Download PDF
Synthesis 2003(10): 1586-1590
DOI: 10.1055/s-2003-40516
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Convenient and Improved Halogenation of 3,5-Diarylisoxazoles Using N-Halosuccinimides

Ruth Ann Day, Jacqueline A. Blake, Chad E. Stephens*
Center for Biotechnology and Drug Design, Department of Chemistry, Georgia State University, Atlanta, GA 30303
Fax: 404-651-1416; e-Mail: checes@panther.gsu.edu;
Further Information

Publication History

Received 4 April 2003
Publication Date:
08 July 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

The convenient C-4 halogenation of 3,5-diarylisoxazoles using N-halosuccinimides (NBS, NCS, or NIS) in acetic acid is described. A strong acid catalyst was required for efficient halogenation of some isoxazoles depending on the substituent on the 5-phenyl ring. Finally, the 4-iodoisoxazoles were found to undergo a novel proto-deiodination upon heating in the presence of H2SO4.

Key words

isoxazoles - halogenation - N-halosuccinimides - iodo cleavage - solvent effects

    References

  • 1 Grunanger P. Paola V.-F. Isoxazoles Part 1   Wiley; New York: 1991. 
    Google Scholar
  • 2 Gershman RE. DeSombre ER. Hanson RN. Hughes A. Abstracts of Papers 224th ACS National Meeting   ACS; Washington DC: 2002.  p.MEDI-385  
    Google Scholar
  • 3 Parmar VS. Sharma NK. Husain M. Watterson AC. Kumar J. Samuelson LA. Cholli AL. Prasad AK. Kumar A. Malhotra S. Kumar N. Jha A. Singh A. Singh I. Himanshu Vats A. Shakil NA. Trikha S. Mukherjee S. Sharma SK. Singh SK. Kumar A. Jha HN. Olsen CE. Stove CP. Bracke ME. Mareel MM. Bioorg. Med. Chem.  2003,  11:  913 
    Google Scholar
  • 4 Heda PB. Ghiya BJ. Asian J. Chem.  1999,  11:  384 
    Google Scholar
  • 5 Gallardo H. Zucca C. Da Silva L. Mol. Crystals Liq. Crystals  2002,  373:  181 
    Google Scholar
  • 6 Khatyr A. Maas H. Calzaferri G. J. Org. Chem.  2002,  67:  6705 
    Google Scholar
  • 7a Brancale A. McGuigan C. Graciela A. Snoeck R. De Clercq E. Balzarini J. Bioorg. Med. Chem. Lett.  2000,  10:  1215 
    CrossrefGoogle Scholar
  • 7b Leeson PD. Baker R. Carling RW. Curtis NR. Moore KW. Williams BJ. Foster AC. Donald AE. Kemp JA. Marshall GR. J. Med. Chem.  1991,  34:  1243 
    CrossrefGoogle Scholar
  • 8 Chan MF. Raju B. Kois A. Castillo RS. Verner EJ. Wu C. Hwang E. Okun I. Stavros F. Balaji VN. Bioorg. Med. Chem. Lett.  1996,  6:  2393 
    CrossrefGoogle Scholar
  • 9a Calle M. Cuadrado P. Gonzalez-Nogal AM. Valero R. Synthesis  2001,  1949 
    CrossrefGoogle Scholar
  • 9b Kromann H. Slok FA. Johansen TN. Krogsgaard-Larsen P. Tetrahedron  2001,  57:  2195 
    CrossrefGoogle Scholar
  • 9c Labadie SS. Synth. Commun.  1994,  25:  709 
    CrossrefGoogle Scholar
  • 9d Cogoli A. Grunanger P. J. Organomet. Chem.  1967,  9:  19 
    CrossrefGoogle Scholar
  • 10 Sokolov SD. Kochetkov NK. Dokl. Akad. Nauk   1964,  156:  1391 
    Google Scholar
  • 11 Sokolov SD. Yudintseva IM. Zh. Org. Khim.  1971,  7:  1765 
    Google Scholar
  • 12 Kochetkov NK. Sokolov SD. Vagurtova NM. Zh. Obshch. Khim.  1961,  31:  2326 
    Google Scholar
  • 13 Kromann H. Slok FA. Johansen TN. Krogsgaard-Larsen P. Tetrahedron  2001,  57:  2195 
    CrossrefGoogle Scholar
  • 14 Gaudiano G. Ricca A. Merlini L. Gazz. Chim. Ital.  1959,  89:  2466 
    Google Scholar
  • 15a Carreno MC. Ruano JLG. Sanz G. Toledo MA. Urbano A. Tetrahedron Lett.  1996,  37:  4081 
    Google Scholar
  • 15b Oberhauser T. J. Org. Chem.  1997,  62:  4504 
    Google Scholar
  • 16 Brown WD. Gouliaev AH. Synthesis  2002,  83 
    Article in Thieme ConnectGoogle Scholar
  • 17 Castanet A.-S. Colobert F. Broutin P.-E. Tetrahedron Lett.  2002,  43:  5047 
    CrossrefGoogle Scholar
  • 18 Sakakibara T. Kume T. Hase T. Chem. Express  1989,  4:  85 
    Google Scholar
  • 19 Comprehensive Heterocyclic Chemistry II   Vol. 3:  Katritzky AR. Rees CW. Scriven EFV. Elsevier Science; New York: 1996.  p.237 
    Google Scholar
  • 20 Chrisope DR. Keel RA. Baumstark AL. Boykin DW. J. Heterocycl. Chem.  1981,  18:  795 
    Google Scholar
  • 21 Felding J. Kristensen J. Bjerregaard T. Sander L. Vedso P. Begtrup M. J. Org. Chem.  1999,  64:  4196 
    CrossrefGoogle Scholar
  • 22 Chen EM. Keefer RM. Andrews LJ. J. Am. Chem. Soc.  1967,  89:  428 
    CrossrefGoogle Scholar
  • 24a Doak KW. Corwin AH. J. Am. Chem. Soc.  1949,  71:  159 
    Google Scholar
  • 24b Choguill HS. Ridd JH. J. Chem. Soc.  1961,  822 
    Google Scholar
  • 25 Choi HY. Chi DY. J. Am. Chem. Soc.  2001,  123:  9202 
    CrossrefPubMedGoogle Scholar
  • 26 Grimmett MR. In Imidazole and Benzimidazole Synthesis   Academic Press; San Diego CA: 1997.  p.213 
    Google Scholar
  • 27 Baumstark AL. Chrisope DR. Keel RA. Boykin DW. J. Heterocycl. Chem.  1980,  17:  1719 
    Google Scholar
23

A volatile pink color developed during the deiodinations which is presumed to be iodine acetate.