Oxidation of Biginelli Reaction Products: Synthesis of 2-Unsubstituted 1,4-Dihydropyrimidines, Pyrimidines, and 2-Hydroxypyrimidines

Abstract

We have devised a new route toward 2-unsubstituted pyrimidine derivatives from the Biginelli product, dihydropyrimidin-2(1H)-thiones in two steps: Oxidation of dihydropyrimidin-2(1H)-thiones using oxone on wet alumina or hydrogen peroxide in the presence of catalytic amount of vanadyl sulfate provided 1,4-dihydropyrimidine, which was further oxidized to 2-unsubstituted pyrimidines by the treatment of KMnO 4 . Oxidation of dihydropyrimidin-2(1H)-ones by KMnO 4 formed 2-hydroxypyrimidine in excellent yield, whereas attempted direct desulfurative aromatization of dihydropyrimidin-2(1H)-thiones by KMnO 4 resulted in the formation of 2-hydroxypyrimidines, the same products obtained in the oxidation of dihydropyrimidin-2(1H)-one.