Pesticidally active heterocyclic derivatives with sulphur containing substituents

Compounds of formula I, wherein the substituents are as defined in claim 1, and the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds, can be used as insecticides and can be prepared in a manner known per se.

RELATED APPLICATION INFORMATION

This application is a 371 of International Application No. PCT/EP2015/067677, filed 31 Jul. 2015, which claims priority to EP 14180130.8, filed 7 Aug. 2014, and EP 14186737.4, filed 29 Sep. 2014, the contents of which are incorporated herein by reference herein.

The present invention relates to pesticidally active, in particular insecticidally active heterocyclic derivatives containing sulphur substituents, 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).

Heterocyclic compounds with pesticidal action are known and described, for example, in WO 2012/086848, WO 2013/018928, WO 2013/191112 and WO 2013/191113.

There have now been found novel pesticidally active heterocyclic derivatives with sulphur containing phenyl and pyridyl substituents.

The present invention accordingly relates to compounds of formula I,

wherein

X is S, SO or SO2;

R1is C3-C6cycloalkyl-C1-C4alkyl mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano, C1-C4haloalkyl and C1-C4alkyl; or

R2aand R2bare, independently from each other, hydrogen, halogen, cyano, C1-C6haloalkyl or C1-C6haloalkyl substituted by one or two substituents selected from the group consisting of hydroxyl, methoxy and cyano; or

R2aand R2bare, independently from each other, C3-C6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano, C1-C4haloalkyl and C1-C4alkyl;

R3is a five- to six-membered, aromatic, partially saturated or fully saturated ring system linked via a nitrogen atom to the ring which contains the substituent G3, said ring system can be mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano, nitro, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl, C1-C4alkyl, C1-C4haloalkyl, C1-C4haloalkoxy, C1-C4alkoxy, C1-C4alkoxy C1-C4alkyl, C1-C4alkylsulfanyl, C1-C4alkylsulfinyl, C1-C4alkylsulfonyl, —C(O)C1-C4alkyl, C1-C4haloalkylsulfanyl, C1-C4haloalkylsulfinyl, C1-C4haloalkylsulfonyl and —C(O)C1-C4haloalkyl; said ring system contains 1, 2 or 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulphur; where said ring system may not contain more than one oxygen atom and not more than one sulfur atom;

agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of the compounds of 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, nitrose 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.

The alkyl groups occurring in the definitions of the substituents can be straight-chain or branched and are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, pentyl, hexyl, nonyl, decyl and their branched isomers. Alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkoxy, alkenyl and alkynyl radicals are derived from the alkyl radicals mentioned. The alkenyl and alkynyl groups can be mono- or polyunsaturated.

Halogen is generally fluorine, chlorine, bromine or iodine. This also applies, correspondingly, to halogen in combination with other meanings, such as haloalkyl or halophenyl.

Alkoxyalkyl groups preferably have a chain length of 1 to 6 carbon atoms.

The cycloalkyl groups preferably have from 3 to 6 ring carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

In the context of this invention, examples of a five- to six-membered, aromatic, partially saturated or fully saturated ring system are pyrazole, pyrrole, pyrrolidine, pyrrolidine-2-one, imidazole, triazole and pyridine-2-one.

In the context of this invention “mono- to polysubstituted” in the definition of the substituents, means typically, depending on the chemical structure of the substituents, monosubstituted to seven-times substituted, preferably monosubstituted to five-times substituted, more preferably mono-, double- or triple-substituted.

In the context of this invention pyrimidine or pyridine as R3may be both linked via any carbon atom to the ring which contains the substituent G3.

The compounds of formula I according to the invention also include hydrates which may be formed during the salt formation.

Preferably R1is C1-C4alkyl, C1-C4haloalkyl, C3-C6cycloalkyl, C3-C6cycloalkyl-C1-C4alkyl, C3-C6cycloalkyl mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano and C1-C4alkyl; or R1is C3-C6cycloalkyl-C1-C4alkyl mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano and C1-C4alkyl;

R3is pyrimidine which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano, C1-C4alkyl, C1-C4haloalkyl, C1-C4haloalkoxy, C1-C4alkoxy, C1-C4haloalkylsulfanyl, C1-C4haloalkylsulfinyl, C1-C4haloalkylsulfonyl and —C(O)C1-C4haloalkyl; or

R3is pyridine which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano, C1-C4alkyl, C1-C4haloalkyl, C1-C4haloalkoxy, C1-C4alkoxy, C1-C4haloalkylsulfanyl, C1-C4haloalkylsulfinyl, C1-C4haloalkylsulfonyl and —C(O)C1-C4haloalkyl; or

R3is a five- to six-membered, aromatic, partially saturated or fully saturated ring system linked via a nitrogen atom to the ring which contains the substituent G3, said ring system can be mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano, C1-C4alkyl, C1-C4haloalkyl, C1-C4haloalkoxy, C1-C4alkoxy, C1-C4alkylsulfanyl, C1-C4alkylsulfinyl, C1-C4alkylsulfonyl and —C(O)C1-C4alkyl, C1-C4haloalkylsulfanyl, C1-C4haloalkylsulfinyl, C1-C4haloalkylsulfonyl and —C(O)C1-C4haloalkyl; and said ring system contains 1, 2 or 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulphur, where said ring system may not contain more than one oxygen atom and not more than one sulfur atom.

More preferably R3is hydrogen, halogen, cyano, nitro, C1-C4alkyl, C1-C4haloalkyl, C3-C6cycloalkyl, C3-C6cycloalkyl-C1-C4alkyl, or is C3-C6cycloalkyl which is mono- or di-substituted by substituents selected from the group consisting of halogen and cyano; or R3is C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, C2-C6haloalkynyl; or

A preferred group of compounds of formula I is represented by the compounds of formula I-1

wherein G1, G2R1and R2aare as defined under formula I above, X is S, SO or SO2; preferably S or SO2, R3is hydrogen, halogen or C1-C4haloalkyl, in particular C1-C4haloalkyl; and agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds.

Also preferred are compounds of formula I-1, wherein G1is C—H; G2is C—H; R1is C1-C4alkyl, C3-C6cycloalkyl-C1-C4alkyl or C3-C6cycloalkyl; R2ais halogen, C1-C4haloalkyl, cyano or C3-C6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano and C1-C4alkyl; and R3is hydrogen, halogen or C1-C4haloalkyl, preferably C1-C4haloalkyl.

Also preferred are compounds of formula I-1, wherein G1is C—H; G2is N; R1is C1-C4alkyl, C3-C6cycloalkyl-C1-C4alkyl or C3-C6cycloalkyl; R2ais halogen, C1-C4haloalkyl, cyano or C3-C6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano and C1-C4alkyl; and R3is hydrogen, halogen or C1-C4haloalkyl.

In other preferred compounds of formula I-1, G1is CR4; wherein R4is as defined under formula I above; G2is C—H; and R1, R2aand R3are as defined under formula I-1 above.

Also preferred are compounds of formula I-1, wherein G1is CR4; wherein R4is as defined under formula I above; G2is C—H; R1is C1-C4alkyl, C3-C6cycloalkyl-C1-C4alkyl or C3-C6cycloalkyl; R2ais halogen, C1-C4haloalkyl, cyano or C3-C6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano and C1-C4alkyl; and R3is hydrogen, halogen or C1-C4haloalkyl.

In a further preferred group of compounds of formula I-1, G1is CR4; wherein R4is as defined under formula I above; G2is C—H; R1is methyl, ethyl, n-propyl, i-propyl or cyclopropylmethyl; R2ais halogen, trifluoromethyl, cyano or is cyclopropyl which can be monosubstituted by cyano; and R3is hydrogen or trifluoromethyl.

Further preferred are compounds of formula I-1, wherein G1is CR4; wherein R4is as defined under formula I above; G2is C—H; R1is ethyl; R2ais trifluoromethyl and R3is hydrogen or trifluoromethyl.

Further preferred are compounds of formula I-1, wherein G1is CR4, wherein R4is as defined under formula I above; G2is N; and R1, R2aand R3are as defined under formula I-1 above.

Also preferred are compounds of formula I-1, wherein G1is CR4; wherein R4is as defined under formula I above; G2is N; R1is C1-C4alkyl, C3-C6cycloalkyl-C1-C4alkyl or C3-C6cycloalkyl; R2ais halogen, C1-C4haloalkyl, cyano or is C3-C6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano and C1-C4alkyl; and R3is hydrogen, halogen or C1-C4haloalkyl.

In another preferred group of compounds of formula I-1, G1is CR4; wherein R4is as defined under formula I above; G2is N; R1is methyl, ethyl, n-propyl, i-propyl or cyclopropylmethyl, R2ais halogen, trifluoromethyl, cyano or is cyclopropyl which can be monosubstituted by cyano; and R3is hydrogen or trifluoromethyl.

Further preferred are compounds of formula I-1, wherein G1is CR4; wherein R4is as defined under formula I above; G2is N; R1is ethyl; R2ais trifluoromethyl; and R3is hydrogen or trifluoromethyl.

Also preferred are compounds of formula I-1, wherein G1is CR4; wherein R4is hydrogen, methyl, cyano, chloro or bromo; G2is N; R1is C1-C4alkyl, C3-C6cycloalkyl-C1-C4alkyl or C3-C6cycloalkyl; R2ais halogen, C1-C4haloalkyl, cyano or C3-C6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano and C1-C4alkyl; and R3is hydrogen, halogen or C1-C4haloalkyl.

Another preferred group of compounds of formula I is represented by the compounds of formula I-2

wherein G1, G2R1and R2aare as defined under formula I above, X is S, SO or SO2; preferably S or SO2; R3is hydrogen, halogen or C1-C4haloalkyl, in particular C1-C4haloalkyl; and agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds.

Also preferred are compounds of formula I-2, wherein G1is C—H; G2is C—H; R1is C1-C4alkyl, C3-C6cycloalkyl-C1-C4alkyl or C3-C6cycloalkyl; R2ais halogen, C1-C4haloalkyl, cyano or C3-C6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano and C1-C4alkyl; and R3is hydrogen, halogen or C1-C4haloalkyl, preferably C1-C4haloalkyl.

Also preferred are compounds of formula I-2, wherein G1is C—H; G2is N; R1is C1-C4alkyl, C3-C6cycloalkyl-C1-C4alkyl or C3-C6cycloalkyl; R2ais halogen, C1-C4haloalkyl, cyano or C3-C6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano and C1-C4alkyl; and R3is hydrogen, halogen or C1-C4haloalkyl.

In other preferred compounds of formula I-2, G1is CR4; wherein R4is as defined under formula I above; G2is C—H; and R1, R2aand R3are as defined under formula I-2 above.

Also preferred are compounds of formula I-2, wherein G1is CR4; wherein R4is as defined under formula I above; G2is C—H; R1is C1-C4alkyl, C3-C6cycloalkyl-C1-C4alkyl or C3-C6cycloalkyl; R2ais halogen, C1-C4haloalkyl, cyano or C3-C6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano and C1-C4alkyl; and R3is hydrogen, halogen or C1-C4haloalkyl.

In a further preferred group of compounds of formula I-2, G1is CR4; wherein R4is as defined under formula I above; G2is C—H; R1is methyl, ethyl, n-propyl, i-propyl or cyclopropylmethyl; R2ais halogen, trifluoromethyl, cyano or is cyclopropyl which can be monosubstituted by cyano; and R3is hydrogen or trifluoromethyl.

Further preferred are compounds of formula I-2, wherein G1is CR4; wherein R4is as defined under formula I above; G2is C—H; R1is ethyl; R2ais trifluoromethyl and R3is hydrogen or trifluoromethyl.

Further preferred are compounds of formula I-2, wherein G1is CR4, wherein R4is as defined under formula I above; G2is N; and R1, R2aand R3are as defined under formula I-2 above.

Also preferred are compounds of formula I-2, wherein G1is CR4; wherein R4is as defined under formula I above; G2is N; R1is C1-C4alkyl, C3-C6cycloalkyl-C1-C4alkyl or C3-C6cycloalkyl; R2ais halogen, C1-C4haloalkyl, cyano or is C3-C6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano and C1-C4alkyl; and R3is hydrogen, halogen or C1-C4haloalkyl.

In another preferred group of compounds of formula I-2, G1is CR4; wherein R4is as defined under formula I above; G2is N; R1is methyl, ethyl, n-propyl, i-propyl or cyclopropylmethyl, R2ais halogen, trifluoromethyl, cyano or is cyclopropyl which can be monosubstituted by cyano; and R3is hydrogen or trifluoromethyl.

Further preferred are compounds of formula I-2, wherein G1is CR4; wherein R4is as defined under formula I above; G2is N; R1is ethyl; R2ais trifluoromethyl; and R3is hydrogen or trifluoromethyl.

Also preferred are compounds of formula I-2, wherein G1is CR4; wherein R4is hydrogen, methyl, cyano, chloro or bromo; G2is N; R1is C1-C4alkyl, C3-C6cycloalkyl-C1-C4alkyl or C3-C6cycloalkyl; R2ais halogen, C1-C4haloalkyl, cyano or C3-C6cycloalkyl which can be mono- or polysubstituted by substituents selected from the group consisting of halogen, cyano and C1-C4alkyl; and R3is hydrogen, halogen or C1-C4haloalkyl.

A further preferred group of compounds of formula I is represented by the compounds of formula I-3a

wherein

X is S, SO or SO2; preferably S or SO2;

R2ais C1-C4haloalkyl or halogen; in particular bromo or CF3;

R3is hydrogen, C1-C4haloalkyl, C3-C6cycloalkyl, or is phenyl which can be monosubstituted by halogen or C1-C4haloalkyl;

G2is CH or N; in particular CH; and

A is CH or N; and agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds.

A further preferred group of compounds of formula I is represented by the compounds of formula I-3

wherein

X is S, SO or SO2; preferably S or SO2;

R3is hydrogen, C1-C4haloalkyl, C3-C6cycloalkyl or phenyl which can be monosubstituted by halogen or C1-C4haloalkyl;

A is CH or N; and agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds.

A further preferred group of compounds of formula I is represented by the compounds of formula I-3 wherein

X is S, SO or SO2; preferably S or SO2;

A is CH or N; and agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds.

In especially preferred compounds of formula I,

X is S or SO2; and

A is CH or N.

The process according to the invention for preparing compounds of formula (I) is carried out in principle by methods known to those skilled in the art, or in analogy to processes described in the literature, for example, in WO 2013/191113 using the appropriate starting materials.

More specifically, the subgroup of compounds of formula I, wherein X is SO (sulfoxide) and/or SO2(sulfone), may be obtained by means of an oxidation reaction of the corresponding sulfide compounds of formula I, wherein X is S, involving reagents such as, for example, m-chloroperoxybenzoic acid (mCPBA), hydrogen peroxide, oxone, sodium periodate, sodium hypochlorite or tert-butyl hypochlorite amongst other oxidants. The oxidation reaction is generally conducted in the presence of a solvent. Examples of the solvent to be used in the reaction include aliphatic halogenated hydrocarbons such as dichloromethane and chloroform; alcohols such as methanol and ethanol; acetic acid; water; and mixtures thereof. The amount of the oxidant to be used in the reaction is generally 1 to 3 moles, preferably 1 to 1.2 moles, relative to 1 mole of the sulfide compounds I to produce the sulfoxide compounds I, and preferably 2 to 2.2 moles of oxidant, relative to 1 mole of of the sulfide compounds I to produce the sulfone compounds I. Such oxidation reactions are disclosed, for example, in WO 2013/018928.

Indazoles, aza-indazoles and/or diaza-indazoles, may be made using processes that are well known and have been described for example in WO 2013/191113; Synlett (2013), 24(12), 1573-1577; Journal of the Chemical Society, Chemical Communications (1991), (20), 1466-7; Organic Letters (2014), 16(11), 3114-3117; or for a review on more general synthesis for this type of derivatives, see for example Science of Synthesis (2002), 12, 227-324 and European Journal of Organic Chemistry (2008), (24), 4073-4095. All of these process could be use to access indazoles derivatives. One possible process is summarized in scheme 1 for compounds of formula I:

Compounds of formula (I) may be prepared by reaction of a compound of formula (II) under reductive cyclisation conditions using a reducing agent, such as trialkyl phosphite (more specifically, for example triethyl phosphite), trialkylphosphine or triphenylphosphine. The principle of this reductive cyclisation is analogous to the known Cadogan reaction. Alternatively, this reaction may be conducted in presence of a metal catalyst, for example a molybdenum(VI) catalyst such as MoO2Cl2(dmf)2[molybdenyl chloride-bis(dimethylformamide)], or more generally with transition metal complexes in combination with a reducing agent such as triethylphosphite, triphenylphosphine or CO. Suitable solvents may include use of excess of the reducing agent (such as triethyl phosphite), or for example toluene or xylene at temperatures between room temperature and 200° C., preferably between 50 and 160° C., optionally under microwave conditions.

Compounds of formula (II) may be prepared (scheme 2) by reaction of aldehyde or ketone derivatives of formula (III) with amine derivatives of formula (IV), usually upon heating and optionally under microwave conditions. The formation of compounds of formula (II) may require water removal, either by azeotropical distillation, or with a drying agent such as for example TiCl4or molecular sieves. The formation of the Schiff bases of formula (II) is very well known to those skilled in the art, and methods are well described in the literature, see for example, Molbank (2006), M514 or March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5th Edition p 1185-1187 and cited documents therein. Suitable solvents may include for example toluene or xylene at temperatures between room temperature and 200° C., preferably between 50 and 160° C.

Compounds of formula (III) are either known, commercially available or may be made by methods known to a person skilled in the art.

Compounds of formula (IV) are either known, commercially available or may be made by methods known to a person skilled in the art.

In an alternative method depicted in scheme 2, compounds of formula I can also be prepared by reacting compounds of formula V, wherein R2a, R2b, G1, G2have the values defined in formula I with a compound of formula (VI) wherein Z is a leaving group like, for example, fluorine, chlorine, bromine or iodine, or an aryl- or alkylsulfonate, or any other similar leaving group. For example, this reaction, called SNAr reaction (aromatic nucleophilic substitution reaction) can be done in a presence of base such as for example sodium, potassium or lithium carbonate, in a solvent such as dimethyl formamide, at temperatures between room temperature and 200° C., with or without microwave irradiation. An example of this type of reaction is described in WO 2007/113596 and Journal of Medicinal Chemistry, 52(22), 7170-7185, 2009. In an alternative method, a compound of formula (VI) wherein Z is chlorine, bromine or iodine, or any other appropriate leaving group, could be coupled with compounds of formula V by using copper catalyst coupling conditions, for example using copper(I) iodide as copper catalyst, with or without an additive such as L-proline or N,N′-dimethylethylenediamine, in presence of a base such as, for example potassium carbonate. Said alternative method is for example described in WO 2006/107771 and WO 2012/083105.

Compounds of formula (V) are either known, commercially available or may be made by methods known to a person skilled in the art.

Compounds of formula (VI) are either known, commercially available or may be made by methods known to a person skilled in the art. One particular example is described in scheme 4.

Compounds of formula (Via), wherein R3, R6, R1, A and G3have the values defined in formula I may be prepared (scheme 4) by oxidation of compounds of formula (XIV). The reaction can be performed with reagents like, for example a peracid as peracetic acid or m-chloroperbenzoic acid, or a hydroperoxide as for example hydrogen peroxide or tert-butylhydroperoxide, or an inorganic oxidant, like a mono-peroxodisulfate salt or potassium permanganate, preferentially meta-chloroperbenzoic acid.

Compounds of formula (XIV) wherein R3, R6, R1, A and G3have the values defined in formula I, may be prepared (scheme 4) by substitution of the two leaving groups (LG) of compounds of formula (VII), LG is, for example Cl or fluorine, by reaction with compounds of formula XI
R1—SH  (XI),

or a salt thereof, wherein R1is as defined in formula I, optionally in the presence of a suitable base, such as alkali metal carbonates, for example sodium carbonate and potassium carbonate, or alkali metal hydrides such as sodium hydride, or alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, in an inert solvent at temperatures preferably between 25-120° C. Examples of solvent to be used include ethers such as THF, ethylene glycol dimethyl ether, tert-butylmethyl ether, and 1,4-dioxane, aromatic hydrocarbons such as toluene and xylene, nitriles such as acetonitrile or polar aprotic solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone or dimethyl sulfoxide. Examples of salts of the compound of formula X include compounds of the formula XIa
R1—S-M  (XIa),

wherein R1is as defined above and wherein M is, for example, sodium or potassium.

Under the similar condition, compounds of formula (IX) may be prepare from compounds of formula (VIII) wherein, LG is, for example Cl or fluorine and LG2is bromide or iodine. The transformation of compounds of formula (IX) to compounds of formula (XIV) via transformation of LG2to R3can be perform by methods well known to a person skilled in the art. For example, compounds of formula (XIV) wherein R6, R1, A and G3have the values defined in formula I and R3is, for example, cyclopropane, alkenyl, alkynyl, aral or heteroaryl can be prepared by a Stille reaction of compounds of formula XIIb wherein Yb2is a trialkyl tin derivative, preferably tri-n-butyl tin, with compounds of formula XIV. Such Stille reactions are usually carried out in the presence of a palladium catalyst, for example tetrakis(triphenylphosphine)palladium(0), or (1,1′bis(diphenylphosphino)-ferrocene)dichloropalladium-dichloromethane (1:1 complex), in an inert solvent such as DMF, acetonitrile, or dioxane, optionally in the presence of an additive, such as cesium fluoride, or lithium chloride, and optionally in the presence of a further catalyst, for example copper(I)iodide. Such Stille couplings are also well known to those skilled in the art, and have been described in for exampleJ. Org. Chem.,2005, 70, 8601-8604, J. Org. Chem.,2009, 74, 5599-5602, andAngew. Chem. Int. Ed.,2004, 43, 1132-1136. Alternatively, compounds of formula (XIV) wherein R6, R1, A and G3have the values defined in formula I and R3is, for example, cyclopropane, alkenyl, alkynyl, aral or heteroaryl can be prepared by a Suzuki reaction, which involves reacting compounds of formula IX, wherein LG is a leaving group, for example, chlorine, bromine or iodine with compounds of formula XIIa, wherein Yb1can be a boron-derived functional group, as for example B(OH)2or B(ORb1)2wherein Rb1can be a C1-C4alkyl group or the two groups ORb1can form together with the boron atom a five membered ring, as for example a pinacol boronic ester. The reaction can be catalyzed by a palladium based catalyst, for example tetrakis(triphenylphosphine)-palladium or (1,1′bis(diphenylphosphino)-ferrocene)dichloropalladium-dichloromethane (1:1 complex), in presence of a base, like sodium carbonate or cesium fluoride, in a solvent or a solvent mixture, like, for example a mixture of 1,2-dimethoxyethane and water, or of dioxane and water, preferably under an inert atmosphere. The reaction temperature can preferentially range from room temperature to the boiling point of the reaction mixture. Such Suzuki reactions are well known to those skilled in the art and have been reviewed, for exampleJ. Orgmet. Chem.576, 1999, 147-168.

Compounds of formula Ib, wherein A, R1, R2a, R2b, R3, R6, G1, G2and G3have the values defined in formula I, can be prepared (scheme 12) by oxidation of compounds of formula Ia, wherein A, R1, R2a, R2b, R3, R6, G1, G2and G3have the values defined in formula I. The reaction can be performed with reagents like, for example a peracid as peracetic acid or m-chloroperbenzoic acid, or a hydroperoxide as for example hydrogen peroxide or tert-butylhydroperoxide, or an inorganic oxidant, like a mono-peroxodisulfate salt or potassium permanganate, preferentially meta-chloroperbenzoic acid. In a similar way, compounds of formula Ic, wherein A, R1, R2a, R2b, R3, R6, G1, G2and G3have the values defined in formula I, can be prepared by oxidation of compounds of formula Ib. These reactions can be performed in various organic or aqueous solvents compatible to these conditions, by temperatures from below 0° C. up to the boiling point of the solvent system and the number of equivalents of oxidant will determinate the degrees of oxidation of the sulphur, e.g. with two or more equivalents of oxidant, the compound of formula Ic can be prepare directly from compound of formula Ia.

Compounds of formula (XV) can be prepared, for example, as described in scheme 6: 1) by reacting compounds of formula (VI) with carbone monoxide in presence of metal catalyst a such as palladium catalyst (for example: palladium(II)acetate) in a alcohol such as methanol or ethanol and optionally in presence of ligan (for example: 1,1′-Ferrocenediyl-bis(diphenylphosphine) and, optionally, in presence of a base (for example: N,N-diethylethanamine). These reaction are well known in literature under the name of “carbonylative cross-coupling of Aryl Halides”. For examples of such reaction, see: Angewandte Chemie, International Edition (2009), 48(23), 4114-4133 orOrganometallics.2008, 27, 5402. 2) by halogenation of compounds of formula (VII) via, first, deprotonative metalation of compounds of formula (VII) to generate the organometallic derived from compounds of formula (VII) at low temperature in presence of an organometallic such as butyllithium, then followed by reaction with an halogen electrophile such as iodine or bromide. This transformation is well known by a person skilled in the art and many reagent could realize this transformation using different organometallic and conditions to generate the organometallic derived from compounds of formula (VII), see for some examples around these types of reaction: Journal of the American Chemical Society 1999, 121(14), 3539-3540 or Angewandte Chemie, International Edition (2014), 53(30), 7928-7932). 3) reduction of the ester of the compound of formula (VIII) to aldehyde via reduction under standard condition: for example in presence of a reduction agent such as Diisobutylaluminium hydride in a solvent such as dichloromethane to give compound of formula (IX). Such reaction are well known by by a person skilled in the art (see for example of this transformation: Comprehensive Organic Transformations A Guide to Functional Group Preparations by Larock, R. C. 1989, p 619 (Publisher VCH Weinheim, Germany)) 4) the reaction of compounds of formula (IX) with compounds of formula (X) in a solvent such as methanol gave compounds of formula (XI) and optionally compounds of formula (XII). 5) heating of compounds of formula (XI) in a solvent such as dimethylformamide in microwaves or not gave compounds of formula (XIV). 6) oxidation of the sulphur group of compound of formula (XIV) in conditions similar as described in scheme 5 gave the desired compounds of formula (XV).

Compounds of formula (X) are either known, commercially available or may be made by methods known to a person skilled in the art.

The reactants can be reacted in the presence of a base. Examples of suitable bases are alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal hydrides, alkali metal or alkaline earth metal amides, alkali metal or alkaline earth metal alkoxides, alkali metal or alkaline earth metal acetates, alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal dialkylamides or alkali metal or alkaline earth metal alkylsilylamides, alkylamines, alkylenediamines, free or N-alkylated saturated or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxides and carbocyclic amines. Examples which may be mentioned are sodium hydroxide, sodium hydride, sodium amide, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N,N-dimethylamine, N,N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinuclidine, N-methylmorpholine, benzyltrimethylammonium hydroxide and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

The reactants can be reacted with each other as such, i.e. without adding a solvent or diluent. In most cases, however, it is advantageous to add an inert solvent or diluent or a mixture of these. If the reaction is carried out in the presence of a base, bases which are employed in excess, such as triethylamine, pyridine, N-methylmorpholine or N,N-diethylaniline, may also act as solvents or diluents.

The reaction is advantageously carried out in a temperature range from approximately −80° C. to approximately +140° C., preferably from approximately −30° C. to approximately +100° C., in many cases in the range between ambient temperature and approximately +80° C.

A compound of formula I can be converted in a manner known per se into another compound of formula I by replacing one or more substituents of the starting compound of formula I in the customary manner by (an)other substituent(s) according to the invention.

Depending on the choice of the reaction conditions and starting materials which are suitable in each case, it is possible, for example, in one reaction step only to replace one substituent by another substituent according to the invention, or a plurality of substituents can be replaced by other substituents according to the invention in the same reaction step.

Salts of compounds of formula I can be prepared in a manner known per se. Thus, for example, acid addition salts of compounds of formula I are obtained by treatment with a suitable acid or a suitable ion exchanger reagent and salts with bases are obtained by treatment with a suitable base or with a suitable ion exchanger reagent.

Salts of compounds of formula I can be converted in the customary manner into the free compounds I, acid addition salts, for example, by treatment with a suitable basic compound or with a suitable ion exchanger reagent and salts with bases, for example, by treatment with a suitable acid or with a suitable ion exchanger reagent.

Salts of compounds of formula I can be converted in a manner known per se into other salts of compounds of formula I, acid addition salts, for example, into other acid addition salts, for example by treatment of a salt of inorganic acid such as hydrochloride with a suitable metal salt such as a sodium, barium or silver salt, of an acid, for example with silver acetate, in a suitable solvent in which an inorganic salt which forms, for example silver chloride, is insoluble and thus precipitates from the reaction mixture.

Depending on the procedure or the reaction conditions, the compounds of formula I, which have salt-forming properties can be obtained in free form or in the form of salts.

The compounds of formula I and, where appropriate, the tautomers thereof, in each case in free form or in salt form, can be present in the form of one of the isomers which are possible or as a mixture of these, for example in the form of pure isomers, such as antipodes and/or diastereomers, or as isomer mixtures, such as enantiomer mixtures, for example racemates, diastereomer mixtures or racemate mixtures, depending on the number, absolute and relative configuration of asymmetric carbon atoms which occur in the molecule and/or depending on the configuration of non-aromatic double bonds which occur in the molecule; the invention relates to the pure isomers and also to all isomer mixtures which are possible and is to be understood in each case in this sense hereinabove and hereinbelow, even when stereochemical details are not mentioned specifically in each case.

Diastereomer mixtures or racemate mixtures of compounds of formula I, in free form or in salt form, which can be obtained depending on which starting materials and procedures have been chosen can be separated in a known manner into the pure diasteromers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and/or chromatography.

Enantiomer mixtures, such as racemates, which can be obtained in a similar manner can be resolved into the optical antipodes by known methods, for example by recrystallization from an optically active solvent, by chromatography on chiral adsorbents, for example high-performance liquid chromatography (HPLC) on acetyl cellulose, with the aid of suitable microorganisms, by cleavage with specific, immobilized enzymes, via the formation of inclusion compounds, for example using chiral crown ethers, where only one enantiomer is complexed, or by conversion into diastereomeric salts, for example by reacting a basic end-product racemate with an optically active acid, such as a carboxylic acid, for example camphor, tartaric or malic acid, or sulfonic acid, for example camphorsulfonic acid, and separating the diastereomer mixture which can be obtained in this manner, for example by fractional crystallization based on their differing solubilities, to give the diastereomers, from which the desired enantiomer can be set free by the action of suitable agents, for example basic agents.

Pure diastereomers or enantiomers can be obtained according to the invention not only by separating suitable isomer mixtures, but also by generally known methods of diastereoselective or enantioselective synthesis, for example by carrying out the process according to the invention with starting materials of a suitable stereochemistry.

N-oxides can be prepared by reacting a compound of the formula I with a suitable oxidizing agent, for example the H2O2/urea adduct in the presence of an acid anhydride, e.g. trifluoroacetic anhydride.

Such oxidations are known from the literature, for example from J. Med. Chem., 32 (12), 2561-73, 1989 or WO 00/15615.

It is advantageous to isolate or synthesize in each case the biologically more effective isomer, for example enantiomer or diastereomer, or isomer mixture, for example enantiomer mixture or diastereomer mixture, if the individual components have a different biological activity.

The compounds of formula I and, where appropriate, the tautomers thereof, in each case in free form or in salt form, can, if appropriate, also be obtained in the form of hydrates and/or include other solvents, for example those which may have been used for the crystallization of compounds which are present in solid form.

The compounds according to the following Tables 1 to 3 below 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. “Ph” represents the phenyl group.

TABLE 1This table discloses the 10 compounds of the formula I-1a:(I-1a)Comp. NoXR1R3A1.001S—CH2CH3CF3CH1.002S(O)2—CH2CH3CF3CH1.003S—CH2CH3CF3N1.004S(O)2—CH2CH3CF3N1.005S—CH2CH3HCH1.006S(O)2—CH2CH3HCH1.007S—CH2CH3HN1.008S(O)2—CH2CH3HN1.009S—CH2CH34—Cl—Ph—N1.010S(O)2—CH2CH34—Cl—Ph—N

and the N-oxides of the compounds of Table 1.

TABLE 2This table discloses 10 compounds of formula I-1b:(I-1b)Comp. NoXR1R3A2.001S—CH2CH3CF3CH2.002S(O)2—CH2CH3CF3CH2.003S—CH2CH3CF3N2.004S(O)2—CH2CH3CF3N2.005S—CH2CH3HCH2.006S(O)2—CH2CH3HCH2.007S—CH2CH3HN2.008S(O)2—CH2CH3HN2.009S—CH2CH34—Cl—Ph—N2.010S(O)2—CH2CH34—Cl—Ph—N

and the N-oxides of the compounds of Table 2.

TABLE 3This table discloses 12 compounds of the formula I-1c:(I-1c)Comp. NoXR1R3AR43.001S—CH2CH3CF3NBr3.002S(O)2—CH2CH3CF3NBr3.003S—CH2CH3CF3NCN3.004S(O)2—CH2CH3CF3NCN3.005S—CH2CH3CF3NCH33.006S(O)2—CH2CH3CF3NCH33.007S—CH2CH3HNBr3.008S(O)2—CH2CH3HNBr3.009S—CH2CH3HNCN3.010S(O)2—CH2CH3HNCN3.011S—CH2CH3HNCH33.012S(O)2—CH2CH3HNCH3

and the N-oxides of the compounds of Table 3.

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 abovementioned animal pests are:

from the order Acarina, for example,

from the order Anoplura, for example,

from the order Coleoptera, for example,

from the order Diptera, for example,

from the order Hemiptera, for example,

from the order Hymenoptera, for example,

from the order Isoptera, for example,

from the order Lepidoptera, for example,

from the order Mallophaga, for example,

from the order Orthoptera, for example,

from the order Psocoptera, for example,

from the order Siphonaptera, for example,

from the order Thysanoptera, for example,

from the order Thysanura, for example,Lepisma saccharina.

The active ingredients according to the invention can be used for controlling, i. e. containing or destroying, pests of the abovementioned type which occur in particular on plants, especially on useful plants and ornamentals in agriculture, in horticulture and in forests, or on organs, such as fruits, flowers, foliage, stalks, tubers or roots, of such plants, and in some cases even plant organs which are formed at a later point in time remain protected against these pests.

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.

The active ingredients according to the invention are especially suitable for controllingAphis craccivora, Diabrotica balteata, Heliothis virescens, Myzus persicae, Plutella xylostellaandSpodoptera littoralisin cotton, vegetable, maize, rice and soya crops. The active ingredients according to the invention are further especially suitable for controllingMamestra(preferably in vegetables),Cydia pomonella(preferably in apples),Empoasca(preferably in vegetables, vineyards),Leptinotarsa(preferably in potatos) andChilo supressalis(preferably in rice).

The term “crops” is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genusBacillus.

In the context of the present invention there are to be understood by δ-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:

1. Bt11 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modifiedZea mayswhich has been rendered resistant to attack by the European corn borer (Ostrinia nubilalisandSesamia nonagrioides) by transgenic expression of a truncated Cry1Ab toxin. Bt11 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.

2. Bt176 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modifiedZea mayswhich has been rendered resistant to attack by the European corn borer (Ostrinia nubilalisandSesamia nonagrioides) by transgenic expression of a Cry1Ab toxin. Bt176 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.

3. MIR604 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Maize which has been rendered insect-resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G-protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810.

6. 1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7 B-1160 Brussels, Belgium, registration number C/NL/00/10. Genetically modified maize for the expression of the protein Cry1F for achieving resistance to certain Lepidoptera insects and of the PAT protein for achieving tolerance to the herbicide glufosinate ammonium.

7. NK603×MON 810 Maize from Monsanto Europe S. A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/GB/02/M3/03. Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810. NK603×MON 810 Maize transgenically expresses the protein CP4 EPSPS, obtained fromAgrobacteriumsp. strain CP4, which imparts tolerance to the herbicide Roundup® (contains glyphosate), and also a Cry1Ab toxin obtained fromBacillus thuringiensissubsp.kurstakiwhich brings about tolerance to certain Lepidoptera, include the European corn borer.

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 exampleFusarium, Anthracnose, orPhytophthora), bacterial (for examplePseudomonas) 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 defense (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 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, WO 2006/128870, EP 1724392, WO 2005/113886 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:

The present invention may be also used to control any insect pests that may be present in turfgrass, including for example beetles, caterpillars, fire ants, ground pearls, millipedes, sow bugs, mites, mole crickets, scales, mealybugs ticks, spittlebugs, southern chinch bugs and white grubs. The present invention may be used to control insect pests at various stages of their life cycle, including eggs, larvae, nymphs and adults.

The present invention may also be used to control insect pests of turfgrass that are thatch dwelling, including armyworms (such as fall armywormSpodoptera frugiperda, and common armywormPseudaletia unipuncta), cutworms, billbugs (Sphenophorusspp., such asS. venatus verstitusandS. parvulus), and sod webworms (such asCrambusspp. 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:Haematopinusspp.,Linognathusspp.,Pediculusspp. andPhtirusspp.,Solenopotesspp.

Of the order Mallophagida:Trimenoponspp.,Menoponspp.,Trinotonspp.,Bovicolaspp.,Werneckiellaspp.,Lepikentronspp.,Damalinaspp.,Trichodectesspp. andFelicolaspp.

Of the order Siphonapterida, for examplePulexspp.,Ctenocephalidesspp.,Xenopsyllaspp.,Ceratophyllusspp.

Of the order Heteropterida, for exampleCimexspp.,Triatomaspp.,Rhodniusspp.,Panstrongylusspp.

Of the subclass Acaria (Acarida) and the orders Meta- and Meso-stigmata, for exampleArgasspp.,Ornithodorusspp.,Otobiusspp.,Ixodesspp.,Amblyommaspp.,Boophilusspp.,Dermacentorspp.,Haemophysalisspp.,Hyalommaspp.,Rhipicephalusspp.,Dermanyssusspp.,Raillietiaspp.,Pneumonyssusspp.,Sternostomaspp. andVarroaspp.

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 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.

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 N.J. (1981).

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-C22fatty acids, especially the methyl derivatives of C12-C18fatty 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, 10thEdition, 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 I/ha, especially from 10 to 1000 I/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.

Suspension concentrateactive ingredients40%propylene glycol10%nonylphenol polyethylene glycol ether (15 mol of ethylene oxide)6%Sodium lignosulfonate10%carboxymethylcellulose1%silicone oil (in the form of a 75% emulsion in water)1%Water32%

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.

Flowable concentrate for seed treatmentactive ingredients40%propylene glycol5%copolymer butanol PO/EO2%Tristyrenephenole with 10-20 moles EO2%1,2-benzisothiazolin-3-one (in the form of a 20% solution0.5%in water)monoazo-pigment calcium salt5%Silicone oil (in the form of a 75% emulsion in water)0.2%Water45.3%

The finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.

Slow Release Capsule Suspension

28 parts of the combination are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51.6 parts of water until the desired particle size is achieved. To this emulsion a mixture of 2.8 parts 1,6-diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed. The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% of the active ingredients. The medium capsule diameter is 8-15 microns. The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.

Formulation types include an emulsion concentrate (EC), a suspension concentrate (SC), a suspo-emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (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.

PREPARATORY EXAMPLES

“Mp” means melting point in ° C. Free radicals represent methyl groups.1H NMR measurements were recorded on Brucker 400 MHz or 300 MHz spectrometers, chemical shifts are given in ppm relevant to a TMS standard. Spectra measured in deuterated solvents as indicated.

Method a (HPLC Purification):

Time (mins)A(%)B(%)060400.16040640607.94060801008.9010096040106040

A solution of 5-methyl-2-(trifluoromethyl)pyridine 1-oxide (Step A, 0.787 g) in sulfuric acid H2SO4(3 ml) was treated with a solution of nitric acid HNO3(4 ml) and sulfuric acid (2 mL) at 0° C. The reaction was stirred two hours at 100° C. Then, the reaction mixture was quenched with ice and the pH was adjusted to 7 by the addition of aqueous sodium hydroxide NaOH (4.0 M). The resulting solution was extracted three times with dichloromethane. The combined organic layers were washed with brine and dried on sodium sulfate and concentrated. The mixture was purified by flash chromatography eluting with hexanes and diethylether to give 5-methyl-4-nitro-2-(trifluoromethyl)pyridine 1-oxide (0.45 g).1H NMR (300 MHz, CDCl3): δ (ppm) 8.42 (s, 1H), 8.22 (s, 1H), 2.68 (s, 3H) ppm.

A mixture of 5-methyl-4-nitro-2-(trifluoromethyl)pyridine (Step C, 0.399 g) and N,N-dimethylformamide dimethyl acetal (0.361 g) in dimethylformamide (2 ml) was stirred at 120° C. for 2 hours. The solvent was evaporated under vacuum and the residue was poured into a mixture of sodium metaperiodate NaIO4(1.192 g) dissolved in tetrahydrofuran (THF) and water (25 ml:25 ml). The mixture was stirred for 16 hours. The reaction mixture was filtered and the water layer was extracted, three times, with ethyl acetate. The combined organic layers were concentrated. The mixture was purified by flash chromatography (hexanes and diethyl ether) to give 4-nitro-6-(trifluoro-methyl)pyridine-3-carbaldehyde (0.405 g).1H NMR (300 MHz, CDCl3): δ (ppm) 10.56 (s, 1H), 9.32 (s, 1H), 8.32 (s, 1H).

To a solution of 6-(trifluoromethyl)-2H-pyrazolo[4,3-c]pyridine (0.5 g) and 3-ethylsulfanyl-2-fluoro-pyridine (0.4 g, prepared as described in EP 341011) in dimethylformamide (5 mL) was added dilithium carbonic acid (0.2 g, 3 mmol). The resulting solution was stirred overnight at 100° C. The reaction was stopped by addition of water and the water layer was extracted, three times, with ethyl acetate. The combined organic layers was dried on magnesium sulfate and concentrated under vacuum. The residue was purified by flash chromatography (cyclohexane/ethyl acetate) to give 2-(3-ethylsulfanyl-2-pyridyl)-6-(trifluoromethyl)pyrazolo[4,3-c]pyridine (compound 1.007, 0.053 g).1H NMR (400 MHz, CDCl3): 9.37 (d, 1H), 8.98 (d, 1H), 8.37 (dd, 1H), 8.14 (s, 1H), 7.86 (dd, 1H), 7.43 (dd, 1H), 2.96 (q, 2H), 1.32 (t, 3H) ppm. The major product of the reaction is the isomer of position.

To a solution of 2-(3-ethylsulfanyl-2-pyridyl)-6-(trifluoromethyl)pyrazolo[4,3-c]pyridine (compound 1.007) (0.044 g) in dichloromethane (2.7 mL) was added meta-chloroperoxybenzoic acid (m-CPBA) (0.080 g). The resulting yellow solution was stirred 2 hours at ambient temperature. The reaction was stopped by addition of water and the water layer was extracted, three times, with dichloromethane. The combined organic layers was washed with a solution of NaOH 1M, dried on magnesium sulfate and concentrated under vacuum. The residue was purified by flash chromatography (cyclohexane/ethyl acetate) to give 2-(3-ethylsulfonyl-2-pyridyl)-6-(trifluoromethyl)pyrazolo[4,3-c]pyridine (compound 1.008, 0.048 g).1H NMR (400 MHz, CDCl3): 9.39 (s, 1H), 8.92 (s, 1H), 8.84 (d, 1H), 8.65 (dd, 1H), 8.04 (s, 1H), 7.76 (dd, 1H), 3.94 (q, 2H), 1.44 (t, 3H) ppm.

A mixture of 2-bromo-3-ethylsulfanyl-5-(trifluoromethyl)pyridine (0.2 g, 0.699 mmol), 6-(trifluoromethyl)-2H-pyrazolo[4,3-c]pyridine (0.399 g, 2.13 mmol), potassium phosphate (0.445 g, 2.097 mmol), iodocopper (0.033 g, 0.175 mmol), and trans-n,n′-dimethyl-1,2-cyclohexanediamine (0.0497 g, 0.055 mL, 0.35 mmol) in toluene (9.1 mL) was stirred and heated at 120° C. for overnight. After cooling, 150 mg of 2-bromo-3-ethylsulfanyl-5-(trifluoromethyl)pyridine and the same quantities of CuI, trans-n,n′-dimethyl-1,2-cyclohexanediamine and potassium phosphate were added to the mixture. The reaction was stirred at 120° C. for an extra night. The reaction was stopped by addition of a solution of water and ethyl acetate. The water layer was extracted, three times, with ethyl acetate. The combined organic layers was washed with brine then water, dried on magnesium sulfate and concentrated under vacuum. The residue was purified by flash chromatography (cyclohexane/ethyl acetate) to give 2-[3-ethylsulfanyl-5-(trifluoromethyl)-2-pyridyl]-6-(trifluoromethyl)pyrazolo[4,3-c]pyridine (0.091 g) and his isomer of position.1H NMR (400 MHz, CDCl3): 9.39 (s, 1H), 9.13 (s, 1H), 8.58 (s, 1H), 8.15 (s, 1H), 8.00 (s, 1H), 3.03 (q, 2H), 1.41 (t, 3H) ppm.

To a solution of 5-bromo-2,3-difluoro-pyridine (commercially available, 13.61 g, 66.65 mmol) and N,N-dimethylformamide (94.4 g, 100 mL) was added sodium ethanethiol (18.44 g, 173.3 mmol) in three portions: the reaction was exothermic. The resulting solution was stirred for two hours at room temperature. The reaction was stopped by addition of a solution of water and ethyl acetate. The water layer was extracted, three times, with ethyl acetate. The combined organic layers was washed with brine then water, dried on magnesium sulfate and concentrated under vacuum. The residue was used without extra purification for the next step.1H NMR (400 MHz, CDCl3): 8.32 (s, 1H), 7.56 (s, 1H), 3.18 (q, 2H), 2.95 (q, 2H), 1.40-1.32 (m, 6H) ppm.

To a solution of 5-bromo-2,3-bis(ethylsulfanyl)pyridine (13.6 g, 48.9 mmol) in dichloromethane (250 mL) cooled with an ice bath, was added meta-chloroperoxybenzoic acid (45.6 g, 198 mmol). The resulting solution was stirred for an hour at room temperature. The reaction was stopped by addition of a solution of sodium thiosulfate and the water layer was extracted, three times, with dichloromethane. The combined organic layers was washed with a solution of NaOH 1M, dried on magnesium sulfate and concentrated under vacuum. The residue was purified by flash chromatography (cyclohexane/ethyl acetate) to give 5-bromo-2,3-bis(ethylsulfonyl)pyridine (6.54 g).1H NMR (400 MHz, CDCl3): 9.00 (s, 1H), 8.76 (s, 1H), 3.78 (q, 2H), 3.64 (q, 2H), 1.44-1.34 (m, 6H) ppm.

To a solution of 6-(trifluoromethyl)-2H-pyrazolo[4,3-c]pyridine (0.4679 g, 2.425 mmol) and 5-bromo-2,3-bis(ethylsulfonyl)pyridine (0.83 g, 2.425 mmol) in dimethylformamide (19 mL) was added dilithium carbonic acid (0.5523 g, 7.276 mmol). The resulting solution was stirred at 130° C. for two hours then, overnight at 110° C. The reaction was stopped by addition of water and ethyl acetate. The water layer was extracted, three times, with ethyl acetate. The combined organic layers was dried on magnesium sulfate and concentrated under vacuum. The residue was purified by HPLC (see Method A) to give 2-(5-bromo-3-ethylsulfonyl-2-pyridyl)-6-(trifluoromethyl)pyrazolo[4,3-c]pyridine (compound P8, 0.017 g).

A 20 mL sealed vial flushed with Argon was charged with 5-bromo-2,3-bis(ethylsulfanyl)pyridine (1.00 g, 3.59 mmol), then phenylboronic acid (1.63 g, 12.9 mmol), tetrakis(triphenylphosphine) palladium(0) (0.208 g, 0.180 mmol), potassium phosphate tribasic (4.72 g, 1.84 mL, 21.6 mmol), toluene (4.33 g, 5 mL, 46.8 mmol) and water (5.000 g, 5 mL, 277.5 mmol). The mixture was then refluxed for 2 hours. The reaction was stopped by addition of a solution of water and ethyl acetate. The water layer was extracted, three times, with ethyl acetate. The combined organic layers were dried on magnesium sulfate and concentrated under vacuum. The residue was purified by flash chromatography (cyclohexane/ethyl acetate) to give the title compound (0.97 g). LC-MS (Method B) RT 1.29 (276, MH+).

Using similar conditions described, the 5-(4-chlorophenyl)-2,3-bis(ethylsulfanyl)pyridine was prepared.

Using similar conditions described in Example P8 (Step B), the title compound (2,3-bis(ethylsulfonyl)-5-phenyl-pyridine) was prepared by reaction of the 2,3-bis(ethylsulfanyl)-5-phenyl-pyridine (prepared as described previously) with m-CPBA in dichloromethane. LC-MS (Method B) RT 0.92 (340, MH+)

Using similar conditions described in Example P8 (Step B), the 5-(4-chlorophenyl)-2,3-bis(ethylsulfonyl)pyridine was prepared by reaction of the 5-(4-chlorophenyl)-2,3-bis(ethylsulfanyl)pyridine (prepared as described previously) with m-CPBA in dichloromethane. LC-MS (Method B) RT 0.99 (374, MH+)

Using similar conditions described in Example P8 (Step B), the 2,3-bis(ethylsulfonyl)-5-[3-(trifluoromethyl)phenyl]pyridine was prepared by reaction of the 2,3-bis(ethylsulfanyl)-5-[3-(trifluoromethyl)phenyl]pyridine (prepared as described previously) with m-CPBA in dichloromethane.

A solution of 3-chloro-6-(trifluoromethyl)pyridazine (4.5 g, 22 mmol, prepared as described in Tetrahedron, 65(21), 4212-4219, 2009), 1,1′-Ferrocenediyl-bis(diphenylphosphine) (0.74 g, 1.3 mmol), palladium(II)acetate (0.10 g, 0.44 mmol), N,N-diethylethanamine (2.7 g, 3.7 mL, 27 mmol), in ethanol (100 mL) was pressurised with CO (25 bar) in a hydrogenation vessel was pressurised with CO (25 bar) and stirred at 120° C. for 5 h. LCMS analysis showed reaction completion after this time. The reaction mixture was then cooled and filtered and the filtrate concentrated in vacuo. The crude product was purified by Comb flash chromatography with a column of 120 g and a gradient of cyclohexane+0-70% ethyl acetate, to give the title compound as a beige solid.

A (2,2,6,6-tetramethyl-1-piperidyl)lithium (TMPLi) solution (0.63 M in THF) was prepared by slow addition of nBuLi (2.17 ml, 5.00 mmol, 2.3 M in hexane) to a solution of (2,2,6,6-tetramethyl-1-piperidyl) in THF (5 ml) at −40° C. with stirring for 30 min at −40° C.

Lithium chloride solution (0.7 Min THF) was prepared by drying lithium chloride (1.2 g) in a flask with septum under vacuum at 140° C. for 5 h. After cooling, dry THF (40 ml) was added and stirring was continued until all salts were dissolved.

In a dry two necked flask (10 ml) under argon, Ethyl-6-(trifluoromethyl)pyridazine-3-carboxylate (0.150 g, 0.681 mmol) was dissolved in tetrahydrofurane (3 mL, 0.681 mmol). and treated with lithium chloride solution in THF (2 mL, 1.50 mmol, prepared as described above) and treated with zinc(II) chloride (1 mL, 0.749 mmol). The resulting mixture was cooled to −78° C. and then TMPLi (1.6 mL, 1.02 mmol, prepared as described above) was added drop wise (10 min) at −78° C. Reaction mixture was stirred 1 hour at −78° C. and then molecular iodine (0.173 g, 0.681 mmol) dissolved in 1 ml of THF was added drop wise and the resulting mixture stirred for a further 20 min at −78° C. LC-MS and GC-MS after this time showed only the desired product. The reaction mixture was allowed to warm to room temperature and quenched with saturated aqueous ammonium chloride, the organic phase washed successively with sodium thiosulfate and brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude was purified by Combi flash chromatography with a column of 12 g and a gradient cyclohexane+0-40% ethyl acetate, to give the title compound.

A solution of ethyl 4-iodo-6-(trifluoromethyl)pyridazine-3-carboxylate (0.3 g, 0.86695 mmol) in dichloromethane (4.5 mL) was cooled down at −78° C. and treated with Diisobutylaluminium hydride (DIBAL, 1.7339 mL, 1.7339 mmol) was added drop wise at −70° C. to −78° C. The reaction mixture was stirred 1 h at −78° C., and then allowed to warm to RT and stirred one night. The reaction mixture was then cooled to 0° C., and quenched carefully with saturated NH4Cl, and then the pH made acidic with 10% HCl. The mixture was extracted with EtOAc (3×), the combined organic layers washed with brine, dried over Na2SO4, filtrated and concentrated in vacuo. The crude product was purified by Combi flash chromatography with a column of 12 g and a gradient cyclohexane+0-60% ethyl acetate to give pure title product.

In a flask under argon, 4-Iodo-6-(trifluoromethyl)pyridazine-3-carbaldehyde (0.077 g, 0.25498 mmol) and (3-ethylsulfanyl-2-pyridyl)hydrazine (prepared in step D, 0.053 g, 0.28 mmol) were stirred in methanol (3.03 g, 3.83 mL, 94.3 mmol) for 48 h at room temperature. LCMS and TLC analysis showed consumption of the starting material to be complete. The reaction mixture was concentrated in vacuo and the crude product purified by Combi flash chromatography with a column of 12 g and a gradient cyclohexane+0-100% ethyl acetate. This gave a mixture of the title compound and 3-ethylsulfanyl-N—[(Z)-[4-iodo-6-(trifluoromethyl) pyridazin-3-yl]methyleneamino]pyridin-2-amine in a ratio of 1:1. This mixture was used in the next step without further purification.

In a microwave vial, the product obtained in step E was dissolved in DMF and the resulting mixture was stirred 10 min at 160° C. under microwave conditions. DMF was removed by evaporation at 65° C. in vacuo, and the residue was dissolved in t-butly methyl ether and water, the organic layer separated and then washed successively with sodium thiosulfate sat aqueous sol, water and brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by Combi flash chromatography with a column of 4 g with a gradient cyclohexane+0-50% ethyl acetate.

1-(3-ethylsulfanyl-2-pyridyl)-6-(trifluoromethyl)pyrazolo[4,3-c]pyridazine (15 mg, 0.046 mmol) was dissolved in dichloromethane (2 mL) and 3-chloroperbenzoic acid (21.7 mg, 0.097 mmol) was added slowly at 0° C. The resulting mixture was stirred 30 min at 0° C. and then over night at RT. After this time, a further 1 eq of m-CPBA was added and reaction mixture was stirred 30 min at RT, by which time LCMS showed reaction completion. The reaction mixture was quenched with 2 ml of NaOH 1 N and 2 ml of sodium thiosulfate sat aqueous sol. The mixture was stirred 10 min, and then the aqueous layer was extracted 3 times with 10 ml of dichloromethane. The combined organic layers were washed with 10 ml of NaOH 1 N, dried over Na2SO4, filtered and concentrated in vacuo to give the title compound as a yellow oil.

TABLE 4Examples of compounds of formula (Ia)(“Ph”represents the phenyl group):(Ia)Comp.No.R1R2R3XAP1CH2CH3CF3HSCH(1.005)P2CH2CH3CF3HSO2CH(1.006)P3CH2CH3CF3HSN(1.007)P4CH2CH3CF3HSO2N(1.008)P5CH2CH3BrHSNP6CH2CH3BrHSO2NP7CH2CH3CF3CF3SO2N(1.004)P8CH2CH3CF3BrSO2NP9CH2CH3CF3cyclopropylSO2NP10CH2CH3CF3PhSO2NP11CH2CH3CF34—ClPhSO2N(1.010)P12CH2CH3CF33—CF3PhSO2N

TABLE 5Examples of compounds of formula (Ia)(Ia)Comp.No.R1R2R3XAPP1CH2CH3CF3HSO2CH(2.006)

The activity of the compositions according to the invention can be broadened considerably, and adapted to prevailing circumstances, by adding other insecticidally, acaricidally and/or fungicidally active ingredients. The mixtures of the compounds of formula I with other insecticidally, acaricidally and/or fungicidally active ingredients may also have further surprising advantages which can also be described, in a wider sense, as synergistic activity. For example, better tolerance by plants, reduced phytotoxicity, insects can be controlled in their different development stages or better behaviour during their production, for example during grinding or mixing, during their storage or during their use. Suitable additions to active ingredients here are, for example, representatives of the following classes of active ingredients: organophosphorus compounds, nitrophenol derivatives, thioureas, juvenile hormones, formamidines, benzophenone derivatives, ureas, pyrrole derivatives, carbamates, pyrethroids, chlorinated hydrocarbons, acylureas, pyridylmethyleneamino derivatives, macrolides, neonicotinoids andBacillus thuringiensispreparations.

The following mixtures of the compounds of formula I with active ingredients are preferred (the abbreviation “TX” means “one compound selected from the group consisting of the compounds described in Tables 1 to 5 of the present invention”):

an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628)+TX,

a soil sterilant selected from the group of substances consisting of iodomethane (IUPAC name) (542) and methyl bromide (537)+TX,

a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] and nitrapyrin (580)+TX,

a virucide selected from the group of substances consisting of imanin (alternative name) [CCN] and ribavirin (alternative name) [CCN]+TX,

a wound protectant selected from the group of substances consisting of mercuric oxide (512)+TX, octhilinone (590) and thiophanate-methyl (802)+TX,

The references in brackets behind the active ingredients, e.g. [3878-19-1] refer to the Chemical Abstracts Registry number. The above described mixing partners are known. Where the active ingredients are included in “The Pesticide Manual” [The Pesticide Manual—A World Compendium; Thirteenth Edition; Editor: C. D. S. TomLin; The British Crop Protection Council], they are described therein under the entry number given in round brackets hereinabove for the particular compound; for example, the compound “abamectin” is described under entry number (1). Where “[CCN]” is added hereinabove to the particular compound, the compound in question is included in the “Compendium of Pesticide Common Names”, which is accessible on the internet [A. Wood;Compendium of Pesticide Common Names, Copyright 1995-2004]; for example, the compound “acetoprole” is described under the internet address http://www.alanwood.net/pesticides/acetoprole.html.

Most of the active ingredients described above are referred to hereinabove by a so-called “common name”, the relevant “ISO common name” or another “common name” being used in individual cases. If the designation is not a “common name”, the nature of the designation used instead is given in round brackets for the particular compound; in that case, the IUPAC name, the 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 Tables 1 to 5 with active ingredients described above comprises a compound selected from Tables 1 to 5 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 Tables 1 to 5 and one or more active ingredients as described above can be applied, for example, in a single “ready-mix” form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a “tank-mix”, and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days. The order of applying the compounds of formula I selected from Tables 1 to 5 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 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.

BIOLOGICAL EXAMPLES

Cotton leaf discs were placed on agar in 24-well microtiter plates and sprayed with aqueous test solutions prepared from 10′000 ppm DMSO stock solutions. After drying the leaf discs were infested with adult white flies. The samples were checked for mortality 6 days after incubation.

The following compounds resulted in at least 80% mortality at an application rate of 200 ppm: P1 and P2.

Maize sprouts, placed on an agar layer in 24-well microtiter plates were treated with aqueous test solutions prepared from 10′000 ppm DMSO stock solutions by spraying. After drying, the plates were infested with L2 larvae (6 to 10 per well). The samples were assessed for mortality 4 days after infestation.

The following compounds resulted in at least 80% mortality at an application rate of 200 ppm:

Soybean leaf 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 were infested with N-2 nymphs. The samples were assessed for growth inhibition in comparison to untreated samples 5 days after infestation.

The following compounds gave an effect of at least 80% in at least one of the two categories (mortality or growth inhibition) at an application rate of 200 ppm:

Sunflower leaf discs were placed on agar in a 24-well microtiter plate and sprayed with aqueous test solutions prepared from 10′000 ppm DMSO stock solutions. After drying, the leaf discs were infested with an aphid population of mixed ages. The samples were assessed for mortality 6 days after infestation.

The following compounds resulted in at least 80% mortality at an application rate of 200 ppm:

Roots of pea seedlings infested with an aphid population of mixed ages were placed directly in the aqueous test solutions prepared from 10′000 DMSO stock solutions. The samples were assessed for mortality 6 days after placing seedlings in test solutions.

The following compounds resulted in at least 80% mortality at a test rate of 24 ppm: P2 and P4.

Test compounds from 10′000 ppm DMSO stock solutions were applied by pipette into 24-well microtiter plates and mixed with sucrose solution. The plates were closed with a stretched Parafilm. A plastic stencil with 24 holes was placed onto the plate and infested pea seedlings were placed directly on the Parafilm. The infested plate was closed with a gel blotting paper and another plastic stencil and then turned upside down. The samples were assessed for mortality 5 days after infestation.

The following compounds resulted in at least 80% mortality at a test rate of 12 ppm: P1 and P3.

24-well microtiter plates with artificial diet were treated with aqueous test solutions prepared from 10′000 ppm DMSO stock solutions by pipetting. After drying, the plates were infested with L2 larvae (10 to 15 per well). The samples were assessed for mortality and growth inhibition in comparison to untreated samples 5 days after infestation.

The following compounds gave an effect of at least 80% in at least one of the two categories (mortality or growth inhibition) at an application rate of 200 ppm:

Cotton leaf discs were placed on agar in 24-well microtiter plates and sprayed with aqueous test solutions prepared from 10′000 ppm DMSO stock solutions. After drying the leaf discs were infested with five L1 larvae. The samples were assessed for mortality, anti-feedant effect, and growth inhibition in comparison to untreated samples 3 days after infestation. Control ofSpodoptera littoralisby a test sample is when at least one of mortality, anti-feedant effect, and growth inhibition is higher than the untreated sample.

The following compounds resulted in at least 80% control at an application rate of 200 ppm:

Test compounds were applied by pipette from 10′000 ppm DMSO stock solutions into 24-well plates and mixed with agar. Lettuce seeds were placed on the agar and the multi well plate was closed by another plate which contains also agar. After 7 days the roots have absorbed the compound and the lettuce has grown into the lid plate. The lettuce leafs were now cut off into the lid plate.Spodopteraeggs were pipetted through a plastic stencil on a humid gel blotting paper and the plate closed with it. The samples were assessed for mortality, anti-feedant effect and growth inhibition in comparison to untreated samples 6 days after infestation.

The following compounds gave an effect of at least 80% in at least one of the three categories (mortality, anti-feedancy, or growth inhibition) at a test rate of 12.5 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 compound resulted in at least 80% mortality at an application rate of 200 ppm: P1.

Sunflower leaf discs were placed on agar in 24-well microtiter plates and sprayed with aqueous test solutions prepared from 10′000 ppm DMSO stock solutions. After drying the leaf discs were infested with athripspopulation of mixed ages. The samples were assessed for mortality 6 days after infestation.

The following compound resulted in at least 80% mortality at an application rate of 200 ppm: P10.

10 to 15Aedeslarvae (L2) together with a nutrition mixture were placed in 96-well microtiter plates. Test compounds were pipetted into the wells. After an incubation period of 2 days insects were assessed for mortality and growth inhibition.

The following compounds gave an effect of at least 80% in at least one of the two categories (mortality or growth inhibition) at a test rate of 5 ppm: P1 and P7.