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Rearrangement of the Active Ester Intermediate During HOBt/EDC Amide Coupling

2004; Wiley; Volume: 2005; Issue: 1 Linguagem: Inglês

10.1002/ejic.200400504

1099-0682

Khaled A. Mahmoud, Yi‐Tao Long, G. Schatte, Heinz‐Bernhard Kraatz,

Synthesis and Biological Evaluation

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 E 1/2 for 2 and 3 were 672 ± 5 and 591 ± 5 mV, respectively. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)