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

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 
• 1b Gentilucci L. Tolomelli A. Squassabia F. Curr. Med. Chem.  2006,  13:  2449 
• For examples, see:
• 2a Jungermann E. Gerecht JF. Krems IJ. J. Am. Chem. Soc.  1956,  78:  172 
• 2b Kurkin AV. Golantsov NE. Karchava AV. Yurovskaya MA. Chem. Heterocycl. Compd. (Engl. Transl.)  2003,  39:  74 
• 3a Evans G. Platts JA. Tomkinson NCO. Org. Biomol. Chem.  2006,  4:  2616 
• 3b Cavill JL. Elliott RL. Evans G. Jones IL. Platts JA. Ruda AM. Tomkinson NCO. Tetrahedron  2006,  62:  410 
• 3c Gibbs TJK. Tomkinson NCO. Org. Biomol. Chem.  2005,  3:  4043 
• 3d Cavill JL. Peters J.-E. Tomkinson NCO. Chem. Commun.  2003,  728 
• 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 
• 5 Kihlberg J. Bergman R. Wickberg B. Acta Chem. Scand. Ser. B  1983,  37:  911 
• 7a Ram S. Ehrenkaufer RE. Synthesis  1988,  91 
• 7b Leuckart R. Ber. Dtsch. Chem. Ges.  1885,  18:  2341 
• 7c Wallach O. Ber. Dtsch. Chem. Ges.  1891,  24:  3992 
• 8 Hoefnagel AJ. Van Bekkum H. Peters JA. J. Org. Chem.  1992,  57:  3916 
• 9 Grieco PA. Larson SD. Fobare WF. Tetrahedron Lett.  1986,  27:  1975 
• 10 Coghlan PA. Easton CJ. J. Chem. Soc., Perkin Trans. 1  1999,  2659 
• 11 Maryanoff BE. Zhang H.-C. Cohen JH. Turchi IJ. Maryanoff CA. Chem. Rev.  2004,  104:  1431 
• 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 
• 13 Bialy L. Díaz-Mochón JJ. Specker E. Keinicke L. Bradley M. Tetrahedron  2005,  61:  8295 
• 14 Heimer EP. Gallo-Torres HE. Felix AM. Ahmad M. Lambros TJ. Scheidl F. Meienhofer J. Int. J. Pept. Protein Res.  1984,  23:  203 

6

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