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.

Calcium, Barium and Strontium apatites: A new generation of catalysts in the Biginelli reaction

“…This reaction was discovered by Pietro Biginelli in 1891 [8,9]. improved significantly over the years and several examples of this reaction were reported with high product yields using different catalysts and ligands [10][11][12]. The influence of polar and non-polar solvent has also been studied [13].…”

2-Oxo-2-polyfluoroalkylethane-1-sulfones and -sulfamides in the three-component reactions leading to pyrimidine derivatives

“…One of the most effective strategies for the construction of pyrimidinone scaffold is the broadly studied Biginelli reaction. [10][11][12] In its traditional form three-component Biginelli cyclocondensation involves a combination of β-ketoester and aromatic aldehyde with urea in protic solvent under acidic conditions resulting in the formation of 3,4-dihydropyrimidin-2(1H)-ones known also as classical ''Biginelli compounds''. Throughout the exploration of the Biginelli reaction potential, by diversifying all three components, the scope of the employed β-dicarbonyl substrates has been extended by their…”

The use of 2,2,6-trimethyl-4H-1,3-dioxin-4-one (TMD) in multicomponent reactions. Synthesis of acetoacetanilides, pyridones and dihydropyrimidines.

“…4 In this study we investigated the reaction of TMD (1) with anilines (2) for the preparation of acetoacetanilides (3) in apolar (toluene and xylene) and polar protic (water) solvents. Additionally, the one pot four component reaction involving 1, 2, urea (4) and benzaldehydes (5) to give Biginelli products (6) was studied ( Figure 1).…”