HU182994B - Process for producing optically active alpha-cyano-3-bracket-phenoxy-benzyl-bracket closed-2-bracket-4-chloro-phenyl-bracket closed-isovaleric acid derivatives - Google Patents

Abstract

A process for the preparation of (S) -2- (4-chlorophenyl) isovalerate of (R, S) -alpha-cyano-3-phenoxybenzyl containing a higher proportion of (S) -2- (4-chlorophenyl) isovalerate (S) -alpha-cyano-3-phenoxybenzyl which involves the crystallization of (S) -2- (4-chlorophenyl) isovalerate from (S) -alpha-cyano-3-phenoxybenzyl from a solution of (S) - 2- (4-chlorophenyl) isovalerate of (R, S) -alpha-cyano-3-phenoxybenzyl in a solvent, in the presence of a basic substance in order to raise the proportion of (S) -2- (4-chlorophenyl) ) (S) -alpha-cyano-3-phenoxybenzyl isovalerate in the porridge, and recovery of the product resulting from the crystallization together with the (S) -2- (4-chlorophenyl) isovalerate of (R, S) -alpha- cyano-3-phenoxybenzyl in mother liquors.

Description

The present invention relates to a process for the preparation of (S) -? - cyano-3- (phenoxybenzyl) -2- (4-chlorophenyl) isovalerate or a large amount of (S) -? - cyano-3- (phenoxybenzyl) -2. - (R, S) -α-cyano-3- (phenoxybenzyl) -2- (4-chlorophenyl) isovalerate containing (4-chlorophenyl) isovalerate.

The a-cyano-3- (phenoxybenzyl) -2- (4-chlorophenyl) isovalerate of formula (1), which is slightly toxic to mammals, has a broad spectrum insecticidal activity (see Japanese Patent Application 26425/74). (OPI) and U.S. Patent No. 3,996,244) contain two asymmetric carbon atoms and thus include four optical isomers.

Below is a-cyano-3- (phenoxybenzyl) -2- (4-chlorophenyl) formula (I) ·

-isovalerate to "fenvalerate";

- (R, S) -α-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate as "fenvalerate A";

- (S) -α-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate as "fenvalerate Aa";

- (R) -α-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate "fenvalerate Αβ";

- (S) -α-cyano-3- (phenoxybenzyl) - (R) -2- (4-chlorophenyl) isovalerate to "fenvalerate αα"; and

- (R) -α-cyano-3- (phenoxybenzyl) - (R) -2- (4-chlorophenyl) isovalerate is called "fenvalerate Ββ".

It has already been reported in the literature that the absolute configuration of the asymmetric carbon atom of the acid moiety is related to the insecticidal activity of the ester. The preparation of (S) -2- (4-chlorophenyl) isovaleric acid is also known.

From this compound an ester having potent insecticidal activity can be prepared [Miyakado et al. Agr. Bio. Chem. 39, 267 (1975)].

Miyakado et al. Have described a process for resolving α-isopropylphenylacetic acids into optically active isomers, and described that the insecticidal activity of phenylacetic acid esters depends on the optically active acid moiety in the molecule.

A 135,013/76. Japanese Patent Specification No. 6,011,125 mentions that the absolute configuration of the asymmetric carbon atom in the alcohol moiety is related to the insecticidal activity of the ester and also describes the preparation of esters having an optically active alcohol moiety. No. 99071/76. Japanese Patent Laid-open No. 6,255 (identical to U.S. Patent No. 825,507) discloses a process for the preparation of fenvalerate isomers containing an optically active alcohol moiety, whereby chromatographic analysis of fenvalerate A on silica gel separates fenvalerate Aa and fenvalerate Αβ. According to the method described in Japanese Patent Publication No. 135,013/76, optically active 3-phenoxy-mandelic acid can be obtained by optical resolution of 3-phenoxy-mandelic acid.

These procedures have proven to be satisfactory in laboratory experiments but are difficult to implement on an industrial scale.

Fenvalerate Aa is very good, having an insecticidal activity of about four times that of racemic fenvalerate (see Japanese Patent Application No. 99071/76, which is identical to U.S. Patent No. 25,825,507).

SUMMARY OF THE INVENTION The present invention relates to a process for the separation of crystalline fenvalerate Αα from fenvalerate A which does not require a process of isomerization catalyst ''); on the other hand, a process for the isomerization of optically active fenvalerate on an asymmetric carbon atom of the alcohol comprising dissolving the optically active fenvalerate in a proton-containing solvent or dissolving the optically active fenvalerate in a solvent in the presence of a basic catalyst.

According to the invention, fenvalerate A can be almost quantitatively converted to fenvalerate Αα if the fenvalerate Λβ-rich mother liquor which remains after separation of the fenvalerate Aa crystals is dissolved in solvent and phenvalerate A 40 on the asymmetric carbon atom in the alcohol moiety, isomerized in the presence or absence. The ratio of fenvalerate Aa to fenvalerate Αβ then returns to equilibrium and the mixture is then recrystallized. The use of process A 45 or the combination of processes A and B allows the fenvalerate Aa to be substantially completely separated from the fenvalerate Αβ.

The present invention also relates to a process comprising the above process A, wherein the crystallization of fenvalerate Aa is carried out in the presence of a basic catalyst (hereinafter "process C"). The basic catalyst causes isomerization of the asymmetric carbon atom of the alcohol moiety. When this catalyst 55 is added to the crystallization system of fenvalerate Aa, fenvalerate Αβ, which is present in the mother liquor in an amount greater than the equilibrium ratio, is converted to fenvalerate Αα as a result of isomerization. This transformation takes place on the asymmetric carbon atom of the alcohol moiety. In this way, more crystalline fenvalerate Αα is obtained than initially present. According to process C, from 100 parts of starting fenvalerate A to 70-90 parts of crystalline fenvalerate Aa can be prepared.

The present invention also relates to the production of fenvalerate A containing greater than 65 of fenvalerate Αα

182,994 so that the fenvalerate Αα obtained in process C is recovered together with the fenvalerate A present in the mother liquor (process. 2 hereinafter). Fenvalerate A, which is present in mother liquor obtained after filtration or otherwise by separation of crystalline fenvalerate Aa in process C. naturally contains fenvalerate Αα. in an amount approximately equal to half the amount of fenvalerate A present therein. Losses are reduced by re-glazing process C in fenvalerate A from the mother liquor recovered in process C, but this is not beneficial as the contamination is greater. In Method D, the crystalline fenvalerate Αα and the mother liquor are both recovered and thus the fenvalerate Αα present in the mother liquor can be effectively used. After crystallization, the mixture is simply concentrated, although there is a possibility that fenvalerate Aa is isomerized to fenvalerate A, since the catalyst is still in the system.

This possible conversion of the compound can be counteracted. for example, by inactivating the catalyst with an acidic material and then concentrating the mixture, although the inactivated catalyst remains in the final product.

If the catalyst, either active or inactivated, is insoluble, it can be removed by filtration. However, if the active or inactivated catalyst 25 is water soluble, it may be removed by adding a water immiscible solvent or a mixture of a water miscible and an immiscible solvent to the reaction mixture, and then washing the solution. Fenvalerate Aa can be used immediately after crystallization or only after inactivation of the catalyst.

According to Method D, fenvalerate containing from 45 to 50 parts fenvalerate Αα and 55 to 50 parts fenvalerate fen / 3 is almost quantitatively convertible in fenvalerate Aa to 35 rich fenvalerate A.

The use of seed crystals in Methods A C and D is not essential, but in the case of large scale production, inoculation of the reaction mixture with a crystal graft is desirable in order to effect crystallization smoothly. In continuous operation, the crystallization system does not always have to be seeded with crystal germ because crystals remain in the reactor.

The invention will now be described in detail.

_{(In our} studies aimed at preparing 45 of the fenvalerate isomers containing an optically active alcohol moiety, we have found that if fenvalerate Λα, fenvalerate B (3 or a mixture of the two is added to the solution of fenvalerate Λ crystalline seed, then selectively only fenvalerate Aa crystallizes.

For the crystallization of the above compound, no conclusions can be drawn from the properties of the racemic fenvalerate lamellae (viscous, oily substance) in the same way. as in the case of pyrethroid-type esters.

Fenvalerate Aa: mp 57.9 ° C, | ^a]: - (. In CHCl _3, c = 6.5) D '= 2.11 °;

Fenvalerate BW: m.p. 59.6 ° C.

[α] D ²⁵ = -12.5 ^; <In CHCIj.c = 3.8).

For example, it is a-cyano-3- (phenoxybenzyl) -2,2-dimethyl-3- (2,2-dichloro-vinyl) -cyclopropanecarboxylate. which is a pyrethroid-type ester and contains the same alcohol moiety as the above compound. no single type of ester is known in crystalline form, although these esters contain a 65 d-trans (R, 3S) acid moiety and an (S), (R) or racemic alcohol moiety. However, a 1: 1 mixture of an d-trans acid moiety and an ester containing an (R) alcohol moiety and an ester containing an 1-trans (IS, 3R) acid moiety and an (S) alcohol moiety (m.p. 0-76.8 ° C) and a 1: 1 mixture of an ester containing a d-trans acid moiety with an alcohol moiety (S) and an ester containing a 1-trans acid moiety and an alcohol moiety (R) (melting point 78). , 5-80 ° C) in crystalline form.

In the alpha-ethynyl-3- (phenoxybenzyl) -2- (4-chlorophenyl) isovalerate, which is a pyrethroid type ester with a very similar chemical structure to the above compound, it is known that the racemic acid moiety and the racemic alcohol moiety is a mixture of two diastereomers (each racemic) and an ester in crystalline form at room temperature which contains an optically active acid moiety. Recrystallization of the ester mixture containing the racemic acid moiety and the racemic alcohol moiety from hexane predominantly crystallizes a diastereomer having a melting point of 87-88 ° C and very insecticidal activity. The ester recovered from the mother liquor is a diastereomer (m.p. 51-52 ° C) with more potent insecticidal activity. However, by this method, no diastereomer can be obtained by selective crystallization from an ester containing an optically active acid moiety (m.p. 61-62 ° C).

In allethrin (alletronyl chrysanthemum), a long-known synthetic pyrethroid-type ester having four diastereomers, only one diastereomer ("crystalline allethrin") is known in crystalline form, which is a d-trans acid moiety and a 1-alcohol moiety. consists of an ester containing a moiety and an ester containing a 1-trans acid moiety and a d-alcohol moiety [see M. Matsui and I. Yamamoto, Natural Occuring Insecticides, M. Jacobson and DG Grosbv Eds., 38-42, Marcel Dekker , Inc., New York (1971.)). No enantiomorphic crystalline allethrin is known. which crystallizes by itself.

These facts show that it is impossible to say in advance about optical isomers or mixtures thereof, whether they can be prepared in crystalline form or sern, and if a particular optical isomer has already been produced as crystals. it is not even known whether the optical isomer can be selectively crystallized from a mixture of this optical isomer with another optical isomer.

The economical uses of the mother liquor obtained in the manufacture of fenvale 50 rate containing the optically active alcohol moiety were also studied and it was found that h; the optically active fenvalerate containing the alcohol moiety (in an unequal amount of R / S) is dissolved in a proton-containing solvent or a mixture of a proton-containing solvent and preferably a basic catalyst is added or dissolved in a proton-free solvent; the asymmetric carbon atom of the alcohol moiety is rapidly isomerized. It is generally believed that a nitrate of mandelic acid 60, such as said ester, is unstable in a proton-containing solvent or in the presence of a basic catalyst, and is expected to cleave the ester bond or decompose the nitrile group. However, in our studies, it has been found that, for the said ester, most of the air undergoes the desired isomerization.

-3182 994

Isomerization of optically active aliphatic nitrile in the presence of a basic catalyst has already been described in the literature (see J. Am. Chem. Soc., 1964, 86, 5457), but the esterification of esters such as those described above in solution has not yet been reported. .

It was also found that by adding a basic catalyst to the solution of fenvalerate A, the crystallization of fenvalerate Aa and the Αβ isomerization of fenvalerate were simultaneously occurring in the mother liquor, so that the production of fenvalerate Aa was very good.

Only solvents in which fenvalerate A is readily soluble and which dissolve fenvalerate Αα only in modest amounts can be used in process A. Examples of such solvents are lower alcohols containing from 1 to 6 carbon atoms, such as ethyl alcohol or methanol, aliphatic or alicyclic hydrocarbons such as pentane, hexane, heptane, cyclohexane and methylcyclohexane, or their derivatives. and mixtures of these solvents with aromatic hydrocarbons such as benzene, toluene and xylene or lower alcohols such as methanol or ethyl alcohol or mixtures of the aforementioned lower alcohols. Methanol is the most preferred solvent.

Examples of proton-free solvents that can be used in process B are aliphatic hydrocarbons such as pentane, hexane or heptane, alicyclic hydrocarbons such as cyclohexane or methylcyclohexane, aromatic hydrocarbons such as benzene, toluene or xylene, halogenated hydrocarbons. For example, chloroform, dichloromethane or carbon tetrachloride or proton-free polar solvents. such as ethyl acetate or acetone. Suitable proton-containing solvents include alcohols, such as ethyl alcohol, methyl alcohol or octyl alcohol, or mixtures thereof. Mixtures of proton-containing solvents with proton-free solvents may also be used. Preferred solvents are lower alcohols such as methyl alcohol or ethyl alcohol, solvent mixtures containing lower alcohols, aliphatic hydrocarbons such as pentane, hexane and heptane, alicyclic hydrocarbons such as cyclohexane and methylcyclohexane, and aliphatic mixtures of hydrocarbons with aromatic hydrocarbons such as benzene, toluene or xylene or other solvents. These solvents may also be used in combination of Processes A and B as described below. Of these solvents, methyl alcohol is particularly preferred. The use of a catalyst is not particularly necessary when a proton-containing solvent such as an alcohol is used, but isomerization is preferably carried out in the presence of a basic catalyst.

If the base used as the catalyst dissolves the optically active fenvalerate, a solvent is not always required.

The catalysts to be used may be selected from the following basic materials: nitrogenous bases, phosphorous bases, metal oxides, metal hydroxides, salts of metals with weak acids such as carbonic acid, silica or hydrogen cyanide and basic ion exchange resins. Preferred examples include ammonia; aliphatic amines such as methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine, n-pentylamine, diethylamine, di-n-propylamine, di-n10 butylamine, triethyl amine, tri-n-propylamine, tri-n-butylamine, cyclohexylamine and ethanolamine; aromatic amines such as aniline, 1-naphthylamine, 2-naphthylamine; quaternary ammonium salts such as tetramethylammonium hydroxide, tetraethylammonium hydroxide and tetra-n-propylammonium hydroxide; nitrogen-containing heterocyclic compounds such as pyridine, quinoline, pyrrolidine and piperidine; bases containing phosphorus such as triphenylphosphine and tri-n-butylphosphine; metal oxides such as calcium oxide, magnesium oxide, beryllium oxide, zinc oxide, silicon oxide, and aluminum oxide; metal hydroxides such as sodium hydroxide, potassium hydroxide, magnesium hydroxide and calcium hydroxide; metal salts of weak acids such as sodium carbonate, potassium carbonate, barium carbonate and potassium cyanide; talc; bentonite; said bases adsorbed on silica gel, alumina or activated carbon; and basic ion-exchange resins containing as basic group an amino or a quaternary ammonium group. Suitable examples of commercially available ion exchange resins include:

DOWEX 2 X 8 (a product of Dow Chemical Company, a highly basic ion exchange resin made from a styrene-divinylbenzene copolymer containing a quaternary ammonium group (NH 3 + OH)).

"AMBERLITE IR-45" [a product of Rohm and Haas Company, which is a N (R) ₂ exchange group. Weakly basic anion exchange resin containing NH (R) and NH ₂ groups].

"AMBERL1T IRA-93" (a product of the Rohm and Haas Company which is a weakly basic basic anion exchange resin (MR-type) containing -N (CH ₃ ) ₂ as exchange group).

"AMBERLIST A-21" [a product of the Rohm and Haas Company which is a weakly basic anion exchange resin (MR-type) containing -N (CH ₃ ) ₂ as the exchange group. which is useful when using non-aqueous solutions) and "AMBERLIST A-27" [a product of Rohm and Haas Company,

Highly basic anion exchange resin (OH-type) containing ³ groups. which is useful when using non-aqueous solutions].

Basic substances which are substantially insoluble in the solvents described above, in particular the basic ion exchange resins, are advantageous in that they are readily removed from the reaction mixture after the isomerization reaction. Instead of the above-mentioned basic catalysts, other materials may be used as catalysts without departing from the spirit of the invention.

According to the present invention, the catalyst can be added to the solution containing the fenvalerate A to be isomerized, or the solution containing the fenvalerate A is loaded on a column filled with said catalyst.

A temperature range in which the ester is not significantly degraded is suitable for the isomerization. Higher temperatures favor isomerization. Thus, an isomerization temperature range of from -50 ° C to the boiling point of the solvent is preferred, more preferably from -20 ° C to 150 ° C.

In Process B, the alcohol (S) / (CR) ratio of the alcohol moiety of the optically active fenvalerate may be any.

182,994

Fenvalerate Aa can advantageously be prepared by combining processes A and B as follows:

(1) adding fenvalerate Aa or fenvalerate Ββ seed crystals to the phenvalerate A solution or fenvalerate Ββ supersaturated with fenvalerate Αα, whereupon fenvalerate Aa crystallizes; (2) separating the fenvalerate Aa crystals obtained in step (1) from the mother liquor by suitable means such as filtration;

3. Isomerizing the mother liquor obtained in step (2) or fenvalerate A At-rich fenvalerate A obtained by concentrating the mother liquor as described above by dissolving the mother liquor in a proton-containing solvent such as a lower alcohol or a proton-containing solvent. dissolving or dissolving the mother liquor in the presence of a basic catalyst in the appropriate solvent;

4. preparing a supersaturated solution of the isomerized fenvalerate A in step (3) to treat this solution again according to the procedure described in step (1), for example by concentrating the supersaturated solution (i.e., distilling off the solvent), fenvalerate It can be prepared by adding the amount or by cooling the solution.

For solvents C and D, any solvent in which fenvalerate A is readily soluble and which dissolves fenvalerate Αα only in a modest amount can be used. Preferred solvents are lower alcohols such as methanol or ethyl alcohol and mixtures of lower alcohols. Suitable solvents include, for example, aliphatic hydrocarbons such as pentane, hexane or heptane, alicyclic hydrocarbons such as cyclohexane or methylcyclohexane, mixtures of these solvents, at least one of these solvents with one aromatic hydrocarbon, e.g. mixtures thereof with benzene, toluene or xylene and mixtures of these hydrocarbons (or mixtures thereof) with lower alcohols. Aromatic hydrocarbons and acetonitrile cannot be used on their own because they are highly soluble in fenvalerate Aa. Among the lower alcohols, methyl alcohol and ethyl alcohol are preferred, with methyl alcohol being most preferred. Methyl alcohol preferably has a water content of less than 5% by weight. Good results are not obtained with isopropyl alcohol or water-containing isopropyl alcohol.

The concentration of fenvalerate A in the solution is from 1 to 90% by weight in terms of yield of crystalline material and rate of crystallization. preferably 20-70% by weight. 50

Nitrogen-containing bases, phosphorus-containing bases, strong bases and basic ion-exchange resins can be used as basic catalysts. Examples of such basic materials include: ammonia: aliphatic amines such as methylamine. ethylamine, n-propylamine, n-butylamine, 55 n-pentylamine, diethylamine, di- (n-propyl) amine, di (n-butyl) amine, triethylamine, tri- (n-propyl) -amine, tri- (n-butyl) -amine. cyclohexylamine and ethanolamine; aromatic amines. thus, aniline, 1-naphthylamine and 2-naphthylamine; quaternary ammonium salts such as tetramethylammonium hydroxide. tetraethylammonium hydroxide and tetra- (n-propyl) ammonium hydroxide; nitrogen-containing heterocyclic compounds such as pyridine, quinoline, pyrrolidine and piperidine; phosphorus-containing bases such as triphenylphosphine and tri-n-butylphosphine; strong bases such as alkali metal 65 or alkaline earth metal hydroxides (i.e., sodium hydroxide or potassium hydroxide); alkali metal or alkaline earth metal alcoholates (i.e., sodium methylate or sodium ethylate); alkali metal or alkaline earth metal amides (i.e., sodium amide or magnesium amide) and alkali metal or alkaline earth metal hydrides (i.e., sodium hydride, potassium hydride or lithium aluminum hydride); and basic ion exchange resins (i.e., DOWEX 2X8 or AMBERLITIR-45).

Of these bases, it is preferable to use ammonia or amines for the production of crystalline material, most preferably ammonia and triethylamine.

Suitable amounts of catalyst are from about 0.01 to about 100 mol%, preferably from 0.1 to 50 mol%, based on the amount of fenvalerate A. A suitable isomerization temperature range for the yield of crystalline material and the rate of crystallization is from about -50 ° C to 50 ° C, preferably from -30 ° C to 15 ° C. It is preferred to stir the solution during isomerization, although this is not a basic requirement. Fenvalerate A used in Methods C and D may contain fenvalerate Αα and fenvalerate Αβ in any ratio.

The following examples further illustrate the invention, but do not limit the scope of the invention.

In these examples, the (R) and (S) isomers of the alcohol moiety were analyzed by gas chromatography under the following conditions:

Column: 10% Silicon DC-QF-1 3mm x 3.0m (Coated on Chromosorb AW-DMCS).

Column temperature: 245 ° C.

Evaporator cabin temperature: 250 ° C.

Nitrogen gas pressure: 2.0 kg / cm ²

Under the above reaction conditions, the retention time of the (S) isomer (fenvalerate Aa) is about 43 minutes and the retention time of the (R) isomer (fenvalerate Αβ) is about 38 minutes.

In the process, of course, the retention time of the esters containing the acid moiety (R) is the reverse, i.e. the retention time of the ester containing the alcohol moiety (fenvalerate Ba) is the same as the retention time of phenvalerate Αβ and ester (fenvalerate Ββ) is the same as that of fenvalerate Αα. so if. the ester containing the (R) acid moiety is present in a certain proportion in the fenvalerate A employed, the peak value of each of the isomers described above being approximately the same as the peak value of their enantiomorphic variant.

The optical purity of the acid moiety of fenvalerate A was determined by hydrogenation of fenvalerate A in ethyl alcohol using platinum oxide as the catalyst to give (S) -2- (4-chlorophenyl) isovacrylic acid. which was then converted to the acid chloride using thionyl chloride. The acid chloride was converted to 1-menthol ester with 1-menthol. The ratio of the two diastereoisomers thus obtained was determined by gas chromatography and the optical purity of the acid moiety was calculated.

Example 7

Fenvalerate A is used as starting material in which the alcohol moiety is 50.5% peak (R) isomer and 49.5% peak (S) isomer, and the acid moiety is 92.8% optical purity. -ancestor. (In the examples where not otherwise stated

182 994, the fenvalerate A used is of the same composition and optical purity as used herein.

As described in Example 1.)

Dissolve 5.0 g of the starting material in 5.0 g of ethyl alcohol and then crystallize (S) -α-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) as a crystalline germ (seed crystal). -isovalerate added. After allowing the mixture to stand at -6 ° C for 4 days, the precipitated crystals were collected by filtration. The filtered solid was washed three times with 2 mL of cold ethyl alcohol (0-5 ° C). This gave 1.27 g of crystalline material, m.p. 57.9 ° C, which was determined by gas chromatography (under the conditions described above for the alcohol moiety of the ester) to be 4% (R) isomer and 96% (S). ) isomer. The filtrate contained 65.5% of the (R) isomer and 34.5% of the (S) isomer according to gas chromatographic analysis in the same way.

Example 2

The procedure of Example 1 was repeated except that fenvalerate Ββ was used as the crystal germ to give 1.32 g of crystalline material. According to gas chromatography analysis of the alcohol fraction of the ester, 3% of the (R) isomer and 97% of the (S) isomer are present in the product.

Example 3

The procedure of Example 1 is repeated, except that 5.5 g of a 1: 5 mixture of benzenehexane is used in place of ethyl alcohol to give 0.62 g of crystalline material. According to gas chromatography analysis of the alcohol content of the ester, 2.7% of the (R) isomer and 97.3% of the (S) isomer are present in the product.

Example 4

The procedure of Example 1 was repeated except that 6 g of methyl alcohol was used in place of ethyl alcohol to give 1.78 g of crystalline material. According to gas chromatography analysis of the alcohol fraction of the ester, 4.5% of the (R) isomer and 95.5% of the (S) isomer are present in the product.

Example 5

Dissolve 5.18 g of fenvalerate A in 5.2 g of methyl alcohol and add 1 mg of fenvalerate Αα as a crystal germ and stir at 2-4 ° C for 1 day. The precipitated crystals are then combined by filtration. The solids on the filter were washed twice with 3 mL of cold hexane (0-5 ° C). Analysis of the crystalline product (1.48 g, 28.6% by weight of fenvalerate A) obtained as a product shows that 3.4% (R) isomer and 96.6% (S) isomer (The analysis is performed as described for the alcohol moiety of the ester). Fenvalerate recovered from the filtrate Analysis of the alcohol moiety contained 68.5% (R) isomer and 31.5% (S) isomer.

Example 6

The starting material used is fenvalerate Al 3, wherein the alcohol moiety is composed of 96.0% peak (R) isomer and 4.0% peak peak (S) isomer. The analysis was carried out by gas chromatography as described above.

Dissolve mg of fenvalerate banβ in 50 ml of ethyl alcohol and store in a glass container for 7 days. When a small portion of the solution thus obtained is analyzed by gas chromatography as described for the alcohol moiety in the ester, it is found that 53.1% of the (R) isomer and 46.9% of the (S) isomer are present. After distilling off the ethyl alcohol under reduced pressure, 48 mg of the isomerized ester is recovered.

Example 7

500 mg of fenvalerate Αβ, similar in composition to that described in Example 6, is dissolved in 50 ml of ethyl alcohol and the solution is left in a glass jar at 40 ° C for 2 days. It is then cooled to room temperature (i.e., 20-30 ° C, same as below), and a small portion of the solution is analyzed by gas chromatography as described in the alcohol fraction analysis of the ester in the solution, 72.1% (R) isomer and 27.9%. % (S) isomer is present. Concentration of the solution under reduced pressure gave 468 mg of the isomerized ester.

Example 8 mg of fenvalerate Αβ, similar in composition to that described in Example 6, was dissolved in 300 ml of ethyl alcohol and stored at -6 ° C for 30 days. A small portion of the solution is then subjected to gas chromatography analysis of the alcohol portion of the ester in the solution, showing the (R) isomer at 64% and the (S) isomer at 36%. After distilling off the ethyl alcohol under reduced pressure, 28 mg of the isomerized ester is recovered.

Example 9

200 mg of fenvalerate Aj3, similar in composition to that described in Example 6, was dissolved in 200 ml of ethyl alcohol and 20 mg of basic-type ion exchange resin (DOWEX 2X8, a trademark of Dow Chemical Company) was added as a catalyst. After 6 hours at 70 ° C, the solution was cooled to room temperature. A small portion is then analyzed by gas chromatography under the same conditions as the alcohol portion of the ester. In solution, the (R) isomer is present at a concentration of 54.3% and the (S) isomer is present in 45.7%.

The catalyst was removed by filtration and the ethyl alcohol was distilled off under reduced pressure to give 195 mg of the isomerized ester.

Example 10 mg of fenvalerate Αβ, similar in composition to that described in Example 6, was dissolved in 5 ml of methyl alcohol and 5 mg of base-type ion exchange resin (DOWEX 2X8) was added as a catalyst. After 6 hours at 60 ° C, the solution was cooled to room temperature and a small portion analyzed by gas chromatography as described for the alcohol portion of the ester in solution. Analysis showed that the (S) isomer was present at 20.1% and the (R) isomer at 79.9%.

The catalyst was removed by filtration, the methyl alcohol was distilled off under reduced pressure to give 48 mg of the isomerized ester.

182,994

Example 11

100 mg of fenvalerate Aj3, similar in composition to that described in Example 6, was dissolved in 100 mg of n-butyl alcohol and then 10 mg of basic type ion exchange resin (DOWEX 2X8) was added as a catalyst. The mixture was heated at 70 ° C for 6 hours. The solution is then cooled to room temperature and a small portion is analyzed by gas chromatography under the same conditions as the alcohol portion of the ester in the solution. The (S) isomer is present in the solution at a concentration of 26.4% and the (R) isomer is 73.6%.

The catalyst was removed by filtration and the n-butyl alcohol was distilled off under reduced pressure to give 94 mg of the isomerized ester.

Example 12

300 mg fenvalerate Αβ of the same composition. as described in Example 6, dissolved in 300 ml of ethyl alcohol and 30 mg of anhydrous potassium carbonate as catalyst. The mixture was heated at 70 ° C for 6 hours. The solution is then cooled to room temperature and a small portion is analyzed by gas chromatography under the conditions described for the alcohol portion of the ester in the solution. In solution, the (R) isomer is present at a concentration of 55.19 and the (S) isomer is 44.9%. The solution was neutralized by adding a solution of 109% ethyl acetate in acetic acid corresponding to the amount of anhydrous potassium carbonate added to the A0 solution of fenvalerate. The ethyl alcohol is then distilled off under reduced pressure and the residue is dissolved in 20 ml of benzene. The solution was washed with water (2 x 5 mL) and the benzene phase was concentrated under reduced pressure. 280 mg of isomerized ester are recovered.

Example 13

The procedure of Example 12 was repeated, except that 30 mg of sodium bicarbonate was used as the catalyst instead of anhydrous potassium carbonate. GC analysis showed that the alcohol portion of the ester contained 68.0% (R) isomer and 32.0% (S) isomer. 288 mg of the isomerized ester can be recovered.

Example 14

210 mg fenvalerate Α / 3 of the same composition. As described in Example 6, 1.90 g of ethyl alcohol was dissolved. The solution was allowed to flow through a column containing 1.5 mL of a basic type ion exchange resin in ethyl alcohol (AMBERLIT IR-45), which is a trademark of Rohm and Gaas Company, for 1.5 hours. fresh ethyl alcohol was passed through the column and the eluates were combined and analyzed by gas chromatography under the same conditions as the alcohol portion of the ester. The solution contained the (R) isomer 64.39 and the (S) isomer 35.79. concentration.

The combined eluate solution was concentrated under reduced pressure to give 202 mg of the isomerized ester.

Example 75

The procedure of Example 14 was repeated, except that a solution of 108 mg of ester in 10 g of ethyl alcohol was used. After the isomerization, the analysis of the ester alcohol radical analysis shows that the (R) isomer is present in 56.7% and the (S) isomer in 43.8%. 103 mg of the ester can be recovered.

Example 16

The procedure described in Example 9 is repeated except that 20 mg of active alumina (a product of Wako Junyaku Co., Ltd. for chromatography) is used as the catalyst instead of the basic type ion exchange resin. After the isomerization, the analysis described for the alcohol moiety of the ester shows that the (R) isomer is present in 61% and the (S) isomer in 39%. 192 mg of isomerized ester can be recovered.

Example 17 mg of fenvalerate Af5, similar in composition to that described in Example 6, was dissolved in a 9: 1 mixture of benzene / ethyl alcohol (200 mg) and 5 mg of ion exchange resin (AMBERLIT IRA-93 from Rom and Haas Company). trademark of one of your products). The mixture was allowed to stand at 70 ° C for 6 hours. The solution is then cooled to room temperature and a small portion is analyzed by gas chromatography under the conditions described for the alcohol portion of the ester in the solution. In solution, the (R) isomer is present at a concentration of 72.4% and the (S) isomer is present in 27.6%.

The catalyst was removed by filtration and the solvent was distilled off under reduced pressure to recover 47 mg of the isomerized ester.

Example 18

104 mg fenvalerate Aj3, of the same composition. as described in Example 6. Dissolve 0.94 g in ethyl alcohol and pass this solution through a glass column filled with 20 ml of a basic type ion exchange resin (AMBERLITE IRA-93) in ethyl alcohol for 10 minutes.

After 50 hours, fresh ethyl alcohol (50 ml) was passed through the column, and the eluates were combined and analyzed by gas chromatography under the conditions described for the alcohol portion of the ester. The combined eluate contains 52.59 (R) isomer and 47.59 (S) isomer. Concentration of the eluate under reduced pressure gave 101 mg of the isomerized ester.

Example 19 z '1 mg of fenvalerate Αβ, similar in composition to that described in Example 6, was dissolved in 800 mg of benzene followed by 20 mg of the basic type ion exchange resin (AMBERL1ST A-21, Rohm and Haas Company) as catalyst. product trademark). The mixture was heated at 70 ° C for 6 hours. The solution is then cooled to room temperature and a small portion is analyzed by gas chromatography under conditions similar to those of the solution.

-7182 994 for the alcohol moiety. Analysis showed that the (R) isomer was present at a concentration of 72.4% and the (S) isomer at 27.6%.

The catalyst was removed by filtration and the benzene was distilled off under reduced pressure to give 194 mg of the isomerized ester.

Example 20

200 mg of fenvalerate Αβ, similar in composition to that described in Example 6, was dissolved in 200 mg of ethyl acetate and then 20 mg of anhydrous potassium carbonate was added as a catalyst. The mixture was heated at 60 ° C for 6 hours. The solution is then cooled to room temperature and a small portion is analyzed by gas chromatography as described for the alcohol portion of the ester present. The solution contains 85.5% of the (R) isomer and 14.5% of the (S) isomer.

The catalyst was removed by filtration, and ethyl acetate was distilled off under reduced pressure to give 197 mg of the isomerized ester.

Example 21

100 mg of fenvalerate Αβ, similar in composition to that described in Example 6, was dissolved in 400 mg of ethyl acetate and 10 mg of base-type ion exchange resin (AMBERLITE IRA-93) was added as catalyst. The mixture was heated at 60 ° C for 6 hours. The solution is then cooled to room temperature and a small portion is analyzed by gas chromatography under the conditions described for the alcohol portion of the ester present. The solution contains 73.8% (R) isomer and 26.2% (S) isomer.

The catalyst was removed by filtration and the ethyl acetate was distilled off under reduced pressure to give 98 mg of the ester.

Example 22

100 mg fenvalerate Αβ of the same composition. as described in Example 6, dissolved in 400 mg nhexane, and 10 mg of the strongly basic type ion exchange resin (AMBERLIST A-27, a trademark of Rohm and Haas Company) was added as a catalyst. The mixture was heated at 60 ° C for 6 hours. The solution was then cooled to room temperature and a small portion analyzed by gas chromatography under the same conditions as described for the alcohol portion of the ester present. Analysis showed that the solution contained 52.4% of the (R) isomer and 47.5% of the (S) isomer.

The catalyst was removed by filtration, and the n-hexane was distilled off under reduced pressure to give 94 mg of the isomerized ester.

Example 23 mg of fenvalerate Αβ, similar in composition to that described in Example 6, was dissolved in 200 mg of dichloromethane and 5 mg of a strongly basic type ion exchange resin (AMBERLIST A-27, OH-type) was added as a catalyst. The mixture was heated at 40 ° C for 6 hours. The solution was then cooled to room temperature and a small portion analyzed by gas chromatography under the same conditions as described for the alcohol portion of the ester present.

The solution contains 62.4% of the (R) isomer and 37.6% of the (S) isomer.

The catalyst was removed by filtration and dichloromethane was distilled off under reduced pressure to give 47 mg of the isomerized ester.

Example 24

250 mg of fenvalerate Αβ, similar in composition to that described in Example 6, is dissolved in 2.25 g of benzene and this solution is a strongly basic type ion exchange resin (AMBERLIST A-27, OH type) as catalyst in 2 hours. containing a glass column. The column was eluted with 150 mL of benzene and eluted for 4 hours. The combined eluates were analyzed by gas chromatography under the conditions described for the alcohol moiety of the ester. The product contains 52.5% of the (R) isomer and 47.5% of the (S) isomer.

Concentration of the eluate under reduced pressure yields 246 mg of isomerized ester.

Example 25

2.59 g of fenvalerate Αβ, similar in composition to that described in Example 6, is dissolved in 5.2 g of ethyl alcohol and 52 mg of triethylamine is added as catalyst. The mixture was allowed to stand at room temperature for 1 day. The sample taken from the solution is then analyzed by gas chromatography under the same conditions as described for the alcohol portion of the ester. Analysis showed that the solution contained 54.5% (R) isomer and 45.5% (S) isomer.

After distilling off the ethyl alcohol and triethylamine under reduced pressure, 2.52 g of isomerized fenvalerate A are recovered.

Example 26

To the filtrate obtained in Example 1, 0.35 g of basic type ion exchange resin (DOWEX 2X8) was added as a catalyst and the mixture was heated at 70 ° C for 6 hours. The solution is then cooled to room temperature and a small portion is analyzed by gas chromatography under the conditions described for the alcohol portion of the ester. The solution contains 51.8% of the (R) isomer and 48.2% of the (S) isomer.

The catalyst was removed by filtration and the ethyl alcohol was distilled off under reduced pressure, and the distillation was continued until the weight of the solution was 7.5 g. To the concentrate was added 1 mg of crystalline fenvalerate Αα as a crystal germ and the mixture was allowed to stand at -5 ° C for 3 days. The precipitated crystals are then combined by filtration. The solids on the filter were washed three times with 0.5 g of cold (0-5 ° C) ethyl alcohol to give 0.46 g of crystalline product, which according to gas chromatography analysis of the alcohol portion of the ester gave At a concentration of 9% and the (S) isomer

Contains 96.1%.

Example 27

An ethyl alcohol solution of the ester, similar in composition to that described in Example 26 (10% concentration: 30 g total solution), was allowed to flow through a column of 100 mL of water for 5 hours. Catalyst in ethyl alcohol

It is filled with 182,994 basic-type ion exchange resins (AMBERLITE IR-45). The column was then eluted with 30 g of fresh ethyl alcohol for 3 hours.

The eluates are combined and the sample taken is analyzed by gas chromatography. According to the analysis carried out under the same conditions as described for the alcohol portion of the ester, the eluate contained 55.3% of the (R) isomer and 44.7% of the (S) isomer.

The eluates were concentrated under reduced pressure to a residual solution of 10 g. To the concentrate was added 4.2 g of fresh fenvalerate A and the mixture was heated to dissolve fenvalerate A. The resulting solution was cooled to room temperature and 10 mg of crystalline fenvalerate erα was added as a crystal germ. The mixture was allowed to stand at -6 ° C for 2 days. The precipitated crystals are then combined by filtration and the filter cake is washed twice with 1.0 g of cold ethyl alcohol (0-5 ° C). This gives 1.02 g of crystalline product which, according to the analysis for the alcohol portion of the ester, contains 3.9% of the (R) isomer and 96.1% of the (S) isomer.

Example 28

Dissolve 5.0 g of fenvalerate A in 5.5 g of benzene / n-hexane (1: 5 by weight) and add 1 mg of crystalline fenvalerate Αα as a crystal germ. The mixture was allowed to stand at -6 ° C for 4 days. The precipitated crystals are then combined by filtration and the filter cake is washed three times with 2 ml of cold n-hexane each time. 0.62 g of crystalline product is obtained, in which the (R) isomer is present in a concentration of 2.7% and the (S) isomer is present in a concentration of 2.7.3% as determined by analysis of the alcohol content of the ester.

0.35 g of a strongly basic type ion exchange resin (AMBERLIST A-27, OH type) was added to the filtrate as a catalyst and the mixture was allowed to stand at 60 ° C for 6 hours. The solution is then cooled to room temperature and a small portion is analyzed by gas chromatography under the conditions described for the alcohol portion of the ester. Analysis showed that the (R) isomer was present in the solution at a concentration of 52.8% and the (S) isomer at a concentration of 47.2%.

The catalyst was removed by filtration and the solvent was distilled off under reduced pressure to a residual weight of 10 g. To the concentrate was then added 1 mg of fenvalerate Αα as a crystal germ, and the mixture was allowed to stand for 3 days at -5 ° C, and the precipitated crystals were combined by filtration and the filter material was washed three times with 0.5 g of cold (0-5 ° C). ), washed with hexane. 0.28 g of crystalline product is obtained in which the (R) isomer is present in a concentration of 3.9% and the (S) isomer is present in a concentration of 96.1%, according to the analysis described for the alcohol portion of the ester.

Example 29

An ester of the same composition as a

In Example 28, the first filtrate was dissolved in benzene / n-hexane (10% concentration; total solution 30 g) and allowed to flow through a glass column over 100 hours, eluting with 100 ml of a highly basic benzene catalyst. type ion exchange resin (AMBERLIST A-27, OH type). The column was then eluted with 30 g of fresh benzene for 3 hours.

The eluates are pooled and a sample of the combined eluate is analyzed by gas chromatography. According to the analysis carried out under the same conditions as described for the alcohol portion of the ester, the (R) isomer is present in the eluate at 53.3% and the (S) isomer at 46.7%. The solvent was distilled off under reduced pressure and 3.5 g of a 1: 5 mixture of benzene / n-hexane was added to the residue. The mixture is heated to 40 ° C to dissolve the residue in the benzene / n-hexane mixture. The resulting solution was cooled to room temperature and 10 mg of crystalline fenvalerate Αα was added as crystalline salt. The mixture was allowed to stand at -6 ° C for 4 days. The precipitated crystals are then combined by filtration and the solids on the filter are washed twice with 1.0 g of cold (0-5 °) hexane. 0.35 g of crystalline product is obtained, in which the (R) isomer is present in a concentration of 3.9% and the (S) isomer is present in a concentration of 96.1%, according to the analysis described for the alcohol portion of the ester.

Example 30

Dissolve 5.82 g of fenvalerate A in 11.6 methyl alcohol, add 1 mg of crystalline fenvalerate Αα as a crystal germ, add 120 mg of triethylamine as catalyst, and stir at 2-4 ° C for 2 days. The precipitated crystals were then combined by filtration and the solids on the filter were washed twice with 5 mL of cold (0-5 ° C) hexane. This gives 4.61 g of crystalline product (79.3% by weight based on fenvalerate A used) in which the (R) isomer at a concentration of 1.4% and the (S) ) isomer at a concentration of 98.6%. Fenvalerate A recovered from the filtrate showed 51.09c (R) isomer and 49.0% (S) isomer in alcohol analysis.

Example 31

Phenvalerate A (6.78 g) was dissolved in methanol (6.8 g), followed by addition of 1 mg of crystalline fenvalerate Aa as a crystal germ and 68 mg of triethylamine as catalyst, and the mixture was stirred overnight at 2-4 ° C. The precipitated crystals are then combined by filtration and the filter cake is washed twice with 5 ml of cold (0-5 ° C) hexane. This gives 5.91 g of crystalline product (fenvalerate A used)

87.2% by weight) of which the analysis of the alcohol portion of the ester showed 2.0% (R) isomer and 98.0% (S) isomer.

Example 32

7.22 g of fenvalerate A is dissolved in 7.2 g of methanol, followed by addition of 1 mg of crystalline fenvalerate Αα as a crystal germ and 43 mg of n-propylamine as catalyst, and the mixture is stirred at 2-4 ° C for one day. . The precipitated crystals are then combined by filtration and the solids on the filter are washed twice with 5 ml of cold (0-5 ° C) hexane. This gives 5.57 g of crystalline product (77.2% by weight of fenvalerate A used) in which the ester alk

Analysis for Hol-9182 994 showed 4.4% (R) isomer and 95.6% (S) isomer.

Example 33

6.49 g of fenvalerate A are dissolved in 6.5 g of methanol, followed by addition of 1 mg of crystalline fenvalerate Aa as a crystalline germ and 47 mg of diethylamine as catalyst, and the mixture is stirred at 2-4 ° C for 1 day. The precipitated crystals are then combined by filtration and the solids on the filter are washed twice with 5 ml of cold (0-5 ° C) hexane. This gives 4.84 g of crystalline product (74.6% by weight of fenvalerate A used), which according to the analysis for the alcoholic portion of the ester is 2.3% (R) isomer and 97.7% (S). ) isomer is present.

Example 34

Fenvalerate A (7.36 g) was dissolved in ethyl alcohol (7.4 g), followed by addition of 1 mg crystalline fenvalerate Aa as a crystal germ and 74 mg triethylamine as catalyst, and the mixture was stirred at 2-4 ° C for 1 day. The precipitated crystals are then combined by filtration and the solids on the filter are washed twice with 3 ml of cold (0-5 ° C) hexane. This afforded 3.04 g of crystalline product (41.3% of fenvalerate A used) in which the (R) isomer at 4.0% and the (S) ) isomer is present at a concentration of 96.0%.

Example 35

7.70 g of fenvalerate A are dissolved in 7.7 g of methanol, followed by addition of 1 mg of crystalline fenvalerate Aa as a crystal germ and 200 mg of triphenylphosphine as catalyst. This mixture was stirred at 2-4 ° C for 1 day and the precipitated crystals were collected by filtration. The solids on the filter were washed twice with 3 mL of cold (0-5 ° C) hexane. 3.60 g of crystalline product (46.8% of the fenvalerate A used) are obtained, which product is found to have an (R) isomer at a concentration of 3.4% and ( S) at a concentration of 96.6%.

Example 36

Phenvalerate A (6.64 g) was dissolved in methanol (6.6 g), followed by addition of 1 mg of crystalline fenvalerate Αα as a crystal germ, 62 mg of aniline as catalyst, and the mixture was stirred at 2-4 ° C for 1 day. The precipitated crystals are then combined by filtration and the solids on the filter are washed twice with cold (0-5 ° C) hexane. This gives 2.99 g of crystalline product (45.1% of the fenvalerate A used) which, according to the analysis of the alcohol moiety of the ester, is 2.9% (R) isomer and 97.1% (S). contains isomer.

Example 37

Dissolve 7.85 g of fenvalerate A in 7.2 g of methanol, add 1 mg of crystalline fenvalerate Aa as a crystal germ, and add 0.71 g of 10% methyl alcohol in tetramethylammonium hydroxide as catalyst. Stir at -4 ° C. The precipitate was then collected by filtration and the solids on the filter were washed twice with 3 mL of cold (0-5 ° C) hexane. This gave 4.05 g of crystalline product (51.6% of the fenvalerate A used) which, according to the analysis of the alcohol moiety of the ester, was 3.8% (R) isomer and 96.2% (S). contains isomer.

Example 38

Dissolve 40.00 g of fenvalerate A in 80 g of methanol, add 1 mg of crystalline fenvalerate Aa as a crystal germ and add 2.00 g of triethylamine as catalyst, and stir at -6 ° C for 1 day. The precipitated crystals are then combined by filtration and the solids on the filter are washed twice with 20 ml of cold methanol (0-5 ° C). This gives 33.36 g of crystalline product (83.4% of the fenvalerate A used), which according to the analysis for the alcohol portion of the ester is 2.3% (R) isomer and 97.7% (S). contains isomer.

Example 39

Dissolve 40.00 g of fenvalerate A in 40 g of methanol, add 1 mg of crystalline fenvalerate Aa as a crystal germ, and add 0.40 g of triethylamine as a catalyst and stir at -6 ° C for 3 days. The precipitated crystals are then combined by filtration and the solids on the filter are washed twice with 20 ml of cold methanol (0-5 ° C). This gave 35.82 g of crystalline product (89.6% of the fenvalerate A used) which, according to the analysis of the alcohol moiety of the ester, contained 2.5% of the (R) isomer and 97.5% of the (S) isomer. .

Example 40

Dissolve 10.00 g of fenvalerate A in 10 g of methanol, add 1 mg of crystalline fenvalerate Aa as a crystal germ, and 0.10 g of pyridine as catalyst, and stir at -6 ° C for 1 day. The precipitated crystals were then collected by filtration and the solids on the filter were washed twice with 5 ml of cold methanol (0-5 ° C). This gives 4.36 g of crystalline product (43.6% of the fenvalerate A used) which, according to the analysis for the alcoholic part of the ester, is 3.0% (R) isomer and 97.0% (S). contains isomer.

Example 41

Dissolve 10.00 g of fenvalerate A in 20 g of methanol and then add 1 mg of crystalline fenvalerate Aa as a crystal germ and 0.20 g of a 40% aqueous solution of methylamine in the catalyst. After stirring for 1 day at -6 ° C, the precipitated crystals are combined by filtration and the solids on the filter are washed twice with 5 ml of cold (0-5 ° C) methanol. This gave 8.52 g of crystalline product (85.2% of the fenvalerate A used) which, according to the analysis of the alcohol content of the ester, was 2.3% (R) isomer and 97.7% (S). contains isomer.

Example 42

Dissolve 40.00 g of fenvalerate A in 80 g of methanol, add 1 mg of crystalline fenvalerate Aa as a crystal germ, and add 0.48 g of 28% aqueous ammonia as a catalyst and keep at -6 ° C for 1 day. stirring at temperature. The precipitated crystals are then combined by filtration and the solids on the filter are washed twice with 20 ml of cold methanol (0-5 ° C). 33.20 g of crystalline product are obtained (m.p. 101)

182,994 (83.0%) of fenvalerate A) containing 2.3% of the (R) isomer and 97.7% of the (S) isomer according to the analysis for the ester alcohol moiety.

Example 43

Dissolve 10.00 g of fenvalerate A in 10 g of methanol, add 1 mg of crystalline fenvalerate Aa as a crystal germ, and 0.10 g of ethylenediamine as catalyst, and stir at -6 ° C for 1 day. The precipitated crystals are then combined by filtration and the solids on the filter are washed twice with 5 ml of cold (0-5 ° C) methyl alcohol. This gives 8.12 g of crystalline product (81.2% of fenvalerate A used), which is 2.6% (R) isomer and 97.4% (S) according to the analysis for the alcoholic portion of the ester. contains isomer.

Example 44

100.00 g of fenvalerate A are dissolved in 200 g of methanol. then 1 mg of crystalline fenvalerate Αα as a crystal germ and 3.00 g of triethylamine as a catalyst are added and the mixture is stirred at -13 ° C for one day. The precipitated crystals are then combined by filtration. and the solids on the filter were washed twice with 50 ml of cold methanol (0-5 ° C). This gave 84.21 g of crystalline product (84.2% by weight of fenvalerate A used) containing 3.0% of the (R) isomer and 97.0% of the (S) isomer according to the analysis described for the alcohol portion of the ester.

Example 45

Dissolve 10.00 g of fenvalerate A in 10 g of methanol and then add 1 mg of crystalline fenvalerate Aa as a crystal germ and 0.10 g of triethylamine as a catalyst. The mixture was stirred at 12 ° C for 1 day. The precipitated crystals were then collected by filtration and the solids on the filter were washed twice with 5 mL of cold (0-5 ° C) methyl alcohol. 7.43 g of crystalline product are obtained (74.3% by weight of fenvalerate A used). containing 1.2% of the (R) isomer and 98.8% of the (S) isomer according to the analysis described for the alcohol portion of the ester.

Example 46

40.00 g of fenvalerate A are dissolved in 60 g of methanol, followed by 10 mg of crystalline fenvalerate Aa as a crystal germ. and 1.95 g of a methyl alkobol in which ammonia is dissolved (ammonia content: 8.3% by weight) are added as a catalyst and the mixture is stirred for one day at -6 [deg.] C. The precipitated crystals are then combined by filtration and the solid on the filter was washed twice with 20 ml of cold methanol (0-5 ° C) to give 34.56 g of crystalline product (86.4% by weight of fenvalerate A used), which was the alcohol portion of the ester. analysis showed 2.3 '' (R) isomer and 97.7% (S) isomer.

Example 47

40.00 g of fenvalerate A are dissolved in 80 g of methylcyclohexane. then 10 mg of fenvalerate Αα as a crystal germ and 9.8 g of methanol in ammonia (8.3 wt.% ammonia) as catalyst were added and the mixture was stirred for 1 day at -6 ° C. The precipitated crystals were then collected by filtration and the solids on the filter were washed twice with 20 ml of cold (0-5 ° C) methylcyclohexane. 31.40 g of crystalline product (78.5% by weight of fenvalerate A used) are obtained, which according to the analysis of the alcohol fraction of the ester is 1.4% (R) isomer and 98.6% (S) contains isomer.

Example 48

Dissolve 40.00 g of fenvalerate A in 10 g of toluene and 70 g of heptane, then add 10 mg of crystalline fenvalerate Αα as a crystal germ and 9.8 g of methanol in ammonia (8.3% by weight) as catalyst. and the mixture was stirred at -6 ° C for one day. The precipitated crystals are then combined by filtration and the solids on the filter are washed twice with 20 ml of cold (0-5 ° C) heptane. 31.72 g of crystalline product (79.3% by weight of fenvalerate A used) are obtained, which according to the analysis of the alcohol portion of the ester is 2.2% (R) isomer and 97.8% (S). ).

Example 49

Dissolve 40.00 g of fenvalerate A in 60 g of methanol, add 10 mg of crystalline fenvalerate Aa as crystal germ, and 38 mg of sodium hydroxide in 1 g of methanol as catalyst, and stir at -6 ° C for 1 day. The activated crystals are then combined by filtration and the solids on the filter are washed twice with 20 ml of cold methanol (0-5 ° C). 23.84 g of crystalline product (59.8% by weight of fenvalerate A used) are obtained, which according to the analysis of the alcohol portion of the ester is 2.8% (R) isomer and 97.2% ( S) contains an isomer.

Example 50

Dissolve 40.00 g of fenvalerate A in 60 g of methanol, add 10 mg of crystalline fenvalerate Αα and add 47 mg of sodium cyanide as a catalyst in 2 g of methyl alcohol. The mixture was stirred at -6 ° C for one day. The precipitated crystals are then combined by filtration and the solids on the filter are washed twice with 20 ml of cold methanol (0-5 ° C). 22.8 g of crystalline product (57.2% by weight of fenvalerate A used) are obtained, which according to the analysis of the alcohol moiety of the ester contains 2.2% of the (R) isomer and 97.8% of the (S) isomer.

Example 57

40.00 g of fenvalerate A (in which the alcohol moiety is present at 51.0% (R) isomer and 49.0% (S) isomer and in which the acidity of the acid moiety is 82.0%) dissolved in alcohol, 10 mg of crystalline fenvalerate Αα was added as a crystal germ and 0.8 g of triethylamine as a catalyst were added and the mixture was stirred at -6 ° C for one day. The precipitated crystals are then combined by filtration and the solids on the filter are washed twice with 20 ml of cold methanol (0-5 ° C). This gives 21.36 g of crystalline product (53.4% by weight of fenvalerate A used), which according to the analysis for the alcoholic portion of the ester is 2.5% (R) isomer and 97.5% (S). ).

-11182 994

Example 52

Dissolve 40.00 g of fenvalerate A in 60 g of methanol, add 10 mg of crystalline fenvalerate Aa as a crystal germ and add 0.8 g of triethylamine as a catalyst and stir at -6 ° C for one day. The reaction mixture was then added to 50 ml of a 1% aqueous hydrochloric acid solution and 50 ml of toluene, and the mixture was fractionated. The resulting aqueous phase is extracted with 50 ml of toluene, the toluene layers are combined and washed twice with 50 ml of water. The toluene was distilled off under reduced pressure to afford fenvalerate Αα-rich fenvalerate A as a light yellow oily substance. Yield: 39.73 g, 99.3% of theory. The oil contained 7.7% of the R) isomer and 92.3% of the (S) isomer according to the analysis described for the alcohol portion of the ester.

Example 53

The same procedure as described in Example 38 is repeated. One day later, a suspension of about 10% by weight was added to a solution of 400 g of fenvalerate A in 600 g of methyl alcohol, cooled to -6 ° C, then 8.0 g of triethylamine was added as a catalyst and Stir at 0 ° C. The precipitated crystals are then combined by filtration and the solids on the filter are washed twice with 200 ml of cold methanol (0-5 ° C). This gave 381.9 g of crystalline product (86.8% by weight of fenvalerate A used), which according to the analysis of the alcohol portion of the ester was 2.4% (R) isomer and 97.6% (S). ).

Example 54

Dissolve 40.00 g of fenvalerate A in 60 g of methanol, add 10 mg of fenvalerate Αα and 0.12 g of 1,5-diazabicyclo [4,3,0) non-5 as crystal germ and add to the mixture and stirred at -6 ° C for one day. The precipitated crystals are then combined by filtration and the solids on the filter are washed twice with 20 ml of cold methanol (0-5 ° C). This gave 32.35 g of crystalline product (80.9% by weight of fenvalerate A used), which according to the analysis for the alcoholic part of the ester was 3.2% (R) isomer and 96.8% (S). ).

Example 55

Dissolve 40.00 g of fenvalerate A in a mixture of 5 g of toluene, 35 g of heptane and 20 g of methanol, add 10 mg of crystalline fenvalerate Αα and 4.8 g of triethylamine and stir at -6 ° C for one day. stirring. The precipitated crystals are then combined by filtration and the solids on the filter are washed twice with 20 ml of cold methanol (0-5 ° C). 23.72 g of crystalline product are obtained (fenvalerate A used)

59.3% by weight) containing 1.6% of the (R) isomer and 98.4% of the (S) isomer according to the analysis described for the alcohol portion of the ester.

Example 56

Dissolve 40.00 g of fenvalerate A in 60 g of methyl alcohol, add 10 mg of fenvalerate Αα and 38 mg of sodium hydroxide in 1 g of methanol as a crystal germ and stir at -6 ° C for one day. The reaction mixture was then added to a mixture of 50 ml of a 1% aqueous hydrochloric acid solution and 50 ml of toluene, and then fractionated. The aqueous phase was extracted with 50 ml of toluene, the toluene layers were combined and washed twice with 50 ml of water. After distilling off the toluene under reduced pressure, fenvalerate Αα-rich fenvalerate A is obtained, which is a light yellow oily substance. Yield: 39.61 g (99.0% of theory). The oil contained 10.8% of the (R) isomer and 89.2% of the (S) isomer according to the analysis described for the alcohol portion of the ester.

Claims (5)

Patent claims A process for the preparation of (S) -α-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate, comprising: a) To a solution of (R, S) -α-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate (S) -α-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate, seed crystals of (R) -α-cyano-3- (phenoxybenzyl) - (R) -2- (4-chlorophenyl) isovalerate, or such seed crystals are added, the solution is crystallized from (S) -α-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate, and the crystalline product is separated from the mother liquor, or b) Crystallization of (R, S) -α-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate from (S) -α-cyano-3- (phenoxybenzyl) ) - (S) -2- (4-chlorophenyl) isovalerate, the crystalline material is separated from the mother liquor, the ester in the mother liquor in a proton-containing solvent or in a solvent mixture containing a proton-containing solvent, optionally in the presence of a basic substance such as catalyst , isomerizing the mother liquor, if desired, after concentration of the mother liquor in the presence of a basic substance, and crystallizing (S) -α-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate and the crystalline product is isolated. (Priority: October 6, 1978) 2. Process (S) -α-cyano-3- (phenoxybenzyl) - (S) -2- (4-chloro · phenyl) isovalerate or large amounts of (S) -α-cyano-3- (phenoxybenzyl) (R, S) -α-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate containing (S) -2- (4-chlorophenyl) isovalerate characterized in that a) from a solution of (R, S) -α-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate or (S) -α-cyano-3- (phenoxybenzyl) ) - (S) -2- (4-chlorophenyl) isovalerate crystallized from (S) -α-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate in the presence of a basic substance as a catalyst. 44: chlorophenyl) isovalerate and the crystalline product are separated, or (b) (R, S) -α-cyano-2-phenoxybenzyl containing a large amount of (S,? -cyano-3- (phenoxybenzyl) - (S) 2- (4-chlorophenyl) isovalerate). ) - (S) -2- (4-chlorophenyl) isovalerate (RS) -α-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate from the solution in the presence of a basic substance as a catalyst, crystallize (S) -α-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate and optionally after removal or deactivation of the catalyst, The crystalline product is isolated from the mother liquor together with (R, S) -acLm 3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate (Priority: October 1, ⁷⁷ ). 3. A process according to claim 1 wherein the (R, S) -a-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate solution is (RS) a-cyano-3- (phenoxybenzenyl) - (S) -2- (4-chlorophenyl) isovalerate with a lower alcohol or a short-chain alcohol; Use a solution of a solvent mixture containing 182,994 alcohols. (Priority: October 6, 1978) The process of claim 1 wherein the (R, S) -a-cyano-3- (phenoxybenzyl) - (S) -2- (4-chlorophenyl) isovalerate solution is formed. a solution of (R, S) -cyano-3- (phenoxybenzyl) (S) -2- (4-chlorophenyl) isovalerate in an aliphatic hydrocarbon, alicyclic hydrocarbon or solvent mixture containing an aliphatic or alicyclic hydrocarbon. (Priority: October 6, 1978) 5. A process according to claim 1, wherein the isomerization is carried out in a proton-containing solvent in which the basic material is insoluble. (Priority: October 6, 1978) 6. A process according to claim 1, wherein the isomerization is carried out in a solvent in which the basic substance is soluble. (Priority: October 7, 1977) A process for carrying out process b) according to claim 1, characterized in that the isomerization is carried out in a proton-free solvent in which the basic substance is insoluble. (Priority: October 11, 1977) 8. The process according to claim 1, wherein the isomerization is carried out in a lower alcohol or a mixture of solvents containing a lower alcohol. (Priority: October 1978) Process for process b) according to claim 1, characterized in that the basic catalyst is alkali metal carbonate, alkaline earth metal carbonate, alkali metal bicarbonate, alkaline earth metal bicarbonate. junctional alumina or a basic ion exchange resin is used. (Priority: October 11, 1977) 10. A process for carrying out process b) according to claim 1, characterized in that the isomerization is carried out by passing the solution through a column filled with a basic substance. (Priority: October 11, 1977) 11. The process of claim 1, wherein the solvent for the isomerization is an aliphatic hydrocarbon, an alicyclic hydrocarbon, or a mixture of aliphatic or alicyclic hydrocarbons. / (Priority: October 11, 1977) I 12. A process according to claim 2, wherein the solvent is methanol. ethyl alcohol or a mixture of solvents containing methyl alcohol or ethyl alcohol. (Priority: October 7, 1977) 13. A process according to claim 12 wherein the solvent is methyl alcohol. (Priority: October 7, 1977) 14. The process of claim 2, wherein the solvent is an aliphatic hydrocarbon, an alicyclic hydrocarbon, or a mixture of an aliphatic hydrocarbon and an aromatic hydrocarbon, or a mixture of an alicyclic hydrocarbon and an aromatic hydrocarbon. (Priority: October 7, 1977) 15. A process according to claim 2, wherein the solvent is pentane, hexane or heptane. (Priority: October 7, 1977) 16. The process according to claim 2, wherein the solvent is a mixture of a solvent and a solvent b), the solvent a) being pentane, hexane or heptane and the solvent b) benzene, toluene or xylene. (Priority: October 7, 1977) 17. The process according to claim 2, wherein the solvent is cyclohexane or methylcyclohexar. (Priority: October 7, 1977) 18. The process of claim 2, wherein the basic material is a nitrogen or phosphorus base. (Priority: October 7, 1977) 19. The process of claim 2, wherein the basic material is ammonia or an organic amine. (Priority: October 7, 1977) 20. The process of claim 2, wherein the basic material is an alkali metal hydroxide, an alkaline earth metal hydroxide, an alkali metal alcoholate, an alkaline earth metal alcoholate, an alkaline earth metal amide, an alkali metal hydride, an alkali metal hydride, a basic ion exchange resin is used. (Priority: October 7, 1977) 21. A process according to claim 20 wherein the basic material is an alkali metal hydroxide or an alkaline earth metal hydroxide. (Priority: October 7, 1977) 22. A process according to claim 2, wherein the solvent is methanol, ethyl alcohol or a mixture of solvents containing methanol or ethyl alcohol. (Priority: October 7, 1977) 23. Process according to claim 2, wherein the solvent is methyl alcohol. (Priority: October 7, 1977) 24. Process according to claim 2, wherein the solvent is an aliphatic hydrocarbon, an alicyclic hydrocarbon, a mixture of an aliphatic and an aromatic hydrocarbon, or a mixture of an alicyclic and an aromatic hydrocarbon. (Priority: October 7, 1977) 25. The process according to claim 2, wherein the solvent is pentane, hexane or heptane. (Priority: October 7, 1977) 26. The process according to claim 2, wherein the solvent is a mixture of a) solvent and a solvent b) and the solvent a) is pentane, hexane or heptane and the solvent b) is benzene, toluene. or xylene. (Priority: October 7, 1977) '7. Process for process b) according to claim 2, characterized in that the solvent used is cyclohexane, methylcyclohexane or a mixture of cyclohexane or methylcyclohexane. (Priority: October 7, 1977) 28. The process of claim 2, wherein the basic material is a nitrogen or phosphorus base. (Priority: October 7, 1977) 29. A process according to claim 2, wherein the basic material is ammonia or an organic amine. (Priority: October 7, 1977) 30. A process according to claim 2, wherein the basic substance is an alkali 13 -13182 994 metal hydroxide, alkaline earth metal hydroxide, alkali metal alcoholate, alkaline earth metal alcoholate, alkali metal amide, alkaline earth metal amide, alkali metal hydride, alkaline earth metal hydride or a basic ion exchange resin. (Priority: October 7, 1977) 31. The process of claim 30, wherein the basic material is an alkali metal hydroxide or an alkaline earth metal hydroxide. (Priority: October 7, 1977) 32. A process for carrying out process b) according to claim 2, wherein after crystallization the basic substance present is removed. (Priority: October 7, 1977) 33. The process of process b) according to claim 2, wherein after crystallization the basic material is neutralized with an acidic material. (Priority: