Download PDF
Synlett 2018; 29(14): 1897-1901
DOI: 10.1055/s-0037-1609579
letter
© Georg Thieme Verlag Stuttgart · New York

Improved One-Pot, Four-Component Strategy to Access ­Functionalized Dihydropyridines by Using 4-(N,N-Dimethylamino)pyridine as a Catalyst

Rathinam Ramesh
a   Department of Chemistry, Periyar University, Periyar Palkalai Nagar, Salem-636011, Tamil Nadu, India   Email: lalitha253@periyaruniversity.ac.in
,
Mani Arivazhagan
a   Department of Chemistry, Periyar University, Periyar Palkalai Nagar, Salem-636011, Tamil Nadu, India   Email: lalitha253@periyaruniversity.ac.in
,
Jan Grzegorz Malecki
b   Department of Crystallography, University of Silesia, Szkolna 9, 40-007 Katowice, Poland
,
Appaswami Lalitha*
a   Department of Chemistry, Periyar University, Periyar Palkalai Nagar, Salem-636011, Tamil Nadu, India   Email: lalitha253@periyaruniversity.ac.in
› Author AffiliationsR.R. thanks the Department of Science and Technology, New Delhi, ­India (Grant No: DST/INSPIRE Fellowship/2012/690) for financial support.
Further Information

Publication History

Received: 18 April 2018

Accepted after revision: 15 June 2018

Publication Date:
20 July 2018 (online)

    Permissions and Reprints All articles of this category


Abstract

A convenient strategy has been developed for the synthesis of structurally diverse novel 1,4-dihydropyridine frameworks bearing a 3-nitrophenyl moiety through a one-pot, four-component reaction with 4-(N,N-dimethylamino)pyridine as a catalyst at room temperature. This tandem process proceeds more effectively than previous catalytic processes.

Key words

dimethylaminopyridine - nitrophenyldihydropyridines - multi­component reactions - nitriles - amines - organocatalysis

Supporting Information

 

  • References and Notes

    • 1a Tang S. Si Y.-Y. Wang Z.-P. Mei K.-R. Chen X. Cheng J.-Y. Zheng J.-S. Liu L. Angew. Chem. Int. Ed. 2015; 54: 5713
      CrossrefPubMed
    • 1b Yatabe T. Jin X. Yamaguchi K. Mizuno N. Angew. Chem. Int. Ed. 2015; 54: 13302
      CrossrefPubMed
    • 1c Deng Y. Gong W. He J. Yu J.-Q. Angew. Chem. Int. Ed. 2014; 53: 6692
      CrossrefPubMed
    • 1d Yoshida M. Mizuguchi T. Namba K. Angew. Chem. Int. Ed. 2014; 53: 14550
      CrossrefPubMed
    • 2a Singh RP. Verma RD. Meshri DT. Shreeve JM. Angew. Chem. Int. Ed. 2006; 45: 3584
      CrossrefPubMed
    • 2b Winkler M. Houk KN. J. Am. Chem. Soc. 2007; 129: 1805
      CrossrefPubMed
  • 3 Triggle DJ. Langs DD. Janis RA. Med. Res. Rev. 1989; 9: 123
    CrossrefPubMed
  • 4 Mason RP. Mak IT. Trumbore MW. Mason PE. Am. J. Cardiol. 1999; 84: 16
  • 5 Aruoma O. Smith C. Cecchini R. Evans P. Halliwell B. Biochem. Pharmacol. 1991; 42: 735
    CrossrefPubMed
  • 6 Kawase M. Shah A. Gaveriya H. Motohashi N. Sakagami H. Varga AJ. Bioorg. Med. Chem. 2002; 10: 1051
    CrossrefPubMed
  • 7 Zamponi GW. Stotz SC. Staples RJ. Andro TM. Nelson JK. Hulubei V. Blumenfeld A. Natale NR. J. Med. Chem. 2003; 46: 87
    CrossrefPubMed
    • 8a Kharkar PS. Desai B. Gaveria H. Varu B. Loriya R. Naliapara Y. Shah A. Kulkarni VM. J. Med. Chem. 2002; 45: 4858
      CrossrefPubMed
    • 8b McCormack JG. Westergaard N. Kristiansen M. Brand CL. Lau J. Curr. Pharm. Des. 2001; 7: 1457
    • 9a Guarna A. Belle C. Machetti F. Occhiato EG. Payne AH. J. Med. Chem. 1997; 40: 1112
      CrossrefPubMed
    • 9b Li Q. Mitscher LA. Shen LL. Med. Res. Rev. 2000; 20: 231
      CrossrefPubMed
    • 9c Stončius S. Orentas E. Butkus E. Öhrström L. Wendt OF. Wärnmark KW. J. Am. Chem. Soc. 2006; 128: 8272
      CrossrefPubMed
    • 9d Mohler ML. Bohl CE. Jones A. Coss CC. Narayanan R. He Y. Hwang DJ. Dalton JT. Miller DD. J. Med. Chem. 2009; 52: 3597
      CrossrefPubMed
    • 10a Simal C. Lebl T. Slawin AM. Z. Smith AD. Angew. Chem. 2012; 124: 3713
      Crossref
    • 10b Jessen HJ. Schumacher A. Shaw T. Pfaltz A. Gademann K. Angew. Chem. Int. Ed. 2011; 50: 4222
      CrossrefPubMed
    • 10c Jiang J. Qing J. Gong L.-Z. Chem. Eur. J. 2009; 15: 7031
      CrossrefPubMed
    • 11a Klusa V. Drugs Future 1995; 20: 135
      Crossref
    • 11b Boer R. Gekeler V. Drugs Future 1995; 20: 499
  • 12 Rotstein BH. Zaretsky S. Rai V. Yudin AK. Chem. Rev. 2014; 114: 8323
    CrossrefPubMed
  • 13 Cioc RC. Ruijter E. Orru RV. A. Green Chem. 2014; 16: 2958
    Crossref
  • 14 Langer P. Chem. Eur. J. 2001; 7: 3858
    CrossrefPubMed
  • 15 Langer P. Synthesis 2002; 2002: 441
    Article in Thieme Connect
  • 16 Khan AT. Lal M. Ali S. Khan M. Tetrahedron Lett. 2011; 52: 5327
    Crossref
  • 17 Xu S. Held I. Kempf B. Mayr H. Steglich W. Zipse H. Chem. Eur. J. 2005; 11: 4751
    CrossrefPubMed
  • 18 Octavio R. de Souza MA. Vasconcellos ML. A. A. Synth. Commun. 2003; 33: 1383
    Crossref
  • 19 Misra M. Pandey S. Pandey VP. Pandey J. Tripathi R. Tripathi RP. Bioorg. Med. Chem. 2009; 17: 625
    CrossrefPubMed
  • 20 Ramesh R. Lalitha A. RSC Adv. 2015; 5: 51188
    Crossref
  • 21 Ramesh R. Lalitha A. Res. Chem. Intermed. 2015; 41: 8009
    Crossref
  • 22 Ramesh R. Maheswari S. Murugesan S. Sandhiya R. Lalitha A. Res. Chem. Intermed. 2015; 41: 8233
    Crossref
  • 23 Ramesh R. Vadivel P. Maheswari S. Lalitha A. Res. Chem. Intermed. 2016; 42: 7625
    Crossref
  • 24 Ramesh R. Lalitha A. ChemistrySelect 2016; 1: 2085
    Crossref
  • 25 Ramesh R. Nagasundaram N. Meignanasundar D. Lalitha A. Res. Chem. Intermed. 2017; 43: 1767
    Crossref
  • 26 Ramesh R. Sankar G. Malecki JG. Lalitha A. J. Iran. Chem. Soc. 2018; 15: 1
    Crossref
  • 27 Ramesh R. Kalisamy P. Malecki JG. Lalitha A. Synlett 2018; 29: 203
    Article in Thieme Connect
  • 28 Ramesh R. Maheswari S. Arivazhagan M. Malecki JG. Lalitha A. Tetrahedron Lett. 2017; 58: 3905
    Crossref
  • 29 Ramesh R. Meignanasundar D. Lalitha A. ChemistrySelect 2017; 2: 10210
    Crossref
  • 30 Ramesh R., Jayamathi J., Karthika C., Malecki J. G., Lalitha A.; Polycyclic Aromat. Compd.; DOI:10.1080/10406638.2018. 1454968.
  • 31 Dimethyl 6-Amino-5-cyano-4-(3-nitrophenyl)-1-phenyl-1,4-dihydropyridine-2,3-dicarboxylate (5l); Typical Procedure 3-Nitrobenzaldehyde (2.5 mmol), malononitrile (2.5 mmol), and DMAP (10 mol%) were dissolved in EtOH (5 mL), and the mixture was stirred at r.t. for 2 min. A solution of DMAD (2.5 mmol) and aniline (2.5 mmol) in EtOH (5 mL) was added slowly, and the resulting mixture was stirred at r.t. for 20 min. When the reaction was complete (TLC; EtOAc–hexane), the solid that formed was collected by filtration, dried, and crystallized from EtOH.
  • 32 Dimethyl 6-Amino-5-cyano-1-(4-methoxyphenyl)-4-(3-nitrophenyl)-1,4-dihydropyridine-2,3-dicarboxylate (5a) Yellow crystals; yield: 1118 mg (96%); mp 194–196 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 3.40 (s, 3 H, COOCH3), 3.55 (s, 3 H, COOCH3), 3.83 (s, 3 H, OCH3), 4.71 (s, 1 H, CH), 5.81 (s, 2 H, NH2), 7.05 (d, J = 8.0 Hz, 2 H, ArH), 7.25 (d, J = 8.0 Hz, 2 H, ArH), 7.79 (d, J = 8.0 Hz, 2 H, ArH), 8.16 (d, J = 8.0 Hz, 2 H, ArH). 13C NMR (100 MHz, DMSO-d6 ): δ = 38.2, 52.0, 52.4, 55.4, 58.4, 103.3, 114.7, 120.6, 121.0, 122.1, 127.2, 130.5, 131.3, 133.5, 142.8, 147.6, 148.0, 151.4, 160.0, 162.7, 164.7.
  • 33 CCDC 1561544 contains the supplementary crystallographic data for compound 5f. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
  • 34 Ghasemzadeh MA. Basir MH. A. Acta Chim. Slov. 2016; 63: 627
    PubMed
  • 35 Kiruthika SE. Perumal PT. RSC Adv. 2014; 4: 3758
    Crossref
  • 36 Sun J. Xia E.-Y. Wu Q. Yan C.-G. Org. Lett. 2010; 12: 3678
    CrossrefPubMed
  • 37 Hadjebia M. Hashtroudib MS. Bijanzadeh HR. Balalaie S. Helv. Chim. Acta 2011; 94: 382
    Crossref
  • 38 Pal S. Choudhury LH. Parvin T. Synth. Commun. 2013; 43: 986
    Crossref
  • 39 Pal S. Singh V. Das P. Choudhury LH. Bioorg. Chem. 2013; 48: 8
    CrossrefPubMed
  • 40 Chen H.-S. Guo R.-Y. Monatsh. Chem. 2015; 146: 1355
    Crossref
  • 41 Ramesh R. Madhesh R. Malecki JG. Lalitha A. ChemistrySelect 2016; 1: 5196
    Crossref
  • 42 Pal S. Khan N. Choudhury LH. J. Heterocycl. Chem. 2014; 51: E156
    Crossref
  • 43 Tabassum S. Govindaraju S. Khan R.-u.-R. Pasha MA. RSC Adv. 2016; 6: 29802
    Crossref