WO2003053905A1 - A process for the production of 1r pyrethroid esters - Google Patents

Abstract

A process for the production of 1R pyrethroid esters of formula (IIIA) or (IIIB), wherein A and B are independently chlorine or bromine or one of A or B is chlorine and the other is trifluoromethyl and R is a pyrethroid alcohol fragment, which process comprises a) resolving pyrethroid acids of formula (IV) where A and B are as defined for compounds of formula (IIIA) and (IIIB) to give a substantially pur 1R cis enantiomer, b) recovering the 1S cis enantiomer, c) optionally converting the 1S cis enantiomer acid to a 1S cis enantiomer anhydride, acid chloride or pyrethroid ester containing the group R where R is a pyrethroid alcohol fragment; d) converting the 1S cis enantiomer from step b) or step c) to the 1R trans isomer; e) optionally purifying the 1R trans isomer from step d) and recycle of the unconverted 1S cis isomer back to step c) or d), f) converting the 1R cis isomer of the acid from step a) into corresponding 1R cis isomers of the pyrethroid esters alone, or together with the product of step d) or e) where the product of step d) or e) is not already a pyrethroid ester containing the group R.

Description

A PROCESS FOR THE PRODUCTION OF IR PYRETHROID ESTERS

The present invention relates to a process for making cyclopropanecarboxylic acid esters and to their use as insecticides. Cyclopropanecarboxylic acid esters are a sub-group of the class of compounds known as pyrethroids, well known in the art as insecticides. Commercially sold compounds include lambda-cyhalothrin, tefluthrin, cypermethrin, permethrin, bifenthrin and deltamethrin.

It is also well known that the insecticidal activity of pyrethroids is greatly affected by their stereochemistry. Pyrethroids are often sold as mixtures of stereoisomers and it is desirable to enhance the proportion of the active isomer over the inactive isomer(s) in these mixtures. Stereoisomerism usually exists at more than one chiral centre in pyrethroids. For pyrethroids that are cyclopropanecarboxylic acid esters, it is most common that the acid portion of the molecule contains two chiral centres with one or more in the alcohol portion. This leads to the existence of cis and trans isomers of the cyclopropanecarboxylic acid portion, each of which can exist in two enantiomeric forms. For example, a number of important pyrethroid insecticides such as lambda-cyhalothrin, alphacypermethrin and bifenthrin are based on cis acids of formula

(I)

where A and B are independently chlorine or bromine or one of A or B is chlorine and the other is trifluoromethyl, but are sold as racemates, by which is meant an equimolar mixture of two enantiomers.

In relation to these stereoisomeric mixtures, it is well known that it is the IR enantiomer that has the greatest insecticidal activity for crop protection applications. For example, in the case of the commercial insecticide cyhalothrin (H),

(ll) it is known from the work of Bentley et al, described in Pesticide Science, 1980, 11, 156, that there is no significant insecticidal activity towards Musca domestica in any of the isomers derived from the IS enantiomer of the cyclopropane carboxylic acid.

It is therefore desirable to be able to make IR pyrethroids selectively. Whilst IR cis esters of the formula (IDA),

(IIIA) where A and B are as defined in relation to formula I and R is a pyrethroid alcohol fragment such as that derived from 4-methyltetrafluorobenzyl alcohol, 3-phenoxybenzyl alcohol, -cyano-3-phenoxybenzyl alcohol, oc-cyano-3-phenoxy-4-fluorobenzyl alcohol and 2-methyl- 3-phenylbenzyl alcohol, are generally the most active insecticide isomers, IR trans esters of formula (IHB)

(IIIB) where A, B and R are as defined in relation to formula IHA are also insecticidally active and have interesting properties e.g. are known, in general, to have lower mammalian toxicity. For these reasons it is desirable to have available processes to make products which contain the IR cis and IR trans isomers of formula (IDA) and (KB) but are substantially free of IS isomers.

Although pyrethroids have been manufactured for over 20 years there is no known process for the commercial synthesis of a mixture containing IR cis and IR trans isomers of formula (IDA) and (IHB) substantially free of IS isomers. In US4780252 a process is disclosed for the resolution of acid of formula (I), where A=C1 and B=CF3, in which the maximum yield of the desired IR enantiomer is 64% of the theoretical amount. Thus 36% of the desired IR enantiomer is lost and there is still present an unwanted byproduct (100% of the undesired IS enantiomer).

In US 5840958, a process is disclosed for the conversion of certain IS cis or trans pyrethroid acids, or their derivatives, into the corresponding IR cis or trans isomers. However, the conversion process reaches an equilibrium and typically the conversion stops when the cis, trans ratio is 20:80. The efficiency of the process for recovery of the desired IR enantiomer therefore cannot exceed 80%. Furthermore, any pyrethroid esters made from 'equilibrium' mixtures will themselves be mixtures of active and inactive isomers.

The applicants have devised a practical process for preparing pyrethroids which contain the IR cis and IR trans isomers of formula (IDA) and (DIB) but are substantially free of IS isomers.

There is therefore provided a process for the production of IR pyrethroid esters of formula mA or mB,

(IIIA) (IIIB) wherein A and B are independently chlorine or bromine or one of A or B is chlorine and the other is trifluoromethyl and R is a pyrethroid alcohol fragment, which process comprises a) resolving pyrethroid acids of formula (IV)

(IV) where A and B are as defined for compounds of formula HIA and TUB to give a substantially pure IR cis enantiomer, b) recovering the IS cis enantiomer c) optionally converting the IS cis enantiomer acid to a IS cis enantiomer anhydride, acid chloride or pyrethroid ester containing the group R where R is a pyrethroid alcohol fragment; d) converting the IS cis enantiomer from step b) or step c) to the IR trans isomer; e) optionally purifying the IR trans isomer from step d) and recycle of the unconverted IS cis isomer back to step c) or d) f) converting the IR cis isomer of the acid from step a) into corresponding IR cis isomers of the pyrethroid esters alone, or together with the product of step d) or e) where the product of step d) or e) is not already a pyrethroid ester containing the group R. It will be appreciated that the flexibility of the above scheme allows a final lR-rich pyrethroid ester product containing both IR cis and IR trans isomers to be produced directly at step f). The ratio of the two enantiomers in mixtures will be related to the efficiency of each of the processing steps. Typical ratios that can be achieved are 50-70% of the pyrethroid derived from the IR enantiomer from step a) and 30-50% of the IR enantiomer, from step f). Alternatively the ester from the product of step f) can be a single isomer of value in its own right. This ester can be blended with an ester produced at step d) or e) so that a composition with any desired ratio of IR cis and IR trans isomers can be produced. It is preferred that in step a) the starting materials are racemic mixtures of cis pyrethroid acids of the formula (I). The products of the process are of IR cis and IR trans isomers of formulas (THA) and (TUB), where A and B are as the preceding descriptions and R is OH or a pyrethroid alcohol fragment such as that derived from 4-methyltetrafluorobenzyl alcohol, 3-phenoxybenzyl alcohol, α-cyano-3-phenoxybenzyl alcohol and 2-methyl-3-phenylbenzyl alcohol.

In one embodiment of step a) the resolving agent is recovered in a form suitable for direct recycle within step a).

A preferred process for step a) is to react the compound of formula (IV) with a substantially optically pure chiral amine, optionally in the presence of a second non-chiral base, in a solvent at between 20-100°C, preferably at 30-70°C to form a diastereoisomeric salt, separating the diastereomeric salt of the desired enantiomer; and converting the salts of each enantiomer separately to the R and S enantiomers by acid or base hydrolysis. Suitable optically active amines for use in the process are the enantiomers of alpha methyl benzylamine or 1- amino-2-indanol and the preferred amine is alpha methyl benzylamine. The preferred molar ratio of amine to acid is 0.4-1.0, most preferably 0.5-0.55. Suitable non-chiral bases are alkali metal hydroxides, carbonates or tertiary amines and the preferred mol ratio is 0.4-0.6, most preferably 0.45-0.55. Suitable solvents are mixtures of water-soluble organic solvents with water, aprotic solvents such as toluene and esters such as ethyl acetate or isopropyl acetate. Preferred solvents are aprotic solvents, and in particular esters such as isopropyl acetate. The separation process may be achieved by any conventional means, for example fractional crystallisation or chromatography. In a preferred process, separation of the desired diastereomeric salt from the undesired salt is achieved by selecting chiral amines that give a diastereomeric salt of the desired enantiomer with different solubility characteristics to the salt of the undesired enantiomer. As a result, the diastereomeric salt of the desired enantiomer can be forced into separate solvent systems, and the salt of the other enantiomer is left in the mother liquors of the reaction mass while the other is removed. The hydrolysis may be carried out using acid or base to dissociate the diastereoisomeric salts, but is preferably carried out with acid using mineral acid such as hydrochloric acid or sulphuric acid. The salt can be dissociated in an aqueous environment and the precipitated acid isolated by conventional means. The dissociation of the salt with acid may be carried out in the presence of the same water-soluble organic solvents with water that are used in the formation of the salt from the chiral amine. The proportion of water-soluble solvent in the solvent-water mixture can be such that the acid formed is substantially insoluble but the liberated amine salt is fully soluble. Alternatively, the salt can be dissociated in the presence of an organic solvent which is capable of dissolving the released acid, and most preferably a solvent that is suitable for use as a reaction medium in step f). Suitable solvents are aromatic hydrocarbons, such as toluene or benzotrifluoride, or aliphatic hydrocarbons such as hexane, heptane or octane. Suitable temperatures are 20-100°C, preferably 40-80°C. The amount of acid used in the hydrolysis should be sufficient to liberate the free acid of formula IDA from the salt and produce an aqueous phase with a pH of <7. In a further aspect of this invention, the aqueous phase produced from dissociation of the salt by any of the stated means is recycled to the start of step a) and in so doing allows recycle of >70% of the amine directly within the process. In step b), the IS enantiomer salt may be recovered by evaporation of the mother liquors and hydrolysis with aqueous acid as in step a) and recovery of the product by filtration or extraction into a solvent. Suitable solvents may also serve as purification solvents for the IS product, and or as the reaction medium for step c). Preferable solvents are aromatic hydrocarbons, such as toluene or benzotrifluoride, or aliphatic hydrocarbons such as hexane, cyclohexane, heptane or octane. Alternatively, in those cases where a water immiscible solvent is used in step a), the salt may be hydrolysed whilst still in solution by addition of aqueous acid. This also serves to recover any resolving agent present as salts in the organic phase and the IS acid is recovered by evaporation of the solvent. The IS enantiomer can be purified by recrystallisation from solvents as indicated above, or by melt crystallisation procedures. It is preferred in step b) to separate any IR isomer and recycle it to step a) as an approximately racemic mixture The reactions of steps c) and f) can be performed under conditions well known in the art. For example acid chlorides may be formed by standard techniques as in 'March 4^th Edition - p437-38' and these acid chlorides may be reacted with an appropriate alcohol using the procedures described in EP-A-31199. The preferred processes for step d) involves heating the product from step c), optionally in the presence of a catalyst, and a free-radical scavenger, so as to achieve the equilibrium mixture of cis and trans isomers. A temperature of 20-200°C, preferably 140-160°C is used and suitable catalysts are tertiary amines, such as triethylamine, or their hydrogen halide salts, tertiary phosphines or quaternary ammonium or phosphonium salts, or Lewis acids such as iron, zinc or titanium chlorides or bromides. The catalyst usage is 0.01 to 10mol%, preferably 0.1-5% most preferably 0.5-1.5%

The procedure of step e) is conveniently carried out by first converting any derivative from step d) to the carboxylic acid, for example by hydrolysis, and then crystallisation of the resultant acid from a solvent. Suitable solvents are hydrocarbons, such as hexane, cyclohexane, octane or aromatic hydrocarbon, such as toluene, benzotrifluoride or mixtures of a C₁-C alcohol and water. The co-product from the purification, a mixture of IS and IR enantiomers can be recycled back to Step c).

In the context of the specification a substantially pure enantiomer means a mixture of enantiomers that contains greater than about 90% of the desired enantiomer. It will be appreciated that there are a number of means for maximising the recovery of the desired enantiomer in a classical resolution of pyrethroid acids, for example by carrying out a very efficient diastereomeric salt separation.

In a further aspect of this invention, Steps a) and b) above may be carried sequentially in the same solvent solution by using the opposite enantiomers of a chiral amine. Thus a solution of the racemic acid is treated with 0.4-0.6 equivalents, preferably 0.45-0.55 equivalents of one enantiomer of a chiral amine so as to precipitate mainly the diastereoisomeric salt of one enantiomer of the acid. After recovery of the diastereoisomeric salt formed as above, the solution is then treated with the opposite enantiomer of the same chiral amine in the same proportions leading to precipitation of the diastereoisomeric salt of the opposite enantiomer of the pyrethroid acid. In this manner it is possible to leave behind in the solvent a substantially racemic mixture of starting acid, which is then suitable for direct recycle. This process avoids the need for secondary treatment of the IS enantiomer to remove the IR for recycle. In a further aspect of this invention, the enantiomer of the acid recovered in step b) can be treated so as to substantially remove the IR enantiomer as substantially racemic material. This allows recovery of the IS enantiomer and the racemic acid is suitable for recycle into step a). In this manner it is possible to make the resolution step substantially quantitative for preparation of both the IR and IS enantiomers. Suitable methods of separating the racemate and the IS or IR enantiomers are, for example, treatment of the product from step b) with a solvent so as to dissolve the substantially pure single enantiomer and leave the racemate as a solid; melt crystallisation in which the racemate crystallises from the mixture leaving the substantially the single enantiomer in the melt. If further purification of any of the resolved acids is required this may be done by standard methods such as recrystallisation. Suitable solvents include aliphatics such as hexane, isohexane or petroleum ethers or aromatic solvents such as toluene. Most preferably the solvent is hexane or isohexane. The purification is performed at 0-100°C, depending upon the solvent of choice. Certain compounds of formula (DD3) are novel and as such form a further aspect of the invention. IR trans isomers arising from step f), when racemic mixtures of cis pyrethroid acids of the formula (IN) are used in step a), have unexpected and useful properties.

In a further aspect of the invention there is therefore provided a process for preparation of IR trans compounds of the formula (DTB)

<^II1B> in which A, B and R have the meanings given previously which process comprises a) resolving pyrethroid acids of formula (I) b) recovering the IS cis enantiomer c) optionally converting the IS cis enantiomer acid to a IS cis enantiomer anhydride, acid chloride or pyrethroid ester containing the group R where R is a pyrethroid alcohol fragment; d) converting the IS cis enantiomer from step b) or step c) to the IR trans isomer; e) optionally purifying the IR trans isomer from step d) and recycle of the unconverted IS cis isomer back to step c) or d) f) if the IR trans isomer from step d) or step e) is an acid, acid chloride or anhydride, converting it to a pyrethroid ester of formula DIB.

Furthermore certain intermediate compounds used in the process are also novel and as such form a further part of the invention. Particular novel compounds include IS cis compounds of the formula (VA) and 7R trans compounds of the formula (VB), where A and B are as defined above

(VA) (VB) and the compounds IR trans-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2- dimethylcyclopropanecarboxylic acid, IR trans-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2- dimethylcyclopropanecarboxylic acid chloride and IS cis-Z 3-(2-chloro-3,3,3-trifluoro-l- propenyl)-2,2-dimethylcyclopropanecarboxylic acid chloride.

By the use of these procedures it is possible to substantially increase the amount of derived insecticidal activity from racemic starting material

Compounds of formula (DIB), either alone or as a mixture with its IR cis isomer of formula (IDA) are hereafter referred to as compounds of formula (DIA/B). The mixtures may be in any ratio provided that the amount of a compound of formula (DD3) is greater than zero. It is preferred that the ratio of DD3:DIA is from 1:99 to 99:1, more preferably from 20:80 to 80:20. The compounds of formula (DIA/B) 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 (DIA B) 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 leaf worm), 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), Locustajnigratoria (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 lotus (broad mite), Brevipalpus spp. (flat mites), Boophϊlus 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 orientalis (cockroach), termites of the Mastotermitidae (for example Mastotermes spp.), the Kalotermitidae (for example Neotermes spp.), the Rhinoter itidae (for example Coptotermes formosanus, Reticulitermesβavipes, 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 vinegar eel worm), 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 novel compound of formula (DIA/B), or a composition containing a novel compound of formula (DIA/B), to a pest, a locus of pest, or to a plant susceptible to attack by a pest. The compounds of formula (DIA/B) are preferably used against insects, acarines or nematodes. In order to apply a compound of formula (DIA/B) to a pest, a locus of pest, or to a plant susceptible to attack by a pest, a compound of formula (DIA/B) is usually formulated into a composition which includes, in addition to the compound of formula (DIA/B), 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 (DIA/B). The composition is generally used for the control of pests such that a compound of formula (DIA/B) 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 (DIA/B) is used at a rate of O.OOOlg 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 novel compound of formula (DIA B) and a suitable carrier or diluent therefore. 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 novel compound of formula (DIA/B). The compounds of formula (DIA/B) 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 (DIA B).

Dustable powders (DP) may be prepared by mixing a compound of formula (DIA B) 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 (DIA/B) 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 (DIA/B) 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 (DIA/B) and one or more powdered solid diluents or carriers, or from pre-formed blank granules by absorbing a compound of formula (DIA/B) (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 (IDA/B) (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 (DIA/B) 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 (DIA B) 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, SOLVESSO 150 and SOLVESSO 200; SOLVESSO 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-Cιo 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 (DIA/B) 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 (DIA/B) 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 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 (DIA/B). SCs may be prepared by ball or bead milling the solid compound of formula (DIA/B) 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 (DTA/B) 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 (DIA/B) and a suitable propellant (for example rc-butane). A compound of formula (DIA/B) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as rc-propanol) to provide compositions for use in non-pressurised, hand-actuated spray pumps.

A compound of formula (DIA/B) 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 (DIA/B) and, optionally, a carrier or diluent therefore. 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 (DIA/B) and they may be used for seed treatment. A compound of formula (DIA B) 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 (DIA/B)). 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 (DIA/B)). A compound of formula (DIA/B) 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 amine 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'søpropyl- and tri- søpropyl-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 olefin 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 (DIA/B) 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 (DIA/B) 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 (DIA/B) (for example 0.0001 to 10%, by weight) depending upon the purpose for which they are to be used.

A compound of formula (DIA/B) 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 (DIA/B). The invention therefore also provides a fertiliser composition comprising a fertiliser and a novel compound of formula (DIA B). The compound of formula (DIA/B) 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, 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 (DIA/B); 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 gamma-cyhalothrin and 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 PBC™.

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 following Examples illustrate the invention. The following GLC method was used to analyse the compounds of the invention:

Column Chiraldex CB 25m, 0.25mm, 25 micron

Carrier gas helium 80°C start temp, for 5 minutes, 2°C/min ramp rate to 120°C, 10°C/min ramp rate to

160°C, final time 2 minutes, total time 31 mins

Injector temp 250°C

Detector temp 250°C Example 1

Preparation of IR cis-Z 3-(2-chIoro-3,3,3-trifluoro-l-propenyl)-2,2-dimethyl cyclopropanecarboxylic acid

A 1L split neck reactor was equipped with a turbine agitator, thermometer, reflux condenser, N₂ . blanket and syringe pump. To the reactor was charged racemic cis-Z 3-(2-chloro-3,3,3-trifluoro- l-propenyl)-2,2-dimethylcyclopropanecarboxylic acid (194.2 g), methanol (800 ml), water (364ml) and 47% sodium hydroxide solution (41 ml). The mixture was heated to 65°C. A mixture of S(-) α-methylbenzylamine (49.5g), water (400 ml) and 37% hydrochloric acid (34 ml) was prepared and charged to the syringe pump. The amine solution was added to the reactor over 4 hr maintaining at 65°C, ~2/3rds in the first hour and the other third over 3 firs. Precipitation occurred ~ ³Λ of the way through the addition. Once all the amine had been added, the reaction was held at 65°C for 30 min, before cooling to 25°C, holding for 30 minutes at 25°C and then filtering off the amine salt (via a no.3 glass sinter). The filter cake was pulled dry and washed with two 160 ml lots of 50% aqueous methanol then with 160 ml water. The solid amine salt was added to water (250 ml) and 37% hydrochloric acid (37 ml) and dichloromethane (200 ml) were added. The mixture was agitated to thoroughly mix then separated. The organic phase was separated, washed and dried over magnesium sulphate. The dried organic layer was then evaporated to give the product 75.1 g, which is 77% of the theoretical yield. The product was found to have a 1R:1S ratio of 99:1. Example 2 Preparation of IS cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2- dimethylcyclopropanecarboxylic acid

A 1L split neck reactor was equipped with a turbine agitator, thermometer, reflux condenser, N₂ blanket and syringe pump. To the reactor was charged racemic cis-Z 3-(2-chloro-3,3,3-trifluoro- l-propenyl)-2,2-dimethylcyclopropanecarboxylic acid (97.1 g), methanol (400 ml), water (182ml) and 47% sodium hydroxide solution (20.5 ml). The mixture was heated to 65°C and the pH was found to be 7.1. A mixture of R(+) α-methylbenzylamine (24.75g), water (200 ml) and 37% hydrochloric acid (17.4 ml) was prepared (pH 7.2 at 25°C) and charged to the syringe pump. The amine solution was added to the reactor over 3 hr maintaining at 65°C. Precipitation occurred ~ % through the addition. Once all the amine had been added, the reaction was held at 65°C for 30 min, before cooling to 25°C and filtering off the amine salt (via a no.3 glass sinter). The filter cake was pulled dry and washed with two 80ml lots of 50% aqueous methanol then with 80ml water. The solid amine salt was added to water (130 ml) and 37% hydrochloric acid (15 ml) and toluene (100 ml) were added. The mixture was heated to 60°C and separated. The > organic phase was washed twice with aqueous hydrochloric acid (15 ml at 37% in 70 ml H₂0). The aqueous phase was extracted with toluene (30 ml). The organic layers were combined and washed (20 ml H₂0), then evaporated in vacuo to give the product 36.4 g, which is 75% of the theoretical yield. The product was found to have a 1S:1R ratio of 99.6:0.4. Example 3

Sequential preparation of IR cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2- dimethylcyclopropanecarboxylic acid and IS cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-

2,2-dimethylcyclopropanecarboxylic acid

Racemic cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethyl-cyclopropanecarboxylic acid (97.7g) was charged to a 2-litre reaction flask fitted with a twin bladed, pitched agitator, thermometer, condenser and syringe pump feed. Isopropyl acetate (600ml) was charged and the reaction mass agitated whilst applying external heating to raise the temperature to 65°C. S-(-) α- methylbenzylamine (25.5g) was dissolved in isopropyl acetate (220ml), in a 500ml reactor, and mixed thoroughly. The solution was used to fill a 50ml syringe pump and then fed into the cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarboxylic acid solution at such a rate that all of the amine solution was charged over 4 hours. Precipitation of the amine salt occurred after ~ 75% of the amine charge had been made. When all of the amine had been charged, a thick slurry was obtained. The mixture was stirred vigorously for 30 minutes before cooling the 20°C (over ~ 40 minutes). The reaction mass was the stirred for a further 30 minutes before filtering on a No 3 sintered glass funnel. The product was pulled down to 'dry land' before three 50ml isopropyl acetate displacement washes were applied. The paste was then air dried, to remove residual solvent to give 59.9g dry solid. The amine salt paste was discharged from the filter into a 1-litre reactor fitted with turbine agitator. Dichloromethane (100ml) was charged to the reactor followed by water (100ml). The mixture was then agitated and hydrochloric acid (250ml 2 molar) was added then stirred for 15 minutes, allowed to separate and the bottom organic layer run off. The aqueous layer was then given two further washes with dichloromethane (2 x 50ml). The organic layers were then combined and washed with water

(100ml), then brine (100ml) and dried with magnesium sulphate. The dichloromethane was then removed by distillation to provide a white solid. The solid (32.8g, 67% of theory yield) was dried under vacuum and analysed and found to have a 1R:1S ratio of 98.7:1.3. The isopropyl acetate mother liquors and washes from the first step were then washed with dilute hydrochloric acid (50ml 2M and 100ml water), water (100ml) and brine (100ml). The isopropyl acetate was then distilled to produce an orange oil, which solidified on cooling. The oil was re- dissolved in fresh isopropyl acetate (600ml) and then treated with the R-(+) α- methylbenzylamine in isopropyl acetate (220ml) in exactly the same way as with the S-(-) amine above. The amine salt paste (64.9gm), was converted to the free acid as above to give the IS cis Z acid (39.2g, 80.0% of theory). The product was found to have a IS: IR ratio of > 99: 1.

The aqueous phases from the first resolution were combined and made alkaline with sodium hydroxide (pH > 10) and extracted with dichloromethane (3 x 50ml washes). The resultant organic layer was washed with water (50ml) and brine (50ml) before topping to produce a clear colourless oil of recovered S-(-) α-methylbenzylamine. The R-(+) α-methylbenzylamine was recovered in the same manner from the second resolution.

The weight of recovered S-(-) α-methylbenzylamine from the first resolution was 25.3gm (-99% recovery). The weight of recovered R-(+) α-methylbenzylamine from the second resolution was 24.0gm (-94% recovery).

Example 4 Sequential preparation of IS cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2- dimethylcyclopropanecarboxylic acid and IR cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)- 2,2-dimethylcyclopropanecarboxylic acid Following the procedure given Example 3 but reversing the order of addition of the chiral amines. Therefore the R-(+) α-methylbenzylamine was used to make the corresponding amine salt of IS cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarboxylic acid first followed by the S-(-)-α methylbenzylamine to make the corresponding IR amine salt second. During the addition of the R-(+)-α methylbenzylamine in the first resolution, the amine salt did not precipitate when all of the amine had been charged. The salt actually precipitated during the cooling process and at ~40°C giving a very thick reaction mass. The IS enantiomer was obtained by slurrying the amine salt paste with water (100ml) and concentrated hydrochloric acid (50ml) together with hexane (100ml) at 60°C until all the solid had dissolved, then the mixture was stirred a further 15 minutes before separating. The aqueous phase was washed with further hexane (2 x 50ml) and the organic phases combined. The hexane solution was then washed with water (100ml) and brine (100ml) before topping to give a white solid. Weight of the isolated free IS enantiomer 34g, comprising >99% of the IS enantiomer equivalent to 70% of theory yield. During the addition of the S-(-) α-methylbenzylamine in the second resolution, the chiral amine salt precipitated earlier, after about 40% of the amine had been charged. The IR enantiomer was isolated in the same way as the IS enantiomer acid using hexane. Weight of the isolated IR enantiomer acid 44g with a IS to IR ratio of -94:6, equivalent to at least 85% theory yield.

Example 5 Sequential preparation of IR cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2- dimethylcyclopropanecarboxylic acid, IS cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2- dimethylcyclopropanecarboxylic acid and racemic cis-Z 3-(2-chloro-3,3,3-trifluoro-l- propenyl)-2,2-dimethylcyclopropanecarboxylic acid for recycle. Racemic cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarboxylic acid (91. lg) was charged to a 2-litre reaction flask fitted with a twin bladed, pitched agitator, thermometer, condenser and syringe pump feed. Isopropyl acetate (600ml) was charged and the reaction mass agitated whilst applying external heating to raise the temperature to 65°C. The S-(-) α-methylbenzylamine (25.5g) was dissolved in isopropyl acetate (220ml), in a 500ml reactor, and mixed thoroughly. The solution was used to fill a 50ml syringe pump and then fed into the cis-Z 3-(2-chloro-3 ,3 ,3-trifluoro- 1 -propenyl)-2,2-dimethylcyclopropanecarboxylic acid solution at such a rate that all of the amine solution was charged over 4 hours. The mixture was stirred vigorously for 30 minutes before cooling the 20°C (over - 40 minutes). The reaction mass was the stirred for a further 30 minutes before filtering on a No 3 sintered glass funnel. The product was pulled down to 'dry land' before three 50ml isopropyl acetate displacement washes were applied. The paste was then air dried, to remove residual solvent, and the mother liquor and washes were combined. IR cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2- dimethylcyclopropanecarboxylic acid was recovered from the amine salt as described in Example 1 to give 33.7g product with a IR to IS ratio of 98:2, equivalent to a yield of 68.0%. The isopropyl acetate mother liquors and washes were washed with dilute hydrochloric acid (50ml 2M HC1 and 100ml water), water (100ml) and brine (100ml). The isopropyl acetate was then distilled to produce an orange oil, which solidified on cooling (63.4gm, with a IR to IS ratio of 20:80). This was slurried with dichloromethane (100ml) for 30 minutes to allow the larger granular crystals to break down. The slurry was filtered on a sintered nutche and pulled down to 'dry land' . The resultant white crystalline solid was washed with 2 x 50ml of cold dichloromethane and pulled dry. The solid product was analysed and found to be close to a racemic mixture (IR cis: IS cis ratio of 49:51). Material retained in the dichloromethane solvent was recovered by distillation to yield a solid (41.1gm) and after analysis found to have a IS to IR ratio of 91 :9, equivalent to a yield of 76%. When account is taken of the racemic acid available for recycle, the yields of IR and IS enantiomers are 85% and 97% respectively.

The isopropyl acetate mother liquors from another similar resolution were evaporated to give 65gm of recovered acid, with a IS to IR ratio of 80:20, which was slurried with cyclohexane (100ml) at room temperature. The resultant crystalline solid obtained (38.6gm) was analysed and found to have a IS to IR ratio of 63:37. Material recovered from the cyclohexane filtrates (19.4gm) was found to have a IS to IR ratio of 94:6 equivalent to a IS yield of 37%.

In a similar manner (62.2gm) of recovered acid (IR: IS ratio of 21 :78) was slurried with isopropyl acetate (100ml) at room temperature. The resultant crystalline solid obtained (8.1gm) was analysed and found to have a 1R:1S ratio of 49:51. Material retained in the isopropyl acetate solvent was analysed and found to have a ratio of IR to IS of 19:81. The solvent solution was allowed to stand for 16 hours and further crystallisation had occurred. The mother liquor was then cooled to 4°C for 6 hours and re-filtered to give a white crystalline solid (10.2g, IR to IS ratio of 48:52) the mother liquor was evaporated to yield a pale yellow solid (49.4g) with a IR to IS ratio of 11:89 equivalent to a yield of 90%.

In a similar manner to the previous example recovered acid (71.2gm) (IR to IS ratio of 18:83) was heated to 95 °C producing a crystalline solid with an orange supernatant oil. After 30 minutes on temperature, the oil was decanted from the crystals and allowed to solidify. The residual crystals (21.8g) after decantation of the oil were analysed and found to have a IR to IS ratio of 36:64. The solidified melt (48.8g) was found to have a IR to IS ratio of 17:83.

Example 6 Preparation of IR cis-Z (+) 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethyl- cyclopropane carboxylic acid chloride

A 1 litre dry/clean jacketed split reaction vessel equipped with agitator, thermometer, condenser, nitrogen blanket and vent to a scrubber system was charged with toluene (450ml) and agitated whilst IR cis-Z (+) 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethyl-cyclopropane carboxylic acid (89.4gm = 0.369mol) was added followed by triethylamine (0.21gm = 2.1mmol). The reaction mixture was then heated to 45°C, using oil circulation on the jacket, and thionyl chloride : (62.0gm = 0.52mol) was then charged over 105 minutes maintaining on temperature. The reaction mass was then agitated for 5 hours at 45°C then tested by GLC for completion of ■ reaction showing 2% residual acid. A further addition of thionyl chloride (4.4gm = 37mmol) was then made and the reaction mass allowed to cool with stirring overnight. The following day, residual thionyl chloride, dissolved sulphur dioxide and hydrogen chloride gases were removed by distillation of about 320ml toluene under vacuum. GC, GCMS and NMR analysis of the product were consistent with the structure of the acid chloride (DIA), A=C1, B=CF3, R=C1. Yield, 175gm of a 54% solution of the acid chloride in toluene, - 97% theory. B.Pt of product = 62.5°C at 8.5mbar 1H NMR (CDC1₃):

6.6(d.d, 1H, vinyl),2.6(m, 1H, cyclopropane), 2.4(d.t, 1H, cyclopropane), 1.4(s, 3H, methyl),

1.3(s, 3H, methyl)

GCMS:

39, 69, 91, 113, 127, 141, 161, 183, 197(100%), 225 [°C]_D ²° = +46 (~ 1 % in dichloromethane) Example 7 Preparation of IS cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2- dimethylcyclopropanecarboxylic acid chloride

A 250ml 3 necked reaction flask was equipped with an overhead stirrer (paddle), thermometer, reflux condenser, nitrogen blanket and pressure equalisation dropping funnel. To the reactor was charged the IS cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarboxylic acid (17.0gm) and hexane (100ml). Triethylamine (0.071g) was then added and the reaction mass was heated to 50°C with agitation. Thionyl chloride (10.8g) was added drop wise over ca. 15 minutes and the reaction monitored for completion by GLC (CPSil 5CB - 50°C (2 mins) the 20°C/min to 250°C and held for 10 minutes). After 2 hrs the reaction had gone to completion and was concentrated by removal of hexane on a rotary evaporator. The resultant product (18.0g) was a nearly colourless oil containing a trace of solid.

Example 8 Telescoped preparation of IS cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethyI cyclopropane carbonyl chloride and thermal isomerisation to prepare IR trans-Z 3-(2- chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarboxylic acid A 500ml 3-necked round bottom flask was equipped with an overhead stirrer, reflux condenser, thermometer, nitrogen blanket and dropping funnel. To the reactor was charged IS cis-Z 3-(2- chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarboxylic acid (33g), hexane (180ml) and triethylamine (60mg), then the mixture was heated with agitation to 50-55°C.

Thionyl chloride (21.3g, 0.160mol) was added drop wise to the reactor over 30 minutes, then the reaction was agitated for a further 2 hours at 50°C. Hexane and excess thionyl chloride were removed by atmospheric distillation, then the reaction was agitated for 2hr at 130°C, 16hr at 140°C, and 16hr at 160°C before allowing to cool to room temperature. The resultant acid chloride was added, with agitation, to a mixture of THF (50ml) and water (150ml) over 20 minutes (exotherm to 35°C). The mixture was agitated for a further hour, and then the pH was adjusted to pH 8 using sodium carbonate (8g) and finally to pH 10 with sodium hydroxide. Carbon dioxide was bubbled through the solution for lOhr and the pH fell to pH 8. The solution was washed with DCM (3 x 100ml), and then stirred with activated carbon (lg) before filtering through celite (washing filter cake with water (2 x 25ml)). The pH was adjusted to pH 2 using cone. Hydrochloric acid (17g) and the solution was extracted with hexane (2 x 100ml) and the organics were washed with water (100ml) and brine (100ml). The hexane solution was concentrated under reduced pressure to remove 150 ml of the hexane then the solution was allowed to cool to room temperature before holding at 4°C for 1 hour. The resultant needle-like crystals were filtered off using a no. 3 sinter and washed with a minimal amount of hexane before pulling dry to give 9.5 g of white solid (97% by GC area% as trans component). Mpt 90°C.

1H NMR (CDC1₃):

6.15(d.d, 1H, vinyl), 2.45(m, 1H, cyclopropane), 1.79(d, 1H, cyclopropane), 1.38(s, 3H, methyl),

1.3(s, 3H, methyl)

GCMS: 36, 51, 59, 69, 77, 91, 101, 115, 127, 141, 149, 161, 169, 177, 186, 197, 207(100%), 216, 227, 242(MI). [oc]_D ²⁰ = +7.69 (0.0104 gm in 10ml of dichloromethane)

Example 9 Thermal isomerisation of IS cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethyl cyclopropane carbonyl chloride

IS cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarbonyl chloride (267.4 gm) was stirred and heated under nitrogen to 140-145°C and maintained at this temperature for 10 hours to complete the isomerisation. The mixture was then cooled to 20-25°C and added dropwise to methanol (240gm) over 1 hour maintaining the temperature at 20°C with external cooling. Sodium hydroxide liquor (180 gm at 47%) was then added over 1 hour at below 20°C. the reaction mass was then stirred at 20-25°C to complete hydrolysis. The methanol was then removed by steam distillation, a small amount of Dispersol OG is added, and the resultant aqueous solution acidified to pH 1 using hydrochloric acid. The precipitated IR trans-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarbonic acid was then filtered, washed and dried.

Yield = 233.4 gm at 95.6% strength, 225.2 gm at 100% = 92.8% yield at a translcis ratio of 76/24

Example 10 Purification of IR trans-Z 3-(2-chIoro-3,3,3-trifluoro-l-propenyl)-2,2- dimethylcyclopropanecarboxylic acid The dried IR trans-Z 3-(2-chloro-3 ,3 ,3-trifluoro- l-propenyl)-2,2-dimethylcyclopropanecarbonic acid (233.4 gm) was stirred in 60% v/v aqueous methanol (485.2 gm) and the mixture heated to 55°C then stirred for a further 30 minutes to ensure complete solution. The temperature was then reduced to 35°C with external cooling, stirring throughout, then maintained at 35°C for 2 hours. A crystalline product separated which was filtered, washed with cold 60% aqueous methanol (150 gm) and dried.

Yield = 98.1 gm at 99.3% strength, 97.4 gm at 100% = 43% yield at a trans/ cis ratio of 99/1

Example 11 Recycle of IR trans Z/1S cis Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2- dimethylcyclopropanecarboxylic acid

A sample of the IR trans/lS cis mixed acids (13.5 gm at 88.8% strength with translcis ratio of 46/54), recovered from the mother liquors from the recrystallisation of crude IR Z 3-(2-chloro- 3 ,3 ,3-trifluoro- l-propenyl)-2,2-dimethylcyclopropanecarboxylic acid , was stirred in toluene (15, ml) and heated to 70°C with a few drops of DMF as thionyl chloride (6 gm) was slowly added drop-wise. The reaction was then stirred;at 75-80°C for 2 hours to complete the conversion to the acid chloride. The toluene was removed from the acid chloride by distillation and the internal temperature raised to 145-150°C and maintained at this temperature for 8 hours to effect isomerisation. The reaction was then cooled to ambient temperature and added to methanol (10 ml) slowly. Sodium hydroxide liquor (6ml of 47%) was then slowly added with stirring maintaining the temperature at less than 45°C then stirred overnight to complete the hydrolysis. The mixture was acidified with hydrochloric acid to a positive test on cong red paper. The product separated, was filtered, washed and dried. Yield = 10.2 gm at 89.75%, 9.2 gm at 100% = 76.4% recovery, with translcis ratio of 80/20.

Example 12 Preparation of IR trans-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethyl cyclopropanecarboxylic acid chloride A 25 ml three-necked flask was equipped with a stirrer bar, thermometer reflux condenser, N₂ blanked and dropping funnel. To the reactor was charged IR trans-Z 3-(2-chloro-3,3,3-trifluoro- l-propenyl)-2,2-dimethylcyclopropanecarboxylic acid (2.2 g), hexane (12 ml) and triethylamine (9 mg). The reaction was heated with agitation to 45-50°C, then the thionyl chloride (1.4g) was introduced over a few minutes. After 1 hr at 45-50°C GC analysis indicated 96% conversion to the acid chloride. The heating was switched off and reaction was allowed to cool with stirring overnight. The reaction mass was concentrated in vacuo to give 2.2 g of a colourless oil (93% yield, 98% by GC area). [oc]_D ²⁰ = -81 (52mg in 10ml of dichloromethane)

Example 13 Preparation of the IR trans (-) enantiomer of (S)-alpha cyano-3-phenoxybenzyl cis-Z 3-(2- chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarboxylate

A 50 ml 3-necked dry flask was equipped with a stirrer bar, thermometer and N₂ blanket. To the reactor was charged (S)-alpha cyano-3-phenoxybenzyl alcohol (2.25g of 80% solution in toluene) in toluene (20 ml), then the solution was cooled to -10°C (MeOH/CO₂ (s) bath). IR trans (-) cis- Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarbonyl chloride (2.2g in 4 ml toluene) was added to the reaction over - 1 hr (by pipette), maintaining at 10°C, then the reaction was stirred for a further 2 hrs at 10°C. Pyridine (1.0 ml) in toluene (2 ml) was then added to the reaction at 5°C (over - 5 mins) GC analysis indicated that the reaction had almost gone to completion instantaneously but it was stirred overnight at room temperature to complete. The reaction mass was washed with aqueous HCl (3 x 15 ml, 2M) then with NaHCO₃ solution (15 ml, 10%) then water (10 ml) then concentrated in vacuo. The crude product was then purified by column chromatography (3 g crude product/60 g silica gel) using a 9:1 petroleum ether:ethyl acetate mixture) to give 3.0 g of a colourless oil after concentrating in vacuo. High vacuum was applied to the oil to drive off any residual solvents. The final product was a colourless sticky oil - 2.7g

1H NMR (CDC1₃):

7.0-7.5(m, 1H, aromatic), 6.4(s, 1H), 6.15(d, 1H, vinyl), 2.5(m, 1H, cyclopropane), 1.85(d, 1H, cyclopropane), 1.30(s, 3H, methyl), 1.25(s, 3H, methyl)

GCMS: 38, 51, 64, 77, 91, 115, 128, 141, 161, 181(100%), 197, 210, 225, 449(MI). [oc]_D ²⁰ = -29.3 (0.0631 gm in 10ml of dichloromethane)

Example 14 Preparation of the IR trans (-) enantiomer of 2,3,5,6-tetrafluoro-4-methylbenzyl cis-Z 3-(2- chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarboxylate

A 25ml 3-necked round bottom flask was equipped with a stirrer bar, nitrogen sparge, thermometer and septum. To the reactor was charged IR trans (-) cis-Z 3-(2-chloro-3,3,3- trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarbonyl chloride (3.0g), which was heated to

45°C with agitation. 2,3,5,6-tetrafluoro-4-methylbenzyl alcohol (2.16g) was added portion wise over lhr. Once the addition was complete, the reaction was stirred for 4.5hr at 45°C before cooling to room temperature. The mixture was re-heated to 50°C and a further 2 charges of the acid chloride were made (0.125g and O.lg) and the reaction was stirred for a further 2hr before cooling to room temperature. The desired product solidified upon cooling to give an off white solid (3.71g, 80% yield).

IH NMR (CDC1₃):

6.1(d, IH, vinyl), 5.2(s broad, CH₂), 2.4(m, IH, cyclopropane), 2.3(t, IH, cyclopropane), 1.80(d, IH, cyclopropane), 1.3(s, 3H, methyl), 1.2(s, 3H, methyl)

GCMS:

127, 141, 161, 177(100%), 197, 225, 269, 383(M⁺.-35).

[oc]_D ²⁰ = -34.8 (0.0892 gm in 10ml of dichloromethane)

Example 15 Preparation of the IR trans (-) 2-methyl-3-phenylbenzyl cis-Z 3-(2-chloro-3,3,3-trifluoro-l- propenyl)-2,2-dimethylcyclopropanecarboxylate

A 50ml 3-necked round bottom flask was equipped with a stirrer bar, nitrogen blanket, thermometer and septum. To the reactor was charged 2-methyl-3-phenylbenzyl alcohol (2.32g ), hexane (7ml) and triethylamine ( 1.26g). The mixture was heated to 50°C with agitation, then IR trans (+ ) cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarbonyl chloride (3.0g) in toluene (3ml) was added over 1 hour using a syringe pump. The reaction was stirred for 2.5 hr at 50°C, then further charges of acid chloride were made (0.2g + O.lg) to balance the alcohol charge. The reaction was stirred for a further 3 hr, an extra triethylamine charge (50mg) was added and the reaction stirred for 1 hr before allowing to cool to room temperature. The reaction mass was diluted with hexane (15ml) then washed with 5M HCl (15ml), sodium carbonate solution (10%, 15ml), water (10ml) and brine (10ml). Concentrated under reduced pressure to give the desired product (4.2g, 81% yield) as an orange sticky oil. 1H NMR (CDC1₃):

7.25(m, 8H, aromatic), 6.1(d.d, IH, vinyl), 5.2(s, 2H, CH₂), 2.5(m, IH, cyclopropane), 2.2(s, 3H, methyl), 1.8(d, IH, cyclopropane), 1.30(s, 3H, methyl), 1.25(s, 3H, methyl) GCMS:

141, 153, 165, 181(100%), 442(M⁺). [ ]_D ²⁰ = -44.2 (0.092 gm in 10ml of dichloromethane)

Example 16 Preparation of the IR cis (+) 2-methyI-3-phenylbenzyl cis-Z 3-(2-chloro-3,3,3-trifluoro-l- propenyI)-2,2-dimethylcyclopropanecarboxylate

A 50ml 3-necked round bottom flask was equipped with a stirrer bar, nitrogen blanket, thermometer and septum. To the reactor was charged 2-methyl-3-phenylbenzyl alcohol (2.32g ), hexane (7ml) and triethylamine ( 1.26g). The mixture was heated to 50°C with agitation, then IR (+) cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarbonyl chloride (3.0g) in toluene (3ml) was added quickly. The reaction temperature rose rapidly to 70°C then was cooled externally to 50°C. Further hexane (5 ml) was added to fluidise the resultant suspension and the mixture was stirred for 3 hr at 50°C. A further charge of acid chloride was made (0.3g - to balance the alcohol charge). The reaction was stirred for a further 18 hr at 50°C. After cooling to room temperature additional hexane (15ml) was charged followed by 5molar HCl (15ml). The two phases were separated and the organic phase was washed successively with sodium carbonate solution (10%, 15ml), water (10ml) and brine (10ml). After drying over magnesium sulphate the solution was evaporated under reduced pressure to give the desired product (3.64g, 73.6% yield) as a pale yellow oil. IH NMR (CDCI₃):

7.3(m, 8H, aromatic), 6.95(d, IH), 5.2(m, 2H, CH₂), 2.2(s, 4H, methyl-aromatic + cyclopropane), 2.05(d, IH, cyclopropane), 1.30(d, 6H, methyl) GCMS: 27, 41, 77, 115, 166, 182(100%), 225, 422(MI).

[oc]_D ²⁰ = +16.2 (0.1238 gmin 10ml of dichloromethane)

EXAMPLE 17 This Example illustrates the pesticidal / insecticidal properties of IR trans tefluthrin prepared according to the process of the invention. The activities of individual compounds were determined using first instar Heliothis virescens larvae. The pests were treated with a liquid composition containing 5 parts per million (ppm) by weight of a compound as the top rate applied. This was diluted further (step-wise) to produce a series of seven rates. Each composition was made by dissolving the compound in an acetone and ethanol (50:50 by volume) mixture and diluting the solution with water containing 0.05% by volume of a wetting agent, SYNPERONIC NP8, until the liquid composition contained the required concentration of the compound. The test procedure adopted comprised supporting twenty larvae on a treated excised cotton leaf on which the pests feed. Pest mortality was assessed three days after treatment. LC50 and LC90 values were calculated by reference to the activity of lambda cyhalothrin with the following results

LC50 LC90

Lambda-cyhalothrin 1 1

Racemic Tefluthrin 8.4 26.9 lR-trans tefluthrin 1.8 4.6 EXAMPLE 18 This Example illustrates the pesticidal / insecticidal properties of IR trans isomers of lambda cyhalothrin, tefluthrin and bifenthrin prepared according to the process of the invention. The activities of individual compounds were determined using second instar multi-resistant Plutella xylostella. The pests were treated with a liquid composition containing 1000 parts per million (ppm) by weight of a compound as the top rate applied. This was diluted further (step- wise) to produce a series of six rates. Each composition was made by dissolving the compound in an acetone and ethanol (50:50 by volume) mixture and diluting the solution with water containing 0.05% by volume of a wetting agent, SYNPERONIC NP8, until the liquid composition contained the required concentration of the compound. The test procedure adopted comprised supporting fifteen larvae a treated excised Chinese cabbage leaf on which the pests feed. Pest mortality was assessed two days after treatment.

LC50 values were calculated by Logit analysis and compared to the¹ corresponding racemic compounds with the following results.

Claims

CLAMS

1. A process for the production of IR pyrethroid esters of formula IDA or DEB,

(IIIA) (IIIB) wherein A and B are independently chlorine or bromine or one of A or B is chlorine and the other is trifluoromethyl and R is a pyrethroid alcohol fragment, which process comprises a) resolving pyrethroid acids of formula (IV)

(IV) where A and B are as defined for compounds of formula IDA and I LIB to give a substantially pure IR cis enantiomer, b) recovering the IS cis enantiomer c) optionally converting the IS cis enantiomer acid to a IS cis enantiomer anhydride, acid chloride or pyrethroid ester containing the group R where R is a pyrethroid alcohol fragment; d) converting the IS cis enantiomer from step b) or step c) to the IR trans isomer; e) optionally purifying the IR trans isomer from step d) and recycle of the unconverted IS cis isomer back to step c) or d) f) converting the IR cis isomer of the acid from step a) into corresponding IR cis isomers of the pyrethroid esters alone, or together with the product of step d) or e) where the product of step d) or e) is not already a pyrethroid ester containing the group R.

2. A process for the preparation of the IR trans compounds of the formula (DIB)

(IIIB)

in which A, B and R have the meanings given in claim 1 which process comprises a) resolving pyrethroid acids of formula (I) where A and B are as defined for formula

(BOB)

(I) b) recovering the IS cis enantiomer c) optionally converting the IS cis enantiomer acid to a IS cis enantiomer anhydride, acid chloride or pyrethroid ester containing the group R where R is a pyrethroid alcohol fragment; d) converting the IS cis enantiomer from step b) or step c) to the IR trans isomer; e) optionally purifying the IR trans isomer from step d) and recycle of the unconverted IS cis isomer back to step c) or d) f) if the IR trans isomer from step d) or step e) is an acid, acid chloride or anhydride, converting it to a pyrethroid ester of formula DTB.

3. A process according to claim 1 or claim 2 wherein a resolving agent used in step a) is recovered in a form suitable for direct recycle within step a).

4. A compound of formula (IDB) wherein A is Cl, B is CF₃ and R is (S) α-cyano 3- phenoxybenzyloxy; 4-methyl-2,3,5,6-tetrafluorobenzyloxy; 2-methyl-3-phenylbenzyloxy or (S) α-cyano 3-phenoxy-4-fluorobenzyloxy.

5. IS cis compounds of the formula (VA) and IR trans compounds of the formula (VB), where A and B are as defined in Claim 1

(VA) (VB)

6. IR trans-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarboxylic acid.

7. IR trans-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarboxylic acid chloride.

8. IS cis-Z 3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarboxylic acid chloride.

9. An insecticidal composition comprising a compound of formula (DEB) as defined in claim 1 where A is Cl, B is CF₃ and R is (S) α-cyano 3-phenoxybenzyloxy; 4-methyl-2,3,5,6- tetrafluorobenzyloxy; 2-methyl-3-phenylbenzyloxy or (S) α-cyano 3-phenoxy-4- fluorobenzyloxy and a carrier or diluent therefor.

10. A composition according to claim 9 which additionally contains a compound of formula (IDA) as defined in claim 1 where A, B and R are as defined in claim 9.

11. A composition according to claim 9 or claim 10 which additionally contains lambda- cyhalothrin or gamma-cyhalothrin.

12. A method of combating and controlling insect pests which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest a compound of formula (EEEB) as defined in claim 9 optionally mixed with a compound of formula (IDA) as defined in claim 10.