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CC BY-NC-ND 4.0 · SynOpen 2021; 05(01): 43-48
DOI: 10.1055/s-0040-1706021
DOI: 10.1055/s-0040-1706021
letter
A Green, Scalable, and Catalyst-Free One-Minute Synthesis of Quinoxalines
Norges Forskningsråd (Research Council of Norway, Grant No. 275043 CasCat).
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.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1706021.
- Supporting Information
Publication History
Received: 03 November 2020
Accepted after revision: 08 January 2021
Article published online:
10 February 2021
© 2021. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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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.
For some recent overviews, see:
For some historical references to the imine formation reaction, see:
For an example of a reaction in refluxing methanol without other additives, see: