Synthesis of Dihydropyrimidinones via Biginelli Reaction by Using Molecular Iodine as Environmentally Friendly Catalyst

Abstract The synthesis of 3,4-dihydropyrimidine-2-ones has been the focus of much interest since they exhibited various biological activities with pharmacology potentials (antibacterial, antitumor, antiviral, and anti-inflammatory). Dihydropyrimidinones could be produced straightforwardly through a one-pot three-component Biginelli reaction involving β-ketoester, aliphatic or aromatic aldehyde, and urea in ethanol under strong acidic conditions with reflux. However, this reaction has drawbacks and pollutes the environment due to the use of strong mineral acids and the production of hostile and toxic wastes that are environmentally unfriendly. Molecular iodine emerges as an environment-benign catalyst, which is non-toxic, mild, inexpensive, and readily available. The present paper reports the synthesis of dihydropyrimidinones by using molecular iodine via Biginelli multicomponent reaction under reflux. The reaction between benzaldehyde or vanillin, ethyl acetoacetate, and urea produced ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate 4a and ethyl 4-(4-hydroxy-3-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 4b in 50 and 54% yields, respectively. This protocol provides an alternative route to access dihydropyrimidinones using commercially available iodine as a catalyst. The structure of the synthesized compounds was established by spectroscopic methods (FTIR, NMR, HRMS).