CS211390B2 - Method of preparation of the + l s + p-alpha-kyano-3-phenoxybenzyl-+ l s + p -2- + l 4-chlophenyl + p isovalerate - Google Patents

Abstract

PURPOSE:To obtain a powerful insecticide in a high yield, by adding a specific catalyst and, preferably a seed crystal, to a solution of alpha-cyano-3-phenoxybenzyl (S)-2-(4-chlorophenyl)-isovalerate, followed by isomerization and crystallization. CONSTITUTION:A soluble basic catalyst such as an organic amine, e.g. triethylamine, etc. is added to a solution of (R,S)-alpha-cyano-3-phenoxybenzyl(S)-2-(4- chlorophenyl)-isovalerate in methanol with or without addition of a seed crytal of any one of isomers. The isovalerate is isomerized and crystallized to give (S)-alpha- cyano- 3-phenoxybenzyl(S)-2-(4-chlorophenyl)-isovalerate having a powerful insecticidal action. EFFECT:Simultaneous isomerization and crystallization can achieve high yields lasily.

Description

(54) Process for the preparation of (S: α-α-cyano-3-phenoxyhenzyl- (S) -2- (4-chlorophenyl) isovalerate

The invention relates to a process for the preparation of (S) -tr-cyanio-3-phenoxybenzyl- (S) -2- (4-chlorophenyl) -sovalerate.

a-Cyano-3-fenioxybenzyl-2 / (4-chlorfenyljisovalerát formula I ₀ CH

CH

it exhibits low mammalian toxicity and insecticidal activity against a considerable amount of insects (as described, for example, in U.S. Pat. No. 3,996,244) and contains two asymmetric carbons per molecule, as a result of which it is known in the form of four optically active isomers.

α-Cyano-3-phenoxybenzyl-2- (4-chlorophenyl) The isovalerate of formula I will be referred to hereinafter as "fenvalerate".

(R, S) -? - cyano-3-phenoxybenzyl- (S) -2- (42

-chlorophenyl isoisoerate will hereinafter be referred to as "fenvalerate A".

(S) -α-cyano-3-phenoxybenzyl- (S) -2- (4-chlorophenyl) isovalerate will be referred to hereinafter as "fenvalerate A _and ".

(R) -α-cyano-3-phenoxybenzyl (S) -2- (4-chlorophenylisovalerate) will be referred to hereinafter as "fenvalerate A _? ".

(S) -α-cyanio-3-phenoxybenzyl- (R) -2- (4-chlorophenylisovalerate) will be referred to hereinafter as "fenvalerate B _a ".

(R) -? - cyano-3-phenoxybenzyl- (R) -2- (4-chlorophenylisovalerate) will be referred to hereinafter as "fenvalerate B _p ".

The relationship of the absolute configuration of the asymmetric carbon atom on the acid residue to the insecticidal activity of the above ester has already been elucidated, and is also known [Miyakado et al., Agr. Bio. Chem., 39, 267 (1975) 1, a process for the preparation of (S) -2- (4-chlorophenyl) isovaleric acid, from which an ester with significant insecticidal activity is derived. Miyakado et al. disclose a method for cleaving α-isopropylphenylacetic acids into their optical antipodes and the insecticidal activity of phenylacetic esters having an optically active acid residue.

The relationship of the absolute configuration of the asymmetric carbon atom of the alcohol moiety to the insecticidal activity of the above es211390

No. 211330 is described in Japanese Published Patent Application OPI 59 646/78, which also describes a process for preparing esters having an optically active alcohol residue.

Japanese Published Patent Application OPI 24 019/78 describes a process for preparing fenvalerate isomers having an optically active residue by chromatography of fenvalerate A on a silica gel column to separate fenvalerate A into fenvalerate A _and -a feinvalerate Aβ.

The method described in Japanese Published Patent Application OPI 59 646/78 relates to optically active 3-phenoxymandelic acid obtained by cleavage of 3-phenoxymandelic acid into its optic antipodes.

While the methods described above are suitable for obtaining these compounds on a laboratory scale, they are completely unsuitable for operational purposes.

Fenvalerate A 'is an excellent insecticidal product whose insecticidal activity is - about four times higher than the insecticidal activity of - racemic - fenvalerate (as disclosed, for example, in Japanese Published Patent Application OPI 24 019/78).

The present invention relates to a process for the preparation of (S) -oxylbenzyl (S) -2- ((R) - (R) -phenyl) isovalerate, characterized in that: Crystallize (S- -K-cyano-3-phenoxybeinzyh (S) -2- (4-chlorophenyl) isovaleate from JR, S) -α-cyano-3-phenoxybenzyl (S) -2- [4] (Chlorophenyl) isovalerate in a - solvent selected from the group consisting of 1 to 5 carbon atoms, 5 to 15 carbon aliphatic hydrocarbons and 5 to 10 carbon alicyclic hydrocarbons, a mixture of two or more of these solvents and a mixed - a solvent comprising - said solvent or - said - mixture - of solvents, an aromatic hydrocarbon of 6 to 10 carbon atoms, in the presence of a base as a catalyst.

Preferably, the solvent is methanol, or ethanol or a mixed solvent, containing methanol or ethanol.

Preferably, methanol is used as the solvent.

The solvent used is preferably an aliphatic hydrocarbon, an alicyclic hydrocarbon, a mixture of an aliphatic hydrocarbon and an aromatic hydrocarbon or a mixture of an alicyclic hydrocarbon and an aromatic hydrocarbon.

Preferably, a solvent selected from the group consisting of pentane, hexane, and heptane is used as solvent.

The solvent is preferably a solvent mixture selected from the group consisting of pentane, hexane and heptane, and a solvent selected from the group consisting of benzene, toluene and xylene. ·

The solvents selected from the group consisting of cyclohexain and methylcyclohexane are preferably further used as solvents.

Catalyst bases used in the process according to the invention are those selected from the group consisting of alkali metal hydroxide, alkaline earth metal hydroxide, alkali metal alcoholate of 1 to 5 carbon atoms, alkaline earth metal alcoholate of 1 to 5 atoms carbon, alkali metal amide, alkaline earth metal amide, alkali metal hydride, alkaline earth metal hydride, basic ion exchange resin, organic amine and ammonia. .

Preferably, the base is a substance selected from the group consisting of an alkali metal hydroxide and an alkaline earth metal hydroxide.

The basic catalyst causes isomerization at the asymmetric carbon atom and the alkyl moiety. The addition of this catalyst to the fenvalerate A crystallization system results in fenvalerate A3, which is present in said mother liquor in an amount greater than the equilibrium ratio, to convert to fenvalerate A _and due to isomerization on the asymmetric carbon- atom in the -alcohol ¹ residue. In this way, it is possible to obtain crystalline fenvalerate Aa in larger amounts than initially present.

In this process, from 70 to 90 parts of crystalline fenvalerate A can be obtained from the original 100 parts of starting fenvalerate A.

Fenvalerate A contained in - the mother liquor from which the fenvalerate Aa crystals were separated by filtration - or by another suitable method - contains fenvalerate Aa in an amount corresponding to about half of the amount of fenvalerate A. Thus, if fenvalerate A is reused in the mother liquor, , a loss reduction is achieved. In practice, however, it is not suitable due to the concentration of impurities.

If the catalyst is an insoluble matter, it can be removed by a conventional separation method such as filtration.

If the catalyst is a water-soluble substance, it can be removed by adding a water-soluble solvent or a mixture of a water-soluble solvent, and a water-insoluble solvent and washing the solution.

In the process according to the invention, the addition of seed crystals is not necessary, although in practice the crystals are added in order to achieve a smooth crystallization process. However, the addition of seed crystals is not necessary in the continuous operation of the process according to the invention, since in the crystallization zone there are always crystals already formed in addition to the newly formed crystals.

Investigating a process for producing fenvalerate isomers having an optically active alcohol residue, it has been found that by adding a seed crystal of fenvalerate Aa, fenvalerate Bp or mixtures thereof to the fenvalerate A solution, only fenvalerate A _and .

Since these are esters of the pyrethroid type, the crystalline form of the above compounds cannot be inferred from the properties of racemic fenvalerate. which is a viscous oily substance.

Fenvalerate A _a : mp = 57.9 ° C; .

[α] D ²¹ = -11.2 ° (in CHCl 3; concentration: 6.5%).

Fenvalerate B ^:

mp = 59.6 ° C; [α] _D 24 = 4-12.5 ° (in CHCl 3; concentration: 3.8%).

For example, α-cyano-3-phenoxybenzyl-2,2-dimethyl-3- (2,2-diclorvinyl) cyclopropanecarboxylate, which is an ester of pyrethroid type and has the same alcoholic residue as the above compound, is not one of its esters having a d-trans- (1R, 3S) -acid residue - α '(S) -. (RJ- or racemic alcohol - the residue known to form a crystalline product).

However, as a mixture of equal parts by weight (melting point = 75-76 ° C). an ester having a d-trans-acid residue. -a (R - [- alcohol] residue and ester having ¹ - 1'-itrans • (1S, 3'R) -acid, residue α (JS-alcohol), and a mixture of equal weight parts (melting point 78.5-80 ° C) of an ester having a d-trans acid residue -a. (S [-alcohol residue, and an ester having a -1-trans acid residue and a (R) -alcohol residue, were obtained in crystalline form.

It has also been found that α-ethynyl-3-phenoxybenzyl-2- (4-chlorophenyl) isovalerate, which is a pyrethroid type ester and has a very similar structure to the above compound, is a mixture (m.p. 46-47 ° C). esters having a racemic acid residue and a racemic alcohol residue, a mixture of two of their diastereoisomers (each racemic) and an ester of said compound having an optically active acid residue crystallized at room temperature. alcohol residue. recrystallized from hexane, crystallized predominantly diastereioisomer having a melting point of 87-88 ° C and exhibiting very weak insecticidal activity. the ester isolated from the mother, liquor. the diastereoisomers (tání- temperature 51-52 ^C C) having a higher insecticidal activity .

On the other hand, when an ester having an optically active acidic residue (melting point 61-62 ° C) is subjected to the above process, the crystallization of the diastereoisomer is not selective.

For allethrin. (allethronylchrysanthemate), which has long been known as a synthetic ester of the pyrethoid type and which has four diastereoisomers, is known. just one . a di-astereoisomer (crystalline allethrin) which is crystalline; it is a diastereoisomer consisting of an ester having a d-trans-acid residue and a 1-alkoxy radical and an ester having a 1-trans acid and a d-alcohol residue (M. Matsui -a. I. Yamamoto, Naturel Occurring Insecticides, M. Jacobson and DG Grosby-Eds, pp. 38-42, Marcel Dekker, Inc., New York (1971)) None of the enantipmiarfal isomers of crystalline allethrin is known. that - would be - in itself crystalline.

It follows from the foregoing that it is completely impossible to foresee. which of the optical isomers or which mixtures thereof are obtained or obtained in crystalline form; and. whether the optical isomer can selectively crystallize from the mixture with the other optical isomers if it is known to be crystalline.

The effective use of the mother liquor, which is obtained as a by-product, has also been studied. preparing fenvalerate having an optically active alcohol moiety, wherein:. It has been found that - by dissolving an optically active γ-α having an -? -? - residue in an - imbalance ratio (R) / (S), in a protonic solvent or mixture. a solvent comprising - a protonic solvent - with the advantageous addition of a basic catalyst - or - by dissolution. . of said fenvalerate in an aprotic solvent, followed by the addition of said basic catalyst, to achieve a rapid isomerization of the asymmetric carbon atom in the alcohol residue.

It has hitherto prevailed that the mandelonitrile ester is in a protonic solvent or in the presence of a basic catalyst. unstable, whereby - an ester bond or a decomposition of the nitrile group is to be - split. However, it has now been found that the above-described ester is predominantly subjected to isomerization conditions.

The isomerization of an optically active aliphatic nitrile in the presence of a basic catalyst is already known (for example, this isomerization has been described in J. Am. Chem. Soc., 86, p. 5457 [1964]). However, isomerization of esters of the type described above in a solvent has not been described.

It has also been found that by adding a basic catalyst to the fenvalerate A solution, crystallization of fenvalerate A 'and isomerization of fenvalerate Αβ in the mother liquor can be achieved simultaneously, resulting in fenvalerate Aa in high yield.

In the following, the process of the invention will be described. in more detail.

Any solvent in which it is present can be used in the process of the invention. fenvalerate A is readily soluble and in which fenvalerate A is only soluble to a very limited extent. Examples of preferred solvents are:

Ί lower alcohols such as methanol or ¹ · ethanol, and mixed solvents containing-lower alcohols.

Examples of other useful solvents include:

aliphatic hydrocarbons such as pentane, hexane or heptane; alicyclic hydrocarbons such as cyclohexane. - him. methylcyclohexane, mixtures of these solvents, mixtures of at least one of these solvents with an aromatic solvent such as benzene, toluene or xylene, and mixtures of these hydrocarbons (or mixtures thereof) with lower alcohols.

The use of aromatic hydrocarbons as well as acetanitriles alone is not suitable in the process according to the invention, since said solvents dissolve fenvalerate A _and to a large extent, undesirable.

Preferred lower alcohols are methanol and ethanol in the process of the invention, with methanol being the most preferred solvent in the present case. When methanol is used, the water content of the methanol should be lower. than 5 ° / o. Advantageous results are not obtained when isopropanol or aqueous isopropanol is used.

In view of the yield of the crystals obtained and the crystallization rate, it is necessary for the concentration of fenvalerate to be obtained. And. in solution - ranged between 1 - and · 90 ° / ₀ - by weight, - the preferred concentration of fenvalerate A being 20 to 70% by weight. ,

The basic substance used in the process of the invention as a catalyst may be selected from an extensive set of basic substances, including, for example:

nitrogen-containing bases, -phosphorus-containing bases, - strong bases and basic-ion exchange resins.

Specific examples of suitable bases include:

ammonia, aliphatic amines such as methylamine, ethylamine, n-propylamine, n-butylamine, -n-pentylamine, diethylamine, di-n-propylamine, di-n-butylamine, triethylamine, tri-n-propylamine, tri-n -butylamine, cyclohexylamine. and ethanolamine, aromatic amines such as aniline, 1-intytylamine and 2-naphthylamine, quaternary ammonium salts such as tetramethylammonium hydroxide, tetraethylamino amine hydroxide and tetra-n-propylammonium hydroxide, nitrogen-containing heterocyclic compounds such as pyridine containing nitrogen , quinoline, pyrrolidine and -piperidine, phosphorus-containing bases such as -triphenylphosphine and tri-n-butylphosphine, strong bases such as alkali metal hydroxides or alkaline earth metal hydroxides (such as hydroxide sodium or potassium hydroxide), alkali or alkaline earth metal alcoholates such as sodium methylate or sodium ethylate, alkali metal or alkaline earth metal amides such as sodium amide or magnesium amide , alkali metal-or alkaline-earth metal hydrides such as sodium hydride, potassium hydride or lithium aluminum hydride, and basic ion-exchange resins, such as, for example, dextrose or amberlite.

In terms of yields of crystals, the preferred bases are ammonia and amines. The most preferred bases are ammonia and triethylamine.

A suitable amount of the catalyst is from 9.01 to 100 mol%, preferably. 0.1 to 50 - mol%, based on fenvalerate A. A suitable isomerization temperature is - a temperature of -50 to 50 ° C (the advantageousness of this temperature is judged in terms of the yield of the crystals obtained and the speed) crystallization). Preferably, the isomerization temperature is -30 to 15 ° C.

At. said isomerization - it is advantageous to stir the solution, even if it is not. necessarily.

Fenvalerate A may contain any ratio. fenvalerate · -A _e -and -fenvalerate -A3.

In order to illustrate the invention in greater detail. are given in the following parts of the description - examples - of the embodiment, which - are only illustrative - of the nature and of the "intrinsic" scope. of the invention - in no way restrict. - In these . - the examples are all. parts, percentages - contents and ratios - by weight, unless otherwise stated.

In these examples. - the (R) -isomer (fenvalerate-AJ) and the (S) -isomer - (fenvalerate A ') of the alcohol residue were analyzed by gas-chromatographic analysis of the following conditions of analysis:

column:

-% - silicone DC-QF-1, diameter = 3 - mm, height - = 3 m, column temperature - 245 ° C, firing chamber temperature = 250 - ° C, nitrogen pressure - = 0.2 MPa.

Under these conditions - the time - delay (S) -isomer (fenvalerate _A) - AI- rovna- 43 minutes residence time - the (R) isomer (fenvalerate N) was 38 minutes · be compared.

In the method, the - esters having the (R) -acid residue have a reverse residence time, i.e., the residence time of an ester having a - (S) -alcohoil residue (fenvalerate -Ba) is the same as u-fenvalerate Αβ and - a residence time. The ester-containing (-R) -alcohol residue (fenvalerate-B1) is the same as fenfenerate. This means that when fenvalerate -A is present in a certain ratio the ester - having - (R) -acidic acid residue, at the peak of each of the above-mentioned isomers, exceeds the pl-to its enantiomer, approximately - in this ratio.

The optical purity of the acidic residue of valerate A was determined as follows:

Fenvalerate A is hydrogenated in ethanol using platinum oxide as a catalyst to give - (S-2- (4-chloro-phenynyl) isovaleric acid, which is then converted to the acid chloride using thionyl chloride. The ratio between the two resulting diastereoisomers is determined by gas chromatography and the optical purity of the acidic residue is calculated from the results obtained.

Example1

5.82 g of fenvalerate A (alcohol - residue:

50.5% of the (RJ-isomer and 49.5% of the (S-isomer)) are dissolved in 11.6 g of methanol, followed by the addition of 1 mg of fenvalerate seed crystal to the solution thus obtained _. 120 mg of triethylamine catalyst are also added to the solution, and the mixture is then stirred at 2-4 DEG C. for two days.

The separated crystals were isolated by filtration. The crystals were washed twice with 5 ml of cold hexane (0-5 ° C) on the filter. The yield of crystalline product was 4.61 g (79.3% by weight based on fenvalerate A used).

By analysis of the crystals obtained, it was determined that with respect to the alcohol residue of the ester: 1.4% of the (R) -isomer and 98.6% of the (S) -isomer were present.

As for the alcohol residue of fenvalerate A isolated from the filtrate, 51 percent of the (R) -isomer -and 49% of the (S) -isomer is present.

Example 2

6.78 g of fenvalerate A of the same composition as in the previous example are dissolved in 6.8 g of methanol, and then 1 mg of fenvalerate Α _α seed is added to the obtained solution. 68 mg of triethylamine catalyst were then added to the solution and the mixture was stirred at 2 to 4 ec for one day. The separated crystals were isolated by filtration. The crystals were washed on the filter twice with 5 ml of cold hexane (0-5 ° C). The yield of the crystalline product is 5.91 g (87.2% by weight of fenvalerate A used).

Analysis of the crystals was stanoveno- that as regards the alcohol moiety of the ester is present: 2 o / ₀ (R-isomer and 98% (S) -isomer.

Example 3

7.22 g of fenvalerate A of the same composition as in the preceding example are dissolved in 7.2 g of methanol and 1 mg of fenvalerate seed Α _{α is} added to the solution thus obtained. 43 mg of n-propylamine as catalyst were added to the solution, and the mixture was stirred at 2-4 DEG C. for one day. The precipitated crystals are then isolated by filtration. These crystals were washed on the filter twice with 5 ml of cold hexane (-0.5 to 5 [deg.] C.).

5.57 g (77.2% wt / wt, based on fenvalerate A used).

Analysis of the crystals obtained showed that 4.4% of the (R) -isomer and 95.6% of the (S) -isomers were present with respect to the alcohol residue of the ester.

Example 4

6.49 g of fenvalerate A of the same composition as in Example 3 are dissolved in 6.5 g of methanol, and 1 mg of fenvalerate Α _α seed is added to the solution thus obtained. 47 mg of diethylamine catalyst was further added to the solution and the mixture was stirred at 2-4 DEG C. for one day. The precipitated crystals were collected by filtration and the crystals were washed twice on the filter with 5 ml of cold hexane (0-5 ° C). The yield of crystals is 4.84 g (74.6% by weight of fenvalerate A).

By analysis of the crystals obtained, it was determined that with respect to the alcohol residue of the ester: 2.3% (Rj-isomer and 97.7% (Sj-isomer) present).

Example 5

7.36 g fenylvalerátu- A same composition as in Example předcházejícím- was dissolved in 7.4 g of ethanol, whereupon to the obtained roztoku- added 1 mg of a seed crystal of fenvalerate _A; 74 mg of triethylamine catalyst are also added to the solution and the mixture is stirred at 2 to 4 ° C for one day. The separated crystals were collected by filtration. The crystals were washed twice with 3 mL cold hexane (0-5 ° C) on the filter. The yield of crystalline product was 3.04 g (corresponding to 41.3% w / w based on fenvalerate-A used).

By analysis of the crystals obtained, it was determined that with respect to the alcohol residue of the ester: 4% (R-isomer and 96% (S) isomer present).

Example 6

7.7 g of fenvalerate A of the same composition as in the previous example were dissolved in 7.7 g of methanol, and 1 mg of fenvalerate Aa seed crystal was added to this solution. 200 mg of triphenylphosphine catalyst are added to the solution and the mixture is stirred at 2-4 ^DEG C. for one day. The separated crystals were isolated by filtration. -Se crystals washed on the filter with 3 ml of hexane chladného- (0 -to 5 ° C), the yield of crystals is - 3.6 g (corresponding to 46.8% ^1-hmotinios tního, vztaženo- used to fenvalerate A).

Analysis of the crystals obtained showed that 3.4% of the (R) -isomers and 96.6% of the (S-isomer) were present as the -alcohol residue of the ester.

2.1139 0

Example 7

6.64 g of fenvalerate A of the same composition as in the previous embodiment are dissolved in 6.6 g of methanol, and 1 mg of fenvalerate seed is added to this solution. And _a . Next, 62 mg of aniline catalyst was added to this solution and the mixture was stirred at 2-4 ° C for one day. The precipitated crystals were collected by filtration and the crystals were washed twice with cold hexane (0-5 ° C) on the filter. The yield of crystals was 2.99 g (corresponding to 45.1 a / _o by weight, based on the fenvalerate A).

Analysis of the crystals obtained showed that 2.9% of the (R) -isomer and 97.1% of the (S) -isomer were present with respect to the alcohol residue of the ester.

Example 8

7.85 g of fenvalerate A of the same composition as above. Example were dissolved in methanol and 7.2 g · the solution thus obtained was added 1 mg of a seed crystal of fenvalerate _and. Next, 0.71 g of a 10% methanolic ¹ % solution of tetraimethylammonium, mhydrioxide as a catalyst is added to the solution, and the mixture is stirred at 2 to 4 ° C for one day.

The separated crystals were collected by filtration. The crystals were washed on the filter twice with 3 mL cold hexane (0-5 ° C). The yield of the crystal was 4.05 g (corresponding to 51.6% by weight, based on the fenvalerate A used).

Analysis of the crystals obtained showed that 3.8% of the (R) -isomer and 96.2% of the [S] -isomer were present with respect to the alcohol residue of the ester.

For example, 9 g of fenvalerate A are dissolved in 80 g of methanol, and 1 mg of fenvalerate Aa seed crystal is added to the solution thus obtained. Next, · discuss this. 2 g of triethylamine catalyst are added to the solution and the mixture is stirred at -6 ° C for one day.

The separated crystals were collected by filtration and the crystals were washed twice with 20 ml of cold methanol (0-5 ° C). The yield of crystals was 33.36 g (corresponding to 83.4% by weight based on the fenvalerate A used).

By analysis of the crystals obtained, it was determined that with respect to the alcohol residue of the ester, it was present: 2.3% of the (R) -isomer and 97.7% of the (Sj -isomer).

EXAMPLE 1 10 g of fenvalerate A are dissolved in 40 g of methanol and 1 mg of fenvalerate seed is added to the solution thus obtained.

AND". Next, 0.4 g of triethylamine catalyst was added to the solution, and the mixture was stirred at -6 ° C for 3 days.

The separated crystals were isolated by filtration. The crystals were washed twice with 20 ml of cold methanol (0-5 ° C). The yield of the crystalline product was 35.82 g (corresponding to

89.6% by weight based on the fenvalerate A) used.

Analysis of the crystals obtained showed that 2.5% of the (R) -isomer and 97.5% of the (S) -isomer were present with respect to the alcohol residue of the ester.

EXAMPLE 11 g of fenvalerate A was dissolved in 10 g of methanol (fenvalerate has the same composition as. In the preceding example) and to the solution thus obtained was added 1 mg of a seed crystal of fenvalerate A _e. Next, 0.1 g of pyridine catalyst was added to the solution, and the mixture was stirred at -6 ° C for one day.

The separated crystals were isolated by filtration. The crystals were washed twice with 5 ml of cold ethanol (0-5 ° C) on the filter. The yield of crystalline product was 4.36 g (corresponding to 43.6% by weight of fenvalerate used).

Analysis of the crystals was determined · that in respect of the alcohol moiety of the ester is present: 3 o / ₀ (R) -isomer and 97% · (S) -isomer.

EXAMPLE 12 g of fenvalerate A of the same composition as in the previous examples are dissolved in 20 g of methanol and 1 mg of fenvalerate Aa seed crystal is added to the solution thus obtained. Next, 0.2 g of a 40% aqueous solution of methylamine as catalyst is added to the solution, and the mixture is stirred for one day at - 6 ° C. The separated crystals were collected by filtration and washed twice with 5 ml of cold methanol (0-5 ° C) on the filter. The yield of crystals is 8.52 g (corresponding to 85.2% by weight, based on the fenvalerate A used).

Analysis of the crystals obtained indicated that 2.3% of the (R) -isomer and 97.7% of the (S) -isomer were the alcohol residue of the ester. .

EXAMPLE 13 g of fenvalerate A of the same composition as in the preceding examples are dissolved in 80 g of methanol and 1 mg of fenvalerate Α _α seed is added to the solution thus obtained. Next, 0.48 g of a 28% aqueous ammonia catalyst solution was added to the solution, and the mixture was stirred at -6 ° C for one day.

The precipitated crystals are then isolated by filtration. The crystals were washed on the filter twice with 20 ml of methanol at 0-5 ° C.

The yield of crystals was 33.2 g (corresponding to

14% by weight, based on fenvalerate A).

By analysis of the examples obtained, it was determined that, with respect to the alcohol residue of the ester, there were: 2.3% · (R) -isomer and 97.7% · (S) -isomer.

Example 14 g of fenvalerate A is dissolved in 10 g of methanol and 1 mg of fenvalerate Aa seed crystal is added to the solution thus obtained. The fenvalerate A used has the same composition as in the previous examples. Next, 0.1 g of ethylenediamine catalyst is added to the solution, and the mixture is stirred at - 6 ^° C for one day.

The separated crystals were isolated by filtration. These crystals were 8.12 g (corresponding to 81.2% cold methanol (0-5 ° C)) and the yield of crystals was 8.12 g (corresponding to · 81.2% by weight based on the fenvalerate A used).

Analysis of the crystals obtained showed that 2.6% of the (R 1 -isomer and 97.4% of the (S) -isomer) were present with respect to the alcohol residue of the ester.

Example 15

100 g of fenvalerate A same composition as in the preceding examples, · are dissolved in 200 g · methanol, and thus the 'resulting solution was added 1 mg · · seed crystal of fenvalerate _and. 3 g of triethylamine catalyst are then added to the solution and the mixture is stirred at -13 ° C for one hour.

The precipitated crystals are then isolated by filtration. The crystals were washed on the filter twice with 50 ml cold methanol (0-5 ° C). The yield of crystals was 84.21 g (corresponding to

84.2% w / w, based on the fenvalerate A used.

The crystals obtained are analyzed by gas chromatography, and it is determined that, with respect to the alcohol residue of the ester, 3% of the (R) -isomer and 97% of the (S-isomer) are present.

Example 16 g of fenvalerate A is dissolved in 10 g of methanol, and 1 mg of fenvalerate A seed is added to the solution thus obtained. The fenvalerate A used has the same composition as in the previous examples. Next, 0.1 g of triethylamine catalyst is added to the solution and the mixture is stirred at 12 ° C for one day.

The precipitated crystals are then isolated by filtration. The crystals were washed twice with 5 ml of cold methanol (0 to 5 ° C) on the filter. The yield of crystalline product was 7.43 g (corresponding to 74.3% by weight based on the fenvalerate A used).

By analysis of the crystals obtained, it was determined that, with respect to the alcohol residue of the ester, 1.2% of the (R 1 -isomer and 98.8% of the (S) -isomer) were present.

EXAMPLE 17 g of fenvalerate A of the same composition as in the preceding examples are dissolved in 60 g of methanol, and 10 mg of fenvalerate Α * seed are added to the solution thus obtained. 1.95 g of methanolic ammonia solution are added to the solution (the ammonia content of this solution being

The catalyst was stirred for 8.3 days and stirred at -6 ° C for one day.

The separated crystals were isolated by filtration. These crystals are washed on the filter twice with 20 ml of cold methanol (0-5 ° C). The yield of the crystalline product was 34.56 g (corresponding to 86.4% by weight based on the fenvalerate A used).

By analysis of the obtained crystals, it was determined that with respect to the alcohol residue of the ester, there were: 2.3% of the (R) -cismer, and. 97.7 percent · of the (S) -isomer.

EXAMPLE 18 g of fenvalerate A of the same composition as in the preceding examples are dissolved in 80 g of methylcyclohexane and then 10 mg of fenvalerate seed Α »is added to the solution thus obtained. To the solution · 9.8 g of methanol solution · ammonia (ammonia content in this solution) are added:

8.3% (w / w) as a catalyst and the mixture was stirred at -6 ° C for one day.

The precipitated crystals are then isolated by filtration. The crystals were washed twice on the filter with 20 ml of cold methylcyclohexane (0-5 ° C). The yield of crystal of the product was 31.4 g (corresponding to 78.5% w / w based on the fenvalerate A used).

Analysis of the crystals obtained indicated that, with respect to the alcohol residue of the ester, there were: 1.4% of the (R) -isomer and 98.6% of the (S) -isomer.

EXAMPLE 19 g of fenvalerate A same composition as in the preceding examples · are dissolved in a mixture of 10 g · · · of toluene and 70 g of heptane, then a · · thus prepared solution was added 10 mg of seed crystal · A _and fenvalerate. Next, 9.8 g of methanolic ammonia solution (ammonia content in this solution: 8.3% by weight) as catalyst are added to the solution and the mixture is stirred at -6 ° C for one day.

The precipitated crystals are then isolated by filtration. These crystals are washed on the filter 2 x 20 ml cold heptane (0-5 ° C).

The yield of the crystalline product is 31.72 g (corresponding to 79.3% by weight, based on the fenvalerate used).

1S

Analysis of the obtained crystals was determined to be; o alcohol residue of the ester is present: 2.2% (Rj-isomer and 97.8 percent (Sj-isomer).

Example 20 g of fenvalerate A are dissolved in 60 g of methanol and k. 10 mg of germinal fenvalerate Α _α is added to the solution thus obtained. 38 mg of sodium hydroxide dissolved in 1 g of methanol as catalyst are added to the solution, and the mixture is then stirred at -6 DEG C. for one time. on.

The separated crystals were isolated by filtration. These crystals were formed. Wash the filter twice with 20 ml of cold methanol (0-5 ° C). The yield of crystalline product was 23.84 g (corresponding to 59.6% by weight of fenvalerate A).

Analysis of the crystals obtained showed that 2.8% of the (R) -isomer and 97.2% of the (S) -isomer were present with respect to the alcohol residue of the ester.

Example 21 g of fenvalerate A of the same composition as. in the preceding examples' were dissolved in 60 grams of methanol, and the solution thus obtained .se .potom added 10 mg of seed crystal of fenvalerate _and. 47 mg of sodium cyanide was added to the solution. as; of the catalyst dissolved in 2 g of methanol and stirred for one day at -6 ° C.

The separated crystals were isolated by filtration. These crystals were washed on the filter twice with 20 ml of cold methanol (0-5 ° C). The yield of crystalline product was 22.8 g (corresponding to 57.2% by weight, based on the fenvalerate A used).

By analysis of the crystals obtained, it was determined that. as regards the alcohol 'residue' of the ester, it is present: 2.2. % (Rj-isomer and 97.8 percent of the (Sj-isomer).

Example A 22 g of fenvalerate (alcohol residue: 51 percent (R-isomer and about 49 / _0th (S) isomer dissolved in 60 g of methanol, and the solution thus obtained was added 10 mg of seed crystal of fenvalerate Aa. To the solution was added 0.8 g of triethylamine catalyst and mixture were stirred at -6 ° C for half a day.

The separated crystals were isolated by filtration. These crystals were washed twice on the filter. 20 ml cold; of methanol (0-5 ° C). The yield of crystalline product was 21.36 g. (corresponding to 53.4% by weight based on the fenvalerate A used).

Analysis of crystals. The alcohol residue of the ester was determined to be 2.5% (Rj-isomer and 97.5% (S) -isome.ru).

EXAMPLE 23 g of fenvalerate A of the same composition as in the previous example are dissolved in 60 g of methanol, and 10 g of germinate are added to the solution thus obtained; of the fenvalerate A crystal. . 0.8 g was added to the solution. triethylamine catalyst and the mixture was stirred at -6 ° C for one day.

50 ml of a 1% aqueous hydrochloric acid solution and 50 ml of toluene are then added to the reaction mixture. The resulting layers were separated. The aqueous layer was extracted with 50 mL of toluene.

The toluene layers were combined and washed twice with 50 ml of water. Toluene was then distilled off under reduced 'pressure, yielding fenvalerate and rich fenvalerate A _u as a pale yellow oily substance. Yield: 39.73 g (99.3% of theory).

Analysis of the obtained. The oil product was determined to be present with respect to the alcohol residue of the ester: 7.7%. (Rj-isomer and 92.3% (Sj-isomer.

Example 24 g of fenvalerate A 'are dissolved in 20 g of petroleum ether. 5 g of isopropanol. After; dissolution, the mixture is cooled to -10 ° C and 1 g of triethylamine and 10 mg of fenvalerate crystal A 'are added. Mixture. is then stirred. . at. at the same temperature for 3 days. . The precipitated crystals are isolated. by filtration and intersecting with 10 ml of cold isopropanol (-5 to -10 ° C) to give 5.61 g of fenvalerate A. The analysis of these crystals revealed that the alcohol residue of the ester contained 98.1% of the isomer. 9% of the (R) isomer.

EXAMPLE 25 g of fenvalerate A are dissolved in a mixed solvent of 1 g of xylene, 12 g of octane and 7 g of methanol. 1.8 ml of a 8.4% ammonia solution in methane was added to the solution, and the mixture was stirred at -20 ° C for a period of time. one day. The precipitated crystals are then isolated by filtration and washed with 5 ml of cold methanol (-15 to -25 ° C) to obtain 8.38 g of fenvalerate Aa. Analysis of these crystals revealed that the alcohol moiety contained an ester

2.3 o / o isomer. (R) and 97.7% of the (S) isomer.

Example 26 g of fenvalerate A 'are dissolved in 13 g of pentain and 7 g of methanol. The solution is then added. 1.8 ml of a 8.4% ammonia in methanol solution and 10 mg of fenvalerate crystal

Aa, whereupon the mixture was stirred at -25 ° C for 3 days. The precipitated crystals were collected by filtration and washed with 10 ml of methanol it chladné17 (-15 to - 25 ^Q C) to give

8.60 g of fenvalerate A '. Analysis of these crystals revealed that the alcohol residue of the ester contained 2.5 o / o of the (R) isomer and 97.5% of the (S) isomer.

Example 27 g of fenvalerate A are dissolved in a mixed solvent of 1 g of carbon tetrachloride, 12 g of hexane and 7 g of ethanol. To the solution was added 0.25 g of triethylamine and 10 mg of fenvalerate crystal A _and the mixture was stirred at -20 ° C for 1 day. The separated crystals are then isolated by filtration and washed with 5 ml of cold ethanol (-15 to -20 ° C) to obtain 7.5 g of fenvalerate A '. Analysis of the crystals revealed that the alcohol residue of the ester contained 3% of the isomer (R) and 97% of the isomer (S).

Example 28 g of fenvalerate A is dissolved in 10 g of n-thanol. 0.1 g of triethylamine and 10 mg of fenvalerate crystal A 'are then added to the solution, followed by stirring at 17 ° C for one day. The precipitated crystals are then isolated by filtration and washed with 5 ml of cold methanol (0 to 5 ° C) to give 5.28 g of fenvalerate A _and crystal analysis showed that the alcohol residue of the ester contained 1% of the isomer. 99% isomer · (S).

Example 29 g of fenvalerate A is dissolved in 15 g of methanol. To the solution was added 0.05 g of a 2.0% sodium methoxide solution in methanol and 10 mg of fenvalerate crystal Aa, followed by stirring at -6 ° C for 1 dine. The separated crystals were then collected by filtration and washed with 10 mg of cold methanol. (-15 to - 25 ° C) to give 7.09 g of fenvalerate _and. Analysis of the crystals revealed that the alcohol residue of the ester contained 3.6% of the isomer (R1 and 96.4% of the isomer (S)).

Claims (8)

pRedmBt A process for the preparation of (S) -α-cyano-3-phenoxybenzyl (S) -2- (4-chlorophenyl) isovalerate, characterized in that (S) -α-cyano-3-phenoxybenzyl- (S) is crystallized. S) -2- (4-chlorophenyl) isovalerate from a solution of (R, S -cyano-3-phenoxybenzyl- (S) -2- (4-chlorophenyl) isovalerate in a solvent selected from the group consisting of C 1 -C 5 alcohol, aliphatic a hydrocarbon of 5 to 15 carbon atoms and an alicyclic hydrocarbon of 5 to 10 carbon atoms, a mixture of two or more of these solvents and a mixed solvent containing said solvent or said mixture of solvents, and an aromatic hydrocarbon of 6 to 10 carbon atoms, in the presence of a base as a catalyst selected from the group consisting of an alkali metal hydroxide, an alkaline earth metal hydroxide, an alkali metal alcoholate of 1 to 5 carbon atoms, an alkaline earth metal alcoholate of 1 to 5 carbon atoms, an alkali metal amide, an alkali earth metal amide in, alkali metal hydride, alkaline earth metal hydride, basic ion exchange resin, ammonia and an organic amine. 2. A process according to claim 1, wherein the solvent is methanol. YNALEZ or ethanol or a mixed solvent containing methanol or ethanol. 3. A process according to claim 1 wherein the solvent is methanol. 4. A process according to claim 1, wherein the solvent is an aliphatic hydrocarbon, an alicyclic hydrocarbon, a mixture of an aliphatic hydrocarbon and an aromatic hydrocarbon, or a mixture of an alicyclic hydrocarbon and an aromatic hydrocarbon. 5. The process according to claim 1, wherein the solvent is selected from the group consisting of pentane, hexane and heptane. 6. A process according to claim 1 wherein the solvent is a mixture of a solvent selected from the group consisting of pentane, hexane and heptane and a solvent selected from the group consisting of benzene, toluene and xylene. 7. The process of claim 1 wherein the solvent is selected from the group consisting of cyclohexane and methylcyclohexane. 8. A process according to claim 1, wherein the base is a substance selected from the group consisting of an alkaline earth metal hydroxide.