Download PDF
Synlett 2011(17): 2577-2579  
DOI: 10.1055/s-0030-1260330
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A General Protocol for the Solvent- and Catalyst-Free Synthesis of 2-Styrylquinolines under Focused Microwave Irradiation

Matteo Staderinia, Nieves Cabezasa, Maria Laura Bolognesib, J. Carlos Menéndez*a
a Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Fax: +34(91)3941822; e-Mail: josecm@farm.ucm.es;
b Dipartimento di Scienze Farmaceutiche, Universitá di Bologna, via Belmeloro 6, 40126 Bologna, Italy
Further Information

Publication History

Received 10 June 2011
Publication Date:
29 September 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

Focused microwave irradiation promoted the very efficient synthesis of 2-styrylquinolines by reaction between quinaldines and benzaldehydes or cinnamaldehydes in the presence of acetic anhydride.

Key words

aldol condensations - heterocycles - quinolines - microwave-assisted synthesis

    References and Notes

  • For reviews of quinoline-related compounds, see:
  • 1a Michael JP. Nat. Prod. Rep.  2008,  25:  166 
    Google Scholar
  • 1b Michael JP. Nat. Prod. Rep.  2007,  24:  223 
    Google Scholar
  • 1c Kouznetsov VV. Vargas Méndez LY. Meléndez Gomez CM. Curr. Org. Chem.  2005,  9:  141 
    Google Scholar
  • 1d Michael JP. Nat. Prod. Rep.  2004,  21:  650 
    Google Scholar
  • 1e Michael JP. Nat. Prod. Rep.  2005,  22:  627 
    Google Scholar
  • 2 Bongarzone S. Bolognesi ML. Curr. Opin. Drug Discovery Dev.  2011,  6:  251 
    Google Scholar
  • For reviews of the potential of integrase inhibitors as anti-HIV agents, see:
  • 3a Makhija MT. Curr. Med. Chem.  2006,  13:  2429 
    Google Scholar
  • 3b Pommier Y. Johnson AA. Marchand C. Nat. Rev. Drug Discovery  2005,  4:  236 
    Google Scholar
  • 3c Andréola ML. De Soultrait VR. Fournier M. Parissi V. Desjobert C. Litvak S. Expert Opin. Ther. Targets  2002,  6:  433 
    Google Scholar
  • 3d d’Angelo J. Mouscadet J.-F. Desmaële D. Zouhiri F. Leh H. Pathol. Biol.  2001,  49:  237 
    Google Scholar
  • 4 Raltegravir, an integrase inhibitor, has recently reached the market as an anti-AIDS agent. For a study of its clinical efficacy, see: Steigbigel RT. Cooper DA. Kumar PN. Eron JE. Schechter M. Markowitz M. Loutfy MR. Lennox JL. Gatell JM. Rockstroh JK. Katlama C. Yeni P. Lazzarin A. Clotet B. Zhao J. Chen J. Ryan DM. Rhodes RR. Killar JA. Gilde LR. Strohmaier KM. Meibohm AR. Miller MD. Hazuda DJ. Nessly ML. DiNubile MJ. Isaacs RD. Nguyen B.-Y. Teppler H. N. Engl. J. Med.  2008,  359:  339 
    CrossrefGoogle Scholar
  • 5a Normand-Bayle M. Bénard C. Zouhiri F. Mouscadet J.-F. Leh H. Thomas C.-M. Mbemba G. Desmaële D. d’Angelo J. Bioorg. Med. Chem. Lett.  2005,  15:  4019 
    Google Scholar
  • 5b Bénard C. Zouhiri F. Normand-Bayle M. Canet M. Desmaële D. Leh H. Mouscadet J.-F. Mbemba G. Thomas C.-M. Bonnenfant S. Le Bret M. d’Angelo J. Bioorg. Med. Chem.  2004,  14:  2473 
    Google Scholar
  • 5c Mousnier A. Leh H. Mouscadet J.-F. Dargemont C. Mol. Pharmacol.  2004,  66:  783 
    Google Scholar
  • 5d Polanski J. Zouhiri F. Jeanson L. Desmaële D. d’Angelo J. Mouscadet J.-F. Gieleciak R. Gasteiger J. Le Bret M. J. Med. Chem.  2002,  45:  4647 
    Google Scholar
  • 5e Yuan H. Parrill AL. Bioorg. Med. Chem.  2002,  10:  4169 
    Google Scholar
  • 5f Oulali M. Labulais C. Leh H. Gill D. Desmaële D. Mekouar K. Zouhiri F. d’Angelo J. Auclair C. Mouscadet J.-F. Le Bret M. J. Med. Chem.  2002,  43:  1949 
    Google Scholar
  • 5g d’Angelo J. Mouscadet J.-F. Desmaele D. Zouhiri F. Leh H. Pathol. Biol.  2001,  49:  237 
    Google Scholar
  • 5h Zouhiri F. Mouscadet J.-F. Mekouar K. Desmaële D. Savouré D. Leh H. Subra F. Le Bret M. Auclair C. d’Angelo J. J. Med. Chem.  2000,  43:  1533 
    Google Scholar
  • 5i Ouali M. Laboulais C. Leh H. Gill D. Desmaele D. Mekouar K. Zouhiri F. d’Angelo J. Auclair C. Mouscadet J.-F. Le Bret M. J. Med. Chem.  2000,  43:  1949 
    Google Scholar
  • 5j Mekouar K. Mouscadet J.-F. Desmaële D. Subra F. Leh H. Savouré D. Auclair C. d’Angelo J. J. Med. Chem.  1998,  41:  2846 
    Google Scholar
  • 6 Bonnenfant S. Thomas CM. Vita C. Subra C. Deprez E. Zouhiri F. Desmaële D. d’Angelo J. Mouscadet J.-F. Leh H. J. Virol.  2004,  78:  5728 
    CrossrefGoogle Scholar
  • 7 Li Q. Min J. Ahn Y.-H. Namm J. Kim EM. Lui R. Kim HY. Ji Y. Wu H. Wisniewski T. Chang Y.-T. ChemBioChem  2007,  8:  1679 
    CrossrefGoogle Scholar
  • 8a Dabiri M. Salehi P. Baghbanzadeh M. Nikcheh MS. Tetrahedron Lett.  2008,  49:  5366 
    Google Scholar
  • 8b Leonard JT. Roy K. Eur. J. Med. Chem.  2008,  43:  81 
    Google Scholar
  • 8c Makhija MT. Curr. Med. Chem.  2006,  13:  2429 
    Google Scholar
  • 8d Bonnenfant S. Thomas C.-M. Vita C. Subra C. Deprez E. Zouhiri F. Desmaele D. d’Angelo J. Mouscadet J.-F. Leh H. J. Virol.  2004,  78:  5728 
    Google Scholar
  • 8e Yuan HB. Parrill AL. Bioorg. Med. Chem.  2002,  10:  4169 
    Google Scholar
  • 9 For a discussion, see: Kappe AO. Angew. Chem. Int. Ed.  2004,  43:  6250 
    CrossrefPubMedGoogle Scholar
  • 10 Musiol R. Podeszwa B. Finster J. Niedbala H. Polansli J. Monatsh. Chem.  2006,  137:  1211 
    CrossrefGoogle Scholar
  • For the preparation of these starting materials, see:
  • 11a Sridharan V. Avendaño C. Menéndez JC. Tetrahedron  2007,  63:  673 
    Google Scholar
  • 11b Fedoryak OD. Dore TM. Org. Lett.  2002,  4:  3419 
    Google Scholar
  • 11c Chen X.-Y. Shi J. Li Y.-M. Wang F.-L. Wu X. Guo Q.-X. Liu L. Org. Lett.  2009,  11:  4426 
    Google Scholar
12

General Experimental Procedure
The suitable quinaldine derivative (1 mmol) and the corresponding aromatic aldehyde (1 equiv) were suspended in Ac2O (0.5 mL) in a pressure-tight microwave tube containing a stirring bar. The reaction mixture was heated under microwave irradiation for 1 h at 130-180 ˚C, with an irradiation power of 200 W, using a CEM Discover SP microwave reactor. The solvent was removed under reduced pressure to give a black residue that was purified by chroma-tography through a silica column using PE-EtOAc (90:10, v/v) as the mobile phase. Characterization data for three representative compounds are given below. For further characterization data, see the Supporting Information.
( E )-2-(4-Fluorostyryl)-6-methoxyquinoline (3h) Pale yellow solid; mp 138-141 ˚C. IR (neat): νmax = 1592.4, 1509.8, 1231.9, 1164.1, 1030.8, 965.4, 856.2, 837.0 cm-¹. ¹H NMR (250 MHz, CDCl3): δ = 3.96 (s, 3 H), 7.08-7.14 (m, 3 H), 7.33 (d, J = 16.6 Hz, 1 H), 7.39 (dd, J = 9.3, 2.8 Hz, 1 H), 7.58-7.65 (m, 4 H), 8.02 (d, J = 8.9 Hz, 1 H), 8.05 (d, J = 8.4 Hz, 1 H). ¹³C NMR (62.9 MHz, CDCl3): δ = 56.0 (CH3), 105.6 (CH), 116.2 (d, J = 21.7 Hz, 2 CH), 119.2 (CH), 122.9 (CH), 128.7 (C), 129.1 (d, J = 8.1 Hz, 2 CH), 130.9 (CH), 132.5 (CH), 133.2 (C), 133.3 (C), 135.7 (CH), 144.6 (C), 153.9 (C), 158.1 (C), 163.21 (d, J = 248.4 Hz, C). Anal. Calcd for C18H14FNO: C, 77.40; H, 5.05; N, 5.01. Found: C, 77.15; H, 5.01; N, 4.77.
( E )-7-Chloro-2-(4-methoxystyryl)quinolone (3j) White solid; mp 149-151 ˚C. IR (neat): νmax = 1604.2, 1511.3, 1408.0, 1250.8, 1177.9, 1032.8, 970.1, 831.8 cm-¹. ¹H NMR (250 MHz, CDCl3): δ = 3.89 (s, 3 H), 6.98 (d, J = 8.7 Hz, 2 H), 7.23 (d, J = 16.1 Hz, 1 H), 7.46 (dd, J = 8.6, 2.1 Hz, 1 H), 7.61-7.75 (m, 5 H), 8.09-8.13 (m, 2 H). ¹³C NMR (62.9 MHz, CDCl3): δ = 55.8 (CH3), 114.7 (2 CH), 120.0 (CH), 125.9 (C), 126.7 (CH), 127.3 (CH), 128.5 (CH), 129.1 (CH), 129.2 (2 CH), 129.5 (C), 135.2 (CH), 135.9 (C), 136.4 (CH), 149.1 (C), 157.7 (C), 160.7 (C). Anal. Calcd for C18H14ClNO: C, 73.10; H, 4.77; N, 4.74. Found: C, 73.19; H, 4.81; N, 4.86.
6-Chloro-2-[(1 E ,3 E )-4-phenylbuta-1,3-dienyl]quinoline (3m) Yellow solid; mp 105-108 ˚C. IR (neat): νmax = 1590.2, 1485.5, 1070.0, 1001.7, 892.3, 825.7, 751.7 cm-¹. ¹H NMR (250 MHz, CDCl3): δ = 6.87-7.15 (m, 3 H), 7.31-7.43 (m, 3 H), 7.52-7.62 (m, 4 H), 7.65 (dd, J = 9.0, 2.3 Hz, 1 H) 7.78 (d, J = 2.3 Hz, 1 H), 8.01 (d, J = 8.9 Hz, 1 H), 8.04 (d, J = 8.5 Hz, 1 H). ¹³C NMR (62.9 MHz, CDCl3): δ = 120.8 (CH), 126.6 (CH), 127.2 (2 CH), 128.2 (C), 128.7 (CH), 128.8 (CH), 129.2 (2 CH), 131.0 (CH), 131.2 (CH), 132.1 (CH), 132.7 (CH), 135.7 (CH), 135.8 (CH), 136.8 (CH), 137.3 (C), 147.1 (C), 156.6 (C). Anal. Calcd for C19H14ClN: C, 78.21; H, 4.84; N, 4.80. Found: C, 78.45; H, 5.01; N, 5.03.