Synlett 2003(13): 2001-2004  
DOI: 10.1055/s-2003-42030
LETTER
© Georg Thieme Verlag Stuttgart · New York

An Efficient and Convenient Approach to the Synthesis of Benzopyrans by a Three-Component Coupling of One-Pot Reaction

Tong-Shou Jin*, Jin-Chong Xiao, Su-Juan Wang, Tong-Shuang Li, Xin-Ru Song
Department of Chemistry, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, P. R. China.
Fax: +86(312)5016914; e-Mail: orgsyn@mail.hbu.edu.cn;
Further Information

Publication History

Received 25 July 2003
Publication Date:
08 October 2003 (online)

Abstract

A general and practical chemistry route to the synthesis of polyfunctionlized benzopyrans using tetrabutylammonium bromide (TBABr) as the catalyst (10 mol%) is described. This method provides several advantages such as neutral conditions, high yields and simple work-up procedure. In addition, water was chosen as a green solvent.

    References

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11

General Procedure for the Preparation of Benzopyrans: A mixture of an aromatic aldehyde (1 mmol), malononitrile (1 mmol), phenol (1 mmol) and TBABr (10 mol%) in H2O (20 mL) was stirred at refluxing for 6 h. The progress of the reaction was monitored by thin layer chromatograph. After completion of the reactions, the mixture was cooled to r.t. and extracted by Et2O and EtOAc. The organic phase was collected and dried over anhyd Na2SO4. Then evaporate the solvent under reduced pressure and get the crude products. The crude products were purified by recrystallization by EtOH. Data of some compounds are shown below:
Compound 4a, 2-Amino-3-cyano-4-(phenyl)-4 H -benzo-chromene. Mp 210-211 °C (from EtOH): IR (KBr): νmax = 3454, 3318, 3020, 2932, 2205, 1656, 1600, 1572, 1450, 1372, 1267, 1100, 1022, 811, 744 cm-1. 1H NMR: δ = 4.90 (s, 1 H, H-4), 7.10 (s 2 H, NH2), 7.07-7.12 (m, 6 H, H-5, H-2′, H-3′, H-4′, H-5′, H-6′), 7.56-7.66 (m, 3 H, H-6, H-8, H-9), 7.94 (d, 1 H, J = 8.4 Hz, H-7 or H-10), 8.23 (d, 1 H, J = 8.4 Hz, H-10 or H-7). Anal. Calcd for C20H14N2O: C, 80.54; H, 4.70; N, 9.39. Found: C, 80.40; H, 4.75; N, 9.37.
Compound 4c, 2-Amino-3-cyano-4-(3-chlorophenyl)-4 H -benzo-chromene. Mp 216-218 °C (from EtOH). IR (KBr): νmax = 3455, 3340, 3023, 2930, 2210, 1645, 1600, 1580, 1470, 1378, 1266, 1030, 816, 750, 700 cm-1. 1H NMR: δ = 4.98 (s, 1 H, H-4), 7.24 (s, 2 H, NH2), 7.12-7.38 (m, 4 H, H-4′, H-5′, H-6′, H-5), 7.23 (s, 1 H, H-2′), 7.56-7.66 (m, 3 H, H-6, H-8, H-9), 7.89 (d, 1 H, J = 8.4 Hz, H-7 or H-10), 8.26 (d, 1 H, J = 8.4 Hz, H-10 or H-7). Anal. Calcd for C20H13ClN2O: C, 72.18; H, 3.91; N, 8.42. Found: C, 72.11; H, 4.01; N, 8.40.
Compound 4d, 2-Amino-3-cyano-4-(2-chlorophenyl)-4 H -benzo-chromene. Mp 236-237 °C (from EtOH). IR (KBr): νmax = 3476, 3320, 2915, 2195, 1664, 1600, 1410, 1360, 1275, 1180, 1040, 805, 750 cm-1. 1H NMR: δ = 5.41 (s, 1 H, CH), 7.20 (s, 2 H, NH2), 7.01 (d, 1 H, J = 8.4 Hz, H-5), 7.25-7.31 (m, 3 H, H-4′, H-5′, H-6′), 7.45 (d, 1 H, J = 8.4 Hz, H-3′), 7.56-7.67 (m, 3 H, H-6, H-8, H-9), 7.89 (d, 1 H, J = 8.4 Hz, H-7 or H-10), 8.24 (d, 1 H, J = 8.4 Hz, H-10 or H-7). Anal. Calcd for C20H13ClN2O: C, 72.18; H, 3.91; N, 8.42. Found: C, 72.11; H, 4.00; N, 8.39.
Compound 4e, 2-Amino-3-cyano-4-(2,4-dichlorophenyl)-4 H -benzo-chromene. Mp 213-215 °C (from EzOH). IR (KBr): νmax = 3454, 3336, 3030, 2186, 1667, 1600, 1572, 1466, 1378, 1200, 1050, 860, 811, 755 cm-1. 1H NMR δ = 5.47 (s, 1 H, H-4), 7.30 (s, 2 H, NH2), 6.98 (d, 1 H, J = 8.4 Hz, H-6′), 7.60 (s, 1 H, H-3′), 7.39-7.59 (m, 2 H, H-5, H-5′), 7.69-7.89 (m, 3 H, H-6, H-8, H-9), 8.03 (d, 1 H, J = 8.4 Hz, H-7 or H-10), 8.25 (d, 1 H, J = 8.4 Hz, H-10 or H-7). Anal. Calcd for C20H12Cl2N2O: C, 65.39; H, 3.27; N, 7.63. Found: C, 65.23; H, 3.25; N, 7.60.
Compound 4f, 2-Amino-3-cyano-4-(4-nitrophenyl)-4 H -benzo-chromene. Mp 239-241 °C (from EtOH). IR (KBr): νmax = 3460, 3335, 2196, 1665, 1600, 1575, 1536, 1500, 1346, 1270, 1195, 1100, 805, 770 cm-1. 1H NMR δ = 5.12 (s, 1 H, H-4), 7.29 (s, 2 H, NH2), 7.05 (d, 1 H, J = 8.4 Hz, H-5), 7.51-7.72 (m, 3 H, H-6, H-8, H-9), 7.52 (d, 2 H, H-2′, H-6′), 7.90 (d, 1 H, J = 8.4 Hz, H-7 or H-10), 8.15 (d, 2 H, H-3′, H-5′), 8.27 (d, 1 H, J = 8.4 Hz, H-10 or H-7). Anal. Calcd for C20H13N3O3: C, 69.97; H, 3.79; N, 12.24. Found: C, 70.09; H, 3.99; N, 12.12.
Compound 4h, 2-Amino-3-cyano-4-(3,4-dioxymethyl-enephenyl)-4 H -benzo-chromene. Mp 242-244 °C (from EtOH). IR (KBr): νmax = 3434, 3320, 2905, 2196, 1670, 1605, 1575, 1490, 1405, 1380, 1225, 1190, 1040, 790, 770 cm-1. 1H NMR δ = 4.88 (s, 1 H, H-4), 5.92 (s, 2 H, CH2), 6.74-6.85 (m, 3 H, H-2′, H-5′, H-6′), 7.10-7.13 (m, 3 H, NH2 + H-5), 7.55-7.65 (m, 3 H, H-6, H-8, H-9), 7.88 (d, 1 H, J = 8.4 Hz, H-7 or H-10), 8.22 (d, 1 H, J = 8.4 Hz, H-10 or H-7). Anal. Calcd for C21H14N2O3: C, 73.68; H, 4.09; N, 8.19. Found: C, 73.70; H, 4.00; N, 8.25.
Compound 4k, 2-Amino-3-cyano-4-(4-dimethylamino-phenyl)-4 H -benzo-chromene. Mp 203-205 °C (from EtOH). IR (KBr): νmax = 3465, 3340, 3090, 2955, 2863, 2806, 2193, 1662, 1605, 1570, 1522, 1400, 1380, 1342, 1262, 1190, 1100, 800, 750 cm-1. 1H NMR δ = 2.84 [s, 6 H, N(CH3)2], 4.75 (s, 1 H, H-4), 7.03-7.10 (m, 3 H, H-5 or NH2), 6.65 (d, 2 H, J = 8.4 Hz, H-2′, H-6′ or H-3′, H-5′), 7.06 (d, 2 H, J = 8.4 Hz, H-3′, H-5′ or H-2′, H-6′), 7.53-7.64 (m, 3 H, H-6, H-8, H-9), 7.88 (d, 1 H, J = 8.4 Hz, H-7 or H-10), 8.24 (d, 1 H, J = 8.4 Hz, H-10 or H-7). Anal. Calcd for C22H19N3O: C, 77.42; H, 5.57; N, 12.32. Found: C, 77.36; H, 5.60; N, 12.23.
Compound 4n, 3-Amino-2-cyano-1-(4-nitrophenyl)-1 H -benzo-chromene. Mp 185-186 °C (from EtOH). IR (KBr): νmax = 3430, 3325, 2190, 1650, 1610, 1582, 1540, 1502, 1340, 1244, 1200, 1070, 810 cm-1. 1H NMR δ = 5.45 (s, 1 H, H-4), 7.20 (s, 2 H, NH2), 7.36-7.52 (m, 3 H, H-6, H-7, H-9 or H-10), 7.69-8.03 (m, 2 H, H-5 and H-8), 7.98 (d, 1 H, J = 9.2 Hz, H-10 or H-9), 7.44 (d, 2 H, H-2′ and H-6′), 8.15 (d, 2 H, H-3′ and H-5′). Anal. Calcd for C20H13N3O3: C, 69.97; H, 3.79; N, 12.24. Found: C, 70.10; H, 3.88; N, 12.08.
Compound 4o, 2-Amino-3-cyano-4-(dioxymethylene-phenyl)-4 H -benzo-chromene. Mp 250-252 °C (from EtOH). IR (KBr): νmax = 3443, 3340, 3045, 2886, 2195, 1657, 1600, 1580, 1500, 1454, 1400, 1234, 1195, 1040, 811, 743 cm-1. 1H NMR δ = 5.25 (s, 1 H, H-4), 5.91 (s, 2 H, -OCH2O-), 6.95 (s, 2 H, NH2), 6.66-6.80 (m, 3 H, H-2′, H-5′, H-6′), 7.86-7.95 (m, 2 H, H-5 or H-8), 7.91 (d, 1 H, J = 8.0 Hz, H-9 or H-10), 7.20-7.49 (m, 3 H, H-6, H-7, H-10). Anal. Calcd for C21H14N2O3: C, 73.68; H, 4.09; N, 8.19; Found: C, 73.72; H, 3.99; N, 8.06.