A Versatile One-Pot Synthesis of Fused Polycyclic Imidazole-naphthoquinone Derivatives through Imidazole-4,5-quinodimethane Generation Followed by Diels-Alder Cycloaddition

Abstract

An efficient procedure for the trapping of an imidazole-4,5-quinodimethane intermediate 3 with quinones in boiling toluene and in the presence of 18-crown-6 is described. In all cases the fully aromatized imidazole-naphthoquinone derivatives were isolated as the main reaction products in satisfactory yields. However, in the case of benzo- and naphthoquinone, aromatized products were also isolated, in which the bromine in the 2-imidazole position was ­replaced by hydrogen, whereas in the case of the asymmetrical 2-phenylbenzoquinone and 5,8-quinoline dione inseparable regioisomeric mixtures were formed.

crown ether - Diels-Alder reactions - imidazole o-qui­nodimethanes - fused imidazolenaphthoquinones - one-pot reaction

References and Notes

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All melting points were determined on a Büchi apparatus and are uncorrected. The ¹H NMR and ¹³C NMR spectra were recorded on a Bruker AM300 spectrometer in CDCl₃ with TMS as internal standard. All coupling constants are given in Hz and chemical shifts are given in ppm.
Selected Data for Compound 4: Mp 125-127 °C. IR (mull) ν_max = 1666, 1604 cm^-1. ¹H NMR²² (300 MHz, CDCl₃): δ = 3.570 (s, 3 H, NMe), 6.418 (m, J = 9.1, 2.6 Hz, 2 H, C-2′, C-6′), 6.982 (d, J = 10.4 Hz, 1 H, C-7 or C-6), 7.014 (d, J = 10.4 Hz, 1 H, C-6 or C-7), 7.365 (m, J = 9.1, 2.6 Hz, 2 H, C-3′, C-5′), 7.900 (d, J = 0.5 Hz, 1 H, C-9), 8.43 (d, J = 0.5 Hz, 1 H, C-4). ¹³C NMR (75 MHz, CDCl₃): δ = 40.3 (NMe), 108.6 (C-9), 114.2 (C-4′), 114.4 (C-2′, C-6′), 116.2 (C-2), 119.6 (C-4), 128.6 (C-8a), 132.6 (C-3′, C-5′), 136.4 (C-4a), 137.1 (C-9a), 138.9 (C-7), 139.4 (C-6), 144.4 (C-1′), 145.6 (C-3a), 184.2 (C-5), 184.5 (C-8). Anal. Calcd (%) for C₁₈H₁₁Br₂N₃O₂ (461.11): C, 46.89; H, 2.40; N 9.11. Found: C, 46.79; H, 2.52; N 8.94.
Selected Data for Compound 7: Mp 235-237 °C. ¹H NMR²² (300 MHz, CDCl₃): δ = 3.590 (s, 3 H, NMe), 6.504 (m, J = 9.1, 2.6 Hz, 2 H, C-2′, C-6′), 7.372 (m, J = 9.1, 2.6 Hz, 2 H, C-3′, C-5′), 7.796 (m, J = 7.9, 7.6, 2.2 Hz, 1 H, C-8 or C-7), 7.817 (m, J = 7.9, 7.6, 2.2 Hz, 1 H, C-7 or C-8), 8.18 (d, J = 0.5 Hz, 1 H, C-11), 8.307 (m, J = 7.9, 2.2, 0.5 Hz, 1 H, C-9 or C-6), 8.34 (s, 1 H, C-2), 8.366 (m, J = 7.9, 2.2, 0.5 Hz, 1 H, C-6 or C-9), 8.82 (d, J = 0.5 Hz, 1 H, C-4). ¹³C NMR (75 MHz, CDCl₃): δ = 41.9 (NMe), 109.9 (C-11), 114.6 (C-4′), 115.2 (C-2′, C-6′), 121.6 (C-4), 127.4 and 127.5 (C-9 and C-6), 129.9 (C-4a), 130.2 (C-10a), 132.5 and 133.8 (C-5a and C-9a), 132.6 (C-3′, C-5′), 134.0 and 134.2 (C-7 and C-8), 135.5 (C-11a), 145.3 (C-3a), 147.1 (C-1′), 147.4 (C-2), 182.7 (C-5), 183.0 (C-10). MS (EI, 70 eV): m/z (%) = 431/433 (72) [M⁺], 416/417 (10) [M - CH₃] ⁺ , 352 (7), 281 (43), 207 (100). Anal. Calcd (%) for C₂₂H₁₄BrN₃O₂ (432.27): C, 61.13; H, 3.26; N 9.72. Found: C, 61.25; H, 3.17; N, 9.65.

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The multiplicities and chemical shifts of the aromatic protons have been confirmed after simulation with program SpinWorks, version 2.2.0, available from ftp://davinci.chem.umanitoba.ca.