Title of Invention

IMPROVED PROCESS FOR THE PREPARATION OF TRANSFLUTHRIN

Abstract

The compound 2,3,5,6-Tetrafluorobenzyl (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylate, which is also called as Transfluthrin, is known to be highly active as an insecticide. This compound is prepared by various methods such as condensation of 2,3,5,6-Tetrafluorobenzyl alcohol and (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylicacid chloride, or by condensation of 2,3,5,6-Tetrafluorobenzyl halide and a suitable salt of (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylicacid. The present improved process involves a relatively simpler novel method of preparation of (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylicacid chloride and condensation of 2,3,5,6-Tetrafluorobenzyl alcohol and (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylicacid chloride, and relatively simpler and cheaper commercial method for the purification of the crude product to obtain highly pure Transfluthrin.

Full Text

FORM 2 THE PATENTS ACT, 1970 (39 of 1970) & The Patents Rules, 2003 COMPLETE SPECIFICATION (See section 10; rule 13) Title: IMPROVED PROCESS FOR THE PREPARATION OF TRANSFLUTHRIN Applicant: Bilag Industries Private Limited, a company incorporated under the Companies Act, 1956 and having its principal place of business at Plot # 306/3, II Phase, G.I.D.C., Vapi, India, The following specification describes the invention. IMPROVED PROCESS FOR THE PREPARATION OF TRANSFLUTHRIN BACKGROUND AND PRIOR ART: The present invention relates to an improved process for preparation of 2,3,5,6-Tetrafluorobenzyl (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylate and improved methods for its purification. 2,3,5,6-Tetrafluorobenzyl (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylate is used as a highly active insecticide particularly against various species of houseflies, mosquitoes and animal pests, as disclosed in literature (U.S. Patent Number 4889872). The insecticide is also listed in The Pesticide Manual, Eleventh Edition, Editor: C.D.S. Tomlin, The British Crop Protection Council, U.K. (1997). It is known from literature that 2,3,5,6-Tetrafluorobenzyl (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylate is prepared in several ways, such as from reaction of optically active (+) 1f?-trans-permethric acid or the salt of (+) 1 R-trans-permethric acid or derivatives of (+) 1f?-trans-permethric acid with 2,3,5,6-tetrafluorobenzyl alcohol or derivatives of 2,3,5,6-tetrafluorobenzyl alcohol. It has been reported in literature that (+) 1R-trans-permethric acid chloride can be reacted with 2,3,5,6-tetrafluorobenzyl alcohol at temperatures ranging between 20° and 100° C in the presence or absence of solvents and if -2- appropriate in presence of acid-binging agents, to obtain 2,3,5,6-Tetrafluorobenzyl (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylate. Both, (+) 1 R-trans-permethric acid chloride and 2,3,5,6-tetrafluorobenzyl alcohol are known compounds. The product is worked up, preferably by distillation. In another variation of the hitherto known processes, the salts (in particular the alkali metal salts) of (+) 1 R-trans-permethric acid are preferably reacted with 2,3,5,6-tetrafluorobenzyl chloride, bromide or tosylate, preferably in the sense of an esterification reaction which is known in literature. The reaction is conducted in presence or absence of an alkylation catalyst. In yet another process reported in literature (European Patent Number EP 0779269), the reaction between (+) 1 R-trans-permethric acid and 2,3,5,6-tetrafluorobenzyl alcohol is accomplished by azeotropic esterification using Toluene as a solvent and sulfuric acid as the esterification catalyst. -3- DRAWBACKS OF PRIOR PROCESSES: The US Patent Number 4889872 describes the compound 2,3,5,6-Tetrafluorobenzyl (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylate as a novel compound, useful for controlling variety of insects and pests. A short process for preparation of this compound is also given. The process uses either optically active (+) 1 R-trans-permethric acid or the salt of (+) 1 R-trans-permethric acid or derivatives of (+) 1 R-trans-permethric acid and 2,3,5,6-tetrafluorobenzyl alcohol or derivatives of 2,3,5,6-tetrafluorobenzyl alcohol. All of these compounds are known in literature. In a variant of the process, the reaction between optically active (+) 1 R-trans-permethric acid chloride and 2,3,5,6-tetrafluorobenzyl alcohol followed by high vacuum distillation of the reaction mass gives only 95% yield of the product. It is known that in general, preparation of an acid chloride itself poses many problems such as formation of impurities like anhydrides. Owing to its sensibility towards heat, the purification of (+) 1 R-trans-permethric acid chloride, in particular by means such as high temperature high vacuum distillation, leads to loss of the trans-isomer thereby forming a mixture of the cis- and trans-isomers to a certain extent. Moreover, such type of high temperature vacuum distillation leads to formation of highly toxic tarry residues, which pose a threat to the environment due to their difficult disposal. The mixture of cis- and trans-isomer is extremely difficult to separate into its cis- and trans-isomer and hence it is not economical. Presence -4- of the cis-isomer of permethric acid chloride in (+) 1f?-trans-permethric acid chloride is undesirable since it can condense easily with 2,3,5,6-tetrafluorobenzyl alcohol to give an undesired cis-isomer of Transfluthrin. This isomer is extremely difficult to remove from the finished Transfluthrin by any commercially viable methods. Thus, commercial preparation of highly pure (+) 1R-trans-permethric acid chloride itself is somewhat challenging. In another variant of the process, the potassium salt of (+) 1R-trans-permethric acid is reacted with 2,3,5,6-tetrafluorobenzyl alcohol in presence of pentamethymethylenetriamine and acetonitrile. After the reaction is completed the workup is conducted by complete evaporation of the solvent followed by extraction of the product in another solvent, petroleum ether, followed by shaking with water and finally evaporating the petroleum ether to obtain only 90% yield of the product. It is quite natural that when multiple solvents are involved in a process, the commercial production becomes more complicated and the process is bound to become more time consuming. Moreover, large number of residual impurities originating from recycled solvents may hamper the purity of the product. High vacuum distillation of such a product is not feasible on commercial scale. Also, the residue of distillation of the product poses problems of its disposal. The process therefore appears to be commercially un-attractive. -5- The European patent number EP 0779269 describes a method for producing 2,3,5,6-Tetrafluorobenzyl (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylate by azeotropic esterification of (+) 1R-trans-permethric acid with 2,3,5,6-tetrafluorobenzyl alcohol in a solvent such as toluene. The process uses 5 to 7 % of concentrated sulfuric acid as catalyst. In a variant of the process, (+) 1R-trans-permethric acid and its only 80% mole equivalent of 2,3,5,6-tetrafluorobenzyl alcohol are reacted in refluxing toluene in presence of sulfuric acid, thereby continuously removing the water formed due to the esterification reaction. After complete reaction of 2,3,5,6-tetrafluorobenzyl alcohol, the reaction mass is cooled and extracted using dilute caustic soda solution for removing the un-reacted (+) 1 R-trans-permethric acid as its sodium salt. The reaction mass is then steam distilled to remove the steam-volatile impurities to obtain Transfluthrin with a yield of 97% based on 2,3,5,6-tetrafluorobenzyl alcohol. Although it has not been explicitly mentioned in the process, it is quite evident that the unreacted sodium salt of (+) 1R-trans-permethric acid needs to be recovered by acidification, isolation by suitable means such as filtration/ extraction into a suitable solvent, purification and drying before it can be re-cycled for use in further production. Therefore the yield of Transfluthrin based on consumption of (+) 1R-trans-permethric acid depends much on the efficiency of its recovery and purification. An imperative loss of the valuable (+) 1R-trans-permethric acid is expected during the recovery and purification steps, and hence -6- the overall yield of Transfluthrin based on consumption of (+) 1R-trans-permethric acid is expected to be appreciably low. -7- -8- DETAILED DESCRIPTION The present invention provides an improved process for preparation of 2,3,5,6-Tetrafluorobenzyl (+) 1f?-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylate. The starting material used is (+) 1R-trans-permethric acid and 2,3,5,6-tetrafluorobenzyl alcohol. The (+) 1R-trans-permethric acid is first converted to its acid chloride, which is not isolated from the reaction mixture. The acid chloride is reacted insitu with 2,3,5,6-tetrafluorobenzyl alcohol to obtain Transfluthrin. The novelty of the present process is that the (+) 1R-trans-permethric acid chloride, which is prepared according to the procedure described herein, need not be purified either by its high vacuum high temperature distillation or by other means. This results in very high yields and also high purity of (+) 1R-trans-permethric acid chloride. The process is designed in such a way that impurities such as anhydrides are minimum, and are easily removed from the reaction mass by a novel, cheap and commercially feasible method described herein. The product obtained by the present process is thus highly pure and is obtained in high yields with respect to both, (+) 1R-trans-permethric acid and 2,3,5,6-tetrafluorobenzyl alcohol, despite that no purification of the intermediate (+) 1R-trans-permethric acid chloride is explicitly done. Another novelty of the present process is that the condensation of (+) 1R-trans-permethric acid chloride and 2,3,5,6-tetrafluorobenzyl alcohol is conducted in such a way that the ensuing side reactions are minimum, and any such process impurities which may arise -9- due to such side reactions are easily eliminated from the product by applying a novel, cheap and commercially attractive workup method described herein. Thus, in accordance with present invention, there is provided an improved process, comprises of chlorinating (+) 1R-trans-permethric acid having Formula (I) with at least one chlorinating agent to produce its acid chloride (+) 1 R-trans-permethric acid chloride having Formula (II), and reacting the (+) 1R-trans-permethric acid chloride with 2,3,5,6-tetrafluorobenzyl alcohol having Formula (III) to form a crude product, and purifying the crude product to give the 2,3,5,6-Tetrafluorobenzyl (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylate having the Formula (IV), in very high yield and purity. The present invention will now be explained in further detail. According to the present invention, it is possible to react (+) 1R-trans-permethric acid having Formula (I) with slight excess of chlorinating agents chosen from the group comprising thionyl chloride, phosphorous trichloride, phorphorous oxychloride and elemental chlorine, more preferably thionyl chloride, to give (+) 1R-trans-permethric acid chloride having the Formula (II). According to the present invention, the above reaction may be conducted in a solventless mode, or by using solvents chosen from the group comprising both, polar and non polar solvents such as methylene dichloride, ethylene dichloride, hexane, heptane, benzene, toluene and xylene, more preferably toluene. Furthermore, the reaction -10- for preparing the acid chloride may be conducted at temperatures ranging from 0 to 110 °C and more preferably between 30 to 90 °C. A chlorination catalyst or acylation catalyst selected from group comprising of pyridine, picolines, formaldehyde, dimethyl formamide, diethyl formamide, diethylamine, triethyamine, di-isobutyl amine and the like may be used in the reaction for complete conversion of the reactants. According to present invention, it is also possible to conduct the reaction without any of these catalysts. The chlorination reaction may be conducted under atmospheric pressure or under vacuum ranging from 100 - 759 Torr, more advantageously under flow of a dry inert gas chosen from nitrogen, helium or argon. The flow of the inert gas through the reaction mass is known to be responsible for pushing the reaction forwards, by further moving out the ensuing by-product gasses from the reaction mass. Whenever a solvent is used for preparation of the acid chloride, it may be removed from the reaction mass after completion of the reaction by partial or total distillation. It is advantageous to partially distil out the solvent under vacuum so that the dissolved gases and any excess of chlorinating agent is removed completely thereby ensuring better purity of the acid chloride. The solvent can also be completely distilled out for obtaining the acid chloride free from dissolved gasses and the chlorinating agent. It is however advantageous to retain some solvent into the acid chloride, so that the time cycle of the process is reduced without affecting the quality of the intermediate acid chloride. In this particular case, the same solvent -11- is used in the subsequent step of condensation of acid chloride with the alcohol, so that only single solvent is involved in the process for obvious advantages. According to a feature of the present invention, the acid chloride may be prepared either by adding the acid to the chlorinating agent or by adding the chlorinating agent to the acid, thereby obtaining similar quality and yield of the acid chloride in either case. The present invention uses the same solvent for condensation of acid chloride with the alcohol as used in preparation of the acid chloride. However, a solventless reaction is also possible. Also, it is possible to choose a different solvent for the purpose. In particular, the solvent for condensation reaction may be chosen from group comprising of both, polar and non polar solvents such as methylene dichloride, ethylene dichloride, hexane, heptane, benzene, toluene and xylene, more preferably toluene. Furthermore, the condensation reaction of the acid chloride and the alcohol may be conducted at temperatures ranging from 0 to 110 °C and more preferably between 30 to 90 °C. The condensation reaction may be conducted under atmospheric pressure or under vacuum ranging from 100 - 759 Torr, and more advantageously underflow of a dry inert gas chosen from nitrogen, helium or argon, preferably nitrogen. The flow of the inert gas through the reaction mass is known to be responsible for pushing the reaction forwards, by further moving out the ensuing hydrogen chloride gas from the reaction mass. According to a feature of the present invention it is possible to add the acid chloride to the alcohol or alcohol to the acid chloride with an equivalent -12- effect. Whenever a solventless mode is adopted for the condensation reaction, it is advantageous to stir the reaction mass more vigorously in order to drive out the ensuing gasses. It is also advantageous to conduct the solventless condensation reaction under partial vacuum ranging from 400 to 759 Torr, preferably between 720 to 750 Torr, so that the removal of by-product gasses is hastened. Whenever a solvent is used in the reaction it is advantageous to conduct the reaction under refluxing conditions or under flow of a dry inert gas as mentioned above, in order to hasten removal of the by-product gasses. According to a feature of the present process, an acid-binding agent or an acid scavenger can be advantageously used for trapping the by-product hydrogen chloride gas. The acid-binding agents or acid scavenger may be chosen from the group comprising of Diethylamine, Triethylamine, pyridine and the like. Whenever an acid scavenger is used for trapping the hydrogen chloride, the hydrochloride salts may be removed from the reaction mass after completion of the condensation reaction by simple methods such as filtration, water washing to the reaction mass and the like, which are known in literature. In case a solvent is used in the condensation reaction, the reaction mass may be purified by conducting single or various combination of procedures selected from water washing, aqueous soda ash solution treatment, aqueous sodium hydroxide solution treatment, aqueous potassium hydroxide solution treatment, aqueous ammonia solution treatment, batch wise steam distillation, continuous mode steam distillation, filtration, solvent distillation under atmospheric pressure or under vacuum, and the like. According to a feature of the -13- present invention, the workup of the condensation reaction mass is effected by solvent distillation under vacuum, continuous steam distillation with or without replenishing the solvent, alkali solution washing followed by dilute acid washing, water washing, and finally removal of the remaining solvent under vacuum to obtain 2,3,5,6-Tetrafluorobenzyl (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylate in very high purity and high yield. The present invention is illustrated with help of following examples, which however should not be construed to limit the scope of the invention. EXAMPLES: Example 1 (a) Preparation of acid chloride To 1250 ml of toluene, 1200 gm of (+) 1R-trans-permethric acid of 99.5% purity and 99.6% optical purity were added, and a solution was prepared by stirring the reaction mixture at 30 °C. The reaction mixture was dehydrated by distilling out 50 ml of toluene under vacuum of 260-360 Torr and by heating the reaction mass to about 45 °C. After completion of dehydration, 2.7 ml of dimethyl formamide were added and dry nitrogen was bubbled through the reaction mass through a gas sparger. 785 gm of thionyl chloride of 99.0 % purity were added under stirring, slowly to the reaction mass in about 6 hours, during which temperature of the reaction mass was held between 40-45 °C. On completion of addition, the -14- mass was stirred for additional 2 hours after which about 700 - 740 Torr vacuum was applied to partially distil out about 950 to 1050 ml of a mixture of thionyl chloride and toluene. A solution containing about 1295 gm (+) 1R-trans-permethric acid chloride in toluene was thus obtained as residual mass. This mixture was used as such without further purification for condensation with 2,3,5,6-Tetrafluorobenzyl alcohol as described below. (b) Condensation of acid chloride and alcohol A solution of 1025 gm 2,3,5,6-Tetrafluorobenzyl alcohol of 99.6% purity and 270 ml toluene was prepared by stirring the mixture at 30 °C. The reaction mixture was dehydrated by distilling out 50 ml of toluene under vacuum of 400-500 Torr and by heating the reaction mass to about 80 - 85 °C. After completion of dehydration, dry nitrogen was bubbled through the reaction mass through a gas sparger. To the reaction mass was added slowly in about 8 hours, the above obtained solution of 1295 gm (+) 1f?-trans-permethric acid chloride in toluene, and the temperature of the reaction mass was maintained at 80 - 85 °C. After completion of the reaction, 370 ml of water and 230 ml toluene were added to the reaction mass. Steam was purged into the reaction mass through a steam sparger and the temperature of the reaction mass was gradually increased from 80-85 °C to about 100 °C. Simultaneously, steam distillation was conducted by distilling out the toluene-water azeotrope. The steam distillation was conducted in a continuous mode by simultaneous addition of toluene and purging steam into -15- the reaction mixture, until most of the impurities were removed completely. The reaction mass was then cooled to about 30 - 32 °C and 4600 ml of toluene were added to dilute the mixture. The reaction mass was washed successively using 1000 ml of a 4% aqueous solution of sodium carbonate, 1250 ml of water, 1250 ml of 0.005% dilute solution of acetic acid to neutralize the aqueous layer, and finally 1250 ml of water to wash out any dissolved salts. The organic phase was filtered through a 1 micron filter after which toluene was recovered by vacuum distillation of the reaction mass, by applying 110 to 210 Torr vacuum initially, and about 4 Torr vacuum towards the end of the distillation. The temperature of the mass was held at 90-98 °C during concentration. Thus 2070 g of Transfluthrin of 99.2% purity and 99.2% optical purity was obtained in 97.5% yield on 2,3,5,6-Tetrafluorobenzyl alcohol and 97% yield on (+) 1f?-trans-permethric acid. Example 2 (a) Preparation of acid chloride The preparation of acid chloride was repeated in a manner similar to Example 1 above, except that phosphorous trichloride was used as chlorinating agent. Also, dimethyl formamide was not used in this reaction. After completion of the reaction, toluene and phosphorous trichloride were removed completely by vacuum distillation to obtain the acid chloride, which was used as such in the condensation step without further purification. (b) Condensation of acid chloride and alcohol -16- The acid chloride obtained from above step was reacted neat with 2,3,5,6-Tetrafluorobenzyl alcohol under same conditions of temperature as in Example 1 (b) above. After completion of the reaction, 5000 ml of toluene were added to the reaction mass and the mixture was worked up exactly as per Example 1 (b) above. 2045 g of Transfluthrin of 99.0% purity and 99.1 % optical purity was obtained in 96.1% yield on 2,3,5,6-Tetrafluorobenzyl alcohol and 95.6% yield on (+) 1R-trans-permethric acid. Example 3 (a) Preparation of acid chloride The preparation of acid chloride was repeated in a manner similar to Example 1(a) above, to obtain a solution containing about 1296 gm (+) 1R-trans-permethric acid chloride in toluene. This mixture was used as such without further purification for condensation with 2,3,5,6-Tetrafluorobenzyl alcohol as described below. (b) Condensation of acid chloride and alcohol The condensation reaction was repeated as per Example 1 (b), except that the steam distillation was not conducted. 2088 g of Transfluthrin of 97.8% purity and 99.0% optical purity was obtained in 96.9% yield on 2,3,5,6-Tetrafluorobenzyl alcohol and 96.4% yield on (+) 1f?-trans-permethric acid. -17- Example 4 (a) Preparation of acid chloride Example 1 (a) was repeated except that the chlorination reaction was conducted at 80-82 °C under reflux in ethylene dichloride and without purging any dry nitrogen through the reaction mass. After completion of the reaction, the solvent was removed completely by vacuum distillation to obtain 1278 gm of residual acid chloride. This acid chloride was 97.2% pure and was used as is without further purification for condensation reaction. (b) Condensation of acid chloride and alcohol Example 1 (b) was repeated except that Ethylene dichloride was used as solvent. The reaction was conducted under refluxing conditions and without purging any dry nitrogen through the reaction mass. The workup was conducted in a manner similar to Example 1 (b) except that temperature of the steam distillation was 60 -65 °C. Thus 2055 g of Transfluthrin of 98.0% purity and 98.1 % optical purity was obtained in 96.4% yield on 2,3,5,6-Tetrafluorobenzyl alcohol and 95.9% yield on (+) 1 R-trans-permethric acid. Example 5 (a) Preparation of acid chloride The preparation of acid chloride was repeated in a manner similar to Example 1 above to obtain a solution containing about 1293 gm (+) 1/?-trans-permethric acid -18- chloride in toluene. This mixture was used as such without further purification for condensation with 2,3,5,6-Tetrafluorobenzyl alcohol as described below. (b) Condensation of acid chloride and alcohol A solution of 1025 gm 2,3,5,6-Tetrafluorobenzyl alcohol of 99.6% purity and 270 ml toluene was prepared by stirring the mixture at 30 °C. The reaction mixture was dehydrated by distilling out 50 ml of toluene under vacuum of 400-500 Torr and by heating the reaction mass to about 80 - 85 °C. After completion of dehydration, the mass was cooled to 25 °C. 600 gm of triethylamine were added to the reaction mass in about 15 minutes and the temperature was held at 25 -30 °C. To the reaction mass was added slowly in about 8 hours, the above obtained solution of 1293 gm (+) 1R-trans-permethric acid chloride in toluene, and the temperature of the reaction mass was maintained at 25 - 30 °C. After completion of the reaction, 1500 ml of water and 5000 ml toluene were added to the reaction mass and the mixture was stirred to dissolve the triethylamine hydrochloride salt formed into water. The aqueous layer was separated and the organic phase was washed with 1200 ml water. The reaction mass was then washed successively using 1500 ml of a 10% aqueous solution of sodium hydroxide, 1250 ml of water, 1250 ml of 0.005% dilute solution of acetic acid to neutralize the aqueous layer, and finally 1250 ml of water to wash out any dissolved salts. The organic phase was filtered through a 1 micron filter after which toluene was recovered by vacuum distillation of the reaction mass, by -19- applying 110-210 Torr vacuum initially, and about 4 Torr vacuum towards the end of the distillation. The temperature of the mass was held at 90-98 °C during concentration. Thus 2082 g of Transfluthrin of 99.3% purity and 99.0% optical purity was obtained in 98.1% yield on 2,3,5,6-Tetrafluorobenzyl alcohol and 97.8% yield on (+) 1 R-trans-permethric acid. -20- CLAIMS We claim: 1. An improved method for the preparation of 2,3,5,6-Tetraflourobenzvl (+) 1R- trans-2,2-dimethvl-3-(2,2-dichlorovinvl)-cvclopropanecarboxylate, the method comprising: chlorinating a (+) 1 R-trans-permethric acid of formula I with at least one chlorinating agent to form an (+) 1 R-trans-permethric acid chloride of formula II; reacting the (+) 1 R-trans-permethric acid chloride of formula II with 2,3,5,6- tetraflourobenzyl alcohol to form a crude product; and, purifying the crude product to obtain the (+) 1R-trans-2,2-dimethyl-3-(2,2- dichlorovinyl)-cyclopropanecarboxylate. 2. The method of claim 1, wherein the chlorinating agent comprises one of a thionyl chloride, phosphorous trichloride, phosphorous oxychloride and elemental chlorine. 3. The method of claim 2, wherein the chlorinating step further comprises: adding the chlorinating agent to the (+) 1 R-trans-permethric acid of formula I. 4. The method of claim 2, wherein the chlorinating step further comprises: -21- adding the (+) 1 R-trans-permethric acid of formula I to the chlorinating agent. 5. The method of claim 1, wherein the chlorinating step further comprises: reacting the (+) 1 R-trans-permethric acid of formula I in the presence of a solvent. 6. The method of claim 5, wherein the solvent comprises at least one of a methylene chloride, ethylene dichloride, hexane, heptane, benzene, toluene, and xylene. 7. The method of claim 1, wherein the chlorinating step further comprises: reacting the (+) 1 R-trans-permethric acid of formula I with the at least one chlorinating agent in the presence of a catalyst. 8. The method of claim 7, wherein the catalyst comprises one of a pyridine, picolines, formaldehyde, dimethyl formaldehyde, diethyl formaldehyde, diethylamine, triethylamine, and di-isobutyl amine. 9. The method of claim 1, wherein reacting step further comprises: adding the (+) 1 R-trans-permethric acid chloride of formula II to the 2,3,5,6-tetraflourobenzyl alcohol. 10. The method of claim 1, wherein the reacting step further comprises: -22- adding the 2,3,5,6-tetraflourobenzyl alcohol to the (+) 1R-trans-permethric acid chloride of formula II. 11. The method of claim 1 further comprising: adding at least one acid-biding agent to the crude product, wherein the acid binding agent is selected from the group comprising diethylamine, triethylamine and pyridine. 12. The method of claim 1, wherein the purifying step further comprises: purifying the crude product using a treatment to give the 2,3,5,6-Tetraflourobenzyl (+) 1 R-trans-2,2-dimethyl-3-(2,2-dichlorovinyl) cyclopropanecarboxylate in a solvent. 13. The method of claim 12, wherein the treatment comprises at least one of a solvent distillation under vacuum, continuous steam distillation without replenishing the solvent, continuous steam distillation while replenishing the solvent, alkali solution washing, dilute acid solution washing, water washing, filtration and trace solvent removal under high vacuum. 14. The method of claim 12, wherein purifying step further comprises: removing the solvent. Dated • day of March, 2005 Signature : Vivek Kathpalia / Avadhut Sawant Nishith Desai Associates -23- ABSTRACT The compound 2,3,5,6-Tetrafluorobenzyl (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylate, which is also called as Transfluthrin, is known to be highly active as an insecticide. This compound is prepared by various methods such as condensation of 2,3,5,6-Tetrafluorobenzyl alcohol and (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylicacid chloride, or by condensation of 2,3,5,6-Tetrafluorobenzyl halide and a suitable salt of (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylicacid. The present improved process involves a relatively simpler novel method of preparation of (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylicacid chloride and condensation of 2,3,5,6-Tetrafluorobenzyl alcohol and (+) 1R-trans-2, 2-dimethyl-3- (2,2-dichlorovinyl)-cyclopropanecarboxylicacid chloride, and relatively simpler and cheaper commercial method for the purification of the crude product to obtain highly pure Transfluthrin. 22 MAR 2005 -24-

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