GB2074573A

GB2074573A - Process for Preparing Cyclopropane Carboxylic Acid Ester Derivatives

Info

Publication number: GB2074573A
Application number: GB8112325A
Authority: GB
Original assignee: Shell Internationale Research Maatschappij BV
Current assignee: Shell Internationale Research Maatschappij BV
Priority date: 1980-04-23
Filing date: 1981-04-21
Publication date: 1981-11-04
Also published as: GB2074573B

Abstract

A process for preparing a mixture of cis-isomers of a compound of formula <IMAGE> wherein R<1> and R<2> are independently selected from chlorine, bromine and methyl, consisting predominantly of the 1R cis S- and 1S cis R- isomers, comprises dissolving a mixture of 1S cis S- and 1R cis R isomers of the compound of formula I, alone or in the presence of 1R cis S- and 1S cis R- isomers, in an organic amine base containing from 5 to 7 carbon atoms and being a secondary amine containing two branched alkyl groups or a tertiary amine, crystallising out from a resulting solution of cis- isomers of formula I in the organic amine base a 1:1 mixture of the 1R cis S- and 1S cis R-isomers, and evaporating off the organic amine base.

Description

SPECIFICATION Process for Preparing Cyclopropane Carboxylic Acid Ester Derivatives This invention relates to the preparation of pesticidal cyclopropane carboxylic acid ester derivatives.

Cyclopropane carboxylic acid ester derivatives of general formula

wherein R' and R2 are independently selected from chlorine, bromine and methyl, are known compounds having pesticidal activity, see for example UK Patent Specification No. 1,413,491 or US Patent No. 4,024,163. These derivatives are members of a class of pesticidal compounds commonly referred to in the art as "pyrethroid insecticides". Compounds of formula I contain two centres of asymmetry in the cyclopropane ring of the acid moiety and a third centre of asymmetry in the alcohol moiety, leading to the existence of eight possible isomers.In general, superior pesticidal activity resides among the compounds having cis-configuration about the cyclopropane ring, as disclosed by ltaya et al in "Synthetic Pyrethroids", ACS Symposium Series 42, Pages 45 to 54, and the isomer which has the greatest pesticidal activity is generally that isomer which is conveniently designated the 1 R cis Sisomer, 1R cis- designating configuration in the acid moiety and S-designating configuration in the alcohol moiety, as described by Elliott et al in Nature, Vol. 248, Pages 710 and 711(1 974).

Attempts to produce 1 R cis S-single isomers rest either on synthesis routes which inherently produce intermediates containing the cyclopropane carboxylic acid moiety in exclusively 1 R cisconfiguration or on a route which involves an opticai resolution step to separate 1 R cis-compounds from 1 S cis-compounds. Esterification of a 1 R cis- intermediate to produce a derivative of formula I above leads to production of a mixture of 1 R cis R- and 1 R cis S- end products. Separation of these end products is possible by physical methods, at least in theory, since the 1 R cis R- and 1 R cis Scompounds are not enantiomers.However, although such separation of 1 R cis R and 1 R cis Scompounds has proved to be relatively readily attainable when R1 and R2 are both bromine atoms, it has proved to be more difficult and more costly in other cases, for example when RI and R2 are both chlorine atoms.

The Applicants have now discovered a surprisingly simple and inexpensive method of increasing the 1 R cis S- isomer content of a mixture of cis- isomers of formula According to the invention there is provided a process for preparing a mixture of cis- isomers of a compound of formula

wherein R' and R2 are independently selected from chlorine, bromine and methyl, consisting predominantly of the 1 R cis- S- and 1S cis R- isomers, which process comprises dissolving a mixture of 1S cis S- and 1 R cis R- isomers of the compound of formula I, alone or in the presence of 1 R cis S- and 1 S cis R- isomers, in an organic amine base containing from 5 to 7 atoms and being a secondary amine containing two branched alkyl groups or a tertiary amine, crystallising out from a resulting solution of cis- isomers of formula I in the organic amine base a 1:1 mixture of the 1 R cis S- and 1 S cis R- isomers, and evaporating off the organic amine base.

It is preferred that R1 and R2 are both chlorine or bromine atoms, and they are preferebly both chlorine atoms.

The organic base causes racemisation to take place at the a-carbon atom of the alcohol moiety of the compound of formula I, so that the mixture of cis- isomers of formula I in solution in the organic base tends to become a racemic solution of all four cis- isomers, i.e. a solution containing equal quantities of 1R cis S-, 1 S cis S-, 1R cis R- and 1 S cis R- isomers, assuming that the initial mixture was optically inactive. However, the organic amine bases which are suitable for use in the process of the invention have the further property of being solvents in which the 1 R cis S-/l S cis R- enantiomer pair of the isomers of formula I is substantially less soluble than the 1 S cis 5-11 R cis R-enantiomer pair.

In the process of the invention, as the 1:1 mixture of the 1 R cis S- and 1 S cis R- isomers crystallises out from the solution of cis- isomers, the solution tends to become relatively depleted in 1 R cis S- and 1S cis R- isomers. This tendency is counterbalanced by the effect of the organic amine base in causing the mkture of cis- isomers to tend to become a racemic mixture of all four cis- isomers. Thus as the 1:1 mixture of 1 R cis S- and 15 cis R- isomers is removed from solution by crystallisation further of the 1 R cis S- and 15 cis R- isomers are formed by racemisation.

If this process were allowed to continue, a final equilibrium would be attained between crystallised 1:1 mixture of 1 R cis S- and 15 cis R- isomers and a solution saturated with 1 R cis S- and 1 S cis R- isomers and containing equivalent amounts of 1 S cis S- and 1 R cis-R isomers. Such a final equilibrium, or its attainment is upset in the process of the invention by the removal by evaporation of the organic amine base. The evaporation causes the remaining solution to become more concentrated, and the combined cr-dstallisaiion/racemisation discussed above continues until all the organic amine base has evaporated off.

As will be readily appreciated by those skilled in the art, the precise isomer constitution of the product of the process will be dependent on the balance between the rate of crystallisation, the rate of racemisation and the rate of evaporation. All of these rates will vary according to temperature. The rate of evaporaticn will also vary according to pressure.

When the starting material is partly or wholly crystalline, in order to ensure complete dissolution of the 1 S cis S- and 1 R cis R- isomers of the compound of formula s, it is preferred to dissolve the mixture of isomers of formula I in the organic amine base at elevated temperature, e.g. a temperature in the range 50 to 800 C, conveniently 60 to 700C. If desired the resulting solution may be filtered in order to ensure the absence of any solid particles in the solution prior to crystallisation. However, when the starting material is in the form of an oil, e.g., in the case of a freshly prepared racemic mixture of cis-isomers, the mixture of isomers of formula I is advantageously dissolved in the organic amine base at ambient temperature.

Crystaliisation may advantageously be effected at ambient temperature or below, and, where elevated temperatures have been employed in order to bring the mixture of c/s- isomers into solution in the organic amine base, crystallisation is preferably effected by cooling the solution to ambient temperature or below.

The optimum temperatures for crystallisation and evaporation will in general be in the range 0 to 200C. Conveniently, crystallisation is initiated by seeding with a few crystals of 1:1 mixture of the 1 R cis S- and 15 cis R- isomers of the compound of formula I.

Those skilled in the art will appreciate that the organic amine base which is evaporated off may readily be condensed and collected in known manner for re-use.

The product of the process of the invention will always contain more than 50 /0 by weight of the 1 R c/s S- and 15 cis R- isomers, and provided that the rate of evaporation of the organic amine base is kept sufficiently slow, and that the initial mixture of cis-isomers was optically inactive the product may consist substantially entirely of a 1:1 mixture of 1 R cis S- end 1 S cis R- isomers of the compound of formula I.

The preferred organic amine bases contain six carbon atoms. Triethylamine and diisopropylamine have been found to be very effective organic amine bases. Of these, triethylamine is particularly preferred.

Although gke presence of small amounts of water in the organic amine base may be tolerated, the amount of water should be less than 2% by weight of the base, advantageously less than 1%, more advantageously less than 0.5%, and the dissolution, crystallisation and evaporation are preferably carried out under substantially anhydrous conditions.

It will be appreciated that the most readily available starting material for the process of the invention will be a racemic mixture of all four c/s- isomers of the compound of formula I, although the process is equally applicable to starting materials containing non-racemic mixtures of cis- isomers.

The product of the process of the invention contains a high proportion of the most pesticidallyactive isomer of the relevant compound of formula I. The invention also extends therefore to a mixture of cis- isomers of a compound of forrnula I consisting predominantly of the 1 R cis S- and 1 S cis Risomers whenever prepared by the process of the invention, to a pesticidal composition comprising the said mixture in association with a suitable carrier therefor, and to a method of combating pests at a locus which comprises applying to the locus an effective amount of the said mixture or a composition containing the said mixture. The constitution of suitable pesticidal compositions is described in the aforementioned U.K. Patent Specification No.1,413,491.

The invention will be further understood from the following Examples, of which Examples 1 and 2 relates to an embodiment of the process of the invention and Examples 3 and 4 relate to tests indicative of the suitability of organic amine systems for use in the process of the invention. Examples 1 to 3 were carried out under substantially anhydrous conditions, the water content of the triethylamine being 0.1% w/w.

Example 1 10 g of a mixture of c/s- isomers of -cyano-3-phenoxybenzyl 3-(2,2-dichlornvinyl)-2,2-dimethyl cyclopropanecarboxylate, in which the by weight ratio of 1 S cis S- and 1 R cis R isomers to 1 R cis Sand 15 cis R- isomers was 2:1, was dissolved in 20 ml of triethylamine with heating to 60 to 700C.

The solution was allowed to cool to ambient temperature, with stirring, and was seeded with a few crystals of a 1:1 mixture of 1 R cis S- and 1 S cis R- isomers of a-cyano-3-phenoxybenzyl 3-(2,2 dichlorovinyl)-2,2-dimethyl-cyclopropane carboxylate. Stirring was continued for 40 hours at ambient temperature and the triethylamine was then stripped off at 200C over a period of one hour to leave 10 g of dry solid material, mp 65-770C, which was shown by gas-liquid chromatography to be a 98.9% pure mixture of c/s- isomers of ct-cyano-3-phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethyl cyclopropane carboxylate and by high performance liquid chromatography to contain 20 parts by weight of the 1 S cis S- and 1 R cis R- isomers and 80 parts by weight of the 1 R cis S- and 1 S cis R isomers.

Example 2 15 g of a mixture of c/s- isomers of a-cyano-3-phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2dimethylcyclopropanecarboxylate, in which the by weight ratio of 1 S cis S- and 1 R cis R- isomers to 1 R cis S- and 1 S cis R-isomers was 1 :1, was dissolved in 30 ml of triethylamine with heating to 60 to 700C. The solution was allowed to cool to ambient temperature, with stirring, and was seeded with a few crystals of a 1:1 mixture of 1:1 mixture of 1 R cis S- and 15 cis R- isomers of a-cyano-3 phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate. After stirring for a further 42 hours at ambient temperature, a slow stream of nitrogen was bubbled through the solution in order to evaporate off the triethylamine.The solid residue, which was substantially dry after 24 hours, was transferred to a round-bottomed flask, washing with 20 ml of 60/80 petroleum ether. Evaporation to dryness at 500C yielded 14.85 g of dry solid material, mp 78-81 OC, which was shown by high performance liquid chromatography to contain greater than 90% by weight of a 1:1 mixture of the 1 R cis S- and 15 cis R- isomers of a-cyano-3-phenoxyben3-(2,2-dichlornvinyl)-2,2- dimethylcyclopropanecarboxylate.

Example 3 For comparison purposes several different organic amines were used as base-solvent systems in the following test procedure. 5.0 g of a mixture of c/s- isomers of o-cyano-3-phenoxybenzyl 3-(2,2dichlorovinyl)-2,2-dimethylcyclopropane carboxylate, in which by weight ratio of 1S cis S- and 1 R cis R- isomers to 1 R cis S- and 15 cis R- isomers was 2:1, was dissolved in 10 ml of the organic amine with heating (to not more than 600 C). The resulting solution was allowed to cool to ambient temperature with stirring, was seeded with a few crystals of a 1:1 mixture of 1 R cis S- and 15 cis Risomers of a-cyano-3-phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate.

Stirring was continued overnight and the solution was then subjected to further treatment, analysis, etc. as appropriate. Results are given in Table I following. Analyses of solutions and end products were effected by high performance liquid chromatography. In cases where crystallisation did not occur at ambient temperature the solutions were cooled to -1 00C in order to attempt to achieve crystallisation.

Table I

fest No. Organic Amine Comments i triethylamine Slow crystallisation. After two days of stirring, precipitate was filtered and dried to give 2.0 g of 98% pure 1:1 mixture of 1 R c/s S- and 1S cis R isomers. Filtrate contained substantially racemic mixture of cis - isomers. No decomposition of starting material detectable.

iidiisopropylamine Slow crystallisation. After two days of stirring, precipitate was filtered and dried to give 2.0 g of a 98% pure 1:1 mixture of 1 R ci S- and 15 cis R- isomers. Filtrate contained substantially racemic mixture of eis - isomers. About 5% decomposition of starting material detected.

iii tri-n-propylamine Rapid crystallisation. After stirring over weekend, precipitate was filtered, washed with 60-80 petroleum ether and dried to give 3.3 g of crystalline material having substantially the same composition as the starting material.

Table I (cont.)

Test No. OrganicAmine Comments iv tri-n-butylamine Slow crystallisation. After stirring over weekend, precipitate was filtered, washed with 60-80 petroleum ether and dried to give 3.9 g of crystalline material having substantially the same composition as the starting material.

v diethylamine No crystallisation. Stirred for two hours at -110 C, still no crystallisation. About 20% decomposition of starting material detected after one day.

vi n-hexylamine No crystallisation. Rapid decomposition of starting material had occurred.

vii n-butylmethyl amine No crystallisation, even after five days. About 50% decomposition of starting material detected after one day. Over 909/0 decomposition detected after nine days.

viii N-cyclohexyl methylamine No crystallisation even after three day. About 50% decomposition of starting material detected after three days.

ix N-cyclohexyl isopropylamine No crystallisation after three days. Very little decomposition of starting material. Solution contained substantially racemic mixture of cis - isomers.

x ethyldiiso propylamine Rapid crystallisation. After stirring over weekend precipitate was filtered and dried to give 3.0 g of crystalline material having substantially the same composition as the starting material.

xi N,N-dimethyl aniline No crystallisation.

xii 2,6-lutidine No crystallisation. No decomposition of starting material detected Isomer composition of starting material unchanged.

Example 4 Experiments to assess the effect of the presence of water in the base-solvent system were effected by the procedure of Example 3. In each case the base-solvent was triethylamine. Results are given in Table II following.

Table II

Test No. % water in Comments triethylamine (wlw) i 0.10 see Table I ii 2 Slow crystallisation. After two days of stirring, precipitate was filtered and dried to give 0.9 g of a 98% pure 1:1 mixture of 1 R cis S- and 1 S cis R- isomers Filtrate contained substantially racemic mixture of cis - isomers.

iii 5 No crystallisation even after five days.

Claims

1. A process for preparing a mixture of c/s- isomers of a compound of formula

wherein R1 and R2 are independently selected from chlorine, bromine and methyl, consisting predominantly of the 1 R cis S- and 1 S cis R- isomers, which process comprises dissolving a mixture of 1 S cis S- and 1 R cis R- isomers of the compound of formula I, alone or in the presence of 1 R cis S- and 1 S cis R- isomers, in an organic amine base containing from 5 to 7 carbon atoms and being a secondary amine containing two branched alkyl groups or tertiary amine, crystallising out from a resulting solution of c/s- isomers of formula I in the organic amine base a 1:1 mixture of the 1 R cis Sand 1 S cis R- isomers, and evaporating off the organic amine base.

2. A process according to Claim 1 wherein R1 and R2 are both chlorine.

3. A process according to Claim 1 or 2 wherein the organic amine base contains six carbon atoms.

4. A process according to Claim 1, 2 or 3 wherein the organic amine base is triethylamine or diisopropylamine.

5. A process according to any one of Claims 1 to 4 wherein dissolution, crystallisation and evaporation are carried out under substantially anhydrous conditions.

6. A process according to any one of Claims 1 to 5 wherein crystallisation and evaporation are effected at ambient temperature or below.

7. A process according to Claim 1 substantially as hereinbefore described with particular reference to Example 1 or Example 2.

8. A mixture of c/s- isomers of a compound of formula I consisting predominantly of the 1 R cis Sand 1 S cis R- isomers whenever prepared by a process according to any one of Claims 1 to 7.

9. A pesticidal composition comprising a mixture according to Claim 8 in association with an inert carrier therefor.

10. A method of combating pests at a locus which comprises applying to the locus a mixture according to Claim 8 or a composition according to Claim 9.