铜催化的交叉偶联反应研究

【作者】 王晔峰；

【导师】 郭庆祥；

【作者基本信息】 中国科学技术大学 ， 有机化学， 2006， 博士

【摘要】 交叉偶联反应是有机化学中一个重要的内容，其在化工和医药中都有着广泛的应用。传统的反应一般需要特定的催化剂和在苛刻的条件下进行反应，对于工业操作和经济上都很有局限性。最近的报道大部分集中在使用了含金属钯的催化剂。尽管这样的交叉偶联反应有较高的效率，然而钯高昂的价格以及其较强的毒性阻碍了这类反应在很多场合中(例如药物合成)的应用。同时，这些催化剂需要使用大量的对环境有很大毒害作用的膦配体。鉴于工业化和环保的需求，研究高效、低毒、便宜和环保的催化体系有着重要的意义。因为相对于钯来说，铜是一种廉价而且低毒的金属。使用铜催化剂来实现交叉偶联，不仅是过渡金属催化领域中的一个新动向，而且是化学工业绿色化进程中的一个挑战性课题。Sonogashira反应是合成含有两个芳香环的取代炔烃的重要手段。我们设计了一种以CuI为催化剂的Sonogashira反应体系，在此体系中可以有效完成各种碘／溴代苯化合物与炔烃的偶联反应。与传统的反应条件相比，它是一种无需Pd催化剂及膦配体参与的反应过程，更利于该反应的工业化应用。芳香硫氰酸化合物也是有机合成中一种重要的起始原料。我们使用CuI为催化剂，在温和的条件下很好地催化了碘代芳香化合物的硫氰酸化反应，真正实现了铜催化的硫氰酸芳香化合物的合成，相对于文献报道的方法更加简便、环保，并且降低了副产品的产生。此外，我们还设计了新的N，N’—芳香取代肼的合成路线，酰肼的首次芳香化反应可以在CuI的催化下完成，其二次芳香化亦可以在铜盐的参与作用下、于很温和的条件下完成。克服了金属钯作为催化剂的使用，相对于钯催化的合成过程，这一方法更加简便、易行、低成本。更多还原

【Abstract】 Cross-coupling reaction is one the important reactions in organic chemistry. It finds wide applications in chemical engineering and medical syntheses. It is very limited for the traditional synthesis methods due to its specific catalyst and exigent parameters. Recent literatures are focused on the palladium catalyst. Although the catalyst favors the higher cross-coupling efficiency, the high price and strong toxicity of palladium hinder the applications of catalyst, such as in the medical syntheses. At the same time, the catalyst needs large amount of phosphine coordinators that is extremely toxic to the environment.To meet the requirement of the industrial and environmental protection, the study on a high efficiency, low toxic, low price and environmental benign catalytic system is of impending importance. Compared with palladium, copper is a kind of low price and low toxic metal. It is a new trend in the transition metal catalyst and a challenging project in the green process for the chemical engineering to use copper as the catalyst.Sonogashira reaction is an important method to synthesize alkyne substitute which consists of two aromatic rings. A Sonogashira reaction system is designed using CuI as the catalyst, in which multi kinds of coupling reactions of iodobenzene or bromobenzene with alkyne can be processed effectively. Compared with traditional synthetic conditions, the designed method does not use palladium catalyst and is processed without phosphine used as ligands, which favors the industrilization of the current method.Aryl thiocyanates are a kind of the important raw materials in organic synthese. CuI is used in the study to catalyze the reactions of iodobenzene in mild reaction parameters, which truly realizes the synthesis of aromatic rhodamic acid compounds using copper as the catalyst. Compared with those methods in the literature, the current one is facile, environmental benign and with low by-product production.Besides, a new synthesis route to N, N’-aromatic diamide substitute is designed. The first aromatic reaction of hydrazide can be accomplished using CuI as the catalyst, while the second one can be achieved at mild reaction conditions when copper acetate is engaged in the reaction. The designed method overcomes the palladium catalyst process, which is facile and low price.更多还原