The Biginelli reaction mechanism has been studied extensively
by several research groups [41]. A pathway for the three
component condensation of urea, ethyl acetoacetate, and aldehyde
to 3,4-dihydropyrimidin-2(1H)-one in the presence of
NH4H2PO4 is given in Scheme 3. The first step is the formation
of an acyl imine intermediate formed by the reaction of the
aldehyde with urea in the presence of the catalyst. Then, the
iminium ion intermediate interacts with ethyl acetoacetate to
produce an open chain ureide that subsequently cyclizes to the
dihydropyrimidinone by removing a water molecule from it.
The empty 3d orbitals of the phosphorous atom in NH4H2PO4
stabilize the iminium ion intermediate by the formation of
coordinative bonds.