Title of Invention	AN IMPROVED PROCESS FOR PREPARATION OF FIPRONIL, AN INSECTICIDE
Abstract	A process for preparation of Fipronil (I) from 5- Amino-1-(2,6-dichloro-4-trifluoromethyl pghenyl)-3-cyano-4-trifluromethyl thio pyrazole (II) by oxidation in trichloro acetic acid enriched medium.

Full Text

FORM 2 THE PATENTS ACT, 1970 (39 of 1970) COMPLETE SPECIFICATION [See section 10] An improved process for preparation of Fipronil, an insecticide Gharda Chemicals Limited B-27 & 29 MIDC, Phase I, Dombivli, 421203, Dist Thane, Maharashtra, India. An Indian company. The following specification particularly describes the nature of the invention and the manner in which it is to be performed : 29 DEC 2005 An improved process for preparation of Fipronil, an insecticide BACKGROUND OF THE INVENTION 1-Aryl pyrazole pesticides such as 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethyl suphinyl pyrazole known as Fipronil, titled in Pesticide Manual, 13th edition, entry No. 354 is an important insecticide discovered by Rhone Poulenc (now BASF AG) in 1987. The known commercial process of manufacture of this product using corrosive and expensive chemical such as Trifluoro acetic acid, need considerable improvement to make it economically viable process. Research for the alternative has led to the invention which is disclosed here. SUMMARY OF THE INVENTION The main object of the present invention is to substitute the corrosive and expensive solvent Trifluoro acetic acid with an inexpensive and easily available solvent trichloro acetic acid, used in admixture with mono or dichloro acetic acids or in a compatible solvent such as methylene dichloride and others. The present invention relates to an improved process of oxidation of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trtfluorornethyl sulphinyl pyrazole using H202 in trichloro acetic acid medium, substituting the hitherto used expensive and corrosive trifluoro acetic acid solvent. Overall, the invention has made the commercial manufacture of the important insecticide Fipronil more process friendly and economically viable. 2 DESCRIPTION OF THE INVENTION The present invention relates to improved oxidation process for preparing 1-aryl pyrazole pesticides, particularly 5-amino-1 -(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethyl suphinyl pyrazole (Formula-I). Wherein, R1 = trifluoromethyl, trifluoromethoxy R2, R3 = Hydrogen, chlorine or bromine which process comprises oxidizing a compound of formula-ll. (Formula-II) Wherein R1, R2 and R3 are as hereinbefore defined, by using trichloro or a mixture of mono, di and tri chloro acetic acid as the medium, in place of trifluoro acetic acid (TFA). The oxidation is carried out using peroxides, particularly, hydrogen peroxide concentrated solutions available commercially. 3 European patent No. 295117 describes the preparation of the compound of formula-l with 3-chloroperbenzoic acid. WO 01 / 30760 describes the process for oxidation of compound of formula-ll to compound of formula-l in trifluoro acetic acid medium with use of a corrosion inhibitor as an improvement to take care of the acidity generated due to Hydrofluoric acid (HF). Oxidation of compounds of the type of formula-ll entails several difficulties, viz., the molecule has to be stable under the conditions of oxidation, oxidation should proceed to the desired level without leaving significant starting materials unreacted and not producing excessive level of sulfonyl derivative etc. Oxidants of the type of per acids, peroxides, persulfates etc have been widely used for effecting the oxidation. The oxidation has been effected in organic solvents, particularly halogenated aliphatics, trifiuoroacetic acid etc. Mineral acids are not useful as a medium for oxidation due to instability of the compound towards strong mineral acids. Trifiuoroacetic acid has been reported to be a good medium for effecting the oxidation, with good conversion and selectivity to the sulphinyl derivative with minimum levels of sulphonyl derivative formation. However, trichloro acetic acid has not been reported as a medium, probably due to its high melting point. Detailed description of innvention :- Several process problems are encountered when trifluoro acetic acid (TFA) is used as a solvent. One major problem is due to corrosion to metal or glass equipments due to liberation of HF. WO 01 / 30760 claims addition of corrosion inhibiting agents like boric acid to prevent this. This may be effective during oxidation, but the TFA being a costly chemical needs to be recovered for process economics. The same patent has claimed use of monochloro benzene addition and distillation of TFA. Further, residual TFA is esterified using alcohol and recovered as ester which needs to be converted back to TFA. Moreover, the TFA distilled out comes as an azeotrope with water and separation of pure TFA from water requires distillation with sulfuric acid addition. This again poses severe corrosion problems to equipments. In short, use of TFA makes commercial operation of the process extremely difficult and expensive. 4 Our research have now led to a solution to this knotty problem and made the process simple and economical. Our search for a substitute of TFA led to the present invention of using Trichloro acetic acid. Trichloro acetic acid being a solid, under the conditions of oxidation, a melting point depressant like dichloro acetic acid, monochloro acetic acid, methylene dichloride, ethylene dichloride, monochlorobenzene etc is added to TCA. Trichloro acetic acid is commercially available at about one tenth the cost of Trifluoro acetic acid and is devoid of the corrosion problems arising due to HF. It is an object of the present invention to provide an industrial process for manufacturing compounds of formula-l, particularly Fipronil in high yield and purity with relatively cheaper and less corrosive chemicals. It is a further object of the present invention to provide a process for manufacturing compounds of Formula-l, particularly Fipronil, using chemicals which do not corrode the equipments used. In a preferred embodiment of the process, Trichloro per acetic acid which is the reactive species is formed "insitu" by contacting hydrogen peroxide with trichloro acetic acid. Other peroxides like tert butyl hydrogen peroxide, per acetic acid etc. can also be used but with no particular advantage. For those skilled in the art, Trichloro per acetic acid can be pre-made and used, but there is no particular advantage in doing so. The quantity of the peroxide used is sufficient to bring out optimal conversion without producing the byproduct sulphonyl derivative and is generally in the range of 1.1 to 1.7 moles, and preferably 1.4 mole per mole of compound-ll. The preferred concentration of the H202 used is 50 to 70%, due to its ready commercial availability. Concentration beyond this range also can be used with suitable adjustments in the water concentration. The temperature of the reaction is chosen so as to have reasonable kinetics for oxidation without decomposing the product. The reaction can be carried out at a temperature range of 0°C to 50°C and preferably in the range of 15-25X and more preferably at 20°C. The quantity of trichloro acetic acid used is sufficient to dissolve the substrate and allow slurry of reaction mass to be stirred properly. 1.0 It to 2.0 It of trichloro acetic acid mixture is used per mole of compound-ll. The composition of the mixture is chosen such as to depress the melting point of the solvent to less than 10°C. It is to be understood that dichloro acetic acid is 5 a poor medium for oxidation and the purpose of its addition is only to depress the m.p. below 10°C, at which temperature oxidation is carried out. 20-30% content of dichloro acetic acid in the trichloro acetic acid is sufficient to achieve this objective. The following examples which are non-limiting illustrate the invention clearly : Example 1 1000 ml of a solvent mixture, containing 700 ml trichloro acetic acid and 300 ml dichloro acetic acid, is taken in a flask and 421 g (1 g mole) of 5-amino-1-(2,6-dichloro-4-trifluoro methylphenyl)-3-cyano-4-trifluoromethyl thio pyrazole is dissolved into it. After stirring for one hour at 20°, 95 g H202 solution (50% w/w) equivalent to 1.4 mole is added over a period of one hour. As the reaction proceeds, solid product precipitate in the reaction mass. The reaction is continued till the conversion is more than 95% as measured by hplc. To the reaction mass, 2 litres water is added, stirred and filtered. The water washed solids are dried in oven at 110°C, resulting in 415 g solids (95% yield), hplc determination by internal standard method showed 92% purity. The filtrate portion is processed by distillation to recover the trichloro acetic acid mixture by conventional method and recycled. Example 2 1500 g of trichloro acetic acid solid is added to 300 ml methylene dichloride. To the solution at 20°C, 421 g (1 g mole) of 5-amino-1-(2,6~dichloro-4-trifluoromethyl thio pyrazole is added and allowed to dissolve. After stirring for 1 hour at 20°C, 93 g H202 solution (50% w/w) (equivalent to 1.36 g mole) is added over a period of 2 hrs. The reaction is continued till the conversion > 95% by hplc area method. The excess H202 is destroyed by using Na2S03 and the solvent methylene dichloride is distilled out under mild vacuum. To the residual mass, 2.0 It water is added, and the precipitated solids are filtered resulting in 410 g buff coloured solids (yield : 93.8%). The solids analyzed by hplc (IS) method showed 92% purity. 6 We claim : 1) A process for preparation of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4- trifluoromethyl suphinyl pyrazole (Fipronil, Formula-I). The process comprise of oxidizing 5-amino-1-(2,6-dichloro-4-trifluoro methylphenyl)-3-cyano-4-trifluoromethyl thio pyrazole (Formula-ll) using H202 in the medium of trichloroacetic acid containing melting point depressants at temperature range of 0-50°C. 2. A process of preparation of Fipronil as claimed in claim 1 wherein melting point depressants are monochloro acetic acid, dichloro acetic acid and halo alkanes, 3. A process of preparation of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethyl suphinyl pyrazole as claimed in claim-1 wherein the reaction temperature of oxidation is in the range of 0-50°C, more preferrably 15-25°C and most preferrably at 20°C. 7 8 4. A process of preparation of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethyl suphinyl pyrazole as claimed in claim-1 wherein the concentration of H2O2 is 50-70% w/w.

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1167-mum-2004-abstract(21-4-2005).doc

1167-mum-2004-abstract(29-12-2005).pdf

1167-mum-2004-cancelled pages(29-12-2005).pdf

1167-mum-2004-claims(granted)-(29-12-2005).doc

1167-mum-2004-claims(granted)-(29-12-2005).pdf

1167-mum-2004-correspondence(29-12-2005).pdf

1167-mum-2004-correspondence(ipo)-(19-1-2006).pdf

1167-mum-2004-form 1(1-11-2004).pdf

1167-mum-2004-form 19(18-11-2004).pdf

1167-mum-2004-form 2(granted)-(29-12-2005).doc

1167-mum-2004-form 2(granted)-(29-12-2005).pdf

1167-mum-2004-form 3(1-11-2004).pdf