The synthesis of substituted imidazo[4,5-d]isothiazoles via the ring annulation of isothiazole diamines: An investigation of the chemical, physical, and biological properties of several novel 5:5 fused analogs of the purine ring system

Article abstract of DOI:10.1021/jo00125a016

A series of imidazo[4,5-d]isothiazoles have been prepared from isothiazole precursors via a strategy employing ring annulation of the appropriate isothiazole diamine. In this manner, several 4,5-diaminoisothiazoles were convected into the corresponding 5-(alkylthio)imidazo[4,5-d]isothiazoles via a two-step, one-pot procedure in good yield. This methodology proved quite general and allows for the introduction of various substituents onto the 3-, 5-, and 6-positions of this ring system. Reaction with Raney nickel destroyed the ring system, presumably through removal of the sulfur at the 1-position, and the 5-mercapto substituent could not be removed selectively. Ring annulation with diethoxymethyl acetate provided the 5-unsubstituted imidazo[4,5-d]isothiazoles but was less general, and only the 3-methyl derivatives could be prepared. Imidazo[4,5-d]isothiazoles bearing no substituents on nitrogen readily underwent alkylation to afford mixtures of the N-4- and N-6-substituted compounds. The chemical and physical properties of these novel heterocycles were studied in detail, and the structure of 3-methyl-5-methanesulfonyl-6-(phenylmethyl)imidazo[4,5-d]isothiazole was verified by single crystal X-ray diffraction studies.