Download PDF
Synthesis 2011(24): 4011-4016  
DOI: 10.1055/s-0031-1289591
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Inexpensive Phthalic Acid Promoted Domino Povarov Reaction between Anilines and N-Vinylamides: An Efficient Preparation of Privileged 4-Substituted 2-Methyl-1,2,3,4-tetrahydroquinoline Scaffolds

Vladimir V. Kouznetsov*a, Diego R. Merchan Arenasa, César J. Ortiz Areniza, Carlos M. Meléndez Gómezb
a Laboratorio de Química Orgánica y Biomolecular, Escuela de Química, Universidad Industrial de Santander, A.A. 678, Bucaramanga, Colombia
Fax: +57(76)349069; e-Mail: kouznet@uis.edu.co; e-Mail: vkuznechnik@gmail.com ;
b Grupo de Investigación en Compuestos Heterocíclicos, Departamento de Química, Facultad de Ciencias, Universidad del Atlántico, Barranquilla, Colombia
Further Information

Publication History

Received 18 August 2011
Publication Date:
08 November 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

An efficient and simple synthesis of new 2-methyl-1,2,3,4-tetrahydroquinolines with C4 amide fragments based on the phthalic acid promoted domino Povarov reaction between anilines and N-vinylamides has been developed.

Key words

2-methyl-1,2,3,4-tetrahydroquinolines - acid-catalyzed Povarov reaction - domino process - phthalic acid - N-vinyl­amides

    References

  • 1 Welsch ME. Snyder SA. Stockwell BR. Curr. Opin. Chem. Biol.  2010,  14:  347 
    Google Scholar
  • 2 Arya P. Joseph R. Gan Z. Rakic B. Chem. Biol.  2005,  12:  163 
    Google Scholar
  • 3 Katritzky AR. Rachwal S. Rachwal B. Tetrahedron  1996,  52:  15031 
    Google Scholar
  • 4 Kouznetsov V. Palma A. Ewert C. Varlamov A.
    J. Heterocycl. Chem.  1998,  35:  761 
    Google Scholar
  • 5 Arya P. Durieux P. Chen Z.-X. Joseph R. Leek DM. J. Comb. Chem.  2004,  6:  54 
    Google Scholar
  • 6 Arya P. Couve-Bonnaire S. Durieux P. Laforce O. Kumar R. Leek DM. J. Comb. Chem.  2004,  6:  735 
    Google Scholar
  • 7 Povarov LS. Russ. Chem. Rev. (Engl. Transl.)  1967,  36:  656 
    Google Scholar
  • 8 Kouznetsov VV. Tetrahedron  2009,  65:  2721 
    Google Scholar
  • 9 Souza M. Pais K. Kaiser C. Peralta M. Ferreira M. Lourenço M. Bioorg. Med. Chem.  2009,  17:  1474 
    Google Scholar
  • 10 Rano T. Sieber-McMaster E. Pelton P. Yang M. Demarest K. Gee-Hong K. Bioorg. Med. Chem. Lett.  2009,  19:  2456 
    Google Scholar
  • 11 Weber L. Drug Discovery Today  2002,  7:  143 
    Google Scholar
  • 12 Biggs-Houck JE. Younai A. Shaw JT. Curr. Opin. Chem. Biol.  2010,  14:  371 
    Google Scholar
  • 13 Povarov LS. Mikhailov BM. Izv. Acad. Nauk USSR, Ser. Khim.  1964,  2221 
    Google Scholar
  • 14 Di Salvo A. Spanedda MV. Ourévitch M. Crousse B. Bonnet-Delpon D. Synthesis  2003,  2231 
    Google Scholar
  • 15 Sridharan V. Avendaño C. Menéndez JC. Tetrahedron  2007,  63:  673 
    Google Scholar
  • Reports on CAN-catalyzed synthesis of 1,2,3,4-tetrahydro-quinolines from aldimines and enamides, see:
  • 16a Han B. Jia X.-D. Jin X.-L. Zhou Y.-L. Yang L. Liu Z.-L. Yu W. Tetrahedron Lett.  2006,  47:  3545 
    Google Scholar
  • 16b Savitha G. Perumal PT. Tetrahedron Lett.  2006,  47:  3589 
    Google Scholar
  • 17a Batey RA. Simoncic PD. Lin D. Smyj RP. Lough AJ. Chem. Commun.  1999,  651 
    Google Scholar
  • 17b Batey RA. Powell DA. Acton A. Lough AJ. Tetrahedron Lett.  2001,  42:  7935 
    Google Scholar
  • 17c Powell DA. Batey RA. Org. Lett.  2002,  4:  2913 
    Google Scholar
  • Recent report on acid-catalyzed synthesis of 4-amido-2-methyl-1,2,3,4-tetrahydroquinolines from anilines and enamides, see:
  • 18a Srinivasa A. Mahadevan K. Hulika V. Synth. Commun.  2009,  39:  33 
    Google Scholar
  • 18b Kavitha C. Hosamani K. Harisha R. Can. J. Chem.  2010,  88:  443 
    Google Scholar
  • 18c Achara K. Hosamania K. Seetharamareddy H. Synth. Commun.  2011,  41:  33 
    Google Scholar
  • 18d Varma P. Srinivasa A. Mahadevan K. Synth. Commun.  2011,  41:  2186 
    Google Scholar
  • 18e Jia X. Ren Y. Huo C. Wang W.-J. Chen X.-N. Xu X.-L. Wang X. Tetrahedron Lett.  2010,  51:  6779 
    Google Scholar
  • 19a Astudillo SL. Gutiérrez CM. Gaete H. Kouznetsov VV. Meléndez GCM. Palenzula A. Vallejos G. Lett. Org. Chem.  2009,  6:  208 
    Google Scholar
  • 19b Kouznetsov VV. Romero Bohórquez AR. Astudillo SL. Synthesis  2009,  4219 
    Google Scholar
  • 19c Romero Bohórquez AR. Kouznetsov VV. Synlett  2010,  970 
    Google Scholar
  • 20 Preparation of SSA, see: Chen W.-Y. Lu J. Synlett  2005,  2293 
    Google Scholar
21

After the treatment of the reaction mixture with NaHCO3 soln, the aqueous phase was treated with sat. HCl soln to recover the phthalic acid. The precipitated acid was filtered and washed with Et2O (3 × 10 mL). Finally, the phthalic acid was reused without the loss of the catalytic activity promoter giving the same results in the model reaction.