Synthesis of Quinoxaline Derivatives via Copper(I)-Catalyzed Cross-Coupling Reaction of 1,2-Dihalobenzenes with N,N′-Disubstituted Ethane-1,2-diamines under Ligand- and Solvent-Free Conditions

Abstract

An efficient ligand- and solvent-free method for the synthesis of quinoxaline derivatives via copper(I)-catalyzed cross-coupling process has been developed. 1,2-Halobenzenes or 1,8-diiodonaphthalene coupled with N,N′-disubstituted ethane-1,2-diamines to give the corresponding products in moderate yields under the reaction conditions.

Key words

ligand-free - solvent-free - quinoxaline derivatives - copper(I)-catalyzed - cross-coupling reaction - 1,4-disubstituted-1,2,3,4-tetrahydroquinoxalines

• References and Notes

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• 9 General Procedure for the Synthesis of Quinoxaline Derivatives An oven-dried Schlenk tube equipped with a Teflon valve was charged with a magnetic stir bar, CuI (0.05 mmol), 1,2-diiodobenzenes or 1,8-diiodonaphthalene a (0.5 mmol), and DBU (1.0 mmol). The tube was placed under vacuum for 20 min and backfilled with N₂. Then N,N′-disubstituted 1,2-diamines b (1.0 mmol) was added through a syringe. The reaction mixture was stirred at 110 °C for 24 h. The reaction was monitored by TLC. When 1,2-diiodobenzenes or 1,8-diiodonaphthalene a consumed completely, the reaction was stopped and purified directly by column chromatography on silica gel to give the pure products c (PE–EtOAc, 10:1 v/v). Typical Analytical Data of 1,4,6-Trimethyl-1,2,3,4-tetrahydroquinoxaline (2c) Brown oil, 62 mg, 70% yield. ¹H NMR (400 MHz, CDCl₃/TMS): δ = 6.51–6.46 (m, 2 H), 6.38 (s, 1 H), 3.37–3.34 (m, 2 H), 3.29–3.27 (m, 2 H), 2.88 (s, 3 H), 2.85 (s, 3 H), 2.26 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃/TMS): δ = 136.95, 134.66, 127.82, 118.26, 111.88, 111.18, 50.28, 50.22, 39.68, 39.22, 21.09. ESI-HRMS: m/z calcd for C₁₁H₁₇N₂ [M + H]⁺: 177.1392; found: 177.1390.