We started to study the three-component Biginelli condensation
catalyzed by silica sulfuric acid by examining
the conditions required for the reaction involving benzaldehyde,
urea and ethyl acetoacetate to afford the
DHPM 4a (R1=Ph, R2=Me, R3=OEt, X=O). A summary of the results obtained is provided in Table 1.
Entries 1–6 show the effect of various solvents on the
yield of the reaction. Although acetonitrile and toluene
afforded the product in high yields, we chose ethanol for
its cheapness and environmental acceptability. Entry 3
describes the yields of five consecutive condensations
leading to 4a. In these experiments the product was
isolated by filtration and washing the solid residues with
ethyl acetate, the remaining catalyst being reloaded with
fresh reagents for further runs. No decrease in the yield
was observed demonstrating that silica sulfuric acid can
be reused as a catalyst in Biginelli condensations. Entry
7 shows the catalytic effect of silica sulfuric acid in the
three-component condensation of benzaldehyde, urea
and ethyl acetoacetate.