J=0.73 Hz, 2 H), 7.58 (d, J=8.07 Hz, 1 H), 6.40 - 6.51 (m, 1 H), 5.40 (s, 1 H), 5.10 (d, J=1 .10 Hz, 1 H), 1 .75 (d, J=6.60 Hz, 3 H), 1 .59 - 1 .68 (m, 1 H), 0.88 - 0.95 (m, 2 H), 0.59 - 0.66 (m, 2 H).
Example 8: Preparation of 3-(1-cvclopropylvinyl)-N-ri-(2-pyrimidin-2-yl-1.2.4-triazol-3-yl)ethyll-5- (trifluoromethyl)benzamide (Compound P8)
Figure imgf000086_0001
(Compound P8)
3-(1-cyclopropylvinyl)-5-(trifluoromethyl)benzoic acid (100 mg, 0.39 mmol, 1 equiv. , prepared in Example 7) and 1-(2-pyrimidin-2-yl-1 ,2,4-triazol-3-yl)ethanamine (97 mg, 0.51 mmol, 1.3 equiv., prepared analog to WO2017/192385, page 30) were dissolved in ethyl acetate (5.9 ml_) and 1- propanephosphonic anhydride (50 wt% in ethylacetate) (0.41 ml_, 0.70 mmol, 1.8 equiv.) and N,N- diisopropylethylamine (0.206 ml_, 1.17 mmol, 3 equiv.) were added. The reaction was stirred for 30 minutes, concentrated and the crude residue was purified by column chromatography (silica, gradient of 70 - 100% ethyl acetate in cyclohexane) providing 3-(1-cyclopropylvinyl)-N-[1-(2-pyrimidin-2-yl-1 ,2,4- triazol-3-yl)ethyl]-5-(trifluoromethyl)benzamide (68%, 113 mg).
LC-MS (method 1): Rt 1 .03, m/z = 429 (M+H)+.
1H-NMR (400 MHz, CDCI3, ppm) <5 = 8.89 (s, 1 H), 8.15 - 8.24 (m, 2 H), 8.02 - 8.06 (m, 1 H), 8.00 (s, 1 H), 7.97 (s, 1 H), 7.76 (s, 1 H), 7.42 (br d, J=7.70 Hz, 1 H), 6.39 - 6.52 (m, 1 H), 3.68 (d, J=8.07 Hz, 1 H), 3.32 (s, 3 H, diastereomer 1), 3.32 (s, 3 H, diastereomer 2), 1 .75 (d, J=6.60 Hz, 3 H), 1 .73 - 1 .75 (m, 2 H), 1 .08 - 1 .20 (m, 1 H), 0.69 - 0.78 (m, 1 H), 0.47 - 0.60 (m, 2 H), 0.26 - 0.35 (m, 1 H).
19F-NMR (376 MHz, CDCI3, ppm) <5 = -62.60 (s, 3 F).
Example 9: Preparation of N-ri-r2-(5-cvano-2-pyridyl)-1.2.4-triazol-3-yllethyll-3-(1- cvclopropylethyl)-5-(trifluoromethyl)benzamide (Compound P9)
Figure imgf000087_0001
(Compound P9)
Step A: Preparation of 3-(1-cvcloprOPylethvD-5-(trifluoiOmethvDbenzoic acid
Figure imgf000087_0002
3-(1-cyclopropylvinyl)-5-(trifluoromethyl)benzoic acid (62 mg, 0.24 mmol, 1 equiv. , prepared in Example 3) was dissolved in methanol (10 ml_) and water (1 ml_) and saturated aqueous sodium bicarbonate
(0.19 ml_). Palladium on Charcoal (10%) (13 mg, 0.012 mmol, 0.05 equiv.) was added and the reaction was hydrogenated under ambient pressure for 17 hours. The reaction mixture was acidified with dilute HCI, diluted with water (2 ml_), filtered, and concentrated. The residue was triturated with acetonitrile (3 x 1 ml) and the combined liquid phase was purified by reverse-phase chromatography (gradient of 10 - 100% acetonitrile in water) providing 3-(1-cyclopropylethyl)-5-(trifluoromethyl)benzoic acid (30 mg).
LC-MS (method 1): Rt 1 .08, m/z = 257 (M-H) .
Ή-NMR (400 MHz, CDCb, ppm) <5 = 8.24 (s, 1 H), 8.22 (s, 1 H), 7.78 (s, 1 H), 2.10 - 2.21 (m, 1 H), 1.42 (d, J=6.97 Hz, 3 H), 0.94 - 1 .06 (m, 1 H), 0.62 - 0.71 (m, 1 H), 0.47 - 0.57 (m, 1 H), 0.26 - 0.35 (m, 1 H), 0.15 - 0.23 (m, 1 H).
Step B: Preparation of N-[1-[2-(5-cvano-2-pyridyl)-1 .2.4-triazol-3-yl1ethyl1-3-(1-cvclopropylethyl)-5- (trifluoromethyl)benzamide (Compound P9)
Figure imgf000087_0003
(Compound P9)
3-(1-cyclopropylethyl)-5-(trifluoromethyl)benzoic acid (30 mg. 0.12 mmol, 1 equiv.) and 1-[2-(5-cyano- 2-pyridyl)-1 ,2,4-triazol-3-yl]ethylammonium chloride (35 mg, 0.14 mmol, 1.2 equiv.) were dissolved in ethyl acetate (1.7 ml_) and 1-propanephosphonic anhydride (50 wt% in ethylacetate) (0.123 ml_, 0.21 mmol, 1.8 equiv.) and N,N-diisopropylethylamine (0.061 ml_, 0.35 mmol, 3 equiv.) were added. The reaction was stirred for 30 minutes, concentrated and the crude residue was purified by column chromatography (silica, gradient of 0 - 83% ethyl acetate in cyclohexane) providing N-[1-[2-(5-cyano-2- pyridyl)-1 ,2,4-triazol-3-yl]ethyl]-3-(1-cyclopropylethyl)-5-(trifluoromethyl)benzamide (74%, 39 mg). LC-MS (method 1): Rt 1.13, m/z = 456 (M+H)+.
Ή-NMR (400 MHz, CDCIs, ppm) <5 = 8.86 - 8.92 (m, 1 H), 8.15 - 8.24 (m, 2 H), 8.04 (s, 1 H), 7.92 (s, 1 H), 7.90 (s, 1 H), 7.60 - 7.68 (m, 2 H), 6.42 - 6.54 (m, 1 H), 2.04 - 2.16 (m, 1 H), 1 .76 (d, J=6.60 Hz, 3 H), 1 .37 (d, J=6.97 Hz, 3 H), 0.90 - 1 .05 (m, 1 H), 0.58 - 0.67 (m, 1 H), 0.42 - 0.51 (m, 1 H), 0.22 - 0.31 (m, 1 H), 0.11 - 0.19 (m, 1 H).
Example 10: Preparation of N-ri-r2-(5-cvano-2-pyridyl)-1.2.4-triazol-3-yllethyll-3-(1-cvclopropyl-
2.2-difluoro-vinyl)-5-(trifluoromethyl)benzamide (Compound P10)
Figure imgf000088_0001
(Compound P10)
Step A: Preparation of methyl 3-(1-cvclopropyl-2.2-difluoro-vinyl)-5-(trifluoromethyl)benzoate
Figure imgf000088_0002
A solution of dibromodifluoromethane (0.067 ml_, 0.70 mmol, 1 .9 equiv.) in tetrahydrofuran (3.7 ml_) was cooled to -78 °C. Next, N-[bis(dimethylamino)phosphanyl]-N-methyl-methanamine (0.275 ml_, 1.29 mmol, 3.5 equiv.) was added dropwise. A white solid started to form and the mixture was allowed to warm to room temperature. A 1 M solution of methyl 3-(cyclopropanecarbonyl)-5- (trifluoromethyl)benzoate (100 mg, 0.37 mmol, 1 equiv., prepared analog to W02006/067445, page 148) in tetrahydrofuran was then added dropwise to the solution and the reaction stirred at room temperature for 3.5 hours. The mixture was diluted with water and then extracted with ethyl acetate twice. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (silica, gradient of 0 - 20% ethyl acetate in cyclohexane) to produce methyl 3-(1 -cyclopropyl-2, 2-difluoro-vinyl)-5- (trifluoromethyl)benzoate (49%, 55 mg) as a colorless oil.
1H-NMR (400 MHz, CDCI3, ppm) <5 = 8.25 (s, 1 H), 8.22 (s, 1 H), 7.83 (s, 1 H), 3.99 (s, 3 H), 1 .63 - 1 .74 (m, 1 H), 0.86 - 0.95 (m, 2 H), 0.43 - 0.50 (m, 2 H). 19F-NMR (376 MHz, CDCI3, ppm) <5 = -62.81 (s, 3 F), -84.88 (d, J=32.90 Hz, 1 F), -85.90 (d, J=32.54 Hz, 1 F).
Step B: Preparation of 3-(1-cvclopropyl-2,2-difluoro-vinyl)-5-(trifluoromethyl)benzoic acid
Figure imgf000089_0001
To a solution of methyl 3-(1-cyclopropyl-2,2-difluoro-vinyl)-5-(trifluoromethyl)benzoate (55 mg, 0.18 mmol, 1 equiv.) in tetrahydrofuran (1.1 ml_) was added an aqueous sodium hydroxide solution (2M) (0.18 ml_, 0.36 mmol, 2.00 equiv.). The reaction mixture was stirred at room temperature for 2 hours, at which point more sodium hydroxide solution (2M) (0.18 ml_, 0.36 mmol, 2.00 equiv.) The reaction was acidified with HCI (2M), diluted with ethyl acetate (30 ml_) and the aqueous layer washed once with ethyl acetate. The combined organic phases were washed with brine (10 ml_), dried with magnesium sulfate, filtered and concentrated under reduced pressure to afford 3-(1 -cyclopropyl-2, 2-difluoro-vinyl)-5- (trifluoromethyl)benzoic acid (86%, 45 mg) as a white solid.
LC-MS (method 1): Rt 1 .08, m/z = 291 (M-H) .
Step C: Preparation of N-[1-[2-(5-cvano-2-pyridyl)-1 .2.4-triazol-3-yl1ethyl1-3-(1-cvclopropyl-2.2-difluoro- vinyl)-5-(trifluoromethyl)benzamide (Compound P10)
Figure imgf000089_0002
(Compound P10)
3-(1-cyclopropyl-2,2-difluoro-vinyl)-5-(trifluoromethyl)benzoic acid (45 mg. 0.15 mmol, 1 equiv.) and 1- [2-(5-cyano-2-pyridyl)-1 ,2,4-triazol-3-yl]ethylammonium chloride (39 mg, 0.15 mmol, 1 equiv.) were dissolved in ethyl acetate (2.3 mL) and 1-propanephosphonic anhydride (50 wt% in ethylacetate) (0.163 mL, 0.28 mmol, 1 .8 equiv.) and N,N-diisopropylethylamine (0.081 mL, 0.46 mmol, 3 equiv.) were added. The reaction was stirred for 3 hours, then more 1-propanephosphonic anhydride (50 wt% in ethylacetate) (0.163 mL, 0.28 mmol, 1 .8 equiv.) was added. After another 30 minutes, the reaction was concentrated and the crude residue was purified by column chromatography (silica, gradient of 0 - 40% ethyl acetate in cyclohexane). The product was the triturated with cyclohexane (2 x 10 mL) and filtered, providing N-[1 -[2-(5-cyano-2-pyridyl)-1 ,2,4-triazol-3-yl]ethyl]-3-(1 -cyclopropyl-2, 2-difluoro-vinyl)-5- (trifluoromethyl)benzamide (35%, 26 mg) as a white solid. LC-MS (method 1): Rt 1.14, m/z = 490 (M+H)+.
Ή-NMR (400 MHz, CDCI3, ppm) <5 = 8.89 (s, 1 H), 8.15 - 8.24 (m, 2 H), 8.02 - 8.06 (m, 1 H), 8.00 (s, 1 H), 7.97 (s, 1 H), 7.76 (s, 1 H), 7.42 (br d, J=7.70 Hz, 1 H), 6.39 - 6.52 (m, 1 H), 3.68 (d, J=8.07 Hz, 1 H), 3.32 (s, 3 H, diastereomer 1), 3.32 (s, 3 H, diastereomer 2), 1 .75 (d, J=6.60 Hz, 3 H), 1 .73 - 1 .75 (m, 2 H), 1 .08 - 1 .20 (m, 1 H), 0.69 - 0.78 (m, 1 H), 0.47 - 0.60 (m, 2 H), 0.26 - 0.35 (m, 1 H).
Example 11: Preparation of 3-r(E)-C-cvclopropyl-N-methoxy-carbonimidovH-N-
(cvclopropylmethyl)-N-ri-(2-pyrimidin-2-yl-1.2.4-triazol-3-yl)ethyll-5-(trifluoromethyl)benzamide
(Compound P11)
Figure imgf000090_0001
(Compound P11)
Step A: Preparation of methyl 3-(C-cvclopropyl-N-methoxy-carbonimidoyl)-5-(trifluoromethyl)benzoate
Figure imgf000090_0002
To a solution of methyl 3-(cyclopropanecarbonyl)-5-(trifluoromethyl)benzoate (0.190 g, 0.70 mmol, 1 equiv., prepared analog to W02006/067445, page 148) in ethanol (2.1 ml_) and water (6.3 ml_) was added O-methylhydroxylamine hydrochloride (0.161 g, 1.88 mmol, 2.70 equiv.) and sodium acetate trihydrate (0.420 g, 3.07 mmol, 4.40 equiv.). The mixture was stirred at 70 °C for 73 hours. The reaction mixture was extracted with ethyl acetate 3 times. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and evaporated under reduced pressure. The crude product was purified by column chromatography (silica, gradient of 0 - 10% ethyl acetate in cyclohexane) to provide methyl 3-(C-cyclopropyl-N-methoxy-carbonimidoyl)-5-(trifluoromethyl)benzoate (48%, 102 mg), colorless oil, as a 1 :1 mixture of E and Z isomers.
1H-NMR (400 MHz, CDCI3, ppm) <5 = 8.33 (s, 0.5 H), 8.28 (s, 1.5 H), 7.93 (s, 0.5 H), 7.89 (s, 0.5 H), 4.01 (s, 1 .5 H), 3.96 - 3.99 (m, 3 H), 3.81 (s, 1 .5 H), 2.10 - 2.20 (0.5 H, m), 1 .66 - 1 .76 (0.5 H, m), 0.98 - 1 .04 (1 H, m), 0.85 - 0.91 (2 H, m), 0.60 - 0.66 (1 H, m).
19F-NMR (376 MHz, CDCI3, ppm, E/Z isomers in 1 :1 ratio) <5 = -62.75 (s, 0.5 F) and -62.78 (s, 0.5 F). Step B: Preparation of 3-(C-cvclopropyl-N-methoxy-carbonimidoyl)-5-(trifluoromethyl)benzoic acid To a solution of methyl 3-(C-cyclopropyl-N-methoxy-carbonimidoyl)-5-(trifluoromethyl)benzoate (101 mg, 0.34 mmol, 1 equiv.) in a mixture of tetrahydrofuran (1 ml_) and water (0.5 ml_) was added lithium hydroxide monohydrate (14.2 mg, 0.34 mmol, 1 equiv.). The reaction mixture was stirred at room temperature for 2 hours. The reaction was acidified with 1 N aqueous hydrochloric acid until pH reached 2 and extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 3-(C-cyclopropyl-N-methoxy- carbonimidoyl)-5-(trifluoromethyl)benzoic acid (93%, 89.2 mg), white solid, as a 1 :1 mixture of E and Z isomers.
LC-MS (method 1): Rt 0.98, m/z = 286 (M-H) .
Ή-NMR (400 MHz, CDCI3, ppm, E/Z isomers in 1 :1 ratio) <5 = 8.42 (s, 0.5 H), 8.34 - 8.39 (m, 1.5 H), 8.01 (s, 0.5 H), 7.97 (s, 0.5 H), 4.04 (s, 1 .5 H), 3.84 (s, 1 .5 H), 2.11 - 2.20 (m, 0.5 H), 1 .70 - 1 .78 (m, 0.5 H), 1 .00 - 1 .09 (m, 1 H), 0.87 - 0.94 (m, 2 H), 0.60 - 0.70 (m, 1 H).
19F-NMR (376 MHz, CDCI3, ppm, E/Z isomers in 1 :1 ratio) <5 = -62.78 (s, 0.5 F) and -62.81 (s, 0.5 F).
Step C: Preparation of 3-[C-cvclopropyl-N-methoxy-carbonimidoyl1-N-(cvclopropylmethvD-N-[1-(2- pyrimidin-2-yl-1 ,2.4-triazol-3-yl)ethyl1-5-(trifluoromethyl)benzamide (Compound P11)
Figure imgf000091_0001
(Compound P11)
A 10 mL round-bottom flask was charged with N-(cyclopropylmethyl)-1-(2-pyrimidin-2-yl-1 ,2,4-triazol-3- yl)ethanamine (72 mg, 0.29 mmol, 1 equiv.), acetonitrile (0.88 mL), N-ethyl-N-isopropyl-propan-2-amine (0.10 mL, 0.59 mmol, 2.0 equiv.), 3-(C-cyclopropyl-N-methoxy-carbonimidoyl)-5- (trifluoromethyl)benzoic acid (89 mg, 0.31 mmol, 1 equiv.) and 1-[bis(dimethylamino)methylene]-1 H- 1 ,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (0.17 g, 0.44 mmol, 1.50 equiv.). The resulting solution was stirred at room temperature for 1 hour. It was then concentrated under reduced pressure and the crude product purified by column chromatography (silica, gradient of 0 - 100% ethyl acetate in cyclohexane) gave 3-[C-cyclopropyl-N-methoxy-carbonimidoyl]-N-(cyclopropylmethyl)-N-[1- (2-pyrimidin-2-yl-1 ,2,4-triazol-3-yl)ethyl]-5-(trifluoromethyl)benzamide (72%, 109 mg), light yellow gum, as a mixture of two diastereomers. LC-MS (method 1): Rt 1.06, m/z = 514 (M+H)+.
Example 12: Preparation of N-ri-r2-(5-cvano-2-pyridyl)-1.2.4-triazol-3-yllethyll-3-r(1- hvdroxycvclopropyl)methyll-5-(trifluoromethyl)benzamide (Compound P12)
Figure imgf000092_0001
(Compound P12)
Step A: Preparation of methyl 2-[3-bromo-5-(trifluoromethvDphenyl1acetate
Figure imgf000092_0002
2-[3-bromo-5-(trifluoromethyl)phenyl]acetic acid (7 g, 24.73 mmol, 1 equiv.) was dissolved in methanol (50 ml_) and concentrated sulfuric acid (0.014 ml_, 0.25 mmol, 0.01 equiv.) was added and the reaction was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and re-dissolved in ethyl acetate, then washed with saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate and filtered. Solvent was removed under reduced pressure to furnish methyl 2-[3-bromo-5-(trifluoromethyl)phenyl]acetate (95%, 6.95 g).
LC-MS (method 1): Rt 1 .09, m/z = 295 (M-H) .
Ή-NMR (400 MHz, CDCIs, ppm) <5 = 7.71 (s, 1 H), 7.66 (s, 1 H), 7.50 (s, 1 H), 3.75 (s, 3 H), 3.69 (s, 2 H). Step B: Preparation of 1-[[3-bromo-5-(trifluoromethyl)phenyl1methyl1cvclopropanol
Figure imgf000092_0003
Methyl 2-[3-bromo-5-(trifluoromethyl)phenyl]acetate (6.95 g, 23.4 mmol, 1 equiv.) was dissolved in tetrahydrofuran (23.4 mL) and the solution was cooled to 0 °C. Titanium isopropoxide (1.4 mL, 4.68 mmol, 0.20 equiv.) was added and the reaction was stirred for 10 minutes. Next, bromo(ethyl)magnesium solution (3M in diethylether) (16 mL, 49.1 mmol, 2.10 equiv.) was added via syringe pump over 2 hours with constant gas evolution. The reaction was then quenched with sulfuric acid (5% aqueous, 200 ml_) and extracted three times with methyl tert-butyl ether (3 x 50 ml_). The combined organic phases were washed with water (20 ml_), brine (20 ml_), dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (silica, gradient of 0 - 65% ethyl acetate in cyclohexane) to provide 1-[[3-bromo-5- (trifluoromethyl)phenyl]methyl]cyclopropanol (46%, 3.15 g).
Ή-NMR (400 MHz, CDCI3, ppm) <5 = 7.69 (s, 2 H), 7.51 (s, 1 H), 2.93 (s, 2 H), 0.88 - 0.93 (m, 2 H), 0.66 - 0.72 (m, 2 H) .
Step C: Preparation of methyl 3-[(1-hvdroxycvclopropyr)methyl1-5-(trifluoromethvDbenzoate
Figure imgf000093_0001
1-[[3-bromo-5-(trifluoromethyl)phenyl]methyl]cyclopropanol (2.2 g, 7.5 mmol, 1 equiv.), [1 ,1 - bis(diphenylphosphino)ferrocene]dichloropalladium(ll) (0.17 g, 0.22 mmol, 0.03 equiv.) and triethylamine (2.9 ml_, 21 mmol, 2.80 equiv.) in methanol (20 ml_) were heated at 90°C for 20 hours under a carbon monoxide atmosphere (10 bar) in a 140 ml_ reactor. After cooling to room temperature, the reaction was concentrated and partitioned between ethyl acetate (40 ml_) and water (40 ml_). The organic phase was further washed with brine (2 x 20 ml_), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by column chromatography (silica, gradient of 0 - 100% ethyl acetate in cyclohexane) providing methyl 3-[(1- hydroxycyclopropyl)methyl]-5-(trifluoromethyl)benzoate (77%. 1.58 g).
LC-MS (method 1): Rt 0.97, m/z = 275 (M+H)+.
1H-NMR (400 MHz, CDCI3, ppm) <5 = 8.21 (s, 1 H), 8.16 - 8.20 (m, 1 H), 7.77 (s, 1 H), 3.98 (s, 3 H), 3.01 (s, 2 H), 0.87 - 0.94 (m, 2 H), 0.67 - 0.75 (m, 2 H).
Step D: Preparation of 3-[(1-hvdroxycvclopropyr)methyl1-5-(trifluoromethvDbenzoic acid
Figure imgf000093_0002
To a solution of 3-[(1-hydroxycyclopropyl)methyl]-5-(trifluoromethyl)benzoate (0.2 g, 0.73 mmol, 1 equiv.) in tetrahydrofuran (2 ml_) and water (2 ml_) was added sodium hydroxide solution (4M) (1 ml_, 4 mmol, 5.5 equiv.) and the mixture stirred for 1 hour. The reaction was diluted with ethyl acetate (20 ml_) and water (10 ml_) and acidified with 1 N HCI. The organic phase was washed with brine (2 x 20 ml_), dried, filtered and concentrated under reduced pressure. The crude residue was purified by column chromatography (silica, gradient of 0 - 100% ethyl acetate in cyclohexane) providing 3-[(1- hydroxycyclopropyl)methyl]-5-(trifluoromethyl)benzoic acid (46%. 87 mg).
LC-MS (method 1): Rt 0.83, m/z = 259 (M-H) .
1H-NMR (400 MHz, DMSO-de, ppm) <5 = 13.41 (s, 1 H), 8.16 (s, 1 H), 8.03 (s, 1 H), 7.89 (s, 1 H), 2.92 (s, 2 H), 0.48 - 0.66 (m, 4 H).
19F-NMR (376 MHz, DMSO-de, ppm) <5 = -56.40 (s, 3 F).
Step E: _ Preparation _ of _ N-[1-[2-(5-cvano-2-pyridvD-1 .2.4-triazol-3-yl1ethyl1-3-[(1- hvdroxycvclopropyr)methyl1-5-(trifluoromethyr)benzamide (Compound P12)
Figure imgf000094_0001
(Compound P12)
3-[(1-hydroxycyclopropyl)methyl]-5-(trifluoromethyl)benzoic acid (87 mg. 0.33 mmol, 1 equiv.) and 1-[2- (5-cyano-2-pyridyl)-1 ,2,4-triazol-3-yl]ethylammonium chloride (100.6 mg, 0.40 mmol, 1.2 equiv.) were dissolved in ethyl acetate (5 mL) and 1-propanephosphonic anhydride (50 wt% in ethylacetate) (0.355 mL, 0.60 mmol, 1 .8 equiv.) and N,N-diisopropylethylamine (0.176 mL, 1.00 mmol, 3 equiv.) were added. The reaction was stirred for 30 minutes, then the reaction was concentrated and the crude residue was purified by column chromatography (silica, gradient of 0 - 100% ethyl acetate in cyclohexane) providing N-[1 -[2-(5-cyano-2-pyridyl)-1 ,2,4-triazol-3-yl]ethyl]-3-[(1 -hydroxycyclopropyl)methyl]-5- (trifluoromethyl)benzamide (54%, 83 mg).
LC-MS (method 1): Rt 0.93, m/z = 458 (M+H)+.
Ή-NMR (400 MHz, DMSO-de, ppm) <5 = 9.29 (d, J=6.97 Hz, 1 H), 9.07 (dd, J=2.20, 0.73 Hz, 1 H), 8.58 (dd, J=8.44, 2.20 Hz, 1 H), 8.25 (s, 1 H), 8.08 (dd, J=8.44, 0.73 Hz, 1 H), 7.97 - 8.01 (m, 2 H), 6.00 - 6.16 (m, 1 H), 2.87 (s, 2 H), 1 .65 (d, J=6.97 Hz, 4 H), 0.49 - 0.66 (m, 4 H).
19F-NMR (376 MHz, DMSO-de, ppm) <5 = -60.86 (s, 3 F).
Table P: Examples of compounds of formula I
Figure imgf000094_0002
Figure imgf000095_0001
Figure imgf000096_0001
Figure imgf000097_0001
Figure imgf000098_0001
The activity of the compositions according to the invention can be broadened considerably, and adapted to prevailing circumstances, by adding other insecticidally, acaricidally and/or fungicidally active ingredients. The mixtures of the compounds of formula I with other insecticidally, acaricidally and/or fungicidally active ingredients may also have further surprising advantages which can also be described, in a wider sense, as synergistic activity. For example, better tolerance by plants, reduced phytotoxicity, insects can be controlled in their different development stages or better behaviour during their production, for example during grinding or mixing, during their storage or during their use.
Suitable additions to active ingredients here are, for example, representatives of the following classes of active ingredients: organophosphorus compounds, nitrophenol derivatives, thioureas, juvenile hormones, formamidines, benzophenone derivatives, ureas, pyrrole derivatives, carbamates, pyrethroids, chlorinated hydrocarbons, acylureas, pyridylmethyleneamino derivatives, macrolides, neonicotinoids and Bacillus thuringiensis preparations.
The following mixtures of a compound of formula I with an active substances are preferred (the abbreviation “TX” means “one compound selected from the compounds defined in Tables A-1 to A-18 and Table P”): an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628) + TX, an insect control active substance selected from Abamectin + TX, Acequinocyl + TX, Acetamiprid + TX, Acetoprole + TX, Acrinathrin + TX, Acynonapyr + TX, Afidopyropen + TX, Afoxolaner + TX, Alanycarb + TX, Allethrin + TX, Alpha-Cypermethrin + TX, Alphamethrin + TX, Amidoflumet + TX, Aminocarb + TX, Azocyclotin + TX, Bensultap + TX, Benzoximate + TX, Benzpyrimoxan + TX, Betacyfluthrin + TX, Beta-cypermethrin + TX, Bifenazate + TX, Bifenthrin + TX, Binapacryl + TX, Bioallethrin + TX, Bioallethrin S)-cyclopentylisomer + TX, Bioresmethrin + TX, Bistrifluron + TX, Broflanilide + TX, Brofluthrinate + TX, Bromophos-ethyl + TX, Buprofezine + TX, Butocarboxim + TX, Cadusafos + TX, Carbaryl + TX, Carbosulfan + TX, Cartap + TX, CAS number: 1632218-00-8 + TX, CAS number: 1808115-49-2 + TX, CAS number: 2032403-97-5 + TX, CAS number: 2044701-44-0 + TX, CAS number: 2128706-05-6 + TX, CAS number: 2246757-58-2 (or 2249718-27-0) + TX, CAS number: 907187-07-9 + TX, Chlorantraniliprole + TX, Chlordane + TX, Chlorfenapyr + TX, Chloroprallethrin + TX, Chromafenozide + TX, Clenpirin + TX, Cloethocarb + TX, Clothianidin + TX, 2- chlorophenyl N-methylcarbamate (CPMC) + TX, Cyanofenphos + TX, Cyantraniliprole + TX, Cyclaniliprole + TX, Cyclobutrifluram + TX, Cycloprothrin + TX, Cycloxaprid + TX, Cycloxaprid + TX, Cyenopyrafen + TX, Cyetpyrafen + TX, Cyflumetofen + TX, Cyfluthrin + TX, Cyhalodiamide + TX, Cyhalothrin + TX, Cypermethrin + TX, Cyphenothrin + TX, Cyproflanilide + TX, Cyromazine + TX, Deltamethrin + TX, Diafenthiuron + TX, Dialifos + TX, Dibrom + TX, Dicloromezotiaz + TX, Diflovidazine + TX, Diflubenzuron + TX, dimpropyridaz + TX, Dinactin + TX, Dinocap + TX,
Dinotefuran + TX, Dioxabenzofos + TX, Emamectin (or Emamectin Benzoate) + TX, Empenthrin + TX, Epsilon - momfluorothrin + TX, Epsilon-metofluthrin + TX, Esfenvalerate + TX, Ethion + TX, Ethiprole + TX, Etofenprox + TX, Etoxazole + TX, Famphur + TX, Fenazaquin + TX, Fenfluthrin + TX, Fenitrothion + TX, Fenobucarb + TX, Fenothiocarb + TX, Fenoxycarb + TX, Fenpropathrin + TX, Fenpyroxymate + TX, Fensulfothion + TX, Fenthion + TX, Fentinacetate + TX, Fenvalerate + TX, Fipronil + TX, Flometoquin + TX, Flonicamid + TX, Fluacrypyrim + TX, Fluazaindolizine + TX, Fluazuron + TX, Flubendiamide + TX, Flubenzimine + TX, Flucitrinate + TX, Flucycloxuron + TX, Flucythrinate + TX, Fluensulfone + TX, Flufenerim + TX, Flufenprox + TX, Flufiprole + TX, Fluhexafon + TX, Flumethrin + TX, Fluopyram + TX, Flupentiofenox + TX, Flupyradifurone + TX, Flupyrimin + TX, Fluralaner + TX, Fluvalinate + TX, Fluxametamide + TX, Fosthiazate + TX, Gamma-Cyhalothrin + TX, Gossyplure™ + TX, Guadipyr + TX, Halofenozide + TX, Halofenozide + TX, Halfenprox + TX, Heptafluthrin + TX, Hexythiazox + TX, Hydramethylnon + TX, Imicyafos + TX, Imidacloprid + TX, Imiprothrin + TX, Indoxacarb + TX, lodomethane + TX, Iprodione + TX, Isocycloseram + TX,
Isothioate + TX, Ivermectin + TX, Kappa-bifenthrin + TX, Kappa-tefluthrin + TX, Lambda-Cyhalothrin + TX, Lepimectin + TX, Lufenuron + TX, Metaflumizone + TX, Metaldehyde + TX, Metam + TX, Methomyl + TX, Methoxyfenozide + TX, Metofluthrin + TX, Metolcarb + TX, Mexacarbate + TX, Milbemectin + TX, Momfluorothrin + TX, Niclosamide + TX, Nicofluprole + TX; Nitenpyram + TX, Nithiazine + TX, Omethoate + TX, Oxamyl + TX, Oxazosulfyl + TX, Parathion-ethyl + TX, Permethrin + TX, Phenothrin + TX, Phosphocarb + TX, Piperonylbutoxide + TX, Pirimicarb + TX, Pirimiphos-ethyl + TX, Pirimiphos-methyl + TX, Polyhedrosis virus + TX, Prallethrin + TX, Profenofos + TX, Profenofos + TX, Profluthrin + TX, Propargite + TX, Propetamphos + TX, Propoxur + TX, Prothiophos + TX, Protrifenbute + TX, Pyflubumide + TX, Pymetrozine + TX, Pyraclofos + TX, Pyrafluprole + TX, Pyridaben + TX, Pyridalyl + TX, Pyrifluquinazon + TX, Pyrimidifen + TX, Pyriminostrobin + TX, Pyriprole + TX, Pyriproxyfen + TX, Resmethrin + TX, Sarolaner + TX, Selamectin + TX, Silafluofen + TX, Spinetoram + TX, Spinosad + TX, Spirodiclofen + TX, Spiromesifen + TX, Spiropidion + TX, Spirotetramat + TX, Sulfoxaflor + TX, Tebufenozide + TX, Tebufenpyrad + TX, Tebupirimiphos + TX, Tefluthrin + TX, Temephos + TX, Tetrachlorantraniliprole + TX, Tetradiphon + TX, Tetramethrin + TX, Tetramethylfluthrin + TX, Tetranactin + TX, Tetraniliprole + TX, Theta-cypermethrin + TX, Thiacloprid + TX, Thiamethoxam + TX, Thiocyclam + TX, Thiodicarb + TX, Thiofanox + TX, Thiometon + TX, Thiosultap + TX, Tioxazafen + TX, Tolfenpyrad + TX, Toxaphene + TX, Tralomethrin + TX, Transfluthrin + TX, Triazamate + TX, Triazophos + TX, Trichlorfon + TX, Trichloronate + TX, Trichlorphon + TX, Triflumezopyrim + TX, Tyclopyrazoflor + TX, Zeta-Cypermethrin + TX, Extract of seaweed and fermentation product derived from melasse + TX, Extract of seaweed and fermentation product derived from melasse comprising urea + TX, amino acids + TX, potassium and molybdenum and EDTA-chelated manganese + TX, Extract of seaweed and fermented plant products + TX, Extract of seaweed and fermented plant products comprising phytohormones + TX, vitamins + TX, EDTA- chelated copper + TX, zinc + TX, and iron + TX, Azadirachtin + TX, Bacillus aizawai + TX, Bacillus chitinosporus AQ746 (NRRL Accession No B-21 618) + TX, Bacillus firmus + TX, Bacillus kurstaki + TX, Bacillus mycoides AQ726 (NRRL Accession No. B-21664) + TX, Bacillus pumilus (NRRL Accession No B-30087) + TX, Bacillus pumilus AQ717 (NRRL Accession No. B-21662) + TX, Bacillus sp. AQ178 (ATCC Accession No. 53522) + TX, Bacillus sp. AQ175 (ATCC Accession No. 55608) +
TX, Bacillus sp. AQ177 (ATCC Accession No. 55609) + TX, Bacillus subtilis unspecified + TX, Bacillus subtilis AQ153 (ATCC Accession No. 55614) + TX, Bacillus subtilis AQ30002 (NRRL Accession No. B-50421) + TX, Bacillus subtilis AQ30004 (NRRL Accession No. B- 50455) + TX, Bacillus subtilis AQ713 (NRRL Accession No. B-21661) + TX, Bacillus subtilis AQ743 (NRRL Accession No. B-21665) + TX, Bacillus thuringiensis AQ52 (NRRL Accession No. B-21619) + TX, Bacillus thuringiensis BD#32 (NRRL Accession No B-21530) + TX, Bacillus thuringiensis subspec. kurstaki BMP 123 + TX, Beauveria bassiana + TX, D-limonene + TX, Granulovirus + TX, Harpin + TX, Helicoverpa armigera Nucleopolyhedrovirus + TX, Helicoverpa zea Nucleopolyhedrovirus + TX, Heliothis virescens Nucleopolyhedrovirus + TX, Heliothis punctigera Nucleopolyhedrovirus + TX, Metarhizium spp. + TX, Muscodor albus 620 (NRRL Accession No. 30547) + TX, Muscodor roseus A3-5 (NRRL Accession No. 30548) + TX, Neem tree based products + TX, Paecilomyces fumosoroseus + TX, Paecilomyces lilacinus + TX, Pasteuria nishizawae + TX, Pasteuria penetrans + TX, Pasteuria ramosa + TX, Pasteuria thornei + TX, Pasteuria usgae + TX, P-cymene + TX, Plutella xylostella Granulosis virus + TX, Plutella xylostella Nucleopolyhedrovirus + TX, Polyhedrosis virus + TX, pyrethrum + TX, QRD 420 (a terpenoid blend) + TX, QRD 452 (a terpenoid blend) + TX, QRD 460 (a terpenoid blend) + TX, Quillaja saponaria + TX, Rhodococcus globerulus AQ719 (NRRL Accession No B-21663) + TX, Spodoptera frugiperda Nucleopolyhedrovirus + TX, Streptomyces galbus (NRRL Accession No.
30232) + TX, Streptomyces sp. (NRRL Accession No. B-30145) + TX, Terpenoid blend + TX, and Verticillium spp.; an algicide selected from the group of substances consisting of bethoxazin [CCN] + TX, copper dioctanoate (IUPAC name) (170) + TX, copper sulfate (172) + TX, cybutryne [CCN] + TX, dichlone (1052) + TX, dichlorophen (232) + TX, endothal (295) + TX, fentin (347) + TX, hydrated lime [CCN] + TX, nabam (566) + TX, quinoclamine (714) + TX, quinonamid (1379) + TX, simazine (730) + TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347)
+ TX; an anthelmintic selected from the group of substances consisting of abamectin (1) + TX, crufomate (1011) + TX, Cyclobutrifluram + TX, doramectin (alternative name) [CCN] + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, eprinomectin (alternative name) [CCN] + TX, ivermectin (alternative name) [CCN] + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, piperazine [CCN] + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) and thiophanate (1435) + TX; an avicide selected from the group of substances consisting of chloralose (127) + TX, endrin (1122) + TX, fenthion (346) + TX, pyridin-4-amine (IUPAC name) (23) and strychnine (745) + TX; a bactericide selected from the group of substances consisting of 1 -hydroxy-1 /-/-pyridine-2-thione (IUPAC name) (1222) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, 8-hydroxyquinoline sulfate (446) + TX, bronopol (97) + TX, copper dioctanoate (IUPAC name) (170) + TX, copper hydroxide (IUPAC name) (169) + TX, cresol [CCN] + TX, dichlorophen (232) + TX, dipyrithione (1105) + TX, dodicin (1112) + TX, fenaminosulf (1144) + TX, formaldehyde (404) + TX, hydrargaphen (alternative name) [CCN] + TX, kasugamycin (483) + TX, kasugamycin hydrochloride hydrate (483) + TX, nickel bis(dimethyldithiocarbamate) (lUPAC name) (1308) + TX, nitrapyrin (580) + TX, octhilinone (590) + TX, oxolinic acid (606) + TX, oxytetracycline (611) + TX, potassium hydroxyquinoline sulfate (446) + TX, probenazole (658) + TX, streptomycin (744) + TX, streptomycin sesquisulfate (744) + TX, tecloftalam (766) + TX, and thiomersal (alternative name) [CCN] + TX; a biological agent selected from the group of substances consisting of Adoxophyes orana GV (alternative name) (12) + TX, Agrobacterium radiobacter (alternative name) (13) + TX, Amblyseius spp. (alternative name) (19) + TX, Anagrapha falcifera NPV (alternative name) (28) + TX, Anagrus atomus (alternative name) (29) + TX, Aphelinus abdominalis (alternative name) (33) + TX, Aphidius colemani (alternative name) (34) + TX, Aphidoletes aphidimyza (alternative name) (35) + TX, Autographa californica NPV (alternative name) (38) + TX, Bacillus firmus (alternative name) (48) + TX, Bacillus sphaericus Neide (scientific name) (49) + TX, Bacillus thuringiensis Berliner (scientific name) (51) + TX, Bacillus thuringiensis subsp. aizawai (scientific name) (51) + TX, Bacillus thuringiensis subsp. israelensis (scientific name) (51) + TX, Bacillus thuringiensis subsp. japonensis (scientific name) (51) + TX, Bacillus thuringiensis subsp. kurstaki (scientific name) (51) + TX,
Bacillus thuringiensis subsp. tenebrionis (scientific name) (51) + TX, Beauveria bassiana (alternative name) (53) + TX, Beauveria brongniartii (alternative name) (54) + TX, Chrysoperla carnea (alternative name) (151) + TX, Cryptolaemus montrouzieri (alternative name) (178) + TX, Cydia pomonella GV (alternative name) (191) + TX, Dacnusa sibirica (alternative name) (212) + TX, Diglyphus isaea (alternative name) (254) + TX, Encarsia formosa (scientific name) (293) + TX, Eretmocerus eremicus (alternative name) (300) + TX, Helicoverpa zea NPV (alternative name) (431) + TX, Heterorhabditis bacteriophora and H. megidis (alternative name) (433) + TX, Hippodamia convergens (alternative name) (442) + TX, Leptomastix dactylopii (alternative name) (488) + TX, Macrolophus caliginosus (alternative name) (491) + TX, Mamestra brassicae NPV (alternative name) (494) + TX, Metaphycus helvolus (alternative name) (522) + TX, Metarhizium anisopliae var. acridum (scientific name) (523) + TX, Metarhizium anisopliae var. anisopliae (scientific name) (523) + TX, Neodiprion sertifer NPV and N. lecontei NPV (alternative name) (575) + TX, Orius spp. (alternative name) (596) + TX, Paecilomyces fumosoroseus (alternative name) (613) + TX, Phytoseiulus persimilis (alternative name) (644) + TX, Spodoptera exigua multicapsid nuclear polyhedrosis virus (scientific name) (741) + TX, Steinernema bibionis (alternative name) (742) + TX, Steinernema carpocapsae (alternative name) (742) + TX, Steinernema feltiae (alternative name) (742) + TX, Steinernema glaseri (alternative name) (742) + TX, Steinernema riobrave (alternative name) (742) + TX, Steinernema riobravis (alternative name) (742) + TX, Steinernema scapterisci (alternative name) (742) + TX, Steinernema spp. (alternative name) (742) + TX, Trichogramma spp. (alternative name) (826) + TX, Typhlodromus occidentalis (alternative name) (844) and Verticillium lecanii (alternative name) (848) + TX; a soil sterilant selected from the group of substances consisting of iodomethane (lUPAC name) (542) and methyl bromide (537) + TX; a chemosterilant selected from the group of substances consisting of apholate [CCN] + TX, bisazir (alternative name) [CCN] + TX, busulfan (alternative name) [CCN] + TX, diflubenzuron (250) + TX, dimatif (alternative name) [CCN] + TX, hemel [CCN] + TX, hempa [CCN] + TX, metepa [CCN] + TX, methiotepa [CCN] + TX, methyl apholate [CCN] + TX, morzid [CCN] + TX, penfluron (alternative name) [CCN] + TX, tepa [CCN] + TX, thiohempa (alternative name) [CCN] + TX, thiotepa (alternative name) [CCN] + TX, tretamine (alternative name) [CCN] and uredepa (alternative name) [CCN] + TX; an insect pheromone selected from the group of substances consisting of (E)-dec-5-en-1-yl acetate with (E)-dec-5-en-1-ol (lUPAC name) (222) + TX, (E)-tridec-4-en-1-yl acetate (lUPAC name) (829) + TX, (E)-6-methylhept-2-en-4-ol (lUPAC name) (541) + TX, (E,Z)-tetradeca-4,10-dien-1-yl acetate (lUPAC name) (779) + TX, (Z)-dodec-7-en-1-yl acetate (lUPAC name) (285) + TX, (Z)-hexadec-11- enal (lUPAC name) (436) + TX, (Z)-hexadec-11 -en-1 -yl acetate (lUPAC name) (437) + TX, (Z)- hexadec-13-en-11 -yn-1 -yl acetate (lUPAC name) (438) + TX, (Z)-icos-13-en-10-one (lUPAC name) (448) + TX, (Z)-tetradec-7-en-1 -al (lUPAC name) (782) + TX, Z)-tetradec-9-en-1-ol (lUPAC name) (783) + TX, (Z)-tetradec-9-en-1-yl acetate (lUPAC name) (784) + TX, (7E,9Z)-dodeca-7,9-dien-1-yl acetate (lUPAC name) (283) + TX, (9Z,11E)-tetradeca-9,11 -dien-1 -yl acetate (lUPAC name) (780) + TX, (9Z,12E)-tetradeca-9,12-dien-1-yl acetate (lUPAC name) (781) + TX, 14-methyloctadec-1-ene (lUPAC name) (545) + TX, 4-methylnonan-5-ol with 4-methylnonan-5-one (lUPAC name) (544) + TX, alpha-multistriatin (alternative name) [CCN] + TX, brevicomin (alternative name) [CCN] + TX, codlelure (alternative name) [CCN] + TX, codlemone (alternative name) (167) + TX, cuelure (alternative name) (179) + TX, disparlure (277) + TX, dodec-8-en-1-yl acetate (lUPAC name) (286)
+ TX, dodec-9-en-1-yl acetate (lUPAC name) (287) + TX, dodeca-8 + TX, 10-dien-1 -yl acetate (lUPAC name) (284) + TX, dominicalure (alternative name) [CCN] + TX, ethyl 4-methyloctanoate (lUPAC name) (317) + TX, eugenol (alternative name) [CCN] + TX, frontalin (alternative name) [CCN] + TX, gossyplure (alternative name) (420) + TX, grandlure (421) + TX, grandlure I (alternative name) (421) + TX, grandlure II (alternative name) (421) + TX, grandlure III (alternative name) (421) + TX, grandlure IV (alternative name) (421) + TX, hexalure [CCN] + TX, ipsdienol (alternative name) [CCN] + TX, ipsenol (alternative name) [CCN] + TX, japonilure (alternative name) (481) + TX, lineatin (alternative name) [CCN] + TX, litlure (alternative name) [CCN] + TX, looplure (alternative name) [CCN] + TX, medlure [CCN] + TX, megatomoic acid (alternative name) [CCN] + TX, methyl eugenol (alternative name) (540) + TX, muscalure (563) + TX, octadeca-2,13-dien-1-yl acetate (lUPAC name) (588) + TX, octadeca-3,13-dien-1-yl acetate (lUPAC name) (589) + TX, orfralure (alternative name) [CCN] + TX, oryctalure (alternative name) (317) + TX, ostramone (alternative name) [CCN] + TX, siglure [CCN] + TX, sordidin (alternative name) (736) + TX, sulcatol (alternative name) [CCN] + TX, tetradec-11 -en-1 -yl acetate (lUPAC name) (785) + TX, trimedlure (839) + TX, trimedlure A (alternative name) (839) + TX, trimedlure Bi (alternative name) (839) + TX, trimedlure B2 (alternative name) (839) + TX, trimedlure C (alternative name) (839) and trunc-call (alternative name) [CCN] + TX; an insect repellent selected from the group of substances consisting of 2-(octylthio)ethanol (lUPAC name) (591) + TX, butopyronoxyl (933) + TX, butoxy(polypropylene glycol) (936) + TX, dibutyl adipate (lUPAC name) (1046) + TX, dibutyl phthalate (1047) + TX, dibutyl succinate (lUPAC name) (1048) + TX, diethyltoluamide [CCN] + TX, dimethyl carbate [CCN] + TX, dimethyl phthalate [CCN] + TX, ethyl hexanediol (1137) + TX, hexamide [CCN] + TX, methoquin-butyl (1276) + TX, methylneodecanamide [CCN] + TX, oxamate [CCN] and picaridin [CCN] + TX; a molluscicide selected from the group of substances consisting of bis(tributyltin) oxide (lUPAC name) (913) + TX, bromoacetamide [CCN] + TX, calcium arsenate [CCN] + TX, cloethocarb (999) + TX, copper acetoarsenite [CCN] + TX, copper sulfate (172) + TX, fentin (347) + TX, ferric phosphate (lUPAC name) (352) + TX, metaldehyde (518) + TX, methiocarb (530) + TX, niclosamide (576) + TX, niclosamide-olamine (576) + TX, pentachlorophenol (623) + TX, sodium pentachlorophenoxide (623) + TX, tazimcarb (1412) + TX, thiodicarb (799) + TX, tributyltin oxide (913) + TX, trifenmorph (1454) + TX, trimethacarb (840) + TX, triphenyltin acetate (lUPAC name) (347) and triphenyltin hydroxide (lUPAC name) (347) + TX, pyriprole [394730-71-3] + TX; a nematicide selected from the group of substances consisting of AKD-3088 (compound code) + TX,
1 ,2-dibromo-3-chloropropane (lUPAC/Chemical Abstracts name) (1045) + TX, 1 ,2-dichloropropane (lUPAC/ Chemical Abstracts name) (1062) + TX, 1 ,2-dichloropropane with 1 ,3-dichloropropene (lUPAC name) (1063) + TX, 1 ,3-dichloropropene (233) + TX, 3,4-dichlorotetrahydrothiophene 1 ,1- dioxide (lUPAC/Chemical Abstracts name) (1065) + TX, 3-(4-chlorophenyl)-5-methylrhodanine (lUPAC name) (980) + TX, 5-methyl-6-thioxo-1 ,3,5-thiadiazinan-3-ylacetic acid (lUPAC name) (1286)
+ TX, 6-isopentenylaminopurine (alternative name) (210) + TX, abamectin (1) + TX, acetoprole [CCN] + TX, alanycarb (15) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, AZ 60541 (compound code) + TX, benclothiaz [CCN] + TX, benomyl (62) + TX, butylpyridaben (alternative name) + TX, cadusafos (109) + TX, carbofuran (118) + TX, carbon disulfide (945) + TX, carbosulfan (119) + TX, chloropicrin (141) + TX, chlorpyrifos (145) + TX, cloethocarb (999) + TX, Cyclobutrifluram + TX, cytokinins (alternative name) (210) + TX, dazomet (216) + TX, DBCP (1045) + TX, DCIP (218) + TX, diamidafos (1044) + TX, dichlofenthion (1051) + TX, dicliphos (alternative name) + TX, dimethoate (262) + TX, doramectin (alternative name) [CCN] + TX, emamectin (291)
+ TX, emamectin benzoate (291) + TX, eprinomectin (alternative name) [CCN] + TX, ethoprophos (312) + TX, ethylene dibromide (316) + TX, fenamiphos (326) + TX, fen pyrad (alternative name) + TX, fensulfothion (1158) + TX, fosthiazate (408) + TX, fosthietan (1196) + TX, furfural (alternative name) [CCN] + TX, GY-81 (development code) (423) + TX, heterophos [CCN] + TX, iodomethane (lUPAC name) (542) + TX, isamidofos (1230) + TX, isazofos (1231) + TX, ivermectin (alternative name) [CCN] + TX, kinetin (alternative name) (210) + TX, mecarphon (1258) + TX, metam (519) + TX, metam-potassium (alternative name) (519) + TX, metam-sodium (519) + TX, methyl bromide (537) + TX, methyl isothiocyanate (543) + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, Myrothecium verrucaha composition (alternative name) (565) + TX, NC-184 (compound code) + TX, oxamyl (602) + TX, phorate (636) + TX, phosphamidon (639) + TX, phosphocarb [CCN] + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) + TX, terbam (alternative name) + TX, terbufos (773) + TX, tetrachlorothiophene (lUPAC/ Chemical Abstracts name) (1422) + TX, thiafenox (alternative name) + TX, thionazin (1434) + TX, triazophos (820) + TX, triazuron (alternative name) + TX, xylenols [CCN] + TX, YI-5302 (compound code) and zeatin (alternative name) (210) + TX, fluensulfone [318290-98-1] + TX, fluopyram + TX; a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] and nitrapyrin (580) + TX; a plant activator selected from the group of substances consisting of acibenzolar (6) + TX, acibenzolar-S-methyl (6) + TX, probenazole (658) and Reynoutha sachalinensis extract (alternative name) (720) + TX; a rodenticide selected from the group of substances consisting of 2-isovalerylindan-1 ,3-dione (lUPAC name) (1246) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (lUPAC name) (748) + TX, alpha- chlorohydrin [CCN] + TX, aluminium phosphide (640) + TX, antu (880) + TX, arsenous oxide (882) + TX, barium carbonate (891) + TX, bisthiosemi (912) + TX, brodifacoum (89) + TX, bromadiolone (including alpha-bromadiolone) + TX, bromethalin (92) + TX, calcium cyanide (444) + TX, chloralose (127) + TX, chlorophacinone (140) + TX, cholecalciferol (alternative name) (850) + TX, coumachlor (1004) + TX, coumafuryl (1005) + TX, coumatetralyl (175) + TX, crimidine (1009) + TX, difenacoum (246) + TX, difethialone (249) + TX, diphacinone (273) + TX, ergocalciferol (301) + TX, flocoumafen (357) + TX, fluoroacetamide (379) + TX, flupropadine (1183) + TX, flupropadine hydrochloride (1183) + TX, gamma-HCH (430) + TX, HCH (430) + TX, hydrogen cyanide (444) + TX, iodomethane (lUPAC name) (542) + TX, lindane (430) + TX, magnesium phosphide (lUPAC name) (640) + TX, methyl bromide (537) + TX, norbormide (1318) + TX, phosacetim (1336) + TX, phosphine (lUPAC name) (640) + TX, phosphorus [CCN] + TX, pindone (1341) + TX, potassium arsenite [CCN] + TX, pyrinuron (1371) + TX, scilliroside (1390) + TX, sodium arsenite [CCN] + TX, sodium cyanide (444) + TX, sodium fluoroacetate (735) + TX, strychnine (745) + TX, thallium sulfate [CCN] + TX, warfarin (851) and zinc phosphide (640) + TX; a synergist selected from the group of substances consisting of 2-(2-butoxyethoxy)ethyl piperonylate (lUPAC name) (934) + TX, 5-(1 ,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone (lUPAC name) (903) + TX, farnesol with nerolidol (alternative name) (324) + TX, MB-599 (development code) (498) + TX, MGK 264 (development code) (296) + TX, piperonyl butoxide (649) + TX, piprotal (1343) + TX, propyl isomer (1358) + TX, S421 (development code) (724) + TX, sesamex (1393) + TX, sesasmolin (1394) and sulfoxide (1406) + TX; an animal repellent selected from the group of substances consisting of anthraquinone (32) + TX, chloralose (127) + TX, copper naphthenate [CCN] + TX, copper oxychloride (171) + TX, diazinon (227) + TX, dicyclopentadiene (chemical name) (1069) + TX, guazatine (422) + TX, guazatine acetates (422) + TX, methiocarb (530) + TX, pyridin-4-amine (lUPAC name) (23) + TX, thiram (804) + TX, trimethacarb (840) + TX, zinc naphthenate [CCN] and ziram (856) + TX; a virucide selected from the group of substances consisting of imanin (alternative name) [CCN] and ribavirin (alternative name) [CCN] + TX; a wound protectant selected from the group of substances consisting of mercuric oxide (512) + TX, octhilinone (590) and thiophanate-methyl (802) + TX; a biologically active substance selected from 1 ,1-bis(4-chloro-phenyl)-2-ethoxyethanol + TX, 2,4- dichlorophenyl benzenesulfonate + TX, 2-fluoro-N-methyl-N-1-naphthylacetamide + TX, 4-chlorophenyl phenyl sulfone + TX, acetoprole + TX, aldoxycarb + TX, amidithion + TX, amidothioate + TX, amiton + TX, amiton hydrogen oxalate + TX, amitraz + TX, aramite + TX, arsenous oxide + TX, azobenzene + TX, azothoate + TX, benomyl + TX, benoxa-fos + TX, benzyl benzoate + TX, bixafen + TX, brofenvalerate + TX, bromo-cyclen + TX, bromophos + TX, bromopropylate + TX, buprofezin + TX, butocarboxim + TX, butoxycarboxim + TX, butylpyridaben + TX, calcium polysulfide + TX, camphechlor + TX, carbanolate + TX, carbophenothion + TX, cymiazole + TX, chino-methionat + TX, chlorbenside + TX, chlordimeform + TX, chlordimeform hydrochloride + TX, chlorfenethol + TX, chlorfenson + TX, chlorfensulfide + TX, chlorobenzilate + TX, chloromebuform + TX, chloromethiuron + TX, chloropropylate + TX, chlorthiophos + TX, cinerin I + TX, cinerin II + TX, cinerins + TX, closantel + TX, coumaphos + TX, crotamiton + TX, crotoxyphos + TX, cufraneb + TX, cyanthoate + TX, DCPM + TX, DDT + TX, demephion + TX, demephion-O + TX, demephion-S + TX, demeton-methyl + TX, demeton- O + TX, demeton-O-methyl + TX, demeton-S + TX, demeton-S-methyl + TX, demeton-S-methylsulfon + TX, dichlofluanid + TX, dichlorvos + TX, dicliphos + TX, dienochlor + TX, dimefox + TX, dinex + TX, dinex-diclexine + TX, dinocap-4 + TX, dinocap-6 + TX, dinocton + TX, dino-penton + TX, dinosulfon + TX, dinoterbon + TX, dioxathion + TX, diphenyl sulfone + TX, disulfiram + TX, DNOC + TX, dofenapyn + TX, doramectin + TX, endothion + TX, eprinomectin + TX, ethoate-methyl + TX, etrimfos + TX, fenazaflor + TX, fenbutatin oxide + TX, fenothiocarb + TX, fenpyrad + TX, fen-pyroximate + TX, fenpyrazamine + TX, fenson + TX, fentrifanil + TX, flubenzimine + TX, flucycloxuron + TX, fluenetil + TX, fluorbenside + TX, FMC 1137 + TX, formetanate + TX, formetanate hydrochloride + TX, formparanate + TX, gamma-HCH + TX, glyodin + TX, halfenprox + TX, hexadecyl cyclopropanecarboxylate + TX, isocarbophos + TX, jasmolin I + TX, jasmolin II + TX, jodfenphos + TX, lindane + TX, malonoben + TX, mecarbam + TX, mephosfolan + TX, mesulfen + TX, methacrifos + TX, methyl bromide + TX, metolcarb + TX, mexacarbate + TX, milbemycin oxime + TX, mipafox + TX, monocrotophos + TX, morphothion + TX, moxidectin + TX, naled + TX, 4-chloro-2-(2-chloro-2-methyl- propyl)-5-[(6-iodo-3-pyridyl)methoxy]pyridazin-3-one + TX, nifluridide + TX, nikkomycins + TX, nitrilacarb + TX, nitrilacarb 1 :1 zinc chloride complex + TX, omethoate + TX, oxydeprofos + TX, oxydisulfoton + TX, pp'-DDT + TX, parathion + TX, permethrin + TX, phenkapton + TX, phosalone + TX, phosfolan + TX, phosphamidon + TX, polychloroterpenes + TX, polynactins + TX, proclonol + TX, promacyl + TX, propoxur + TX, prothidathion + TX, prothoate + TX, pyrethrin I + TX, pyrethrin II + TX, pyrethrins + TX, pyridaphenthion + TX, pyrimitate + TX, quinalphos + TX, quintiofos + TX, R-1492 + TX, phosglycin + TX, rotenone + TX, schradan + TX, sebufos + TX, selamectin + TX, sophamide + TX, SSI- 121 + TX, sulfiram + TX, sulfluramid + TX, sulfotep + TX, sulfur + TX, diflovidazin + TX, tau-fluvalinate + TX, TEPP + TX, terbam + TX, tetradifon + TX, tetrasul + TX, thiafenox + TX, thiocarboxime + TX, thiofanox + TX, thiometon + TX, thioquinox + TX, thuringiensin + TX, triamiphos + TX, triarathene + TX, triazophos + TX, triazuron + TX, trifenofos + TX, trinactin + TX, vamidothion + TX, vaniliprole + TX, bethoxazin + TX, copper dioctanoate + TX, copper sulfate + TX, cybutryne + TX, dichlone + TX, dichlorophen + TX, endothal + TX, fentin + TX, hydrated lime + TX, nabam + TX, quinoclamine + TX, quinonamid + TX, simazine + TX, triphenyltin acetate + TX, triphenyltin hydroxide + TX, crufomate + TX, piperazine + TX, thiophanate + TX, chloralose + TX, fenthion + TX, pyridin-4-amine + TX, strychnine + TX, 1 -hydroxy-1 H-pyridine-2-thione + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide + TX, 8- hydroxyquinoline sulfate + TX, bronopol + TX, copper hydroxide + TX, cresol + TX, dipyrithione + TX, dodicin + TX, fenaminosulf + TX, formaldehyde + TX, hydrargaphen + TX, kasugamycin + TX, kasugamycin hydrochloride hydrate + TX, nickel bis(dimethyldithiocarbamate) + TX, nitrapyrin + TX, octhilinone + TX, oxolinic acid + TX, oxytetracycline + TX, potassium hydroxyquinoline sulfate + TX, probenazole + TX, streptomycin + TX, streptomycin sesquisulfate + TX, tecloftalam + TX, thiomersal + TX, Adoxophyes orana GV + TX, Agrobacterium radiobacter + TX, Amblyseius spp. + TX, Anagrapha falcifera NPV + TX, Anagrus atomus + TX, Aphelinus abdominalis + TX, Aphidius colemani + TX, Aphidoletes aphidimyza + TX, Autographa californica NPV + TX, Bacillus sphaericus Neide + TX, Beauveria brongniartii + TX, Chrysoperla carnea + TX, Cryptolaemus montrouzieri + TX, Cydia pomonella GV + TX, Dacnusa sibirica + TX, Diglyphus isaea + TX, Encarsia formosa + TX, Eretmocerus eremicus + TX, Heterorhabditis bacteriophora and H. megidis + TX, Hippodamia convergens + TX, Leptomastix dactylopii + TX, Macrolophus caliginosus + TX, Mamestra brassicae NPV + TX, Metaphycus helvolus + TX, Metarhizium anisopliae var. acridum + TX, Metarhizium anisopliae var. anisopliae + TX, Neodiprion sertifer NPV and N. lecontei NPV + TX, Orius spp. + TX, Paecilomyces fumosoroseus + TX, Phytoseiulus persimilis + TX, Steinernema bibionis + TX, Steinernema carpocapsae + TX, Steinernema feltiae + TX, Steinernema glaseri + TX, Steinernema riobrave + TX, Steinernema riobravis + TX, Steinernema scapterisci + TX, Steinernema spp. + TX, Trichogramma spp. + TX, Typhlodromus occidentalis + TX , Verticillium lecanii + TX, apholate + TX, bisazir + TX, busulfan + TX, dimatif + TX, hemel + TX, hempa + TX, metepa + TX, methiotepa + TX, methyl apholate + TX, morzid + TX, penfluron + TX, tepa + TX, thiohempa + TX, thiotepa + TX, tretamine + TX, uredepa + TX, (E)-dec-5-en-1-yl acetate with (E)-dec-5-en-1-ol + TX, (E)-tridec-4-en-1-yl acetate + TX, (E)-6- methylhept-2-en-4-ol + TX, (E,Z)-tetradeca-4,10-dien-1-yl acetate + TX, (Z)-dodec-7-en-1-yl acetate + TX, (Z)-hexadec-11-enal + TX, (Z)-hexadec-l 1 -en-1 -yl acetate + TX, (Z)-hexadec-13-en-11 -yn-1 -yl acetate + TX, (Z)-icos-13-en-10-one + TX, (Z)-tetradec-7-en-1-al + TX, (Z)-tetradec-9-en-1-ol + TX, (Z)- tetradec-9-en-1-yl acetate + TX, (7E,9Z)-dodeca-7,9-dien-1-yl acetate + TX, (9Z,11 E)-tetradeca-9,11- dien-1-yl acetate + TX, (9Z,12E)-tetradeca-9,12-dien-1-yl acetate + TX, 14-methyloctadec-1-ene + TX, 4-methylnonan-5-ol with 4-methylnonan-5-one + TX, alpha-multistriatin + TX, brevicomin + TX, codlelure + TX, codlemone + TX, cuelure + TX, disparlure + TX, dodec-8-en-1-yl acetate + TX, dodec-9-en-1-yl acetate + TX, dodeca-8 + TX, 10-dien-1 -yl acetate + TX, dominicalure + TX, ethyl 4-methyloctanoate + TX, eugenol + TX, frontalin + TX, grandlure + TX, grandlure I + TX, grandlure II + TX, grandlure III + TX, grandlure IV + TX, hexalure + TX, ipsdienol + TX, ipsenol + TX, japonilure + TX, lineatin + TX, litlure + TX, looplure + TX, medlure + TX, megatomoic acid + TX, methyl eugenol + TX, muscalure + TX, octadeca-2,13-dien-1-yl acetate + TX, octadeca-3,13-dien-1-yl acetate + TX, orfralure + TX, oryctalure + TX, ostramone + TX, siglure + TX, sordidin + TX, sulcatol + TX, tetradec-11 -en-1 -yl acetate + TX, trimedlure + TX, trimedlure A + TX, trimedlure Bi + TX, trimedlure B2 + TX, trimedlure C + TX, trunc-call + TX, 2-(octylthio)-ethanol + TX, butopyronoxyl + TX, butoxy(polypropylene glycol) + TX, dibutyl adipate + TX, dibutyl phthalate + TX, dibutyl succinate + TX, diethyltoluamide + TX, dimethyl carbate + TX, dimethyl phthalate + TX, ethyl hexanediol + TX, hexamide + TX, methoquin-butyl + TX, methylneodecanamide + TX, oxamate + TX, picaridin + TX, 1-dichloro-1-nitroethane + TX, 1 ,1-dichloro- 2,2-bis(4-ethylphenyl)-ethane + TX, 1 ,2-dichloropropane with 1 ,3-dichloropropene + TX, 1-bromo-2- chloroethane + TX, 2,2,2-trichloro-1-(3,4-dichloro-phenyl)ethyl acetate + TX, 2,2-dichlorovinyl 2- ethylsulfinylethyl methyl phosphate + TX, 2-(1 ,3-dithiolan-2-yl)phenyl dimethylcarbamate + TX, 2-(2- butoxyethoxy)ethyl thiocyanate + TX, 2-(4,5-dimethyl-1 ,3-dioxolan-2-yl)phenyl methylcarbamate + TX, 2-(4-chloro-3,5-xylyloxy)ethanol + TX, 2-chlorovinyl diethyl phosphate + TX, 2-imidazolidone + TX, 2- isovalerylindan-1 ,3-dione + TX, 2-methyl(prop-2-ynyl)aminophenyl methylcarbamate + TX, 2- thiocyanatoethyl laurate + TX, 3-bromo-1-chloroprop-1-ene + TX, 3-methyl-1-phenylpyrazol-5-yl dimethyl-carbamate + TX, 4-methyl(prop-2-ynyl)amino-3,5-xylyl methylcarbamate + TX, 5,5-dimethyl-3- oxocyclohex-1-enyl dimethylcarbamate + TX, acethion + TX, acrylonitrile + TX, aldrin + TX, allosamidin + TX, allyxycarb + TX, alpha-ecdysone + TX, aluminium phosphide + TX, aminocarb + TX, anabasine + TX, athidathion + TX, azamethiphos + TX, Bacillus thuringiensis delta endotoxins + TX, barium hexafluorosilicate + TX, barium polysulfide + TX, barthrin + TX, Bayer 22/190 + TX, Bayer 22408 + TX, beta-cyfluthrin + TX, beta-cypermethrin + TX, bioethanomethrin + TX, biopermethrin + TX, bis(2- chloroethyl) ether + TX, borax + TX, bromfenvinfos + TX, bromo-DDT + TX, bufencarb + TX, butacarb + TX, butathiofos + TX, butonate + TX, calcium arsenate + TX, calcium cyanide + TX, carbon disulfide + TX, carbon tetrachloride + TX, cartap hydrochloride + TX, cevadine + TX, chlorbicyclen + TX, chlordane + TX, chlordecone + TX, chloroform + TX, chloropicrin + TX, chlorphoxim + TX, chlorprazophos + TX, cis-resmethrin + TX, cismethrin + TX, clocythrin + TX, copper acetoarsenite + TX, copper arsenate + TX, copper oleate + TX, coumithoate + TX, cryolite + TX, CS 708 + TX, cyanofenphos + TX, cyanophos + TX, cyclethrin + TX, cythioate + TX, d-tetramethrin + TX, DAEP + TX, dazomet + TX, decarbofuran + TX, diamidafos + TX, dicapthon + TX, dichlofenthion + TX, dicresyl + TX, dicyclanil + TX, dieldrin + TX, diethyl 5-methylpyrazol-3-yl phosphate + TX, dilor + TX, dimefluthrin + TX, dimetan + TX, dimethrin + TX, dimethylvinphos + TX, dimetilan + TX, dinoprop + TX, dinosam + TX, dinoseb + TX, diofenolan + TX, dioxabenzofos + TX, dithicrofos + TX, DSP + TX, ecdysterone + TX, El 1642 + TX, EMPC + TX, EPBP + TX, etaphos + TX, ethiofencarb + TX, ethyl formate + TX, ethylene dibromide + TX, ethylene dichloride + TX, ethylene oxide + TX, EXD + TX, fenchlorphos + TX, fenethacarb + TX, fenitrothion + TX, fenoxacrim + TX, fenpirithrin + TX, fensulfothion + TX, fenthion-ethyl + TX, flucofuron + TX, fosmethilan + TX, fospirate + TX, fosthietan + TX, furathiocarb + TX, furethrin + TX, guazatine + TX, guazatine acetates + TX, sodium tetrathiocarbonate + TX, halfenprox + TX, HCH + TX, HEOD + TX, heptachlor + TX, heterophos + TX, HHDN + TX, hydrogen cyanide + TX, hyquincarb + TX, IPSP + TX, isazofos + TX, isobenzan + TX, isodrin + TX, isofenphos + TX, isolane + TX, isoprothiolane + TX, isoxathion + TX, juvenile hormone I + TX, juvenile hormone II + TX, juvenile hormone III + TX, kelevan + TX, kinoprene + TX, lead arsenate + TX, leptophos + TX, lirimfos + TX, lythidathion + TX, m-cumenyl methylcarbamate + TX, magnesium phosphide + TX, mazidox + TX, mecarphon + TX, menazon + TX, mercurous chloride + TX, mesulfenfos + TX, metam + TX, metam-potassium + TX, metam-sodium + TX, methanesulfonyl fluoride + TX, methocrotophos + TX, methoprene + TX, methothrin + TX, methoxychlor + TX, methyl isothiocyanate + TX, methylchloroform + TX, methylene chloride + TX, metoxadiazone + TX, mirex + TX, naftalofos + TX, naphthalene + TX, NC-170 + TX, nicotine + TX, nicotine sulfate + TX, nithiazine + TX, nornicotine + TX, 0-5-dichloro-4-iodophenyl O-ethyl ethylphosphonothioate + TX, O,O-diethyl 0-4-methyl-2-oxo-2H-chromen-7-yl phosphorothioate + TX, O,O-diethyl 0-6-methyl-2-propylpyrimidin-4-yl phosphorothioate + TX, O,O,O',O'-tetrapropyl dithiopyrophosphate + TX, oleic acid + TX, para-dichlorobenzene + TX, parathion-methyl + TX, pentachlorophenol + TX, pentachlorophenyl laurate + TX, PH 60-38 + TX, phenkapton + TX, phosnichlor + TX, phosphine + TX, phoxim-methyl + TX, pirimetaphos + TX, polychlorodicyclopentadiene isomers + TX, potassium arsenite + TX, potassium thiocyanate + TX, precocene I + TX, precocene II + TX, precocene III + TX, primidophos + TX, profluthrin + TX, promecarb + TX, prothiofos + TX, pyrazophos + TX, pyresmethrin + TX, quassia + TX, quinalphos-methyl + TX, quinothion + TX, rafoxanide + TX, resmethrin + TX, rotenone + TX, kadethrin + TX, ryania + TX, ryanodine + TX, sabadilla) + TX, schradan + TX, sebufos + TX, SI-0009 + TX, thiapronil + TX, sodium arsenite + TX, sodium cyanide + TX, sodium fluoride + TX, sodium hexafluorosilicate + TX, sodium pentachlorophenoxide + TX, sodium selenate + TX, sodium thiocyanate + TX, sulcofuron + TX, sulcofuron-sodium + TX, sulfuryl fluoride + TX, sulprofos + TX, tar oils + TX, tazimcarb + TX, TDE + TX, tebupirimfos + TX, temephos + TX, terallethrin + TX, tetrachloroethane + TX, thicrofos + TX, thiocyclam + TX, thiocyclam hydrogen oxalate + TX, thionazin + TX, thiosultap + TX, thiosultap-sodium + TX, tralomethrin + TX, transpermethrin + TX, triazamate + TX, trichlormetaphos-3 + TX, trichloronat + TX, trimethacarb + TX, tolprocarb + TX, triclopyricarb + TX, triprene + TX, veratridine + TX, veratrine + TX, XMC + TX, zetamethrin + TX, zinc phosphide + TX, zolaprofos + TX, and meperfluthrin + TX, tetramethylfluthrin + TX, bis(tributyltin) oxide + TX, bromoacetamide + TX, ferric phosphate + TX, niclosamide-olamine + TX, tributyltin oxide + TX, pyrimorph + TX, trifenmorph + TX, 1 ,2-dibromo-3-chloropropane + TX, 1 ,3-dichloropropene + TX, 3,4- dichlorotetrahydrothio-phene 1 ,1-dioxide + TX, 3-(4-chlorophenyl)-5-methylrhodanine + TX, 5-methyl-6- thioxo-1 ,3,5-thiadiazinan-3-ylacetic acid + TX, 6-isopentenylaminopurine + TX, 2-fluoro-N-(3- methoxyphenyl)-9H-purin-6-amine + TX, benclothiaz + TX, cytokinins + TX, DCIP + TX, furfural + TX, isamidofos + TX, kinetin + TX, Myrothecium verrucaria composition + TX, tetrachlorothiophene + TX, xylenols + TX, zeatin + TX, potassium ethylxanthate + TX .acibenzolar + TX, acibenzolar-S-methyl + TX, Reynoutria sachalinensis extract + TX, alpha-chlorohydrin + TX, antu + TX, barium carbonate + TX, bisthiosemi + TX, brodifacoum + TX, bromadiolone + TX, bromethalin + TX, chlorophacinone + TX, cholecalciferol + TX, coumachlor + TX, coumafuryl + TX, coumatetralyl + TX, crimidine + TX, difenacoum + TX, difethialone + TX, diphacinone + TX, ergocalciferol + TX, flocoumafen + TX, fluoroacetamide + TX, flupropadine + TX, flupropadine hydrochloride + TX, norbormide + TX, phosacetim + TX, phosphorus + TX, pindone + TX, pyrinuron + TX, scilliroside + TX, -sodium fluoroacetate + TX, thallium sulfate + TX, warfarin + TX, -2-(2-butoxyethoxy)ethyl piperonylate + TX, 5-(1 ,3-benzodioxol-5-yl)-3- hexylcyclohex-2-enone + TX, farnesol with nerolidol + TX, verbutin + TX, MGK 264 + TX, piperonyl butoxide + TX, piprotal + TX, propyl isomer + TX, S421 + TX, sesamex+ TX, sesasmolin + TX, sulfoxide + TX, anthraquinone + TX, copper naphthenate + TX, copper oxychloride + TX, dicyclopentadiene + TX, thiram + TX, zinc naphthenate + TX, ziram + TX, imanin + TX, ribavirin + TX, chloroinconazide + TX, mercuric oxide + TX, thiophanate-methyl + TX, azaconazole + TX, bitertanol + TX, bromuconazole + TX, cyproconazole + TX, difenoconazole + TX, diniconazole -+ TX, epoxiconazole + TX, fenbuconazole + TX, fluquinconazole + TX, flusilazole + TX, flutriafol + TX, furametpyr + TX, hexaconazole + TX, imazalil- + TX, imiben-conazole + TX, ipconazole + TX, metconazole + TX, myclobutanil + TX, paclobutrazole + TX, pefurazoate + TX, penconazole + TX, prothioconazole + TX, pyrifenox + TX, prochloraz + TX, propiconazole + TX, pyrisoxazole + TX, -simeconazole + TX, tebucon-azole + TX, tetraconazole + TX, triadimefon + TX, triadimenol + TX, triflumizole + TX, triticonazole + TX, ancymidol + TX, fenarimol + TX, nuarimol + TX, bupirimate + TX, dimethirimol + TX, ethirimol + TX, dodemorph + TX, fenpropidin + TX, fenpropimorph + TX, spiroxamine + TX, tridemorph + TX, cyprodinil + TX, mepanipyrim + TX, pyrimethanil + TX, fenpiclonil + TX, fludioxonil + TX, benalaxyl + TX, furalaxyl + TX, -metalaxyl -+ TX, Rmetalaxyl + TX, ofurace + TX, oxadixyl + TX, carbendazim + TX, debacarb + TX, fuberidazole -+ TX, thiabendazole + TX, chlozolinate + TX, dichlozoline + TX, myclozoline- + TX, procymidone + TX, vinclozoline + TX, boscalid + TX, carboxin + TX, fenfuram + TX, flutolanil + TX, mepronil + TX, oxycarboxin + TX, penthiopyrad + TX, thifluzamide + TX, dodine + TX, iminoctadine + TX, azoxystrobin + TX, dimoxystrobin + TX, enestroburin + TX, fenaminstrobin + TX, flufenoxystrobin + TX, fluoxastrobin + TX, kresoxim-methyl + TX, metominostrobin + TX, trifloxystrobin + TX, orysastrobin + TX, picoxystrobin + TX, pyraclostrobin + TX, pyrametostrobin + TX, pyraoxystrobin + TX, ferbam + TX, mancozeb + TX, maneb + TX, metiram + TX, propineb + TX, zineb + TX, captafol + TX, captan + TX, fluoroimide + TX, folpet + TX, tolylfluanid + TX, bordeaux mixture + TX, copper oxide + TX, mancopper + TX, oxine-copper + TX, nitrothal-isopropyl + TX, edifenphos + TX, iprobenphos + TX, phosdiphen + TX, tolclofos-methyl + TX, anilazine + TX, benthiavalicarb + TX, blasticidin-S + TX, chloroneb -+ TX, chloro-tha-lonil + TX, cyflufenamid + TX, cymoxanil + TX, cyclobutrifluram + TX, diclocymet + TX, diclomezine -+ TX, dicloran + TX, diethofencarb + TX, dimethomorph -+ TX, flumorph + TX, dithianon + TX, ethaboxam + TX, etridiazole + TX, famoxadone + TX, fenamidone + TX, fenoxanil + TX, ferimzone + TX, fluazinam + TX, fluopicolide + TX, flusulfamide + TX, fluxapyroxad + TX, -fenhexamid + TX, fosetyl-aluminium -+ TX, hymexazol + TX, iprovalicarb + TX, cyazofamid + TX, methasulfocarb + TX, metrafenone + TX, pencycuron + TX, phthalide + TX, polyoxins + TX, propamocarb + TX, pyribencarb + TX, proquinazid + TX, pyroquilon + TX, pyriofenone + TX, quinoxyfen + TX, quintozene + TX, tiadinil + TX, triazoxide + TX, tricyclazole + TX, triforine + TX, validamycin + TX, valifenalate + TX, zoxamide + TX, mandipropamid + TX, flubeneteram + TX, isopyrazam + TX, sedaxane + TX, benzovindiflupyr + TX, pydiflumetofen + TX, 3-difluoromethyl-1 -methyl-1 H-pyrazole-4-carboxylic acid (3',4',5'-trifluoro-biphenyl-2-yl)-amide + TX, isoflucypram + TX, isotianil + TX, dipymetitrone + TX, 6-ethyl-5,7-dioxo-pyrrolo[4,5][1 ,4]dithiino[1 ,2-c]isothiazole-3-carbonitrile + TX, 2-(difluoromethyl)-N-[3- ethyl-1 ,1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX, 4-(2,6-difluorophenyl)-6-methyl-5-phenyl- pyridazine-3-carbonitrile + TX, (R)-3-(difluoromethyl)-1-methyl-N-[1 ,1 ,3-trimethylindan-4-yl]pyrazole-4- carboxamide + TX, 4-(2-bromo-4-fluoro-phenyl)-N-(2-chloro-6-fluoro-phenyl)-2,5-dimethyl-pyrazol-3- amine + TX, 4- (2- bromo- 4- fluorophenyl) - N- (2- chloro- 6- fluorophenyl) - 1 , 3- dimethyl- 1 H- pyrazol- 5- amine + TX, fluindapyr + TX, coumethoxystrobin (jiaxiangjunzhi) + TX, Ivbenmixianan + TX, dichlobentiazox + TX, mandestrobin + TX, 3-(4,4-difluoro-3,4-dihydro-3,3-dimethylisoquinolin-1- yl)quinolone + TX, 2-[2-fluoro-6-[(8-fluoro-2-methyl-3-quinolyl)oxy]phenyl]propan-2-ol + TX, oxathiapiprolin + TX, tert-butyl N-[6-[[[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2- pyridyl]carbamate + TX, pyraziflumid + TX, inpyrfluxam + TX, trolprocarb + TX, mefentrifluconazole + TX, ipfentrifluconazole+ TX, 2-(difluoromethyl)-N-[(3R)-3-ethyl-1 ,1-dimethyl-indan-4-yl]pyridine-3- carboxamide + TX, N'-(2,5-dimethyl-4-phenoxy-phenyl)-N-ethyl-N-methyl-formamidine + TX, N'-[4-(4,5- dichlorothiazol-2-yl)oxy-2,5-dimethyl-phenyl]-N-ethyl-N-methyl-formamidine + TX, [2-[3-[2-[1-[2-[3,5- bis(difluoromethyl)pyrazol-1-yl]acetyl]-4-piperidyl]thiazol-4-yl]-4,5-dihydroisoxazol-5-yl]-3-chloro- phenyl] methanesulfonate + TX, but-3-ynyl N-[6-[[(Z)-[(1-methyltetrazol-5-yl)-phenyl- methylene]amino]oxymethyl]-2-pyridyl]carbamate + TX, methyl N-[[5-[4-(2,4-dimethylphenyl)triazol-2- yl]-2-methyl-phenyl]methyl]carbamate + TX, 3-chloro-6-methyl-5-phenyl-4-(2,4,6- trifluorophenyl)pyridazine + TX, pyridachlometyl + TX, 3-(difluoromethyl)-1-methyl-N-[1 ,1 ,3- trimethylindan-4-yl]pyrazole-4-carboxamide + TX, 1 -[2-[[1 -(4-chlorophenyl)pyrazol-3-yl]oxymethyl]-3- methyl-phenyl]-4-methyl-tetrazol-5-one + TX, 1-methyl-4-[3-methyl-2-[[2-methyl-4-(3,4,5- trimethylpyrazol-1-yl)phenoxy]methyl]phenyl]tetrazol-5-one + TX, aminopyrifen + TX, ametoctradin + TX, amisulbrom + TX, penflufen + TX, (Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino- N,3-dimethyl-pent-3-enamide + TX, florylpicoxamid + TX, fenpicoxamid + TX, tebufloquin + TX, ipflufenoquin + TX, quinofumelin + TX, isofetamid + TX, N-[2-[2,4-dichloro-phenoxy]phenyl]-3- (difluoromethyl)-1-methyl-pyrazole-4-carboxamide + TX, N-[2-[2-chloro-4-
(trifluoromethyl)phenoxy]phenyl]-3-(difluoromethyl)-1 -methyl-pyrazole-4-carboxamide + TX, benzothiostrobin + TX, phenamacril + TX, 5-amino-1 ,3,4-thiadiazole-2-thiol zinc salt (2:1) + TX, fluopyram + TX, flutianil + TX, fluopimomide + TX, pyrapropoyne + TX, picarbutrazox + TX, 2- (difluoromethyl)-N-(3-ethyl-1 ,1-dimethyl-indan-4-yl)pyridine-3-carboxamide + TX, 2- (difluoromethyl) - N- ((3R) - 1 , 1 , 3- trimethylindan- 4- yl) pyridine- 3- carboxamide + TX, 4-[[6-[2-(2,4-difluorophenyl)-1 ,1- difluoro-2-hydroxy-3-(1 ,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile + TX, metyltetraprole + TX, 2- (difluoromethyl) - N- ((3R) - 1 , 1 , 3- trimethylindan- 4- yl) pyridine- 3- carboxamide + TX, a- (1 , 1- dimethylethyl) - a- [4'- (trifluoromethoxy) [1 , G- biphenyl] - 4- yl] -5- pyrimidinemethanol + TX, fluoxapiprolin + TX, enoxastrobin + TX, 4-[[6-[2-(2,4-difluorophenyl)-1 ,1-difluoro-2-hydroxy-3-(1 ,2,4- triazol-1-yl)propyl]-3-pyridyl]oxy] benzonitrile + TX, 4-[[6-[2-(2,4-difluorophenyl)-1 ,1-difluoro-2-hydroxy- 3-(5-sulfanyl-1 ,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy] benzonitrile + TX, 4-[[6-[2-(2,4-difluorophenyl)-1 ,1- difluoro-2-hydroxy-3-(5-thioxo-4H-1 ,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile + TX, trinexapac + TX, coumoxystrobin + TX, zhongshengmycin + TX, thiodiazole copper + TX, zinc thiazole + TX, amectotractin + TX, iprodione + TX, N-octyl-N'-[2-(octylamino)ethyl]ethane-1 ,2-diamine + TX; N'-[5- bromo-2-methyl-6-[(1 S)-1 -methyl-2-propoxy-ethoxy]-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX, N'- [5-bromo-2-methyl-6-[(1 R)-1 -methyl-2-propoxy-ethoxy]-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX, N'- [5-chloro-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5- bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-isopropyl-N-methyl-formamidine + TX (these compounds may be prepared from the methods described in WO2015/155075); N'-[5-bromo-2- methyl-6-(2-propoxypropoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX (this compound may be prepared from the methods described in IPCOM000249876D); N-isopropyl-N’-[5-methoxy-2-methyl-4- (2, 2, 2-trifluoro-1 -hydroxy-1 -phenyl-ethyl)phenyl]-N-methyl-formamidine+ TX, N’-[4-(1 -cyclopropyl- 2, 2, 2-trifluoro-1-hydroxy-ethyl)-5-methoxy-2-methyl-phenyl]-N-isopropyl-N-methyl-formamidine + TX (these compounds may be prepared from the methods described in WO2018/228896); N-ethyl-N’-[5- methoxy-2-methyl-4-[(2-trifluoromethyl)oxetan-2-yl]phenyl]-N-methyl-formamidine + TX, N-ethyl-N’-[5- methoxy-2-methyl-4-[(2-trifuoromethyl)tetrahydrofuran-2-yl]phenyl]-N-methyl-formamidine + TX (these compounds may be prepared from the methods described in WO2019/110427); N-[(1 R)-1-benzyl-3- chloro-1 -methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1 S)-1 -benzyl-3-chloro-1 - methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1 R)-1 -benzyl-3, 3, 3-trifluoro-1-methyl- propyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1 S)-1 -benzyl-3, 3, 3-trifluoro-1 -methyl-propyl]-8- fluoro-quinoline-3-carboxamide + TX, N-[(1 R)-1 -benzyl-1 ,3-dimethyl-butyl]-7,8-difluoro-quinoline-3- carboxamide + TX, N-[(1 S)-1 -benzyl-1 ,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide + TX, 8- fluoro-N-[(1 R)-1-[(3-fluorophenyl)methyl]-1 ,3-dimethyl-butyl]quinoline-3-carboxamide + TX, 8-fluoro-N- [(1 S)-1 -[(3-fluorophenyl)methyl]-1 ,3-dimethyl-butyl]quinoline-3-carboxamide + TX, N-[(1 R)-1 -benzyl- 1 ,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1S)-1 -benzyl-1 ,3-dimethyl-butyl]-8- fluoro-quinoline-3-carboxamide + TX, N-((1 R)-1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro- quinoline-3-carboxamide + TX, N-((1S)-1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro-quinoline-3- carboxamide + TX (these compounds may be prepared from the methods described in WO2017/153380); 1-(6,7-dimethylpyrazolo[1 ,5-a]pyridin-3-yl)-4, 4, 5-trifluoro-3, 3-dimethyl-isoquinoline + TX, 1-(6,7-dimethylpyrazolo[1 ,5-a]pyridin-3-yl)-4, 4, 6-trifluoro-3, 3-dimethyl-isoquinoline + TX, 4,4- difluoro-3,3-dimethyl-1-(6-methylpyrazolo[1 ,5-a]pyridin-3-yl)isoquinoline + TX, 4,4-difluoro-3,3- dimethyl-1-(7-methylpyrazolo[1 ,5-a]pyridin-3-yl)isoquinoline + TX, 1-(6-chloro-7-methyl-pyrazolo[1 ,5- a]pyridin-3-yl)-4,4-difluoro-3, 3-dimethyl-isoquinoline + TX (these compounds may be prepared from the methods described in WO2017/025510); 1 -(4, 5-dimethylbenzimidazol-1-yl)-4, 4, 5-trifluoro-3, 3-dimethyl- isoquinoline + TX, 1 -(4, 5-dimethylbenzimidazol-1-yl)-4,4-difluoro-3, 3-dimethyl-isoquinoline + TX, 6- chloro-4,4-difluoro-3,3-dimethyl-1 -(4-methylbenzimidazol-1 -yl)isoquinoline + TX, 4,4-difluoro-1 -(5- fluoro-4-methyl-benzimidazol-1 -yl)-3, 3-dimethyl-isoquinoline + TX, 3-(4,4-difluoro-3,3-dimethyl-1 - isoquinolyl)-7,8-dihydro-6H-cyclopenta[e]benzimidazole + TX (these compounds may be prepared from the methods described in WO2016/156085); N-methoxy-N-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3- yl]phenyl]methyl]cyclopropanecarboxamide + TX, N,2-dimethoxy-N-[[4-[5-(trifluoromethyl)-1 ,2,4- oxadiazol-3-yl]phenyl]methyl]propanamide + TX, N-ethyl-2-methyl-N-[[4-[5-(trifluoromethyl)-1 ,2,4- oxadiazol-3-yl]phenyl]methyl]propanamide + TX, 1-methoxy-3-methyl-1-[[4-[5-(trifluoromethyl)-1 ,2,4- oxadiazol-3-yl]phenyl]methyl]urea + TX, 1 ,3-dimethoxy-1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3- yl]phenyl]methyl]urea + TX, 3-ethyl-1-methoxy-1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3- yl]phenyl]methyl]urea + TX, N-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide + TX, 4,4-dimethyl-2-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one + TX, 5,5-dimethyl-2-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one + TX, ethyl 1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]pyrazole-4-carboxylate + TX, N,N-dimethyl- 1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]-1 ,2,4-triazol-3-amine + TX. The compounds in this paragraph may be prepared from the methods described in WO 2017/055473, WO 2017/055469, WO 2017/093348 and WO 2017/118689; 2-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3- pyridyl]-1-(1 ,2,4-triazol-1-yl)propan-2-ol + TX (this compound may be prepared from the methods described in WO 2017/029179); 2-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1 ,2,4-triazol-1- yl)propan-2-ol + TX (this compound may be prepared from the methods described in WO 2017/029179); 3-[2-(1 -chlorocyclopropyl)-3-(2-fluorophenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile + TX (this compound may be prepared from the methods described in WO 2016/156290); 3-[2-(1- chlorocyclopropyl)-3-(3-chloro-2-fluoro-phenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile + TX (this compound may be prepared from the methods described in WO 2016/156290); (4- phenoxyphenyl)methyl 2-amino-6-methyl-pyridine-3-carboxylate + TX (this compound may be prepared from the methods described in WO 2014/006945); 2,6-Dimethyl-1 H,5H-[1 ,4]dithiino[2,3-c:5,6- c']dipyrrole-1 ,3,5,7(2H,6H)-tetrone + TX (this compound may be prepared from the methods described in WO 2011/138281); N-methyl-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]benzenecarbothioamide + TX; N-methyl-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]benzamide + TX; (Z,2E)-5-[1-(2,4- dichlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide + TX (this compound may be prepared from the methods described in WO 2018/153707); N'-(2-chloro-5-methyl-4-phenoxy- phenyl)-N-ethyl-N-methyl-formamidine + TX; N'-[2-chloro-4-(2-fluorophenoxy)-5-methyl-phenyl]-N- ethyl-N-methyl-formamidine + TX (this compound may be prepared from the methods described in WO 2016/202742); 2-(difluoromethyl)-N-[(3S)-3-ethyl-1 ,1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX (this compound may be prepared from the methods described in WO 2014/095675); (5-methyl-2- pyridyl)-[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methanone + TX, (3-methylisoxazol-5-yl)-[4- [5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methanone + TX (these compounds may be prepared from the methods described in WO 2017/220485); 2-oxo-N-propyl-2-[4-[5-(trifluoromethyl)-1 ,2,4- oxadiazol-3-yl]phenyl]acetamide + TX (this compound may be prepared from the methods described in WO 2018/065414); ethyl 1-[[5-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]-2-thienyl]methyl]pyrazole-4- carboxylate + TX (this compound may be prepared from the methods described in WO 2018/158365) ; 2,2-difluoro-N-methyl-2-[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]acetamide + TX, N-[(E)- methoxyiminomethyl]-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]benzamide + TX, N-[(Z)- methoxyiminomethyl]-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]benzamide + TX, N-[N-methoxy-C- methyl-carbonimidoyl]-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]benzamide + TX (these compounds may be prepared from the methods described in WO 2018/202428); microbials including: Acinetobacter Iwoffii + TX, Acremonium alternatum + TX + TX, Acremonium cephalosporium + TX + TX, Acremonium diospyri + TX, Acremonium obclavatum + TX, Adoxophyes orana granulovirus (AdoxGV) (Capex®) + TX, Agrobacterium radiobacter strain K84 (Galltrol-A®) + TX, Alternaria alternate + TX, Alternaria cassia + TX, Alternaria destruens (Smolder®) + TX, Ampelomyces quisqualis (AQ10®) + TX, Aspergillus flavus AF36 (AF36®) + TX, Aspergillus flavus NRRL 21882 (Aflaguard®) + TX, Aspergillus spp. + TX, Aureobasidium pullulans + TX, Azospirillum + TX, (MicroAZ® + TX, TAZO B®) + TX, Azotobacter + TX, Azotobacter chroocuccum (Azotomeal®) + TX, Azotobacter cysts (Bionatural Blooming Blossoms®) + TX, Bacillus amyloliquefaciens + TX, Bacillus cereus + TX, Bacillus chitinosporus strain CM-1 + TX, Bacillus chitinosporus strain AQ746 + TX, Bacillus licheniformis strain HB-2 (Biostart™ Rhizoboost®) + TX, Bacillus licheniformis strain 3086 (EcoGuard® + TX, Green Releaf®) + TX, Bacillus circulans + TX, Bacillus firmus (BioSafe® + TX, BioNem-WP® + TX, VOTiVO®) + TX, Bacillus firmus strain 1-1582 + TX, Bacillus macerans + TX, Bacillus marismortui + TX, Bacillus megaterium + TX, Bacillus mycoides strain AQ726 + TX, Bacillus papillae (Milky Spore Powder®) + TX, Bacillus pumilus spp. + TX, Bacillus pumilus strain GB34 (Yield Shield®) + TX, Bacillus pumilus strain AQ717 + TX, Bacillus pumilus strain QST 2808 (Sonata® + TX, Ballad Plus®) + TX, Bacillus spahericus (VectoLex®) + TX, Bacillus spp. + TX, Bacillus spp. strain AQ175 + TX, Bacillus spp. strain AQ177 + TX, Bacillus spp. strain AQ178 + TX, Bacillus subtilis strain QST 713 (CEASE® + TX, Serenade® + TX, Rhapsody®) + TX, Bacillus subtilis strain QST 714 (JAZZ®) + TX, Bacillus subtilis strain AQ153 + TX, Bacillus subtilis strain AQ743 + TX, Bacillus subtilis strain QST3002 + TX, Bacillus subtilis strain QST3004 + TX, Bacillus subtilis var. amyloliquefaciens strain FZB24 (Taegro® + TX, Rhizopro®) + TX, Bacillus thuringiensis Cry 2Ae + TX, Bacillus thuringiensis Cry1 Ab + TX, Bacillus thuringiensis aizawai GC 91 (Agree®) + TX, Bacillus thuringiensis israelensis (BMP123® + TX, Aquabac® + TX, VectoBac®) + TX, Bacillus thuringiensis kurstaki (Javelin® + TX, Deliver® + TX, CryMax® + TX, Bonide® + TX, Scutella WP® + TX, Turilav WP ® + TX, Astuto® + TX, Dipel WP® + TX, Biobit® + TX, Foray®) + TX, Bacillus thuringiensis kurstaki BMP 123 (Baritone®) + TX, Bacillus thuringiensis kurstaki HD-1 (Bioprotec-CAF / 3P®) + TX, Bacillus thuringiensis strain BD#32 + TX, Bacillus thuringiensis strain AQ52 + TX, Bacillus thuringiensis var. aizawai (XenTari® + TX, DiPel®) + TX, bacteria spp. (GROWMEND® + TX, GROWSWEET® + TX, Shootup®) + TX, bacteriophage of Clavipacter michiganensis (AgriPhage®) + TX, Bakflor® + TX, Beauveria bassiana (Beaugenic® + TX, Brocaril WP®) + TX, Beauveria bassiana GHA (Mycotrol ES® + TX, Mycotrol O® + TX, BotaniGuard®) + TX, Beauveria brongniartii (Engerlingspilz® + TX, Schweizer Beauveria® + TX, Melocont®) + TX, Beauveria spp. + TX, Botrytis cineria + TX, Bradyrhizobium japonicum (TerraMax®) + TX, Brevibacillus brevis + TX, Bacillus thuringiensis tenebrionis (Novodor®) + TX, BtBooster + TX, Burkholderia cepacia (Deny® + TX, Intercept® + TX, Blue Circle®) + TX, Burkholderia gladii + TX, Burkholderia gladioli + TX, Burkholderia spp. + TX, Canadian thistle fungus (CBH Canadian Bioherbicide®) + TX, Candida butyri + TX, Candida famata + TX, Candida fructus + TX, Candida glabrata + TX, Candida guilliermondii + TX, Candida melibiosica + TX, Candida oleophila strain O + TX, Candida parapsilosis + TX, Candida pelliculosa + TX, Candida pulcherrima + TX, Candida reukaufii + TX, Candida saitoana (Bio-Coat® + TX, Biocure®) + TX, Candida sake + TX, Candida spp. + TX, Candida tenius + TX, Cedecea dravisae + TX, Cellulomonas flavigena + TX, Chaetomium cochliodes (Nova-Cide®) + TX, Chaetomium globosum (Nova-Cide®) + TX, Chromobacterium subtsugae strain PRAA4-1T (Grandevo®) + TX, Cladosporium cladosporioides + TX, Cladosporium oxysporum + TX, Cladosporium chlorocephalum + TX, Cladosporium spp. + TX, Cladosporium tenuissimum + TX, Clonostachys rosea (EndoFine®) + TX, Colletotrichum acutatum + TX, Coniothyrium minitans (Cotans WG®) + TX, Coniothyrium spp. + TX, Cryptococcus albidus (YIELDPLUS®) + TX, Cryptococcus humicola + TX, Cryptococcus infirmo- miniatus + TX, Cryptococcus laurentii + TX, Cryptophlebia leucotreta granulovirus (Cryptex®) + TX, Cupriavidus campinensis + TX, Cydia pomonella granulovirus (CYD-X®) + TX, Cydia pomonella granulovirus (Madex® + TX, Madex Plus® + TX, Madex Max/ Carpovirusine®) + TX, Cylindrobasidium laeve (Stumpout®) + TX, Cylindrocladium + TX, Debaryomyces hansenii + TX, Drechslera hawaiinensis + TX, Enterobacter cloacae + TX, Enterobacteriaceae + TX, Entomophtora virulenta (Vektor®) + TX, Epicoccum nigrum + TX, Epicoccum purpurascens + TX, Epicoccum spp. + TX, Filobasidium floriforme + TX, Fusarium acuminatum + TX, Fusarium chlamydosporum + TX, Fusarium oxysporum (Fusaclean® / Biofox C®) + TX, Fusarium proliferatum + TX, Fusarium spp. + TX, Galactomyces geotrichum + TX, Gliocladium catenulatum (Primastop® + TX, Prestop®) + TX, Gliocladium roseum + TX, Gliocladium spp. (SoilGard®) + TX, Gliocladium virens (Soilgard®) + TX, Granulovirus (Granupom®) + TX, Halobacillus halophilus + TX, Halobacillus litoralis + TX, Halobacillus trueperi + TX, Halomonas spp. + TX, Halomonas subglaciescola + TX, Halovibrio variabilis + TX, Hanseniaspora uvarum + TX, Helicoverpa armigera nucleopolyhedrovirus (Helicovex®) + TX, Helicoverpa zea nuclear polyhedrosis virus (Gemstar®) + TX, Isoflavone - formononetin (Myconate®) + TX, Kioeckera apiculata + TX, Kioeckera spp. + TX, Lagenidium giganteum (Laginex®) + TX, Lecanicillium longisporum (Vertiblast®) + TX, Lecanicillium muscarium (Vertikil®) + TX, Lymantria Dispar nucleopolyhedrosis virus (Disparvirus®) + TX, Marinococcus halophilus + TX, Meira geulakonigii + TX, Metarhizium anisopliae (Met52®) + TX, Metarhizium anisopliae (Destruxin WP®) + TX, Metschnikowia fruticola (Shemer®) + TX, Metschnikowia pulcherrima + TX, Microdochium dimerum (Antibot®) + TX, Micromonospora coerulea + TX, Microsphaeropsis ochracea + TX, Muscodor albus 620 (Muscudor®) + TX, Muscodor roseus strain A3-5 + TX, Mycorrhizae spp. (AMykor® + TX, Root Maximizer®) + TX, Myrothecium verrucaria strain AARC-0255 (DiTera®) + TX, BROS PLUS® + TX, Ophiostoma piliferum strain D97 (Sylvanex®) + TX, Paecilomyces farinosus + TX, Paecilomyces fumosoroseus (PFR-97® + TX, PreFeRal®) + TX, Paecilomyces linacinus (Biostat WP®) + TX, Paecilomyces lilacinus strain 251 (MeloCon WG®) + TX, Paenibacillus polymyxa + TX, Pantoea agglomerans (BlightBan C9-1®) + TX, Pantoea spp. + TX, Pasteuria spp. (Econem®) + TX, Pasteuria nishizawae + TX, Penicillium aurantiogriseum + TX, Penicillium billai (Jumpstart® + TX, TagTeam®) + TX, Penicillium brevicompactum + TX, Penicillium frequentans + TX, Penicillium griseofulvum + TX, Penicillium purpurogenum + TX, Penicillium spp. + TX, Penicillium viridicatum + TX, Phlebiopsis gigantean (Rotstop®) + TX, phosphate solubilizing bacteria (Phosphomeal®) + TX, Phytophthora cryptogea + TX, Phytophthora palmivora (Devine®) + TX, Pichia anomala + TX, Pichia guilermondii + TX, Pichia membranaefaciens + TX, Pichia onychis + TX, Pichia stipites + TX, Pseudomonas aeruginosa + TX, Pseudomonas aureofasciens (Spot-Less Biofungicide®) + TX, Pseudomonas cepacia + TX, Pseudomonas chlororaphis (AtEze®) + TX, Pseudomonas corrugate + TX, Pseudomonas fluorescens strain A506 (BlightBan A506®) + TX, Pseudomonas putida + TX, Pseudomonas reactans + TX, Pseudomonas spp. + TX, Pseudomonas syringae (Bio-Save®) + TX, Pseudomonas viridiflava + TX, Pseudomons fluorescens (Zequanox®) + TX, Pseudozyma fioccuiosa strain PF-A22 UL (Sporodex L®) + TX, Puccinia canaliculate + TX, Puccinia thlaspeos (Wood Warrior®) + TX, Pythium paroecandrum + TX, Pythium oligandrum (Polygandron® + TX, Polyversum®) + TX, Pythium periplocum + TX, Rhanella aquatilis + TX, Rhanella spp. + TX, Rhizobia (Dormal® + TX, Vault®) + TX, Rhizoctonia + TX, Rhodococcus globerulus strain AQ719 + TX, Rhodosporidium diobovatum + TX, Rhodosporidium toruloides + TX, Rhodotorula spp. + TX, Rhodotorula glutinis + TX, Rhodotorula graminis + TX, Rhodotorula mucilagnosa + TX, Rhodotorula rubra + TX, Saccharomyces cerevisiae + TX, Salinococcus roseus + TX, Sclerotinia minor + TX, Sclerotinia minor (SARRITOR®) + TX, Scytalidium spp. + TX, Scytalidium uredinicola + TX, Spodoptera exigua nuclear polyhedrosis virus (Spod-X® + TX, Spexit®) + TX, Serratia marcescens + TX, Serratia plymuthica + TX, Serratia spp. + TX, Sordaria fimicola + TX, Spodoptera littoralis nucleopolyhedrovirus (Littovir®) + TX, Sporobolomyces roseus + TX, Stenotrophomonas maltophilia + TX, Streptomyces ahygroscopicus + TX, Streptomyces albaduncus + TX, Streptomyces exfoliates + TX, Streptomyces galbus + TX, Streptomyces griseoplanus + TX, Streptomyces griseoviridis (Mycostop®) + TX, Streptomyces lydicus (Actinovate®) + TX, Streptomyces lydicus WYEC-108 (ActinoGrow®) + TX, Streptomyces violaceus + TX, Tilletiopsis minor + TX, Tilletiopsis spp. + TX, Trichoderma asperellum (T34 Biocontrol®) + TX, Trichoderma gamsii (Tenet®) + TX, Trichoderma atroviride (Plantmate®) + TX, Trichoderma hamatum TH 382 + TX, Trichoderma harzianum rifai (Mycostar®) + TX, Trichoderma harzianum T-22 (Trianum-P® + TX, PlantShield HC® + TX, RootShield® + TX, Trianum-G®) + TX, Trichoderma harzianum T-39 (Trichodex®) + TX, Trichoderma inhamatum + TX, Trichoderma koningii + TX, Trichoderma spp. LC 52 (Sentinel®) + TX, Trichoderma lignorum + TX, Trichoderma longibrachiatum + TX, Trichoderma polysporum (Binab T®) + TX, Trichoderma taxi + TX, Trichoderma virens + TX, Trichoderma virens (formerly Gliocladium virens GL-21) (SoilGuard®) + TX, Trichoderma viride + TX, Trichoderma viride strain ICC 080 (Remedier®) + TX, Trichosporon pullulans + TX, Trichosporon spp. + TX, Trichothecium spp. + TX, Trichothecium roseum + TX, Typhula phacorrhiza strain 94670 + TX, Typhula phacorrhiza strain 94671 + TX, Ulocladium atrum + TX, Ulocladium oudemansii (Botry-Zen®) + TX, Ustilago maydis + TX, various bacteria and supplementary micronutrients (Natural II®) + TX, various fungi (Millennium Microbes®) + TX, Verticillium chlamydosporium + TX, Verticillium lecanii (Mycotal® + TX, Vertalec®) + TX, Vip3Aa20 (VIPtera®) + TX, Virgibaclillus marismortui + TX, Xanthomonas campestris pv. Poae (Camperico®) + TX, Xenorhabdus bovienii + TX, Xenorhabdus nematophilus ;
Plant extracts including: pine oil (Retenol®) + TX, azadirachtin (Plasma Neem Oil® + TX, AzaGuard®
+ TX, MeemAzal® + TX, Molt-X® + TX, Botanical IGR (Neemazad® + TX, Neemix®) + TX, canola oil (Lilly Miller Vegol®) + TX, Chenopodium ambrosioides near ambrosioides (Requiem®) + TX, Chrysanthemum extract (Crisant®) + TX, extract of neem oil (Trilogy®) + TX, essentials oils of Labiatae (Botania®) + TX, extracts of clove rosemary peppermint and thyme oil (Garden insect killer®) + TX, Glycinebetaine (Greenstim®) + TX, garlic + TX, lemongrass oil (GreenMatch®) + TX, neem oil + TX, Nepeta cataria (Catnip oil) + TX, Nepeta catarina + TX, nicotine + TX, oregano oil (MossBuster®)
+ TX, Pedaliaceae oil (Nematon®) + TX, pyrethrum + TX, Quillaja saponaria (NemaQ®) + TX, Reynoutria sachalinensis (Regalia® + TX, Sakalia®) + TX, rotenone (Eco Roten®) + TX, Rutaceae plant extract (Soleo®) + TX, soybean oil (Ortho ecosense®) + TX, tea tree oil (Timorex Gold®) + TX, thymus oil + TX, AGNIQUE® MMF + TX, BugOil® + TX, mixture of rosemary sesame pepermint thyme and cinnamon extracts (EF 300®) + TX, mixture of clove rosemary and peppermint extract (EF 400®) + TX, mixture of clove pepermint garlic oil and mint (Soil Shot®) + TX, kaolin (Screen®) + TX, storage glucam of brown algae (Laminarin®); pheromones including: blackheaded fireworm pheromone (3M Sprayable Blackheaded Fireworm Pheromone®) + TX, Codling Moth Pheromone (Paramount dispenser-(CM)/ Isomate C-Plus®) + TX, Grape Berry Moth Pheromone (3M MEC-GBM Sprayable Pheromone®) + TX, Leafroller pheromone (3M MEC - LR Sprayable Pheromone®) + TX, Muscamone (Snip7 Fly Bait® + TX, Starbar Premium Fly Bait®) + TX, Oriental Fruit Moth Pheromone (3M oriental fruit moth sprayable pheromone®) + TX, Peachtree Borer Pheromone (Isomate-P®) + TX, Tomato Pinworm Pheromone (3M Sprayable pheromone®) + TX, Entostat powder (extract from palm tree) (Exosex CM®) + TX, (E + TX,Z + TX,Z)- 3 + TX,8 + TX,11 Tetradecatrienyl acetate + TX, (Z + TX,Z + TX,E)-7 + TX,11 + TX,13- Hexadecatrienal + TX, (E + TX,Z)-7 + TX,9-Dodecadien-1-yl acetate + TX, 2-Methyl-1 -butanol + TX, Calcium acetate + TX, Scenturion® + TX, Biolure® + TX, Check-Mate® + TX, Lavandulyl senecioate; Macrobials including: Aphelinus abdominalis + TX, Aphidius ervi (Aphelinus-System®) + TX, Acerophagus papaya + TX, Adalia bipunctata (Adalia-System®) + TX, Adalia bipunctata (Adaline®) + TX, Adalia bipunctata (Aphidalia®) + TX, Ageniaspis citricola + TX, Ageniaspis fuscicollis + TX, Amblyseius andersoni (Anderline® + TX, Andersoni-System®) + TX, Amblyseius californicus (Amblyline® + TX, Spical®) + TX, Amblyseius cucumeris (Thripex® + TX, Bugline cucumeris®) + TX, Amblyseius fallacis (Fallacis®) + TX, Amblyseius swirskii (Bugline swirskii® + TX, Swirskii-Mite®) + TX, Amblyseius womersleyi (WomerMite®) + TX, Amitus hesperidum + TX, Anagrus atomus + TX, Anagyrus fusciventris + TX, Anagyrus kamali + TX, Anagyrus loecki + TX, Anagyrus pseudococci (Citripar®) + TX, Anicetus benefices + TX, Anisopteromalus calandrae + TX, Anthocoris nemoralis (Anthocoris-System®) + TX, Aphelinus abdominalis (Apheline® + TX, Aphiline®) + TX, Aphelinus asychis + TX, Aphidius colemani (Aphipar®) + TX, Aphidius ervi (Ervipar®) + TX, Aphidius gifuensis + TX, Aphidius matricariae (Aphipar-M®) + TX, Aphidoletes aphidimyza (Aphidend®) + TX, Aphidoletes aphidimyza (Aphidoline®) + TX, Aphytis lingnanensis + TX, Aphytis melinus + TX, Aprostocetus hagenowii + TX, Atheta coriaria (Staphyline®) + TX, Bombus spp. + TX, Bombus terrestris (Natupol Beehive®) + TX, Bombus terrestris (Beeline® + TX, Tripol®) + TX, Cephalonomia stephanoderis +
TX, Chilocorus nigritus + TX, Chrysoperla carnea (Chrysoline®) + TX, Chrysoperla carnea (Chrysopa®) + TX, Chrysoperla rufilabris + TX, Cirrospilus ingenuus + TX, Cirrospilus quadristriatus + TX, Citrostichus phyllocnistoides + TX, Closterocerus chamaeleon + TX, Closterocerus spp. + TX, Coccidoxenoides perminutus (Planopar®) + TX, Coccophagus cowperi + TX, Coccophagus lycimnia + TX, Cotesia fiavipes + TX, Cotesia plutellae + TX, Cryptolaemus montrouzieri (Cryptobug® + TX, Cryptoline®) + TX, Cybocephalus nipponicus + TX, Dacnusa sibirica + TX, Dacnusa sibirica (Minusa®) + TX, Diglyphus isaea (Diminex®) + TX, Delphastus catalinae (Delphastus®) + TX, Delphastus pusillus + TX, Diachasmimorpha krausii + TX, Diachasmimorpha longicaudata + TX, Diaparsis jucunda + TX, Diaphorencyrtus aligarhensis + TX, Diglyphus isaea + TX, Diglyphus isaea (Miglyphus® + TX, Digline®) + TX, Dacnusa sibirica (DacDigline® + TX, Minex®) + TX, Diversinervus spp. + TX, Encarsia citrina + TX, Encarsia formosa (Encarsia max® + TX, Encarline® + TX, En- Strip®) + TX, Eretmocerus eremicus (Enermix®) + TX, Encarsia guadeloupae + TX, Encarsia haitiensis + TX, Episyrphus balteatus (Syrphidend®) + TX, Eretmoceris siphonini + TX, Eretmocerus californicus + TX, Eretmocerus eremicus (Ercal® + TX, Eretline e®) + TX, Eretmocerus eremicus (Bemimix®) + TX, Eretmocerus hayati + TX, Eretmocerus mundus (Bemipar® + TX, Eretline m®) +
TX, Eretmocerus siphonini + TX, Exochomus quadripustulatus + TX, Feltiella acarisuga (Spidend®) + TX, Feltiella acarisuga (Feltiline®) + TX, Fopius arisanus + TX, Fopius ceratitivorus + TX, Formononetin (Wirless Beehome®) + TX, Franklinothrips vespiformis (Vespop®) + TX, Galendromus occidentalis + TX, Goniozus legneri + TX, Flabrobracon hebetor + TX, Harmonia axyridis (HarmoBeetle®) + TX, Heterorhabditis spp. (Lawn Patrol®) + TX, Heterorhabditis bacteriophora (NemaShield HB® + TX, Nemaseek® + TX, Terranem-Nam® + TX, Terranem® + TX, Larvanem® + TX, B-Green® + TX, NemAttack ® + TX, Nematop®) + TX, Heterorhabditis megidis (Nemasys H® + TX, BioNem H® + TX, Exhibitline hm® + TX, Larvanem-M®) + TX, Hippodamia convergens + TX, Hypoaspis aculeifer (Aculeifer-System® + TX, Entomite-A®) + TX, Hypoaspis miles (Hypoline m® + TX, Entomite-M®) + TX, Lbalia leucospoides + TX, Lecanoideus floccissimus + TX, Lemophagus errabundus + TX, Leptomastidea abnormis + TX, Leptomastix dactylopii (Leptopar®) + TX, Leptomastix epona + TX, Lindorus lophanthae + TX, Lipolexis oregmae + TX, Lucilia caesar (Natufly®) + TX, Lysiphlebus testaceipes + TX, Macrolophus caliginosus (Mirical-N® + TX, Macroline c® + TX, Mirical®) + TX, Mesoseiulus longipes + TX, Metaphycus flavus + TX, Metaphycus lounsburyi + TX, Micromus angulatus (Milacewing®) + TX, Microterys flavus + TX, Muscidifurax raptorellus and Spalangia cameroni (Biopar®) + TX, Neodryinus typhlocybae + TX, Neoseiulus californicus + TX, Neoseiulus cucumeris (THRYPEX®) + TX, Neoseiulus fallacis + TX, Nesideocoris tenuis (NesidioBug® + TX, Nesibug®) + TX, Ophyra aenescens (Biofly®) + TX, Orius insidiosus (Thripor-I®
+ TX, Oriline i®) + TX, Orius laevigatus (Thripor-L® + TX, Oriline I®) + TX, Orius majusculus (Oriline m®) + TX, Orius strigicollis (Thripor-S®) + TX, Pauesia juniperorum + TX, Pediobius foveolatus + TX, Phasmarhabditis hermaphrodita (Nemaslug®) + TX, Phymastichus coffea + TX, Phytoseiulus macropilus + TX, Phytoseiulus persimilis (Spidex® + TX, Phytoline p®) + TX, Podisus maculiventris (Podisus®) + TX, Pseudacteon curvatus + TX, Pseudacteon obtusus + TX, Pseudacteon tricuspis + TX, Pseudaphycus maculipennis + TX, Pseudleptomastix mexicana + TX, Psyllaephagus pilosus +
TX, Psyttalia concolor (complex) + TX, Quadrastichus spp. + TX, Rhyzobius lophanthae + TX, Rodolia cardinalis + TX, Rumina decollate + TX, Semielacher petiolatus + TX, Sitobion avenae (Ervibank®) + TX, Steinernema carpocapsae (Nematac C® + TX, Millenium® + TX, BioNem C® + TX, NemAttack®
+ TX, Nemastar® + TX, Capsanem®) + TX, Steinernema feltiae (NemaShield® + TX, Nemasys F® + TX, BioNem F® + TX, Steinernema-System® + TX, NemAttack® + TX, Nemaplus® + TX, Exhibitline sf® + TX, Scia-rid® + TX, Entonem®) + TX, Steinernema kraussei (Nemasys L® + TX, BioNem L® + TX, Exhibitline srb®) + TX, Steinernema riobrave (BioVector® + TX, BioVektor®) + TX, Steinernema scapterisci (Nematac S®) + TX, Steinernema spp. + TX, Steinernematid spp. (Guardian Nematodes®) + TX, Stethorus punctillum (Stethorus®) + TX, Tamarixia radiate + TX, Tetrastichus setifer + TX, Thripobius semiluteus + TX, Torymus sinensis + TX, Trichogramma brassicae (Tricholine b®) + TX, Trichogramma brassicae (Tricho-Strip®) + TX, Trichogramma evanescens + TX, Trichogramma minutum + TX, Thchogramma ostriniae + TX, Trichogramma platneh + TX, Trichogramma pretiosum + TX, Xanthopimpla stemmator, other biologicals including: abscisic acid + TX, bioSea® + TX, Chondrostereum purpureum (Chontrol Paste®) + TX, Colletotrichum gloeosporioides (Collego®) + TX, Copper Octanoate (Cueva®) + TX, Delta traps (Trapline d®) + TX, Erwinia amylovora (Harpin) (ProAct® + TX, Ni-HIBIT Gold CST®) +
TX, Ferri-phosphate (Ferramol®) + TX, Funnel traps (Trapline y®) + TX, Gallex® + TX, Grower's Secret® + TX, Homo-brassonolide + TX, Iron Phosphate (Lilly Miller Worry Free Ferramol Slug & Snail Bait®) + TX, MCP hail trap (Trapline f®) + TX, Microctonus hyperodae + TX, Mycoleptodiscus terrestris (Des-X®) + TX, BioGain® + TX, Aminomite® + TX, Zenox® + TX, Pheromone trap (Thripline ams®) + TX, potassium bicarbonate (MilStop®) + TX, potassium salts of fatty acids (Sanova®) + TX, potassium silicate solution (Sil-Matrix®) + TX, potassium iodide + potassiumthiocyanate (Enzicur®) + TX, SuffOil-X® + TX, Spider venom + TX, Nosema locustae (Semaspore Organic Grasshopper Control®) + TX, Sticky traps (Trapline YF® + TX, Rebell Amarillo®) + TX and Traps (Takitrapline y + b®) + TX; and a safener, such as benoxacor + TX, cloquintocet (including cloquintocet-mexyl) + TX, cyprosulfamide + TX, dichlormid + TX, fenchlorazole (including fenchlorazole-ethyl) + TX, fenclorim + TX, fluxofenim + TX, furilazole + TX, isoxadifen (including isoxadifen-ethyl) + TX, mefenpyr (including mefenpyr-diethyl) + TX, metcamifen + TX and oxabetrinil + TX.
The references in brackets behind the active ingredients, e.g. [3878-19-1] refer to the Chemical Abstracts Registry number. The above described mixing partners are known. Where the active ingredients are included in "The Pesticide Manual" [The Pesticide Manual - A World Compendium; Thirteenth Edition; Editor: C. D. S. TomLin; The British Crop Protection Council], they are described therein under the entry number given in round brackets hereinabove for the particular compound; for example, the compound "abamectin" is described under entry number (1). Where "[CCN]" is added hereinabove to the particular compound, the compound in question is included in the "Compendium of Pesticide Common Names", which is accessible on the internet [A. Wood; Compendium of Pesticide Common Names. Copyright © 1995-2004]; for example, the compound "acetoprole" is described under the internet address http://www.alanwood.net/pesticides/acetoprole.html.
Most of the active ingredients described above are referred to hereinabove by a so-called "common name", the relevant "ISO common name" or another "common name" being used in individual cases. If the designation is not a "common name", the nature of the designation used instead is given in round brackets for the particular compound; in that case, the lUPAC name, the lUPAC/Chemical Abstracts name, a "chemical name", a "traditional name", a "compound name" or a "develoment code" is used or, if neither one of those designations nor a "common name" is used, an "alternative name" is employed. “CAS Reg. No” means the Chemical Abstracts Registry Number. The active ingredient mixture of the compounds of formula I selected from the compounds defined in the Tables A-1 to A-18 and Table P with active ingredients described above comprises a compound selected from Tables A-1 to A-18 and Table P and an active ingredient as described above preferably in a mixing ratio of from 100:1 to 1 :6000, especially from 50:1 to 1 :50, more especially in a ratio of from 20:1 to 1 :20, even more especially from 10:1 to 1 :10, very especially from 5:1 and 1 :5, special preference being given to a ratio of from 2:1 to 1 :2, and a ratio of from 4:1 to 2:1 being likewise preferred, above all in a ratio of 1 :1 , or 5:1 , or 5:2, or 5:3, or 5:4, or 4:1 , or 4:2, or 4:3, or 3:1 , or 3:2, or 2:1 , or 1 :5, or 2:5, or 3:5, or 4:5, or 1 :4, or 2:4, or 3:4, or 1 :3, or 2:3, or 1 :2, or 1 :600, or 1 :300, or 1 :150, or 1 :35, or 2:35, or 4:35, or 1 :75, or 2:75, or 4:75, or 1 :6000, or 1 :3000, or 1 :1500, or 1 :350, or 2:350, or 4:350, or 1 :750, or 2:750, or 4:750. Those mixing ratios are by weight.
The compounds and mixtures as described above can be used in a method for controlling pests, which comprises applying a composition comprising a compound or mixture as described above to the pests or their environment, with the exception of a method for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body.
The mixtures comprising a compound of formula I selected from the compounds defined in the Tables A-1 to A-18 and Table P and one or more active ingredients as described above can be applied, for example, in a single “ready-mix” form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a “tank-mix”, and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days. The order of applying the compounds of formula I and the active ingredients as described above is not essential for working the present invention.
The compositions according to the invention can also comprise further solid or liquid auxiliaries, such as stabilizers, for example unepoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soya oil), antifoams, for example silicone oil, preservatives, viscosity regulators, binders and/or tackifiers, fertilizers or other active ingredients for achieving specific effects, for example bactericides, fungicides, nematocides, plant activators, molluscicides or herbicides.
The compositions according to the invention are prepared in a manner known per se, in the absence of auxiliaries for example by grinding, screening and/or compressing a solid active ingredient and in the presence of at least one auxiliary for example by intimately mixing and/or grinding the active ingredient with the auxiliary (auxiliaries). These processes for the preparation of the compositions and the use of the compounds I for the preparation of these compositions are also a subject of the invention.
The application methods for the compositions, that is the methods of controlling pests of the abovementioned type, such as spraying, atomizing, dusting, brushing on, dressing, scattering or pouring - which are to be selected to suit the intended aims of the prevailing circumstances - and the use of the compositions for controlling pests of the abovementioned type are other subjects of the invention. Typical rates of concentration are between 0.1 and 1000 ppm, preferably between 0.1 and 500 ppm, of active ingredient. The rate of application per hectare is generally 1 to 2000 g of active ingredient per hectare, in particular 10 to 1000 g/ha, preferably 10 to 600 g/ha.
A preferred method of application in the field of crop protection is application to the foliage of the plants (foliar application), it being possible to select frequency and rate of application to match the danger of infestation with the pest in question. Alternatively, the active ingredient can reach the plants via the root system (systemic action), by drenching the locus of the plants with a liquid composition or by incorporating the active ingredient in solid form into the locus of the plants, for example into the soil, for example in the form of granules (soil application). In the case of paddy rice crops, such granules can be metered into the flooded paddy-field.
The compounds of formula I of the invention and compositions thereof are also be suitable for the protection of plant propagation material, for example seeds, such as fruit, tubers or kernels, or nursery plants, against pests of the abovementioned type. The propagation material can be treated with the compound prior to planting, for example seed can be treated prior to sowing. Alternatively, the compound can be applied to seed kernels (coating), either by soaking the kernels in a liquid composition or by applying a layer of a solid composition. It is also possible to apply the compositions when the propagation material is planted to the site of application, for example into the seed furrow during drilling. These treatment methods for plant propagation material and the plant propagation material thus treated are further subjects of the invention. Typical treatment rates would depend on the plant and pest/fungi to be controlled and are generally between 1 to 200 grams per 100 kg of seeds, preferably between 5 to 150 grams per 100 kg of seeds, such as between 10 to 100 grams per 100 kg of seeds.
The term seed embraces seeds and plant propagules of all kinds including but not limited to true seeds, seed pieces, suckers, corns, bulbs, fruit, tubers, grains, rhizomes, cuttings, cut shoots and the like and means in a preferred embodiment true seeds.
The present invention also comprises seeds coated or treated with or containing a compound of formula I. The term "coated or treated with and/or containing" generally signifies that the active ingredient is for the most part on the surface of the seed at the time of application, although a greater or lesser part of the ingredient may penetrate into the seed material, depending on the method of application. When the said seed product is (re)planted, it may absorb the active ingredient. In an embodiment, the present invention makes available a plant propagation material adhered thereto with a compound of formula I. Further, it is hereby made available, a composition comprising a plant propagation material treated with a compound of formula I. Seed treatment comprises all suitable seed treatment techniques known in the art, such as seed dressing, seed coating, seed dusting, seed soaking and seed pelleting. The seed treatment application of the compound formula I can be carried out by any known methods, such as spraying or by dusting the seeds before sowing or during the sowing/planting of the seeds.
The compounds of the invention can be distinguished from other similar compounds by virtue of greater efficacy at low application rates and/or different pest control, which can be verified by the person skilled in the art using the experimental procedures, using lower concentrations if necessary, for example 10 ppm, 5 ppm, 2 ppm, 1 ppm or 0.2 ppm; or lower application rates, such as 300, 200 or 100, mg of Al per m2. The greater efficacy can be observed by an increased safety profile (against non-target organisms above and below ground (such as fish, birds and bees), improved physicochemical properties, or increased biodegradability).
In each aspect and embodiment of the invention, "consisting essentially" and inflections thereof are a preferred embodiment of "comprising" and its inflections, and "consisting of and inflections thereof are a preferred embodiment of "consisting essentially of” and its inflections.
The disclosure in the present application makes available each and every combination of embodiments disclosed herein.
It should be noted that the disclosure herein in respect of a compound of formula I applies equally in respect of a compound of each of formulae I*, I’a, laa, I’aa, and IA, and Tables A-1 to A-18. Further the preferred enantiomer of formula I’a or I’aa applies also to compounds of Tables A-1 to A-18 and Table P. Also, made available herein is an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer and/or N-oxide of the compound of formula formulae I*, I’a, laa, , I’aa, and IA, and Tables A- 1 to A-18 and Table P.
Biological Examples:
The Examples which follow serve to illustrate the invention. Certain compounds of the invention can be distinguished from known compounds by virtue of greater efficacy at low application rates, which can be verified by the person skilled in the art using the experimental procedures outlined in the Examples, using lower application rates if necessary, for example 50 ppm, 24 ppm, 12.5 ppm, 6 ppm, 3 ppm, 1.5 ppm, 0.8 ppm or 0.2 ppm.
Example B1 : Diabrotica balteata (Corn root worm)
Maize sprouts placed onto an agar layer in 24-well microtiter plates were treated with aqueous test solutions prepared from 10Ό00 ppm DMSO stock solutions by spraying. After drying, the plates were infested with L2 larvae (6 to 10 per well). The samples were assessed for mortality and growth inhibition in comparison to untreated samples 4 days after infestation.
The following compounds gave an effect of at least 80% control in at least one of the two categories (mortality or growth inhibition) at an application rate of 200 ppm:
P.1 , P.2, P.5, P.8, P.9, P.10, P.11
Example B2: Euschistus herns (Neotropical Brown Stink Bug)
Soybean leaves on agar in 24-well microtiter plates were sprayed with aqueous test solutions prepared from 10Ό00 ppm DMSO stock solutions. After drying the leaves were infested with N2 nymphs. The samples were assessed for mortality and growth inhibition in comparison to untreated samples 5 days after infestation.
The following compounds gave an effect of at least 80% control in at least one of the two categories (mortality or growth inhibition) at an application rate of 200 ppm:
P.1 , P.8
Example B3: Chilo suppressalis (Striped rice stemborer)
24-well microtiter plates with artificial diet were treated with aqueous test solutions prepared from 10Ό00 ppm DMSO stock solutions by pipetting. After drying, the plates were infested with L2 larvae (6-8 per well). The samples were assessed for mortality, anti-feeding effect, and growth inhibition in comparison to untreated samples 6 days after infestation. Control of Chilo suppressalis by a test sample is given when at least one of the categories mortality, anti-feedant effect, and growth inhibition is higher than the untreated sample.
The following compounds resulted in at least 80% control in at least one of the three categories (mortality, anti-feedant or growth inhibition) at an application rate of 200 ppm:
P.2, P.3, P.4, P.5, P.7, P.8, P.9, P.10, P.13
Example B4: Plutella xylostella (Diamond back moth)
24-well microtiter plates with artificial diet were treated with aqueous test solutions prepared from 10Ό00 ppm DMSO stock solutions by pipetting. After drying, Plutella eggs were pipetted through a plastic stencil onto a gel blotting paper and the plate was closed with it. The samples were assessed for mortality and growth inhibition in comparison to untreated samples 8 days after infestation.
The following compounds gave an effect of at least 80% control in at least one of the two categories (mortality or growth inhibition) at an application rate of 200 ppm:
P.1 , P.2, P.3, P.4, P.5, P.6, P.7, P.8, P.9, P.10, P.11
Example B5: Spodoptera littoralis (Egyptian cotton leaf worm)
Cotton leaf discs were placed onto agar in 24-well microtiter plates and sprayed with aqueous test solutions prepared from 10Ό00 ppm DMSO stock solutions. After drying the leaf discs were infested with five L1 larvae. The samples were assessed for mortality, anti-feeding effect, and growth inhibition in comparison to untreated samples 3 days after infestation. Control of Spodoptera littoralis by a test sample is given when at least one of the categories mortality, anti-feedant effect, and growth inhibition is higher than the untreated sample.
The following compounds resulted in at least 80% control in at least one of the three categories (mortality, anti-feedant or growth inhibition) at an application rate of 200 ppm:
P.1 , P.2, P.3, P.5, P.7, P.8, P.9, P.10
Example B6: Plutella xylostella (Diamondback Moth)
96-well microtiter plates containing artificial diet were treated with aqueous test solutions, prepared from 10Ό00 ppm DMSO stock solutions, by a liquid handling robot. After drying, eggs (~30 per well) were infested onto a netted lid which was suspended above the diet. The eggs hatch and L1 larvae move down to the diet. The samples were assessed for mortality 9 days after infestation.
The following compounds gave an effect of at least 80% control at an application rate of 500 ppm:
P.1 , P.11 , P.14
Example 7: Mvzus persicae (Green peach aphid). Intrinsic activity
Test compounds prepared from 10Ό00 ppm DMSO stock solutions were applied by pipette into 24- well microtiter plates and mixed with sucrose solution. The plates were closed with a stretched Parafilm. A plastic stencil with 24 holes was placed onto the plate and infested pea seedlings were placed directly on the Parafilm. The infested plate was closed with a gel blotting paper and another plastic stencil and then turned upside down. The samples were assessed for mortality 5 days after infestation.
The following compounds resulted in at least 80% control at a test rate of 12 ppm:
P1
Example 8: Thrips tabaci (Onion thrips) Feedinq/Contact activity
Sunflower leaf discs were placed on agar in 24-well microtiter plates and sprayed with aqueous test solutions prepared from 10Ό00 ppm DMSO stock solutions. After drying the leaf discs were infested with a thrips population of mixed ages. The samples were assessed for mortality 6 days after infestation.
The following compounds resulted in at least 80% control at an application rate of 200 ppm:
P.1

Claims

1. A compound of the formula I
Figure imgf000125_0001
wherein:
A is N or CRY; Q is
Figure imgf000125_0002
Q a or Qb
R1 is hydrogen; Ci-C6alkyl, Ci-C6alkyl substituted with one substituent selected from CN, C(0)NH2, C(0)0H, NO2, and -Si(CH3)3, Ci-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C3- C4cycloalkyl- Ci-C2alkyl, C3-C4cycloalkyl- Ci-C2alkyl substituted with 1 or 2 halo atoms; oxetan-3-yl- CH2-, benzyl, or benzyl substituted with halo or Ci-C3haloalkyl;
R2a is Ci-C3alkyl, Ci-C3haloalkyl, Ci- Cshaloalkylthio, Ci- Csalkoxy, Ci- Cshaloalkoxy, halo, NO2, SFs, CN, C(0)NH2, C(0)0H, C(S)NH2;
R2b is C3-C6-cycloalkyl-Ci-C6alkyl optionally substituted with one to three substituents independently selected from bromine, iodine, chlorine, fluorine, OH, cyano, Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C2-C6alkynyl, =0, =CH2, =CF2, =CCl2, =N-Ci-C3alkoxy, and =CMe2; or C3-C6-cycloalkylidenemethyl optionally substituted with one to three substituents independently selected from halo, cyano, Ci- C3alkyl, Ci-C3haloalkyl, and Ci- Csalkoxy;
R3 is Ci-C3alkyl or Ci-C3haloalkyl;
R4 is pyridine, pyrimidine, pyrazine or pyridazine; or
R4 is pyridine, pyrimidine, pyrazine or pyridazine each of which, independently of each other, is substituted with one to two substituents independently selected from Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C3-C4cycloalkyl, halo, hydroxyl, CN, Ci-C6haloalkoxy, C2-C6haloalkenyloxy, C2- Cehaloalkynyloxy, and C3-C4halocycloalkoxy;
R4a is pyridine, pyrimidine, pyrazine, pyridazine; or R4a is pyridine, pyrimidine, pyrazine or pyridazine each of which, independently of each other, is substituted with one to three substituents independently selected from Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C3-C4cycloalkyl, halogen, hydroxyl, cyano, and Ci-C3haloalkoxy; or R4a is Y1 , Y2, Y3, and Y4
Figure imgf000126_0001
Y1 Y2 Y3 Y4 wherein, R a, R b, and R , independently of each other and independently of Y1 to Y4, are selected from hydrogen, halogen, CN, Ci-C3alkyl, Ci-C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy, and Ci- C3haloalkoxy;
R5 is hydrogen, Ci-C3alkyl, Ci-C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy, C3-C4alkoxyC(0)-, (Ci- C3alkoxy)2CH-, halogen, CN, NH2C(0), amino (i.e NH2), (Ci-C3alkyl)amino, di(Ci-C3alkyl)amino, hydroxy, C3-C4halocycloalkyl, C3-C4cyanocycloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2- Cehaloalkynyl, Ci-C4haloalkylsulfanyl, Ci-C4haloalkylsulfinyl, Ci-C4haloalkylsulfonyl, Ci- C4alkylsulfanyl, Ci-C4alkylsulfinyl, Ci-C4alkylsulfonyl, Ci-C3alkoxy-Ci-C3alkyl, Ci-C3alkoxy-Ci- C3alkoxy-Ci-C3alkyl, (Ci-C3alkyl)sulfonylamino, (Ci-C3alkyl)sulfonyl(Ci-C3alkyl)amino, (Ci- C3alkyl)NHC(0), (Ci-C3alkyl)2NC(0), (Ci-C3cycloalkyl)NHC(0), (Ci-C3cycloalkyl)(Ci-C3alkyl)NC(0), (Ci-C3alkyl)C(0)(Ci-C3alkyl)N, (Ci-C3alkyl)C(0)NH, (Ci-C3alkyl)C(0), (Ci-C3alkoxy)C(0), HC(O), diphenylmethanimine, Ci-C3haloalkoxy, phenyl, or a 5-membered heteroaromatic ring; or R5 is phenyl substituted with one to three substituents selected from Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C3-C4cycloalkyl, halogen, CN and hydroxyl; or
R5 is a 5-membered heteroaromatic ring substituted with one to three substituents selected from Ci- C3alkyl, Ci-C3haloalkyl, Ci-C3alkoxy, C3-C4cycloalkyl, halogen, CN and hydroxyl;
R53 and Rsb are, independently of each other, selected from hydrogen, halogen, CN, Ci-C3alkyl, Ci- C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy, and Ci-C3haloalkoxy; and
RY is independently selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, CN and cyclopropyl; or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer and N-oxide of the compound of formula I; provided in the instance there are two fluorine substituents on R2b, R2b is not cyclopropyl-CF2-.
2. The compound according to claim 1 wherein A is CH.
3. The compound according to either claim 1 or claim 2 wherein Ri is hydrogen, Ci-C3alkyl, or C3-C4cycloalkyl-Ci-C2alkyl.
4. The compound according to any one of claims 1 to 3 wherein Råa is halogen, Ci-C3haloalkyl, Ci-C3haloalkylthio, Ci-C3alkoxy, Ci-C3haloalkoxy, or CN.
5 The compound according to any one of claims 1 to 4 wherein Råb is. C3-C6-cycloalkyl-Ci- C6alkyl; C3-C6-cycloalkyl-Ci-C6alkyl substituted with one to three substituents independently selected from bromine, iodine, chlorine, fluorine, OH, cyano, Ci-C3alkyl, Ci-C3haloalkyl, Ci- C3alkoxy, C2- C6alkynyl, =0, =CH2, =CF2, =CCI2, _=N-Ci-C3alkoxy, and =CMe2; C3-C6-cycloalkylidenemethyl; or C3- C6-cycloalkylidenemethyl substituted with one to three substituents independently selected from halo, cyano, Ci-C3alkyl, Ci-C3haloalkyl, and Ci- C3alkoxy.
6. The compound according to any one of claims 1 to 5 wherein R3 is Ci-C3alkyl or Ci- C3haloalkyl.
7. The compound according to any one of claims 1 to 6 wherein Q is Qa, and R4 is pyridine, or pyrimidine; wherein the pyridine or pyrimidine, independently of each other, is optionally substituted with one substituent selected from Ci-C3alkyl, Ci-C3haloalkyl, Ci-C3alkoxy, C3-C4cycloalkyl, halo, hydroxyl, CN, Ci-C6haloalkoxy, C2-C6haloalkenyloxy, C2-C6haloalkynyloxy, C3-C4halocycloalkoxy, and C3-C6cycloalkylCi-C4haloalkoxy; and Rs is hydrogen, methyl, trifluoromethoxy, methoxy, cyclopropyl, 2,2-difluroroethoxy, 2,2,2-trifluroroethoxy, difluoromethoxy, 2,2,2-trifluroroethyl, chloro, bromo, methoxyethoxy, methylcarbonyl, or methoxycarbonyl.
8. The compound according to any one of claims 1 to 6 wherein Q is Qb, and R4a is pyridine, pyrimidine, pyrazine or pyridazine, wherein the pyridine, pyrimidine, pyrazine or pyridazine, independent of each other, is optionally substituted with one substituent selected from Ci-C3haloalkyl, C3-C4cycloalkyl, halogen, cyano, Ci-C3haloalkoxy and selected from Y-1 to Y-4; Rsa is hydrogen, halogen, CN, Ci-C3alkyl, Ci-C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy or Ci-C3haloalkoxy; Rsb is hydrogen, halogen, CN, Ci-C3haloalkyl, C3-C4cycloalkyl, Ci-C3alkoxy, or Ci-C3haloalkoxy; and R4a, R’4a and R c independently of each other, are hydrogen, halogen, CN, Ci-C3alkyl, Ci-C3haloalkyl, C3- C4cycloalkyl, Ci-C3alkoxy, and Ci-C3haloalkoxy.
9. A composition comprising a compound as defined in any one of claims 1 to 8, one or more auxiliaries and diluent, and optionally one or more other active ingredients.
10. A method
(i) of combating and controlling insects, acarines, nematodes or molluscs which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound as defined in any one of claims 1 to 8 or a composition as defined claim 9; or (ii) for the protection of plant propagation material from the attack by insects, acarines, nematodes or molluscs, which comprises treating the propagation material or the site, where the propagation material is planted, with an effective amount of a compound as defined in any one of claims 1 to 8 or a composition as defined claim 9; or
(iii) of controlling parasites in or on an animal in need thereof comprising administering an effective amount of a compound as defined in any one of claims 1 to 8 or a composition as defined claim 9.
11. A plant propagation material, such as a seed, comprising, or treated with or adhered thereto, a compound as defined in any one of claims 1 to 8 or a composition as defined claim 9.
12. A compound of formula K
Figure imgf000128_0001
wherein A is as defined in either claim 1 or 2; Råa is as defined in either claim 1 or 4; and F¾b is as defined in either claim 1 or 5, provided in the instance there are two fluorine substituents on R2b, R2b is not cyclopropyl-CF2-.
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