Synthesis 2017; 49(18): 4191-4198
DOI: 10.1055/s-0036-1588856
special topic
© Georg Thieme Verlag Stuttgart · New York

Chemoselectivity in the Synthesis of 1,2,3-Triazoles from Enolizable Ketones, Primary Alkylamines, and 4-Nitrophenyl Azide

Tomas Opsomer, Joice Thomas*, Wim Dehaen*
  • Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium   Email: wim.dehaen@chem.kuleuven.be
Tomas Opsomer is a doctoral fellow of FWO Vlaanderen (1154417N). Mass spectrometry was made possible by the support of the Hercules Foundation of the Flemish Government (grant 20100225–7).
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Publication History

Received: 30 March 2017

Accepted after revision: 08 May 2017

Publication Date:
07 June 2017 (eFirst)

Published as part of the Special Topic Modern Cyclization Strategies in Synthesis

Abstract

In recent years, several organocatalytic/metal-free synthetic pathways towards 1,2,3-triazoles have been reported. One of them is a general metal-free route towards the synthesis of 1,5-di- or fully-substituted 1,2,3-triazoles, designed by our group and named the ‘triazolization’ reaction of ketones. Limitations of this route were encountered in reactions with more activated ketones, where the corresponding 1-(4-nitrophenyl)-1,2,3-triazole was found back as the major product. Interestingly, three different triazoles are formed when 1,3-diphenylacetone is used as the ketone. In the present work, 1,3-diphenylacetone was used as a model substrate to investigate the chemoselectivity of our metal-free route under different reaction circumstances. This led to the conclusion that the formation of the desired 1,2,3-triazole is favored in apolar solvents, at high temperatures, and in the presence of acetic acid. By using one equivalent of acetic acid, previously inaccessible fully decorated 1,2,3-triazoles can be synthesized from simple α-arylketones in moderate to high yields.

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