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Synlett 2018; 29(11): 1447-1450
DOI: 10.1055/s-0037-1609846
DOI: 10.1055/s-0037-1609846
letter
One-Pot Selective Synthesis of Multisubstituted Quinoxalin-2(1H)-ones by a Ugi 4CR/Catalytic Aza-Wittig Sequence
Authors
We gratefully acknowledge financial support of this work by the National Natural Science Foundation of China (No. 21572075 and 21172085).
Further Information
Publication History
Received: 07.02.2018
Accepted after revision: 05 April 2018
Publication Date:
23 May 2018 (online)
Abstract
A facile, one-pot synthesis of multisubstituted quinoxalin-2(1H)-ones via a Ugi 4CR/catalytic aza-Wittig sequence has been developed. In the presence of a catalytic amount of 3-methyl-1-phenyl-2-phospholene 1-oxide, the reaction of 2-aminobenzoyl azides, aldehydes, ketoacids, and isocyanides selectively produces quinoxalin-2(1H)-ones as the sole products in high yields.
Key words
quinoxalin-2(1H)-ones - 2-aminobenzoyl azide - Ugi reaction - catalytic aza-Wittig reactionSupporting Information
- Supporting Information (PDF) (opens in new window)
1H and 13C NMR spectra of compounds 5h, 5k, and 7a–o for this article are available free of charge via the Internet at https://doi.org/10.1055/s-0037-1609846.
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References and Notes
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- 24 General procedure for the preparation of Ugi intermediates 5: A mixture of 2-aminobenzoyl azide 1 (1 mmol), aldehyde 2 (1 mmol), ketoacid 3 (1 mmol), and isocyanide 4 (1 mmol) was stirred in methanol (5 mL) at room temperature for 8–12 h, after the reaction was complete, the precipitate was filtered to give 5
- 25 Compound 5h: Yield: 90%; white solid; mp 115–117 °C; 1H NMR (CDCl3, 600 MHz): δ = 7.99–6.69 (m, 12 H, Ar-H), 6.53–6.13 (m, 1 H, NH), 6.04–5.97 (m, 1 H, CH), 2.26–2.05 (m, 3 H, CH3), 1.38–1.36 (m, 9 H, 3CH3); 13C NMR (CDCl3, 100 MHz): δ = 189.3, 170.7, 168.6, 166.1, 139.2, 134.5, 134.2, 134.1, 133.6, 133.2, 132.3, 131.3, 130.9, 129.8, 129.6, 128.6, 128.4, 128.0, 65.1, 51.5, 28.2, 20.7; IR (KBr): 2142, 1707, 1690, 1675, 1638 cm–1. Anal. Calcd for C28H26ClN5O4: C, 63.22; H, 4.93; N, 13.16; Found: C, 63.00; H, 4.98; N, 13.26
- 26 General procedure for the preparation of quinoxalin-2(1H)-ones 7: A mixture of 2-aminobenzoyl azide 1 (1 mmol), aldehyde 2 (1 mmol), ketoacid 3 (1 mmol), and isocyanide 4 (1 mmol) was stirred in methanol (5 mL) at room temperature for 8–12 h, then the solvent was removed under reduced pressure at room temperature. Toluene (5 mL) and 3-methyl-1-phenyl-2-phospholene 1-oxide (0.01 g, 0.05 mmol) were added to the reaction vessel and the reaction mixture was heated to 110 °C for 2–3 h to form quinoxalin-2(1H)-ones 7. The solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel (ether/petroleum ether, 1:4, v/v) to give 7. Compound 7a: Yield: 75%; white solid; mp 220–223 °C. 1H NMR (CDCl3, 600 MHz): δ = 8.20–8.19 (m, 2 H, Ar-H), 7.90 (s, 1 H, Ar-H), 7.49–7.41 (m, 4 H, Ar-H), 7.31–7.21 (m, 5 H, Ar-H), 6.75 (s, 1 H, NH), 6.09 (s, 1 H, CH), 2.22 (s, 3 H, CH3), 1.30 (s, 9 H, 3CH3); 13C NMR (CDCl3, 150 MHz): δ = 166.0, 154.9, 136.9, 135.4, 134.4, 132.4, 132.3, 131.4, 131.3, 130.6, 129.5, 129.4, 129.1, 128.1, 127.7, 126.9, 117.2, 61.6, 52.0, 28.3, 19.5; MS (EI, 70 eV): m/z (%) = 459 (5) [M+], 386 (12), 360 (75), 331 (28), 104 (100). Anal. Calcd for C27H26ClN3O2: C, 70.50; H, 5.70; N, 9.14; Found: C, 70.58; H, 5.64; N, 9.20