Reactivity study of 4-hydroxy-2H-chromene-2-thione and 4-hydroxy-2H-thiochromene-2-thione with tertiary butyl nitrite and aromatic amines: Environmentally benign synthesis of new hydrazone derivatives

The synthesis of biologically active coumarin-based hydrazone derivatives was achieved through one-pot three-component reaction of 4-hydroxy-2H-chromene-2-thiones (1a-e) with aniline derivatives (2a-t) and tertiary butyl nitrite under solvent- and catalyst-free conditions in 76-86% yields. Similarly, the reaction of 4-hydroxydithiocoumarin (5a-d) with aniline (2a-e & 2h) and tertiary butyl nitrite under identical reaction conditions provided the products in 79-85% yield through a four-component reaction. It is observed that in both cases, C=S at the C2 position is converted into C=O. However, the intermediate products derived from 4-hydroxydithicoumarin (5a) react further with another molecule of aniline (2a) by converting it into a thioester. The reactivity pattern of 4-hydroxy-2H-chromene-2-thione (1a) and 4-hydroxydithiocoumarin (5a) was observed as they both follow different pathways to furnish two different kinds of product. In addition to these, this reaction was found to be exergonic through quantum chemical analysis of the mechanistic steps. This protocol offers broad substrate scope and tolerance for various functional groups, high yields, and shorter reaction time.