不对称卟啉化合物合成过程中传递及分离规律研究

Contraposing some problems presently existing in the rapid synthetic reactions of asymmetric porphyrin compounds such as poor product selectivities,low yields and difficult separation and purification due to the diffusion of different substrates, less disparity in transfer velocities of different substrates and unclear transfer rules, the objectives of this project will aim at improving the diffusion rates of different reactant aldehydes and forming a gradient transfer to affect the reaction speeds of aldehyde and pyrrole. Thus, the reaction speeds of different substrates will be effectively controlled and the synthetic yields of asymmetric porphyrins will increase greatly. At the same time, the rapid and gradient separation will be realized by selecting the appropriate separatory columns. And further, the separation yields of target products will be improved and the synthetic rules in large-scale preparation of asymmetric porphyrins will be deeply investigated. The core science problems of large-scale synthesizing asymmetric porphyrins with the condensation of various aldehydes and pyrrole including the relationship between the structures or diffusion velocities of reactant aldehydes and the reaction activities, selectivities and yields of products will be emphatically investigated. By effectively controlling the transfer and separation velocity, the large-scale synthesis of asymmetric porphyrins will be realized, which greatly increasing the selectivities and yields of products and simplifying the operation of products separation and purification. The investigation of improving the yields of asymmetric porphyrin products by gradient diffusions and separation methods has not been reported in the present literatures. And then the research results will provide important fundermental data and theorical basis for the large-scale synthesis of asymmetric porphyrins in high yields.

针对目前不对称卟啉化合物合成过程中因反应快、不同底物醛扩散、传递速度差小而难以控制、且反应规律不清导致产物选择性差、收率低，产物分离纯化困难的问题，本项目旨在通过调控不同反应物醛的扩散速度，形成梯度传递来影响其与吡咯的反应速度，调控不同底物之间的反应速度，大幅度地提高不对称卟啉的合成收率。同时通过选择合适的分离柱，实现产物的梯度分离，进一步提高目前产物的分离收率，探讨规模化制备不对称卟啉化合物的规律；重点研究多种醛与吡咯发生缩合规模化制备不对称卟啉化合物的核心科学问题- - 原料醛的结构和扩散速度与卟啉产物选择性和收率之间的关系，通过调控传递和分离速度，实现不对称卟啉的规模化合成，以期大幅度地提高不对称卟啉产物的选择性和收率，并使其分离纯化更加简单、有效。通过梯度扩散反应和分离方法提高产物收率的研究尚未见文献报道，且研究结果将对不对称卟啉高收率的规模化合成提供重要的基础数据和理论依据。

针对目前不对称卟啉化合物合成过程中因反应快、不同底物醛的扩散、传递速度差别小而而造成合成反应及产物难以控制、且反应规律不清导致产物选择性差、收率低，产物分离纯化困难等问题，本项目对不对称卟啉的合成方法及影响因素进行了全面系统深入的研究。包括系统地探索了A3B型和A2B2型不对称卟啉的合成方法，研究了反应溶剂、温度、催化剂、氧化剂、反应时间、加料顺序以及底物中取代基等因素对反应收率的影响，并对后处理过程进行了改进，优化了反应条件，提高了不对称卟啉产物的选择性,并使其分离纯化过程更加简单、有效，使反应的收率得到大幅度的提高。发展的一锅法合成A3B型卟啉方法的收率最高可达到22.8%，并实现不对称卟啉的规模化合成，为不对称卟啉及其金属卟啉的合成及广泛应用打下了坚实的基础。此外，还通过密度泛函理论（DFT）和化学计量学方法对相关影响因素进行了理论研究。同时，还采用所合成的不对称卟啉对仿生催化氧气氧化环己烷制备己二酸的方法进行了改进研究，发现催化剂的催化活性与共催化剂的极性紧密相关，产物的总选择性和己二酸的选择性分别高达96.3%和50.9%。最后，还扩展研究了所合成的卟啉及其类似物在茶叶及酒等天然产物中微量成分光谱分析、香精香料合成及质量控制等方面的应用，并取得了较大进展。