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Synlett 2011(10): 1389-1394  
DOI: 10.1055/s-0030-1260563
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Rapid and Efficient Access to 4-Substituted 2-Amino-4H-chromenes Catalyzed by InCl3

Neelakandan Vidhya Lakshmi, Selvarangam E. Kiruthika, Paramasivan T. Perumal*
Organic Chemistry Division, Central Leather Research Institute, Adyar, Chennai 600 020, India
Fax: +91(44)24911589; e-Mail: ptperumal@gmail.com;
Further Information

Publication History

Received 17 February 2011
Publication Date:
13 May 2011 (online)

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Abstract

A series of 4-substituted 2-amino-4H-chromenes was synthesized via a simple and efficient one-pot synthesis from salicylaldehyde, malononitrile, and a few cyclic nucleophiles using indium trichloride as a catalyst. The methodology affords high yields of products in short reaction times.

Key words

chromenes - salicylaldehyde - indium(III) chloride - ­malononitrile - three-component

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16

Experimental Procedure for the Synthesis of 2-Amino-4 H -chromene 4a (Table 2, Entry 1)
To a stirred mixture of salicylaldehyde 1 (1 mmol) and malononitrile (2, 1 mmol) in EtOH, 3-methyl-1-phenyl-1H-pyrazol-5 (4H)-one (3, 1 mmol) and InCl3 (20 mol%) were added. The reaction mixture was stirred until complete conversion of the product as indicated by TLC (Table  [²] ). The solid formed was filtered, dried, and recrystallized from EtOH to obtain the pure product in good yield (85%) 4a. 2-Amino-4-(5-hydroxy-3-methyl-1-phenyl-1 H -pyrazol-4-yl)-4 H -chromene-3-carbonitrile (4a, Table 2, Entry 1) White solid; mp 150-152 ˚C. IR (KBr): νmax = 3418, 3328, 3072, 2185, 1587 cm-¹. ¹H NMR (500 MHz, DMSO-d 6): δ = 1.94 (s, 3 H), 2.04 (s, 1 H, OH, D2O exchangeable), 4.78 (s, 1 H), 6.78 (s, 2 H, NH2, D2O exchangeable), 6.96 (d, 1 H, J = 8.4 Hz), 7.01-7.06 (m, 2 H), 7.14-7.17 (m, 2 H), 7.38 (t, 2 H, J = 8.0 Hz), 7.68 (d, 2 H, J = 8.4 Hz). ¹³C NMR (125 MHz, DMSO-d 6): δ = 29.2, 31.2, 54.6, 115.8, 116.1, 119.1, 119.5, 121.2, 121.4, 123.2, 125.2, 125.5, 128.5, 129.4, 147.5, 149.1, 160.9. MS: m/z = 344.5 [M+]. Anal. Calcd (%) for C20H16N4O2: C, 69.76; H, 4.68; N, 16.27. Found: C, 69.70; H, 4.72; N, 16.23.

17

2-Amino-8-ethoxy-4-(2-oxo indolin-3-yl)-4 H -chromene-3-carbonitrile (6b, Table 3, Entry 2) White solid; mp 178-180 ˚C. IR (KBr): νmax = 3614, 3189, 2183, 1698, 1583, 1476, 1422, 1334, 1269, 1217, 1076, 751 cm-¹. ¹H NMR (500 MHz, DMSO-d 6): δ = 1.20 (t, 3 H, 6.9Hz), 3.58 (d, 1 H, 3.1 Hz), 3.86-3.93 (m, 2 H), 4.19 (d, 1 H, J = 3.1 Hz), 6.58 (d, 1 H, J = 7.7 Hz), 6.66 (d, 1 H, J = 7.7 Hz), 6.76 (d, 1 H, J = 8.4 Hz), 6.81 (t, 1 H, J = 6.9 Hz), 6.86 (t, 1 H, J = 7.7 Hz), 7.01 (t, 1 H, J = 7.7 Hz), 7.06 (s, 2 H, NH2, D2O exchangeable), 7.13 (d, 1 H, J = 7.7 Hz), 10.39 (s, 1 H, NH, D2O exchangeable). ¹³C NMR (125 MHz, DMSO-d 6): δ = 15.03, 37.8, 52.9, 53.3, 64.7, 109.65, 113.3, 119.5, 121.2, 121.7, 124.2, 127.2, 128.6, 139.8, 143.5, 146.3, 162.4, 177.2. MS: m/z = 347.2 [M+]. Anal. Calcd (%) for C20H17N3O3: C, 69.15; H, 4.93; N, 12.10. Found: C, 69.13; H, 4.90; N, 12.08.

18

2-Amino-8-methoxy-4-(4,4-dimethyl-2,6-dioxocyclo-hexyl)-4 H -chromene-3-carbonitrile (8h, Table 4, Entry 8) White solid; mp 150-152 ˚C. IR (KBr): νmax = 3336, 3162, 2209, 1704, 1635, 1508, 1390, 1028 cm-¹. ¹H NMR (500 MHz, DMSO-d 6): δ = 1.05 (s, 3 H), 1.06 (s, 3 H), 2.48 (s, 2 H), 2.52 (s, 2 H), 3.72 (s, 3 H), 3.95 (d, 1 H, J = 3.1 Hz), 4.50 (d, 1 H, J = 3.1 Hz), 6.70-6.73 (m, 2 H), 7.17-7.19 (m, 1 H), 7.61 (s, 2 H, NH2, D2O exchangeable). ¹³C NMR (125 MHz, DMSO-d 6): δ = 26.6, 27.0, 32.3, 55.9, 101.9, 109.2, 111.8, 112.2, 113.8, 117.5, 130.6, 151.6, 152.0, 160.3, 165.6, 168.4, 197.0. MS: m/z = 340.1 [M+]. Anal. Calcd (%) for C19H20N2O4: C, 67.05; H, 5.92; N, 8.23. Found: C, 67.03; H, 5.86; N, 8.27.