CC BY-NC-ND 4.0 · Synlett 2025; 36(04): 383-388
Electrosynthesis of Quinoxalines via Intermolecular Cyclization/Dehydrogenation of Ketones with o -Phenylenediamines
Yi Tao
b
The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, 161099, P. R. of China
,
Jiahui Zhang
a
College of Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang, 161006, P. R. of China
,
Yangyang Hu
a
College of Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang, 161006, P. R. of China
,
Huiying Liu
a
College of Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang, 161006, P. R. of China
b
The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, 161099, P. R. of China
,
Jingwen Sun
a
College of Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang, 161006, P. R. of China
,
Lei Liu∗
a
College of Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang, 161006, P. R. of China
› Author Affiliations We are grateful for the financial support provided by the Science and Technology Planning Project of Qiqihar (LSFGG-2023025).
Abstract
In this study, we proposed a novel electrochemical dehydrogenative synthetic method for preparing 2-substituted quinoxalines by intermolecular cyclization of aryl alkyl ketones and o -phenylenediamines. This method gave various quinoxalines in yields ranging from 35% to 71%. This novel protocol employs mild reaction conditions and offers moderate to excellent yields, a wide substrate scope, and broad functional-group compatibility. Furthermore, a late-stage functionalization and the wide substrate scope demonstrated the synthetic utility of this protocol.
Key words
quinoxalines -
electrochemistry -
cyclization -
green chemistry -
dehydrogenation
Supporting Information
Supporting information for this article is available online at https://doi.org/10.1055/a-2339-2832.
Supporting Information
Publication History
Received: 15 May 2024
© 2024. The Author(s). 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/)
Georg Thieme Verlag KG
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Quinoxalines 3aa–be; General Procedure
A tube was charged with the appropriate ketone 1 (0.5 mmol, 1.0 equiv), amine 2 (0.75 mmol, 1.5 equiv), KI (0.25 mmol, 0.5 equiv), H2 C2 O4 ·2 H2 O (0.5 mmol, 1.0 equiv),
n
Bu4 NI (0.25 mmol, 0.5 equiv), and DMA (6 mL). The tube was then equipped with a graphite felt anode and a Pt foam cathode, and its contents were subjected to constant-current (15.0 mA) electrolysis at 100 °C for 24 h. After complete consumption of the starting material, the mixture was extracted with EtOAc, and the organic layer was dried (Na2 SO4 ), filtered, and concentrated. The residue was purified by column chromatography (silica gel, EtOAc–hexane).
2-Phenylquinoxaline (3aa)17a
Yellow solid; yield: 70 mg (68%). 1 H NMR (600 MHz, CDCl3 ): δ = 9.33 (s, 1 H), 8.22–8.19 (m, 2 H), 8.15 (ddd, J = 22.2, 8.4, 1.8 Hz, 2 H), 7.77 (dddd, J = 23.4, 8.4, 7.2, 1.2 Hz, 2 H), 7.59–7.52 (m, 3 H). 13 C NMR (150 MHz, CDCl3 ): δ = 152.2, 143.7, 142.7, 141.8, 137.1, 130.7, 130.6, 130.0, 129.9, 129.5, 129.4, 127.9.
2-(4-Bromophenyl)quinoxaline (3ak)17b
Yellow solid; yield: 63 mg (44%). 1 H NMR (600 MHz, CDCl3 ): δ = 9.27 (s, 1 H), 8.11 (ddd, J = 8.4, 6.4, 2.0 Hz, 2 H), 8.08–8.04 (m, 2 H), 7.80–7.72 (m, 2 H), 7.70–7.65 (m, 2 H). 13 C NMR (150 MHz, CDCl3 ): δ = 150.4, 142.6, 142.0, 141.5, 135.4, 132.1, 130.3, 129.6, 129.4, 129.0, 128.8, 124.8.
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