N-Acylureas in Peptide Synthesis: An X-Ray Diffraction and IR-Absorption Study

An X-ray diffraction analysts of two N-acyl derivatives of symmetrical dialkylureas, N-[N^α-(benzyloxycarbonyl)-L -valyl] -N, N′-diisopropylurea ( 1 ) and N-{Nα(tert-butyloxy)carbonyl -L -valyl}-N-N′-dicyclohexylurea ( 2 ), and one N-acyl derivative of an unsymmetrical N-N′-dialkylurea, N-[N^α-(benzyloxycarbonyl)-L -valyl] -N′-(tert-butyl)-N-ethylurea ( 3 ), has been performed. It was established that it is the least hindered O-acylisourca N-atom that attacks intramolecularly the carbonyl group of the N^α-protected amino acid activated by the unsymmetrical carbodiimide to form the major rearrangement product. The occurrence and nature of intra- and intermolecularly H? bonded forms of the N-acylureas in the crystal state were also assessed. It was also shown that soluble N-acylureas may compete with intermolecular (peptide)N? H…O?C(peptide) H-bonds in CH₂Cl₂.