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Updated: Jul 14, 2026

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions
Published on: July 28, 2022
Competing general and specific base catalysis in SNAr reactions with azole nucleophiles
Tong Gao1, Charlotte C Newman1, Mary E Pozefsky1
1Department of Chemistry, Williams College, Williamstown, MA 01267, USA. akt2@williams.edu.
Abstract:
Protic nucleophiles undergoing SNAr reactions with moderately activated electrophiles are subject to base catalysis, with deprotonation occurring prior to or during the addition step. Herein, we describe competing modes of base catalysis in SNAr with azole nucleophiles, in which the dominant pathway is governed by the nucleophile pKa. Characterization of the specific- and general-base-catalyzed mechanisms was enabled by Hammett analyses of reactions with nucleophiles of varying acidity. Under specific-base catalysis, the addition transition states involve significant negative charge character on the electrophile (ρ > 3.5) that is relatively insensitive to the identity of the base. In contrast, general-base-catalyzed addition transition states involve a smaller degree of negative charge character (ρ < 2) that is influenced by the base, with some evidence for involvement of the base counterion. Intermediate ρ values are observed when the nucleophile pKa matches that of the base, consistent with competing general- and specific-base catalyzed mechanisms.
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