Synlett 2013; 24(14): 1851-1855
DOI: 10.1055/s-0033-1339332
letter
© Georg Thieme Verlag Stuttgart · New York

Novel Synthesis of 3-Aryl-4-hydroxybenzofurans via Four-Component Reaction from Substituted Nitrostyrenes, Aromatic Aldehydes, Cyclohexan-1,3-diones, and Ammonium Acetate

Yan Li
a   School of Chemistry and Chemical Engineering, Yangzhou University, 180 Siwangting Street, Yangzhou 225002, P. R. of China   Fax: +86(514)87975244   eMail: wangcd@yzu.edu.cn
,
Hui Liu
a   School of Chemistry and Chemical Engineering, Yangzhou University, 180 Siwangting Street, Yangzhou 225002, P. R. of China   Fax: +86(514)87975244   eMail: wangcd@yzu.edu.cn
,
Liang Sun
b   Yancheng Orgunion Pharmaceutical Sci & Tech Co., Ltd., 39 Huanghe Road, Yancheng 224400, P. R. of China
,
Juanjuan Liu
a   School of Chemistry and Chemical Engineering, Yangzhou University, 180 Siwangting Street, Yangzhou 225002, P. R. of China   Fax: +86(514)87975244   eMail: wangcd@yzu.edu.cn
,
Zhiheng Xue
a   School of Chemistry and Chemical Engineering, Yangzhou University, 180 Siwangting Street, Yangzhou 225002, P. R. of China   Fax: +86(514)87975244   eMail: wangcd@yzu.edu.cn
,
Juan Yao
a   School of Chemistry and Chemical Engineering, Yangzhou University, 180 Siwangting Street, Yangzhou 225002, P. R. of China   Fax: +86(514)87975244   eMail: wangcd@yzu.edu.cn
,
Cunde Wang*
a   School of Chemistry and Chemical Engineering, Yangzhou University, 180 Siwangting Street, Yangzhou 225002, P. R. of China   Fax: +86(514)87975244   eMail: wangcd@yzu.edu.cn
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Publikationsverlauf

Received: 20. April 2013

Accepted after revision: 10. Juni 2013

Publikationsdatum:
30. Juli 2013 (online)


Abstract

An one-pot-reaction methodology was developed to synthesize a variety of polysubstituted 3-aryl-2-arylmethylene amino-4-hydroxybenzofurans from substituted β-nitrostyrenes, aromatic aldehydes, ammonium acetate, and cyclohexane-1,3-diones for the generation of a wide range of structurally interesting and pharmacologically significant compounds. The reaction pathway involves Michael addition of substituted nitrostyrenes and cyclohexane-1,3-diones, then nucleophilic addition of 2-(2-nitro-1-phenylethyl)cyclohexane-1,3-dione and Schiff base generated from aromatic aldehyde and ammonium acetate and intramolecular cyclization, followed by dehydroaromatization to afford the corresponding 3-aryl-2-arylmethyleneamino-4-hydroxybenzofurans.

Supporting Information

 
  • References and Notes

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  • 50 General Procedure for the Preparation of Polysubstituted 4-Hydroxybenzofurans The appropriate β-nitrostyrene (1 mmol), appropriate aromatic aldehyde (2 mmol), NH4OAc (115 mg, 1.5 mmol), and piperidine (43 mg, 0.5 mmol) were dissolved in DMF (15 mL) at r.t., then to the resultant mixture cyclohexane-1,3-dione or 5-(4-chlorophenyl)cyclohexane-1,3-dione (1 mmol) was added dropwise under stirring and refluxing for 30 min. The reaction mixture was stirred under reflux for ca. 7 h, and the completion of reaction was confirmed by TLC (EtOAc–hexanes, 1:10). After the completion of reaction, the reaction mixture was cooled to r.t. Removal of solvent by vacuum distillation, the residues were diluted with CH2Cl2 (20 mL). Subsequently, the resultant solution was washed with H2O (10 mL) and brine (10 mL), dried over anhyd Na2SO4. The crude product was purified by flash chromatography (silica gel; EtOAc–hexanes, 1:20) to give product 4. 2-(4-Chlorobenzylideneamino)-3-(4-methoxy-phenyl)benzofuran-4-ol (4a) Mp 179–181 °C (MeOH–CH2Cl2). 1 H NMR (600 MHz, CDCl3): δ = 9.21 (s, 1 H), 8.07 (d, J = 7.8 Hz, 1 H), 7.57 (d, J = 8.4 Hz, 2 H), 7.34 (d, J = 7.8 Hz, 1 H), 7.28 (t, J = 7.8 Hz, 1 H), 7.22 (t, J = 7.2 Hz, 1 H), 7.18 (t, J = 8.4 Hz, 1 H), 7.01–7.04 (m, 3 H), 6.63 (d, J = 7.8 Hz, 1 H), 5.26 (s, 1 H), 3.83 (s, 3 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 158.58, 151.99, 151.34, 150.29, 149.65, 135.24, 132.61, 130.94, 130.33, 129.00, 127.42, 126.00, 125.96, 123.06, 115.68, 114.22, 113.43, 108.23, 102.87, 54.38 ppm. IR (KBr): 3381, 2962, 1603, 1511, 1404, 1385, 1309, 1247, 1159, 1037, 813. 779 cm–1. MS (EI): m/z (%) = 376.32 (100) [M – 1]+. Anal. Calcd for C22H16ClNO3 (%): C, 69.94; H, 4.27; N, 3.71. Found: C, 70.20; H, 4.39; N, 3.72. 2-(2-Methoxybenzylideneamino)-6-(4-chlorophenyl)-3-(4-methoxyphenyl)benzofuran-4-ol (4b) Mp 223–224 °C (MeOH–CH2Cl2). 1 H NMR (600 MHz, CDCl3): δ = 9.33 (s, 1 H), 8.07 (d, J = 7.8 Hz, 1 H), 7.66 (d, J = 7.2 Hz, 2 H), 7.56 (d, J = 7.2 Hz, 2 H), 7.39–7.42 (m, 3 H), 7.28 (s, 1 H), 7.08 (d, J = 7.8 Hz, 2 H), 6.99 (t, J = 7.2 Hz, 1 H), 6.44 (t, J = 8.4 Hz, 1 H), 6.93 (s, 1 H), 5.38 (s, 1 H), 3.95 (s, 3 H), 3.90 (s, 3 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 159.90, 159.61, 153.41, 152.76, 152.43, 150.54, 139.52, 138.71, 133.52, 132.88, 131.27, 129.00, 128.39, 127.60, 125.24, 124.31, 120.92, 116.39, 114.62, 113.17, 111.22, 108.37, 102.30, 55.70, 55.43 ppm. IR (KBr): 3504, 2923, 2834, 1597, 1510, 1358, 1247, 1173, 1062, 813, 747 cm–1. MS (EI): m/z (%) = 484.64 (100) [M + 1]+. Anal. Calcd for C29 H22ClNO4 (%): C, 71.97; H, 4.58; N, 2.89. Found: C, 72.02; H, 4.81; N, 2.78.
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