An Efficient Three-Component Synthesis of Benzimidazo[1,2-a]-quinoline-6-carbonitriles

Abstract

An efficient three-component synthesis of benzimidazo[1,2-a]quinoline-6-carbonitriles is described. Condensation reaction of a benzene-1,2-diamine and a cyclohexane-1,3-dione gave an enamine intermediate, which on treatment with an arylidenemalononitrile in water–ethanol (1:1) afforded the title compounds in good to excellent yields.

Key words

benzene-1,2-diamines - cyclohexane-1,3-diones - arylidene­malononitriles - benzimidazo[1,2-a]quinoline-6-carbonitriles - multicomponent reactions

• References and Notes

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• 12 General Procedure for the Preparation of Product 7a–l, Exemplified with 7a A mixture of benzene-1,2-diamine (0.108 g, 1 mmol) and cyclohexane-1,3-dione (0.112 g, 1 mmol) in EtOH–H₂O (1:1, 3 mL) was stirred at 70 °C for 1 h. After nearly complete conversion into the corresponding enamine, as was indicated by TLC monitoring, benzylidenemalononitrile (0.154 g, 1 mmol) and t-BuOK (0.011 g, 0.1 mmol), were added to the mixture and stirring was continued for further 3 h at 70 °C. Next, HCl (37%, 1 mmol) was added, and the mixture was allowed to stir for more 3 h at 70 °C. After completion of the reaction as was indicated by TLC monitoring, the reaction mixture was cooled and stirring was continued for 15 min at ambient temperature. The resulting precipitate was filtered, washed with EtOH–H₂O (1:1), and dried to afford the pure product 7a. 4-Oxo-5-phenyl-1,2,3,4-tetrahydro[1,3]benzimidazo[1,2-a]quinoline-6-carbonitrile (7a) Yield 0.270 g, (80%); pale yellow solid; mp 243–245 °C. IR (KBr): 2229 (CN), 1686 (C=O), 1580, 1500, 1446, 1410, 1380, 1356, 1306, 1249, 1193, 1123, 1019, 937, 757, 703 cm^–1. ¹H NMR (300.1 MHz, DMSO-d ₆): δ = 2.30 (quin, J = 6.6 Hz, 2 H, CH₂CH ₂CH₂), 2.60 (t, J = 6.7 Hz, 2 H, CH₂C=O), 3.89 (t, J = 6.0 Hz, 2 H, CCH₂), 7.31–7.36 (m, 2 H, 2 × CH), 7.43–7.50 (m, 3 H, 3 × CH), 7.54 (t, J = 7.8 Hz, 1 H, CH), 7.70 (t, J = 7.6 Hz, 1 H, CH), 8.02 (d, J = 8.0 Hz, 1 H, CH), 8.47 (d, J = 8.6 Hz, 1 H, CH). ¹³C NMR (75.5 MHz, DMSO-d ₆): δ = 20.9, 28.9 and 37.5 (3 × CH₂), 99.8 (C–CN), 114.6 (C), 116.7 (CN), 117.1, 119.9, 122.9 and 126.9 (4 × CH), 127.8 (2 × CH), 127.9 (2 × CH), 128.2 (CH), 130.2, 137.6, 145.3, 145.8, 150.1 and 156.1 (6 × C), 193.5 (C=O). MS: m/z (%) = 337 (100) [M⁺], 312 (58), 299 (4), 280 (43), 255 (19), 140 (13), 127 (19), 115 (18), 102 (30), 91 (32), 77 (49), 55 (26), 41 (24). Anal. Calcd for C₂₂H₁₅N₃O (337.38): C, 78.32; H, 4.48; N, 12.45. Found: C, 78.26; H, 4.54; N, 12.37. 5-(4-Nitrophenyl)-4-oxo-1,2,3,4-tetrahydro[1,3]benzimidazo[1,2-a]quinoline-6-carbonitrile (7c) Yield 0.325 g (85%); pale yellow solid; mp 267–269 °C. IR (KBr): 2230 (CN), 1677 (C=O), 1581, 1511, 1494, 1449, 1416, 1376, 1337, 1303, 1247, 1198, 1128, 1017, 930, 850, 766, 730, 691 cm^–1. ¹H NMR (400.1 MHz, DMSO-d ₆): δ = 2.31 (quin, J = 6.7 Hz, 2 H, CH₂CH ₂CH₂), 2.61 (t, J = 6.7 Hz, 2 H, CH₂C=O), 3.92 (t, J = 6.3 Hz, 2 H, CCH₂), 7.58 (t, J = 7.8 Hz, 1 H, CH), 7.66 (d, J = 9.0 Hz, 2 H, 2 × CH), 7.73 (t, J = 7.8, Hz, 1 H, CH), 8.05 (d, J = 8.2, Hz, 1 H, CH), 8.35 (d, J = 9.0 Hz, 2 H, 2 × CH), 8.50 (d, J = 8.6 Hz, 1 H, CH). ¹³C NMR (75.5 MHz, DMSO-d ₆): δ = 19.8, 28.9 and 37.2 (3 × CH₂) 99.9 (C–CN), 114.2 (C), 116.1 (CN), 117.2 and 120.0 (2 × CH), 123.16 (2 × CH), 123.17 and 127.2 (2 × CH), 129.3 (2 × CH), 130.2, 144.9, 145.3, 145.4, 147.2, 147.8 and 156.4 (7 × C), 193.6 (C=O). MS: m/z (%) = 382 (15) [M⁺], 352 (9), 334 (5), 308 (6), 291 (32), 263 (28), 232 (17), 208 (18), 173 (28), 153 (19), 135 (38), 115 (54), 105 (50), 93 (82), 77 (100), 65 (91), 55 (71), 41 (86). Anal. Calcd for C₂₂H₁₄N₄O₃ (382.38): C, 69.10; H, 3.69; N, 14.65. Found: C, 69.03; H, 3.75; N, 14.63.
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