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Updated: May 12, 2026

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
Studies on the regioselective nucleophilic aromatic substitution (S(N)Ar) reaction of 2-substituted
Stephanie Scales1, Sarah Johnson, Qiyue Hu
1La Jolla Laboratories, Pfizer, Inc., 10770 Science Center Drive, San Diego, California 92121, United States. stephanie.scales@pfizer.com
Abstract:
Differences in regioselectivity were observed during the S(N)Ar reaction of amines with unsymmetrical 3,5-dichloropyrazines. This study revealed that when the 2-position of the pyrazine was occupied with an electron-withdrawing group (EWG), nucleophilic attack occurred preferentially at the 5-position. When the 2-position was substituted with an electron-donating group (EDG), nucleophilic attack occurred preferentially at the 3-position. These results are reported along with a computational rationale for the experimental observations based on the Fukui index at the reacting centers.
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