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Synlett 2010(12): 1793-1796  
DOI: 10.1055/s-0030-1258088
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Preparation of Pyrimidine-N-oxides by Condensation of Functionalized Enamides with Hydroxylamine Hydrochloride

Reinhold Zimmer, Tilman Lechel, Giaime Rancan, Mrinal K. Bera, Hans-Ulrich Reissig*
Freie Universität Berlin, Institut für Chemie und Biochemie, Takustr. 3, 14195 Berlin, Germany
Fax: +49(30)83855367; e-Mail: hans.reissig@chemie.fu-berlin.de;
Further Information

Publication History

Received 8 April 2010
Publication Date:
11 June 2010 (online)

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Abstract

β-Alkoxy-β-ketoenamides and hydroxylamine hydrochloride smoothly provide pyrimidine-N-oxides under very mild conditions. Alkyl, aryl, and heteroaryl substituents are compatible with this new method. By treatment with acetic acid anhydride these pyrimidine-N-oxides undergo a rearrangement furnishing highly functionalized 6-acetoxymethyl-substituted pyrimidine derivatives in good yields. Our method, which is based on a three-component reaction of alkoxyallenes, nitriles, and carboxylic acids, therefore constitutes a highly flexible route to densely substituted pyrimidine derivatives.

Key words

pyrimidines - N-oxides - enamides - hydroxylamine - condensation - 3,3-sigmatropic rearrangement

    References

  • Reviews dealing with various aspects of lithiated alkoxyallene chemistry:
  • 1a Zimmer R. Synthesis  1993,  165 
    Google Scholar
  • 1b Zimmer R. Khan FA. J. Prakt. Chem.  1996,  338:  92 
    Google Scholar
  • 1c Reissig H.-U. Schade W. Okala Amombo MG. Pulz R. Hausherr A. Pure Appl. Chem.  2002,  74:  175 
    Google Scholar
  • 1d Zimmer R. Reissig H.-U. In Modern Allene Chemistry   Vol. 1:  Krause N. Hashmi ASK. Wiley-VCH; Weinheim: 2004.  Chap. 8. p.425-492  
    Google Scholar
  • 1e Brasholz M. Reissig H.-U. Zimmer R. Acc. Chem. Res.  2009,  42:  45 
    Google Scholar
  • 1f Pfrengle F. Reissig H.-U. Chem. Soc. Rev.  2010,  39:  549 
    Google Scholar
  • 1g Lechel T. Reissig H.-U. Pure Appl. Chem.  2010,  82:  No. 9 
    Google Scholar
  • 2a Flögel O. Dash J. Brüdgam I. Hartl H. Reissig H.-U. Chem. Eur. J.  2004,  10:  4283 
    Google Scholar
  • 2b Flögel O, and Reissig H.-U. inventors; DE  10336497. 
  • 2c Dash J. Lechel T. Reissig H.-U. Org. Lett.  2007,  9:  5541 
    Google Scholar
  • 2d Lechel T. Dash J. Reissig H.-U. Eur. J. Org. Chem.  2008,  3647 
    Google Scholar
  • 2e Lechel T. Dash J. Hommes P. Lentz D. Reissig H.-U. J. Org. Chem.  2010,  75:  726 
    Google Scholar
  • 2f Lechel T. Dash J. Eidamshaus C. Brüdgam I. Lentz D. Reissig H.-U. Org. Biomol. Chem.  2010, in press; DOI: 10.1039/B925468D
    Google Scholar
  • 2g Synthesis of chiral pyridine derivatives: Eidamshaus C. Reissig H.-U. Adv. Synth. Catal.  2009,  351:  1162 
    Google Scholar
  • 3a Lechel T. Möhl S. Reissig H.-U. Synlett  2009,  1059 
    Google Scholar
  • 3b Lechel T. Reissig H.-U. Eur. J. Org. Chem.  2010,  2555 
    Google Scholar
  • 4a Lechel T, and Reissig H.-U. inventors; DE 10 049  431.3. 
  • 4b Lechel T. Lentz D. Reissig H.-U. Chem. Eur. J.  2009,  15:  5432 
    Google Scholar
  • Pyrimidine-N-oxide chemistry, review:
  • 5a Yamanaka H. Sakamoto T. Niitsuma S. Heterocycles  1990,  31:  923 
    Google Scholar
  • Acetoxylations:
  • 5b Sakamoto T. Yoshizawa H. Kaneda S. Yamanaka H. Chem. Pharm. Bull.  1984,  32:  728 
    Google Scholar
  • Chlorination to chloromethylpyrimidines:
  • 5c Sakamoto T. Kaneda S. Hama Y. Yamanaka H. Heterocycles  1983,  20:  991 
    Google Scholar
  • Conversion to isoxazoles:
  • 5d Kato T. Yamanaka H. Yasuda N. J. Org. Chem.  1967,  32:  3593 
    Google Scholar
  • Reactions with electrophiles:
  • 5e Tikhonov AYa. Volodarskii LB. Vakolova OA. Podgornaya MI. Chem. Heterocycl. Compd.  1981,  17:  89 
    Google Scholar
  • 6 Review on hetero-Cope rearrangements, see: Blechert S. Synthesis  1989,  71 
    Article in Thieme ConnectGoogle Scholar
  • 7 For a recent review on perfluoroalkylsulfonates, see: Högermeier J. Reissig H.-U. Adv. Synth. Catal.  2009,  351:  2747 
    CrossrefGoogle Scholar
  • Reviews on pyrimidine chemistry:
  • 8a Brown DJ. In Comprehensive Heterocyclic Chemistry   Vol. 3:  Katritzky AR. Rees CW. Pergamon Press; Oxford: 1984.  Chap. 2.13.
    Google Scholar
  • 8b Eicher T. Hauptmann S. Chemie der Heterocyclen   Thieme; Stuttgart: 1994.  p.398 
    Google Scholar
  • 8c Gilchrist TL. Heterocyclenchemie   Neunhoeffer H. Wiley-VCH; Weinheim: 1995.  p.270 
    Google Scholar
  • 8d Hoffmann MG. In Houben-Weyl Methoden der Organischen Chemie   Vol. E9:  Schaumann E. Thieme; Stuttgart: 1996. 
    Google Scholar
  • 8e Von Angerer S. Sci. Synth.   Vol. 16:  Yamamoto Y. Thieme; Stuttgart: 2004.  p.379 
    Google Scholar
  • 8f Lamberth C. Heterocycles  2006,  68:  561 
    Google Scholar
  • 8g Radi M. Schenone S. Botta M. Org. Biomol. Chem.  2009,  7:  2841 
    Google Scholar
  • For recent publications on pyrimidine synthesis, see:
  • 8h Nara SJ. Jha M. Brinkhorst J. Zemanek TJ. Pratt DA. J. Org. Chem.  2008,  73:  9326 
    Google Scholar
  • 8i Hill MD. Movassaghi M. Chem. Eur. J.  2008,  14:  6836 
    Google Scholar
  • 8j Bannwarth P. Grée D. Grée R. Tetrahedron Lett.  2010,  51:  2413 
    Google Scholar