纳米氧化铜催化C-H官能团化合成杂环衍生物及催化机理研究

Heterocycles are one of the most important structural motifs in pharmaceutically active compounds and natural products. Searching efficient methods for the synthesis of heterocycles and their derivatives have received great interests from the perspective of medicinal chemistry and organic synthesis. Considering the preference of modern green chemistry for more environmentally friendly materials, the development of an efficient reaction system with recyclable nanometer catalysts is highly desirable. The project will focused on the preparation of nano copper oxide with different structures and developing their catalytic application on the synthesis of heterocycles including C-N, C-O,C-S through C-H functionalization. Nano CuO catalyst with high efficiency and high selectivity will be found through investigating the effects of different nanostructures on catalytic activity. The effects of catalyst, base, solvent, temperature, and reaction time will be studied. The scope and functional group compatibility of the nano CuO catalyzed oxidative C-H functionalization will be investigated in the optimal reaction conditions. Furthermore, the mechanism of this nano catalyzed reaction will be investigated by XRD and SEM analysis of the catalysts after the reaction and ICP analysis of the leaching of the copper from the CuO after the reaction. It is noteworthy that nano CuO could be recycled and will have the potential as an ideal catalyst for the industrial production because of their stability and availability.

杂环是一类重要的结构单元，在天然产物、药物化学、有机合成等领域有着广泛应用。使用高效、价廉、可回收循环使用的纳米催化剂通过C-H 官能团化反应合成杂环及其衍生物具有重要的研究意义。本申请旨在制备多种形貌的氧化铜纳米结构，通过纳米氧化铜催化剂对C-H官能团化（构筑C-N、C-O、C-S键等）反应活性和选择性研究，探索催化剂形貌、结构对催化活性的影响，筛选出高效率、可循环、绿色化的催化体系，并将该体系应用于构筑含C-N、C-S、C-O键等杂环衍生物合成领域，发展新型杂环衍生物的合成方法。探索电子效应、立体效应对反应的影响，研究底物的范围，官能团的适用性。利用现代物理和化学手段（XRD、SEM、TEM、NMR、MS、ICP等），通过研究反应的中间体，催化反应前后催化剂的组成、成分、形貌，反应液中铜离子浓度等探索催化反应机理。

本项目以纳米氧化铜催化C–H官能团化构筑C–C、C–N、C–O、C–S键为研究目标，制备了多种形貌的氧化铜，对其进行了物相鉴定和形貌表征。实现了纳米氧化铜催化的杂环C–H芳基化和烯基化；纳米氧化铜催化炔烃C–H烯基化，立体选择性合成(Z/E)-共轭烯炔，特别是高产率合成了顺式共轭烯炔和不对称共轭二炔；拓展了纳米氧化铜在C–H官能团化合成含氮杂环衍生物中的应用，实现了氧化铜纳米粒子催化醇氧化，进一步与脒环化合成喹唑啉，与苄醇、炔、偕胺肟等反应构筑C–N键，高产率的合成三唑及嘧啶类杂环化合物。通过对反应前后催化剂的XRD和EDS表征及反应后有机溶液进行的原子吸收光谱(AAS)分析，发现催化剂在反应前后没有发生改变，证明反应是非均相催化过程。反应方法简单、高效、产物易分离提纯，催化剂性质稳定，反应后可以回收重复利用。在本项目的资助下，我们还发展了一种在室温水相中，铜/TMEDA催化C–S键的偶联反应合成N-取代苯并杂环类化合物的新方法以及醋酸铜催化N–H键的活化、C–N/N–N键的串联来合成1,2,4-三唑类衍生物和醋酸铜催化脒的盐酸盐与醇在弱碱存在下以空气为氧化剂高效合成1,3,5-三嗪类衍生物。