Potassium tert-Butoxide Promoted Cycloaddition Reaction for the Synthesis of 1,5-Disubstituted 1,2,3-Triazoles from Aromatic Azides and Trimethylsilyl-Protected Alkynes

Abstract

The cycloaddition reaction of aromatic azides and trimethylsilyl alkynes upon treatment with desilylating reagents was investigated. In the process, the use of t-BuOK in wet DMF generated 1,5-disubstituted 1,2,3-triazoles regioselectively in moderate to good yields at ambient temperature.

Key words

alkynes - azides - cycloaddition - triazoles - desilylation

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• 11 Synthesis of 1,2,3-Triazoles; General Procedure: To a mixture of azide (1.0 mmol) and TMS-alkyne (1.0 mmol) in DMF (2.0 mL) with a trace of H₂O (2 mg), was added t-BuOK (1.0 mmol). The reaction mixture was stirred under air at room temperature. After 24 hours, the reaction mixture was quenched by addition of sat. aq NH₄Cl (5 mL) and the mixture was poured into EtOAc (45 mL) and washed with H₂O (3 × 15 mL). The organic layer was dried over anhydrous Na₂SO₄ and filtered. The solvent was removed under reduced pressure and the residue was purified by flash chromatography (silica gel; EtOAc–petroleum ether)
• 12 Analytic data of selected products: 1-(4-Methoxyphenyl)-5-phenyl-1H-1,2,3-triazole (3d): Yield: 71%; pale-yellow solid; mp 83–85 °C; IR (KBr): 3112, 2931, 1511, 763 cm^–1; ¹H NMR (CDCl₃, 400 MHz): δ = 3.83 (s, 3 H), 6.92 (d, J = 8.8 Hz, 2 H), 7.22–7.24 (m, 2 H), 7.27 (d, J = 8.8 Hz, 2 H), 7.32–7.36 (m, 3 H), 7.85 (s, 1 H); ¹³C NMR (CDCl₃, 100 MHz): δ = 55.4, 114.4, 126.5, 126.7, 128.4, 128.7, 129.0, 129.5, 133.0, 137.6, 160.0; HRMS (ESI): m/z [M + H]⁺ calcd for C₁₅H₁₃N₃O: 252.1131; found: 252.1133. 1-Phenyl-5-p-tolyl-1H-1,2,3-triazole (3l): Yield: 79%; pale-yellow solid; mp 150–151 °C; IR (KBr): 3106, 2924, 1494, 762 cm^–1; ¹H NMR (CDCl₃, 400 MHz): δ = 2.35 (s, 3 H), 7.10–7.15 (m, 4 H), 7.35–7.39 (m, 2 H), 7.42–7.44 (m, 3 H), 7.83 (s, 1 H); ¹³C NMR (CDCl₃, 100 MHz): δ = 21.2, 123.7, 125.1, 128.4, 129.1, 129.2, 129.5, 133.1, 133.2, 136.7, 137.8, 139.3. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₅H₁₃N₃: 236.1182; found: 236.1182