Unambiguous synthesis of 1-methyl-3-hydroxypyrazoles

✍ Scribed by Diane Zimmermann; Povl Krogsgaard-Larsen; Jean-Daniel Ehrhardt; Ulf Madsen; Yves L Janin

• Publisher: Elsevier Science
• Year: 1998
• Tongue: French
• Weight: 525 KB
• Volume: 54
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(98)00579-1

✦ Synopsis

2,

oxazoles were used as intermediates in a new method for preparation of Nl-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 l-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 l-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.