Download PDF
Synlett 2011(5): 707-711  
DOI: 10.1055/s-0030-1259549
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

ZnCl2-Catalyzed Intramolecular Cyclization Reaction of 2-Aminochalcones Using Polymer-Supported Selenium Reagent: Synthesis of 2-Phenyl-4-quinolones and 2-Phenyl-2,3-dihydroquinolin-4(1H)-one

E Tang*, Bangzheng Chen, Lianpeng Zhang, Wen Li, Jun Lin
School of Chemical Science and Technology, Yunnan University, Kunming 650091, P. R. of China
Fax: +86(871)5033725; e-Mail: tange@ynu.edu.cn;
Further Information

Publication History

Received 27 November 2010
Publication Date:
15 February 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

A new and efficient method for the synthesis of 2-phenyl-4-quinolones and 2-phenyl-2,3-dihydroquinolin-4(1H)-ones is described. The reaction involves ZnCl2-mediated polystyrene-supported selenium-induced intramolecular cyclization of 2-amino­chalcones and subsequent traceless or functionalizing cleavage of selenium linker.

Key words

polystyrene-supported selenium reagent - intramolecular cyclization - zinc chloride - 2-phenyl-4-quinolones - 2-phenyl-2 - 3-dihydroquinolin-4(1H)-one

    References and Notes

  • 1a Osawa T, Ohta H, Akimoto K, Harada K, Soga H, and Jinno Y. inventors; EP  0343574. 
  • 1b Huang L.-J. Hsieh M.-C. Teng C.-M. Lee K.-H. Kuo S.-C. Bioorg. Med. Chem.  1998,  6:  1657 
    Google Scholar
  • 1c Llinàs-Brunet M. Bailey MD. Ghiro E. Gorys V. Halmos T. Poirier M. Rancourt J. Goudreau N. J. Med. Chem.  2004,  47:  6584 
    Google Scholar
  • 1d Frutos RP. Haddad N. Houpis IN. Johnson M. Smith-Keenan LL. Fuchs V. Yee NK. Farina V. Faucher A.-M. Brochu C. Haché B. Duceppe J.-S. Beaulieu P. Synthesis  2006,  2563 
    Google Scholar
  • Selected references on 2-aryl-4-quinolones as antitumor agents:
  • 2a Hadjeri M. Peiller E.-L. Beney C. Deka N. Lawson MA. Dumontet C. Boumendjel A. J. Med. Chem.  2004,  47:  4964 
    Google Scholar
  • 2b Ferlin MG. Chiarelotto G. Gasparotto V. Via LD. Pezzi V. Barzon L. Palu G. Castagliuolo I. J. Med. Chem.  2005,  48:  3417 
    Google Scholar
  • 2c Gasparotto V. Castagliuolo I. Chiarelotto G. Pezzi V. Montanaro D. Brun P. Palu G. Viola G. Ferlin MG. J. Med. Chem.  2006,  49:  1910 
    Google Scholar
  • 3a Reitsema RH. Chem. Rev.  1948,  43:  43 
    Google Scholar
  • 3b Katritzky AR. Lagowski JM. In Advances in Heterocyclic Chemistry   Vol. 1:  Katritzky AR. Academic Press; New York: 1963.  p.339-437  
    Google Scholar
  • 3c Mphahlele MJ. El-Nahas AM. J. Mol. Struct.  2004,  688:  129 
    Google Scholar
  • 4a Li JJ. Conrad-Limpach Reaction in Name Reactions: A Collection of Detailed Reaction Mechanisms   2nd ed.:  Springer; Berlin: 2003.  p.81 
    Google Scholar
  • 4b Staskun B. Israelstam SS. J. Org. Chem.  1961,  26:  3191 
    Google Scholar
  • For methods utilizing Eaton’s reagent:
  • 4c Zewge D. Chen C.-Y. Deer C. Dormer PG. Hughes DL. J. Org. Chem.  2007,  72:  4276 
    Google Scholar
  • Niementowski methods:
  • 4d Fuson RC. Burness DM. J. Am. Chem. Soc.  1946,  68:  1270 
    Google Scholar
  • 5a Beifuss U. Ledderhose S. Synlett  1997,  313 
    Google Scholar
  • 5b Strekowski L. Wydra RL. Cegla MT. Czarny A. Harden DB. Patterson SE. Battiste MA. Coxon JM. J. Org. Chem.  1990,  55:  4777 
    Google Scholar
  • 6 Torii S. Okumoto H. Xu LH. Sadakane M. Shostakovsky MV. Ponomaryov AB. Kalinin VN. Tetrahedron  1993,  49:  6773 
    CrossrefGoogle Scholar
  • 7 Fürstner A. Hupperts A. Ptock A. Janssen E. J. Org. Chem.  1994,  59:  5215 
    CrossrefGoogle Scholar
  • 8 Tollari S. Cenini S. Ragaini F. Cassar L. J. Chem. Soc., Chem. Commun.  1994,  1741 
    Google Scholar
  • 9 Huang X. Liu ZX. J. Org. Chem.  2002,  67:  6731 
    CrossrefGoogle Scholar
  • 10 Petragnani N. Stefanib HA. Valdugab CJ. Tetrahedron  2001,  57:  1411 
    CrossrefGoogle Scholar
  • 11 Nicolaou KC. Pfefferkorn JA. Cao GQ. Kim S. Kessabi J. Org. Lett.  1999,  1:  807 
    CrossrefGoogle Scholar
  • 12a Yanada K. Fujita T. Yanada R. Synlett  1998,  971 
    Google Scholar
  • 12b Fujita K. Taka H. Oishi A. Ikeda Y. Taguchi Y. Fujie K. Saeki T. Sakuma M. Synlett  2000,  1509 
    Google Scholar
  • 12c Nicolaou KC. Pfefferkorn JA. Cao G.-Q. Angew Chem. Int. Ed.  2000,  39:  734 
    Google Scholar
  • 12d Nicolaou KC. Pfefferkorn JA. Barluenga S. Mitchell HJ. Roecker AJ. Cao G.-Q. J. Am. Chem. Soc.  2000,  122:  9968 
    Google Scholar
  • 13a Huang X. Tang E. Xu WM. J. Comb. Chem.  2005,  7:  802 
    Google Scholar
  • 13b Tang E. Huang X. Xu WM. Tetrahedron  2004,  60:  9963 
    Google Scholar
  • 13c Xu WM. Huang X. Tang E. J. Comb. Chem.  2005,  7:  726 
    Google Scholar
  • 14a Clémence F. Le Martret O. Collard J. J. Heterocycl. Chem.  1984,  21:  1345 
    Google Scholar
  • 14b Dubroeucq M.-C, Bains EL, Paris J.-M, Marne VS, and Renault C. inventors; US  5017576. 
  • 14c Hadjeri M. Mariotte A.-M. Boumendjel A. Chem. Pharm. Bull.  2001,  49:  1352 
    Google Scholar
  • 14d Ding D. Li X. Wang X. Du Y. Shen J. Tetrahedron Lett.  2006,  47:  6997 
    Google Scholar
  • 15 Nicolaou KC. Pastor J. Barluenga S. Winssinger N. Chem. Commun.  1998,  1947 
    Google Scholar
16

Benzeneselenenyl bromide was prepared by the reaction of diphenyldiselenide (1.0 equiv) and bromine (1.0 equiv) in CH2Cl2 at r.t. for 1 hour.

17

General Procedure for Obtaining 4-Quinolone 4 via Route A
An oven-dried 50 mL round-bottomed flask was charged with a suspension of the swollen polystyrene-supported selenenyl bromide (Br: 0.99 mmol/g) resin (1.0 g) in dry CH2Cl2 (20 mL). ZnCl2 (40 mol%) was added. After stirring for 0.5 hour at r.t., substituted 2-aminochalcone 5 (5.0 mmol) was added, and the reaction was stirred for another 12 hours. The resin 3 was collected by filtration, washed with H2O (4 × 20 mL), THF-H2O (v/v = 3:1; 2 × 20 mL), THF (2 × 15 mL), MeOH (2 × 15 mL) and CH2Cl2 (2 × 15 mL) and dried in vacuo. To a flask containing the suspension of the swollen resin 3 in THF (20 mL) was added 30% H2O2 aq (1.0 mL), and the mixture was stirred for 1 hour at 0 ˚C, followed by 20 min at r.t. After the reaction, the mixture was filtered, and the resin was washed with CH2Cl2 (2 × 20 mL). The filtrate was washed with H2O (2 × 10 mL), dried over MgSO4, and evaporated to dryness in vacuo.
1-Benzyl-2-phenyl-4-quinolone (4a) ¹H NMR (500 MHz, CDCl3): δ = 8.53 (1 H, d, J = 7.8 Hz), 7.56 (1 H, m), 7.45-7.26 (10 H, m), 6.98 (2 H, d, J = 7.3 Hz), 6.56 (1 H, s), 5.33 (2 H, s). ¹³C NMR (125 MHz, CDCl3): δ = 176.81, 155.64, 140.94, 135.98, 135.21, 132.57, 129.74, 128.98, 128.64, 128.01, 127.64, 126.65, 126.49, 125.34, 125.22, 124.09, 117.30, 112.59, 52.36. IR (KBr): νmax = 1608, 1486, 763 cm-¹. HRMS: m/z calcd for C22H18NO [M + H]+: 312.1388; found: 312.1385.

18

General Procedure for the Preparation of 2-Phenyl-2,3-dihydroquinolin-4 (1 H )-one (9)
An oven-dried schlenk tube was charged with a suspension of the swollen resin 7 (0.5 g) in dry toluene (10 mL) under nitrogen atmosphere, and tributyltin hydride (0.291 g, 1.0 mmol) or allyltributylstannane (0.331 g, 1.0 mmol) and 2,2′-azobisisobutyronitrile (AIBN, 0.082 g, 0.5 mmol) were added after which the reaction mixture was heated to 90 ˚C for 2 hours. After cooling, the suspension was poured into a fritted funnel, and the resin was washed with CH2Cl2 (2 × 10 mL). The filtrate was then concentrated and 10% HCl (5 mL) was added, and the resulting solution was washed with hexanes (3 × 10 mL). The aqueous phase was then neutralized with 10% NaOH and extracted with Et2O (2 × 10 mL). The combined organic layers were washed with brine (10 mL), dried over MgSO4, and concentrated to afford the product 9.
1-Acetyl-2-phenyl-2,3-dihydroquinolin-4 (1 H )-one (9a) ¹H NMR (400 MHz, CDCl3): δ = 2.43 (3 H, s), 3.22-3.28 (1 H, m), 3.35-3.40 (1 H, m), 6.47 (1 H, br), 7.15-7.22 (7 H, m), 7.44-7.48 (1 H, m), 7.93 (1 H, d, J = 7.6 Hz). ¹³C NMR (100 MHz, CDCl3): δ = 193.1, 170.0, 141.7, 137.9, 134.3, 128.5, 127.5, 127.2, 126.7, 126.0, 125.4, 125.0, 54.6, 42.5, 23.3. IR (film): νmax = 1693, 1682, 1663, 1601, 1461, 694 cm-¹. HRMS: m/z calcd for C17H15NO2: 265.1103; found: 265.1100.