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

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Abstract

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.

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Acknowledgements

We are grateful to Mr. A. Panagiotou and Prof. A. Tasiopoulos (Department of Chemistry, University of Cyprus) for the collection of the diffraction data and the Laboratory of Instrumental Analysis (University of Patras) for the NMR spectra and the Elemental Analysis.

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Authors and Affiliations

  1. Department of Chemistry, University of Patras, 26504, Patras, Greece

    Eleanna Vachlioti, Stefania Kalantzi, Dionissios Papaioannou & Vassilios Nastopoulos

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  1. Eleanna Vachlioti
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  2. Stefania Kalantzi
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  3. Dionissios Papaioannou
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  4. Vassilios Nastopoulos
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Correspondence to Vassilios Nastopoulos.

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Vachlioti, E., Kalantzi, S., Papaioannou, D. et al. Synthesis, Spectroscopy and Crystal Structure Analysis of N1,N3-dicyclohexyl-N1-(all-trans-retinoyl)urea. J Chem Crystallogr 52, 260–269 (2022). https://doi.org/10.1007/s10870-021-00917-x

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