It is a chemical reaction in organic chemistry in which three molecules, urea, aldehyde and β-keto ester are reacted together in presence of an acid catalyst to form a cyclic compound as final product called dihydropyrimidones.
Mechanism:
Multiple paths have been proposed over the years for this reaction. The mechanism that is accepted by most scientists include a three steps process in which a series of reactions occurs step by step.
Step-I: Nucleophilic addition of urea on
aldehyde in presence of acid is followed by dehydration to form benzylidene
urea (A).
Step-II: Deprotonation of β-keto ester form a carbanion which reacts with
benzylidene urea formed in step I.
Step-III: Cyclization occurs by nucleophilic
substitution resulting into dehydration and a 6 membered ring called
dihydropyrimidone is formed.
Salient Features:
1. Cyclization happens with attack of
amine group on ketonic group because ketone has more electrophilic carbonyl
than ester. +M effect of methoxy group lower down the electrophilicity of
carbonyl carbon.
Examples:
Ex-1
Ex-2
References:
1. 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.
2. Y. Ma, C. Qian, L.
Wang, M. Yang, J. Org. Chem., 2000, 65,
3864-3868.