摘要
合成头孢呋辛的关键中间体3-去氨甲酰基头孢呋辛(DCC)由3-去乙酰基-7-氨基头孢烷酸(D-7-ACA)溶液与酰氯试剂缩合得到,其中利用高浓度NaOH溶液将D-7-ACA溶解在水和甲醇中是第一步。而D-7-ACA中的β-内酰胺环在强碱性条件下容易发生开环反应,造成收率不高。传统反应釜不能精确控制体系的pH、混合效果差,因此溶解得到的D-7-ACA溶解浓度低。采用一种膜分散微反应器,实现了高效溶解D-7-ACA,并研究了D-7-ACA在不同初始浓度、不同温度和pH条件下的降解动力学。接着详细探讨了pH、温度和循环流速等因素对膜分散微反应器溶解D-7-ACA的影响。结果显示,利用膜分散微反应器在最优条件下得到的D-7-ACA溶解浓度为76.50 mg/ml,DCC收率为91.90%,相比传统搅拌法分别提高了5.91%和5.61%。
3-Decarbamoyl-cefuroxime(DCC),the key intermediate for the synthesis of cefuroxime,is obtained by condensing the 3-deacetyl-7-aminocephalosporanic acid(D-7-ACA)solution with the acid chloride.The dissolution of D-7-ACA in water and methanol using high concentration NaOH solution is the first step.However,theβ-lactam ring in D-7-ACA is prone to ring-opening reaction under strong alkaline condition,resulting in low yield.The D-7-ACA dissolution has low concentration and low efficiency in a traditional tank,due to the imprecise pH control and poor micro-mixing.Therefore,a new membrane dispersion microreactor was designed and used to dissolute D-7-ACA.Firstly,the degradation kinetics of D-7-ACA at different concentration,temperature and pH value were investigated.Then the effects of the pH,temperature,and circulation flow rate on the dissolution concentration were investigated carefully.The results showed that the concentration of the D-7-ACA solution is about 76.50 mg/ml,and the target product DCC yield is about 91.90%under the optimal conditions using membrane dispersion microreactor,which were increased by 5.91%and 5.61%,respectively,compared to using traditional reactor.The microreactor provides a good choice for industrially dissolving pH-sensitive drugs.
作者
谢煜
张民
胡卫国
王玉军
骆广生
XIE Yu;ZHANG Min;HU Weiguo;WANG Yujun;LUO Guangsheng(State Key Laboratory of Chemical Engineering,Department of Chemical Engineering,Tsinghua University,Beijing 100084,China;NCPC Hebei Huamin Parmaceutical Co.Ltd.,Shijiazhuang 050031,Hebei,China)
出处
《化工学报》
EI
CSCD
北大核心
2023年第2期748-755,共8页
CIESC Journal
基金
国家自然科学基金项目(21878169,21991102)
国家重点研发计划项目(2019YFA0905100)
清华大学自主科研计划项目(2018Z05JZY010)。
