Efficient synthesis of pure monotosylated beta-cyclodextrin and its dimers

6-O-Monotosyl-beta-cyclodextrin (mono-Ts-beta CD) is one of the most important intermediates in the production of substituted beta CD. So far, performing the monotosylation reaction and, in particular, the purification steps was challenging, relied on toxic solvents, and resulted in long and expensive procedures at, importantly, low yields. Here, the reaction of cyclodextrin with p-toluenesulfonyl chloride in aqueous environment is described to obtain a highly pure mono-Ts-beta CD, for which a single-step purification with a cation exchange resin was applied. With this synthetic route and purification, yields could be increased from typically <10-15% to 35%, and organic solvents could be avoided. As characterized by FTIR, mass spectrometry, elemental analysis, and NMR, mono-Ts-beta CD was obtained with a molar purity of >98 mol %. From mono-Ts-beta CD, beta-cyclodextrin dimers linked by ethylenediamine (bis-Et-beta CD) were successfully prepared (yield 93%, purity 96 mol %) in a one-step approach using an anion exchange resin to trap leaving groups that typically interfere in the reaction. This synthesis procedure with a direct collection of side-products may be a general strategy applicable for nucleophilic substitution of tosylated cyclodextrins. (c) 2013 Elsevier Ltd. All rights reserved.