Further Information
Literature
Related Reactions
Passerini
Reaction
Ugi Reaction
Multicomponent
Reactions
Biginelli Reaction
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
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.
Recent Literature
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.
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.
N-Bromosuccinimide as an Almost Neutral Catalyst for Efficient Synthesis of
Dihydropyrimidinones Under Microwave Irradiation
H. Hazarkhani, B. Karimi, Synthesis, 2004, 1239-1242.
Catalysis of the Biginelli Reaction by Ferric and Nickel Chloride
Hexahydrates. One-Pot Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones
J. Lu, Y. Bai, Synthesis,
2002, 466-470.
