Affiliation: Department of Chemistry, University of Coimbra, Rua Larga 3004-535, Coimbra, Portugal.
A small library of twenty-two 3,4-dihydropyrimidin-2(1H)-ones and twenty-one thiones was synthesized under microwave irradiation using acetic acid as both solvent and catalyst. The oxidation of 3,4-dihydropyrimidin-2(1H)-ones to the corresponding pyrimidin-2(1H)-ones was systematically studied with heterogeneous and homogeneous oxidants. Microwave- assisted oxidation using potassium peroxydisulfate in an acetonitrile/water mixture at 100°C for 10 minutes produced the desired compounds in high yields for the majority of the 3,4-dihydropyrimidin-2(1H)-ones used. The decrease in the reaction yield observed in the case of 3,4-dihydropyrimidin-2(1H)-ones with bulky substituents at the C4 position was rationalized resorting to theoretical calculations. The oxidation of 3,4-dihydropyrimidine-2(1H)-thiones was also extensively studied. Using potassium peroxydisulfate or other powerful oxidants, such as oxone or hydrogen peroxide, pyrimidine-2(1H)-thione was not observed. However, evidence for the formation of this compound was obtained using 2,3-dichloro-5,6-dicyanobenzoquinone as oxidant under microwave irradiation. Electronic structure calculations indicate the stability of the 1,4-dihydropyrimidinethiol tautomer, which is deemed responsible for the different reactivity of these compounds.