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DOI: 10.1055/s-2008-1032106
Expedient Entry into 1,4-Dihydroquinoxalines and Quinoxalines via a Novel Variant of Isocyanide-Based MCR
Publication History
Publication Date:
26 February 2008 (online)
Abstract
A novel multicomponent reaction of o-phenylenediamines with aldehydes and isonitriles yields 1,4-dihydroquinoxalines. These intermediates are unstable under reaction conditions. They undergo oxidation with DDQ to furnish 33-54% isolated yields of the respective quinoxalines. This reaction is general for aromatic 1,2-diamines. Monoalkylated aryl 1,2-diamines lead to stable 1,4-dihydroquinoxalines.
Key words
combinatorial chemistry - dehydrogenations - multicomponent reactions - isocyanides - quinoxalines
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References and Notes
New address: M. Krasavin, Department of Chemistry, McGill University, Montreal, Quebec H3A 2K6, Canada.
12Analytical Data for Selected CompoundsCompound 5b: pale yellow solid, mp 156-157ºC. 1H NMR (300 MHz, DMSO-d 6): δ = 7.50-7.59 (m, 7 H), 7.21-7.31 (m, 5 H), 6.34 (s, 1 H, NH), 3.64 (unresolved dd, 2 H, NHCH2), 2.93 (unresolved t, 2 H, NHCH2CH2), 2.37 (s, 3 H), 2.33 (s, 3 H). 13C NMR (75 MHz, DMSO-d 6): δ = 150.0, 145.7, 140.3, 140.1, 139.6, 137.3, 135.5, 133.5, 129.6, 129.2 (two signals overlapped), 128.9, 128.8, 128.2, 126.4, 125.7, 42.9, 34.7, 20.2, 19.7. LCMS: m/z = 354 [M + 1]. HRMS (EI): m/z calcd for C24H23N3: 353.4710; found: 353.4711.Compound 5g: grey solid, mp 203 °C (decomp.). 1H NMR (400 MHz, DMSO-d 6): δ = 12.95 (br s, 1 H, COOH), 8.33 (d, J = 1.5 Hz, 1 H), 8.04 (dd, J = 8.6, 1.8 Hz, 1 H), 7.74 (m, 2 H), 7.64 (d, J = 8.6 Hz, 1 H), 7.55 (m, 3 H), 6.61 (d, J = 6.6 Hz, 1 H, NH), 4.46 (m, 1 H, NHCH), 2.00 (m, 2 H), 1.65 (m, 2 H), 1.54 (m, 4 H). 13C NMR (75 MHz, DMSO-d 6): δ = 167.5 (COOH), 150.9, 148.2, 144.3, 136.7, 135.6, 130.8, 130.1, 129.8, 129.3, 128.9, 126.1, 125.8, 52.9, 32.2, 24.0. LCMS: m/z = 334 [M + 1]. HRMS (EI): m/z calcd for C20H19N3O2: 333.3933; found: 333.3932.Compound 5h: yellow sticky solid, mp 68-69 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 7.86 (dd, J = 3.8, 0.9 Hz, 1 H), 7.83 (dd, J = 5.1, 0.9 Hz, 1 H), 7.78 (dd, J = 8.2, 1.1 Hz, 1 H), 7.62 (dd, J = 8.4, 1.1 Hz, 1 H), 7.55 (ddd, J = 8.4, 6.8, 1.1 Hz, 1 H), 7.37 (ddd, J = 8.2, 6.8, 1.3 Hz, 1 H), 7.27 (dd, J = 5.1, 3.8 Hz, 1 H), 6.87 (t, J = 5.3 Hz, NHCH2), 3.70 (dt, J d = 5.3, J t = 5.1 Hz, 2 H, NHCH2), 3.62 (t, J = 5.1 Hz, 2 H, MeOCH2), 3.31 (s, 3 H, OCH3). 13C NMR (75 MHz, DMSO-d 6): δ = 149.4, 140.9, 140.8, 140.0, 136.4, 130.3, 130.0, 128.7, 128.4, 128.2, 125.9, 124.8, 70.3, 58.4, 40.7. LCMS: m/z = 286 [M + 1]. HRMS (EI): m/z calcd for C15H15N3OS: 285.3703; found: 285.3703.
13Crystallographic data (excluding structure factors) for the structure 5b have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 671798. Copies of the data can be obtained free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44 (1223)336033 or e-mail: deposit@ccdc.cam.ac.uk].
16Characterization Data for 8Brown oil. 1H NMR (300 MHz, DMSO-d 6): δ = 8.79 (dd, J = 5.1, 1.8 Hz, 1 H), 8.50 (d, J = 7.3 Hz, 1 H), 7.73 (br s, 1 H, NH), 7.64 (m, 2 H), 7.53-7.59 (m, 4 H), 7.28-7.35 (m, 4 H), 7.22 (m, 1 H), 3.72 (dd, J = 14.2, 7.2 Hz, 2 H, NHCH2CH2), 2.98 (t, J = 7.2 Hz, 2 H, NHCH2CH2). 13C NMR (75 MHz, DMSO-d 6): δ = 158.4, 151.6, 147.0, 142.1, 136.7, 135.0, 134.9, 133.6, 130.1, 129.6, 128.5, 127.9, 127.2, 126.4, 125.8, 43.6, 35.2. LCMS: m/z = 327 [M + 1]. HRMS (EI): m/z calcd for C21H18N4: 326.4044; found: 326.4047.
17Characterization Data for 10Off-white solid, mp 110-112 °C. 1H NMR (300 MHz, DMSO-d 6): δ = 7.24 (m, 3 H), 7.15 (m, 2 H), 6.86 (m, 1 H), 6.83 (m, 1 H), 6.72 (ddd, J = 7.6, 7.5, 1.6 Hz, 1 H), 6.53 (dd, J = 7.5, 1.6 Hz, 1 H), 5.47 (s, 1 H, dihydroquinaxoline-NH), 4.24 (br s, 1 H, NH-cycloC 7H13), 3.52 (s, 3 H, NCH3), 3.48 (m, 1 H, NHCH), 1.72-1.82 (m, 2 H), 1.44-1.67 (m, 8 H), 1.18-1.35 (m, 2 H). 13C NMR (75 MHz, DMSO-d 6): δ = 149.8, 140.5, 132.1, 132.0, 128.8, 127.7, 126.4, 120.3, 119.9, 114.5, 113.0, 58.7, 53.4, 37.2, 36.6, 30.6, 28.3, 28.1, 24.7, 24.5. LCMS: m/z = 334 [M + 1]. HRMS (EI): m/z calcd for C22H27N3: 333.4806; found: 333.4803.
18Characterization Data for 12Brown viscous oil. 1H NMR (400 MHz, DMSO-d 6): δ = 8.33 (dd, J = 4.9, 1.3 Hz, 1 H), 7.89 (dd, J = 7.6, 1.3 Hz, 1 H), 7.56 (m, 2 H), 7.51 (m, 3 H), 7.07 (dd, J = 4.9, 7.6 Hz, 1 H), 4.55 (t, J = 6.3 Hz, 2 H, MeOCH2), 3.65 (t, J = 6.3 Hz, 2 H, NHCH2), 3.30 (s, 3 H, OCH3), 3.24 (m, 1 H, NHCH), 1.44 (m, 2 H), 1.30-1.40 (m, 6 H), 1.21 (m, 2 H), 0.95 (m, 2 H). 13C NMR (75 MHz, DMSO-d 6): δ = 154.2, 149.0, 146.1, 139.8, 139.5, 136.1, 130.0, 129.0, 127.4, 117.1, 114.2, 68.3, 58.4, 58.0 (one signal obscured by DMSO sept). LCMS: m/z = 379 [M + 1]. HRMS (EI): m/z calcd for C23H30N4O: 378.5218; found: 378.5221.