A Simple Method for the Synthesis of Functionalised Chromenes via Vinylogous Michael Addition of α,α-Dicyanoalkenes on Iminocoumarin Derivatives

 

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Abstract

A one-pot synthesis of 2-amino-4H-chromenes was achieved in good yields from three-component reaction of salicyl­aldehyde, malononitrile, and α,α-dicyanoalkenes catalysed by triethylamine.

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General Procedure for the Synthesis of 2-Amino Chromenes 4a-h from Salicylaldehyde, Malononitrile, and α,α-Dicyanoalkenes 3a-h - Representative Procedure for 2-Amino-4-(3,3-dicyano-2-phenylallyl)-4 H -chromene-3-carbonitrile (4a)
To a stirred mixture of salicylaldehyde (1 mmol) and malononitrile (1 mmol) in EtOH, vinyl malononitrile 3a (1.5 mmol), and Et₃N (0.5 mmol) were added. The reaction mixture was stirred at r.t. for the appropriate time (Table  [²] ). After complete conversion as indicated by TLC, the mixture was concentrated under vacuo and subjected to chromatographic purification over silica gel (Merck; 100-200 mesh; EtOAc-hexane, 3:7) to obtain chromene 4a (78%).
Spectral Data of 2-Amino-4-(3,3-dicyano-2-phenylallyl)-4 H -chromene-3-carbonitrile (4a, Table 2, Entry 1) Pale pink solid; yield 78%. ^¹H NMR (500 MHz, DMSO-d ₆): δ = 3.18 (dd, J ₁ = 7.65 Hz, J ₂ = 5.35 Hz, 1 H), 3.31 (dd, J ₁ = 5.35 Hz, J ₂ = 8.4 Hz, 1H), 3.56 (t, J = 5.35 Hz, 1 H), 6.93 (d, J = 7.6 Hz, 1 H), 7.09 (s, 2 H, D₂O exchangeable), 7.13 (t, J = 6.1 Hz, 4 H), 7.28 (t, J = 8.4 Hz, 1 H) 7.53 (m, 3 H) 7.65 (d, J = 7.6 Hz, 1 H). ^¹³C NMR (125 MHz, DMSO-d ₆): δ = 35.6, 48.1, 52.7, 86.1, 113.2, 113.7, 116.5, 121.0, 122.8, 125.2, 128.8, 128.9, 128.9, 129.2, 129.4, 129.4, 132.6, 134.5, 149.6, 162.7, 177.0. IR (KBr): ν_max = 3384, 3326, 2183, 1653, 1423, 1050, 757 cm^-¹. ESI-MS: 339 [M + 1]. Anal. Calcd (%) for C₂₁H₁₄N₄O: C, 74.54; H, 4.17; N, 16.56. Found: C, 75.97; H, 4.11; N, 15.71.
Spectral Data of 3-Amino-1-[2-(dicyanomethylene)-4-methylpentyl]-1 H -benzo[ f ]chromene-2-carbonitrile (6) Pale brown solid; yield 70%. ^¹H NMR (500 MHz, CDCl₃): δ = 0.86 (d, J = 6.1 Hz, 3 H), 1.01 (d, J = 6.15 Hz, 3 H), 1.91 (m, 1 H), 2.42 (dd, J ₁ = 8.4 Hz, J ₂ = 4.6 Hz, 1 H) 2.59 (dd, J ₁ = 6.85 Hz, J ₂ = 6.15 Hz, 1 H), 2.85 (dd, J ₁ = 9.2 Hz, J ₂ = 3.8 Hz, 1 H), 3.00 (dd, J ₁ = 3.8 Hz, J ₂ = 8.45 Hz, 1 H), 4.55 (dd, J ₁ = 4.6 Hz, J ₂ = 4.6 Hz, 1 H), 5.00 (s, 2 H, D₂O exchangeable), 7.20 (d, J = 9.15 Hz, 1 H), 7.52 (t, J = 6.9 Hz, 1 H), 7.64 (t, J = 7.65 Hz, 1 H), 7.85 (m, 3 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 22.2, 22.8, 29.2, 32.6, 43.2, 45.1, 56.5, 89.5, 111.7, 112.0, 115.1, 116.9, 119.6, 121.5, 125.7, 128.0, 129.3, 129.7, 130.0, 131.5, 147.7, 161.9, 180.1. IR (KBr): ν_max = 3434, 3327, 2959, 2183, 1643 cm^-¹. ESI-MS: 369 [M + 1]. Anal. Calcd (%) for C₂₃H₂₀N₄O: C, 74.98; H, 5.47; N, 15.21%. Found: C, 74.87; H, 5.11; N, 15.11.

Crystallographic data for compound 4m in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplemental publication No. CCDC-796193. 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 email: deposit@ccdc.cam.ac.uk].

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