Synlett 2006(17): 2791-2794  
DOI: 10.1055/s-2006-950267
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis and Characterization of [1]Benzopyrano[4,3-d][1,3]benzooxazocin-13-one and its Derivatives

Jen-Fei Wang, Yuan-Xiu Liao, Pei-Yu Kuo, Yung-Her Gau, Ding-Yah Yang*
Department of Chemistry, Tunghai University, 181, Taichung-Kang Rd. Sec. 3, Taichung 40704, Taiwan
Fax: +886(4)23590426; e-Mail: yang@thu.edu.tw;
Weitere Informationen

Publikationsverlauf

Received 21 June 2006
Publikationsdatum:
09. Oktober 2006 (online)

Abstract

This work describes the efficient synthesis of functionalized cleft molecules 6, 6a, 16, 16a, 17, 19 and 20 derived from benzopyrano[4,3-d][1,3]benzooxazocin-13-one. X-ray crystal structure analysis of compounds 6a and 16a revealed that the cleft angles of the planes of the benzopyran moiety and the p-methoxybenzene ring are 109.4° and 108.6°, respectively. The conformation of the aromatic ring at the bridgehead of 16, 16a and 20 is restricted by the gem-dimethyl groups on the C-9 position and the methyl group on the nitrogen atom in the ring.

    References and Notes

  • 1 Tröger J. J. Prakt. Chem.  1887,  36:  225 
  • 2 Demeunynck M. Tatibouet A. Recent Developments in Tröger’s Base Chemistry, In Progress in Heterocyclic Chemistry   Vol. 11:  Gribble GW. Gilchrist TL. Pergamon; Oxford, UK: 1999.  p.1 
  • 3 Bailly C. Laine W. Demeunynck M. Lhomme J. Biochem. Biophys. Res. Commun.  2000,  273:  681 
  • 4 Johnson RA. Gorman RR. Wnuk RJ. Crittenden NJ. Aiken JW. J. Med. Chem.  1993,  36:  3202 
  • 5a Harmata M. Kahraman M. Tetrahedron: Asymmetry  2000,  11:  2875 
  • 5b Blaser HU. Jalett HP. Lottenbach W. Studer M. J. Am. Chem. Soc.  2000,  122:  12675 
  • 6 Levkin PA. Strelenko YA. Lyssenko KA. Schurig V. Kostyanovsky RG. Tetrahedron: Asymmetry  2003,  14:  2059 
  • 7 Chen JS. Watson WH. Kagan J. Agdeppa DA. Chen S.-A. Acta Crystallogr., Sect. B: Struct. Crystallogr. Cryst. Chem.  1978,  34:  3627 
  • 8 Molina P. Arques A. Tarraga A. del Rosario Obon M. Tetrahedron  1998,  54:  997 
  • 9 Stoncius S. Butkus E. Zyilinskas A. Larsson K. Ohrstrom L. Berg U. Warnmark K. J. Org. Chem.  2004,  69:  5196 
  • 10 Naemura K. Fukunaga R. Komatsu M. Yamanaka M. Chikamatsu H. Bull. Chem. Soc. Jpn.  1989,  62:  83 
  • 11 Harmata M. Murray T. J. Org. Chem.  1989,  54:  3761 
  • 12 Harmata M. Kahraman M. Tetrahedron Lett.  1999,  40:  4133 
  • 15 Annunziata R. Cinquini M. Cozzi F. Molteni V. Schupp O. Tetrahedron  1997,  53:  9715 
  • 16 Huang JL. Liu HG. Yang DY. Bioorg. Med. Chem. Lett.  2003,  13:  927 
  • 17 Chen DU. Kuo PY. Yang DY. Bioorg. Med. Chem. Lett.  2005,  15:  2665 
  • 19 Kimber MC. Try AC. Painter L. Harding MM. Turner P. J. Org. Chem.  2000,  65:  3024 
13

Representative Procedure for the Preparation of 6a.
To a solution of 11a (100 mg, 0.4 mmol) in benzene (10 mL) was added six drops of SOCl2. The mixture was stirred for 10 min at r.t., and the solution was then evaporated. The crude product was added to 4-hydroxycoumarin (162 mg, 1.0 mmol) and excess Et3N in benzene (10 mL). After the mixture was stirred for another 10 min at r.t., the solution was evaporated. Then, H2O (5 mL) was added to the mixture and the product was extracted twice with CH2Cl2. The combined organic extracts were dried over MgSO4, filtered and concentrated. The resulting crude product was purified by column chromatography (EtOAc-hexane, 1:9) to give a light orange solid with a 45% yield; mp 210-211 °C. 1H NMR (300 MHz, CDCl3): δ = 8.36 (d, J = 9.0 Hz, 2 H), 7.96 (dd, J = 8.1, 1.8 Hz, 1 H), 7.85 (d, J = 8.7 Hz, 2 H), 7.55 (td, J = 9.0, 1.8 Hz, 2 H), 7.32 (td, J = 6.9, 1.5 Hz, 2 H), 7.20 (td, J = 7.5, 1.5 Hz, 1 H), 6.87 (td, J = 9.3, 1.8 Hz, 2 H), 2.86 (s, 3 H), 2.41, 2.30 (ABdq, J = 13.5, 2.7 Hz, 2 H), 1.26 (t, J = 3.0 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 161.6, 158.2, 152.2, 148.2, 148.0, 142.7, 131.9, 127.9, 127.8, 127.4, 126.6, 124.2, 124.0, 122.2, 119.5, 116.8, 115.5, 112.3, 105.6, 92.2, 36.6, 34.6, 29.6. IR (KBr): ν = 2361, 1703, 1342, 1030 cm-1. HRMS (EI): m/z calcd for C25H18N2O5: 426.1216; found: 426.1219 [M+].

14

Representative Procedure for the Preparation of 16a.
To a solution of 15a (100 mg, 0.29 mmol) in CH2Cl2 (10 mL) was added 4-hydroxycoumarin (47 mg, 0.29 mmol) and a catalytic amount of p-TsOH. After the mixture was stirred at 80 °C for 16 h and cooled to r.t., H2O (10 mL) was added and the product was extracted twice with CH2Cl2. The combined organic extracts were dried over MgSO4, filtered and concentrated. The resulting crude product was purified by column chromatography (1:9 EtOAc-hexane) to give a yellow solid with a 85% yield; mp 317-318 °C. 1H NMR (300 MHz, CDCl3): δ = 8.38 (dd, J = 8.7, 2.4 Hz, 1 H), 8.30 (dd, J = 8.7, 2.4 Hz, 1 H), 8.02 (dd, J = 8.7, 1.8 Hz, 1 H), 7.88 (dd, J = 8.4, 1.8 Hz, 1 H), 7.61 (dd, J = 8.7, 1.8 Hz, 1 H), 7.54 (ddd, J = 8.1, 7.2, 1.8 Hz, 1 H), 7.34-7.28 (m, 2 H), 7.08 (d, J = 2.7 Hz, 1 H), 6.76 (d, J = 8.7 Hz, 1 H), 6.71 (dd, J = 8.7, 2.7 Hz, 1 H), 3.80 (s, 3 H), 3.77 (s, 1 H), 2.81 (s, 3 H), 0.94 (s, 3 H), 0.91 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 161.9, 158.0, 153.1, 152.3, 148.0, 144.4, 136.7, 131.8, 130.2, 130.0, 127.4, 124.0, 123.5, 122.8, 122.2, 116.8, 115.2, 113.7, 113.5, 113.2, 105.8, 99.9, 55.7, 42.2, 36.3, 34.8, 23.2, 22.8. IR (KBr): ν = 2939, 1626, 1572, 1343, 1184, 811 cm-1. HRMS (EI): m/z calcd for C28H24N2O6: 484.1634; found: 484.1636 [M+].

18

Crystallographic data (excluding structure factors) for 6a and 16a have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication numbers CCDC-263524 and CCDC-263525, respectively. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033.