金属催化条件下酰胺类化合物的合成研究

发布时间：2018-03-20 22:02

本文选题：金属　切入点：催化　出处：《兰州大学》2017年硕士论文　论文类型：学位论文

【摘要】：酰胺键在生命体构建过程中所扮演着极为重要的角色。例如,蛋白质(包括酶)中的肽键就是酰胺键。同时,酰胺键也广泛存在于很多天然产物和现代医药分子中。因此,很多生物学家和化学家一直将酰胺键的构建放在首要位置。尽管酰胺键的构建方法有很多种,但是其中的大部分还是涉及到偶联剂的使用,这就增加了合成的成本。因此,两者之间的矛盾促使我们继续探究催化条件下合成酰胺键的方法。本文以金属催化条件下,合成酰胺类化合物这个问题为中心,分别合成了α-苯磺酰胺基酮和含异VA唑啉环的酰胺。与此同时,对以上两种产物的生成机理加以研究。具体内容如下:一:异VA唑啉环在有机合成以及药物研究中意义重大,含异VA唑啉环的酰胺类化合物为医药研究提供了更多的选择。在室温下,β,γ-不饱和酮肟在碘苯二乙酸(PIDA)和三氟甲烷磺酸锌(Zn(OTf)2)共同作用下,发生σC-C键裂解,得到氧化腈和互补的含烯键的碳正离子中间体。后者与体系中的腈反应,得到N-烯丙基酰胺。接下来二者发生分子间的1,3-偶极环加成反应,得到了含异VA唑啉环的酰胺。二:鉴于氮自由基难以生成,且与炔键的加成比较困难,我们设想以N-氟代双苯磺酰亚胺(NFSI)为氮自由基前体,与芳基丙炔酸反应,能否合成双苯磺酰基取代的炔烃。实验结果表明,生成了α-苯磺酰胺基酮。反应的机理可能为:在一价铜盐和银盐及配体存在下,N-氟代双苯磺酰胺(NFSI)生成磺酰胺自由基,该自由基区域选择性地加到炔银中间体中距离芳环比较远的一端,得到高活性的烯基自由基。该中间体紧接着发生1,4-芳基迁移伴并伴随脱二氧化硫。然后,发生氧化/水的亲核进攻/半频哪醇重排,最终生成α-苯磺酰胺基酮。
[Abstract]:Amide bonds play an extremely important role in the construction of life forms. For example, peptide bonds in proteins (including enzymes) are amide bonds. At the same time, amide bonds are widely found in many natural products and modern medicine molecules. Many biologists and chemists have always put the construction of amide bonds at the top of the list. Although there are many ways to construct amide bonds, most of them involve the use of coupling agents, which increases the cost of synthesis. The contradiction between the two has prompted us to continue to explore the method for the synthesis of amide bonds under catalytic conditions. This paper centers on the problem of the synthesis of amides under the condition of metal catalysis. 伪 phenylsulfonamide ketones and amides containing isoVA azoline ring were synthesized respectively. At the same time, the formation mechanism of the two products was studied. The main contents are as follows: 1. IsoVA azoline ring is of great significance in organic synthesis and drug research. At room temperature, 尾, 纬 -unsaturated ketone oxime (尾, 纬 -unsaturated ketone oxime) cleavage 蟽 C-C bond under the action of PIDA) and zinc trifluoromethane sulfonate ZnOTfN 2). Nitrile oxide and complementary carbon cationic intermediate containing allene bond are obtained. The latter reacts with nitrile in the system to obtain N-allyl amide. In view of the difficulty of the formation of nitrogen radical and the difficulty of addition with acetylene bond, we imagine that N-fluorobis sulfonimide (NFSI) is used as the precursor of nitrogen free radical to react with aryl propionic acid. The experimental results show that 伪 -benzenesulfonamide ketones have been formed. The mechanism of the reaction may be that in the presence of monovalent copper salts and silver salts and ligands, N-fluorobenzenesulfonamide (NFSI) forms sulfonamide free radicals. The free radical is regioselective added to the end of the silver alkyne intermediate, which is far away from the aromatic ring, and a highly active alkenyl radical is obtained. The intermediate is followed by 1 ~ (4) -aryl migration accompanied by the removal of sulfur dioxide. The nucleophilic attack of oxidation / water / rearrangement of semitronarol was carried out and 伪 -benzenesulfonamide ketone was formed.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O622.6

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