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

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-l-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 ana-lysis 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) Angstrom]. 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. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).