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Journal of Flow Chemistry

, Volume 2, Issue 1, pp 8–19 | Cite as

Safe Generation and Synthetic Utilization of Hydrazoic Acid in a Continuous Flow Reactor

  • Bernhard Gutmann
  • David Obermayer
  • Jean-Paul Roduit
  • Dominique M. Roberge
  • C. Oliver Kappe
Full Paper

Abstract

Hydrazoic acid (HN3) was used in a safe and reliable way for the synthesis of 5-substitued-1H-tetrazoles and for the preparation of N-(2-azidoethyl)acylamides in a continuous flow format. Hydrazoic acid was generated in situ either from an aqueous feed of sodium azide upon mixing with acetic acid, or from neat trimethylsilyl azide upon mixing with methanol. For both processes, subsequent reaction of the in situ generated hydrazoic acid with either organic nitriles (tetrazole formation) or 2-oxazolines (ring opening to β-azido-carboxamides) was performed in a coil reactor in an elevated temperature/pressure regime. Despite the explosive properties of HN3, the reactions could be performed safely at very high temperatures to yield the desired products in short reaction times and in excellent product yields. The scalability of both protocols was demonstrated for selected examples. Employing a commercially available benchtop flow reactor, productivities of 18.9 g/h of 5-phenyltetrazole and 23.0 g/h of N-(1-azido-2-methylpropan-2-yl)acetamide were achieved.

Keywords

flow chemistry hydrazoic acid microreactor process intensification tetrazoles 

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Copyright information

© Akadémiai Kiadó 2012

Authors and Affiliations

  • Bernhard Gutmann
    • 1
  • David Obermayer
    • 1
  • Jean-Paul Roduit
    • 2
  • Dominique M. Roberge
    • 2
  • C. Oliver Kappe
    • 1
  1. 1.Christian Doppler Laboratory for Microwave Chemistry and Institute of ChemistryKarl-Franzens-University GrazGrazAustria
  2. 2.Microreactor TechnologyLonza AGVispSwitzerland

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