Research On The Preparation Art Of Regent And Its Intermediates

The Regent, a new type of benzyl pyrazole pestcide, was developed by Luonapulangke agriculture company in 1987 and commercialized in 1993. Its general name is Fipronil, chemical name is 5-amino-3-cyano-1-(2,6-dichlorine-4-trifluoromethylbenzyl)-4-trifluorome -thylsulfinylpyrazole. Because of its novel structure , unique mechanism, and high activity, it has been honored as new generation high-tech pesticide internationally.This article relates to the procedure for the preparation of Fipronil and its art optimazation using p-chlorobenzotrifluoride as the starting material .Firstly, The starting material was nitrated by HNO₃/H₂SO₄, then the nitro group in3,5-dinitro-4-chlorobenzotrifluoride was replaced by chlorine using chlorine gas. Then using 3,4,5-trichlorobenzotrifluoride as starting material to prepare 2,6-dichloro-4-trifluoromethylaniline through three routines, The direct ammonolysis method may realize the maximum use of the atom and it meets the modern green chemistry requirement. But the reaction must carry on under the high temperature and high pressure condition, and side reaction had occurred, the conversion was high, but the yield of the product was only 68%. DMF amination method, the reaction activity of 3,4,5-trichlorobenzotrifluoride is high, therefore the reaction was produced 2,3-dichloro-5-trifluoromethyl N,N-dimethylanilineand 2,6-dicllloro-4-trifluoromethyl N, N-dimethylaniline (the selectivity of two product was 43:57), the conversion rate was: 91%. In order to separate the two products need rectificate under vacuum. Hydrozinolysis and hydrogenolysis reduction with high yield and excellent selectivity was the best process among the three. So, the final route chose hydrozinolysis and hydrogenolysis reduction method.The synthesis of Regent divides into two routes,one conventional method takes 2,6-dichloro-4-trifluomethylaniline as intermediate .First the intermediate became diazonium salt, then reacted with ethyl 2,3-dicyano propionate and finally in the presence of ammonia closed the loop to obtain 5-amino-3-cyano-1-(2,6-dichlorine-4-trifluoromethylbenzyl)pyrazole. Another route use 2,6-dichloro-4-trifluoromethylhydrazine as intermediate ,first it was reacted with fumanitrile ,then oxidized by cupric chloride and finally close the loop under the base condition to prepare 5-amino-3-cyano-1-(2,6-dichlorine-4-trifluoromethylbenzyl)pyrazole.At last using dimethylamine tosylate and sodium salt of trifluoromethanesulfinic acid and sulfinic chloride to replce trifluoromethylsulfenyl chloride used in traditional method reacted with 5-amino-3-cyano-1-(2,6-dichlorine-4-trifiuoromethylbenzyl)pyrazole in one step to obtain 5-amino-3-cyano-1-(2,6-dichlorine-4-trifluoromethylbenzyl)-4-trifluoromethylsulfinyl -pyrazole. Each intermediate was characterised by IR, MS, ¹H NMR and it proved the structure was correct.After optimization of the experiment condition ,the overall yield of aniline route can reach 38.8%, and the total yield of hydrozine route can reach 35.8%.