WO2023110473A1 - Heterocyclic compounds for the control of invertebrate pests - Google Patents

Heterocyclic compounds for the control of invertebrate pests Download PDF

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Publication number
WO2023110473A1
WO2023110473A1 PCT/EP2022/084332 EP2022084332W WO2023110473A1 WO 2023110473 A1 WO2023110473 A1 WO 2023110473A1 EP 2022084332 W EP2022084332 W EP 2022084332W WO 2023110473 A1 WO2023110473 A1 WO 2023110473A1
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Prior art keywords
alkyl
haloalkyl
compounds
formula
cycloalkyl
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PCT/EP2022/084332
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French (fr)
Inventor
Karsten Koerber
Nikolas HUWYLER
Julia Pedroni
Erik Gilberg
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Basf Se
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Priority claimed from EP21214494.3A external-priority patent/EP4198033A1/en
Application filed by Basf Se filed Critical Basf Se
Publication of WO2023110473A1 publication Critical patent/WO2023110473A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the invention relates to compounds of formula I wherein
  • V is O or S and II is N; or
  • V is N and II is O or S;
  • R 11 is CN, NO 2 , NR 12 R 13 , C(O)NH 2 , C(S)NH 2 , C(O)OH, OR 14 , Si(CH 3 ) 3 ; Ci-C 6 -alkyl; C Ce-haloalkyl; C 2 -Ce-alkenyl; C 2 -C6-haloalkenyl; C 2 -Ce-alkynyl; C 2 -C6-haloalkynyl; C3- C4-cycloalkyl-Ci-C 2 -alkyl, which ring is unsubstituted or substituted with 1 or 2 halogen; 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, which rings are unsubstituted or substituted with halogen, Ci-Cs-haloalkyl, and/or CN;
  • R 11a is NR 12 R 13 , C(O)NH 2 , C(S)NH 2 , C(O)OH, OR 14 , Si(CH 3 ) 3 ; Ci-C 6 -haloalkyl; C 2 -C 6 - alkenyl; C 2 -Ce-haloalkenyl; C 2 -Ce-alkynyl; C 2 -Ce-haloalkynyl; C3-C6-cycloalkyl-Ci-C 2 - alkyl, which ring is unsubstituted or substituted with 1 or 2 halogen; 3- to 6-mem- bered heterocyclyl, which rings are unsubstituted or substituted with halogen, C1-C3- haloalkyl, and/or CN;
  • R 12 , R 13 are independently from each other H, Ci-C4-alkyl, Ci-C4-alkoxy, Ci-C4-haloal- koxy, Ci-C4-haloalkyl, Cs-Ce-cycloalkyl, C(O)-Ci-C4-alkyl, C(O)-Ci-C4-haloalkyl, C(O)-C 3 -C 4 -cycloalkyl, C(O)-C 3 -C 4 -halocycloalkyl, C(O)NH-Ci-C 4 -alkyl, C(O)NH-C C4-haloalkyl, C(O)N(Ci-C4-alkyl)-Ci-C4-alkyl, C(O)N(Ci-C4-haloalkyl)-Ci-C4-alkyl, C(O)N(Ci-C 4 -haloalkyl)-Ci-C4-
  • R 14 is H, Ci-C4-alkyl, Ci-C4-haloalkyl, Cs-Ce-cycloalkyl, Cs-Ce-halocyclo-alkyl, C3-C4-cy- cloalkyl-Ci-C2-alkyl, C3-C4-halocycloalkyl-Ci-C2-alkyl, C(O)-Ci-C4-alkyl, C(O)-Ci-C4- haloalkyl, C(O)-C3-C4-cycloalkyl, C(O)-C3-C4-halocycloalkyl, or phenyl which is unsubstituted or partially or fully substituted with R 3 ;
  • R 2 is H, CN, Ci-Cs-alkyl, Ci-Cs-haloalkyl, C2-C3-alkynyl;
  • R 3 is halogen, CN, NO2, Ci-C4-alkyl, Cs-Ce-cycloalkyl, Ci-Ce-haloalkyl, Ci-Ce-halocycloalkyl, OR 14 , S(O) m -R 14 ; wherein rings are unsubstituted or substituted with R 3a ;
  • R 3a halogen, CN, NO2, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci-C4-alkoxy-Ci-C4-alkyl, C1-C4- haloalkoxy, C3-C4-cycloalkyl, C3-C4-halocycloalkyl, S(O) m -Ci-C4-alkyl, S(O) m -Ci-C4- haloalkyl, S(O) m -C3-C4-cycloalkyl, S(O) m -C3-C4-halocycloalkyl n is 0, 1 , 2, or 3;
  • R 4 is H, halogen, CN, Ci-Ce-alkyl, Cs-Ce-cycloalkyl, Ci-Ce-haloalkyl, Ci-Ce-halocycloalkyl, C2- C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, each optionally substituted by R 41 ; S(O) m -Ci- C4-alkyl, S(O) m -Ci-C4-haloalkyl, S(O) m -C3-C6-cycloalkyl, S(O) m -C3-Ce-halocycloalkyl, NR 12 R 13 , C(O)NR 12 R 13 , C(O)OR 14 , 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, which rings are unsubstituted or substituted with R 3 ;
  • R 41 is H, OR 15 , NR 12 R 13 , CN, Ci-C 4 -alkyl, Ci-C 4 -haloalkyl, C 3 -C 6 -cycloalkyl, C(O)-Ci-C 4 - alkyl, C(O)-Ci-C4-haloalkyl, C(O)-C3-C4-cycloalkyl, C(O)-C3-C4-halocycloalkyl, C(O)NH-Ci-C 4 -alkyl, C(O)NH-Ci-C 4 -haloalkyl, C(O)N(Ci-C 4 -alkyl)-Ci-C 4 -alkyl, C(O)N(Ci-C4-haloalkyl)-Ci-C4-alkyl, C(O)N(Ci-C4-haloalkyl)-Ci-C4-alkyl, C(O)N(C
  • R 15 is H, Ci-C4-alkyl, or Ci-C4-haloalkyl, Cs-Ce-cycloalkyl, Ci-Ce-halocycloalkyl, which carbon chains are unsubstituted or partially or fully substituted with R 11 ; or 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, which rings are unsubstituted or substituted with R 3 ;
  • W is N and T is CR 4a ;
  • W is CH and T is N;
  • W is CH and T is CR 4a ;
  • R 4a is as defined for R 4 ; and the N-oxides, stereoisomers, and agriculturally or veterinarily acceptable salts thereof.
  • the invention also provides agricultural compositions comprising at least one compound of formula I, a stereoisomer thereof and/or an agriculturally acceptable salt thereof and at least one liquid and/or solid carrier, especially at least one inert liquid and/or solid agriculturally acceptable carrier.
  • the invention also provides a veterinary composition
  • a veterinary composition comprising at least one compound of formula I, a stereoisomer thereof and/or a veterinarily acceptable salt thereof and at least one liquid and/or solid carrier, especially at least one inert veterinarily liquid and/or solid acceptable carrier.
  • the invention also provides a method for controlling invertebrate pests which method comprises treating the pests, their food supply, their habitat or their breeding ground or a cultivated plant, plant propagation materials (such as seed), soil, area, material or environment in which the pests are growing or may grow, or the materials, cultivated plants, plant propagation materials (such as seed), soils, surfaces or spaces to be protected from pest attack or infestation with a pesticidally effective amount of a compound of formula I or a salt thereof as defined herein.
  • the invention also relates to plant propagation material, in particular seed, comprising at least one compound of formula I and/or an agriculturally acceptable salt thereof.
  • the invention further relates to a method for treating or protecting an animal from infestation or infection by parasites which comprises bringing the animal in contact with a parasiticidally effective amount of a compound of formula I or a veterinarily acceptable salt thereof. Bringing the animal in contact with the compound I, its salt or the veterinary composition of the invention means applying or administering it to the animal.
  • WO 2019/197468, WO 2021/013719, WO 2010/129497, US 2008/242708, and US 2018/057486 describe structurally closely related active compounds. These compounds are mentioned to be useful for combating invertebrate pests.
  • a suitable reagent III Y is a nucleophilic leaving group, such as a halide, mesylate, or tosylate, preferably Br or Cl.
  • the reaction can be effected under conditions known from literature.
  • This transformation is usually carried out at temperatures from -10°C to +110°C, preferably from 0°C to 25°C, in an inert solvent and in the presence of a base [cf. WO 2002100846 and S. M. Somagond, Heterocycl. Commun. 2017, 317],
  • the starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of III, based on II.
  • Compounds II can be obtained by reaction of an amino compound IV with a carboxylic acid V )
  • This transformation is usually carried out at temperatures of from -20°C to 50°C, preferably from 0°C to 25°C, in an inert solvent, in the presence of a peptide coupling reagent and optionally in the presence of a base [cf. A. El-Faham, Chem. Rev. 2011 , 6557], or in two steps by preparation of an intermediate acyl chloride from V under conditions known from literature, e.g. by reaction with SOC or oxalyl chloride in dimethylformamide (DMF) (cf. Schaefer et al, Organic Syntheses 1929, 32), followed by reaction with IV in the presence of a base, optionally under Schotten-Baumann conditions (Baumann, Chem. Ber.
  • DMF dimethylformamide
  • Suitable peptide coupling reagents are, e.g., dicyclohexylcarbodiimide, diisopropylcarbodiimide, 1-ethyl-3-(3'-dime- thylaminopropyl)carbodiimide hydrochloride, or chloro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate, which are commonly used together with catalytic, stoichiometric, excess amounts of additives, such as 1 -hydroxybenzotriazole, 1-hydroxy-7-aza-benzotriazole, 4-(dime- thylamino)pyridine, and/or 1 -methylimidazole.
  • additives such as 1 -hydroxybenzotriazole, 1-hydroxy-7-aza-benzotriazole, 4-(dime- thylamino)pyridine, and/or 1 -methylimidazole.
  • Suitable solvents are halogenated hydrocarbons, such as dichloromethane (DCM) or 1 ,2-di- chloroethane, ethers, such as diethylether, tetrahydrofuran (THF) or 1 ,4-dioxane, or high-boiling solvents such as DMF, preferably DCM or DMF, or in aqueous media.
  • DCM dichloromethane
  • ethers such as diethylether, tetrahydrofuran (THF) or 1 ,4-dioxane
  • high-boiling solvents such as DMF, preferably DCM or DMF, or in aqueous media.
  • Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal hydroxides, such as LiOH, NaOH, KOH, or Ca(OH)2, alkali metal and alkaline earth metal carbonates, such as Na2COs, K2CO3, or CS2CO3, alkali metal bicarbonates, such as NaHCOs, or organic bases, for example tertiary amines, such as triethylamine, diisopropylethylamine, N- methylpiperidine, or basic aromatic rings, such as pyridine, 2,4,6-collidine, 2,6-lutidine, or 4-(di- methylamino)pyridine, or bicyclic amines, such as 1 ,8-diazabicylo[5.4.0]undec-7-ene (DBU), 1 ,5-diazabicyclo[4.3.0]non-5-ene (DBN), or 1 ,4-diazabicyclo[2.2.2]
  • triethylamine, diisopropylethylamine, and NaOH are generally employed in stoichiometric or excess amounts; however, they can also be used in catalytic amounts or, if appropriate, as the solvent.
  • the starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of IV based on V.
  • Suitable solvents are alcohols, such as methanol, ethanol, n-propanol, 2-propanol, or n-butanol, or water, preferably methanol. It is also possible to use mixtures of the aforementioned solvents.
  • Suitable reagents are ammonium acetate (NH4AC), ammonium formate, NH4OH, NH4CI, ammonia, or primary amines R 1 NH2.
  • Suitable reducing agents are NaBHsCN, sodium triacetoxyborohydride, or NaBH4. Preference is given to ammonium acetate and NaBHsCN, resp.
  • Compounds VI can be obtained by Grignard reaction of a compound VII.
  • This transformation is usually carried out at temperatures of from -78°C to 25 °C, preferably from -10°C to 10 °C, in an inert solvent [cf. W02020081999],
  • Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane, and petrol ether, aromatic hydrocarbons such as toluene, o-, m-, and p-xylene, ethers such as diethylether, diisopropylether, tert.-butylmethylether, dioxane, anisole, and THF, preferably THF or 2- methyltetrahydrofuran. It is also possible to use mixtures of the solvents mentioned.
  • the starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of VIII, based on VII.
  • Compounds VII can be obtained by amidation of a carboxylic acid IX with an amine X under conditions known in the art.
  • This transformation is usually carried out at temperatures of from -10°C to 45°C, preferably from 0°C to 25°C, in an inert solvent, in the presence of a peptide coupling reagent and a base [cf. WO2019121374],
  • Suitable solvents are aromatic hydrocarbons such as toluene, o-, m-, and p-xylene, halogenated hydrocarbons such as methylene chloride, chloroform, DCM, and chlorobenzene, ethers such as diethylether, diisopropylether, tert.-butylmethylether, dioxane, anisole, and THF, nitrils such as acetonitrile, and propionitrile, moreover DMF; preferably DCM. It is also possible to use mixtures of the solvents mentioned.
  • Suitable bases are, in general, inorganic compounds, moreover organic bases, e.g. tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to triethylamine and diisopropylethylamine.
  • the bases are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.
  • Suitable peptide coupling reagents are peptide coupling reagents such as for example 1-ethyl- 3-(3'-dimethylaminopropyl)carbodiimide hydrochloride, O-(7-Azabenzotriazol-1-yl)-N,N,N',N'- tetramethyluronium hexafluorophosphate, 1-[eis(dimethylamino)methylene]-1 H-benzotriazolium hexafluorophosphate(l-) 3-oxide.
  • peptide coupling reagents such as for example 1-ethyl- 3-(3'-dimethylaminopropyl)carbodiimide hydrochloride, O-(7-Azabenzotriazol-1-yl)-N,N,N',N'- tetramethyluronium hexafluorophosphate, 1-[eis(dimethylamino)methylene]-1 H-benz
  • the reagents are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.
  • the starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of X, based on IX.
  • This transformation is usually carried out at temperatures of from -10°C to 65 °C, preferably from 0°C to 40 °C, in an inert solvent, in the presence of LiOH [cf. WO2018029126],
  • Suitable solvents are ethers such as diethylether, diisopropylether, tert.-butylmethylether, dioxane, anisole, and THF, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, and tert.-butanol, moreover DMSO, DMF, dimethylacetamide (DMA), and water, preferably alcohols, ethers and water; in particular THF, methanol, and water. It is also possible to use mixtures of the solvents mentioned.
  • ethers such as diethylether, diisopropylether, tert.-butylmethylether, dioxane, anisole, and THF
  • alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, and tert.-butanol
  • DMSO dimethylacetamide
  • LiOH is generally employed in equimolar amounts or in excess.
  • Esters XII are obtainable from compounds XIII in a Stille coupling of XIII with an ester XIV, whererin X is a halogen, preferably Br.
  • the Stille coupling reaction is usually carried out at temperatures from 50°C to 150°C, preferably from 70°C to 120°C, in an inert solvent in the presence of one or more catalysts and optionally in the presence of one or more additives and a base
  • Suitable solvents are aromatic hydrocarbons such as toluene, o-, m-, p-xylene, and mesitylene, or ethers such as THF and 1 ,4-dioxane, preferably toluene or 1 ,4-dioxane. It is also possible to use mixtures of the aforementioned solvents.
  • Suitable catalysts are palladium complexes, such as tetrakis(triphenylphosphine)palladium, tris(dibenzylideneacetone)dipalladium, palladium diacetate, dichloro-bis(triphenylphosphine)palladium, and [1 ,1 '-bis(diphenylphos- phino)ferrocene]dichloropalladium, preferably dichlorobis(triphenylphosphine)palladium.
  • palladium complexes such as tetrakis(triphenylphosphine)palladium, tris(dibenzylideneacetone)dipalladium, palladium diacetate, dichloro-bis(triphenylphosphine)palladium, and [1 ,1 '-bis(diphenylphos- phino)ferrocene]dichloropalladium, preferably dichlorobis(triphenylpho
  • Suitable optional catalysts are common ligands, such as dicyclohexyl[2',4',6'-tris(propan-2- yl)[1,1'-biphenyl]-2-yl]phosphine or triphenylphosphine.
  • Suitable additives are, in general, inorganic compounds, such as cesium fluoride and cuprous iodide. The starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of XIV, based on XIII.
  • This transformation is usually carried out at temperatures of from -78°C to 25°C, preferably from -78°C to 0°C, in an inert solvent, in the presence of a bromine source and a base [cf. WO2019222154)].
  • Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane, and petrol ether, aromatic hydrocarbons such as toluene, o-, m-, and p-xylene, halogenated hydrocarbons such as methylene chloride, chloroform, and chlorobenzene, ethers such as diethylether, diisopropylether, tert.-butylmethylether, dioxane, anisole, and THF, preferably ethers such as THF. It is also possible to use mixtures of the solvents mentioned.
  • Suitable bases are, in general, inorganic compounds, such as alkali metal amides, such as lithium diisopropylamide or lithium hexamethyl disilazide or sodium hexamethyl disilazide. Particular preference is given to lithium hexamethyl disilazide.
  • the bases are generally employed in equimolar amounts, in excess or, if appropriate, as solvent.
  • Suitable bromine sources are bromine or N-bromo succinimide (NBS).
  • the bromine sources are generally employed in in equimolar amounts or in excess.
  • the starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of NBS, based on XV.
  • Tin compounds XVIII are obtainable from compounds XVI with an organotin compound such as bis(tributyltin) XVII.
  • Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane, and petrol ether, aromatic hydrocarbons such as toluene, o-, m-, and p-xylene, ethers such as diethylether, diisopropylether, tert.-butylmethylether, dioxane, anisole, and THF, moreover, DMF and DMA, preferably ethers and aromatic hydrocarbons such as 1 ,4-dioxane or toluene. It is also possible to use mixtures of the solvents mentioned.
  • Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal hydroxides, such as LiOH, NaOH, KOH, and Ca(OH) 2 , alkali metal and alkaline earth metal carbonates such as l_i 2 CC>3, Na 2 CO3, K 2 COs and also alkali metal bicarbonates such as sodium bicarbonate, articular preference is given to carbonate bases such as Na 2 CO3.
  • the bases are generally employed in catalytic amounts; however, they can be also used in equimolar amounts, in excess or, if appropriate, as solvent.
  • the starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of XVII, based on XVI.
  • reaction mixtures are worked up in a customary manner, for example by mixing with water, separating the phases and, if appropriate, chromatographic purification of the crude products.
  • Some of the intermediates and end products are obtained in the form of colourless or slightly brownish viscous oils which are purified or freed from volatile components under reduced pressure and at moderately elevated temperature. If the intermediates and end products are obtained as solids, purification can also be carried out by recrystallization or digestion.
  • organic moieties groups mentioned in the above definitions of the variables are - like the term halogen - collective terms for individual listings of the individual group members.
  • the prefix Cn-Cm indicates in each case the possible number of carbon atoms in the group.
  • radical partially or fully substituted by a radical means that in general the group is substituted with same or different radicals.
  • alkyl as used herein and in the alkyl moieties of alkylamino, alkylcarbonyl, alkylthio, alkylsulfinyl, alkylsulfonyl and alkoxyalkyl denotes in each case a straight-chain or branched alkyl group having usually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, more preferably from 1 to 3 carbon atoms.
  • alkyl group examples include methyl (Me), ethyl (Et), n-propyl (n-Pr), iso-propyl, n-butyl (Bu), 2-butyl, iso-butyl, tert-butyl, n-pentyl, 1 -methyl butyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1 , 1-dimethylpropyl, 1 ,2-dimethylpropyl, 1 -methylpentyl, 2-methylpentyl, 3-methylpentyl, 4- methylpentyl, 1 , 1-dimethylbutyl, 1 ,2-dimethylbutyl, 1 ,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-di- methylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethy
  • haloalkyl as used herein and in the haloalkyl moieties of haloalkylcarbonyl, haloalkoxycarbonyl, haloalkylthio, haloalkylsulfonyl, haloalkylsulfinyl, haloalkoxy and haloalkoxyalkyl, denotes in each case a straight-chain or branched alkyl group having usually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, wherein the hydrogen atoms of this group are partially or totally replaced with halogen atoms.
  • Preferred haloalkyl moieties are selected from Ci-C4-haloalkyl, more preferably from Ci-Cs-haloalkyl or Ci-C2-haloalkyl, in particular from Ci-C2-fluoroalkyl such as fluoromethyl, difluoromethyl, trifluoromethyl, 1 -fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, and the like.
  • alkoxy denotes in each case a straight-chain or branched alkyl group which is bonded via an oxygen atom and has usually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms.
  • alkoxy group examples are methoxy, ethoxy, n-propoxy, iso-propoxy, n-butyloxy, 2-butyloxy, iso-butyloxy, tert.-butyloxy, and the like.
  • alkoxyalkyl refers to alkyl usually comprising 1 to 10, frequently 1 to 4, preferably 1 to 2 carbon atoms, wherein 1 carbon atom carries an alkoxy radical usually comprising 1 to 4, preferably 1 or 2 carbon atoms as defined above. Examples are CH2OCH3, CH2- OC2H5, 2-(methoxy)ethyl, and 2-(ethoxy)ethyl.
  • haloalkoxy denotes in each case a straight-chain or branched alkoxy group having from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, wherein the hydrogen atoms of this group are partially or totally replaced with halogen atoms, in particular fluorine atoms.
  • Preferred haloalkoxy moieties include C1-C4- haloalkoxy, in particular Ci-C2-fluoroalkoxy, such as fluoromethoxy, difluoromethoxy, trifluoromethoxy, 1 -fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-flu- oroethoxy, 2-chloro-2,2-difluoro-ethoxy, 2,2dichloro-2-fluorethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy and the like.
  • Ci-C2-fluoroalkoxy such as fluoromethoxy, difluoromethoxy, trifluoromethoxy, 1 -fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-flu- oroe
  • alkylthio (alkylsulfanyl: S-alkyl)
  • haloalkylthio refers to an alkylthio group as mentioned above wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and/or iodine.
  • haloalkylsulfinyl refers to an alkylsulfinyl group as mentioned above wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and/or iodine.
  • haloalkylsulfonyl refers to an alkylsulfonyl group as mentioned above wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and/or iodine.
  • haloalkylcarbonyl refers to an alkylcarbonyl group as mentioned above, wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and/or iodine.
  • alkoxycarbonyl refers to an alkylcarbonyl group as defined above, which is bonded via an oxygen atom to the remainder of the molecule.
  • haloalkoxycarbonyl refers to an alkoxycarbonyl group as mentioned above, wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and/or iodine.
  • alkenyl denotes in each case a hydrocarbon radical containing one double bond, having usually 2 to 10, frequently 2 to 6, preferably 2 to 4 carbon atoms, e.g. vinyl, allyl (2-propen-1-yl), 1-propen-1-yl, 2-propen-2-yl, methallyl (2-methylprop-2-en-1-yl), 2-buten-1- yl, 3-buten-1-yl, 2-penten-1-yl, 3-penten-1-yl, 4-penten-1-yl, 1-methylbut-2-en-1-yl, 2-ethylprop- 2-en-1-yl and the like.
  • haloalkenyl refers to an alkenyl group as defined above, wherein the hydrogen atoms are partially or totally replaced with halogen atoms.
  • alkynyl denotes in each case a hydrocarbon radical containing one triple bond, having usually 2 to 10, frequently 2 to 6, preferably 2 to 4 carbon atoms, e.g.
  • ethynyl propargyl (2-propyn-1-yl), 1-propyn-1-yl, 1-methylprop-2-yn-1-yl), 2-butyn-1-yl, 3-butyn- 1-yl, 1-pentyn-1-yl, 3-pentyn-1-yl, 4-pentyn-1-yl, 1-methylbut-2-yn-1-yl, 1-ethylprop-2-yn-1-yl and the like.
  • haloalkynyl refers to an alkynyl group as defined above, wherein the hydrogen atoms are partially or totally replaced with halogen atoms.
  • cycloalkyl as used herein and in the cycloalkyl moieties of cycloalkoxy and cycloalkylthio denotes in each case a monocyclic cycloaliphatic radical having usually from 3 to 10 or from 3 to 6 carbon atoms, such as cyclopropyl (CC3H5), cyclobutyl (CC4H7), cyclopentyl (CC5H9), cyclohexyl (cCeHn), cycloheptyl, cyclooctyl, cyclononyl and cyclodecyl or cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
  • halocycloalkyl as used herein and in the halocycloalkyl moieties of halocycloalkoxy and halocycloalkylthio denotes in each case a monocyclic cycloaliphatic radical having usually from 3 to 10 C atoms or 3 to 6 C atoms, wherein at least one, e.g. 1 , 2, 3, 4 or 5 of the hydrogen atoms, are replaced by halogen, in particular by fluorine or chlorine.
  • Examples are 1- and 2-fluo- rocyclopropyl, 1 ,2-, 2,2- and 2,3-difluorocyclopropyl, 1 ,2,2-trifluorocyclopropyl, 2, 2, 3, 3- tetrafl uo- rocyclpropyl, 1- and 2-chlorocyclopropyl, 1 ,2-, 2,2- and 2,3-dichlorocyclopropyl, 1 , 2, 2-tri chlorocyclopropyl, 2,2,3,3-tetrachlorocyclpropyl, 1-,2- and 3-fluorocyclopentyl, 1 ,2-, 2,2-, 2,3-, 3,3-, 3,4-, 2,5-difluorocyclopentyl, 1-,2- and 3-chlorocyclopentyl, 1 ,2-, 2,2-, 2,3-, 3,3-, 3,4-, 2,5-difluorocyclopentyl, 1-,2- and 3-chlorocyclopentyl, 1 ,2-, 2,2-
  • halocycloalkenyl as used herein and in the halocycloalkenyl moieties of halocyclo- alkenyloxy and halocycloalkenylthio denotes in each case a monocyclic singly unsaturated nonaromatic radical having usually from 3 to 10, e.g. 3 or 4 or from 5 to 10 carbon atoms, preferably from 3- to 8 carbon atoms, wherein at least one, e.g. 1 , 2, 3, 4 or 5 of the hydrogen atoms, are replaced by halogen, in particular by fluorine or chlorine. Examples are 3,3-difluorocyclopropen- 1-yl and 3,3-dichlorocyclopropen-1-yl.
  • carrier or “carbocyclyl” includes in general a 3- to 12-membered, preferably a 3- to 8-membered or a 5- to 8-membered, more preferably a 5- or 6-membered mono-cyclic, non-aromatic ring comprising 3 to 12, preferably 3 to 8 or 5 to 8, more preferably 5 or 6 carbon atoms.
  • the term “carbocycle” covers cycloalkyl and cycloalkenyl groups as defined above.
  • heterocycle or “heterocyclyl” includes in general 3- to 12-membered, preferably 3- to 6-membered, in particular 6-membered monocyclic heterocyclic non-aromatic radicals.
  • the heterocyclic non-aromatic radicals usually comprise 1, 2, 3, 4 or 5, preferably 1, 2 or 3 heteroatoms selected from N, O, and S as ring members, wherein S-atoms as ring members may be present as S, SO, or SO2.
  • Examples of 5- or 6-membered heterocyclic radicals comprise saturated or unsaturated, non-aromatic heterocyclic rings, such as oxiranyl, oxetanyl, thietanyl, thietanyl-S-oxid (S-oxothietanyl), thietanyl-S-dioxid (S-dioxothiethanyl), pyrrolidinyl, pyrrolinyl, pyrazolinyl, tetrahydrofuranyl, dihydrofuranyl, 1,3-dioxolanyl, thiolanyl, S-oxothiolanyl, S-dioxo- thiolanyl, dihydrothienyl, S-oxodi hydrothienyl, S-dioxodihydrothienyl, oxazolidinyl, oxazolinyl, thi- azolinyl, ox
  • oxothiopyranyl S-dioxothiopyranyl, dihydrothiopyranyl, S-oxodi- hydrothiopyranyl, S-dioxodihydrothiopyranyl, tetrahydrothiopyranyl, S-oxotetrahydrothiopyranyl, S-dioxotetrahydrothiopyranyl, morpholinyl, thiomorpholinyl, S-oxothiomorpholinyl, S-dioxothio- morpholinyl, thiazinyl and the like.
  • heteroaromatic radicals include monocyclic 5- or 6-membered heteroaromatic radicals comprising as ring members 1, 2, 3 or 4 heteroatoms selected from N, O, and S.
  • 5- or 6-mem- bered heteroaromatic radicals include pyridyl, i.e. 2-, 3-, or 4-pyridyl, pyrimidinyl, i.e. 2-, 4- or 5- pyrimidinyl, pyrazinyl, pyridazinyl, i.e. 3- or 4-pyridazinyl, thienyl, i.e. 2- or 3-thienyl, furyl, i.e. 2- or 3-furyl, pyrrolyl, i.e.
  • 2- or 3-pyrrolyl oxazolyl, i.e. 2-, 3- or 5-oxazolyl, isoxazolyl, i.e. 3-, 4- or 5-isoxazolyl, thiazolyl, i.e. 2-, 3- or 5-thiazolyl, isothiazolyl, i.e. 3-, 4- or 5-isothiazolyl, pyrazolyl, i.e. 1-, 3-, 4- or 5-pyrazolyl, i.e. 1-, 2-, 4- or 5-imidazolyl, oxadiazolyl, e.g.
  • heteroaryl also includes bicyclic 8 to 10-membered heteroaromatic radicals comprising as ring members 1 , 2 or 3 heteroatoms selected from N, O, and S, wherein a 5- or 6-membered heteroaromatic ring is fused to a phenyl ring or to a 5- or 6- membered heteroaromatic radical.
  • Examples of a 5- or 6-membered heteroaromatic ring fused to a phenyl ring or to a 5- or 6-membered heteroaromatic radical include benzofuranyl, benzothienyl, indolyl, indazolyl, benzimidazolyl, benzoxathiazolyl, benzoxadiazolyl, benzothiadiazolyl, benzoxazinyl, chinolinyl, isochinolinyl, purinyl, 1 ,8-naphthyridyl, pteridyl, pyrido[3,2-d]pyrimidyl or pyridoimidazolyl and the like.
  • These fused hetaryl radicals may be bonded to the remainder of the molecule via any ring atom of 5- or 6-membered heteroaromatic ring or via a carbon atom of the fused phenyl moiety.
  • alkylene refers to alkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, heterocycloalkenyl and alkynyl as defined above, respectively, which are bonded to the remainder of the molecule, via two atoms, preferably via two carbon atoms, of the respective group, so that they represent a linker between two moieties of the molecule.
  • variables of the compounds of the formula I have the following meanings, these meanings, both on their own and in combination with one another, being particular embodiments of the compounds of the formula I.
  • Embodiments and preferred compounds of the invention for use in pesticidal methods and for insecticidal application purposes are outlined in the following paragraphs.
  • the compounds I are present in form of a mixture of compounds I. A and I.B, wherein compound I.A with S-configuration of the carbon atom neighboring the nitrogen is present in an amount of more than 50% by weight, in particular of at least 70% by weight, more particularly of at least 85% by weight, specifically of at least 90% by weight, based on the total weight of compounds I.A and I.B.
  • the method comprises the step of contacting the plant, parts of it, its propagation material, the pests, their food supply, habitat or breeding grounds with a pesticidally effective amount of a compound of formula I.A.
  • R 1 is preferably H, Ci-Ce-alkyl, Cs-Ce-alkynyl, Cs-Ce-cycloalkyl, or Ci-C4-alkyl-C3-C6-cycloalkyl, more preferably H, Ci-Ce-alkyl, or Ci-C4-alkyl-C3-C6-cycloalkyl, particularly H or CH 2 -cC3H 5 .
  • R 2 is preferably CH 3 .
  • X is preferably CH or CR 3 , particularly CH. Such compounds correspond to Formula 1.1
  • X is N.
  • Such compounds correspond to formula 1.2.
  • R 3 is preferably halogen, CN, Ci-C4-haloalkyl, Ci-C4-haloalkoxy, C3-C4-cycloalkyl unsubstituted or substituted with one or more CN, C3-C4-halocycloalkyl, S(O) m -Ci-C4-alkyl, S(O) m -Ci-C4- haloalkyl, S(O) m -C3-C4-cycloalkyl, S(O) m -C3-C4-halocycloalkyl, S(O) m -(substituted phenyl).
  • Index m in R 3 is preferably 2.
  • Index n is preferably 2.
  • R 3 groups stand preferably in positions 3 and 5.
  • R 3 is preferably halogen, CN, Ci-C4-haloalkyl, Ci-C4-haloalkoxy, C3- C4-cycloalkyl, C3-C4-halocycloalkyl, S(O) m -Ci-C4-alkyl, S(O) m -Ci-C4-haloalkyl, S(O) m -C3-C4-cy- cloalkyl, S(O) m -C3-C4-halocycloalkyl, or
  • R 4 is preferably H.
  • R 4a is preferably different from H.
  • R 4a is preferably H, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci-C4-haloalkoxy, C1- C4-alkoxy-Ci-C4-alkyl, C(O)NH-Ci-Ce-alkyl, S(O) m -Ci-C4-alkyl, or phenyl unsubstituted or substituted with one or more groups R 3 .
  • R 4a is preferably halogen, CN, C(O)NH2, or C(O)NH-Ci-Ce-alkyl.
  • the ring formed by R 12 and R 13 together with the nitrogen atom they are bound to, is unsubstituted or substituted with a radical different from oxo.
  • V is O and U is N, or V is N and U is O.
  • V is S and U is N, or V is N and U is S.
  • V is O or S, and II is N.
  • Another embodiment relates to compounds I.V with V being O (Formula I. O).
  • Another embodiment relates to compounds I.V with V being S (Formula I. VS).
  • V is N and U is O or S.
  • Such compounds correspond to formula I.U
  • Another embodiment relates to compounds I.U with U being O (Formula LUO).
  • Another embodiment relates to compounds I.U with U being S (Formula I. US).
  • T is CR 4a .
  • W is N and T is CR 4a .
  • Such compounds correspond to formula LT.
  • W is CH and T is N.
  • Such compounds correspond to formula I.W.
  • W is CH and T is CR 4a .
  • Such compounds correspond to formula I.P.
  • R 1 and (R 3 ) n for a compound corresponds in each case to one row of Table A
  • R 1 and (R 3 ) n for a compound corresponds in each case to one row of Table A
  • compound(s) of the invention refers to compound(s) of formula I, or “compound(s) I”, and includes their salts, tautomers, stereoisomers, and N-oxides.
  • the invention also relates to agrochemical compositions comprising an auxiliary and at least one compound I.
  • An agrochemical composition comprises a pesticidally effective amount of a compound I.
  • An agrochemical composition comprises a pesticidally effective amount of a compound I.
  • compositions e.g. solutions, emulsions, suspensions, dusts, powders, pastes, granules, pressings, capsules, and mixtures thereof.
  • composition types are suspensions (e.g. SC, OD, FS), emulsifiable concentrates (e.g. EC), emulsions (e.g. EW, EO, ES, ME), capsules (e.g. CS, ZC), pastes, pastilles, wettable powders or dusts (e.g. WP, SP, WS, DP, DS), pressings (e.g. BR, TB, DT), granules (e.g.
  • compositions types are defined in the “Catalogue of pesticide formulation types and international coding system”, Technical Monograph No. 2, 6th Ed. May 2008, CropLife International.
  • Suitable auxiliaries are solvents, liquid carriers, solid carriers or fillers, surfactants, dispersants, emulsifiers, wetters, adjuvants, solubilizers, penetration enhancers, protective colloids, adhesion agents, thickeners, humectants, repellents, attractants, feeding stimulants, compatibilizers, bactericides, anti-freezing agents, anti-foaming agents, colorants, tackifiers and binders.
  • Suitable solvents and liquid carriers are water and organic solvents.
  • Suitable solid carriers or fillers are mineral earths.
  • Suitable surfactants are surface-active compounds, e.g. anionic, cationic, nonionic, and amphoteric surfactants, block polymers, polyelectrolytes. Such surfactants can be used as emulsifier, dispersant, solubilizer, wetter, penetration enhancer, protective colloid, or adjuvant. Surfactants are listed in McCutcheon’s, Vol.1: Emulsifiers & Detergents, McCutcheon’s Directories, Glen Rock, USA, 2008 (International or North American Ed.). Suitable anionic surfactants are alkali, alkaline earth, or ammonium salts of sulfonates, sulfates, phosphates, carboxylates.
  • Suitable nonionic surfactants are alkoxylates, N-subsituted fatty acid amides, amine oxides, esters, sugar-based surfactants, polymeric surfactants.
  • Suitable cationic surfactants are quaternary surfactants.
  • the agrochemical compositions generally comprise between 0.01 and 95%, preferably between 0.1 and 90%, and most preferably between 0.5 and 75%, by weight of active substance.
  • the active substances are employed in a purity of from 90% to 100%, preferably from 95% to 100%.
  • oils, wetters, adjuvants, or fertilizer may be added to the active substances or the compositions comprising them as premix or, if appropriate not until immediately prior to use (tank mix).
  • These agents can be admixed with the compositions according to the invention in a weight ratio of 1 : 100 to 100: 1.
  • the user applies the composition according to the invention usually from a predosage device, a knapsack sprayer, a spray tank, a spray plane, or an irrigation system.
  • the agrochemical composition is made up with water, buffer, and/or further auxiliaries to the desired application concentration and the ready-to-use spray liquor or the agrochemical composition according to the invention is thus obtained.
  • 20 to 2000 liters of the ready-to-use spray liquor are applied per hectare of agricultural useful area.
  • the compounds I are suitable for use in protecting crops, plants, plant propagation materials, e.g. seeds, or soil or water, in which the plants are growing, from attack or infestation by animal pests. Therefore, the invention also relates to a plant protection method, which comprises contacting crops, plants, plant propagation materials, e.g. seeds, or soil or water, in which the plants are growing, to be protected from attack or infestation by animal pests, with a pesticidally effective amount of a compound I.
  • the compounds I are also suitable for use in combating or controlling animal pests. Therefore, the invention also relates to a method of combating or controlling animal pests, which comprises contacting the animal pests, their habitat, breeding ground, or food supply, or the crops, plants, plant propagation materials, e.g. seeds, or soil, or the area, material or environment in which the animal pests are growing or may grow, with a pesticidally effective amount of a compound I.
  • the compounds I are effective through both contact and ingestion to any and all developmental stages, such as egg, larva, pupa, and adult.
  • the compounds I can be applied as such or in form of compositions comprising them.
  • the application can be carried out both before and after the infestation of the crops, plants, plant propagation materials by the pests.
  • contacting includes both direct contact (applying the compounds/compositions directly on the animal pest or plant) and indirect contact (applying the compounds/compositions to the locus).
  • animal pest includes arthropods, gastropods, and nematodes.
  • Preferred animal pests according to the invention are arthropods, preferably insects and arachnids, in particular insects.
  • plant includes cereals, e.g. durum and other wheat, rye, barley, triticale, oats, rice, or maize (fodder maize and sugar maize I sweet and field corn); beet, e.g. sugar beet, or fodder beet; fruits, e.g. pomes, stone fruits, or soft fruits, e.g. apples, pears, plums, peaches, nectarines, almonds, cherries, papayas, strawberries, raspberries, blackberries or gooseberries; leguminous plants, e.g. beans, lentils, peas, alfalfa, or soybeans; oil plants, e.g.
  • rapeseed (oilseed rape), turnip rape, mustard, olives, sunflowers, coconut, cocoa beans, castor oil plants, oil palms, ground nuts, or soybeans; cucurbits, e.g. squashes, pumpkins, cucumber or melons; fiber plants, e.g. cotton, flax, hemp, or jute; citrus fruit, e.g. oranges, lemons, grapefruits or mandarins; vegetables, e.g. eggplant, spinach, lettuce (e.g. iceberg lettuce), chicory, cabbage, asparagus, cabbages, carrots, onions, garlic, leeks, tomatoes, potatoes, cucurbits or sweet peppers; lauraceous plants, e.g.
  • Preferred plants include potatoes, sugar beets, tobacco, wheat, rye, barley, oats, rice, corn, cotton, soybeans, rapeseed, legumes, sunflowers, coffee, or sugar cane; fruits; vines; ornamentals; or vegetables, e.g. cucumbers, tomatoes, beans or squashes.
  • seed embraces seeds and plant propagules including true seeds, seed pieces, suckers, corms, bulbs, fruit, tubers, grains, cuttings, cut shoots, and means preferably true seeds.
  • Pesticidally effective amount means the amount of active ingredient needed to achieve an observable effect on growth, including the effects of necrosis, death, retardation, prevention, and removal, destruction, or otherwise diminishing the occurrence and activity of the target organism.
  • the pesticidally effective amount can vary for the various compounds/compositions used in the invention.
  • a pesticidally effective amount of the compositions will also vary according to the prevailing conditions e.g. desired pesticidal effect and duration, weather, target species, locus, mode of application.
  • the rate of application of the active ingredients of this invention may be in the range of 0.0001 g to 4000 g per hectare, e.g. from 1 g to 2 kg per hectare or from 1 g to 750 g per hectare, desirably from 1 g to 100 g per hectare.
  • the compounds I are also suitable for use against non-crop insect pests.
  • compounds I can be used as bait composition, gel, general insect spray, aerosol, as ultra-low volume application and bed net (impregnated or surface applied).
  • non-crop insect pest refers to pests, which are particularly relevant for non-crop targets, e.g. ants, termites, wasps, flies, ticks, mosquitoes, bed bugs, crickets, or cockroaches, such as: Aedes aegypti, Musca domestica, Tribolium spp.; termites such as Reticulitermes flavipes, Coptotermes formosanus; roaches such as Blatella germanica, Periplaneta Americana; ants such as Solenopsis invicta, Linepithema humile, and Camponotus pennsylvanicus.
  • the bait can be a liquid, a solid or a semisolid preparation (e.g. a gel).
  • the typical content of active ingredient is from 0.001 wt% to 15 wt%, desirably from 0.001 wt% to 5 wt% of active compound.
  • the compounds I and its compositions can be used for protecting wooden materials such as trees, board fences, sleepers, frames, artistic artifacts, etc. and buildings, but also construction materials, furniture, leathers, fibers, vinyl articles, electric wires and cables etc. from ants, termites and/or wood or textile destroying beetles, and for controlling ants and termites from doing harm to crops or human beings (e.g. when the pests invade into houses and public facilities or nest in yards, orchards or parks).
  • Customary application rates in the protection of materials are, e.g., from 0.001 g to 2000 g or from 0.01 g to 1000 g of active compound per m 2 treated material, desirably from 0.1 g to 50 g per m 2 .
  • Insecticidal compositions for use in the impregnation of materials typically contain from 0.001 to 95 wt%, preferably from 0.1 to 45 wt%, and more preferably from 1 to 25 wt% of at least one repellent and/or insecticide.
  • the compounds of the invention are especially suitable for efficiently combating animal pests e.g. arthropods, and nematodes including: insects from the sub-order of Auchenorrhyncha, e.g. Amrasca biguttula, Empoasca spp., Ne- photettix virescens, Sogatella furcifera, Mahanarva spp., Laodelphax striatellus, Nilaparvata lugens, Diaphorina citrr',
  • insects from the sub-order of Auchenorrhyncha e.g. Amrasca biguttula, Empoasca spp., Ne- photettix virescens, Sogatella furcifera, Mahanarva spp., Laodelphax striatellus, Nilaparvata lugens, Diaphorina citrr',
  • Lepidoptera e.g. Helicoverpa spp., Heliothis virescens, Lobesia botrana, Ostrinia nubilalis, Plu-tella xylostella, Pseudoplusia includens, Scirpophaga incertulas, Spodoptera spp., Trichop- lusia ni, Tuta absoluta, Cnaphalocrocis medialis, Cydia pomonella, Chilo suppressalis, Anticar- sia gemmatalis, Agrotis ipsilon, Chrysodeixis includens',
  • True bugs e.g. Lygus spp.
  • Stink bugs such as Euschistus spp., Halyomorpha halys, Nezara viridula, Piezodorus guildinii, Dichelops furcatus',
  • Thrips e.g. Frankliniella spp., Thrips spp., Dichromothrips corbettii;
  • Aphids e.g. Acyrthosiphon pisum, Aphis spp., Myzus persicae, Rhopalosiphum spp., Schi- zaphis graminum, Megoura viciae.,
  • Whiteflies e.g. Trialeurodes vaporariorum, Bemisia spp.;
  • Coleoptera e.g. Phyllotreta spp., Melanotus spp., Meligethes aeneus, Leptinotarsa decimline- ata, Ceutorhynchus spp., Diabrotica spp., Anthonomus grandis, Atomaria linearia, Agriotes spp., Epilachna spp.;
  • Flies e.g. Delia spp., Ceratitis capitate, Bactrocera spp., Liriomyza spp.;
  • Mosquitoes (Diptera), e.g. Aedes aegypti, A. albopictus, A. vexans, Anastrepha ludens, Anopheles maculipennis, A. crucians, A. albimanus, A. gambiae, A. freeborni, A. leucosphyrus, A. minimus, A. quadrimaculatus;
  • Coccoidea e.g. Aonidiella aurantia, Ferrisia virgate.
  • Anthropods of class Arachnida e.g. Penthaleus major, Tetranychus spp.;
  • Nematodes e.g. Heterodera glycines, Meloidogyne sp., Pratylenchus spp., Caenorhabditis el- egans.
  • the compounds I are suitable for use in treating or protecting animals against infestation or infection by parasites. Therefore, the invention also relates to the use of a compound of the invention for the manufacture of a medicament for the treatment or protection of animals against infestation or infection by parasites. Furthermore, the invention relates to a method of treating or protecting animals against infestation and infection by parasites, which comprises orally, topically or parenterally administering or applying to the animals a parasiticidally effective amount of a compound I.
  • the invention also relates to the non-therapeutic use of compounds of the invention for treating or protecting animals against infestation and infection by parasites. Moreover, the invention relates to a non-therapeutic method of treating or protecting animals against infestation and infection by parasites, which comprises applying to a locus a parasiticidally effective amount of a compound I.
  • the compounds of the invention are further suitable for use in combating or controlling parasites in and on animals. Furthermore, the invention relates to a method of combating or controlling parasites in and on animals, which comprises contacting the parasites with a parasitically effective amount of a compound I.
  • the invention also relates to the non-therapeutic use of compounds I for controlling or combating parasites. Moreover, the invention relates to a non-therapeutic method of combating or controlling parasites, which comprises applying to a locus a parasiticidally effective amount of a compound I.
  • the compounds I can be effective through both contact (via soil, glass, wall, bed net, carpet, blankets, or animal parts) and ingestion (e.g. baits). Furthermore, the compounds I can be applied to any and all developmental stages.
  • the compounds I can be applied as such or in form of compositions comprising them.
  • locus means the habitat, food supply, breeding ground, area, material or environment in which a parasite is growing or may grow outside of the animal.
  • parasites includes endo- and ectoparasites. In some embodiments of the invention, endoparasites can be preferred. In other embodiments, ectoparasites can be preferred. Infestations in warm-blooded animals and fish include lice, biting lice, ticks, nasal bots, keds, biting flies, muscoid flies, flies, myiasitic fly larvae, chiggers, gnats, mosquitoes and fleas.
  • the compounds of the invention are especially useful for combating the following parasites: Cimex lectularius, Rhipicephalus sanguineus, and Ctenocephalides felis.
  • animal includes warm-blooded animals (including humans) and fish.
  • mammals such as cattle, sheep, swine, camels, deer, horses, pigs, poultry, rabbits, goats, dogs and cats, water buffalo, donkeys, fallow deer and reindeer, and also in furbearing animals such as mink, chinchilla and raccoon, birds such as hens, geese, turkeys and ducks and fish such as fresh- and salt-water fish such as trout, carp and eels.
  • domestic animals such as dogs or cats.
  • the compounds I may be applied in total amounts of 0.5 mg/kg to 100 mg/kg per day, preferably 1 mg/kg to 50 mg/kg per day.
  • the compounds I may be formulated as animal feeds, animal feed premixes, animal feed concentrates, pills, solutions, pastes, suspensions, drenches, gels, tablets, boluses and capsules.
  • the dosage form chosen should provide the animal with 0.01 mg/kg to 100 mg/kg of animal body weight per day of the compounds I, preferably with 0.5 mg/kg to 100 mg/kg of animal body weight per day.
  • the compounds I may be administered to animals parenterally, e.g., by intrarumi- nal, intramuscular, intravenous or subcutaneous injection.
  • the compounds I may be dispersed or dissolved in a physiologically acceptable carrier for subcutaneous injection.
  • the compounds I may be formulated into an implant for subcutaneous administration.
  • the compounds I may be transdermally administered to animals.
  • the dosage form chosen should provide the animal with 0.01 mg/kg to 100 mg/kg of animal body weight per day of the compounds I.
  • the compounds I may also be applied topically to the animals in the form of dips, dusts, powders, collars, medallions, sprays, shampoos, spot-on and pour-on formulations and in ointments or oil-in-water or water-in-oil emulsions.
  • dips and sprays usually contain 0.5 ppm to 5,000 ppm and preferably 1 ppm to 3,000 ppm of the compounds I.
  • the compounds I may be formulated as ear tags for animals, particularly quadrupeds e.g. cattle and sheep.
  • Oral solutions are administered directly.
  • Solutions for use on the skin are trickled on, spread on, rubbed in, sprinkled on or sprayed on. Gels are applied to or spread on the skin or introduced into body cavities.
  • Pour-on formulations are poured or sprayed onto limited areas of the skin, the active compound penetrating the skin and acting systemically. Pour-on formulations are prepared by dissolving, suspending, or emulsifying the active compound in suitable skin-compatible solvents or solvent mixtures.
  • Emulsions can be administered orally, dermally or as injections.
  • Suspensions can be administered orally or topically/dermally.
  • Semi-solid preparations can be administered orally or topically/dermally.
  • the active compound is mixed with suitable excipients, if appropriate with addition of auxiliaries, and brought into the desired form.
  • compositions which can be used in the invention can comprise generally from about 0.001 to 95% of the compound I.
  • Ready-to-use preparations contain the compounds acting against parasites, preferably ectoparasites, in concentrations of 10 ppm to 80% by weight, preferably from 0.1 to 65% by weight, more preferably from 1 to 50% by weight, most preferably from 5 to 40% by weight.
  • Preparations which are diluted before use contain the compounds acting against ectoparasites in concentrations of 0.5 to 90% by weight, preferably of 1 to 50% by weight. Furthermore, the preparations comprise the compounds of formula I against endoparasites in concentrations of 10 ppm to 2% by weight, preferably of 0.05 to 0.9% by weight, very particularly preferably of 0.005 to 0.25% by weight.
  • Solid formulations which release compounds of the invention may be applied in total amounts of 10 mg/kg to 300 mg/kg, preferably 20 mg/kg to 200 mg/kg, most preferably 25 mg/kg to 160 mg/kg body weight of the treated animal in the course of three weeks.
  • Method A HPLC: Shimadzu Nexera LIHPLC + Shimadzu LCMS-2020, ESI; Column: Phenom- enex Kinetex 1.7pm XB-C18 100A, 2.1x50mm; Mobile phase: A: water + 0.1 % TFA; B: ACN; Temperature: 60°C; Gradient: 5% B to 100% B in 1.5 min; 100% B 0.25 min; Flow: 0.8 mL/min to 1.0 mL/min in 1.51 min; MS: ESI positive; Mass range (m/z): 100-700.
  • Method B LC: Shimadzu LC-30AD, ESI; Column: Kinetex EVO C18 5pm 2.1x30mm; Mobile phase: A: water + 0.04% TFA; B: ACN + 0.02% TFA; Temperature: 40°C; Gradient: 5% B to 100% B in 2.5 min; 100% B to 5% B in 0.02min; 5% B for 0.5min; Flow: 0.8mL/min; MS: ESI positive; Mass range: 100-2000.
  • Step 1 Preparation of ethyl 4-bromooxazole-5-carboxylate
  • Step 4 Preparation of ethyl 4-[5-(difluoromethoxy)pyrimidin-2-yl]oxazole-5-carboxylate
  • reaction mixture was quenched with saturated aqueous NH 4 CI solution (50mL) and extracted with CH2CI2 (2x50 mL), the organic layer was washed with brine (20mL), dried over Na 2 SO4, concentrated, and purified by silica gel column (petrol ether/EtOAc 100:0 to 40:60) to give the title compound (44 mg, 51% yield) as a white solid.
  • Step 8 Preparation of 1-[4-[5-(difluoromethoxy)pyrimidin-2-yl]oxazol-5-yl]ethanamine
  • Step 9 Preparation of 3-bromo-N-[1-[4-[5-(difluoromethoxy)pyrimidin-2-yl]oxazol-5-yl]ethyl]-5- (trifluoromethyl)benzamide (1-1)
  • Step 1 Preparation of ethyl 5-pyrimidin-2-yloxazole-4-carboxylate
  • Step 4 Preparation of 3-(difluoromethoxy)-N-[1-(5-pyrimidin-2-yloxazol-4-yl)ethyl]-5-(trifluoro- methyl)benzamide (I-3)
  • Step 5 Preparation of 3-(difluoromethoxy)-N-ethyl-N-[1-(5-pyrimidin-2-yloxazol-4-yl)ethyl]-5- (trifluoromethyl)benzamide (I-5)
  • Step 1 Preparation of methyl 5-pyrimidin-2-ylthiazole-4-carboxylate
  • Step 4 Preparation of /V-[1-(5-pyrimidin-2-ylthiazol-4-yl)ethyl]-3,5-bis(trifluoromethyl)ben- zamide (1-11)
  • Step 5 Preparation of /V-[1-(4-pyrimidin-2-ylthiazol-5-yl)ethyl]-3,5-bis(trifluoromethyl)ben- zamide (1-17)
  • Step 1 Preparation of ethyl 4-bromooxazole-5-carboxylate
  • Step 2 Preparation of ethyl 4-tributylstannyloxazole-5-carboxylate
  • Step 3 Preparation of ethyl 4-(6-chloropyrimidin-4-yl)oxazole-5-carboxylate
  • Step 6 Preparation of 1-[4-(6-chloropyrimidin-4-yl)oxazol-5-yl]-/ ⁇ /-(cyclopropylmethyl)ethana- mine
  • Step 7 Preparation of 3-chloro-/V-[1-[4-(6-chloropyrimidin-4-yl)oxazol-5-yl]ethyl]-/ ⁇ /-(cyclo- propylmethyl)-5-(trifluoromethyl)benzamide
  • Step 8 Preparation of methyl 6-[5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]-(cyclopropylme- thyl)amino]ethyl]oxazol-4-yl]pyrimidine-4-carboxylate
  • reaction mixture was filtered, concentrated and purified by silica gel chromatography (petrol ether/EtOAc 100:0 to 30:70) to give methyl 6-[5-[1-[[3-chloro-5-(trifluorome- thyl)benzoyl]-(cyclopropylmethyl)amino]ethyl]oxazol-4-yl]pyrimidine-4-carboxylate (55mg, 58% yield) as a yellow oil.
  • Step 9 Preparation of 6-[5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]-(cyclopropylme- thyl)amino]ethyl]oxazol-4-yl]pyrimidine-4-carboxamide (1-21)
  • the active compound was dissolved at the desired concentration in a mixture of 1 :1 (vol:vol) distilled water : acetone.
  • Surfactant Karl HV was added at a rate of 0.01% (vol/vol).
  • the test solution was prepared on the day of use.
  • Leaves of cabbage were dipped in test solution and air-dried. Treated leaves were placed in petri dishes lined with moist filter paper and inoculated with ten 3rd instar larvae. Mortality was recorded 72 hours after treatment. Feeding damages were also recorded using a scale of 0- 100%.
  • test unit consisted of 96-well-microtiter plates containing liquid artificial diet under an artificial mem brane.
  • the compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were pipetted into the aphid diet, using a custom built pipetter, at two replications.
  • aphids were placed on the artificial membrane inside the microtiter plate wells. The aphids were then allowed to suck on the treated aphid diet and incubated at about 23 ⁇ 1°C and about 50 ⁇ 5 % relative humidity for 3 days. Aphid mortality and fecundity was then visually assessed.
  • test unit For evaluating control of tobacco budworm (Heliothis virescens) the test unit consisted of 96- well-microtiter plates containing an insect diet and 15-25 H. virescens eggs.
  • the compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were sprayed onto the insect diet at 10 pl, using a custom-built micro atomizer, at two replications.
  • microtiter plates were incubated at about 28 ⁇ 1°C and about 80 ⁇ 5 % relative humidity for 5 days. Egg and larval mortality was then visually assessed. In this test, compounds 1-1 , I-2, I-4, 1-10, and 1-11 , resp., at 2500 ppm showed at least 75% mortality in comparison with untreated controls.
  • test unit consisted of 96-well- microtiter plates containing an insect diet and 5-10 A. grandis eggs.
  • the compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were sprayed onto the insect diet at 5 pl, using a custom-built micro atomizer, at two replications.
  • microtiter plates were incubated at about 25 ⁇ 1°C and about 75 ⁇ 5 % relative humidity for 5 days. Egg and larval mortality was then visually assessed.
  • the active compounds were formulated by a Tecan liquid handler in 100% cyclohexanone as a 10,000-ppm solution supplied in tubes.
  • the 10,000-ppm solution was serially diluted in 100% cyclohexanone to make interim solutions.
  • These served as stock solutions for which final dilutions were made by the Tecan in 50% acetone:50% water (v/v) into 10 or 20ml glass vials.
  • a nonionic surfactant (Kinetic®) was included in the solution at a volume of 0.01% (v/v).
  • the vials were then inserted into an automated electrostatic sprayer equipped with an atomizing nozzle for application to plants/insects.
  • Lima bean plants (variety Sieva) were grown 2 plants to a pot and selected for treatment at the 1st true leaf stage. Test solutions were sprayed onto the foliage by an automated electrostatic plant sprayer equipped with an atomizing spray nozzle. The plants were dried in the sprayer fume hood and then removed from the sprayer. Each pot was placed into perforated plastic bags with a zip closure. Ten to 11 armyworm larvae were placed into the bag and the bags zipped closed. Test plants were maintained in a growth room at about 25°C and about 20-40% relative humidity for 4 days, avoiding direct exposure to fluorescent light (14:10 light:dark photoperiod) to prevent trapping of heat inside the bags. Mortality and reduced feeding were assessed 4 days after treatment, compared to untreated control plants.
  • test unit For evaluating control of yellow fever mosquito (Aedes aegypti) the test unit consisted of 96- well-microtiter plates containing 200pl of tap water per well and 5-15 freshly hatched A. aegypti larvae.
  • the active compounds were formulated using a solution containing 75% (v/v) water and 25% (v/v) DMSO. Different concentrations of formulated compounds or mixtures were sprayed onto the insect diet at 2.5pl , using a custom-built micro atomizer, at two replications.
  • microtiter plates were incubated at 28 ⁇ 1°C, 80 ⁇ 5 % RH for 2 days. Larval mortality was then visually assessed.

Abstract

The invention relates to compounds of formula (I) wherein the variables have the meanings as defined in the specification, to compositions comprising them, to active compound combinations comprising them, and to their use for protecting growing plants and animals from attack or infestation by invertebrate pests, furthermore, to seed comprising such compounds.

Description

Heterocyclic compounds for the control of invertebrate pests
Description
The invention relates to compounds of formula I
Figure imgf000002_0001
wherein
V is O or S and II is N; or
V is N and II is O or S;
R1 is H, OH, Ci-Ce-alkyl, Ci-Ce-haloalkyl, Cs-Ce-cycloalkyl, Cs-Ce-halocycloalkyl, Ci-Cs-alk- oxy, Ci-C4-alkyl-C3-C6-cycloalkyl, Ci-C4-alkyl-C3-C6-halocycloalkyl, which groups are unsubstituted, or partially or fully substituted with R11; or C(=N-R11)R12, C(O)R11a;
R11 is CN, NO2, NR12R13, C(O)NH2, C(S)NH2, C(O)OH, OR14, Si(CH3)3; Ci-C6-alkyl; C Ce-haloalkyl; C2-Ce-alkenyl; C2-C6-haloalkenyl; C2-Ce-alkynyl; C2-C6-haloalkynyl; C3- C4-cycloalkyl-Ci-C2-alkyl, which ring is unsubstituted or substituted with 1 or 2 halogen; 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, which rings are unsubstituted or substituted with halogen, Ci-Cs-haloalkyl, and/or CN;
R11a is NR12R13, C(O)NH2, C(S)NH2, C(O)OH, OR14, Si(CH3)3; Ci-C6-haloalkyl; C2-C6- alkenyl; C2-Ce-haloalkenyl; C2-Ce-alkynyl; C2-Ce-haloalkynyl; C3-C6-cycloalkyl-Ci-C2- alkyl, which ring is unsubstituted or substituted with 1 or 2 halogen; 3- to 6-mem- bered heterocyclyl, which rings are unsubstituted or substituted with halogen, C1-C3- haloalkyl, and/or CN;
R12, R13 are independently from each other H, Ci-C4-alkyl, Ci-C4-alkoxy, Ci-C4-haloal- koxy, Ci-C4-haloalkyl, Cs-Ce-cycloalkyl, C(O)-Ci-C4-alkyl, C(O)-Ci-C4-haloalkyl, C(O)-C3-C4-cycloalkyl, C(O)-C3-C4-halocycloalkyl, C(O)NH-Ci-C4-alkyl, C(O)NH-C C4-haloalkyl, C(O)N(Ci-C4-alkyl)-Ci-C4-alkyl, C(O)N(Ci-C4-haloalkyl)-Ci-C4-alkyl, C(O)N(Ci-C4-haloalkyl)-Ci-C4-haloalkyl, C(O)NH-Ci-C4-alkoxy, C(O)NH-Ci-C4-halo- alkoxy, C(O)NH-Ci-C4-alkoxy-Ci-C4-alkyl, C(O)NH-Ci-C4-alkoxy-Ci-C4-haloalkyl; C(O)NH-phenyl, C(O)NH-3-6-membered heterocyclyl or 5- or 6-membered hetaryl, C(O)NH-Ci-C4-alkyl-phenyl, C(O)NH-Ci-C4-alkyl-3-6-membered heterocyclyl or 5- or 6-membered hetaryl, which rings are unsubstituted or substituted with halogen, Ci- Cs-haloalkyl, and/or CN; S(O)m-Ci-C4-haloalkyl, S(O)m-C3-C6-cycloalkyl, S(O)m-C3- Ce-halocycloalkyl; 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, which rings are unsubstituted or substituted with halogen, Ci-Cs-haloalkyl, and/or CN; or R12 and R13 together with the nitrogen atom they are bound to form a 3-6 membered saturated, partially unsaturated, or aromatic heterocycle, which may contain 1 or 2 additional heteroatoms selected from N, O and S, wherein S may be partially or fully oxidized, and which is unsubstituted or substituted with R3 and/or oxo; or R12and R13 together with the nitrogen atom they are bound to form a group N=S(=O)R14aR14b, wherein R14a and R14b are defined as R14; m is 0, 1 , or 2;
R14 is H, Ci-C4-alkyl, Ci-C4-haloalkyl, Cs-Ce-cycloalkyl, Cs-Ce-halocyclo-alkyl, C3-C4-cy- cloalkyl-Ci-C2-alkyl, C3-C4-halocycloalkyl-Ci-C2-alkyl, C(O)-Ci-C4-alkyl, C(O)-Ci-C4- haloalkyl, C(O)-C3-C4-cycloalkyl, C(O)-C3-C4-halocycloalkyl, or phenyl which is unsubstituted or partially or fully substituted with R3;
R2 is H, CN, Ci-Cs-alkyl, Ci-Cs-haloalkyl, C2-C3-alkynyl;
R3 is halogen, CN, NO2, Ci-C4-alkyl, Cs-Ce-cycloalkyl, Ci-Ce-haloalkyl, Ci-Ce-halocycloalkyl, OR14, S(O)m-R14; wherein rings are unsubstituted or substituted with R3a;
R3a halogen, CN, NO2, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci-C4-alkoxy-Ci-C4-alkyl, C1-C4- haloalkoxy, C3-C4-cycloalkyl, C3-C4-halocycloalkyl, S(O)m-Ci-C4-alkyl, S(O)m-Ci-C4- haloalkyl, S(O)m-C3-C4-cycloalkyl, S(O)m-C3-C4-halocycloalkyl n is 0, 1 , 2, or 3;
R4 is H, halogen, CN, Ci-Ce-alkyl, Cs-Ce-cycloalkyl, Ci-Ce-haloalkyl, Ci-Ce-halocycloalkyl, C2- C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, each optionally substituted by R41; S(O)m-Ci- C4-alkyl, S(O)m-Ci-C4-haloalkyl, S(O)m-C3-C6-cycloalkyl, S(O)m-C3-Ce-halocycloalkyl, NR12R13, C(O)NR12R13, C(O)OR14, 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, which rings are unsubstituted or substituted with R3;
R41 is H, OR15, NR12R13, CN, Ci-C4-alkyl, Ci-C4-haloalkyl, C3-C6-cycloalkyl, C(O)-Ci-C4- alkyl, C(O)-Ci-C4-haloalkyl, C(O)-C3-C4-cycloalkyl, C(O)-C3-C4-halocycloalkyl, C(O)NH-Ci-C4-alkyl, C(O)NH-Ci-C4-haloalkyl, C(O)N(Ci-C4-alkyl)-Ci-C4-alkyl, C(O)N(Ci-C4-haloalkyl)-Ci-C4-alkyl, C(O)N(Ci-C4-haloalkyl)-Ci-C4-haloalkyl, C(O)NH-Ci-C4-alkoxy, C(O)NH-Ci-C4-haloalkoxy, C(O)NH-Ci-C4-alkoxy-Ci-C4-alkyl, C(O)NH-Ci-C4-alkoxy-Ci-C4-haloalkyl; C(O)NH-phenyl, C(O)NH-3-6-membered heterocyclyl or 5- or 6-membered hetaryl, C(O)NH-Ci-C4-alkyl-phenyl, C(O)NH-CI-C4- alkyl-3-6-membered heterocyclyl or 5- or 6-membered hetaryl, which rings are unsubstituted or substituted with halogen, Ci-Cs-haloalkyl, and/or CN; S(O)m-Ci-C4- haloalkyl, S(O)m-C3-C4-cycloalkyl, S(O)m-C3-C4-halocycloalkyl; 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, which rings are unsubstituted or substituted with halogen, Ci-Cs-haloalkyl, and/or CN;
R15 is H, Ci-C4-alkyl, or Ci-C4-haloalkyl, Cs-Ce-cycloalkyl, Ci-Ce-halocycloalkyl, which carbon chains are unsubstituted or partially or fully substituted with R11; or 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, which rings are unsubstituted or substituted with R3;
W is N and T is CR4a; or
W is CH and T is N; or
W is CH and T is CR4a;
R4a is as defined for R4; and the N-oxides, stereoisomers, and agriculturally or veterinarily acceptable salts thereof.
The invention also provides agricultural compositions comprising at least one compound of formula I, a stereoisomer thereof and/or an agriculturally acceptable salt thereof and at least one liquid and/or solid carrier, especially at least one inert liquid and/or solid agriculturally acceptable carrier.
The invention also provides a veterinary composition comprising at least one compound of formula I, a stereoisomer thereof and/or a veterinarily acceptable salt thereof and at least one liquid and/or solid carrier, especially at least one inert veterinarily liquid and/or solid acceptable carrier.
The invention also provides a method for controlling invertebrate pests which method comprises treating the pests, their food supply, their habitat or their breeding ground or a cultivated plant, plant propagation materials (such as seed), soil, area, material or environment in which the pests are growing or may grow, or the materials, cultivated plants, plant propagation materials (such as seed), soils, surfaces or spaces to be protected from pest attack or infestation with a pesticidally effective amount of a compound of formula I or a salt thereof as defined herein.
The invention also relates to plant propagation material, in particular seed, comprising at least one compound of formula I and/or an agriculturally acceptable salt thereof.
The invention further relates to a method for treating or protecting an animal from infestation or infection by parasites which comprises bringing the animal in contact with a parasiticidally effective amount of a compound of formula I or a veterinarily acceptable salt thereof. Bringing the animal in contact with the compound I, its salt or the veterinary composition of the invention means applying or administering it to the animal. WO 2019/197468, WO 2021/013719, WO 2010/129497, US 2008/242708, and US 2018/057486 describe structurally closely related active compounds. These compounds are mentioned to be useful for combating invertebrate pests.
Nevertheless, there remains a need for highly effective and versatile agents for combating invertebrate pests. It is therefore an object of the invention to provide compounds having a good pesticidal activity and showing a broad activity spectrum against a large number of different invertebrate pests, especially against difficult to control pests, such as insects.
It has been found that these objects can be achieved by compounds of formula I as depicted and defined below, and by their stereoisomers, salts, tautomers and N-oxides, in particular their agriculturally acceptable salts.
Compounds I with R1 being different from H can be obtained by reaction of a compound II in which R1 = H with a suitable reagent III. In formula III, Y is a nucleophilic leaving group, such as a halide, mesylate, or tosylate, preferably Br or Cl. The reaction can be effected under conditions known from literature.
Figure imgf000005_0001
This transformation is usually carried out at temperatures from -10°C to +110°C, preferably from 0°C to 25°C, in an inert solvent and in the presence of a base [cf. WO 2002100846 and S. M. Somagond, Heterocycl. Commun. 2017, 317],
The starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of III, based on II.
Compounds II can be obtained by reaction of an amino compound IV with a carboxylic acid V )
Figure imgf000005_0002
This transformation is usually carried out at temperatures of from -20°C to 50°C, preferably from 0°C to 25°C, in an inert solvent, in the presence of a peptide coupling reagent and optionally in the presence of a base [cf. A. El-Faham, Chem. Rev. 2011 , 6557], or in two steps by preparation of an intermediate acyl chloride from V under conditions known from literature, e.g. by reaction with SOC or oxalyl chloride in dimethylformamide (DMF) (cf. Schaefer et al, Organic Syntheses 1929, 32), followed by reaction with IV in the presence of a base, optionally under Schotten-Baumann conditions (Baumann, Chem. Ber. 1886, 3218). Suitable peptide coupling reagents are, e.g., dicyclohexylcarbodiimide, diisopropylcarbodiimide, 1-ethyl-3-(3'-dime- thylaminopropyl)carbodiimide hydrochloride, or chloro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate, which are commonly used together with catalytic, stoichiometric, excess amounts of additives, such as 1 -hydroxybenzotriazole, 1-hydroxy-7-aza-benzotriazole, 4-(dime- thylamino)pyridine, and/or 1 -methylimidazole.
Suitable solvents are halogenated hydrocarbons, such as dichloromethane (DCM) or 1 ,2-di- chloroethane, ethers, such as diethylether, tetrahydrofuran (THF) or 1 ,4-dioxane, or high-boiling solvents such as DMF, preferably DCM or DMF, or in aqueous media.
Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal hydroxides, such as LiOH, NaOH, KOH, or Ca(OH)2, alkali metal and alkaline earth metal carbonates, such as Na2COs, K2CO3, or CS2CO3, alkali metal bicarbonates, such as NaHCOs, or organic bases, for example tertiary amines, such as triethylamine, diisopropylethylamine, N- methylpiperidine, or basic aromatic rings, such as pyridine, 2,4,6-collidine, 2,6-lutidine, or 4-(di- methylamino)pyridine, or bicyclic amines, such as 1 ,8-diazabicylo[5.4.0]undec-7-ene (DBU), 1 ,5-diazabicyclo[4.3.0]non-5-ene (DBN), or 1 ,4-diazabicyclo[2.2.2]octane (DABCO). Particular preference is given to triethylamine, diisopropylethylamine, and NaOH. The bases are generally employed in stoichiometric or excess amounts; however, they can also be used in catalytic amounts or, if appropriate, as the solvent.
The starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of IV based on V.
Compounds IV can be obtained by reductive amination of a compound VI.
Figure imgf000006_0001
This transformation is usually carried out at temperatures of from 0°C to 130°C, preferably from 20°C to 70°C, generally in alcoholic and/or aqueous media and in the presence of a reagent and a reducing agent [cf. WO2021037614], Suitable solvents are alcohols, such as methanol, ethanol, n-propanol, 2-propanol, or n-butanol, or water, preferably methanol. It is also possible to use mixtures of the aforementioned solvents. Suitable reagents are ammonium acetate (NH4AC), ammonium formate, NH4OH, NH4CI, ammonia, or primary amines R1NH2. Suitable reducing agents are NaBHsCN, sodium triacetoxyborohydride, or NaBH4. Preference is given to ammonium acetate and NaBHsCN, resp. Compounds VI can be obtained by Grignard reaction of a compound VII.
R2-MgBr
VIII
VI
Figure imgf000007_0001
This transformation is usually carried out at temperatures of from -78°C to 25 °C, preferably from -10°C to 10 °C, in an inert solvent [cf. W02020081999],
Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane, and petrol ether, aromatic hydrocarbons such as toluene, o-, m-, and p-xylene, ethers such as diethylether, diisopropylether, tert.-butylmethylether, dioxane, anisole, and THF, preferably THF or 2- methyltetrahydrofuran. It is also possible to use mixtures of the solvents mentioned.
The starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of VIII, based on VII.
Compounds VII can be obtained by amidation of a carboxylic acid IX with an amine X under conditions known in the art.
CH3
N.
H OCH3
X
VII
Figure imgf000007_0002
This transformation is usually carried out at temperatures of from -10°C to 45°C, preferably from 0°C to 25°C, in an inert solvent, in the presence of a peptide coupling reagent and a base [cf. WO2019121374],
Suitable solvents are aromatic hydrocarbons such as toluene, o-, m-, and p-xylene, halogenated hydrocarbons such as methylene chloride, chloroform, DCM, and chlorobenzene, ethers such as diethylether, diisopropylether, tert.-butylmethylether, dioxane, anisole, and THF, nitrils such as acetonitrile, and propionitrile, moreover DMF; preferably DCM. It is also possible to use mixtures of the solvents mentioned.
Suitable bases are, in general, inorganic compounds, moreover organic bases, e.g. tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to triethylamine and diisopropylethylamine. The bases are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.
Suitable peptide coupling reagents are peptide coupling reagents such as for example 1-ethyl- 3-(3'-dimethylaminopropyl)carbodiimide hydrochloride, O-(7-Azabenzotriazol-1-yl)-N,N,N',N'- tetramethyluronium hexafluorophosphate, 1-[eis(dimethylamino)methylene]-1 H-benzotriazolium hexafluorophosphate(l-) 3-oxide.
The reagents are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.
The starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of X, based on IX.
Compounds IX are obtained by ester cleavage of esters XII under conditions known in the art.
Figure imgf000008_0001
This transformation is usually carried out at temperatures of from -10°C to 65 °C, preferably from 0°C to 40 °C, in an inert solvent, in the presence of LiOH [cf. WO2018029126],
Suitable solvents are ethers such as diethylether, diisopropylether, tert.-butylmethylether, dioxane, anisole, and THF, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, and tert.-butanol, moreover DMSO, DMF, dimethylacetamide (DMA), and water, preferably alcohols, ethers and water; in particular THF, methanol, and water. It is also possible to use mixtures of the solvents mentioned.
LiOH is generally employed in equimolar amounts or in excess.
Esters XII are obtainable from compounds XIII in a Stille coupling of XIII with an ester XIV, whererin X is a halogen, preferably Br.
Figure imgf000008_0002
The Stille coupling reaction is usually carried out at temperatures from 50°C to 150°C, preferably from 70°C to 120°C, in an inert solvent in the presence of one or more catalysts and optionally in the presence of one or more additives and a base [cf. H. Lin et al., Bioorg Med Chem Lett 2010, 679], Suitable solvents are aromatic hydrocarbons such as toluene, o-, m-, p-xylene, and mesitylene, or ethers such as THF and 1 ,4-dioxane, preferably toluene or 1 ,4-dioxane. It is also possible to use mixtures of the aforementioned solvents. Suitable catalysts are palladium complexes, such as tetrakis(triphenylphosphine)palladium, tris(dibenzylideneacetone)dipalladium, palladium diacetate, dichloro-bis(triphenylphosphine)palladium, and [1 ,1 '-bis(diphenylphos- phino)ferrocene]dichloropalladium, preferably dichlorobis(triphenylphosphine)palladium. Further suitable optional catalysts are common ligands, such as dicyclohexyl[2',4',6'-tris(propan-2- yl)[1,1'-biphenyl]-2-yl]phosphine or triphenylphosphine. Suitable additives are, in general, inorganic compounds, such as cesium fluoride and cuprous iodide. The starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of XIV, based on XIII.
Compounds XIV can be obtained from esters XV by bromination with N-bromosuccinimide (NBS) or similar procedures under conditions known in the art.
Figure imgf000009_0001
This transformation is usually carried out at temperatures of from -78°C to 25°C, preferably from -78°C to 0°C, in an inert solvent, in the presence of a bromine source and a base [cf. WO2019222154)].
Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane, and petrol ether, aromatic hydrocarbons such as toluene, o-, m-, and p-xylene, halogenated hydrocarbons such as methylene chloride, chloroform, and chlorobenzene, ethers such as diethylether, diisopropylether, tert.-butylmethylether, dioxane, anisole, and THF, preferably ethers such as THF. It is also possible to use mixtures of the solvents mentioned.
Suitable bases are, in general, inorganic compounds, such as alkali metal amides, such as lithium diisopropylamide or lithium hexamethyl disilazide or sodium hexamethyl disilazide. Particular preference is given to lithium hexamethyl disilazide. The bases are generally employed in equimolar amounts, in excess or, if appropriate, as solvent.
Suitable bromine sources are bromine or N-bromo succinimide (NBS). The bromine sources are generally employed in in equimolar amounts or in excess.
The starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of NBS, based on XV.
Compounds XV are commercially available.
Tin compounds XVIII are obtainable from compounds XVI with an organotin compound such as bis(tributyltin) XVII.
(SnBu3)2 XVII
XVIII
Figure imgf000009_0002
Pd(PPh
This transformation is usually carried out at temperatures of from 10°C to 120 °C, preferably from 25°C to 110°C, in an inert solvent, in the presence of a base [cf. US20120225857)]. Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane, and petrol ether, aromatic hydrocarbons such as toluene, o-, m-, and p-xylene, ethers such as diethylether, diisopropylether, tert.-butylmethylether, dioxane, anisole, and THF, moreover, DMF and DMA, preferably ethers and aromatic hydrocarbons such as 1 ,4-dioxane or toluene. It is also possible to use mixtures of the solvents mentioned.
Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal hydroxides, such as LiOH, NaOH, KOH, and Ca(OH)2, alkali metal and alkaline earth metal carbonates such as l_i2CC>3, Na2CO3, K2COs and also alkali metal bicarbonates such as sodium bicarbonate, articular preference is given to carbonate bases such as Na2CO3. The bases are generally employed in catalytic amounts; however, they can be also used in equimolar amounts, in excess or, if appropriate, as solvent.
The starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of XVII, based on XVI.
Compounds XVI are known in the art, commercially available, or obtainable for such compounds by derivatization.
The reaction mixtures are worked up in a customary manner, for example by mixing with water, separating the phases and, if appropriate, chromatographic purification of the crude products. Some of the intermediates and end products are obtained in the form of colourless or slightly brownish viscous oils which are purified or freed from volatile components under reduced pressure and at moderately elevated temperature. If the intermediates and end products are obtained as solids, purification can also be carried out by recrystallization or digestion.
If individual compounds I cannot be obtained by the routes described above, they can be prepared by derivatization of other compounds I.
However, if the synthesis yields mixtures of isomers, a separation is generally not necessarily required since in some cases the individual isomers can be interconverted during work-up for use or during application (for example under the action of light, acids or bases). Such conversions may also take place after use, for example in the treatment of plants in the treated plant, or in the pest to be controlled.
The organic moieties groups mentioned in the above definitions of the variables are - like the term halogen - collective terms for individual listings of the individual group members. The prefix Cn-Cm indicates in each case the possible number of carbon atoms in the group.
The term “partially or fully substituted” by a radical means that in general the group is substituted with same or different radicals.
The term “halogen” denotes in each case fluorine, bromine, chlorine, or iodine, in particular fluorine, chlorine, or bromine. The term "alkyl" as used herein and in the alkyl moieties of alkylamino, alkylcarbonyl, alkylthio, alkylsulfinyl, alkylsulfonyl and alkoxyalkyl denotes in each case a straight-chain or branched alkyl group having usually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, more preferably from 1 to 3 carbon atoms. Examples of an alkyl group are methyl (Me), ethyl (Et), n-propyl (n-Pr), iso-propyl, n-butyl (Bu), 2-butyl, iso-butyl, tert-butyl, n-pentyl, 1 -methyl butyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1 , 1-dimethylpropyl, 1 ,2-dimethylpropyl, 1 -methylpentyl, 2-methylpentyl, 3-methylpentyl, 4- methylpentyl, 1 , 1-dimethylbutyl, 1 ,2-dimethylbutyl, 1 ,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-di- methylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1 , 1 ,2-trimethylpropyl, 1 ,2,2-trime- thylpropyl, 1-ethyl-1-methylpropyl, and 1-ethyl-2-methylpropyl.
The term "haloalkyl" as used herein and in the haloalkyl moieties of haloalkylcarbonyl, haloalkoxycarbonyl, haloalkylthio, haloalkylsulfonyl, haloalkylsulfinyl, haloalkoxy and haloalkoxyalkyl, denotes in each case a straight-chain or branched alkyl group having usually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, wherein the hydrogen atoms of this group are partially or totally replaced with halogen atoms. Preferred haloalkyl moieties are selected from Ci-C4-haloalkyl, more preferably from Ci-Cs-haloalkyl or Ci-C2-haloalkyl, in particular from Ci-C2-fluoroalkyl such as fluoromethyl, difluoromethyl, trifluoromethyl, 1 -fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, and the like.
The term "alkoxy" as used herein denotes in each case a straight-chain or branched alkyl group which is bonded via an oxygen atom and has usually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms. Examples of an alkoxy group are methoxy, ethoxy, n-propoxy, iso-propoxy, n-butyloxy, 2-butyloxy, iso-butyloxy, tert.-butyloxy, and the like.
The term "alkoxyalkyl" as used herein refers to alkyl usually comprising 1 to 10, frequently 1 to 4, preferably 1 to 2 carbon atoms, wherein 1 carbon atom carries an alkoxy radical usually comprising 1 to 4, preferably 1 or 2 carbon atoms as defined above. Examples are CH2OCH3, CH2- OC2H5, 2-(methoxy)ethyl, and 2-(ethoxy)ethyl.
The term "haloalkoxy" as used herein denotes in each case a straight-chain or branched alkoxy group having from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, wherein the hydrogen atoms of this group are partially or totally replaced with halogen atoms, in particular fluorine atoms. Preferred haloalkoxy moieties include C1-C4- haloalkoxy, in particular Ci-C2-fluoroalkoxy, such as fluoromethoxy, difluoromethoxy, trifluoromethoxy, 1 -fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-flu- oroethoxy, 2-chloro-2,2-difluoro-ethoxy, 2,2dichloro-2-fluorethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy and the like. The term "alkylthio "(alkylsulfanyl: S-alkyl)" as used herein refers to a straight-chain or branched saturated alkyl group having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms (= Ci-C4-alkylthio), more preferably 1 to 3 carbon atoms, which is attached via a sulfur atom.
The term "haloalkylthio" as used herein refers to an alkylthio group as mentioned above wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and/or iodine.
The term "alkylsulfinyl" (alkylsulfoxyl: S(=O)-alkyl), as used herein refers to a straight-chain or branched saturated alkyl group (as mentioned above) having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms (= Ci-C4-alkylsulfinyl), more preferably 1 to 3 carbon atoms bonded through the sulfur atom of the sulfinyl group at any position in the alkyl group.
The term "haloalkylsulfinyl" as used herein refers to an alkylsulfinyl group as mentioned above wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and/or iodine.
The term "alkylsulfonyl" (S(=O)2-alkyl) as used herein refers to a straight-chain or branched saturated alkyl group having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms (= Ci-C4-al- kylsulfonyl), preferably 1 to 3 carbon atoms, which is bonded via the sulfur atom of the sulfonyl group at any position in the alkyl group.
The term "haloalkylsulfonyl" as used herein refers to an alkylsulfonyl group as mentioned above wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and/or iodine.
The term "alkylcarbonyl" refers to an alkyl group as defined above, which is bonded via the carbon atom of a carbonyl group (C=O) to the remainder of the molecule.
The term "haloalkylcarbonyl" refers to an alkylcarbonyl group as mentioned above, wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and/or iodine.
The term "alkoxycarbonyl" refers to an alkylcarbonyl group as defined above, which is bonded via an oxygen atom to the remainder of the molecule.
The term "haloalkoxycarbonyl” refers to an alkoxycarbonyl group as mentioned above, wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and/or iodine.
The term "alkenyl" as used herein denotes in each case a hydrocarbon radical containing one double bond, having usually 2 to 10, frequently 2 to 6, preferably 2 to 4 carbon atoms, e.g. vinyl, allyl (2-propen-1-yl), 1-propen-1-yl, 2-propen-2-yl, methallyl (2-methylprop-2-en-1-yl), 2-buten-1- yl, 3-buten-1-yl, 2-penten-1-yl, 3-penten-1-yl, 4-penten-1-yl, 1-methylbut-2-en-1-yl, 2-ethylprop- 2-en-1-yl and the like.
The term "haloalkenyl" as used herein refers to an alkenyl group as defined above, wherein the hydrogen atoms are partially or totally replaced with halogen atoms. The term "alkynyl" as used herein denotes in each case a hydrocarbon radical containing one triple bond, having usually 2 to 10, frequently 2 to 6, preferably 2 to 4 carbon atoms, e.g. ethynyl, propargyl (2-propyn-1-yl), 1-propyn-1-yl, 1-methylprop-2-yn-1-yl), 2-butyn-1-yl, 3-butyn- 1-yl, 1-pentyn-1-yl, 3-pentyn-1-yl, 4-pentyn-1-yl, 1-methylbut-2-yn-1-yl, 1-ethylprop-2-yn-1-yl and the like.
The term "haloalkynyl" as used herein refers to an alkynyl group as defined above, wherein the hydrogen atoms are partially or totally replaced with halogen atoms.
The term "cycloalkyl" as used herein and in the cycloalkyl moieties of cycloalkoxy and cycloalkylthio denotes in each case a monocyclic cycloaliphatic radical having usually from 3 to 10 or from 3 to 6 carbon atoms, such as cyclopropyl (CC3H5), cyclobutyl (CC4H7), cyclopentyl (CC5H9), cyclohexyl (cCeHn), cycloheptyl, cyclooctyl, cyclononyl and cyclodecyl or cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
The term "halocycloalkyl" as used herein and in the halocycloalkyl moieties of halocycloalkoxy and halocycloalkylthio denotes in each case a monocyclic cycloaliphatic radical having usually from 3 to 10 C atoms or 3 to 6 C atoms, wherein at least one, e.g. 1 , 2, 3, 4 or 5 of the hydrogen atoms, are replaced by halogen, in particular by fluorine or chlorine. Examples are 1- and 2-fluo- rocyclopropyl, 1 ,2-, 2,2- and 2,3-difluorocyclopropyl, 1 ,2,2-trifluorocyclopropyl, 2, 2, 3, 3- tetrafl uo- rocyclpropyl, 1- and 2-chlorocyclopropyl, 1 ,2-, 2,2- and 2,3-dichlorocyclopropyl, 1 , 2, 2-tri chlorocyclopropyl, 2,2,3,3-tetrachlorocyclpropyl, 1-,2- and 3-fluorocyclopentyl, 1 ,2-, 2,2-, 2,3-, 3,3-, 3,4-, 2,5-difluorocyclopentyl, 1-,2- and 3-chlorocyclopentyl, 1 ,2-, 2,2-, 2,3-, 3,3-, 3,4-, 2,5-dichlo- rocyclopentyl and the like.
The term “halocycloalkenyl” as used herein and in the halocycloalkenyl moieties of halocyclo- alkenyloxy and halocycloalkenylthio denotes in each case a monocyclic singly unsaturated nonaromatic radical having usually from 3 to 10, e.g. 3 or 4 or from 5 to 10 carbon atoms, preferably from 3- to 8 carbon atoms, wherein at least one, e.g. 1 , 2, 3, 4 or 5 of the hydrogen atoms, are replaced by halogen, in particular by fluorine or chlorine. Examples are 3,3-difluorocyclopropen- 1-yl and 3,3-dichlorocyclopropen-1-yl.
The term "cycloalkenylalkyl" refers to a cycloalkenyl group as defined above which is bonded via an alkyl group, such as a Ci-Cs-alkyl group or a Ci-C4-alkyl group, in particular a methyl group (= cycloalkenylmethyl), to the remainder of the molecule.
The term “carbocycle” or “carbocyclyl” includes in general a 3- to 12-membered, preferably a 3- to 8-membered or a 5- to 8-membered, more preferably a 5- or 6-membered mono-cyclic, non-aromatic ring comprising 3 to 12, preferably 3 to 8 or 5 to 8, more preferably 5 or 6 carbon atoms. Preferably, the term “carbocycle” covers cycloalkyl and cycloalkenyl groups as defined above.
The term “heterocycle” or "heterocyclyl" includes in general 3- to 12-membered, preferably 3- to 6-membered, in particular 6-membered monocyclic heterocyclic non-aromatic radicals. The heterocyclic non-aromatic radicals usually comprise 1, 2, 3, 4 or 5, preferably 1, 2 or 3 heteroatoms selected from N, O, and S as ring members, wherein S-atoms as ring members may be present as S, SO, or SO2. Examples of 5- or 6-membered heterocyclic radicals comprise saturated or unsaturated, non-aromatic heterocyclic rings, such as oxiranyl, oxetanyl, thietanyl, thietanyl-S-oxid (S-oxothietanyl), thietanyl-S-dioxid (S-dioxothiethanyl), pyrrolidinyl, pyrrolinyl, pyrazolinyl, tetrahydrofuranyl, dihydrofuranyl, 1,3-dioxolanyl, thiolanyl, S-oxothiolanyl, S-dioxo- thiolanyl, dihydrothienyl, S-oxodi hydrothienyl, S-dioxodihydrothienyl, oxazolidinyl, oxazolinyl, thi- azolinyl, oxathiolanyl, piperidinyl, piperazinyl, pyranyl, dihydropyranyl, tetrahydropyranyl, 1 ,3- and 1,4-dioxanyl, thiopyranyl, S. oxothiopyranyl, S-dioxothiopyranyl, dihydrothiopyranyl, S-oxodi- hydrothiopyranyl, S-dioxodihydrothiopyranyl, tetrahydrothiopyranyl, S-oxotetrahydrothiopyranyl, S-dioxotetrahydrothiopyranyl, morpholinyl, thiomorpholinyl, S-oxothiomorpholinyl, S-dioxothio- morpholinyl, thiazinyl and the like. Examples for heterocyclic ring also comprising 1 or 2 carbonyl groups as ring members comprise pyrrolidin-2-onyl, pyrrolidin-2,5-dionyl, imidazolidin-2- onyl, oxazolidin-2-onyl, thiazolidin-2-only, and the like.
The term "hetaryl" includes monocyclic 5- or 6-membered heteroaromatic radicals comprising as ring members 1, 2, 3 or 4 heteroatoms selected from N, O, and S. Examples of 5- or 6-mem- bered heteroaromatic radicals include pyridyl, i.e. 2-, 3-, or 4-pyridyl, pyrimidinyl, i.e. 2-, 4- or 5- pyrimidinyl, pyrazinyl, pyridazinyl, i.e. 3- or 4-pyridazinyl, thienyl, i.e. 2- or 3-thienyl, furyl, i.e. 2- or 3-furyl, pyrrolyl, i.e. 2- or 3-pyrrolyl, oxazolyl, i.e. 2-, 3- or 5-oxazolyl, isoxazolyl, i.e. 3-, 4- or 5-isoxazolyl, thiazolyl, i.e. 2-, 3- or 5-thiazolyl, isothiazolyl, i.e. 3-, 4- or 5-isothiazolyl, pyrazolyl, i.e. 1-, 3-, 4- or 5-pyrazolyl, i.e. 1-, 2-, 4- or 5-imidazolyl, oxadiazolyl, e.g. 2- or 5-[1 ,3,4]oxadia- zolyl, 4- or 5-(1 ,2,3-oxadiazol)yl, 3- or 5-(1,2,4-oxadiazol)yl, 2- or 5-(1 ,3,4-thiadiazol)yl, thiadia- zolyl, e.g. 2- or 5-(1,3,4-thiadiazol)yl, 4- or 5-(1,2,3-thiadiazol)yl, 3- or 5-(1,2,4-thiadiazol)yl, tria- zolyl, e.g. 1H-, 2H- or 3H-1,2,3-triazol-4-yl, 2H-triazol-3-yl, 1H-, 2H-, or 4H-1,2,4-triazolyl and te- trazolyl, i.e. 1H- or 2H-tetrazolyl. The term "hetaryl" also includes bicyclic 8 to 10-membered heteroaromatic radicals comprising as ring members 1 , 2 or 3 heteroatoms selected from N, O, and S, wherein a 5- or 6-membered heteroaromatic ring is fused to a phenyl ring or to a 5- or 6- membered heteroaromatic radical. Examples of a 5- or 6-membered heteroaromatic ring fused to a phenyl ring or to a 5- or 6-membered heteroaromatic radical include benzofuranyl, benzothienyl, indolyl, indazolyl, benzimidazolyl, benzoxathiazolyl, benzoxadiazolyl, benzothiadiazolyl, benzoxazinyl, chinolinyl, isochinolinyl, purinyl, 1 ,8-naphthyridyl, pteridyl, pyrido[3,2-d]pyrimidyl or pyridoimidazolyl and the like. These fused hetaryl radicals may be bonded to the remainder of the molecule via any ring atom of 5- or 6-membered heteroaromatic ring or via a carbon atom of the fused phenyl moiety.
The terms "heterocyclylalkyl" and "hetarylalkyl" refer to heterocyclyl or hetaryl, respectively, as defined above which are bonded via a Ci-Cs-alkyl group or a Ci-C4-alkyl group, in particular a methyl group (= heterocyclylmethyl or hetaryl methyl, respectively), to the remainder of the molecule.
The term “arylalkyl” and "phenylalkyl" refer to aryl as defined above and phenyl, respectively, which are bonded via Ci-Cs-alkyl group or a Ci-C4-alkyl group, in particular a methyl group (= arylmethyl or phenylmethyl), to the remainder of the molecule, examples including benzyl, 1- phenylethyl, 2-phenylethyl, 2-phenoxyethyl etc.
The terms “alkylene”, “cycloalkylene”, “heterocycloalkylene”, “alkenylene”, “cycloalkenylene”, “heterocycloalkenylene” and “alkynylene” refer to alkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, heterocycloalkenyl and alkynyl as defined above, respectively, which are bonded to the remainder of the molecule, via two atoms, preferably via two carbon atoms, of the respective group, so that they represent a linker between two moieties of the molecule.
In a particular embodiment, the variables of the compounds of the formula I have the following meanings, these meanings, both on their own and in combination with one another, being particular embodiments of the compounds of the formula I.
Embodiments and preferred compounds of the invention for use in pesticidal methods and for insecticidal application purposes are outlined in the following paragraphs.
With respect to the variables, the particularly preferred embodiments of the intermediates correspond to those of the compounds of the formula I.
In a preferred embodiment, the compounds I are present in form of a mixture of compounds I. A and I.B, wherein compound I.A with S-configuration of the carbon atom neighboring the nitrogen is present in an amount of more than 50% by weight, in particular of at least 70% by weight, more particularly of at least 85% by weight, specifically of at least 90% by weight, based on the total weight of compounds I.A and I.B.
Figure imgf000015_0001
In one particularly preferred embodiment of the invention, the method comprises the step of contacting the plant, parts of it, its propagation material, the pests, their food supply, habitat or breeding grounds with a pesticidally effective amount of a compound of formula I.A. R1 is preferably H, Ci-Ce-alkyl, Cs-Ce-alkynyl, Cs-Ce-cycloalkyl, or Ci-C4-alkyl-C3-C6-cycloalkyl, more preferably H, Ci-Ce-alkyl, or Ci-C4-alkyl-C3-C6-cycloalkyl, particularly H or CH2-cC3H5.
R2 is preferably CH3.
X is preferably CH or CR3, particularly CH. Such compounds correspond to Formula 1.1
Figure imgf000016_0001
In another embodiment X is N. Such compounds correspond to formula 1.2.
Figure imgf000016_0002
R3 is preferably halogen, CN, Ci-C4-haloalkyl, Ci-C4-haloalkoxy, C3-C4-cycloalkyl unsubstituted or substituted with one or more CN, C3-C4-halocycloalkyl, S(O)m-Ci-C4-alkyl, S(O)m-Ci-C4- haloalkyl, S(O)m-C3-C4-cycloalkyl, S(O)m-C3-C4-halocycloalkyl, S(O)m-(substituted phenyl). Index m in R3 is preferably 2. Index n is preferably 2.
R3 groups stand preferably in positions 3 and 5.
In another embodiment R3 is preferably halogen, CN, Ci-C4-haloalkyl, Ci-C4-haloalkoxy, C3- C4-cycloalkyl, C3-C4-halocycloalkyl, S(O)m-Ci-C4-alkyl, S(O)m-Ci-C4-haloalkyl, S(O)m-C3-C4-cy- cloalkyl, S(O)m-C3-C4-halocycloalkyl, or
S(O)m-R14, wherein R14 is phenyl, which is partially substituted with R3a.
R4 is preferably H. R4a is preferably different from H.
In another embodiment R4a is preferably H, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci-C4-haloalkoxy, C1- C4-alkoxy-Ci-C4-alkyl, C(O)NH-Ci-Ce-alkyl, S(O)m-Ci-C4-alkyl, or phenyl unsubstituted or substituted with one or more groups R3.
In another embodiment R4a is preferably halogen, CN, C(O)NH2, or C(O)NH-Ci-Ce-alkyl.
In one embodiment the ring formed by R12 and R13 together with the nitrogen atom they are bound to, is unsubstituted or substituted with a radical different from oxo. In a preferred embodiment V is O and U is N, or V is N and U is O.
In another embodiment V is S and U is N, or V is N and U is S.
In a preferred embodiment V is O or S, and II is N. Such compounds correspond to formula
I.V
Figure imgf000017_0003
Another embodiment relates to compounds I.V with V being O (Formula I. O).
Another embodiment relates to compounds I.V with V being S (Formula I. VS).
In another embodiment V is N and U is O or S. Such compounds correspond to formula I.U
Figure imgf000017_0001
Another embodiment relates to compounds I.U with U being O (Formula LUO).
Another embodiment relates to compounds I.U with U being S (Formula I. US).
Compounds of formulae I. VO and I.IIO are particularly preferred.
In another embodiment compounds of formula I. US are particularly preferred.
In a particularly preferred embodiment T is CR4a.
In a preferred embodiment W is N and T is CR4a. Such compounds correspond to formula LT.
In another embodiment W is CH and T is N. Such compounds correspond to formula I.W.
In another embodiment W is CH and T is CR4a. Such compounds correspond to formula I.P.
Figure imgf000017_0002
Compounds I.T and compounds I.P are particularly preferred. In particular with a view to their use, preference is given to the compounds of formula I compiled in the tables below, which compounds correspond to formulae I.LIO.T, I.LIO.W, I.LIO.P, I.VO.T, I.VO.W, I.VO.P, I.LIS.T, I.LIS.W, and I.LIS.P. Each of the groups mentioned for a substituent in the tables is furthermore per se, independently of the combination in which it is mentioned, a particularly preferred aspect of the substituent in question.
Figure imgf000018_0001
Table 1
Compounds of formula I.VO.W* in which and R4 is H, X is CH and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 2
Compounds of formula I.VO.W* in which and R4 is H, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 3
Compounds of formula I.VO.W* in which and R4 is CN, X is CH and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 4
Compounds of formula I.VO.W* in which and R4 is CN, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A Table 5
Compounds of formula I.VO.W* in which R4 is C(=O)-NH2, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 6
Compounds of formula I.VO.W* in which R4 is C(=O)-NH2, X is N and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 7
Compounds of formula I.VO.W* in which R4 is C(=O)-NHCH3, X is CH and the combination of
R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 8
Compounds of formula I.VO.W* in which R4 is C(=O)-NHCH3, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 9
Compounds of formula I.LIO.W* in which R4 is H, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 10
Compounds of formula I.LIO.W* in which R4 is H, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 11
Compounds of formula I.LIO.W* in which R4 is CN, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 12
Compounds of formula I.LIO.W* in which R4 is CN, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 13
Compounds of formula I.LIO.W* in which R4 is C(=O)-NH2, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 14
Compounds of formula I.LIO.W* in which R4 is C(=O)-NH2, X is N and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 15
Compounds of formula I.LIO.W* in which R4 is C(=O)-NHCH3, X is CH and the combination of
R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 16
Compounds of formula I.LIO.W* in which R4 is C(=O)-NHCH3, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A Table 17
Compounds of formula I.VO.T* in which R4a is H, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 18
Compounds of formula I.VO.T* in which R4a is H, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 19
Compounds of formula I.VO.T* in which R4a is CN, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 20
Compounds of formula I.VO.T* in which R4a is CN, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 21
Compounds of formula I.VO.T* in which R4a is OCHF2, X is CH and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 22
Compounds of formula I.VO.T* in which R4a is OCHF2, X is N and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 23
Compounds of formula I.VO.T* in which R4a is OCF3, X is CH and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 24
Compounds of formula I.VO.T* in which R4a is OCF3, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 25
Compounds of formula I.VO.T* in which R4a is Br, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 26
Compounds of formula I.VO.T* in which R4a is Br, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 27
Compounds of formula I.IIO.T* in which R4a is H, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 28
Compounds of formula I.IIO.T* in which R4a is H, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A Table 29
Compounds of formula I.LIO.T* in which R4a is CN, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 30
Compounds of formula I.LIO.T* in which R4a is CN, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 31
Compounds of formula I.LIO.T* in which R4a is OCHF2, X is CH and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 32
Compounds of formula I.LIO.T* in which R4a is OCHF2, X is N and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 33
Compounds of formula I.LIO.T* in which R4a is OCF3, X is CH and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 34
Compounds of formula I.LIO.T* in which R4a is OCF3, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 35
Compounds of formula I.LIO.T* in which R4a is Br, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 36
Compounds of formula I.LIO.T* in which R4a is Br, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 37
Compounds of formula I.VO.P* in which R4a is H, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 38
Compounds of formula I.VO.P* in which R4a is H, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 39
Compounds of formula I.VO.P* in which R4a is CN, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 40
Compounds of formula I.VO.P* in which R4a is CN, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A Table 41
Compounds of formula I.VO.P* in which R4a is OCHF2, X is CH and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 42
Compounds of formula I.VO.P* in which R4a is OCHF2, X is N and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 43
Compounds of formula I.VO.P* in which R4a is OCF3, X is CH and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 44
Compounds of formula I.VO.P* in which R4a is OCF3, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 45
Compounds of formula I.VO.P* in which R4a is Br, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 46
Compounds of formula I.VO.P* in which R4a is Br, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 47
Compounds of formula I.IIO.P* in which R4a is H, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 48
Compounds of formula I.IIO.P* in which R4a is H, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 49
Compounds of formula I.IIO.P* in which R4a is CN, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 50
Compounds of formula I.IIO.P* in which R4a is CN, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 51
Compounds of formula I.IIO.P* in which R4a is OCHF2, X is CH and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 52
Compounds of formula I.IIO.P* in which R4a is OCHF2, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A Table 53
Compounds of formula I.LIO.P* in which R4a is OCF3, X is CH and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 54
Compounds of formula I.LIO.P* in which R4a is OCF3, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 55
Compounds of formula I.LIO.P* in which R4a is Br, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 56
Compounds of formula I.LIO.P* in which R4a is Br, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 57
Compounds of formula I.LIS.W* in which R4 is H, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 58
Compounds of formula I.LIS.W* in which R4 is H, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 59
Compounds of formula I.LIS.W* in which R4 is CN, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 60
Compounds of formula I.LIS.W* in which R4 is CN, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 61
Compounds of formula I.LIS.W* in which R4 is C(=O)-NH2, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 62
Compounds of formula I.LIS.W* in which R4 is C(=O)-NH2, X is N and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 63
Compounds of formula I.LIS.W* in which R4 is C(=O)-NHCH3, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 64
Compounds of formula I.LIS.W* in which R4 is C(=O)-NHCH3, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A Table 65
Compounds of formula I.LIS.T* in which R4a is H, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 66
Compounds of formula I.LIS.T* in which R4a is H, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 67
Compounds of formula I.LIS.T* in which R4a is CN, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 68
Compounds of formula I.LIS.T* in which R4a is CN, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 69
Compounds of formula I.LIS.T* in which R4a is OCHF2, X is CH and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 70
Compounds of formula I.LIS.T* in which R4a is OCHF2, X is N and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 71
Compounds of formula I.LIS.T* in which R4a is OCF3, X is CH and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 72
Compounds of formula I.LIS.T* in which R4a is OCF3, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 73
Compounds of formula I.LIS.T* in which R4a is Br, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 74
Compounds of formula I.LIS.T* in which R4a is Br, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 75
Compounds of formula I.LIS.P* in which R4a is H, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 76
Compounds of formula I.LIS.P* in which R4a is H, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A Table 77
Compounds of formula I.LIS.P* in which R4a is CN, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 78
Compounds of formula I.LIS.P* in which R4a is CN, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 79
Compounds of formula I.LIS.P* in which R4a is OCHF2, X is CH and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 80
Compounds of formula I.LIS.P* in which R4a is OCHF2, X is N and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 81
Compounds of formula I.LIS.P* in which R4a is OCF3, X is CH and the combination of R1 and
(R3)n for a compound corresponds in each case to one row of Table A
Table 82
Compounds of formula I.LIS.P* in which R4a is OCF3, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 83
Compounds of formula I.LIS.P* in which R4a is Br, X is CH and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table 84
Compounds of formula I.LIS.P* in which R4a is Br, X is N and the combination of R1 and (R3)n for a compound corresponds in each case to one row of Table A
Table A
Figure imgf000025_0001
Figure imgf000025_0002
Figure imgf000026_0002
Figure imgf000026_0001
Figure imgf000027_0002
Figure imgf000027_0001
The term “compound(s) of the invention” refers to compound(s) of formula I, or “compound(s) I”, and includes their salts, tautomers, stereoisomers, and N-oxides.
The invention also relates to agrochemical compositions comprising an auxiliary and at least one compound I. An agrochemical composition comprises a pesticidally effective amount of a compound I.
An agrochemical composition comprises a pesticidally effective amount of a compound I.
The compounds I can be converted into customary types of agro-chemical compositions, e.g. solutions, emulsions, suspensions, dusts, powders, pastes, granules, pressings, capsules, and mixtures thereof. Examples for composition types are suspensions (e.g. SC, OD, FS), emulsifiable concentrates (e.g. EC), emulsions (e.g. EW, EO, ES, ME), capsules (e.g. CS, ZC), pastes, pastilles, wettable powders or dusts (e.g. WP, SP, WS, DP, DS), pressings (e.g. BR, TB, DT), granules (e.g. WG, SG, GR, FG, GG, MG), insecticidal articles (e.g. LN), as well as gel formulations for the treatment of plant propagation materials e.g. seeds (e.g. GF). These and further compositions types are defined in the “Catalogue of pesticide formulation types and international coding system”, Technical Monograph No. 2, 6th Ed. May 2008, CropLife International.
Suitable auxiliaries are solvents, liquid carriers, solid carriers or fillers, surfactants, dispersants, emulsifiers, wetters, adjuvants, solubilizers, penetration enhancers, protective colloids, adhesion agents, thickeners, humectants, repellents, attractants, feeding stimulants, compatibilizers, bactericides, anti-freezing agents, anti-foaming agents, colorants, tackifiers and binders.
Suitable solvents and liquid carriers are water and organic solvents. Suitable solid carriers or fillers are mineral earths.
Suitable surfactants are surface-active compounds, e.g. anionic, cationic, nonionic, and amphoteric surfactants, block polymers, polyelectrolytes. Such surfactants can be used as emulsifier, dispersant, solubilizer, wetter, penetration enhancer, protective colloid, or adjuvant. Surfactants are listed in McCutcheon’s, Vol.1: Emulsifiers & Detergents, McCutcheon’s Directories, Glen Rock, USA, 2008 (International or North American Ed.). Suitable anionic surfactants are alkali, alkaline earth, or ammonium salts of sulfonates, sulfates, phosphates, carboxylates. Suitable nonionic surfactants are alkoxylates, N-subsituted fatty acid amides, amine oxides, esters, sugar-based surfactants, polymeric surfactants. Suitable cationic surfactants are quaternary surfactants.
The agrochemical compositions generally comprise between 0.01 and 95%, preferably between 0.1 and 90%, and most preferably between 0.5 and 75%, by weight of active substance. The active substances are employed in a purity of from 90% to 100%, preferably from 95% to 100%.
Various types of oils, wetters, adjuvants, or fertilizer may be added to the active substances or the compositions comprising them as premix or, if appropriate not until immediately prior to use (tank mix). These agents can be admixed with the compositions according to the invention in a weight ratio of 1 : 100 to 100: 1.
The user applies the composition according to the invention usually from a predosage device, a knapsack sprayer, a spray tank, a spray plane, or an irrigation system. Usually, the agrochemical composition is made up with water, buffer, and/or further auxiliaries to the desired application concentration and the ready-to-use spray liquor or the agrochemical composition according to the invention is thus obtained. Usually, 20 to 2000 liters of the ready-to-use spray liquor are applied per hectare of agricultural useful area.
The compounds I are suitable for use in protecting crops, plants, plant propagation materials, e.g. seeds, or soil or water, in which the plants are growing, from attack or infestation by animal pests. Therefore, the invention also relates to a plant protection method, which comprises contacting crops, plants, plant propagation materials, e.g. seeds, or soil or water, in which the plants are growing, to be protected from attack or infestation by animal pests, with a pesticidally effective amount of a compound I.
The compounds I are also suitable for use in combating or controlling animal pests. Therefore, the invention also relates to a method of combating or controlling animal pests, which comprises contacting the animal pests, their habitat, breeding ground, or food supply, or the crops, plants, plant propagation materials, e.g. seeds, or soil, or the area, material or environment in which the animal pests are growing or may grow, with a pesticidally effective amount of a compound I.
The compounds I are effective through both contact and ingestion to any and all developmental stages, such as egg, larva, pupa, and adult.
The compounds I can be applied as such or in form of compositions comprising them.
The application can be carried out both before and after the infestation of the crops, plants, plant propagation materials by the pests.
The term "contacting" includes both direct contact (applying the compounds/compositions directly on the animal pest or plant) and indirect contact (applying the compounds/compositions to the locus).
The term “animal pest” includes arthropods, gastropods, and nematodes. Preferred animal pests according to the invention are arthropods, preferably insects and arachnids, in particular insects.
The term “plant” includes cereals, e.g. durum and other wheat, rye, barley, triticale, oats, rice, or maize (fodder maize and sugar maize I sweet and field corn); beet, e.g. sugar beet, or fodder beet; fruits, e.g. pomes, stone fruits, or soft fruits, e.g. apples, pears, plums, peaches, nectarines, almonds, cherries, papayas, strawberries, raspberries, blackberries or gooseberries; leguminous plants, e.g. beans, lentils, peas, alfalfa, or soybeans; oil plants, e.g. rapeseed (oilseed rape), turnip rape, mustard, olives, sunflowers, coconut, cocoa beans, castor oil plants, oil palms, ground nuts, or soybeans; cucurbits, e.g. squashes, pumpkins, cucumber or melons; fiber plants, e.g. cotton, flax, hemp, or jute; citrus fruit, e.g. oranges, lemons, grapefruits or mandarins; vegetables, e.g. eggplant, spinach, lettuce (e.g. iceberg lettuce), chicory, cabbage, asparagus, cabbages, carrots, onions, garlic, leeks, tomatoes, potatoes, cucurbits or sweet peppers; lauraceous plants, e.g. avocados, cinnamon, or camphor; energy and raw material plants, e.g. corn, soybean, rapeseed, sugar cane or oil palm; tobacco; nuts, e.g. walnuts; pistachios; coffee; tea; bananas; vines; hop; sweet leaf (Stevia); natural rubber plants or ornamental and forestry plants, shrubs, broad-leaved trees or evergreens, eucalyptus; turf; lawn; grass. Preferred plants include potatoes, sugar beets, tobacco, wheat, rye, barley, oats, rice, corn, cotton, soybeans, rapeseed, legumes, sunflowers, coffee, or sugar cane; fruits; vines; ornamentals; or vegetables, e.g. cucumbers, tomatoes, beans or squashes.
The term “seed” embraces seeds and plant propagules including true seeds, seed pieces, suckers, corms, bulbs, fruit, tubers, grains, cuttings, cut shoots, and means preferably true seeds.
"Pesticidally effective amount" means the amount of active ingredient needed to achieve an observable effect on growth, including the effects of necrosis, death, retardation, prevention, and removal, destruction, or otherwise diminishing the occurrence and activity of the target organism. The pesticidally effective amount can vary for the various compounds/compositions used in the invention. A pesticidally effective amount of the compositions will also vary according to the prevailing conditions e.g. desired pesticidal effect and duration, weather, target species, locus, mode of application.
For use in treating crop plants, e.g. by foliar application, the rate of application of the active ingredients of this invention may be in the range of 0.0001 g to 4000 g per hectare, e.g. from 1 g to 2 kg per hectare or from 1 g to 750 g per hectare, desirably from 1 g to 100 g per hectare.
The compounds I are also suitable for use against non-crop insect pests. For use against said non-crop pests, compounds I can be used as bait composition, gel, general insect spray, aerosol, as ultra-low volume application and bed net (impregnated or surface applied).
The term “non-crop insect pest” refers to pests, which are particularly relevant for non-crop targets, e.g. ants, termites, wasps, flies, ticks, mosquitoes, bed bugs, crickets, or cockroaches, such as: Aedes aegypti, Musca domestica, Tribolium spp.; termites such as Reticulitermes flavipes, Coptotermes formosanus; roaches such as Blatella germanica, Periplaneta Americana; ants such as Solenopsis invicta, Linepithema humile, and Camponotus pennsylvanicus.
The bait can be a liquid, a solid or a semisolid preparation (e.g. a gel). For use in bait compositions, the typical content of active ingredient is from 0.001 wt% to 15 wt%, desirably from 0.001 wt% to 5 wt% of active compound.
The compounds I and its compositions can be used for protecting wooden materials such as trees, board fences, sleepers, frames, artistic artifacts, etc. and buildings, but also construction materials, furniture, leathers, fibers, vinyl articles, electric wires and cables etc. from ants, termites and/or wood or textile destroying beetles, and for controlling ants and termites from doing harm to crops or human beings (e.g. when the pests invade into houses and public facilities or nest in yards, orchards or parks). Customary application rates in the protection of materials are, e.g., from 0.001 g to 2000 g or from 0.01 g to 1000 g of active compound per m2 treated material, desirably from 0.1 g to 50 g per m2.
Insecticidal compositions for use in the impregnation of materials typically contain from 0.001 to 95 wt%, preferably from 0.1 to 45 wt%, and more preferably from 1 to 25 wt% of at least one repellent and/or insecticide.
The compounds of the invention are especially suitable for efficiently combating animal pests e.g. arthropods, and nematodes including: insects from the sub-order of Auchenorrhyncha, e.g. Amrasca biguttula, Empoasca spp., Ne- photettix virescens, Sogatella furcifera, Mahanarva spp., Laodelphax striatellus, Nilaparvata lugens, Diaphorina citrr',
Lepidoptera, e.g. Helicoverpa spp., Heliothis virescens, Lobesia botrana, Ostrinia nubilalis, Plu-tella xylostella, Pseudoplusia includens, Scirpophaga incertulas, Spodoptera spp., Trichop- lusia ni, Tuta absoluta, Cnaphalocrocis medialis, Cydia pomonella, Chilo suppressalis, Anticar- sia gemmatalis, Agrotis ipsilon, Chrysodeixis includens',
True bugs, e.g. Lygus spp., Stink bugs such as Euschistus spp., Halyomorpha halys, Nezara viridula, Piezodorus guildinii, Dichelops furcatus',
Thrips, e.g. Frankliniella spp., Thrips spp., Dichromothrips corbettii;
Aphids, e.g. Acyrthosiphon pisum, Aphis spp., Myzus persicae, Rhopalosiphum spp., Schi- zaphis graminum, Megoura viciae.,
Whiteflies, e.g. Trialeurodes vaporariorum, Bemisia spp.;
Coleoptera, e.g. Phyllotreta spp., Melanotus spp., Meligethes aeneus, Leptinotarsa decimline- ata, Ceutorhynchus spp., Diabrotica spp., Anthonomus grandis, Atomaria linearia, Agriotes spp., Epilachna spp.;
Flies, e.g. Delia spp., Ceratitis capitate, Bactrocera spp., Liriomyza spp.;
Mosquitoes (Diptera), e.g. Aedes aegypti, A. albopictus, A. vexans, Anastrepha ludens, Anopheles maculipennis, A. crucians, A. albimanus, A. gambiae, A. freeborni, A. leucosphyrus, A. minimus, A. quadrimaculatus;
Coccoidea, e.g. Aonidiella aurantia, Ferrisia virgate.,
Anthropods of class Arachnida (Mites), e.g. Penthaleus major, Tetranychus spp.;
Nematodes, e.g. Heterodera glycines, Meloidogyne sp., Pratylenchus spp., Caenorhabditis el- egans.
The compounds I are suitable for use in treating or protecting animals against infestation or infection by parasites. Therefore, the invention also relates to the use of a compound of the invention for the manufacture of a medicament for the treatment or protection of animals against infestation or infection by parasites. Furthermore, the invention relates to a method of treating or protecting animals against infestation and infection by parasites, which comprises orally, topically or parenterally administering or applying to the animals a parasiticidally effective amount of a compound I.
The invention also relates to the non-therapeutic use of compounds of the invention for treating or protecting animals against infestation and infection by parasites. Moreover, the invention relates to a non-therapeutic method of treating or protecting animals against infestation and infection by parasites, which comprises applying to a locus a parasiticidally effective amount of a compound I.
The compounds of the invention are further suitable for use in combating or controlling parasites in and on animals. Furthermore, the invention relates to a method of combating or controlling parasites in and on animals, which comprises contacting the parasites with a parasitically effective amount of a compound I.
The invention also relates to the non-therapeutic use of compounds I for controlling or combating parasites. Moreover, the invention relates to a non-therapeutic method of combating or controlling parasites, which comprises applying to a locus a parasiticidally effective amount of a compound I.
The compounds I can be effective through both contact (via soil, glass, wall, bed net, carpet, blankets, or animal parts) and ingestion (e.g. baits). Furthermore, the compounds I can be applied to any and all developmental stages.
The compounds I can be applied as such or in form of compositions comprising them.
The term "locus" means the habitat, food supply, breeding ground, area, material or environment in which a parasite is growing or may grow outside of the animal.
As used herein, the term “parasites” includes endo- and ectoparasites. In some embodiments of the invention, endoparasites can be preferred. In other embodiments, ectoparasites can be preferred. Infestations in warm-blooded animals and fish include lice, biting lice, ticks, nasal bots, keds, biting flies, muscoid flies, flies, myiasitic fly larvae, chiggers, gnats, mosquitoes and fleas.
The compounds of the invention are especially useful for combating the following parasites: Cimex lectularius, Rhipicephalus sanguineus, and Ctenocephalides felis.
As used herein, the term “animal” includes warm-blooded animals (including humans) and fish. Preferred are mammals, such as cattle, sheep, swine, camels, deer, horses, pigs, poultry, rabbits, goats, dogs and cats, water buffalo, donkeys, fallow deer and reindeer, and also in furbearing animals such as mink, chinchilla and raccoon, birds such as hens, geese, turkeys and ducks and fish such as fresh- and salt-water fish such as trout, carp and eels. Particularly preferred are domestic animals, such as dogs or cats.
The compounds I may be applied in total amounts of 0.5 mg/kg to 100 mg/kg per day, preferably 1 mg/kg to 50 mg/kg per day. For oral administration to warm-blooded animals, the compounds I may be formulated as animal feeds, animal feed premixes, animal feed concentrates, pills, solutions, pastes, suspensions, drenches, gels, tablets, boluses and capsules. For oral administration, the dosage form chosen should provide the animal with 0.01 mg/kg to 100 mg/kg of animal body weight per day of the compounds I, preferably with 0.5 mg/kg to 100 mg/kg of animal body weight per day.
Alternatively, the compounds I may be administered to animals parenterally, e.g., by intrarumi- nal, intramuscular, intravenous or subcutaneous injection. The compounds I may be dispersed or dissolved in a physiologically acceptable carrier for subcutaneous injection. Alternatively, the compounds I may be formulated into an implant for subcutaneous administration. In addition, the compounds I may be transdermally administered to animals. For parenteral administration, the dosage form chosen should provide the animal with 0.01 mg/kg to 100 mg/kg of animal body weight per day of the compounds I.
The compounds I may also be applied topically to the animals in the form of dips, dusts, powders, collars, medallions, sprays, shampoos, spot-on and pour-on formulations and in ointments or oil-in-water or water-in-oil emulsions. For topical application, dips and sprays usually contain 0.5 ppm to 5,000 ppm and preferably 1 ppm to 3,000 ppm of the compounds I. In addition, the compounds I may be formulated as ear tags for animals, particularly quadrupeds e.g. cattle and sheep.
Oral solutions are administered directly.
Solutions for use on the skin are trickled on, spread on, rubbed in, sprinkled on or sprayed on. Gels are applied to or spread on the skin or introduced into body cavities.
Pour-on formulations are poured or sprayed onto limited areas of the skin, the active compound penetrating the skin and acting systemically. Pour-on formulations are prepared by dissolving, suspending, or emulsifying the active compound in suitable skin-compatible solvents or solvent mixtures.
Emulsions can be administered orally, dermally or as injections.
Suspensions can be administered orally or topically/dermally.
Semi-solid preparations can be administered orally or topically/dermally.
For the production of solid preparations, the active compound is mixed with suitable excipients, if appropriate with addition of auxiliaries, and brought into the desired form.
The compositions which can be used in the invention can comprise generally from about 0.001 to 95% of the compound I.
Ready-to-use preparations contain the compounds acting against parasites, preferably ectoparasites, in concentrations of 10 ppm to 80% by weight, preferably from 0.1 to 65% by weight, more preferably from 1 to 50% by weight, most preferably from 5 to 40% by weight.
Preparations which are diluted before use contain the compounds acting against ectoparasites in concentrations of 0.5 to 90% by weight, preferably of 1 to 50% by weight. Furthermore, the preparations comprise the compounds of formula I against endoparasites in concentrations of 10 ppm to 2% by weight, preferably of 0.05 to 0.9% by weight, very particularly preferably of 0.005 to 0.25% by weight.
Solid formulations which release compounds of the invention may be applied in total amounts of 10 mg/kg to 300 mg/kg, preferably 20 mg/kg to 200 mg/kg, most preferably 25 mg/kg to 160 mg/kg body weight of the treated animal in the course of three weeks.
A. Preparation examples
The compounds were characterized by melting point determination, by NMR spectroscopy or by the mass-to-charge ratio ([m/z]) and retention time (RT; [min]), as determined by mass spectrometry (MS) coupled with HPLC analysis (HPLC-MS = high performance liquid chromatography-coupled mass spectrometry) or LC analysis (LC-MS = liquid chromatography-coupled mass spectrometry).
Method A: HPLC: Shimadzu Nexera LIHPLC + Shimadzu LCMS-2020, ESI; Column: Phenom- enex Kinetex 1.7pm XB-C18 100A, 2.1x50mm; Mobile phase: A: water + 0.1 % TFA; B: ACN; Temperature: 60°C; Gradient: 5% B to 100% B in 1.5 min; 100% B 0.25 min; Flow: 0.8 mL/min to 1.0 mL/min in 1.51 min; MS: ESI positive; Mass range (m/z): 100-700.
Method B: LC: Shimadzu LC-30AD, ESI; Column: Kinetex EVO C18 5pm 2.1x30mm; Mobile phase: A: water + 0.04% TFA; B: ACN + 0.02% TFA; Temperature: 40°C; Gradient: 5% B to 100% B in 2.5 min; 100% B to 5% B in 0.02min; 5% B for 0.5min; Flow: 0.8mL/min; MS: ESI positive; Mass range: 100-2000.
Example 1 : Preparation of 3-bromo-N-[1-[4-[5-(difluoromethoxy)pyrimidin-2-yl]oxazol-5- yl]ethyl]-5-(trifluoromethyl)benzamide (1-1)
Step 1 : Preparation of ethyl 4-bromooxazole-5-carboxylate
To a solution of ethyl oxazole-5-carboxylate (4.5g, 31.9mmol) in THF (45mL) and DMF (45mL) was added LiHMDS (35.1 mL of a 1 M solution in THF, 35.1mmol) dropwise at -60°C under N2 and stirred for 0.5h. Then, a solution of NBS (5.67g, 31 ,9mmol) in DMF (10mL) was added slowly at -60°C. The reaction mixture was stirred for 1 h at -60°C. TLC (petrol ether/EtOAc 5:1) showed that the reaction was completed. The reaction mixture was quenched with saturated aqueous NH4CI solution (100mL) and extracted with EtOAc (2x50mL). Combined organic layers were washed with brine (50mL), dried over Na2SO4, concentrated, and purified by silica gel column chromatography (petrol ether/EtOAc 100:0 to 12:88) to give the title compound (4g, 57% yield).
1H-NMR (400MHz, CDCI3) 6= 7.93 (s, 1 H), 4.43 (q, 2H), 1.42 (t, 3H). Step 2: Preparation of 2-chloro-5-(difluoromethoxy)pyrimidine
To a solution of 2-chloropyrimidin-5-ol (15g, 115mmol) in DMF (240mL) was added sodium 2- chloro-2,2-difluoro-acetate (26.3g, 172mmol) and K2CO3 (31.7g, 230mmol) at 20-25°C. The reaction mixture was stirred for 4h at 80°C. TLC (petrol ether/EtOAc 3:1) showed that the reaction was completed. The reaction mixture was filtered, and the filtrate was poured into ice-water (300mL). After extracting with EtOAc (3x100 mL), the organic layer was washed with brine (2x50mL), dried over Na2SC>4, concentrated, and purified by silica gel column chromatography (petrol ether/EtOAc 100:0 to 18:82) to give the title compound (7g, 34% yield).
1H-NMR (400MHz, CDCI3) 6= 8.54 (s, 2H), 6.41-6.81 (m, 1 H).
Step 3: Preparation of tributyl-[5-(difluoromethoxy)pyrimidin-2-yl]stannane
To a solution of 2-chloro-5-(difluoromethoxy)pyrimidine (7g, 38.78mmol) in DMF (140mL) was added [1 ,T-Bis(di-tert-butylphosphino)ferrocene]dichloropalladium(ll) (2.5g, 3.88mmol) at 25°C under N2, stirred for 15min, then Sn2Bue (33.7g, 58.2mmol) was added under N2. The mixture was stirred for 16h at 120°C under N2 before TLC (petrol ether/EtOAc 10:1) showed that the reaction was completed. The reaction mixture was cooled down, then poured into H2O (200mL), extracted with MTBE (3x100mL) and washed with brine (100mL). After drying over Na2SO4, the mixture was filtered, concentrated, and purified by silica gel column chromatography (petrol ether/EtOAc 100:0 to 10:90) to give the title compound (5g, 59% yield).
1H-NMR (400MHz, CDCI3) 6= 8.61 (s, 2H), 6.37-6.80 (m, 1 H), 1.62-1.69 (m, 6H), 1.36-1.40 (m, 6H), 1.15-1.23 (m, 6H), 0.89 (t, 9H).
Step 4: Preparation of ethyl 4-[5-(difluoromethoxy)pyrimidin-2-yl]oxazole-5-carboxylate
To a suspension of ethyl 4-bromooxazole-5-carboxylate (from step 1 , 8.2g, 37.43mmol), Cui (1.2g, 6.24mmol) and Pd(PPh3)4 (3.6g, 3.12mmol) in toluene (250mL) was added a solution of tributyl-[5-(difluoromethoxy)pyrimidin-2-yl]stannane (13.6g, 31.19mmol) in toluene (30mL) at 25°C. The mixture was stirred for 16h at 100°C, at which time completion was determined by TLC (petrol ether/EtOAc 10:1). The reaction mixture was filtered, and the filtrate was concentrated and purified by silica gel column chromatography (petrol ether/EtOAc 100:0 to 40:60) to give the title compound (4.8 g, 53% yield).
1H-NMR (400MHz, CDCI3) 6= 8.78 (s, 2H), 8.03-8.12 (m, 1 H), 6.46-6.90 (m, 1 H), 4.42 (q, 2H), 1.36 (t, 3H).
Step 5: Preparation of 4-[5-(difluoromethoxy)pyrimidin-2-yl]oxazole-5-carboxylic acid
To a solution of ethyl 4-[5-(difluoromethoxy)pyrimidin-2-yl]oxazole-5-carboxylate (4.8g, 16.84mmol) in THF/ H2O (120mL, 5:1) was added LiOHxH2O (1.41g, 33.68mmol) and the mixture was stirred for 1h at 0°C. TLC (petrol ether/EtOAc 1 :1) showed that the reaction was completed and the reaction mixture was poured into H2O (100mL). After extracting with MTBE (20mL), the aqueous layer was separated and then adjusted pH to 3 with 1 N HCI aq., then extracted with EtOAc (8x50mL), dried over Na2SO4, filtered, and concentrated to give the title compound (2.8 g, 65% yield).
1H-NMR (400MHz, DMSO-d6) 5= 9.06 (s, 2 H), 8.77 (s, 1 H), 7.29-7.70 (m, 1 H).
Step 6: Preparation of 4-[5-(difluoromethoxy)pyrimidin-2-yl]-N-methoxy-N-methyl-oxazole-5- carboxamide
To a solution of 4-[5-(difluoromethoxy)pyrimidin-2-yl]oxazole-5-carboxylic acid (2.8g, 10.89mmol) in DMF (45mL) was added 1-[bis(dimethylamino)methylene]-1 H-1 ,2,3-triazolo[4,5- b]pyridinium 3-oxide hexafluorophosphate (6.2g, 16.33mmol), triethylamine (TEA; 2.75g, 27.22mmol) and N,O-dimethylhydroxylamine hydrochloride (1.59g, 9.73mmol) at 25°C, and the mixture was stirred for 12h. TLC (EtOAc 100%) showed that the reaction was completed. The reaction mixture was quenched with H2O (100mL) and extracted with EtOAc (6x50mL), the organic layer was dried over Na2SO4, concentrated and purified by silica gel column (petrol ether/EtOAc/EtOH 100:0:0 to 40:45:15) to give the title compound (850mg, 26% yield).
1H-NMR (400MHz, CD3OD) 5= 8.76 (s, 2H), 8.44 (s, 1 H), 6.89-7.28 (m, 1 H), 3.61 (br s, 3H), 3.38 (br s, 3H).
Step 7: Preparation of 1-[4-[5-(difluoromethoxy)pyrimidin-2-yl]oxazol-5-yl]ethanone
To a solution of 4-[5-(difluoromethoxy)pyrimidin-2-yl]-N-methoxy-N-methyl-oxazole-5-carbox- amide (100mg, 0.33mmol) in CH2CI2 (10mL) was added MeMgBr (0.33mL, 3M in THF, 0.99mmol) dropwise at -60°C and the mixture was stirred for 0.5h. TLC (EtOAc) showed that the reaction was completed. The reaction mixture was quenched with saturated aqueous NH4CI solution (50mL) and extracted with CH2CI2 (2x50 mL), the organic layer was washed with brine (20mL), dried over Na2SO4, concentrated, and purified by silica gel column (petrol ether/EtOAc 100:0 to 40:60) to give the title compound (44 mg, 51% yield) as a white solid.
1H-NMR (400MHz, CDCI3) 6= 8.79 (s, 2H), 8.07 (s, 1 H), 6.48-6.88 (m, 1 H), 2.67 (s, 3H).
Step 8: Preparation of 1-[4-[5-(difluoromethoxy)pyrimidin-2-yl]oxazol-5-yl]ethanamine
To a solution of 1-[4-[5-(difluoromethoxy)pyrimidin-2-yl]oxazol-5-yl]ethanone (300mg, 1.17mmol) in EtOH (15mL) was added NH4OAC (900mg, 11.7mmol), NHs-solution (7M in MeOH, 9mL) at 25°C and stirred for 1 h, before NaBHsCN (222mg, 3.53mmol) was added. After 16h at 50°C, LCMS showed the reaction was completed. The reaction mixture was quenched with H2O (10mL), concentrated, and extracted with EtOAc (3x50mL). The organic layer was washed with brine (20mL), dried over Na2SO4 and concentrated to give the title compound (300 mg, crude). 1H-NMR (400MHz, DMSO-d6) 5= 8.86 (s, 2H), 8.39 (s, 1 H), 7.40 (s, 1 H), 4.89 (q, 1 H), 1.38 (d, 3H).
Step 9: Preparation of 3-bromo-N-[1-[4-[5-(difluoromethoxy)pyrimidin-2-yl]oxazol-5-yl]ethyl]-5- (trifluoromethyl)benzamide (1-1)
To a solution of 1-[4-[5-(difluoromethoxy)pyrimidin-2-yl]oxazol-5-yl]ethanamine (316mg, 1.18mmol) in DMF (2mL) was added 1-[bis(dimethylamino)methylene]-1 H-1 ,2,3-triazolo[4,5- b]pyridinium 3-oxide hexafluorophosphate (672mg, 1.77mmol), TEA (298mg, 2.95mmol) and a solution of 3-bromo-5-(trifluoromethyl)benzoic acid (300mg, 1.18mmol) in DMF (3mL) at 25°C. The mixture was stirred for 12h at 25°C, before TLC (petrol ether/EtOAc 3:1) showed that the reaction was completed. The reaction mixture was poured into H2O (30mL), extracted with EtOAc (2x20 mL) and the organic layer was washed with brine (20mL). After drying over Na2SC>4, the mixture was concentrated in vacuum and purified by silica gel column chromatography (petrol ether/EtOAc 100:0 to 25:75), then triturated with MTBE (5 mL) to give the title compound (260 mg, 43% yield).
1H-NMR (400MHz, CDCI3) 5= 9.15 (br d, 1 H), 8.76-8.84 (m, 2H), 8.18 (s, 1 H), 7.99 (s, 1 H), 7.93 (s, 1 H), 7.91 (s, 1 H), 6.46-6.87 (m, 1 H), 5.96-6.14 (m, 1 H), 1.63 (d, 3H).
LCMS: calculated mass: 506.0; observed mass: 507.0.
Example 2: Preparation of 3-(difluoromethoxy)-N-ethyl-N-[1-(5-pyrimidin-2-yloxazol-4-yl)ethyl]- 5-(trifluoromethyl)benzamide (I-5)
Step 1 : Preparation of ethyl 5-pyrimidin-2-yloxazole-4-carboxylate
To a solution of pyrimidine-2-carbonyl chloride (8g, 56.3mmol) in THF (80mL) was added TEA (24mL, 169mmol) and ethyl 2-isocyanoacetate (13g, 112.6mmol) dropwise at 0°C. The mixture was stirred at 25°C for 4 h, before TLC (EtOAc) showed that the reaction was completed. The reaction solution was poured into H2O (200mL), extracted with EtOAc (3x80mL) and combined organic layers were washed with brine (200mL). After drying over Na2SO4, the mixture was filtered, concentrated and purified by silica gel chromatography to give the title compound (7.5 g, 53% yield).
1H-NMR (400MHz, CDCI3) 5= 8.92-8.87 (m, 2H), 8.07-7.97 (m, 1 H), 7.37-7.30 (m, 1 H), 4.51- 4.39 (m, 2H), 1.39 (t, 3H).
Step 2: Preparation of 1-(5-pyrimidin-2-yloxazol-4-yl)ethanone
To a solution of MeMgBr (11 ,9mL, 35.6mmol, 3M in Et20) and TEA (11 ,4mL, 82.2mmol) in toluene (60mL) was added a solution of ethyl 5-pyrimidin-2-yloxazole-4-carboxylate (3g, 13.7mmol) in toluene (60mL) at 0°C under N2. The mixture was stirred for 4h and gradually warmed to 20-25°C. TLC (petrol ether/EtOAc 1 :1) showed the reaction was completed. The reaction mixture was quenched with saturated aqueous NH4CI (200mL) and extracted with EtOAc (5x100mL). The organic layer was washed with brine (40mL), dried over Na2SC>4, concentrated, and purified by silica gel column chromatography to give the title compound (1.3 g, 50% yield).
1H-NMR (400MHz, CDCI3) 6= 8.91 (d, 2H), 8.01 (s, 1 H), 7.36 (t, 1 H), 2.71 (s, 3H).
Step 3: Preparation of 1-(5-pyrimidin-2-yloxazol-4-yl)ethanamine
To a solution of 1-(5-pyrimidin-2-yloxazol-4-yl)ethanone (1.5g, 7.93mmol) in EtOH (75mL) was added NH4OAc (6.1g, 79.3mmol), NH3 (7M in MeOH, 45mL) at 25°C, stirred for 0.5h, before NaBH3CN (1.5g, 23.8mmol) was added and the mixture was stirred for 12h at 50°C. LCMS showed the reaction was completed. The reaction mixture was quenched with H2O (10mL), concentrated, and extracted with EtOAc (4x40 mL), the organic layer was dried over Na2SO4, concentrated to give the title compound (2 g, crude).
1H-NMR (400MHz, CDCI3) 5= 8.97 (d, 2H), 8.52 (s, 1 H), 7.50-7.52 (m, 1 H), 5.25 (q, 1 H), 1.54 (d, 3H).
Step 4: Preparation of 3-(difluoromethoxy)-N-[1-(5-pyrimidin-2-yloxazol-4-yl)ethyl]-5-(trifluoro- methyl)benzamide (I-3)
To a solution of 3-(difluoromethoxy)-5-(trifluoromethyl)benzoic acid (100mg, 0.39mmol) in DMF (1mL) was added 1-[bis(dimethylamino)methylene]-1 H-1 ,2,3-triazolo[4,5-b]pyridinium 3- oxide hexafluorophosphate (222mg, 0.585mmol), TEA (118mg, 1.17mmol) and a solution of 1- (5-pyrimidin-2-yloxazol-4-yl)ethanamine (74mg, 0.39mmol) in DMF (1mL) at 25°C. The mixture was stirred for 12h at 25°C, when TLC (petrol ether/EtOAc 1 :1) showed the reaction was completed. The reaction mixture was poured into H2O (15mL), extracted with EtOAc (2x15mL), the organic layer was washed with brine (20mL), dried over Na2SO4, concentrated and purified by prep-TLC (petrol ether/EtOAc 1 :1) to give the title compound (70mg, 42% yield) as white solid.
1H-NMR (400MHz, CDCI3) 5= 8.89 (d, 2H), 8.63 (br d, 1 H), 8.03 (s, 1 H), 7.91 (s, 1 H), 7.83 (s, 1 H), 7.52 (s, 1 H), 7.30 (t, 1 H), 6.40-6.82 (m, 1 H), 5.99-6.16 (m, 1 H), 1.62 (d, 3H).
LCMS: calculated mass: 428.1 ; observed mass: 429.1
Step 5: Preparation of 3-(difluoromethoxy)-N-ethyl-N-[1-(5-pyrimidin-2-yloxazol-4-yl)ethyl]-5- (trifluoromethyl)benzamide (I-5)
To a solution of 3-(difluoromethoxy)-N-[1-(5-pyrimidin-2-yloxazol-4-yl)ethyl]-5-(trifluorome- thyl)benzamide (500mg, 1.17mmol) in THF (5mL) was added NaH (56mg, 1.405mmol) at 0°C under N2. After 0.5h, EtOTf (312mg, 1.755mmol) was added slowly dropwise at 0°C, and the mixture was allowed to reach room temperature over 2h. TLC (petrol ether/EtOAc 1 :1) showed the reaction was completed. The reaction mixture was poured into saturated aqueous NH4CI (20mL), extracted with EtOAc (2x20 mL) and the organic layer was washed with brine (20mL). After drying over Na2SC>4, the mixture was concentrated and purified by preparative HPLC (neutral) to give the title compound (85 mg, 17% yield).
1H-NMR (400MHz, DMSO-d6) 5= 8.63 (br d, 2H), 8.52 (s, 1 H), 7.48 (s, 1 H), 7.08-7.46 (m, 4H), 5.91-6.15 (m, 1 H), 3.52-3.76 (m, 2H), 1.61 (d, 3H), 1.11 (br t, 3H).
LCMS: calculated mass: 456.1 ; observed mass: 457.1
Example 3: Preparation of /V-[1-(5-pyrimidin-2-ylthiazol-4-yl)ethyl]-3,5-bis(trifluoromethyl)ben- zamide (1-11)
Step 1 : Preparation of methyl 5-pyrimidin-2-ylthiazole-4-carboxylate
To a solution of methyl 5-bromothiazole-4-carboxylate (10.0g, 45.03mmol) in toluene (100mL) was added Cui (4.29g, 22.52mmol), Pd(PPha)4 (5.2g, 4.503mmol) and tributyl(pyrimidin-2- yl)stannane (33.2g, 90.06mmol) at 25°C under N2. The mixture was heated to 120°C and stirred for 16h. TLC (petrol ether/EtOAc 1 :1) showed the reaction was completed. Aq. KF was added and stirred for 30min. The resulting mixture was filtered, quenched with water (50mL) and extracted with EtOAc (3x100mL). The combined organic phase was washed with brine (100mL), dried over Na2SO4, filtered, concentrated and purified by silica gel chromatography (petrol ether/EtOAc 1 :1) to give methyl 5-pyrimidin-2-ylthiazole-4-carboxylate (2.78g, 28% yield) as a yellow solid.
1H-NMR (400MHz, CDCI3) 5= 8.84 (s, 1 H), 8.77 (d, J=5.00Hz, 2H), 7.24 (t, J=4.94Hz, 1 H), 3.97 (s, 3H).
Step 2: Preparation of 1-(5-pyrimidin-2-ylthiazol-4-yl)ethenone
To a solution of TEA (7.615g, 75.39mmol) in toluene (15mL) was added MeMgBr (3M in diethyl ether, 15mL) dropwise at 0°C under N2. A solution of methyl 5-pyrimidin-2-ylthiazole-4-car- boxylate (2.78g, 12.566mmol) in toluene (15mL) was added at 0°C under N2. The mixture was stirred at 25°C for 4h. LCMS showed the reaction was completed. The mixture was quenched with water (90mL) and extracted with EtOAc (3x60mL). The combined organic phase was washed with brine (60mL), dried over Na2SO4, filtered, concentrated and purified by preparative HPLC (NH4HCO3) to give 1-(5-pyrimidin-2-ylthiazol-4-yl)ethenone (0.46g, 18% yield) as a yellow solid.
1H-NMR (400MHz, CDCI3) 5= 8.82 (s, 1 H), 8.75-8.78 (m, 2H), 7.24 (t, J=4.94Hz, 1 H), 2.72 (s, 3H).
Step 3: Preparation of 1-(5-pyrimidin-2-ylthiazol-4-yl)ethanamine
To a solution of 1-(5-pyrimidin-2-ylthiazol-4-yl)ethenone (0.46g, 2.24mmol) in MeOH (35mL) was added NH3 (7M in MeOH, 7mL) and NH4OAC (1.727g, 22.4mmol) at 25°C. The mixture was stirred for 2h, then NaCNBHs (0.423g, 6.72mmol) was added. The resulting mixture was stirred at 25°C for 2h and at 50°C for 16h. TLC (DCM/MeOH 10:1) showed the reaction was completed. The mixture was concentrated, quenched with water (5m L) and extracted with DCM/2- propanol (3:1 , 3x1 OmL). The combined organic phase was dried over Na2SO4, filtered and concentrated to give 1-(5-pyrimidin-2-ylthiazol-4-yl)ethanamine (0.7g, crude) as a yellow oil.
Step 4: Preparation of /V-[1-(5-pyrimidin-2-ylthiazol-4-yl)ethyl]-3,5-bis(trifluoromethyl)ben- zamide (1-11)
To a solution of 3,5-bis(trifluoromethyl)benzoic acid (1.222g, 4.73mmol) in ACN (5mL) was added N-methylimidazole (0.78mmol, 9.462mmol) and chloro-N,N,N',N'-tetramethylforma- midinium hexafluorophosphate (1.326g, 4.73mmol) at 25°C. A solution of 1-(5-pyrimidin-2-ylthi- azol-4-yl)ethanamine (0.65g, 3.154mmol) in ACN (5mL) was added and stirred at 25°C for 3h. LCMS showed the reaction was completed. The mixture was quenched with water (20mL) and extracted with EtOAc (3x20mL). The combined organic phase was dried over Na2SC>4, concentrated and purified by silica gel chromatography (petrol ether/EtOAc 3:1) to give /V-[1-(5-pyrim- idin-2-ylthiazol-4-yl)ethyl]-3,5-bis(trifluoromethyl)benzamide (0.37g, 26% yield) as a white solid.
1H-NMR (400MHz, CDCI3) 6= 8.84 (d, J=3.50Hz, 2H), 8.82 (s, 1 H), 8.30 (s, 3H), 8.00 (s, 1 H), 7.23 (t, J=4.88Hz, 1 H), 6.52-6.65 (m, 1 H), 1.66 (d, J=6.75Hz, 3H).
Example 4: Preparation of /V-[1-(4-pyrimidin-2-ylthiazol-5-yl)ethyl]-3,5-bis(trifluoromethyl)ben- zamide (1-17)
Step 1 : Preparation of 1-(4-chlorothiazol-5-yl)ethanol
To a solution of 4-chlorothiazole-5-carbaldehyde (5.0g, 34mmol) in THF (50mL) was added MeMgBr (3M in diethyl ether, 17mL, 51 mmol) at 0°C under N2. The mixture was stirred at 25°C for 16h. TLC (petrol ether/EtOAc 1 :1) showed the reaction was completed. The reaction solution was quenched with NH4CI (aq., 50mL) and extracted with EtOAc (3x50mL). The combined organic phase was washed with brine (50mL), dried over Na2SO4, filtered, concentrated and purified by silica gel chromatography (petrol ether/EtOAc 2:1) to give 1-(4-chlorothiazol-5-yl)ethanol (4g, 72% yield) as a yellow oil.
1H-NMR (400MHz, CDCI3) 6= 8.85 (s, 1 H), 2.74 (s, 3H).
Step 2: Preparation of 1-(4-chlorothiazol-5-yl)ethanone
To a solution of 1-(4-chlorothiazol-5-yl)ethanol (4g, 24.5mmol) in DCE (50mL) was added MnO2 (20.6g, 245mmol) at 25°C. The mixture was heated to 100°C and stirred for 16h. TLC (petrol ether/EtOAc 1 :1) showed the reaction was completed. The reaction solution was filtered and concentrated. The crude was purified by silica gel chromatography (petrol ether/EtOAc 2:1) to give 1-(4-chlorothiazol-5-yl)ethenone (3g, 76% yield) as a yellow solid. 1H-NMR (400MHz, CDCI3) 6= 8.62 (s, 1 H), 5.27 (q, J=6.42Hz, 1 H), 2.66 (br s, 1 H), 1.57 (d, J=6.38Hz, 3H).
Step 3: Preparation of 1-(4-pyrimidin-2-ylthiazol-5-yl)ethanone
To a solution of 1-(4-chlorothiazol-5-yl)ethenone (1g, 6.19mmol) in DMF (10mL) was added tributyl(pyrimidin-2-yl)stannane (4.43g, 9.28mmol), LiCI (26mg, 0.619mmol), Cui (118mg, 0.619mmol) and Pd(PPh3)4 (715mg, 0.619mmol) at 20°C under N2. The reaction mixture was stirred for 2h at 150°C under microwave irradiation. TLC (petrol ether/EtOAc 1 :1) showed the reaction was completed. The reaction mixture was quenched with NH4CI (aq., 50mL) and extracted with EtOAc (3x50mL). The combined organic phase was washed with brine (3x50mL), dried over Na2SO4, filtered, concentrated and purified by preparative HPLC (NH4HCO3) to give 1-(4-pyrimidin-2-ylthiazol-5-yl)ethenone (500mg, 20% yield) as a yellow solid.
1H-NMR (400MHz, CDCI3) 6= 8.90 (d, J=4.88Hz, 2H), 8.01 (s, 1 H), 7.35 (t, J=4.88Hz, 1 H), 2.71 (s, 3H).
Step 4: Preparation of 1-(4-pyrimidin-2-ylthiazol-5-yl)ethanamine
To a solution of 1-(4-pyrimidin-2-ylthiazol-5-yl)ethenone (500mg, 2.44mmol) in MeOH (50mL) and NH3 (7M in MeOH, 10mL) was added NH4OAc (1.88g, 24.4mmol) at 20°C. The resulting mixture was stirred for 30min. Then NaCNBH3 (306mg, 4.87mmol) was added. The mixture was heated to 50°C and stirred for 16h. TLC (EtOAc) showed the reaction was completed. The reaction mixture was concentrated and quenched with water (100mL) extracted with DCM/2-propa- nol (3:1 ; 3x100mL). The combined organic phase was dried over Na2SO4, filtered, concentrated and purified by silica gel chromatography (DCM/MeOH 5:1) to give 1-(4-pyrimidin-2-ylthiazol-5- yl)ethanamine (200mg, 40% yield) as a yellow solid.
1H-NMR (400MHz, CDCI3) 6= 8.94 (s, 1 H), 8.91 (d, J=4.88Hz, 2H), 7.42 (t, J=4.94Hz, 1 H), 5.21 (q, J=6.59Hz, 1 H), 1.56 (d, J=6.63Hz, 3H).
Step 5: Preparation of /V-[1-(4-pyrimidin-2-ylthiazol-5-yl)ethyl]-3,5-bis(trifluoromethyl)ben- zamide (1-17)
To a solution of 1-(4-pyrimidin-2-ylthiazol-5-yl)ethanamine (200mg, 0.97mmol) and TEA (147mg, 1.45mmol) in DCM (10mL) was added a solution of 3,5-bis(trifluoromethyl)benzoyl chloride (295mg, 1.07mmol) in DCM (1 mL) at 0°C under N2. The reaction mixture was stirred for 12h at the same temperature. TLC (petrol ether/EtOAc 1 :1) showed the reaction was completed. The mixture was quenched with NH4CI (aq., 30mL) and extracted with DCM (2x30mL). The organic phase was washed with brine (30mL), dried over Na2SO4, filtered, concentrated and purified by silica gel chromatography (petrol ether/EtOAc 1 :1) to give /V-[1-(4-pyrimidin-2- ylthiazol-5-yl)ethyl]-3,5-bis(trifluoromethyl)benzamide (100mg, 23% yield) as a yellow solid. 1H-NMR (400MHz, CDCI3) 6= 8.90-8.96 (m, 3H), 8.41 (s, 2H), 8.17 (s, 1 H), 7.42 (t, J=4.94Hz, 1 H), 6.50 (d, J=6.88Hz, 1 H), 1.76 (d, J=6.88Hz, 3H).
LCMS: calculated mass: 446.1 ; observed mass: 447.2
Example 5: Preparation of 6-[5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]-(cyclopropylme- thyl)amino]ethyl]oxazol-4-yl]pyrimidine-4-carboxamide (1-21)
Step 1 : Preparation of ethyl 4-bromooxazole-5-carboxylate
To a solution of ethyl oxazole-5-carboxylate (25g, 177.3mmol) in THF/DMF (1 :1 ; 500mL) was added LiHMDS (195mL, 195.0mmol) dropwise at -60°C under N2. The reaction mixture was stirred for 30min. Then a solution of NBS (31.56g, 177.3mmol) in DMF (100mL) was added slowly at -60°C. The reaction mixture was stirred for 2h. TLC (petrol ether/EtOAc 10:1) showed the reaction was completed. The mixture was quenched with NH4CI (aq. sat., 1.5L) and extracted with MTBE (2x300mL). The combined organic phase was washed with brine (100mL), dried over Na2SO4, filtered, concentrated and purified by silica gel chromatography (petrol ether/EtOAc 100:0 to 10:90) to give ethyl 4-bromooxazole-5-carboxylate (30g, 39% yield) as a yellow solid.
1H-NMR (400MHz, CDCI3) 6= 7.94 (s, 1 H), 4.43 (q, J=7.15Hz, 2H), 1.42 (t, J=7.09Hz, 3H).
Step 2: Preparation of ethyl 4-tributylstannyloxazole-5-carboxylate
To a solution of ethyl 4-bromooxazole-5-carboxylate (100g, 456mmol) in toluene (1000mL) was added (SnBu3)2 (400g, 685mmol) and Pd(PPh3)4 (10g, 8.65mmol) at 25°C under N2. The reaction mixture was heated to 125°C for 16h. TLC (petrol ether/EtOAc 5:1) showed the reaction was completed. The mixture was quenched with water (2L) and extracted with EtOAc (3x1 L). The combined organic phase was dried over Na2SO4, filtered, concentrated und purified by silica gel chromatography (petrol ether/EtOAc 1 :99 to 20:80) to give ethyl 4-tributylstannylox- azole-5-carboxylate (153g, crude, 46% yield) as a yellow oil.
Step 3: Preparation of ethyl 4-(6-chloropyrimidin-4-yl)oxazole-5-carboxylate
To a solution of ethyl 4-tributylstannyloxazole-5-carboxylate (32g, 74.2mmol) in DMF (320mL) was added 4,6-dichloropyrimidine (11g, 74.2mmol), Cui (1.4g, 7.4mmol), LiCI (6.3g, 148.5mmol) and Pd(PPh3)4 (3.5g, 3.03mmol) at 20°C. The reaction mixture was heated to 80°C and stirred for 16h. LCMS showed the reaction was completed. The mixture was quenched with water (500mL) and extracted with EtOAc (3x500mL). The combined organic phase was dried over Na2SO4, filtered, concentrated and purified by silica gel chromatography (petrol ether/EtOAc 30:70 to 45:55) to give ethyl 4-(6-chloropyrimidin-4-yl)oxazole-5-carboxylate (18g, 32% yield) as a brown oil. 1H-NMR (400MHz, CDCI3) 6= 9.14 (s, 1 H), 8.29 (s, 1 H), 8.10 (s, 1 H), 4.47 (q, J=7.1 Hz, 2H), 1.43 (t, J=7.2Hz, 3H).
Step 4: Preparation of 1-[4-(6-chloropyrimidin-4-yl)oxazol-5-yl]ethanone
To a solution of TEA (1.2g, 12mmol) in toluene (10mL) was added MeMgBr (3M, 2.6mL, 8mmol) dropwise at 0°C under N2. The reaction mixture was stirred for 10min at 0°C. Then a solution of ethyl 4-(6-chloropyrimidin-4-yl)oxazole-5-carboxylate (1g, 4mmol) in toluene (5mL) was added to the above mixture dropwise at 0°C. The reaction mixture was stirred for 3h at 0°C. TLC (petrol ether/EtOAc 1 :1) showed the reaction was completed. The crude was poured into NH4CI (aq. sat., 50mL) and extracted with EtOAc (2x30mL). The combined organic phase was washed with brine, dried over Na2SO4, filtered, concentrated and purified by silica gel chromatography (petrol ether/EtOAc 30:70 to 50:50) to give 1-[4-(6-chloropyrimidin-4-yl)oxazol-5- yl]ethenone (500mg, 56% yield) as a yellow oil.
1H-NMR (400MHz, CDCI3) 6= 9.13 (s, 1 H), 8.40 (s, 1 H), 8.08 (s, 1 H), 2.71 (s, 3H).
Step 5: Preparation of 1-[4-(6-chloropyrimidin-4-yl)oxazol-5-yl]ethanamine
To a solution of 1-[4-(6-chloropyrimidin-4-yl)oxazol-5-yl]ethenone (5.6g, 29.6mmol) in EtOH (280mL) was added NH4OAc (22.8g, 296mmol) and NH3 (7M in MeOH, 155mL) at 25°C. The reaction mixture was stirred for 1h at 25°C. Then NaCNBHs (5.6g, 88.8mmol) was added. The reaction mixture was heated to 50°C and stirred for 16h. LCMS showed the reaction was completed. The reaction mixture was quenched with water (200mL) and extracted with EtOAc (3x300mL). The combined organic phase was dried over Na2SO4 filtered, concentrated and purified by silica gel chromatography (DCM:MeOH=50:1 to 10:1) to give 1-[4-(6-chloropyrimidin-4- yl)oxazol-5-yl]ethanamine (1.5g, crude) as a brown oil.
1H-NMR (400MHz, CDCI3) 5= 8.96 (s, 1 H), 8.00 (s, 1 H), 7.86 (s, 1 H), 5.02 (q, J=6.7Hz, 1 H), 1.57 (br d, J=6.9Hz, 3H).
Step 6: Preparation of 1-[4-(6-chloropyrimidin-4-yl)oxazol-5-yl]-/\/-(cyclopropylmethyl)ethana- mine
To a solution of 1-[4-(6-chloropyrimidin-4-yl)oxazol-5-yl]ethanamine (0.8g, 3.57mmol) in MeOH (8mL) was added cyclopropanecarbaldehyde (0.25g, 3.57mmol) and AcOH (cat. 5 drops). The reaction mixture was stirred for 5min at 20°C.Then NaCNBHs (0.45g, 7.14mmol) was added at 0°C and the mixture was stirred for 1 ,5h at this temperature. LCMS showed the reaction was completed. The mixture was quenched with water (15mL) and extracted with EtOAc (3x15mL). The combined organic phase was dried over Na2SO4, filtered, and concentrated to give 1-[4-(6- chloropyrimidin-4-yl)oxazol-5-yl]-/\/-(cyclopropylmethyl)ethanamine (650mg, crude), which was used in the next step without further purification. Step 7: Preparation of 3-chloro-/V-[1-[4-(6-chloropyrimidin-4-yl)oxazol-5-yl]ethyl]-/\/-(cyclo- propylmethyl)-5-(trifluoromethyl)benzamide
To a solution of 1-[4-(6-chloropyrimidin-4-yl)oxazol-5-yl]-/\/-(cyclopropylmethyl)ethanamine (150mg, 0.54mmol) in DCM (4mL) was added TEA (109mg, 1.08mmol) and a solution of 3- chloro-5-(trifluoromethyl)benzoyl chloride (157mg, 0.65mmol) in DCM at 0°C under N2. The reaction mixture was stirred for 1h at this temperature. TLC (petrol ether/EtOAc 3:1) showed the reaction was completed. The mixture was quenched with water (10mL) and extracted with DCM 2x10mL). The combined organic phase was washed with brine (10mL), dried over Na2SO4, filtered, concentrated and purified by silica gel chromatography to give 3-chloro-/V-[1-[4-(6-chloro- pyrimidin-4-yl)oxazol-5-yl]ethyl]-/V-(cyclopropylmethyl)-5-(trifluoromethyl)benzamide (90mg, 34% yield) as a yellow oil.
1H-NMR (400MHz, CDCI3) 6= 8.17-8.90 (m, 1 H), 7.83-7.99 (m, 2H), 7.61 (s, 1 H), 7.48 (d, J=7.00Hz, 2H), 6.07-6.33 (m, 1 H), 3.19-3.60 (m, 2H), 1.78 br s, 3H), 0.83-1.06 (m, 1 H), 0.53 (br d, J=7.63Hz, 2H), 0.05-0.39 (m, 2H).
Step 8: Preparation of methyl 6-[5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]-(cyclopropylme- thyl)amino]ethyl]oxazol-4-yl]pyrimidine-4-carboxylate
To a solution of 3-chloro-/V-[1-[4-(6-chloropyrimidin-4-yl)oxazol-5-yl]ethyl]-/\/-(cyclopropylme- thyl)-5-(trifluoromethyl)benzamide (90mg, 0.186mmol) in MeOH (15mL) was added Pd(dppf)CI2 (100mg, cat.) and TEA (56mg, 0.558mmol) at 15°C. The reaction mixture was purged with CO thrice and stirred at 60°C for 5h. TLC (petrol ether/EtOAc 3:1) showed the reaction was completed. The reaction mixture was filtered, concentrated and purified by silica gel chromatography (petrol ether/EtOAc 100:0 to 30:70) to give methyl 6-[5-[1-[[3-chloro-5-(trifluorome- thyl)benzoyl]-(cyclopropylmethyl)amino]ethyl]oxazol-4-yl]pyrimidine-4-carboxylate (55mg, 58% yield) as a yellow oil.
LCMS: calculated mass: 508; observed mass: 509
Step 9: Preparation of 6-[5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]-(cyclopropylme- thyl)amino]ethyl]oxazol-4-yl]pyrimidine-4-carboxamide (1-21)
A solution of methyl 6-[5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]-(cyclopropylmethyl)ami- no]ethyl]oxazol-4-yl]pyrimidine-4-carboxylate (55mg, 0.108mmol) in NH3 (7M in MeOH, 2mL) was stirred for 2h at 15°C. TLC (petrol ether/EtOAc 1 :1) showed the reaction was completed. The reaction mixture was concentrated to give 6-[5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]-(cy- clopropylmethyl)amino]ethyl]oxazol-4-yl]pyrimidine-4-carboxamide (50mg, 94% yield) as a yellow solid. 1H-NMR (400MHz, DMSO-d6) 6= 8.61-9.49 (m, 2H), 8.27-8.43 (m, 2H), 8.01 (s, 1 H) 7.65-7.85 (m, 2H), 7.48-7.63 (m, 1 H), 5.88-6.15 (m, 1 H), 3.41-3.75 (m, 2H), 1.63-1.79 (m, 3H), 0.95-1.16 (m, 1 H), 0.43 (br s, 2H), 0.11-0.34 (m, 2H).
LCMS: calculated mass: 493.1 ; observed mass: 494.1.
Figure imgf000046_0001
Figure imgf000047_0001
II. Evaluation of pesticidal activity:
The activity of the compounds of formula I of the invention can be demonstrated and evaluated by the following biological tests.
B.1 Diamond back moth (Plutella xylostella)
The active compound was dissolved at the desired concentration in a mixture of 1 :1 (vol:vol) distilled water : acetone. Surfactant (Kinetic HV) was added at a rate of 0.01% (vol/vol). The test solution was prepared on the day of use.
Leaves of cabbage were dipped in test solution and air-dried. Treated leaves were placed in petri dishes lined with moist filter paper and inoculated with ten 3rd instar larvae. Mortality was recorded 72 hours after treatment. Feeding damages were also recorded using a scale of 0- 100%.
In this test, compounds 1-1, I-2, I-3, I-4, I-5, and I-6, resp., at 300 ppm showed at least 75% mortality in comparison with untreated controls.
B.2 Green Peach Aphid (Myzus persicae)
For evaluating control of green peach aphid (Myzus persicae) through systemic means the test unit consisted of 96-well-microtiter plates containing liquid artificial diet under an artificial mem brane.
The compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were pipetted into the aphid diet, using a custom built pipetter, at two replications.
After application, 5-8 adult aphids were placed on the artificial membrane inside the microtiter plate wells. The aphids were then allowed to suck on the treated aphid diet and incubated at about 23±1°C and about 50±5 % relative humidity for 3 days. Aphid mortality and fecundity was then visually assessed.
In this test, compounds I-3, I-4, I-5, I-6, I-7, 1-10, and 1-13, resp., at 2500 ppm showed at least 75% mortality in comparison with untreated controls.
B.4 Tobacco budworm (Heliothis virescens)
For evaluating control of tobacco budworm (Heliothis virescens) the test unit consisted of 96- well-microtiter plates containing an insect diet and 15-25 H. virescens eggs.
The compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were sprayed onto the insect diet at 10 pl, using a custom-built micro atomizer, at two replications.
After application, microtiter plates were incubated at about 28±1°C and about 80±5 % relative humidity for 5 days. Egg and larval mortality was then visually assessed. In this test, compounds 1-1 , I-2, I-4, 1-10, and 1-11 , resp., at 2500 ppm showed at least 75% mortality in comparison with untreated controls.
B.5 Boll weevil (Anthonomus grandis)
For evaluating control of boll weevil (Anthonomus grandis) the test unit consisted of 96-well- microtiter plates containing an insect diet and 5-10 A. grandis eggs.
The compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were sprayed onto the insect diet at 5 pl, using a custom-built micro atomizer, at two replications.
After application, microtiter plates were incubated at about 25±1°C and about 75±5 % relative humidity for 5 days. Egg and larval mortality was then visually assessed.
In this test, compounds 1-1 , I-4, I-5, I-6, I-7, I-9, 1-10, 1-11 , 1-12, and 1-13, resp., at 2500 ppm showed at least 75% mortality in comparison with untreated controls.
B.6. Southern armyworm (Spodoptera eridania), 2nd instar larvae
The active compounds were formulated by a Tecan liquid handler in 100% cyclohexanone as a 10,000-ppm solution supplied in tubes. The 10,000-ppm solution was serially diluted in 100% cyclohexanone to make interim solutions. These served as stock solutions for which final dilutions were made by the Tecan in 50% acetone:50% water (v/v) into 10 or 20ml glass vials. A nonionic surfactant (Kinetic®) was included in the solution at a volume of 0.01% (v/v). The vials were then inserted into an automated electrostatic sprayer equipped with an atomizing nozzle for application to plants/insects. Lima bean plants (variety Sieva) were grown 2 plants to a pot and selected for treatment at the 1st true leaf stage. Test solutions were sprayed onto the foliage by an automated electrostatic plant sprayer equipped with an atomizing spray nozzle. The plants were dried in the sprayer fume hood and then removed from the sprayer. Each pot was placed into perforated plastic bags with a zip closure. Ten to 11 armyworm larvae were placed into the bag and the bags zipped closed. Test plants were maintained in a growth room at about 25°C and about 20-40% relative humidity for 4 days, avoiding direct exposure to fluorescent light (14:10 light:dark photoperiod) to prevent trapping of heat inside the bags. Mortality and reduced feeding were assessed 4 days after treatment, compared to untreated control plants.
In this test, compounds 1-1 , I-2, I-3, I-4, I-6, 1-10, and 1-11 , resp., at 300 ppm showed at least 75% mortality in comparison with untreated controls.
B.7 Yellow fever mosquito (Aedes aegypti)
For evaluating control of yellow fever mosquito (Aedes aegypti) the test unit consisted of 96- well-microtiter plates containing 200pl of tap water per well and 5-15 freshly hatched A. aegypti larvae. The active compounds were formulated using a solution containing 75% (v/v) water and 25% (v/v) DMSO. Different concentrations of formulated compounds or mixtures were sprayed onto the insect diet at 2.5pl , using a custom-built micro atomizer, at two replications.
After application, microtiter plates were incubated at 28±1°C, 80±5 % RH for 2 days. Larval mortality was then visually assessed.
In this test, compounds 1-1 , I-2, I-3, I-4, I-6, I-7, 1-10, 1-11 , 1-12, and 1-13, resp., at 2500 ppm showed at least 75% mortality in comparison with untreated controls.

Claims

Claims . Compounds of formula I
Figure imgf000051_0001
wherein
V is O or S and II is N; or
V is N and II is O or S;
R1 is H, OH, Ci-Ce-alkyl, Ci-Ce-haloalkyl, Cs-Ce-cycloalkyl, Cs-Ce-halocycloalkyl, C1-C5- alkoxy, Ci-C4-alkyl-C3-C6-cycloalkyl, Ci-C4-alkyl-C3-C6-halocycloalkyl, which groups are unsubstituted, or partially or fully substituted with R11; or C(=N-R11)R12, C(O)R11a;
R11 is CN, NO2, NR12R13, C(O)NH2, C(S)NH2, C(O)OH, OR14, Si(CH3)3; Ci-C6-al- kyl; Ci-Ce-haloalkyl; C2-Ce-alkenyl; C2-C6-haloalkenyl; C2-Ce-alkynyl; C2-Ce- haloalkynyl; C3-C4-cycloalkyl-Ci-C2-alkyl, which ring is unsubstituted or substituted with 1 or 2 halogen; 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, which rings are unsubstituted or substituted with halogen, Ci-Cs-haloalkyl, and/or CN;
R11a is NR12R13, C(O)NH2, C(S)NH2, C(O)OH, OR14, Si(CH3)3; Ci-C6-haloalkyl; C2- Ce-alkenyl; C2-C6-haloalkenyl; C2-Ce-alkynyl; C2-C6-haloalkynyl; Cs-Ce-cycloal- kyl-Ci-C2-alkyl, which ring is unsubstituted or substituted with 1 or 2 halogen; 3- to 6-membered heterocyclyl, which rings are unsubstituted or substituted with halogen, Ci-Cs-haloalkyl, and/or CN;
R12, R13 are independently from each other H, Ci-C4-alkyl, Ci-C4-alkoxy, C1-C4- haloalkoxy, Ci-C4-haloalkyl, Cs-Ce-cycloalkyl, C(O)-Ci-C4-alkyl, C(O)-Ci-C4- haloalkyl, C(O)-C3-C4-cycloalkyl, C(O)-C3-C4-halocycloalkyl, C(O)NH-CI-C4- alkyl, C(O)NH-Ci-C4-haloalkyl, C(O)N(Ci-C4-alkyl)-Ci-C4-alkyl, C(O)N(CI-C4- haloalkyl)-Ci-C4-alkyl, C(O)N(Ci-C4-haloalkyl)-Ci-C4-haloalkyl, C(O)NH-CI-C4- alkoxy, C(O)NH-Ci-C4-haloalkoxy, C(O)NH-Ci-C4-alkoxy-Ci-C4-alkyl, C(O)NH- Ci-C4-alkoxy-Ci-C4-haloalkyl; C(O)NH-phenyl, C(O)NH-3-6-membered heterocyclyl or 5- or 6-membered hetaryl, C(O)NH-Ci-C4-alkyl-phenyl, C(O)NH-Ci- C4-alkyl-3-6-membered heterocyclyl or 5- or 6-membered hetaryl, which rings are unsubstituted or substituted with halogen, Ci-Cs-haloalkyl, and/or CN; S(O)m-Ci-C4-haloalkyl, S(O)m-C3-C6-cycloalkyl, S(O)m-C3-C6-halocycloalkyl; 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, which rings are unsubstituted or substituted with halogen, Ci-Cs-haloalkyl, and/or CN; or R12 and R13 together with the nitrogen atom they are bound to form a 3-6 membered saturated, partially unsaturated, or aromatic heterocycle, which may contain 1 or 2 additional heteroatoms selected from N, O and S, wherein S may be partially or fully oxidized, and which is unsubstituted or substituted with R3 and/or oxo; or R12and R13 together with the nitrogen atom they are bound to form a group N=S(=O)R14aR14b, wherein R14a and R14b are defined as R14; m is 0, 1 , or 2;
R14 is H, Ci-C4-alkyl, Ci-C4-haloalkyl, Cs-Ce-cycloalkyl, Cs-Ce-halocyclo-alkyl, C3- C4-cycloalkyl-Ci-C2-alkyl, C3-C4-halocycloalkyl-Ci-C2-alkyl, C(O)-Ci-C4-alkyl, C(O)-Ci-C4-haloalkyl, C(O)-C3-C4-cycloalkyl, C(O)-C3-C4-halocycloalkyl, or phenyl which is unsubstituted or partially or fully substituted with R3;
R2 is H, CN, Ci-Cs-alkyl, Ci-Cs-haloalkyl, C2-C3-alkynyl;
R3 is halogen, CN, NO2, Ci-C4-alkyl, Cs-Ce-cycloalkyl, Ci-Ce-haloalkyl, Ci-Ce-halocyclo- alkyl, OR14, S(O)m-R14; wherein rings are unsubstituted or substituted with R3a;
R3a halogen, CN, NO2, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci-C4-alkoxy-Ci-C4-alkyl, C1- C4-haloalkoxy, C3-C4-cycloalkyl, C3-C4-halocycloalkyl, S(O)m-Ci-C4-alkyl, S(O)m-Ci-C4-haloalkyl, S(O)m-C3-C4-cycloalkyl, S(O)m-C3-C4-halocycloalkyl n is 0, 1 , 2, or 3;
R4 is H, halogen, CN, Ci-Ce-alkyl, Cs-Ce-cycloalkyl, Ci-Ce-haloalkyl, Ci-Ce-halocycloal- kyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, each optionally substituted by R41; S(O)m-Ci-C4-alkyl, S(O)m-Ci-C4-haloalkyl, S(O)m-C3-C6-cycloalkyl, S(O)m-C3-Ce- halocycloalkyl, NR12R13, C(O)NR12R13, C(O)OR14, 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, which rings are unsubstituted or substituted with R3;
R41 is H, OR15, NR12R13, CN, Ci-C4-alkyl, Ci-C4-haloalkyl, C3-C6-cycloalkyl, C(O)- Ci-C4-alkyl, C(O)-Ci-C4-haloalkyl, C(O)-C3-C4-cycloalkyl, C(O)-C3-C4-halocy- cloalkyl, C(O)NH-Ci-C4-alkyl, C(O)NH-Ci-C4-haloalkyl, C(O)N(Ci-C4-alkyl)-C C4-alkyl, C(O)N(Ci-C4-haloalkyl)-Ci-C4-alkyl, C(O)N(Ci-C4-haloalkyl)-Ci-C4- haloalkyl, C(O)NH-Ci-C4-alkoxy, C(O)NH-Ci-C4-haloalkoxy, C(O)NH-C C4- alkoxy-Ci-C4-alkyl, C(O)NH-Ci-C4-alkoxy-Ci-C4-haloalkyl; C(O)NH-phenyl, C(O)NH-3-6-membered heterocyclyl or 5- or 6-membered hetaryl, C(O)NH-Ci- C4-alkyl-phenyl, C(O)NH-Ci-C4-alkyl-3-6-membered heterocyclyl or 5- or e- membered hetaryl, which rings are unsubstituted or substituted with halogen, Ci-Cs-haloalkyl, and/or CN; S(O)m-Ci-C4-haloalkyl, S(O)m-C3-C4-cycloalkyl, S(O)m-C3-C4-halocycloalkyl; 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, which rings are unsubstituted or substituted with halogen, Ci-Cs-haloalkyl, and/or CN;
R15 is H, Ci-C4-alkyl, or Ci-C4-haloalkyl, Cs-Ce-cycloalkyl, Ci-Ce-halocycloal- kyl, which carbon chains are unsubstituted or partially or fully substituted with R11; or 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, which rings are unsubstituted or substituted with R3;
W is N and T is CR4a; or
W is CH and T is N; or
W is CH and T is CR4a;
R4a is as defined for R4; and the N-oxides, stereoisomers, and agriculturally or veterinarily acceptable salts thereof.
2. Compounds of formula I according to claim 1 , wherein R1 is H or CH2-CC3H5.
3. Compounds of formula I according to claim 1 or 2, wherein R2 is CH3.
4. Compounds of formula I according to any of claim 1 to 3, wherein R3 is halogen, CN, C1-
C4-haloalkyl, Ci-C4-haloalkoxy, C3-C4-cycloalkyl unsubstituted or substituted with one or more CN, C3-C4-halocycloalkyl, S(O)m-Ci-C4-alkyl, S(O)m-Ci-C4-haloalkyl, S(O)m-C3-C4- cycloalkyl, S(O)m-C3-C4-halocycloalkyl, or
S(O)m-R14, wherein R14 is phenyl, which is partially substituted with R3a.
5. Compounds of formula I according to any of claim 1 to 4, wherein n is 2 and R3 is in positions 3 and 5.
6. Compounds of formula I according to any one of claims 1 to 5, wherein X is CH.
7. Compounds of formula I according to any one of claims 1 to 6, wherein R4 is H, and R4a is H, Ci-Cs-alkyl, Ci-Cs-haloalkyl, Ci-Cs-haloalkoxy, C(O)NH-Ci-Ce-alkyl, C(O)N(Ci-Ce-al- kyl)2, S(O)m-Ci-C4-alkyl, or phenyl unsubstituted or substituted with one or more groups R3 as defined in claim 4.
8. Compounds of formula I according to any one of claims 1 to 6, wherein R4 is H, and R4a is H, CN, halogen preferably Br, C(O)NH2, C(O)NH-Ci-C4-alkyl, and halogenmethoxy preferably OCHF2.
9. Compounds of formula I according to any one of the preceding claims, wherein T is CR4a.
10. Compounds of formula I according to any one of claims 1 to 9, which correspond to formula I.UO
Figure imgf000054_0001
11. Compounds of formula I according to any one of claims 1 to 9, which correspond to formula I. VO
Figure imgf000054_0002
12. Compounds of formula I according to any one of claims 1 to 9, which correspond to formula I. US
Figure imgf000054_0003
13. Compounds of formula I according to any one of the preceding claims, which correspond to formula I.T
Figure imgf000054_0004
14. Compounds of formula I according to any one of the preceding claims, which consist mainly of the isomer I. A.
Figure imgf000055_0001
15. An agricultural or veterinary composition comprising at least one compound according to any one of claims 1 to 14 and/or at least one agriculturally or veterinarily acceptable salt thereof, and at least one inert liquid and/or solid agriculturally or veterinarily acceptable carrier.
16. An agricultural composition for combating animal pests comprising at least one compound as defined in any of claims 1 to 14 and at least one inert liquid and/or solid acceptable carrier and, if desired, at least one surfactant.
17. A method for combating or controlling invertebrate pests, which method comprises contacting said pest or its food supply, habitat or breeding grounds with a pesticidally effective amount of at least one compound as defined in any one of claims 1 to 14.
18. A method for protecting growing plants from attack or infestation by invertebrate pests, which method comprises contacting a plant, or soil or water in which the plant is growing, with a pesticidally effective amount of at least one compound as defined in any of claims 1 to 14.
19. Seed comprising a compound as defined in any of claims 1 to 14, or the enantiomers, diastereomers or salts thereof, in an amount of from 0.1 g to 10 kg per 100 kg of seed.
20. A method for treating or protecting an animal from infestation or infection by invertebrate pests which comprises bringing the animal in contact with a pesticidally effective amount of at least one compound of the formula I as defined in any of claims 1 to 14, a stereoisomer thereof and/or at least one veterinarily acceptable salt thereof.
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