Process for the Preparation of Beta and Theta cypermethrin

Background of the invention

Cypermethrin is a synthetic pyrethroid used as an insecticide in large-scale commercial agricultural applications. It behaves as a fast-acting neurotoxin in insects. The IUPAC name of Cypermethrin is (R,S)-alpha-cyano-3-phenoxybenzyl(lRS)-cis,trans-3-(2,2-dichlorinyl)-2,2-dimethylcyclopropane-carboxylate. It's chemical structure is represented below:

Structurally, the molecule embodies three chiral centers, two in cyclopropane ring and one on the alpha cyano carbon. Thus there are four pairs of enantiomers possible for Cypermethrin, represented below:

These isomers are commonly grouped into four cis and four trans isomers. A 1:1 mixture of the two enantiomers (R)-a-cyano-3-phenoxybenzyl (lS)-trans-3-(2,2-dichlorovinyl)-2,2-dimethyl cyclopropane carboxylate and (S)-a-cyano-3-phenoxyben2yl (lR)-trans-3-(2,2-dichlorovinyl)- 2,2-dimethylcyclopropanecarboxylate represent the theta cypermethrin while an enantiomeric mixture (R)-a-cyano-3-phenoxybenzyl (1R)cis-3-(2,2-dichlorovinyl)-2,2-dimethylcycopropanecarboxylate and (R) -a-cyano-3-phenoxy benzyl (1S)-cis-3-(2,2-dichlorovinyl)-2,2-dimethylcycopropanecarboxylate in ratio 2:3 with the enantiomeric pair (S)-a-cyano-3-phenoxybenzyl (R)-trans-3-(2,2-dichlorovinyl)-2,2-dimethylcycopropanecarboxylate and (R)-a-cyano-3-phenoxybenzyl (IS)-trans-3-(2,2-dichlorovinyl)-2,2- dimethylcycopropanecarboxylate of beta cypermethrin.

The prior art processes viz., US 4845126, involves the epimerization to isolate the Theta cypermethrins (1:1 mixture of 1RtansS and 1StransR). In this invention, triethylamine were used as base in presence of tertiary butylhydroxy toluene as catalyst at 30 °C for 24 hours. The obtained crude isomeric mixture were crystallized in isopropyl alcohol in 75% of yield with 99.5% purity.

Also, US 4997970, 4409150 involve either the asymmetric synthesis or chiral separation to isolate of 1ReisS, 1ScisR, 1RtransS and 1StransR cypermethrins.

The present invention deals with a simple and efficient process for the isolation of beta and theta cypermethrin in very good yields and in high purity without involving asymmetric synthesis and chiral separation techniques.

Detailed Description of the invention

In the present invention, comprising two enantiomeric pairs in ratio 2:3 of 1 Scis-aR+1Rcis- aS and 1 Strans-aR+1Rtrans-aS (beta-cypermethrin) is represented as la; and the 1:1 mixture of enantiomeric pairs consisting of 1Rtrans-aS and 1Strans- (theta-cypermethrin) is represented as lb.

According to the present invention, beta-cypermethrin la is crystallizing out from cypermethrin of formula I in a suitable organic base and in a protic solvent; and also in the presence of little amounts of inorganic base and 2,6-di-tert-butyl-p-cresol as a catalyst. The organic bases that can be employed are triethylamine, diisopropylamine each independently or combinations thereof; and in the presence of potassium hydroxide. The protic solvents are isopropyl alcohol, tert-butyl alcohol and ethanol wherein the preferable organic base is triethylamine and the most preferable base combination is triethylamine and diisopropylamine; the most preferable protic solvent is isopropyl alcohol. The most preferable temperature range to carry out the said reaction is 8-10° C for 84 hrs.

The resulting crystalline product predominantly comprises the enantiomeric mixture of cis-2 and trans-2 in the ratio 2:3 substantially free from cis-1 and trans-1. The novel process has the advantage that it does not involve any asymmetric synthesis or optical resolution step. Thus, the present invention provides selected isomer pairs la which enables the highly economical preparation.

Another aspect of the invention is the process of preparation of theta-cypermethrin lb. According to the process, theta-cypermethrin crystallizes out from trans cypermethrin in an organic base and aliphatic hydrocarbon while stirring. The temperature at which the organic base is added is critical and the purity and yield of the final product depends upon the temperature at which addition is carried out. The reaction is carried out in the presence of organic bases like triethylamine, trimethyl amine and diisopropyl amine and in the presence of aliphatic hydrocarbons like hexane and cyclohexane wherein triethyl amine is the most preferred base and hexane is the most preferred solvent. The range of temperature is 5 - 20° C, wherein 15 - 20° C is the preferred temperature and 20° C is the most preferred temperature. The stirring is continued for a minimum period of 24 - 36 hours wherein 36 hours is the most preferred time period. The resulting crystalline product comprises the enantiomeric mixture of IRtrans-aS and 1Strans-aR in high yields and purity.

Example 1 (la)
150 g of cypermethrin mixture (comprising two enantiomeric pairs of cis and trans in ratio (41:59) and 153 ml of isopropyl alcohol was introduced into 500 ml of 4 neck RB flask with stirring. To the above mixture triethylamine (7.5 g), diisopropylamine (7.5 g), 2,6-di-tert-butyl-p-cresol (0.45 g), and KOH (0.45 g) are added and stirring continued at room temperature. After 3 hours, the mass is cooled to 8 - 10° C and maintained for 84 hours. After completion of the reaction, the mass is cooled to 0° C, and 155 ml of isopropyl alcohol was added and maintained for 3 hours. The residue is filtered (epimerized cis & trans mixture) and washed twice with 100 ml of cold isopropyl alcohol (0° C). The residue thus obtained (155 g) is crystallized in hexane and dried atmospherically. Thus 117.5 g of white crystalline produce is obtained in 78.3 % of yield. Analysis by HPLC showed the ratio of cis : trans ratio of 2:3 in 97.9% purity.

Example 2 (lb)
100 g of trans cypermethrin (trans min 98%), 70 ml of triethylamine was introduced into a 500 mL 4 neck RB flask and stirred at 20° C. for 36 hours. After complete epimerization, 85 ml of hexane was added, and maintained for 1 hour; the residue was filtered, washed with 100 ml of cold hexane (20° C). The resulting residue was crystallized in hexane to obtain pure epimerized product (yield 72-75%). Analysis by HPLC showed the trans isomer in 99.4% purity.

Claims

1. A process for the preparation of beta cypermethrin which involves treating cypermethrin mixture comprising two enantiomeric pairs of cis and trans in ratio (41:59) with organic bases, 2,6-di-tert-butyl-p-cresol and KOH in the presence of protic solvents.

2. A process for the preparation of theta cypermethrin which involves treating trans cypermethrin with an organic base at a temperature range of 5- 20° C and for a period of 24 - 36 hours in the presence of aliphatic hydrocarbons.