Regioselective N/C-Heterocyclization of Allenylindium Bromide Across Aryl Azides: One-Pot Synthesis of 5-Methyl-1,2,3-triazoles

Abstract

An unprecedented, one-pot regioselective synthesis of 1,5-disubstituted 1,2,3-triazoles through N/C-heterocyclization of allenylindium bromide across aryl azides is described. The synthesis is carried out under mild conditions in aqueous medium and proceeds regioselectively in moderate to good yields.

Key words

heterocyclization - aryl azides - 1,2,3-triazoles - allenylindium bromide - regioselective reactions

• References and Notes

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• 17 Typical Procedure for the Synthesis of 1-Phenyl-5-methyl-1,2,3-triazole (6a, Table 2): In a typical procedure, a suspension of indium powder (0.344 g, 3 mmol, 100 mesh, 99.99% pure), and propargyl bromide (00.238 g, 2 mmol) in THF–H₂O (1:1; 20 mL) was stirred at an ambient temperature for 3 h until the metal dissolved completely to form allenylindium bromide. Phenyl azide (0.238 g, 2 mmol) was charged into the reaction mixture at ambient conditions over a period of 2 min. After 5 min, n-butylamine (5 mol%) was charged into the reaction mixture as an additive and the reaction was allowed to stir at 50 °C for 6 h till TLC proved a significant conversion. The reaction was finally quenched with aq NH₄Cl solution (10 mL) followed by dilution with another 50 mL. The organic layer was separated and the aqueous layer was extracted with CH₂Cl₂ (2 × 20 mL). The combined organic layers were dried (anhyd Na₂SO₄) and evaporated under reduced pressure to afford a crude product, which was subjected to chromatography (Alumina, mean pore diameter 60 Å, eluent: n-hexane–EtOAc gradient) to afford pure 1-phenyl-5-methyl-1,2,3-triazole as a pale yellow solid (0.244 g, 1.54 mmol, 77%); mp 61–62 °C. IR (KBr): 1234, 1494, 1549, 1593, 2922, 3138 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 2.37 (s, 3 H), 7.48–7.50 (m, 2 H), 7.52–7.58 (m, 3 H), 7.70 (s, 1 H). ¹³C NMR (400 MHz, CDCl₃): δ = 10.3, 125.6, 129.6, 129.8, 130.6, 138.5, 141.2. HRMS (ESI–TOF): m/z [M + H]⁺ for C₉H₉N₃: 160.0796.
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• 20 Most of the compounds (6a–m) are already known in the literature through the methods discussed in the main text along with the required references. However, full spectral details of all unknown analogues have been provided in the supporting information.