Acid Catalyzed N-Alkylation of Pyrazoles with Trichloroacetimidates
Rowan I. L. Meador, Nilamber A. Mate, John D. Chisholm
Organics · pp. 111–121 · Published 24 May 2022
10.3390/org3020009Abstract
N-Alkyl pyrazoles are important heterocycles in organic and medicinal chemistry, demonstrating a wide range of biological activity. A new method for the N-alkylation of pyrazoles has been developed using trichloroacetimidate electrophiles and a Brønsted acid catalyst. These reactions provide ready access to N-alkyl pyrazoles which are present in a variety of medicinally relevant lead structures. Benzylic, phenethyl and benzhydryl trichloroacetimidates provide good yields of the N-alkyl pyrazole products. Unsymmetrical pyrazoles provide a mixture of the two possible regioisomers, with the major product being controlled by sterics. This methodology provides an alternative to other alkylation methods that require strong base or high temperature.
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