Isothiazolopyridines. I. Synthesis and Spectra of Isothiazolo[3,4-b]-, 3-Amino-isothiazolo[4,3-b]-, Isothiazolo[5,4-b]-, and 3-Methylisothiazolo[5,4-c]pyridines. Preparation and Spectra of Some 2,3- and 3,4-Disubstituted Pyridines

Abstract

Isothiazolo[3,4-b]pyridine was synthesized from 2-aminonicotinonitrile in three steps: by the reaction with ammonia and hydrogen sulfide to produce 2-aminothionicotinamide; oxidative cyclization with hydrogen peroxide to give 3-aminoisothiazolo[3,4-b]pyridine, followed by diazotization and reduction with hypophosphorous acid. 3-Aminoisothiazolo[4,3-b]pyridine was prepared in a similar way from 3-aminopicolinonitrile via 3-aminothiopicolinamide. Isothiazolo[5,4-b]pyridine was synthesized from 2-chloronicotinonitrile in three steps: by the reduction with formic acid in the presence of Raney nickel to obtain 2-chloronicotinaldehyde; transformation of the latter into 2-thiocyanonicotinaldehyde; and finally cyclization with ammonia to obtain isothiazolo[5,4-b]pyridine. 3-Methylisothiazolo[5,4-c]pyridine was prepared by cyclization of 4-acetyl-3-thiocyanopyridine with ammonia. N.m.r. and u.v. spectra of the isothiazolopyridines, their derivatives, and the pyridine intermediates were recorded and interpreted.