One-Pot, Three-Component Copper-Catalysed ‘Click’ Triazole Synthesis Utilising the Inexpensive, Shelf-Stable Diazotransfer Reagent Imidazole-1-sulfonyl Azide Hydrochloride

Abstract

A practical and efficient one-pot procedure for the regioselective synthesis of functionalised 1,4-disubstituted 1,2,3-triazoles from primary amines and terminal acetylenes has been established utilising the inexpensive, shelf-stable diazotransfer reagent imidazole-1-sulfonyl azide hydrochloride.

Key words

cycloaddition - triazole - combinatorial chemistry - di­azotransfer reagent - one-pot reaction

References and Notes

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12

Typical Reaction Procedure
To a solution of 1H-imidazole-1-sulfonyl azide˙HCl (210 mg, 1 mmol) in MeOH (6 mL) was added benzylamine (0.109 mL, 1.00 mmol), phenylacetylene (0.110 mL, 1.00 mmol), copper(II) sulfate pentahydrate (25 mg, 0.1 mmol), sodium ascorbate (40 mg, 0.2 mmol), and Et₃N (0.139 mL, 1.00 mmol) under nitrogen. The resulting suspension was stirred or shaken at r.t. for 20 h. The mixture was concen-trated onto SiO₂ and purified by flash chromatography (SiO₂), elution gradient 10-90% Et₂O in isohexane. Pure fractions were evaporated to give 1-benzyl-4-phenyl-1H-1,2,3-triazole (211 mg, 90%) as a white solid. HRMS: m/z calcd: 236.1188 [M + H]⁺; found: 236.1178 [M + H]⁺. ^¹H NMR (500.3 MHz, CDCl₃): δ = 7.81 (m, 2 H), 7.66 (s, 1 H), 7.35 (m, 8 H), 5.58 (s, 2 H). ^¹³C NMR (125.8 MHz, CDCl₃): δ = 148.26, 134.69, 130.53, 129.19, 128.89, 128.20, 128.09, 125.72, 119.51, 54.27. Mp 120.8-122 ˚C;^¹4 120-122 ˚C.