CS211391B2 - Method of preparation of the + l s + p -alpha-kyano-3-phenoxybenzyl - + l s + p-2- + l 4-chlorphenyl isovalerate - Google Patents

Description

(54) Preparation of (S) -α-cyano-3-phenoxybenzyl (S) -2- (4-chlorophenyl) isovalerate

The invention relates to a process for the preparation of (S) -α-cyano-3-phenoxybenzyl- (S) -2- (4-chlorophenyl) -isovalerate.

ar-cyano-3-fenoxybe.nzyl-2- (4-chlorophenyl) isovalerate of the formula I ₀ CH

CH'ω exhibits low mammalian toxicity and insecticidal activity against a significant amount of insects (as described, for example, in U.S. Pat. No. 3,696,244) and contains two asymmetric carbons per molecule, as a result of which it is known in the form of four optical isomers.

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

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

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

(R) -? - cyano-3-phenoxybenzyl (S) -2- (4-chlorophemylisovalerate) will hereinafter be referred to as "fenvalerate A /‘ ".

(S) -α-cyano-3-phenoxybenzyl- (R) -2- (4-phenylphenyl) isovalerate will hereinafter be referred to as "fenvalerate B".

(R) -2-cyano-3-phenoxybenzyl- (R) -2- (4-chlorophenyl) isovalerate will hereinafter be referred to as "fenvalerate B /‘ ".

The relationship of the absolute configuration of the asymmetric carbon atom on the acid moiety to the insecticidal activity of the above ester has already been elucidated and is well known (Miyakado et al., Agr. Bia Chem., 39, 267 (1975)) for the preparation of acid (S) - 2- (4-chlorophenyl iisovaleric), from which an ester with significant insectieidic activity is derived Miyakado et al.

The relationship of the absolute configuration of the asymmetric carbon atom of the alcohol moiety to the ipsectclidic activity of the above ester is described in Japanese published patent application OPI 59646/78, which also describes a process for preparing esters having an optically active alcohol moiety.

In Japanese Patent OPI 24019/78 describes the preparation způsoh fenvalerátového isomer having an optically active moiety, fenvalerate A chromatography on a silica column in order to divide feinvalerátu A _A fenvalerate and fenvalerate. A _s .

The method described in Japanese Published Application OPI 59646/78 relates to optically active 3-phenoxymandelic acid obtained by resolution of 3-phenoxymandelic acid into its optical 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 _K is an excellent insecticidal product whose insecticidal activity is about four times higher than the insecticidal activity of raicemic fenvalerate (see, for example, Japanese Published Patent Application OPI 24019/78 J.

The subject of the invention is a method of preparation. (S-.alpha.-cyano-3-phenoxybenzyl- (S, -2- (4-chlorophenyl)) isovalerate, characterized in that, to the (R, SJ-.alpha.-cyano-3-phenoxybenzyl- (S) -2- (4-chlorophenyl) isovalerate in an alcohol having 1 to 6 carbon atoms or in a mixed solvent containing the alcohol or an aliphatic hydrocarbon having 5 to 10 carbon atoms or an alicyclic hydrocarbon having 5 to 10 carbon atoms or in a mixed solvent containing the aliphatic hydrocarbon or alicyclic hydrocarbon, add (S1-a-cyano-3-phenoxybenzyl- (S) -2-. (4-chlorophenyl) iso-valerate), (R) -a seed crystal. -cyano-3-phenoxybenzyl (RJ-2- (4-chlorophenyl) isovalerate or mixtures thereof, followed by (S) -α-cyano-3-phenoxybenzyl (S) -2- (4-chloro) enylisisovalerate does not crystallize out of solution and the crystals of this (S) -α-cyano-3-phenoxybenzyl (S) -2- (4-chlorophemyl) isovalerate are separated from the mother liquor.

In a search for a process for producing fenvalerate isomer having an optically active alcohol residue, it has been found that by adding a seed crystal of fenvalerate A, fenvalerate B or a mixture thereof to the fenvalerate A solution, only fenvalerate A 'is selectively crystallized.

Since they are esters of the pyrethroid or type, the crystalline form of the above-mentioned compounds cannot be judged on the basis of racemic properties. fenvalerate, which is a viscous oily substance.

Fenvalerate A ₍ λ: mp ~ 57.9 ° C, [α] ²¹ = -11.2 ° (in CHCl 3, concentration = 6.5,%).

Fenvalerate B ^:

. mp = 59.6 ° C; _{[a] D} 24 ₌ + 12.5 DEG (in CHCl concentration = 3.8%).

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

However, as a mixture of equal parts by weight (melting point 75-76.8 ° C) of an ester having a d-itraus-acid residue and (R 1 -alcohol), and an ester having 1-trans- (1S, 3R) an acid residue and an (S) -alcohol residue as well as a mixture of equal parts by weight (melting point 78.5-80 ° C) of an ester having a d-trans acid residue and an (S) -alcohol residue and an ester having 1 -trans-acid residue and (R 1 -alcohol residue) were obtained in crystalline form.

It was also. found that for α-ethynyl-3-phenoxybenzyl-2- (4-chlorophenyl) isovalerate, which is an ester of pyrethroid type a, having 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 diastereoisomers thereof (each racemic) and an ester of said compound having an optically active acid residue crystallized at room temperature. When an ester mixture with a racemic acid moiety and a racemic alcohol moiety is recrystallized from hexane, the diaistereoiscimer, having a melting point of 87-88 ° C, exhibits very poor insecticidal activity. The ester isolated from the mother liquor is a diisomeric isomer (melting point 51-52 ° C) having higher insecticidal activity.

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

For alletrin (which is allethronylchrysarnthemate), which has long been known as: a synthetic ester of the pyrethroid type or having four diastereoisomers, only one diastereoisomer (crystalline allethrin) is known which is crystalline; it is a diastereoisomer consisting of an ester having a d-trans acidic moiety and a 1-alkcholic moiety and an ester having a 1-tansanic acid, a new moiety and a d-alcohol moiety [M. Matsui and I. Yamamoto, Naturel Occuring Insecticides, M. Jacobson and D. G. Grosby Eds., Pp. 38-42, Marcel Dekker, inc., New York (1971)]. None of the enautiomeric isomers are known to be crystalline per se.

It follows from the above that it is completely impossible to predict which of the optical isomers or their mixtures is obtained in crystalline form and whether the optical iso211391 mer can selectively crystallize from the mixture with other optical isomers if O 'is known. that is crystalline.

Also, the effective use of the mother liquor obtained as a by-product in the preparation of fenvalerate having an optically active alcohol residue has been studied, and it has been found that by dissolving the optically active fenvalerate having an alcohol residue in an unbalanced (R) / (S) ratio, solvent or a mixed solvent containing a protonic solvent, preferably adding a basic catalyst or dissolving said fenvalerate in an aprotic solvent and then adding said basic catalyst, results in rapid isomerization of the asymmetric carbon atom in the alcohol moiety.

Until now, the general opinion that mandelic nitrile ester is. in a protomic solvent or: unstable in the presence of a basic catalyst to break down the ester bond or decompose the nitrile group. However, it has now been found that the ester described above is predominantly isomeric under the conditions.

Isomerization of optically active aliphatic. nitrile in the presence of a basic catalyst is already known (for example, this isomerization is described in J. Am. Chem. Soc., 86, 5457 (1964)]. However, the isomerization of an ester 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 _c and isomerization of fenvalerate Α _β in the mother liquor can be achieved simultaneously, resulting in fenvalerate A in high yield.

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

Any solvent in which fenvalerate A is soluble and which dissolves fenvalerate A only to a very limited extent can be used in the process of the invention. Examples of solvents that may be used in the present case are: lower alcohols having 1 to 6 carbon atoms, such as methanol or ethanol, and aliphatic or alicyclic hydrocarbons, such as pentaimide hexane, heptane, cyclohexane and methyl yclohexane, either alone, or mixtures thereof, and mixtures of these solvents with aromatic hydrocarbons such as benzene, toluene and xylene, and with lower alcohols such as methanol or ethanol, the mixed solvents containing the lower alcohols being preferably solvents in this case.

The most preferred solvent is methanol.

In order that the invention may be more fully understood, the following examples are given by way of illustration and not by way of limitation. In these examples, all parts, percentages and ratios are by weight unless otherwise indicated.

In these examples, the (RJ-isomer (fenvalerate Αβ) and (SJ-isomer (fenvalerate A ₍ )) of the alcohol residue were analyzed by gas chromatography under the following analysis conditions:

column:

10% silicone, diameter = 3 mm, height = 3 m, column temperature = 245 ° C;

Evaporation chamber temperature = 250 ^° C; nitrogen pressure = 0.2 MPa.

Under these conditions, the residence time (SJ-isomer (fenvalerate A _a )) was 43 minutes and the residence time of the (R) -isomer (fenvalerate Αβ) was 38 minutes.

In this: Methods are esters having (RJ acid residue reverse residence time, i.e. the residence time of the ester having: (SJ-alkohoílový residue (fenvalerate _B) is the same as fenvalerate Αβ and the residence time of the ester having the (R-alcohol radical ( fenvalerate „β) is the same as: u. fenvalerate A "This means that if fenvalerate A is present in a certain ratio, the ester having, (RJ-acid residue, then the peak of each: the above isomer exceeds the peak of its Eiruantiomer in about this ratio.

The optical purity of the acid residue of fenvalerate A was determined as follows:

Fenvalerate A is hydrogenated in ethanol using platinum oxide as a catalyst to give (S) -2- (4-chlorophenyl) isovaleric acid, which is then converted to the acid chloride using thionyl chloride, which acid is then converted to the 1-methoester with 1- The ratio between the two resulting diastereoisomers is determined by gas chromatography and the optical purity of the acid residue is sealed from the results obtained.

Example 1

As starting material, fenvalerate A is used, the alcohol residue of which is 50.5% of the peak (RJ-isomer and 49.5% of the peak is (SJ-isomer), the acidic residue having an optical purity of 92.8%. expressly stated, fenvalerate A of the same composition and purity as in this example will also be used in other examples.

g of this starting material is dissolved in 5 g of ethyl alcohol, and 1 mg of (S) -α-cyano-3-phenoxybenzyl- (S-2- (4-chlorophenyl) isovalerate is added to the solution obtained. The mixture was allowed to stand for 4 days at -6 ^° C.

The separated crystals are then collected by filtration. The crystals were rinsed on the filter with 2 mL of cold ethanol (0-5 ° C). The yield of crystalline product having a melting point of 57.9 ° C is 1.27 g.

It was determined by gas chromatography that, for the alcohol residue of said ester, 4% (Rj-isomer and 96% (Sj-isomer) was present. For the alcohol residue of the ester in the filtrate, 65.5% (Rj-) was present. of the isomer and 34.5% (S-isomer. Example 2)

The starting material used was fenvalerate A of the same composition as in the previous Example 1.

g of this starting material is dissolved in 5 g of ethyl alcohol and 1 mg of fenvalerate Β _β seed is added. · The thus obtained mixture was allowed to stand for 4 days at a temperature of -6 C ^Q

The separated crystals are then collected by filtration. The crystals were washed on the filter .třikrál 2 .ml cold ethanol (0-5 C ^Q). The yield of the crystalline product is 1.32 g. By analysis of the crystals, it was determined that, as regards the alcohol residue of the ester, 3% (Rj-isomer and 97% (Sj-isomer) were present. Example 3

Envalerate A of the same composition as in the preceding examples is used as starting material.

g of this starting material is dissolved in 5.5 g of a mixture of benzene and n-hexane (1: 5 weight ratio), and 1 mg of (S-a-cyano-3-phenoxybenzyl- (S) - 2- (4-Chloro-phenyl) -isovalerate, thus obtained, was allowed to stand for 4 days at -6 ° C.

The precipitated crystals are collected by filtration at about ^1. These crystals are washed three times with 2 ml of cold ethanol (0-5 ° C) on the filter. The yield of crystals is 0.62 g. By analysis of the crystals, it was determined that 2.7% (Rj-isomer and 97.3% (Sj-isomer) were present with respect to the alcohol residue of the ester.

Example 4

As starting material, fenvalerate A of the same composition as in the preceding examples was used.

g of this starting material is dissolved in 6 g of methanol, and 1 mg of (S, a-cyano-3-phenoxybenzyl- (S) -2- (4-chlorophenyl) isovalerate) is added to the obtained solution. the resulting mixture was allowed to stand for 4 days at -6 ° C.

The separated crystals are then collected by filtration. The crystals were washed three times with 2 ml cold ethanol (0-5 ° C) on the filter. The yield of the crystalline product was 1.78 g. an alcohol residue of the ester is present

4.5% (R) -isomer and about 95.5 / ₀ (S) -isomer.

Example 5

5.18 g tenvalerátu A same composition as in the preceding examples were dissolved in 5.2 g of methanol, and the solution thus obtained was added 1 mg of a seed crystal of fenvalerate · _A. The resulting mixture was then stirred at 2-4 ° C for one day.

The precipitated crystals are isolated by filtration; these crystals were washed twice with 3 mL cold hexane (0-5 ° C) on the filter. The yield of crystals is 1.48 g (which represents

28.6% by weight, based on the amount of fenvalerate A) used.

Analysis of the crystals obtained revealed that ^: e for the alcohol residue of the ester, 3.4% (Rj-isomer and 96.6 percent (Sj-isomer) is present. For the alcohol residue of fenvalerate A isolated from the filtrate, 68.5% (Rj-isomer) is present. isomer and 31.5 percent (S-isomer.

Example 6

The procedure of Example 1 is followed, except that instead of ethanol, 10 g of n-butanol is used in admixture with 5 g of hexane. After 8 days, 0.91 g of precipitated crystals were collected by filtration. These crystals were found to contain (R i -isomer and (S i -isoamer) in ratio

4.6: 95.4.

Example 7

The procedure of Example 1 is repeated, except that a mixture of 5 g of ethanol and 5 g of diethyl ether is used instead of ethyl alcohol. After 8 days, 0.39 g of precipitated crystals was collected by filtration.

Example 8

The procedure of Example 1 is repeated, except that a mixture of 40 g of hexane and 10 g of ethyl acetate is used instead of ethanol. After 8 days, 0.26 g of crystals were collected by filtration.

Example 9

The procedure of Example 4 was repeated except that the temperature at which the mixture was allowed to stand was -25 ° C instead of -6 ° C. 1.84 g of crystals were isolated.

Example 1 a d 10

The procedure of Example 5 was repeated except that 3.6 g of fenvalerate A was used,

1.8 g of methanol and 20 ° C. 0.43 g of crystals are obtained.

Correction to PVP No. 211 391 (51) Int Cl. ³ A 01 N 37/02, A 01 N 31/12

Header - author of the invention place: AKETA KOCHICHI, ... right: AKETA KOHICHI, ...

Office for Inventions and Objections

Claims (1)

PRKDMlT A process for the preparation of (S) -α-cyano-3-phenoxybenzyl- (S) -2- (4-chlorophenyl) isovalerate, characterized in that to a solution of (R, S) -α-cyano-3-phenoxybenzyl 1- Of (S) -2- (4-chlorophenyl) isovalerate in an alcohol having 1 to 6 carbon atoms or in a mixed solvent containing the alcohol, or an aliphatic hydrocarbon having 5 to 10 carbon atoms or an adicyclic hydrocarbon having 5 to 10 carbon atoms or in a mixed solvent containing the N-alkyl, which aliphatic or alicyclic hydrocarbon adds (S) -α-cyano-3-phenoxybenzyl (S) -2- (4-chlorophenyl) isovalerate, (R) -α-cyano-3- seed. phenoxybenzyl (R) -2- (4-chlorophenyl) isovalerate or mixtures thereof, then (S) -α-cyano-3-phenoxybenzyl (S-2- (4-chlorophenyl) isovalerate crystallized from solution and the crystals of this (S) -α-cyano-3-phenoxybenzyl- (S) -2- (4-chlorophenylisovalerate) are separated from the mother liquor.