A scalable, metal-, azide- and halogen-free method for the preparation of triazoles

Peter R. Clark, Glynn D. Williams, Jerome F. Hayes, Nicholas C. O. Tomkinson

Research output: Contribution to journalArticle

Abstract

A scalable metal-, azide-, and halogen-free method for the synthesis of substituted 1,2,3-triazoles has been developed. The reaction proceeds through a 3-component coupling of α-ketoacetals, tosyl hydrazide, and a primary amine. The reaction shows outstanding functional-group tolerance with respect to both the α-ketoacetal and amine coupling partners, providing access to 4-, 1,4-, 1,5-, and 1,4,5-substituted triazoles in excellent yield. This robust method results in densely functionalised 1,2,3-triazoles that remain challenging to prepare by azide–alkyne cycloaddition (AAC, CuAAC, RuAAC) methods and can be scaled in either batch or flow reactors. Methods for the chemoselective reaction of either aliphatic amines or anilines are also described, revealing some of the potential of this novel and highly versatile transformation.

Original languageEnglish
Pages (from-to)6740-6744
Number of pages5
JournalAngewandte Chemie International Edition
Volume59
Issue number17
Early online date15 Jan 2020
DOIs
Publication statusPublished - 20 Apr 2020

Keywords

  • 1,2,3-triazole
  • azide-free
  • α-ketoacetals
  • amines
  • heterocycles

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