Synthesis,Spectroscopy and Crystal Structure Analysis of N1,N3-dicyclohexyl-N1-(all-trans-retinoyl)urea

The title compound, C₃₃H₅₀N₂O₂, is a side product in the reaction of all-trans-retinoic acid (atRA) with N-hydroxysuccinimide, in the presence of the coupling agent N,N′-dicyclohexylcarbodiimide, which produces the ‘active’ ester succinimidyl all-trans-retinoate as the product. It crystallizes in the orthorhombic Pbca space group. The compound was characterized by ¹H-NMR, ¹³C-NMR, ESI–MS and IR spectroscopy and its structure was determined by single-crystal X-ray diffraction. For example in the ¹³C-NMR spectrum, diagnostic peaks are those of the two amide carbonyl C atoms at δ 169.5 and 154.2 ppm, the ten olefinic C atoms of the unsaturated chain of atRA moiety at δ 149.0, 139.3, 137.7, 137.3, 134.9, 130.2, 130.0, 129.4, 128.5 and 121.5 ppm and the two methine C atoms of the N,N′-dicyclohexylurea moiety at δ 57.9 and 49.5 ppm. Detailed analysis of its molecular and supramolecular structure showed that close-packing principles (elongated shape/large hydrophobic region of the molecule) together with chemical factors (N–H?O and C–H?O intermolecular interactions) direct the 3D self-assembly process in the crystalline state. Hirshfeld surface analysis was employed, a powerful approach to quickly and easily gain insight into molecular environments in the crystalline state.

Graphical Abstract

The synthesis and X-ray structure of 1-((2E, 4E, 6E, 8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-enyl)nona-2,4,6,8-tetraenoyl)-1,3-dicyclohexylurea, a side product in the synthesis of succinimidyl all-trans-retinoate, is reported; Hirshfeld surface analysis was employed to identify intermolecular interactions.