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

Abstract Four new cucurbiturils Cy n CB[6] containing n ( n = 1, 2, 4, 5) cyclohexyl equatorial units have been synthesized to complete the family of known Cy 3 CB[6] and Cy 6 CB[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 Cy 6 CB[6] is around 30 times more soluble than Cy 1 CB[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.