Also known as: Biginelli pyrimidone synthesis
The Biginelli reaction is a one-pot three-component organic reaction between a β-keto ester, an aryl aldehyde, and urea to produce pyrimidones under acidic conditions. This reaction begins with protonation of the aldehyde by the acid and is followed by attack of the amine from urea. Proton transfer steps then result in a protonated alcohol which leaves as water to form an N-acyliminium ion intermediate. The intermediated is then attacked by the enol form of the β-keto ester. Reaction of the other amine group to the carbonyl produces a cyclic intermediate. Proton transfer steps, the release of water, and deprotonation result in the final pyrimidone product.
Biginelli, P. Ber. Dtsch. Chem. Ges. 1891, 24, 1317–1319.
Biginelli, P. Ber. Dtsch. Chem. Ges. 1891, 24, 2962–2967.