SUBSTITUTED 6-CARBOXY-1,2-BENZISOTHIAZOLE-1,1-DIOXIDES

摘要

1327482 1,2 - Benzisothiazole - 1,1 - dioxide derivatives LOVENS KEMISKE FABRIK PRODUKTIONSAKTIESELSKAB 25 June 1971 [30 June 1970] 31718/70 Heading C2C Novel compounds of formula and salts and esters thereof, wherein NHR 1 is in the 4 or 5 position and R 1 is a C 3-8 aliphatic hydrocarbon radical or a mononuclear aromatically or mononuclear heterocyclically substituted methyl or ethyl radical and R 2 an optionally substituted phenyl group substituent or R 1 and R 2 may be halogen, C 1-6 alkyl, halo-(C 1-6 )- alkyl, carboxy, carb-(C 1-6 )-alkoxy, carbamyl, optionally esterified or etherified hydroxy groups, etherified mercapto groups or di-(C 1-6 )- alkyl-amino radicals are prepared either by alkylation of a compound of Formula II or by dehydrogenation of a compound of Formula V or by reaction of a compound of Formula VI wherein Y is halogen, with a compound R 1 NH 2 and in all cases interconnection yields acids, esters and salts in known manner. Intermediates of Formula II above are prepared in the manner described in Specification 1,327,483 as are the various starting materials and intermediates therefor. Intermediates of Formula VI above are prepared by using a 5-amino-2-halo-toluene as the starting substance which by reaction with unsubstituted or substituted benzoylhalide under Friedel Crafts conditions is converted into the corresponding 4 - benzoyl - 5 - benzoylamino-2- halotoluene which in turn is converted into the corresponding 5 - amino - 4 - benzoyl - 2 - halotoluene. In a subsequent step the latter compound is diazotized and reacted with SO 2 in the presence of cupric chloride dihydrate to form the corresponding 4-benzoyl-5-chlorosulphonyl- 2-halotoluene which by reaction with ammonia is converted into the corresponding 5-halo-6- methyl - 3 - phenyl - 1,2 - benzisothiazole-1,1- dioxide, the methyl group of which is finally converted into a carboxylic acid group by oxidation with potassium permanganate. Pharmaceutical compositions in conventional forms for enteral and parenteral administration and having diuretic and saluretic activity comprise an above novel compound and a diluent.