CS257093B1 - Catalyst of epimerization of α-cyanobenzyl esters of carboxylic acids - Google Patents

Abstract

The epimerization catalyst of -cyanobenzyl esters of carboxylic acids of general formula I, where R represents a carboxylic acid residue with at least one asymmetric carbon and where X and Y represent a hydrogen atom or a halogen atom, consists in the fact that its effective catalytic component is an alkali metal fluoride or ammonium fluoride, optionally fixed on an inorganic support.

Description

The present invention relates to a catalyst for the epimerization of alpha-cyanobenzyl esters of formula I, wherein R is a carboxylic acid residue with at least one asymmetric atom and wherein X and Y are hydrogen or halogen, the configuration being changed at the benzylic carbon marked by an asterisk .

Epimerization is defined as a configuration change at one asymmetric center of a compound containing at least two asymmetric atoms / E. L. Eliel Stereochemistry of Carbon Compounds, page 39, McGraw-Hill, New York 1962].

It is known that some of the compounds of formula I exhibit biological activity, particularly insectioid activity. Furthermore, it is known that the biological activity of the individual stereoisomers of a compound of formula I is often very different (see, e.g., Pestic.). Sci. 1980, 11, 202].

Therefore, in order to achieve an enhanced biological effect, it is preferable to prepare only a particular stereoisomer or a combination of stereoisomers of a compound of formula I. To achieve this goal, the process of epimetizing the compounds of formula I on benzylic carbon is also used.

Pat. 1,599,876 /.

The epimerization of the compounds of the formula I takes place only in the presence of catalysts.

Various bases selected from ammonia, amines, alkali and quaternary hydroxides, alkali carbonates, alkoxides, amides, hydrides, ion exchangers, talc and bentonite have been used as catalysts (see, e.g., EP 0 036 775, Fr. Pat. 2,375,161 /. However, their catalytic action is not always entirely satisfactory. A disadvantage of some of the catalysts of this group is the low activity, allowing to work only at impractically elevated temperatures (e.g. alkali carbonates, talc, bentonite. When working with other catalysts of this group, undesirable side reactions (hydrolysis, aminolysis, re-esterification, etc.) often occur, making the isolation difficult and reducing the yields of the desired products.

The above-mentioned disadvantages are overcome by the novel alpha-cyanobenzyl ester epimerization catalyst according to the invention, characterized in that the active ingredient is an alkali metal fluoride or ammonium fluoride, optionally fixed on an inorganic carrier.

The epimerization of the compounds of the formula I proceeds smoothly even at 0 ° C, without undesirable side reactions.

The catalyst according to the invention makes it possible to influence the product composition of the emiperlization reaction by selecting conditions. In one method of using the catalyst of the invention, both the starting and the resulting stereoisomers of the compound of formula (I) exist during epimerization in one phase and are not precipitated from solution or solution. from melt. The epimerization in this embodiment results in a mixture of stereoisomers in which diastereoisomers of differing configuration on benzyl carbon are present in a ratio corresponding to thermodynamic equilibrium. This thermodynamic ratio can usually be changed only to a small extent by the choice of temperature or solvent.

In another method of using the catalyst according to the invention, epimerization is carried out under conditions characterized in that one or more stereoisomeric components of the compound of the formula (I) formed during epimerization are gradually eliminated from the solution or from the melt in the form of crystals. The resulting composition of the stereoisomeric mixture then does not correspond to the equilibrium ratios valid in the single-phase system, and can be influenced very fundamentally by the choice of solvent, its amount and temperature in individual cases.

The catalyst of the invention may be advantageously applied in the epimerization of compounds of formula I wherein the carboxyl radical R is a cyclopropanecarboxylic acid radical of formula II wherein z is an alkyl or alkenyl radical of 1 to 5 carbon atoms optionally substituted with 1 to 4 halogen atoms.

This class of compounds of formula (I) is known to have some stereoisomers having an absolute S configuration at the benzyl carbon having a much higher insectioid activity than the corresponding diastereoisomers having an absolute R configuration at this carbon.

By the epimerization carried out in the presence of a catalyst according to the invention, it is possible to transform a less active isomer or a less active mixture of diastereoisomers into a more effective diastereoisomer or a more effective diastereoisomer mixture.

The above operation is particularly suitable for compounds of formula I in which the residue R has the structure of formula II, wherein the absolute configuration of the cyclopropane ring is IR, 2R or IR, 3S.

The catalyst according to the invention can be used in a very wide weight range, but preferably in the range of 0.1 to 10 weight percent. After emiperization, the catalyst can be separated into products by conventional isolation procedures and reused in the next catalytic cycle.

The use of a catalyst according to the invention is illustrated by the following non-limiting examples.

He did

QR, 3R, alpha-10-.alpha.-cyano-3-phenoxybenzyl-2,2-dimethyl-3 (dichlorvinyl) -cyclopropanecarboxylate of formula I wherein R = II, X = Y = H, Z = 2,2, 2- dichlorvinyl /.

g of the ester of formula I [1R, 3R, alpha-R, S 16.5 ° (10%, benzene)] is dissolved in 40 ml of isopropyl alcohol and 2 g of freshly overburdened potassium fluoride is added. The mixture was stirred at 0 ° C for 120 hours, then cooled to -5 ° C and the precipitated crystalline solid was filtered off with suction. It is washed with ice-cold isopropyl alcohol and air-dried. There was thus obtained the ester I of the .beta.1R, 3R .alpha.-alpha configuration. 60 ° C, = + 34 ° (1, chloroform).

Example 2

A mixture of? 1R, 3R, alpha-sj, and [1S, 3S, alpha-R] esters of formula I wherein R, X, Y, Z have the same meaning as in Example 1.

The procedure is as in Example 1, but starting from a mixture of all four possible isomers having the cis, [1R, 3R, alpha-s], [1R,

3R, alpha1], [1S, 3S, afla-sj] and [1S, 3S, afla-Ø]. It was isolated as described in Example 1 to give an almost quantitative yield of mixtures of [? 1R, 3R, alpha-s] and [1S, -3S, alpha-R1 esters I, m.p. 80 ° C.

Example 3

The procedure of Example 2 was followed using only 1/10 of potassium fluoride, i.e. 0.2 g. The yield after 3 days at room temperature was better than 98%.

Example 4

Comparison of fluoride activity of various cations for epimerization of an ester of formula I wherein R = II, X = Y = H, z = 2,2-dichlorvinyl, a mixture of all isomers with the cis position of substituents at the 1 and 3 positions of the cyclopropane ring.

0.416 (1 mmol) of enantiomeric pair of 1R, 3R, afla-s] and [1S, 3S, alpha-Rj ester of the formula I were weighed, where R, X, Y are as defined above and dissolved in 0.82 ml of isopropyl alcohol . The amount and type of catalyst as well as the% epimerization after 48 hours at room temperature are shown in the table.

Cat. Amount % epimerization nBu ^ NF 1 mmol of solution ³ 68% NH ₄ F 37 mg 80% NaF 42 mg 7.0% KF 58 mg 96%

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

Example 5

Epimerization of a mixture of esters of formula (I) wherein R = 11, X = Y = H, Z = 2,2-dichlorvinyl, the 1R, 3R, alpha-sj and pLS, 3Salpha1, 3 configuration by the action of various solid support supported catalysts.

The reaction was carried out with 0.1 g of a 1: 1 mixture of the two isomers of the ester of formula I in 3 ml and of toluene toluene in the presence of 0.1 g of basic alumina or anchored catalyst. The following table shows the results of epimerization, whereby the thermodynamic equilibrium was measured, ie the representation of all cis-isomers at the 1 and 3 positions in virtually the same ratio of 1: 1: 1: 1.

Effective Cat. /% / Temperature Epimerization time none 25 to 80 no response 100 16 hours

KD / 1 * / 25 8 days

Example 6 [1R, 3R, alpha-.alpha.-.Alpha.] -. Alpha.-cyano-3-phenoxybenzyl-3- (2,2-dibromvinyl) -2,2-dimethylcyclopropanecarboxylate / 1, R = II, X = Y = H, Z = 2,2-dibromvinyl].

2g of a mixture of esters of formula I wherein R = formula II, X = Y = H, and Z-2,2-dibromvinyl having the [[IR, 3R, alpha-s] and [1R, 3R, af and la-R] configurations D = + 14 ° (1%, benzene), is dissolved in 5 ml of isopropyl alcohol in the presence of 0.4 g of annealed KF. After stirring for 12 hours at room temperature, the crystalline product is filtered off with suction, washed with cold isopropanol and air-dried. Obtained practically quantitatively kofigurace ester [lR, 3R, alpha-s] _t m.p. 100 ° C, R 20

J = + 25 ° (1, chloroform).

Example 7 R, 3R, alpha-sj and [ls, 3S alpha-Rj isomers of alpha-cyano-3-phenoxybenzyl-3- / 2-chloro-3,3,3-? -trifluoroprop-1-en-1-yl (2,2-dimethylcyclopropanecarboxylate), 1, R = 11, X = Y = H, Z = (Z-2-chloro-3,3,3-trifluoroprop-1-ene) 1-yl //.

Mixture of stereoisomers of formula I with the configuration [IR, 3R, alpha-sj, [[1R, 3R, alpha-R], [1S,

3S, alpha-s] and [1S, 3S, alpha-R], (20 g) are dissolved in 50 isopropanol. 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 sucked off after cooling to -5 DEG C., washed with isopropanol and air-dried. This gives 19 g (95%) of a mixture of esters of formula I wherein R, X, Y and,

Z have the foregoing meaning of the [1R, 3R, afla-S] and [1S, 3S, alpha-R] configurations, m.p. Mp 49-50 ° C.

Example 8 R, 3R, alpha-.alpha.-.Alpha.-alpha-cyano-3-phenocy-4-fluorobenzyl-2,2-dimethyl-3- (2,2-dichlorvinyl) -cyclopropanecarboxylate (1, R = II, X = 4) -F, Y = H, Z = 2,2-dichlorvinyl).

g of the ester of formula I wherein R, X, Y and Z have the afore said meanings, configuration £ lR, 3R, alpha- / R, S /] exhibiting [jéťj ²⁰ - + 7.5 ° / c = 2.0 The chloroform is dissolved in 25 ml of isopropanol, 0.8 g of potassium fluoride is added and the mixture is stirred at 20 DEG C. for 40 hours, then cooled to 0 DEG C., the product is filtered off with suction, washed and dried. lR, 3R, alpha-sj weighs 9.86 g / 98.6% /, having mp 50-52 ° C for about £ ^ / _ ² θ / c = 0, chloroform /.

Example 9

A mixture of [s] -alda-cyano-3-phenoxybenzyl-S-2- (4-chlorophenyl) -isomalerate and its [r] - [r] isomer. (Ester of formula I, R = 2, (4-chlorophenyl) isovalerate, X = Y = H).

[rs] -α-cyano-3-phenoxybenzyl-RS -2- (4-chlorophenyl) -isovalerate (commercial name Fenvalerate), containing all four possible isomers in a ratio of 1: 1: 1: 1, 50 g (purity 98%) Dissolve in 100 ml of isopropyl alcohol, add 1 g of freshly calcined potassium fluoride and stir at -10 ° C for 12 hours. The precipitated crystals are filtered off with suction, washed with isopropanol and dried. The product is a mixture of an ester of formula I wherein R, X, Y, Z are as defined above, with a [sj - [sj and [R_] - [r] configuration of 22 g (44%) in a 1: 1 ratio . The mother liquors are reacted again.

Example 10

A mixture of R 1, R 3, alpha-R 3, and R 15, 3 R, alpha-R 3 esters of formula I wherein R = II, X = Y = H and Z = 2,2,2-trichloroethyl.

4.18 g (20 mmol) of a mixture of all cis isomers of the ester of formula (I), wherein R, X, Y, Z are as defined above, are dissolved in 8.3 ml of isopropyl alcohol and 0.4 g of freshly burned potassium fluoride is added. The mixture is stirred under the conditions of Example 1 and isolated as described therein.

The above mixture of isomers is obtained in a yield of 80%.

Claims (2)

A catalyst for the epimerization of alpha-cyanobenzyl carboxylic acid esters of the general formula I, wherein R represents a carboxylic acid residue with at least one asymmetric carbon and wherein X and Υ are hydrogen or halogen, characterized in that the active catalyst component is an alkali metal fluoride or ammonium fluoride. 2. Catalyst according to claim 1, characterized in that the active ingredient is fixed on an inorganic carrier.