Biginelli reaction

[9][10] Dihydropyrimidinones, the products of the Biginelli reaction, are widely used in the pharmaceutical industry as calcium channel blockers,[11] antihypertensive agents, and alpha-1-a-antagonists.

[14] According to a mechanism proposed by Sweet in 1973 the aldol condensation of ethylacetoacetate 1 and the aryl aldehyde is the rate-limiting step leading to the carbenium ion 2.

[15] This mechanism is superseded by one by Kappe in 1997: This scheme begins with rate determining nucleophilic addition by the urea to the aldehyde.

The β-ketoester then adds to the imine bond and consequently the ring is closed by the nucleophilic attack by the amine onto the carbonyl group.

Atul Kumar has reported first enzymatic synthesis for Biginelli reaction via yeast catalysed protocol in high yields.