Organocatalyzed Synthesis of Dihydropyrimidinone/Thiones via Biginelli Condensation Reaction

Compounds containing 3,4-dihydropyrimidonone/thione frameworks are best known for theirbiological and pharmacological activities. Due to the therapeutic properties of some 3,4-dihydropyrimidonones (DHPMs) and their applications in the pharmaceutical industry, discoveryefficient and cost-effective methods for the synthesis of these compounds is a concernof many organic chemists. In general, the main method for the synthesis of DHPMs is a onepotmulticomponent reaction (MCR) of 1,3-dicarbonyl compounds, various aldehydes, andurea/thiourea derivatives called Biginelli reaction. Generally, this MCR has been catalyzedusing various reagents such as Lewis acids, organoacids, organic and inorganic bases, inorganicacids, nanomaterials, supported catalysts, and metal-organic frameworks [1-3]. In thepresent work, we have synthesized 2-benzyl-1-sulfopyridin-1-ium via sulfonation processandused it to the synthesis of DHPMs through a MCR technique. The three-component reactionof ethyl acetoacetate, various aromatic aldehydes, and urea/thiourea under solvent conditionin the presence of 2-benzyl-1-sulfopyridin-1-ium led to the formation of 3,4-dihydropyrimidonone/thione heterocycles in good to excellent yields (Fig. 1). This procedurehas notable features, including relatively shorter reaction times, simplicity, and environmentallyfriendliness.