Indium-Mediated One-Pot Synthesis of New 4-Allyl-2-amino-4H-chromenes in Water

Abstract

A one-pot synthesis of new 4-allyl-2-amino-4H-chromene-3-carbonitriles was achieved in good yields by indium-mediated three-component reaction of salicylaldehyde and malononitrile with different allyl bromides in water.

Key words

chromenes - indium - malononitrile - allyl bromide - water

References and Notes

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10

General Procedure for the Synthesis of 2-Amino-chromenes 4a-k and 7a,b from Salicylaldehyde, Malononitrile and Allyl Bromide/Prenyl Bromide; Representative Procedure for 4-Allyl-2-amino-4 H -chromene-3-carbonitrile (4a; Table 1, entry 1): A mixture of salicylaldehyde (1 mmol) and malononitrile (1 mmol) in H₂O (10 mL) was stirred for about 15-20 min. Allyl bromide (1.5 mmol), indium (1.05 mmol) and NaI (1.55 mmol) were then added and the mixture was stirred at r.t. for the appropriate time (Table  [¹] ). After complete conversion as indicated by TLC, the reaction was quenched with few drops of 1 N HCl solution. The mixture was extracted with Et₂O and the Et₂O extract was washed with brine, dried (Na₂SO₄) and evaporated to leave the crude product which was purified by column chromatography over silica gel (Merck, 60-120 mesh, EtOAc-hexane, 1:9) to furnish pure product 4a (80%).

11

2-Amino-4-(1,1-dimethylprop-2-en-1-yl)-4 H -chromene-3-carbonitrile (4b; Table 1, entry 2): white solid; mp 182-184 ˚C. IR (KBr): 3439, 3341, 2971, 2177, 1635, 1572, 1411, 1261, 764 cm^-¹. ^¹H NMR (500 MHz, DMSO-d ₆): δ = 0.84 (s, 3 H), 0.89 (s, 3 H), 3.21 (s, 1 H), 4.73 (d, 1 H, J = 17.6 Hz), 4.86 (d, 1 H, J = 10.7 Hz), 5.71 (dd, 1 H, J = 17.6, 10.7 Hz), 6.90 (br s, 2 H, NH₂, D₂O exchangeable), 6.96 (d, 1 H, J = 8.4 Hz), 7.07 (t, 1 H, J = 7.6 Hz), 7.12 (d, 1 H, J = 6.9 Hz), 7.20 (t, 1 H, J = 6.9 Hz). ^¹³C NMR (75 MHz, DMSO-d ₆): δ = 22.9, 23.9, 44.2, 45.6, 52.2, 112.5, 115.6, 122.0, 123.0, 123.4, 127.8, 129.9, 145.1, 150.8, 163.4. MS: m/z = 240 [M⁺]. Anal. Calcd for C₁₅H₁₆N₂O: C, 74.97; H, 6.71; N, 11.66. Found: C, 74.94; H, 6.65; N, 11.62.

13

1-Allyl-3-amino-1 H -benzo[ f ]chromene-2-carbonitrile (7a; Scheme 4): light yellow solid; mp 250-252 ˚C. IR (KBr): 3435, 3365, 2966, 2186, 1733, 1643, 1563, 1411, 1216, 817 cm^-¹. ^¹H NMR (500 MHz, DMSO-d ₆): δ = 2.39 (t, 2 H, J = 6.1 Hz), 4.26 (t, 1 H, J = 5.4 Hz), 4.80 (d, 1 H, J = 16.8 Hz), 4.86 (d, 1 H, J = 9.9 Hz), 5.52 (m, 1 H), 6.91 (br s, 2 H, NH₂, D₂O exchangeable), 7.14 (d, 1 H, J = 9.2 Hz), 7.41 (t, 1 H, J = 6.9 Hz), 7.52 (t, 1 H, J = 8.5 Hz), 7.78 (d, 1 H, J = 9.2 Hz), 7.86 (d, 1 H, J = 8.5 Hz), 7.97 (d, 1 H, J = 8.4 Hz). ^¹³C NMR (75 MHz, DMSO-d ₆): δ = 32.0, 40.7, 53.9, 116.3, 116.5, 118.1, 120.9, 122.8, 124.8, 127.1, 128.6, 128.7, 129.8, 130.7, 133.8, 147.2, 161.7. MS: m/z = 262 [M⁺]. Anal. Calcd for C₁₇H₁₄N₂O: C, 77.84; H, 5.38; N, 10.68. Found: C, 77.80; H, 5.32; N, 10.62.