Rearrangement of the active ester intermediate during HOBt/EDC amide coupling

Khaled Mahmoud, Yi Tao Long, Gabriele Schatte, Heinz Bernhard Kraatz

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

3-{[1′-(tert-Butyloxycarbonylamino)ferrocen-1-yl]carbonyl} -benzotriazole 1-oxide (3) has been successfully separated during the synthesis of benzotriazol-1-yl 1′-(tert-butyloxycarbonylamino)ferrocene-1- carboxylate (2) as an active ester for peptide coupling. The yield of 3 increased by using polar, rather than nonpolar solvents. The two compounds have been fully characterized and studied by X-ray crystallography and spectroscopic methods. The active ester derivative 2 formed a urethane bond with the glycine ethyl ester while the N-oxide 3 did not react. The X-ray structural analysis of 3 shows strong intermolecular hydrogen bonding involving the urethane group and the N-oxide of an adjacent molecule [N-O⋯H-N = 2.859(2) Å]. No hydrogen bonding is present in the solid state for compound 2, while solution studies indicate the presence of intramolecular hydrogen bonding. Both complexes display a quasi-reversible single one-electron oxidation, the halfwave potentials E1/2 for 2 and 3 were 672 ± 5 and 591 ± 5 mV, respectively.

Original languageEnglish
Pages (from-to)173-180
Number of pages8
JournalEuropean Journal of Inorganic Chemistry
Issue number1
DOIs
Publication statusPublished - 7 Jan 2005
Externally publishedYes

Fingerprint

Amides
Oxides
Hydrogen bonds
Esters
Urethane
X ray crystallography
Structural analysis
Derivatives
X rays
Oxidation
Peptides
Molecules
Electrons
1-hydroxybenzotriazole
hydroxide ion
glycine ethyl ester
ferrocene
benzotriazole

Keywords

  • Amide coupling
  • Amino acid
  • Electrochemistry
  • Ferrocene
  • Hydroxybenzotriazole

ASJC Scopus subject areas

  • Inorganic Chemistry

Cite this

Rearrangement of the active ester intermediate during HOBt/EDC amide coupling. / Mahmoud, Khaled; Long, Yi Tao; Schatte, Gabriele; Kraatz, Heinz Bernhard.

In: European Journal of Inorganic Chemistry, No. 1, 07.01.2005, p. 173-180.

Research output: Contribution to journalArticle

Mahmoud, Khaled ; Long, Yi Tao ; Schatte, Gabriele ; Kraatz, Heinz Bernhard. / Rearrangement of the active ester intermediate during HOBt/EDC amide coupling. In: European Journal of Inorganic Chemistry. 2005 ; No. 1. pp. 173-180.
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AB - 3-{[1′-(tert-Butyloxycarbonylamino)ferrocen-1-yl]carbonyl} -benzotriazole 1-oxide (3) has been successfully separated during the synthesis of benzotriazol-1-yl 1′-(tert-butyloxycarbonylamino)ferrocene-1- carboxylate (2) as an active ester for peptide coupling. The yield of 3 increased by using polar, rather than nonpolar solvents. The two compounds have been fully characterized and studied by X-ray crystallography and spectroscopic methods. The active ester derivative 2 formed a urethane bond with the glycine ethyl ester while the N-oxide 3 did not react. The X-ray structural analysis of 3 shows strong intermolecular hydrogen bonding involving the urethane group and the N-oxide of an adjacent molecule [N-O⋯H-N = 2.859(2) Å]. No hydrogen bonding is present in the solid state for compound 2, while solution studies indicate the presence of intramolecular hydrogen bonding. Both complexes display a quasi-reversible single one-electron oxidation, the halfwave potentials E1/2 for 2 and 3 were 672 ± 5 and 591 ± 5 mV, respectively.

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