# Switching N-Alkylation Regioselectivity of Trifluoromethylated Pyrazoles Guided by Functional Group Tuning

## TL;DR

This paper shows how to control where alkylation occurs in pyrazole rings using functional group tuning.

## Contribution

A new method for controlling alkylation regioselectivity in trifluoromethylated pyrazoles using hydrazone substituents is introduced.

## Key findings

- Hydrazone substituents influence the alkylation selectivity of (trifluoromethyl)pyrazoles.
- Reaction conditions for synthesizing 3- and 5-(trifluoromethyl)pyrazoles were developed.
- All regioisomers formed from bis-pyrazolyl NH-ketazine alkylation were isolated and confirmed.

## Abstract

The similar properties of the nitrogen atoms in azole ring complicate the regioselective N-functionalization of pyrazoles. This work demonstrates the role of the hydrazone substituent in the control of the alkylation selectivity of (trifluoromethyl)pyrazoles. Reaction conditions for the synthesis of 3- and 5-(trifluoromethyl)pyrazoles were developed, and all types of regioisomers formed under the alkylation of bis-pyrazolyl NH-ketazine were isolated. The structures of the synthesized compounds were confirmed by NMR spectroscopy and XRD data.