An update on a greener organocatalytic chemical approach for the synthesis of Biginelli adducts

Abstract 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 venerable centenary reaction was then named the Biginelli reaction or Biginelli condensation reaction. Among the Biginelli adducts, 3,4-dihydropyrimidinones/thiones are remarkably important due to their wide spectrum of therapeutic and pharmacological applications, including antiviral, antitumor, antibacterial, and anti-inflammatory activities. Biginelli adducts have also emerged as calcium channel blockers, antihypertensive agents, and α-adrenergic antagonists. Thus many synthetic methodologies have been developed for the synthesis of Biginelli adducts. This chapter presents an update and discusses the state-of-the-art synthetic approaches based on environment-friendly organocatalysis for obtaining a series of 3,4-dihydropyrimidinones/thiones. Additionally, overviews of the mechanism of the Biginelli reaction as well as the main biological activities of the class of compounds called Biginelli adducts are presented, covering the literature up to 2019.