Fluorinated and Non-Fluorinated 1,4-Diarylpyrazoles via MnO<sub>2</sub>-Mediated Mechanochemical Deacylative Oxidation of 5-Acylpyrazolines

A solvent-free two-step synthesis of polyfunctionalized pyrazoles under ball-milling mechanochemical conditions was developed. The protocol comprises (3 + 2)-cycloaddition of in situ generated nitrile imines and chalcones, followed by oxidation of the initially formed 5-acylpyrazolines with activate...

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Bibliographic Details
Main Authors: Greta Utecht-Jarzyńska, Anna Kowalczyk, Marcin Jasiński
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/23/8446
Description
Summary:A solvent-free two-step synthesis of polyfunctionalized pyrazoles under ball-milling mechanochemical conditions was developed. The protocol comprises (3 + 2)-cycloaddition of in situ generated nitrile imines and chalcones, followed by oxidation of the initially formed 5-acylpyrazolines with activated MnO<sub>2</sub>. The second step proceeds via an exclusive deacylative pathway, to give a series of 1,4-diarylpyrazoles functionalized with a fluorinated (CF<sub>3</sub>) or non-fluorinated (Ph, COOEt, Ac) substituent at C(3) of the heterocyclic ring. In contrast, MnO<sub>2</sub>-mediated oxidation of a model isomeric 4-acylpyrazoline proceeded with low chemoselectivity, leading to fully substituted pyrazole as a major product formed via dehydrogenative aromatization. The presented approach extends the scope of the known methods carried out in organic solvents and enables the preparation of polyfunctionalized pyrazoles, which are of general interest in medicine and material sciences.
ISSN:1420-3049