K2S2O8-promoted one-pot synthesis of N-substituted quinazolinones via tandem annulation using DMSO and terminal alkynes

Abstract

A three-component reaction involving 2-aminobenzamide, phenylacetylene, and DMSO in the presence of K₂S₂O₈ as an oxidant has been developed to access a wide range of N-substituted quinazolinones. In this methodology, DMSO functions both as a solvent and as a source of various synthons, facilitating key C–C and C–X bond formations via tandem annulation. This reaction offers several advantages, such as being metal-free and cost-effective, and proceeding under mild conditions that efficiently promote the transformation. This methodology enables the synthesis of various quinazolinone compounds by a tandem one-pot reaction in moderate to good yields. Mechanistic insights supported by deuterium labeling and control experiments, suggest the participation of DMSO-derived intermediates and confirm the proposed reaction mechanism. This environmentally benign protocol offers a direct and scalable method to access bioactive heterocycles of pharmaceutical relevance.