Synlett 2016; 27(13): 1957-1962
DOI: 10.1055/s-0035-1561659
letter
© Georg Thieme Verlag Stuttgart · New York

Safe Generation and Direct Use of Chlorine Azide in Flow Chemistry: 1,2-Azidochlorination of Olefins and Access to Triazoles

Baptiste Leforestiera, b, Markus Vögtle*a
  • aNovartis Institutes for Biomedical Research, Fabrikstrasse 2, 4056 Basel, Switzerland
  • bEcole Nationale Supérieure des Ingénieurs en Arts Chimiques Et Technologiques (INPT-ENSIACET), 4 allée Emile Monso, 31030 Toulouse, France   Email: markus.voegtle@novartis.com
Further Information

Publication History

Received: 23 March 2016

Accepted after revision: 03 May 2016

Publication Date:
06 June 2016 (eFirst)

Dedicated to Abdul Nachtigaller

Abstract

A safe, fast procedure for the formation of chlorine azide and its trapping by 1,2-addition reaction on olefins is described. ClN3 was generated in situ from NaN3 and NaOCl in the presence of acetic acid, hosted in an organic phase to avoid decomposition and exposed to various alkenes. A copper-catalyzed click reaction then afforded triazoles from the resulting addition products. Telescoping of both reactions was enabled by an in-line workup and subsequent liquid–liquid separation.

Supporting Information

 
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  • 14 General Procedure ‘Method A’: A solution of organic substrate and acetic acid in toluene (2 mL, 0.18 M and 1.27 M, respectively) and a solution of sodium azide and sodium hypochlorite in H2O (2 mL, 0.67 M and 0.60 M respectively) were combined at a T-piece and reacted at 20 °C in a 10-mL PFA coiled tube reactor (1mm diameter). The combined stream was collected in a vigorously stirred vial containing NaHCO3 (4 mL, sat aq) and was left to stir for 5–10 min. The biphasic mixture was extracted with CH2Cl2 (3 × 5 mL), the combined organics were dried over Na2SO4, concentrated under reduced pressure. When necessary, the crude product was purified by flash chromatography (silica gel, heptane–EtOAc).
  • 15 1-(2-Azido-1-chloroethyl)-3-nitrobenzene (1a): Isolated as a yellow oil (73 mg, 0.32 mmol, 92%); Rf (20% EtOAc in hexane) 0.17. 1H NMR (400 MHz, CDCl3): δ = 8.31 (t, J = 2.0 Hz, 1 H, ArH), 8.24 (ddd, J = 8.3, 2.3, 1.0 Hz, 1 H, ArH), 7.77 (dt, J = 7.8, 1.3 Hz, 1 H, ArH), 7.60 (t, J = 8.0 Hz, 1 H, ArH), 5.05 (t, J = 6.7 Hz, 1 H, CHCl), 3.84 (dd, J = 12.9, 6.8 Hz, 1 H, CHaHbN3), 3.75 (dd, J = 12.9, 6.8 Hz, 1 H, CHaHbN3). 13C NMR (101 MHz, CDCl3): δ = 148.7, 140.4, 133.6, 130.2, 124.2, 122.7, 59.5, 57.8.
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  • 18 1-[2-Chloro-2-(4-chlorophenyl)propyl]-4-(4-methoxyphenyl)-1H-1,2,3-triazole (8a′): Isolated as a white solid (69 mg, 0.191 mmol, 95 %). 1H NMR (400 MHz, CDCl3): δ = 7.70 (d, J = 8.2 Hz, 2 H, ArH), 7.57 (s, 1 H, CHtriazole), 7.48 (d, J = 8.6 Hz, 2 H, ArH), 7.37 (d, J = 8.5 Hz, 2 H, ArH), 6.95 (d, J = 7.9 Hz, 2 H, ArH), 4.88 (s, 2 H, CH2), 3.83 (s, 3 H, OMe), 1.96 (s, 3 H, Me). 13C NMR (101 MHz, CDCl3): δ = 159.9, 140.0, 134.9, 129.0, 128.0, 127.2, 123.1, 120.2, 114.4, 70.0, 62.6, 55.5, 28.7. MS (ESI): m/z = 362.1 [M + H]+.