Solvent free synthesis of 3,4-dihydropyrimidine-2-(1H)-ones/thiones catalyzed by zinc aluminate spinel nanoparticles

The Biginelli reaction is an acid-catalyzed, three component, reaction between an aldehyde, β-ketoester or β-diketone and urea or thiourea. Dihydropyrimidinones (DHPMs) and their derivatives have attracted considerable interest due to their wide spectra of biological activities such as antiviral, antitumor, antibacterial, anti-inflammatory and antihypertensive. The multi-component DHPM-yielding Biginelli reaction was first established in 1893 and was ignored for many years until recently [1,2]. Particular enantiomers are progressively more important for drug applications. Chiral detection allows one enantiomer to treat a disease, while another one may be harmful. An asymmetric carbon exists at the 4-position of the dihydropyrimidone ring and they are generally formulated as racemic mixtures. The absolute configuration in the center of the molecule can have important biological and pharmacological effects. In many cases chiral dihydropyrimidones have exhibited higher activities or, in the case of enantiomers, a contrary pharmacological activity [3,4]. We report herein, the usage of zinc aluminate nanoparticles as a new catalyst for three component condensation of an aldehyde, ethyl acetoacetate and urea/thiourea under solvent free conditions (scheme 1) at 100 °C to afford the corresponding 3,4-dihydropyrimidine-2-(1H)-ones/thiones (DHPMs) in good to excellent yields.