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Synlett 2004(9): 1628-1630  
DOI: 10.1055/s-2004-829060
LETTER
© Georg Thieme Verlag Stuttgart · New York

Preparation of 2-Substituted Benzimidazoles and Related Heterocycles Directly from Activated Alcohols Using TOP Methodology

Cecilia D. Wilfred, Richard J. K. Taylor*
University of York, Heslington, York, UK, YO10 5DD, UK
Fax: +44(1904)434523; e-Mail: rjkt1@york.ac.uk;
Further Information

Publication History

Received 3 March 2004
Publication Date:
01 July 2004 (online)

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Abstract

A one-pot procedure for preparing 2-substituted benzimidazoles directly from activated alcohols in good to excellent yields using a new Tandem Oxidation Process (TOP) is reported. The use of this methodology to prepare 2-substituted benzoxazoles and 2-substituted benzothiazoles is also described.

Key words

2-substituted benzimidazoles - 2-substituted benzoxazoles - 2-substituted benzothiazoles - tandem oxidation procedure - one-pot

    References

  • For reviews see:
  • 1a Grimmett MR. In Comprehensive Heterocyclic Chemistry II   Vol. 3:  Katrizky AR. Rees CW. Scriven EFV. Elsevier Science Ltd.; Oxford: 1996.  Chap. 3.02.
    Google Scholar
  • 1b Grimmett MR. Imidazole and Benzimidazole Synthesis   Academic Press; San Diego: 1997. 
    Google Scholar
  • 2 Figge A. Altenbach HJ. Brauer DJ. Tielmann P. Tetrahedron: Asymmetry  2002,  13:  137 
    CrossrefGoogle Scholar
  • 3 Alcalde E. Dinares I. Perez-Garcia L. Roca T. Synthesis  1992,  395 
    Article in Thieme ConnectGoogle Scholar
  • 4 Matsushita H. Lee SY. Joung M. Clapham B. Janda KD. Tetrahedron Lett.  2004,  45:  313 
    CrossrefGoogle Scholar
  • 5a Göker H. Kus C. Boykin DW. Yildiz S. Altanar N. Bioorg. Med. Chem.  2002,  10:  2589 
    Google Scholar
  • 5b Kus C. Boykin DW. Göker H. Heterocycl. Comm.  2002,  8:  215 ; and references therein
    Google Scholar
  • 6 Kondo T. Yang S. Huh K.-T. Kobayashi M. Kotachi S. Watanabe Y. Chem. Lett.  1991,  1275 
    Google Scholar
  • For recent lead references see:
  • 7a Reid M. Rowe DJ. Taylor RJK. Chem. Commun.  2003,  2284 
    CrossrefGoogle Scholar
  • 7b Kanno H. Taylor RJK. Tetrahedron Lett.  2002,  43:  7337 
    CrossrefGoogle Scholar
  • 8 Raw S. Wilfred CD. Taylor RJK. Chem. Commun.  2003,  2286 
    CrossrefGoogle Scholar
  • 9 Encyclopedia of Reagents for Organic Synthesis   Vol. 5:  Paquette LA. John Wiley; Chichester: 1995.  p.3229 
    Google Scholar
  • 11 Lázár L. Göblyös A. Evanics F. Bernáth G. Fülöp F. Tetrahedron  1998,  54:  13639 
    CrossrefGoogle Scholar
  • 12 Pivsa-Art S. Satoh T. Kawamura Y. Miura M. Nomura M. Bull. Chem. Soc. Jpn.  1998,  71:  467 
    CrossrefGoogle Scholar
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Representative Experimental Procedure:
Activated manganese dioxide (Aldrich 21764-6, 0.653 g, 7.50 mmol) was added to a mixture of benzyl alcohol (0.054 g, 0.50 mmol), N-methyl 1,2-phenylenediamine (0.15 mL, 1.25 mmol), HCl in Et2O (2 M, 0.04 mL, 15 mol%) and 4 Å molecular sieves (0.5 g) in dry toluene (12 mL). The mixture was stirred at 105 °C for 18 h. The mixture was cooled to ca. 50 ºC, hot filtered through Celite®, and the residue washed with excess CH2Cl2. The combined organic fractions were concentrated in vacuo and the residue purified using column chromatography on silica (petroleum ether-EtOAc, 3:1) to give 1-methyl-2-phenylbenzimidazole (1a, 0.094 g, 90%) as a brown solid, Rf = 0.3 (petroleum ether-EtOAc, 2:1); mp 96 °C, lit.12 mp 94-95 °C. The spectroscopic data obtained were consistent with those reported in the literature.12