Aim and Objective: DABCO salts were evaluated as catalysts for the Biginelli reaction between 4-
methoxybenzaldehyde, urea and ethyl acetoacetate under solvent-free conditions. 1,4-Diazabicyclo [2.2.2] octane
triflate was found to be a simple, inexpensive, highly efficient catalyst for Biginelli reaction for a variety
aromatic aldehyde with urea and ethyl acetoacetate at 80°C afforded corresponding 3,4-dihydropyrimidinones
in 50-99% yields after 30-120 minutes. 1,3-Cyclohexadione was used in place of ethyl acetoacetate in the absence
of urea this methodology is giving hexahydro xanthene derivatives in good to excellent yields after 3-4
Materials and Method: DABCO salt 4 (5 mol%), 4-methoxybenzaldehyde (0.73 mmol) and urea (0.73 mmol)
were stirred for 10 minutes at 80°C, then ethyl acetoacetate (1.5 equiv.) was added and reaction mixture was
stirred at 80°C for specified time. The resulting solution was stirred continuously and progress of the reaction
was followed by TLC. The crude reaction mixture was purified by flash column chromatography on silica gel
(hexane/ethyl acetate (1:2)) to give pure desired product.
Results: Reaction conditions of the Biginelli reaction were optimized using 4-methoxybenzaldehyde (0.73
mmol), urea (0.73 mmol), and ethyl acetoacetate (5 equiv.) as model substrates catalyzed by 1,4-Diazabicyclo
[2.2.2] octane triflate (5 mol%) in a different solvents, screening of different catalysts and different temperatures.
Neat condition was found to be the best for the Biginelli condensation and corresponding 3,4-
dihydropyrimidinones was obtained in good to excellent yields. When the reaction was carried out with benzaldehyde
derivatives and cyclohexane-1,3-dione in place of ethyl acetoacetate in the absence of urea, solely
corresponding hexahydro xanthene derivatives were obtained in 61-91% yields.
Conclusion: In conclusion, we have applied salts of 1,4-Diaza-bicyclo [2.2.2] octane as catalysts in the Biginelli
condensation and corresponding 3,4-dihydropyrimidinones were obtained in 50- 99% yields under solvent
free conditions. This methodology is having advantages like simple work-up; low loading of catalyst and reaction
was performed at moderate temperature under solvent-free conditions.