The Synthesis Of Furosemide CAIHONG PENG

Furosemide is an important diuretic, and has been used widely in clinic.In this paper, the synthesis of furosemide through chlorosulfonation, aminate, condensation with furfurylamine from 2,4-dichloro-benzoic acid has been studied. And the route is selected because of the available raw materials, short reaction steps, moderate reaction condition and high yield ect.To get the high yield of the whole reaction route, orthogonal test and single-factor optimization is adopted in this paper. In the first step, the yield is 98.96% when 0.lmol 2,4-dichloro-benzoic acid is heated with 0.55mol chlorosulfonic acid ,0.06mol auxiliary material A and 2.0g catalyzer B at 140℃ for 6 hours. In the second step, 96.05% yield is obtained when 4.5mol ammonia and lmol 2,4-dichloro-5- chlorosulfonyl benzoic acid react at 30℃ for 5 hours. In the third step, lmol 2,4-dichloro-5-sulfamoyl- benzoic acid is heated with 4mol furfurylamine, 3mol solvent C and lmol sodium bicarbonate at 130℃ for 5 hours, the precipitation washed with isopropanol, acidified with acetic acid and recrystallized from 95% ethanol. The yield is 57.40% and the purity is 99.18%. The whole yield is 54.56% camparing with 2,4-dichlorobenzoic acid.