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Continuous-Flow Synthesis of 1-Substituted Benzotriazoles from Chloronitrobenzenes and Amines in a C[BOND]N Bond Formation/Hydrogenation/Diazotization/Cyclization Sequence

Authors

  • Dr. Mao Chen,

    1. Department of Chemistry, Room 18-490, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
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  • Prof. Dr. Stephen L. Buchwald

    Corresponding author
    1. Department of Chemistry, Room 18-490, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
    • Department of Chemistry, Room 18-490, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
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  • We thank Novartis International AG for funding. We thank Dr. Nathan Jui and Dr. Christine Nguyen for assistance with the preparation of this manuscript. MIT has patents on some of the ligands and precatalysts used in this work from which S.L.B. receives royalty payments.

Abstract

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Two approaches have been developed for the regiospecific continuous-flow synthesis of 1-substituted benzotriazoles. They begin with either an SNAr reaction at high temperature or Pd catalysis and involve consecutive multiphase processes, allowing the multistep synthesis of benzotriazoles to take place in an efficient manner (see picture).

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