This acid-catalyzed, three-component reaction between an aldehyde, a ß-ketoester and urea constitutes a rapid and facile synthesis of dihydropyrimidones, which are interesting compounds with a potential for pharmaceutical application.
Mechanism of the Biginelli Reaction
The first step in the mechanism is believed to be the condensation between the aldehyde and urea, with some similarities to the Mannich Condensation. The iminium intermediate generated acts as an electrophile for the nucleophilic addition of the ketoester enol, and the ketone carbonyl of the resulting adduct undergoes condensation with the urea NH2 to give the cyclized product.
Combined Role of the Asymmetric Counteranion-Directed Catalysis (ACDC) and Ionic Liquid Effect for the Enantioselective Biginelli Multicomponent Reaction
H. G. O. Alvim D. L. J. Pinheiro, V. H. Carvalho-Silva, M. Fioramonte, F. C. Gozzo, W. A. da Silva, G. W. Amarante, B. A. D. Neto, J. Org. Chem., 2018, 83, 12143-12153.
N-Substituted Ureas and Thioureas in Biginelli Reaction Promoted by Chlorotrimethylsilane: Convenient Synthesis of N1-Alkyl-, N1-Aryl-, and N1,N3-Dialkyl-3,4-Dihydropyrimidin-2(1H)-(thi)ones
S. V. Ryabukhin, A. S. Plaskon, E. N. Ostapchuk, D. M. Volochnyuk, A. A. Tolmachev, Synthesis, 2007, 417-427.
Organocatalytic Application of Ionic Liquids: [bmim][MeSO4] as a Recyclable Organocatalyst in the Multicomponent Reaction for the Preparation of Dihydropyrimidinones and -thiones
S. R. Roy, P. S. Jadhavar, K. Seth, K. K. Sharma, A. K. Chakraborti, Synthesis, 2011, 2261-2267.
Ferric chloride/tetraethyl orthosilicate as an efficient system for synthesis of dihydropyrimidinones by Biginelli reaction
I. Cepanec, M. Litvić, A. Bartolinčić, M. Lovrić, Tetrahedron, 2005, 61, 4275-4280.
Ruthenium(III) Chloride-Catalyzed One-Pot Synthesis of 3,4-Dihydropyrimidin-2-(1H)-ones under Solvent-Free Conditions
J. H. Schauble, E. A. Trauffer, P. P. Deshpande, R. D. Evans, Synthesis, 2005, 1333-1339.