Synthesis of Dihydropyrimidinones and Thiones by Multicomponent Reactions: Strategies Beyond the Classical Biginelli Reaction

Abstract

The three-component Biginelli reaction for the synthesis of dihydropyrimidinone and corresponding dihydropyrimidine­thiones (DHPMs) has been known for more than a century. Consistent attention has been paid to the study of Biginelli reaction owing to the significant biological and pharmaceutical merits of DHPMs. In the view of molecular diversity, the development of new multicomponent reactions that provide DHPMs bearing novel functional structures has emerged as a central issue in recent years. This account systematically summarizes the multicomponent reaction syntheses of novel DHPMs that are not accessible through the classical Biginelli reaction. 1 Introduction 2 Synthesis of DHPMs via Modification of Classical Biginelli Substrates 2.1 Using β-Keto Ester Alternatives 2.2 Using Urea/Thiourea Alternatives 2.3 Using Aldehyde Alternatives 3 Synthesis of DHPMs via Other Multicomponent Reactions 4 Conclusions