HU197292B - Process for preparing cyclopropane carboxylic acid esters - Google Patents

Abstract

Compounds of formula (I> <IMAGE> wherein R<2> stands for hydrogen or -CN group R<3> stands for substituted, mono- or bicyclic group optionally containing hetero atom or alkyl having 1-4 carbon atoms, R<4> stands for hydrogen atom or alkyl having 1-4 carbon atoms, R<5> stands for hydrogen atom or alkyl having 1-4 carbon atoms, R<6> stands for substituted alkyl having 1-4 carbon atoms or <IMAGE> wherein R<1> stands for halogen atom or methyl, R<7> stands for hydrogen atom, R<6> and R<7> taken together stands for substituted or unsubstituted alkylene having 1-4 carbon atoms, are prepared by reacting a salt of the corresponding carboxylic acid or a salt of its alkyl ester with a chloroformate and eliminating carbon dioxide from the unstable mixed anhydride thus obtained. The compounds prepared according to the invention are obtained in highly pure quality and can be used as insecticides without further purification.

Description

The present invention relates to a process for the preparation of pyrethroid derivatives of formula (I).

As used herein, the substituents have the following meanings:

rl meaning port, halogen, or methyl R ² meaning port, or a CN atom R ³ meaning Or 3-phenoxyphenyl 1,3,4,5,6,7 -hexahydro-1,3-dioxo-2H-iso- indolyl, R ⁴ meaning methyl, R® meaning methyl, R® meaning C = CH rr where R ¹ is as defined above R ⁷ is hydrogen

There are several known methods for the preparation of pyrethroid esters having the insecticidal activity of formula (I):

The alcohol component is reacted with the halide of the carboxylic acid of formula II or the anhydride of the acid (U.S. Patent No. 4,024,163, U.S. Patent No. 2,947,127). The reaction of the salts of the carboxylic acids of formula II with m-phenoxybenzyl halide was reported in 85-92% yield (German Patent No. 2,437,882). The esterification of the carboxylic acid salt of the formula (II) with the aryl sulfonates of the alcohol component has also been described in a two-phase system with a phase transfer catalyst (EP 67 461).

Transesterification processes are also known, for example, from the etherification of the ethyl ester of the acid of formula II with m-phenoxybenzaldehyde cyanohydride acetate (U.S. Patent No. 4,288,610).

The above procedures generally provide the desired pyrethroid derivative in good yield, but often include undesirable reports of the esterification reaction, so that side reactions due to the degradation of the acid halides and the presence of impurities are often expected in the case of acylation with acid halides. The unstable and sensitive acid halide is difficult to purify. The complexity of the acid halide preparation, the difficulty of recovering the tertiary bases used for subsequent acylation, environmental problems, etc. make it difficult to apply these methods in large-scale industry. In the case of acylation with anhydride, only one acyl group is utilized due to insufficient reactivity.

The aryl sulfonates of the corresponding alcohol components can be prepared in up to 90% yield. The most commonly used tosyl chloride is an expensive reagent.

In the case of transesterification it is difficult to achieve complete conversion and the target product is always contaminated with the starting materials.

On the other hand, in acylations with acid halides and anhydrides, as well as in the transesterification processes, the cis-trans isomer ratio of the desired pyrethroid derivative differs from the cis-trans ratio of the starting pyrethroid derivative due to the reaction isomerization.

The process of the present invention provides the desired pyrethroid esters in an economical, pure and gentle manner, avoiding the aforementioned difficulties.

Our procedure is detailed below.

The present invention relates to a process for preparing cyclopropenecarboxylic acid esters of formula (I)

- wherein R ^2, R ^3, R ^4, R ^s, R® and ^R7 are as defined above are prepared by reacting (II) cyclopropanecarboxylic acid compound of formula alkálifámhidrcxidal or acid salt in an aqueous or organic solvent with an organic base where R ⁴ , R ⁵ , R ⁶ and R ⁷ are as defined above - Chloroformate (III)

with an equivalent amount of R ² and R ³ as defined above, in a solvent medium at 0-100 ° C, and from the resulting mixed anhydride of formula (IV)

- wherein R ^2, R ^3, R ^4, R ^5, R® and ^R7 are as defined above by elimination of carbon dioxide from 30 to 100 ° C, optionally 0.01-0.5 equivalents of basic catalyst, and the reaction mixture recovering the product in a known manner.

Our process is based on the observation that the carbonic acid esters of the cyclopropane carboxylic acids, first prepared by us, are unstable, are capable of rearrangement by loss of carbon dioxide, whereby the cyclopropane carboxylic acid esters of the cyclopropane carboxylic acids are bonded to the alcoholic esters.

The starting cyclopropane carboxylic acid of formula (II) may exist in the form of various isomers, as is evident from its formula (a). The present invention relates to both cis and trans isomers and mixtures thereof, as well as optically active forms and racemates. Similarly, the final products are present in various isomeric forms, especially when R ² is -CN. Our patent protection covers all isomers and all mixtures thereof.

The carboxylic acids of formula (II) may be reacted with the chloroformic acid ester (III) in the form of its salts with an alkali hydroxide or organic base. The carboxylic acid salt of formula (II) is prepared in an aqueous or organic solvent medium.

The chloroformic acid esters of formula (III) are new. They can be prepared from the corresponding alcohol with phosgene in chlorobenzene medium in the presence of 3 triethylamine acid scavengers. The physicochemical data of some chloroformic acid esters that may be advantageously employed in the reaction are given below;

specific gravity: from ^20th op: fp. of chloroformic acid-m-phenoxy-benzyl ester 1155 1.5845 120-130 / mm Hg chloro formic acid-methanol-tetrahydrophthalimido 28-30 ° C chloro formic acid metafenoxi cyanohydrin 1189 1.5725 135-142 / mm Hg

Preferably, the salt of the carboxylic acid of formula (II) is reacted in an aqueous or organic solvent medium according to formula (IU). with ester. In an aqueous medium, an alkali salt (preferably sodium, potassium, or ammonium salt) of the carboxylic acid (II) is generally reacted. It is also advantageous to add a low boiling point, water immiscible solvent for this method. The latter facilitates the processing of the reaction mixture.

When working in the presence of anhydrous organic solvent, it is preferable to use the tertiary amine salt of the carboxylic acid.

The reaction mixture temporarily produces the mixed anhydride of formula (IV), from which the carbon dioxide is eliminated to form the final product. It is preferred to use chlorinated hydrocarbons as the solvent.

Carbon dioxide elimination, which begins at room temperature, may be appropriately promoted or accelerated. Thus, various catalysts, alkali hydroxides or organic bases may be advantageously used. According to the present invention, the use of traces of pyridine has proven to be particularly useful. In this case, the reaction is carried out at 50-60 ° C for 1 hour. 4 '

The elimination of carbon dioxide can also be accelerated thermally, preferably at a temperature of 50-70 ° C.

The reaction mixture is worked up in a manner known per se. When working in anhydrous organic solvent 4, the precipitated salts are filtered off and the filtrate is evaporated to give the final product in very pure form. In a two-phase aqueous system, the phases are separated and the pyrethroid ester is recovered from the organic phase. its use as a tin insecticide as an active ingredient generally does not require further purification.

The process of the present invention provides the final product with excellent purity in very good yield. There is no change in the ratio of isomers or racemization of optically active starting materials.

The present invention is advantageously applicable to the preparation of various pyrethroid esters commercially available 6 '. Particularly preferred is 2,2-dimethyl-3- (2,2-dimethyl-vinyl) -cyclopropanecarboxylic acid or 2,2-dimethyl-3- (2,2-dichloro-vinyl) -cyclopropenecarboxylic acid 6 or 2 , 2-dimethyl-3- (2,2-dibromo-vinyl) -cyclopropanecarboxylic acid salt or any of its isomeric forms is reacted with m-phenoxybenzyl ester of chloroformic acid or tetrahydrophthalimidomethyl ester of chloroformic acid, or with chloroformic acid -m-phenoxybenzaldehyde cyanohydrin.

Details of our procedure are given in the Examples.

Examples

Example 1

209 g / mole of 3- (2,2-dichloroethenyl) -2,2-dimethylcyclopropanecarboxylic acid (cis) trans ratio 40 (60) are dissolved in 1 liter of 1,2-dichloroethane and 140 ml (1 mole) of triethylamine are added. and 10 ml (0.124 mol) of pyridine and 263 g (1 mol) of chloroformic acid m-phenoxybenzyl ester are added dropwise over 10-15 minutes with stirring. Immediate salting out begins and the temperature rises to 2831 ° C while carbon dioxide decomposition begins. After the addition was complete, the mixture was heated to 55-60 ° C and stirred at this temperature for 1 hour.

During this time the carbon dioxide release is completed. After cooling, the mixture is stirred with 1 liter of water, the organic phase is separated off, the aqueous phase is extracted with 200 ml of dichloromethane, and the organic phases are combined, washed twice with 2 x 200 ml of 2X sodium hydroxide solution and twice with 200 ml of hydrochloric acid. , dichloroethane is distilled off. The product was 376 g of (3-phenoxyphenyl) methyl-3- (2,2-dichloroethenyl) -2,2-dimethylcyclopropanecarboxylate in 97X purity. Yield: 93.3%, Isomer ratio: 40 (60-cis) tran 3z. M.p. 32-35 ° C.

Example 2

Dissolve 209 g (1 mol) of 3- (2,2-dichloroethenyl) -2,2-dimethylcyclopropanecarboxylic acid in 25 (75 cis) trans isomer ratio in a solution of 40 g (1 mol) of sodium hydroxide in 1 liter of water. After adding pyridine (1 ml) and dichloroethane (1 liter), m-phenoxybenzyl ester of chloroformic acid (263 g, 1 mol) was added dropwise over 10-15 minutes with constant stirring.

starting from 408 g of (RS) -alpha-cyano-3-phenoxyphenylmethyl- (1RS) -cis-3- (2,2-dichloro-vinyl) -2,2-dimethyl-cyclopropanecarboxylate (96% purity). With a yield of 94.1%.

Mp: 80-82 ° C.

Carbon dioxide starts immediately and the temperature rises to 30-35 ° C. After the addition, the mixture was heated to 55-60 ° C for 1 hour. After cooling, the phases are separated, the aqueous phase is extracted with 200 ml of dichloroethane, and the organic phases are combined and the dichloroethane is dried after distillation. The product was (3-phenoxyphenyl) methyl-3- (2,2-dichloroethenyl) -2,2-dimethylcyclopropenecarboxylate (378 g, 94.7%, pure isomer ratio). Mp 28-30 ° C.

Example 3

237 g (1 mol) of emulsion 42 (58 cis-trans isomeric ratio of 3- (2,2-dichloroethenyl)] (2,2-idmethylcyclopropanecarboxylic acid) and 25 ml of 27 tX sodium hydroxide is stirred at 65-70 [deg.] C. for two hours, then another 25 ml of sodium hydroxide are added and stirring is continued for a further 3 hours. The mixture is then poured into 500 ml of boiling water, sedimented for 1 hour and the phases are separated. The organic phase was dried and filtered to give 135 g (0.57 mole) of 3- (2,2-dichloroethenyl) -2,2-dimethylcyclopropanecarboxylic acid ester (cis-trans 55/45). dus fraction ') For the aqueous phase having a 25/75 cis-trans isomer ratio

3- (2,2-Dichloroethenyl) -2,2-dimethylcyclopropane sodium salt containing 4 ml of pyridine and 400 ml of dichloroethane was added dropwise with 113 g (0.43 mole) of chloroformic acid over a period of 10 to 15 minutes under constant stirring. m-phenoxy-benzyl ester. In the following, the procedure of Example 2 is followed. 163 g of 98X-oe 25/75 cis-trans isomer ratio of (3-phenoxyphenyl) methyl-3- (2,2-dichloroethenyl) -2,2-dimethylcyclopropanecarboxylate, yield 95, IX. . Mp: 28-30 "C.

Example 4

Example 1 was followed. Starting materials were 168 g (1 mol) of chrysanthemic acid with 20/80 cis / trans isomer ratio and 244 g (1 mol) of chloroformate in tetrahydrophthalimidomethyl ester. Dichloromethane is used as solvent instead of dichloroethane. The product was 320 97X-pure with 20/80 cis / trans isomer ratio (1,3,4,5,6,7-hexahydro-1,3-dioxide-2H-isoindol-2-yl) methyl-2,2- dimethyl 3 - (- 2-methyl-1-propenyl) cyclopropane carboxylate in 93.7X yield. Mp 64-70 ° C.

Example 5

The above procedure was prepared from 209 g (1 mol) of (1RS) -cis-2,2-dimethyl-3- (2,2-dichloro-vinyl) -cyclopropenecarboxylic acid and 287.5 g (1 mol) of chloroformate. m- fe noxi- be nzalde hydrocyanic acid6. example

(1RS) -cis-2,2-Dimethyl-3- (2,2-dibromo-vinyl) -cyclopropanecarboxylic acid (298 g, 1 mol) and m-phenoxybenzaldehyde (287.5 g, 1 mol) in chloroformate with cyanohydrin, the product (RS) -alpha-cyano-3-phenoxybenzyl- (1RS) cis-3- (2,2-dibromovinyl) -2,2-dimethylcyclopropanecarboxylate (486 g) was obtained, 96X purity with 92.2X production. Mp: 98-100 ° C.

Example 7

To a 250 ml round-bottomed flask equipped with a stirrer, a thermometer, a reflux condenser and a gas inlet, add 100 ml of chlorobenzene, 20 g of m-phenoxybenzyl alcohol (0.1 mol) and 10.1 g of triethylamine (0.1 mol), and stir continuously. Cool to 0-5 ° C. An equivalent amount of phosgene is introduced by means of a manostatic regulator, ensuring that the temperature does not rise above 10 ° C. Gas introduction time approx. 50-60 minutes. Subsequently, the temperature of the reaction mixture was raised to 30 ° C and stirred for another half hour. The reaction mixture was poured into ice water (300 ml), the organic phase was separated and washed with 5 x sodium carbonate solution (3 x 200 ml). After drying, the chlorobenzene is distilled off in vacuo. 25.0 g of chloroformate are obtained in the form of m-phenoxybenzyl ester. Yield: 96X (its physico-chemical constants are described in the description).

Claims (4)

PATENT CLAIMS A process for the preparation of cyclopropanecarboxylic acid esters of the formula I wherein R ² is hydrogen or cyano, R ³ is 3-phenoxyphenyl or 1, 3, 4, 5, 6, 7-hexahydro-1,3-dioxo-2H-isoindolyl, R ⁴ is methyl R ^s is methyl ^R 1 R ^e is C = CRR 1 - wherein R ¹ is a halogen atom or a methyl group R ⁷ is a hydrogen atom, characterized in that it is a salt of a cyclopropanecarboxylic acid of the formula II with an alkali metal hydroxide or an organic base in an aqueous or organic solvent medium - wherein R ^4, R ^s, R * yy ^R7 as defined in (III) of formula klórhangyaaavéezter - wherein R ¹ and R ³ are reacted with the equivalent amount above in a solvent medium at 0-100 ° C and from the resulting mixed anhydride of formula (TV) - wherein R ^J, R ^3, R *, R ^s, R * and R ⁷ are as defined above - by elimination of carbon dioxide from 30 to 100 ° C, optionally from 0.01 to 0.5 equivalents of basic catalyst, and the reaction mixture recovering the product in a known manner. The process according to claim 1, wherein the organic solvent is dichloroethane or dichloromethane. 3. A process according to claim 1 or 2, wherein the catalyst is selected from the group consisting of alkali metal hydroxides or organic bases. 4. A process according to any one of claims 1 to 3, characterized in that the coloring of the veic anhydride is carried out at a temperature between 50 and 70 ° C.