Unambiguous synthesis of 1-methyl-3-hydroxypyrazoles

Abstract

2,3-Dihydropyrazolo[3,2- b]oxazoles were used as intermediates in a new method for preparation of N1-methyl-3-hydroxypyrazoles. Synthesis of this bicyclic system was achieved either by alkylation of 3-hydroxypyrazole with 1,2-dibromoethane or, with better yields, by cyclization of 1-tosyl-2-(2-hydroxyethyl)pyrazol-3-ones via a nitrogen to oxygen transfer of the tosyl group. Alkylation with methyl trifluoromethanesulfonate followed by dihydrooxazole ring-opening with sodium iodide, led to the 1-methyl-2-(2-iodoethyl)pyrazoles. Removal of the iodoethyl chain on N2 to give the target 3-hydroxypyrazoles was achieved either via a cyanation and then a decyanoethylation reaction or via an elimination of hydrogen iodide, followed by an iodine-based oxidation of the resulting vinylic derivative. Using the latter method, 1-methyl-3-hydroxypyrazoles were obtained in 58–73% yields from the corresponding 2,3-dihydropyrazolo[3,2- b]oxazoles.