Patent Application
20240383873
The present invention relates to pesticidally active, in particular insecticidally active cyclic amine, preferably azetidinyl-, pyrrolidinyl-, piperidinyl- and piperazinyl-pyridinyl carbonyl compounds, to processes for their preparation, to compositions comprising those compounds, and to their use for controlling animal pests, including arthropods and in particular insects or representatives of the order Acarina.
WO2015032280, CN106316931, WO2017195703, WO2019039429, WO 2019082808, JP 2019077618, JP 2019085371 and WO2021053161 describe certain azetidinyl-, pyrrolidinyl-, piperidinyl- or piperazinyl-pyridinyl carbonyl compounds for use for controlling pests that damage plants.
There have now been found novel pesticidally azetidinyl-, pyrrolidinyl-, piperdinyl- and piperazinyl-pyridinyl carbonyl compounds.
The present invention accordingly relates, in a first aspect, to a compound of the formula (I)
Compounds of formula (I) which have at least one basic centre can form, for example, acid addition salts, for example with strong inorganic acids such as mineral acids, for example perchloric acid, sulfuric acid, nitric acid, nitrous acid, a phosphorus acid or a hydrohalic acid, with strong organic carboxylic acids, such as C1-C4alkanecarboxylic acids which are unsubstituted or substituted, for example by halogen, for example acetic acid, such as saturated or unsaturated dicarboxylic acids, for example oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid or phthalic acid, such as hydroxycarboxylic acids, for example ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid, or such as benzoic acid, or with organic sulfonic acids, such as C1-C4alkane- or arylsulfonic acids which are unsubstituted or substituted, for example by halogen, for example methane- or p-toluenesulfonic acid. Compounds of formula (I) which have at least one acidic group can form, for example, salts with bases, for example mineral salts such as alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts, or salts with ammonia or an organic amine, such as morpholine, piperidine, pyrrolidine, a mono-, di- or tri-lower-alkylamine, for example ethyl-, diethyl-, triethyl- or dimethylpropylamine, or a mono-, di- or trihydroxy-lower-alkylamine, for example mono-, di- or triethanolamine.
In each case, the compounds of formula (I) according to the invention are in free form, in oxidized form as a N-oxide or in salt form, e.g. an agronomically usable salt form.
N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen containing heteroaromatic compounds. They are described for instance in the book “Heterocyclic N-oxides” by A. Albini and S. Pietra, CRC Press, Boca Raton 1991.
The compounds of formula (I) according to the invention also include hydrates which may be formed during the salt formation.
The term “C1-Cn-alkyl” as used herein refers to a saturated straight-chain or branched hydrocarbon radical attached via any of the carbon atoms having 1 to n carbon atoms, for example, any one of the radicals methyl, ethyl, n-propyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, or 1-ethyl-2-methylpropyl.
The term “C2-Cn-alkenyl” as used herein refers to a straight or branched alkenyl chain having form two to n carbon atoms and one or two double bonds, for example, ethenyl, prop-I-enyl, but-2-enyl.
The term “C2-Cn-alkynyl” as used herein refers to a straight or branched alkynyl chain having from two to n carbon atoms and one triple bond, for example, ethynyl, prop-2-ynyl, but-3-ynyl,
The term “C3-Cn-cycloalkyl” as used herein refers to 3-n membered cycloalkyl groups such as cyclopropane, cyclobutane, cyclopropane, cyclopentane and cyclohexane.
The term “C1-Cn-alkoxy” as used herein refers to a straight-chain or branched saturated alkyl radical having 1 to n carbon atoms (as mentioned above) which is attached via an oxygen atom, i.e., for example, any one of the radicals methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy or 1,1-dimethylethoxy. The term “haloC1-Cn-alkoxy” as used herein refers to a C1-Cn-alkoxy radical where one or more hydrogen atoms on the alkyl radical is replaced by the same or different halo atom(s)—examples include trifluoromethoxy, 2-fluoroethoxy, 3-fluoropropoxy, 3,3,3-trifluoropropoxy, 4-chlorobutoxy. Two neighboring substituents of a phenyl ring may form together with the carbons of the phenyl ring a 5- or 6-membered ring. Examples are —OCF2O—, —OCF2CF2O—.
Halogen is generally fluorine, chlorine, bromine or iodine. This also applies, correspondingly, to halogen in combination with other meanings, such as haloalkyl.
The term “C1-Cn-haloalkyl” as used herein refers to a straight-chain or branched saturated alkyl radical attached via any of the carbon atoms having 1 to n carbon atoms (as mentioned above), where some or all of the hydrogen atoms in these radicals may be replaced by fluorine, chlorine, bromine and/or iodine, i.e., for example, any one of chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl, 2,2-difluoropropyl, 2,3-difluoropropyl, 2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl, 3,3,3-trichloropropyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl, 1-(fluoromethyl)-2-fluoroethyl, 1-(chloromethyl)-2-chloroethyl, 1-(bromomethyl)-2-bromoethyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl or nonafluorobutyl. According a term “C1-C2fluoroalkyl” would refer to a C1-C2alkyl radical which carries 1, 2, 3, 4, or 5 fluorine atoms, for example, any one of difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl or pentafluoroethyl. Similarly, the term “C2-Cn-haloalkenyl” or “C2-Cn-haloalkynyl” as used herein refers to a C2-Cn-alkenyl or C2-Cn-alkynyl moiety respectively substituted with one or more halo atoms which may be the same or different. Similarly, the term “C3-Cn-halocycloalkyl” as used herein refers to a C3-Cn-cycloakyl group substituted with one or more halo atoms which may be the same or different.
The term “C1-Cn-cyanoalkyl” as used herein refers to C1-Cn-alkyl radical having 1 to n carbon atoms (as mentioned above), where one of the hydrogen atoms in the radical is be replaced by a cyano group: for example, cyano-methyl, 2-cyano-ethyl, 2-cyano-propyl, 3-cyano-propyl, 1-(cyano-methyl)-2-ethyl, 1-(methyl)-2-cyano-ethyl, 4-cyanobutyl, and the like. Similarly, the term “C2-Cn-cyanoalkenyl” or “C2-Cn-cyanoalkynyl” or “C3-Cn-cyanocycloalkyl” refers to a C2-Cn-alkenyl or C2-Cn-alkynyl or C3-Cn-cycloalkyl moiety respectively substituted with one of the hydrogen atoms in the corresponding moiety being replaced by a cyano group.
The term “4 to 6 membered non-aromatic heterocyclic ring system in which one or two carbons is replaced by nitrogen, oxygen, sulfur, or sulfonyl,” as used herein refers to a cyclic group where one or two carbon atoms in the ring are replaced independently by nitrogen, oxygen, sulfur, or sulfonyl, and the ring is attached via a carbon, or a nitrogen atom to remainder of the compound. Examples are azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, 2-oxopyrrolidinyl, 2-oxotetrahydrofuranyl, 1,1-dioxo-1,2-thiazolidinyl, 1,3-dioxolanyl, 1,3-dithiolanyl, 2-oxooxazolidinyl, piperidinyl, tetrahydropyranyl, 2-oxopiperidinyl, 1,1-dioxothiazinanyl, 2-oxotetrahydropyranyl, 1,3-dioxolanyl, 1,3-dithianyl, 2-oxo-1,3-oxazinanyl.
The term “5 or 6 membered monocyclic heteroaryl” as used herein refers to a 5 or 6 membered aromatic ring having 1 to 3 carbon atoms replaced independently by nitrogen, sulfur, or oxygen. Examples are pyridyl (or pyridinyl), pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl (e.g. 1.2.4 triazoyl), furanyl, thiophenyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl and thiadiazolyl.
The term “8, 9 or 10 membered bicyclic heteroaryl” as used herein refers to a 8, 9 or 10 membered aromatic ring made up of two rings, having 1 to 4 carbon atoms replaced independently by nitrogen, sulfur, or oxygen (the heteroatoms can be in one ring or distributed amongst the two). Examples are purinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, indolyl, indazolyl, 2,1,3-benzoxadiazolyl, 2,1,3-benzothiadiazolyl benzimidazolyl, benzothiophenyl, benzoxazolyl, benzothiazolyl, imidazo[1,2-a]pyridinyl, imidazo[4,5-b]pyridinyl, imidazo[2,1-b]thiazole and imidazo[2,1-b][1,3,4]thiadiazolyl.
The term “C1-Cn-alkoxy-C1-Cn-alkyl” as used herein refers to an alkyl radical substituted with a C1-Cn-alkoxy group. Examples are methoxymethyl, methoxyethyl, ethoxymethyl and propoxymethyl. Similarly, the term “C2-Cn-alkenyloxy-C1-Cn-alkyl” or “C2-C6-alkynyloxy-C1-C6-alkyl” or “C3-C6-cycloalkoxy-C1-C6-alkyl” refers to the C1-Cn-alkyl radical being substituted with a C2-Cn-alkenyloxy, C2-C6-alkynyloxy or C3-C6-cycloalkoxy group respectively.
The term “C1-Cnhaloalkylsulfanyl” as used herein refers to a C1-Cnhaloalkyl moiety linked through a sulfur atom.
The term “C1-Cnalkylsulfonyl” as used herein refers to a C1-Cnalkyl moiety linked through the sulfur atom of the S(═O)2 group.
The term “C1-Cn-alkylsulfonyl-C1-Cn-alkyl” as used herein refers to an a C1-Cnalkyl radical substituted with a C1-Cnalkylsulfonyl group.
The term “C1-Cn-alkylsulfonyl-C3-Cn-cycloalkyl” as used herein refers to a C3-Cn-cycloalkyl radical substituted with a C1-Cnalkylsulfonyl group.
The term “C1-Cn-alkylsulfonyl-C3-Cn-cycloalkyl” as used herein refers to a C3-Cn-cycloalkyl radical substituted with a C1-Cnalkylsulfonyl group.
The term “C1-Cn-alkylcarbonyl” as used herein refers to a C1-Cn-alkyl moiety linked through the carbon atom of the carbonyl (C═O) group.
The term “C1-Cn-alkylcarbamoyl” as used herein refers to a C1-Cn-alkyl moiety linked through the NHC(═O) group.
The term “—O—C1-2haloalkanediyl-O—” as used herein refers to adjacent positions on the phenyl ring being connected to the oxygen atoms of the —O—C1-2haloalkanediyl-O— group and the oxygen atoms being linked by 1 to 2 carbon atoms substituted with one or more halogen atoms. Examples are —OCF2O— and —OCF2CF2O—.
As used herein, the term “controlling” refers to reducing the number of pests, eliminating pests and/or preventing further pest damage such that damage to a plant or to a plant derived product is reduced.
As used herein, the term “pest” refers to insects, and molluscs that are found in agriculture, horticulture, forestry, the storage of products of vegetable origin (such as fruit, grain and timber); and those pests associated with the damage of man-made structures. The term pest encompasses all stages in the life cycle of the pest.
As used herein, the term “effective amount” refers to the amount of the compound, or a salt thereof, which, upon single or multiple applications provides the desired effect.
An effective amount is readily determined by the skilled person in the art, by the use of known techniques and by observing results obtained under analogous circumstances. In determining the effective amount a number of factors are considered including, but not limited to: the type of plant or derived product to be applied; the pest to be controlled & its lifecycle; the particular compound applied; the type of application; and other relevant circumstances.
Embodiments according to the invention are provided as set out below.
In an embodiment of each aspect of the invention, R1 is
In an embodiment of each aspect of the invention, R2 is
In an embodiment of each aspect of the invention, R3 is
In an embodiment of each aspect of the invention, R4 is
In an embodiment of each aspect of the invention, Q is
In an embodiment of each aspect of the invention, R5 is independently selected from
In an embodiment of each aspect of the invention, R6 is independently selected from
In an embodiment of each aspect of the invention, R7, independent of the A and Y groups, is
In an embodiment of each aspect of the invention, R8, independent of the A and Y groups, is
In an embodiment of each aspect of the invention, R9, independent of the A and Y groups, is
In an embodiment of each aspect of the invention, R10, independent of the A and Y groups, is
In an embodiment of each aspect of the invention, R11, independent of the A and Y groups, is
In an embodiment of each aspect of the invention, R12, independent of the A and Y groups, is
In an embodiment of each aspect of the invention, R11 and R12 together with the carbon to which they are attached form a C3-C4-cycloalkyl, preferably cyclopropyl.
In an embodiment of each aspect of the invention, R13, independent of the A and Y groups, is
In an embodiment of each aspect of the invention, R14, independent of the A and Y groups, is
In an embodiment of each aspect of the invention, R15, independent of the A and Y groups, is
In an embodiment of each aspect of the invention, R16, independent of the A and Y groups, is
In an embodiment of each aspect of the invention, R17, independent of the A and Y groups, is
The present invention, accordingly, makes available a compound of formula (I) having the substituents R1, R2, R3, R4 and Q as defined above in all combinations/each permutation. Accordingly, made available, for example, is a compound of formula (I) with R1 being of the first aspect (i.e. R1 is CN or C(═S)NH2; R2 being embodiment B (i.e. R2 is hydrogen); R3 being embodiment A (i.e. R3 is H, OH, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C2-C6-alkenyl, C2-C6-haloalkenyl, C2-C6-alkynyl, C2-C6-haloalkynyl, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkoxy-C1-C6-alkyl, C1-C6-haloalkoxy-C1-C6-alkyl, C2-C6-alkenyloxy-C1-C6-alkyl, C2-C6-haloalkenyloxy-C1-C6-alkyl, C2-C6-alkynyloxy-C1-C6-alkyl, C2-C6-haloalkynyloxy-C1-C6-alkyl, C3-C6-cycloalkoxy-C1-C6-alkyl, C3-C6-halocycloalkoxy-C1-C6-alkyl, C1-C6-alkylsulfonyl-C1-C6-alkyl; C1-C6-alkylsulfonyl-C3-C6-cycloalkyl, C1-C6-cyanoalkyl, or C3-C6-cyanocycloalkyl); R4 being embodiment B (i.e. R4 is phenyl substituted with 1 to 3 independently selected substituents R5, 5 or 6 membered monocyclic heteroaryl substituted with 1 to 3 independently selected substituents R6, or 8, 9 or 10 membered bicyclic substituted with 1 to 3 independently selected substituents R6); Q being embodiment B (i.e. Q is a cyclic amine represented by the formula IIa, where both p1 and p2 are 1, X is hydrogen; and Y is selected from the formulae Y1 to Y32 (as defined in the first aspect) wherein the arrow indicates the connection to the cyclic amine of formula IIa); R5 is embodiment C (i.e. R5 is independently selected from halogen, cyano, pentafluoro-λ6-sulfanyl, C1-C3-alkyl, C1-C3-haloalkyl, C3-C4-cycloalkyl, C3-C4-halocycloalkyl, C3-C4-cyano-cycloalkyl, C1-C3-alkoxy, C1-C3-haloalkoxy, C1-C3-alkylcarbonyl, C1-C3-alkylcarbamoyl, and —O—C1-2haloalkanediyl-O—); and R6 is embodiment F (i.e. R6 is independently selected fluorine, bromine, chlorine, methyl, ethyl, isopropyl, trifluoroethyl, trifluoromethyl, difluoromethyl, cyclopropyl, trifluoromethoxy, difluoromethoxy, acetyl and methylcarbamoyl).
In an embodiment of each aspect of the invention, the compound of the formula (I) has
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano or C(═S)NH2, as R2 hydrogen, as R3 C1-C6-alkyl, cyclopropyl, C1-C6-haloalkyl, C2-C6-alkenyl, C2-C6-haloalkenyl, C2-C6-alkynyl, C2-C6-haloalkynyl, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C1-C6-alkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C2-alkylsulfonyl-C1-C2-alkyl; C1-C2-alkylsulfonyl-cyclopropyl, C1-C2-cyanoalkyl, or cyano-cyclopropyl; as R4 2,1,3-benzoxadiazolyl, phenyl substituted with 1 to 3 substituents independently selected from halogen, pentafluoro-λ6-sulfanyl, C1-C4-alkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C3-C6-cyanocycloalkyl, cyano, C1-C4-haloalkylsulfanyl, C1-C4-alkylsulfonyl, —O—CF2—O—, and C1-C4-haloalkoxy, or one of thiophenyl, pyridyl (or pyridinyl), and pyrazolyl—each substituted with 1 to 2 substituents independently selected from fluorine, chlorine, methyl, ethyl, isopropyl, cyclopropyl, trifluoromethyl, difluoromethyl, trifluoromethoxy, and difluoromethoxy; as Q cyclic amine represented by the formula IIa, where both p1 and p2 are 1, X is hydrogen; and Y is selected from the formulae Y1 to Y32 (as defined in the first aspect) wherein the arrow indicates the connection to the cyclic amine of formula IIa.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano or C(═S)NH2, as R2 hydrogen, as R3 is methyl, ethyl, cyclopropyl, difluoromethyl, trifluoromethyl, cyclopropanyl, methoxy, ethoxy, methoxymethyl, ethoxymethyl, methysulfonylmethyl, methysulfonylcyclopropyl, cyano-methyl or cyano-cyclopropyl; as R4 2,1,3-benzoxadiazolyl, phenyl substituted with 1 to 3 substituents independently selected from iodo, bromo, chloro, fluoro, pentafluoro-λ6-sulfanyl, methyl, cyclopropyl, trifluoromethyl, trifluoroethyl, —O—CF2—O—, trifluoromethoxy, trifluoromethylsulfanyl, cyano, and methylsulfonyl, or one of thiophenyl, pyridyl (or pyridinyl), and pyrazolyl—each substituted with 1 to 2 substituents independently selected from fluorine, chlorine, methyl, ethyl, isopropyl, cyclopropyl, trifluoromethyl, difluoromethyl, trifluoromethoxy, and difluoromethoxy; as Q cyclic amine represented by the formula IIa, where both p1 and p2 are 1, X is hydrogen; and Y is selected from the formulae Y1 to Y32 (as defined in the first aspect) wherein the arrow indicates the connection to the cyclic amine of formula IIa.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano, as R2 hydrogen, as R3 methyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxymethyl, ethoxymethyl, methysulfonylmethyl, methysulfonylcyclopropyl, cyano-methyl or cyano-cyclopropyl; as R4 2,1,3-benzoxadiazolyl, phenyl substituted with 1 to 3 substituents independently selected from iodo, bromo, chloro, fluoro, pentafluoro-λ6-sulfanyl, methyl, cyclopropyl, trifluoromethyl, —O—CF2—O—, trifluoromethoxy, trifluoromethylsulfanyl, cyano, and methylsulfonyl, or one of thiophenyl, pyridyl (or pyridinyl), and pyrazolyl—each substituted with 1 to 2 substituents independently selected from fluorine, chlorine, methyl, ethyl, isopropyl, cyclopropyl, trifluoromethyl, difluoromethyl, trifluoromethoxy, and difluoromethoxy; as Q cyclic amine represented by the formula IIa, where both p1 and p2 are 1, X is hydrogen or hydroxyl; and Y is selected from the formulae Y1 to Y32 (as defined in the first aspect) wherein the arrow indicates the connection to the cyclic amine of formula IIa.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano, as R2 hydrogen, as R3 methyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxymethyl, ethoxymethyl, methysulfonylmethyl, methysulfonylcyclopropyl, cyano-methyl or cyano-cyclopropyl; as R4 2,1,3-benzoxadiazolyl, phenyl substituted with 1 to 3 substituents independently selected from iodo, bromo, chloro, fluoro, pentafluoro-λ6-sulfanyl, methyl, cyclopropyl, trifluoromethyl, —O—CF2—O—, trifluoromethoxy, trifluoromethylsulfanyl, cyano, and methylsulfonyl, or one of thiophenyl, pyridyl (or pyridinyl), and pyrazolyl—each substituted with 1 to 2 substituents independently selected from fluorine, chlorine, methyl, ethyl, isopropyl, cyclopropyl, trifluoromethyl, difluoromethyl, trifluoromethoxy, and difluoromethoxy; as Q cyclic amine represented by the formula IIa, where both p1 and p2 are 1, X is hydrogen or hydroxyl; and Y is selected from the formulae Y1, Y2, Y3, Y8, Y9, Y13, Y18, Y19, Y28 (as defined in the first aspect) wherein the arrow indicates the connection to the cyclic amine of formula IIa.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano, as R2 hydrogen, as R3 methyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxymethyl, ethoxymethyl, methysulfonylmethyl, methysulfonylcyclopropyl, cyano-methyl or cyano-cyclopropyl; as R4 2,1,3-benzoxadiazolyl, phenyl substituted with 1 to 3 substituents independently selected from iodo, bromo, chloro, fluoro, pentafluoro-λ6-sulfanyl, methyl, cyclopropyl, trifluoromethyl, —O—CF2—O—, trifluoromethoxy, trifluoromethylsulfanyl, cyano, and methylsulfonyl, or one of thiophenyl, pyridyl (or pyridinyl), and pyrazolyl—each substituted with 1 to 2 substituents independently selected from fluorine, chlorine, methyl, ethyl, isopropyl, cyclopropyl, trifluoromethyl, difluoromethyl, trifluoromethoxy, and difluoromethoxy; as Q cyclic amine represented by the formula IIa, where both p1 and p2 are 1, X is hydrogen or hydroxyl; and Y is Y1 or Y19 (as defined in the first aspect) wherein the arrow indicates the connection to the cyclic amine of formula IIa.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano, as R2 hydrogen, as R3 methyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxymethyl, ethoxymethyl, methysulfonylmethyl, methysulfonylcyclopropyl, cyano-methyl or cyano-cyclopropyl; as R4 2,1,3-benzoxadiazolyl, or phenyl substituted with 1 to 3 substituents independently selected from iodo, bromo, chloro, fluoro, pentafluoro-λ6-sulfanyl, methyl, cyclopropyl, trifluoromethyl, —O—CF2—O—, trifluoromethoxy, trifluoromethylsulfanyl, cyano, and methylsulfonyl; as Q cyclic amine represented by the formula IIa, where both p1 and p2 are 1, X is hydrogen or hydroxyl; and Y is selected from the formulae Y1, Y2, Y3, Y8, Y9, Y13, Y18, Y19, Y28 (as defined in the first aspect) wherein the arrow indicates the connection to the cyclic amine of formula IIa.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano, as R2 hydrogen, as R3 methyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxymethyl, ethoxymethyl, methysulfonylmethyl, methysulfonylcyclopropyl, cyano-methyl or cyano-cyclopropyl; as R4 2,1,3-benzoxadiazolyl, phenyl substituted with 1 to 3 substituents independently selected from iodo, bromo, chloro, fluoro, pentafluoro-λ6-sulfanyl, methyl, cyclopropyl, trifluoromethyl, —O—CF2—O—, trifluoromethoxy, trifluoromethylsulfanyl, cyano, and methylsulfonyl or one of thiophenyl, pyridyl (or pyridinyl), and pyrazolyl—each substituted with 1 to 2 substituents independently selected from fluorine, chlorine, methyl, ethyl, isopropyl, cyclopropyl, trifluoromethyl, difluoromethyl, trifluoromethoxy, and difluoromethoxy; as Q cyclic amine represented by the formula IIa, where both p1 and p2 are 1, X is hydrogen or hydroxyl; and Y is dimethylsulfamoyl, ethyl(methyl)sulfamoyl, methylsulfamoyl, ethylsulfamoyl, sulfamoyl, dimethylsulfamoyl-methyl, [ethyl(methyl)-sulfamoyl]methyl, methylsulfamoyl-methyl, ethylsulfamoyl-methyl, sulfamoylmethyl, dimethylsulfamoyl amino, ethylsulfonylamino, methylsulfamoyl-amino, methyl(methyl-sulfamoyl)amino, dimethylsulfamoyl(methyl)amino, 2-(dimethylamino)-2-oxo-ethyl, 2-(methylamino)-2-oxo-ethyl, 2-amino-2-oxo-ethyl, 2-(dimethylamino)-2-oxo-ethoxy, methylsulfonyloxy, [acetyl(methyl)-amino]methyl, 1-(cyanocyclo-propyl)methoxy, acetamidomethyl, cyano-methyl, cyano-ethyl, or methylsulfonyl-methoxy.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano, as R2 hydrogen, as R3 methyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxymethyl, ethoxymethyl, methysulfonylmethyl, methysulfonylcyclopropyl, cyano-methyl or cyano-cyclopropyl; as R4 2,1,3-benzoxadiazolyl, phenyl substituted with 1 to 3 substituents independently selected from iodo, bromo, chloro, fluoro, trifluoromethyl, —O—CF2—O— and trifluoromethoxy, or one of thiophenyl, pyridyl (or pyridinyl), and pyrazolyl—each substituted with 1 to 2 substituents independently selected from fluorine, chlorine, methyl, ethyl, isopropyl, cyclopropyl, trifluoromethyl, difluoromethyl, trifluoromethoxy, and difluoromethoxy; as Q cyclic amine represented by the formula IIa, where both p1 and p2 are 1, X is hydrogen or hydroxyl; and Y is dimethylsulfamoyl, ethyl(methyl)sulfamoyl, methylsulfamoyl, ethylsulfamoyl, sulfamoyl, dimethylsulfamoyl-methyl, [ethyl(methyl)-sulfamoyl]methyl, methylsulfamoyl-methyl, ethylsulfamoyl-methyl, sulfamoylmethyl, dimethylsulfamoyl amino, ethylsulfonylamino, methylsulfamoyl-amino, methyl(methyl-sulfamoyl)amino, dimethylsulfamoyl(methyl)amino, 2-(dimethylamino)-2-oxo-ethyl, 2-(methylamino)-2-oxo-ethyl, 2-amino-2-oxo-ethyl, 2-(dimethylamino)-2-oxo-ethoxy, methylsulfonyloxy, [acetyl(methyl)-amino]methyl, 1-(cyanocyclo-propyl)methoxy, acetamidomethyl, cyano-methyl, cyano-ethyl, or methylsulfonyl-methoxy.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano, as R2 hydrogen, as R3 methyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxymethyl, ethoxymethyl, methysulfonylmethyl, methysulfonylcyclopropyl, cyano-methyl or cyano-cyclopropyl; as R4 2,1,3-benzoxadiazolyl, or phenyl substituted with 1 to 3 substituents independently selected from iodo, bromo, chloro, fluoro, trifluoromethyl, —O—CF2—O— and trifluoromethoxy; as Q cyclic amine represented by the formula IIa, where both p1 and p2 are 1, X is hydrogen or hydroxyl; and Y is dimethylsulfamoyl, ethyl(methyl)sulfamoyl, methylsulfamoyl, ethylsulfamoyl, sulfamoyl, dimethylsulfamoyl-methyl, [ethyl(methyl)-sulfamoyl]methyl, methylsulfamoyl-methyl, ethylsulfamoyl-methyl, sulfamoylmethyl, dimethylsulfamoyl amino, ethylsulfonylamino, methylsulfamoyl-amino, methyl(methyl-sulfamoyl)amino, dimethylsulfamoyl(methyl)amino, 2-(dimethylamino)-2-oxo-ethyl, 2-(methylamino)-2-oxo-ethyl, 2-amino-2-oxo-ethyl, 2-(dimethylamino)-2-oxo-ethoxy, methylsulfonyloxy, [acetyl(methyl)-amino]methyl, 1-(cyanocyclo-propyl)methoxy, acetamidomethyl, cyano-methyl, cyano-ethyl, or methylsulfonyl-methoxy.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano, as R2 hydrogen, as R3 methyl, cyclopropyl, methoxymethyl, difluoromethyl, or trifluoromethyl, as R4 2,1,3-benzoxadiazolyl, or phenyl substituted with 1 to 3 substituents independently selected from iodo, bromo, chloro, fluoro, trifluoromethyl, —O—CF2—O— and trifluoromethoxy; as Q cyclic amine represented by the formula IIa, where both p1 and p2 are 1, X is hydrogen or hydroxyl; and Y is dimethylsulfamoyl, ethyl(methyl)sulfamoyl, methylsulfamoyl, ethylsulfamoyl, sulfamoyl, dimethylsulfamoyl-methyl, [ethyl(methyl)-sulfamoyl]methyl, methylsulfamoyl-methyl, ethylsulfamoyl-methyl, sulfamoylmethyl, dimethylsulfamoyl amino, ethylsulfonylamino, methylsulfamoyl-amino, methyl(methyl-sulfamoyl)amino, dimethylsulfamoyl(methyl)amino, 2-(dimethylamino)-2-oxo-ethyl, 2-(methylamino)-2-oxo-ethyl, 2-amino-2-oxo-ethyl, 2-(dimethylamino)-2-oxo-ethoxy, methylsulfonyloxy, [acetyl(methyl)-amino]methyl, 1-(cyanocyclo-propyl)methoxy, acetamidomethyl, cyano-methyl, cyano-ethyl, or methylsulfonyl-methoxy.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano, as R2 hydrogen, as R3 cyclopropyl, methoxymethyl, difluoromethyl, or trifluoromethyl, as R4 2,1,3-benzoxadiazolyl, or phenyl substituted with 1 to 3 substituents independently selected from bromo, chloro, fluoro, trifluoromethyl, and —O—CF2—O—; as Q cyclic amine represented by the formula IIa, where both p1 and p2 are 1, X is hydrogen; and Y is dimethylsulfamoyl, ethyl(methyl)sulfamoyl, methylsulfamoyl, ethylsulfamoyl, sulfamoyl, or acetamidomethyl.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano or C(═S)NH2, as R2 hydrogen, as R3 methyl, difluoromethyl, trifluoromethyl, methoxymethyl, ethoxymethyl, methysulfonylmethyl, methysulfonylcyclopropyl, cyano-methyl or cyano-cyclopropyl; as R4 phenyl substituted with 1 to 3 substituents independently selected from halogen, pentafluoro-λ6-sulfanyl, C1-C4-alkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C3-C6-cyano-cycloalkyl, cyano, C1-C4-haloalkylsulfanyl, C1-C4-alkylsulfonyl and C1-C4-haloalkoxy, or one of thiophenyl, pyridyl (or pyridinyl), and pyrazolyl—each substituted with 1 to 2 substituents independently selected from from halogen, C1-C4-alkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C3-C6-cyanocycloalkyl, and C1-C4-haloalkoxy; as Q cyclic amine represented by the formula IIb, where both p1 and p2 are 1, A is selected from the formulae A1 to A12 (as defined in the first aspect) wherein the arrow indicates the connection to the cyclic amine of formula IIb.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano, as R2 hydrogen, as R3 methyl, difluoromethyl, trifluoromethyl, methoxymethyl, ethoxymethyl, methysulfonylmethyl, methysulfonylcyclopropyl, cyano-methyl or cyano-cyclopropyl; as R4 phenyl substituted with 1 to 3 substituents independently selected from halogen, pentafluoro-λ6-sulfanyl, C1-C4-alkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C3-C6-cyano-cycloalkyl, cyano, C1-C4-haloalkylsulfanyl, C1-C4-alkylsulfonyl and C1-C4-haloalkoxy, or one of thiophenyl, pyridyl (or pyridinyl), and pyrazolyl—each substituted with 1 to 2 substituents independently selected from halogen, C1-C4-alkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C3-C6-cyanocycloalkyl, and C1-C4-haloalkoxy; as Q cyclic amine represented by the formula IIb, where both p1 and p2 are 1, A is selected from the formulae A1 to A12 (as defined in the first aspect) wherein the arrow indicates the connection to the cyclic amine of formula IIb.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano, as R2 hydrogen, as R3 methyl, difluoromethyl, trifluoromethyl, methoxymethyl, ethoxymethyl, methysulfonylmethyl, methysulfonylcyclopropyl, cyano-methyl or cyano-cyclopropyl; as R4 phenyl substituted with 1 to 3 substituents independently selected from halogen, pentafluoro-λ6-sulfanyl, C1-C4-alkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C3-C6-cyano-cycloalkyl, cyano, C1-C4-haloalkylsulfanyl, C1-C4-alkylsulfonyl and C1-C4-haloalkoxy; as Q cyclic amine represented by the formula IIb, where both p1 and p2 are 1, A is selected from the formulae A1 to A12 (as defined in the first aspect) wherein the arrow indicates the connection to the cyclic amine of formula IIb.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano, as R2 hydrogen, as R3 methyl, difluoromethyl, trifluoromethyl, methoxymethyl, ethoxymethyl, methysulfonylmethyl, methysulfonylcyclopropyl, cyano-methyl or cyano-cyclopropyl; as R4 phenyl substituted with 1 to 3 substituents independently selected from halogen, pentafluoro-λ6-sulfanyl, C1-C4-alkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C3-C6-cyano-cycloalkyl, cyano, C1-C4-haloalkylsulfanyl, C1-C4-alkylsulfonyl and C1-C4-haloalkoxy; as Q cyclic amine represented by the formula IIb, where both p1 and p2 are 1, A is selected from the formulae A2, A6 and A7 (as defined in the first aspect) wherein the arrow indicates the connection to the cyclic amine of formula IIb.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano or C(═S)NH2, as R2 hydrogen, as R3 methyl, difluoromethyl, trifluoromethyl, methoxymethyl, ethoxymethyl, methysulfonylmethyl, methysulfonylcyclopropyl, cyano-methyl or cyano-cyclopropyl; as R4 phenyl substituted with 1 to 3 substituents independently selected from iodo, bromo, chloro, fluoro, pentafluoro-λ6-sulfanyl, methyl, cyclopropyl, trifluoromethyl, trifluoromethoxy, trifluoromethylsulfanyl, cyano, and methylsulfonyl; as Q cyclic amine represented by the formula IIb, where both p1 and p2 are 1, A is methylcarbamoyl, ethylcarbamoyl, iso-propyl-carbamoyl, 1-cyano-cyclo-propanecarbonyl, 2-cyano-2-methyl-propanoyl, 2-cyanoacetyl, (1-cyano-cyclopropyl)methyl, 2-(methylamino)-2-oxo-ethyl, 2-(ethylamino)-2-oxo-ethyl, 2-(dimethylamino)-2-oxo-ethyl, 2-[diethyl-amino]-2-oxo-ethyl], 2-[[ethyl(methyl)-amino]-2-oxo-ethyl], 1,1-dimethyl-2-(methylamino)-2-oxo-ethyl, 2-(dimethylamino)-1,1-dimethyl-2-oxo-ethyl], 2-methoxy-1,1-dimethyl-ethyl, 2-methoxyethyl, or 3-methoxy-propanoyl.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano, as R2 hydrogen, as R3 methyl, difluoromethyl, trifluoromethyl, methoxymethyl, ethoxymethyl, methysulfonylmethyl, methysulfonylcyclopropyl, cyano-methyl or cyano-cyclopropyl; as R4 phenyl substituted with 1 to 3 substituents independently selected from iodo, bromo, chloro, fluoro, trifluoromethyl, trifluoromethoxy and —OCF2O—; as Q cyclic amine represented by the formula IIb, where both p1 and p2 are 1, A is methylcarbamoyl, ethylcarbamoyl, iso-propyl-carbamoyl, 1-cyano-cyclo-propanecarbonyl, 2-cyano-2-methyl-propanoyl, 2-cyanoacetyl, (1-cyano-cyclopropyl)methyl, 2-(methylamino)-2-oxo-ethyl, 2-(ethylamino)-2-oxo-ethyl, 2-(dimethylamino)-2-oxo-ethyl, 2-[diethyl-amino]-2-oxo-ethyl], 2-[ethyl(methyl)-amino]-2-oxo-ethyl], 1,1-dimethyl-2-(methylamino)-2-oxo-ethyl, 2-(dimethylamino)-1,1-dimethyl-2-oxo-ethyl], 2-methoxy-1,1-dimethyl-ethyl, 2-methoxyethyl, or 3-methoxy-propanoyl.
In an embodiment of each aspect of the invention, the compound of formula (I) has as R1 cyano, as R2 hydrogen, as R3 methyl, difluoromethyl, trifluoromethyl; as R4 phenyl substituted with 1 to 3 substituents independently selected from iodo, bromo, chloro, fluoro, trifluoromethyl, trifluoromethoxy and —OCF2O—; as Q cyclic amine represented by the formula IIb, where both p1 and p2 are 1, A is methylcarbamoyl, ethylcarbamoyl, iso-propyl-carbamoyl, 1-cyano-cyclo-propanecarbonyl, 2-cyano-2-methyl-propanoyl, 2-cyanoacetyl, (1-cyano-cyclopropyl)methyl, 2-(methylamino)-2-oxo-ethyl, 2-(ethylamino)-2-oxo-ethyl, 2-(dimethylamino)-2-oxo-ethyl, 2-[diethyl-amino]-2-oxo-ethyl], 2-[ethyl(methyl)-amino]-2-oxo-ethyl], 1,1-dimethyl-2-(methylamino)-2-oxo-ethyl, 2-(dimethylamino)-1,1-dimethyl-2-oxo-ethyl], 2-methoxy-1,1-dimethyl-ethyl, 2-methoxyethyl, or 3-methoxy-propanoyl.
In a second aspect, the present invention makes available a composition comprising a compound of formula (I) as defined in the first aspect, one or more auxiliaries and diluent, and optionally one more other active ingredient.
In a third aspect, the present invention makes available a method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound as defined in the first aspect or a composition as defined in the second aspect.
In a fourth aspect, the present invention makes available a method for the protection of plant propagation material from the attack by insects, acarines, nematodes or molluscs, which comprises treating the propagation material or the site, where the propagation material is planted, with an effective amount of a compound of formula (I) as defined in the first aspect or a composition as defined in the second aspect.
In a fifth aspect, the present invention makes available a plant propagation material, such as a seed, comprising, or treated with or adhered thereto, a compound of formula (I) as defined in the first aspect or a composition as defined in the second aspect.
The present invention in a further aspect provides a method of controlling parasites in or on an animal in need thereof comprising administering an effective amount of a compound of the first aspect. The present invention further provides a method of controlling ectoparasites on an animal in need thereof comprising administering an effective amount of a compound of formula (I) as defined om the first aspect. The present invention further provides a method for preventing and/or treating diseases transmitted by ectoparasites comprising administering an effective amount of a compound of formula (I) as defined in the first aspect, to an animal in need thereof.
Compounds of formula (I) can be prepared by those skilled in the art following known methods. More specifically compounds of formulae I, and I′a, and intermediates therefor can be prepared as described below in the schemes and examples. Certain stereogenic centers have been left unspecified for the clarity and are not intended to limit the teaching of the schemes in any way.
The process according to the invention for preparing compounds of formula (I) is carried out by methods known to those skilled in the art.
The compounds of formula (I) are new and can be prepared by reacting an acid III in which R1, R2, R3, and R4 are as previously defined with an amine IV-a or IV-b in which X, Y, A, p1, p2, q1 and q2 are as previously defined using known amide coupling reagents, such as 1-[bis(dimethylamino)-methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) and a base, for example Hunig's base, in a suitable solvent, for example dimethylformamide (DMF) or dimethylacetamide (DMA) according to scheme 1. Piperidines IV-a or piperazines IV-b are commercially available, known from the literature or can be prepared by the person skilled in the art.
Alternatively the compounds of formula (I) can be prepared by reacting an acid chloride V in which R1, R2, R3 and R4 are as previously defined with an amine IV-a or IV-b in which X, Y, A, p1, p2, q1 and q2 are as previously defined in the presence of a base, for example triethylamine or pyridine, and a suitable solvent, for example dichloromethane (DCM), tetrahydrofuran (THF) or toluene, according to scheme 2.
The acid chloride V in which R1, R2, R3 and R4 are as previously defined can be prepared from the corresponding acid III in which R1, R2, R3 and R4 are as previously defined by treatment with for example, oxalyl chloride or thionyl chloride in the presence of catalytic quantities of DMF in inert solvents such as DCM or THE at temperatures between 20° C. to 100° C., preferably 25° C. according to scheme 3.
The acid III in which R1, R2, R3 and R4 are as previously defined can be prepared by hydrolysis of the corresponding ester VI in which in which R1, R2, R3 and R4 are as previously defined and Rx=C1-C6-alkyl under basic conditions, for example using an inorganic base such as lithium hydroxide, sodium hydroxide, potassium hydroxide or potassium carbonate in water, methanol, ethanol or THF, according to scheme 4.
The ester VI in which R1, R2, R3 and R4 are as previously defined can be prepared by reaction of the pyridone VII in which R1, R2, R3, R4 and Rx are as previously defined with an alkylating reagent VIII in which R4 is as previously defined and LG1 is a leaving group, such as a halogen, e.g. bromine, chlorine, iodine, or a mesylate in the presence of a base, for example an inorganic base such as lithium hydroxide, sodium hydroxide, potassium hydroxide or potassium carbonate, and a suitable solvent, for example water, methanol, ethanol, acetone, THF, DMF or toluene according to scheme 5. It might be advantageous to add sodium iodide or a phase-transfer catalyst, for example tetrabutylammonium bromide or tetrabutylammonium iodide.
Alternatively, the ester VI can be prepared by reacting the pyridine IX in which R1, R2, R3, Rx are as previously defined and LG2 is a leaving group, such as a halogen, e.g. fluorine, bromine, chlorine, iodine, or a mesylate with an alcohol X in the presence of a base, for example sodium hydride, lithium hydroxide, sodium hydroxide, potassium hydroxide or potassium carbonate and a suitable solvent, for example THF, DMF or toluene, according to scheme 6.
Alternatively, the compounds of formula (I) can be obtained by reaction of the pyridone XI in which R1, R2, R3 and Q are as previously defined with an alkylating reagent VIII in which R4 is as previously defined and LG1 is a leaving group, such as a halogen, e.g. bromine, chlorine, iodine, or a mesylate in the presence of a base, for example an inorganic base such as lithium hydroxide, sodium hydroxide, potassium hydroxide or potassium carbonate, in a suitable solvent, for example water, methanol, ethanol, acetone, THF, DMF or toluene a according to scheme 7. It might be advantageous to add sodium iodide or a phase-transfer catalyst, for example tetrabutylammonium bromide or tetrabutylammonium iodide.
Alternatively, the compounds of formula (I) can be prepared by reacting the pyridine XII in which R1, R2, R3 and Q are as previously defined and LG2 is a leaving group, such as a halogen, e.g. fluorine, bromine, chlorine, iodine, or a mesylate with an alcohol X in the presence of a base, for example sodium hydride, lithium hydroxide, sodium hydroxide, potassium hydroxide or potassium carbonate and a suitable solvent, for example THF, DMF or toluene according to scheme 8.
Compounds of formula XII in which R1, R2, R3 and Q are as previously defined and LG2 is a leaving group can be obtained by treating a pyridone XI in which R1, R2, R3 and Q are as previously defined with a halogenation reagent, such as phosphorus oxychloride or oxalyl chloride or mesylchloride according to scheme 9.
Pyridones XI in which R1, R2, R3 and Q are as previously defined can be prepared by reacting an acid XIII in which R1, R2 and R3 are as previously defined with an amine IV-a or IV-b in which X, Y, A, p1, p2, q1 and q2 are as previously defined using known amide coupling reagents, such as HATU and a base, for example Hunig's base, in a suitable solvent, for example DMF or DMA according to scheme 10.
Alternatively the compounds of formula XI in which R1, R2, R3 and Q are as previously defined can be prepared by reacting an acid chloride XIV in which R1, R2 and R3 are as previously defined with an amine IV-a or IV-b in the presence of a base, for example triethylamine or pyridine, and a suitable solvent, for example DCM, THE or toluene, according to scheme 11.
The acid chloride XIV in which R1, R2 and R3 are as previously defined can be prepared from the corresponding acid XIII in which R1, R2 and R3 are as previously defined by treatment with for example, oxalyl chloride or thionyl chloride in the presence of catalytic quantities of DMF in inert solvents such as DCM or THE at temperatures between 20° C. to 100° C., preferably 25° C. according to scheme 12.
The acid XIII in which R1, R2 and R3 are as previously defined can be prepared by hydrolysis of the corresponding ester XV in which R1, R2, R3 and Rx are as previously defined under basic conditions, for example using an inorganic base such as lithium hydroxide, sodium hydroxide, potassium hydroxide or potassium carbonate in water, methanol, ethanol or THF. Esters of the formula XV in which R1, R2, R3 and Rx are as previously defined are known in the literature, for example Y. Xie et al., Pest Manag. Sci. 2017, 73, 945-952, or can be prepared by the person skilled in the art.
The compounds of formula (I) according to the following Tables 1 to 57 can be prepared according to the methods described above. The examples which follow are intended to illustrate the invention and show preferred compounds of formula (I), in the form of a compound of formula (I-a).
Each of Tables 1 to 36, which follow the Table M below, comprises 2486 compounds of the formula (I-a) in which R1, R3 and R5 have the values given in each row in Table M, and Y and X have the values given in the relevant Tables 1 to 36.
Thus compound 1.1 corresponds to a compound of formula (I-a) where R1, R3 and R5 are as defined in row 1 of Table M and where Y and X are as defined in Table 1; compound 14.14 corresponds to a compound of formula (I-a) where R1, R3 and R5 are as defined in row 14 of Table M and where Y and X are as defined in Table 14; and so on.
Table 1: This table discloses the 2486 compounds 1.1 to 1.2486 of the formula (I-a), wherein Y is dimethylsulfamoyl, X is hydrogen and R1, R3 and R5 are as defined in Table M. For example, compound No. 1.1 has the following structure:
Table 2: This table discloses the 2486 compounds 2.1 to 2.2486 of the formula (I-a), wherein Y is ethyl(methyl)sulfamoyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 3: This table discloses the 2486 compounds 3.1 to 3.2486 of the formula (I-a), wherein Y is methylsulfamoyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 4: This table discloses the 2486 compounds 4.1 to 4.2486 of the formula (I-a), wherein Y is ethylsulfamoyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 5: This table discloses the 2486 compounds 5.1 to 5.2486 of the formula (I-a), wherein Y is sulfamoyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 6: This table discloses the 2486 compounds 6.1 to 6.2486 of the formula (I-a), wherein Y is dimethylsulfamoyl-methyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 7: This table discloses the 2486 compounds 7.1 to 7.2486 of the formula (I-a), wherein Y is [ethyl(methyl)-sulfamoyl]methyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 8: This table discloses the 2486 compounds 8.1 to 8.2486 of the formula (I-a), wherein Y is methylsulfamoyl-methyl, X is hydroxyl and R1, R3 and R5 are as defined in Table M.
Table 9: This table discloses the 2486 compounds 9.1 to 9.2486 of the formula (I-a), wherein Y is ethylsulfamoyl-methyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 10: This table discloses the 2486 compounds 10.1 to 10.2486 of the formula (I-a), wherein Y is sulfamoylmethyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 11: This table discloses the 2486 compounds 11.1 to 11.2486 of the formula (I-a), wherein Y is dimethylsulfamoyl amino, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 12: This table discloses the 2486 compounds 12.1 to 12.2486 of the formula (I-a), wherein Y is ethylsulfonylamino, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 13: This table discloses the 2486 compounds 13.1 to 13.2486 of the formula (I-a), wherein Y is methylsulfamoyl-amino, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 14: This table discloses the 2486 compounds 14.1 to 14.2486 of the formula (I-a), wherein Y is methyl(methyl-sulfamoyl)amino, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 15: This table discloses the 2486 compounds 15.1 to 15.2486 of the formula (I-a), wherein Y is dimethylsulfamoyl(methyl)amino, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 16: This table discloses the 2486 compounds 16.1 to 16.2486 of the formula (I-a), wherein Y is methyl(methyl-sulfonyl)amino, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 17: This table discloses the 2486 compounds 17.1 to 17.2486 of the formula (I-a), wherein Y is [methyl(methyl-sulfonyl)amino]-methyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 18: This table discloses the 2486 compounds 18.1 to 18.2486 of the formula (I-a), wherein Y is 2-(dimethylamino)-2-oxo-ethyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 19: This table discloses the 2486 compounds 19.1 to 19.2486 of the formula (I-a), wherein Y is 2-(methylamino)-2-oxo-ethyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 20: This table discloses the 2486 compounds 20.1 to 20.2486 of the formula (I-a), wherein Y is 2-amino-2-oxo-ethyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 21: This table discloses the 2486 compounds 21.1 to 21.2486 of the formula (I-a), wherein Y is 2-(dimethylamino)-2-oxo-ethoxy, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 22: This table discloses the 2486 compounds 22.1 to 22.2486 of the formula (I-a), wherein Y is dimethylcarbamoylamino, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 23: This table discloses the 2486 compounds 23.1 to 23.2486 of the formula (I-a), wherein Y is methylcarbamoyl-amino, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 24: This table discloses the 2486 compounds 24.1 to 24.2486 of the formula (I-a), wherein Y is methanesulfon-amidomethyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 25: This table discloses the 2486 compounds 25.1 to 25.2486 of the formula (I-a), wherein Y is methylsulfonyloxy, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 26: This table discloses the 2486 compounds 26.1 to 26.2486 of the formula (I-a), wherein Y is (2-methoxy-acetyl)amino, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 27: This table discloses the 2486 compounds 27.1 to 27.2486 of the formula (I-a), wherein Y is [acetyl(methyl)-amino]methyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 28: This table discloses the 2486 compounds 28.1 to 28.2486 of the formula (I-a), wherein Y is 1-(cyanocyclo-propyl)methoxy, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 29: This table discloses the 2486 compounds 29.1 to 29.2486 of the formula (I-a), wherein Y is 2-ethoxy-2-oxo-ethyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 30: This table discloses the 2486 compounds 30.1 to 30.2486 of the formula (I-a), wherein Y is acetamidomethyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 31: This table discloses the 2486 compounds 31.1 to 31.2486 of the formula (I-a), wherein Y is [acetyl(ethyl)amino]methyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 32: This table discloses the 2486 compounds 32.1 to 32.2486 of the formula (I-a), wherein Y is methylsulfonyl-methoxy, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 33: This table discloses the 2486 compounds 33.1 to 33.2486 of the formula (I-a), wherein Y is ethylsulfonyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 34: This table discloses the 2486 compounds 34.1 to 34.2486 of the formula (I-a), wherein Y is [dimethylcarbamoyl(methyl)amino]methyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 35: This table discloses the 2486 compounds 35.1 to 35.2486 of the formula (I-a), wherein Y is 2-acetamidoethoxy, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Table 36: This table discloses the 2486 compounds 36.1 to 36.2486 of the formula (I-a), wherein Y is 2-[acetyl(methyl)amino] ethyl, X is hydrogen and R1, R3 and R5 are as defined in Table M.
Specific examples of compounds of the present invention are represented by the formula (I-b) in the following Tables 37 to 57:
Each of Tables 37 to 57 below, comprises 2486 compounds of the formula (I-b) in which R1, R3 and R5 have the values given in each row in Table M, and A has the values given in the relevant Tables 37 to 57. Thus compound 37.1 corresponds to a compound of formula (I-b) where R1, R3 and R5 are as defined in row 1 of Table M and where A is as defined in Table 37; compound 50.14 corresponds to a compound of formula (I-b) where R1, R3 and R5 are as defined in row 14 of Table M and where A is as defined in Table 50; and so on.
Table 37: This table discloses the 2486 compounds 37.1 to 37.2486 of the formula (I-b), wherein A is methylcarbamoyl, and R1, R3 and R5 are as defined in Table M. For example, compound No. 37.1 has the following structure:
Table 38: This table discloses the 2486 compounds 38.1 to 38.2486 of the formula (I-b), wherein A is ethylcarbamoyl, and R1, R3 and R5 are as defined in Table M.
Table 39: This table discloses the 2486 compounds 39.1 to 39.2486 of the formula (I-b), wherein A is iso-propyl-carbamoyl, and R1, R3 and R5 are as defined in Table M.
Table 40: This table discloses the 2486 compounds 40.1 to 40.2486 of the formula (I-b), wherein A is 1-cyano-cyclo-propanecarbonyl, and R1, R3 and R5 are as defined in Table M.
Table 41: This table discloses the 2486 compounds 41.1 to 41.2486 of the formula (I-b), wherein A is 2-cyano-2-methyl-propanoyl and R1, R3 and R5 are as defined in Table M.
Table 42: This table discloses the 2486 compounds 42.1 to 42.2486 of the formula (I-b), wherein A is 2-cyanoacetyl, and R1, R3 and R5 are as defined in Table M.
Table 43: This table discloses the 2486 compounds 43.1 to 43.2486 of the formula (I-b), wherein A is (1-cyano-cyclopropyl)methyl, and R1, R3 and R5 are as defined in Table M.
Table 44: This table discloses the 2486 compounds 44.1 to 44.2486 of the formula (I-b), wherein A is 2-(methylamino)-2-oxo-ethyl, and R1, R3 and R5 are as defined in Table M.
Table 45: This table discloses the 2486 compounds 45.1 to 45.2486 of the formula (I-b), wherein A is 2-(ethylamino)-2-oxo-ethyl and R1, R3 and R5 are as defined in Table M.
Table 46: This table discloses the 2486 compounds 46.1 to 46.2486 of the formula (I-b), wherein A is 2-(dimethylamino)-2-oxo-ethyl, and R1, R3 and R5 are as defined in Table M.
Table 47: This table discloses the 2486 compounds 47.1 to 47.2486 of the formula (I-b), wherein A is 2-[diethyl-amino]-2-oxo-ethyl], and R1, R3 and R5 are as defined in Table M.
Table 48: This table discloses the 2486 compounds 48.1 to 48.2486 of the formula (I-b), wherein A is 2-[ethyl(methyl)-amino]-2-oxo-ethyl] and R1, R3 and R5 are as defined in Table M.
Table 49: This table discloses the 2486 compounds 49.1 to 49.2486 of the formula (I-b), wherein A is 1,1-dimethyl-2-(methylamino)-2-oxo-ethyl, and R1, R3 and R5 are as defined in Table M.
Table 50: This table discloses the 2486 compounds 50.1 to 50.2486 of the formula (I-b), wherein A is 2-(dimethylamino)-1,1-dimethyl-2-oxo-ethyl, and R1, R3 and R5 are as defined in Table M.
Table 51: This table discloses the 2486 compounds 51.1 to 51.2486 of the formula (I-b), wherein A is 2-methoxy-1,1-dimethyl-ethyl, and R1, R3 and R5 are as defined in Table M.
Table 52: This table discloses the 2486 compounds 52.1 to 52.2486 of the formula (I-b), wherein A is 2-methoxyethyl, and R1, R3 and R5 are as defined in Table M.
Table 53: This table discloses the 2486 compounds 53.1 to 53.2486 of the formula (I-b), wherein A is 3-methoxy-propanoyl, and R1, R3 and R5 are as defined in Table M.
Table 54: This table discloses the 2486 compounds 54.1 to 54.2486 of the formula (I-b), wherein A is (4-chloro-phenyl)methyl, and R1, R3 and R5 are as defined in Table M.
Table 55: This table discloses the 2486 compounds 55.1 to 55.2486 of the formula (I-b), wherein A is 2-(cyclopropyl-amino)-2-oxo-ethyl, and R1, R3 and R5 are as defined in Table M.
Table 56: This table discloses the 2486 compounds 56.1 to 56.2486 of the formula (I-b), wherein A is 1-cyano-cyclopropane-carbonyl, and R1, R3 and R5 are as defined in Table M.
Table 57: This table discloses the 2486 compounds 56.1 to 57.2486 of the formula (I-b), wherein A is 1-(dimethylcarbamoyl)-cyclopropyl, and R1, R3 and R5 are as defined in Table M.
Also made available are certain intermediate compounds of the amine of formulae XI-a, XI-b, XII-a, XII-b, some of which are novel.
Accordingly, made available herein are:
The compounds of formula (I) according to the invention are preventively and/or curatively valuable active ingredients in the field of pest control, even at low rates of application, which have a very favorable biocidal spectrum and are well tolerated by warm-blooded species, fish and plants. The active ingredients according to the invention act against all or individual developmental stages of normally sensitive, but also resistant, animal pests, such as insects or representatives of the order Acarina. The insecticidal or acaricidal activity of the active ingredients according to the invention can manifest itself directly, i. e. in destruction of the pests, which takes place either immediately or only after some time has elapsed, for example during ecdysis, or indirectly, for example in a reduced oviposition and/or hatching rate.
Examples of the above mentioned animal pests are:
In a further aspect, the invention may also relate to a method of controlling damage to plant and parts thereof by plant parasitic nematodes (Endoparasitic-, Semiendoparasitic- and Ectoparasitic nematodes), especially plant parasitic nematodes such as root knot nematodes, Meloidogyne hapla, Meloidogyne incognita, Meloidogyne javanica, Meloidogyne arenaria and other Meloidogyne species; cyst-forming nematodes, Globodera rostochiensis and other Globodera species; Heterodera avenae, Heterodera glycines, Heterodera schachtii, Heterodera trifolii, and other Heterodera species; Seed gall nematodes, Anguina species; Stem and foliar nematodes, Aphelenchoides species; Sting nematodes, Belonolaimus longicaudatus and other Belonolaimus species; Pine nematodes, Bursaphelenchus xylophilus and other Bursaphelenchus species; Ring nematodes, Criconema species, Criconemella species, Criconemoides species, Mesocriconema species; Stem and bulb nematodes, Ditylenchus destructor, Ditylenchus dipsaci and other Ditylenchus species; Awl nematodes, Dolichodorus species; Spiral nematodes, Heliocotylenchus multicinctus and other Helicotylenchus species; Sheath and sheathoid nematodes, Hemicycliophora species and Hemicriconemoides species; Hirshmanniella species; Lance nematodes, Hoploaimus species; false rootknot nematodes, Nacobbus species; Needle nematodes, Longidorus elongatus and other Longidorus species; Pin nematodes, Pratylenchus species; Lesion nematodes, Pratylenchus neglectus, Pratylenchus penetrans, Pratylenchus curvitatus, Pratylenchus goodeyi and other Pratylenchus species; Burrowing nematodes, Radopholus similis and other Radopholus species; Reniform nematodes, Rotylenchus robustus, Rotylenchus reniformis and other Rotylenchus species; Scutellonema species; Stubby root nematodes, Trichodorus primitivus and other Trichodorus species, Paratrichodorus species; Stunt nematodes, Tylenchorhynchus claytoni, Tylenchorhynchus dubius and other Tylenchorhynchus species; Citrus nematodes, Tylenchulus species; Dagger nematodes, Xiphinema species; and other plant parasitic nematode species, such as Subanguina spp., Hypsoperine spp., Macroposthonia spp., Melinius spp., Punctodera spp., and Quinisulcius spp.
The compounds of the invention may also have activity against the molluscs. Examples of which include, for example, Ampullariidae; Arion (A. ater, A. circumscriptus, A. hortensis, A. rufus); Bradybaenidae (Bradybaena fruticum); Cepaea (C. hortensis, C. Nemoralis); ochlodina; Deroceras (D. agrestis, D. empiricorum, D. laeve, D. reticulatum); Discus (D. rotundatus); Euomphalia; Galba (G. trunculata); Helicelia (H. itala, H. obvia); Helicidae Helicigona arbustorum); Helicodiscus; Helix (H. aperta); Limax (L. cinereoniger, L. flavus, L. marginatus, L. maximus, L. tenellus); Lymnaea; Milax (M. gagates, M. marginatus, M. sowerbyi); Opeas; Pomacea (P. canaticulata); Vallonia and Zanitoides.
The active ingredients according to the invention can be used for controlling, i. e. containing or destroying, pests of the abovementioned type which occur in particular on plants, especially on useful plants and ornamentals in agriculture, in horticulture and in forests, or on organs, such as fruits, flowers, foliage, stalks, tubers or roots, of such plants, and in some cases even plant organs which are formed at a later point in time remain protected against these pests.
Suitable target crops are, in particular, cereals, such as wheat, barley, rye, oats, rice, maize or sorghum; beet, such as sugar or fodder beet; fruit, for example pomaceous fruit, stone fruit or soft fruit, such as apples, pears, plums, peaches, almonds, cherries or berries, for example strawberries, raspberries or blackberries; leguminous crops, such as beans, lentils, peas or soya; oil crops, such as oilseed rape, mustard, poppies, olives, sunflowers, coconut, castor, cocoa or ground nuts; cucurbits, such as pumpkins, cucumbers or melons; fibre plants, such as cotton, flax, hemp or jute; citrus fruit, such as oranges, lemons, grapefruit or tangerines; vegetables, such as spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes or bell peppers; Lauraceae, such as avocado, Cinnamonium or camphor; and also tobacco, nuts, coffee, eggplants, sugarcane, tea, pepper, grapevines, hops, the plantain family and latex plants.
In a particular embodiment, a compound of the formula (I) controls mites, rust mites and spider mites in crops, tress, and plants selected from vegetables (especially tomatoes and cucurbits), citrus, pome fruits, stone fruit, tree nuts, cotton, tropical crops, avocados, ornamentals, beans, soybean, strawberry, and grapes.
The compositions and/or methods of the present invention may be also used on any ornamental and/or vegetable crops, including flowers, shrubs, broad-leaved trees and evergreens.
For example the invention may be used on any of the following ornamental species: Ageratum spp., Alonsoa spp., Anemone spp., Anisodontea capsenisis, Anthemis spp., Antirrhinum spp., Aster spp., Begonia spp. (e.g. B. elatior, B. semperflorens, B. tubereux), Bougainvillea spp., Brachycome spp., Brassica spp. (ornamental), Calceolaria spp., Capsicum annuum, Catharanthus roseus, Canna spp., Centaurea spp., Chrysanthemum spp., Cineraria spp. (C. maritime), Coreopsis spp., Crassula coccinea, Cuphea ignea, Dahlia spp., Delphinium spp., Dicentra spectabilis, Dorotheantus spp., Eustoma grandiflorum, Forsythia spp., Fuchsia spp., Geranium gnaphalium, Gerbera spp., Gomphrena globosa, Heliotropium spp., Helianthus spp., Hibiscus spp., Hortensia spp., Hydrangea spp., Hypoestes phyllostachya, Impatiens spp. (I. walleriana), Iresines spp., Kalanchoe spp., Lantana camara, Lavatera trimestris, Leonotis leonurus, Lilium spp., Mesembryanthemum spp., Mimulus spp., Monarda spp., Nemesia spp., Tagetes spp., Dianthus spp. (carnation), Canna spp., Oxalis spp., Bellis spp., Pelargonium spp. (P. peltatum, P. Zonale), Viola spp. (pansy), Petunia spp., Phlox spp., Plecthranthus spp., Poinsettia spp., Parthenocissus spp. (P. quinquefolia, P. tricuspidata), Primula spp., Ranunculus spp., Rhododendron spp., Rosa spp. (rose), Rudbeckia spp., Saintpaulia spp., Salvia spp., Scaevola aemola, Schizanthus wisetonensis, Sedum spp., Solanum spp., Surfinia spp., Tagetes spp., Nicotinia spp., Verbena spp., Zinnia spp. and other bedding plants.
For example the invention may be used on any of the following vegetable species: Allium spp. (A. sativum, A. cepa, A. oschaninii, A. Porrum, A. ascalonicum, A. fistulosum), Anthriscus cerefolium, Apium graveolus, Asparagus officinalis, Beta vulgarus, Brassica spp. (B. Oleracea, B. Pekinensis, B. rapa), Capsicum annuum, Cicer arietinum, Cichorium endivia, Cichorum spp. (C. intybus, C. endivia), Citrillus lanatus, Cucumis spp. (C. sativus, C. melo), Cucurbita spp. (C. pepo, C. maxima), Cyanara spp. (C. scolymus, C. cardunculus), Daucus carota, Foeniculum vulgare, Hypericum spp., Lactuca sativa, Lycopersicon spp. (L. esculentum, L. lycopersicum), Mentha spp., Ocimum basilicum, Petroselinum crispum, Phaseolus spp. (P. vulgaris, P. coccineus), Pisum sativum, Raphanus sativus, Rheum rhaponticum, Rosemarinus spp., Salvia spp., Scorzonera hispanica, Solanum melongena, Spinacea oleracea, Valerianella spp. (V. locusta, V. eriocarpa) and Vicia faba.
Preferred ornamental species include African violet, Begonia, Dahlia, Gerbera, Hydrangea, Verbena, Rosa, Kalanchoe, Poinsettia, Aster, Centaurea, Coreopsis, Delphinium, Monarda, Phlox, Rudbeckia, Sedum, Petunia, Viola, Impatiens, Geranium, Chrysanthemum, Ranunculus, Fuchsia, Salvia, Hortensia, rosemary, sage, St. Johnswort, mint, sweet pepper, tomato and cucumber.
The active ingredients according to the invention are especially suitable for controlling Aphis craccivora, Diabrotica balteata, Heliothis virescens, Myzus persicae, Plutella xylostella and Spodoptera littoralis in cotton, vegetable, maize, rice and soya crops. The active ingredients according to the invention are further especially suitable for controlling Mamestra (preferably in vegetables), Cydia pomonella (preferably in apples), Empoasca (preferably in vegetables, vineyards), Leptinotarsa (preferably in potatoes) and Chilo supressalis (preferably in rice).
The compounds of formula (I) are particularly suitable for control of mites, spider mites and rust mites, for example, Acarapis spp; Acarapis woodi; Acarus siro; Acarus spp; Aceria sheldoni; Aculops pelekassi; Aculops spp; Aculus schlechtendali; Aculus spp; Amblyseius fallacis; Brevipalpus spp; Brevipalpus phoenicis; Bryobia praetiosa; Bryobia rubrioculus; Caloglyphus spp; Cheyletiella blakei; Cheyletiella spp; Cheyletiella yasguri; Chorioptes bovis; Chorioptes spp; Cytodites spp; Demodex bovis; Demodex caballi; Demodex canis; Demodex caprae; Demodex equi; Demodex ovis; Demodex spp; Demodex suis; Dermanyssus gallinae; Dermanyssus spp; Eotetranychus spp; Eotetranychus willamettei; Epitrimerus pyri; Eriophyes ribis; Eriophyes spp; Eriophyes vitis; Eutetranychus spp; Halotydeus destructor; Hemitarsonemus spp; Knemidocoptes spp; Laminosioptes spp; Listrophorus spp; Myobia spp; Neoschongastia xerothermobia; Neotrombicula autumnalis; Neotrombicula desaleri; Notoedres cati; Notoedres spp; Oligonychus coffeae; Oligonychus ilicis; Oligonychus spp; Ornithocheyletia spp; Ornithonyssus bursa; Ornithonyssus spp; Ornithonyssus sylviarum; Otodectes cynotis; Otodectes spp; Panonychus citri; Panonychus spp; Panonychus ulmi; Phyllocoptruta oleivora; Phyllocoptruta spp.; Phytoseiulus spp.; Pneumonyssoides caninum; Polyphagotarsonemus latus; Polyphagotarsonemus spp; Psorergates ovis; Psorergates spp; Psoroptes cuniculi; Psoroptes equi; Psoroptes ovis; Psoroptes spp; Pterolichus spp; Raillietia spp; Rhizoglyphus spp; Sarcoptes bovis; Sarcoptes canis; Sarcoptes caprae; Sarcoptes equi; Sarcoptes ovis; Sarcoptes rupicaprae; Sarcoptes spp; Sarcoptes suis; Steneotarsonemus spinki; Steneotarsonemus spp; Sternostoma spp; Tarsonemus spp; Tetranychus cinnabarinus; Tetranychus kanzawai; Tetranychus spp; Tetranychus urticae; Trombicula akamushi; Trombicula spp; Typhlodromus occidentalis; Tyrophagus spp; Varroa jacobsoni; Varroa spp; Vasates lycopersici; and Zetzellia mali.
In an embodiment, a compound of formula (I) are especially suitable for controlling one or more of: Aceria sheldoni; Aculus lycopersici; Aculus pelekassi; Aculus schlechtendali; Brevipalpus phoenicis; Brevipalpus spp.; Bryobia rubrioculus; Eotetranychus carpini; Eotetranychus spp.; Epitrimerus pyri; Eriophyes piri; Eriophyes spp.; Eriophyes vitis; Eutetranychus africanus; Eutetranychus orientalis; Oligonychus pratensis; Panonychus citri; Panonychus ulmi; Phyllocoptes vitis; Phyllocoptruta oleivora; Polyphagotarsonemus latus; Tetranychus cinnabarinus; Tetranychus kanzawai; Tetranychus spp.; and Tetranychus urticae.
In a further embodiment, a compound of formula (I) are more especially suitable for controlling one or more of: Aceria sheldoni; Aculus pelekassi; Brevipalpus phoenicis; Brevipalpus spp.; Eriophyes piri; Eriophyes vitis; Eutetranychus africanus; Eutetranychus orientalis; Oligonychus pratensis; Panonychus ulmi; Phyllocoptes vitis; Phyllocoptruta oleivora; Polyphagotarsonemus latus; Tetranychus cinnabarinus; Tetranychus kanzawai; Tetranychus spp.; and Tetranychus urticae.
The term “crops” is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins, for example insecticidal proteins from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as δ-endotoxins, e.g. Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vip1, Vip2, Vip3 or Vip3A; or insecticidal proteins of bacteria colonising nematodes, for example Photorhabdus spp. or Xenorhabdus spp., such as Photorhabdus luminescens, Xenorhabdus nematophilus; toxins produced by animals, such as scorpion toxins, arachnid toxins, wasp toxins and other insect-specific neurotoxins; toxins produced by fungi, such as Streptomycetes toxins, plant lectins, such as pea lectins, barley lectins or snowdrop lectins; agglutinins; proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors; ribosome-inactivating proteins (RIP), such as ricin, maize-RIP, abrin, luffin, saporin or bryodin; steroid metabolism enzymes, such as 3-hydroxysteroidoxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidases, ecdysone inhibitors, HMG-COA-reductase, ion channel blockers, such as blockers of sodium or calcium channels, juvenile hormone esterase, diuretic hormone receptors, stilbene synthase, bibenzyl synthase, chitinases and glucanases.
In the context of the present invention there are to be understood by 6-endotoxins, for example Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), for example Vip1, Vip2, Vip3 or Vip3A, expressly also hybrid toxins, truncated toxins and modified toxins. Hybrid toxins are produced recombinantly by a new combination of different domains of those proteins (see, for example, WO 02/15701). Truncated toxins, for example a truncated Cry1Ab, are known. In the case of modified toxins, one or more amino acids of the naturally occurring toxin are replaced. In such amino acid replacements, preferably non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G-recognition sequence is inserted into a Cry3A toxin (see WO 03/018810).
Examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0 374 753, WO 93/07278, WO 95/34656, EP-A-0 427 529, EP-A-451 878 and WO 03/052073.
The processes for the preparation of such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. Cryl-type deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP-A-0 367 474, EP-A-0 401 979 and WO 90/13651.
The toxin contained in the transgenic plants imparts to the plants tolerance to harmful insects. Such insects can occur in any taxonomic group of insects, but are especially commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and moths (Lepidoptera).
Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available. Examples of such plants are: YieldGard® (maize variety that expresses a Cry1Ab toxin); YieldGard Rootworm® (maize variety that expresses a Cry3Bb1 toxin); YieldGard Plus® (maize variety that expresses a Cry1Ab and a Cry3Bb1 toxin); Starlink® (maize variety that expresses a Cry9C toxin); Herculex I® (maize variety that expresses a Cry1Fa2 toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a Cry1Ac toxin); Bollgard I® (cotton variety that expresses a Cry1Ac toxin); Bollgard II® (cotton variety that expresses a Cry1Ac and a Cry2Ab toxin); VipCot® (cotton variety that expresses a Vip3A and a Cry1Ab toxin); NewLeaf® (potato variety that expresses a Cry3A toxin); NatureGard®, Agrisure® GT Advantage (GA21 glyphosate-tolerant trait), Agrisure® CB Advantage (Bt11 corn borer (CB) trait) and Protecta®.
Further examples of such transgenic crops are:
Transgenic crops of insect-resistant plants are also described in BATS (Zentrum für Biosicherheit und Nachhaltigkeit, Zentrum BATS, Clarastrasse 13, 4058 Basel, Switzerland) Report 2003, (http://bats.ch).
The term “crops” is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called “pathogenesis-related proteins” (PRPs, see e.g. EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818 and EP-A-0 353 191. The methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
Crops may also be modified for enhanced resistance to fungal (for example Fusarium, Anthracnose, or Phytophthora), bacterial (for example Pseudomonas) or viral (for example potato leafroll virus, tomato spotted wilt virus, cucumber mosaic virus) pathogens.
Crops also include those that have enhanced resistance to nematodes, such as the soybean cyst nematode.
Crops that are tolerance to abiotic stress include those that have enhanced tolerance to drought, high salt, high temperature, chill, frost, or light radiation, for example through expression of NF-YB or other proteins known in the art.
Antipathogenic substances which can be expressed by such transgenic plants include, for example, ion channel blockers, such as blockers for sodium and calcium channels, for example the viral KP1, KP4 or KP6 toxins; stilbene synthases; bibenzyl synthases; chitinases; glucanases; the so-called “pathogenesis-related proteins” (PRPs; see e.g. EP-A-0 392 225); antipathogenic substances produced by microorganisms, for example peptide antibiotics or heterocyclic antibiotics (see e.g. WO 95/33818) or protein or polypeptide factors involved in plant pathogen defence (so-called “plant disease resistance genes”, as described in WO 03/000906).
Further areas of use of the compositions according to the invention are the protection of stored goods and store rooms and the protection of raw materials, such as wood, textiles, floor coverings or buildings, and also in the hygiene sector, especially the protection of humans, domestic animals and productive livestock against pests of the mentioned type.
The present invention provides a compound of the first aspect for use in therapy. The present invention provides a compound of the first aspect, for use in controlling parasites in or on an animal. The present invention further provides a compound of the first aspect, for use in controlling ectoparasites on an animal. The present invention further provides a compound of the first aspect, for use in preventing and/or treating diseases transmitted by ectoparasites.
The present invention provides the use of a compound of the first aspect, for the manufacture of a medicament for controlling parasites in or on an animal. The present invention further provides the use of a compound of the first aspect, for the manufacture of a medicament for controlling ectoparasites on an animal. The present invention further provides the use of a compound of the first aspect, for the manufacture of a medicament for preventing and/or treating diseases transmitted by ectoparasites.
The present invention provides the use of a compound of the first aspect, in controlling parasites in or on an animal. The present invention further provides the use of a compound of the first aspect, in controlling ectoparasites on an animal.
The term “controlling” when used in context of parasites in or on an animal refers to reducing the number of pests or parasites, eliminating pests or parasites and/or preventing further pest or parasite infestation.
The term “treating” when used in context of parasites in or on an animal refers to restraining, slowing, stopping or reversing the progression or severity of an existing symptom or disease. The term “preventing” when used in context of parasites in or on an animal refers to the avoidance of a symptom or disease developing in the animal.
The term “animal” when used in context of parasites in or on an animal may refer to a mammal and a non-mammal, such as a bird or fish. In the case of a mammal, it may be a human or non-human mammal. Non-human mammals include, but are not limited to, livestock animals and companion animals. Livestock animals include, but are not limited to, cattle, camellids, pigs, sheep, goats and horses. Companion animals include, but are not limited to, dogs, cats and rabbits.
A “parasite” is a pest which lives in or on the host animal and benefits by deriving nutrients at the host animal's expense. An “endoparasite” is a parasite which lives in the host animal. An “ectoparasite” is a parasite which lives on the host animal. Ectoparasites include, but are not limited to, acari, insects and crustaceans (e.g. sea lice). The Acari (or Acarina) sub-class comprises ticks and mites. Ticks include, but are not limited to, members of the following genera: Rhipicaphalus, for example, Rhipicaphalus (Boophilus) microplus and Rhipicephalus sanguineus; Amblyomrna; Dermacentor; Haemaphysalis; Hyalomma; Ixodes; Rhipicentor; Margaropus; Argas; Otobius; and Ornithodoros. Mites include, but are not limited to, members of the following genera: Chorioptes, for example Chorioptes bovis; Psoroptes, for example Psoroptes ovis; Cheyletiella; Dermanyssus; for example Dermanyssus gallinae; Ortnithonyssus; Demodex, for example Demodex canis; Sarcoptes, for example Sarcoptes scabiei; and Psorergates. Insects include, but are not limited to, members of the orders: Siphonaptera, Diptera, Phthiraptera, Lepidoptera, Coleoptera and Homoptera. Members of the Siphonaptera order include, but are not limited to, Ctenocephalides felis and Ctenocephatides canis. Members of the Diptera order include, but are not limited to, Musca spp.; bot fly, for example Gasterophilus intestinalis and Oestrus ovis; biting flies; horse flies, for example Haematopota spp. and Tabunus spp.; Haematobia, for example Haematobia irritans; Stomoxys; Lucilia; midges; and mosquitoes. Members of the Phthiraptera class include, but are not limited to, blood sucking lice and chewing lice, for example Bovicola Ovis and Bovicola Bovis.
The term “effective amount” when used in context of parasites in or on an animal refers to the amount or dose of the compound of the invention, or a salt thereof, which, upon single or multiple dose administration to the animal, provides the desired effect in or on the animal. The effective amount can be readily determined by the attending diagnostician, as one skilled in the art, by the use of known techniques and by observing results obtained under analogous circumstances. In determining the effective amount a number of factors are considered by the attending diagnostician, including, but not limited to: the species of mammal; its size, age, and general health; the parasite to be controlled and the degree of infestation; the specific disease or disorder involved; the degree of or involvement or the severity of the disease or disorder; the response of the individual; the particular compound administered; the mode of administration; the bioavailability characteristics of the preparation administered; the dose regimen selected; the use of concomitant medication; and other relevant circumstances.
The compounds of the invention may be administered to the animal by any route which has the desired effect including, but not limited to topically, orally, parenterally' and subcutaneously. Topical administration is preferred. Formulations suitable for topical administration include, for example, solutions, emulsions and suspensions and may take the form of a pour-on, spot-on, spray-on, spray race or dip. In the alternative, the compounds of the invention may be administered by means of an ear tag or collar.
Salt forms of the compounds of the invention include both pharmaceutically acceptable salts and veterinary acceptable salts, which can be different to agrochemically acceptable salts. Pharmaceutically and veterinary acceptable salts and common methodology for preparing them are well known in the art. See, for example, Gould, P. L., “Salt selection for basic drugs”, International Journal of Pharmaceutics, 33: 201-217 (1986); Bastin, R. J., et al. “Salt Selection and Optimization Procedures for Pharmaceutical New Chemical Entities”, Organic Process Research and Development, 4: 427-435 (2000); and Berge, S. M., et al., “Pharmaceutical Salts”, Journal of Pharmaceutical Sciences, 66: 1-19, (1977). One skilled in the art of synthesis will appreciate that the compounds of the invention are readily converted to and may be isolated as a salt, such as a hydrochloride salt, using techniques and conditions well known to one of ordinary skill in the art. In addition, one skilled in the art of synthesis will appreciate that the compounds of the invention are readily converted to and may be isolated as the corresponding free base from the corresponding salt.
The present invention also provides a method for controlling pests (such as mosquitoes and other disease vectors; see also http://www.who.int/malaria/vector_control/irs/en/). In one embodiment, the method for controlling pests comprises applying the compositions of the invention to the target pests, to their locus or to a surface or substrate by brushing, rolling, spraying, spreading or dipping. By way of example, an IRS (indoor residual spraying) application of a surface such as a wall, ceiling or floor surface is contemplated by the method of the invention. In another embodiment, it is contemplated to apply such compositions to a substrate such as non-woven or a fabric material in the form of (or which can be used in the manufacture of) netting, clothing, bedding, curtains and tents.
In one embodiment, the method for controlling such pests comprises applying a pesticidally effective amount of the compositions of the invention to the target pests, to their locus, or to a surface or substrate so as to provide effective residual pesticidal activity on the surface or substrate. Such application may be made by brushing, rolling, spraying, spreading or dipping the pesticidal composition of the invention. By way of example, an IRS application of a surface such as a wall, ceiling or floor surface is contemplated by the method of the invention so as to provide effective residual pesticidal activity on the surface. In another embodiment, it is contemplated to apply such compositions for residual control of pests on a substrate such as a fabric material in the form of (or which can be used in the manufacture of) netting, clothing, bedding, curtains and tents.
Substrates including non-woven, fabrics or netting to be treated may be made of natural fibres such as cotton, raffia, jute, flax, sisal, hessian, or wool, or synthetic fibres such as polyamide, polyester, polypropylene, polyacrylonitrile or the like. The polyesters are particularly suitable. The methods of textile treatment are known, e.g. WO 2008/151984, WO 2003/034823, U.S. Pat. No. 5,631,072, WO 2005/64072, WO2006/128870, EP 1724392, WO 2005113886 or WO 2007/090739.
Further areas of use of the compositions according to the invention are the field of tree injection/trunk treatment for all ornamental trees as well all sort of fruit and nut trees.
In the field of tree injection/trunk treatment, the compounds according to the present invention are especially suitable against wood-boring insects from the order Lepidoptera as mentioned above and from the order Coleoptera, especially against woodborers listed in the following tables A and B:
Agrilus planipennis
Anoplura glabripennis
Xylosandrus crassiusculus
X. mutilatus
Tomicus piniperda
Agrilus anxius
Agrilus politus
Agrilus sayi
Agrilus vittaticolllis
Chrysobothris femorata
Texania campestris
Goes pulverulentus
Goes tigrinus
Neoclytus acuminatus
Neoptychodes trilineatus
Oberea ocellata
Oberea tripunctata
Oncideres cingulata
Saperda calcarata
Strophiona nitens
Corthylus columbianus
Dendroctonus frontalis
Dryocoetes betulae
Monarthrum fasciatum
Phloeotribus liminaris
Pseudopityophthorus pruinosus
Paranthrene simulans
Sannina uroceriformis
Synanthedon exitiosa
Synanthedon pictipes
Synanthedon rubrofascia
Synanthedon scitula
Vitacea polistiformis
The present invention may be also used to control any insect pests that may be present in turfgrass, including for example beetles, caterpillars, fire ants, ground pearls, millipedes, sow bugs, mites, mole crickets, scales, mealybugs, ticks, spittlebugs, southern chinch bugs and white grubs. The present invention may be used to control insect pests at various stages of their life cycle, including eggs, larvae, nymphs and adults.
In particular, the present invention may be used to control insect pests that feed on the roots of turfgrass including white grubs (such as Cyclocephala spp. (e.g. masked chafer, C. lurida), Rhizotrogus spp. (e.g. European chafer, R. majalis), Cotinus spp. (e.g. Green June beetle, C. nitida), Popillia spp. (e.g. Japanese beetle, P. japonica), Phyllophaga spp. (e.g. May/June beetle), Ataenius spp. (e.g. Black turfgrass ataenius, A. spretulus), Maladera spp. (e.g. Asiatic garden beetle, M. castanea) and Tomarus spp.), ground pearls (Margarodes spp.), mole crickets (tawny, southern, and short-winged; Scapteriscus spp., Gryllotalpa africana) and leatherjackets (European crane fly, Tipula spp.).
The present invention may also be used to control insect pests of turfgrass that are thatch dwelling, including armyworms (such as fall armyworm Spodoptera frugiperda, and common armyworm Pseudaletia unipuncta), cutworms, billbugs (Sphenophorus spp., such as S. venatus verstitus and S. parvulus), and sod webworms (such as Crambus spp. and the tropical sod webworm, Herpetogramma phaeopteralis).
The present invention may also be used to control insect pests of turfgrass that live above the ground and feed on the turfgrass leaves, including chinch bugs (such as southern chinch bugs, Blissus insularis), Bermudagrass mite (Eriophyes cynodoniensis), rhodesgrass mealybug (Antonina graminis), two-lined spittlebug (Propsapia bicincta), leafhoppers, cutworms (Noctuidae family), and greenbugs.
The present invention may also be used to control other pests of turfgrass such as red imported fire ants (Solenopsis invicta) that create ant mounds in turf.
In the hygiene sector, the compositions according to the invention are active against ectoparasites such as hard ticks, soft ticks, mange mites, harvest mites, flies (biting and licking), parasitic fly larvae, lice, hair lice, bird lice and fleas.
Examples of such parasites are:
Of the order Anoplurida: Haematopinus spp., Linognathus spp., Pediculus spp. and Phtirus spp., Solenopotes spp.
Of the order Mallophagida: Trimenopon spp., Menopon spp., Trinoton spp., Bovicola spp., Werneckiella spp., Lepikentron spp., Damalina spp., Trichodectes spp. and Felicola spp.
Of the order Diptera and the suborders Nematocerina and Brachycerina, for example Aedes spp., Anopheles spp., Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Chrysops spp., Hybomitra spp., Atylotus spp., Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp., Oestrus spp., Hypoderma spp., Gasterophilus spp., Hippobosca spp., Lipoptena spp. and Melophagus spp.
Of the order Siphonapterida, for example Pulex spp., Ctenocephalides spp., Xenopsylla spp., Ceratophyllus spp.
Of the order Heteropterida, for example Cimex spp., Triatoma spp., Rhodnius spp., Panstrongylus spp.
Of the order Blattarida, for example Blatta orientalis, Periplaneta americana, Blattelagermanica and Supella spp.
Of the subclass Acaria (Acarida) and the orders Meta- and Meso-stigmata, for example Argas spp., Ornithodorus spp., Otobius spp., Ixodes spp., Amblyomma spp., Boophilus spp., Dermacentor spp., Haemophysalis spp., Hyalomma spp., Rhipicephalus spp., Dermanyssus spp., Raillietia spp., Pneumonyssus spp., Sternostoma spp. and Varroa spp.
Of the orders Actinedida (Prostigmata) and Acaridida (Astigmata), for example Acarapis spp., Cheyletiella spp., Ornithocheyletia spp., Myobia spp., Psorergates spp., Demodex spp., Trombicula spp., Listrophorus spp., Acarus spp., Tyrophagus spp., Caloglyphus spp., Hypodectes spp., Pterolichus spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp. and Laminosioptes spp.
The compositions according to the invention are also suitable for protecting against insect infestation in the case of materials such as wood, textiles, plastics, adhesives, glues, paints, paper and card, leather, floor coverings and buildings.
The compositions according to the invention can be used, for example, against the following pests: beetles such as Hylotrupes bajulus, Chlorophorus pilosis, Anobium punctatum, Xestobium rufovillosum, Ptilinuspecticornis, Dendrobium pertinex, Ernobius mollis, Priobium carpini, Lyctus brunneus, Lyctus africanus, Lyctus planicollis, Lyctus linearis, Lyctus pubescens, Trogoxylon aequale, Minthesrugicollis, Xyleborus spec., Tryptodendron spec., Apate monachus, Bostrychus capucins, Heterobostrychus brunneus, Sinoxylon spec. and Dinoderus minutus, and also hymenopterans such as Sirexjuvencus, Urocerus gigas, Urocerus gigas taignus and Urocerus augur, and termites such as Kalotermes flavicollis, Cryptotermes brevis, Heterotermes indicola, Reticulitermes flavipes, Reticulitermes santonensis, Reticulitermes lucifugus, Mastotermes darwiniensis, Zootermopsis nevadensis and Coptotermes formosanus, and bristletails such as Lepisma saccharina. The compounds of formulae I, and I′a, or salts thereof, are especially suitable for controlling one or more pests selected from the family: Noctuidae, Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae, Meloidogynidae, and Heteroderidae. In a preferred embodiment of each aspect, a compound TX (where the abbreviation “TX” means “one compound selected from the compounds defined in Tables 1 to 57 and Tables P1 to P2”) controls one or more of pests selected from the family: Noctuidae, Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae, Meloidogynidae, and Heteroderidae.
The compounds of formulae I, and I′a, or salts thereof, are especially suitable for controlling one or more of pests selected from the genus: Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp. In a preferred embodiment of each aspect, a compound TX (where the abbreviation “TX” means “one compound selected from the compounds defined in Tables 1 to 57 and Tables P1 to P2”) controls one or more of pests selected from the genus: Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp.
The compounds of formulae I, and I′a, or salts thereof, are especially suitable for controlling one or more of Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis includens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum padi, and Chilo suppressalis.
In a preferred embodiment of each aspect, a compound TX (where the abbreviation “TX” means “one compound selected from the compounds defined in Tables 1 to 57 and Tables P1 to P2”) controls one or more of Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis includens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum Padia, and Chilo Suppressalis, such as Spodoptera littoralis+TX, Plutella xylostella+TX; Frankliniella occidentalis+TX, Thrips tabaci+TX, Euschistus heros+TX, Cydia pomonella+TX, Nilaparvata lugens+TX, Myzus persicae+TX, Chrysodeixis includens+TX, Aphis craccivora+TX, Diabrotica balteata+TX, Rhopalosiphum Padi+TX, and Chilo suppressalis+TX.
In an embodiment, of each aspect, one compound from Tables 1 to 57 and Tables P1 to P2 is suitable for controlling Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis includens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum Padia, and Chilo Suppressalis in cotton, vegetable, maize, cereal, rice and soya crops.
In an embodiment, one compound from Tables 1 to 57 and Tables P1 to P2 is suitable for controlling Mamestra (preferably in vegetables), Cydia pomonella (preferably in apples), Empoasca (preferably in vegetables, vineyards), Leptinotarsa (preferably in potatoes) and Chilo supressalis (preferably in rice).
Compounds according to the invention may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against insects or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (against non-target organisms above and below ground (such as fish, birds and bees), improved physico-chemical properties, or increased biodegradability). In particular, it has been surprisingly found that certain compounds of formula (I) may show an advantageous safety profile with respect to non-target arthropods, in particular pollinators such as honey bees, solitary bees, and bumble bees. Most particularly, Apis mellifera.
The compounds according to the invention can be used as pesticidal agents in unmodified form, but they are generally formulated into compositions in various ways using formulation adjuvants, such as carriers, solvents and surface-active substances. The formulations can be in various physical forms, e.g. in the form of dusting powders, gels, wettable powders, water-dispersible granules, water-dispersible tablets, effervescent pellets, emulsifiable concentrates, microemulsifiable concentrates, oil-in-water emulsions, oil-flowables, aqueous dispersions, oily dispersions, suspo-emulsions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (with water or a water-miscible organic solvent as carrier), impregnated polymer films or in other forms known e.g. from the Manual on Development and Use of FAO and WHO Specifications for Pesticides, United Nations, First Edition, Second Revision (2010). Such formulations can either be used directly or diluted prior to use. The dilutions can be made, for example, with water, liquid fertilisers, micronutrients, biological organisms, oil or solvents.
The formulations can be prepared e.g. by mixing the active ingredient with the formulation adjuvants in order to obtain compositions in the form of finely divided solids, granules, solutions, dispersions or emulsions. The active ingredients can also be formulated with other adjuvants, such as finely divided solids, mineral oils, oils of vegetable or animal origin, modified oils of vegetable or animal origin, organic solvents, water, surface-active substances or combinations thereof.
The active ingredients can also be contained in very fine microcapsules. Microcapsules contain the active ingredients in a porous carrier. This enables the active ingredients to be released into the environment in controlled amounts (e.g. slow-release). Microcapsules usually have a diameter of from 0.1 to 500 microns. They contain active ingredients in an amount of about from 25 to 95% by weight of the capsule weight. The active ingredients can be in the form of a monolithic solid, in the form of fine particles in solid or liquid dispersion or in the form of a suitable solution. The encapsulating membranes can comprise, for example, natural or synthetic rubbers, cellulose, styrene/butadiene copolymers, polyacrylonitrile, polyacrylate, polyesters, polyamides, polyureas, polyurethane or chemically modified polymers and starch xanthates or other polymers that are known to the person skilled in the art. Alternatively, very fine microcapsules can be formed in which the active ingredient is contained in the form of finely divided particles in a solid matrix of base substance, but the microcapsules are not themselves encapsulated.
The formulation adjuvants that are suitable for the preparation of the compositions according to the invention are known per se. As liquid carriers there may be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, alpha-pinene, d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropylbenzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxy-propanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol, propionic acid, propyl lactate, propylene carbonate, propylene glycol, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylenesulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol, and alcohols of higher molecular weight, such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, N-methyl-2-pyrrolidone and the like.
Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed husks, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar substances.
A large number of surface-active substances can advantageously be used in both solid and liquid formulations, especially in those formulations which can be diluted with a carrier prior to use. Surface-active substances may be anionic, cationic, non-ionic or polymeric and they can be used as emulsifiers, wetting agents or suspending agents or for other purposes. Typical surface-active substances include, for example, salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; salts of alkylarylsulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol/alkylene oxide addition products, such as nonylphenol ethoxylate; alcohol/alkylene oxide addition products, such as tridecylalcohol ethoxylate; soaps, such as sodium stearate; salts of alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryltrimethylammonium chloride, polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and di-alkylphosphate esters; and also further substances described e.g. in McCutcheon's Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood New Jersey (1981).
Further adjuvants that can be used in pesticidal formulations include crystallisation inhibitors, viscosity modifiers, suspending agents, dyes, anti-oxidants, foaming agents, light absorbers, mixing auxiliaries, antifoams, complexing agents, neutralising or pH-modifying substances and buffers, corrosion inhibitors, fragrances, wetting agents, take-up enhancers, micronutrients, plasticisers, glidants, lubricants, dispersants, thickeners, antifreezes, microbicides, and liquid and solid fertilisers.
The compositions according to the invention can include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl esters of such oils or mixtures of such oils and oil derivatives. The amount of oil additive in the composition according to the invention is generally from 0.01 to 10%, based on the mixture to be applied. For example, the oil additive can be added to a spray tank in the desired concentration after a spray mixture has been prepared. Preferred oil additives comprise mineral oils or an oil of vegetable origin, for example rapeseed oil, olive oil or sunflower oil, emulsified vegetable oil, alkyl esters of oils of vegetable origin, for example the methyl derivatives, or an oil of animal origin, such as fish oil or beef tallow. Preferred oil additives comprise alkyl esters of C8-C22 fatty acids, especially the methyl derivatives of C12-C18 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid(methyl laurate, methyl palmitate and methyl oleate, respectively). Many oil derivatives are known from the Compendium of Herbicide Adjuvants, 10th Edition, Southern Illinois University, 2010.
The inventive compositions generally comprise from 0.1 to 99% by weight, especially from 0.1 to 95% by weight, of compounds of the present invention and from 1 to 99.9% by weight of a formulation adjuvant which preferably includes from 0 to 25% by weight of a surface-active substance. Whereas commercial products may preferably be formulated as concentrates, the end user will normally employ dilute formulations.
The rates of application vary within wide limits and depend on the nature of the soil, the method of application, the crop plant, the pest to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. As a general guideline compounds may be applied at a rate of from 1 to 2000 l/ha, especially from 10 to 1000 l/ha.
Preferred formulations can have the following compositions (weight %):
The following Examples further illustrate, but do not limit, the invention.
The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.
The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment.
Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.
Ready-for-use dusts are obtained by mixing the combination with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed.
The combination is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.
The finely ground combination is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.
The finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
The finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
28 parts of the combination are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51.6 parts of water until the desired particle size is achieved. To this emulsion a mixture of 2.8 parts 1,6-diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed. The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% of the active ingredients. The medium capsule diameter is 8-15 microns. The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.
Formulation types include an emulsion concentrate (EC), a suspension concentrate (SC), a suspo-emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK), a dispersible concentrate (DC), a wettable powder (WP), a soluble granule (SG) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.
Spectra were recorded on a Mass Spectrometer from Waters (SQD Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Full Scan, Capillary: 3.00 kV, Cone range: 41 V, Source Temperature: 150° C., Desolvation Temperature: 500° C., Cone Gas Flow: 50 L/Hr, Desolvation Gas Flow: 1000 L/Hr, Mass range: 110 to 800 Da) and a H-Class UPLC from Waters: Quaternary pump, heated column compartment and diode-array detector. Column: Acquity UPLC HSS T3 C18, 1.8 μm, 30×2.1 mm, Temp: 40° C., DAD Wavelength range (nm): 200 to 400, Solvent Gradient: A=water+5% Acetonitrile+0.1% HCOOH, B=Acetonitrile+0.05% HCOOH: gradient: 0 min 10% B; 0.-0.2 min 10-50% B; 0.2-0.7 min 50-100% B; 0.7-1.3 min 100% B; 1.3-1.4 min 100-10% B; 1.4-1.6 min 10% B; Flow (mL/min) 0.6.
Spectra were recorded on a Mass Spectrometer from Agilent Technologies (6410 Triple Quadrupole mass spectrometer) equipped with an equipped with an electrospray source (Polarity: positive or negative ions, MS2 Scan, Capillary: 4.00 kV, Fragmentor: 100 V, Desolvatation Temperature: 350° C., Gas Flow: 11 L/min, Nebulizer Gas: 45 psi, Mass range: 110 to 1000 Da) and a 1200 Series HPLC from Agilent: quaternary pump, heated column compartment and diode-array detector. Column: KINETEX EVO C18, 2.6 μm, 50×4.6 mm, Temp: 40° C., DAD Wavelength range (nm): 210 to 400, Solvent Gradient: A=95% (water+0.1% HCOOH): 5% Acetonitrile, B=Acetonitrile with 0.1% HCOOH: gradient: 0 min 10% B; 0.9-1.8 min 100% B; 1.8-2.2 min 100-10% B; 2.2-2.5 min 10% B, Flow rate (mL/min) 1.8.
Spectra were recorded on a Mass Spectrometer from Waters (Acquity QDa Mass Spectrometer) equipped with an electrospray source (Polarity: Positive and Negative Polarity Switch), Capillary: 0.8 kV, Cone range: 25 V, Extractor: V (No extractor voltage for QDa detector) Source Temperature: 120° C., Desolvation Temperature: 600° C., Cone Gas Flow: 50 L/h, Desolvation Gas Flow: 1000 L/h, Mass range: 110 to 850 Da) and an Acquity UPLC from Waters: Quaternary solvent manager, heated column compartment, diode-array detector. Column: Waters UPLC HSS T3, 1.8 μm, 30×2.1 mm, Temp: 40° C., PDA Wavelength range (nm): 230 to 400, Solvent Gradient: A=Water with 0.1% formic acid: Acetonitrile: 95: 5 v/v, B=Acetonitrile with 0.05% formic acid: Gradient: 0 min-1.0 min, 10% B-90% A; 1.0 min-4.50 min 10%-100% B; 4.51 min-5.30 min, 100% B, 0% A; 5.31 min-5.50 min 100%-10% B; 5.51 min-6.00 min, 10% B, 90% A; Flow (ml/min) 0.6.
Spectra were recorded on a Mass Spectrometer from Agilent Technologies (6410 Triple Quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, MS2 Scan, Capillary: 7.00 kV, Fragmentor: 120 V, Desolvatation Temperature: 350° C., Gas Flow: 11 L/min, Nebulizer Gas: 40 psi, Mass range: 110 to 1000 Da) and a 1200 Series HPLC from Agilent: quaternary pump, heated column compartment and diode-array detector. Column: KINETEX EVO C18, 2.6 μm, 50×4.6 mm, Temp: 40° C., Detector VWD Wavelength: 254 nm, Solvent Gradient: A=water+5% Acetonitrile+0.1% HCOOH, B=Acetonitrile+0.1% HCOOH: gradient: 0 min 10% B, 90% A; 0.9-1.8 min 100% B; 1.8-2.2 min 100-10% B; 2.2-2.5 min 10% B; Flow (mL/min) 1.8.
Spectra were recorded on a Mass Spectrometer from Waters (SQD, SQDII Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions, Capillary: 3.00 kV, Cone range: 30 V, Extractor: 2.00 V, Source Temperature: 150° C., Desolvation Temperature: 350° C., Cone Gas Flow: 50 l/h, Desolvation Gas Flow: 650 l/h, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment, diode-array detector and ELSD detector. Column: Waters UPLC HSS T3, 1.8 μm, 30×2.1 mm, Temp: 60° C., DAD Wavelength range (nm): 210 to 500, Solvent Gradient: A=water+5% MeOH+0.05% HCOOH, B=Acetonitrile+0.05% HCOOH, gradient: 10-100% B in 1.2 min; Flow (ml/min) 0.85.
Instrument specifications: Agilent 1100 Series LC/MSD system with DADELSD Alltech 2000ES and Agilent LC\MSD VL (G1956B), SL (G1956B) mass-spectrometer. Agilent 1200 Series LC/MSD system with DAD\ELSD Alltech 3300 and Agilent LC\MSD G6130A, G6120B mass-spectrometer.
Agilent Technologies 1260 Infinity LC/MSD system with DAD\ELSD Alltech 3300 and Agilent; LC\MSD G6120B mass-spectrometer. Agilent Technologies 1260 Infinity II LC/MSD system with DAD\ELSD G7102A 1290 Infinity II and Agilent LC\MSD G6120B mass-spectrometer. Agilent 1260 Series LC/MSD system with DAD\ELSD and Agilent LC\MSD (G6120B) mass-spectrometer. UHPLC Agilent 1290 Series LC/MSD system with DAD\ELSD and Agilent LC\MSD (G6125B) mass-spectrometer.
All the LC/MS data were obtained using positive/negative mode switching.
Column Agilent Poroshell 120 SB-C18 4.6×30 mm 2.7 μm with UHPLC Guard Infinity Lab Poroshell 120 SB-C18 4.6×5 mm 2.7 μm, Temperature 60 C
Spectra were recorded on a Mass Spectrometer (ACQUITY UPLC) from Waters (SQD, SQDII Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.0 kV, Cone: 30V, Extractor: 3.00 V, Source Temperature: 150° C., Desolvation Temperature: 400° C., Cone Gas Flow: 60 L/hr, Desolvation Gas Flow: 700 L/hr, Mass range: 140 to 800 Da) and an Acquity UPLC from Waters: Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3, 1.8 μm, 30×2.1 mm, Temp: 60° C., DAD Wavelength range (nm): 210 to 400, Solvent Gradient: A=Water/Methanol 9:1,0.1% formic acid, B=Acetonitrile+0.1% formic acid, gradient: 0-100% B in 2.5 min; Flow (ml/min) 0.75
The following abbreviations are used in the experimental description below: s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet, RT=retention time, min=minutes.
A solution of sodium ethoxide (1.1 eq) in ethanol (20% w/w) was added slowly at 4° C. to a suspension of 2-cyano-acetamide (5.9 g, 70.2 mmol, 1 eq) and the mixture was stirred for 15 minutes. Then a solution ethyl-2-(ethoxymethylene)-4,4,4-trifluoro-3-oxo-butanoate (17 g, 70.1 mmol) in 34 ml of ethanol was added under ice cooling. The reaction mixture was stirred 16 hours and allowed to reach room temperature. Then the reaction mixture was poured into ice-cold solution of 1 N hydrochloric acid. The resulting mixture was diluted with ice-cold water and stirred for 20 minutes. The precipitate was filtered, washed twice with ice-cold water and dried. 12.4 g of ethyl 5-cyano-6-hydroxy-2-(trifluoromethyl)pyridine-3-carboxylate were obtained in a purity higher than 95% determined by quantitative NMR. 1H-NMR [ppm] in CDCl3: 1.29 (t, 3H), 4.29 (q, 2H), 8.27 (s, 1H).
To a solution of ethyl 5-cyano-6-hydroxy-2-(trifluoromethyl)pyridine-3-carboxylate (3.00 g, 11.5 mmol) in acetone (57.7 mL) was added potassium carbonate (4.88 g, 34.6 mmol, 3 eq) and sodium iodide (364 mg, 2.31 mmol, 0.2 eq) followed by addition of 2-fluoro-5-(trifluoromethyl)-benzyl bromide (4.45 g, 17.3 mmol, 1.5 eq). The reaction mixture was stirred at 70° C. for 3 hours and cooled to room temperature. The reaction mixture was filtered an the residue was washed with acetone. The acetone solution was concentrated under vacuum and the residue was purified by combi-flash silica-gel to afford 4.55 g of ethyl 5-cyano-6-[[2-fluoro-5-(trifluoromethyl)phenyl]methoxy]-2-(trifluoromethyl)-pyridine-3-carboxylate as a yellow solid. 1H-NMR [ppm] in CDCl3: 1.42 (t, 3H), 4.45 (q, 2H), 5.71 (s, 2H), 7.24-7.27 (m, 1H), 7.66-7.70 (m, 1H), 7.90-7.99 (m, 1H), 8.43 (s, 1H); LC-MS (method 3): RT=1.21 min; [M+H]+=437.
To a solution of ethyl 5-cyano-6-[[2-fluoro-5-(trifluoromethyl)phenyl]methoxy]-2-(trifluoromethyl)-pyridine-3-carboxylate (4.5 g, 10.3 mmol) in THE (25.8 mL)/water (12.4 mL) was added Lithium hydroxide monohydrate (1.01 g, 41.3 mmol, 4 eq). The reaction mixture was stirred at room temperature until complete consumption of the starting material (monitored by TLC). The reaction mixture was diluted with ethyl acetate and acidified with hydrochloric acid. The phases were separated and the aqueous layer was extracted three times with ethyl acetate. The combined extracts were dried over sodium sulphate and concentrated. The residue was titurated with a small amount of dichloromethan to give 1.63 g of 5-cyano-6-[[2-fluoro-5-(trifluoromethyl)phenyl]methoxy]-2-(trifluoromethyl)pyridine-3-carboxylic acid as a white solid. 1H-NMR [ppm] in DMSO-d6: 5.69 (s, 2H), 7.55 (t, 1H), 7.83-7.90 (m, 1H), 8.08-8.12 (m, 1H), 8.84 (s, 1H), 14.15 (br, s, 1H); LC-MS (method 3): RT=1.02 min; [M+H]+=409.
To a solution of tert-butyl 4-chlorosulfonylpiperidine-1-carboxylate (200 mg, 0.705 mmol) and pyridine (0.17 mL, 2.11 mmol, 3 eq) in acetonitrile (5 mL) was added a solution (8 mol/L) of methylamine in ethanol (0.705 mmol). The reaction was stirred at room temperature for 30 minutes. The reaction mixture was poured into water and extracted with ethyl acetate. The combined organic layers were washed with a 0.1 N HCl solution and saturated aqueous NaCl solution, dried over magnesium sulphate, and concentrated under reduced pressure to afford 160 mg of tert-butyl 4-(methylsulfamoyl)piperidine-1-carboxylate as a yellow solid. 1H-NMR [ppm] in CDCl3: 1.79 (s, 9H), 2.40-2.60 (m, 2H), 2.67-2-78 (m, 2H), 3.10 (s, 3H), 3.46-3.58 (m, 2H), 3.70-3.82 (m, 1H), 3.95-4.06 (m, 2H); LC-MS (method 3): RT=0.76 min; [M−H]−=277.
tert-butyl 4-(methylsulfamoyl)piperidine-1-carboxylate (150 mg, 0,539 mmol) was dissolved in 1,4-dioxane (5 mL) and a solution (4 mol/L) of hydrogen chloride in 1,4-dioxane (1.08 mmol, 2.2 eq) was added. The reaction mixture was stirred at room temperature for 4 hours and then the solvent was evapourated. The crude product was used for the next step without further purification.
To a solution of 5-cyano-6-[[2-fluoro-5-(trifluoromethyl)phenyl]methoxy]-2-(trifluoromethyl)pyridine-3-carboxylic acid (130 mg, 0.315 mmol) in ethyl acetate (15 mL) was added N-methylpiperidine-4-sulfonamide (0.3468 mmol, 1.1 eq) followed by addition of T3P coupling reagent (0.34 mL of a 50% solution in ethyl acetate, 0.5675 mmol, 1.8 eq) and N,N-diisopropyl-ethylamine (0.27 mL, 1.58 mmol, 5 eq). The reaction mixture was stirred at room temperature for one hour. The reaction was quenched with a solution of NaHCO3 and extracted three times with ethyl acetate. The combined organic layers were washed with water and brine, dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified with Combiflash (cyclohexane/ethylacetate 100%/0%->0%/100%) to afford 95 mg of 1-[5-cyano-6-[[2-fluoro-5-(trifluoromethyl)phenyl]methoxy]-2-(trifluoromethyl)pyridine-3-carbonyl]-N-methyl-piperidine-4-sulfonamide as a white solid.
1H-NMR [ppm] in CDCl3: 1.64-1.98 (m, 2H), 2.04-2.18 (m, 1H), 2.23-2.33 (m, 1H), 2.78-3.00 (m, 1H), 2.82 and 2.84 (2 s, 3H), 3.01-3.23 (m, 2H), 3.51 (t, 1H), 4.00-4.10 (m, 1H), 4.83 (dd, 1H), 5.65 (s, 2H), 7.21-7.32 (m, 1H), 7.64-7.73 (m, 1H), 7.87-7.95 (m, 1H), 7.94 and 8.01 (2 s, 1H). LC-MS (method 3): RT=1.02 min; [M+H]+=569.
Ethyl 5-cyano-6-hydroxy-2-(trifluoromethyl)pyridine-3-carboxylate (27.5 g, 106 mmol; Example P1, step 1) was dissolved in ethanol (846 mL) and potassium hydroxide (20.9 g, 19.9 mL, 317 mmol, 3.0 eq) dissolved in ethanol (211 mL) was added. The reaction mixture was stirred under reflux for 20 hours. Then the reaction mixture was diluted with ethyl acetate and 2 N hydrochloric acid. The mixture was extracted three times with ethyl acetate. The combined organic layer was washed two times with water and once with brine, dried over sodium sulfate and the solvent was removed. 24.0 g of 5-cyano-6-hydroxy-2-(trifluoromethyl)-pyridine-3-carboxylic acid were obtained as a yellow solid. 1H-NMR [ppm] in DMSO-d6: 8.69 (s, 1H), 13.85 (broad s, 2H). LC-MS (method 2): RT=0.24 min; [M+H]+=233.
To a solution of 5-cyano-6-hydroxy-2-(trifluoromethyl)pyridine-3-carboxylic acid (1.40 g, 5.7 mmol) and N,N-dimethylpiperidin-1-ium-4-sulfonamide chloride (1.50 g, 6.3 mmol, 1.1 eq) in DMF (14 mL) was added N,N-diisopropyl-ethylamine (3.0 mL, 2.20 g, 17 mmol, 3.0 eq) followed by the addition of the coupling reagent HATU (2.7 g, 6.9 mmol, 1.2 eq). The reaction mixture was stirred at room temperature for 12 hours. Then the mixture was concentrated under vacuum to dryness and the residue was purified by RP chromatography (MeCN/water 10 to 80%) and subsequent tituration with petroleum ether to give 1.80 g of 1-[5-cyano-6-hydroxy-2-(trifluoromethyl)pyridine-3-carbonyl]-N,N-dimethyl-piperidine-4-sulfonamide. 1H-NMR [ppm] in DMSO-d6: 1.30-1.50 (m, 1H), 1.59-1.74 (m, 1H), 1.76-1.90 (m, 1H), 1.98-2.08 (m, 1H), 2.82 (s, 3H), 2.85 (s, 3H), 3.05-3.22 (m, 1H), 3.45-3.75 (m, 3H), 4.50-4.60 (m, 1H), 8.28, 8.44 (2 broad s, 1H).
To solution of 1-[5-cyano-6-hydroxy-2-(trifluoromethyl)pyridine-3-carbonyl]-N,N-dimethyl-piperidine-4-sulfonamide (250 mg, 0.584 mmol) in acetonitrile (2.5 mL) was added cesium carbonate (381 mg, 1.17 mmol, 2.0 eq) and 5-(chloromethyl)-2,2-difluoro-1,3-benzodioxole (254 mg, 1.17 mmol, 2.0 eq). The reaction mixture was heated at 70° C. for 3 hours. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was extracted with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified via combiflash (10-80% ethylacetate/cyclohexane) to afford 191 mg of 1-[5-Cyano-6-[(2,2-difluoro-1,3-benzodioxol-5-yl)methoxy]-2-(trifluoromethyl)pyridine-3-carbonyl]-N,N-dimethyl-piperidine-4-sulfonamide. 1H-NMR [ppm] in CDCl3: 1.58-1.90 (m, 2H), 1.92-2.06 (m, 1H), 2.12-2.20 (broad d, 1H), 2.78-2.95 (m, 1H), 2.91 (s, 3H), 2.92 (s, 3H), 3.03-3.20 (m, 1H), 3.22 (broad t, 1H), 3.41-3.55 (m, 1H), 4.75 (broad t, 1H), 5.52 (s, 2H), 7.09 (d, 1H), 7.25-7.45 (m, 2H), 8.00 and 8.12 (2 s, 1H). LC-MS (method 1): RT=1.11 min; [M+H]+=577.
A mixture of tert-butyl 4-oxopiperidine-1-carboxylate (20.0 g, 100.4 mmol) and ethyl 2-(triphenyl-lambda5-phosphanylidene)acetate (35.0 g, 100.5 mmol) in toluene (400 mL) were refluxed for 24 hours at 100° C. The reaction mixture was concentrated and the residue was purified using combiflash (15-20% of ethyl acetate in cyclohexane) to afford 22.0 g of tert-butyl 4-(2-ethoxy-2-oxo-ethylidene)piperidine-1-carboxylate as white solid. 1H-NMR [ppm] in CDCl3: 1.25 (t, 3H), 1.45 (s, 9H), 2.25 (t, 2H), 2.91 (t, 2H), 3.42-3.54 (m, 4H), 4.13 (q, 2H), 5.69 (s, 1H).
To a flask was charged with palladium on carbon (10% on activated carbon; Degussa, Wet) (0.22 g, 2.0 mmol, 0.22 g) was added a solution of tert-butyl 4-(2-ethoxy-2-oxo-ethylidene)piperidine-1-carboxylate (5.00 g, 19 mmol) in methanol (50 mL), and the reaction stirred under hydrogen atmosphere (1 bar) until complete consumption of starting material. The reaction mixture was filtered through celite pad and the filtrate was concentrated under vacuum to give 5.00 g of tert-butyl 4-(2-ethoxy-2-oxo-ethyl)piperidine-1-carboxylate. 1H-NMR [ppm] in CDCl3: 1.01-1.14 (m, 2H), 1.26 (t, 3H), 1.37 (s, 9H), 1.56-1.65 (m, 2H), 1.76-1.92 (m, 1H), 2.15 (d, 2H), 2.57-2.70 (m, 2H), 3.91-4.09 (m, 2H), 4.05 (q, 2H).
tert-Butyl 4-(2-ethoxy-2-oxo-ethyl)piperidine-1-carboxylate (5.00 g, 18.4 mmol) was dissolved in ethanol (30 mL) and an aqueous solution sodium hydroxide (92.1 mmol, 5 eq) in water was added. The reaction mixture was stirred at 90° C. for 1 hour. The reaction mixture was cooled to room temperature and an aqueous solution of 2M hydrochloric acid was added dropwise slowly on an ice bath to adjust the pH to 2. The mixture was extracted with ethyl acetate (3 times 20 mL). The combined organic phases were washed with a saturated sodium chloride solution (20 mL), dried over anhydrous sodium sulfate, and concentrated to afford 4.20 g of 2-(1-tert-butoxycarbonyl-4-piperidyl)acetic acid. 1H-NMR [ppm] in CDCl3: 1.17 (qd, 2H), 1.44 (s, 9H), 1.65 (broad d, 2H), 1.81-2.00 (m, 1H), 2.27 (d, 2H), 2.72 (broad t, 2H), 4.08 (broad s, 2H), 9.92-10.88 (broad s, 1H).
2-(1-tert-butoxycarbonyl-4-piperidyl)acetic acid (1.50 g, 6.2 mmol) and triethylamine (0.95 g, 1.3 mL, 9.2 mmol, 1.5 eq) were dissolved in tetrahydrofuran (28 mL) and cooled to −10′C. Isobutylchloro-formate (1.30 g, 1.2 mL, 9.2 mmol, 1.5 eq) was added slowly and the reaction mixture was stirred at 10° C. for 15 minutes. Dimethylamine (20 mmol, 2.0 mol/L, 3.2 eq) was subsequently added and the mixture was stirred at room temperature for 16 hours. The reaction mixture was quenched with a saturated aqueous solution of NaHCO3and extracted with ethyl acetate (3 times 20 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give the crude tert-butyl 4-[2-(dimethylamino)-2-oxo-ethyl]piperidine-1-carboxylate. 1H-NMR [ppm] in CDCl3: 1.12 (qd, 2H), 1.41 (s, 9H), 1.69 (broad d, 2H), 1.90-2.03 (m, 1H), 2.18-2.25 (m, 2H), 2.69 (broad t, 2H), 2.91 (s, 3H), 2.97 (s, 3H), 4.05 (broad s, 2H).
To a solution of tert-butyl 4-[2-(dimethylamino)-2-oxo-ethyl]piperidine-1-carboxylate (540 mg, 2.00 mmol) in 1,4-dioxane (2 mL) was added a solution of hydrogen chloride in 1,4-dioxane (9.985 mmol, 4 mol/L, 5 eq) and the reaction was stirred at room temperature overnight. The reaction mixture was concentrated to give the crude salt of N,N-dimethyl-2-(4-piperidyl)acetamide (400 mg). 1H-NMR [ppm] in DMSO-d6: 1.40 (dq, 2H), 1.79 (br d, 2H), 1.80-2.03 (m, 1H), 2.25 (d, 2H), 2.75-2.90 (m, 2H), 2.80 (s, 3H), 2.95 (s, 3H), 3.18 (br d, 2H), 8.97 (broad s, 1H), 9.13 (broad s, 1H).
To a stirred solution of 5-cyano-6-[[2-fluoro-5-(trifluoromethyl)phenyl]methoxy]-2-(trifluoromethyl)-pyridine-3-carboxylic acid (300.0 mg, 0.7349 mmol; Example P1—step 3) in ethyl acetate (7.3 mL) was added N,N-dimethyl-2-piperidin-1-ium-4-yl-acetamide chloride (198 mg, 0.955 mmol, 1.3 eq), N,N-diisopropylethylamine (0.39 mL, 2.21 mmol, 3 eq) followed by addition of a solution of T3P coupling reagent (1.31 mL, 2.21 mmol, 3 eq; 50% solution in ethyl acetate). The resulting light yellow solution was stirred at room temperature for 16 hours. Then water was added the mixture was extracted three times with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by combiflash (90% ethyl acetate in cyclohexane) to afford 150 mg of 2-[1-[5-cyano-6-[[2-fluoro-5-(trifluoromethyl)phenyl]methoxy]-2-(trifluoromethyl)pyridine-3-carbonyl]-4-piperidyl]-N,N-dimethyl-acetamide as a white solid. 1H-NMR [ppm] in CDCl3: 1.10 (dq, 1H), 1.15-1.33 (m, 1H), 1.77 (t, 1H), 1.92 (t, 1H), 2.15-2.35 (m, 3H), 2.77-2.91 (m, 1H), 2.96 (s, 3H), 3.01 (s, 3H), 3.05-3.20 (m, 1H), 3.31 (t, 1H), 4.72 (t, 1H), 5.64 (s, 2H), 7.22-7.26 (m, 1H), 7.63-7.68 (m, 1H), 7.88-7.94 (m, 2H); LC-MS (method 2): RT=1.45 min; [M+HP]=561, m.p.: 143-145° C.
To a solution of 5-cyano-6-[[2-fluoro-5-(trifluoromethyl)phenyl]methoxy]-2-(trifluoromethyl)pyridine-3-carboxylic acid (1.00 g, 2.45 mmol) in ethyl acetate (36.7 mL) was added 1-BOC-pipperazine (0.684 g, 3.67 mmol, 1.50 eq), followed by addition of the coupling reagent T3P as a 50% solution in ethyl acetate (2.81 g, 2.63 mL, 4.41 mmol, 1.80 eq) and N,N-diisopropylethylamine (1.58 g, 2.13 mL, 12.2 mmol, 5.00 eq). The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with a saturated solution of NaHCO3 and water, and extracted twice with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified via Combiflash to afford 1.01 g of tert-butyl 4-[5-cyano-6-[[2-fluoro-5-(trifluoromethyl)phenyl]methoxy]-2-(trifluoromethyl)pyridine-3-carbonyl]piperazine-1-carboxylate as a white solid. 1H-NMR [ppm] in CDCl3: 1.48 (s, 9H), 3.19 (t, 2H), 3.35-3.43 (m, 2H), 3.45-3.62 (m, 2H), 3.64-3.73 (m, 1H), 3.80-3.89 (m, 1H), 5.67 (s, 2H), 7.23-7.30 (m, 1H), 7.64-7.72 (m, 1H), 7.91 (dd, 1H), 7.96 (s, 1H). LC-MS (method 3): RT=1.19 min; [M+H]+=577.
To a solution of tert-butyl 4-[5-cyano-6-[[2-fluoro-5-(trifluoromethyl)phenyl]methoxy]-2-(trifluoromethyl)pyridine-3-carbonyl]piperazine-1-carboxylate (4.57 g, 7.93 mmol) in dioxane (30 mL) was added a solution of hydrochloric acid (4.0 mol/L in dioxane) under cooling. The reaction mixture was stirred at room temperature overnight. Then the reaction mixture was diluted with methanol and treated with basic resin until the pH was basic. The mixture was filtered and the filtrate was concentrated in vacuo to obtain 3.86 g of 2-[[2-fluoro-5-(trifluoromethyl)phenyl]methoxy]-5-(piperazine-1-carbonyl)-6-(trifluoromethyl)pyridine-3-carbonitrile as a pale brown solid. 1H-NMR [ppm] in DMSO-d6: 2.60-2.72 (m, 2H), 2.74-2.84 (m, 1H), 3.02-3.22 (m, 2H), 3.40-3.75 (m, 3H), 5.64 (s, 2H), 7.54 (t, 1H), 7.82-7.92 (m, 1H), 8.06 (dd, 1H), 8.65 (s, 1H).
To a solution of 2-[[2-fluoro-5-(trifluoromethyl)phenyl]methoxy]-5-(piperazine-1-carbonyl)-6-(trifluoromethyl)pyridine-3-carbonitrile (600 mg, 1.20 mmol) in acetonitrile (10 mL) and potassium carbonate (253 mg, 1.80 mmol, 1.5 eq) and methyl bromoacetate (226 mg, 1.44 mmol, 1.2 eq) were added at 0° C. The reaction mixture was stirred at room temperature overnight, then quenched with water (20 mL) and extracted with ethyl acetate (3 times10 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to obtain 656 mg of crude methyl 2-[4-[5-cyano-6-[[2-fluoro-5-(trifluoromethyl)phenyl]methoxy]-2-(trifluoromethyl)pyridine-3-carbonyl]piperazin-1-yl]acetate as an off-white solid. 1H-NMR [ppm] in CDCl3: 2.48-2.60 (m, 2H), 3.60-2.75 (m, 2H), 3.18-3.32 (m, 1H), 3.30 (s, 2H), 3.62-3.92 (m, 3H), 3.75 (s, 3H), 5.66 (s, 2H), 7.26 (t, 1H), 7.62-7.71 (m, 1H), 7.90 (dd, 1H), 7.96 (s, 1H).
To solution of methyl 2-[4-[5-cyano-6-[[2-fluoro-5-(trifluoromethyl)phenyl]methoxy]-2-(trifluoromethyl)pyridine-3-carbonyl]piperazin-1-yl]acetate (650 g, 1.067 mmol) in tetrahydrofuran (6 mL) was added a solution of lithium hydroxide monohydrate (71 mg, 1.60 mmol, 1.50 eq) in water (2 mL) at 10° C. The reaction mixture was stirred at room temperature for 12 hours. After completion, the reaction mixture was concentrated in vacuo, acidified with an aqueous 1 N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. 1H-NMR [ppm] in DMSO-d6: 2.90-3.07 (m, 1H), 3.20-3.45 (m, 2H), 3.43-3.65 (m, 3H), 3.75-4.10 (m, 4H), 5.66 (s, 2H), 7.55 (t, 1H), 7.82-7.93 (m, 1H), 8.07 (dd, 1H), 8.73 (s, 1H).
To a solution of 2-[4-[5-cyano-6-[[2-fluoro-5-(trifluoromethyl)phenyl]methoxy]-2-(trifluoromethyl)pyridine-3-carbonyl]piperazin-1-yl]acetic acid (330 mg, 0.556 mmol) in ethyl acetate (6.6 mL) was added N,N-diisopropylethylamine (145 mg, 1.11 mmol, 2 eq) under stirring followed by addition of a solution of dimethylamine in ethanol (0.6113 mmol, 1.1 eq) and the coupling reagent T3P (1.67 mmol, 3 eq; 50% in ethylacetate). The reaction mixture was stirred at room temperature overnight. After the completion of the reaction the reaction mixture was quenched with saturated aqueous NaHCO3 solution (10 mL) and extracted with ethyl acetate (3 times 20 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The crude material was purified by combiflash (50-100% ethyl acetate: cyclohexane) to afford 150 mg of 2-[4-[5-cyano-6-[[2-fluoro-5-(trifluoromethyl)phenyl]methoxy]-2-(trifluoromethyl)pyridine-3-carbonyl]piperazin-1-yl]-N,N-dimethyl-acetamide as a white solid. 1H-NMR [ppm] in CDCl3: 2.42-2.58 (m, 2H), 2.58-2.74 (m, 2H), 2.96 (s, 3H), 3.05 (s, 3H), 3.20-3.32 (m, 4H), 3.76-3.94 (m, 2H), 5.65 (s, 2H), 7.25 (t, 1H), 7.61-7.70 (m, 1H), 7.89 (d, 1H), 7.94 (s, 1H). LC-MS (method 1): RT=1.00 min; [M+H]+=562.
The compounds in Tables P1 were prepared as described in the examples above or similar methodology.
The compounds in Table P1 can be prepared as described in the examples above or similar methodology. The following abbreviations are used in the table below: RT=retention time, min=minutes.
The compounds in Table P1 can be prepared as described in the examples above or similar methodology. The following abbreviations are used in the table below: RT=retention time, m=minutes.
The activity of the compositions according to the invention can be broadened considerably, and adapted to prevailing circumstances, by adding other insecticidally, acaricidally and/or fungicidally active ingredients. The mixtures of the compounds of formula (I) with other insecticidally, acaricidally and/or fungicidally active ingredients may also have further surprising advantages which can also be described, in a wider sense, as synergistic activity. For example, better tolerance by plants, reduced phytotoxicity, insects can be controlled in their different development stages or better behaviour during their production, for example during grinding or mixing, during their storage or during their use.
Suitable additions to active ingredients here are, for example, representatives of the following classes of active ingredients: organophosphorus compounds, nitrophenol derivatives, thioureas, juvenile hormones, formamidines, benzophenone derivatives, ureas, pyrrole derivatives, carbamates, pyrethroids, chlorinated hydrocarbons, acylureas, pyridinylmethyleneamino derivatives, macrolides, neonicotinoids and Bacillus thuringiensis preparations.
The following mixtures of a compound of formula (I) with an active substances are preferred (the abbreviation “TX” means “one compound selected from the compounds defined in Tables 1 to 57 and Tables P1 to P2”):
The references in brackets behind the active ingredients, e.g. [3878-19-1] refer to the Chemical Abstracts Registry number. The above described mixing partners are known. Where the active ingredients are included in “The Pesticide Manual” [The Pesticide Manual—A World Compendium; Thirteenth Edition; Editor: C. D. S. TomLin; The British Crop Protection Council], they are described therein under the entry number given in round brackets hereinabove for the particular compound; for example, the compound “abamectin” is described under entry number (1). Where “[CCN]” is added hereinabove to the particular compound, the compound in question is included in the “Compendium of Pesticide Common Names”, which is accessible on the internet [A. Wood; Compendium of Pesticide Common Names, Copyright © 1995-2004]; for example, the compound “acetoprole” is described under the internet address http://www.alanwood.net/pesticides/acetoprole.html.
Most of the active ingredients described above are referred to hereinabove by a so-called “common name”, the relevant “ISO common name” or another “common name” being used in individual cases. If the designation is not a “common name”, the nature of the designation used instead is given in round brackets for the particular compound; in that case, the IUPAC name, the IUPAC/Chemical Abstracts name, a “chemical name”, a “traditional name”, a “compound name” or a “development code” is used or, if neither one of those designations nor a “common name” is used, an “alternative name” is employed. “CAS Reg. No” means the Chemical Abstracts Registry Number.
The active ingredient mixture of the compounds of formula (I) selected from the compounds defined in the Tables 1 to 57 and Tables P1 to P2 with active ingredients described above comprises a compound selected from one compound defined in the Tables 1 to 57 and Tables P1 to P2 and an active ingredient as described above preferably in a mixing ratio of from 100:1 to 1:6000, especially from 50:1 to 1:50, more especially in a ratio of from 20:1 to 1:20, even more especially from 10:1 to 1:10, very especially from 5:1 and 1:5, special preference being given to a ratio of from 2:1 to 1:2, and a ratio of from 4:1 to 2:1 being likewise preferred, above all in a ratio of 1:1, or 5:1, or 5:2, or 5:3, or 5:4, or 4:1, or 4:2, or 4:3, or 3:1, or 3:2, or 2:1, or 1:5, or 2:5, or 3:5, or 4:5, or 1:4, or 2:4, or 3:4, or 1:3, or 2:3, or 1:2, or 1:600, or 1:300, or 1:150, or 1:35, or 2:35, or 4:35, or 1:75, or 2:75, or 4:75, or 1:6000, or 1:3000, or 1:1500, or 1:350, or 2:350, or 4:350, or 1:750, or 2:750, or 4:750. Those mixing ratios are by weight.
The mixtures as described above can be used in a method for controlling pests, which comprises applying a composition comprising a mixture as described above to the pests or their environment, with the exception of a method for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body.
The mixtures comprising a compound of formula (I) selected from the compounds defined in the Tables 1 to 57 and Tables P1 to P2 and one or more active ingredients as described above can be applied, for example, in a single “ready-mix” form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a “tank-mix”, and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days. The order of applying the compounds of formula (I) and the active ingredients as described above is not essential for working the present invention.
The compositions according to the invention can also comprise further solid or liquid auxiliaries, such as stabilizers, for example unepoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soya oil), antifoams, for example silicone oil, preservatives, viscosity regulators, binders and/or tackifiers, fertilizers or other active ingredients for achieving specific effects, for example bactericides, fungicides, nematocides, plant activators, molluscicides or herbicides.
The compositions according to the invention are prepared in a manner known per se, in the absence of auxiliaries for example by grinding, screening and/or compressing a solid active ingredient and in the presence of at least one auxiliary for example by intimately mixing and/or grinding the active ingredient with the auxiliary (auxiliaries). These processes for the preparation of the compositions and the use of the compounds I for the preparation of these compositions are also a subject of the invention.
The application methods for the compositions, that is the methods of controlling pests of the abovementioned type, such as spraying, atomizing, dusting, brushing on, dressing, scattering or pouring—which are to be selected to suit the intended aims of the prevailing circumstances—and the use of the compositions for controlling pests of the abovementioned type are other subjects of the invention. Typical rates of concentration are between 0.1 and 1000 ppm, preferably between 0.1 and 500 ppm, of active ingredient. The rate of application per hectare is generally 1 to 2000 g of active ingredient per hectare, in particular 10 to 1000 g/ha, preferably 10 to 600 g/ha.
A preferred method of application in the field of crop protection is application to the foliage of the plants (foliar application), it being possible to select frequency and rate of application to match the danger of infestation with the pest in question. Alternatively, the active ingredient can reach the plants via the root system (systemic action), by drenching the locus of the plants with a liquid composition or by incorporating the active ingredient in solid form into the locus of the plants, for example into the soil, for example in the form of granules (soil application). In the case of paddy rice crops, such granules can be metered into the flooded paddy-field.
The compounds of formula (I) of the invention and compositions thereof are also be suitable for the protection of plant propagation material, for example seeds, such as fruit, tubers or kernels, or nursery plants, against pests of the abovementioned type. The propagation material can be treated with the compound prior to planting, for example seed can be treated prior to sowing. Alternatively, the compound can be applied to seed kernels (coating), either by soaking the kernels in a liquid composition or by applying a layer of a solid composition. It is also possible to apply the compositions when the propagation material is planted to the site of application, for example into the seed furrow during drilling. These treatment methods for plant propagation material and the plant propagation material thus treated are further subjects of the invention. Typical treatment rates would depend on the plant and pest/fungi to be controlled and are generally between 1 to 200 grams per 100 kg of seeds, preferably between 5 to 150 grams per 100 kg of seeds, such as between 10 to 100 grams per 100 kg of seeds.
The term seed embraces seeds and plant propagules of all kinds including but not limited to true seeds, seed pieces, suckers, corns, bulbs, fruit, tubers, grains, rhizomes, cuttings, cut shoots and the like and means in a preferred embodiment true seeds.
The present invention also comprises seeds coated or treated with or containing a compound of formula I. The term “coated or treated with and/or containing” generally signifies that the active ingredient is for the most part on the surface of the seed at the time of application, although a greater or lesser part of the ingredient may penetrate into the seed material, depending on the method of application. When the said seed product is (re)planted, it may absorb the active ingredient. In an embodiment, the present invention makes available a plant propagation material adhered thereto with a compound of formula I. Further, it is hereby made available, a composition comprising a plant propagation material treated with a compound of formula I.
Seed treatment comprises all suitable seed treatment techniques known in the art, such as seed dressing, seed coating, seed dusting, seed soaking and seed pelleting. The seed treatment application of the compound formula (I) can be carried out by any known methods, such as spraying or by dusting the seeds before sowing or during the sowing/planting of the seeds.
The compounds of the invention can be distinguished from other similar compounds by virtue of greater efficacy at low application rates and/or different pest control, which can be verified by the person skilled in the art using the experimental procedures, using lower concentrations if necessary, for example 10 ppm, 5 ppm, 2 ppm, 1 ppm or 0.2 ppm; or lower application rates, such as 300, 200 or 100, mg of Al per m2. The greater efficacy can be observed by an increased safety profile (against non-target organisms above and below ground (such as fish, birds and bees), improved physico-chemical properties, or increased biodegradability).
In each aspect and embodiment of the invention, “consisting essentially” and inflections thereof are a preferred embodiment of “comprising” and its inflections, and “consisting of” and inflections thereof are a preferred embodiment of “consisting essentially of” and its inflections.
The disclosure in the present application makes available each and every combination of embodiments disclosed herein.
The Examples which follow serve to illustrate the invention. Certain compounds of the invention can be distinguished from known compounds by virtue of greater efficacy at low application rates, which can be verified by the person skilled in the art using the experimental procedures outlined in the Examples, using lower application rates if necessary, for example 50 ppm, 24 ppm, 12.5 ppm, 6 ppm, 3 ppm, 1.5 ppm, 0.8 ppm or 0.2 ppm.
Bean leaf discs on agar in 24-well microtiter plates were sprayed with aqueous test solutions prepared from 10'000 ppm DMSO stock solutions. After drying the leaf discs were infested with a mite population of mixed ages. The samples were assessed for mortality on mixed population (mobile stages) 8 days after infestation.
The following compounds resulted in at least 80% mortality at an application rate of 200 ppm: P1.1, P1.2, P1.3, P1.4, P1.5, P1.6, P1.7, P1.8, P.1.9, P1.10, P1.12, P1.13, P1.14, P1.15, P1.18, P1.19, P1.20, P1.21, P1.22, P1.23, P1.24, P1.25, P1.26, P1.27, P1.28, P1.29, P1.30, P1.32, P1.33, P1.35, P1.36, P1.37, P1.38, P1.43, P1.44, P1.45, P1.46, P1.47, P1.48, P1.49, P1.51, P1.52, P1.54, P1.56, P1.60, P1.61, P1.62, P1.63, P1.64, P1.65, P1.66, P1.67, P1.68, P1.69, P1.70, P1.71, P1.72, P1.73, P1.74, P1.75, P1.76, P1.77, P1.78, P1.80, P1.83, P1.84, P1.85, P1.86, P1.89, P1.90, P1.91, P1.92, P1.93, P1.94, P1.95, P1.97, P1.98, P1.100, P1.101, P1.102, P1.103, P1.104, P1.105, P1.106, P1.107, P1.108, P1.109, P1.110, P1.111, P1.112, P1.113, P1.114, P1.115, P1.116, P1.117, P1.118, P1.119, P1.120, P1.122, P1.123, P1.124, P1.125, P1.126, P1.127, P1.128, P1.129, P1.130, P1.131, P1.132, P1.133, P1.134, P1.135, P1.136, P1.137, P1.138, P1.139, P1.141, P1.142, P1.143, P1.144, P1.145, P1.146, P1.147, P1.148, P1.149, P1.150, P1.151, P1.152, P1.153, P1.154, P1.155, P1.156, P1.157, P1.158, P1.159, P1.160, P1.161, P1.162, P1.163, P1.164, P1.165, P1.166, P1.167, P2.1, P2.2, P2.3, P2.4, P2.5, P2.6, P2.7, P2.8, P2.9, P2.10, P2.11, P2.12, P2.13, P2.15, P2.16, P2.17, P2.18, P2.19, P2.20, P2.21, P2.22, P2.23, P2.24, P2.26, P2.27, P2.32, P2.33, P2.35, P2.37, P2.38, P2.39, P2.40, P2.41, P2.42, P2.43, P2.44, P2.45, P2.46, P2.51, P2.54, P2.55.
| Number | Date | Country | Kind |
|---|---|---|---|
| 202111017793 | Apr 2021 | IN | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2022/060093 | 4/14/2022 | WO |
