Interaction of β-cyclodextrin with tosyl chloride in an aqueous alkaline medium

Abstract

The regioselective functionalisation of the cyclodextrin matrix provides the possibility of purposefully altering the ability of cyclodextrins to form inclusion compounds, as well as to ensure their solubility, thus expanding the scope of their practical application [1, 2]. The most significant and promising trend in the selective modification of β-cyclodextrins consists in the preparation of tosyl derivatives, given that the substitution of such nucleophilic reagents as iodide, azide, thioacetate, hydroxylamine, alkylamide or polyalkylamide for the tosyl group results in the corresponding monosubstituted derivatives. In this study, we impl emented a method for the synthesis of mono-6-O-(p-toluenesulphonyl)-β-cyclodextrin, which was improved by β-cyclodextrin reacting with tosyl chloride in an aqueous medium in the presence of a base. The reaction of β-cyclodextrin with tosyl chloride in an aqueous alkaline medium produced a 58% yield of mono -6- O-(p-toluenesulphonyl)-β-cyclodextrin not requiring additional purification. The optimal concentrations of β-cyclodextrin and tosyl chloride were found to be 0.0032 mol/l and 0.0015 mol/l, respectively. It was shown that a decrease in the rate of filtering the unreacted tosyl chloride out of the reaction mixture is acc ompanied by an increase in the proportion of ditosyl derivatives and mono(3,6-anhydro)-β-cyclodextrin resulting from the intramolecular cyclisation of mono-6-O-(p-toluenesulphonyl)-β-cyclodextrin at room temperature under alkaline conditions. The structure of the obtained mono-6-O-(p-toluenesulphonyl)-β-cyclodextrin was confirmed using Proton NMR Spectroscopy. The proton NMR spectrum of the product resulting from the reaction of β-cyclodextrin with tosyl chloride contains signals corresponding to a tosyl radical: a singlet (2.42 ppm) and two doublets (7.41–7.43 ppm) produced by hydrogens of the benzene ring having radicals in the para position. Monosubstitution was confirmed by comparing the integrated intensities of signals produced by the protons of the cyclodextrin skeleton and the protons from the aromatic part of the reaction product. Their ratio indicated that only one of the seven primary hydroxyl groups of β-cyclodextrin was substituted.