Isomeric benzothiazines and, particularly, 1,2-benzothiazines display a broad spectrum of" biological activity [1][2][3]. Of particular interest in connection with the possibility of their purposeful modification are 3-amino-l,2-benzothiazine 1,1dioxides. The latter, however, have thus far remained difficult to obtain, and little study has been devoted to them [3].
Continuing our study of nucleophilic substitution in a series of functionally substituted halo arenes [4] we have discovered the possibility of a new approach to the synthesis of 3-amino-1,2-benzothiazine 1, I-dioxides.
The synthesis of 4-substituted 3-amino-7-nitro-2H-1,2-benzothiazine 1, l-dioxides III-X (Table I) is accomplished by the reaction of substituted acetonitrites I with 5-rfitro-2-chlorobenzenesulfonamides II in the presence of alkali metal carbonates (K2CO 3, Cs2CO3).
The formation of the benzothiazine ring can be conceived of as follows: the carbanion generated from the substituted acetonitrile by the action of a base --the alkali metal carbonate --replaces the chlorine atom; this is followed by intramolecular addition of the NH group of the sulfonamide to the cyano group with subsequent isomerization of the molecule.
Characteristic absorption bands of stretching vibrations of a primary amino group at 3280-3425 cm -1 are observed in the IR spectra of Ill-X; the conjugated cyano group in HI and IV shows up at 2180 and 2210 cm -1 , respectively, while the absorption of a sulfonarnido group is observed in the form of an intense band at 1310-1365 cm -1 . The UV spectra of products IIt-X are characterized by the presence of a long-wave maximum at 390-448 nm (log e 4. I0-4.71).