Tetrahydrothiophene-cucurbit(n)urils and Preliminary Studies on Their Recognition Properties

Abstract

Substituted cucurbit[n]urils (Q[n]) feature substituent(s) on the convex face of their macrocycle structures. The incorporation of substituents on Q[n] is known to affect the physical and/or chemical properties of the derivatives, e.g. solubility and binding affinity, but also provides a means to functionalising Q[n], which could facilitate further elaboration, an ongoing challenge.

Inspired by studies on fully-substituted cyclopentano-Q[n]s, this thesis investigates an alternative 5-membered ring substituent, tetrahydrothiophene (THT) for the synthesis of THTnQ[n] as well as preliminary investigations of their recognition properties and synthetic potential for modification. As a model for the modification of THTnQ[n], we investigated the modification of THT-glycoluril diether (THTGE), the precursor to THTnQ[n], which included oxidation to a sulfoxide followed by Pummerer rearrangement reaction.

Modifications of synthetic conditions required for the synthesis of THTnQ[n] where n > 5 were investigated. The effect of using alkali metal ions and guest molecules as templates to achieve this objective is discussed. Also the benefits and limitations of employing methanesulfonic acid as both an alternative solvent and acid catalyst have been explored. Clear evidence is provided for the synthesis of THT5Q[5] and THT6Q[6] in 71% and 17% yield, respectively, with preliminary evidence of THTQ[7]-like product in 12% yield.

The chemical recognition properties of THT5Q[5] (for CH4, CH2F2, and CH3Cl gases) and THT6Q[6] (for the hydrochloride salts of 1-cyclopentamine and 1,8-octanediamine) were investigated and compared to classical Q[5 and 6].

The surprising finding of THT5Q[5]∙KCl crystalline salt, showing two sets of THT5Q[5] signals in 1H NMR spectrum led to the discovery that a Cl- ion resided in the cavity in solution which is released slowly. The presence of the Cl- ion in the cavity of the solid was established by solid state (SS) 35Cl NMR. This was further supported by the SS 35Cl NMR spectra of Q[5]∙KCl and dioxane@Q[6]∙KCl crystals as comparison. The rates of Cl- release from THT5Q[5] and Q[5] cavity were studied in solution with changes in temperature and in KCl/D2O solutions.

Other reactions discussed are the oxidation of THT5Q[5] which gave isomers of the sulfoxide of THT5Q[5] ((SO)5Q[5]) and a synthetic approach to the preparation of partially-substituted THT2Q[6] which resulted in isomers of the THT2Q[6] and also a monosubstituted THTQ[6].