CS264503B1 - Process for preparing enantiomeric pairs of .alpha.-cyanobenzyl esters of cyclopropanecarboxylic acids - Google Patents

Abstract

yl esters of cyclopropanecarboxylic acids (57) Z

Description

The present invention relates to a process for the preparation of enantiomeric pairs of cyclopropanecarboxylic acid α-cyanobenzyl esters of the general formula I, in which X and Y are hydrogen or halogen and in which Z represents a C 1 -C 5 alkenyl group substituted with 2 to 4 halogen atoms. In particular, the invention relates to a process for preparing enantiomeric pairs of formula I in the [αS, 1R, 3R; α-R, 1S, 3S] epimerization of an enantiomeric pair of the same formula in the [α-R, 1R, 3R] configuration; [alpha] -S, 1S, 3S]. Epimerization changes the configuration on the benzylic carbon designated by a in Formula I. The practical significance of this epimerization lies in the different insecticidal activity of said enantiomeric pairs. Indeed, it is known (see, e.g., M. Elliott, A.W. Farnham, N.J. Jones, D.M. Doderlund: Pestic. Sci. 9, 112, 1972) that enantiomeric pairs of the formula with the [α-S, 1R, 3R configuration]; α-R, 1S, 3S] exhibit insecticidal activity in orders of magnitude higher than the corresponding enantiomeric pairs of the [α-R, 1R, 3R] configuration; α-S, 1S, 3S].

It is known that epimerization of said enantiomeric pairs requires the presence of a catalyst. Until now, the catalysts used are ammonia, amines, alkali carbonates and hydroxides (see, e.g., Fr. Pat. 2,481,274, Fr. Pat. 2,481,275, Fr. Pat.

470 117). However, the action of these catalysts is not always entirely satisfactory. Some of the catalysts in this group exhibit low efficiency, allowing operation only at impractically high temperatures. When working with other catalysts of this group, side reactions (hydrolysis, aminolysis, etc.) are often used. There are also some difficulties in handling and separating these catalysts.

These disadvantages are overcome by a process for preparing enantiomeric pairs of the general formula (I) in the [α-S, 1R, 3R] configuration; α-R, 1S, 3S] according to the invention, characterized in that the enantiomeric pair of the general formula (I) is of the [α-R, 1R, 3R; α-S, 1S, 3S], either alone or in admixture with the corresponding product of formula (I) of the [α-S, 1R, 3R] configuration; α-R, 1S, 3S] is treated at a temperature of -10 ° C to 80 ° C with an alkali or ammonium fluoride optionally fixed to an inorganic carrier, optionally in an inert organic solvent.

The reaction proceeds smoothly, practically in quantitative yield. The process according to the invention can be carried out in two different ways. In the first process, epimerization is carried out under conditions where the products remain dissolved in the reaction medium. In this case, a mixture is formed comprising the enantiomeric pairs [α-S, 1R, 3R; αR, 1S, 3S] and [α-R, 1R, 3R; α-S, 1S, 3S] in equilibrium, thermodynamic ratio. This mixture should be separated into individual enantiomeric pairs by methods known per se (e.g., crystallization) and undesired enantiomeric pair [α-R, 1R, 3R; aS, 1S, 3S] should be returned to the next epimerization cycle.

In a second, more preferred procedure, epimerization is carried out under conditions wherein the enantiomeric pair [α-S, 1R, 3R; α-R, 1S, 3S] is gradually precipitated from the solution or melt in the form of crystals. In this process, with the appropriate choice of reaction parameters (e.g., amount and nature of solvent, temperature) and appropriate configuration, a practically quantitative yield of the desired enantiomeric pair can be obtained in a single epimerization cycle.

The epimerization according to the invention can be carried out in an inert organic solvent selected from the group of alcohols, ethers, nitriles, amides, sulfoxides and aromatic hydrocarbons, or it can also be carried out without solvent. In order to increase the catalytic activity in some solvents, it is advantageous to use an inorganic carrier of a large surface fluoride catalyst (e.g. alumina).

It is not necessary to start with the pure enantiomeric pair [α-R, 1R, 3R; α-S, 1S, 3Sj. It is preferred to start from a mixture of enantiomeric pairs [α-R, 1R, 3R; αS, 1S, 3S] and [α-S, 1R, 3R; α-R, 1S, 3S],

The preparation of the present invention is illustrated by the following non-limiting examples.

Example 1 [1R, 3R, α-S], and [1S, 3S, α-R] Ester I (X = Y = H, Z = 2,2-dichlorvinyl).

g a mixture of isomer I of the ester I having the cis configuration at positions 1 and 3 of the cyclopropane ring consisting of 20% isomer [1R, 3R, α-S1, 1S, 3S, aR] and 30% isomer [1R, 3R, α-RJ, 1S, 3S, aS] is dissolved in 40 ml of isopropyl alcohol and 2 g of freshly overburdened potassium fluoride is added. The mixture was stirred at room temperature for 20 hours, then cooled to -5 ° C and stirring was continued for a further 12 hours. The cold mixture was filtered off with suction, the crude crystalline substance was washed with ice-cold isopropanol and air-dried. This gave 19.6 g (98%) of ester I as an enantiomeric pair of [1R, 3R, α-S] and [1S, 3S, α-R] configuration, m.p. 80 ° C.

Example 2

The procedure of Example 1 was carried out except that only a tenth of 0.2 g was used in the catalyst. The yield after three days at room temperature was better than 98% by weight. Example 3

Comparison of fluoride activity of different cations for epimerization of ester I, mixture of all isomers with cis position of substituents at positions 1 and 3 of cyclopropane ring.

0.416 g (1 mmol) of ester I was weighed and dissolved in 0.82 ml of isopropyl alcohol. The amount and type of catalyst and% epimerization after 48 hours at room temperature are shown in the following table.

CS 264 503 Bl

Cat. amount % epimerization nBu ₄ NF 1 mmol of ³ 'solution 68% NH ₄ F 37 mg 80% NaF 42 mg 70% KF 58 mg 96%

^a) in this case, a commercially available solution of fluoride in tetrahydrofuran was several times from dry toluene and then used immediately for the reaction.

Example 4

Epimerization of a mixture of esters I of the [1R, 3R, α-S] and [1S, 3S, α-R] configurations by the action of various solid-supported catalysts (X = Y = H, Z-2,2-dichlorvinyl).

The reaction was carried out with 0.1 g of a mixture of both ester I isomers in 3 ml of absolute toluene in the presence of 0.1 g of basic alumina. Woelm, optionally with anchored catalyst. The following table shows the results of epimerization, with the aim of achieving thermodynamic equilibrium, that is to say the proportion of all isomers having the cis configuration at the 1 and 3 positions in practically the same ratio of 1: 1: 1: 1.

Effective Cat. (%) temperature epimerization time none 25-80 reacts

KF (1%) 25 8 days

Example 5 [1R, 3R, aS] and [1R, 3S, aR] isomers of α-cyano-3-phenoxybenzyl-3- (Z-2-chloro-3,3,3-trifluoroprop-1-en-1-yl) -2 2-dimethylcyclopropanecarboxylate (I, X = Y = H, Z = (Z-2-chloro-3,3,3-trifluoroprop-1-en-1-yl)).

1: 1: 1: 1 [1R, 3R, α-S], [1R, 3R, α-R], 1: 1: 1: 1 configuration of stereoisomers having cyclopropane at positions 1 and 3 The cis-ring configuration (20 g) was dissolved in 50 ml of isopropyl alcohol. In the presence of freshly calcined potassium fluoride (1 g), the mixture is stirred at room temperature for 36 hours, after which the precipitated crystals are suction filtered, washed with isopropanol and air-dried after cooling to -5 ° C. This gave 19 g (95%) of a mixture of esters I having the [1R, 3R, α-S] and [1S 3 S, α-R] configuration, 11.49-50 ° C.

Example 6 [1R, 3R, aS] and [1S, 3S, aR] -α-cyano-3-phenoxy-4-fluorobenzyl-2,2-dimethyl-3- (2,2-dichlorvinyl) cyclopropanecarboxylate (1, X = 4) -F, Y = H,

Z = 2,2-dichlorvinyl).

g of the isomeric mixture of esters I of configuration [1R, 3R, aP, S and 1S, 3S, aR, S] is dissolved in 20 ml of isopropyl alcohol, 0.8 g of calcined potassium fluoride is added and the mixture is stirred for 40 hours at 20 ° C The mixture is then cooled to 0 [deg.] C. and the product is filtered off with suction, washed and dried. The resulting mixture of [1R, 3R, aS] and [1S, 3S, a-R] configuration weighs 9.86 g (98.6%) ·

Example 7 [1R, 3R, α-S] and [1S, 3S, α-R] Ester I (X = Y = H, Z = 2,2-dichlorvinyl).

g of a mixture of ester I isomers of 60% enantiomeric pair [1R, 3R, cc-S] and [1S, 3S, α-Rj] and 40% enantiomeric pair [1R, 3R, aR 'and [1S, 3S, gS] is dissolved in 4 ml of isopropyl alcohol, 0.2 g of freshly over-heated KF is added and 1.95 g (98%) of ester I is obtained as enantiomeric pair [1R, 3R, aS] and [tS, 3S, and -RJ, 1.1. 80 ° C.

Claims (4)

A process for the preparation of an enantiomeric pair of the [αS, 1R, 3R: αR, 1S, 3S] α-cyano-3-phenoxybenzyl esters of the cyclopropanoic acids of the general formula 1 wherein X and Y are hydrogen or halogen and Z is alkenyl; 1 to 5 carbon atoms and in each case substituted with 2 to 4 halogen atoms, characterized in that the enantiomeric pair has the configuration [aR, 1R, 3R; α-S, 1S, 3S] of the general formula I, optionally in admixture with the product of configuration [α-S, 1R, 3R; The α-R, 1S, 3S] of the general formula I, in which X, Y and Z have the same meaning for both enantiomeric pairs, reacts at -10 to 80 ° C with an alkali or ammonium fluoride optionally fixed on an inorganic carrier, optionally in an inert solvent. 2. A process according to claim 1, wherein the enantiomeric pairs of the [alpha-R, 1R, 3R] configuration are treated; α-S, 1S, 3S] and [α-S, 1R, 3R; and R, 1S, 3S] of formula I, which are in a molar ratio of 4: 6 to 6: 4. 3. A process according to claim 1, wherein the inert solvent is an alcohol having a carbon number of 2 to 6. 4. A process according to claim 1, wherein the inert solvent is selected from the group of ethers, nitriles, amides, sulfoxides or aromatic hydrocarbons.