UNAMBIGUOUS SYNTHESIS OF 1-METHYL-3-HYDROXYPYRAZOLES

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-hydroxypyr azole with 1,2-dibromoethane or, with better yields, by cyclization of 1-tosyl-2-(2-hydroxyethyl)pyrazol-3-ones via a nitrogen to oxygen tra nsfer of the tosyl group. Alkylation with methyl trifluoromethanesulfo nate followed by dihydrooxazole ring-opening with sodium iodide, led t o the 1-methyl-2-(2-iodoethyl)pyrazoles. Removal of the iodoethyl chai n on N2 to give the target 3-hydroxypyrazoles was achieved either via a cyanation and then a decyanoethylation reaction or via an eliminatio n of hydrogen iodide, followed by an iodine-based oxidation of the res ulting vinylic derivative. Using the latter method, 1-methyl-3-hydroxy pyrazoles were obtained in 58-73% yields from the corresponding 2,3-di hydropyrazolo [3,2-b]oxazoles. (C) 1998 Elsevier Science Ltd. All righ ts reserved.