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 ‐{ N α( 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 Hbonded 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)NH…OC(peptide) H‐bonds in CH 2 Cl 2 .