Synthesis of 1,2,4-benzothiadiazines via readily generated iminium ions

Alo, B.I. ; Adegoke, E.A. ; Ligali-Ali, M. ; Adesogan, E.K. (1986)


A general method for the regiospecific synthesis of 1,2,4-benzothiadiazines, which are powerful diuretics and antihypertensive agents, has been developed. The N-arysulphonylprolyl chlorides (5)–(7) reacted instantaneously with silver trifluoromethanesulphonate at room temperature to give the iminium salts (9)–(11) which provided the nitroamines (13)–(15) in quantitative yield. Reductive cyclisation of the nitroamines led to the tetrahydro-1H-pyrrolo[1,2-b][1,2,4]benzothiadiazine 5,5-dioxides (17)–(20) in very good yields. No optimisation of yields was attempted. Efficient methods for the synthesis of some new substituted N-(nitrobenzenesulphonyl)-pyrrolidinecarboxylic acids (1)–(4), which were not readily available, are also described.