Download PDF
Synthesis 2003(10): 1553-1558
DOI: 10.1055/s-2003-40525
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Studies on Isocyanides and Related Compounds: A Facile Synthesis of 1,6-Dihydro-6-oxopyrazine-2-carboxylic Acid Derivatives via Ugi Four-Component Condensation

Cristina Faggia, María García-Valverdeb, Stefano Marcaccini*c, Roberto Pepinoc, Ma. Cruz Pozoc
a CRIST, Centro Interdipartimentale di Cristallografia, Università di Firenze, via della Lastruccia 3, 50019 Sesto Fiorentino (FI), Italy
b Departamento de Química, Facultad de Ciencias, Universidad de Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, Spain
c Dipartimento di Chimica Organica ‘Ugo Schiff’, Università di Firenze, via della Lastruccia 13, 50019 Sesto Fiorentino (FI), Italy
e-Mail: stefano.marcaccini@unifi.it;
Further Information

Publication History

Received 8 March 2003
Publication Date:
08 July 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

The Ugi four-component condensation (U-4CC) between arylglyoxals 7, amines 6, benzoylformic acid (4) and isocyanides 5 afforded the expected products 8 which were cyclized in a 5+1 fashion with ammonium acetate to give 1,N-disubstituted 4-aryl-1,6-dihydro-6-oxo-5-phenylpyrazine-2-carboxamides 9 in good yields. Evidence for the assigned structures 9 was provided by 13C NMR spectra and X-ray analysis of 9a.

Key words

Ugi reaction - cyclizations - heterocycles - isocyanides - pyrazine ring synthesis

    References

  • 1 Barlin GB. In The Pyrazines   Weissberger A. Taylor EC. Wiley-Interscience; New York: 1982.  p.49-52  
    Google Scholar
  • Reviews:
  • 2a Marcaccini S. Torroba T. Org. Prep. Proc. Int.  1993,  25:  141 
    CrossrefGoogle Scholar
  • 2b Bossio R. Marcaccini S. Pepino R. Synthesis  1994,  765 
    CrossrefGoogle Scholar
  • 2c Bossio R. Marcaccini S. Pepino R. Tetrahedron Lett.  1995,  36:  2325 
    CrossrefGoogle Scholar
  • 2d Bossio R. Marcaccini S. Pepino R. Torroba T. J. Org. Chem.  1996,  61:  2202 
    CrossrefGoogle Scholar
  • 2e Bossio R. Marcaccini S. Pepino R. Torroba T. J. Chem. Soc., Perkin Trans. 1  1996,  229 
    CrossrefGoogle Scholar
  • 2f Bossio R. Fernández Marcos C. Marcaccini S. Pepino R. Tetrahedron Lett.  1997,  38:  2519 
    CrossrefGoogle Scholar
  • 2g Bossio R. Fernández Marcos C. Marcaccini S. Pepino R. Synthesis  1997,  1389 
    CrossrefGoogle Scholar
  • 2h Bossio R. Marcaccini S. Pepino R. Torroba T. Heterocycles  1999,  50:  463 
    CrossrefGoogle Scholar
  • 2i Marcaccini S. Pepino R. Polo C. Pozo MC. Synthesis  2001,  85 
    CrossrefGoogle Scholar
  • 2j Marcaccini S. Pepino R. Pozo MC. Tetrahedron Lett.  2001,  42:  2727 
    CrossrefGoogle Scholar
  • Reviews:
  • 3a Ugi I. Dömling A. Hörl W. Endeavour  1994,  18:  115 
    Google Scholar
  • 3b Armstrong RW. Combs AP. Tempest P. Brown SD. Keating TA. Acc. Chem. Res.  1996,  29:  123 
    Google Scholar
  • 3c Ugi I. Dömling A. Angew. Chem., Int. Ed.  2000,  39:  3168 
    Google Scholar
  • 3d Dömling A. Comb. Chem. High Throughput Screening  1998,  1:  1 
    Google Scholar
  • 3e Bienaymé H. Hulme C. Oddon G. Schmitt P. Chem.-Eur. J.  2000,  6:  3321 
    Google Scholar
  • 4a Janvier P. Bienaymé H. Zhu J. Angew. Chem. Int. Ed.  2002,  41:  4291 
    CrossrefGoogle Scholar
  • 4b Owens TD. Semple JE. Org. Lett.  2001,  3:  3301 
    CrossrefGoogle Scholar
  • 4c Tempest P. Pettus L. Gore V. Hulme C. Tetrahedron Lett.  2003,  44:  1947 
    CrossrefGoogle Scholar
  • 5 Bossio R. Fernández Marcos C. Marcaccini S. Pepino R. Heterocycles  1997,  45:  1589 
    CrossrefGoogle Scholar
  • Arylglyoxals are useful starting products in isocyanide-based multi-component reactions:
  • 6a Beck B. Magnin-Lachaux M. Herdtweck E. Dömling A. Org. Lett.  2001,  3:  2875 
    CrossrefGoogle Scholar
  • 6b Zhang C. Moran EJ. Woiwode TF. Short KM. Mjalli AMM. Tetrahedron Lett.  1996,  37:  751 
    CrossrefGoogle Scholar
  • 6c Sung K. Wu S.-H. Chen P.-I. Tetrahedron  2002,  58:  5599 
    CrossrefGoogle Scholar
  • 7 Gastaldi C. Princivalle E. Gazz. Chim. Ital.  1928,  58:  412 
    Google Scholar
  • 8a Nishio T. Tokunaga N. Kondo M. Omote Y. J. Chem. Soc., Perkin Trans. 1  1988,  2921 
    Google Scholar
  • 8b Devys M. Barbier M. Kollmann A. Bousquet J.-F. Tetrahedron Lett.  1982,  23:  5409 
    Google Scholar
  • 8c Nishio T. J. Heterocycl. Chem.  1998,  35:  655 
    Google Scholar
  • 9 Kong YC. Kim K. J. Heterocycl. Chem.  1999,  36:  911 
    Google Scholar
  • 10 Gokel GW. Widera RP. Weber WP. Org. Synth.  1976,  55:  96 
    Google Scholar
  • 11 Ugi I. Meyr R. Lipinsky M. Bodesheim F. Rosendahl F. Org. Synth., Coll. Vol. 5   Wiley; New York: 1973.  p.300 
    Google Scholar
  • 12 Lipp M. Dallaker F. Köcker IM. Monatsh. Chem.  1959,  90:  48 
    Google Scholar
  • 13 Ugi I. Meyr R. Org. Synth.  1961,  41:  101 
    Google Scholar
  • 14 Riley HA. Gray AR. Org. Synth., Coll. Vol. 2   Wiley; New York: 1948.  p.509 
    Google Scholar
  • 15 Venien F. Brault A. Kerfanto M. C. R. Acad. Sci. Paris. Ser. C  1968,  266:  1650 
    Google Scholar
  • 16 Walker N. Stuart D. Acta Crystallogr., Sect. A  1983,  39:  158 
    Google Scholar
  • 17 Altomare A. Burla MC. Camalli M. Cascarano GL. Giacovazzo C. Guagliardi A. Moliterni AG. Polidori G. Spagna R. J. Appl. Crystallogr.  1999,  32:  115 
    CrossrefGoogle Scholar
  • 18 Sheldrick GM. SHELXL97: Program for Crystal Structure Refinement   University of Göttingen; Germany: 1997. 
    Google Scholar
19

Crystallographic data have been deposited at Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK and are available from there under the deposition number CCDC179438.