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ChemicalBook CAS DataBase List Chlorothiazide
58-94-6

Chlorothiazide synthesis

1synthesis methods
Chlorothiazide, 1,1-dioxide 6-chloro-2H-1,2,4-benzothiadiazin-7-sulfonamide (21.3.3) is synthesized in the exact same manner, is all thiazide diuretics. 3- Chloroaniline (or 3-trifluoromethylaniline) undergoes sulfoylchlorination by chlorosulfonic acid, forming 4,6-sulfonochloride-3-chloroaniline (21.3.1), the reaction of which with ammonia gives 4,6-sulfonylamido-3-chloroaniline (21.3.2). Heating this with formamide leads to formation of chlorothiazide (21.3.3).

-

Yield:-

Reaction Conditions:

at 90 - 100; for 5 h;

Steps:

1

100 g of 5-chloro-2,4-disulfamylaniline was suspended in 500 ml of about 98% formic acid. The obtained suspension was heated at a temperature of about 90-100° C. The solid was precipitated out from the clear suspension at 90-92° C. The suspension was maintained at the same temperature for 5 hours. The hot suspension was cooled to 25-30° C. and the obtained solid was filtered followed by washing with acetone to get 94 gm of Chlorothiazide.

References:

US2011/263579,2011,A1 Location in patent:Page/Page column 9

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