An Efficient Method to Synthesize Benzofurans and Naphthofurans

Chongfeng Pan; Jie Yu; Yuqing Zhou; Zhiyong Wang; Ming-Ming Zhou

doi:10.1055/s-2006-944204

LETTER

An Efficient Method to Synthesize Benzofurans and Naphthofurans

Chongfeng Pan^a, Jie Yu^a, Yuqing Zhou^a, Zhiyong Wang*^a, Ming-Ming Zhou^b
^a Hefei National Laboratory for Physical Science at Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, P. R. of China
Fax: +86(551)3603185; e-Mail: zwang3@ustc.edu.cn;
^b Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, One Gustave L. Levy Place, New York, NY 10029-6574, USA

Abstract

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Abstract

A new method for synthesis of benzofurans and naphthofurans from 2-hydroxystilbene derivatives via an intermolecular cyclization is reported in this study with up to 94% isolated yield.

Key words

benzofuran - naphthofuran - iodine - cyclization - synthesis

Volltext

Referenzen

References and Notes

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1d Ohemeng KA. Appollina MA. Nguyen VN. Schwender CF. Singer M. Steber M. Ansell J. Argentieri D. Hageman W. J. Med. Chem. 1994, 37: 3663

1e Pieters L. Dyck SV. Gao M. Bai R. Hamel E. Vlietinck A. Lemiere G. J. Med. Chem. 1999, 42: 5475

1f Wallez V. Durieux-Poissonnier S. Chavatte P. Boutin JA. Audinot V. Nicolas J.-P. Bennejean C. Delagrange P. Renard P. Lesieur D. J. Med. Chem. 2002, 45: 2788

1g Park KK. Jeong J. Tetrahedron 2005, 61: 545 ; and references cited therein

2a Horton DA. Bourne GT. Smythe ML. Chem. Rev. 2003, 103: 893 ; and references cited therein

2b Willis MC. Taylor D. Gillmore AT. Org. Lett. 2004, 6: 4755

2c McKiernan GJ. Hartley RC. Org. Lett. 2003, 5: 4389

2d Kraus GA. Zhang N. Verkade JG. Nagarajan M. Kisanga PB. Org. Lett. 2000, 2: 2409

2e Clerici A. Porta O. J. Org. Chem. 1990, 55: 1240

2f Yue D. Yao T. Larock RC. J. Org. Chem. 2005, 70: 10292 ; and references cited therein

2g Kraus GA. Schroeder JD. Synlett 2005, 2504

3 Pan C. Ma Z. Yu J. Zhang Z. Hui A. Wang Z. Synlett 2005, 1922

4a Rychnovsky SD. Bartlett PA. J. Am. Chem. Soc. 1981, 103: 3963

4b Pan C.-F. Zhang Z.-H. Sun G.-J. Wang Z.-Y. Org. Lett. 2004, 6: 3059

5

Optimized Procedure for the Synthesis of the PBF.
Hydroxystilbene (1 mmol) was dissolved in 7 mL of anhyd THF, and then K₂CO₃ (8 mmol) was added with stirring at r.t. After 5 min, I₂ (8 mmol) was added in one portion. The mixture was stirred at r.t. for 2 h, and then sat. aq NaHCO₃ solution (20 mL) was added. NaHSO₃ was slowly added to the system until the excess I₂ was completely reduced. The system was subsequently extracted with Et₂O, 3 × 20 mL. The organic layer was dried over anhyd MgSO₄, evaporated, and purified by chromatography on silica gel to give the product. 2-(4-Chlorophenyl)benzofuran: ¹H NMR (300 MHz, CDCl₃): δ = 7.78 (dd, J = 6.5, 1.8 Hz, 2 H), 7.59-7.49 (m, 2 H), 7.41 (d, J = 6.5 Hz, 2 H), 7.32-7.20 (m, 2 H), 7.00 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 155.07, 154.94, 124.48, 129.28, 129.19, 126.44, 126.29, 124.71, 123.25, 121.15, 111.34, 101.90. IR (film): 1580, 1487, 1451, 1404, 1256, 1093 cm^-1. HRMS: m/z calcd for C₁₄H₉ ³⁵ClO: 228.0342; found: 228.0351.
2-Phenylbenzofuran: ¹H NMR (400 MHz, CDCl₃): δ = 7.87 (dd, J = 8.5, 1.4 Hz, 2 H), 7.52-7.23 (m, 7 H), 7.03 (d, J = 0.9 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 155.94, 154.91, 130.52, 129.25, 128.80, 128.56, 124.96, 124.27, 122.95, 120.91, 111.19, 101.31. IR (film): 2926, 2856, 1562, 1470, 1455, 1121 cm^-1. HRMS: m/z calcd for C₁₄H₁₀O: 194.0732; found: 194.0728.
2-(4-Methylphenyl)benzofuran: ¹H NMR (300 MHz, CDCl₃): δ = 7.75 (d, J = 8.1 Hz, 2 H), 7.57-7.49 (m, 2 H), 7.26-7.21 (m, 4 H), 6.95 (s, 1 H), 2.39 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 156.36, 154.94, 138.72, 129.62, 129.51, 127.92, 125.05, 124.13, 123.00, 120.88, 111.23, 100.70, 21.51. IR (film): 2919, 1617, 1502, 1450, 1258, 1167, 1111, 1034 cm^-1. HRMS: m/z calcd for C₁₅H₁₂O: 208.0888; found: 208.0885.
4-(Benzofuran-2-yl)phenyl Acetate: ¹H NMR (300 MHz, CDCl₃): δ = 7.87 (d, J = 8.9 Hz, 2 H), 7.59-7.56 (m, 1 H), 7.53-7.50 (m, 1 H), 7.31-7.16 (m, 4 H), 6.98 (d, J = 0.9 Hz, 1 H), 2.32 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 169.35, 155.25, 155.02, 150.92, 129.30, 128.35, 126.15, 124.45, 123.11, 122.12, 121.05, 111.27, 101.50, 21.20. IR (film): 2927, 1750, 1498, 1451, 1374, 1218, 1194 cm^-1. HRMS: m/z calcd for C₁₆H₁₂O₃: 252.0786; found: 252.0790.
2-(2-Methoxyphenyl)benzofuran: ¹H NMR (300 MHz, CDCl₃): δ = 8.07 (dd, J = 7.7, 1.7 Hz, 1 H), 7.60-7.58 (m, 1 H), 7.5 (d, J = 7.9 Hz, 1 H), 7.35 (d, J = 0.5 Hz, 1 H), 7.32-7.18 (m, 3 H), 7.10-6.99 (m, 2 H), 4.00 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 156.63, 154.03, 152.31, 129.93, 129.35, 127.18, 124.22, 122.76, 121.15, 120.89, 119.52, 111.17, 110.94, 106.45, 55.54. IR (film): 3063, 2936, 2837, 1603, 1585, 1493, 1448, 1282, 1249, 1018 cm^-1. HRMS: m/z calcd for C₁₅H₁₂O₂: 224.0837; found: 224.0831.
5-Bromo-2-phenylbenzofuran: ¹H NMR (300 MHz, CDCl₃): δ = 7.84 (dd, J = 8.5, 1.5 Hz, 2 H), 7.72-7.68 (m, 1 H), 7.47-7.36 (m, 5 H), 6.95 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 157.35, 153.72, 131.33, 130.02, 129.11, 128.96, 127.19, 125.18, 123.59, 116.13, 112.70, 100.74. IR (film): 3091, 2923, 2853, 1605, 1578, 1491, 1450, 1440 cm^-1. HRMS: m/z calcd for C₁₄H₉ ⁷⁹BrO: 271.9837; found: 271.9833.
2-(4-Methoxyphenyl)naphtho[2,1- b ]furan: ¹H NMR (300 MHz, CDCl₃): δ = 8.14 (d, J = 8.0 Hz, 1 H), 7.93 (d, J = 8.0 Hz, 1 H), 7.87-7.83 (m, 2 H), 7.70-7.64 (m, 2 H), 7.60-7.54 (m, 1 H), 7.50-7.44 (m, 1 H), 7.37 (s, 1 H), 7.02-6.98 (m, 2 H), 3.86 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.97, 155.73, 152.21, 130.59, 128.90, 127.68, 126.30, 126.23, 124.91, 124.71, 124.58, 123.73, 123.62, 114.47, 112.33, 99.01, 55.49. IR (film): 1606, 1498, 1251, 1024 cm^-1. HRMS: m/z calcd for C₁₉H₁₄O₂: 274.0994; found: 274.0987.
2-(4-Methylphenyl)naphtho[2,1- b ]furan: ¹H NMR (300 MHz, CDCl₃): δ = 8.15 (d, J = 8.2 Hz, 1 H), 7.93 (d, J = 8.2 Hz, 1 H), 7.81 (d, J = 8.1 Hz, 2 H), 7.72-7.65 (m, 2 H), 7.60-7.55 (m, 1 H), 7.50-7.45 (m, 2 H), 7.27 (d, J = 8.1 Hz, 2 H), 2.40 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 155.80, 152.30, 138.34, 130.56, 129.63, 128.89, 128.06, 127.72, 126.25, 124.97, 124.74, 124.58, 123.59, 112.35, 99.83, 21.46. IR (film): 2916, 2857, 1501, 1384 cm^-1. HRMS:
m/z calcd for C₁₉H₁₄O: 258.1045; found: 258.1053.
2-Phenylnaphtho[2,1- b ]furan: ¹H NMR (300 MHz, CDCl₃): δ = 8.17 (dd, J = 0.6, 7.8 Hz, 1 H), 7.96-7.91 (m, 3 H), 7.74-7.67 (m, 2 H), 7.62-7.57 (m, 1 H), 7.52-7.45 (m, 4 H), 7.38-7.33 (m, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 155.53, 152.51, 130.80, 130.59, 128.96, 128.94, 128.38, 127.77, 126.38, 125.31, 124.80, 124.69, 123.59, 112.41, 100.58. IR (film): 3053, 2924, 2854, 1628, 1603, 1488 cm^-1. HRMS: m/z calcd for C₁₈H₁₂O: 244.0888; found: 244.0890.
2-(4-Chlorophenyl)naphtho[2,1- b ]furan: ¹H NMR (300 MHz, CDCl₃): δ = 8.15 (d, J = 8.1 Hz, 1 H), 7.94 (d, J = 8.1 Hz, 1 H), 7.84 (d, J = 8.6 Hz, 2 H), 7.73 (d, J = 9.0 Hz, 1 H), 7.67 (d, J = 9.0 Hz, 1 H), 7.62-7.57 (m, 1 H), 7.52-7.47 (m, 2 H), 7.43 (d, J = 8.6 Hz, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 154.33, 152.55, 134.08, 130.58, 129.23, 129.17, 128.96, 127.69, 126.50, 125.93, 125.65, 124.81, 124.56, 123.52, 112.32, 100.98. IR (film): 1585, 1481, 1383, 1277, 1266, 1167 cm^-1. HRMS: m/z calcd for C₁₈H₁₁ ³⁵ClO: 278.0498; found: 278.0511.
Methyl 4-(Naphtho[2,1- b ]furan-2-yl)benzoate: ¹H NMR (300 MHz, CDCl₃): δ = 8.17-8.11 (m, 3 H), 7.97-7.93 (m, 3 H), 7.75 (d, J = 8.9 Hz, 1 H), 7.71 (d, J = 8.9 Hz, 1 H), 7.62-7.58 (m, 2 H), 7.53-7.47 (m, 1 H), 3.94 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 166.85, 154.28, 153.05, 134.77, 130.65, 130.35, 129.54, 129.04, 127.80, 126.71, 126.30, 124.98, 124.54, 124.45, 123.56, 112.41, 102.72, 52.31.
IR (film): 1715, 1607, 1435, 1411, 1340, 1278, 1179, 1107 cm^-1. HRMS: m/z calcd for C₂₀H₁₄O₃: 302.0943; found: 302.0951.
2-(2-Chlorophenyl)naphtho[2,1- b ]furan: ¹H NMR (300 MHz, CDCl₃): δ = 8.20 (dd, J = 8.1, 0.5 Hz, 1 H), 8.10 (dd, J = 7.9, 1.7 Hz, 1 H), 8.00 (d, J = 0.5 Hz, 1 H), 7.94 (d, J = 7.9 Hz, 1 H), 7.75 (d, J = 9.0 Hz, 1 H), 7.67 (d, J = 9.0 Hz, 1 H), 7.62-7.57 (m, 1 H), 7.52-7.46 (m, 2 H), 7.41-7.35 (m, 1 H), 7.29-7.23 (m, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 151.87, 151.47, 130.99, 130.52, 129.15, 128.89, 128.80, 128.74, 127.95, 127.06, 126.52, 126.03, 124.73, 124.44, 123.60, 112.16, 106.50. IR (film): 3060, 2924, 1629, 1590, 1521, 1469, 1385, 1172 cm^-1. HRMS: m/z calcd for C₁₈H₁₁ ³⁵ClO: 278.0498; found: 278.0505.
2-(2-Bromophenyl)naphtho[2,1- b ]furan: ¹H NMR (300 MHz, CDCl₃): δ = 8.21 (d, J = 8.1 Hz, 1 H), 8.03-8.01 (m, 2 H), 7.95 (d, J = 8.1 Hz, 1 H), 7.77-7.66 (m, 3 H), 7.63-7.58 (m, 1 H), 7.52-7.40 (m, 2 H), 7.24-7.17 (m, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 152.60, 152.00, 134.40, 131.15, 130.49, 129.62, 129.16, 128.89, 127.92, 127.59, 126.52, 125.99, 124.73, 124.20, 123.60, 120.48, 112.23, 106.18. IR (film): 2925, 1626, 1585, 1465, 1416, 1384, 1168 cm^-1. HRMS: m/z calcd for C₁₈H₁₁ ⁷⁹BrO: 321.9993; found: 321.9985.
2-(2-Methoxyphenyl)naphtho[2,1- b ]furan: ¹H NMR (300 MHz, CDCl₃): δ = 8.22 (d, J = 8.0 Hz, 1 H), 8.12 (dd, J = 7.7, 1.7 Hz, 1 H), 7.94 (d, J = 8.0 Hz, 1 H), 7.83 (s, 1 H), 7.73-7.66 (m, 2 H), 7.61-7.55 (m, 1 H), 7.49-7.44 (m, 1 H), 7.35-7.29 (m, 1 H), 7.13-7.07 (m, 1 H), 7.03 (d, J = 8.3 Hz, 1 H), 4.05 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 156.35, 151.87, 151.49, 130.51, 129.07, 128.86, 128.00, 126.90, 126.20, 125.12, 125.07, 124.47, 123.72, 120.97, 119.70, 112.24, 111.22, 105.53, 55.62. IR (film): 3058, 3000, 1626, 1597, 1584, 1491, 1462, 1445, 1380, 1250 cm^-1. HRMS: m/z calcd for C₁₉H₁₄O₂: 274.0994; found: 274.0991.
2-(3,5-Dimethoxyphenyl)naphtho[2,1- b ]furan: ¹H NMR (300 MHz, CDCl₃): δ = 8.16 (d, J = 8.1 Hz, 1 H), 7.94 (d, J = 8.1 Hz, 1 H), 7.74-7.67 (m, 2 H), 7.62-7.57 (m, 1 H), 7.50-7.46 (m, 2 H), 7.09 (d, J = 1.3 Hz, 2 H), 6.48 (s, 1 H), 3.90 (s, 6 H). ¹³C NMR (75 MHz, CDCl₃): δ = 161.33, 155.34, 152.45, 132.51, 130.58, 128.95, 127.76, 126.43, 125.47, 124.73, 124.60, 123.59, 112.39, 102.91, 101.10, 100.99, 55.63. IR (film): 3002, 2936, 2837, 1597, 1561, 1460, 1424, 1385, 1266, 1204, 1157 cm^-1. HRMS: m/z calcd for C₂₀H₁₆O₃: 304.1099; found: 304.1099.
2-(Naphthalen-1-yl)naphtho[2,1- b ]furan: ¹H NMR (300 MHz, CDCl₃): δ = 8.56 (d, J = 8.1 Hz, 1 H), 8.21 (d, J = 8.1 Hz, 1 H), 7.98-7.88 (m, 4 H), 7.75 (s, 2 H), 7.63-7.50 (m, 6 H). ¹³C NMR (75 MHz, CDCl₃): δ = 155.17, 152.67, 134.15, 130.78, 130.58, 129.44, 128.95, 128.78, 128.50, 127.83, 127.28, 127.01, 126.45, 126.23, 125.68, 125.45, 125.39, 124.71, 124.45, 123.62, 112.49, 105.08. IR (film): 3053, 2924, 1629, 1524, 1509, 1385 cm^-1. HRMS: m/z calcd for C₂₂H₁₄O: 294.1045; found: 294.1032.
4-(Naphtho[2,1- b ]furan-2-yl)pyridine: ¹H NMR (300 MHz, CDCl₃): δ = 8.70-8.67 (m, 2 H), 8.16 (dd, J = 8.0, 2.2 Hz, 1 H), 7.95 (d, J = 8.1 Hz, 1 H), 7.80-7.59 (m, 6 H), 7.54-7.51 (m, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 152.96, 152.18, 150.28, 137.26, 130.43, 128.88, 127.55, 126.80, 126.70, 124.97, 123.96, 123.29, 118.29, 112.14, 103.82.
IR (film): 1602, 1538, 1519, 1414, 1384 cm^-1. HRMS: m/z calcd for C₁₇H₁₁NO: 245.0841; found: 245.0839.
Methyl Naphtho[2,1- b ]furan-2-carboxylate: ¹H NMR (300 MHz, CDCl₃): δ = 8.14 (d, J = 7.9 Hz, 1 H), 8.00 (s, 1 H), 7.95 (d, J = 7.9 Hz, 1 H), 7.86 (d, J = 9.0 Hz, 1 H), 7.70-7.61 (m, 2 H), 7.56-7.51 (m, 1 H), 4.01 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.98, 154.17, 144.90, 130.65, 129.33, 129.13, 128.13, 127.43, 125.56, 123.44, 122.86, 113.10, 112.84, 52.44. IR (film): 2952, 1731, 1586, 1551, 1439, 1331, 1282, 1227, 1206, 1171, 1117 cm^-1. HRMS: m/z calcd for C₁₄H₁₀O₃: 226.0630; found: 226.0644.
3-Methyl-2-phenylbenzofuran: ¹H NMR (300 MHz, CDCl₃): δ = 7.81 (dd, J = 8.5, 1.3 Hz, 2 H), 7.52-7.45 (m, 4 H), 7.38-7.24 (m, 3 H), 2.48 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 153.93, 150.80, 131.56, 131.30, 128.72, 127.96, 126.82, 124.43, 122.45, 119.39, 111.37, 111.04, 9.55.
IR (film): 3059, 2924, 1600, 1450, 1259, 1211, 1109, 1068 cm^-1. HRMS: m/z calcd for C₁₅H₁₂O: 208.0888; found: 208.0895.
2,3-Diphenylnaphtho[2,1- b ]furan: ¹H NMR (300 MHz, CDCl₃): δ = 7.90 (d, J = 8.0 Hz, 1 H), 7.76-7.70 (m, 2 H), 7.57-7.52 (m, 8 H), 7.40-7.35 (m, 1 H), 7.29-7.19 (m, 4 H). ¹³C NMR (75 MHz, CDCl₃): δ = 151.52, 150.17, 134.84, 131.05, 130.98, 130.67, 129.46, 129.06, 128.49, 128.27, 127.86, 126.32, 126.08, 124.34, 123.72, 123.16, 119.65, 112.27. IR (film): 3056, 2925, 2854, 1602, 1524, 1502, 1483, 1443, 1393, 1344, 1393 cm^-1. HRMS: m/z calcd for C₂₄H₁₆O: 320.1201; found: 320.1193.
3-Methyl-2-phenylnaphtho[1,2- b ]furan: ¹H NMR (300 MHz, CDCl₃): δ = 8.37 (d, J = 8.3 Hz, 1 H), 7.94-7.87 (m, 3 H), 7.68-7.44 (m, 6 H), 7.39-7.33 (m, 1 H), 2.55 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 150.26, 149.27, 131.79, 131.71, 128.71, 128.49, 127.58, 126.55, 126.49, 126.26, 125.00, 123.10, 121.33, 120.25, 118.05, 112.60, 9.71.
IR (film): 2923, 1604, 1491, 1446, 1384 cm^-1. HRMS:
m/z calcd for C₁₉H₁₄O: 258.1045; found: 258.1051.
2-(2-Phenylprop-1-enyl)cyclohexa-2,5-diene-1,4-dione: ¹H NMR (300 MHz, CDCl₃): δ = 7.68-7.63 (m, 2 H), 7.59-7.55 (m, 2 H), 7.38-7.21 (m, 4 H), 7.09 (t, J = 7.5 Hz, 1 H), 1.83 (d, J = 0.5 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 201.74, 171.39, 138.38, 138.33, 128.71, 128.26, 125.36, 124.89, 124.76, 122.28, 119.63, 113.52, 24.46. IR (film): 2926, 2855, 1721, 1612, 1476, 1462 cm^-1. HRMS: m/z calcd for C₁₅H₁₂O₂: 204.0837; found: 224.0829.
4b,9b-Dihydrobenzo[ b ]benzofuro[2,3- d ]furan: ¹H NMR (300 MHz, CDCl₃): δ = 7.53 (dd, J = 0.8, 7.5 Hz, 2 H), 7.30-7.25 (m, 2 H), 6.99-6.94 (m, 2 H), 6.86 (d, J = 8.2 Hz, 2 H), 6.28 (s, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 160.18, 131.46, 126.68, 124.56, 121.27, 110.95, 86.59. IR (film): 3051, 2923, 2852, 1602, 1483, 1464, 1326, 1314, 1241, 1225, 1173 cm^-1. HRMS: m/z calcd for C₁₄H₁₀O₂: 210.0681; found: 210.0678.
5,7-Di- tert -butyl-2-phenylbenzofuran: ¹H NMR (300 MHz, CDCl₃): δ = 7.86 (dd, J = 7.5, 1.4 Hz, 2 H), 7.47-7.24 (m, 5 H), 6.97 (s, 1 H), 1.58 (s, 9 H), 1.39 (s, 9 H). ¹³C NMR (75 MHz, CDCl₃): δ = 155.27, 151.47, 145.87, 133.90, 131.10, 129.51, 128.91, 128.34, 124.91, 119.25, 115.17, 101.60, 35.04, 34.71, 32.09, 30.24. IR (film): 3108, 2958, 2867, 1607, 1466, 1406, 1391, 1362, 1280, 1244, 1163
cm^-1. HRMS: m/z calcd for C₂₂H₂₆O: 306.1984; found: 306.1973.