PDF herunterladen
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;
Weitere Informationen

Publikationsverlauf

Received 11 November 2003
Publikationsdatum:
12. Februar 2004 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

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 
    Google Scholar
  • 1b Vega JA. Cueto S. Ramos A. Vaquero JJ. Garcia-Navio JL. Alvarez-Builla J. Ezquerra J. Tetrahedron Lett.  1996,  37:  6413 
    Google Scholar
  • 1c Almena I. Diaz-Ortiz A. Diez-Barra E. de la Hoz A. Loupy A. Chem. Lett.  1996,  333 
    Google Scholar
  • 1d Carrillo-Munoz JR. Bouvet D. Guibe-Jampel E. Loupy A. Petit A. J. Org. Chem.  1996,  61:  7746 
    Google Scholar
  • 1e Herradon B. Morcuende A. Valverde S. Synlett  1995,  61:  455 
    Google Scholar
  • 1f Forfar I. Cabil do P. Claramunt RM. Elguero J. Chem. Lett.  1994,  2079 
    Google Scholar
  • 2a Khalafi-Nezhad A. Soltani Rad MN. Hakimelahi GH. Helv. Chim. Acta  2003,  86:  2396 
    CrossrefGoogle Scholar
  • 2b Khalafi-Nezhad A. Mokhtari B. Soltani Rad MN. Tetrahedron Lett.  2003,  44:  7325 
    CrossrefGoogle Scholar
  • 2c Khalafi-Nezhad A. Alamdari F. Zekri N. Tetrahedron  2000,  56:  7503 
    CrossrefGoogle Scholar
  • 2d Khalafi-Nezhad A. Hashemi A. Iran. J. Chem. Chem. Eng.  2001,  20:  9 ; Chem. Abstr. 2002, 137, 232608
    CrossrefGoogle Scholar
  • 2e Khalafi-Nezhad A. Hashemi A. J. Chem. Res., Synop.  1999,  720 
    CrossrefGoogle Scholar
  • 3a Microwave in Organic Synthesis   Loupy A. Wiely-VCH; Weinheim: 2002. 
    CrossrefGoogle Scholar
  • 3b Hayes BL. Microwave Synthesis: Chemistry at the Speed of Light   CEM Publishing; Mathews, NC: 2002. 
    CrossrefGoogle Scholar
  • 3c Varma RS. Advances in Green Chemistry: Chemical Synthesis Using Microwave Irradiation   Astra Zeneca Research Foundation, Kavitha Printers; Bangalore, India: 2002. 
    CrossrefGoogle Scholar
  • 3d Ahluwalia VK. Aggarwal R. Organic Synthesis: Special Techniques   Alpha Science International Ltd.; Pangbourne / U.K.: 2001.  Chap. 3. p.90-114  
    CrossrefGoogle Scholar
  • 3e Microwave-Enhanced Chemistry. Fundamental, Sample Preparation, and Applications   Kingston HM. Haswell SJ. American Chemical Society; Washington / D.C.: 1997. 
    CrossrefGoogle Scholar
  • 3f Lew A. Krutzik PO. Hart ME. Chamberlin AR. J. Comb. Chem.  2002,  4:  95 
    CrossrefGoogle Scholar
  • 3g Larhed M. Moberg C. Hallberg A. Acc. Chem. Res.  2002,  35:  717 
    CrossrefGoogle Scholar
  • 3h Wathey B. Tierney J. Lidstrom P. Westman J. Drug Discovery Today  2002,  7:  373 
    CrossrefGoogle Scholar
  • 3i Kuhnert N. Angew. Chem. Int. Ed.  2002,  41:  1863 
    CrossrefGoogle Scholar
  • 3j Lidstorm P. Tierney J. Wathey B. Westman J. Tetrahedron  2001,  57:  9225 
    CrossrefGoogle Scholar
  • 3k Perreux L. Loupy A. Tetrahedron  2001,  57:  9199 
    CrossrefGoogle Scholar
  • 3l Varma RS. Green Chem.  1999,  1:  43 
    CrossrefGoogle Scholar
  • 3m Caddick S. Tetrahedron  1995,  51:  10403 
    CrossrefGoogle Scholar
  • 4 Declercq E. In Advance in Antiviral Drug Design   Vol.1:  Johnsson NG. Jai; Greenwich: 1993.  p.88-164  
    Google Scholar
  • 5 Munter T. Cotrell L. Stuart H. Kronberg L. Watson WP. Golding BT. Chem. Res. Toxicol.  2002,  15:  1549 
    CrossrefGoogle Scholar
  • 7a Kondo K. Sato T. Takemoto K. Chem. Lett.  1973,  967 
    Google Scholar
  • 7b DiMenna WS. Piantadosi C. J. Med. Chem.  1978,  21:  1073 
    Google Scholar
  • 7c Martin JC. Smee DF. Verheyden JPH. J. Org. Chem.  1985,  50:  755 
    Google Scholar
  • 7d Biggadike K. Borthwick AD. Exall AM. Kirk BE. Roberts SM. Youds P. J. Chem. Soc., Chem. Commun.  1987,  1083 
    Google Scholar
  • 7e Novikov MS. Ozerov AA. Brel AK. Boreko EI. Vladyko GV. Korobchenko LV. Khim.-Farm. Zh.  1991,  25:  35 ; Chem. Abstr. 1992, 116, 128848
    Google Scholar
  • 7f Brodfuehrer PR. Howell HG. Sapino C. Vemishetti P. Tetrahedron Lett.  1994,  35:  3243 
    Google Scholar
  • 7g Allart B. Busson R. Razenski J. Van Aerschot A. Herdewign P. Tetrahedron  1999,  55:  6527 
    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 
    Google Scholar
  • 7i Guan H.-P. Ksebuti NB. Kern EK. Zemlicka J. J. Org. Chem.  2000,  65:  5177 
    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 
    Google Scholar
  • 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. 
    Google Scholar
  • 9 Khalafi-Nezhad A. Soltani Rad MN. Khoshnood A. Synthesis  2003,  2552 
    Artikel in Thieme ConnectGoogle Scholar
  • 10 Vogel AI. Practical Organic Chemistry   Longman, Green and Co.; London: 1954.  p.161-176  
    Google Scholar
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