Aniline-2,4-disulfonamide

A great advance in potency was achieved with the 1,2,4-benzothiadiazine 1,1-dioxide chlorothiazide (190), a cyclized aniline-2,4-disulfonamide which is a weaker inhibitor of carbonic anhydrase than acetazolamide, but a more powerful diuretic. The major contribution to diuretic activity in these compounds must come from some factor other than the inhibition of carbonic anhydrase since a ten-fold increase in activity was seen in the reduced compound hydrochlorothiazide (191 R1 = R2 = H, R3 = CI) which has only one-tenth of... 

B) Preparation of 4-Amino-2-Chloro-5-(Methylsulfamyl)Benzenesulfonamide The 5-sub-stituted-2,4-dlsulfamyl anilines may be prepared by procedures described in the literature, for example, the general procedures in Monatsch. Chem. vol. 48, p 87 (1927), which involves the treatment of a m-substituted aniline with from 10 to 20 parts by weight of chlorosulfonic acid followed by the gradual addition of from about 90 to 170 parts by weight of sodium chloride. The resultant mixture is heated at approximately 150°C for about 2 hours after which the reaction mixture is poured into water and the resultant 5-substituted aniline-2,4-disulfonyl chloride is filtered and is then treated with concentrated ammonium hydroxide or suitable amine by standard procedures to obtain the corresponding disulfonamide. 

---