SI8111051A8 - Process for obtaining mixture of cis-isomeres of ester's derivatives of cyclopropane carboxylic acid - Google Patents

Description

PROCEDURE FOR OBTAINING A CIS-ISOMER MIXTURE OF CYCLOPROPANECARBOXYLIC ACID DERIVATIVES

TECHNICAL AREAS

The invention relates to the field of production of organic compounds with pesticidal action, and in particular relates to a process for the preparation of a cis-isomer mixture of cyclo-propanecarboxylic acid ester derivatives According to the International Patent Classification, the invention is classified in class C 07C 121 / ^; A 01Nj $ / <20.

TECHNICAL_PROBLEM

The invention solves the problem of obtaining a mixture of cis-isomers of cyclopropanecarboxylic acid ester derivatives with an increased content of 1R cis S-isomers.

BACKGROUND OF THE INVENTION

Cyclopropanecarboxylic acid ester derivatives of formula

(I)

2 in which R and R are independently denoted by chlorine, bromine iii are known compounds which. have pesticidal activity, methyl groups, see e.g.

UK Patent Application No.1,413,491 iii US Patent No.4,024,163. These derivatives belong to the class of pesticidal compounds commonly known in the art as pyrethroid insecticides. The compounds of formula I contain two centers of asymmetry in the cyclopropanecarboxylic ring on the acid group and a third center of asymmetry in the alcoholic species, leading to the respect of eight possible isomers. Generally, the superior activity of the pesticidal character is in the compounds having the cis configuration around the cyclopropane ring, as described in Italya et al in Synthetic Pyrethroids, ACS Symposium Series 42, pages 45 to 54, and the isomer having the highest pesticidal activity is generally the one an isomer conventionally labeled 1R cis Sisomer, wherein 1R cis- denotes a configuration in an alcoholic species, as described in Elliott et al in Mature, Vol.248, pages 710 and 711 (1974).

Attempts to produce 1R cis S-individual isomers consist iii in synthetic pathways that necessarily produce intermediates containing a cyclopropane carboxylic acid group in -only 1R cis-configuration iii and a mode involving an optical decomposition phase to separate 1R cis-compound from 1S cis -unions. The esterification of the 1R cis intermediate to produce the derivatives of formula I above leads to the production of the mixture

1R cis R- and 1R cis S- end products. The separation of these end products is possible by physical process, at least theoretically, since '

The 1R cis R- and 1R cis S-compounds are not enantiomers. However, although such separation of 1R cis R and 1R cis S1 2 compounds has been shown to be relatively easy to achieve when both R and R are bromine atoms, it has been shown to be much more difficult and expensive in other cases, for example, when R and R both chlorine atoms.

DESCRIPTION OF THE TECHNICAL PROBLEM SOLUTION

WITH EXAMPLES

According to the invention, an unexpectedly simple and inexpensive process for increasing the content of 1R cis S- isomers in a cis-isomer mixture of formula I has now been discovered by a new process for preparing a cis-isomer mixture of compounds of formula I.

Thus, according to the invention, there is provided a method for producing a mixture of cis-isomers of a compound of the formula:

CH.

CO - C

2 in which R IR is independently selected from chlorine, bronze and methyl, consisting predominantly of the IR cis-S- and IS cis R-isomers, the method comprising dissolving a mixture of IS cis S- and IR cis R-isomers of the compound of formula I, independently or in the presence of the IR cis S- and 13 cis R-isomers, in an organic amine base containing from 5 to 7 atoms and which is a secondary amine containing two branched alkyl groups iii is tertiaryamine, crystallization from the resulting cis- isomers of formula I in the organic amine base 1: 1 are mixtures of the IR cis S- and IS cis R-isoisers, and evaporation of the organic amine base.

2

Preferably S and R are both chlorine or bromine atoms, and preferably both chlorine atoms.

The organic base causes racemization on the alpha-carbon atom of an alcoholic type of a compound of formula I, such that a mixture of the cl3-isomer of formula I in solution in an organic base tends to become a racemic solution of all Four cis-isomers, i.e., a solution containing equal amounts of IR cis S- ,

IS cis S—, IR cis Ib 1 The IS cis F. isomer implies that the initial f mixture was optically inactive. However, organic amine bases that are suitable for use in the process of the 4rz invention have the further property that solvents in which IR is a cis S- / 1S cis R-enantiomer pair

The D ⁷ isomers of formula I are substantially less soluble. of IS cis S- / 1R cis R-enentic nerve pair.

In the process of the invention, a 1: 1 mixture of IR els S- and IS cis Ri z cabinets crystallizes from a solution of cis-isomers, the solution tends to become relatively depleted in the IR ci3 S- and IS cis R-isomers. To this tendency to her

- 4 counteracts the effect of the organic amine base by forcing the cis-isomer mixture to seek to become a racemic mixture of all four cisisomers. Thus, a mixture of the IR cis S- and IS cis R-isomers is separated from the crystallization solution and a further amount of IR cis S- and IS cis R-isomers forms racemization. "

If this process is to be continued, the final equilibrium between the 1: 1 crystalline mixture of the IR cis S- and IS cis R-isomers and the solution anchored with the IR cis S- and IS cis R- isomers and containing the equivalent amounts will be achieved. IS cis S- and IR cis R-isomers. Such a final equilibrium, or its attainment, is elaborated in the process of the invention by removal by evaporation of an organic amine base. Evaporation forces the remaining solution to become more concentrated, so the crystallized crystallization / racemization discussed above continues until all the organic base has evaporated.

As will be readily understood by one skilled in the art, the precise isomeric composition of the products of the process depends on the equilibrium between the crystallization rate, the racemization rate and the evaporation rate.

All of these speeds vary depending on the temperature. Evaporation rate will also vary depending on the pressure.

When the starting material is partially or fully crystalline, in order to ensure complete dissolution of the IS cis S- and IR cis R-isomers of the compounds of formula I, it is desirable to dissolve the mixture of isomers of formula I in an organic amine base at a higher temperature, e.g. at a temperature in the range of 50 to 80 ° C, preferably 60 to 70 ° C. If necessary, the resulting solution can be filtered to ensure that no solid solids are present in the solution prior to crystallization. However, when the starting material is in the form of an oil, e.g., in the case of a freshly prepared racemic cis-isomer mixture, the mixture of isomers of formula I is suitably dissolved in an organic amine base at ordinary temperature.

t · *

Crystallization can conveniently be carried out at ordinary temperature. "J iii below this and, when higher temperatures are used to bring the cls-isomer mixture to solution in an organic amine base, crystallization is preferably carried out by cooling the solution at ordinary temperature or below this.

The optimum temperatures for crystallization and evaporation are generally in the range of 0 to 20 ° C. Suitably, crystallization is initiated by pelleting with several 1: 1 crystals of a mixture of IR cls S- and IS cls R-isomers of compounds of formula I.

It will be appreciated by the skilled artisan that the evaporating organic amine base can be easily condensed and collected in a known manner for reuse.

The product of the processes of the invention will always contain more than 50% by weight. IR cls of the S- and IS cls of the R-isomers, and under the condition that the evaporation rate of the organic amine base was maintained to be satisfactorily low, and that the initial mixture of cls-isomers was optically inactive, the product may consist essentially of a completely 1: 1 mixture IR cls S- and IS cls P-isomers of compounds of formula I

Preferred organic amine bases contain 6 carbon atoms. It is smoked that triethylamine and diisonorpylamine are very effective organic amine bases. Of these, triotylamine is particularly preferred.

Although the presence of small amounts of water in the organic amine base can be tolerated, the amount of water should be less than 2% tougher. from the base, more preferably less than 0.5%, and dissolution, crystallization and evaporation are preferably carried out under substantially anhydrous conditions.

It will be appreciated that the most accessible starting material for the purposes of the invention will be a racemic mixture of all four clB-isomers of the compounds of formula I, although the process is equally applicable to starting materials containing nc-racemic cis-isomer mixtures.

- 6 The product of the process of the invention contains a large amount of the posticidal most active isomer of the corresponding compound of formula I. Ptonalak also extends to a mixture of cls-isomers of the compound of formula I containing the predominantly IR cis S- and IS cis R-isomers whenever made by the process of the invention. suppresses pesticide preparations comprising said mixture together with a suitable carrier therefor, as well as a pest control process at a site comprising administering to the site an effective amount of said mixture or a preparation containing said mixture. The composition of suitable pesticidal preparations is described in the previously cited Π.K. Patent Application to Mo. 1,413,491.

The invention will be further understood by the following Examples, of which Examples 1 and 2 will relate to the implementation of the process of the invention and Examples 3 and 4 refer to tests that are indicative of the suitability of organic amine systems for use in the pc3 step of the invention. Examples 1 to 3 were thrown under substantially anhydrous conditions, and the water content of triethylamine was 0.1¾ w / w.

Example 1 g of a mixture of the cis 9-Isomer alpha-c ± yano-3-phenoxybenzyl-3- (2,2-dichlorovinyl) -2,2-dimethylcyclopropanecarboxylate, in which the weight of 3 IS cis S- and IR cis R Isomers according to 1 P The S-1 IS cis iz -isomers were 2: 1, dissolved in 20 ml of triethylamine with heating at 60 to 70 ° C.

- ¹

The solution was allowed to cool to ordinary temperature with stirring, and pelleted with several crystals of a lil ^ mixture of IR cia S - I IS cis Risomers of alpha-cyano-3-phenoxybenzyl-3- (2,2-dichlorovinyl) -2. 2-dimethylcyclopropanecarboxylate. Stirring was continued for 40 hours at ambient temperature and the triethylamine was then separated at 20 ° C for a period of one hour leaving 10 g of dry solid material, m.p. 65-77 ° C, which was shown by gas-liquid chromatography to be 98.9% pure mixture of the Cls-isomer of the alpha-cyano-3-phenoxybenzyl-3- (2,2-dichlorovinyl) r

Ί

2,2-dimethylcyclopropanecarboxylate and toSnoir. high performance chromatograph to contain 20 wt. parts of IS cis S- and IR cis R-lzoner 1 80 wt. parts of the IR cis S- and IS cic R-isomers.

v

Example 2 g of a mixture of Cls-isomers of alpha-cyano-3-phenoxybenzyl-3- (2,2-dichlorovinyl) -2,2-dinethylcyclopropanecarboxylate, in which the weight ratio of IS cis S- and IR cis Ri z one to IR cis The S- and IS cis of R-isomers were 1: 1, dissolved in 30 ml of triethylamine with boiling at 60 dc at 70 ° C. The solution was allowed to cool to ordinary temperature with stirring, and pelleted with several crystals of lt1 mixture of IR cis S- and IS cis R-isomers alpha [alpha] -cyanc-3-phenbenzibenzyl-3- (2,2-dichlorovinyl) 0 -2,2-dimethylcyclopropanecarboxylate. After stirring for a further 42 hours at ordinary temperature, a gentle stream of nitrogen conducts the oe through the solution to evaporate the triethylamine. the solid residue, which was essentially dry for 24 hours, was transferred to a round bottom balloon and washed with 20 ml of 60/80 petroleum ether. Steaming to dryness at 50 ° C yields 14.S5 g of dry solid, m.p. 78-81 ° C, which has been shown to have a high performance liquid chromatograph with a zskb of more than 90% by weight. 1: 1 mixtures of IR cis Si IS cis of R-isomers of alpha-cyano-3-phenoxybenzyl-3- (2,2-dichlorovinyl) -2,2-dimethylcyclopropanecarboxylate.

Example 3

For the purpose of comparison, several racial organic amines were used as the base-solvent system in the following test procedure. 5.0 g of a mixture of the cis-isomer of alpha [alpha] -cyano-3-f enoxybenzyl-3- (2,2-dichlorovinyl) -2,2-dimethyl cyclopropanecarboxylate, in which the weight ratio of IS cis S- and IR is cis The IR cis of S- and IS cis by R-isomers was 2: 1, dissolved in ml of organic amine aa by heating (not more than € 0 ° C). The resulting solution was allowed to cool to ordinary temperature aa by stirring, plating a few crystals of 1: 1 mixture of IR cis S-1 IS el R-isomers r

And alpha-cyano-3-phenoxybibenzyl-3- (2,2-dichlorovinyl) -2,2'-dimethylcyclo..J propanecarboxylate. The I-faching is continued overnight and the solution is then further treated, analine, etc. but a breast need. The results are given in Table I which aLedi. Analyzes of solutions and end-products were performed by high performance perfomers. In cases where crystallization did not occur at ordinary temperature, the solutions were cooled to -10 ° C in order to attempt crystallization.

* TABLE I

Test Ko. Organic amine Comment i triethylamine Light crystallization. After 2 days of stirring, the precipitate was filtered off and dried to give 2.0 g of 98% pure 1: 1 mixture of IR cls S- and IS cls R isomers. The filtrate contained an essentially racemic mixture of cis-isomers. Not at night Detect starting material. ii dii2opropilaain Light crystallization. After 2 days of stirring, the precipitate was filtered off and dried to give 2.0 g of 98% pure 1: 1 mixture of IR cls S- and IS cia of the R-isomer. The filtrate contained essentially a racemic cla-izc — era. Friday · about 5% decomposition of the starting material was observed. iii tri-n-propylamine Crystallization slows. After stirring over the weekend, the precipitate was filtered off, washed with 60-80 petroleum ether and dried to give 3.3 σ of crystalline material having essentially the same composition as the starting material iv tri-n-butllarain Legan crystallization. After mixing over

on the weekends, the precipitate is filtered, washed with edbtVapetto ^ etethtaliooguzAthal ^ ala having essentially the same composition as the starting material <5

I

v diethylamine No crystallization. The cache is given for 2 days at -1Q ° C, however there is no crystallization. After 1 day, about 20% of starting material was started. you nghexilanin No crystallization. Rapid decay of starting material is reported. vii npbuti Your name is lamin Noma crystallization, even after 5 days. After 1 day, about 50% decay of the starting material is observed. viii N-cyclohexylraotyl- amine There is no crystallization even after three days. After three days, about 50% decay of starting material is observed. ix N-Cyclohexyl zontopilamine No crystallization after 3 days. Very little decay of starting material. It's a solution remained essential racemskl with garbage cls-iso- raera. X ethylcyclopropyl- anin Rapid crystallization. After stirring over the weekend, the taiog was filtered and dried to give 3.0 g of crystalline material having essentially the same composition as the starting material. xi K, N-dimethylaniline No crystallization. xii 2, £ -lutidine Messia of crystallization. No decomposition of the starting material was detected. Isonemes 3 starting material composition unchanged.

Example 4

Experiments were conducted to estimate the effect of the presence of water in the base-solution systemS using the procedure of Example 3. In each case, the base-solvent was triethylamine. The results are given in Table II below.

”10 -

TABLE II

Test Mo. % water in triethylamine Comment (w / w) i 0.10 see Table I ii 2 Light crystallization. After 2 days stirring, the precipitate was filtered and dried to give 0.9 g 98% Pure 1: 1 mixtures of IR cla S- and 15 cis P.-iso- nera. The filtrate contained the essential racerase cis-isomer mixture. iii 5 No crystallization Even after 5 days.

»

Dos.73679 K 1817 YUG 08/19/1986 P-1051/81

THE APPLICANT'S STATEMENT OF THE BEST KNOWLEDGE METHOD FOR THE ECONOMIC USE OF THE APPLICATION FORMED and 1R cis R-isomers according to 1 R cis S- and 1S cis R-isomers was 1: 1, dissolved in 30 ml of triethylamine with heating at 60 to 70 ° C. The solution was allowed to cool to ordinary temperature with stirring, and pelleted with several 1: 1 crystals of a mixture of 1R cis S- and 1S cis-R-isomers of alpha-cyano-3-phenoxybenzyl-3- (2,2-dichlorovinyl ) Of 2,2-dimethylcyclopropane carboxylate. After stirring for a further 42 h at ambient temperature, a gentle stream of nitrogen was passed through the solution to evaporate the triethylamine. the solid residue, which was essentially dry after 24 h, was transferred to a round bottom balloon and washed with 20 ml of 60/80 petroleum ether. Evaporation to dryness at 50 ° C yields 14.85 g of dry solid material tt78-8l ° C, which is demonstrated by high performance liquid chromatography with more than 90% by weight of a mixture of 1R cis S- and 1S cis R-isomers alpha -cyano-3-phenoxybenzyl-3- (2,2-dichlorovinyl) -2,2-dimethylcyclopropanecarboxylate.

SHELL INTERNATIONALE RESEARCH MAATSCHAPPIJ B.V., represented by: -

f

Dos.73679

P-1051/81

K 1817 YUG 03/30/1987, - / 2-

Claims (3)

PATENT REQUIREMENTS: A process for the preparation of a mixture of cis-isomers of cyclopropanecarboxylic acid ester derivatives of the formula: 1 2 in which R and R are both chlorine, which comprises 1R cis S- and 1S cis R-isomers, kneading 1S cis S- and 1R cis R-isomers of compounds of formula I, alone or dissolved in triethylamine or diisopropylamine in the presence of 1R cis S- and 1S cis R-isomers 60-70 ° C, which is a 1: 1 mixture of 1R cis S- and 1S cis-R isomers crystallized from the resulting cis-isomer solution of formula (I), and the amine is evaporated, 2. The process of claim 1, wherein the dissolution, crystallization and evaporation are carried out under anhydrous conditions. A process according to claims 1-2, characterized in that crystallization and evaporation are carried out at a temperature of 0-20 ° C.