Unexpected Aldehyde-Catalyzed Reaction of Imidazole N-Oxides with Ethyl Cyanoacetate

Abstract

The reaction of 2-unsubstituted imidazole N-oxides with ethyl cyanoacetate and aromatic aldehydes leads to the formation of ethyl 2-cyano-2-(1,3-dihydro-2H-imidazole-2-ylidene)acetates. The reaction proceeds through an initial [3+2] cycloaddition, followed by cleavage of the cycloadduct and regeneration of the aldehyde, which essentially plays a catalytic role.

Key words

imidazole oxides - 1,3-dipolar cycloaddition - reaction mechanism - organocatalysis - multicomponent reaction - [3+2] cycloaddition

• References and Notes

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• 8 Compounds 4a–n; General Procedure A solution of the appropriate imidazole N-oxide 1 (1 mmol), nitrile 3 (1 mmol), and aldehyde 2 (1 mmol) in DMF (4 mL) was stirred at 100 °C for 5 h. The solvent was removed under reduced pressure, and the residue was purified by column chromatography (silica gel, EtOAc). Ethyl (2E)-(1-Benzyl-4,5-dimethyl-1,3-dihydro-2H-imidazol-2-ylidene)(cyano)acetate (4a) White solid; yield: 255 mg (86%); mp 164–166 °C. IR (KBr): 3208, 2983, 2183 (CN), 1639, 1568, 1475, 1440, 1369, 1321, 1305, 1261, 1248, 1209, 1132, 1087, 1034, 975, 779, 732, 705, 693, 533, 457 cm^–1. ¹H NMR (300 MHz, DMSO-d ₆): δ = 11.91 (s, 1 H), 7.40–7.25 (m, 2 H), 7.05 (d, J = 7.1 Hz, 3 H), 5.41 (s, 2 H), 4.06 (q, J = 7.1 Hz, 2 H), 2.12 (s, 3 H), 1.95 (s, 3 H), 1.17 (t, J = 7.1 Hz, 3 H). ¹³C NMR (151 MHz, DMSO-d ₆): δ = 168.40, 145.23, 136.31, 128.72, 127.44, 126.61, 125.98, 121.11, 120.75, 120.08, 58.38, 46.33, 14.71, 8.91, 7.85. HRMS-ESI: m/z [M + H]⁺ calcd for C₁₇H₂₀N₃O₂: 298.1555; found: 298.1550. (1-Benzyl-4,5-dimethyl-1,3-dihydro-2H-imidazol-2-ylidene)[(4-chlorophenyl)sulfonyl]acetonitrile (4n) White solid; yield: 204 mg (51%); mp 203–205 °C. IR (KBr): 3294, 2160 (CN), 1651, 1558, 1474, 1435, 1389, 1335, 1312, 1296, 1273, 1142, 1088, 1049, 1011, 933, 825, 795, 756, 717, 633, 579, 478 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 12.44 (s, 1 H), 7.58 (d, J = 11.1 Hz, 2 H), 7.49 (d, J = 11.2 Hz, 2 H), 7.34–7.06 (m, 3 H), 6.81 (d, J = 8.1 Hz, 2 H), 5.22 (s, 2 H), 2.15 (s, 3 H), 1.94 (s, 3 H). ¹³C NMR (101 MHz, DMSO-d ₆): δ = 147.63, 143.24, 138.95, 138.03, 132.00, 131.47, 130.39, 129.49, 128.84, 126.46, 126.01, 122.83, 54.62, 49.75, 11.86, 11.04. HRMS-ESI: m/z [M + H]⁺ calcd for C₂₀H₁₉ClN₃O₂S: 400.0886; found: 400.0881.