Simple and improved conditions have been found to carry out the Biginelli reaction for the synthesis of 3, 4-dihydropyrimidin-2 (1H) - one derivatives. This synthesis was performed in the presence of 12-molybdophosphoric acid (H3PMo12O40) as catalyst. These reactions were performed under solvent free conditions with microwave irradiation as the energy source. Compared with the classical Biginelli reaction conditions, this new method has the advantage of excellent yields (76–96%). The advantages of this novel protocol include the excellent yield, operational simplicity, short time, and the avoidance of the use of organic solvents and friendly preparation. Products were identified using physical and spectroscopic data.