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Synlett 2007(10): 1573-1576  
DOI: 10.1055/s-2007-982531
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Mild and Efficient Method for the One-Pot Monocarboxymethylation of Primary Amines

Timothy J. K. Gibbs, Michael Boomhoff, Nicholas C. O. Tomkinson*
School of Chemistry, Main Building, Cardiff University, Park Place, Cardiff, CF10 3AT, UK
Fax: +44(29)20874030; e-Mail: tomkinsonnc@cardiff.ac.uk;
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Publication History

Received 23 January 2007
Publication Date:
06 June 2007 (online)

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Abstract

A mild and efficient method for the monocarboxymethylation of primary amines that takes place under aqueous conditions at room temperature is described. Treatment of an aqueous solution of a variety of primary amines with two equivalents of glyoxylic acid leads to the N-formyl glycine derivatives. Direct hydrolysis of the crude reaction solution leads to the products of amine mono­carboxymethylation in good to excellent yield.

Key words

metal-free synthesis - amino acids - glycine derivatives

    References and Notes

  • For recent reviews, see:
  • 1a Rajesh BM. Iqbal J. Curr. Pharm. Biotech.  2006,  7:  247 
    Google Scholar
  • 1b Gentilucci L. Tolomelli A. Squassabia F. Curr. Med. Chem.  2006,  13:  2449 
    Google Scholar
  • For examples, see:
  • 2a Jungermann E. Gerecht JF. Krems IJ. J. Am. Chem. Soc.  1956,  78:  172 
    Google Scholar
  • 2b Kurkin AV. Golantsov NE. Karchava AV. Yurovskaya MA. Chem. Heterocycl. Compd. (Engl. Transl.)  2003,  39:  74 
    Google Scholar
  • 3a Evans G. Platts JA. Tomkinson NCO. Org. Biomol. Chem.  2006,  4:  2616 
    Google Scholar
  • 3b Cavill JL. Elliott RL. Evans G. Jones IL. Platts JA. Ruda AM. Tomkinson NCO. Tetrahedron  2006,  62:  410 
    Google Scholar
  • 3c Gibbs TJK. Tomkinson NCO. Org. Biomol. Chem.  2005,  3:  4043 
    Google Scholar
  • 3d Cavill JL. Peters J.-E. Tomkinson NCO. Chem. Commun.  2003,  728 
    Google Scholar
  • 4 These conditions were derived from a report by Jørgensen for the formation of 4-benzyl-1-methylimidazolidine-2-carboxylic acid from the reaction of glyoxylic acid and N-methyl-3-phenylpropane-1,2-diamine. See: Halland N. Hazell RG. Jørgensen KA. J. Org. Chem.  2002,  67:  8331 
    Google Scholar
  • 5 Kihlberg J. Bergman R. Wickberg B. Acta Chem. Scand. Ser. B  1983,  37:  911 
    Google Scholar
  • 7a Ram S. Ehrenkaufer RE. Synthesis  1988,  91 
    Google Scholar
  • 7b Leuckart R. Ber. Dtsch. Chem. Ges.  1885,  18:  2341 
    Google Scholar
  • 7c Wallach O. Ber. Dtsch. Chem. Ges.  1891,  24:  3992 
    Google Scholar
  • 8 Hoefnagel AJ. Van Bekkum H. Peters JA. J. Org. Chem.  1992,  57:  3916 
    Google Scholar
  • 9 Grieco PA. Larson SD. Fobare WF. Tetrahedron Lett.  1986,  27:  1975 
    Google Scholar
  • 10 Coghlan PA. Easton CJ. J. Chem. Soc., Perkin Trans. 1  1999,  2659 
    Google Scholar
  • 11 Maryanoff BE. Zhang H.-C. Cohen JH. Turchi IJ. Maryanoff CA. Chem. Rev.  2004,  104:  1431 
    Google Scholar
  • 12 For a typical example, see: Chambers MS. Street LJ. Goodacre S. Hobbs SC. Hunt P. Jelley RA. Matassa VG. Reeve AJ. Sternfeld F. Beer MS. Stanton JA. Rathbone D. Watt AP. MacLeod AM. J. Med. Chem.  1999,  42:  691 
    Google Scholar
  • 13 Bialy L. Díaz-Mochón JJ. Specker E. Keinicke L. Bradley M. Tetrahedron  2005,  61:  8295 
    Google Scholar
  • 14 Heimer EP. Gallo-Torres HE. Felix AM. Ahmad M. Lambros TJ. Scheidl F. Meienhofer J. Int. J. Pept. Protein Res.  1984,  23:  203 
    Google Scholar
6

All compounds prepared were characterised by mp, 1H NMR, 13C NMR, IR, MS and HRMS.