A regioselective sustainable neat approach to naphtho[2,3-b]thiophene-4,9-dione: detailed mechanistic study and DFT analysis

Abstract

An environment friendly simple, solvent-free, and lower E-factor technique has been developed for synthesizing anticancer property-containing substituted naphtho[2,3-b]thiophene-4,9-dione derivatives via a one-pot three-component reaction using active methylene compounds, alkyl/aryl isothiocyanate, and 1,4-naphthoquinone derivatives. The reaction proceeds through the regioselective Michael addition between the di-anionic intermediate and 1,4-naphthoquinone derivatives, followed by a domino reaction, which has been established via DFT study. Finally, it undergoes a Krapcho reaction followed by aromatization in a basic environment, yielding the desired product naphtho[2,3-b]thiophene-4,9-dione. The reluctant addition of a di-anionic intermediate to the naphthalene-1,4-dione or 2-bromonaphthalene-1,4-dione in the solvent medium has been overcome using a neat approach. Practicability of the methodology has been enhanced via gram scale solvent-free cascade reaction. The wide substrate scope, biological activity, sustainability, and detailed mechanistic study make our reaction more acceptable in the current scenario.