Tandem regioselective synthesis of tetrazoles and related heterocycles using iodine

Abstract

A one-pot, tandem process has been developed for the synthesis of a library of tetrazoles from aryl isothiocyanates. Condensation of aryl isothiocyanates with ammonia, and aryl amines (R-NH₂) provided mono, 1,3-disubstituted symmetrical and unsymmetrical thioureas, which on desulfurization with molecular iodine (I₂) led to formation of the corresponding heterocumulene (cyanamides or carbodiimides). The in situ generated heterocumulene on subsequent treatment with sodium azide at room temperature gave corresponding tetrazoles. The product regioselectivity for unsymmetrical 1,3-disubstituted thioureas was found to be correlated with the basicities (pK_a's) of the parent amines attached to the thiourea. Aryl-sec-alkyl unsymmetrical thioureas gave thioamido guanidino products rather than the 5-aminotetrazoles produced by HgCl₂ mediation of the reaction. Bis-thioureas derived from aryl isothiocyanates and hydrazine gave thiadiazoles exclusively.