洛芬合成过程高效羰基化反应可循环催化体系的构建

The preparation of dual-functionalized ionic liquids catalysts by coupling of active metal carbonyl & ethyleneoxy groups and its carbonylation in α-aryl ethanol to α-arylpropionic acids through thermoregulated phase transfer catalysis(TPTC) will be investigated. The efficiently seperation, recovery and reuse of the ctalytic systems may be realized，meanwhile the catalytic activity can also be effectively increased. The metal carbonyls which own catalytic activities of carbonylation and the ethyleneoxy groups which can control the performance of thermoregulated phase transfer will be simultaneously assembled into ionic liquids to form dual-functionalized ILs catalysts for carbonylation. Unlike the previous methods of transformation the ligands,the TPSC process,i.e., efficient homogeneous reaction under higher temperature and two phase effective seperation under lower temperature, may be carried out by coupling of the TPTC units and catalytic active units.The loss of noble metal catalysts can also be eliminated in the past TPTC system due to the shedding of the ligand. The active principle of new catalytic system and the difference between TPTC and conventional model may be found out.This reseach will provide the basis for the application of TPTC dual-functionalized ILs in the synthesis of Ibuprofen-type drugs.

本项目拟将活性羰基金属和亚乙氧基结构单元耦合，创制新型双功能化离子液体催化剂并将其应用于α-芳基乙醇羰基化制α-芳基丙酸洛芬类药物的温控相转移催化反应过程，有效提高催化活性和实现催化剂的高效分离回收循环回用。与以往通过改造配体完成贵金属均相催化剂回收相比，本项目利用离子液体的结构设计性将温控相转移结构单元和催化活性结构单元同时组装到同一离子液体中，赋予催化反应体系"高温均相高效反应，低温两相有效分离"性能，消除因配体脱落可能造成的贵金属催化剂流失现象。通过温控相转移催化反应新体系与常规模型反应的结果比较，探索它们之间的差异以及产生差异的原因，提出新反应体系的催化活性原理，为温控双功能化离子液体在α-芳基丙酸洛芬类药物合成过程应用提供依据。

本项目利用离子液体的结构可设计性，首次将含有温控相转移功能的亚乙氧基结构单元和具有羰基化催化活性的羰基金属结构单元耦合组装到同一离子液体中，创制了新型双功能化离子液体催化剂；并成功将其应用于α-芳基乙醇羰基化制α-芳基丙酸洛芬类药物的温控相转移催化反应过程，赋予了新催化反应体系“高温均相高效反应，低温两相有效分离”性能，有效提高了催化活性和实现了催化剂的高效分离回收循环回用，提出了新催化体系下的反应机理。研究表明：随着聚醚链长度的增长，催化剂的流失明显减少；链长为22的催化剂回收循环使用8次，未出现明显活性下降，催化剂损失∠0.2%。该研究为温控双功能化离子液体催化剂在α-芳基丙酸洛芬类药物合成过程应用提供了较为坚实的理论依据，有望为羰基化、氢化、不对称合成等均相有机合成反应解决催化体系的循环回用和提高催化活性提供新途径和新思路。