Aim and Objective: The Biginelli reaction, first reported in 1893, is one great example of the important
multicomponent reactions reported from 1893. Under the same conditions, the influence of the common
catalysts on the yield of the Biginelli reaction was investigated.
Materials and Method: To a round-bottom flask equipped with a spherical condenser were added 1,3-
dicarbonyl compound (1.0 eq), urea (1.45 eq), aromatic aldehyde (1.0 eq), catalyst and methanol. The mixture
was heated at reflux for 16 h. After cooling off, the mixture was filtered and washed with cold methanol to give
DHPMs. Reaction solution was further purified by recrystallization with petroleum ether and ethyl acetate. Six
catalytic systems, different 1,3-dicarbonyl compounds and different substituted aromatic aldehydes with varied
substitutions are described for the Biginelli reaction. An analysis was also performed to study the factors that
affect the yield of the reaction.
Results: When 1,3-dicarbonyl compound was ethyl acetoacetate, the CuCl/ conc.H2SO4 system gave the
highest yield (90.5%). While when acetoacetamide was used, the yields of DHPMs in presence of PTSA/conc.
HCl, conc. HCl or FeCl3•6H2O were all over 90%. Nine DHPMs with different substituents were obtained.
Conclusion: The Lewis acid or mixed catalyst had no significant advantage over a single protonic acid as
catalyst. Conc. HCl as the catalyst was found to be the most effective condition for the preparation of DHPMs.
The aromatic aldehyde with weak electron-withdrawing substituent such as Br resulted in the best yield.