A Novel Preparation and Purification of Ethyl-β-Cyclodextrins

Abstract

Ethyl-β-cyclodextrin can be widely used for controlled release of drugs, but its application is greatly limited due to the use of toxic ethylation reagents such as diethyl sulfate, chloroethane, and iodoethane in previous synthesis processes. This article expands the application range of ethyl-β-cyclodextrin by using green ethylation reagent instead of previously toxic ethyl reagents to synthesize ethyl-βcyclodextrin. Ethyl-β-cyclodextrins were studied by reaction with diethyl carbonate and β-cyclodextrin in DMF using anhydrous potassium carbonate as catalyst, During the reaction process, in order to avoid oxidation, the samples were kept in a protective atmosphere of N<sub>2</sub> flow. A new green synthesis process for ethyl-cyclodextrins, using silica gel chromatography to synthesize and purify four substituted 6-O-ethyl-cyclodextrins. Their structures were characterized by IR, MS, <sup>1</sup>H-NMR, and <sup>13</sup>C-NMR. The final product with a yield of 4% was obtained by chromatographic separation using acetonitrile-concd aq NH<sub>3</sub>-H<sub>2</sub>O-EtOAc (6:1:3:1) as the eluent. IR data indicate that the obtained product is the expected product. <sup>13</sup>C-NMR characterization indicates that the substitution position of the product is at position 6, <sup>1</sup>H-NMR, and MS characterization indicate that the degree of substitution of the product is 4. This synthesis method takes full advantage of the spatial selectivity of β-cyclodextrin. The method is green and simple. The target product is synthesized in one step, which is superior to previous reports.