Organocatalyzed Biginelli Reactions: A Greener Chemical Approach for the Synthesis of Biologically Active 3,4-Dihydropyrimidin-2(1H)-ones/-thiones

In 1893, the Italian chemist Pietro Biginelli described the multicomponent cyclocondensation reaction between ethyl acetoacetate, an appropriate aryl aldehyde, and urea under acid catalysis in ethanolic solution. This reaction was then named Biginelli reaction or Biginelli condensation reaction, and has celebrated its 120th anniversary of the disclosure in 2013. Among the Biginelli adducts, 3,4-dihydropyrimidinones/thiones are remarkably important due to the wide spectrum of therapeutic and pharmacological applications including antiviral, antitumor, antibacterial, and anti-inflammatory activities. Biginelli adducts also have emerged as calcium channel blockers, antihypertensive agents, and α-adrenergic antagonists. Thus, many synthetic methodologies were developed for the synthesis of Biginelli adducts. This chapter describes and discusses the state-of-the-art of synthetic approaches based on environmental-friendly organocatalysis for obtaining a series of 3,4-dihydropyrimidinones/thiones. Additionally, overviews of the mechanism of Biginelli reaction as well as the main biological activities of such class of compounds are presented.