Abstract: Fluorinated pyrazoles play important roles in medicinal chemistry, drug discovery, agrochemistry, and coordination chemistry. Although fluorinated compounds have many benefits, the preparation of functionalized fluorinated pyrazoles, partly N-difluoromethylpyrazoles, remains challenging. Here, selective oxidation of the methyl group in 1-(difluoromethyl)-3-methyl-1H-pyrazole and 1-(difluoromethyl)-5-methyl-1H-pyrazoles to prepare the corresponding pyrazole-3- and pyrazole-5-carboxylic acids was described. The carboxylic acids were transformed into a broad range of new functionalized derivatives: esters, alcohols, aldehydes, amines, amides, nitriles, and chloro derivatives. The crystal structure of the initial carboxylic acid derivatives has been determined from single-crystal X-ray analysis, which provided unambiguous proof of the regiochemistry of all prepared 1-difluoromethyl-pyrazoles. Note, in the crystalline structure of substituted pyrazole-3-carboxylic acid, the formation of dimers via double hydrogen bonds of O–H···O between molecules was observed, while the pyrazole-5-carboxylic acid derivative forms chains via hydrogen bonds of O–H···NPz.

Cite: Ugrak B. , Dutova T. , Rusak V. , Xia D. , Tretyakov E.
Efficient Access to Functionalized N -Difluoromethylpyrazoles
ACS Omega. 2026. DOI: 10.1021/acsomega.5c09033 WOS Scopus OpenAlex

Dates:

Submitted:	Sep 1, 2025
Published print:	Feb 4, 2026

Identifiers:

Web of science:	WOS:001684027800001
Scopus:	2-s2.0-105030356045
OpenAlex:	W7127574486

Citing:

DB	Citing
OpenAlex	Нет цитирований
Scopus	Нет цитирований

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