Study of the reaction between carbamoyl azides of α-N-protected amino acids and hydrazine monohydrate

Two simple and efficient synthetic methods for the preparation of semicarbazide amino acid derivatives are reported. The procedures involve reaction between the carbamoyl azides of α-N-protected amino acids and hydrazine monohydrate: 4-[(alkoxycarbonylamino)(alkyl)methyl]semicarbazides 1 are obtained when hydrazine is added to the separated tetrahydrofuran (THF) solution containing the carbamoyl azide at 0 °C, whereas 1-[(alkoxycarbonylamino)(alkyl)methyl-carbamoyl]-4-[(alkoxycarbonylamino)(alkyl) methyl]semicarbazides 4 are produced by adding hydrazine directly into the final THF/aqueous buffer (KH₂PO₄) biphasic mixture containing the prepared carbamoyl azide at 50 °C, respectively. NMR experimental data obtained from samples dissolved in [D₆]dimethyl sulfoxide suggest a dimeric association for semicarbazides 4 with intermolecular hydrogen bonds. Moreover, the ESI-MS-MS spectra reveal some interesting common features.