Download PDF
Synthesis 2003(5): 0691-0694
DOI: 10.1055/s-2003-38071
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Studies on Isocyanides and Related Compounds; A Facile Synthesis of Functionalized 3(2H)-Pyridazinones via Ugi Four-Component Condensation

Carlos F. Marcosa, Stefano Marcaccini*b, Roberto Pepinob, Cecilia Poloa, Tomás Torrobac
a Departamento de Química Orgánica, Facultad de Veterinaria, Universidad de Extremadura, 10071 Cáceres, Spain
b Dipartimento di Chimica Organica ‘Ugo Schiff’, Università di Firenze, via della Lastruccia 13, 50019 Sesto Fiorentino (FI), Italy
e-Mail: stefano.marcaccini@unifi.it;
c Departamento de Química, Facultad de Ciencias, Universidad de Burgos, 09001 Burgos, Spain
Further Information

Publication History

Received 14 January 2002
Publication Date:
21 March 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

The reaction between diarylglyoxal monohydrazones 1, isocyanides 2, aldehydes 3a-c, and methylene active acids 4 afforded a series of 3(2H)-pyridazinones 5 in a very simple manner. The intermediate Ugi four-component condensation products were never observed because of their tendency to cyclize. When the less reactive cyclopentanone (3d) is used instead of aldehydes 3a-c, satisfactory yields of 3(2H)-pyridazinones 7 were obtained by employing the pre-formed azine 8.

Key words

heterocycles - hydrazones - Knoevenagel condensation - isocyanides - condensation - Ugi reaction

    References

  • 1a Mátyus P. J. Heterocycl. Chem.  1988,  35:  1075 
    Google Scholar
  • 1b Coates WJ. In Comprehensive Heterocyclic Chemistry   Vol. 6:  Katritzky AR. Rees CW. Pergamon Press; Oxford: 1996.  p.1 
    Google Scholar
  • 1c Dal Piaz V. Ciciani G. Giovannoni MP. Acta Chim. Slov.  1994,  41:  189 
    Google Scholar
  • 2a Marcaccini S. Torroba T. Org. Prep. Proc. Int.  1993,  25:  141 
    Google Scholar
  • 2b Bossio R. Marcaccini S. Papaleo S. Pepino R. J. Heterocycl. Chem.  1994,  31:  397 
    Google Scholar
  • 2c Bossio R. Marcaccini S. Pepino R. Synthesis  1994,  765 
    Google Scholar
  • 2d Bossio R. Marcaccini S. Pepino R. Paoli P. J. Heterocycl. Chem.  1994,  31:  729 
    Google Scholar
  • 2e Bossio R. Marcaccini S. Pepino R. J. Heterocycl. Chem.  1995,  32:  1115 
    Google Scholar
  • 2f Bossio R. Marcaccini S. Pepino R. Torroba T. J. Chem. Soc., Perkin Trans. 1  1996,  229 
    Google Scholar
  • 2g Bossio R. Marcaccini S. Pepino R. Torroba T. J. Org. Chem.  1996,  61:  2202 
    Google Scholar
  • 2h Bossio R. Marcos CF. Marcaccini S. Pepino R. Tetrahedron Lett.  1997,  38:  2519 
    Google Scholar
  • 2i Bossio R. Marcos CF. Marcaccini S. Pepino R. Heterocycles  1997,  45:  1589 
    Google Scholar
  • 2j Bossio R. Marcos CF. Marcaccini S. Pepino R. Synthesis  1997,  1389 
    Google Scholar
  • 2k Bossio R. Marcaccini S. Pepino R. Torroba T. Heterocycles  1999,  50:  463 
    Google Scholar
  • 2l Bossio R. Marcaccini S. Pepino R. Torroba T. Synthesis  1993,  783 
    Google Scholar
  • 2m Bossio R. Marcaccini S. Pepino R. Liebigs Ann. Chem.  1994,  527 
    Google Scholar
  • 3a King JA. McMillan FH. J. Am. Chem. Soc.  1952,  74:  3222 
    Google Scholar
  • 3b Buchman R. Scozzie JA. Ariyan ZS. Heilman RD. Rippin DJ. Pyne WJ. Powers LJ. Matthews RJ. J. Med. Chem.  1980,  23:  1398 
    Google Scholar
  • 3c Pitarch L. Coronas R. Mallol J. Eur. J. Med. Chem. Chim. Ther.  1974,  9:  644 
    Google Scholar
  • 4 Curtius T. Kastner R. J. Prakt. Chem.  1911,  83:  215 
    Google Scholar
  • 5 van Alpher J. Recl. Trav. Chim. Pays-Bas  1929,  48:  1199 
    Google Scholar
  • 6 Gokel GW. Widera RP. Weber WP. Org. Synth.  1976,  55:  96 
    Google Scholar
  • 7 Ugi I. Meyr R. Org. Synth.  1961,  41:  101 
    Google Scholar
  • 8 Gabriel S. Ber. Dtsch. Chem. Ges.  1881,  14:  833 
    Google Scholar
  • 9 Strube RE. Org. Synth., Coll. Vol. 4   Wiley; London: 1963.  p.417 
    Google Scholar
10

The singlet signals of the methyl groups and the multiplet signal of H-1 of the cyclohexane ring are overlapped.

11

After repeated recrystallizations we were unable to obtain satisfactory analytical data for this compound.