Synlett 2012; 23(15): 2179-2182
DOI: 10.1055/s-0031-1290445
letter
© Georg Thieme Verlag Stuttgart · New York

Copper-Catalysed Multicomponent Click Synthesis of 5-Alkynyl 1,2,3-Triazoles under Ambient Conditions

Francisco Alonso*
a  Departamento de Química Orgánica, Facultad de Ciencias and Instituto de Síntesis Orgánica (ISO), Universidad de Alicante, Apdo. 99, 03080 Alicante, Spain, Fax: +34(965)903549   Email: [email protected]
,
Yanina Moglie
a  Departamento de Química Orgánica, Facultad de Ciencias and Instituto de Síntesis Orgánica (ISO), Universidad de Alicante, Apdo. 99, 03080 Alicante, Spain, Fax: +34(965)903549   Email: [email protected]
,
Gabriel Radivoy
b  Departamento de Química, Instituto de Química del Sur (INQUISUR-CONICET), Universidad Nacional del Sur, Avenida Alem 1253, 8000 Bahía Blanca, Argentina
,
Miguel Yus
a  Departamento de Química Orgánica, Facultad de Ciencias and Instituto de Síntesis Orgánica (ISO), Universidad de Alicante, Apdo. 99, 03080 Alicante, Spain, Fax: +34(965)903549   Email: [email protected]
› Author Affiliations
Further Information

Publication History

Received: 02 May 2012

Accepted after revision: 24 June 2012

Publication Date:
08 August 2012 (online)


Dedicated to the memory of Professor Guy Solladié

Abstract

Copper(I) oxide has been found to effectively catalyse the multicomponent click synthesis of fully substituted 5-alkynyl 1,2,3-triazoles from organic halides, sodium azide, and terminal ­alkynes in methanol under ambient conditions.

Supporting Information

 
  • References and Notes

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  • 18 General Procedure for the Synthesis of 5-Alkynyl 1,2,3-triazoles 3 The organic halide (1, 0.5 mmol), alkyne (2, 1.0 mmol), and NaN3 (39.0 mg, 0.6 mmol) were added to a reactor tube containing a suspension of Cu2O (1.4 mg, 0.01 mmol) in MeOH (2 mL). The reaction mixture was stirred at r.t. without the exclusion of air and monitored by TLC, GLC, and/or 1H NMR spectroscopy until total conversion of the starting materials. H2O (2 mL) was added to the mixture, followed by extraction with EtOAc (3 × 10 mL). The resulting organic phase was evaporated under vacuum, and the residue was purified by column chromatography (silica gel, hexane–EtOAc). 1-Benzyl-4-(p-tolyl)-5-(p-tolylethynyl)-1H-1,2,3-triazole (3ab) Starting from benzyl bromide (1a, 60 μL, 0.5 mmol), 1-ethynyl-4-methylbenzene (2b, 127 μL, 1.0 mmol), NaN3 (39.0 mg, 0.6 mmol), and Cu2O (1.4 mg, 0.01 mmol) in MeOH (2 mL), 3ab was isolated as a pale orange solid (145 mg, 80%); mp 81.9–84.0 °C; Rf = 0.66 (hexane–EtOAc = 7:3). IR (neat): ν = 3034, 2919, 1518, 1496, 1455, 1362, 1001, 815, 726, 692 cm–1. 1H NMR (300 MHz, CDCl3): δ = 8.07 (d, J = 8.1 Hz, 2 H), 7.42–7.30 (m, 7 H), 7.25 (d, J = 8.1 Hz, 2 H), 7.21 (d, J = 8.1 Hz, 2 H), 5.65 (s, 2 H), 2.39 (s, 3 H), 2.38 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 148.2, 140.2, 138.6, 134.9, 131.6, 129.6, 129.5, 128.9, 128.6, 128.2, 127.6, 126.2, 118.6, 117.2, 102.6, 77.4, 75.3, 53.0, 21.8, 21.5. MS (70 eV): m/z (%) = 364 (11) [M+ + 1), 363 (39) [M+], 334 (10), 245 (19), 244 (100), 203 (15), 127 (15), 91 (23). HRMS: m/z calcd for C25H21N3: 363.1735; found: 363.1726.