WO2025201636A1 - Pesticidally-active 2,2-dihalocyclopropyl compounds - Google Patents

Pesticidally-active 2,2-dihalocyclopropyl compounds

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Publication number
WO2025201636A1
WO2025201636A1 PCT/EP2024/058217 EP2024058217W WO2025201636A1 WO 2025201636 A1 WO2025201636 A1 WO 2025201636A1 EP 2024058217 W EP2024058217 W EP 2024058217W WO 2025201636 A1 WO2025201636 A1 WO 2025201636A1
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WIPO (PCT)
Prior art keywords
optionally substituted
substituents independently
independently selected
spp
c4alkyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/EP2024/058217
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French (fr)
Inventor
Pierre Joseph Marcel Jung
Thorben MUELLER
Marisa ETEROVIC
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Syngenta Crop Protection AG Switzerland
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Syngenta Crop Protection AG Switzerland
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Publication of WO2025201636A1 publication Critical patent/WO2025201636A1/en
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • 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
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing within the same carbon skeleton a carboxylic group or a thio analogue, or a derivative thereof, and a carbon atom having only two bonds to hetero atoms with at the most one bond to halogen, e.g. keto-carboxylic acids
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • A01P7/02—Acaricides
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • A01P7/04—Insecticides
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C233/10—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an unsaturated carbon skeleton containing rings other than six-membered aromatic rings
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    • C07C239/00—Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
    • C07C239/08—Hydroxylamino compounds or their ethers or esters
    • C07C239/20—Hydroxylamino compounds or their ethers or esters having oxygen atoms of hydroxylamino groups etherified
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    • C07C255/24—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton
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    • C07C255/46—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of non-condensed rings
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    • C07C255/00—Carboxylic acid nitriles
    • C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C255/58—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
    • C07C255/60—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton at least one of the singly-bound nitrogen atoms being acylated
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    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
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    • C07C317/28—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
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    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/38—Nitrogen atoms
    • C07D231/40—Acylated on said nitrogen atom
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D233/24—Radicals substituted by nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D249/14—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D261/14—Nitrogen atoms
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    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/182—Radicals derived from carboxylic acids
    • C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
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    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
    • C07D335/02—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
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    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Definitions

  • the present invention relates to pesticidally active, and in particular, insecticidally active, 2,2- dihalocyclopropyl compounds, to compositions comprising those compounds, and to their use for controlling insect and acarine pests.
  • Insecticidally-active 2,2-dihalocyclopropyl compounds are known from WO 95/09151 , DE 41 04 377, EP 0 468 927, US 5,326,901 and EP 0 387 974. It has now been found that further 2,2- dihalocyclopropyl compounds have such properties.
  • WO 03/062265 discloses te/Y-butyl (E)-4-(2,2-difluorocyclopropyl)but-2-enoate as a synthesis intermediate in the preparation of compounds with hepatitis C virus (HCV) protease inhibitory activity.
  • HCV hepatitis C virus
  • X is halogen
  • A is -OR;
  • R is hydrogen, Ci-Cealkyl, Ci-C4haloalkyl, C2-C6alkenyl, C2-C4haloalkenyl, C2-C6alkynyl, C2- C4haloalkynyl, Ci-C4nitroalkyl, Ci-C4alkoxyCi-C4alkyl, or Ci-C4haloalkoxyCi-C4alkyl; or
  • R is Ci-C2alkyl monosubstituted by:
  • a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R 3 ,
  • R 1 is phenyl optionally substituted by 1 to 3 substituents independently selected from R 3 , C3- Cecycloalkyl optionally substituted by 1 to 3 substituents independently selected from R 3 , a 4- to 6- membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R 3 , a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R 3 , or a 9- or 10-membered heteroaromatic bicyclic ring system comprising 1 to 4 nitrogen atoms, or 0, 1 or 2 nitrogen atoms and a single atom selected from O or S, wherein the heteroaromatic bicyclic ring is optionally substituted by 1 to 3 substituents independently selected from
  • R 1 is Ci-C2alkyl mono-substituted by:
  • a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R 3 ,
  • a 4- to 6-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R 3 , or
  • R 1 is wherein Y is O or -CH2-;
  • R 2 is hydrogen, cyano, Ci-Cealkyl, Ci-C4haloalkyl, Ci-C4alkoxy, Ci-C4haloalkoxy, C2-Cealkenyl, C2-C4haloalkenyl, C2-Cealkynyl, C2-C4haloalkynyl, Ci-C4cyanoalkyl, Ci-C4nitroalkyl, Ci-C alkoxyCi- C4alkyl, Ci-C4haloalkoxyCi-C4alkyl, or -C(O)Ci-C4alkyl; or
  • R 4 is Ci-Cealkyl, Ci-C4haloalkyl, Ci-Cealkoxy, Ci-Cehaloalkoxy, Cs-Cecycloalkyl or phenyl optionally substituted by 1 to 3 substituents independently selected from R 3 , a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R 3 , or a 4- to 6-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R 3 ; or
  • R 4 is Ci-C2alkyl mono-substituted by: (i) a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R 3 ,
  • a 4- to 6-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R 3 , or
  • R 4 is -NH(Ci-Cealkyl), -NH(Ci-C 6 alkenyl), -N(Ci-C6alkenyl)(Ci-C 6 alkyl), -NH(Ci-C 6 alkynyl), - N(Ci-C6alkynyl)(Ci-Cealkyl), -N(Ci-Cealkyl)2, -NH(C3-C6cycloalkyl), -N(C3-C6cycloalkyl)(Ci-C6alkyl), or - NH(phenyl) or -NH(CH2phenyl), wherein phenyl is optionally substituted by 1 to 3 substituents independently selected from R 8 ;
  • R 5 is Ci-Cealkyl, Ci-C4haloalkyl, Ci-Cealkoxy, Ci-C4haloalkoxy, Cs-Cecycloalkyl, 3-(2,2- dihalocyclopropyl)prop-1-en-1-yl, benzyloxy, benzylamine, or phenyl optionally substituted by 1 to 3 substituents independently selected from R 8 , a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R 8 , or a 5- to 6-membered saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R 8 ;
  • R 6 and R 7 are independently selected from hydrogen, fluoro or chloro
  • R 8 is halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy, Ci-C4haloalkoxy or Ci- C 4 alkylNHSO2-; or a salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, with the proviso that the compound of Formula (I) is not te/Y-butyl (E)-4-(2,2- difluorocyclopropyl)but-2-enoate.
  • an agrochemical composition comprising an insecticidally or acaricidally effective amount of a compound of formula (I) as defined according to the invention.
  • a compound according to Formula (I) as an insecticide or acaricide.
  • the use may exclude methods for the treatment of the human or animal body by surgery or therapy.
  • nitro means an -NO2 group.
  • Ci-Cealkyl refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to six carbon atoms, and which is attached to the rest of the molecule by a single bond.
  • Ci-C4alkyl, Ci-Cealkyl and Ci-C2alkyl are to be construed accordingly.
  • Examples of Ci-Cealkyl include, but are not limited to, methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, and 1 ,1 -dimethylethyl (f-butyl).
  • C1- C4alkylene refers to the corresponding definition of Ci-C4alkyl, except that such radical is attached to the rest of the molecule by two single bonds.
  • Examples of Ci-C4alkylene are -CH2- and - CH2CH2-.
  • Ci-C4haloalkyl refers to a Ci-C4alkyl radical as generally defined above substituted by one or more of the same or different halogen atoms.
  • Ci-C4haloalkyl include, but are not limited to fluoromethyl, fluoroethyl, difluoromethyl, trifluoromethyl, 2,2-difluoroethyl, 2,2,2- trifluoroethyl, and 3,3,3-trifluoropropyl.
  • Ci-C4haloalkyl refers to a radical of the formula R a O- where R a is a Ci- Cealkyl radical as generally defined above.
  • the term "Ci-C4alkoxy” should be construed accordingly. Examples of O-Cealkoxy include, but are not limited to, methoxy, ethoxy, propoxy, iso-propoxy, and t- butoxy.
  • Ci-C4haloalkoxy refers to a Ci-C4alkoxy group as defined above substituted by one or more of the same or different halogen atoms.
  • Examples of Ci-C4haloalkoxy include, but are not limited to, fluoromethoxy, difluoromethoxy, fluoroethoxy, trifluoromethoxy, and trifluoroethoxy.
  • C2-C6alkenyl refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one double bond that can be of either the (E)- or ( ⁇ -configuration, having from two to six carbon atoms, which is attached to the rest of the molecule by a single bond.
  • C2-C4alkenyl should be construed accordingly. Examples of C2-Cealkenyl include, but are not limited to, prop-1-enyl, allyl (prop-2-enyl), and but-1-enyl.
  • C2-C4haloalkenyl refers to a C2-C4alkenyl radical as generally defined above substituted by one or more of the same or different halogen atoms.
  • C2-C4haloalkynyl refers to a C2-C4alkynyl radical as generally defined above substituted by one or more of the same or different halogen atoms.
  • Ci-C4alkoxyCi-C4alkyl refers to a radical of the formula R y -O-R x - where R y is a Ci-C4alkyl radical as generally defined above, and Rx is a Ci-C4alkylene radical as generally defined above.
  • Ci-C4haloalkoxyCi-C4alkyl refers to a radical of the formula R y -O-R x - where R y is a Ci-C4alkyl radical as generally defined above substituted by one or more of the same or different halogen atoms, and R x is a Ci-C4alkylene radical as generally defined above.
  • Ci-C4cyanoalkyl refers to a Ci-C4alkyl radical as generally defined above substituted by a cyano group.
  • Ci-C4nitroalkyl refers to a Ci-C4alkyl radical as generally defined above substituted by a nitro group.
  • Ci-C4alkylsulfanyl refers to a radical of the formula R X S- wherein R x is a Ci-C4alkyl radical as generally defined above.
  • Ci-C4haloalkylsulfanyl refers to a Ci-C4alkylsulfanyl radical as generally defined above substituted by one or more of the same or different halogen atoms.
  • Ci-C4alkylsulfinyl refers to a radical of the formula R X S(O)- wherein Rx is a Ci-C4alkyl radical as generally defined above.
  • Ci-C4haloalkylsulfinyl refers to a Ci-C4alkylsulfinyl radical as generally defined above substituted by one or more of the same or different halogen atoms.
  • Ci-C4alkylsulfonyl refers to a radical of the formula R X S(O)2- wherein Rx is a Ci-C4alkyl radical as generally defined above.
  • Ci-C4haloalkylsulfonyl refers to a Ci-C4alkylsulfonyl radical as generally defined above substituted by one or more of the same or different halogen atoms.
  • Ci-C4alkylsulfonylCi-C4alkyl refers to a radical of the formula R y S(O)2Rx- where R y is a Ci-C4alkyl radical as generally defined above, and Rx is a Ci-C4alkylene radical as generally defined above.
  • Examples of a 5- or 6-membered heteroaromatic ring system which is monocyclic and which comprises 1 to 4 heteroatoms selected from nitrogen, oxygen an sulfur, include pyridyl, pyrimidyl, pyrrolyl, pyrazolyl, furyl, thienyl, imidazolyl, isoxazolyl, oxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, pyrazinyl, pyridazinyl and triazinyl. These rings systems will not comprise contiguous oxygen and sulfur atoms.
  • Examples of a 9- or 10-membered heteroaromatic ring system which is bicyclic and which comprises 1 to 4 heteroatoms selected from nitrogen, oxygen an sulfur, include quinazolinyl, isoquinolinyl, indolizinyl, isobenzofuranylnaphthyridinyl, quinoxalinyl, cinnolinyl, phthalazinyl, benzothiazolyl, benzoxazolyl, benzotriazolyl, indazolyl, indolyl, tetrahydroquinolynyl, benzofuryl, benzisofuryl, benzothienyl, benzisothienyl, isoindolyl, naphthyridinyl, benzisothiazolyl, benzisoxazolyl, benzoxazolyl, benzotriazinyl, purinyl, pteridinyl, indolizinyl, phenylpyri
  • Examples of a 4- to 6-membered saturated or partially saturated heterocyclic ring system which is monocyclic and which comprises 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, include dihydropyranyl, tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, isoxazolidinyl, isothiazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, imidazolidinyl, oxadiazolidinyl, thiadiazolidinyl, dihydrofuranyl, dihydrothienyl, pyrrolinyl, isoxazolinyl, dihydropyrazolyl, dihydrooxazolyl, piperidinyl, dioxanyl, tetrahydropyranyl, hexahydropyridazinyl, hexahydropyrimidinyl, oxiranyl, morpholin
  • the compounds of formula (I) according to the invention 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, a phosphorus acid or a hydrohalic acid, with strong organic carboxylic acids, such as Ci-C4alkylcarboxylic 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-C4-alkane- or arylsulfonic acids which are unsubstituted or substituted, for example
  • 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- or tri-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- or tri-lower-alkylamine, for example ethyl-, die
  • asymmetric carbon atoms in a compound of Formula (I) means that the compounds may occur in chiral isomeric forms, i.e., enantiomeric or diastereomeric forms. Also, atropisomers may occur as a result of restricted rotation about a single bond.
  • Formula (I) is intended to include all those possible isomeric forms and mixtures thereof. The present invention includes all those possible isomeric forms and mixtures thereof for a compound of Formula (I).
  • Formula (I) is intended to include all possible tautomers (including lactam-lactim tautomerism and ketoenol tautomerism) where present. The present invention includes all possible tautomeric forms for a compound of Formula (I).
  • A is -OR, wherein:
  • R is hydrogen, Ci-Cealkyl, Ci-C4haloalkyl, C2-Cealkenyl, C2-C4haloalkenyl, C2-Cealkynyl, C2- C4haloalkynyl, Ci-C4nitroalkyl, Ci-C4alkoxyCi-C4alkyl, or Ci-C4haloalkoxyCi-C4alkyl; or R is phenyl optionally substituted by 1 , 2 or 3 substituents independently selected from R 3 , Ce-Cecycloalkyl optionally substituted by 1 , 2 or 3 substituents independently selected from R 3 , or a 4- to 6- membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R 3 ; or R is Ci-C2alkyl monosubstituted by: (i)
  • R is hydrogen, Ci-Cealkyl, Ci-C2fluoroalkyl, C2-C4alkenyl, C2-C4fluoroalkenyl, C2- C4alkynyl, C2-C4fluoroalkynyl, Ci-C2nitroalkyl, Ci-C2alkoxyCi-C2alkyl, or Ci-C2fluoroalkoxyCi-C2alkyl; or R is phenyl optionally substituted by a single substituent selected from R 3 , benzyl optionally substituted by a single substituent selected from R 3 , or (pyrazolyl)methyl optionally substituted by a single substituent selected from R 3 , wherein R 3 is halogen, cyano, nitro, hydroxyl, formyl, Ci-C4alkyl, C1- C4fluoroalkyl, C2-C4alkenyl, C2-C4alkynyl, cyclopropyl, -
  • R is hydrogen, Ci-Cealkyl, phenyl, benzyl, or (1-methylpyrazol-4-yl)methyl. Even more preferably, R is hydrogen, methyl, ethyl, n- propyl, /so-propyl, te/Y-butyl, phenyl, benzyl, or (1-methylpyrazol-4-yl)methyl.
  • A is -NR 1 R 2 , wherein:
  • R 1 is wherein Y is O or -CH2-;
  • R 2 is hydrogen, Ci-Cealkyl, Ci-C4haloalkyl, Ci-C4alkoxy, Ci-C4haloalkoxy, C2-Cealkenyl, C2- C4haloalkenyl, C2-Cealkynyl, C2-C4haloalkynyl, Ci-C4cyanoalkyl, Ci-C4nitroalkyl, Ci-C4alkoxyCi-C4alkyl, Ci-C4haloalkoxyCi-C4alkyl, or -C(O)Ci-C4alkyl.
  • R 1 and R 2 together with the nitrogen atom they share, form a 4- to 6-membered saturated or partially saturated heterocyclic ring system, further comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R 8 , or R 1 and R 2 , together with the nitrogen atom they share, form a 9-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S.
  • R 4 is Ci-C4alkyl, phenyl optionally substituted by 1 or 2 substituents independently selected from R 3 , a 5- or 6-membered heteroaromatic ring system which comprises 1 or 2 nitrogen atoms, wherein the heteroaromatic ring is optionally substituted by 1 or 2 substituents independently selected from R 3 , a 5 or 6-membered saturated or partially saturated heterocyclic ring system which comprises 1 nitrogen atom, wherein the heterocyclic ring is optionally substituted by 1 or 2 substituents independently selected from R 3 , Ci-C2alkyl mono-substituted by a 5- or 6-membered heteroaromatic ring system which comprises 1 or 2 nitrogen atoms, wherein the heteroaromatic ring is optionally substituted by a single substituent selected from R 3 , or -NH(Ci-C4alkyl); and
  • R 1 is methyl mono-substituted by:
  • R 3 is fluoro, chloro, bromo, cyano, methyl, ethyl, iso-propyl, tert-butyl, difluoromethyl, trifluoromethyl, cyclopropyl, methoxy, ethoxy, difluoromethoxy, phenyl, acetamidomethyl, acetyl(methyl)amino, acetamido, ethylsulfamoyl, ethylsulfonylamino, cyanomethyl, 1-cyano-1 -methylethyl, cyanocyclopropyl; and
  • R 4 is ethyl, iso-propyl, methylamino, a ring selected from phenyl, pyridyl, pyrrolidinyl and piperidyl each optionally substituted by 1 or 2 substituents independently selected from R 3 , or methyl mono-substituted by pyridyl which is optionally substituted by a single substituent selected from R 3 .
  • R 5 is ethyl, iso-propyl, tert-butyl 3-(2,2-dihalocyclopropyl)prop-1-en-1-yl, benzyloxy, or benzylamine, or a ring selected from phenyl, pyridyl, pyrrolidinyl and piperidyl each optionally substituted by 1 or 2 substituents independently selected from R 8 .
  • R 2 is hydrogen, Ci-C4alkyl, Ci-C4fluoroalkyl, Ci-C4alkoxy, Ci-C4fluoroalkoxy, C2- C4alkenyl, C2-C4alkynyl, cyanomethyl, nitromethyl, Ci-C2alkoxyCi-C2alkyl, or -C(O)Ci-C4alkyl. More preferably, R 2 is hydrogen, methyl or cyanomethyl. Even more preferably, R 2 is hydrogen.
  • R 3 is halogen, cyano, nitro, hydroxyl, formyl, Ci-Cealkyl, Ci-C4haloalkyl, C2-Cealkenyl, C2- C4haloalkenyl, C2-Cealkynyl, C2-C4haloalkynyl, Cs-Cecycloalkyl, Cs-Cehalocycloalkyl, Ci-C4alkylsulfanyl, Ci-C4alkylsulfinyl, Ci-C4alkylsulfonyl, Ci-C4haloalkylsulfanyl, Ci-C4haloalkylsulfinyl, C1- C 4 haloalkylsulfonyl, -C(O)Ci-C 4 alkyl, -C(O)NH(Ci-C 4 alkyl), -C(O)N(Ci-C4alkyl) 2 , Ci-C 4 alk
  • R 3 is halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, C3- Cecycloalkyl, Ci-C4alkoxy, Ci-C4haloalkoxy, phenyl, -Ci-C4alkylNHC(O)Ci-C4alkyl, -NC(O)(Ci- C4alkyl)Ci-C4alkyl, -NHC(O)Ci-C4alkyl, Ci-C4alkylNHS(O)2-, -NHS(O)2Ci-C4alkyl, Ci-C4cyanoalkyl, or Cs-Cecycloalkyl substituted by cyano.
  • R 3 is fluoro, chloro, bromo, cyano, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, trifluoromethyl, cyclopropyl, methoxy, ethoxy, difluoromethoxy, phenyl, acetamidomethyl, acetyl(methyl)amino, acetamido, ethylsulfamoyl, ethylsulfonylamino, cyanomethyl, 1- cyano-1 -methyl-ethyl, cyanocyclopropyl.
  • R 4 is Ci-Cealkyl, Ci-C4haloalkyl, Ci-Cealkoxy, Ci-Cehaloalkoxy, Cs-Cecycloalkyl or phenyl optionally substituted by 1 , 2 or 3 substituents independently selected from R 3 , a 5- or 6-membered heteroaromatic ring system comprising 1 , 2 or 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R 3 , or a 4- to 6-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R 3 ; or R 4 is Ci-C2alkyl monosubstituted by: (i) a 5- or 6-membered heteroaromatic ring system comprising 1 , 2 or 3
  • R 4 is Ci-C 4 alkyl, Ci-C 4 fluoroalkyl, Ci-C 4 alkoxy, -NH(Ci-C 4 alkyl), -NH(C 2 -C 4 alkenyl), - N(C 2 -C 4 alkenyl)(Ci-C 4 alkyl), -NH(C 2 -C 4 alkynyl), -N(C 2 -C 4 alkynyl)(Ci-C 4 alkyl), -N(Ci-C 4 alkyl) 2 , -NH(C 3 - Cecycloalkyl), -N(C3-C6cycloalkyl)(Ci-C 4 alkyl), or -NH(phenyl) or -NH(CH 2 phenyl), or R 4 is phenyl, benzyl, pyridyl, (pyridyl)methyl, pyrrolidinyl or piperidinyl wherein each ring is
  • silyl derivatives such as (Chlorodifluoromethyl)trimethylsilane or (bromodifluoromethyl)trimethylsilane preferably under phase transfer catalysis conditions at temperatures from 80°C to 150°C (see for example Chemical Communications (2011), 47(8), 2411-2413, European Journal of Organic Chemistry (2019), 2019(7), 1669-1676 or Chemical Communications (2021), 57(3), 319-322.
  • in situ carbenoid generation include, for example, the use of trifluoromethane in presence of a base, such as sodium hydroxide, preferably under phase transfer catalysis conditions or the use of ester derivatives such as ethyl bromodifluoroacetate, preferably under phase transfer catalysis conditions in the appropriate solvent such as tetrahydrofuran or/and anisole (see for example WO 2022/003584).
  • a base such as sodium hydroxide
  • ester derivatives such as ethyl bromodifluoroacetate
  • solvent such as tetrahydrofuran or/and anisole
  • carbenoid species wherein X is Cl or Br.
  • carbenoid species could be generated from a halogenate derivative such as dichlorofluoromethane, tribromofluoromethane or dibromofluoromethane in presence of a base, such as sodium hydroxide or butyllithium or reagents such as titanium tetrachloride, lithium aluminum hydride, under phase transfer catalysis conditions or not (see for example Russian Chemical Bulletin (2019), 68(7), 1391-1401 , Journal of Organic Chemistry (2012), 77(21), 9893-9899, Science of Synthesis (2006), 34, 245-265, Tetrahedron Letters 1988, p 6749 or Journal of Organic Chemistry (1990), 55(2), 589-94)).
  • a base such as sodium hydroxide or butyllithium or reagents
  • titanium tetrachloride lithium aluminum hydride
  • carbenoid species wherein X is Cl or Br could be generated from the use of ester, acid or salt of acid derivatives such as sodium dibromofluoroacetate, ethyl dibromofluoroacetate under phase transfer catalysis conditions or not, in the appropriate solvent such as dichloromethane and under or not presence of a catalyst, such as silver derivatives or a base or not, such as sodium hydroxide (see for example, Organic & Biomolecular Chemistry (2021), 19(21), 4678-4684), Journal of Fluorine Chemistry (2016), 209, 49-55.
  • ester, acid or salt of acid derivatives such as sodium dibromofluoroacetate, ethyl dibromofluoroacetate under phase transfer catalysis conditions or not
  • a catalyst such as silver derivatives or a base or not, such as sodium hydroxide
  • reagents could be used to generate carbenoid species wherein X is Cl or Br, for example, polyhalogenated carbonyl compounds such as 1 ,1 ,3,3-tetrachloro-1 ,3-difluoroacetone in the appropriate solvent such as dichloromethane and under presence or not of a base, such as sodium methoxide (see for example Tetrahedron Letters (1967), (29), 2773-6 or Recueil des Travaux Chimiques des Pays-Bas et de la Amsterdam 1947 p 419.
  • a base such as sodium methoxide
  • reagents that could be used to generate carbenoid species wherein X is Cl or Br are, for example, by reaction with a compound of formula (II): with a suitable organometallic precursor such as phenyl(fluorodichloromethyl) mercury (see for example: Journal of Organic Chemistry (1970), 35(5), 1297-302 or Journal of Organometallic Chemistry (1968), 11 (1), P9-P12), or with diazirines (see for example: Journal of the American Chemical Society (2005), 127(8), 2408-2409).
  • organometallic precursor such as phenyl(fluorodichloromethyl) mercury
  • compounds (IV) where Xoo is halogen, preferably chlorine, are formed by treatment of a compound of formula (la) wherein R is hydrogen and Ra is as described in Scheme 2, with, for example, oxalyl chloride orthionyl chloride in the presence of catalytic quantities of /V,/V-dimethylformamide (DMF) in inert solvents such as methylene chloride or tetrahydrofuran at temperatures between 20 to 100°C, and preferably 25°C.
  • DMF /V,/V-dimethylformamide
  • an activated species (IV) wherein Xoo is X01 or Xcc respectively, in an inert solvent, such as pyridine or tetrahydrofuran THF, optionally in the presence of a base, such as triethylamine, at temperatures between 50-180°C; followed by ii) treatment of the activated species (IV) with an amine reagent of formula (V) or a salt thereof (such as a hydrohalide salt, preferably a hydrochloride or a hydrobromide salt, or any other equivalent salt), wherein R 1 and R 2 is as defined in the present invention, optionally in the presence of a base, such as triethylamine or pyridine, in an inert solvent such as dichloromethane, tetrahydro
  • compounds of formula (lb), wherein R 1 and R 2 are as defined in the present invention, and Ra is as described in Scheme 2 may be prepared by the reaction of a compound of formula (la), wherein R is as described in the present invention and Ra is as described in Scheme 2, by methods known to those skilled in the art and described in, for example, by heating compounds of formula (la), wherein R is alkyl or benzyl, and Ra is as described in scheme 2, in the presence of amine (V), with or without solvent such as methanol or water, and with or without presence of a catalyst, such as Lewis acid derivatives optionally in the presence of a base, such as triethylamine, at temperatures of 50 to 250°C, optionally under microwave irradiation.
  • amine (V) with or without solvent such as methanol or water
  • a catalyst such as Lewis acid derivatives optionally in the presence of a base, such as triethylamine
  • Compound of formula (Ic), wherein Ra is as described in Scheme 3, may be prepared by reaction of a compound of formula (la), wherein Ra is as described in scheme 3 and wherein R is alkyl or a benzyl via hydrolysis.
  • a base such as potassium hydroxide or lithium hydroxide
  • a solvent such as, for instance, tetrahydrofuran or methanol.
  • the hydrolysis could be done in the presence of acid, such as trifluoroacetic acid or hydrochloric acid with or without a solvent.
  • the reaction is carried out at a temperature of from -120°C to +130°C, preferably from -100°C to 100°C.
  • These types of reaction are well known to those skilled in the art, see for example, Synthetic Organic Methodology: Comprehensive Organic Transformations. A Guide to Functional Group Preparations, Larock, R. C. 1989 p 981.
  • Compounds of formula (la), wherein R is as defined in the present invention, and Ra is as described in scheme 4 may be prepared by: i) activation of a compound of formula (Ic), wherein Ra is as described in Scheme 4 by methods known to those skilled in the art and described in, for example, Tetrahedron, 2005, 61 (46), 10827- 10852, to form an activated species (IV), wherein Ra is as described in Scheme 4 and wherein Xoo is halogen, preferably chlorine.
  • compounds (IV) where Xoo is halogen, preferably chlorine are formed by treatment of (Ic) wherein Ra as described in Scheme 4, with, for example, oxalyl chloride or thionyl chloride in the presence of catalytic quantities of /V,/V-dimethylformamide (DMF) in inert solvents such as methylene chloride or tetra hydrofuran at temperatures between 20 to 100°C, preferably 25°C.
  • DMF /V,/V-dimethylformamide
  • an activated species (IV) wherein Xoo is X01 or X02, respectively, in an inert solvent, such as pyridine or tetra hydrofuran (THF), optionally in the presence of a base, such as triethylamine, at temperatures between 50-180°C, followed by ii) treatment of the activated species (IV) with an alcohol reagent of formula (VI) ROH, wherein R is as defined in the present invention, optionally in the presence of a base, such as triethylamine or pyridine, in an inert solvent such as dichloromethane, tetrahydrofuran, dioxane or toluene, at temperatures between 0 and 50°C, to form the compounds of formula (la).
  • an inert solvent such as pyridine or tetra hydrofuran (THF)
  • a base such as triethylamine
  • esters of formula (la), wherein R is as defined in the present invention, and Ra is as described in Scheme 4 may be prepared by reaction of esterification in acid medium by known methods, described in the literature.
  • ester compounds of formula la wherein R a is as described in Scheme 4 may be prepared from the corresponding carboxylic acid compounds of formula (Ic), by reaction with an alcohol of formula ROH (VI), wherein R is as described in the present invention, optionally in the presence of an acid (such as sulfuric acid).
  • an acid such as sulfuric acid
  • benzoyl acid activated by derivation in acyl chloride or activation via treatment with, for example, 1- ethyl-3-(3-dimethylaminopropyl) carbodiimide or dicyclohexyl carbodiimide will generate an activated species that may be reacted with homoallyl alcohol.
  • the deprotection could be made by hydrolysis in presence of a base such as sodium hydroxyl or potassium carbonate in solvent such as methanol, ethanol, or water.
  • a base such as sodium hydroxyl or potassium carbonate
  • solvent such as methanol, ethanol, or water.
  • the reaction is carried out at a temperature of from 0°C to +100°C; followed by iv) oxidation of the alcohol of formula (VIII) to obtain compounds of formula (IX).
  • This transformation is very well known and could be made by methods known to a person skilled in the art (see for example Comprehensive Organic Transformations. A Guide to Functional Group Preparations. Edited by Richard C. Larock 1989 p 604, VCH publishers).
  • a compound of formula (la) may be prepared by reaction of a compound of formula (IX), wherein Rb is as described in Scheme 5 via Wittig reaction with Wittig reagent such as, for example, methyl (triphenylphosphoranylidene)acetate or ethyl 2-(triphenylphosphaneylidene) acetate in the presence of an inert solvent, such as, for example, toluene, tetrahydrofuran, or dichloromethane at a temperature of from 0°C to reflux.
  • a compound of formula (Ic) may be prepared by reaction of a compound of formula (la), wherein R is alkyl via hydrolysis.
  • the hydrolysis can be done with water and a base, such as potassium hydroxide or lithium hydroxide, in the absence or in the presence of a solvent, such as, for instance, tetrahydrofuran or methanol.
  • a base such as potassium hydroxide or lithium hydroxide
  • the hydrolysis is done in the presence of acid, such as trifluoroacetic acid or hydrochloric acid.
  • the reaction is carried out at a temperature of from -120°C to +130°C, preferably from -100°C to 100°C. This transformation is well known and could be made by methods known to a person skilled in the art (see for example Comprehensive Organic Transformations. A Guide to Functional Group Preparations. Edited by Richard C. Larock 1989 p 981 , VCH publishers)
  • suitable bases may include 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 alkylsilylamides, 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 ,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.
  • 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 per se.
  • 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.
  • Enantiomeric 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 cellulose, 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 di
  • 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 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 may be well-tolerated by warm-blooded species, fish and plants.
  • the compounds of formula (I) may have a beneficial safety profile towards non-target species, such as bees, and accordingly a good toxicity profile.
  • the active ingredients according to the invention may act against all or individual developmental stages of normally sensitive, but also resistant 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 pests are: from the order Acarina, 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
  • 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,
  • 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.
  • the active ingredients according to the invention may especially be suitable for controlling Aphis craccivora, Diabrotica balteata, Thrips tabaci, Euschistus heros, 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).
  • 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, ecd
  • 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 CrylAc toxin), Bollgard I® (cotton variety that expresses a
  • 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 CrylAb toxin. Bt1 1 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
  • 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.
  • 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. 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).
  • ion channel blockers such as blockers for sodium and calcium channels
  • the viral KP1 , KP4 or KP6 toxins stilbene synthases, bibenzyl synthases, chitinases, glucanases, the so-called
  • compositions according to the invention are the protection of stored goods and store ambients 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 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
  • 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, orto 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, orto 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.
  • 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.
  • 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.
  • 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 Table:
  • 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
  • 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).
  • 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, B/issus 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, B/issus insularis
  • Bermudagrass mite Eriophyes cynodoniensis
  • rhodesgrass mealybug Antonina graminis
  • two-lined spittlebug Propsapia bicincta
  • 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.
  • red imported fire ants Solenopsis invicta
  • 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.
  • 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., Lucilia spp., Chrysom
  • Heteropterida for example Cimex spp., Triatoma spp., Rhodnius spp., Panstrongylus spp.,
  • Argas spp. 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.
  • Acarapis spp. for example 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. and Laminosioptes spp..
  • 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 or addditives, such as carriers, solvents and surface-active substances.
  • formulation adjuvants or addditives such as carriers, solvents and surface-active substances.
  • the formulations can be in various physical forms, e.g.
  • 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.
  • 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.
  • Surfaceactive 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.
  • 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 %
  • 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 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 waterto 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.
  • 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.
  • 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.
  • the present invention makes available a pesticidal composition
  • a pesticidal composition comprising a compound of the first aspect, one or more formulation additives and a carrier.
  • 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 group consisting of a compound A1 to A237 listed in Table A (below) or a specific compound listed in Tables 1 to 10 (below): an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628) + TX; 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
  • 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, Rhodococc
  • TX methylneodecanamide [CCN] + TX, oxamate [CCN] + TX, and picaridin [CCN] + TX; a molluscicide selected from the group of substances consisting of bis(tributyltin) oxide (IUPAC 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 (IUPAC name) (352) + TX, metaldehyde (518) + TX, methiocarb (530) + TX, niclosamide (576) + TX, niclosamide-olamine (576) + TX, pentachlorophenol (623) + TX, sodium pentachlorophenoxide (623) +
  • 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®, Serenade®, 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®, Rhizopro®) + TX, Bacillus thuringiensis Cry 2Ae + TX, Bacillus thuringiensis Cry1 Ab + TX, Bacillus thuringiensis aizawai GC 91 (Agree®) + TX, Bacillus thuringiensis israelensis (BMP123®, Aquabac®, VectoBac®) + TX, Bacillus thuringiensis kurstaki (Javelin®, Deliver®, CryMax®, Bonide®, Scutella WP®, Turilav WP®, Astuto®, Dipel WP®, Biobit®, Foray®) + TX, Bacillus thuringiensis kurstaki BMP 123 (Baritone®) + TX, Bacillus thuringiensis kurstaki HD-1 (Bioprotec-CAF 1 3P®) + TX, Bac
  • 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®, 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®, Prestop®) + TX, Gliocladium roseum + TX, Gliocladium spp.
  • Pasteuria spp. Econem® + TX, Pasteuria nishizawae + TX, Penicillium aurantiogriseum + TX, Penicillium billai (Jumpstart®, 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
  • Rhodosporidium diobovatum + TX Rhodosporidium toruloides + TX, Rhodotorula spp.
  • Trichoderma asperellum T34 Biocontrol®
  • Trichoderma gamsii TX
  • Trichoderma atroviride Plantmate®
  • Trichoderma harzianum rifai My costar® + TX
  • Trichoderma harzianum -22 Trianum-P®, Plantshield HC®, Rootshield®, 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®, Vertalec®) + TX, Vip3Aa20 (VIPtera®) + TX, Virgibaclillus marismortui + TX, Xanthomonas campestris pv. Poae (Camperico®) + TX, Xenorhabdus bovienii + TX, and Xenorhabdus
  • Plant extracts including: pine oil (Retenol®) + TX, azadirachtin (Plasma Neem Oil®, AzaGuard®, MeemAzal®, Molt-X®) + TX, Botanical IGR (Neemazad®, 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 (Catn
  • 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®, Andersoni-System®) + TX, Amblyseius californicus (Amblyline®, Spical®) + TX, Amblyseius cucumeris (Thripex®, Bugline cucumeris®) + TX, Amblyseius fallacis (Fallacis®) + TX, Amblyseius swirskii (Bugline swirskii®, Swir
  • TX Bombus terrestris (Natupol Beehive®) + TX, Bombus terrestris (Beeline®, 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 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, Trichogramma ostriniae + TX, Trichogramma platneri + TX, Trichogramma pretiosum + TX, Xanthopimpla stemmator + TX other biologicals including: abscisic acid + TX, bioSea® + TX, Chondrostereum purpureum (Chontrol Paste®) + TX, Colletotrichum gloeospori
  • antibacterial agents selected from the group of:
  • Bacillus subtilis strain BU1814 (VELONDIS® PLUS, VELONDIS® FLEX and VELONDIS® EXTRA from BASF SE) + TX
  • Bacillus subtilis var. amyloliquefaciens strain FZB24 having Accession No. DSM 10271 (available from Novozymes as TAEGRO® or TAEGRO® ECO (EPA Registration No. 70127-5)) + TX
  • Bacillus sp. in particular strain D747 (available as DOUBLE NICKEL® from Kumiai Chemical Industry Co., Ltd.), having Accession No.
  • fungi examples of which are Aureobasidium pullulans, in particular blastospores of strain DSM14940, blastospores of strain DSM 14941 or mixtures of blastospores of strains DSM14940 and DSM14941 (e.g., BOTECTOR® and BLOSSOM PROTECT® from bio-ferm, CH) + TX; Pseudozyma aphidis (as disclosed in WO2011/151819 by Yissum Research Development Company of the Hebrew University of Jerusalem) + TX; Saccharomyces cerevisiae, in particular strains CNCM No. 1-3936, CNCM No. 1-3937, CNCM No. 1-3938 or CNCM No. 1-3939 (as disclosed in WO 2010/086790 from Lesaffre et Compagnie, FR) + TX;
  • Aureobasidium pullulans in particular blastospores of strain DSM14940, blastospores of strain DSM 14941 or
  • CABI 353812 e.g. BIOKUPRUMTM by AgriLife
  • TX Chaetomium globosum (available as RIVADIOM® by Rivale) + TX
  • Coniothyrium minitans, in particular strain CON/M/91-8 accesion No. DSM9660, e.g.
  • Trichoderma atroviride in particular strain SC1 (Accession No. CBS 122089, WO 2009/116106 and U.S. Patent No. 8,431 ,120 (from Bi-PA)
  • strain 77B T77 from Andermatt Biocontrol
  • strain LU132 e.g. Sentinel from
  • TrichoPlus from BASF + TX
  • Trichoderma gamsii (formerly T. viride), strain ICC080 (IMI CC 392151 CABI, e.g. BioDerma by AGROBIOSOL DE MEXICO, S.A. DE C.V.) + TX
  • Trichoderma gamsii (formerly T. viride), strain ICC 080 (IMI CC 392151 CABI) (available as BIODERMA® by AGROBIOSOL DE MEXICO, S.A. DE C.V.) + TX
  • Trichoderma harmatum having Accession No. ATCC 28012 + TX
  • Trichoderma harzianum strain T-22 e.g.
  • Trichoderma harzianum strain DB 103 (available as T-GRO® 7456 by Dagutat Biolab) + TX
  • Trichoderma polysporum strain IMI 206039 (e.g. Binab TF WP by BINAB Bio-Innovation AB, Sweden) + TX
  • Trichoderma stromaticum having Accession No. Ts3550 (e.g. Tricovab by CEPLAC, Brazil) + TX
  • Trichoderma virens also known as Gliocladium virens
  • strain GL-21 e.g.
  • biological control agents having an effect for improving plant growth and/or plant health selected from the group of:
  • (3.1) bacteria examples of which are Azospirillum brasilense (e.g., VIGOR® from KALO, Inc.) + TX; Azospirillum lipoferum (e.g., VERTEX-IFTM from TerraMax, Inc.) + TX; Azorhizobium caulinodans, in particular strain ZB-SK-5 + TX; Azotobacter chroococcum, in particular strain H23 + TX; Azotobacter vinelandii, in particular strain ATCC 12837 + TX; a mixture of Azotobacter vinelandii and Clostridium pasteurianum (available as INVIGORATE® from Agrinos) + TX; Bacillus amyloliquefaciens pm414 (LOLI-PEPTA® from Biofilm Crop Protection) + TX; Bacillus amyloliquefaciens SB3281 (ATCC # PTA- 7542, WO 2017/205258) + TX; Bacillus
  • (4.2) fungi examples of which are Beauveria bassiana strain ATCC 74040 (e.g. NATURALIS® from Intrachem Bio Italia) + TX; Beauveria bassiana strain GHA (Accession No. ATCC74250, e.g. BOTANIGUARD® ES and MYCONTROL-O® from Laverlam International Corporation) + TX; Beauveria bassiana strain ATP02 (Accession No.
  • the mixtures comprising a compound of formula (I) selected from a compound A1 to A237 listed in Table A (below) or a specific compound listed in Tables 1 to 10 (below) 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) selected from a compound A1 to A237 listed in Table A (below) or a specific compound listed in Tables 1 to 10 (below) and the active ingredients as described above is not essential for working the present invention.
  • 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.
  • the compounds 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.
  • a further aspect is a plant propagation material comprising by way of treatment or coating one or more compounds of formula (I) according to the invention, optionally also comprising a colour pigment.
  • Table 1 provides 23 specific compounds of formula (I) wherein X is F, and A is as defined in the below Table Z1 .
  • Table Z1
  • Table 4 provides 16 specific compounds of formula (Id) wherein X is F, and R 5 is as defined in the below Table Z2.
  • Table 5 provides 16 specific compounds of formula (Id) (compounds 5.24 to 5.39) wherein X is Cl, and R 5 is as defined above in Table Z2.
  • Table 6 provides 16 specific compounds of formula (Id) (compounds 6.24 to 6.39) wherein X is Br, and R 5 is as defined above in Table Z2.
  • Table Z3 Table 8 provides 11 specific compounds of formula (le) (compounds 8.40 to 8.50), wherein X is Cl and R 2 and R 4 are as defined above in Table Z3.
  • Compounds of Formula (I) 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 (including improved crop tolerance), improved physicochemical properties, or increased biodegradability).
  • LC/MS means Liquid Chromatography Mass Spectrometry and the description of the apparatus and the method A is outlined below.
  • the characteristic LC/MS values obtained for each compound were the retention time (“Rt”, recorded in minutes (min)) and the measured molecular ion (M+H) + and/or (M-
  • Spectra were recorded on a Mass Spectrometer from Waters Corporation (SQD, SQDII or QDA Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions), Capillary: 0.8-3.00 kV, Cone: 5-30 V, Source Temperature: 120-150°C, Desolvation Temperature: 350-600°C, Cone Gas Flow: 50-150 l/h, Desolvation Gas Flow: 650-1000 l/h, Mass range: 100 to 900 Da and an Acquity UPLC from Waters Corporation: Binary pump, heated column compartment , diode-array detector and ELSD.
  • Spectra were recorded on a Mass Spectrometer from Waters (SQD2 or QDA Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: Positive and Negative Polarity Switch), Capillary: 0.8-3.00 kV, Cone range: 25 Source Temperature: 120-150°C, Desolvation Temperature: 500-600°C, Cone Gas Flow: 50 L/h, Desolvation Gas Flow: 1000 L/h, Mass range: 110 to 850 Da) and an Acquity UPLC from Waters: Quaternary solvent manager, heated column compartment , diode-array detector.
  • Spectra were recorded on a Mass Spectrometer from Agilent Technologies (MSD-IQ mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, MS2 Scan, Capillary: 3.5 kV, Fragmentor: 110 V, Desolvation Temperature: 325°C, Gas Flow: 13 L/min, Nebulizer Gas: 55 psi, Mass range: 110 to 850 Da) and a 1290 Series HPLC from Agilent: quaternary pump, heated column compartment and diode-array detector.
  • MSD-IQ mass spectrometer mass spectrometer equipped with an electrospray source (Polarity: positive or negative ions, MS2 Scan, Capillary: 3.5 kV, Fragmentor: 110 V, Desolvation Temperature: 325°C, Gas Flow: 13 L/min, Nebulizer Gas: 55 psi, Mass range: 110 to 850 Da) and a 1290 Series HPLC from Agilent:
  • Step 1 Preparation of te/Y-butyl (E)-4-(2,2-difluorocyclopropyl) but-2-enoate
  • 3-buten-1-ol (5.00 g, 5.93 mL, 66.6 mmol, 1.00 eq) was diluted into 2- methyl THF (66.6 mL) to form a colorless solution. Then triethylamine (10.1 g, 13.9 mL, 99.8 mmol, 1 .50 eq) was added. Then benzoyl chloride (10.4 g, 8.59 mL, 73.2 mmol, 1 .10 eq) was added slowly with a syringe over 8 min. The resulting white suspension was stirred at room temperature for 18 h. The reaction was followed by TLC and GC-MS.
  • but-3-enyl benzoate 1000 mg, 1.0 equiv., 5.39 mmol
  • diglyme 5.00 mL
  • sodium dichlorofluoroacetate 2.79 g, 3.0 equiv., 16.2 mmol
  • diglyme 15.0 mL
  • syringe-pump The mixture was filtrated, washed with 10 mL tert- butyl methyl ether. Then the filtrate was quenched with sat.
  • reaction mixture was quenched with water and diluted with ethyl acetate.
  • desired material was extracted with ethyl acetate, the combined organic layers were washed with water, brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure.
  • Step 1 Preparation of 2-(2-bromo-2-fluorocyclopropyl) ethyl benzoate
  • the reaction mixture was diluted with sodium bicarbonate solution (100 mL), extracted with dichloromethane (3 x 200 mL). The combined organic layers were washed with brine (100 mL), dried over Sodium sulfate, and concentrated under reduced pressure to get crude compound.
  • the crude was purified by CombiFlash column chromatography using (0 to 100%) ethyl acetate in hexanes. Pure fractions were combined and evaporated under reduced pressure to afford tert-butyl (E)-4-(2-bromo-2- fluorocyclopropyl) but-2-enoate (3.50 g, 11.9 mmol, yield: 54%).
  • reaction mixture was stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC (50% Ethyl acetate/hexanes) and it showed no starting material.
  • Reaction mixture was diluted with water (200 mL) and then extracted with ethyl acetate (2 X 20 mL). The combined organic layers were washed with brine (10 mL), dried over Sodium sulfate, and concentrated under reduced pressure to afford crude reaction mixture.
  • the crude compound was purified by CombiFlash column chromatography (CombiFlash, 0 to 100% hexane/ethyl acetate).
  • the resulting reaction mixture was stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC (50% ethyl acetate/hexanes) and it showed no starting material.
  • the reaction mixture was diluted with water (20 mL), then extracted with ethyl acetate (2 x 20 mL). The combined organic layers were washed with brine (10 mL), dried over sodium sulfate, and concentrated under reduced pressure to afford crude reaction mixture.
  • the crude compound was purified by CombiFlash column chromatography (CombiFlash, 0 to 100% hexane/ethyl acetate).
  • the following compounds resulted in at least 80% mortality at an application rate of 200 ppm.
  • Myzus persicae Green peach aphid: Systemic activity.
  • Roots of pea seedlings infested with an aphid population of mixed ages were placed directly into aqueous test solutions prepared from 10,000 DMSO stock solutions. The samples were assessed for mortality 6 days after placing seedlings into test solutions.
  • Tetranychus urticae (Two-spotted spider mite): Feeding/contact activity.
  • Bean leaf discs on agar in 24-well microtiter plates were sprayed with aqueous test solutions prepared from 10,000 ppm DMSO stock solutions. After drying the leaf discs were infested with a mite population of mixed ages. The samples were assessed for mortality on mixed population (mobile stages) 8 days after infestation.
  • the following compounds resulted in at least 80% mortality at an application rate of 200 ppm: A6, A11 , A14, A26, A30, A31 , A38, A46, A55, A57, A60, A72, A74, A75, A79, A84, A91 , A11 1 , A113, A134, A138, A139, A140, A174, A180, A185, A217, A218, A219, A220, A236.
  • Aphis craccivora Black bean aphid - mixed population: Systemic/feeding.
  • Pea seedlings infested with mixed aged aphid population were placed into glass vials with aqueous test solutions prepared from 10,000 ppm DMSO stock solutions. After 5 days, test samples were assessed for mortality.

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Abstract

A compound 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 or acaricides.

Description

PESTICIDALLY-ACTIVE 2,2-DIHALOCYCLOPROPYL COMPOUNDS
The present invention relates to pesticidally active, and in particular, insecticidally active, 2,2- dihalocyclopropyl compounds, to compositions comprising those compounds, and to their use for controlling insect and acarine pests.
Insecticidally-active 2,2-dihalocyclopropyl compounds are known from WO 95/09151 , DE 41 04 377, EP 0 468 927, US 5,326,901 and EP 0 387 974. It has now been found that further 2,2- dihalocyclopropyl compounds have such properties.
WO 03/062265 discloses te/Y-butyl (E)-4-(2,2-difluorocyclopropyl)but-2-enoate as a synthesis intermediate in the preparation of compounds with hepatitis C virus (HCV) protease inhibitory activity.
According to the present invention, there is provided a compound of Formula (I): wherein:
X is halogen; and
A is -OR; wherein
R is hydrogen, Ci-Cealkyl, Ci-C4haloalkyl, C2-C6alkenyl, C2-C4haloalkenyl, C2-C6alkynyl, C2- C4haloalkynyl, Ci-C4nitroalkyl, Ci-C4alkoxyCi-C4alkyl, or Ci-C4haloalkoxyCi-C4alkyl; or
R is phenyl optionally substituted by 1 to 3 substituents independently selected from R3, C3- Cecycloalkyl optionally substituted by 1 to 3 substituents independently selected from R3, or a 4- to 6- membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R3; or
R is Ci-C2alkyl monosubstituted by:
(i) a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R3,
(ii) phenyl optionally substituted by 1 to 3 substituents independently selected from R3, (iii) a 4- to 6-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R3, or
(iv) Cs-Cecycloalkyl optionally substituted by 1 to 3 substituents independently selected from R3; or
A is -NR1R2; wherein
R1 is hydrogen, hydroxy, Ci-Cealkyl, Ci-C4haloalkyl, Ci-Cealkoxy, Ci-C4haloalkoxy, C2- Cealkenyl, C2-C4haloalkenyl, C2-Cealkynyl, C2-C4haloalkynyl, Ci-C4alkylsulfanyl, Ci-C4alkylsulfinyl, C1- C4haloalkylsulfanyl, Ci-C4haloalkylsulfinyl, phenoxy, -N=C(H)Ph, -NHCi-C4alkyl, -N(Ci-C4alkyl)2, C1- C4alkoxy substituted by a cyclopropyl group, Ci-C4nitroalkyl, Ci-C4alkoxyCi-C4alkyl, Ci-C4haloalkoxyCi- C4alkyl, Ci-C4alkylsulfonylCi-C4alkyl, -SC>2R4 or -C(0)R5; or
R1 is phenyl optionally substituted by 1 to 3 substituents independently selected from R3, C3- Cecycloalkyl optionally substituted by 1 to 3 substituents independently selected from R3, a 4- to 6- membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R3, a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R3, or a 9- or 10-membered heteroaromatic bicyclic ring system comprising 1 to 4 nitrogen atoms, or 0, 1 or 2 nitrogen atoms and a single atom selected from O or S, wherein the heteroaromatic bicyclic ring is optionally substituted by 1 to 3 substituents independently selected from R3; or
R1 is Ci-C2alkyl mono-substituted by:
(i) a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R3,
(ii) phenyl optionally substituted by 1 to 3 substituents independently selected from R3,
(iii) a 4- to 6-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R3, or
(iv) Cs-Cecycloalkyl optionally substituted by 1 to 3 substituents independently selected from R3; or
R1 is wherein Y is O or -CH2-; and
R2 is hydrogen, cyano, Ci-Cealkyl, Ci-C4haloalkyl, Ci-C4alkoxy, Ci-C4haloalkoxy, C2-Cealkenyl, C2-C4haloalkenyl, C2-Cealkynyl, C2-C4haloalkynyl, Ci-C4cyanoalkyl, Ci-C4nitroalkyl, Ci-C alkoxyCi- C4alkyl, Ci-C4haloalkoxyCi-C4alkyl, or -C(O)Ci-C4alkyl; or
R1 and R2, together with the nitrogen atom they share, form a 4- to 6-membered saturated or partially saturated heterocyclic ring system, further comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R8, or R1 and R2, together with the nitrogen atom they share, form a 9- membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S;
R3 is halogen, cyano, nitro, hydroxyl, formyl, Ci-Cealkyl, Ci-C4haloalkyl, C2-Cealkenyl, C2- C4haloalkenyl, C2-Cealkynyl, C2-C4haloalkynyl, Cs-Cecycloalkyl, Cs-Cehalocycloalkyl, Ci-C4alkylsulfanyl, Ci-C4alkylsulfinyl, Ci-C4alkylsulfonyl, Ci-C4haloalkylsulfanyl, Ci-C4haloalkylsulfinyl, C1- C4haloalkylsulfonyl, -C(O)Ci-C4alkyl, -C(O)NH(Ci-C4alkyl), -C(O)N(Ci-C4alkyl)2, Ci-C4alkoxy, C1- C4haloalkoxy, phenyl, Ci-C4alkylNHC(O)Ci-C4alkyl, Ci-C4alkylC(O)NHCi-C4alkyl, -NC(O)(Ci- C4alkyl)Ci-C4alkyl, -NHC(O)Ci-C4alkyl , Ci-C4alkylNHS(O)2-, -NHS(O)2Ci-C4alkyl, Ci-C4cyanoalkyl, or Cs-Cecycloalkyl substituted by a cyano;
R4 is Ci-Cealkyl, Ci-C4haloalkyl, Ci-Cealkoxy, Ci-Cehaloalkoxy, Cs-Cecycloalkyl or phenyl optionally substituted by 1 to 3 substituents independently selected from R3, a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R3, or a 4- to 6-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R3; or
R4 is Ci-C2alkyl mono-substituted by: (i) a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R3,
(ii) phenyl optionally substituted by 1 to 3 substituents independently selected from R3,
(iii) a 4- to 6-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R3, or
(iv) Cs-Cecycloalkyl optionally substituted by 1 to 3 substituents independently selected from R3; or
R4 is -NH(Ci-Cealkyl), -NH(Ci-C6alkenyl), -N(Ci-C6alkenyl)(Ci-C6alkyl), -NH(Ci-C6alkynyl), - N(Ci-C6alkynyl)(Ci-Cealkyl), -N(Ci-Cealkyl)2, -NH(C3-C6cycloalkyl), -N(C3-C6cycloalkyl)(Ci-C6alkyl), or - NH(phenyl) or -NH(CH2phenyl), wherein phenyl is optionally substituted by 1 to 3 substituents independently selected from R8;
R5 is Ci-Cealkyl, Ci-C4haloalkyl, Ci-Cealkoxy, Ci-C4haloalkoxy, Cs-Cecycloalkyl, 3-(2,2- dihalocyclopropyl)prop-1-en-1-yl, benzyloxy, benzylamine, or phenyl optionally substituted by 1 to 3 substituents independently selected from R8, a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R8, or a 5- to 6-membered saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R8;
R6 and R7 are independently selected from hydrogen, fluoro or chloro;
R8 is halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy, Ci-C4haloalkoxy or Ci- C4alkylNHSO2-; or a salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, with the proviso that the compound of Formula (I) is not te/Y-butyl (E)-4-(2,2- difluorocyclopropyl)but-2-enoate.
Surprisingly, it has been found that the novel compounds of Formula (I) have, for practical purposes, a very advantageous level of biological activity for protecting plants against insects and acarines. According to a second aspect of the invention, there is provided an agrochemical composition comprising an insecticidally or acaricidally effective amount of a compound of formula (I) as defined according to the invention.
According to a third aspect of the invention, there is provided a method of controlling insects or acarines which comprises applying an insecticidally or acaricidally effective amount of a compound of formula (I) as defined according to the invention, or a composition comprising this compound as active ingredient, to an insect or acarine pest, a locus of the pest (preferably a plant), to a plant susceptible to attack by the pest or to a plant propagation material thereof (such as a seed). According to this particular aspect of the invention, the method may exclude methods for the treatment of the human or animal body by surgery or therapy.
According to a fourth aspect of the invention, there is provided the use of a compound according to Formula (I) as an insecticide or acaricide. According to this particular aspect of the invention, the use may exclude methods for the treatment of the human or animal body by surgery or therapy.
In accordance with the third and fourth aspects of the invention, the compound of Formula (I) may also comprise te/Y-butyl (E)-4-(2,2-difluorocyclopropyl)but-2-enoate.
As used herein, the term "halogen" or “halo” refers to fluorine (fluoro), chlorine (chloro), bromine (bromo) or iodine (iodo), preferably fluorine, chlorine or bromine.
As used herein, cyano means a -CN group.
As used herein, the term “hydroxyl” or “hydroxy” means an -OH group.
As used herein, nitro means an -NO2 group.
As used herein, formyl means a -C(O)H group.
As used herein, the term "Ci-Cealkyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to six carbon atoms, and which is attached to the rest of the molecule by a single bond. Ci-C4alkyl, Ci-Cealkyl and Ci-C2alkyl are to be construed accordingly. Examples of Ci-Cealkyl include, but are not limited to, methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, and 1 ,1 -dimethylethyl (f-butyl). A “C1- C4alkylene” group refers to the corresponding definition of Ci-C4alkyl, except that such radical is attached to the rest of the molecule by two single bonds. Examples of Ci-C4alkylene, are -CH2- and - CH2CH2-.
As used herein, the term "Ci-C4haloalkyl" refers to a Ci-C4alkyl radical as generally defined above substituted by one or more of the same or different halogen atoms. Examples of Ci-C4haloalkyl include, but are not limited to fluoromethyl, fluoroethyl, difluoromethyl, trifluoromethyl, 2,2-difluoroethyl, 2,2,2- trifluoroethyl, and 3,3,3-trifluoropropyl. As used herein, the term "Ci-Cealkoxy" refers to a radical of the formula RaO- where Ra is a Ci- Cealkyl radical as generally defined above. The term "Ci-C4alkoxy" should be construed accordingly. Examples of O-Cealkoxy include, but are not limited to, methoxy, ethoxy, propoxy, iso-propoxy, and t- butoxy.
As used herein, the term "Ci-C4haloalkoxy" refers to a Ci-C4alkoxy group as defined above substituted by one or more of the same or different halogen atoms. Examples of Ci-C4haloalkoxy include, but are not limited to, fluoromethoxy, difluoromethoxy, fluoroethoxy, trifluoromethoxy, and trifluoroethoxy.
As used herein, the term "C2-C6alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one double bond that can be of either the (E)- or (^-configuration, having from two to six carbon atoms, which is attached to the rest of the molecule by a single bond. The term "C2-C4alkenyl" should be construed accordingly. Examples of C2-Cealkenyl include, but are not limited to, prop-1-enyl, allyl (prop-2-enyl), and but-1-enyl.
As used herein, the term "C2-C4haloalkenyl" refers to a C2-C4alkenyl radical as generally defined above substituted by one or more of the same or different halogen atoms.
As used herein, the term "C2-C6alkynyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one triple bond, having from two to six carbon atoms, and which is attached to the rest of the molecule by a single bond. The term "C2-C4alkynyl" should be construed accordingly. Examples of C2-Cealkynyl include, but are not limited to, prop-1 -ynyl, propargyl (prop-2-ynyl), and but-1-ynyl.
As used herein, the term "C2-C4haloalkynyl" refers to a C2-C4alkynyl radical as generally defined above substituted by one or more of the same or different halogen atoms.
As used herein, the term "Cs-Cecycloalkyl" refers to a stable, monocyclic ring radical which is saturated or partially unsaturated and contains 3 to 6 carbon atoms. C3-C4cycloalkyl is to be construed accordingly. Examples of Cs-Cecycloalkyl include, but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclopenten-1-yl, cyclopenten-3-yl, and cyclohexen-3-yl.
As used herein, the term "Cs-Cehalocycloalkyl" refers to a Cs-Cecycloalkyl ring as defined above substituted by one or more of the same or different halogen atoms.
As used herein, the term "Ci-C4alkoxyCi-C4alkyl" refers to a radical of the formula Ry-O-Rx- where Ry is a Ci-C4alkyl radical as generally defined above, and Rx is a Ci-C4alkylene radical as generally defined above.
As used herein, the term "Ci-C4haloalkoxyCi-C4alkyl" refers to a radical of the formula Ry-O-Rx- where Ry is a Ci-C4alkyl radical as generally defined above substituted by one or more of the same or different halogen atoms, and Rx is a Ci-C4alkylene radical as generally defined above.
As used herein, the term “Ci-C4cyanoalkyl” refers to a Ci-C4alkyl radical as generally defined above substituted by a cyano group.
As used herein, the term “Ci-C4nitroalkyl” refers to a Ci-C4alkyl radical as generally defined above substituted by a nitro group. As used herein, the term “Ci-C4alkylsulfanyl” refers to a radical of the formula RXS- wherein Rx is a Ci-C4alkyl radical as generally defined above.
As used herein, the term “Ci-C4haloalkylsulfanyl” refers to a Ci-C4alkylsulfanyl radical as generally defined above substituted by one or more of the same or different halogen atoms.
As used herein, the term “Ci-C4alkylsulfinyl” refers to a radical of the formula RXS(O)- wherein Rx is a Ci-C4alkyl radical as generally defined above.
As used herein, the term “Ci-C4haloalkylsulfinyl” refers to a Ci-C4alkylsulfinyl radical as generally defined above substituted by one or more of the same or different halogen atoms.
As used herein, the term “Ci-C4alkylsulfonyl” refers to a radical of the formula RXS(O)2- wherein Rx is a Ci-C4alkyl radical as generally defined above.
As used herein, the term “Ci-C4haloalkylsulfonyl” refers to a Ci-C4alkylsulfonyl radical as generally defined above substituted by one or more of the same or different halogen atoms.
As used herein, the term "Ci-C4alkylsulfonylCi-C4alkyl" refers to a radical of the formula RyS(O)2Rx- where Ry is a Ci-C4alkyl radical as generally defined above, and Rx is a Ci-C4alkylene radical as generally defined above.
Examples of a 5- or 6-membered heteroaromatic ring system, which is monocyclic and which comprises 1 to 4 heteroatoms selected from nitrogen, oxygen an sulfur, include pyridyl, pyrimidyl, pyrrolyl, pyrazolyl, furyl, thienyl, imidazolyl, isoxazolyl, oxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, pyrazinyl, pyridazinyl and triazinyl. These rings systems will not comprise contiguous oxygen and sulfur atoms.
Examples of a 9- or 10-membered heteroaromatic ring system, which is bicyclic and which comprises 1 to 4 heteroatoms selected from nitrogen, oxygen an sulfur, include quinazolinyl, isoquinolinyl, indolizinyl, isobenzofuranylnaphthyridinyl, quinoxalinyl, cinnolinyl, phthalazinyl, benzothiazolyl, benzoxazolyl, benzotriazolyl, indazolyl, indolyl, tetrahydroquinolynyl, benzofuryl, benzisofuryl, benzothienyl, benzisothienyl, isoindolyl, naphthyridinyl, benzisothiazolyl, benzisoxazolyl, benzoxazolyl, benzotriazinyl, purinyl, pteridinyl, indolizinyl, phenylpyridyl, and pyridylphenyl. These rings systems will not comprise contiguous oxygen and sulfur atoms.
Examples of a 4- to 6-membered saturated or partially saturated heterocyclic ring system, which is monocyclic and which comprises 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, include dihydropyranyl, tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, isoxazolidinyl, isothiazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, imidazolidinyl, oxadiazolidinyl, thiadiazolidinyl, dihydrofuranyl, dihydrothienyl, pyrrolinyl, isoxazolinyl, dihydropyrazolyl, dihydrooxazolyl, piperidinyl, dioxanyl, tetrahydropyranyl, hexahydropyridazinyl, hexahydropyrimidinyl, oxiranyl, morpholinyl and piperazinyl. These rings systems will not comprise contiguous oxygen and sulfur atoms.
The compounds of formula (I) according to the invention, 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, a phosphorus acid or a hydrohalic acid, with strong organic carboxylic acids, such as Ci-C4alkylcarboxylic 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-C4-alkane- 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- or tri-lower-alkylamine, for example ethyl-, diethyl-, triethyl- or dimethylpropylamine, or a mono-, di- or trihydroxy-lower-alkylamine, for example mono-, di- or triethanolamine.
The presence of one or more possible asymmetric carbon atoms in a compound of Formula (I) means that the compounds may occur in chiral isomeric forms, i.e., enantiomeric or diastereomeric forms. Also, atropisomers may occur as a result of restricted rotation about a single bond. Formula (I) is intended to include all those possible isomeric forms and mixtures thereof. The present invention includes all those possible isomeric forms and mixtures thereof for a compound of Formula (I). Likewise, Formula (I) is intended to include all possible tautomers (including lactam-lactim tautomerism and ketoenol tautomerism) where present. The present invention includes all possible tautomeric forms for a compound of Formula (I).
In each case, the compounds of Formula (I) according to the invention are in free form, in oxidized form as an N-oxide, in covalently hydrated form, or in salt form, e.g., an agronomically usable or agrochemically acceptable 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 salt formation.
The following list provides definitions, including preferred definitions, for substituents X, A, R1, R2, R3, R4, R5, R6, R7 and R8 with reference to the compounds of Formula (I) of the present invention. For any one of these substituents, any of the definitions given below may be combined with any definition of any other substituent given below or elsewhere in this document.
X is halogen. Preferably, X is fluoro, chloro, bromo.
In certain embodiments of the invention, X is fluoro.
In certain embodiments of the invention, X is chloro. In certain embodiments of the invention, X is bromo.
In certain embodiments of the invention, A is -OR, wherein:
R is hydrogen, Ci-Cealkyl, Ci-C4haloalkyl, C2-Cealkenyl, C2-C4haloalkenyl, C2-Cealkynyl, C2- C4haloalkynyl, Ci-C4nitroalkyl, Ci-C4alkoxyCi-C4alkyl, or Ci-C4haloalkoxyCi-C4alkyl; or R is phenyl optionally substituted by 1 , 2 or 3 substituents independently selected from R3, Ce-Cecycloalkyl optionally substituted by 1 , 2 or 3 substituents independently selected from R3, or a 4- to 6- membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R3; or R is Ci-C2alkyl monosubstituted by: (i) a 5- or 6-membered heteroaromatic ring system comprising 1 , 2 or 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R3, (ii) phenyl optionally substituted by 1 , 2 or 3 substituents independently selected from R3, (iii) a 4- to 6- membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R3, or (iv) Ce-Cecycloalkyl optionally substituted by 1 , 2 or 3 substituents independently selected from R3.
Preferably, R is hydrogen, Ci-Cealkyl, Ci-C2fluoroalkyl, C2-C4alkenyl, C2-C4fluoroalkenyl, C2- C4alkynyl, C2-C4fluoroalkynyl, Ci-C2nitroalkyl, Ci-C2alkoxyCi-C2alkyl, or Ci-C2fluoroalkoxyCi-C2alkyl; or R is phenyl optionally substituted by a single substituent selected from R3, benzyl optionally substituted by a single substituent selected from R3, or (pyrazolyl)methyl optionally substituted by a single substituent selected from R3, wherein R3 is halogen, cyano, nitro, hydroxyl, formyl, Ci-C4alkyl, C1- C4fluoroalkyl, C2-C4alkenyl, C2-C4alkynyl, cyclopropyl, -C(O)Ci-C4alkyl, -C(O)NH(Ci-C4alkyl), - C(O)N(Ci-C4alkyl)2, Ci-C4alkoxy, Ci-C4fluoroalkoxy, phenyl. More preferably, R is hydrogen, Ci-Cealkyl, phenyl, benzyl, or (1-methylpyrazol-4-yl)methyl. Even more preferably, R is hydrogen, methyl, ethyl, n- propyl, /so-propyl, te/Y-butyl, phenyl, benzyl, or (1-methylpyrazol-4-yl)methyl.
In certain embodiments of the invention, A is -NR1R2, wherein:
R1 is hydrogen, hydroxy, Ci-Cealkyl, Ci-C4haloalkyl, Ci-Cealkoxy, Ci-C4haloalkoxy, C2- Cealkenyl, C2-C4haloalkenyl, C2-Cealkynyl, C2-C4haloalkynyl, Ci-C4alkylsulfanyl, Ci-C4alkylsulfinyl, C1- C4haloalkylsulfanyl, Ci-C4haloalkylsulfinyl, phenoxy, -N=C(H)Ph, -NHCi-C4alkyl, -N(Ci-C4alkyl)2, C1- C4alkoxy substituted by a cyclopropyl group, Ci-C4nitroalkyl, Ci-C4alkoxyCi-C4alkyl, Ci-C4haloalkoxyCi- C4alkyl, Ci-C4alkylsulfonylCi-C4alkyl, -SO2R4 or -C(O)R5; or R1 is phenyl optionally substituted by 1 , 2 or 3 substituents independently selected from R3, Ce-Cecycloalkyl optionally substituted by 1 , 2 or 3 substituents independently selected from R3, a 4- to 6- membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R3, a 5- or 6-membered heteroaromatic ring system comprising 1 , 2 or 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R3, or a 9- or 10-membered heteroaromatic bicyclic ring system comprising 1 to 4 nitrogen atoms, or 0, 1 or 2 nitrogen atoms and a single atom selected from O or S, wherein the heteroaromatic bicyclic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R3; or R1 is Ci-C2alkyl mono-substituted by: (i) a 5- or 6-membered heteroaromatic ring system comprising 1 , 2 or 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R3, (ii) phenyl optionally substituted by 1 , 2 or 3 substituents independently selected from R3, (iii) a 4- to 6-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R3, or (iv) Cs-Cecycloalkyl optionally substituted by 1 , 2 or 3 substituents independently selected from R3; or
R1 is wherein Y is O or -CH2-; and
R2 is hydrogen, Ci-Cealkyl, Ci-C4haloalkyl, Ci-C4alkoxy, Ci-C4haloalkoxy, C2-Cealkenyl, C2- C4haloalkenyl, C2-Cealkynyl, C2-C4haloalkynyl, Ci-C4cyanoalkyl, Ci-C4nitroalkyl, Ci-C4alkoxyCi-C4alkyl, Ci-C4haloalkoxyCi-C4alkyl, or -C(O)Ci-C4alkyl.
Alternatively, R1 and R2, together with the nitrogen atom they share, form a 4- to 6-membered saturated or partially saturated heterocyclic ring system, further comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R8, or R1 and R2, together with the nitrogen atom they share, form a 9-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S.
In some preferred embodiments, R1 is selected from hydrogen, hydroxy, Ci-C4alkyl, C1- C4haloalkyl, Ci-C4alkoxy, Ci-C4alkynyl, phenoxy, -N=C(H)Ph, -NHCi-C4alkyl, -N(Ci-C4alkyl)2, C1- C4alkoxy substituted by a cyclopropyl group, Ci-C4alkoxyCi-C4alkyl, Ci-C4alkylsulfonylCi-C4alkyl, - SO2R4 or -C(O)R5; phenyl optionally substituted by 1 , 2 or 3 substituents independently selected from R3, C4-C6cycloalkyl optionally substituted by 1 or 2 substituents independently selected from R3, a 4- to 6- membered saturated or partially saturated heterocyclic ring system which comprises 1 or 2 heteroatoms individually selected from N, O, and S wherein the heterocyclic ring is optionally substituted by 1 or 2 substituents independently selected from R3, a 5- or 6-membered heteroaromatic ring system which comprises 1 , 2 or 3 heteroatoms individually selected from N, O, and S, or 9- or 10-membered heteroaromatic bicyclic ring system which comprises 1 to 4 nitrogen atoms, wherein the heteroaromatic bicyclic ring system is optionally substituted by 1 or 2 substituents independently selected from R3; or R1 is selected from Ci-C2alkyl mono-substituted by:
(i) a 5- or 6-membered heteroaromatic ring system which comprises 1 or 2 nitrogen atoms, and wherein the heteroaromatic ring is optionally substituted by a single substituent selected from R3,
(ii) phenyl optionally substituted by a single substituent selected from R3,
(iii) a 4- or 5-membered saturated or partially saturated heterocyclic ring system which comprises 1 or 2 oxygen atoms, or
(iv) C3-C5cycloalkyl optionally substituted by 1 or 2 substituents independently selected from R3; wherein Y is O or -CH2-; wherein
R3 is halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, Cs-Cecycloalkyl, Ci-C4alkoxy, Ci- C4haloalkoxy, phenyl, -Ci-C4alkylNHC(O)Ci-C4alkyl, -NC(O)(Ci-C4alkyl)Ci-C4alkyl, -NHC(O)Ci-C4alkyl, Ci-C4alkylNHS(O)2-, -NHS(O)2Ci-C4alkyl, Ci-C4cyanoalkyl, or Cs-Cecycloalkyl substituted by cyano;
R4 is Ci-C4alkyl, phenyl optionally substituted by 1 or 2 substituents independently selected from R3, a 5- or 6-membered heteroaromatic ring system which comprises 1 or 2 nitrogen atoms, wherein the heteroaromatic ring is optionally substituted by 1 or 2 substituents independently selected from R3, a 5 or 6-membered saturated or partially saturated heterocyclic ring system which comprises 1 nitrogen atom, wherein the heterocyclic ring is optionally substituted by 1 or 2 substituents independently selected from R3, Ci-C2alkyl mono-substituted by a 5- or 6-membered heteroaromatic ring system which comprises 1 or 2 nitrogen atoms, wherein the heteroaromatic ring is optionally substituted by a single substituent selected from R3, or -NH(Ci-C4alkyl); and
R5 is Ci-C4alkyl, 3-(2,2-dihalocyclopropyl)prop-1-en-1-yl, benzyloxy, benzylamine, phenyl optionally substituted by 1 to 2 substituents independently selected from R8, a 5- or 6-membered heteroaromatic ring system comprising 1 or 2 nitrogen atoms, wherein the heteroaromatic ring is optionally substituted by 1 or 2 substituents independently selected from R8, or a 5- to 6-membered saturated heterocyclic ring system comprising 1 N atom, wherein the heterocyclic ring is optionally substituted by 1 to 2 substituents independently selected from R8.
In some preferred embodiments, R1 is methyl mono-substituted by:
(i) a 5- or 6-membered heteroaromatic ring system which comprises 1 or 2 nitrogen atoms, and wherein the heteroaromatic ring is optionally substituted by a single substituent selected from R3, (ii) phenyl optionally substituted by a single substituent selected from R3,
(iii) a 4- or 5-membered saturated or partially saturated heterocyclic ring system which comprises 1 or 2 oxygen atoms, or
(iv) C3-C5cycloalkyl optionally substituted by 1 or 2 substituents independently selected from R3; wherein Y is O or -CH2-.
In some preferred embodiments, R1 is selected from hydrogen, hydroxy, methyl, ethyl, isopropyl, difluoroethyl, methoxy, ethoxy, n-propoxy, iso-propoxy, prop-2-ynyl, phenoxy, -N=C(H)Ph, methylamino, dimethylamino, cyclopropylmethoxy, 2-methoxyethyl, 2-methylsulfonylethyl, -SO2R4 or -C(O)R5; or phenyl optionally substituted by 1 , 2 or 3 substituents independently selected from R3; or cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, piperidyl, tetrahydrothiopyranyl, morpholino, dihydroisoxazolyl, dihydropyrazolyl, thienyl, thiazolyl, isoxazolyl, pyrazolyl, triazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, A/-pyrazolo[1 ,5-a]pyridinyl, quinolyl, or [1 ,2,4]triazolo[1 ,5-a]pyridinyl, optionally substituted by 1 or 2 substituents independently selected from R3; or methyl mono-substituted by a ring selected from imidazolyl, pyridyl, pyridazinyl, phenyl, oxetanyl, 1 ,3-dioxolanyl, cyclopropyl, cyclobutyl, or cyclo pentyl, wherein each ring is optionally substituted by 1 or 2 substituents independently selected from R3; or 2,3- dihydrobenzofuranyl or 2,2-difluoro-1 ,3-benzodioxolyl; wherein
R3 is fluoro, chloro, bromo, cyano, methyl, ethyl, iso-propyl, tert-butyl, difluoromethyl, trifluoromethyl, cyclopropyl, methoxy, ethoxy, difluoromethoxy, phenyl, acetamidomethyl, acetyl(methyl)amino, acetamido, ethylsulfamoyl, ethylsulfonylamino, cyanomethyl, 1-cyano-1 -methylethyl, cyanocyclopropyl; and
R4 is ethyl, iso-propyl, methylamino, a ring selected from phenyl, pyridyl, pyrrolidinyl and piperidyl each optionally substituted by 1 or 2 substituents independently selected from R3, or methyl mono-substituted by pyridyl which is optionally substituted by a single substituent selected from R3.
R5 is ethyl, iso-propyl, tert-butyl 3-(2,2-dihalocyclopropyl)prop-1-en-1-yl, benzyloxy, or benzylamine, or a ring selected from phenyl, pyridyl, pyrrolidinyl and piperidyl each optionally substituted by 1 or 2 substituents independently selected from R8.
Preferably, R2 is hydrogen, Ci-C4alkyl, Ci-C4fluoroalkyl, Ci-C4alkoxy, Ci-C4fluoroalkoxy, C2- C4alkenyl, C2-C4alkynyl, cyanomethyl, nitromethyl, Ci-C2alkoxyCi-C2alkyl, or -C(O)Ci-C4alkyl. More preferably, R2 is hydrogen, methyl or cyanomethyl. Even more preferably, R2 is hydrogen.
Preferably, R1 and R2, together with the nitrogen atom they share, form a 4-, 5- or 6-membered saturated or partially saturated heterocyclic ring system optionally further comprising a single group selected from -O-, -S-, -N(H)- or =N-, wherein the ring system is optionally substituted by 1 or 2 substituents independently selected from fluoro, chloro, cyano, methyl, ethyl, methoxy, and more preferably, R1 and R2, together with the nitrogen atom they share, form an isoxazolidinyl, 3,4-dihydro- pyrazolyl, thiomorpholinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, or 2,3-dihydropyrrolo[2,3- b]pyridin-1-yl group optionally substituted by 1 or 2 substituents independently selected from fluoro, chloro, cyano, methyl, ethyl, methoxy.
R3 is halogen, cyano, nitro, hydroxyl, formyl, Ci-Cealkyl, Ci-C4haloalkyl, C2-Cealkenyl, C2- C4haloalkenyl, C2-Cealkynyl, C2-C4haloalkynyl, Cs-Cecycloalkyl, Cs-Cehalocycloalkyl, Ci-C4alkylsulfanyl, Ci-C4alkylsulfinyl, Ci-C4alkylsulfonyl, Ci-C4haloalkylsulfanyl, Ci-C4haloalkylsulfinyl, C1- C4haloalkylsulfonyl, -C(O)Ci-C4alkyl, -C(O)NH(Ci-C4alkyl), -C(O)N(Ci-C4alkyl)2, Ci-C4alkoxy, C1- C4haloalkoxy, phenyl, Ci-C4alkylNHC(O)Ci-C4alkyl, Ci-C4alkylC(O)NHCi-C4alkyl, -NC(O)(Ci- C4alkyl)Ci-C4alkyl, -NHC(O)Ci-C4alkyl , Ci-C4alkylNHS(O)2-, -NHS(O)2Ci-C4alkyl, Ci-C4cyanoalkyl, or Cs-Cecycloalkyl substituted by a cyano.
In some embodiments of the invention, R3 is halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, C3- Cecycloalkyl, Ci-C4alkoxy, Ci-C4haloalkoxy, phenyl, -Ci-C4alkylNHC(O)Ci-C4alkyl, -NC(O)(Ci- C4alkyl)Ci-C4alkyl, -NHC(O)Ci-C4alkyl, Ci-C4alkylNHS(O)2-, -NHS(O)2Ci-C4alkyl, Ci-C4cyanoalkyl, or Cs-Cecycloalkyl substituted by cyano.
In some embodiments of the invention, R3 is fluoro, chloro, bromo, cyano, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, trifluoromethyl, cyclopropyl, methoxy, ethoxy, difluoromethoxy, phenyl, acetamidomethyl, acetyl(methyl)amino, acetamido, ethylsulfamoyl, ethylsulfonylamino, cyanomethyl, 1- cyano-1 -methyl-ethyl, cyanocyclopropyl.
R4 is Ci-Cealkyl, Ci-C4haloalkyl, Ci-Cealkoxy, Ci-Cehaloalkoxy, Cs-Cecycloalkyl or phenyl optionally substituted by 1 , 2 or 3 substituents independently selected from R3, a 5- or 6-membered heteroaromatic ring system comprising 1 , 2 or 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R3, or a 4- to 6-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R3; or R4 is Ci-C2alkyl monosubstituted by: (i) a 5- or 6-membered heteroaromatic ring system comprising 1 , 2 or 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R3, (ii) phenyl optionally substituted by 1 , 2 or 3 substituents independently selected from R3, (iii) a 4- to 6-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R3, or (iv) Cs-Cecycloalkyl optionally substituted by 1 , 2 or 3 substituents independently selected from R3; or R4 is -NH(Ci-Cealkyl), -NH(C2-C4alkenyl), -N(C2-C4alkenyl)(Ci-C6alkyl), -NH(C2-C4alkynyl), -N(C2- C4alkynyl)(Ci-C4alkyl), -N(Ci-C4alkyl)2, -NH(C3-C6cycloalkyl), -N(C3-C6cycloalkyl)(Ci-C4alkyl), or - NH(phenyl) or -NH(CH2phenyl), wherein phenyl is optionally substituted by 1 , 2 or 3 substituents independently selected from R8.
Preferably, R4 is Ci-C4alkyl, Ci-C4fluoroalkyl, Ci-C4alkoxy, -NH(Ci-C4alkyl), -NH(C2-C4alkenyl), - N(C2-C4alkenyl)(Ci-C4alkyl), -NH(C2-C4alkynyl), -N(C2-C4alkynyl)(Ci-C4alkyl), -N(Ci-C4alkyl)2, -NH(C3- Cecycloalkyl), -N(C3-C6cycloalkyl)(Ci-C4alkyl), or -NH(phenyl) or -NH(CH2phenyl), or R4 is phenyl, benzyl, pyridyl, (pyridyl)methyl, pyrrolidinyl or piperidinyl wherein each ring is optionally substituted by 1 or 2 substituents independently selected from R3, wherein R3 is halogen, cyano, nitro, hydroxyl, formyl, Ci-C4alkyl, Ci-C4fluoroalkyl, C2-C4alkenyl, C2-C4alkynyl, cyclopropyl, -C(O)Ci-C4alkyl, -C(O)NH(Ci- C4alkyl), -C(O)N(Ci-C4alkyl)2, Ci-C4alkoxy, Ci-C4fluoroalkoxy, phenyl, benzyl. More preferably, R4 is Ci- C4alkyl, or R4 is phenyl, benzyl, pyridyl or (pyridyl)methyl wherein each ring is optionally substituted by 1 or 2 substituents independently selected from R3, wherein R3 is fluoro, chloro, cyano, methyl, ethyl, n- propyl, /so-propyl, te/Y-butyl, difluoromethyl, trifluoromethyl, cyclopropyl, methoxy, ethoxy, n-propoxy, /so-propoxy, tert-butoxy, difluoromethoxy, trifluoromethoxy, phenyl, benzyl.
R5 is Ci-Cealkyl, Ci-C4haloalkyl, Ci-Cealkoxy, Ci-C4haloalkoxy, Cs-Cecycloalkyl, or 3-(2,2- dihalocyclopropyl)prop-1-en-1-yl, benzyloxy, benzylamine, or phenyl optionally substituted by 1 , 2 or 3 substituents independently selected from R8, a 5- or 6-membered heteroaromatic ring system comprising 1 , 2 or 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R8, or a 5- to 6- membered saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R8.
Preferably, R5 is Ci-C4alkyl, Ci-C4fluorooalkyl, Ci-C4alkoxy, Ci-C4fluoroalkoxy, Cs-Cecycloalkyl, benzyloxy, benzylamine, or phenyl optionally substituted by 1 or 2 substituents independently selected from R8, a 5- or 6-membered heteroaromatic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 or 2 substituents independently selected from R8, or a 5- to 6-membered saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 or 2 substituents independently selected from R8. More preferably, R5 is is Ci-C4alkyl, benzyloxy, or benzylamine, or phenyl, pyridyl, piperidyl, pyrrolidinyl, wherein each ring is optionally substituted by 1 , 2 or 3 substituents independently selected from R3, wherein R3 is fluoro, chloro, methyl, ethyl, methoxy, trifluoromethyl. In certain embodiments of the invention, R5 may be Ci-C4alkyl, or 3-(2,2-dihalocyclopropyl)prop- 1 -en-1 -yl, benzyloxy, benzylamine, or phenyl optionally substituted by 1 to 2 substituents independently selected from R8, a 5- or 6-membered heteroaromatic ring system comprising 1 or 2 nitrogen atoms, wherein the heteroaromatic ring is optionally substituted by 1 or 2 substituents independently selected from R8, or a 5- to 6-membered saturated heterocyclic ring system comprising 1 N atom, wherein the heterocyclic ring is optionally substituted by 1 to 2 substituents independently selected from R8. Otherwise, in certain embodiments of the invention, R5 is ethyl, iso-propyl, tert-butyl or 3-(2,2- dihalocyclopropyl)prop-1-en-1-yl, benzyloxy, benzylamine, or a ring selected from phenyl, pyridyl, pyrrolidinyl and piperidyl each optionally substituted by 1 or 2 substituents independently selected from R8.
R6 and R7 are independently selected from hydrogen, fluoro or chloro.
R8 is halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy, Ci-C4haloalkoxy or Ci- C4alkylNHSO2-. Preferably, R8 is fluoro, chloro, methyl, ethyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy or Ci-C2alkylNH-SC>2-.
Preferably, the compound according to Formula (I) is selected from a compound A1 to A237 listed in Table A (below) or a compound disclosed in Tables 1 to 10 (below).
In some embodiments, in a compound according to Formula (I) of the invention:
Compounds of the present invention can be made as shown in the following schemes 1 to 5, in which, unless otherwise stated, the definition of each variable is as defined herein for a compound of formula (I).
Compounds of formula (la), (1 b) and (Ic) wherein X, A, R1, R2, Ra and Rb are as defined herein, can be readily prepared. A typical example of such a synthesis is shown in Scheme 1 below.
The present compound of formula (I) contains an olefinic double bond in the (^-configuration. However, it remains a possibility that in a given sample the corresponding (Z)-isomer may be present in certain amounts as outlined below. When X is not fluorine, for example X is chlorine or bromine, compounds of formula (I) may be a mixture of isomers and diastereoisomers. The ratio between different diastereoisomers may be variable and may be determined by 1H NMR spectrometry. For example, to illustrate this: The process according to the invention for preparing compounds of formula (I) is carried out by methods generally known to those skilled in the art. Compounds of formula (I), wherein X and A are as defined in the present invention, can be readily prepared, by analogy, according to Journal of Medicinal Chemistry (2016), 59(2), 624-646, Bioorganic & Medicinal Chemistry Letters (2008), 18(14), 4219-4223, Journal of Organic Chemistry (2017), 82(19), 10376-10387. Typical examples of such synthesis are shown below for compounds of formula (I).
Scheme 1 : Process A - General cyclopropanation. wherein PG is protecting group
A compound of formula (III), wherein X is as defined in the present invention, can be prepared by cyclopropanation of an alkene of formula (II). Reactions of cyclopropanation are well-known and may include reaction of a compound of formula (II) with reactive carbenoid species generate or not in situ.
For example, carbenoid species wherein X is F, may be generated from trimethylsilyl difluoro(fluorosulfonyl)acetate (TFDA) at temperatures from 80°C to 200°C in the presence of sodium fluoride as described in J Fluor Chem (2004), 125, 459, in WO 20/17106607. Or, alternatively, by reaction of the compound of formula (II) with sodium chlorodifluoroacetate dissolved in a solvent such as diglyme, at temperatures from 100°C to 200°C, optionally under microwave irradiation (see for example US 5,089,662 or Chemistry Letters (2005), 34(10), 1440-1441), or alternatively, by reaction of the compound of formula (II) with a suitable organometallic precursor such as phenyl(trifluoromethyl) mercury or bis(trifluoromethyl)cadmium dissolved in a solvent such as benzene or toluene, in presence or not of sodium iodide at temperatures from -50°C to 150°C (see for example: e-EROS Encyclopedia of Reagents for Organic Synthesis (2006), 1 -3 or Journal of Organometallic Chemistry (1995), 503(2), C51-C54). Or, alternatively, by reaction of the compound of formula (II) with silyl derivatives such as (Chlorodifluoromethyl)trimethylsilane or (bromodifluoromethyl)trimethylsilane preferably under phase transfer catalysis conditions at temperatures from 80°C to 150°C (see for example Chemical Communications (2011), 47(8), 2411-2413, European Journal of Organic Chemistry (2019), 2019(7), 1669-1676 or Chemical Communications (2021), 57(3), 319-322. Other methods for in situ carbenoid generation include, for example, the use of trifluoromethane in presence of a base, such as sodium hydroxide, preferably under phase transfer catalysis conditions or the use of ester derivatives such as ethyl bromodifluoroacetate, preferably under phase transfer catalysis conditions in the appropriate solvent such as tetrahydrofuran or/and anisole (see for example WO 2022/003584).
Another similar examples are for carbenoid species, wherein X is Cl or Br. These carbenoid species could be generated from a halogenate derivative such as dichlorofluoromethane, tribromofluoromethane or dibromofluoromethane in presence of a base, such as sodium hydroxide or butyllithium or reagents such as titanium tetrachloride, lithium aluminum hydride, under phase transfer catalysis conditions or not (see for example Russian Chemical Bulletin (2019), 68(7), 1391-1401 , Journal of Organic Chemistry (2012), 77(21), 9893-9899, Science of Synthesis (2006), 34, 245-265, Tetrahedron Letters 1988, p 6749 or Journal of Organic Chemistry (1990), 55(2), 589-94)). Alternatively, carbenoid species wherein X is Cl or Br, could be generated from the use of ester, acid or salt of acid derivatives such as sodium dibromofluoroacetate, ethyl dibromofluoroacetate under phase transfer catalysis conditions or not, in the appropriate solvent such as dichloromethane and under or not presence of a catalyst, such as silver derivatives or a base or not, such as sodium hydroxide (see for example, Organic & Biomolecular Chemistry (2021), 19(21), 4678-4684), Journal of Fluorine Chemistry (2018), 209, 49-55. Journal of Organic Chemistry 1981 , 46 (22)p 446-4450 or Organic Letters (2022), 24(29), 5417-5421 and cited references), or by reaction of the compound of formula (II) with silyl derivatives such as fluorodichloromethyl)trimethylsilane or fluorodibromomethyl)trimethylsilane, preferably under phase transfer catalysis conditions at temperature ranged from 80°C to 150°C (see for example Chemical Communications (2021), 57(3), 319-322). Other reagents could be used to generate carbenoid species wherein X is Cl or Br, for example, polyhalogenated carbonyl compounds such as 1 ,1 ,3,3-tetrachloro-1 ,3-difluoroacetone in the appropriate solvent such as dichloromethane and under presence or not of a base, such as sodium methoxide (see for example Tetrahedron Letters (1967), (29), 2773-6 or Recueil des Travaux Chimiques des Pays-Bas et de la Belgique 1947 p 419. Other reagents that could be used to generate carbenoid species wherein X is Cl or Br are, for example, by reaction with a compound of formula (II): with a suitable organometallic precursor such as phenyl(fluorodichloromethyl) mercury (see for example: Journal of Organic Chemistry (1970), 35(5), 1297-302 or Journal of Organometallic Chemistry (1968), 11 (1), P9-P12), or with diazirines (see for example: Journal of the American Chemical Society (2005), 127(8), 2408-2409). These types of reactions are known to a person skilled in the art and can be prepared according to known methods described in these reviews, see for example: Studies of reactions of fluorinated carbenes and lithium carbenoids Hahnfeld, Jerry L (1975) PhD, 243 pages, ChemMedChem (2022), 17(21), e202200365, Emerging Fluorinated Motifs (2020), 1 , 135-194 or Science of Synthesis Fluorine (2006), 245-266.
Scheme 2: Process B - General amination.
Compounds of formula (lb), wherein R1 and R2 are as defined in the present invention, and Ra is as described in Scheme 2 may be prepared by: i) activation of a compound of formula (la), wherein R is hydrogen, and Ra is as described in Scheme 2, by methods known to those skilled in the art and described in, for example, Tetrahedron, 2005, 61 (46), 10827-10852, to form an activated species (IV), wherein Ra is as described in Scheme 2 and wherein Xoo is halogen, preferably chlorine. For example, compounds (IV) where Xoo is halogen, preferably chlorine, are formed by treatment of a compound of formula (la) wherein R is hydrogen and Ra is as described in Scheme 2, with, for example, oxalyl chloride orthionyl chloride in the presence of catalytic quantities of /V,/V-dimethylformamide (DMF) in inert solvents such as methylene chloride or tetrahydrofuran at temperatures between 20 to 100°C, and preferably 25°C. Alternatively, treatment of compounds of formula (la) with, for example, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide or dicyclohexyl carbodiimide will generate an activated species (IV), wherein Xoo is X01 or Xcc respectively, in an inert solvent, such as pyridine or tetrahydrofuran THF, optionally in the presence of a base, such as triethylamine, at temperatures between 50-180°C; followed by ii) treatment of the activated species (IV) with an amine reagent of formula (V) or a salt thereof (such as a hydrohalide salt, preferably a hydrochloride or a hydrobromide salt, or any other equivalent salt), wherein R1 and R2 is as defined in the present invention, optionally in the presence of a base, such as triethylamine or pyridine, in an inert solvent such as dichloromethane, tetrahydrofuran, dioxane or toluene, at temperatures between 0 and 50°C, to form the compounds of formula (lb). Certain bases, such as pyridine and triethylamine, may be employed successfully as both base and solvent.
These types of reaction are well known to those skilled in the art, see for example, Synthetic Organic Methodology: Comprehensive Organic Transformations. A Guide to Functional Group Preparations, Larock, R. C. 1989 p 972.
Alternatively, compounds of formula (lb), wherein R1 and R2 are as defined in the present invention, and Ra is as described in Scheme 2 may be prepared by the reaction of a compound of formula (la), wherein R is as described in the present invention and Ra is as described in Scheme 2, by methods known to those skilled in the art and described in, for example, by heating compounds of formula (la), wherein R is alkyl or benzyl, and Ra is as described in scheme 2, in the presence of amine (V), with or without solvent such as methanol or water, and with or without presence of a catalyst, such as Lewis acid derivatives optionally in the presence of a base, such as triethylamine, at temperatures of 50 to 250°C, optionally under microwave irradiation. These types of reaction are well known to those skilled in the art, see for example, Synthetic Organic Methodology: Comprehensive Organic Transformations. A Guide to Functional Group Preparations, Larock, R. C. 1989 p 987.
Scheme 3: Process C - Hydrolysis.
Compound of formula (Ic), wherein Ra is as described in Scheme 3, may be prepared by reaction of a compound of formula (la), wherein Ra is as described in scheme 3 and wherein R is alkyl or a benzyl via hydrolysis. For instance, in the case where R is methyl or ethyl, the hydrolysis can be done with water and a base, such as potassium hydroxide or lithium hydroxide, in the absence or in the presence of a solvent, such as, for instance, tetrahydrofuran or methanol. In the case where R is, for example, te/Y-butyl, the hydrolysis could be done in the presence of acid, such as trifluoroacetic acid or hydrochloric acid with or without a solvent. The reaction is carried out at a temperature of from -120°C to +130°C, preferably from -100°C to 100°C. These types of reaction are well known to those skilled in the art, see for example, Synthetic Organic Methodology: Comprehensive Organic Transformations. A Guide to Functional Group Preparations, Larock, R. C. 1989 p 981.
Scheme 4: Process D - Esterification.
Compounds of formula (la), wherein R is as defined in the present invention, and Ra is as described in scheme 4 may be prepared by: i) activation of a compound of formula (Ic), wherein Ra is as described in Scheme 4 by methods known to those skilled in the art and described in, for example, Tetrahedron, 2005, 61 (46), 10827- 10852, to form an activated species (IV), wherein Ra is as described in Scheme 4 and wherein Xoo is halogen, preferably chlorine. For example, compounds (IV) where Xoo is halogen, preferably chlorine, are formed by treatment of (Ic) wherein Ra as described in Scheme 4, with, for example, oxalyl chloride or thionyl chloride in the presence of catalytic quantities of /V,/V-dimethylformamide (DMF) in inert solvents such as methylene chloride or tetra hydrofuran at temperatures between 20 to 100°C, preferably 25°C. Alternatively, treatment of compounds of formula (Ic) with, for example, 1 -ethyl-3-(3- dimethylaminopropyl)carbodiimide or dicyclohexyl carbodiimide will generate an activated species (IV), wherein Xoo is X01 or X02, respectively, in an inert solvent, such as pyridine or tetra hydrofuran (THF), optionally in the presence of a base, such as triethylamine, at temperatures between 50-180°C, followed by ii) treatment of the activated species (IV) with an alcohol reagent of formula (VI) ROH, wherein R is as defined in the present invention, optionally in the presence of a base, such as triethylamine or pyridine, in an inert solvent such as dichloromethane, tetrahydrofuran, dioxane or toluene, at temperatures between 0 and 50°C, to form the compounds of formula (la). Certain bases, such as pyridine and triethylamine, may be employed successfully as both base and solvent. These types of reaction are well known to those skilled in the art, see for example, Synthetic Organic Methodology: Comprehensive Organic Transformations. A Guide to Functional Group Preparations, Larock, R. C.
1989 p 966.
Alternatively, compounds of formula (la), wherein R is as defined in the present invention, and Ra is as described in Scheme 4 may be prepared by reaction of esterification in acid medium by known methods, described in the literature. In particular, ester compounds of formula la wherein Ra is as described in Scheme 4, may be prepared from the corresponding carboxylic acid compounds of formula (Ic), by reaction with an alcohol of formula ROH (VI), wherein R is as described in the present invention, optionally in the presence of an acid (such as sulfuric acid). Such esterification methods are well known to a person skilled in the art.
Scheme 5
Deprotection
Cyclopropanation
(ii) (iii)
(VIII) wherein PG is a protecting group and LG a leaving group;
Compounds of formula (la) or (Ic), wherein R is as defined in the present invention, and Rb as described in scheme 5 may be prepared by i) protection of the homoallyl alcohol with a protecting group such as benzoyl. Many protecting groups could be used (see for example Protective Groups in Organic Synthesis, Third Edition, Greene, Theodora W.; Wuts, Peter G. M. 1999, Publisher John Wiley and Sons, Inc. p 17). For example, the use of benzoyl acid activated by derivation in acyl chloride or activation via treatment with, for example, 1- ethyl-3-(3-dimethylaminopropyl) carbodiimide or dicyclohexyl carbodiimide will generate an activated species that may be reacted with homoallyl alcohol. This type of reaction is very well known to those skilled in the art and described in, for example, Tetrahedron, 2005, 61 (46), 10827-10852; followed by ii) cyclopropanation with a carbene, using condition described in Scheme 1 , to synthesized compounds of formula (III) where in Rb is as described in the scheme 5; followed by iii) Deprotection of the protecting group using various methods, as function of the protecting group use (see for example Protective Groups in Organic Synthesis, Third Edition, Greene, Theodora W.; Wuts, Peter G. M. 1999, Publisher John Wiley and Sons, Inc. p 17). For example, if the protecting group is benzoyl, the deprotection could be made by hydrolysis in presence of a base such as sodium hydroxyl or potassium carbonate in solvent such as methanol, ethanol, or water. The reaction is carried out at a temperature of from 0°C to +100°C; followed by iv) oxidation of the alcohol of formula (VIII) to obtain compounds of formula (IX). This transformation is very well known and could be made by methods known to a person skilled in the art (see for example Comprehensive Organic Transformations. A Guide to Functional Group Preparations. Edited by Richard C. Larock 1989 p 604, VCH publishers). For example, compound of formula (IX) may be prepared by reaction of a compound of formula (VIII), wherein Rb is as described in Scheme 5 via oxidation with the Dess-Martin reagent in the presence of an inert solvent, such as, for example, dichloromethane, in presence or not of a base such as sodium bicarbonate at a temperature of from 0°C to 50°C; followed by v) Compound of formula (la) may be prepared by reaction of a compound of formula (IX), wherein Rb is as described in Scheme 5 via a Wittig reaction. This transformation is very well known and could be made by methods known to a person skilled in the art ((see for example, Kurti, Laszlo; Czako, Barbara; (Editors) Strategic Applications of Named Reactions in Organic Synthesis (2005) p 486 or Comprehensive Organic Transformations. A Guide to Functional Group Preparations. Edited by Richard C. Larock 1989 p 173, VCH publishers. For example, a compound of formula (la) may be prepared by reaction of a compound of formula (IX), wherein Rb is as described in Scheme 5 via Wittig reaction with Wittig reagent such as, for example, methyl (triphenylphosphoranylidene)acetate or ethyl 2-(triphenylphosphaneylidene) acetate in the presence of an inert solvent, such as, for example, toluene, tetrahydrofuran, or dichloromethane at a temperature of from 0°C to reflux. vi) A compound of formula (Ic) may be prepared by reaction of a compound of formula (la), wherein R is alkyl via hydrolysis. For instance, in the case where R is methyl or ethyl, the hydrolysis can be done with water and a base, such as potassium hydroxide or lithium hydroxide, in the absence or in the presence of a solvent, such as, for instance, tetrahydrofuran or methanol. In the case where R is, for example, te/Y-butyl, the hydrolysis is done in the presence of acid, such as trifluoroacetic acid or hydrochloric acid. The reaction is carried out at a temperature of from -120°C to +130°C, preferably from -100°C to 100°C. This transformation is well known and could be made by methods known to a person skilled in the art (see for example Comprehensive Organic Transformations. A Guide to Functional Group Preparations. Edited by Richard C. Larock 1989 p 981 , VCH publishers)
In accordance with the reactions described in any of Schemes 1 to 5, examples of suitable bases may include 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 alkylsilylamides, 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.
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.
A compound of formula (I) can be converted in a manner known per se into another compound of formula (I) by replacing one or more substituents of the starting compound of formula (I) in the customary manner by (an)other substituent(s) according to the invention.
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 per se. 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 salt-forming properties, can be obtained in free form or in the form of salts.
The compounds of formula (I) and, where appropriate, the tautomer’s 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 herein below, even when stereochemical details are not mentioned specifically in each case.
Diastereomeric mixtures or racemic 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 diastereomers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and/or chromatography.
Enantiomeric 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 cellulose, 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.
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 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 may be well-tolerated by warm-blooded species, fish and plants. The compounds of formula (I) may have a beneficial safety profile towards non-target species, such as bees, and accordingly a good toxicity profile. The active ingredients according to the invention may act against all or individual developmental stages of normally sensitive, but also resistant 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 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, 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., Euschistus spp. (stinkbugs), 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., Pianococcus 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 erytreae7
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., Eldana saccharina, Ephestia spp., Epinotia spp., Estigmene acrea, Etiella zinckinella, Eucosma spp., Eupoecilia ambiguella, Euproctis spp., Euxoa spp., Feltia jaculiferia, Gra- pholita 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, Tuta 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.
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, latex plants and ornamentals.
The active ingredients according to the invention may especially be suitable for controlling Aphis craccivora, Diabrotica balteata, Thrips tabaci, Euschistus heros, 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 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 8-endotoxins, e.g. CrylAb, CrylAc, Cry1 F, Cry1 Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vip1 , Vip2, Vip3 or Vip3A, 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 8-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 CrylAc toxin), Bollgard I® (cotton variety that expresses a CrylAc toxin), Bollgard II® (cotton variety that expresses a CrylAc and a Cry2Ab toxin), VipCot® (cotton variety that expresses a Vip3A and a CrylAb 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 CrylAb toxin. Bt1 1 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 x 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 fur 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 ambients 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 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. A further object of the invention is therefore a substrate selected from nonwoven and fabric material comprising a composition which contains a compound of formula I.
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, orto 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 03/034823, US 5631072, WO 2005/64072, WO 2006/128870, EP 1724392, WO 20051 13886 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 Table:
Examples of exotic woodborers of economic importance.
Table B. Examples of native woodborers of economic importance.
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, B/issus 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 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 or addditives, 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 per se. 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, /V,/V-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, methoxypropanol, 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, tetra hydro furfury I alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, A/-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. Surfaceactive 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 dialkylphosphate 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.
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 waterto 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. 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. 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 (EG), 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.
In a further aspect, the present invention makes available a pesticidal composition comprising a compound of the first aspect, one or more formulation additives and a carrier.
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 the compounds of formula (I) with active ingredients are preferred (the abbreviation “TX” means “one compound selected from the group consisting of a compound A1 to A237 listed in Table A (below) or a specific compound listed in Tables 1 to 10 (below): an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628) + TX; 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, S-bioallethrin + 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: 2095470-94-1 + TX, CAS number: 2377084-09-6 + TX, CAS number: 1445683-71-5 + TX, CAS number: 2408220-94-8 + TX, CAS number: 2408220-91-5 + TX, CAS number: 1365070-72-9 + TX, CAS number: 2171099-09-3 + TX, CAS number: 2396747-83-2 + TX, CAS number: 2133042-31-4 + TX, CAS number: 2133042-44-9 + TX, CAS number: 1445684-82-1 + TX, CAS number: 1445684-82-1 + TX, CAS number: 1922957-45-6 + TX, CAS number: 1922957-46- 7 + TX, CAS number: 1922957-47-8 + TX, CAS number: 1922957-48-9 + TX, CAS number: 2415706- 16-8 + TX, CAS number: 1594624-87-9 + TX, CAS number: 1594637-65-6 + TX, CAS number: 1594626-19-3 + TX, CAS number: 1990457-52-7 + TX, CAS number: 1990457-55-0 + TX, CAS number: 1990457-57-2 + TX, CAS number: 1990457-77-6 + TX, CAS number: 1990457-66-3 + TX, CAS number: 1990457-85-6 + TX, CAS number: 2220132-55-6 + TX, CAS number: 1255091-74-7 + TX, CAS number: 2719848-60-7 + TX, CAS number: 1956329-03-5 + 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, cyenopyrafen + TX, cyetpyrafen (or etpyrafen) + 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, , fenmezoditiaz + TX, fenitrothion + TX, fenobucarb + TX, fenothiocarb + TX, fenoxycarb + TX, fenpropathrin + TX, fenpyroximate + 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, fluchlordiniliprole + 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, flupyroxystrobin + TX, flupyrimin + TX, fluralaner + TX, fluvalinate + TX, fluxametamide + TX, fosthiazate + TX, gamma- cyhalothrin + TX, guadipyr + TX, halofenozide + TX, halfenprox + TX, heptafluthrin + TX, hexythiazox + TX, hydramethylnon + TX, imicyafos + TX, imidacloprid + TX, imiprothrin + TX, indazapyroxamet + TX, indoxacarb + TX, iodomethane + TX, iprodione + TX, isocycloseram + TX, isothioate + TX, ivermectin + TX, kappa-bifenthrin + TX, kappa-tefluthrin + TX, lambda-Cyhalothrin + TX, ledprona + TX, lepimectin + TX, lotilaner + 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, 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, spirobudifen + TX; spirodiclofen + TX, spiromesifen + TX, spiropidion + TX, spirotetramat + TX, spidoxamat + 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, tigolaner + TX, tiorantraniliprole + TX; tioxazafen + TX, tolfenpyrad + TX, toxaphene + TX, tralomethrin + TX, transfluthrin + TX, triazamate + TX, triazophos + TX, trichlorfon + TX, trichloronate + TX, trichlorphon + TX, trifluenfuronate + 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. + TX; 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) + TX, 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) + TX, and thiophanate (1435) + TX; an avicide selected from the group of substances consisting of chloralose (127) + TX, endrin (1 122) + TX, fenthion (346) + TX, pyridin-4-amine (IUPAC name) (23) + TX, and strychnine (745) + TX; a bactericide selected from the group of substances consisting of 1 -hydroxy-1 /7-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 (1 112) + TX, fenaminosulf (1144) + TX, formaldehyde (404) + TX, hydrargaphen (alternative name) [CCN] + TX, kasugamycin (483) + TX, kasugamycin hydrochloride hydrate (483) + TX, nickel bis(dimethyldithiocarbamate) (IUPAC 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) + TX, and Verticillium lecanii (alternative name) (848) + TX; a soil sterilant selected from the group of substances consisting of iodomethane (IUPAC name) (542) + TX, 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 -M-
(alternative name) [CCN] + TX, tepa [CCN] + TX, thiohempa (alternative name) [CCN] + TX, thiotepa (alternative name) [CCN] + TX, tretamine (alternative name) [CCN] + TX, 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 (IUPAC name) (222) + TX, (E)-tridec-4-en-1-yl acetate (IUPAC name) (829) + TX, (E)-6-methylhept-2-en-4-ol (IUPAC name) (541) + TX, (E,Z)-tetradeca-4,10-dien-1-yl acetate (IUPAC name) (779) + TX, (Z)-dodec-7-en-1-yl acetate (IUPAC name) (285) + TX, (Z)-hexadec-11- enal (IUPAC name) (436) + TX, (Z)-hexadec-11-en-1-yl acetate (IUPAC name) (437) + TX, (Z)- hexadec-13-en-11-yn-1-yl acetate (IUPAC name) (438) + TX, (Z)-icos-13-en-10-one (IUPAC name) (448) + TX, (Z)-tetradec-7-en-1-al (IUPAC name) (782) + TX, (Z)-tetradec-9-en-1-ol (IUPAC name) (783) + TX, (Z)-tetradec-9-en-1-yl acetate (IUPAC name) (784) + TX, (7E,9Z)-dodeca-7,9-dien-1-yl acetate (IUPAC name) (283) + TX, (9Z,11 E)-tetradeca-9,11-dien-1-yl acetate (IUPAC name) (780) + TX, (9Z,12E)-tetradeca-9,12-dien-1-yl acetate (IUPAC name) (781) + TX, 14-methyloctadec-1-ene (IUPAC name) (545) + TX, 4-methylnonan-5-ol with 4-methylnonan-5-one (IUPAC 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 (IUPAC name) (286) + TX, dodec-9-en-1-yl acetate (IUPAC name) (287) + TX, dodeca-8 + TX, 10-dien-1-yl acetate (IUPAC name) (284) + TX, dominicalure (alternative name) [CCN] + TX, ethyl 4-methyloctanoate (IUPAC name) (317) + TX, eugenol (alternative name) [CCN] + TX, frontalin (alternative name) [CCN] + TX, Gossyplure® (alternative name; 1 :1 mixture of the (Z,E) and (Z,Z) isomers of hexadeca-7,11-dien- 1 -yl-acetate) (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 (IUPAC name) (588) + TX, octadeca-3,13-dien-1-yl acetate (IUPAC 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 (IUPAC 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) TX, and trunc-call (alternative name) [CCN] + TX; an insect repellent selected from the group of substances consisting of 2-(octylthio)ethanol (IUPAC name) (591) + TX, butopyronoxyl (933) + TX, butoxy(polypropylene glycol) (936) + TX, dibutyl adipate (IUPAC name) (1046) + TX, dibutyl phthalate (1047) + TX, dibutyl succinate (IUPAC 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] + TX, and picaridin [CCN] + TX; a molluscicide selected from the group of substances consisting of bis(tributyltin) oxide (IUPAC 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 (IUPAC 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 (IUPAC name) (347) + TX, triphenyltin hydroxide (IUPAC name) (347) + TX, and 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 (IUPAC/ Chemical Abstracts name) (1062) + TX, 1 ,2-dichloropropane with 1 ,3- dichloropropene (IUPAC 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 (IUPAC name) (980) + TX, 5-methyl-6-thioxo-1 ,3,5-thiadiazinan-3- ylacetic acid (IUPAC 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, fenpyrad (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 (IUPAC 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 verrucaria 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 (IUPAC/ 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) + TX, zeatin (alternative name) (210) + TX, fluensulfone [318290-98-1] + TX, and fluopyram + TX; a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] + TX, 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) + TX, and Reynoutria sachalinensis extract (alternative name) (720) + TX; a rodenticide selected from the group of substances consisting of 2-isovalerylindan-1 ,3-dione (IUPAC name) (1246) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, alphachlorohydrin [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 (IUPAC name) (542) + TX, lindane (430) + TX, magnesium phosphide (IUPAC name) (640) + TX, methyl bromide (537) + TX, norbormide (1318) + TX, phosacetim (1336) + TX, phosphine (IUPAC 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) + TX, and zinc phosphide (640) + TX; a synergist selected from the group of substances consisting of 2-(2-butoxyethoxy)ethyl piperonylate (IUPAC name) (934) + TX, 5-(1 ,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone (IUPAC 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) + TX, 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 (IUPAC name) (23) + TX, thiram (804) + TX, trimethacarb (840) + TX, zinc naphthenate [CCN] + TX, 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) + TX, and thiophanate-methyl (802) + TX; a biologically active substance selected from 1 ,1-bis(4-chlorophenyl)-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, benoxafos + TX, benzyl benzoate + TX, bixafen + TX, brofenvalerate + TX, bromocyclen + TX, bromophos + TX, bromopropylate + TX, buprofezin + TX, butocarboxim + TX, butoxycarboxim + TX, butylpyridaben + TX, calcium polysulfide + TX, camphechlor + TX, carbanolate + TX, carbophenothion + TX, cymiazole + TX, chinomethionat + 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, dinopenton + 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, fenpyroximate + TX, fenpyrazamine + TX, fenson + TX, fentrifanil + TX, flubenzimine + TX, flucycloxuron + TX, fluenetil + TX, fluorbenside + TX, FMC 1 137 + 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-11-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-dichlorophenyl)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 dimethylcarbamate + 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, tenth ion-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, 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-dichlorotetrahydrothiophene 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, anisiflupurin + 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, imibenconazole + TX, ipconazole + TX, metconazole + TX, myclobutanil + TX, paclobutrazole + TX, pefurazoate + TX, penconazole + TX, proth ioconazole + TX, pyrifenox + TX, prochloraz + TX, propiconazole + TX, pyrisoxazole + TX, simeconazole + TX, tebuconazole + 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, R-metalaxyl + 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, chlorothalonil + 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, flumetylsulforim + TX, fluopicolide + TX, fluoxytioconazole + 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 -y I] acety l]-4-pipe ridy l]th iazo I-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, metarylpicoxamid + TX, tebufloquin + TX, ipflufenoquin + TX, quinofumelin + TX, isofetamid + TX, ethyl 1-[[4-[[2-(trifluoromethyl)- 1 ,3-dioxolan-2-yl]methoxy]phenyl]methyl]pyrazole-3-carboxylate + TX (may be prepared from the methods described in WO 2020/056090), ethyl 1-[[4-[(Z)-2-ethoxy-3,3,3-trifluoro-prop-1- enoxy]phenyl]methyl]pyrazole-3-carboxylate + TX (may be prepared from the methods described in WO 2020/056090), methyl N-[[4-[1-(4-cyclopropyl-2,6-difluoro-phenyl)pyrazol-4-yl]-2-methyl- phenyl]methyl]carbamate + TX (may be prepared from the methods described in WO 2020/097012), methyl N-[[4-[1 -(2,6-difluoro-4-isopropyl-phenyl)pyrazol-4-yl]-2-methyl-phenyl]methyl]carbamate + TX (may be prepared from the methods described in WO 2020/097012), 6-chloro-3-(3-cyclopropyl-2-fluoro- phenoxy)-N-[2-(2,4-dimethylphenyl)-2,2-difluoro-ethyl]-5-methyl-pyridazine-4-carboxamide + TX (may be prepared from the methods described in WO 2020/109391), 6-chloro-N-[2-(2-chloro-4-methyl- phenyl)-2,2-difluoro-ethyl]-3-(3-cyclopropyl-2-fluoro-phenoxy)-5-methyl-pyridazine-4-carboxamide + TX (may be prepared from the methods described in WO 2020/109391), 6-chloro-3-(3-cyclopropyl-2-fluoro- phenoxy)-N-[2-(3,4-dimethylphenyl)-2,2-difluoro-ethyl]-5-methyl-pyridazine-4-carboxamide + TX (may be prepared from the methods described in WO 2020/109391), 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, flufenoxadiazam + 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 ,1 '-biphenyl]-4-yl]-5- pyrimidinemethanol + TX, fluoxapiprolin + TX, enoxastrobin + TX, methyl (Z)-3-methoxy-2-[2-methyl-5-[4-(trifluoromethyl)triazol-2- yl]phenoxy]prop-2-enoate + TX, methyl (Z)-3-methoxy-2-[2-methyl-5-(4-propyltriazol-2- yl)phenoxy]prop-2-enoate + TX, methyl (Z)-2-[5-(3-isopropylpyrazol-1-yl)-2-methyl-phenoxy]-3- methoxy-prop-2-enoate + TX, methyl (Z)-3-methoxy-2-[2-methyl-5-(3-propylpyrazol-1-yl)phenoxy]prop- 2-enoate + TX, methyl (Z)-3-methoxy-2-[2-methyl-5-[3-(trifluoromethyl)pyrazol-1-yl]phenoxy]prop-2- enoate + TX (these compounds may be prepared from the methods described in W02020/079111), methyl (Z)-2-(5-cyclohexyl-2-methyl-phenoxy)-3-methoxy-prop-2-enoate + TX, methyl (Z)-2-(5- cyclopentyl-2-methyl-phenoxy)-3-methoxy-prop-2-enoate + TX (these compounds may be prepared from the methods described in W02020/193387), 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, seboctylamine + 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 WO2019/1 10427); 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- [(1 S)-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-((1 S)-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 -y I) isoq u inol i n e + 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, Altemaria 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 (MicroAZ®, 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 (e.g, Biostart™, formerly Rhizoboost®) + TX, Bacillus licheniformis strain 3086 (EcoGuard®, Green Releaf®) + TX, Bacillus circulans + TX, Bacillus firmus (BioSafe®, BioNem-WP®, 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®, 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®, Serenade®, 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®, Rhizopro®) + TX, Bacillus thuringiensis Cry 2Ae + TX, Bacillus thuringiensis Cry1 Ab + TX, Bacillus thuringiensis aizawai GC 91 (Agree®) + TX, Bacillus thuringiensis israelensis (BMP123®, Aquabac®, VectoBac®) + TX, Bacillus thuringiensis kurstaki (Javelin®, Deliver®, CryMax®, Bonide®, Scutella WP®, Turilav WP®, Astuto®, Dipel WP®, Biobit®, Foray®) + TX, Bacillus thuringiensis kurstaki BMP 123 (Baritone®) + TX, Bacillus thuringiensis kurstaki HD-1 (Bioprotec-CAF 1 3P®) + TX, Bacillus thuringiensis strain BD#32 + TX, Bacillus thuringiensis strain AQ52 + TX, Bacillus thuringiensis var. aizawai (XenTari®, DiPei®) + TX, bacteria spp. (GROWMEND®, GROWSWEET®X, Shootup®) + TX, bacteriophage of Clavipacter michiganensis (AgriPhage®) + TX, Bakflor® + TX, Beauveria bassiana (Beaugenic®, Brocaril WP®) + TX, Beauveria bassiana GHA (Mycotrol ES®, Mycotrol O®, BotaniGuard®) + TX, Beauveria brongniartii (Engerlingspilz®, Schweizer Beauveria®, 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®, Intercept®, 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®, 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®, Madex® Plus, Madex® Max, Carpovirusine Evo2®) + 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®, 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, Kloeckera apiculata + TX, Kloeckera 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, Muscodorroseus strain A3- 5 + TX, Mycorrhizae spp. (AMykor®, 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®, 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®, 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 flocculosa strain PF-A22 UL (Sporodex L®) + TX, Puccinia canaliculata + TX, Puccinia thlaspeos (Wood Warrior®) + TX, Pythium paroecandrum + TX, Pythium oligandrum (Polygandron®, Polyversum®) + TX, Pythium periplocum + TX, Rhanella aquatilis + TX, Rhanella spp. + TX, Rhizobia (Dormal®, 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®, 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 (My costar®) + TX, Trichoderma harzianum -22 (Trianum-P®, Plantshield HC®, Rootshield®, 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®, Vertalec®) + TX, Vip3Aa20 (VIPtera®) + TX, Virgibaclillus marismortui + TX, Xanthomonas campestris pv. Poae (Camperico®) + TX, Xenorhabdus bovienii + TX, and Xenorhabdus nematophilus + TX
Plant extracts including: pine oil (Retenol®) + TX, azadirachtin (Plasma Neem Oil®, AzaGuard®, MeemAzal®, Molt-X®) + TX, Botanical IGR (Neemazad®, 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 ® (Regalia®, Sakalia®) + TX, rotenone (Eco Roten®) + TX, Rutaceae plant extract (Soleo®) + TX, soybean oil (Ortho ecosense®) + TX, Melaleuca alternifolia extract (also called 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®) +TX; 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®, 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, (3E,8Z,11Z)-3,8,11- Tetradecatrienyl acetate + TX, (7Z,11Z,13E)-7,11 ,13-Hexadecatrienal + TX, (E,Z)-7,9-Dodecadien-1-yl acetate + TX, 2-Methyl-1 -butanol + TX, Calcium acetate + TX, Scenturion® + TX, Biolure® + TX, Check- Mate® + TX, Lavandulyl senecioate + TX;
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®, Andersoni-System®) + TX, Amblyseius californicus (Amblyline®, Spical®) + TX, Amblyseius cucumeris (Thripex®, Bugline cucumeris®) + TX, Amblyseius fallacis (Fallacis®) + TX, Amblyseius swirskii (Bugline swirskii®, 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®, 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®, 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 (Pianopar®) + TX, Coccophagus cowperi + TX, Coccophagus lycimnia + TX, Cotesia flavipes + TX, Cotesia plutellae + TX, Cryptolaemus montrouzieri (Cryptobug®, 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®, Digline®) + TX, Dacnusa sibirica (DacDigline®, Minex®) + TX, Diversinervus spp. + TX, Encarsia citrina + TX, Encarsia formosa (Encarsia max®, Encarline®, 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®, Eretline e®) + TX, Eretmocerus eremicus (Bemimix®) + TX, Eretmocerus hayati + TX, Eretmocerus mundus (Bemipar®, 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, Habrobracon hebetor + TX, Harmonia axyridis (HarmoBeetle®) + TX, Heterorhabditis spp. (Lawn Patrol®) + TX, Heterorhabditis bacteriophora (NemaShield HB®, Nemaseek®, Terranem-Nam®, Terranem®, Larvanem®, B-Green®, NemAttack®, Nematop®) + TX, Heterorhabditis megidis (Nemasys H®, BioNem H®, Exhibitline hm®, Larvanem-M®) + TX, Hippodamia convergens + TX, Hypoaspis aculeifer (Aculeifer-System®, Entomite-A®) + TX, Hypoaspis miles (Hypoline m®, 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®, Macroline c®, 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®, Nesibug®) + TX, Ophyra aenescens (Biofly®) + TX, Orius insidiosus (Thripor-I®, Online i®) + TX, Orius laevigatus (Thripor-L®, Online I®) + TX, Orius majusculus (Online 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®, 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®, Millenium®, BioNem C®, NemAttack®, Nemastar®, Capsanem®) + TX, Steinernema feltiae (NemaShield®, Nemasys F®, BioNem F, Steinernema-System®, NemAttack®, Nemaplus®, Exhibitline st®, Scia-rid®, Entonem®) + TX, Steinernema kraussei (Nemasys L®, BioNem L®, Exhibitline srb®) + TX, Steinernema riobrave (BioVector®, 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, Trichogramma ostriniae + TX, Trichogramma platneri + TX, Trichogramma pretiosum + TX, Xanthopimpla stemmator + TX 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®, Ni-HIBIT Gold CST®) + TX, fatty acids derived from a natural by-product of extra virgin olive oil (FLIPPER®), 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 (Si I- Matrix®) + TX, potassium iodide + potassiumthiocyanate (Enzicur®) + TX, SuffOil-X® + TX, Spider venom + TX, Nosema locustae (Semaspore Organic Grasshopper Control®) + TX, Sticky traps (Trapline YF®, Rebell Amarillo®) + TX and Traps (Takitrapline y + b®) + TX;
(1) antibacterial agents selected from the group of:
(1.1) bacteria, examples of which are Bacillus mojavensis strain R3B (Accession No. NCAIM (P) B001389) (WO 2013/034938) from Certis USA LLC + TX; Bacillus pumilus, in particular strain BU F-33, having NRRL Accession No. 50185 (CARTISSA® from BASF, EPA Reg. No. 71840-19) + TX; Bacillus subtilis, in particular strain QST713/AQ713 (SERENADE OPTI or SERENADE ASO from Bayer CropScience LP, US, having NRRL Accession No. B21661 , U.S. Patent No. 6,060,051) + TX; Bacillus subtilis strain BU1814, (VELONDIS® PLUS, VELONDIS® FLEX and VELONDIS® EXTRA from BASF SE) + TX; Bacillus subtilis var. amyloliquefaciens strain FZB24 having Accession No. DSM 10271 (available from Novozymes as TAEGRO® or TAEGRO® ECO (EPA Registration No. 70127-5)) + TX; Bacillus subtilis CX-9060 from Certis USA LLC + TX; Bacillus sp., in particular strain D747 (available as DOUBLE NICKEL® from Kumiai Chemical Industry Co., Ltd.), having Accession No. FERM BP-8234, U.S. Patent No. 7,094,592 + TX; Paenibacillus sp. strain having Accession No. NRRL B-50972 or Accession No. NRRL B-67129, WO 2016/154297 + TX; Paenibacillus polymyxa, in particular strain AC- 1 (e.g. TOPSEED® from Green Biotech Company Ltd.) + TX; Pantoea agglomerans, in particular strain E325 (Accession No. NRRL B-21856) (available as BLOOMTIME BIOLOGICAL™ FD BIOPESTICIDE from Northwest Agri Products) + TX; Pseudomonas proradix (e.g. PRORADIX® from Sourcon Padena) + TX; and
(1.2) fungi, examples of which are Aureobasidium pullulans, in particular blastospores of strain DSM14940, blastospores of strain DSM 14941 or mixtures of blastospores of strains DSM14940 and DSM14941 (e.g., BOTECTOR® and BLOSSOM PROTECT® from bio-ferm, CH) + TX; Pseudozyma aphidis (as disclosed in WO2011/151819 by Yissum Research Development Company of the Hebrew University of Jerusalem) + TX; Saccharomyces cerevisiae, in particular strains CNCM No. 1-3936, CNCM No. 1-3937, CNCM No. 1-3938 or CNCM No. 1-3939 (as disclosed in WO 2010/086790 from Lesaffre et Compagnie, FR) + TX;
(2) biological fungicides selected from the group of:
(2.1) bacteria, examples of which are Agrobacterium radiobacter strain K84 (e.g. GALLTROL-A® from AgBioChem, CA) + TX; Agrobacterium radiobacter strain K1026 (e.g. NOGALL™ from BASF SE) + TX; Bacillus subtilis var. amyloliquefaciens strain FZB24 having Accession No. DSM 10271 (available from Novozymes as TAEGRO® or TAEGRO® ECO (EPA Registration No. 70127-5)) + TX; Bacillus amyloliquefaciens, in particular strain D747 (available as Double Nickel™ from Kumiai Chemical Industry Co., Ltd., having accession number FERM BP-8234, US Patent No. 7,094,592) + TX; Bacillus amyloliquefaciens strain F727 (also known as strain MBI110) (NRRL Accession No. B-50768, WO 2014/028521) (STARGUS® from Marrone Bio Innovations) + TX; Bacillus amyloliquefaciens strain FZB42, Accession No. DSM 23117 (available as RHIZOVITAL® from ABiTEP, DE) + TX; Bacillus amyloliquefaciens isolate B246 (e.g. AVOGREEN™ from University of Pretoria) + TX; Bacillus licheniformis, in particular strain SB3086, having Accession No. ATCC 55406, WO 2003/000051 (available as ECOGUARD® Biofungicide and GREEN RELEAF™ from Novozymes) + TX; Bacillus licheniformis FMCH001 and Bacillus subtilis FMCH002 (QUARTZO® (WG) and PRESENCE® (WP) from FMC Corporation) + TX; Bacillus methylotrophicus strain BAC-9912 (from Chinese Academy of Sciences’ Institute of Applied Ecology) + TX; Bacillus mojavensis strain R3B (Accession No. NCAIM (P) B001389) (WO 2013/034938) from Certis USA LLC + TX; Bacillus mycoides, isolate, having Accession No. B-30890 (available as BMJ TGAI® or WG and LifeGard™ from Certis USA LLC) + TX; Bacillus pumilus, in particular strain QST2808 (available as SONATA® from Bayer CropScience LP, US, having Accession No. NRRL B-30087 and described in U.S. Patent No. 6,245,551) + TX; Bacillus pumilus, in particular strain GB34 (available as Yield Shield® from Bayer AG, DE) + TX; Bacillus pumilus, in particular strain BU F-33, having NRRL Accession No. 50185 (available as part of the CARTISSA product from BASF, EPA Reg. No. 71840-19) + TX; Bacillus subtilis, in particular strain QST713/AQ713 (available as SERENADE OPTI or SERENADE ASO from Bayer CropScience LP, US, having NRRL Accession No. B21661 and described in U.S. Patent No. 6,060,051) + TX; Bacillus subtilis Y1336 (available as BIOBAC® WP from Bion-Tech, Taiwan, registered as a biological fungicide in Taiwan under Registration Nos. 4764, 5454, 5096 and 5277) + TX; Bacillus subtilis strain MBI 600 (available as SUBTILEX from BASF SE), having Accession Number NRRL B-50595, U.S. Patent No. 5,061 ,495 + TX; Bacillus subtilis strain GB03 (available as Kodiak® from Bayer AG, DE) + TX; Bacillus subtilis strain BU1814, (available as VELONDIS® PLUS, VELONDIS® FLEX and VELONDIS® EXTRA from BASF SE) + TX; Bacillus subtilis CX-9060 from Certis USA LLC + TX; Bacillus subtilis KTSB strain (FOLI ACTIVE® from Donaghys) + TX; Bacillus subtilis IAB/BS03 (AVIV™ from STK Bio-Ag Technologies, PORTENTO® from Idai Nature) + TX; Bacillus subtilis strain Y1336 (available as BIOBAC® WP from Bion-Tech, Taiwan, registered as a biological fungicide in Taiwan under Registration Nos. 4764, 5454, 5096 and 5277) + TX; Paenibacillus epiphyticus (WO 2016/020371) from BASF SE + TX; Paenibacillus polymyxa ssp. plantarum (WO 2016/020371) from BASF SE + TX; Paenibacillus sp. strain having Accession No. NRRL B-50972 or Accession No. NRRL B-67129, WO 2016/154297 + TX; Pseudomonas chlororaphis strain AFS009, having Accession No. NRRL B-50897, WO 2017/019448 (e.g., HOWLER™ and ZIO® from AgBiome Innovations, US) + TX; Pseudomonas chlororaphis, in particular strain MA342 (e.g. CEDOMON®, CERALL®, and CEDRESS® by Bioagri and Koppert) + TX; Pseudomonas fluorescens strain A506 (e.g. BLIGHTBAN® A506 by NuFarm) + TX; Pseudomonas proradix (e.g. PRORADIX® from Sourcon Padena) + TX; Streptomyces griseoviridis strain K61 (also known as Streptomyces galbus strain K61) (Accession No. DSM 7206) (MYCOSTOP® from Verdera, PREFENCE® from BioWorks, cf. Crop Protection 2006, 25, 468-475) + TX; Streptomyces lydicus strain WYEC108 (also known as Streptomyces lydicus strain WYCD108US) (ACTINO-IRON® and ACTINOVATE® from Novozymes) + TX; and
(2.2) fungi, examples of which are Ampelomyces quisqualis, in particular strain AQ 10 (e.g. AQ 10® by IntrachemBio Italia) + TX; Ampelomyces quisqualis strain AQ10, having Accession No. CNCM 1-807 (e.g., AQ 10® by IntrachemBio Italia) + TX; Aspergillus flavus strain NRRL 21882 (products known as AFLA-GUARD® from Syngenta/ChemChina) + TX; Aureobasidium pullulans, in particular blastospores of strain DSM14940 + TX; Aureobasidium pullulans, in particular blastospores of strain DSM 14941 + TX; Aureobasidium pullulans, in particular mixtures of blastospores of strains DSM14940 and DSM 14941 (e.g. Botector® by bio-ferm, CH) + TX; Chaetomium cupreum (Accession No. CABI 353812) (e.g. BIOKUPRUM™ by AgriLife) + TX; Chaetomium globosum (available as RIVADIOM® by Rivale) + TX; Cladosporium cladosporioides, strain H39, having Accession No. CBS122244, US 2010/0291039 (by Stichting Dienst Landbouwkundig Onderzoek) + TX; Coniothyrium minitans, in particular strain CON/M/91-8 (Accession No. DSM9660, e.g. Contans ® from Bayer CropScience Biologies GmbH) + TX; Cryptococcus flavescens, strain 3C (NRRL Y-50378), (B2.2.99) + TX; Dactylaria Candida + TX; Dilophosphora alopecuri (available as TWIST FUNGUS®) + TX; Fusarium oxysporum, strain Fo47 (available as FUSACLEAN® by Natural Plant Protection) + TX; Gliocladium catenulatum (Synonym: Clonostachys rosea f. catenulate) strain J1446 (e.g. Prestop ® by Lallemand) + TX; Gliocladium roseum (also known as Clonostachys rosea f rosea), in particular strain 321 U from Adjuvants Plus, strain ACM941 as disclosed in Xue A.G (Efficacy of Clonostachys rosea strain ACM941 and fungicide seed treatments for controlling the root tot complex of field pea, Can. J. Plant Sci. 2003, 83(3): 519-524), or strain IK726 (Jensen DF, et al. Development of a biocontrol agent for plant disease control with special emphasis on the near commercial fungal antagonist Clonostachys rosea strain ’IK726’, Australasian Plant Pathol. 2007,36(2), 95-101) + TX; Lecanicillium lecanii (formerly known as Verticillium lecanii) conidia of strain KV01 (e.g. Vertalec® by Koppert/Arysta) + TX; Metschnikowia fructicola, in particular strain NRRL Y-30752, (B2.2.3) + TX; Microsphaeropsis ochracea + TX; Muscodor roseus, in particular strain A3-5 (Accession No. NRRL 30548) + TX; Penicillium steckii (DSM 27859, WO 2015/067800) from BASF SE + TX; Penicillium vermiculatum + TX; Phlebiopsis gigantea strain VRA 1992 (ROTSTOP® C from Danstar Ferment) + TX; Pichia anomala, strain WRL-076 (NRRL Y-30842), U.S. Patent No. 7,579,183 + TX; Pseudozyma flocculosa, strain PF-A22 UL (available as SPORODEX® L by Plant Products Co., CA) + TX; Saccharomyces cerevisiae, in particular strain LASO2 (from Agro-Levures et Derives), strain LAS117 cell walls (CEREVISANE® from Lesaffre, ROMEO® from BASF SE), strains CNCM No. 1-3936, CNCM No. 1-3937, CNCM No. 1-3938, CNCM No. 1-3939 (WO 2010/086790) from Lesaffre et Compagnie, FR + TX; Simplicillium lanosoniveum + TX; Talaromyces flavus, strain V117b + TX; Trichoderma asperelloides JM41 R (Accession No. NRRL B-50759) (TRICHO PLUS® from BASF SE) + TX; Trichoderma asperellum, in particular, strain kd (e.g. T-Gro from Andermatt Biocontrol) + TX; Trichoderma asperellum, in particular strain SKT-1 , having Accession No. FERM P-16510 (e.g. ECOHOPE® from Kumiai Chemical Industry), strain T34 (e.g. T34 Biocontrol by Biocontrol Technologies S.L., ES) or strain ICC 012 from Isagro + TX; Trichoderma atroviride, in particular strain SC1 (Accession No. CBS 122089, WO 2009/116106 and U.S. Patent No. 8,431 ,120 (from Bi-PA)), strain 77B (T77 from Andermatt Biocontrol) or strain LU132 (e.g. Sentinel from Agrimm Technologies Limited) + TX; Trichoderma atroviride, strain CNCM 1-1237 (e.g. Esquive® WP from Agrauxine, FR) + TX; Trichoderma atroviride, strain no. V08/002387 + TX; Trichoderma atroviride, strain NMI no. V08/002388 + TX; Trichoderma atroviride, strain NMI no. V08/002389 + TX; Trichoderma atroviride, strain NMI no. V08/002390 + TX; Trichoderma atroviride, strain LC52 (e.g. Tenet by Agrimm Technologies Limited) + TX; Trichoderma atroviride, strain ATCC 20476 (IMI 206040) + TX; Trichoderma atroviride, strain T11 (IMI352941/ CECT20498) + TX; Trichoderma atroviride, strain SKT-1 (FERM P-16510), JP Patent Publication (Kokai) 11-253151 A + TX; Trichoderma atroviride, strain SKT-2 (FERM P-1651 1), JP Patent Publication (Kokai) 11-253151 A + TX; Trichoderma atroviride, strain SKT-3 (FERM P-17021), JP Patent Publication (Kokai) 11-253151 A + TX; Trichoderma fertile (e.g. product TrichoPlus from BASF) + TX; Trichoderma gamsii (formerly T. viride), strain ICC080 (IMI CC 392151 CABI, e.g. BioDerma by AGROBIOSOL DE MEXICO, S.A. DE C.V.) + TX; Trichoderma gamsii (formerly T. viride), strain ICC 080 (IMI CC 392151 CABI) (available as BIODERMA® by AGROBIOSOL DE MEXICO, S.A. DE C.V.) + TX; Trichoderma harmatum + TX; Trichoderma harmatum, having Accession No. ATCC 28012 + TX; Trichoderma harzianum strain T-22 (e.g. Trianum-P from Andermatt Biocontrol or Koppert) or strain Cepa SimbT5 (from Simbiose Agro) + TX; Trichoderma harzianum + TX; Trichoderma harzianum rifai T39 (e.g. Trichodex® from Makhteshim, US) + TX; Trichoderma harzianum, strain ITEM 908 (e.g. Trianum-P from Koppert) + TX; Trichoderma harzianum, strain TH35 (e.g. Root-Pro by Mycontrol) + TX; Trichoderma harzianum, strain DB 103 (available as T-GRO® 7456 by Dagutat Biolab) + TX; Trichoderma polysporum, strain IMI 206039 (e.g. Binab TF WP by BINAB Bio-Innovation AB, Sweden) + TX; Trichoderma stromaticum, having Accession No. Ts3550 (e.g. Tricovab by CEPLAC, Brazil) + TX; Trichoderma virens (also known as Gliocladium virens), in particular strain GL-21 (e.g. SoilGard by Certis, US) + TX; Trichoderma virens strain G-41 , formerly known as Gliocladium virens (Accession No. ATCC 20906) (e.g., ROOTSHIELD® PLUS WP and TURFSHIELD® PLUS WP from BioWorks, US) + TX; Trichoderma viride, strain TV1 (e.g. Trianum-P by Koppert) + TX; Trichoderma viride, in particular strain B35 (Pietr et al., 1993, Zesz. Nauk. A R w Szczecinie 161 : 125-137) + TX; mixtures ofTrichoderma asperellum strain ICC 012 (also known as Trichoderma harzianum ICC012), having Accession No. CABI CC IMI 392716 and Trichoderma gamsii (formerly T. viride) strain ICC 080, having Accession No. IMI 392151 (e.g., BIO-TAM™ from Isagro USA, Inc. or BIODERMA® by Agrobiosol de Mexico, S.A. de C.V.) + TX; Ulocladium oudemansii strain U3, having Accession No. NM 99/06216 (e.g., BOTRY-ZEN® by Botry-Zen Ltd, New Zealand and BOTRYSTOP® from BioWorks, Inc.) + TX; Verticillium albo-atrum (formerly V. dahliae), strain WCS850 having Accession No. WCS850, deposited at the Central Bureau for Fungi Cultures (e.g., DUTCH TRIG® by Tree Care Innovations) + TX; Verticillium chlamydosporium + TX;
(3) biological control agents having an effect for improving plant growth and/or plant health selected from the group of:
(3.1) bacteria, examples of which are Azospirillum brasilense (e.g., VIGOR® from KALO, Inc.) + TX; Azospirillum lipoferum (e.g., VERTEX-IF™ from TerraMax, Inc.) + TX; Azorhizobium caulinodans, in particular strain ZB-SK-5 + TX; Azotobacter chroococcum, in particular strain H23 + TX; Azotobacter vinelandii, in particular strain ATCC 12837 + TX; a mixture of Azotobacter vinelandii and Clostridium pasteurianum (available as INVIGORATE® from Agrinos) + TX; Bacillus amyloliquefaciens pm414 (LOLI-PEPTA® from Biofilm Crop Protection) + TX; Bacillus amyloliquefaciens SB3281 (ATCC # PTA- 7542, WO 2017/205258) + TX; Bacillus amyloliquefaciens TJ1000 (available as QUIKROOTS® from Novozymes) + TX; Bacillus amyloliquefaciens, in particular strain IN937a + TX; Bacillus amyloliquefaciens, in particular strain FZB42 (e.g. RHIZOVITAL® from ABiTEP, DE) + TX; Bacillus amyloliquefaciens BS27 (Accession No. NRRL B-5015) + TX; Bacillus cereus family member EE128 (NRRL No. B-50917) + TX; Bacillus cereus family member EE349 (NRRL No. B-50928) + TX; Bacillus cereus, in particular strain BP01 (ATCC 55675, e.g. MEPICHLOR® from Arysta Lifescience, US) + TX; Bacillus firmus, in particular strain CNMC 1-1582 (e.g. VOTIVO® from BASF SE) + TX; Bacillus mycoides BT155 (NRRL No. B-50921) + TX; Bacillus mycoides EE118 (NRRL No. B-50918) + TX; Bacillus mycoides EE141 (NRRL No. B-50916) + TX; Bacillus mycoides BT46-3 (NRRL No. B-50922) + TX; Bacillus pumilus, in particular strain QST2808 (Accession No. NRRL No. B-30087) + TX; Bacillus pumilus, in particular strain GB34 (e.g. YIELD SHIELD® from Bayer Crop Science, DE) + TX; Bacillus siamensis, in particular strain KCTC 13613T + TX; Bacillus subtilis, in particular strain QST713/AQ713 (having NRRL Accession No. B-21661 and described in U.S. Patent No. 6,060,051 , available as SERENADE® OPTI or SERENADE® ASO from Bayer CropScience LP, US) + TX; Bacillus subtilis, in particular strain AQ30002 (Accession No. NRRL No. B-50421 and described in U.S. Patent Application No. 13/330,576) + TX; Bacillus subtilis, in particular strain AQ30004 (NRRL No. B-50455 and described in U.S. Patent Application No. 13/330,576) + TX; Bacillus subtilis strain BU1814, (available as TEQUALIS® from BASF SE), Bacillus subtilis rm303 (RHIZOMAX® from Biofilm Crop Protection) + TX; Bacillus thuringiensis BT013A (NRRL No. B-50924) also known as Bacillus thuringiensis 4Q7 + TX; a mixture of Bacillus licheniformis FMCH001 and Bacillus subtilis FMCH002 (available as QUARTZO® (WG), PRESENCE® (WP) from FMC Corporation) + TX; Bacillus subtilis, in particular strain MBI 600 (e.g. SUBTILEX® from BASF SE) + TX; Bacillus tequilensis, in particular strain NII-0943 + TX; Bradyrhizobium japonicum (e.g. OPTIMIZE® from Novozymes) + TX; Delftia acidovorans, in particular strain RAY209 (e.g. BIOBOOST® from Brett Young Seeds) + TX; Mesorhizobium cicer (e.g., NODULATOR from BASF SE) + TX; Lactobacillus sp. (e.g. LACTOPLANT® from LactoPAFI) + TX; Rhizobium leguminosarium biovar viciae (e.g., NODULATOR from BASF SE) + TX; Pseudomonas proradix (e.g. PRORADIX® from Sourcon Padena) + TX; Pseudomonas aeruginosa, in particular strain PN1 + TX; Rhizobium leguminosarum, in particular bv. viceae strain Z25 (Accession No. CECT 4585) + TX; Paenibacillus polymyxa, in particular strain AC-1 (e.g. TOPSEED® from Green Biotech Company Ltd.) + TX; Serratia marcescens, in particular strain SRM (Accession No. MTCC 8708) + TX; Sinorhizobium meliloti strain NRG-185-1 (NITRAGIN® GOLD from Bayer CropScience) + TX; Thiobacillus sp. (e.g. CROPAID® from Cropaid Ltd UK) + TX; and
(3.2) fungi, examples of which are Purpureocillium lilacinum (previously known as Paecilomyces lilacinus) strain 251 (AGAL 89/030550, e.g. BioAct from Bayer CropScience Biologies GmbH) + TX; Penicillium bilaii, strain ATCC 22348 (e.g. Jumpstart® from Acceleron BioAg), Talaromyces flavus, strain V117b + TX; Trichoderma atroviride strain CNCM 1-1237 (e.g. Esquive® WP from Agrauxine, FR), Trichoderma viride, e.g. strain B35 (Pietr et al., 1993, Zesz. Nauk. A R w Szczecinie 161 : 125-137) + TX; Trichoderma atroviride strain LC52 (also known as Trichoderma atroviride strain LU132, e.g. Sentinel® from Agrimm Technologies Limited) + TX; Trichoderma atroviride strain SC1 described in W02009/116106) + TX; Trichoderma asperellum strain kd (e.g. T-Gro from Andermatt Biocontrol) + TX; Trichoderma asperellum strain (Eco-T from Plant Health Products, ZA) + TX, Trichoderma harzianum strain T-22 (e.g. Trianum-P from Andermatt Biocontrol or Koppert) + TX; Myrothecium verrucaria strain AARC-0255 (e.g. DiTera™ from Valent Biosciences) + TX; Penicillium bilaii strain ATCC ATCC20851 + TX; Pythium oligandrum strain M1 (ATCC 38472, e.g. Polyversum from Bioprepraty, CZ) + TX; Trichoderma virens strain GL-21 (e.g. SoilGard® from Certis, USA) + TX; Verticillium albo-atrum (formerly V. dahliae) strain WCS850 (CBS 276.92, e.g. Dutch Trig from Tree Care Innovations) + TX; Trichoderma atroviride, in particular strain no. V08/002387, strain no. NMI No. V08/002388, strain no. NMI No. V08/002389, strain no. NMI No. V08/002390 + TX; Trichoderma harzianum strain ITEM 908, Trichoderma harzianum, strain TSTh20 + TX; Trichoderma harzianum strain 1295-22 + TX; Pythium oligandrum strain DV74 + TX; Rhizopogon amylopogon (e.g. Myco-Sol from Agri-Enterprise, LLC, formerly Helena Chemical Company) + TX; Rhizopogon fulvigleba (e.g. Myco-Sol from Agri-Enterprise, LLC, formerly Helena Chemical Company) + TX; Trichoderma virens strain GI-3 + TX;
(4) insecticidally active biological control agents selected from
(4.1) bacteria, examples of which are Agrobacterium radiobacter strain K84 (Galltrol from AgBiochem Inc.) + TX; Bacillus amyloliquefaciens, in particular strain PTS-4838 (e.g. AVEO from Valent Biosciences, US) + TX; Bacillus firmus, in particular strain CNMC 1-1582 (e.g. VOTIVO® from BASF SE) + TX; Bacillus mycoides, isolate J. (e.g. BmJ from Certis USA LLC.) + TX; Bacillus sphaericus, in particular Serotype H5a5b strain 2362 (strain ABTS-1743) (e.g. VECTOLEX® from Valent BioSciences, US) + TX; Bacillus thuringiensis subsp. aizawai, in particular strain ABTS-1857 (SD-1372, e.g. XENTARI® from Valent BioSciences) + TX; Bacillus thuringiensis subsp. aizawai, in particular serotype H-7 (e.g. FLORBAC® WG from Valent BioSciences, US) + TX; Bacillus thuringiensis israelensis strain BMP 144 (e.g. AQUABAC® by Becker Microbial Products IL) + TX; Bacillus thuringiensis subsp. israelensis (serotype H-14) strain AM65-52 (Accession No. ATCC 1276) (e.g. VECTOBAC® by Valent BioSciences, US) + TX; Bacillus thuringiensis subsp. aizawai strain GC-91 + TX; Bacillus thuringiensis var. Colmeri (e.g. TIANBAOBTC by Changzhou Jianghai Chemical Factory) + TX; Bacillus thuringiensis var. japonensis strain Buibui + TX; Bacillus thuringiensis subsp. kurstaki strain BMP 123 (from Becker Microbial Products, IL, BARITONE from Bayer CropScience) + TX; Bacillus thuringiensis subsp. kurstaki strain HD-1 (e.g. DIPEL® ES from Valent BioSciences, US) + TX; Bacillus thuringiensis var. kurstaki strain EVB-113-19 (e.g., BIOPROTEC® from AEF Global) + TX; Bacillus thuringiensis subsp. kurstaki strain ABTS 351 + TX; Bacillus thuringiensis subsp. kurstaki strain PB 54 + TX; Bacillus thuringiensis subsp. kurstaki strain SA 11 (JAVELIN from Certis, US) + TX; Bacillus thuringiensis subsp. kurstaki strain SA 12 (THURICIDE from Certis, US) + TX; Bacillus thuringiensis subsp. kurstaki strain EG 2348 (LEPINOX® from Certis, US) + TX; Bacillus thuringiensis subsp. kurstaki strain EG 7841 (CRYMAX® from Certis, US) + TX; Bacillus thuringiensis subsp. tenebrionis strain NB 176 (SD-5428, e.g. NOVODOR® FC from BioFa DE) + TX; Brevibacillus laterosporus (LATERAL® from Ecolibrium Biologicals) + TX; Burkholderia spp., in particular Burkholderia rinojensis strain A396 (also known as Burkholderia rinojensis strain MBI 305) (Accession No. NRRL B-50319); WO 2011/106491 and WO 2013/032693; e.g. MBI206 TGAI and ZELTO® from Marrone Bio Innovations) + TX; Chromobacterium subtsugae, in particular strain PRAA4-1T (e.g. MBI-203; e.g. GRANDEVO® from Marrone Bio Innovations) + TX; Lecanicillium muscarium Ve6 (MYCOTAL from Koppert) + TX; Paenibacillus popilliae (formerly Bacillus popilliae + TX; e.g. MILKY SPORE POWDER™ or MILKY SPORE GRANULAR™ from St. Gabriel Laboratories) + TX; Pasteuria nishizawae strain Pn1 (CLARIVA from Syngenta/ChemChina) + TX;Serratia entomophila (e.g. INVADE® by Wrightson Seeds) + TX; Serratia marcescens, in particular strain SRM (Accession No. MTCC 8708) + TX;Trichoderma asperellum (TRICHODERMAX from Novozymes) + TX; Wolbachia pipientis ZAP strain (e.g., ZAP MALES® from MosquitoMate) + TX; and
(4.2) fungi, examples of which are Beauveria bassiana strain ATCC 74040 (e.g. NATURALIS® from Intrachem Bio Italia) + TX; Beauveria bassiana strain GHA (Accession No. ATCC74250, e.g. BOTANIGUARD® ES and MYCONTROL-O® from Laverlam International Corporation) + TX; Beauveria bassiana strain ATP02 (Accession No. DSM 24665) + TX; Isaria fumosorosea (previously known as Paecilomyces fumosoroseus) strain Apopka 97 (PREFERAL® from SePRO) + TX; Metarhizium anisopliae 3213-1 (deposited under NRRL accession number 67074 disclosed in WO 2017/066094; Pioneer Hi-Bred International) + TX; Metarhizium robertsii 15013-1 (deposited under NRRL accession number 67073) + TX; Metarhizium robertsii 23013-3 (deposited under NRRL accession number 67075) + TX; Paecilomyces lilacinus strain 251 (MELOCON® from Certis, US) + TX; Zoophtora radicans + TX;
(5) Viruses selected from the group consisting of Adoxophyes orana (summer fruit tortrix) granulosis virus (GV) + TX; Cydia pomonella (codling moth) granulosis virus (GV) + TX; Helicoverpa armigera (cotton bollworm) nuclear polyhedrosis virus (NPV) + TX; Spodoptera exigua (beet armyworm) mNPV + TX; Spodoptera frugiperda (fall armyworm) mNPV + TX; Spodoptera littoralis (African cotton leafworm) NPV + TX;
(6) Bacteria and fungi which can be added as ’inoculant’ to plants or plant parts or plant organs and which, by virtue of their particular properties, promote plant growth and plant health selected from Agrobacterium spp. + TX; Azorhizobium caulinodans + TX; Azospirillum spp. + TX; Azotobacter spp. + TX; Bradyrhizobium spp. + TX; Burkholderia spp., in particular Burkholderia cepacia (formerly known as Pseudomonas cepacia) + TX; Gigaspora spp., or Gigaspora monosporum + TX; Glomus spp. + TX; Laccaria spp. + TX; LactoBacillus buchneri + TX; Paraglomus spp. + TX; Pisolithus tinctorus + TX; Pseudomonas spp. + TX; Rhizobium spp., in particular Rhizobium trifolii + TX; Rhizopogon spp. + TX; Scleroderma spp. + TX; Suillus spp. + TX; Streptomyces spp. + TX;
(7) Plant extracts and products formed by microorganisms including proteins and secondary metabolites which can be used as biological control agents, selected from Allium sativum (NEMGUARD from Eco-Spray; BRALIC from ADAMA) + TX; Armour-Zen + TX; Artemisia absinthium + TX; Azadirachtin (e.g. AZATIN XL from Certis, US) + TX; Biokeeper WP + TX; Brassicaceae extract, in particular oilseed rape powder or mustard powder + TX; Cassia nigricans + TX; Celastrus angulatus + TX; Chenopodium anthelminticum + TX; Chitin + TX; Dryopteris filix-mas + TX; Equisetum arvense + TX; Fortune Aza + TX; Fungastop + TX; Chenopodium quinoa saponin extract from quinoa seeds (e.g. Heads Up® (Saponins of Quinoa) from Heads Up plant Protectants, CA) + TX; naturally occurring Blad polypeptide extracted from Lupin seeds (PROBLAD® from Certis EU) + TX; naturally occurring Blad polypeptide extracted from Lupin seeds (FRACTURE® from FMC) + TX; Pyrethrum/Pyrethrins + TX; Quassia amara + TX; Quercus + TX; Quillaja extract (QL AGRI 35 from BASF) + TX; Reynoutria sachalinensis extract (REGALLIA®, REGALIA® MAXX from Marrone Bio) + TX; "Requiem ™ Insecticide" + TX; Rotenone + TX; ryania/ryanodine + TX; Symphytum officinale + TX; Tanacetum vulgare + TX; Thymol + TX; Thymol mixed with Geraniol (CEDROZ from Eden Research) + TX; Thymol mixed with Geraniol and Eugenol (MEVALONE® from Eden Research) + TX; Triact 70 + TX; TriCon + TX; Tropaeulum majus + TX; Melaleuca alternifolia extract (TIMOREX GOLD from STK) + TX; Urtica dioica + TX; Veratrin + TX; and Viscum album + 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 IUPAC name, the lUPAC/Chemical Abstracts name, a "chemical name", a "traditional name", a "compound name" or a "development code" is used. “CAS Reg. No” means the Chemical Abstracts Registry Number.
The ratio (by weight) of active ingredient mixture of the compounds of formula (I) selected from a compound A1 to A237 listed in Table A (below) or a specific compound listed in Tables 1 to 10 with active ingredients described above is 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.
The mixtures as described above can be used in a method for controlling pests, which comprises applying a composition comprising a 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 a compound A1 to A237 listed in Table A (below) or a specific compound listed in Tables 1 to 10 (below) 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) selected from a compound A1 to A237 listed in Table A (below) or a specific compound listed in Tables 1 to 10 (below) and the active ingredients as described above is not essential for working the present invention.
In a further aspect, the present invention provides a combination of active ingredients comprising a compound defined in the first aspect, and one or more further active ingredients (whether chemical or biological).
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 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.
A further aspect is a plant propagation material comprising by way of treatment or coating one or more compounds of formula (I) according to the invention, optionally also comprising a colour pigment.
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. Table 1 provides 23 specific compounds of formula (I) wherein X is F, and A is as defined in the below Table Z1 . Table Z1
Table 2 provides 23 specific compounds of formula (I) (compounds 2.1 to 2.23), wherein X is Cl; and A is as defined above in Table Z1 . Table 3 provides 23 specific compounds of formula (I) (compounds 3.1 to 3.23), wherein X is Br; and A is as defined above in Table Z1 .
Table 4 provides 16 specific compounds of formula (Id) wherein X is F, and R5 is as defined in the below Table Z2.
Table Z2
Table 5 provides 16 specific compounds of formula (Id) (compounds 5.24 to 5.39) wherein X is Cl, and R5 is as defined above in Table Z2. Table 6 provides 16 specific compounds of formula (Id) (compounds 6.24 to 6.39) wherein X is Br, and R5 is as defined above in Table Z2.
Table 7 provides 11 specific compounds of formula (le) wherein X is F, and R2 and R4 are as defined below in Table Z.3.
Table Z3 Table 8 provides 11 specific compounds of formula (le) (compounds 8.40 to 8.50), wherein X is Cl and R2 and R4 are as defined above in Table Z3.
Table 9 provides 11 specific compounds of formula (le) (compounds 9.40 to 9.50), wherein X is Br and R2 and R4 are as defined above in Table Z3.
Table 10 provides the 3 specific compounds 10.01 to 10.03 according to Formula (I) as follows:
EXAMPLES
The Examples which follow serve to illustrate the invention.
The 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, 12.5 ppm, 6 ppm, 3 ppm, 1.5 ppm, 0.8 ppm or 0.2 ppm, or lower application rates, such as 300, 200 or 100 mg of Al per m2.
Compounds of Formula (I) 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 (including improved crop tolerance), improved physicochemical properties, or increased biodegradability).
Throughout this description, temperatures are given in degrees Celsius (°C) and “mp.” means melting point.
LC/MS means Liquid Chromatography Mass Spectrometry and the description of the apparatus and the method A is outlined below. The characteristic LC/MS values obtained for each compound were the retention time (“Rt”, recorded in minutes (min)) and the measured molecular ion (M+H)+ and/or (M-
H) .
1 H NMR measurements were recorded on Brucker 400 MHz or 300 MHz spectrometers, chemical shifts are given in ppm relevant to a tetramethylsilane (TMS) standard. Spectra are measured in deuterated solvents (eg, dimethyl sulfoxide (DMSO)) as indicated.
LCMS Methods:
Method A (HSS): HSS QC method
Spectra were recorded on a ACQUITY Mass Spectrometer from Waters Corporations (SQD or SQDII Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.0 kV, Cone: 30V, Extractor: 3.00 V, Source Temperature: 150°C, Desolvation Temperature: 400°C, Cone Gas Flow: 60 L/hr, Desolvation Gas Flow: 700 L/hr, Mass range: 140 to 800 Da) and an ACQUITY UPLC from Waters Corporations with solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3, 1.8 pm, 30 x 2.1 mm, Temp: 60 °C, DAD Wavelength range (nm): 210 to 400, Solvent Gradient: A = Water/Methanol 9:1 + 0.1 % formic acid, B= Acetonitrile + 0.1 % formic acid, gradient: 0-100% B in 2.5 min; Flow (ml/min) 0.75.
Method B
Spectra were recorded on a Mass Spectrometer from Waters Corporation (SQD, SQDII or QDA Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions), Capillary: 0.8-3.00 kV, Cone: 5-30 V, Source Temperature: 120-150°C, Desolvation Temperature: 350-600°C, Cone Gas Flow: 50-150 l/h, Desolvation Gas Flow: 650-1000 l/h, Mass range: 100 to 900 Da and an Acquity UPLC from Waters Corporation: Binary pump, heated column compartment , diode-array detector and ELSD. Column: Waters UPLC HSS T3, 1 .8 pm, 30 x 2.1 mm, Temp: 60 °C, DAD Wavelength range (nm): 210 to 400, Runtime: 1.5 min; Solvents: A = water + 5% MeOH + 0.05 % HCOOH, B= Acetonitrile + 0.05 % HCOOH; Flow (mL/min) 0.85, Gradient: 10% B isocratic for 0.2 min, then 10-100% B in 1.0 min, 100% B isocratic for 0.2min, 100-10% B in 0.05 min, 10% B isocratic for 0.05 min.
Method C:
Spectra were recorded on a Mass Spectrometer from Waters (SQD2 or QDA Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: Positive and Negative Polarity Switch), Capillary: 0.8-3.00 kV, Cone range: 25 Source Temperature: 120-150°C, Desolvation Temperature: 500-600°C, Cone Gas Flow: 50 L/h, Desolvation Gas Flow: 1000 L/h, Mass range: 110 to 850 Da) and an Acquity UPLC from Waters: Quaternary solvent manager, heated column compartment , diode-array detector. Column: Acquity UPLC HSS T3 C18, 1.8 pm, 30 x 2.1 mm, Temp: 40 °C, DAD Wavelength range (nm): 200 to 400, Solvent Gradient: A = water + 5% Acetonitrile + 0.1 % HCOOH, B= Acetonitrile + 0.05 % HCOOH: gradient: 0 min 10% B; 0.-0.2 min 10-50% B; 0.2-0.6 min 50-100% B; 0.6-1 .3 min 100% B; 1 .3-1 .4 min 100-10% B; 1 .4-1 .6 min 10% B; Flow (mL/min) 0.6.
Method D:
Spectra were recorded on a Mass Spectrometer from Agilent Technologies (6410 Triple Quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, MS2 Scan, Capillary: 4.00 kV, Fragmentor: 100 V, Desolvation Temperature: 350°C, Gas Flow: 11 L/min, Nebulizer Gas: 45 psi, Mass range: 110 to 1000 Da) and a 1200 Series HPLC from Agilent: quaternary pump, heated column compartment and VWD detector. Column: KINETEX EVO C18, 2.6 pm, 50 x 4.6 mm, Temp: 40 °C, Detector VWD Wavelength: 254 nm, Solvent Gradient: A = water + 5% Acetonitrile + 0.1 % HCOOH, B= Acetonitrile + 0.1 % HCOOH: gradient: 0 min 10% B, 90%A; 0.9-1 .8 min 100% B; 1 .8-2.2 min 100-10% B; 2.2-2.5 min 10%B; Flow (mL/min) 1.8.
Method E:
Spectra were recorded on a Mass Spectrometer from Agilent Technologies (MSD-IQ mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, MS2 Scan, Capillary: 3.5 kV, Fragmentor: 110 V, Desolvation Temperature: 325°C, Gas Flow: 13 L/min, Nebulizer Gas: 55 psi, Mass range: 110 to 850 Da) and a 1290 Series HPLC from Agilent: quaternary pump, heated column compartment and diode-array detector. Column: AGILENT POROSHELL 120 EC-C18, 1.9 pm, 50 x 2.1 mm, Temp: 40 °C, DAD Wavelength range (nm): 190 to 400, Solvent Gradient: A = water + 5% Acetonitrile + 0.1 % HCOOH, B= Acetonitrile + 0.1 % HCOOH: gradient: 0-0.5 min 10% B, 90%A; 1 .2-1 .5 min 95% B, 05 %A; 1 .8-2.5 min 10%B, 90%A; Flow (mL/min) 0.8
Example 1 : Synthesis of benzyl (E)-4-(2,2-difluorocyclopropyl)but-2-enoate (compound A134).
Step 1 : Preparation of but-3-en-1-yl benzoate:
A 250 mL round bottom flask equipped with nitrogen balloon and charged with but-3-en-1-ol (50.0 g, 693 mmol) in 2-methyl THF (500 mL) was added N,N-diethylethanamine (211 g, 2080 mmol) and benzoyl chloride (97.5 g, 693 mmol) at 0 °C, the resulting reaction mixture was stirred at room temperature for 16 h. The progress of the reaction was monitored by thin-layer chromatography (TLC) (50% ethyl acetate/hexane). The reaction mixture was diluted with water (500 mL), extracted with ethyl acetate (3 x 200 mL). The combined organic layers were washed with brine (300 mL), dried over sodium sulfate, and concentrated under reduced pressure to afford crude reaction mixture. The resulting crude residue was purified by combi flash column chromatography using (0 to 100%) ethyl acetate in hexanes.
Pure fractions were combined and evaporated under reduced pressure to afford But-3-en-1-yl benzoate (110 g, 624 mmol, yield: 90 %).
1H NMR (400 MHz, DMSO-cfe): 8.05 - 8.02 (m, 2H), 7.57 - 7.53 (m, 1 H), 7.45 - 7.41 (m, 2H), 5.91 - 5.84 (m, 1 H), 5.21 - 5.02 (m, 2H), 4.37 (t, 2H),2.55 - 2.50 (m, 2H). Step 2: Preparation of 2-(2,2-difluorocyclopropyl) ethyl benzoate 100 mL round bottom flask equipped with nitrogen balloon and charged with but-3-enyl benzoate (1.00 g, 5.67 mmol) and sodium fluoride (23.8 mg, 0.567 mmol) at 100 °C was added trimethylsilyl 2,2-difluoro-2-fluorosulfonyl-acetate (4261 mg, 17.0 mmol) added in three intervals and stirred at 100 °C for 16 h. The progress of the reaction was monitored by TLC (50% ethyl acetate/hexane) and it showed no starting material. The reaction mixture was diluted with water (50.0 mL), extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with brine (50 mL), dried over sodium sulfate, and concentrated under reduced pressure to afford crude reaction mixture. The resulting crude residue was purified by combi flash column chromatography using (0 to 100%) ethyl acetate in hexanes. Pure fractions were combined and evaporated under reduced pressure to afford 2-(2,2-difluorocyclopropyl) ethyl benzoate (400 mg, 1.75 mmol, yield: 30.8 %).
1H NMR (400 MHz, CDCb): 6 8.06 - 8.04 (m, 2H), 7.59 - 7.55(m, 1 H), 7.47 - 7.43 (m, 2H), 4.44 - 4.36 (m, 2H), 2.01 - 1 .89 (m, 2H), 1.71 - 1 .64 (m, 1 H), 1 .49 - 1 .44 (m, 1 H), 1 .04 - 1 .00 (m, 1 H).
Step 3: Preparation of 2-(2,2-difluorocyclopropyl) ethan-1-ol
500 mL round bottom flask equipped with nitrogen balloon and charged with 2-(2,2- difluorocyclopropyl) ethyl benzoate (9.00 g, 39.8 mmol), 10 % aq. sodium hydroxide (90.0 mL, 0 mmol) was added and stirred at reflux for 8 h. The progress of the reaction was monitored by TLC (50% ethyl acetate/Hexane) and it showed no starting material. The reaction mixture was diluted with water (50.0 mL) and acidified with 2 N hydrogen chloride (50 mL) extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with brine (50 mL), dried over sodium sulfate, and concentrated under reduced pressure to afford 2-(2,2-difluorocyclopropyl) ethan-1-ol (4.00 g, 29.5 mmol, yield: 74.1 %). The crude compound was used, without extra purification for next step.
Step 4: Preparation of 2-(2,2-difluorocyclopropyl) acetaldehyde
A 250 mL round bottom flask equipped with nitrogen balloon and charged with 2-(2,2- difluorocyclopropyl) ethanol (4.00 g, 32.8 mmol) in dichloromethane (100 mL) at 0 °C was added (1 ,1- diacetoxy-3-oxo-1 Iambda5, 2-benziodoxol-1-yl) acetate (16.7 g, 39.3 mmol) in three intervals and stirred at room temperature for 2 h. The progress of the reaction was monitored by TLC (50% ethyl acetate/hexane) and it showed no starting material. The reaction mixture was diluted with sodium bicarbonate solution (100.0 mL), extracted with dichloromethane (3 x 200 mL). The combined organic layers were washed with brine (100 mL), dried over sodium sulfate, and concentrated under reduced pressure to afford 2-(2,2-difluorocyclopropyl) acetaldehyde (3.00 g, 17.5 mmol, yield: 53.4 %). The crude was used, without extra purification for next step.
Step 5: Preparation of benzyl (E)-4-(2,2-difluorocyclopropyl) but-2-enoate
A 100 mL round bottom flask was equipped with an argon balloon and charged with 2-(2,2- difluorocyclopropyl) acetaldehyde (1.00 g, 8.33 mmol) in dichloromethane (50 mL), the reaction mass was then cooled to 0 C and benzyl 2-(tnphenyl-lambda5-phosphanyhdene) acetate (3759 mg, 9.16 mmol) was added at 0 °C. The reaction mixture was stirred at room temperature for 12 h. The progress of the reaction was monitored by TLC (50% ethyl acetate/hexane) and it showed no starting material. The reaction mixture was diluted with sodium bicarbonate solution (100.0 mL), extracted with dichloromethane (3 x 200 mL). The combined organic layers were washed with brine (100 mL), dried over sodium sulfate, and concentrated under reduced pressure. The resulting crude residue was purified by combi flash column chromatography using (0 to 100%) ethyl acetate in hexanes. Pure fractions were combined and evaporated under reduced pressure to afford benzyl (E)-4-(2,2-difluorocyclopropyl) but- 2-enoate (400 mg, 1.57 mmol, yield: 18.9 %).
1H NMR (400 MHz, CDCb): 6 7.39 - 7.31 (m, 5H), 7.05 - 6.98(m, 1 H), 5.99 - 5.94 (m, 1 H), 5.18 (s, 2H), 2.40 - 2.30 (m, 2H), 1 .65 - 1 .45 (m, 2H), 1 .00 - 0.96 (m, 1 H).
Example 2: Synthesis of (E)-N-(4-(2,2-difluorocyclopropyl) but-2-enoyl)-4-methylbenzamide (compound A87).
A 50 mL round bottom flask equipped with argon balloon and charged with (E)-4-(2,2- difluorocyclopropyl) but-2-enoic acid (500 mg, 3.08 mmol) in dichloromethane (10 mL) at 0 °C, oxalyl chloride (783 mg, 6.17 mmol) was added and the reaction mixture was stirred at reflux temperature for 2 h. Progress of the reaction was monitored by TLC. The reaction mixture was concentrated under reduced pressure to get crude. 4-methylbenzamide (417 mg, 3.08 mmol) in dimethylformamide (10 mL) at 0 °C, sodium hydride (96.2 mg, 4.01 mmol) was added portion wise, and the reaction mixture was stirred at room temperature for 30 min, then the above crude in dimethylformamide was added to this at 0 °C and the reaction mixture was stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC (50% ethyl acetate/hexane) and it showed no starting material. The reaction mixture was diluted with sodium bicarbonate solution (10.0 mL), extracted with dichloromethane (3 x 50 mL). The combined organic layers were washed with brine (50 mL), dried over Sodium sulfate, and concentrated under reduced pressure to offered crude reaction mass. The resulting crude residue was purified by combi flash column chromatography using (0 to 100%) ethyl acetate in hexanes. Pure fractions were combined and evaporated under reduced pressure to afford (E)-N-(4-(2,2- difluorocyclopropyl) but-2-enoyl)-4-methylbenzamide (110 mg, 0.35 mmol, yield: 11 .5 %). 1H NMR (400 MHz, CDCb): 6 8.51 (s, 1 H), 8.08 - 7.05 (m, 2H), 7.35 -7.01 (m, 4H), 2.56 - 2.36 (m, 5H), 1 .65 - 1 .51 (m, 2H), 1 .00 - 0.96 (m, 1 H).
Example 3: Synthesis of (E)-4-(2,2-difluorocyclopropyl) but-2-enoic acid (compound A138).
Step 1 : Preparation of te/Y-butyl (E)-4-(2,2-difluorocyclopropyl) but-2-enoate
A 100 mL two-necked round bottom flask was equipped with nitrogen balloon was charged with 2-(2,2-difluorocyclopropyl) acetaldehyde (80.0 %, 350 mg, 2.33 mmol) in dichloromethane (10 mL), was added (te/Y-butoxycarbonylmethylene) triphenyl phosphorane (1053 mg, 2.80 mmol) at 0° C and the reaction mixture was stirred at room temperature for 12 h. The progress of the reaction was monitored by TLC (30% ethyl acetate/hexane), and it showed no starting material. The reaction mixture was diluted with water (50 mL) and extracted with dichloromethane (3 x 50 mL). The combined organic layer washed with brine (20 mL), dried over sodium sulfate, and concentrated under reduced pressure to get the crude. The crude residue was purified by combi flash column chromatography (0 to 50% ethyl acetate /hexane). Pure fractions were combined and concentrated under reduced pressure to afford tert-butyl (E)-4-(2,2- difluorocyclopropyl) but-2-enoate (210 mg, 0.770 mmol, yield: 33 %).
1H NMR (400 MHz, DMSO-cfe): 6 6.86-6.82 (m, 1 H), 5.87-5.83 (d, 1 H), 2.33-2.30 (m, 2H), 1 .85- 1.79 (m, 1 H), 1.74-1.73 (m, 1 H), 1.51 (s, 9H), 1.23 - 1.121 (m, 1 H).
Step 2: Preparation of (E)-4-(2,2-difluorocyclopropyl) but-2-enoic acid
A 50 mL two-necked round bottom flask was equipped with nitrogen balloon was charged with te/Y-butyl (E)-4-(2,2-difluorocyclopropyl) but-2-enoate (100 mg, 0.412 mmol) in dichloromethane (3 mL) was added trifluoroacetic acid (0.2 mL) at 0 °C, and the resulting reaction mixture was stirred at room temperature for 3h. The progress of the reaction was monitored by TLC (30% ethyl acetate/hexane), and it showed no starting material. The reaction mixture was concentrated under reduced pressure and the crude was co-d isti lied with dichloromethane to obtain (E)-4-(2,2-difluorocyclopropyl) but-2-enoic acid (65 mg, 0.266 mmol, yield: 7.26 %).
1H NMR (400 MHz, DMSO-cfe): 6 6.86-6.82 (m, 1 H), 5.87-5.83 (d, J = 8.2 Hz, 1 H), 2.34-2.31 (m, 2H), 1.86-1.80 (m, 1 H), 1.65-1.61 (m, 1 H), 1.23-1.19 (m, 1 H);
Example 4: Preparation of (E)-4-(2-chloro-2-fluoro-cyclopropyl) but-2-enoic acid (compound A86).
Step 1 : Preparation of but-3-enyl benzoate
At room temperature, 3-buten-1-ol (5.00 g, 5.93 mL, 66.6 mmol, 1.00 eq) was diluted into 2- methyl THF (66.6 mL) to form a colorless solution. Then triethylamine (10.1 g, 13.9 mL, 99.8 mmol, 1 .50 eq) was added. Then benzoyl chloride (10.4 g, 8.59 mL, 73.2 mmol, 1 .10 eq) was added slowly with a syringe over 8 min. The resulting white suspension was stirred at room temperature for 18 h. The reaction was followed by TLC and GC-MS. The reaction medium was filtered through a sintered disc filter funnel and solid cake was washed with ethyl acetate x2. A saturated sodium bicarbonate aq. solution was added to the filtrate and extraction was carried out with ethyl acetate x3. The combined organic layers were dried over sodium sulphate, filtered through a sintered disc filter funnel, and concentrated under reduced pressure at 40°C. This crude (solid deposition on Isolute) was purified by Combi flash chromatography (220 g cartridge) with a gradient of cyclohexane/ethyl acetate. The matching fractions were evaporated under reduced pressure at 40°C to afford 12.763 g of but-3-enyl benzoate.
LC-MS (Method B): rt = 0.99 min, MS ES+ = 177 (M+H+)
1H NMR (400 MHz, CDCb) 6 ppm 8.03-8.06 (2 H, m), 7.56 (1 H, tt), 7.41-7.47 (2 H, m), 5.83- 5.94 (1 H, m), 5.10-5.21 (2 H, m), 4.39 (2 H, t), 2.54 (2 H, qt).
Step 2: Preparation of (2-chloro-2-fluoro-cyclopropyl) ethyl benzoate
Under argon, in a 3-neck-round-bottomed flask but-3-enyl benzoate (1000 mg, 1.0 equiv., 5.39 mmol) was dissolved in diglyme (5.00 mL) and the solution was heated to reflux. Then, sodium dichlorofluoroacetate (2.79 g, 3.0 equiv., 16.2 mmol) was dissolved in diglyme (15.0 mL) and added slowly over a period of 3 h using a syringe-pump. The mixture was filtrated, washed with 10 mL tert- butyl methyl ether. Then the filtrate was quenched with sat. solution of sodium bicarbonate and extracted with 2 x 8 mL tert-buty I methyl ether. The organic layer was washed with water, brine, dried over sodium sulphate, filtrated, and evaporated, purified twice by Isco combi flash Rf using cyclohexane/ ethyl acetate as eluent to give 179mg of the desired compound. The compound was used without extra purification for the next step.
Step 3: Preparation of 2-(2-chloro-2-fluoro-cyclopropyl) ethanol
Under argon, in a SUPELCO test tube (2-chloro-2-fluoro-cyclopropyl) ethyl benzoate (850 mg, I .OOequiv., 3.33 mmol) was dissolved in methanol (10.2 mL) and cooled to 0°C. Then, potassium hydroxide 2M (4.80 equiv., 16.0 mmol, 7.99 mL) was added dropwise at 0°C, and the mixture was stirred for 2h and allowed the mixture to warm at room temperature. The mixture was quenched with brine and extracted with 3x10ml tertbutyl methyl ether. The organic layer was washed with water, brine, dried over sodium sulphate, filtrated, and carefully evaporated at 40°C until 80 mbar to give 432 mg of colorless oil of 2-(2-chloro-2-fluoro-cyclopropyl) ethanol.
1H NMR (400 MHz, MeOD-c/4) 6 ppm 3.67 (dt, J = 3.8, 6.3 Hz, 2H), 1 .85 - 1 .73 (m, 1 H), 1 .72 - 1.55 (m, 2H), 1.46 - 0.86 (m, 2H).
Step 4: Preparation of 2-(2-chloro-2-fluoro-cyclopropyl) acetaldehyde
2-(2-chloro-2-fluoro-cyclopropyl) ethanol (422 mg, I .OOequiv., 2.80 mmol) was dissolved in dichloromethane (12.7 mL) and cooled to 0°C. Dess-Martin periodinane (1440 mg, 1.15 equiv., 3.22 mmol) was added in portions at 0°C, stirred for 10 minutes at 0°C, then the mixture was allowed to stir at room temperature overnight. The mixture was cooled to 0°C, carefully quenched with 10% sodium thiosulphate-solution, followed by addition of a saturated solution sodium bicarbonate then extracted with 3x10ml dichloromethane. The combinate organic layer was washed with brine, dried over sodium sulphate, filtrated, and carefully evaporated at 40°C until 300 mbar to give 400mg of colorless oil of 2- (2-chloro-2-fluoro-cyclopropyl) acetaldehyde.
1H NMR (400 MHz, CDCb) 6 ppm 9.98 - 9.69 (m, 1 H), 8.23 (dd, 1 H), 2.81 - 2.53 (m, 2H), 2.04 - 1.90 (m, 1 H), 1.86 - 1.73 (m, 1 H), 1.54 (td, 1 H), 1.32 - 1.15 (m, 1 H)
Step 5: Preparation of tert-butyl (E)-4-(2-chloro-2-fluoro-cyclopropyl) but-2-enoate
Under argon, in a round-bottomed flask 2-(2-chloro-2-fluoro-cyclopropyl) acetaldehyde (380 mg, 1.00equiv., 2.56 mmol) was stirred in dichloromethane (11.4 mL) and cooled to 5°C.Then (tert-butoxy carbonyl methylene) triphenyl phosphorane (1180 mg, 1.20 equiv., 3.07 mmol) was carefully added. After the addition was completed, the mixture was allowed to stir at room temperature. The mixture was quenched with water and extracted with 2 x 10 mL of dichloromethane. The organic layer was washed with water, brine, dried over sodium sulphate, filtrated, and evaporated. Purification on combi flash to give 229 mg of colorless oil of tert-butyl (E)-4-(2-chloro-2-fluoro-cyclopropyl) but-2-enoate.
1H NMR (400 MHz, MeOD-c/4) 6 ppm 6.91 (td, 1 H), 5.88 (td, 1 H), 2.46 - 2.30 (m, 2H), 1.85 - 1 .60 (m, 2H), 1 .49 (s, 9H), 1 .35 - 1 .17 (m, 2H).
Step 6: Preparation of (E)-4-(2-chloro-2-fluoro-cyclopropyl) but-2-enoic acid
Under argon, in a round-bottomed flask tert-butyl (E)-4-(2-chloro-2-fluoro-cyclopropyl) but-2- enoate (181 mg, 1.00 equiv., 0.694 mmol) was dissolved in dichloromethane (2.72 mL) and cooled to 5°C. Then trifluoroacetic acid (160 mg, 2.00 equiv., 1 .39 mmol, 0.108 mL) was carefully added dropwise at 5°-10°C. After the addition was completed, the mixture was allowed to stir at room temperature. The mixture was carefully evaporated to dryness. This crude material was dissolved in tertbutyl methyl ether and then was then washed with water, following by brine, dried over sodium sulphate, filtrated, and evaporated to give the (E)-4-(2-chloro-2-fluoro-cyclopropyl) but-2-enoic acid (128 mg).
1H NMR (400 MHz, CDCb) 6 ppm 11 .42 - 10.22 (m, 1 H), 7.14 (m, 1 H), 5.98 (td, 1 H), 2.59 - 2.30 (m, 2H), 1.81 - 1 .67 (m, 1 H), 1 .67 - 0.92 (m, 3H). Example 5: Preparation of (Z) and (E)-4-(2-chloro-2-fluoro-cyclopropyl)-N-(2-pyridyl) but-2-enamide
A mixture of (E)-4-(2-chloro-2-fluoro-cyclopropyl) but-2-enoic acid (80,0 mg, 0,426 mmol, 1.00 eq.), 2-aminopyridine (48,5 mg, 0,51 1 mmol, 1.20 eq.), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (91 ,6 mg, 0,468 mmol, 1.10 eq.), 1-hydroxy-7-azabenzotriazole (66,4 mg, 0,468 mmol, 1.10 eq.) and triethylamine (130 mg, 1 ,28 mmol, 0,180 mL, 3.00 eq.) in acetonitrile (2,40 mL) was stirred at room temperature for 16 hours. The reaction mixture was quenched with water and diluted with ethyl acetate. The desired material was extracted with ethyl acetate, the combined organic layers were washed with water, brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified over a silica gel cartridge (cyclohexane/ethyl acetate: ethanol (3:1)) to afford a mixture of (Z) and (E)-4-(2-chloro-2-fluoro-cyclopropyl)-N-(2-pyridyl) but-3-enamide (by-product) + (Z)- and (E)-4-(2-chloro-2-fluoro-cyclopropyl)-N-(2-pyridyl) but-2-enamide as a yellow resin. The two isomers were separated by reverse phase (water/acetonitrile).
(Z) and (E)-4-(2-chloro-2-fluoro-cyclopropyl)-N-(2-pyridyl) but-3-enamide:
1H NMR (400 MHz, CDCb) 6 ppm 1.48-1.68 (m, 2 H) 2.21-2-57 (m, 1 H) 3.24-3.46 (m, 2 H) 5.39-5.52 (m, 1 H) 5.87-5.99 (m, 1 H) 7.12-7.17 (m, 1 H) 7.78-7.87 (m, 1 H) 8.27-8.31 (m, 1 H) 8.31-8.35 (m, 1 H) 8.80-9.03 (s, 1 H).
(Z) and (E)-4-(2-chloro-2-fluoro-cyclopropyl)-N-(2-pyridyl) but-2-enamide:
1H NMR (400 MHz, CDCb) 6 ppm 1 .59 - 1 .81 (m, 2 H) 1 .85 - 2.03 (m, 1 H) 2.36 - 2.58 (m, 2 H) 6.18 - 6.31 (m, 1 H) 7.14 - 7.26 (m, 1 H) 7.31 - 7.39 (m, 1 H) 7.94 - 8.06 (m, 1 H) 8.19 - 8.30 (m, 1 H) 8.58 (d, 1 H) 10.22 - 10.60 (m, 1 H).
Example 6: Preparation of (E)-4-(2-bromo-2-fluoro-cyclopropyl) but-2-enoic acid (compound 84).
Step 1 : Preparation of 2-(2-bromo-2-fluorocyclopropyl) ethyl benzoate
A 50 mL two neck round bottom flask equipped with argon balloon was charged with but-3-enyl benzoate (13.0 g, 73.8 mmol, prepared as in Example 1 , step 1) in dichloromethane (30 mL) and water (100 mL) at 0 °C were added dibromo(fluoro)methane (28.3 g, 148 mmol), benzyl(triethyl)ammonium chloride (1.68 g, 7.38 mmol) and sodium hydroxide (100 mmol/L, 3689 mL, 369 mmol) drop wise. The resulting reaction mixture was stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC (80% ethyl acetate/hexanes) and it showed no starting material. The reaction mixture was quenched with water (200 mL) and then extracted with dichloromethane (2 x 200 mL). The combined organic layers were washed with brine (300 mL), dried over sodium sulfate, and concentrated under reduced pressure. The crude compound was purified by CombiFlash column chromatography (CombiFlash, 0 to 100% hexane/ethyl acetate). Pure fractions were combined and evaporated under reduced pressure to afford 2-(2-bromo-2-fluorocyclopropyl) ethyl benzoate (2.50 g, 8.53 mmol, yield: 11.6%). 1H NMR (400 MHz, CDCb): 8.08 - 8.04 (m, 2H), 7.59 - 7.55 (m, 1 H), 7.47 - 7.43 (m, 2H), 4.49
- 4.41 (m, 2H), 2.08 - 1 .44 (m, 4H), 1 .28 - 1 .00 (m, 1 H).
Step 2: Preparation of 2-(2-bromo-2-fluorocyclopropyl) ethan-1-ol
A 100 mL three neck round bottom flask equipped with argon balloon was charged with 2-(2- bromo-2-fluoro-cyclopropyl) ethyl benzoate (90.0%, 1.00 g, 3.13 mmol) in methanol (10.0 mL)/ dichloromethane (30.0 mL) was added potassium hydroxide (0.176 g, 3.13 mmol) at rt. The resulting reaction mixture was stirred at room temperature for 3 h. The progress of the reaction was monitored by TLC (80% ethyl acetate/hexanes) and it showed no starting material. Reaction mixture was diluted with water (100 mL) and then extracted with dichloromethane (3 x 50 mL). The combined organic layers were washed with brine (30 mL), dried over sodium sulfate, and concentrated under reduced pressure to afford 2-(2-bromo-2-fluoro-cyclopropyl) ethanol (1 .50 g). The compound was used without purification and data to the next step.
Step 3: Preparation of 2-(2-bromo-2-fluorocyclopropyl) acetaldehyde
A 250 mL round bottom flask equipped with nitrogen balloon and charged with 2-(2-bromo-2- fluoro-cyclopropyl) ethanol (30.0%, 5.70 g, 9.34 mmol) in dichloromethane (250 mL) at 0 °C was added Dess-Martin periodinane (5.94 g, 14.0 mmol) in three interval and stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC (50% ethyl acetate/hexane) and it showed no starting material. The reaction mixture was diluted with sodium bicarbonate solution (50 mL), extracted with dichloromethane (3 X 100 mL). The combined organic layers were washed with brine (100 mL), dried over sodium sulfate, and concentrated under reduced pressure to afford 2-(2-bromo-2- fluorocyclopropyl) acetaldehyde (5.00 g, 11.0 mmol, crude). The crude compound was used for next step. (As compound is highly volatile.)
Step 4: Preparation of tert-butyl (E)-4-(2-bromo-2-fluorocyclopropyl) but-2-enoate
A 100 mL round bottom flask equipped with argon balloon and charged with 2-(2-bromo-2- fluoro-cyclopropyl) acetaldehyde (70.0%, 5.70 g, 22.0 mmol) in dichloromethane (250 mL), then reaction mass was cooled to 0 °C and tert-butyl 2-(triphenyl-lambda5-phosphanylidene) acetate (9.96 g, 26.5 mmol) was added at same temperature (0 °C). The reaction mixture was stirred at room temperature for 12 h. The progress of the reaction was monitored by TLC (50% ethyl acetate/hexane) and it showed no starting material. The reaction mixture was diluted with sodium bicarbonate solution (100 mL), extracted with dichloromethane (3 x 200 mL). The combined organic layers were washed with brine (100 mL), dried over Sodium sulfate, and concentrated under reduced pressure to get crude compound. The crude was purified by CombiFlash column chromatography using (0 to 100%) ethyl acetate in hexanes. Pure fractions were combined and evaporated under reduced pressure to afford tert-butyl (E)-4-(2-bromo-2- fluorocyclopropyl) but-2-enoate (3.50 g, 11.9 mmol, yield: 54%).
1H NMR (400 MHz, CDCb): 6 6.93 - 6.85 (m, 1 H), 5.90 -5.85 (m, 1 H), 2.45 - 2.26 (m, 2H), 1.75 - 1 .56 (m, 1 1 H), 1 .22 - 0.95 (m, 1 H).
Step 5: Preparation of 4-(2-bromo-2-fluoro-cyclopropyl) but-2-enoic acid
A 250 mL two-neck round bottom flask was equipped with nitrogen balloon was charged with te/Y-butyl (E)-4-(2-bromo-2-fluoro-cyclopropyl) but-2-enoate (90.0%, 3.00 g, 9.67 mmol) in dichloromethane (50.0 mL) at room temperature was added trifluoroactetic acid (1 .44 mL, 19.3 mmol). The resulting reaction mixture was stirred at room temperature for 4 h. The progress of the reaction was monitored by TLC (30% ethyl acetate/hexane), and it showed no starting material. The reaction mixture was concentrated under reduced pressure to afford crude residue. The crude residue was diluted with dichloromethane (30 mL) and the organic layer was washed with water (30 mL) and brine (30 mL) dried over Sodium sulfate and concentrated under reduced pressure to afford 4-(2-bromo-2-fluoro- cyclopropyl) but-2-enoic acid (1.55 g, 6.88 mmol, yield: 71.1 %).
1H NMR (400 MHz, DMSO-cfe): 6 12.2 (S, 1 H), 6.91 -6.84 (m, 1 H), 5.92 - 5.84 (m, 1 H), 2.41 - 2.28 (m, 2H), 1.85 - 1.11 (m, 3H).
Example 7: Preparation of (E)-4-(2-bromo-2-fluorocyclopropyl)-N-(4-methoxyphenyl) but-2-enamide (compound A83).
A 250 mL two neck round bottom flask equipped with argon balloon was charged with diastereomeric mixture of 4-(2-bromo-2-fluoro-cyclopropyl) but-2-enoic acid (500 mg, 2.24 mmol), 4-fluoroaniline (0.299 g, 2.69 mmol) in dimethyl formamide (10 mL) were added 1-(3- Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.645 g, 3.36 mmol), 1-Hydroxybenzotriazol (0.454 g, 3.36 mmol) & triethylamine (0.681 g, 6.73 mmol) at room temperature. The resulting reaction mixture was stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC (50% Ethyl acetate/hexanes) and it showed no starting material. Reaction mixture was diluted with water (200 mL) and then extracted with ethyl acetate (2 X 20 mL). The combined organic layers were washed with brine (10 mL), dried over Sodium sulfate, and concentrated under reduced pressure to afford crude reaction mixture. The crude compound was purified by CombiFlash column chromatography (CombiFlash, 0 to 100% hexane/ethyl acetate). Pure fractions were combined and evaporated under reduced pressure to afford 4-(2-bromo-2-fluoro-cyclopropyl)-N-(4-fluorophenyl) but-2-enamide (98.0%, 0.400 g, 1.24 mmol, yield: 55.3%).
1H NMR (400 MHz, DMSO-cfe): 6 10.10 - 10.03 (m, 1 H), 7.68 - 7.56 (m, 2H), 7.17 - 7.11 (m, 2H), 6.88 - 6.83 (m, 0.4H), 6.24 - 6.20 (m, 0.4H), 5.84 - 5.82 (m, 0.8H), 5.42 - 5.28 (m, 0.9H), 3.28 - 3.25 (m, 0.7H), 3.11 - 3.01 (m, 0.4H), 2.53 - 2.32 (m, 1 ,6H), 1 .83 - 1 .22 (m, 3H).
Example 8: Preparation of (E)-4-(2-bromo-2-fluorocyclopropyl)-N-(4-methoxyphenyl) but-2-enamide (compound A208).
A 250 mL two neck round bottom flask equipped with argon balloon was charged with 4-(2- bromo-2-fluoro-cyclopropyl) but-2-enoic acid (500 mg, 2.24 mmol) and 4-methoxyaniline (0.331 g, 2.69 mmol) in dimethyl formamide (10.0 mL) at room temperature were added 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride (0.645 g, 3.36 mmol), 1 -hydroxybenzotriazole (0.454 g, 3.36 mmol) and triethylamine (0.681 g, 6.73 mmol) at room temperature. The resulting reaction mixture was stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC (50% ethyl acetate/hexanes) and it showed no starting material. The reaction mixture was diluted with water (20 mL), then extracted with ethyl acetate (2 x 20 mL). The combined organic layers were washed with brine (10 mL), dried over sodium sulfate, and concentrated under reduced pressure to afford crude reaction mixture. The crude compound was purified by CombiFlash column chromatography (CombiFlash, 0 to 100% hexane/ethyl acetate). Pure fractions were combined and evaporated under reduced pressure to afford 4-(2-bromo-2-fluoro-cyclopropyl)-N-(4-fluorophenyl) but-2-enamide (400 mg, 1.24 mmol, yield: 55.3%).
1H NMR (400 MHz, DMSO-cfe): 6 9.90 - 9.83 (m, 1 H), 7.57 -7.46 (m, 2H), 6.90 - 6.77 (m, 2H), 6.22 - 6.19 (m, 0.4H), 5.85 - 5.83 (m, 0.4H), 5.26 - 5.12 (m, 0.4H), 3.77 (m, 3H), 3.25 - 3.05 (m, 0.9H), 2.51 - 2.31 (m, 1.7H), 2.13 - 1.22 (m, 3H).
Example 9: General protocol to prepare amide derivatives of Formula (I). acid
Analysis by UPLC-MS (Method A)
To a solution of acid (0.200 mmol, 1 .00 eq.) and A/,/V-diisopropylethylamine (1.200 mmol, 6.00 eq.) in acetonitrile (1 mL/mmol), the amine corresponding to the desired -NR1R2 group was added (0.400 mmol, 2.00 eq.) and then propylphosphonic anhydride (T3P) 50% in ethyl acetate (0.400 mmol, 2.00 eq.). The reaction mixtures were stirred at room temperature for 16 hours. The solvent was evaporated. To the residues were added dimethylacetamide and methanol (1 :1). The crude mixtures were purified by reversed-phase (RP) preparative HPLC then concentrated and dried under vacuum. The compounds A1 to A81 , A89 to A133 and A142 to A237 may be prepared by analogy with the reactions above.
Table A: This table discloses compounds of the formula (I):
BIOLOGICAL EXAMPLES: Myzus persicae (Green peach aphid): Feeding/contact activity. Sunflower leaf discs were placed onto agar in a 24-well microtiter plate and sprayed with aqueous test solutions prepared from 10,000 ppm DMSO stock solutions. After drying, the leaf discs were infested with an aphid population of mixed ages. The samples were assessed for mortality 6 days after infestation
The following compounds resulted in at least 80% mortality at an application rate of 200 ppm.
A89, A115, A133, A138, A139
Myzus persicae (Green peach aphid) Feeding/Contact activity
Eggplant leaf discs were placed onto agar in a 24-well microtiter plate and sprayed with aqueous test solutions prepared from 10'000 ppm DMSO stock solutions. After drying, the leaf discs were infested with an aphid population of mixed ages. The samples were assessed for mortality 6 days after infestation.
The following compounds resulted in at least 80% growth inhibition at an application rate of 200 ppm:
A3, A6, A11 , A18, A27, A30, A31 , A32, A45, A46, A47, A51 , A53, A57, A59, A60, A66, A68, A70, A72, A74, A75, A79, A82, A84, A85, A169, A181 , A185, A218
Myzus persicae (Green peach aphid): Systemic activity.
Roots of pea seedlings infested with an aphid population of mixed ages were placed directly into aqueous test solutions prepared from 10,000 DMSO stock solutions. The samples were assessed for mortality 6 days after placing seedlings into test solutions.
The following compounds resulted in at least 80% mortality at a test rate of 24 ppm:
A3, A14, A20, A24, A25, A30, A37, A53, A56, A59, A79, A81 , A91 , A95, A96, A102, A103, A104, A106, A108, A110, A111 , A117, A120, A126, A130, A132, A135, A138, A139, A153, A159, A165, A166, A170, A172, A174, A185, A186, A195, A203, A210, A218, A231 , A232, A235.
Tetranychus urticae (Two-spotted spider mite): Feeding/contact activity.
Bean leaf discs on agar in 24-well microtiter plates were sprayed with aqueous test solutions prepared from 10,000 ppm DMSO stock solutions. After drying the leaf discs were infested with a mite population of mixed ages. The samples were assessed for mortality on mixed population (mobile stages) 8 days after infestation.
The following compounds resulted in at least 80% mortality at an application rate of 200 ppm: A6, A11 , A14, A26, A30, A31 , A38, A46, A55, A57, A60, A72, A74, A75, A79, A84, A91 , A11 1 , A113, A134, A138, A139, A140, A174, A180, A185, A217, A218, A219, A220, A236. Aphis craccivora (Black bean aphid - mixed population): Systemic/feeding.
Pea seedlings infested with mixed aged aphid population were placed into glass vials with aqueous test solutions prepared from 10,000 ppm DMSO stock solutions. After 5 days, test samples were assessed for mortality.
The following compounds resulted in at least 80% mortality at a test rate of 12.5 ppm:
A3, A11 , A14, A18, A19, A21 , A22, A25, A26, A30, A37, A53, A59, A60, A62, A64, A65, A66, A69, A70, A72, A75, A76, A79, A89, A91 , A94, A95, A96, A102, A103, A104, A106, A107, A108, A110, A111 , A115, A117, A119, A120. A121 , A124, A126, A130, A131 , A132, A133, A134. A135, A136, A138,
A139, A148, A151 , A153, A156, A157, A158, A159, A185, A202, A203, A204, A210, A213, A216, A218,
A222, A228 , A235, A237.

Claims

CLAIMS:
1 . A compound of Formula (I): wherein:
X is halogen; and
A is -OR; wherein
R is hydrogen, Ci-Cealkyl, Ci-C4haloalkyl, C2-Cealkenyl, C2-C4haloalkenyl, C2-Cealkynyl, C2- C4haloalkynyl, Ci-C4nitroalkyl, Ci-C4alkoxyCi-C4alkyl, or Ci-C4haloalkoxyCi-C4alkyl; or
R is phenyl optionally substituted by 1 to 3 substituents independently selected from R3, C3- Cecycloalkyl optionally substituted by 1 to 3 substituents independently selected from R3, or a 4- to 6- membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R3; or
R is Ci-C2alkyl monosubstituted by:
(i) a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R3,
(ii) phenyl optionally substituted by 1 to 3 substituents independently selected from R3,
(iii) a 4- to 6-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R3, or
(iv) Cs-Cecycloalkyl optionally substituted by 1 to 3 substituents independently selected from R3; or
A is -NR1R2; wherein R1 is hydrogen, hydroxy, Ci-Cealkyl, Ci-C4haloalkyl, Ci-Cealkoxy, Ci-C4haloalkoxy, C2- Cealkenyl, C2-C4haloalkenyl, C2-C6alkynyl, C2-C4haloalkynyl, Ci-C4alkylsulfanyl, Ci-C4alkylsulfinyl, C1- C4haloalkylsulfanyl, Ci-C4haloalkylsulfinyl, phenoxy, -N=C(H)Ph, -NHCi-C4alkyl, -N(Ci-C4alkyl)2, C1- C4alkoxy substituted by a cyclopropyl group, Ci-C4nitroalkyl, Ci-C4alkoxyCi-C4alkyl, Ci-C4haloalkoxyCi- C4alkyl, Ci-C4alkylsulfonylCi-C4alkyl, -SC>2R4 or -C(0)R5; or
R1 is phenyl optionally substituted by 1 to 3 substituents independently selected from R3, C3- Cecycloalkyl optionally substituted by 1 to 3 substituents independently selected from R3, a 4- to 6- membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R3, a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R3, or a 9- or 10-membered heteroaromatic bicyclic ring system comprising 1 to 4 nitrogen atoms, or 0, 1 or 2 nitrogen atoms and a single atom selected from O or S, wherein the heteroaromatic bicyclic ring is optionally substituted by 1 to 3 substituents independently selected from R3; or
R1 is Ci-C2alkyl mono-substituted by:
(i) a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R3,
(ii) phenyl optionally substituted by 1 to 3 substituents independently selected from R3,
(iii) a 4- to 6-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R3, or
(iv) Cs-Cecycloalkyl optionally substituted by 1 to 3 substituents independently selected from R3; wherein Y is O or -CH2-; and
R2 is hydrogen, cyano, Ci-Cealkyl, Ci-C4haloalkyl, Ci-C4alkoxy, Ci-C4haloalkoxy, C2-C6alkenyl, C2-C4haloalkenyl, C2-C6alkynyl, C2-C4haloalkynyl, Ci-C4cyanoalkyl, Ci-C4nitroalkyl, Ci-C4alkoxyCi- C4alkyl, Ci-C4haloalkoxyCi-C4alkyl, or -C(O)Ci-C4alkyl; or
R1 and R2, together with the nitrogen atom they share, form a 4- to 6-membered saturated or partially saturated heterocyclic ring system, further comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R8, or R1 and R2, together with the nitrogen atom they share, form a 9- membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S;
R3 is halogen, cyano, nitro, hydroxyl, formyl, Ci-Cealkyl, Ci-C4haloalkyl, C2-Cealkenyl, C2- C4haloalkenyl, C2-Cealkynyl, C2-C4haloalkynyl, Cs-Cecycloalkyl, Cs-Cehalocycloalkyl, Ci-C4alkylsulfanyl, Ci-C4alkylsulfinyl, Ci-C4alkylsulfonyl, Ci-C4haloalkylsulfanyl, Ci-C4haloalkylsulfinyl, C1- C4haloalkylsulfonyl, -C(O)Ci-C4alkyl, -C(O)NH(Ci-C4alkyl), -C(O)N(Ci-C4alkyl)2, Ci-C4alkoxy, C1- C4haloalkoxy, phenyl, Ci-C4alkylNHC(O)Ci-C4alkyl, Ci-C4alkylC(O)NHCi-C4alkyl, -NC(O)(Ci- C4alkyl)Ci-C4alkyl, -NHC(O)Ci-C4alkyl , Ci-C4alkylNHS(O)2-, -NHS(O)2Ci-C4alkyl, Ci-C4cyanoalkyl, or Cs-Cecycloalkyl substituted by a cyano;
R4 is Ci-Cealkyl, Ci-C4haloalkyl, Ci-Cealkoxy, Ci-Cehaloalkoxy, Cs-Cecycloalkyl or phenyl optionally substituted by 1 to 3 substituents independently selected from R3, a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R3, or a 4- to 6-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R3; or
R4 is Ci-C2alkyl mono-substituted by:
(i) a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R3,
(ii) phenyl optionally substituted by 1 to 3 substituents independently selected from R3,
(iii) a 4- to 6-membered saturated or partially saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R3, or
(iv) Cs-Cecycloalkyl optionally substituted by 1 to 3 substituents independently selected from R3; or
R4 is -NH(Ci-Cealkyl), -NH(Ci-C6alkenyl), -N(Ci-C6alkenyl)(Ci-C6alkyl), -NH(Ci-C6alkynyl), - N(Ci-Cealkynyl)(Ci-Cealkyl), -N(Ci-Cealkyl)2, -NH(C3-C6cycloalkyl), -N(C3-C6cycloalkyl)(Ci-C6alkyl), or - NH(phenyl) or -NH(CH2phenyl), wherein phenyl is optionally substituted by 1 to 3 substituents independently selected from R8;
R5 is Ci-Cealkyl, Ci-C4haloalkyl, Ci-Cealkoxy, Ci-C4haloalkoxy, Ce-Cecycloalkyl, or 3-(2,2- dihalocyclopropyl)prop-1-en-1-yl, benzyloxy, benzylamine, or phenyl optionally substituted by 1 to 3 substituents independently selected from R8, a 5- or 6-membered heteroaromatic ring system comprising 1 to 3 heteroatoms individually selected from N, O, and S, wherein the heteroaromatic ring is optionally substituted by 1 to 3 substituents independently selected from R8, or a 5- to 6-membered saturated heterocyclic ring system comprising 1 or 2 heteroatoms individually selected from N, O, and S, wherein the heterocyclic ring is optionally substituted by 1 to 3 substituents independently selected from R8;
R6 and R7 are independently selected from hydrogen, fluoro or chloro;
R8 is halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy, Ci-C4haloalkoxy or Ci- C4alkylNHSO2-; or a salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, with the proviso that the compound of Formula (I) is not te/Y-butyl (E)-4-(2,2- difluorocyclopropyl)but-2-enoate.
2. A compound according to claim 1 , wherein X is fluoro, chloro or bromo, and preferably fluoro.
3. A compound according to claim 1 or claim 2, wherein A is -OR.
4. A compound according to any one of claims 1 to 3, wherein R is hydrogen, Ci-Cealkyl, phenyl, benzyl or (1-methylpyrazol-4-yl)methyl.
5. A compound according to claim 1 or claim 2, wherein A is -NR1R2.
6. A compound according to claim 5, wherein R1 is selected from: hydrogen, hydroxy, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy, Ci-C4alkynyl, phenoxy, - N=C(H)Ph, -NHCi-C4alkyl, -N(Ci-C4alkyl)2, Ci-C4alkoxy substituted by a cyclopropyl group, Ci- C4alkoxyCi-C4alkyl, Ci-C4alkylsulfonylCi-C4alkyl, -SO2R4 or -C(O)R5; phenyl optionally substituted by 1 to 3 substituents independently selected from R3, C4- Cecycloalkyl optionally substituted by 1 or 2 substituents independently selected from R3, a 4- to 6- membered saturated or partially saturated heterocyclic ring system which comprises 1 or 2 heteroatoms individually selected from N, O, and S wherein the heterocyclic ring is optionally substituted by 1 or 2 substituents independently selected from R3, a 5- or 6-membered heteroaromatic ring system which comprises 1 to 3 heteroatoms individually selected from N, O, and S, or 9- or 10-membered heteroaromatic bicyclic ring system which comprises 1 to 4 nitrogen atoms, wherein the heteroaromatic bicyclic ring system is optionally substituted by 1 or 2 substituents independently selected from R3;
Ci-C2alkyl mono-substituted by:
(i) a 5- or 6-membered heteroaromatic ring system which comprises 1 or 2 nitrogen atoms, and wherein the heteroaromatic ring is optionally substituted by a single substituent selected from R3,
(ii) phenyl optionally substituted by a single substituent selected from R3,
(iii) a 4- or 5-membered saturated or partially saturated heterocyclic ring system which comprises 1 or 2 oxygen atoms, or
(iv) C3-C5cycloalkyl optionally substituted by 1 or 2 substituents independently selected from R3; wherein Y is O or -CH2-;
R3 is halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, Cs-Cecycloalkyl, Ci-C4alkoxy, Ci- C4haloalkoxy, phenyl, -Ci-C4alkylNHC(O)Ci-C4alkyl, -NC(O)(Ci-C4alkyl)Ci-C4alkyl, -NHC(O)Ci-C4alkyl, Ci-C4alkylNHS(O)2-, -NHS(O)2Ci-C4alkyl, Ci-C4cyanoalkyl, or Cs-Cecycloalkyl substituted by cyano; and
R4 is Ci-C4alkyl, phenyl optionally substituted by 1 or 2 substituents independently selected from R3, a 5- or 6-membered heteroaromatic ring system which comprises 1 or 2 nitrogen atoms, wherein the heteroaromatic ring is optionally substituted by 1 or 2 substituents independently selected from R3, a 5 or 6-membered saturated or partially saturated heterocyclic ring system which comprises 1 nitrogen atom, wherein the heterocyclic ring is optionally substituted by 1 or 2 substituents independently selected from R3, Ci-C2alkyl mono-substituted by a 5- or 6-membered heteroaromatic ring system which comprises 1 or 2 nitrogen atoms, wherein the heteroaromatic ring is optionally substituted by a single substituent selected from R3, or -NH(Ci-C4alkyl);
R5 is Ci-C4alkyl, 3-(2,2-dihalocyclopropyl)prop-1-en-1-yl, or phenyl optionally substituted by 1 to 2 substituents independently selected from R8, a 5- or 6-membered heteroaromatic ring system comprising 1 or 2 nitrogen atoms, wherein the heteroaromatic ring is optionally substituted by 1 or 2 substituents independently selected from R8, or a 5- to 6-membered saturated heterocyclic ring system comprising 1 N atom, wherein the heterocyclic ring is optionally substituted by 1 to 2 substituents independently selected from R8.
7. A compound according to claim 6, wherein R1 is methyl mono-substituted by:
(i) a 5- or 6-membered heteroaromatic ring system which comprises 1 or 2 nitrogen atoms, and wherein the heteroaromatic ring is optionally substituted by a single substituent selected from R3,
(ii) phenyl optionally substituted by a single substituent selected from R3,
(iii) a 4- or 5-membered saturated or partially saturated heterocyclic ring system which comprises 1 or 2 oxygen atoms, or
(iv) C3-C5cycloalkyl optionally substituted by 1 or 2 substituents independently selected from R3; wherein Y is O or -CH2-.
8. A compound according to any one of claims 5 or 6, wherein R1 is selected from: hydrogen, hydroxy, methyl, ethyl, isopropyl, difluoroethyl, methoxy, ethoxy, n-propoxy, isopropoxy, prop-2-ynyl, phenoxy, -N=C(H)Ph, methylamino, dimethylamino, cyclopropylmethoxy, 2- methoxyethyl, 2-methylsulfonylethyl, -S02R4 or -C(0)R5; or phenyl optionally substituted by 1 to 3 substituents independently selected from R3; or cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, piperidyl, tetrahydrothiopyranyl, morpholino, dihydroisoxazolyl, dihydropyrazolyl, thienyl, thiazolyl, isoxazolyl, pyrazolyl, triazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, A/-pyrazolo[1 ,5-a]pyridinyl, quinolyl, or [1 ,2,4]triazolo[1 ,5-a]pyridinyl, optionally substituted by 1 or 2 substituents independently selected from R3; or methyl mono-substituted by a ring selected from imidazolyl, pyridyl, pyridazinyl, phenyl, oxetanyl, 1 ,3-dioxolanyl, cyclopropyl, cyclobutyl, or cyclopentyl, wherein each ring is optionally substituted by 1 or 2 substituents independently selected from R3; or
2,3-dihydrobenzofuranyl, or 2,2-difluoro-1 ,3-benzodioxolyl; and wherein R3 is fluoro, chloro, bromo, cyano, methyl, ethyl, iso-propyl, tert-butyl, difluoromethyl, trifluoromethyl, cyclopropyl, methoxy, ethoxy, difluoromethoxy, phenyl, acetamidomethyl, acetyl(methyl)amino, acetamido, ethylsulfamoyl, ethylsulfonylamino, cyanomethyl, 1-cyano-1 -methylethyl, or cyanocyclopropyl; and
R4 is ethyl, iso-propyl, dimethylamino, a ring selected from phenyl, pyridyl, pyrrolidinyl and piperidyl each optionally substituted by 1 or 2 substituents independently selected from R3, or methyl mono-substituted by pyridyl which is optionally substituted by a single substituent selected from R3.
R5 is ethyl, iso-propyl, tert-butyl or 3-(2,2-dihalocyclopropyl)prop-1-en-1-yl, or a ring selected from phenyl, pyridyl, pyrrolidinyl and piperidyl each optionally substituted by 1 or 2 substituents independently selected from R8.
9. A compound according to any one of claims 5 to 8, wherein R2 is hydrogen, methyl or cyanomethyl, and preferably hydrogen.
10. A compound according to any one of claims 1 , 2 or 5, wherein R1 and R2, together with the nitrogen atom they share, form a 4-, 5- or 6-membered saturated or partially saturated heterocyclic ring system optionally further comprising a single group selected from -O-, -S-, -N(H)- or =N-, wherein the ring system is optionally substituted by 1 or 2 substituents independently selected from fluoro, chloro, cyano, methyl, ethyl, methoxy.
11. A compound according to claim 10, wherein R1 and R2, together with the nitrogen atom they share, form an isoxazolidinyl, 3,4-dihydro-pyrazolyl, thiomorpholinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, or 2,3-dihydropyrrolo[2,3-b]pyridin-1-yl group optionally substituted by 1 or 2 substituents independently selected from fluoro, chloro, cyano, methyl, ethyl, methoxy.
12. An agrochemical composition comprising an insecticidally or acaricidally effective amount of a compound according to any one of claims 1 to 11 .
13. The composition according to claim 12, further comprising at least one additional active ingredient and/or an agrochemically-acceptable diluent or carrier.
14. A method of controlling insects or acarines, which comprises applying an insecticidally or acaricidally effective amount of a compound of formula (I) as defined in any one of claims 1 to 11 , or a composition comprising this compound as active ingredient, to a pest, a locus of pest (preferably a plant), to a plant susceptible to attack by a pest or to plant a propagation material thereof (such as a seed).
15. Use of a compound according to any one of claims 1 to 10 as an insecticide or an acaricide.
PCT/EP2024/058217 2023-03-31 2024-03-27 Pesticidally-active 2,2-dihalocyclopropyl compounds Pending WO2025201636A1 (en)

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