A divergent and selective synthesis of isomeric benzoxazoles from a single N-Cl imine
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Updated: May 27, 2026
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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Cheng-yi Chen1, Teresa Andreani, Hongmei Li
1Process Chemistry, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. cheng_chen@merck.com
Abstract:
A divergent and regioselective synthesis of either 3-substituted benzisoxazoles or 2-substituted benzoxazoles from readily accessible ortho-hydroxyaryl N-H ketimines is described. The reaction proceeds in two distinct pathways through a common N-Cl imine intermediate: (a) N-O bond formation to form benzisoxazole under anhydrous conditions and (b) NaOCl mediated Beckmann-type rearrangement to form benzoxazole, respectively. The reaction path also depends on the electronic nature of the aromatic ring, with the electron-rich aromatic rings favoring the rearrangement and the electron-deficient rings favoring the N-O bond formation. A Beckmann-type rearrangement mechanism via net [1,2]-aryl migration for the formation of 2-substituted benzoxazole is proposed.
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