Patent Application
20250107528
The invention relates to compounds of formula I
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 2017/192385, WO2020/070049, WO2020/201079, WO2020/201398, WO2020/208036, WO2021/037614, WO2021/122656, WO2021/068179, and WO2021/069575 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 A wherein R4 is bound via O or N (compounds of formula A.a) can be prepared from the corresponding compounds II by a carbonylation reaction, using 0.01 to 0.2 equivalents of a palladium complex, such as palladium diacetate, bis(benzonitrile)dichloropalladium, bis(dibenzylideneacetone)palladium, or tris(dibenzylideneacetone)dipalladium, and 0.01 to 0.2 equivalents of a ligand, such as triphenylphosphine, 1,1-bis(diphenylphosphino)ferrocene, or 1,3-bis(diphenylphosphino)propane, as catalysts, in the presence of 1 to 5 equivalents of a suitable nucleophilic reagent, such as an alcohol or a primary or a secondary amine, in an inert solvent such as toluene, xylenes, mesitylene, MeCN, tetrahydrofurane (THF), 1,4-dioxane, dimethylsulfoxide (DMSO), or optionally using the nucleophilic reagent as the solvent, and optionally in the presence of additives such as triethylamine, diisopropylethylamine, NaOAc, KOAc, CsOAc, Na2CO3, K2CO3, Cs2CO3, NaHCO3, KHCO3, and/or molecular sieves, at temperatures between 25° C. and 180° C., preferably between 25° C. and the boiling point of the solvent, and in the presence of carbon monoxide gas at pressures between 1 and 50 bar (cf. Beller et al., Angew. Chem. Int. Ed. 2009, 4114 (and references therein); Takeuchi et al., J. Mol. Catal. 1991, 277). In addition, using similar catalysts and additives as above, compounds I wherein X is 0 and R4 is C-bound can be obtained from the corresponding compounds II by Stille reactions with alkoxyalkenylstannanes and subsequent enol ether hydrolysis (cf. H. Lin et al., Bioorg Med Chem Lett 2010, 679; Eastwood et al., Bioorg Med Chem Lett 2010, 1697). In compounds A the variables are as defined for formula I. Compounds II are known from WO2020070049.
Compounds I can be obtained by condensation of a compound A, with an amine, hydroxylamine, hydrazine, or derivatives thereof, in a solvent such as (or solvent mixture composed of) dichloromethane (DCM), chloroform, benzene, toluene, xylenes, mesitylene, 1,4-dioxane, methanol, ethanol, 2-propanol, and/or water, at temperatures from 0° C. to the boiling point of the solvent or solvent mixture, and optionally with concomitant water removal, e.g. by using a Dean-Stark apparatus, or molecular sieves, or salts such as MgSO4 or Na2SO4, and optionally in the presence of 0.05 to 1 equivalent of an additive such as formic acid, acetic acid, hydrochloric acid, p-toluenesulfonic acid, NaOAc, KOAc, NaOH, or KOH (cf. G. Heinisch et al., Heterocycles 1996, 151; J. Liu, Bioorg Med Chem 2008, 1096, provided that R4 is not 0- or N-bound).
In general, compounds I wherein R5 is OH (compounds of formula I.d) can be converted to the corresponding compounds I wherein R5 is OR15 (compounds of formula I.e) with alkylating reagents such as alkyl halides, alkyl tosylates, or alkyl mesylates and following procedures known from literature (cf. Khomutov et al., Amino Acids 2010, 38, 509; Abele et al., Synthetic Communications 1998, 28, 2621; Kocak et al., Synthetic Communications 2007, 37, 1155).
Compounds I wherein R4 is NH2 (compounds of formula I.b1) can be obtained from compounds Ill by addition of a suitable nucleophile, such as hydroxylamine, hydrazine, or a derivative thereof, optionally in the presence of 1 to 2 equivalents of a base such as NaOH, KOH, Na2CO3, K2CO3, or Cs2CO3, and in a solvent such as (or solvent mixture composed of) methanol, ethanol, 2-propanol, and/or water, and at temperatures ranging from 0° C. to the boiling point of the solvent or solvent mixture (cf. Tiemann, Chem. Ber. 1884, 17, 126; Gobis et al., Acta Pol Pharm (Drug Research) 2006, 39).
Compounds III can be obtained by reaction of compounds II with 1 to 2 equivalents of Zn(CN)2 in the presence of 0.01 to 0.2 equivalents of a transition-metal complex, such as palladium diacetate, palladium trifluoroacetate, tris(dibenzylideneacetone)dipalladium, tetrakis(triphenylphosphine)palladium, or nickel dichloride, and 0.01 to 0.2 equivalents of a ligand, such as 2-[di(tertbutyl)phosphino]-1,1′-binaphthyl, 1,1-bis(diphenylphosphino)ferrocene, or BINAP, as catalysts, and 0.1 to 0.5 equivalents of zinc powder or zinc flakes as a cocatalyst, and optionally with 1 to 3 equivalents of a base, such as 4-(dimethylamino)pyridine or sodium tert-butoxide, in a solvent such as dimethylformamide (DMF), N,N-dimethylacetamide (DMA), or acetonitrile, at temperatures between 25° C. and 150° C., preferably between 25° C. and the boiling point of the solvent (cf. A. Littke et al., Org. Lett. 2007, 1711).
Compounds I wherein R5 is OR15 and R4 is NH2 (compounds I.e1) can be converted to compounds I wherein R5 is OR15 and R4 is NR12R13 (compounds i.e2) in two steps by reaction with sodium nitrite in aqueous HCl followed by substitution of the chloride with HNR12R13 (cf. K. Gobis et al., Acta Pol Pharm (Drug Research) 2006, 39; A. M. Martsynkevich et al., Russ. Chem. Bull. Int. Ed. 2011, 521).
If individual compounds I cannot be obtained by the routes described above, they can be prepared by derivatization of other compounds I.
The reaction mixtures are worked up in a customary manner, for example by mixing with water, extracting with an appropriate organic solvent, 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.
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, 2-butyl, iso-butyl, tert-butyl, npentyl, 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-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 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 C1-C4-haloalkyl, more preferably from C1-C3-haloalkyl or C1-C2-haloalkyl, in particular from C1-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 C1-C2-fluoroalkoxy, such as fluoromethoxy, difluoromethoxy, trifluoromethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoro-ethoxy, 2,2dichloro-2-fluoromethoxy, 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 (=C1-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)—C1-C6-alkyl), as used herein refers to a straightchain or branched saturated alkyl group (as mentioned above) having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms (=C1-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 (=C1-C4-alkylsulfonyl), 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 singly unsaturated hydrocarbon radical 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 singly unsaturated hydrocarbon radical 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 mono- or bicyclic, preferably 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 (cC6H11), 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 mono- or bicyclic, preferably 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-fluorocyclopropyl, 1,2-, 2,2- and 2,3-difluorocyclopropyl, 1,2,2-trifluorocyclopropyl, 2,2,3,3-tetrafluorocyclpropyl, 1- and 2-chlorocyclopropyl, 1,2-, 2,2- and 2,3-dichlorocyclopropyl, 1,2,2-trichlorocyclopropyl, 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-dichlorocyclopentyl and the like.
The term “cycloalkenyl” as used herein and in the cycloalkenyl moieties of cycloalkenyloxy and cycloalkenylthio denotes in each case a mono- or bicyclic, preferably 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. Examples are cyclopenten-1-yl, and cyclohexen-1-yl.
The term “halocycloalkenyl” as used herein and in the halocycloalkenyl moieties of halocycloalkenyloxy and halocycloalkenylthio denotes in each case a mono- or bicyclic, preferably 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.
The term “cycloalkenylalkyl” refers to a cycloalkenyl group as defined above which is bonded via an alkyl group, such as a C1-C5-alkyl group or a C1-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-dioxothiolanyl, dihydrothienyl, S-oxodihydrothienyl, S-dioxodihydrothienyl, oxazolidinyl, oxazolinyl, thiazolinyl, oxathiolanyl, piperidinyl, piperazinyl, pyranyl, dihydropyranyl, tetrahydropyranyl, 1,3- and 1,4-dioxanyl, thiopyranyl, S.oxothiopyranyl, S-dioxothiopyranyl, dihydrothiopyranyl, S-oxodihydrothiopyranyl, S-dioxodihydrothiopyranyl, tetrahydrothiopyranyl, S-oxotetrahydrothiopyranyl, S-dioxotetrahydrothiopyranyl, morpholinyl, thiomorpholinyl, S-oxothiomorpholinyl, S-dioxothiomorpholinyl, 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-membered 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]oxadiazolyl, 4- or 5-(1,2,3-oxadiazol)yl, 3- or 5-(1,2,4-oxadiazol)yl, 2- or 5-(1,3,4-thiadiazol)yl, thiadiazolyl, 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, triazolyl, 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 tetrazolyl, 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 C1-C5-alkyl group or a C1-C4-alkyl group, in particular a methyl group (=heterocyclylmethyl or hetarylmethyl, 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 C1-C5-alkyl group or a C1-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.
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.
Preferably R1 is H, C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C3-C6-cycloalkyl, or C1-C4-alkyl-C3-C6-cycloalkyl. Particularly R1 is H or CH2-cC3H5.
Preferably R2 is CH3.
R3 is preferably halogen, CN, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C4-cycloalkyl, C3-C4-halocycloalkyl, S(O)m—C1-C4-alkyl, S(O)m—C1-C4-haloalkyl, S(O)m—C3-C4-cycloalkyl, S(O)m—C3-C4-halocycloalkyl. Index m in R3 is preferably 2. Index n is preferably 2.
In one embodiment Q is CH or CR3, preferably CH. Such compounds correspond to formula I.1
In another embodiment Q is N. Such compounds correspond to formula I.2
R3 groups stand preferably in positions 3 and 5.
In another embodiment R3 is preferably halogen, CN, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C4-cycloalkyl, C3-C4-halocycloalkyl, S(O)m—C1-C4-alkyl, S(O)m—C1-C4-haloalkyl, S(O)m—C3-C4-Cycloalkyl, S(O)m—C3-C4-halocycloalkyl, or
In another embodiment of formula I compounds R3 is halogen, CN, NO2, C1-C4-alkyl, C3-C6-cycloalkyl, C1-C6-haloalkyl, C1-C6-halocycloalkyl, OR14, S(O)m—R14; wherein rings are unsubstituted or substituted with R11.
In another embodiment of formula I compounds R3 is halogen, CN, NO2, C1-C4-alkyl, C3-C6-cycloalkyl, C1-C6-haloalkyl, C1-C6-halocycloalkyl, OR14, S(O)m—R14; wherein rings are unsubstituted or substituted with one or more CN, OH, C1-C4-alkoxy.
In another embodiment of formula I compounds R3 is C3-C6-cycloalkyl unsubstituted or substituted with one or more CN, OH, C1-C4-alkoxy.
R4 is preferably H, C1-C3-alkyl, or C1-C3-haloalkyl.
In another embodiment R4 is H, C1-C3-alkyl, C1-C3-haloalkyl, or NR12R13 wherein R12 and R13 are independently from each other H or C1-C3-alkyl.
R5 is preferably OH, C1-C3-alkoxy, or C1-C3-haloalkoxy.
In a preferred embodiment R5 is OH, C1-C3-alkoxy, C1-C3-haloalkoxy, or NR12R13, wherein R12 and R13 are independently from each other H or C(O)NR121R131, with R121, and R131 being preferably independently from each other H, C1-C3-alkyl, or C3-C4-cycloalkyl-C1-C2-alkyl.
In another preferred embodiment R5 is NR12R13, wherein R12 and R13 form, together with the N atom they are bound to, a 4- to 7-membered heterocycle unsubstituted or substituted with R3a wherein R3a is preferably halogen, C1-C4-alkyl, C1-C4-haloalkyl, or oxo.
R5 is present as E-/Z-isomers of formula I. The E-isomer is preferred, particularly in formula I compounds wherein R5 is OR15 and R4 is H or alkyl, such as CH3.
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 formula I.1*, and I.2*, resp. 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.
Compounds of formula I.1* in which R1 is H, R4 is H, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is H, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is H, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is H, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is H, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is H, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is H, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is CH2CH2CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is CH2CH2CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is CH2CH2CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is CH2CH2CH3, and the combination of X and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is CH2CH2CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is CH2CH2CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is CH2CH2CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is CH(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is CH(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is CH(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is CH(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is CH(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is CH(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is CH(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is C(═O)NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is C(═O)NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is C(═O)NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is C(═O)NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is C(═O)NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is C(═O)NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is C(═O)NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is C(═O)NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is C(═O)NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is C(═O)NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is C(═O)NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is C(═O)NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is C(═O)NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is C(═O)NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is C(═O)NHC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is C(═O)NHC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is C(═O)NHC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is C(═O)NHC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is C(═O)NHC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is C(═O)NHC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is C(═O)NHC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is C(═O)N(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is C(═O)N(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is C(═O)N(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is C(═O)N(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is C(═O)N(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is C(═O)N(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is C(═O)N(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is C(═O)N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is C(═O)N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is C(═O)N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is C(═O)N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is C(═O)N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is C(═O)N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is C(═O)N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is C(═O)OCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is C(═O)OCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is C(═O)OCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is C(═O)OCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is C(═O)OCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is C(═O)OCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is C(═O)OCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is C(═O)OC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is C(═O)OC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is C(═O)OC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is C(═O)OC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is C(═O)OC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is C(═O)OC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is C(═O)OC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is NHCH2CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is NHCH2CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is NHCH2CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is NHCH2CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is NHCH2CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is NHCH2CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is NHCH2CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is H, R4 is 4,5-dihydrooxazol-2-yl, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH3, R4 is 4,5-dihydrooxazol-2-yl, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is C2H5, R4 is 4,5-dihydrooxazol-2-yl, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC3H5, R4 is 4,5-dihydrooxazol-2-yl, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is 4,5-dihydrooxazol-2-yl, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2CH═CH2, R4 is 4,5-dihydrooxazol-2-yl, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2C≡CH, R4 is 4,5-dihydrooxazol-2-yl, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is H, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is H, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is H, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is H, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is H, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is H, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is H, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is CH2CH2CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is CH2CH2CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is CH2CH2CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is CH2CH2CH3, and the combination of X and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is CH2CH2CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is CH2CH2CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is CH2CH2CH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is CH(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is CH(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is CH(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is CH(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is CH(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is CH(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is CH(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is C(═O)NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is C(═O)NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is C(═O)NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is C(═O)NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is C(═O)NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is C(═O)NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is C(═O)NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is C(═O)NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is C(═O)NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is C(═O)NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is C(═O)NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is C(═O)NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is C(═O)NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is C(═O)NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is C(═O)NHC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is C(═O)NHC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is C(═O)NHC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is C(═O)NHC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is C(═O)NHC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is C(═O)NHC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is C(═O)NHC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is C(═O)N(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is C(═O)N(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is C(═O)N(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is C(═O)N(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is C(═O)N(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is C(═O)N(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is C(═O)N(CH3)2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is C(═O)N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is C(═O)N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is C(═O)N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is C(═O)N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is C(═O)N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is C(═O)N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is C(═O)N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is C(═O)OCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is C(═O)OCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is C(═O)OCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is C(═O)OCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is C(═O)OCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is C(═O)OCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is C(═O)OCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is C(═O)OC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is C(═O)OC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is C(═O)OC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is C(═O)OC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is C(═O)OC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is C(═O)OC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is C(═O)OC2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is NH2, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is NHCH3, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is N(CH3)C2H5, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is NHCH2CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is NHCH2CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is NHCH2CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is NHCH2CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.1* in which R1 is CH2-cC5H9, R4 is NHCH2CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is NHCH2CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is NHCH2CN, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is H, R4 is 4,5-dihydrooxazol-2-yl, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH3, R4 is 4,5-dihydrooxazol-2-yl, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is C2H5, R4 is 4,5-dihydrooxazol-2-yl, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC3H5, R4 is 4,5-dihydrooxazol-2-yl, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2-cC5H9, R4 is 4,5-dihydrooxazol-2-yl, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2CH═CH2, R4 is 4,5-dihydrooxazol-2-yl, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
Compounds of formula I.2* in which R1 is CH2C≡CH, R4 is 4,5-dihydrooxazol-2-yl, and the combination of NR5 and (R3)n for a compound corresponds in each case to one row of Table A
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/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:
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 intraruminal, 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 1.
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 1. 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.
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 UHPLC+Shimadzu LCMS-2020, ESI; Column: Phenomenex Kinetex 1.7 μm XB-C18 100A, 2.1×50 mm; 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 μm 2.1×30 mm; 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 0.02 min; 5% B for 0.5 min; Flow: 0.8 mL/min; MS: ESI positive; Mass range: 100-2000.
To a mixture of 1-(3-chloropyrazin-2-yl)ethanone (10 g, 63.8 mmol) and NH4OAc (60.4 g, 957.8 mmol) in EtOH (500 mL) were added NaBH3CN (12.04 g, 191.4 mmol) and NH3/MeOH (150 mL, 7N) at 30° C. The mixture was stirred at 50° C. until completion was determined by LCMS (16 h). The reaction mixture was quenched with H2O (100 mL) and concentrated to remove MeOH and EtOH. 6N aq. NaOH was added to adjust the pH of the residue to 11 and the resulting mixture was extracted with EtOAc (3×100 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated. The crude product was purified by preparative HPLC (NH4HCO3) to deliver 1-(3-chloropyrazin-2-yl)ethanamine (10 g, 50% yield) as a white solid.
1H-NMR (400 MHz, DMSO-d6): δ=8.70 (d, J=2.4 Hz, 1H), 8.47 (d, J=2.5 Hz, 1H), 4.50 (q, J=6.7 Hz, 1H), 1.37 (d, J=6.8 Hz, 3H).
To a mixture of 3,5-bis(trifluoromethyl)benzoic acid (19.65 g, 76.14 mmol) and chloro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate (21.36 g, 76.14 mmol) in MeCN (200 mL) were added N-methylimidazole (16.7 g, 203.2 mmol) and 1-(3-chloropyrazin-2-yl)ethanamine (8.0 g, 50.8 mmol) at 30° C. The reaction mixture was stirred until completion was determined by TLC (PE:EtOAc=3:1, Rf=0.45; 16 h). The reaction mixture was quenched with H2O (50 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated. The crude product was purified by chromatographic column on silica gel (eluent: 12% EtOAc in PE) to deliver N-[1-(3-chloropyrazin-2-yl)ethyl]-3,5-bis(trifluoromethyl)benzamide (13 g, 43% yield) as a yellow solid.
1H NMR (400 MHz, DMSO-d6): δ=9.53 (d, J=6.8 Hz, 1H), 8.65 (d, J=2.5 Hz, 1H), 8.55 (s, 2H), 8.46 (d, J=2.5 Hz, 1H), 8.33 (s, 1H), 5.53 (dq, J=6.8 Hz, J=6.9 Hz, 1H), 1.56 (d, J=6.9 Hz, 3H).
To a solution of N-[1-(3-chloropyrazin-2-yl)ethyl]-3,5-bis(trifluoromethyl)benzamide (1.0 g, 2.51 mmol) in DMF (10 mL) were added Zn(CN)2 (330 mg, 2.76 mmol) and Pd(PPh3)4 (350 mg, 0.30 mmol) at 20° C., and the resulting mixture was purged with N2 for 3 min. The vial was sealed and subjected to microwave irradiation (Biotage Smith Synthesis, 130° C., 10 min). Completion was determined by TLC (PE:EtOAc=3:1, Rf=0.4). The reaction mixture was filtered through a celite pad, the filter cake was washed with EtOAc (50 mL), and the filtrate was concentrated. The crude product was purified by chromatographic column on silica gel (eluent: 17% EtOAc in PE) to deliver N-[1-(3-cyanopyrazin-2-yl)ethyl]-3,5-bis(trifluoromethyl)benzamide (2.6 g, 45% yield) as a yellow solid.
1H-NMR (400 MHz, CDCl3): δ 8.77 (d, J=2.3 Hz, 1H), 8.70 (d, J=2.4 Hz, 1H), 8.28 (s, 2H), 8.04 (s, 1H), 7.37-7.28 (m, 1H), 5.84-5.73 (m, 1H), 1.74 (d, J=6.8 Hz, 3H).
To a solution of N-[1-(3-cyanopyrazin-2-yl)ethyl]-3,5-bis(trifluoromethyl)benzamide (1.1 g, 2.8 mmol) in EtOH (20 mL) were added HONH2·HCl (238 mg, 3.36 mmol) and triethylamine (575 mg, 5.6 mmol) at 30° C. The resulting mixture was stirred at 80° C. for 2.5 h, until completion was determined by TLC (PE:EtOAc=3:1, Rf=0.3). The reaction mixture was quenched with H2O (10 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated. The crude product was purified by chromatographic column on silica gel (25% EtOAc in PE) to deliver N-[1-[3-[N′-hydroxycarbamimidoyl]pyrazin-2-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (I-3, 600 mg, 51% yield) as a white solid.
1H-NMR (400 MHz, DMSO-d6) 5=10.21 (s, 1H), 9.42 (d, J=7.2 Hz, 1H), 8.62 (d, J=2.4 Hz, 1H), 8.57 (d, J=2.3 Hz, 1H), 8.54 (s, 2H), 8.30 (s, 1H), 6.12 (dq, J=6.8 Hz, J=7.2 Hz, 1H), 5.96 (s, 2H), 1.54 (d, J=6.8 Hz, 3H).
LCMS: 421.1 (desired); 422.0 (observed).
To a solution of N-[1-[3-[N′-hydroxycarbamimidoyl]pyrazin-2-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (I-3, 600 mg, 1.42 mmol) in MeOH (4.8 mL) was added a solution of KOH (72 mg, 1.28 mmol) in H2O (1.2 mL). Next, Mel (182 mg, 1.28 mmol) was added dropwise at 30° C. The reaction was stirred for 16 h, until completion was determined by TLC (PE:EtOAc=3:1, Rf=0.4). The reaction mixture was quenched with H2O (10 mL) and the pH of the resulting mixture was adjusted to 7 by addition of 1N aq. HCl. The resulting mixture was extracted with EtOAc (3×30 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated. The crude product was purified by chromatographic column on silica gel (20% EtOAc in PE) to deliver N-[1-[3-[N′-methoxycarbamimidoyl]pyrazin-2-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (I-5, 145 mg, 23% yield) as a yellow solid.
1H-NMR (400 MHz, DMSO-d6) 5=9.43 (d, J=7.0 Hz, 1H), 8.65 (d, J=2.3 Hz, 1H), 8.58 (d, J=2.3 Hz, 1H), 8.53 (s, 2H), 8.30 (s, 1H), 6.21 (s, 2H), 5.98 (dq, J=6.8 Hz, J=7.0 Hz, 1H), 3.80 (s, 3H), 1.58 (d, J=6.8 Hz, 3H).
LCMS: 435.1 (desired); 436.1 (observed).
To a stirred solution of N-[1-(3-chloropyrazin-2-yl)ethyl]-3,5-bis(trifluoromethyl)benzamide (1 g, 2.5 mmol) in toluene (100 mL) were added tributyl(1-ethoxyvinyl)stannane (1.1 g, 3.0 mmol) and Pd(PPh3)2Cl2 (0.1 g, 0.25 mmol) at 25° C. The reaction mixture was stirred for 12 h at 110° C. under an atmosphere of N2, at which time completion was determined by TLC (PE:EtOAc=3:1). The reaction mixture was cooled down to 25° C. and aq. sat. KF (100 mL) was added. The mixture was stirred for 30 min, then filtered through a celite pad. The filtrate was extracted with EtOAc (3×40 mL). The combined organic layers were washed with brine (60 mL), dried over Na2SO4, and concentrated to furnish N-[1-[3-(1-ethoxyvinyl)pyrazin-2-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (1.0 g, crude) as a thick yellow oil. The crude product was employed in the next step without further purification.
1H-NMR (400 MHz, CDCl3) δ=8.54 (s, 2H), 8.27 (s, 2H), 8.01 (s, 1H), 7.71 (br d, J=7.5 Hz, 1H), 5.86-6.02 (m, 1H), 4.87 (d, J=2.6 Hz, 1H), 4.60 (d, J=2.6 Hz, 1H), 3.96-4.17 (m, 2H), 1.59 (d, J=6.5 Hz, 3H), 1.50 (t, J=7.0 Hz, 3H).
To a stirred solution of N-[1-[3-(1-ethoxyvinyl)pyrazin-2-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (4.3 g, 9.93 mmol) in THF (60 mL) was added aq. HCl (2M, 60 mL) dropwise at 0° C. The mixture was stirred for 2 h at 20° C., until completion was determined by TLC (PE:EtOAc=3:1). The reaction mixture was diluted with H2O (100 mL), extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine (100 mL), dried over Na2SO4, and concentrated to deliver N-[1-(3-acetylpyrazin-2-yl)ethyl]-3,5-bis(trifluoromethyl)benzamide (1.5 g, 37% yield) as a white solid.
1H-NMR (400 MHz, CDCl3) 5=8.71 (d, J=2.3 Hz, 1H), 8.63 (d, J=2.3 Hz, 1H), 8.25 (s, 2H), 8.01 (s, 1H), 7.60 (br d, J=7.8 Hz, 1H), 6.03-6.17 (m, 1H), 2.79 (s, 3H), 1.65 (d, J=6.8 Hz, 3H).
To a stirred solution of N-[1-(3-acetylpyrazin-2-yl)ethyl]-3,5-bis(trifluoromethyl)benzamide (400 mg, 0.987 mmol) in EtOH (10 mL) were added NaOAc (0.162 g, 1.97 mmol) and MeONH2—HCl (0.082 g, 0.987 mmol) at 20° C. The reaction mixture was stirred for 12 h at 50° C., at which time completion was observed by LCMS. The reaction mixture was diluted with H2O (10 mL) and extracted with EtOAc (3×30 mL). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, and concentrated. The residue was purified by chromatographic column on silica gel (PE:EtOAc=100:0 to 82:18) to deliver N-[1-[3-[N-methoxy-C-methyl-carbonimidoyl]pyrazin-2-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (I-1, 0.258 g, 60% yield) as a white solid.
1H-NMR (400 MHz, CDCl3) δ=8.57 (d, J=2.4 Hz, 1H), 8.53 (d, J=2.4 Hz, 1H), 8.01 (s, 1H), 8.26 (s, 2H), 7.66 (br d, J=7.8 Hz, 1H), 6.07 (dq, J=7.8, 6.7 Hz, 1H), 2.36 (s, 3H), 4.12 (s, 3H), 1.65 (d, J=6.50 Hz, 3H).
LCMS: 434.12 (calculated); 435.0 (observed).
To a stirred solution of 3-(1-cyanocyclopropyl)-N-[1-[3-(N-methoxy-C-methyl-carbonimidoyl)pyrazin-2-yl]ethyl]-5-(trifluoromethyl)benzamide (150 mg, 0.348 mmol, prepared via the same synthetic route as 1-1) in DMF (5 mL) was added NaH (28 mg, 0.696 mmol) in portions at 0° C. The reaction mixture was stirred for 30 min at 0° C. and then heated to 80° C. A solution of bromomethylcyclopropane (70 mg, 0.522 mmol) in DMF (5 mL) was added dropwise at 80° C. and stirred at this temperature for 12 h. The reaction mixture was cooled to RT, quenched with NH4Cl (aq. 10 mL) and extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine (4×5 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative-HPLC (NH4HCO3) to deliver 3-(1-cyanocyclopropyl)-N-(cyclopropylmethyl)-N-[1-[3-(N-methoxy-C-methyl-carbonimidoyl)pyrazin-2-yl]ethyl]-5-(trifluoromethyl)benzamide (I-9, 50 mg, 15% yield) as a yellow syrup.
1H-NMR (400 MHz, CDCl3) δ=8.64 (d, J=2.45 Hz, 1H), 8.61 (d, J=2.45 Hz, 1H), 7.64 (s, 1H), 7.46 (s, 1H), 7.42 (s, 1H), 5.96 (br s, 1H), 3.80 (s, 3H), 3.35-3.47 (m, 1H), 3.18-3.28 (m, 1H), 2.10 (s, 3H), 1.81-1.85 (m, 2H), 1.69 (d, J=6.97 Hz, 3H), 1.59-1.63 (m, 2H), 0.85-0.90 (m, 1H), 0.31-0.43 (m, 2H), 0.13-0.10 (m, 2H).
To a stirred solution of 1-(3-chloropyrazin-2-yl)ethenone (200 mg, 3.2 mmol) in THF (20 mL) at RT were added cyclopropylmethanamine (109 mg, 0.364 mmol) and Ti(i-PrO)4 (364 mg; 1.282 mmol). The reaction mixture was stirred for 12 h at RT and then stirred at 50° C. for 4 h. TLC (PE:EtOAc=1:1) showed complete conversion. The reaction mixture was cooled to RT, then EtOH (10 mL) was added and NaBH3CN (121 mg, 1.923 mmol) was added in portions. TLC (PE:EtOAc=1:1) showed the reaction was completed after 12 h at RT. The reaction mixture was quenched with water (30 mL), filtered and the filtrate was extracted with EtOAc (3×20 mL). The organic layers were washed with brine (20 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by chromatographic column on silica gel (PE:EtOAc=100:0 to 16:84) to deliver 1-(3-chloropyrazin-2-yl)-N-(cyclopropylmethyl)ethanamine (94 mg, 35% yield) as a yellow syrup.
1H-NMR (400 MHz, CDCl3) δ=8.50 (d, J=2.38 Hz, 1H), 8.25 (d, J=2.38 HZ, 1H), 4.37 (q, J=6.65 Hz, 1H), 2.51 (dd, J=11.73, 6.21 Hz, 1H), 2.05 (dd, J=11.67, 7.53 Hz, 1H), 1.38 (d, J=6.65 Hz, 3H), 0.83-1.00 (m, 1H), 0.43 (td, J=7.87, 2.45 Hz, 2H), 0.06-0.14 (m, 2H).
To a stirred solution of 3-chloro-5-(4-fluorophenyl)sulfonyl-benzoic acid (100 mg, 0.318 mmol) in ACN (5 mL) were added chloro-N,N,N′,N′-tetramethylformamidinium-hexafluorophosphate (134 mg, 0.477 mmol), N-methylimidazole (78 mg; 0.995 mmol) and 1-(3-chloropyrazin-2-yl)-N-(cyclopropylmethyl)ethanamine (81 mg, 0.382 mmol) at RT. LC-MS showed the reaction was completed after 12 h. The reaction mixture was quenched with water (10 mL) and extracted with EtOAc (3×8 mL). The combined organic layers were washed with brine (10 mL) dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative TLC (PE:EtOAc=1:1) to deliver 3-chloro-N-[1-(3-chloropyrazin-2-yl)ethyl]-N-(cyclopropylmethyl)-5-(4-fluorophenyl)sulfonyl-benzamide (50 mg, 31% yield) as a yellow oil.
1H-NMR (400 MHz, CDCl3) δ=8.51 (d, J=2.38 Hz, 1H), 8.27 (d, J=2.38 Hz, 1H), 7.94-8.00 (m, 2H), 7.88 (br s, 1H), 7.61 (s, 1H), 7.23 (br t, J=8.50 Hz, 2H), 4.42 (q, J=6.71 Hz, 1H), 2.56 (dd, J=11.76, 6.25 Hz, 1H), 2.09-2.13 (m, 1H), 1.43 (d, J=6.63 Hz, 3H), 0.93-0.98 (m, 1H), 0.44-0.48 (m, 2H), 0.21-0.33 (m, 1H), 0.05-0.10 (m, 1H).
To a stirred solution of 3-chloro-N-[1-(3-chloropyrazin-2-yl)ethyl]-N-(cyclopropylmethyl)-5-(4-fluorophenyl)sulfonyl-benzamide (300 mg, 0.662 mmol) in toluene (8 mL) were added tributyl(1-ethoxyvinyl)stannane (287 mg, 0.795 mmol) and Pd(PPh3)2Cl2 (100 mg, cat.) at RT. The sealed vial was irradiated in the microwave for 1 h at 130° C. TLC (PE:EtOAc=3:1) showed the reaction was completed. The reaction mixture was concentrated under reduced pressure. The residue was diluted with aq. KF (10 mL) and stirred for 30 min. The reaction mixture was filtered through a celite pad and the filtrate was extracted with EtOAc (3×30 mL). The combined organic layers were washed with brine (6 ml), dried over Na2SO4, filtered and concentrated under reduced pressure to deliver 3-chloro-N-(cyclopropylmethyl)-N-[1-[3-(1-ethoxyvinyl)pyrazin-2-yl]ethyl]-5-(4-fluorophenyl)sulfonyl-benzamide (4.3 g, crude) as a yellow oil. The crude product was employed in the next step without further purification.
To a stirred solution of 3-chloro-N-(cyclopropylmethyl)-N-[1-[3-(1-ethoxyvinyl)pyrazin-2-yl]ethyl]-5-(4-fluorophenyl)sulfonyl-benzamide (1.3 g, 2.39 mmol) in THF (20 mL) was added HCl (aq., 2N, 10 mL) at RT. The reaction mixture was stirred for 4 h at RT. TLC (PE:EtOAc=1:1) showed the reaction was completed. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by chromatographic column on silica gel (PE:EtOAc=100:0 to 35:65) to deliver N-[1-(3-acetylpyrazin-2-yl)ethyl]-3-chloro-N-(cyclopropylmethyl)-5-(4-fluorophenyl)sulfonyl-benzamide (500 mg, 70% yield) as a yellow solid.
To a stirred solution of N-[1-(3-acetylpyrazin-2-yl)ethyl]-3-chloro-N-(cyclopropylmethyl)-5-(4-fluorophenyl)sulfonyl-benzamide (500 mg, 0.971 mmol) in EtOH (5 mL) were added NaOAc (159 mg, 1.94 mmol) and O-methylhydroxylamine hydrochloride (122 mg, 1.45 mmol) at RT. The reaction mixture was heated to 50° C. and stirred for 12 h. LC-MS showed the reaction was completed. The reaction mixture was concentrated under reduced pressure, quenched with water (10 ml) and extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine (5 mL), dried over Na2SO4, filtered and concentrated under reduced, pressure. The residue was purified by chromatographic column on silica gel (PE:EtOAc=100:0 to 50:50) to deliver 3-chloro-N-(cyclopropylmethyl)-5-(4-fluorophenyl)sulfonyl-N-[1-[3-(N-methoxy-C-methyl-carbonimidoyl)pyrazin-2-yl]ethyl]benzamide (I-17, 268 mg, 51% yield) as a yellow solid.
1H-NMR (400 MHz, CDCl3) δ=8.64 (s, 1H), 8.61 (s, 1H), 8.03-8.09 (m, 3H), 7.64 (br s, 1H), 7.58 (s, 1H), 7.45 (br t, J=8.58 Hz, 2H), 5.94 (br d, J=1.91 Hz, 1H), 3.73 (br s, 3H), 3.13-3.42 (m, 2H), 2.03-2.14 (m, 3H), 1.65 (br d, J=6.79 Hz, 3H), 0.65-0.97 (m, 1H), 0.23-0.41 (m, 2H), −0.28-0.09 (m, 2H).
To a stirred solution of N-[1-[3-(N′-hydroxycarbamimidoyl)pyrazin-2-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (3 g, 7.1 mmol) in HCl (aq., 6N, 30 mL) at 0° C. was added dropwise a solution of NaNO2 (735 mg, 10.6 mmol) in water (2 mL). The reaction mixture was stirred for 3 h at RT. LCMS showed the reaction was completed. The reaction mixture was extracted with EtOAc (3×50 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to deliver 3-[1-[[3,5-bis(trifluoromethyl)benzoyl]amino]ethyl]-N-hydroxypyrazine-2-carboximidoyl chloride (3 g, crude) as a yellow solid. The crude product was employed in the next step without further purification
To a stirred solution of 3-[1-[[3,5-bis(trifluoromethyl)benzoyl]amino]ethyl]-N-hydroxy-pyrazine-2-carboximidoyl chloride (500 mg, 1.1 mmol) in THF (10 mL) was added dropwise N-methylethanamine (80 mg, 1.4 mmol) at RT. The reaction mixture was stirred for 16 h at RT under N2 atmosphere. TLC (PE:EtOAc=1:1) showed the reaction was completed. The reaction mixture was concentrated under reduced pressure and the crude was purified by chromatographic column on silica gel (PE:EtOAc=1:1) to deliver N-[1-[3-(N-ethyl-N′-hydroxy-N-methyl-carbamimidoyl)pyrazin-2-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (I-170, 300 mg, 59% yield) as a yellow syrup.
1H-NMR (400 MHz, CDCl3) δ=8.86 (d, J=1.63 Hz, 1H), 8.74 (s, 1H), 8.47 (s, 2H), 8.18 (s, 1H), 5.26-5.47 (m, 1H), 3.37 (br d, J=7.25 Hz, 2H), 1.72 (d, J=6.88 Hz, 3H), 1.27 (t, J=7.13 Hz, 3H).
With appropriate modification of the starting materials, the procedures given in the synthesis descriptions were used to obtain further compounds I. The compounds obtained in this manner are listed in the table that follows, together with physical data.
compounds of formula I* (R2 = CH3)
If not otherwise specified, the 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)
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-7, I-8, I-9, I-12, I-13, I-14, I-15, I-18, I-19, I-21, I-35, I-50, I-83, I-93, I-99, I-120, I-121, I-123, I-126, I-127, I-130, I-131, I-132, I-152, I-159, I-169, I-170, I-174, I-176, and I-180, resp., at 2500 ppm showed at least 75% mortality in comparison with untreated controls.
B.2 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 μl, 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 I-1, I-3, I-5, I-7, I-10, I-11, I-12, I-13, I-14, I-15, I-16, I-19, I-21, I-22, I-23, I-24, I-30, I-33, I-35, I-53, I-61, I-64, I-75, I-76, I-77, I-78, I-81, I-82, I-83, I-87, I-89, I-90, I-92, I-93, I-95, I-102, I-105, I-111, I-112, I-113, I-114, I-120, I-121, I-123, I-125, I-127, I-129, I-130, I-131, I-133, I-136, I-140, I-144, I-148, I-150, I-151, I-155, I-157, I-158, I-159, I-167, I-169, I-170, I-171, I-172, I-174, I-180, and I-181, resp., at 2500 ppm showed at least 75% mortality in comparison with untreated controls.
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 μl, 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 I-1, I-3, I-4, I-5, I-7, I-8, I-10, I-11, I-12, I-13, I-14, I-15, I-16, I-17, I-18, I-19, I-21, I-22, I-23, I-24, I-30, I-34, I-35, I-39, I-40, I-41, I-46, I-48, I-50, I-53, I-58, I-59, I-60, I-61, I-64, I-71, I-74, I-75, I-76, I-78, I-83, I-85, I-87, I-88, I-89, I-90, I-93, I-95, I-99, I-102, I-103, I-104, I-107, I-108, I-111, I-112, I-114, I-115, I-117, I-118, I-120, I-121, I-122, I-123, I-125, I-126, I-127, I-128, I-129, I-130, I-131, I-132, I-133, I-134, I-135, I-136, I-140, I-142, I-144, I-147, I-148, I-150, I-155, I-157, I-158, I-159, I-160, I-162, I-167, I-169, I-170, I-171, I-172, I-174, I-176, I-179, I-180, I-181, I-183, I-184, and I-188, resp., at 2500 ppm showed at least 75% mortality in comparison with untreated controls.
B.4. 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 20 ml glass vials. A non-ionic 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 auto-mated 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 I-1, I-4, I-5, I-7, I-9, I-10, I-11, I-12, I-13, I-14, I-15, I-16, I-17, I-18, I-19, I-21, I-22, I-23, I-24, I-30, I-41, I-46, I-47, I-57, I-64, I-75, I-76, I-77, I-78, I-81, I-82, I-83, I-87, I-89, I-93, I-95, I-100, I-102, I-103, I-104, I-106, I-107, I-111, I-112, I-113, I-114, I-115, I-120, I-121, I-122, I-123, I-125, I-126, I-127, I-128, I-129, I-130, I-131, I-133, I-134, I-135, I-136, I-139, I-140, I-144, I-145, I-148, I-150, I-151, I-155, I-156, I-157, I-159, I-167, I-171, and I-172, resp., at 300 ppm at least 75% mortality in comparison with untreated controls.
B.5 Yellow Fever Mosquito (Aedes aegypti)
For evaluating control of yellow fever mosquito (Aedes aegypti) the test unit consisted of 96-well-microtiter plates containing 200 μl 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 μl, 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 I-1, I-2, I-3, I-4, I-5, I-7, I-8, I-9, I-10, I-11, I-12, I-13, I-14, I-15, I-16, I-17, I-18, I-19, I-21, I-22, I-23, I-24, I-25, I-26, I-30, I-33, I-35, I-38, I-39, I-40, I-41, I-42, I-43, I-44, I-46, I-47, I-48, I-49, I-50, I-51, I-55, I-56, I-57, I-59, I-62, I-64, I-69, I-70, I-71, I-74, I-75, I-76, I-77, I-78, I-79, I-81, I-82, I-83, I-85, I-87, I-90, I-91, I-92, I-93, I-94, I-95, I-97, I-99, I-100, I-102, I-103, I-104, I-105, I-107, I-111, I-112, I-113, I-114, I-115, I-117, I-118, I-119, I-120, I-121, I-122, I-123, I-124, I-125, I-126, I-127, I-128, I-129, I-130, I-131, I-132, I-133, I-134, I-135, I-136, I-140, I-144, I-145, I-148, I-150, I-151, I-153, I-154, I-155, I-157, I-158, I-159, I-160, I-161, I-163, I-167, I-169, I-170, I-171, I-172, I-173, I-174, I-176, I-180, I-181, I-183, I-186, and I-187, resp., at 2500 ppm showed at least 75% mortality in comparison with untreated controls.
| Number | Date | Country | Kind |
|---|---|---|---|
| 21192611.8 | Aug 2021 | EP | regional |
| 21192612.6 | Aug 2021 | EP | regional |
| 21210113.3 | Nov 2021 | EP | regional |
| 21215023.9 | Dec 2021 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2022/072642 | 8/12/2022 | WO |
