clorexolone

Originator

Speciatensol,Specia,France,1966

The Uses of clorexolone

Chlorexolone is a sulfonamide based antibiotic.

The Uses of clorexolone

Chlorexolone is a low-ceiling sulfonamide diuretic.

Definition

ChEBI: Clorexolone is an organic molecular entity.

Manufacturing Process

4-Chlorophthalimide (263 g) was reacted in amyl alcohol (2.6 l) with cyclohexylamine (143.5 g, 1 mol) at reflux temperature for 16 hours to give N-cyclohexyl-4-chlorophthalimide (250 g, 66%) as a solid, MP 134°C to 136°C.
N-Cyclohexyl-1-chlorophthalimide (250 g) was dissolved in glacial acetic acid (2.5 l), concentrated hydrochloric acid (555 ml) and tin (278 g) were added and the suspension was heated on a steam bath for 16 hours. The cooled solution was filtered and concentrated to dryness in vacuo to give a white solid. This solid was dissolved in water and the precipitated oil extracted with chloroform. The chloroform solution was dried and concentrated in vacuo to give a solid which, after recrystallization, yielded 5-chloro-2- cyclohexylisoindolin-1-one (43%), MP 140°C to 142°C.
5-Chloro-2-cyclohexylisoindolin-1-one (102.9 g) was dissolved in concentrated sulfuric acid (665 ml); potassium nitrate (723 g) in concentrated sulfuric acid (166 ml) was added at 0 °C. The reaction mixture was allowed to warm to room temperature and stirred at 25°C for 12 hours. The reaction mixture was poured onto ice to give a cream solid which, after recrystallization from benzene, gave 5-chloro-2-cyclohexyl-6-nitroisoindolin-1-one (46.7 g, 44%) as a white solid, MP 164°C to 168°C.
5-Chloro-2-cyclohexyl-6-nitroisoindolin-1-one (93.9 g) was reduced in concentrated hydrochloric acid (1,970 ml) with stannous chloride (376 g). The reaction temperature rose to 70°C. The resulting solution was cooled in ice and filtered. The product was washed well with water, filtered and dried to give 6-amino-5-chloro-2-cyclohexylisoindolin-1-one (74.1 g, 87.6%) which, after recrystallization from benzene, had a MP of 216°C to 218°C.
6-Amino-5-chloro-2-cyclohexylisoindolin-1-one (42.5 g) was dissolved in concentrated hydrochloric acid (425 ml) and the solution diazotized by the addition of sodium nitrite (21.25 g) in water (125 ml). The resulting diazonium salt solution was added to a solution of liquid sulfur dioxide (93 ml) in glacial acetic acid (243 ml) containing cuprous chloride (2.25 g). A yellow solid was precipitated; this was filtered off, washed, dried and recrystallized from benzene to give 5-chloro-2-cyclohexylisoindolin-1-one-6-sulfonyl chloride (45 g, 80%) as a cream solid, MP 171°C to 174°C.
This sulfonyl chloride (23.7 g) was reacted with liquid ammonia (237 ml) to give 5-chloro-2-cyclohexyl-6-sulfamoylisoindolin-1-one (14.2 g, 53%). MP 259°C to 261°C.

Therapeutic Function

Diuretic