亚铜催化的选择性N,X-(X=O,N)偶联反应机理的实验研究

Copper(I)-catalyzed Ullmann reactions are the classical methods for the formation of carbon-heteroatom bonds. However, most of the reported reaction substrates are relatively simple, and the selective coupling reactions of reaction substrates containing multiple nucleophilic groups are less reported. In order to broaden the substrate scope of selective coupling reaction, the reaction mechanism, including a detailed understanding of chemical reaction pathways, the main driven forces of chemo-selectivity and their determinants must be clearly explained. In recent years, the mechanism of chemo-selectivities in copper(I)-catalyzed N-, O-arylation of amino alcohols have been studied by the method of theoretical calculation. However, different results were obtained when different computing methods and experimental models were applied. The mechanism of other reaction substrates were mostly speculated from the experiment phenomena of selective coupling reactions; it's difficult to make a uniform conclusion on the selective mechanism. Therefore, other experimental ways need to be applied to determine the mechanism of selective coupling reaction. By combining the mostly studied C-N and C-O coupling reactions, we intend to study the mechanism of selective N, X-（X=O, N, the same below）coupling reaction by experimental methods, for example, characterizing the key intermediates, tracking the reaction process by spectrograms, designing of comparative experiments and kinetic reactions. Through the separation and characterization of reaction intermediates and the reaction of intermediates with aryl halides, the preferred reaction pathway of selective N-, X- coupling reaction will be demonstrated. Comparative analysis of the reaction rate constant, activation energy and other kinetic parameters of the formation and conversion reactions of reaction intermediates will make the main driven force of the selective coupling reactions and their determinants clear. From the above-mentioned experimental studies, the detailed mechanism of selective N-, X- coupling reaction will be confirmed, which will provide theoretical basis and guidance for synthesizing a greater variety of more complex organics.

亚铜催化的Ullmann反应是构建碳杂键的经典方法，然而多数反应底物比较简单，含多官能团复杂底物的选择性偶联反应报道较少。为了拓展复杂底物的范围，必须了解反应的具体路径、驱动力及其决定因素。目前，仅通过理论计算的方法对氨基醇的选择性偶联反应机理进行了研究，得到了不同的机理结论；其他底物的机理研究多是基于实验现象的简单推测，无法得到统一的结论。因此，需要采用不同的机理探索手段，来确定选择性偶联反应的机理。本课题拟在报道较多的C-N、C-O偶联反应基础上，采用中间体确认、谱图跟踪、对比实验、动力学研究等手段，对选择性N-, X-（X=O, N，下同）偶联反应机理进行研究。通过中间体的分离确认及其与卤代芳烃的反应，确定选择性偶联反应的优势路径；通过比较逐级反应的动力学参数，探讨选择性偶联反应的决定步骤及其决定因素。最后，明确提出N, X-选择性偶联反应的机理，为合成更复杂的有机物提供理论指导。

反应中间体的分离和确认是一类重要的探讨反应机理的方法。我们选择有机反应中常见的酰胺类、咪唑及邻菲罗啉类化合物做反应底物，用中间体分离确认、谱图跟踪等方法研究了复杂偶联反应的反应机理。首先，以1,1'-双（二苯基膦）二茂铁的二氯桥做反应前驱体，甲醇钠或氢化钠做碱，二氯甲烷作溶剂、氮气环境室温条件下和，得到了6个酰胺类反应中间体（62%-80%），并得到了其中2个配合物的单晶结构，发现羰基取代基较胺基取代基能更大程度地影响中间体的生成；差热热重实验结果表明：该类中间体的热分解温度均高于230℃，说明中间体能稳定存在于高温的偶联反应中；在温度110℃，溶剂DMF，氮气环境中，模拟了中间体和碘苯（及对甲碘苯）的偶联反应，以中等产率（60%-75%）得到了12个芳基取代酰胺类化合物；用谱图跟踪方法研究了中间体和卤代芳烃的反应，发现1.5~2小时后，中间体开始减少，10~12小时后，偶联反应达到饱和。其次，以三苯基膦和双(2-二苯基膦)苯醚做辅助配体，Cu(CH3CN)4•BF4做反应前驱体，氢氧化钾或氢氧化钠做碱（或不加碱），二氯甲烷和甲醇混合物做溶剂，氮气环境室温条件下，制备了一系列同时含邻菲罗啉和咪唑基团的中性（12个）和离子型（2个）配合物（产率68%-92%），并得到了其中5个中间体的单晶结构；荧光光谱结果表明：离子型中间体基本不发光，多数中性中间体（8个）能发射强烈的黄光或橙黄光；密度泛函计算表明取代基能影响中性配合物的电荷密度、前线轨道的成份和含量等电子传输性质；在温度120℃，溶剂DMSO，氮气环境中，模拟了中性配合物和碘苯的偶联反应，以中等产率（62%-78%）得到了12个芳基取代咪唑-邻菲罗啉类化合物。最后，得到了6个基于咪唑-取代邻菲罗啉类化合物的中性配合物，研究了其发光性及热稳定性。总之，在不同反应条件下制备出不同的反应中间体，并对反应中间体和卤代芳烃的反应性进行研究，力求明确复杂反应物偶联反应过程的更多细节，从而对不同种类偶联反应反应条件的优化提供理论指导。