三氟甲磺酸盐催化体系下羧酸酰化的傅克反应研究

Metal triflates as novel types of Lewis acid catalysts have been applied to a variety of organic transformations due to its high activities, low catalyst loadings and recyclable characteristics, but still suffer from some major drawbacks such as narrow substrate types, and difficult catalyst recovery and purification associated with some reaction systems. This project proposes to prepare highly efficient and readily recoverable metal triflates catalysts incorporated within the mesochannels of MCM-41 and SBA-15 and to study its catalytic intermolecular and intramolecular Friedel-Crafts acylations with carboxylic acids in place of acid chlorides and acid anhydrides as acylating agents under microwave assistance and further applied the new catalytic system to prepare some important drugs and intermediates. The methods for catalyst recovery and recycling and plausible catalytic mechanism will be elucidated. Our project can provide the theoretic support for the application of these metal triflates in industry.

新型路易斯酸催化剂三氟甲磺酸盐因其用量少、活性高、可回收套用等优点被应用于各种有机反应中，但也存在底物适应范围窄、小量反应中催化剂难以回收纯化等问题。本项目拟把三氟甲磺酸盐类催化剂负载于介孔分子筛MCM-41和SBA-15载体上，制备出高效易回收的反应催化体系；以羧酸代替酰氯和酸酐为酰化试剂，微波辅助条件下进行分子间及分子内的傅克反应，并应用于医药中间体的合成中；探索催化剂的回收套用方法，考察反应机理，揭示反应规律，为三氟甲磺酸盐类催化剂的工业应用奠定理论基础。

新型路易斯酸催化剂三氟甲磺酸盐因其用量少、活性高、可回收套用等优点被应用于各种有机反应中，但也存在底物适应范围窄、小量反应中催化剂难以回收纯化等问题。项目研究之初，我们采用浸渍法把三氟甲磺酸盐类催化剂负载于介孔分子筛MCM-41和SBA-15载体上，并把制备的负载催化剂M(OTf)x/MCM-41和M(OTf)x/SBA-15应用于傅克化反应中。然后，在Yb(OTf)3/MCM-41催化下我们以羧酸替代酰氯和酸酐为酰化试剂与萘酚和苯酚衍生物进行分子间傅克酰基化反应，合成了一系列羟基芳酮类化合物；为进一步拓展研究范围，我们以2-苯氧基烟酸和2-苯硫基烟酸为底物，在Yb(OTf)3/SBA-15催化下进行分子内傅克酰基化反应，合成了一系列1-氮氧杂蒽酮和1-氮杂硫杂蒽酮类化合物；在合成氧杂蒽酮和硫杂蒽酮时，我们以离子液体[BMI][PF6]为溶剂，缩短了反应时间、提高了产物收率。其次，我们对负载催化剂经过滤、洗涤、干燥简单步骤进行回收，套用四次催化效果未见显著降低。此外，我们把负载催化剂应用在喹诺酮类抗癌药物的合成中，对合成的喹诺酮类化合物进行了体外抗肿瘤活性研究，并利用Discovery Studio软件进行了分子模拟研究。相关研究结果，已发表研究论文2篇，申请中国发明专利5项，获授权专利2项，培养本科生7名。