Biginelli reaction

The Biginelli reaction is a reaction in the field of organic chemistry and one of the multi-component reactions. About the Biginelli reported the Italian chemist Pietro Biginelli of the University of Florence for the first time in 1893. It is an acid-catalyzed cyclocondensation of ethyl acetoacetate, benzaldehyde and urea. This gives a 3,4- dihydropyrimidine -2 (1H )-one:

Application

The scope of this heterocycle synthesis is significantly greater. All three reactants may be varied widely, so that a large number of different multiple functionalized pyrimidine derivatives accessible through the Biginelli reaction. So you can also use in ortho -, meta- or para -substituted aromatic aldehydes instead of benzaldehyde. Even with heteroaromatic aldehydes, the reaction proceeds smoothly. When using aliphatic aldehydes the reaction yields are usually lower. Derivatives of aldoses can also be used as the aldehyde. Instead of acetoacetic many other CH -acidic compounds such as 3- Oxocarbonsäurethioester, 1,3- diketones, etc. can be used as starting material in the Biginelli reaction. The urea component is varied as well. With thiourea, substituted ureas and thioureas and guanidines with the Biginelli reaction also works.

The Biginelli reaction can be catalyzed by means of a Brønsted acid and / or a Lewis acid such as boron trifluoride. The solid-phase synthesis using different immobilized reactants is known.

Dihydropyrimidinone, the products of the Biginelli reaction, are often used as drugs.

Mechanism

The reaction mechanism in this case runs, the example mentioned in the introduction reactants, according to the following scheme: