Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

A series of β-cyclodextrin dimers selectively permethylated on the primary or secondary rim with two different types of spacers have been synthesized effectively utilizing conventional and newly developed methods. Their structure analyses by ¹H NMR and NOESY NMR imply the dependence of molecular symmetry on the type of spacer. The ability of synthesized dimers to increase the solubility of tetracene in DMSO was evaluated and compared to native cyclodextrins and their methylated derivatives. The newly synthesized compounds expressed better effectiveness than other tested supramolecular hosts.

four new CD dimers from 6-azido partially methylated β-CD derivatives with two types of spacers between CD moieties. A new method for preparing β-CDs with selectively methylated primary rim based on the remarkable methylation ability of methyl tosylate with relatively mild bases at solvent-free conditions has been developed. It has been proved that using Lewis acid in the phosphine imide reactions with CDs can increase the reactivity of some low-reactive compounds, giving better yields and reducing the reaction time. The UV measurements have confirmed an increase in solubility of tetracene in DMSO in the presence of some CD derivatives. The partially methylated CD dimers are more than twice effective in solubilization than the compounds with one CD unit in the molecule in the molar ratio, implying that both CD fragments are engaged in complexation with tetracene. The compounds possessing hydroxy groups on the secondary rim generally perform worse than those with a methylated secondary rim. ITC studies and tetracene’s increased solubility prove the host–guest interaction’s existence.

Lebedinskiy, K.; Lobaz, V.; Jindřich, J. Beilstein J. Org. Chem. 2022, 18, 1596–1606. doi:10.3762/bjoc.18.170