WO2002057263A1

WO2002057263A1 - 8-azabicyclo "3.2.1.! octanes as insecticides

Info

Publication number: WO2002057263A1
Application number: PCT/GB2002/000154
Authority: WO
Inventors: Roger Salmon
Original assignee: Syngenta Ltd
Current assignee: Syngenta Ltd
Priority date: 2001-01-17
Filing date: 2002-01-15
Publication date: 2002-07-25
Anticipated expiration: 2003-07-17

Abstract

A compound of formula (I): wherein A is-CH2-CH2-or-CH=CH-; R2 is hydrogen, CHO, COOC¿1?-C10 alkyl, optionally substituted C2-C10 alkyl, substituted methyl, optionally substituted C1-C10 alkoxy, optionally substituted C2-C10 alkenyloxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C2-C10 alkenyl, optionally substituted C3-C10 alkynyl or optionally substituted C3-C7 cycloakyl; and acid addition salts, quaternary ammonium salts, quaternary ammonium salts and N-oxides derived therefrom. The compounds are useful as insecticides.

Description

8-AZABICYCLO -3.2.1.!OCTANES AS INSECTICIDES

This invention relates to novel bicyclic amine compounds, to processes for preparing them, to insecticidal compositions comprising them and to methods of combating and controlling insect pests therewith.

In WO96/37494 there are disclosed various insecticidal compounds based upon bicyclic amines. The applicants have found a small group of compounds which have a particular substitution pattern and which are particularly active as insecticides.

Therefore there is provided a compound of general formula I:

wherein A is -CH₂-CH₂- or -CH=CH-;

R² is hydrogen, CHO, COO -Cio alkyl, optionally substituted C₂-C_ΪO alkyl, substituted methyl, optionally substituted -C-_.0 alkoxy, optionally substituted C₂-C-_.o alkenyloxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₂-Cι.o alkenyl, optionally substituted C3-C10 alkynyl or optionally substituted C₃.C cycloalkyl; and acid addition salts, quaternary ammonium salts and N-oxides derived therefrom.

When the alkyl, aryl, heteroaryl, alkenyl, alkynyl, alkoxy, alkenyloxy and cycloalkyl groups R carry a substituent, the substituents are one or more groups independently selected from halogen, cyano, hydroxy, nitro, haloalkyl, amino, acylamino, HO₂C, -β alkoxy (itself optionally substituted by

alkoxy), aryl(Cι_₄)alkoxy, -βalkylcarbonyl, Ci- ₆alkoxycarbonyl, Ci-6- kylaminocarbonyl, di(Ci-₆ alkyl)aminocarbonyl, phenyl, halophenyT, d-₆ alkylphenyl, Cι.₆alkoxycarbonyl-phenyl, -e alkoxyphenyl, heteroaryl, aryloxy, arylcarbonyloxy, heteroaryloxy, heterocyclyl, heterocyclyloxy, C₃- cycloalkyl, C₃.₇ cycloalkyloxy, C5-7 cycloalkenyl and phosphonato groups. When R² is substituted methyl the substituents are one or more groups independently selected from halogen, cyano, hydroxy, nitro, haloalkyl, amino, acylamino, HO₂C, Cj.₆ alkoxy (itself optionally substituted by Cι_₆ alkoxy), aiyl(Cj.-₄)arkoxy, d-βalkylcarbonyl, C_t-ealkoxycarbonyl, Q-eal-j-ylaminocarbonyl, di(C!-₆ alkyl)aminocarbonyl, phenyl, halophenyl, Ci-β alkylphenyl, Cι-₆arkoxycarbonyl- phenyl, Q-β alkoxyphenyl, heteroaryl, aryloxy, arylcarbonyloxy, heteroaryloxy, heteroeyclyl, heterocyclyloxy, C₃. cycloalkyl, C₃. cycloalkyloxy, C5.7 cycloalkenyl and phosphonato groups.

Where a group has more than one substituent the substituents may be the same or different.

The expression " alkyl" refers to fully saturated straight or branched hydrocarbon chains having from one to ten, preferably one to six carbon atoms. Examples include methyl, ethyl, nj-tropyl, iso-propyl, r^butyl, t^butyl and r hexyl. Expressions such as "alkoxy" and "haloalkyl" should be construed accordingly.

Alkenyl and alkynyl moieties can be in the form of straight or branched chains of 2 to 10 preferably 2 to 6 carbon atoms, and the alkenyl moieties, where appropriate, can be of either the (E)- or ©-configuration. Examples are vinyl, allyl and ethynyl and propargyl. Expressions such as "alkenyloxy" and "haloalkenyl" should be construed accordingly.

In the context of the present specification the terms "aryl" and "aromatic ring system" refer to ring systems which may be mono-, bi- or tricyclic. Examples of such rings include phenyl, naphthalenyl, anthracenyl or phenanthrenyl, preferably phenyl. In addition, the term "heteroaryl" refers to an aromatic ring system containing at least one heteroatom and consisting either of a single ring or of two or more fused rings. Preferably, single rings will contain up to three and bicyclic systems up to four heteroatoms which will preferably be chosen from nitrogen, oxygen and sulphur. Examples of such groups include furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl,

1,2,5-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, benzofuryl, benzisofuryl, benzothienyl, benzisothienyl, indolyl, isoindolyl, indazolyl, benzothiazolyl, benzisothiazolyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, benzotriazinyl, purinyl, pteridinyl and indolizinyl. Preferred examples of heteroaromatic radicals include pyridyl, pyrimidyl, triazinyl, thienyl, furyl, oxazolyl, isoxazolyl, and thiazolyl.

As used herein, the term "halogen" includes fluorine, chlorine, bromine and iodine. Haloalkyl groups are alkyl groups which are substituted with one or more of the same or different halogen atoms and are, for example, CF₃, CF₂C1, CH₂CF₃, CH₂CH₂CF₃, CH₂(CF₂)₂CH₃, CH₂CHF₂or CH₂CF₂CF₂CF₃.

The terms heterocycle and heterocyclyl refer to a non-aromatic ring containing up to 10 atoms including one or more (preferably one or two) heteroatoms selected from O, S and N. Examples of such rings include 1,3-dioxolane, tetrahydrofuran and morpholine. It is preferred that heterocyclyl is optionally substituted by -₆ alkyl.

Cycloalkyl includes cyclopropyl, cyclopentyl and cyclohexyl. A is preferably -CH₂-CH₂-.

Preferably R² is hydrogen, COO -Cio alkyl_. optionally substituted C₂-do alkyl, substituted methyl, optionally substituted C1-Q₀ alkoxy, optionally substituted C-₂- ₀ alkenyloxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₂-Cι₀ alkenyl, optionally substituted C₃-Cιo alkynyl or optionally substituted C₃. C₇ cycloalkyl; or

R is C1-₆ alkyl substituted by one or more substituents independently selected from halo, cyano, CONR⁴R⁵, CO₂R⁶, phenyl, halophenyl or pyridyl; C₂-₆ alkenyl; C₂,₆ haloalkenyl; C₂_6 alkynyl; C₂.₆ haloalkynyl; d-6 alkoxy; CHO; CO₂R⁷; phenyl (optionally substituted by halo or CO R⁸) or phosphonatomethyl where R⁴ and R⁵ are independently C₁.₆ alkyl or R⁴ and R⁵ together with the nitrogen atom to which they are attached form a 5 or 6 membered ring which optionally contains a further heteroatom selected from N, O or S and which is optionally substituted by one or more methyl groups; and R⁶, R⁷ and R⁸ are independently Cι_ 6 alkyl; or

R² is d-₆ alkyl substituted by one or more substituents independently selected from halo, cyano, CONR⁴R⁵, CO₂R⁶, phenyl, halophenyl or pyridyl; C₂-₆ alkenyl; C .₆ haloalkenyl; C₂_₆ alkynyl; C₂-₆ haloalkynyl; Cι-₆ alkoxy; CO₂R⁷; phenyl (optionally substituted by halo or CO₂R⁸) or phosphonatomethyl where R⁴ and R⁵ are independently Cι-₆ alkyl or R⁴ andR⁵ together with the nitrogen atom to which they are attached form a 5 or 6 membered ring which optionally contains a further heteroatom selected from N, O or S and which is optionally substituted by one or more methyl groups; and R⁶, R⁷ and R⁸ are independently d- ₆ alkyl; or

R² is C₂-₆ fluoroalkyl, c anoCι_₃ alkyl, CHR⁹CO₂R⁶, CHR¹⁰CONR⁴R⁵, pyridylmethyl, benzyl, halobenzyl, C₃_₅ alkenyl, C₃_s fluoroalkenyl, C₃-₅ alkynyl, CHO, CO₂R⁷, phenyl, fluorophenyl, methoxycarbonylphenyl or CH₂P(O)(OR^{1 J})(OR¹²) where R⁴, R⁵, R⁶ and R⁷ are as defined above, R⁹ and R¹⁰ are independently selected from H or C e alkyl and R¹¹ and R¹² are independently C-..₆ alkyl; or

R² is C₂-6 fluoroalkyl, cyanoC_w alkyl, CHR⁹CO₂R⁶, CHR^CONR^⁵, pyridylmethyl, benzyl, halobenzyl, C₃_5 alkenyl, C₃-₅ fluoroalkenyl, C₃_₅ alkynyl, CO₂R⁷, phenyl, fluorophenyl, methoxycarbonylphenyl or CH₂P(O)(OR¹ ^(OR¹²) where R⁴, R⁵, R⁶ and R⁷ are as defined above, R⁹ and R¹⁰ are independently selected from H or C₁_6 alkyl and R^π and R¹² are independently C_\_₆ alkyl; or

R² is C₂.6 fluoroalkyl, cyanoCι_₃ alkyl, CHR⁹CO₂R⁶, CHR¹⁰CONR⁴R⁵, pyridylmethyl, benzyl, halobenzyl, C₃_₅ alkenyl, C₃-₅ fluoroalkenyl, C₃.₅ alkynyl, CHO, CO₂R⁷, phenyl, fluorophenyl, methoxycarbonylphenyl or CH₂P(O)(ORⁿ)(OR¹²) where R⁴, R⁵, R⁶ and R⁷ are as defined above, R⁹ and R¹⁰ are independently selected from H or C-_..₆ alkyl and R¹¹ and R¹² are independently Q.₆ alkyl; or

R² is C₂.6 fluoroalkyl, cyanoCι_₃ alkyl, CHR⁹CO₂R⁶, CHR¹⁰CONR⁴R⁵, pyridylmethyl, benzyl, halobenzyl, C₃-₅ alkenyl, C₃_₅ fluoroalkenyl, C₃_s alkynyl, CO₂R⁷, phenyl, fluorophenyl, methoxycarbonylphenyl or CH₂P(O)(OR¹ *)(OR¹²) where R⁴, R⁵, R⁶ and R⁷ are as defined above, R⁹ and R¹⁰ are independently selected from H or C-.-₆ alkyl and R¹¹ and R¹² are independently Q-β alkyl; or

R² is C₂-₆ fluoroalkyl, cyanoCι.₃ alkyl, CHO or CO₂R⁷ where R⁷ is as defined above; or

R² is C₂-6 fluoroalkyl, cyanoCι.₃ alkyl or CO₂R⁷ where R⁷ is as defined above; or R² represents C₂_s alkyl substituted by 2 to 9 fluorine atoms, especially C₂.₃ alkyl substituted by 2 to 5 fluorine atoms.

The formula I given above is intended to include tautomeric forms of the structure drawn, as well as physically distinguishable modifications of the compounds which may arise, for example, from different ways in which the molecules are arranged in a crystal lattice, or from the inability of parts of the molecule to rotate freely in relation to other parts, known as "rotameric forms" or "rotamers", or from geometrical isomerism, or from intra-molecular or inter-molecular hydrogen bonding, or otherwise. The compounds of the invention can exist in enantiomeric forms and some can also exist in both enantiomeric and diastereoisomeric forms. The invention includes all individual forms and mixtures thereof in all proportions.

It will be appreciated that the bicyclic amine compounds of formula I are capable of existing in more than one isomeric form since the groups R² and the substituted pyridine ring may be positioned in either an exo or endo relationship, and the present invention embraces within its scope both exo and endo forms and mixtures thereof and also any further isomeric variants arising from cis and trans substitution patterns or chiral centres present in R¹ or R². Suitable acid addition salts include those with an inorganic acid such as hydrochloric, hydrobromic, sulfuric, nitric and phosphoric acids, or an organic carboxylic acid such as oxalic, tartaric, lactic, butyric, toluic, hexanoic and phthalic acids, or sulphonic acids such as methane, benzene and toluene sulphonic acids.

Specific compounds of formula I according to the invention include those set out in Table I below.

TABLE I

The preparation of the compounds of formula (I) may be accomplished by use of one or more of the synthetic techniques described in WO96/37494 and further illustrated in the Examples.

In a further aspect the invention provides a method of combating insect and like pests at a locus by applying to the locus or the pests an insecticidally-effective amount of an insecticidal composition comprising the compounds of Formula I or an acid addition salt thereof.

The compounds of formula (I) can be used to combat and control infestations of insect pests such as Lepidoptera, Diptera, Hemiptera, Thysanoptera, Orthoptera, Dictyoptera, Coleoptera, Siphonaptera, Hymenoptera and Isoptera and also other invertebrate pests, for example, acarine, nematode and mollusc pests. Insects, acarines, nematodes and molluscs are hereinafter collectively referred to as pests. The pests which may be combated and controlled by the use of the invention compounds include those pests associated with agriculture (which term includes the growing of crops for food and fibre products), horticulture and animal husbandry, companion animals, forestry and the storage of products of vegetable origin (such as fruit, grain and timber); those pests associated with the damage of man-made structures and the transmission of diseases of man and animals; and also nuisance pests (such as flies).

Examples of pest species which may be controlled by the compounds of formula (I) include: Myzus persicae (aphid), Aphis gossypii (aphid), Aphis fabae (aphid), Lygus spp.

(capsids), Dysdercus spp. (capsids), Nilaparvata lugens (planthopper), Nephotettixc incticeps (leafhopper), Nezara spp. (stinkbugs), Euschistus spp. (stinkbugs), Leptocorisa spp. (stinkbugs), Frankliniella occidentalis (thrip), Thrips spp. (thrips), Leptinotarsa decemlineata (Colorado potato beetle), Anthonomus grandis (boll weevil), Aonidiella spp. (scale insects), Trialeurodes spp. (white flies), Bemisia tabaci (white fly), Ostrinia nubilalis (European corn borer), Spodoptera littoralis (cotton leafworm), Heliothis virescens (tobacco budworm), Helicoverpa armigera (cotton bollworm), Helicoverpa zea (cotton bollworm), Sylepta derogata (cotton leaf roller), Pieris brassicae (white butterfly), Plutella xylostella (diamond back moth), Agrotis spp. (cutworms), Chilo suppressalis (rice stem borer), Locusta. migratoria (locust), Chortiocetes terminifera (locust), Diabrotica spp. (rootworms), Panonychus ulmi (European red mite), Panonychus citri (citrus red mite), Tetranychus urticae (two-spotted spider mite), Tetranychus cinnabarinus (carmine spider mite), Phyllocoptruta oleivora (citrus rust mite), Polyphagotarsonemus latus (broad mite), Brevipalpus spp. (flat mites), Boophilus microplus (cattle tick), Dermacentor variabilis (American dog tick), Ctenocephalides felis (cat flea), Liriomyza spp. (leafminer), Musca domestica (housefly), Aedes aegypti (mosquito), Anopheles spp. (mosquitoes), Culex spp. (mosquitoes), Lucillia spp. (blowflies), Blattella germanica (cockroach), Periplaneta americana (cockroach), Blatta orientάlis (cockroach), termites of the Mastotermitidae (for example Mastotermes spp.), the Kalotermitidae (for example Neotermes spp.), the Rhinotermitidae (for example Coptotermes formosanus, Reticulitermes flavipes, R. speratu, R. virginicus, R. hesperus, and R. santonensis) and the Termitidae (for example Globitermes sulphureus), Solenopsis geminata (fire ant), Monomorium pharaonis (pharaoh's ant),

Damalinia spp. and Linognathus spp. (biting and sucking lice), Meloidogyne spp. (root knot nematodes), Globodera spp. and Heterodera spp. (cyst nematodes), Pratylenchus spp. (lesion nematodes), Rhodopholus spp. (banana burrowing nematodes), Tylenchulus spp.(citrus nematodes), Haemonchus contortus (barber pole worm), Caenorhabditis elegans_(vinegax eelworm), Trichostrongylus spp. (gastro intestinal nematodes) and Deroceras reticulatum (slug).

The invention therefore provides a method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I), or a composition containing a compound of formula (I), to a pest, a locus of pest, or to a plant susceptible to attack by a pest. The compounds of formula (I) are preferably used against insects, acarines or nematodes.

In order to apply a compound of formula (I) to a pest, a locus of pest, or to a plant susceptible to attack by a pest, a compound of formula (I) is usually formulated into a composition which includes, in addition to the compound of formula (I), a suitable inert diluent or carrier and, optionally, a surface active agent (SFA). SFAs are chemicals which are able to modify the properties of an interface (for example, liquid/solid, liquid/air or liquid/liquid interfaces) by lowering the interfacial tension and thereby leading to changes in other properties (for example dispersion, emulsification and wetting). It is preferred that all compositions (both solid and liquid formulations) comprise, by weight, 0.0001 to 95%, more preferably 1 to 85%, for example 5 to 60%, of a compound of formula (I). The composition is generally used for the control of pests such that a compound of formula (I) is applied at a rate of from O.lg tolOkg per hectare, preferably from lg to 6kg per hectare, more preferably from lg to 1kg per hectare.

When used in a seed dressing, a compound of formula (0 is used at a rate of 0.000 lg to lOg (for example O.OOlg or 0.05g), preferably 0.005g to lOg, more preferably 0.005g to 4g, per kilogram of seed.

In another aspect the present invention provides an insecticidal, acaricidal, nematicidal or molluscicidal composition comprising an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I) and a suitable carrier or diluent therefor. The composition is preferably an insecticidal, acaricidal or nematicidal composition.

In a still further aspect the invention provides a method of combating and controlling pests at a locus which comprises treating the pests or the locus of the pests with an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a composition comprising a compound of formula (I). The compounds of formula (I) are preferably used against insects, acarines or nematodes.

The compositions can be chosen from a number of formulation types, including dustable powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL), emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (both oil in water (EW) and water in oil (EO)), micro-emulsions (ME), suspension concentrates (SC), aerosols, fogging/smoke formulations, capsule suspensions (CS) and seed treatment formulations. The formulation type chosen in any instance will depend upon the particular purpose envisaged and the physical, chemical and biological properties of the compound of formula (I). Dustable powders (DP) may be prepared by mixing a compound of formula (I) with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other organic and inorganic solid carriers) and mechanically grinding the mixture to a fine powder. Soluble powders (SP) may be prepared by mixing a compound of formula (I) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulphate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water dispersibility/solubility. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water soluble granules (SG). Wettable powders (WP) may be prepared by mixing a compound of formula (I) with one or more solid diluents or carriers, one or more wetting agents and, preferably, one or more dispersing agents and, optionally, one or more suspending agents to facilitate the dispersion in liquids. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water dispersible granules (WG).

Granules (GR) may be formed either by granulating a mixture of a compound of formula (I) and one or more powdered solid diluents or carriers, or from pre-formed blank granules by absorbing a compound of formula (I) (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a compound of formula (I) (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates, mineral carbonates, sulphates or phosphates) and drying if necessary. Agents which are commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils). One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).

Dispersible Concentrates (DC) may be prepared by dissolving a compound of formula (I) in water or an organic solvent, such as a ketone, alcohol or glycol ether. These solutions may contain a surface active agent (for example to improve water dilution or prevent crystallisation in a spray tank). Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may be prepared by dissolving a compound of formula (I) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents). Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLNESSO 150 and SOLNESSO 200; SOLNESSO is a Registered Trade Mark), ketones (such as cyclohexanone or methylcyclohexanone) and alcohols (such as benzyl alcohol, furfuryl alcohol or butanol), N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethyl amides of fatty acids (such as C₈-Ci;o fatty acid dimethylamide) and chlorinated hydrocarbons. An EC product may spontaneously emulsify on addition to water, to produce an emulsion with sufficient stability to allow spray application through appropriate equipment. Preparation of an EW involves obtaining a compound of formula (I) either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70°C) or in solution (by dissolving it in an appropriate solvent) and then emulsifiying the resultant liquid or solution into water containing one or more SFAs, under high shear, to produce an emulsion. Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents which have a low solubility in water.

Microemulsions (ME) may be prepared by mixing water with a blend of one or more solvents with one or more SFAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation. A compound of formula (I) is present initially in either the water or the solvent/SFA blend. Suitable solvents for use in MEs include those hereinbefore described for use in in ECs or in EWs. An ME may be either an oil-in-water or a water-in-oil system (which system is present may be determined by conductivity measurements) and may be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation. An ME is suitable for dilution into water, either remaining as a microemulsion or forming a conventional oil-in-water emulsion.

Suspension concentrates (SC) may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of formula (I). SCs may be prepared by ball or bead milling the solid compound of formula (I) in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle. Alternatively, a compound of formula (I) may be dry milled and added to water, containing agents hereinbefore described, to produce the desired end product.

Aerosol formulations comprise a compound of formula (I) and a suitable propellant (for example n-butane). A compound of formula (I) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as n-propanol) to provide compositions for use in non-pressurised, hand-actuated spray pumps. A compound of formula (I) may be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating, in an enclosed space, a smoke containing the compound.

Capsule suspensions (CS) may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerisation stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of formula (I) and, optionally, a carrier or diluent therefor. The polymeric shell may be produced by either an interfacial polycondensation reaction or by a coacervation procedure. The compositions may provide for controlled release of the compound of formula (I) and they may be used for seed treatment. A compound of formula (I) may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.

A composition may include one or more additives to improve the biological performance of the composition (for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of formula (I)). Such additives include surface active agents, spray additives based on oils, for example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), and blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of formula (I)). A compound of formula (I) may also be formulated for use as a seed treatment, for example as a powder composition, including a powder for dry seed treatment (DS), a water soluble powder (SS) or a water dispersible powder for slurry treatment (WS), or as a liquid composition, including a flowable concentrate (FS), a solution (LS) or a capsule suspension (CS). The preparations of DS, SS, WS, FS and LS compositions are very similar to those of, respectively, DP, SP, WP, SC and DC compositions described above. Compositions for treating seed may include an agent for assisting the adhesion of the composition to the seed (for example a mineral oil or a film-forming barrier).

Wetting agents, dispersing agents and emulsifying agents may be surface SFAs of the cationic, anionic, amphoteric or non-ionic type. Suitable SFAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and arnine salts. Suitable anionic SFAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, calcium dodecylbenzenesulphonate, butylnaphthalene sulphonate and mixtures of sodium di- z-røpropyl- and tri-z^'sopropyl-naphthalene sulphonates), ether sulphates, alcohol ether sulphates (for example sodium laureth-3-sulphate), ether carboxylates (for example sodium laureth-3-carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately mono-esters) or phosphorus pentoxide (predominately di-esters), for example the reaction between lauryl alcohol and tetraphosphoric acid; additionally these products may be ethoxylated), sulphosuccinamates, paraffin or olefine sulphonates, taurates and lignosulphonates.

Suitable SFAs of the amphoteric type include betaines, propionates and glycinates. Suitable SFAs of the non-ionic type include condensation products of alkylene oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; simple esters (for example fatty acid polyethylene glycol esters); amine oxides (for example lauryl dimethyl amine oxide); and lecithins.

Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).

A compound of formula (I) may be applied by any of the known means of applying pesticidal compounds. For example, it may be applied, formulated or unformulated, to the pests or to a locus of the pests (such as a habitat of the pests, or a growing plant liable to infestation by the pests) or to any part of the plant, including the foliage, stems, branches or roots, to the seed before it is planted or to other media in which plants are growing or are to be planted (such as soil surrounding the roots, the soil generally, paddy water or hydroponic culture systems), directly or it may be sprayed on, dusted on, applied by dipping, applied as a cream or paste formulation, applied as a vapour or applied through distribution or incorporation of a composition (such as a granular composition or a composition packed in a water-soluble bag) in soil or an aqueous environment.

A compound of formula (I) may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods, or applied by land or aerial irrigation systems.

Compositions for use as aqueous preparations (aqueous solutions or dispersions) are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being added to water before use. These concentrates, which may include DCs, SCs, ECs, EWs, MEs SGs, SPs, WPs, WGs and CSs, are often required to withstand storage for prolonged periods and, after such storage, to be capable of addition to water to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. Such aqueous preparations may contain varying amounts of a compound of formula (I) (for example 0.0001 to 10%, by weight) depending upon the purpose for which they are to be used. A compound of formula (I) may be used in mixtures with fertilisers (for example nitrogen-, potassium- or phosphorus-containing fertilisers). Suitable formulation types include granules of fertiliser. The mixtures suitably contain up to 25% by weight of the compound of formula (I).

The invention therefore also provides a fertiliser composition comprising a fertiliser and a compound of formula (I).

The compound of formula (I) may be the sole active ingredient of the composition or it may be admixed with one or more additional active ingredients such as a pesticide, fungicide such as azoxystrobin, synergist, herbicide or plant growth regulator where appropriate. An additional active ingredient may: provide a composition having a broader spectrum of activity or increased persistence at a locus; synergise the activity or complement the activity (for example by increasing the speed of effect or overcoming repellency) of the compound of formula (I); or help to overcome or prevent the development of resistance to individual components. The particular additional active ingredient will depend upon the intended utility of the composition. Examples of suitable pesticides include the following: a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate, esfenvalerate, deltamethrin, cyhalothrin (in particular lambda-cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids (for example ethofenprox), natural pyrethrin, tetramethrin, s-bioallethrin, fenfluthrin, prallethrin or 5-benzyl-3-furylmethyl-(E)-(lR,3S)-2,2-dimethyl- 3-(2-oxothiolan-3-ylidenemethyl)cyclopropane carboxylate; b) Organophosphates, such as, profenofos, sulprofos, acephate, methyl parathion, azinphos-methyl, demeton-s-methyl, heptenophos, thiometon, fenamiphos, monocrotophos, profenofos, triazophos, methamidophos, dimethoate, phosphamidon, malathion, chlorpyrifos, phosalone, terbufos, fensulfothion, fonofos, phorate, phoxim, pirimiphos-methyl, pirimiphos-ethyl, fenitrothion, fosthiazate or diazinon; c) Carbamates (including aryl carbamates), such as pirimicarb, triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencarb, aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur, methomyl or oxamyl; d) Benzoyl ureas, such as diflubenzuron, triflumuron, hexaflumuron, flufenoxuron or chlorfluazuron; e) Organic tin compounds, such as cyhexatin, fenbutatin oxide or azocyclotin; f) Pyrazoles, such as tebufenpyrad and fenpyroximate; g) Macrolides, such as avermectins or milbemycins, for example abamectin, emamectin benzoate, ivermectin, milbemycin, spinosad or azadirachtin; h) Hormones or pheromones; i) Organochlorine compounds such as endosulfan, benzene hexachloride, DDT, chlordane or dieldrin; j) Amidines, such as chlordimeform or amitraz; k) Fumigant agents, such as chloropicrin, dichloropropane, methyl bromide or metam;

1) Chloronicotinyl compounds such as imidacloprid, thiacloprid, acetamiprid, nitenpyram or thiamethoxam; m) Diacylhydrazines, such as tebufenozide, chromafenozide or methoxyfenozide; n) Diphenyl ethers, such as diofenolan or pyriproxifen; o) Indoxacarb; p) Chlorfenapyr; or q) Pymetrozine. In addition to the major chemical classes of pesticide listed above, other pesticides having particular targets may be employed in the composition, if appropriate for the intended utility of the composition. For instance, selective insecticides for particular crops, for example stemborer specific insecticides (such as cartap) or hopper specific insecticides (such as buprofezin) for use in rice may be employed. Alternatively insecticides or acaricides specific for particular insect species/stages may also be included in the compositions (for example acaricidal ovo-larvicides, such as clofentezine, flubenzimine, hexythiazox or tetradifon; acaricidal motilicides, such as dicofol or propargite; acaricides, such as bromopropylate or chlorobenzilate; or growth regulators, such as hydramethylnon, cyromazine, methoprene, chlorfluazuron or diflubenzuron).

Examples of suitable synergists for use in the compositions include piperonyl butoxide, sesamex, safroxan and dodecyl imidazole. Suitable herbicides and plant-growth regulators for inclusion in the compositions will depend upon the intended target and the effect required.

An example of a rice selective herbicide which may be included is propanil. An

/ example of a plant growth regulator for use in cotton is PIX™.

Some mixtures may comprise active ingredients which have significantly different physical, chemical or biological properties such that they do not easily lend themselves to the same conventional formulation type. In these circumstances other formulation types may be prepared. For example, where one active ingredient is a water insoluble solid and the other a water insoluble liquid, it may nevertheless be possible to disperse each active ingredient in the same continuous aqueous phase by dispersing the solid active ingredient as a suspension (using a preparation analogous to that of an SC) but dispersing the liquid active ingredient as an emulsion (using a preparation analogous to that of an EW). The resultant composition is a suspoemulsion (SE) formulation.

The invention is illustrated by the following examples.

EXAMPLE 1

This Example illustrates the preparation of compound 1 of Table 1: 8-benzyl-endo-3-cyano- exo-3-(5-ethoxypyrid-3-yl)-8-azabicyclo[3.2.1]octane.

8-Benzyl-exo-3-(5-chloropyrid-3-yl)-endo-3-cvano-8-azabicyclor3.2.11octane (10g) was dissolved in anhydrous N,N-dimethylformamide (lOOmL) and treated with sodium ethoxide (16g) with stirring under an atmosphere of nitrogen. The mixture was heated to 75 °C for llh, cooled to ambient temperature then water (1L) was added. The mixture was taken to pH 8 with concentrated hydrochloric acid then extracted with a mixture of diethyl ether and n- hexane(l:l by volume; 2x500mL). The extracts were combined, washed with water (3x300mL), dried (magnesium sulfate) then evaporated under reduced pressure to give a yellow oil. The oil was triturated with ethyl acetate and the solid obtained was washed with hexane to give the required product as a pale yellow solid, 5.3g. 1H NMR (CDCl₃)δ: 1.48(3H, t); 2.16-2.44(8H, m); 3.36-3.40(2H, m); 3.58(2H, s); 4.14(2H, q); 7.20-7.40(6H, m);,8.25(lH, m); 8.42(1H, d).

EXAMPLE 2 This Example illustrates the preparation of compound 2 of Table 1: endo-3-cyano-exo-3-(5- ethoxypyrid-3-yl)-8-azabicyclo[3.2. l]octane.

8-Benzyl-endo-3-cyano-exo-3-(5-ethoxypyrid-3-yl)-8-azabicyclor3.2.1 Joctane (0.64g) was dissolved in methanol (lOmL) and ammonium formate ( 1.60g) added followed by 5% palladium on charcoal (0.075g, catalyst). The mixture was stirred at 50°C for 2.5h, cooled to ambient temperature then filtered to remove the catalyst. The filtrate was evaporated under reduced pressure and the residue treated with aqueous sodium carbonate. The mixture was extracted with dichloromethane (twice), the extracts were combined then dried (magnesium sulfate). The solvent was evaporated under reduced pressure to give the required product as a colourless solid, 0.46g, m.p. 72-74°C. 1H NMR (CDCl₃)δ: 1.44(3H, t); 1.72(1H, broad signal); 1.90-2.00(2H, m); 2.18-2.37(4H, m); 2.44-2.53(2H, q); 3.70-3.80(2H, m); 4.12(2H, q); 7.32-7.35(lH, dd); 8.24(1H, d); 8.39(1H, d).

EXAMPLE 3 This Example illustrates the preparation of compound 3 of Table 1: endo-3-cyano-exo-3-(5- ethoxypyrid-3-yl)-8-formyl-8-azabicyclo[3.2.1]octane. endo-3-Cyano-exo-3-(5-ethoxypyrid-3-yl)-8-azabicyclo[3.2.1]octane ( 0.50g) in dry dichloromethane (30mL) containing diisopropylethylamine (0.42mL) was stirred at ambient temperature and acetyl formate (0.19g, prepared from acetyl chloride and sodium formate) was added. The mixture was stirred for 0.5h, evaporated under reduced pressure and the residue fractionated by chromatography (silica; acetonitrile) to give the required product as a colourless solid, 0.41g, m.p. 125-127°C. 1H NMR (CDCl₃)δ: 1.45(3H, t); 2.10-2.60(8H, m); 4.12(2H, q); 4.28-4.36(lH, m); 4.82- 4.88(1H, m); 7.26(1H, dd); 8.20(1H, s); 8.28(1H, d); 8.34(1H, d).

EXAMPLE 4 This Example illustrates the preparation of compound 4 of Table 1: endo-3-cyano-8- ethoxycarbonyl-exo-3-(5-ethoxypyrid-3-yl)-8-azabicyclo[3.2.1]octane. endo-3-Cyano-exo-3-(5-ethoxypyrid-3-yl)-8-azabicycloF3.2.Hoctane ( 0.46g) in dry dichloromethane (20mL) containing diisopropylethylamine (0.37mL) were stirred at 0°C and ethyl chloroformate (0.18g) was added dropwise. On complete addition the mixture was stirred for 2h at ambient temperature then evaporated under reduced pressure, the residue was fractionated by chromatography (silica; diethyl ether) to give the required product as a colourless gum, 0.49g.

1H NMR (CDCl₃)δ: 1.30(3H, t); 1.48(3H, t); 2.14-2.22(2H, m); 2.28-2.40(4H, broad signal);

2.40-2.52(2H, m); 4.08-4.26(4H, m); 4.50(2H, broad signal); 7.28(1H, dd); 8.26(1H, d); 8.32(1H, d).

EXAMPLE 5

This Example illustrates the preparation of compound 5 of Table 1: endo-3-cyano-8-(2- cyanoethyl)-exo-3-(5-ethoxypyrid-3-yl)-8-azabicyclo[3.2.1]octane. endo-3-Cyano-exo-3-(5-ethoxypyrid-3-yl)-8-azabicyclo[3.2.1]octane ( 0.50g) in ethanol (25mL) containing diisopropylethylamine (0.37mL) were treated with sodium iodide

(O.OlOg) and 3-bromopropionitrile (0.18mL) with stirring. The mixture was heated to reflux for 18h then cooled to ambient temperature. The solvent was evaporated under reduced pressure and the residue was fractionated by chromatography (silica; ethyl acetate) to give the required product as a yellow gum, 0.36g. 1H NMR (CDCl₃)δ: 1.46(3H, t); 2.05-2.15(2H, m); 2.26-2.48(6H, m); 2.52(2H, t); 2.68(2H, t); 3.40-3.48(2H, m); 4.13(2H, q); 7.30(1H, m); 8.25(1H, d); 8.38(1H, d).

EXAMPLE 6 This Example illustrates the preparation of compound 6 of Table 1: endo-3-cyano-exo-3-(5- ethoxypyrid-3-yl)-8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2. l]octane.

To a stirred solution of trifluoromethane sulfonic anhydride (5.6g) in dry 1,2-dichloroethane (mL) at -30°C was added dropwise a mixture of 2,2,2-trifluoroethanol (2.2g) and cuisopropylethylamine (2.9g) under an atmosphere of nitrogen maintaining the reaction mixture between -(20-30)°C during the addition. On complete addition, the mixture was stirred for a further 2h at -30°C then allowed to warm to ambient temperature to produce a solution of 2,2,2-trifluoroethyl trifluoromethane sulfonate. To this solution was added endo- 3-cyano- °--3-(5-ethoxypyrid-3-yl)-8-azabicyclo[3.2.1]octane (5.1 g) followed by dry dichloroethane (15mL) containing diisopropylethylamine (3.5g). The mixture was heated to reflux with stirring for 3h then stored at ambient temperature for 18h. The solution was diluted with dichloromethane (150mL), washed with water (2xl00mL) then dried (magnesium sulfate). The solvent was evaporated under reduced pressure and the residual oil fractionated by chromatography (silica; hexane to hexane/ethyl acetate, 4: 1 by volume) to give the required product as a colourless solid, 3.6g, mp 60-61 °C. 1H NMR (CDCl₃)δ: 1.46(3H, t); 2.04-2.14(2H, m); 2.26-2.50(6H, m); 2.90(2H, q); 3.40- 3.50(2H, m); 4.14(2H, q); 7.30 (1H, dd); 8.26(1H, d); 8.39(1H, d).

EXAMPLE 7

This Example illustrates the insecticidal properties of the compounds of Formula I. The activity of the the compounds of Formula I was determined using a variety of pests. The pests were treated with a liquid composition containing 500 parts per million (ppm) by weight of the compound unless otherwise stated. The compositions were made by dissolving the compound in acetone and ethanol (50:50) mixture and diluting the solutions with water containing 0.05% by weight of a wetting agent sold under the trade name "SYNPERONIC" NP8 until the liquid composition contained the required concentration of the compound. "SYNPERONIC" is a Registered Trade Mark.

The test procedure adopted with regard to each pest was basically the same and comprised supporting a number of the pests on a medium which was usually a substrate, a host plant or a foodstuff on which the pests feed, and treating either or both the medium and the pests with the compositions. The mortality of the pests was then assessed at periods usually varying from two to five days after the treatment.

The results of the tests against peach aphid (Myzus persicae) are presented in Table II. The results indicate a grading of mortality (score) designated as A, B or C wherein C indicates less than 40% mortality, B indicates 40-79% mortality and A indicates 80-100% mortality; "-" indicates that either the compound was not tested or no meaningful result was obtained. In this test Chinese cabbage leaves were infested with aphids, the infested leaves were sprayed with the test composition, and the mortality assessed after 3 days.

TABLE π

Claims

A compound of formula (I):

wherein A is -CH₂-CH₂- or -CH=CH-;

R² is hydrogen, CHO, COOCi-Cio alkyl, optionally substituted C₂-C₁₀ alkyl, substituted methyl, optionally substituted Q-do alkoxy, optionally substituted C₂-C₁₀ alkenyloxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₂-C₁o alkenyl, optionally substituted C₃-do alkynyl or optionally substituted C₃.C cycloalkyl; and acid addition salts, quaternary ammonium salts and N-oxides derived therefrom.

A compound according to claim 1 wherein A is -CH₂-CH₂-.

A compound according to claim 1 or claim 2 wherein R² is hydrogen, COOQ-Cio alkyl, optionally substituted C₂-Cιo alkyl, substituted methyl, optionally substituted Cι- Qo alkoxy, optionally substituted C₂-C1₀ alkenyloxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted C₂-C₁o alkenyl, optionally substituted C₃-do alkynyl or optionally substituted C₃-C7 cycloalkyl.

4. A compound according to any preceding claim wherein R is Cι.₆ alkyl substituted by one or more substituents independently selected from halo, cyano, CONR⁴R⁵, CO₂R⁶, phenyl, halophenyl or pyridyl; C₂-6 alkenyl; C₂.₆ haloalkenyl; C₂.₆ alkynyl; C₂.₆ haloalkynyl; d_₆ alkoxy; CHO; CO₂R⁷; phenyl (optionally substituted by halo or CO₂R⁸) or phosphonatomethyl where R⁴ and R⁵ are independently d-e alkyl or R⁴ and R⁵ together with the nitrogen atom to which they are attached form a 5 or 6 membered ring which optionally contains a further heteroatom selected from N, O or S and which is optionally substituted by one or more methyl groups; and R⁶, R⁷ and R⁸ are independently Cι-₆ alkyl.

5. A compound according to any preceding claim wherein R² is C₂-₆ fluoroalkyl, cyanoCi- ₃ alkyl, CHR⁹CO₂R⁶, CHR¹⁰CONR⁴R⁵, pyridylmethyl, benzyl, halobenzyl, C₃-₅ alkenyl, C₃-5 fluoroalkenyl, C₃,5 alkynyl, CHO, CO₂R⁷, phenyl, fluorophenyl, methoxycarbonylphenyl or CH₂P(O)(OR^π)(OR¹²) where R⁴, R⁵, R⁶ and R⁷ are as defined in claim 4, R⁹ and R¹⁰ are independently selected from H or d.₆ alkyl and R^{1 !} and R¹² are independently d.₆ alkyl.

6. A compound according to any preceding claim wherein R² is C₂.g fluoroalkyl, cyanoCi- ₃ alkyl, CHO or CO₂R⁷ where R⁷ is d-₆ alkyl.

7. A compound according to any preceding claim wherein R is C₂-₅ alkyl substituted by 2 to 9 fluorine atoms, especially C .₃ alkyl substituted by 2 to 5 fluorine atoms.

8. An insecticidal acaricidal and nematicidal composition comprising an insecticidally, acaricidally or nematicidally effective amount of a compound of formula I according to claim 1.

9. A method of combating and controlling acarine or nematode pests at a locus which comprises treating the pests or the locus of the pests with an effective amount of a compound of formula I according to claim 1.