柠檬酸解离钛配位络合药物在4AA制备中的应用  

Application of Citric Acid Dissociated Titanium Coordination Complex in 4AA Preparation

作　　者：莫德欢 叶敏 张雁 毕鸿亮 张所德 MO De-huan;YE Min;ZHANG Yan;BI Hong-liang;ZHANG Suo-de(Guangdong Academy of Science,Guangzhou 510070,China;Guangdong Institute of Bio-Medicinal Technology,Zhuhai 519090,China)

机构地区：[1]广东省科学院,广东广州510070 [2]广东省生物医药技术研究所,广东珠海519090

出　　处：《化工管理》2020年第19期101-103,共3页Chemical Engineering Management

基　　金：广东省科学院2018年实施创新驱动发展能力建设专项资金项目(2018GDASCX-0805);广东省科学院2018年实施创新驱动发展能力建设专项资金项目(2018GDASCX-080)。

摘　　要：四氯化钛作为反应物,在(3R,4R)-3-[(R)-1-叔丁基二甲基硅氧乙基]-4-乙酰氧基-2-氮杂环丁酮(4AA)合成过程中参与成环反应,钛离子与产物也容易形成络合。在pH<4的醇溶液中,柠檬酸竞争配位钛离子,将产物解离进入有机相。通过单因素试验筛选醇溶剂为异丙醇,可选择(1+1)盐酸或磷酸调节pH至4以下,结果显示最佳解离条件为:40%柠檬酸溶液48.0g;异丙醇浓度为0.5%,用量200mL;反应时间30min;解离产物收率76.7%。Titanium tetrachloride,as a reactant,takes part in the cyclization reaction during the synthesis of 4AA,and titanium ion and the product are easy to form complexation.In the alcohol solution with pH<4,citric acid competes for the coordination of titanium ion and dissociates the product into the organic phase.Through single factor test,isopropanol is selected as the alcohol solvent,and(1+1)hydrochloric acid or phosphoric acid can be selected to adjust the pH below 4.The best dissociation conditions are:48.0g 40%citric acid solution;0.5%isopropanol,200mL dosage,30min reaction time,and 76.7%yield of dissociation products.

关 键 词：钛络合物 配位 解离 4AA 

分 类 号：TQ465[化学工程—制药化工] O641.4[理学—物理化学]