Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
  • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
  • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
  • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
  • A01N43/647—Triazoles; Hydrogenated triazoles
  • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
• • 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
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
  • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
  • A61K31/4965—Non-condensed pyrazines
  • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P33/00—Antiparasitic agents
  • A61P33/10—Anthelmintics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P33/00—Antiparasitic agents
  • A61P33/14—Ectoparasiticides, e.g. scabicides
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
  • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings

Definitions

• the invention also provides agricultural compositions comprising at least one compound of for- mula 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 accepta- ble carrier.
• the invention also provides a veterinary composition comprising at least one compound of for- mula I, a stereoisomer thereof and/or a veterinarily acceptable salt thereof and at least one liq- uid 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 com- prises 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 materi- als (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 effec- tive amount of a compound of formula I or a veterinarily acceptable salt thereof. Bringing the an- imal in contact with the compound I, its salt or the veterinary composition of the invention means applying or administering it to the animal.
• WO 2017/192385, WO2020/070049, WO2021/037614, WO2021/122645, WO2021/068179, and WO2021/069575 describe structurally closely related active compounds. These compounds are mentioned to be useful for combating invertebrate pests.
• R 1 has the meaning as in formula I, and Y is a nucleophilic leav- ing group, such as a halide, preferably Br or Cl.
• Y is a nucleophilic leav- ing group, such as a halide, preferably Br or Cl.
• the alkylation can be effected under standard conditions known from literature. This transformation is usually carried out at temperatures of 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].
• 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 base [cf. A. El-Faham, Chem. Rev. 2011, 6557], or alternatively in two steps by preparation of an intermediate acyl chloride from V under conditions known from literature, e.g. by reaction with thionyl chloride or oxalyl chloride in dimethylformamide (cf.
• Suitable peptide coupling reagents are, for example, dicyclohexylcarbodi- imide, diisopropylcarbodiimide, 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride, or chloro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate, which are commonly used to- gether with catalytic, stoichiometric, excess amounts of additives, such as 1-hydroxybenzotria- zole, 1-hydroxy-7-aza-benzotriazole, 4-(dimethylamino)pyridine, and/or 1-methylimidazole.
• additives such as 1-hydroxybenzotria- zole, 1-hydroxy-7-aza-benzotriazole, 4-(dimethylamino)pyridine, and/or 1-methylimidazole.
• Suitable solvents are halogenated hydrocarbons, such as dichloromethane (DCM) or 1,2-di- chloroethane, ethers, such as diethylether, tetrahydrofurane (THF) or 1,4-dioxane, or high-boil- ing solvents such as dimethylformamide (DMF), preferably DCM or DMF, or in aqueous media.
• DCM dichloromethane
• ethers such as diethylether, tetrahydrofurane (THF) or 1,4-dioxane
• high-boil- ing solvents such as dimethylformamide (DMF), preferably DCM or DMF, or in aqueous media.
• DMF dimethylformamide
• 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 Na 2 CO 3 , K 2 CO 3 , or Cs 2 CO 3 , alkali metal bicarbonates, such as NaHCO 3 , or organic bases, e.g.
• 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 Na 2 CO 3 , K 2 CO 3 , or Cs 2 CO 3
• alkali metal bicarbonates such as NaHCO 3
• organic bases e.g.
• tertiary amines such as triethylamine, diisopropylethylamine, N-methylpi- peridine, or basic aromatic rings, such as pyridine, 2,4,6-collidine, 2,6-lutidine, or 4-(dimethyla- mino)pyridine, or bicyclic amines, such as 1,8-diazabicylo[5.4.0]undec-7-ene (DBU), 1,5-di- azabicyclo[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.
• DBU 1,8-diazabicylo[5.4.0]undec-7-ene
• DBN 1,5-di- azabicyclo[4.3.0]non-5-ene
• DABCO 1,4-diazabicyclo[2.
• 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. 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 rea- gent and a reducing agent [cf. WO2021037614].
• Suitable solvents are alcohols, such as metha- nol, ethanol, n-propanol, 2-propanol, or n-butanol, or water, preferably methanol. It is also possi- ble to use mixtures of the aforementioned solvents.
• Suitable reagents are ammonium acetate (NH 4 Ac), ammonium formate, NH 4 OH, NH 4 Cl, or ammonia.
• Suitable reducing agents are NaBH 3 CN, sodium triacetoxyborohydride, or NaBH 4 . Preference is given to ammonium acetate and NaBH 3 CN, resp.
• Compounds VI are obtainable from compounds VII in a two-step sequence consisting of Stille coupling of VII with an alkoxyalkenylstannane such as VIII followed by hydrolysis of the resulting enol ether moiety to the ketone VI.
• the Stille coupling reaction is usually carried out at temperatures from 50°C to 150°C, prefera- bly from 70°C to 120°C, in an inert solvent in the presence of one or more catalysts and option- ally 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)pal- ladium, and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium, preferably dichlorobis(tri- phenylphosphine)palladium.
• palladium complexes such as tetrakis(triphenylphosphine)palladium, tris(dibenzylideneacetone)dipalladium, palladium diacetate, dichloro-bis(triphenylphosphine)pal- ladium, and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium, preferably dichlorobis(tri- phenylphosphine)
• Suitable optional catalysts are com-mon ligands, such as dicyclohexyl[2′,4′,6′-tris(propan-2-yl)[1,1′-biphenyl]-2-yl]phosphine or tri-phenylphosphine.
• Suita- ble additives are, in general, inorganic compounds, such as cesium fluo-ride and cuprous io- dide. 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.
• the hydrolysis is usually carried out at temperatures from -20°C to 40°C, preferably from 0°C to 25°C, in aqueous acidic media containing aqueous HCl at concentrations between 0.5M and 3M and optionally containing an organic solvent such as acetonitrile, acetone, THF, or methanol (cf H. Lin et al., Bioorg Med Chem Lett 2010, 679).
• Compounds VII are obtainable from triazoles IX.
• group Z is a leaving group, e.g. a halide, such as I, Br, and Cl, or a sulfonate, such as triflate or mesylate.
• This transformation is usually carried out at temperatures from 0°C to 100°C, preferably from 10°C to 60°C, in an inert solvent and in the presence of a base [cf. J. Bradshaw et al., J. Hetero- cycl. Chem.1986, 361].
• Suitable solvents are halogenated hydrocarbons, such as DCM, 1,2- dichloroethane, or chloroform, ethers, such as diethylether, tert-butylmethylether, dioxane, or THF, nitriles, such as acetonitrile or propionitrile, alcohols, such as methanol or ethanol, and po- lar aprotic solvents, such as dimethyl sulfoxide (DMSO), DMF, or dimethylacetamide (DMA), preferably acetonitrile. It is also possible to use mixtures of the aforementioned solvents.
• DMSO dimethyl sulfoxide
• DMA dimethylacetamide
• Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal hydrides, such as NaH, KH, alkali metal and alkaline earth metal carbonates, such as Na 2 CO 3 , K 2 CO 3 , or Cs 2 CO 3 , alkali metal bicarbonates, such as NaHCO 3 , or organic bases, e.g. tertiary amines such as triethylamine or diisopropylethylamine. Preference is given to K 2 CO 3 .
• the bases are generally employed in equimolar amounts; however, they can also be used in excess or, if appropriate, as solvent.
• the starting materials are generally reacted with one another in equimolar amounts.
• Triazole IX is obtainable from compound XI by reaction with 1 to 1.5 equivalents of hydrazine hydrate XII in acetic acid (AcOH) as solvent, optionally using an alcohol, such as methanol, eth- anol, or 2-propanol, or an ether, such as 1,4-dioxane, as a cosolvent, at temperatures from 25°C to 110°C, as known from literature (cf. Lin et al, J. Org. Chem.1979, 4160; Wrobleski et al, J. Med. Chem.2019, 8973).
• compounds VII can be directly obtained from com- pound XI by reaction with a substituted hydrazine of the type R 4 NH-NH 2 .
• Compound XI is obtainable from commercially available 3-chloropyrazine-2-carboxamide (XII) by reaction with N,N-dimethylformamide dimethyl acetal (DMFDMA). This transformation is usually carried out using 1.5 to 3 equivalents of DMFDMA at tempera- tures from 0°C to 100°C, preferably from 25°C to 90°C, in an inert solvent [cf. Lin et al, J. Org. Chem.1979, 4160; Wrobleski et al, J. Med. Chem.2019, 8973].
• Suitable solvents are halogen- ated hydrocarbons, such as DCM and 1,2-dichloroethane, ethers, such as THF, aromatic sol- vents, such as toluene, and polar aprotic solvents, such as DMSO, preferably DCM.
• halogen- ated hydrocarbons such as DCM and 1,2-dichloroethane
• ethers such as THF
• aromatic sol- vents such as toluene
• polar aprotic solvents such as DMSO, preferably DCM.
• Intermediate compounds (Int) are novel.
• the variables in formula (Int) are as defined for formula I.
• reaction mixtures are worked up in a customary manner, e.g. by mixing with water, ex- tracting with an appropriate organic solvent, separating the phases and, if appropriate, chroma- tographic 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 pre- pared by derivatization of other compounds I.
• radical partially or fully substituted by a radical means that in general the group is substi- tuted with same or different radicals.
• halogen denotes in each case fluorine, bromine, chlorine, or iodine, in particular flu- orine, chlorine, or bromine.
• 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, pref- erably 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, 2-butyl, iso-butyl, tert-butyl, n-pentyl, 1-methylbutyl, 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,
• haloalkyl as used herein and in the haloalkyl moieties of haloalkylcarbonyl, haloal- koxycarbonyl, haloalkylthio, haloalkylsulfonyl, haloalkylsulfinyl, haloalkoxy and haloalkoxyalkyl, denotes in each case a straight-chain or branched alkyl group having usually from 1 to 10 car- bon 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 C 1 -C 4 -haloalkyl, more preferably from C 1 -C 3 -haloalkyl or C 1 -C 2 -haloalkyl, in particular from C 1 -C 2 -fluoroalkyl such as fluoromethyl, difluoromethyl, trifluo- romethyl, 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, fre- quently 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 com- prising 1 to 4, preferably 1 or 2 carbon atoms as defined above. Examples are CH 2 OCH 3 , CH 2 - OC 2 H 5 , 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.
• haloalkoxy moieties include C 1 -C 4 - haloalkoxy, in particular C 1 -C 2 -fluoroalkoxy, such as fluoromethoxy, difluoromethoxy, trifluoro- methoxy, 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, penta- fluoroethoxy and the like.
• C 1 -C 4 - haloalkoxy in particular C 1 -C 2 -fluoroalkoxy, such as fluoromethoxy, difluoromethoxy, trifluoro- methoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoro
• 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, bro- mine 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 singly unsaturated hydrocarbon rad- ical having usually 2 to 10, frequently 2 to 6, preferably 2 to 4 carbon atoms, e.g.
• 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 singly unsaturated hydrocarbon rad- ical having usually 2 to 10, frequently 2 to 6, preferably 2 to 4 carbon atoms, e.g. ethynyl, pro- pargyl (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 cycloal- kylthio denotes in each case a monocyclic cycloaliphatic radical having usually from 3 to 10 or from 3 to 6 carbon atoms, such as cyclopropyl (cC 3 H 5 ), cyclobutyl (cC 4 H 7 ), cyclopentyl (cC 5 H 9 ), cyclohexyl (cC 6 H 11 ), cycloheptyl, cyclooctyl, cyclononyl and cyclodecyl or cyclopropyl, cyclobu- tyl, 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-tetrafluo- rocyclpropyl, 1- and 2-chlorocyclopropyl, 1,2-, 2,2- and 2,3-dichlorocyclopropyl, 1,2,2-trichloro- cyclopropyl, 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.
• cycloalkenyl as used herein and in the cycloalkenyl moieties of cycloalkenyloxy and cycloalkenylthio denotes in each case a mono- or bicyclic, preferably monocyclic, singly unsatu- rated non-aromatic 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. Examples are cyclopenten-1-yl, and cyclohexen-1-yl.
• halocycloalkenyl as used herein and in the halocycloalkenyl moieties of halocyclo- alkenyloxy and halocycloalkenylthio denotes in each case a monocyclic singly unsaturated non- aromatic 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.
• heterocyclic non-aromatic radicals usually comprise 1, 2, 3, 4 or 5, preferably 1, 2 or 3 heteroa- toms selected from N, O, and S as ring members, wherein S-atoms as ring members may be present as S, SO, or SO 2 .
• Examples of 5- or 6-membered heterocyclic radicals comprise satu- rated 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-oxodihydrothienyl, S-dioxodihydrothienyl, oxazolidinyl, oxazolinyl, thi- azol
• heterocyclic ring also comprising 1 or 2 car- bonyl groups as ring members
• ring members comprise pyrrolidin-2-onyl, pyrrolidin-2,5-dionyl, imidazolidin-2- onyl, oxazolidin-2-onyl, thiazolidin-2-only, and the like.
• heteroaryl 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.
• 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, benzo- thienyl, indolyl, indazolyl, benzimidazolyl, benzoxathiazolyl, benzoxadiazolyl, benzothiadiazolyl, benzoxazinyl, chinolinyl, isochinolinyl, purinyl, 1,8-naphthyridyl, pteridyl, pyrido[3,2-d]pyrimidyl or pyridoimidazolyl and the like.
• 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, cy- cloalkenyl, 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 respec- tive group, so that they represent a linker between two moieties of the molecule.
• 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 par- ticular 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 particularly preferred embodiments of the intermediates cor- respond to those of the compounds of the formula I.
• 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 ni- trogen 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 H, C 1 -C 6 -alkyl, C 3 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, or C 1 -C 4 -alkyl-C 3 -C 6 -cycloalkyl.
• R 2 is CH 3 .
• X is preferably CH or CR 3 , particularly CH. Such compounds correspond to Formula I.1 In another embodiment X is N. Such compounds correspond to formula I.2.
• R 3 is preferably halogen, CN, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkoxy, C 3 -C 4 -cycloalkyl unsubsti- tuted or substituted with one or more CN, C 3 -C 4 -halocycloalkyl, S(O) m -C 1 -C 4 -alkyl, S(O) m -C 1 -C 4 - haloalkyl, S(O) m -C 3 -C 4 -cyclo ⁇ alkyl, S(O) m -C 3 -C 4 -halocyclo ⁇ alkyl.
• Index m in R 3 is preferably 2.
• Index n is preferably 2.
• R 3 is preferably halogen, CN, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkoxy, C 3 - C 4 -cycloalkyl unsubstituted or substituted with one or more R 3a , wherein R 3a is preferably CN, OH, C 1 -C 4 -alkoxy.
• 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, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkoxy, C 3 - C 4 -cycloalkyl, C 3 -C 4 -halocycloalkyl, S(O) m -C 1 -C 4 -alkyl, S(O) m -C 1 -C 4 -haloalkyl, S(O) m -C 3 -C 4 -cy- cloalkyl, S(O) m -C 3 -C 4 -halocycloalkyl, or S(O)m-R 14 , wherein R 14 is phenyl, which is partially substituted with R 3a .
• R 3 is halogen, CN, NO 2 , C 1 -C 4 -alkyl, C 3 -C 6 - cycloalkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -halocycloalkyl, OR 14 , S(O) m -R 14 ; wherein rings are unsubsti- tuted or substituted with R 11 .
• R 4 is preferably C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, CH 2 C(O)NH-C 1 -C 6 -al- kyl, S(O) m -C 1 -C 4 -alkyl, or phenyl unsubstituted or substituted with one or more groups R 3 .
• preference is given to the compounds of formula I com- piled in the tables below, which compounds correspond to formula I.1* ,and I.2*, resp..
• 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), emulsifia- ble 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 formula- tions for the treatment of plant propagation materials e.g. seeds (e.g. GF).
• compositions types are defined in the “Catalogue of pesticide formulation types and interna- tional coding system”, Technical Monograph No.2, 6th Ed. May 2008, CropLife International.
• Suitable auxiliaries are solvents, liquid carriers, solid carriers or fillers, surfactants, disper- sants, emulsifiers, wetters, adjuvants, solubilizers, penetration enhancers, protective colloids, adhesion agents, thickeners, humectants, repellents, attractants, feeding stimulants, compatibil- izers, 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 am- photeric surfactants block polymers, polyelectrolytes.
• Such surfactants can be used as emulsi- fier, dispersant, solubilizer, wetter, penetration enhancer, protective colloid, or adjuvant.
• Surfac- tants 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.
• Suit- able 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 be- tween 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).
• compositions according to the invention 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 agrochem- ical composition is made up with water, buffer, and/or further auxiliaries to the desired applica- tion 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.
• the invention also relates to a plant protection method, which comprises con- tacting 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.
• the compounds I are effective through both contact and ingestion to any and all developmen- tal 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 di- rectly 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 / 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, nectar- ines, almonds, cherries, papayas, strawberries, raspberries, blackberries or gooseberries; legu- minous plants, e.g.
• 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
• fi- ber plants e.g. cotton, flax, hemp, or jute
• citrus fruit e.g. oranges, lemons, grapefruits or man-structures
• vegetables e.g. eggplant, spinach, lettuce (e.g.
• iceberg lettuce chicory, cabbage, as- paragus, cabbages, carrots, onions, garlic, leeks, tomatoes, potatoes, cucurbits or sweet pep- pers; 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.
• 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
• coffee tea
• bananas vines
• hop sweet leaf
• Pre- ferred 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 or- ganism.
• 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 accord- ing to the prevailing conditions e.g. desired pesticidal effect and duration, weather, target spe- cies, locus, mode of application.
• desired pesticidal effect and duration e.g. desired pesticidal effect and duration, weather, target spe- cies, locus, mode of application.
• the rate of application of the active in- gredients 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, aero- sol, 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 tar- gets, 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, ter- mites 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 citri; 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.
• 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.
• the invention also relates to the use of a compound of the in- vention 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, topi- cally 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 treat- ing 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 in- fection 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 para- sites in and on animals.
• the invention relates to a method of combating or control- ling 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 combat- ing parasites.
• the invention relates to a non-therapeutic method of combating or con- trolling 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).
• the compounds I can be ap- plied 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 environ- ment 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, rab- bits, goats, dogs and cats, water buffalo, donkeys, fallow deer and reindeer, and also in furbear- ing 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, prefera- bly 1 mg/kg to 50 mg/kg per day.
• the compounds I may be formulated as ani- mal feeds, animal feed premixes, animal feed concentrates, pills, solutions, pastes, suspen- sions, 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, pow- ders, 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 com- pound penetrating the skin and acting systemically. Pour-on formulations are prepared by dis- solving, 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 excipi- ents, 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 ecto- parasites, 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.
• 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 particu- larly 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 UHPLC + Shimadzu LCMS-2020, ESI; Column: Phenom- enex Kinetex 1.7 ⁇ m XB-C18100A, 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 C18.5 ⁇ m 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.
• HPLC/MS Agilent 1260 HPLC MSD: 6125B single quadrupole MSD; Column: Luna C182.0x50mm 5 ⁇ m; Mobile phase: A: 0.04% TFA in water; B: 0.02% TFA in ACN; Tempera- ture: 40°C; Gradient: 5% B for 0.4min; 5% B to 95% B in 2.6 min; 95% B for 1 min; 95% B to 5% B in 0.01min; 5% B for 0.5min; Flow: 1.0mL/min; MS: ES-API positive; Mass range: 100–1000.
• Example 1 Preparation of 3-bromo-N-[1-[3-[1-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]pyrazin-2- yl]ethyl]-5-(trifluoromethyl)benzamide [I1-1]
• Step 1 Synthesis of (N)-3-chloro-N-(dimethylaminomethylene)pyrazine-2-carboxamide To a solution of 3-chloropyrazine-2-carboxamide (3g, 0.0191mol) in DCM (30mL) was added DMF-dimethyl acetal (4.5g, 0.0382mol) at 20°C.
• Step 2 Synthesis of 2-chloro-3-(1H-1,2,4-triazol-3-yl)pyrazine To a solution of (N)-3-chloro-N-(dimethylaminomethylene)pyrazine-2-carboxamide (3g, 0.0141mol) in 1,4-dioxane (30mL) was added NH 2 NH 2 xH 2 O (1.4g, 0.0283mol) and AcOH (30mL) at 20°C.
• Step 3 Synthesis of 2-chloro-3-[1-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]pyrazine
• 2-chloro-3-(1H-1,2,4-triazol-3-yl)pyrazine 1.6g, 0.0088mol
• MeCN MeCN
• 2,2,2-trifluoroethyl trifluoromethanesulfonate 2.45g, 0.0106mol
• K 2 CO 3 2.276g, 0.0176mol
• Step 4 Synthesis of 2-(1-ethoxyvinyl)-3-[1-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]pyrazine
• 2-chloro-3-[1-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]pyrazine (3.8g, 0.0144mol) in toluene (100mL) was added tributyl(1-ethoxyvinyl)stannane (5.21g, 0.0144mol) and Pd(PPh 3 ) 2 Cl 2 (1g) at 25°C.
• the reaction mixture was stirred for 12h at 110°C. LCMS showed the reaction was completed.
• Step 5 Synthesis of 1-[3-[1-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]pyrazin-2-yl]ethanone
• 2-(1-ethoxyvinyl)-3-[1-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]pyrazine 3.g, 0.0103mol
• THF aqueous HCl
• LCMS showed the reaction was completed.
• the reaction mixture was diluted with H 2 O (50mL), extracted with EtOAc (3x20 mL).
• Step 6 Synthesis of 1-[3-[1-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]pyrazin-2-yl]ethanamine
• NH 4 OAc 3.69g, 48mmol
• NaBH 3 CN 602mg, 9.59mmol
• reaction mixture was concentrated and quenched with H 2 O (50mL), the pH was adjusted to pH ⁇ 10 with aq. NaOH.
• the mixture was extracted with DCM/iPrOH (3/1, 3x20mL), the combined organic phases were dried over Na 2 SO 4 and concen- trated to give crude 1-[3-[1-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]pyrazin-2-yl]ethanamine (500mg, crude), which was used in the next step without further purification.
• Step 7 Synthesis of 3-bromo-N-[1-[3-[1-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]pyrazin-2- yl]ethyl]-5-(trifluoromethyl)benzamide
• 3-bromo-5-(trifluoromethyl)benzoic acid 0.94g, 0.00184mol
• MeCN MeCN
• N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate 0.73g, 0.00276mol
• N-methylimidazole 0.53g, 0.0055mol
• 1-[3-[1-(2,2,2-trifluoroethyl)-1,2,4-tria- zol-3-yl]pyrazin-2-yl]ethanamine 0.5g, 0.00184mol
• Example 2 Preparation of 2,6-dichloro-N-[1-[3-(1-phenyl-1,2,4-triazol-3-yl)pyrazin-2- yl]ethyl]pyridine-4-carboxamide [I2-1]
• Step 1 Preparation of 2-chloro-3-[1-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]pyrazine
• 3-chloro-N-(dimethylaminomethylene)pyrazine-2-carboxamide (84g, 376.2mmol) in 1,4-dioxan (840ml) was added [(4-methoxyphenyl)methylamino]ammonium chlo- ride (142g, 752.4mmol) at 15°C and stirred for 30min.
• Step 2 Preparation of 1-[3-[1-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]pyrazin-2-yl]etha- none: To a solution of a mixture of 2-chloro-3-[1-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]py- razine and 2-chloro-3-[2-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]pyrazine (66g, 218.7mmol) in DMF was added Pd(PPh 3 ) 2 Cl 2 (15.3g, 21.87mmol) and tributyl(1-ethoxyvinyl)stannane (18.5g, 328.1mmol) at 15°C.
• reaction mixture was heated to 100°C and stirred for 16h. TCL (EtOAc) showed that the reaction was completed.
• the reaction mixture was poured into KF (aq. sat, 1L) and stirred for 2.5h. The mixture was filtered and the filtrate was extracted with EtOAc (3x1L). The combined organic phase was dried over Na 2 SO 4 , filtered and concentrated under reduced pressure.
• Step 3 Preparation of 1-[3-(1H-1,2,4-triazol-3-yl)pyrazin-2-yl]ethanone: A solution of 1-[3-[1- [(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]pyrazin-2-yl]ethanone and 1-[3-[2-[(4-methoxy- phenyl)methyl]-1,2,4-triazol-3-yl]pyrazin-2-yl]ethanone (5.7g, 18.43mmol) in TFA (57ml) was stirred at 80°C for 16h. LC-MS showed the reaction was completed.
• Step 5 Preparation of 1-[3-[1-(4-aminophenyl)-1,2,4-triazol-3-yl]pyrazin-2-yl]ethanone: To a solution of 1-[3-[1-(4-nitrophenyl)-1,2,4-triazol-3-yl]pyrazin-2-yl]ethanone (4.4g, 14.18mmol) in MeOH (45ml) was added SnCl 2 (8.067g, 42.54mmol) at 15°C. The reaction mixture was heated to 80°C and stirred for 3h. LC-MS showed the reaction was completed. The mixture was con- centrated and then quenched with water (20ml). The pH was adjusted to pH ⁇ 9 with NaOH (aq.
• Step 6 Preparation of 1-[3-(1-phenyl-1,2,4-triazol-3-yl)pyrazin-2-yl]ethanone: To a solution of 1-[3-[1-(4-aminophenyl)-1,2,4-triazol-3-yl]pyrazin-2-yl]ethanone (720mg, 2.57mmol) in DMF (8mL) was added NaNO 2 (355mg, 5.14mmol) and Et 2 O . BF 3 (725mg, 5.14mmol) at 15°C. The reaction mixture was heated to 50°C and stirred for16h. LC-MS showed reaction was com- pleted.
• Step 7 Preparation of 1-[3-(1-phenyl-1,2,4-triazol-3-yl)pyrazin-2-yl]ethanamine: To a solution of 1-[3-(1-phenyl-1,2,4-triazol-3-yl)pyrazin-2-yl]ethenone (450mg, 1.70mmol) in MeOH (30mL) was added NH 3 in MeOH (7M, 6mL) and NH 4 OAc (1.308g, 17.0mmol) at 15°C. The reaction mixture was stirred for 3h. Then the mixture was heated to 50°C and stirred for 16h. LC-MS showed the reaction was completed.
• Step 8 Preparation of 2,6-dichloro-N-[1-[3-(1-phenyl-1,2,4-triazol-3-yl)pyrazin-2-yl]ethyl]pyri- dine-4-carboxamide [I2-1]: To a solution of 1-[3-(1-phenyl-1,2,4-triazol-3-yl)pyrazin-2-yl]ethana- mine (433mg, 2.53mmol) in ACN (4mL) was added NMI (370mg, 4.506mmol) and TCFH (631mg, 2.253mmol) at 15°C.
• Example 3 Preparation of 3-chloro-N-[1-[3-[1-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]py- razin-2-yl]ethyl]-5-(trifluoromethyl)benzamide [I1-4]
• Step 1 Preparation of 1-[3-[1-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]pyrazin-2-yl]ethana- mine To a solution of 1-[3-[1-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]pyrazin-2-yl]ethanone and 1-[3-[2-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]pyrazin-2-yl]ethanone (10g, 32.4mmol) in MeOH (1L) was added NH 3 in MeOH (7M, 100mL
• Step 2 Preparation of 3-chloro-N-[1-[3-[1-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]pyrazin- 2-yl]ethyl]-5-(trifluoromethyl)benzamide (I1-4)
• TEA 6.5g, 64.4mmol
• HATU HATU (18.4g, 48.4mmol
• Example 5 Preparation of 3-chloro-N-[1-[3-[1-(3,3-dichloroallyl)-1,2,4-triazol-3-yl]pyrazin-2- yl]ethyl]-5-(trifluoromethyl)benzamide [I1-11] To a solution of 3-chloro-N-[1-[3-(1H-1,2,4-triazol-3-yl)pyrazin-2-yl]ethyl]-5-(trifluorome- thyl)benzamide (1g, 2.52mmol) in ACN (20mL) was added 1,1,3-trichloroprop-1-ene (367mg, 5.04mmol) and K 2 CO 3 (696mg, 5.04mmol) at 20°C.
• Example 6 Preparation of 3-chloro-N-[1-[3-(1-isopropyl-1,2,4-triazol-3-yl)pyrazin-2-yl]ethyl]-N- methyl-5-methylsulfonyl-benzamide [I1-5] To a solution of 3-chloro-N-[1-[3-(1-isopropyl-1,2,4-triazol-3-yl)pyrazin-2-yl]ethyl]-5-methyl- sulfonyl-benzamide (I1-7, 300mg, 0.67mmol) in DMF (5mL) was added NaH (24mg, 1mmol) portionwise at 0°C.
• test solutions were prepared as follow: The active compound was dissolved at the desired concentration in a mixture of 1:1 (vol:vol) distilled water : acetone. The test solution was prepared on the day of use. The activity of the compounds of formula I of the present invention can be demonstrated and evaluated by the following biological tests.
• B.1 Green Peach Aphid Myzus persicae
• 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.
• aphid diet us- ing a custom built pipetter, at two replications.
• 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.
• B.3 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 ⁇ l, using a custom-built micro atomizer, at two replications. After application, microtiter plates were incubated at about 25 ⁇ 1°C and about 75 ⁇ 5 % rela- tive humidity for 5 days. Egg and larval mortality was then visually assessed.
• Test plants were maintained in a growth room at about 25oC 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 re- prised feeding were assessed 4 days after treatment, compared to untreated control plants. In this test, compounds I1-1, I1-2, I1-3, I1-4, I1-5, I1-6, I1-7, I1-8, I1-10, I1-12, I1-13, and I1-14, resp., at 300 ppm at least 75 % mortality in comparison with untreated controls.
• B.5 Yellow fever mosquito (Aedes aegypti)
• the test unit consisted of 96- well-microtiter plates containing 200 ⁇ l 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 2.5 ⁇ l, 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.
• Treated petals are placed into individual re-sealable plastic along with about 20 adult thrips. All test arenas are held under dark condition and a temperature of about 28°C for duration of the assay. The per- cent mortality is recorded 72 hours after treatment.
• B.7 APHICR Black bean aphid; Aphis craccivora
• the active compound is dissolved at the desired concentration in a mixture of 1:1 (vol:vol) dis- tilled water : acetone.
• Surfactant Ker
• the test solution is prepared at the day of use.
• Potted (Kord traditional square pots Size 3” and 2.5” in depth) bush beans are cleaned with the apical leaves removed using pointed forceps, leaving only the cotyledon leaves. Plants are inoculated with about 30 mixed-stage aphid colony 24 hours before spraying. Potted bean plants are sprayed with the test solutions using a DeVilbiss hand atomizer (20-30 psi). Treated plants are allowed to air-dry in the laboratory for about an hour before placing them inside the holding room maintained at 27°C, 50% RH and 72 hours light conditions. Stem of the treated bean plants are inserted in the slit of cut circle filter paper to catch the falling dead aphids. As- sessment of population reduction (% mortality) is done after 72 hours. The tables show % mortality in comparison to untreated controls.

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