A small library of twenty-two 3,4-dihydropyrimidin-2(1H)-ones and twenty-onethiones 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 studiedwith heterogeneous and homogeneous oxidants. Microwave-assisted oxidation using potassium peroxydisulfate in an acetonitrile/water mixture at 100 ºC for 10 minutesproduces 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 peroxydisulfateorother 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 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.
Biginelli, electronic calculation, dihydropyrimidines, 3, 4-dihydropyrimidin-2(1H)-ones, 1, 4-dihydropyrimidine,
1, 4-dihydropyrimidinethiol, 3, 4-dihydropyrimidine-2(1H)-thiones, microwave, monastrol, oxidation, potassium peroxydisulfate,
pyrimidin-2(1H)-ones, pyrimidine-2(1H)-thiones, synthesis, tautomers
Department of Chemistry, Universityof Coimbra, Rua Larga 3004-535, Coimbra, Portugal.