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 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.
Recent Literature
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.
By using Yb(OTf)3 as a catalyst and under solvent-free reaction
conditions, the yields of the one-pot Biginelli reaction can be increased while
the reaction time was shortened. In addition, the catalyst can be easily
recovered and reused. It not only led to economical automation but also reduces
hazardous pollution to achieve environmentally friendly processes.
Y. Ma, C. Qian, L. Wang, M. Yang, J. Org. Chem., 2000,
65, 3864-3868.
Indium(III) Chloride-Catalyzed One-Pot Synthesis of Dihydropyrimidinones by
a Three-Component Coupling of 1,3-Dicarbonyl Compounds, Aldehydes, and Urea: An
Improved Procedure for the Biginelli Reaction
B. C. Ranu, A. Hajra, U. Jana, J. Org. Chem., 2000,
65, 6270-6272.
A New Substrate for the Biginelli Cyclocondensation: Direct Preparation of
5-Unsubstituted 3,4-Dihydropyrimidin-2(1H)-ones from a β-Keto Carboxylic Acid
J. C. Bussolari, P. A. McDonell, J. Org. Chem., 2000,
65, 6777-6779.
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.
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.
Efficient Biginelli Synthesis of 2-Aminodihydropyrimidines under Microwave
Irradiation
F. Felluga, F. Benedetti, F. Berti, S. Drioli, G. Regini,
Synlett, 2018, 29, 986-992.
