A Facile Synthesis of Benzofuroisocoumarins from C-2 Arylated 1,3-Indanediones

Abstract

Refluxing 2-hydroxy-2-(2′-hydroxy-aryl/naphthyl)-1,3-indanediones in ethyleneglycol with a catalytic amount of tri­ethylamine produces benzofuroisocoumarins after a short reaction time (15 min) in very good yields.

Key words

benzofuroisocoumarins - ninhydrin - phenols - hetero­cycles - catalysis

References

• 1a Barry RD. Chem. Rev.  1964,  64:  229 
• 1b Kiselyov AS. Tetrahedron Lett.  1995,  36:  493 
• 1c Goff DA. Zuckermann RN. J. Org. Chem.  1995,  60:  5748 
• 1d Sugimoto A. Shinba-Tanaka H. Ishikawa M. Synthesis  1995,  431 
• 1e Dickinson J. Nat. Prod. Rep.  1993,  10:  71 
• 2a Hill RA. Naturally Occurring Isocoumarins, In Progress in the Chemistry of Organic Natural Compounds   Vol. 49:  Springer Verlag; New York: 1986.  p.1 
• 2b Livingstone R. In Rodd’s Chemistry of Carbon Compounds   Part E, Vol. IV:  Caffey S. Elsevier; New York: 1977.  p.290 
• 3a Naser-Hijazi B. Stolze B. Zanker KS. Second Proceedings of the International Society of the Coumarin Investigators   Springer; Berlin: 1994. 
• 3b Murray RDH. Mendez J. Brown SA. The Natural Coumarins: Occurrence, Chemistry, and Biochemistry   Wiley; New York: 1982. 
• 4 Yoshikawa M. Harada E. Naitoh Y. Inoue K. Matsuda H. Shimoda H. Yamahara J. Murakami N. Chem. Pharm. Bull.  1994,  42:  2225 
• 5a Matsuda H. Shimoda H. Yamahara J. Yoshikawa M. Bioorg. Med. Chem. Lett.  1998,  8:  215 
• 5b Shimoda H. Matsuda H. Yamahara J. Yoshikawa M. Biol. Pharm. Bull.  1988,  21:  809 
• 6 Whyte AC. Gloer JB. Scott JA. Mallock D. J. Nat. Prod.  1996,  59:  765 
• 7 Nozawa K. Yamada M. Tsuda Y. Kawai K. Nakajima S. Chem. Pharm. Bull.  1981,  29:  2689 
• 8 Furuta T. Fukuyama Y. Asakawa Y. Phytochemistry  1986,  25:  517 
• 9a Korte DE. Hegedeus LS. Wirth RK. J. Org. Chem.  1977,  42:  1329 
• 9b Batu G. Stevenson R. J. Org. Chem.  1980,  45:  1532 
• 9c Larock RC. Varaprath S. Lau HH. Fellows CA. J. Am. Chem. Soc.  1984,  106:  5274 
• 9d Izumi T. Nishimoto Y. Kohei K. Kasahara A. J. Heterocycl. Chem.  1990,  27:  1419 
• 9e Liao H.-Y. Cheng C.-H. J. Org. Chem.  1995,  60:  3711 
• 9f Sashida H. Kawamukai A. Synthesis  1999,  1145 
• 9g Kinder MA. Kopf J. Margaretha P. Tetrahedron  2000,  56:  6763 
• 9h Bellina F. Ciucci D. Vergamini P. Rossi R. Tetrahedron  2000,  56:  2533 
• 9i Tuanli Y. Larock RC. J. Org. Chem.  2003,  68:  5936 
• 9j Larock RC. Doty MJ. Han X. J. Org. Chem.  1999,  64:  8770 
• 9k Sakamoto T. Kondo Y. Yamanaka H. Heterocycles  1988,  27:  453 
• 9l Sakamoto T. Kondo Y. Yasuhara A. Yamanaka H. Tetrahedron  1991,  47:  1877 
• 9m Sakamoto T. An-naka M. Kondo Y. Yamanaka H. Chem. Pharm. Bull.  1986,  34:  2754 
• 9n Sakamoto T. An-naka M. Kondo Y. Araki T. Yamanaka H. Chem. Pharm. Bull.  1988,  36:  1890 
• 9o Wang L. Shen W. Tetrahedron Lett.  1998,  39:  7625 
• 9p Cherry K. Parrain J.-L. Thibonnet J. Duchene A. Abarbri M. J. Org. Chem.  2005,  70:  6669 
• 9q Kundu NG. Pal M. J. Chem. Soc., Chem. Commun.  1993,  86 
• 9r Kundu NG. Pal M. Nandi B. J. Chem. Soc., Perkin Trans. 1  1998,  561 
• 10 Yamaguchi S. Uchiuzoh Y. Sanada K. J. Heterocycl. Chem.  1995,  32:  419 
• 11a Kundu SK. Pramanik A. Patra A. Synlett  2002,  823 
• 11b Kundu SK. Pramanik A. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  2004,  43:  595 
• 11c Kundu SK. Patra A. Pramanik A. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  2004,  43:  604 
• 11d Kundu SK. Das S. Pramanik A. J. Chem. Res.  2004,  781 
• 11e Das S. Pramanik A. Fröhlich R. Patra A. Tetrahedron  2004,  60:  10197 
• 11f Das S. Fröhlich R. Pramanik A. J. Chem. Res.  2005,  572 
• 12a Poupelin J.-P. Saint-Ruf G. Perche J.-C. Roussey J.-C. Laude B. Narcisse G. Bakri-Logeais F. Hubert F. Eur. J. Med. Chem.  1980,  15:  253 
• 12b Poupelin J.-P. Saint-Ruf G. Perche J.-C. Lacroix R. Uchida-Ernouf G. Narcisse G. Hubert F. Eur. J. Med. Chem.  1979,  14:  171 
• 12c Bullington JL. Dodd JH. J. Org. Chem.  1993,  58:  4833 
• 12d Schmitt G. Dinh An N. Poupelin J.-P. Vebrel J. Laude B. Synthesis  1984,  758 
• 15a

  X-ray crystal structure analysis for 4d: formula C₁₆H₁₀O₃, M = 250.24, colorless crystal 0.30 × 0.10 × 0.10 mm, a = 7.069 (1), b = 12.326 (1), c = 13.217 (1) Å, V = 1151.6 (2) ų, ρ_calcd = 1.443 gcm^-3, µ = 0.819 mm^-1, empirical absorption correction (0.791 ≤ T ≤ 0.923), Z = 4, orthorhombic, space group P2₁2₁2₁ (No. 19), λ = 1,54178 Å, T = 223 K, ω and φ scans, 4448 reflections collected (±h, ±k, ±l), [(sinθ)/l] = 0.60 Å^-1, 1958 independent (R _int = 0.031) and 1852 observed reflections [I ≥ 2 σ(I)], 173 refined parameters, R = 0.044, wR ² = 0.118, max residual electron density 0.20 (-0.19) eÅ^-3, Flack parameter 0.3 (3), hydrogens calculated and refined as riding atoms. Data set was collected with a Nonius Kappa CCD diffractometer. Programs used:

• 15b

  Data collection: COLLECT (Nonius B.V., 1998)

• 15c Data reduction, Denzo-SMN: Otwinowski Z. Minor W. Methods Enzymol.  1997,  276:  307 
• 15d Absorption correction, Denzo: Otwinowski Z. Borek D. Majewski W. Minor W. Acta Crystallogr., Sect. A  2003,  59:  228 
• 15e Structure solution SHELXS-97: Sheldrick GM. Acta Crystallogr., Sect. A  1990,  46:  467 
• 15f Structure refinement: Sheldrick GM. SHELXL-97   Universität Göttingen; Germany: 1997. 
• 15g

  Graphics: SCHAKAL (E. Keller, 1997)

• 15h

  Crystallographic data (excluding structure factors) for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication CCDC-285096. Copies of the data can be obtained free of charge on application to The Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax [phone],
  e-mail: [e-mail]].

13

Adducts 2j-p; General Procedure A mixture of ninhydrin (0.25 g, 1.4 mmol) and the appropriate phenol, 1j-p (4.2 mmol) was refluxed in AcOH for the time indicated in Table [1] . Then the cold reaction mixture was poured into ice cold H₂O and was left to sit undisturbed overnight. The crystalline solid product was filtered and washed with H₂O. Recrystallization(acetone) gave pure products 2. 2j (as hemiketal 3j) IR (KBr): 3497, 3415, 1703, 1602, 1457, 1288, 1182, 955, 771 cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 8.08 (1 H, d, J = 7.8 Hz), 7.84 (1 H, t, J = 7.5 Hz), 7.81 (1 H, d, J = 7.7 Hz), 7.60 (1 H, t, J = 7.5 Hz), 7.39 (1 H, d, J = 7.6 Hz), 7.29 (1 H, d, J = 7.9 Hz), 6.92 (1 H, t, J = 7.8 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 198.0, 153.5, 148.0, 137.4, 134.1, 132.3, 131.5, 125.6, 125.3, 124.0, 123.5, 123.0, 116.5, 109.5, 82.9. Anal. Calcd for C₁₅H₉ClO₄: C, 62.40; H, 3.14. Found: C, 62.53; H, 3.22. 2o (as hemiketal 3o) IR (KBr): 3304, 1725, 1692, 1607, 1296, 1235, 1098, 1012, 871 cm^-1. ¹H NMR (300 MHz, acetone-d ₆): δ = 8.18 (1 H, s), 8.10-7.89 (3 H, m), 7.82-7.79 (1 H, m), 7.71-7.69 (1 H, m), 7.09 (1 H, s), 6.92 (1 H, d, J = 8.5 Hz), 6.11 (1 H, s), 4.34 (2 H, q, J = 7.0 Hz), 1.36 (3 H, t, J = 7.1 Hz). ¹³C NMR (75 MHz, acetone-d ₆): δ = 198.1, 165.1, 160.7, 148.7, 136.8, 134.5, 133.6, 131.3, 127.4, 126.0, 125.1, 124.1, 123.2, 111.7, 110.4, 82.1, 60.4, 13.8. Anal. Calcd for C₁₈H₁₄O₆: C, 66.25; H, 4.32. Found: C, 66.34; H, 4.25.

14

Benzofuroisocoumarins 4a-p; General Procedure Et₃N (cat., 0.5 mL) was added to substrates 2a-p (1.4 mmol) in ethyleneglycol (5 mL) and refluxed for 15 min until the solution turned a red color. Then the cold reaction mixture was acidified with HCl (6 N) to pH 6 and the solid product separated. After extraction with CHCl₃, work-up was carried out as usual. The residue from the CHCl₃ layer was purified by column chromatography over silica gel (EtOAc-petroleum ether). 4b IR (KBr): 1728 (CO) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 8.40 (1 H, d, J = 8.2 Hz), 7.95 (1 H, d, J = 7.1 Hz), 7.88-7.83 (1 H, m), 7.63-7.52 (2 H, m), 7.29-7.23 (2 H, m), 2.61 (3 H, s). ¹³C NMR (125 MHz, CDCl₃): δ = 162.1 (CO), 153.3, 138.2, 135.63, 135.59, 132.0, 130.0, 128.4, 128.2, 124.3, 123.0, 119.9, 119.8, 119.1, 116.6, 15.1. Anal. Calcd for C₁₆H₁₀O₃: C, 76.79; H, 4.03. Found: C, 76.88; H, 4.15. 4e IR (KBr): 1730 (CO) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 8.39 (1 H, d, J = 8.0 Hz), 7.93 (1 H, d, J = 7.6 Hz), 7.87-7.82 (1 H, m), 7.56-7.51 (1 H, m), 7.18 (1 H, d, J = 7.6 Hz), 7.05 (1 H, d, J = 7.6 Hz), 3.57-3.48 (1 H, m), 2.74 (3 H, s), 1.42 (6 H, d, J = 7.0 Hz). ¹³C NMR (125 MHz, CDCl₃): δ = 162.2 (CO), 152.4, 139.3, 135.5, 135.0, 132.0, 130.9, 130.1, 129.2, 128.2, 125.2, 124.2, 119.8, 119.3, 118.6, 28.4, 23.1 (2 C), 18.6. Anal. Calcd for C₁₉H₁₆O₃: C, 78.06; H, 5.52. Found: C, 78.21; H, 5.63. 4f IR (KBr): 1746 (CO) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 8.39 (1 H, d, J = 7.9 Hz), 7.98 (1 H, d, J = 7.8 Hz), 7.87-7.81 (1 H, m), 7.58-7.52 (1 H, m), 7.37 (1 H, d, J = 7.8 Hz), 7.30-7.25 (1 H, m), 6.95 (1 H, d, J = 7.9 Hz), 4.07 (3 H, s). ¹³C NMR (125 MHz, CDCl₃): δ = 162.0 (CO), 146.1, 143.7, 138.0, 137.0, 135.7, 132.0, 129.9, 128.5, 125.1, 121.2, 120.1, 119.8, 111.2, 109.2, 56.6. Anal. Calcd for C₁₆H₁₀O₄: C, 72.18; H, 3.78. Found: C, 72.31; H, 3.65. 4h IR (KBr): 1734 (CO) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 8.67 (1 H, d, J = 8.1 Hz), 8.42 (1 H, d, J = 8.0 Hz), 8.00-7.83 (4 H, m), 7.72-7.67 (2 H, m), 7.60-7.52 (2 H, m). ¹³C NMR (75 MHz, CDCl₃): δ = 161.7 (CO), 152.0, 139.4, 135.3, 134.9, 131.7, 130.5, 129.6, 128.5, 128.0, 127.7, 127.4, 126.4, 125.7, 124.6, 119.2, 118.6, 113.6, 112.6. Anal. Calcd for C₁₉H₁₀O₃: C, 79.71; H, 3.52. Found: C, 79.62; H, 3.63. 4j IR (KBr): 1747 (CO) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 8.41 (1 H, d, J = 8.0 Hz), 8.02 (1 H, d, J = 7.7 Hz), 7.92-7.86 (1 H, m), 7.70 (1 H, dd, J = 7.6, 1.1 Hz), 7.63-7.58 (1 H, m), 7.45 (1 H, dd, J = 7.6, 1.1 Hz), 7.31 (1 H, m). ¹³C NMR (75 MHz, CDCl₃): δ = 161.1 (CO), 149.5, 137.1, 136.2, 135.4, 131.6, 128.9, 128.6, 126.8, 124.8, 120.8, 119.8, 119.5, 117.9, 117.2. Anal. Calcd for C₁₅H₇ClO₃: C, 66.55; H, 2.61. Found: C, 66.69; H, 2.78. 4o IR (KBr): 1745 (CO) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 8.52 (1 H, d, J = 1.6 Hz), 8.40 (1 H, d, J = 7.9 Hz), 8.16 (1 H, dd, J = 8.8, 1.6 Hz), 7.92-7.85 (2 H, m), 7.63-7.56 (2 H, m), 4.43 (2 H, q, J = 7.1 Hz), 1.44 (3 H, t, J = 7.1 Hz). ¹³C NMR (125 MHz, CDCl₃): δ = 166.3 (CO₂Et), 161.5 (CO), 156.5, 137.7, 137.1, 135.8, 132.1, 129.5, 129.1, 128.6, 127.2, 121.4, 120.0, 119.6, 112.7, 112.6, 61.7, 14.7. Anal. Calcd for C₁₈H₁₂O₅: C, 70.13; H, 3.92. Found: C, 70.27; H, 4.04.