KR850001176B1 - Process for preparing cyclopropane carboxylic acid ester derivatives - Google Patents

Abstract

The 1(R)-cis-(S) [C(1) of cyclopropane ring and benzylic C atom and 1(S)-cis-(R) isomers of esters I (R1 and R2 independently are Cl, Br, Me) were sepd. by recrystn. from dialkylamines (both alkyl groups are branched) and tertiary amines; the isomers sepd. are useful as pesticides. A mixt. of 1(S)-cis-(S)-I (R1=R2=Cl) [1(S)-cis-(S)-II , 1(R)-cis-(R)-II, 1(R)-cis-(S)-II, and 1(S)-cis-(R)-II was dissolved in Et3N at 60-70≰C, the soln. was stirred at room temp., and seeded The Et3N was removed by a stream of N1 and the residue was worked up to give a 1:1 mixt. of 1(R)-cis-(S)-II and 1(S)-cis-(R)-II.

Description

Method for preparing cyclopropane carboxylic acid ester derivative

The present invention relates to a method for preparing a cyclopropane carboxylic acid ester derivative having an insecticidal action.

The general structural formula of the cyclopropane carboxylic acid ester derivative is as follows, and it is known to be an insecticidal compound if it is possible to see examples of British Patent No. 1,413,491 or US Patent No. 4,024,163.

菊劑)라고 부르는 살충력이 있는 화합물에 속한다. 구조식 I의 화합물에는 두개의 비대칭 중심이 시클로프로판 고리의 산성성분에 있고 세번째 비대칭 중심은 알코올 성분중에 있어서 모두 8개의 가능한 이성질체가 존재한다.In the above formula, R ¹ and R ² are each a chlorine, bromine or methyl group. These derivatives are usually from

It belongs to a compound with insecticidal properties called iii). In the compound of formula I, two asymmetric centers exist in the acidic component of the cyclopropane ring and the third asymmetric center has all eight possible isomers in the alcohol component.

In general, excellent insecticidal properties are described in Itaya et al, Synthetic Pyrethroids, Acs Symposium Series 42, p. 45-54, cis-coordination around the cyclopropane ring, the most insecticidal isomers according to Elliot et al. [Elliott et al, Nature, Vol. 248. P. 710-711, (1974)] isomers represented by the 1R cis S-isomer, which is a coordinating isomer represented by 1R cis- in acidic components and an S-coordination in alcoholic components.

To provide a 1R cis S-monoisomer by a synthetic route that uniquely produces an intermediate with a cyclopropane carboxylic acid component with only 1R cis-coordination, the horn separates the 1R cis-compound from the 1S cis-compound. By a path comprising an optical splitting step. The esterification of 1R cis-intermediates to prepare derivatives of formula I results in the mixing of the final product of 1R cis 1R cis S-.

Since 1R cis R- and 1R cis S-compounds are not enantiomers, separation of these final products is possible, at least theoretically, by physical means. However, the separation of 1R cis R- and 1R cis S-compounds can be relatively easy when R ¹ and R ² are both bromine atoms, e.g. when R ¹ and R ² are both chlorine atoms. The case turned out to be much more difficult and expensive.

We have found a single economical way to increase the content of the 1R cis S-isomer in a mixture of sit-isomers having the structure I.

The present invention provides a mixture of 1S cis S- and 1R cis R-isomers, which are compounds of formula I, alone or in the presence of 1R cis S- and 1S cis R-isomers, having 5-7 atoms and having two side chain alkyl groups. Dissolved in an organic amine base such as a secondary amine or a tertiary amine, and a 1: 1 mixture of 1R cis S- and 1S cis R-isomers is determined from a solution of the cis-isomer of Structural Formula I in the organic amine base. The present invention relates to a process for preparing a cis-isomer mixture having the following structure consisting mainly of 1R cis S- and 1S cis R-isomers by evaporating off the organic amine base.

In the above formula, R ¹ and R ² are each a chlorine, bromine or methyl group. It is preferable that both R ¹ and R ² be chlorine or bromine atoms, but both are preferably chlorine atoms.

The organic base causes racemization at the α carbon atom in the alcohol component of the compound of formula (I), so that the cis-isomer mixture of formula (I) in the organic base solution is a total of four cis in the organic base solution, assuming that the initial mixture is optically inert. A racemic solution of isomers, that is, a solution containing the same amount of isomers such as 1R cis S-, 1S cis S-, 1R cis R- and 1S cis R-. However, suitable organic amine bases for use in the process of the invention are solvents in which the enantiomeric pairs of 1R cis S- and 1S cis R- in the isomers of Formula I are less soluble than the enantiomeric pairs of 1S cis S- and 1R cis R. It has properties as.

In the process of the invention, the solution tends to be depleted of the 1R cis S- and 1S cis R-isomers as the 1: 1 mixture of 1R cis S- and 1S cis R-isomers is crystallized out of the cis-isomer solution. . This tendency is offset because the organic amine base has the effect of making the cis-isomer mixture a racemic mixture of the total four cis-isomers.

Thus, as the 1: 1 mixture of 1R cis S- and 1S cis R-isomers are removed from the solution by crystallization, the 1R cis S- and 1S cis R-isomers are further produced by racemization.

Continuing with the process, a 1: 1 mixture of crystallized 1R cis S- and 1S cis R-isomers and 1R cis S- and 1S cis R-isomers are saturated and equal amounts of 1R cis S- and 1S cis R- Final equilibrium is achieved between the solutions containing the isomers.

In the process of the present invention this final equilibrium is broken when the organic amine base is removed by evaporation.

The evaporation causes the remaining solution to be more concentrated and eventually combines the above crystallization and racemization until all organic amine bases have evaporated.

As will be appreciated by those skilled in the art, the exact isomer content in the product depends on the balance between crystallization rate, racemization rate and evaporation rate. Both of these rates vary with temperature. The rate of evaporation also varies with pressure.

When some or all of the starting material is crystalline, the compounds of formula I allow the 1S cis S- and 1R cis R-isomers to dissolve completely, the isomeric mixture of formula I is dissolved in organic amine base at elevated temperature, i. It is better to set the temperature in the range of 60-70 ° C. If necessary, the resulting solution is filtered and crystallized by removing solid particles from the solution. However, if the starting material is an oily state, i.e. a racemic mixture of newly prepared cis-isomers, it is preferable to dissolve the isomeric mixture of formula I in organic amine base at room temperature. Crystallization is preferably performed at room temperature or below room temperature, and when the temperature is high enough to dissolve the cis-isomer mixture in a solution of an organic amine base, the solution is preferably cooled to room temperature or below room temperature to crystallize. The optimum temperature range for crystallization and evaporation is usually 0-20 ° C. Crystallization can be conveniently initiated by inoculation using several crystals of a 1: 1 mixture of the 1R cis S- and 1S cis R-isomers in the compound of formula I.

As can be seen from the conventional method, the organic amine base to be evaporated can be easily condensed, collected and used again by a known method.

Among the products produced by the process according to the invention, the 1R cis S- and 1S cis R-isomer content is usually 50% by weight and the evaporation rate of the organic amine base is kept sufficiently low and the initial mixture of cis-isomers is optically inert. This product is usually in the form of a complete 1: 1 mixture of 1R cis S- and 1S cis R-isomers in the compound of formula (I).

Among the suitable organic amine bases are six carbon atoms. Treethylamine and diisopropylamine were found to be extremely effective as organic amine bases. Among them, triethylamine is particularly preferable.

It can be said that even if a small amount of water is present in the organic amine base, the amount of water should be 2% by weight or less with respect to the base, but it should be 1% or less and 0.5% or less. In addition, dissolution, crystallization and evaporation are preferably carried out under an anhydrous state.

It can be seen that the most readily available starting material in the process of the present invention is a racemic mixture of all four cis-isomers of the compound of formula I, in which the starting material contains a non-racemic mixture of cis-isomers. The same applies to.

The product by the process of the invention contains a large proportion of the most insecticidal isomers of the compounds of formula (I). The present invention thus applies also to cis-isomer mixtures of compounds of formula I consisting primarily of 1R cis S- and 1S cis R-isomers, together with suitable carriers, pesticide compositions and compositions containing these mixtures or It also includes methods for administering effective amounts of mixtures to pest control in the area of interest. Suitable pesticide compositions are detailed in British Patent No. 1,413,491.

The present invention will be described in detail according to the embodiment. Examples 1 and 2 are specific examples of the present invention and Examples 3 and 4 are test examples relating to the suitability of organic amines for use in the method of the present invention. In Examples 1-3, triethylamine was carried out under an almost anhydrous state with a water content of 0.1% w / w.

Example 1

3- (2,2-dichlorovinyl) -2,2-dimethylcyclopropanecarboxylic acid α having a weight ratio of 1S cis S- and 1R cis R isomers to 1R cis S- and 1S cis R-isomers 2: 1. 10 g of a cis-isomer mixture of cyano-3-phenoxybenzyl was dissolved in 20 ml of triethylamine while heating to 60-70 ° C. Cool the solution to room temperature with stirring and 1 of the 1R cis S- and 1S cis R-isomers of 3- (2,2-dichlorovinyl) -2,2-dimethylcyclopropane carboxylic acid α-cyano-3-phenoxybenzyl : 1 The mixture was inoculated with several crystals. After stirring at room temperature for 40 hours, triethylamine was separated at 20 ° C for at least 1 hour to obtain 10 g of a dry solid having a melting point of 65-77 ° C. Gas-liquid chromatography of this material showed a 98.9% pure mixture of 3- (2,2-dichlorovinyl) -2,2-dimethylcyclopropane carboxylic acid α-cyano-3-phenoxybenzyl and was a high performance liquid. The results by high performance liquid chromatography showed 20 parts by weight of the IS cis S- and 1R cis R-isomers and 80 parts by weight of the 1R cis S- and 1S cis R-isomers.

Example 2

3- (2,2-dichlorovinyl) -2,2-dimethylcyclopropanecarboxylic acid α- with a weight ratio of 1S cis S- and 1R cis S-isomer to 1R cis S- and 1S cis R-isomer 1: 1. 15 g of the cis-isomer mixture of cyano-3-phenoxybenzyl was dissolved in 30 ml of triethylamine while heating to 60-70 ° C. The solution is cooled to room temperature with stirring and 1R cis S- and 1S cis R-isomer 1 of 3- (2,2-dichlorovinyl) -2,2-dimethylcyclopropanecarboxylic acid α-cyano-3-phenoxybenzyl: Inoculated with several crystals of 1 mixture. After stirring for another 42 hours at room temperature, nitrogen was slowly introduced into the solution to evaporate triethylamine. After 24 hours, the almost dried solid residue was transferred to a round bottom flask and washed with 20 ml of 60/80 petroleum ether. 14.85 g of a dry solid material having a melting point of 78-81 ° C. was evaporated to dryness at 50 ° C. and treated with high performance liquid chromatography to obtain 3- (2,2-dichlorovinyl) -2,2-dimethylcyclopropane carboxylic acid. The 1: 1 mixture of the 1R cis S- and 1S cis R-isomers of α-cyano-3-phenoxybenzyl contains at least 90% by weight.

Example 3

For comparison purposes, several different organic amines were used as base-solvent systems in the following manner. Ie 3- (2,2-dichlorovinyl) -2,2, -dimethylcyclopropanecarboxylic acid α having a weight ratio of 1S cis S- and 1R cis R-isomer to 1R cis S- and 1S cis R-isomer 2: 1. 5.0 g of a mixture of cis-isomers of cyano-3-phenoxybenzyl were dissolved (not to be more than 60 ° C) while heating in 10 ml of an organic amine. The prepared solution was cooled to room temperature with stirring and 1R cis S- and 1S cis R- of 3- (2,2-dichlorovinyl) -2,2-dimethylcyclopropanecarboxylic acid α-cyano-3-phenoxybenzyl Inoculated with several crystals of a 1: 1 mixture of isomers. After continuing stirring overnight, the solution was further processed and analyzed.

The results are shown in Table 1. The solution and the final product were analyzed by high performance liquid chromatography. When crystallization did not occur at room temperature, the solution was crystallized by cooling to -10 ° C.

TABLE 1

Example 4

Experiments were carried out to determine the effects of water present in the base-solvent system and evaluated according to the method of Example 3. In each case triethylamine was used as the base-solvent. The results are shown in Table 2.

TABLE 2

Claims (1)

The 1S cis S- and 1R cis R-isomer mixtures of the compounds of formula I, in the presence of 1R cis S- and 1S cis R-isomers, are secondary or tertiary amines having 5-7 carbon atoms and having two branched alkyl groups. Dissolved in phosphorus organic amine base and seeded with a crystal of a 1: 1 mixture of 1R cis S- and 1S cis R-isomers in a solution of the cis-isomer of formula I in the organic amine base and evaporating the Sykes organic amine base Thus, a process for preparing a mixture of cis-isomers of formula I consisting primarily of 1R cis S- and 1S cis R-isomers.

Where R is^Oneand R³Are each selected from chlorine, bromine or methyl groups.