Synthesis of the CD ester derivatives

The benzoyl acid ester CD is an important intermediate in CD modification. Selecting the appropriate nucleophile (iodide, azide, thio-amyl acetate and hydroxylamine, alkyl amines) to attack the carbon atoms which connect with tosyl, can trigger nucleophilic substitution reaction. Then, series of functional CD sulfonate derivatives can be obtained. 

Dissolve the pre-treated dry -CD in dry pyridine, and mix with the dry pyridine solution of p-TsCl. Stir rapidly in the ice bath for cooling to 0°C. Keep the reaction solution for 24 h under 4°C, and then for another 24 h at room temperature. Finally, add 1 mL of distilled water to stop the reaction. Most of the pyridine should be removed under a low pressure and below 40°C. The residue is dissolved in hot distilled water to remove the insoluble material after vacuum evaporation. The crude product should be soaked in ether. Filter the liquor to get the white powder, and re-crystallize in water for four times, then vacuum dry for 4h. The final yield is 32% [11]. 

Dissolve 8.0 g fi-CD in 320 mL NaOH (0.15mol/L) aqueous solution at room temperature. Drop 8.0 g of the prepared solution in the toluene sulfonyl chloride (p-TsCl) solution which contains little acetonitrile. While stirring the reaction buffer, add Imol/L NaOH solution continuously to maintain the pH above 12.5. In order to terminate the reaction, pour Imol/L HCl into the buffer. Filter the unreacted p-TsCl and desalt by dialysis. After vacuum evaporation, add 400 mL of methanol. Filter the insoluble components and then vacumn evaporate. 

The resulting product needs to be dissolved in hot water, followed by the cooling process, i.e. store in the fridge for 1 week. Filter the white precipitate. Then vacuum evaporate to obtain the final product. The yield is about 53%. After purification the yield is about 42% [12]. 

Dissolve the silylated /3-CD in 50 mL pyridine. Add 1.3 g DMAP and 2.1 g p-TsCl and keep the mixture at 50°C for 24 h. Concentrate the reaction solution by vacuum evaporation. Extract the residue by ethyl acetate. After washing the filter cake by HCl and NaHCOa continuously, the product is purified by column separation and the yield is about 58% [13]. 

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