The reaction mechanism of the Biginelli reaction is a series of bimolecular reactions leading to the desired dihydropyrimidinone. 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. The nucleophilic addition of urea gives the intermediate
4, which quickly dehydrates to give the desired product
5. This mechanism is superseded by one by Kappe in 1997: This scheme begins with rate determining nucleophilic addition by the urea to the aldehyde.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 ensuing condensation step is catalyzed by the addition of acid, resulting in the imine nitrogen. 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. This final step ensues a second condensation and results in the Biginelli compound. ==Advances in Biginelli reaction==