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Synlett 2004(14): 2525-2528  
DOI: 10.1055/s-2004-834819
LETTER
© Georg Thieme Verlag Stuttgart · New York

Direct Carbodiimide-Mediated Conjugation of Carboxylates Using ­Pyridinium p-Toluenesulfonate and Tertiary Amines as Additives

Simon Ficht, Lars Röglin, Matthias Ziehe, David Breyer, Oliver Seitz*
Institut für Chemie der Humboldt-Universität zu Berlin, Institut für Chemie, Brook-Taylor-Str. 2, 12489 Berlin, Germany
Fax: +49(30)20937266; e-Mail: oliver.seitz@chemie.hu-berlin.de;
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Publikationsverlauf

Received 4 August 2004
Publikationsdatum:
20. Oktober 2004 (online)

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Abstract

The use of carboxylates in the carbodiimide-mediated coupling to amines was investigated. The addition of pyridinium p-toluenesulfonate (PPTS) and a tertiary amine was found to significantly improve acylation yields by up to 70%.

Key words

amides - coupling - carbodiimides - carboxylates - solid-phase synthesis

    References

  • 1 Albert JS. Hamilton AD. In Encyclopedia of Reagents for Organic Synthesis   Vol. 3:  Paquette LA. Wiley; Chichester: 1995. 
    Suche in Google Scholar
  • 2 Williams A. Ibrahim IT. Chem. Rev.  1981,  81:  589 
    CrossrefSuche in Google Scholar
  • 3 Han SY. Kim YA. Tetrahedron  2004,  60:  2447 
    CrossrefSuche in Google Scholar
  • 4 Molina P. Fresneda PM. Delgado S. J. Org. Chem.  2003,  68:  489 
    CrossrefSuche in Google Scholar
  • 5 Shelkov R. Nahmany M. Melman A. Org. Biomol. Chem.  2004,  2:  397 
    CrossrefSuche in Google Scholar
  • 6 Araki J. Kuga S. Magoshi J. J. Appl. Polym. Sci.  2002,  85:  1349 
    CrossrefSuche in Google Scholar
  • 7 Stadler A. Kappe CO. Tetrahedron  2001,  57:  3915 
    CrossrefSuche in Google Scholar
  • 8 Khorana HG. Chem. Rev.  1953,  53:  145 
    CrossrefSuche in Google Scholar
  • 9a König W. Geiger R. Chem. Ber.  1973,  106:  3626 
    CrossrefPubMedSuche in Google Scholar
  • 9b König W. Geiger R. Chem. Ber.  1970,  103:  788 
    CrossrefPubMedSuche in Google Scholar
  • 10 Galan AA. In Encyclopedia of Reagents for Organic Synthesis   Vol. 6:  Paquette LA. Wiley; Chichester: 1995. 
    Suche in Google Scholar
  • 11 Schmidt E. Striewsky W. Chem. Ber.  1941,  74B:  1285 
    Suche in Google Scholar
  • 12a

    General Procedure for the Carbodiimide-Mediated Amidation: The carboxylic acid or carboxylate was diluted/suspended in DMF to yield a 0.1 M concentration. Under stirring HOBt (1 equiv), PPTS (specified amount), carbodiimide (1 equiv) and DIPEA (2 equiv when mentioned) was added. After 10 min 1 equiv of amine was added. The resulting mixture was stirred for 4 h and analyzed by RP-HPLC.

  • 12b

    HPLC was performed on a Gilson 1105 HPLC-system (Nebula series) using a reversed phase Nucleodur C-18 Gravity 3 µm column (Macherey-Nagel, Düren) and a detection wavelength of 254 nm. Eluents: A: 98.9% H2O, 1% MeCN (HPLC-grade, Biosolve BV, Valkenswaard, NL) 0.1% TFA (Peptide Synthesis Grade, Biosolve BV); B: 98.9% MeCN, 1% H2O, 0.1% TFA. Gradient: 3-80% B in 20 min followed by 5 min 80% B (Phloxine B, Erythrosin B: Gradient: 3-100% B in 20 min followed by 5 min 80% B).

  • 13 Sheehan JC. Hess GP. J. Am. Chem. Soc.  1955,  77:  1067 
    CrossrefSuche in Google Scholar
14

HPLC was performed on a Gilson 1105 HPLC-system (Nebula series) using a reverse-phase Nucleodur C-18 Gravity 3 µm column (Macherey-Nagel, Düren) and detection wavelengths of 260 nm and 450 nm. Eluents: A: 98.9% H2O, 1% MeCN (HPLC-grade, Biosolve BV, Valkenswaard, NL) 0.1% TFA (Peptide Synthesis Grade, Biosolve BV); B: 98.9% MeCN, 1% H2O, 0.1% TFA. Gradient: 3-30% B in 30 min.