酰氯法制备布洛芬-聚乙二醇酯

Synthesis and Characterization of Ibuprofen-Polyethylene Glycol Ester wth New Methods

分别用氯化亚砜(方法1)、草酰氯(方法2)两种方法将布洛芬[2-(4-异丁基苯基)丙酸]活化成2-(4-异丁基苯基)丙酰氯(Ⅰ),再与聚乙二醇(PEG)的端羟基反应生成PEG修饰的布洛芬-聚乙二醇酯,即2-(4-异丁基苯基)丙酸-聚乙二醇酯(Ⅱ)。分别用核磁共振(1H-NMR)、红外光谱(IR)和凝胶渗透色谱(GPC)对其进行了表征,结果表明成功合成了含布洛芬端基的PEG大单体,分子量分布窄,d为1.047。溶解性试验表明Ⅱ的水溶性很好。草酰氯法反应条件温和,产率更高,说明草酰氯法更优。

Ibuprofen-polyethylene glycol ester（Ⅱ）,2-（4-isobutylphenyl） propionic acid-polyethylene glycol ester,could be designed and obtained from the reaction of polyethylene glycol（PEG） with 2-（4-isobutylphenyl） propionic acyl chloride（Ⅰ）,which was prepared in high yield by the reaction of ibuprofen with thionyl chloride（method 1） or oxalyl chloride（method 2）.The structure analysis and characterization of Ⅱ were studied by 1H nuclear magnetic resonance spectrum（1H-NMR）,infrared spectrum（IR） and gel permeation in chromatography（GPC） method.The results show that Ⅱ is synthesized successfully,and the molecule distribution of Ⅱ is 1.047.Ⅱ is dissolvable in most organic solvents such as CH2Cl2,CHCl3,THF,DMF and DMSO.The solubility of Ⅱ has been improved in aqueous solutions.Compared with method 1,the method 2 has the advantages of milder reaction condition,higher yield.