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Synlett 2009(9): 1391-1394  
DOI: 10.1055/s-0029-1217175
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

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

Neal M. Smith*, Michelle J. Greaves, Robert Jewell, Matthew W. D. Perry, Michael J. Stocks, Jeffrey P. Stonehouse
Department of Medicinal Chemistry, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leics, LE11 5RH, UK
Fax: +44(1509)644925; e-Mail: neal.smith@astrazeneca.com;
Further Information

Publication History

Received 11 February 2009
Publication Date:
13 May 2009 (online)

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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

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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.