Study On Synthesis Of Hetero Telechelic Poly(Ethylene Glycol) Derivatives

Chemical modification, as an important way to improve clinical and biological properties of biological molecules, has been widely researched and applied in biological medicine, health, food, chemistry, and many other fields. Recently, the preparation of chemical modifier has triggered the enthusiasm of chemical researchers all over the world. Polyethylene glycol(PEG) and its derivatives is one kind of modifier mainly applied in the chemical modification techniques. End group plays a decisive role in the study of the application of PEG and its derivatives. PEG has different characteristics and plays different roles due to different end groups, so it also has practical advantages and prospect in application.Tetraethylene glycol was used as the starting material to synthetize single and double functional group tetraethylene glycol derivatives. The main research is the synthetic route of PEG derivatives and the corresponding technological conditions. First of all, by optimizing the proportion of tetraethylene glycol with p-toluene sulfonyl chloride the tetraethylene glycol single p-toluene sulfonyl reaction was achieved. Then through the simple extraction twice, it is easy to get tetraethylene glycol p-toluene sulfonic acid ester with no separation of column chromatography. And then tetraethylene glycol single azide alcohol was synthetized by azide reaction. Again tetraethylene glycol amine was obtained through hydrogenation reduction method. By the addition of two carbonate two tertiary butyl ester, amino group was transferred amide group. It was transformed into sulfonic acid ester by the reaction with addition of methyl sulfonyl chloride. The coupling reaction of tetraethylene glycol sodium salt, made the growth of tetraethylene glycol chain. Finaly the preparation of hetero telechelic group compounds containing eight ethylene glycol unit was finished by the reaction of diethylene glycol acid anhydride.The target compounds synthesis process of reaction, post processing and product purification process were detailed exploration. The target compound was fully characterized by NMR and mass spectrometry to determine the molecular structure. The purity was determined by the ELSD due to none UV absorbtion of target compound. The entire synthesis process was optimized. Taking the mature experimental method, the pilot test study with scale 60 times was finished. The results showed that the bifunctional PEG derivatives was synthesized successfully, the purity of 99%, expanding the application range of PEG derivatives.