Synthesis of Cucurbit[6]uril Derivatives and Insights into Their Solubility in Water

• Published in: European journal of organic chemistry 2013-06, Vol.2013 (18), p.3857-3865
• Main Authors: Lewin, Véronique, Rivollier, Julie, Coudert, Sylvie, Buisson, David-Alexandre, Baumann, Delphine, Rousseau, Bernard, Legrand, François-Xavier, Kouřilová, Hana, Berthault, Patrick, Dognon, Jean-Pierre, Heck, Marie-Pierre, Huber, Gaspard
• Format: Article
• Language: English
• Subjects: Host-guest systems; Macrocycles; Noncova­lent interactions; Solubility
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201300229

Four new cucurbiturils CynCB[6] containing n (n = 1, 2, 4, 5) cyclohexyl equatorial units have been synthesized to complete the family of known Cy3CB[6] and Cy6CB[6] derivatives. A new CB[6] member bearing a propanediurea unit has also been prepared. The CB[6] derivatives show better solubility in pure water than native CB[6]. One cyclohexyl unit is sufficient to enhance the solubility in water by a factor of 170 with respect to CB[6], and Cy6CB[6] is around 30 times more soluble than Cy1CB[6]. The cyclohexane moieties, by limiting or impeding the formation of intermolecular C–H···O hydrogen bonds, may explain this increase in solubility. The effect of modification of the molecular shape on the solubility was assessed by liquid‐state NMR spectroscopy and DFT calculations. New molecules derived from cucurbit[6]uril with either a propanediurea unit or cyclohexane moieties have been synthesized. Their solubility in pure water increased with the number of these nonclassical units. This can be explained in terms of changes in intermolecular C–H···O hydrogen bonding rather than in the molecular shape.