Download PDF
Synthesis 2004(4): 583-589  
DOI: 10.1055/s-2004-815968
PAPER
© Georg Thieme Verlag Stuttgart · New York

Microwave-Assisted Ring Opening of Epoxides with Pyrimidine Nucleobases: A Rapid Entry into C -Nucleoside Synthesis

A. Khalafi-Nezhad*, M. N. Soltani Rad, A. Khoshnood
Department of Chemistry, College of Science, Shiraz University, Shiraz 71454, Iran
Fax: +98(711)2280926; e-Mail: khalafi@chem.susc.ac.ir;
Further Information

Publication History

Received 11 November 2003
Publication Date:
12 February 2004 (online)

    Permissions and Reprints All articles of this category

Abstract

Microwave irradiation strongly accelerates the regio­selective nucleophilic ring opening of epoxides by pyrimidine nucleobases. In the presence of tetrabutylammonium bromide (TBAB), various bases were elaborated to determine the proper base in which it can activate N1 rather than N3 for alkylation. It was shown that MgO not only could serve as an eligible base, but also enhanced the selectivity and tendency of N1 for alkylation as compared with N3. The use of microwave irradiation provided dominant regioselective synthesis of N1-β-hydroxyalkylpyrimidines in moderate to good yields with a reaction time of less than 7 minutes.

Key words

microwave - uracil - epoxides - TBAB - magnesium oxide­

    References

  • 1a Langa F. de la Cruz P. de la Hoz A. Diaz-Ortiz A. Diez-Barra E. Contemp. Org. Synth.  1997,  65:  373 
    Search in Google Scholar
  • 1b Vega JA. Cueto S. Ramos A. Vaquero JJ. Garcia-Navio JL. Alvarez-Builla J. Ezquerra J. Tetrahedron Lett.  1996,  37:  6413 
    Search in Google Scholar
  • 1c Almena I. Diaz-Ortiz A. Diez-Barra E. de la Hoz A. Loupy A. Chem. Lett.  1996,  333 
  • 1d Carrillo-Munoz JR. Bouvet D. Guibe-Jampel E. Loupy A. Petit A. J. Org. Chem.  1996,  61:  7746 
    Search in Google Scholar
  • 1e Herradon B. Morcuende A. Valverde S. Synlett  1995,  61:  455 
    Search in Google Scholar
  • 1f Forfar I. Cabil do P. Claramunt RM. Elguero J. Chem. Lett.  1994,  2079 
  • 2a Khalafi-Nezhad A. Soltani Rad MN. Hakimelahi GH. Helv. Chim. Acta  2003,  86:  2396 
    CrossrefSearch in Google Scholar
  • 2b Khalafi-Nezhad A. Mokhtari B. Soltani Rad MN. Tetrahedron Lett.  2003,  44:  7325 
    CrossrefSearch in Google Scholar
  • 2c Khalafi-Nezhad A. Alamdari F. Zekri N. Tetrahedron  2000,  56:  7503 
    CrossrefSearch in Google Scholar
  • 2d Khalafi-Nezhad A. Hashemi A. Iran. J. Chem. Chem. Eng.  2001,  20:  9 ; Chem. Abstr. 2002, 137, 232608
    CrossrefSearch in Google Scholar
  • 2e Khalafi-Nezhad A. Hashemi A. J. Chem. Res., Synop.  1999,  720 
    Crossref
  • 3a Microwave in Organic Synthesis   Loupy A. Wiely-VCH; Weinheim: 2002. 
    Crossref
  • 3b Hayes BL. Microwave Synthesis: Chemistry at the Speed of Light   CEM Publishing; Mathews, NC: 2002. 
    Crossref
  • 3c Varma RS. Advances in Green Chemistry: Chemical Synthesis Using Microwave Irradiation   Astra Zeneca Research Foundation, Kavitha Printers; Bangalore, India: 2002. 
    Crossref
  • 3d Ahluwalia VK. Aggarwal R. Organic Synthesis: Special Techniques   Alpha Science International Ltd.; Pangbourne / U.K.: 2001.  Chap. 3. p.90-114  
    Crossref
  • 3e Microwave-Enhanced Chemistry. Fundamental, Sample Preparation, and Applications   Kingston HM. Haswell SJ. American Chemical Society; Washington / D.C.: 1997. 
    Crossref
  • 3f Lew A. Krutzik PO. Hart ME. Chamberlin AR. J. Comb. Chem.  2002,  4:  95 
    CrossrefSearch in Google Scholar
  • 3g Larhed M. Moberg C. Hallberg A. Acc. Chem. Res.  2002,  35:  717 
    CrossrefSearch in Google Scholar
  • 3h Wathey B. Tierney J. Lidstrom P. Westman J. Drug Discovery Today  2002,  7:  373 
    CrossrefSearch in Google Scholar
  • 3i Kuhnert N. Angew. Chem. Int. Ed.  2002,  41:  1863 
    CrossrefSearch in Google Scholar
  • 3j Lidstorm P. Tierney J. Wathey B. Westman J. Tetrahedron  2001,  57:  9225 
    CrossrefSearch in Google Scholar
  • 3k Perreux L. Loupy A. Tetrahedron  2001,  57:  9199 
    CrossrefSearch in Google Scholar
  • 3l Varma RS. Green Chem.  1999,  1:  43 
    CrossrefSearch in Google Scholar
  • 3m Caddick S. Tetrahedron  1995,  51:  10403 
    CrossrefSearch in Google Scholar
  • 4 Declercq E. In Advance in Antiviral Drug Design   Vol.1:  Johnsson NG. Jai; Greenwich: 1993.  p.88-164  
    Search in Google Scholar
  • 5 Munter T. Cotrell L. Stuart H. Kronberg L. Watson WP. Golding BT. Chem. Res. Toxicol.  2002,  15:  1549 
    CrossrefSearch in Google Scholar
  • 7a Kondo K. Sato T. Takemoto K. Chem. Lett.  1973,  967 
  • 7b DiMenna WS. Piantadosi C. J. Med. Chem.  1978,  21:  1073 
    Search in Google Scholar
  • 7c Martin JC. Smee DF. Verheyden JPH. J. Org. Chem.  1985,  50:  755 
    Search in Google Scholar
  • 7d Biggadike K. Borthwick AD. Exall AM. Kirk BE. Roberts SM. Youds P. J. Chem. Soc., Chem. Commun.  1987,  1083 
  • 7e Novikov MS. Ozerov AA. Brel AK. Boreko EI. Vladyko GV. Korobchenko LV. Khim.-Farm. Zh.  1991,  25:  35 ; Chem. Abstr. 1992, 116, 128848
    Search in Google Scholar
  • 7f Brodfuehrer PR. Howell HG. Sapino C. Vemishetti P. Tetrahedron Lett.  1994,  35:  3243 
    Search in Google Scholar
  • 7g Allart B. Busson R. Razenski J. Van Aerschot A. Herdewign P. Tetrahedron  1999,  55:  6527 
    Search in Google Scholar
  • 7h Allart B. Khan K. Rosemeyer H. Schepers G. Hendrix C. Rothenbacher K. Seela F. Van Aerschot A. Herdewign P. Chem. Eur. J.  1999,  5:  2424 
    Search in Google Scholar
  • 7i Guan H.-P. Ksebuti NB. Kern EK. Zemlicka J. J. Org. Chem.  2000,  65:  5177 
    Search in Google Scholar
  • 7j Pederson DS. Boesen T. Eldrup AB. Kiaer B. Madsen C. Henriksen U. Dahl O. J. Chem. Soc., Perkin Trans.1  2001,  1656 
  • 8 The phase-transfer catalyst (PTC)-mediated microwave-assisted organic reaction is well established and fully demonstrated (see Ref.1,5 and all references cited therein). However, in this reaction, TBAB not only absorbs the microwave irradiation but also generates in situ heat and increases the temperature higher than its melting point (100-103 °C). Under these conditions, TBAB creates the homogeneous media whose resemblance is not far from ionic liquids concept. For monographies on ionic liquid, see: Wasserscheid P. Welton T. Ionic Liquids in Synthesis   Wiley-VCH; Weinheim: 2002. 
  • 9 Khalafi-Nezhad A. Soltani Rad MN. Khoshnood A. Synthesis  2003,  2552 
    Thieme Connect
  • 10 Vogel AI. Practical Organic Chemistry   Longman, Green and Co.; London: 1954.  p.161-176  
6

Rodriguez, H.; Perez, R.; Suarez, M.; Lam, A.; Cabrales, N.; Loupy, A. Fifth International Electronic Conference on Synthetic Organic Chemistry (ESCOC-5); http://www.mdpi.net/escoc-5/e0004/e0004.html