GB2075011A

GB2075011A - Process for Preparing Cyclopropane Carboxylic Acid Ester Derivatives

Info

Publication number: GB2075011A
Application number: GB8112344A
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: 1981-11-11
Also published as: GB2075011B

Abstract

A process for preparing a 1:1 mixture of 1R cis S- and 1S cis R- isomers substantially free of 1S cis S- and 1R cis R- isomers of a compound of formula: <IMAGE> wherein R<1> and R<2> are each independently selected from chlorine, bromine and methyl 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 organic amine base containing from 5 to 7 carbon atoms and being a secondary amine containing two branched alkyl groups or a tertiary amine, and crystallising out from the 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 substantially free of 1S cis S- and 1R cis R- isomers.

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. 4,024,1 63. 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 Itaya 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, 1 R cis- designating configuration in the acid moiety and S-designating configuration in the alcohol moiety, as described by Elliott eft at in Nature, Vol. 248, Pages 710 and 711(1974).

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 optical 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 1R 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 R' and R2 are both bromine atoms, it has proved to be more difficult and more costly in other cases, for example when R' and R2 are both chlorine atoms.

Copending UK Patent Application No. 8037693 (Applicants' reference K 1801) describes and claims a compound of formula I in the form of a 1:1 mixture of the 1 R cis S- and 1S cis R- isomers substantially free of 1S cis S- and 1 R cis R- isomers. Such a compound contains, weight for weight, up to four times as much of the most pesticidally active (1 R cis S-) isomer of a compound of formula I as a compound containing equal weights of all eight isomers of formula I.

According to the present invention, there is provided a process for preparing a 1:1 mixture of 1 R cis S- and 1 S cis R- isomers substantially free of 1S cis S- and 1 R cis R- isomers of a compound of formula

wherein R' and R2 are each independently selected from chlorine, bromine and methyl, 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 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, and crystallising out from a resulting solution of cis isomers of formula I in the organic amine base a 1::1 mixture of the 1 P cis S- and 15 cis P- isomers substantially free of 1S cis S-and 1 R cis R-isomers.

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

The organic amine 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 amine base tends to become a racemic solution of all four cis- isomers, i.e. a solution containing equal quantities of 1 R cis S-, 1 S cis S-, 1 R cis R- and 1S cis R- isomers, assuming that the initial mixture was optically inactive.

The Applicants have made the surprising discovery that the organic amine bases which are capable of use in the process of the invention not only have the property of causing racemisation at the carbon atom of the alcohol moiety of the compound of formula I but are also solvents in which the 1 R cis 5-11 S cis R- enantiomer pair of the isomers of formula I is substantially less soluble than the 1 S cis S-/1 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 15 cis R-isomers. This tendency is counter-balanced by the effect of the organic amine base in causing the mixture 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 quantities of the 1 R cis S- and 1 S cis R- isomers are formed by racemisation.

This process continues until some further action is taken, e.g. removal of the crystallised 1:1 mixture of 1 R cis S- and 1 S cis R- isomers, for example by filtration, or until a final equilibrium is attained.

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

Although the 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 in the organic amine base and crystallisation from the resulting solution are preferably effected under substantially anhydrous conditions.

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 I, 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 800C, 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 use of a freshly prepared racemic mixture of cisisomers, the mixture of isomers of formula I is advantageously dissolved in the organic amine base at ambient temperature.

Crystallisation may advantageously be effected at ambient temperature or below, and, where elevated temperatures have been employed in order to bring the mixture of cis- 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 will be dependent, at least in part, on the concentrations of the cis- isomers of the compound of formula I in the solution, as will be readily understood by those skilled in the art, but in general will 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 1 S cis Risomers of the compound of formula I.

Recovery of the crystalline 1:1 mixture of the 1 R cis S- and 1 S cis R- isomers from the supernatant solution may be effected by methods such as filtration, centrifugation or decantation.

The remaining solution may then be concentrated and further crystallisation effected from the concentrated solution, or additional amounts of the cis- isomers of the compound of formula I may be dissolved in it and crystallisation effected from the resulting solution.

It will readily be appreciated that the most readily available starting material for the process of the invention will be a racemic mixture of all four cis- isomers of the compound of formula I, although the process is equally applicable to starting materials containing unequal mixtures of cis- isomers. Thus the process of the invention has the advantage that it yields a product which contains a high proportion of the most pesticidally-active isomer of the relevant compound of formula I and that it does not invoive any asymmetric synthesis or optical resolution steps.

The invention also extends to the 1:1 mixture of 1 R cis S- and 15 cis R- isomers of a compound of formula I substantially free of 15 cis S- and 1 R cis R-isomers 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 appiying 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 to 5, and 7 were carried out under substantially anhydrous conditions, the water content of the triethylamine being 0.1% w/w.

Example 1 5.8 g of a crystallised racemic mixture of cis- isomers of a-cyano-3-phenoxybenzyl 3-(2,2dichlorovinyl)-2,2-dimethylcyclopropane carboxylate (mp 58-770C) was dissolved in 10 ml of triethylamine with heating 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 15 cis R- isomers of a- cyano-3-phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate.The precipitate which crystallised out was separated off and dried to give 3.4 g of colourless crystals mp 80-830C which were shown by high performance liquid chromatography to contain 94% by weight of a 1:1 mixture of the 1 R cis S- and 15 cis R-isomers of the starting material.

Concentration of the filtrate to half its volume followed by crystallisation, as above, gave a further 1.3 g of colourless crystals mp 82-840C which were shown by high performance liquid chromatography to contain greater than 94% by weight of a 1:1 mixture of the 1 R cis S- and 1S cis R isomers.

Similar analysis of the triethylamine solution remaining after the second crystallisation showed the ratio of the concentrations of the 1 S cis S- and 1 R cis R- isomers to those of the 1 R cis S- and 1 S cis R- isomers to be about 16:9.

Thus in two treatment steps a 94% pure 1:1 mixture of 1 R cis S- and 1 S cis R- isomers of the starting material was obtained in 81% yield.

Example 2 106 g of a mixture of cis- isomers of a-cyano-3-phenoxy-benzyl 3-(2,2-dichlorovinyl)-2,2dimethylcyclopropane carboxylate containing 42% by weight of the 1 S cis S- and 1 R cis R- isomers and 58% by weight of the 1 R cis S- and 15 cis R- isomers was dissolved in 212 ml of triethylamine with stirring and heating to 700C. The solution was allowed to cool with stirring and at 300C was seeded with a few crystals of a 1:1 mixture of 1 R cis S- and 15 cis R- isomers of a-cyano-3phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate.Stirring was continued and after 58 hours, having reached an end temperature of 21 OC, the solid material which had separated out was filtered off, sucked dry, and further dried in a vacuum oven at 550C to give 72.9 g of crystalline product, mp 82-840C, which was shown by high performance liquid chromatography to contain 95% by weight of a 1:1 mixture of the 1 R cis S- and 1S cis R- isomers of the starting material.

The filtrate was concentrated to 70 mi, heated to 700C and allowed to cool with stirring and seeding foliowed by isolation of solid material as above, yielding a further 1 5.3 g of crystalline product, mp 82-840C, containing 95% by weight of a 1:1 mixture of the 1 R cis S- and 1 S cis R- isomers.

The filtrate from this second step was concentrated to 25 ml and treated as in the second step to give a further 7.7 g of crystalline product, mp 83--840C, containing 95% by weight of a 1:1 mixture of the 1 R cis S- and 1 S cis R- isomers.

Thus in three treatment steps a 95% pure 1:1 mixture of 1 R cis S- and 1 S cis R- isomers of the starting material was obtained in 90% yield.

Example 3 118.7 g of a mixture of cis- isomers of a-cyano-3-phenoxylbenzyl 3-(2,2-dichlorovinyl)-2,2dimethylcyclopropane carboxylate containing 69% by weight of the 15 cis S- and 1 R cis R- isomers and 31% by weight of the 1 R cis S- and 15 cis R- isomers was dissolved in 236 ml of triethylamine and the solution was subject to treatment similar to Example 2. 61.7 g of crystalline product, mp 81830C, containing 95% by weight of a 1:1 mixture of the 1 R cis S- and 15 cis R- isomers was obtained.

The filtrate was concentrated to 70 ml and treated as in the second step of Example 2 to give a further 24.4 g of crystalline product, mp 76-800C, containing 90% by weight of a 1:1 mixture of the 1Pcis S- and 1S cis R- isomers.

Thus in two treatment steps 73% by weight of the starting material was obtained in the form of a greater than 90% pure 1:1 mixture of the 1 R cis S- and 15 cis R- isomers.

Example 4 906 g of a mixture of cis- isomers of a-cyano-3-phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2dimethylcyclopropane carboxylate containing 42% by weight of the 1 S cis S- and 1 R cis R- isomers and 58% by weight of the 1 R cis S and 1S cis R isomers was dissolved in 1812 ml of triethylamine with heating to 700C. The resulting solution was filtered through a No. 3 porosity sinter and was allowed to cool whilst being stirred with a polytetrafluoroethylene-bladed paddle. At 260C the solution was seeded with a few crystals of a 1:1 mixture of 1 R cis S- and 15 cis R- isomers of a-cyano-3- phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate.Stirring was continued for two days, the solution reaching an end temperature of 200 C. The solid material which had separated out was filtered off, sucked dry, washed once with 500 ml of 60-80 petroleum ether at -100C and dried to constant weight in a vacuum oven at ambient temperature, to give 638 g of crystalline product, mp 82-840C, which was shown by high performance liquid chromatography to contain 94% by weight of a 1:1 mixture of the 1 R cis S- and 1 S cis R- isomers of the starting material.

The filtrate was concentrated to 800 ml, heated to 600 C, allowed to cool with stirring and seeded at 300C with a few crystals of a 1:1 mixture of the 1 R cis S- and 15 cis R- isomers of a-cyano-3phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate.Stirring was continued for three days, the solution reaching an end temperature of 23 OC. The solid, material which had separated out was filtered off, sucked dry, washed once with 200 ml of triethylamine at -1 00C and once with 200 ml of 60-80 petroleum ether at 00C and dried as above to give a further 1 78 g of crystalline product, mp 83-850C, containing 98% by weight of a 1:1 mixture of the 1 R cis S- and 15 cis R isomers.

The filtrate from this second step was concentrated to 200 ml and treated similarly as in the second step, but with stirring for five days, to give further 51 g of crystalline product, mp 82-840C, containing 92% by weight of 1:1 mixture of the 1 R cis S- and 1 S cis R- isomers.

Thus in three treatment steps a 94% pure 1:1 mixture of 1 R cis S- and 1 S cis R- isomers of the starting material was obtained in greater than 95% yield.

Example 5 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 cis- isomers of a-cyano-3-phenoxybenzyl 3-(2,2dichlorovinyl)-2,2-dimethylcyclopropane carboxylate, in which by weight ratio of 15 cis S- and 1 R cis R- isomers to 1 R cis S- and 1 S 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, and was seeded with a few crystals of a 1:1 mixture of 1R 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

Test No. OrganicAmine Comments 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 cis S- and 15 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 cis S- and 15 cis R- isomers. Filtrate contained substantially racemic mixture of cis- 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. 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 -1 OOC, 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-butylmethylamine No crystallisation, even after five days. About 50% decomposition of starting material detected after one day. Over 90% decomposition detected after nine days.

Table I

Test No. Organic Amine Comments | viii N-cyclohexylmethyl No crystallisation even after three days.

amine About 50% decomposition of starting material detected after three days.

ix N-cyclohexylisopropyl- No crystallisation after three days. Very amine little decomposition of starting material.

Solution contained substantially racemic mixture of cis- isomers.

x ethyldiisopropylamine Rapid crystallisation. After stirring over weekened preciptate was filtered and dried to give 3.0 g of crystalline material having substantially the same composition as the starting material.

xi N,N-dimethylaniline No crystallisation.

xii 2,6-lutidine No crystallisation. No decomposition of starting material detected. Isomer composition of starting material unchanged l Example 6 Experiments to assess the effect of the presence of water in the base-solvent system were effected by the procedure of Example 5. In each case the base-solvent was triethylamine. Results are given in Table 2 following.

Table II

% water in Test No. triethylamine (w/w) Comments i 0.10 seeTablel | 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. Filtrtate contained substantially racemic mixture of cis- isomers.

iii 5 No crystallisation even after five days.

Example 7 3125 g of a freshly prepared racemic mixture of cis- isomers of a-cyano-3-phenoxybenzyl 3-(2,2dichlorovinyl)-2,2-dimethylcyclopropane carboxylate, purity 96.3% by weight, in the form of a yellow oil was dissolved in 4.65 litres of triethylamine at ambient temperature. The solution was seeded with a few crystals of a 1:1 mixture of 1 R cis S- and 15 cis R- isomers of a-cyano-3-phenoxybenzyl 3-(2,2dichlorovinyl)-2,2-dimethylcyciopropane carboxylate and was stirred for 24 hours at 1 50C. The precipitate which crystallised out was filtered off, washed with 750 ml of cold triethylamine and with 1 litre of 60-80 petroleum ether and dried to give 1738 g of colourless crystals mp 81-830C.

The filtrate was evaporated to about 1400 g of an oil which was dissolved in 2 litres of triethylamine at ambient temperature. The solution was seeded as above and stirred for 48 hours at 1 50C. The precipitate which crystallised out was filtered off, washed with 500 ml of cold triethylamine and with 500 ml of 60-80 petroleum ether and dried to give 864 g of colourless crystals mp 81.5- 83.50C.

The filtrate was evaporated at about 511 g of an orange oil which was dissolved in 750 ml of triethylamine at ambient temperature. Treatment as above, with stirring at 1 50C for 48 hours, yielded a further 96 g of colourless crystals, mp 82.5-840C.

The combined crystalline product (overall yield 2698 g, 86% by weight) was shown by high performance liquid chromatography to contain 94% by weight of a 1:1 mixture of the 1 R cis S- and 15 cis R- isomers of a-cyano-3-phenoxybenzyl 3-(2,2-dichlorovinyl)-3,3-dimethylcyclopropane carboxylate.

Claims

1. A process for preparing a 1:1 mixture of 1 R cis S- and 15 cis R- isomers substantially free of 1 S cis S- and 1 R cis R- isomers of a compound of formula

wherein R' and R2 are each independently selected from chlorine, bromine and methyl, 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 15 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, and crystallising out from the resulting solution of cis- isomers of formula I in the organic amine base a 1::1 mixture of the 1 R cis S- and 15 cis R- isomers substantially free of,i S cis S- and 1 R cis R- isomers.

2. A process according to claim 1 wherein R' 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 in the organic amine base and crystallisation from the resulting solution are effected under substantially anhydrous conditions.

6. A process according to any one of Claims 1 to 5 wherein crystallisation from the solution is effected at ambient temperature or below.

7. A process according to Claim 1 substantially as hereinbefore described with particular reference to any one of the Examples.

8. A 1:1 mixture of 1 R cis S- and 15 cis R- isomers of a compound of formula I substantially free of 15 cis S- and 1 R cis R- isomers whenever prepared by a process according to any one of Claims 1 to 7.

9. A pesticidal composition comprising a 1:1 mixture of 1 R cis S- and 15 cis R- isomers of a compound of formula I 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 1:1 mixture of 1 R cis S- and 15 cis R- isomers of compound of formula I according to Claim 8 or a composition according to Claim 9.