A Convenient One-Pot Synthesis Of Valdecoxib

Valdecoxib is a new COX-2inhibitor which belongs to nonsteroidal anti-inflammatory drugs. It has strong functions that resist the inflammation and ease pain. The reported previous work shows that only53.5%yield in the last step was obtained in a very harsh condition.In this paper, a new method for synthesizing valdecoxib is reported. Phenyl acetone was converted to4-(2-acetonyl)-benzenesulfonilamide through chlorosulfonation and ammonification. Then the desired product was obtained by cyclization in the presence of alkali and benzohydroximinoyl chloride, which was obtained by reaction of benzaldehyde with hydroxylamine followed by chlorination. Also,4-(2-acetonyl)-benzenesulfonilamide can be converted to desired product through condensation reaction with ethyl benzonate,followed by oximation and cyclization.The optimum condition for chlorosulfonation and ammonification were1:8:10in molar ratio for phenyl acetone, chlorosulfonic acid and ammonia respectively, with yield of71%for chlorosulfonation using N2as additive and90.20%for ammonification, both reactions were conducted at20℃.20%NaOH solution was used during cyclization and a good yield of93.77%was obtained in the last step. Hydrochloric acid was used as solvents to carry on chlorination during preparation of benzohydroximinoyl chloride. The final product was confirmed by ’HNMR and MS.