One-Pot Synthesis of [1,2,3]Triazolo[1,5-a]quinoxalin-4(5H)-ones by a Metal-Free Sequential Ugi-4CR/Alkyne–Azide Cycloaddition Reaction

Abstract

A convenient and one-pot approach to prepare [1,2,3]triazolo[1,5-a]quinoxalin-4(5H)-ones by a metal-free sequential Ugi-4CR/alkyne–azide cycloaddition reaction has been developed. The reaction of 2-azidobenzenamines, aldehydes, propiolic acids, and isocyanides produced the Ugi adducts, which were transformed to the [1,2,3]triazolo[1,5-a]quinoxalin-4(5H)-ones in moderate to good yields via alkyne–azide cycloaddition reaction.

Key words

one-pot - metal-free - [1,2,3]triazolo[1,5-a]quinoxalin-4(5H)-one - Ugi reaction - alkyne–azide cycloaddition reaction

• References and Notes

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• 24 Preparation of [1,2,3]Triazolo[1,5-a]quinoxalin-4(5H)-ones 6: General Procedure A mixture of 2-azidobenzenamines 1 (1 mmol), aldehydes 2 (1 mmol), propiolic acid 3 (1 mmol), and isocyanide 4 (1 mmol) were stirred in methanol (5 mL) at room temperature for 12–24 h, then the solvent was removed completely under reduced pressure. DMF (5 mL) was added to the reaction system, and the reaction mixture was heated to 90 °C for 1–2 h to form [1,2,3]triazolo[1,5-a]quinoxalin-4(5H)-ones 6. Later, poured the reaction mixture into water, extracted with ethyl acetate three times, and washed with water three times. The combined organic layer was subsequently dried over anhydrous Na₂SO₄ and filtered. After the solvent was evaporated under vacuum, the residue was purified by recrystallization (diethyl ether/petroleum ether = 1:10, v/v) to afford 6.
• 25 Compound 6a: white solid (yield 412 mg, 85%); mp 236–237 °C. ¹H NMR (600 MHz, CDCl₃): δ = 8.54 (s, 1 H, Ar-H), 8.31 (d, J = 7.2 Hz, 2 H, Ar-H), 7.49–7.33 (m, 10 H, Ar-H), 6.69 (s, 1 H, NH), 5.86 (d, J = 10.8 Hz, 1 H, CH), 1.32 (s, 9 H, 3 CH₃) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 165.9, 155.1, 149.3, 134.5, 132.2, 129.5, 129.3, 129.2, 129.0, 128.9, 128.7, 128.3, 124.8, 122.5, 121.2, 118.1, 117.0, 52.3, 28.5, 18.4 ppm. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₇H₂₅ClN₅O₂: 486.1691; found: 486.1694.