Controlled Pyrazole-Hydrazone Annulation: Regiodivergent Synthesis of 1H- and 2H‑Pyrazolo[3,4‑d]pyridazinones

An efficient and controlled site-selective annulation of 3,5-diethoxycarbonyl 4-hydrazonyl pyrazoles is described. The relative proportion of the products is affected by hydrazone intermediate configuration, reaction temperature, and Lewis acid employed. At a temperature of 110–120 °C, the reaction...

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Bibliographic Details
Published in:Journal of organic chemistry 2023-08, Vol.88 (15), p.11140-11149
Main Authors: Rosa, Fernanda Andreia, Jacomini, Andrey Petita, Vieira da Silva, Michael Jackson, Pianoski, Karlos Eduardo, Poletto, Julia, Francisco, Camila Botin, de Souza Fernandes, Cleverton, Martinelli, Vinicius, Pontes, Rodrigo Meneghetti, Back, Davi Fernando, Moura, Sidnei, Basso, Ernani Abicht
Format: Article
Language:English
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Summary:An efficient and controlled site-selective annulation of 3,5-diethoxycarbonyl 4-hydrazonyl pyrazoles is described. The relative proportion of the products is affected by hydrazone intermediate configuration, reaction temperature, and Lewis acid employed. At a temperature of 110–120 °C, the reaction preferentially afforded 1H-pyrazolo­[3,4-d]­pyridazin-7­(6H)-ones, whereas using Yb­(OTf)3 in MeCN reflux, 2H-pyrazolo­[3,4-d]­pyridazin-7­(6H)-ones were favored. Computational investigations were performed to clarify the mechanism and the origin of the regiodivergence.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.3c01117