The Use of Calcium Carbide in the Synthesis of 1-Monosubstituted Aryl 1,2,3-Triazole via Click Chemistry

Abstract

The synthesis of 1-monosubstituted aryl 1,2,3-triazoles was achieved using calcium carbide as a source of acetylene. The copper-catalyzed 1,3-dipolar cycloaddition reactions were carried out without nitrogen protection and in a MeCN-H₂O mixture. The yields ranged from moderate to excellent. The reaction conditions were found to be successful for aryl azide reactants, including analogues with various functionalities.

Key words

calcium carbide - 1-monosubstitued 1,2,3-triazole - copper-catalyzed - click chemistry

References and Notes

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8

General Procedure for the Synthesis of 2 (Conditions A)
To a flask were added MeCN-H₂O mixture (12 mL
v/v = 2:1), azide (0.5 mmol), CuI (19 mg, 0.1 mmol), Na ascorbate (20 mg, 0.1 mmol), CaC₂ (42 mg, 0.65 mmol). The mixture was stirred at r.t., and the reaction was monitored by TLC. After reaction completed, the system was neutralized to pH = 5 with aq HCl (6%), and the mixture was then extracted with EtOAc (3 × 30 mL). The organic layer was separated, washed with H₂O and sat. brine, and dried over anhyd NaSO₄. Evaporation of the solvent gave the crude product, which was subjected to column chromatography (silica gel, EtOAc-PE) to afford 1-substitued 1,2,3-triazoles 2.

9

General Procedure for the Synthesis of 2 (Conditions B)
To a sealed tube were added MeCN-H₂O mixture (12 mL
v/v = 2:1), azide (0.5 mmol), CuI (19 mg, 0.1 mmol), Na ascorbate (20 mg, 0.1 mmol), CaC₂ (42 mg, 0.65 mmol). The mixture was stirred at 90 ˚C, and the reaction was monitored by TLC. After reaction completed, the system was neutralized to pH = 5 with aq HCl (6%), and the mixture was then extracted with EtOAc (3 × 30 mL). The organic layer was separated, washed with H₂O and sat. brine, and dried over anhyd NaSO₄. Evaporation of the solvent gave the crude product, which was subjected to column chromatography (silica gel, EtOAc-PE) to afford
1-substitued 1,2,3-triazoles 2.

10

All compounds gave satisfactory analytical and spectral data.
Selected Data
(E)-1-[4-(2-Bromovinyl)phenyl]-1H-1,2,3-triazole (2j): yellow solid, mp 147.8-148.1 ˚C. IR (KBr): 1599, 1511, 1435, 977, 783 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 8.00 (1 H, s), 7.85 (1 H, s), 7.73 (2 H, d, J = 9.0 Hz), 7.46 (2 H, d, J = 9.0 Hz), 7.16 (1 H, d, J = 13.8 Hz), 6.88 (1 H, d, J = 13.8 Hz). ^¹³C NMR (125 MHz, CDCl₃): δ = 136.5, 136.4, 135.7, 134.5, 127.3, 121.5, 120.8, 108.3. ESI-MS: m/z (%) = 251(99) [M + 2]⁺, 249(100) [M⁺]. HRMS: m/z calcd for C₁₀H₈ ⁷⁹BrN₃: 248.9902; found: 248.9906
(E)-1-[2-(2-Bromovinyl)phenyl]-1H-1,2,3-triazole (2k): yellow solid, mp 100.9-101.5 ˚C. IR (KBr): 1609, 1496, 1507, 1447, 1193, 983, 783 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.89 (1 H, s), 7.80 (1 H, s), 7.59-7.57 (1 H, m), 7.52-7.46 (2H, m), 7.42 (1 H, d, J = 8.0 Hz), 6.84 (1 H, d, J = 14.0 Hz), 6.78 (1 H, d, J = 14.0 Hz). ^¹³C NMR (125 MHz, CDCl₃): δ = 134.3, 134.0, 131.7, 131.6, 130.1, 129.1, 127.1, 126.5, 125.7, 110.6. ESI-MS: m/z (%) = 251(99)
[M + 2]⁺, 249(100) [M⁺]. HRMS: m/z calcd for C₁₀H₈ ⁷⁹BrN₃: 248.9902; found: 248.9908.