A Green, Scalable, and Catalyst-Free One-Minute Synthesis of Quinoxalines

Abstract

A highly efficient and catalyst-free protocol is reported for the synthesis of quinoxalines via the classical cyclocondensation reaction between aryldiamines and dicarbonyl compounds. Remarkably simple and green reaction conditions employing methanol as solvent afforded medium to excellent yield of quinoxalines after only one-minute reaction time at ambient temperature. The conditions allow at least 10 gram scale synthesis of quinoxalines and should be a preferred starting point for optimization and method of choice for applications in the synthetic community.

Key words

quinoxaline - diamine - condensation - diketone - green

Publikationsverlauf

Eingereicht: 03. November 2020

Angenommen nach Revision: 08. Januar 2021

Artikel online veröffentlicht:
10. Februar 2021

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• 41 Typical ProcedureIn a 25 mL round-bottom flask was added benzene-1,2-diamine (1a, 100 mg, 0.925 mmol) which was dissolved in MeOH (5 mL). To the stirred solution, glyoxal (2a, 40%, 134 mg, 0.11 mL, 0.925 mmol) was added and the mixture stirred for 1 min at ambient temperature, followed by quenching with water (10 mL), dilution with ethyl acetate (50 mL), and washing with water (30 mL). The water layer was extracted with ethyl acetate (2 × 30 mL), the organic layers were combined, and dried over anhydrous Na₂SO₄. The drying agent was removed by filtration, and the solvent was evaporated under reduced pressure to obtain the desired product 3a as a yellowish liquid (0.111 g, 93%) without column purification (GC purity >99%). ¹H NMR (400 MHz, CDCl₃): δ = 8.84 (s, 2 H), 8.11 (dd, J = 6.4, 3.5 Hz, 2 H), 7.78 (dd, J = 6.4, 3.5 Hz, 2 H). ¹³C NMR (101 MHz, CDCl₃): δ = 145.0, 143.1, 130.1, 129.5.From 1-gram-scale SynthesisCompound 3w was obtained as golden-yellow solid (1.710 g, 94%) without column purification (GC purity >99%). ¹H NMR (400 MHz, CDCl₃): δ = 8.51 (d, J = 1.9 Hz, 1 H), 8.33–8.21 (m, 4 H), 7.95 (dt, J = 7.8, 1.1 Hz, 1 H), 7.89–7.80 (m, 3 H), 7.75 (dtd, J = 13.2, 7.7, 1.8 Hz, 2 H), 7.60–7.51 (m, 1 H), 7.48–7.41 (m, 2 H), 7.18 (dddd, J = 7.7, 6.3, 5.1, 1.2 Hz, 2 H). ¹³C NMR (101 MHz, CDCl₃): δ = 195.7, 157.1, 157.0, 154.1, 153.6, 148.7, 148.7, 142.9, 140.2, 138.8, 137.1, 136.8, 136.8, 132.9, 132.5, 130.4, 130.2, 129.9, 128.6, 124.4, 124.2, 123.4, 123.3.
• 42 Although there are only 3 novel compounds produced in this study, we have provided the NMR spectra for all entries in order to demonstrate the purity of the products after the indicated procedure. These can be found in the Supporting Information.