New Synthesis Of Sulfonbutyl Ether-β-Cyclodextrin And The Process Optimization

In this paper,the sulfobutyl ether-β-cyclodextrins with low degrees of substitution were synthesized by using the alkaline electrolyzed water as the medium,β-cyclodextrin and 1,4-butane sultone as raw materials,and this new process is conducted by water bath heating and microwave heating method respectively.The structural characterization and the calculation of the degrees of substitution of the products were carried out by means of ¹H NMR,¹³C NMR,FT-IR,MS and element analysis.The reliability of the results calculated by different methods was compared.The effects of the molar ratio ofβ-cyclodextrin and 1,4-butane sultone,reaction temperature,reaction time and p H of alkaline electrolyzed water on the degrees of substitution were studied.The effects of reaction temperature,reaction time and p H of alkaline electrolyzed water on the yield of 3-substituted sulfobutyl ether-β-cyclodextrin were investigated by response surface methodology,and the process optimization model was established to obtain the process conditions with the maximum yield.The results showed that:（1）the sulfobutyl etherβ-cyclodextrin with degrees of substitution of 2,2.5 and 3 were synthesized in this paper.Compared with the water bath heating method,the reaction time of microwave heating method can be reduced from more than ten hours to 2-3 hours,and the yields of the product can be increased by 5-9%.At the same time,the degrees of substitution of the product and the utilization rate of the raw materials are also higher under the same conditions;Using0.5 MPa external pressure,polyvinylidene fluoride with membrane number of G-142and polyamide hollow fiber nanofiltration membrane with membrane number of H-1,the separation effect of sulfobutyl ether-β-cyclodextrin andβ-cyclodextrin is obvious,which can be applied to the industrial production of sulfobutyl ether-β-cyclodextrin.（2）The results showed that the hydroxyl groups at C-2 and C-6 have substitution reactions.The S-O stretching vibration peak at 537 cm^-1 and the C-S stretching vibration peak at 605 cm^-1 showed that the sulfobutyl group has successfully grafted ontoβ-cyclodextrin.The mass spectrum showed that the product was a mixture of various degrees of substitution,and the degree of substitution showed a normal distribution.In addition,the results of substitution degree calculated by NMR and MS are higher and the results of substitution degree calculated by elemental analysis are reliable.（3）In response surface methodology,the yield of 3-substituted sulfobutyl ether-β-cyclodextrin was used as the response value.The optimum process conditions were:the reaction temperature was 77℃,the reaction time was 2.75 h,the p H of alkaline electrolyzed water was 12.7,and the yield of the product reached 70.3%.