双功能水溶性酰肼吡啶类-N-氧化物的设计、合成及催化性能研究

Copper-catalyzed Ullmann-type C-N coupling reaction is one of the most effective methods to construct the C-N bonds and the types, structures and stability of the ligands play vital roles in the catalytic system activities. However, these catalytic reactions still have some limitations such as narrow substrate scope, which limit their practical applications. Moreover, the wildly used organic solvent in this kind of reaction is not beneficial for the development of green chemistry. Ongoing the development of green chemistry, in this study, we will focus on the design and synthesis of a series of novel bifunctional water-soluble hydrazinepyridine-N-oxides derivatives as the ligands for copper-catalyzed C-N coupling in water. We will establish a highly efficient and wide groups tolerance catalytic system (copper/hydrazinepyridine-N-oxides) by studying the effect of the alkyl/alkoxy chain length, hindrance and electricty of the ligands. Promoted by the catalytic system, a variety of aryl halides or aryl boronic acid will be aminated with several amines and nitrogen-containing heterocycles in water, which will provide a fast and environmentally friendly synthetic methods for constructing the C-N bonds. We will also study the catalytic mechanism, based on the copper-ligand complexes structures and the structure-activity relationships (SARs) of the ligands, to further optimize the reaction conditions led to more complicated substrates being synthesized.

铜催化的Ullmann型反应是有机合成化学中构建C-N键的有效手段之一，其中催化剂配体的类型、结构和稳定性对催化体系的活性起着至关重要的作用。然而，铜催化体系目前还普遍存在底物适用性不高等因素限制了该反应的实际应用，同时该类反应中广泛使用的有机溶剂也不利于绿色化学的发展。本研究根据当前绿色化学发展趋势，从分子设计角度出发，拟设计合成系列双功能水溶性酰肼吡啶类-N-氧化物（既作配体又作相转移催化剂），用作水相铜催化C-N偶联反应的催化剂配体；通过改变配体烷基/烷氧基链长度、空间结构和电子效应，开发出具有高催化活性和广泛底物适用性的催化体系，实现水相芳基卤代物或芳基硼酸和胺或含氮杂环的偶联，为构建C-N键提供一种快速和环境友好的合成方法。进一步通过合成金属铜配合物，并依据配体结构与催化活性的构-效关系等，研究该催化反应的反应机理，为进一步优化反应以实现更多更复杂底物在温和条件下合成奠定基础。

铜催化的Ullmann型反应是有机合成化学中构建C-N键的有效手段之一，其中催化剂配体的类型、结构和稳定性对催化体系的活性起着至关重要的作用。然而，该反应仍存在催化效率不高、底物适用性不广等不足，限制了该类反应的实际应用，且该类反应中广泛使用的有机溶剂也不利于绿色化学的发展。基于此，本项目通过三年的工作，主要开展了三方面的研究：①从配体结构设计出发，合成了系列水溶性酰肼吡啶类-N-氧化物，并建立了三种铜/配体催化体系，实现了水相/水介质中碳-氮键的构建；②为实现催化剂循环、低金属溢出和减少金属在产物中的残留污染，建立了MOF-199和Cu-MOF-74催化的C-N和C-CN键的构建方法；③建立了Cu/Ag共催化的脱羧氨化反应，为芳香胺的选择性N-芳基化提供了一种新的选择。本项目的研究工作进一步发展和完善了C-N/CN偶联反应方法，为该类反应提供了新的思路。