TITLE:
Iron(II) Triflate Catalyzed Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones via the Biginelli Reaction
AUTHORS:
Kyle A. Lyth, Rem Quintin V. David, Nicholas M. Edelen, Habiba Hamitova, Magnum L. McManigal, Rylan B. Nelson, Ram S. Mohan
KEYWORDS:
Aldehydes, Biginelli Reaction, 3, 4-Dihydropyrimidin-2(1H)-ones, Green Chemistry, Iron(II) Triflate, Multicomponent Reactions
JOURNAL NAME:
Green and Sustainable Chemistry,
Vol.16 No.2,
May
26,
2026
ABSTRACT: The synthesis of dihydropyrimidinones is of interest due to their biological activities. A common method for their synthesis is the Biginelli reaction, which is a one-pot multicomponent reaction of an aldehyde, urea and a β-ketoester. The Biginelli reaction is typically catalyzed by a Br?nsted or Lewis acid. However, many of these catalysts, such as BF3?Et2O and AlCl3 are corrosive and/or toxic. Herein, we report the iron(II) triflate-catalyzed (10.0 mol%, 22 - 24 h) synthesis of dihydropyrimidinones via the Biginelli reaction in isopropanol as a solvent. The reaction is also reported in two other solvents, benzotrifluoride (a useful replacement for CH2Cl2) and 2-methyltetrahydrofuran, a bio-derived solvent. Iron(II) salts are attractive catalysts because of their low cost, low toxicity, and ease of handling.