铜催化邻卤芳基N-磺酰腙异构化和环化合成1H-吲唑类化合物的方法研究

发布时间：2018-12-11 20:48

【摘要】：1H-吲唑类化合物具有广泛的生物活性,包括抗炎,抗癌,抗抑郁,抗HIV和抗生素活性。因此,对1H-吲唑类化合物的合成的研究引起了人们相当大的兴趣,大量的努力致力于开发构造1H-吲唑骨架的有效方法。合成1H-吲唑化合物传统的方法,一般通过苯胺的重氮化或亚硝基化反应,或者是通过叠氮化合物的环加成反应制备。这些方法通常需要高毒性或不稳定的试剂,例如胼、硝基、重氮或叠氮化合物,并且需要非常苛刻反应条件。在制备吲唑的众多方法中,最有效的途径之一是由邻卤代芳基N-磺酰腙的催化环化。目前,已经有些课题组报道了以Z构型邻卤代芳基N-磺酰腙为原料合成1H-吲唑化合物,但是E构型.邻卤代芳基N-磺酰腙仍然不适用。由于腙中的C=N双键的异构化在化学转化中有很广泛的应用潜力,因而引起相当大的关注。通常,这种双键的异构化可以通过光化学或加热来实现。在本工作中,我们提出一种新的异构化方法。在温和的条件下,用一水合醋酸铜作催化剂来实现腙中的C=N双键的异构化,然后通过分子内高效的C-N键的偶联反应,提供了一种通过E/Z混合构型的邻卤代芳基N-磺酰腙方便制备1H-吲唑的新方法。与之前报道的一些方法相比,此合成1H-吲唑的新方法具有试剂成本低,操作方便,产率较高以及底物范围广的优点。此方法还经过了实验证明,适用于克量级别的反应,因此具有很好的应用价值。本方法为该类化合物的合成提供了方便。
[Abstract]:1 H-indazole compounds have a wide range of biological activities, including anti-inflammatory, anti-cancer, anti-depressant, anti-HIV and antibiotic activities. Therefore, the study on the synthesis of 1H-indazole compounds has attracted considerable interest, and a lot of efforts have been devoted to the development of an effective method for the construction of 1H-indazole skeleton. The traditional method of synthesizing 1H-indazole compounds is usually prepared by diazotization or nitrite reaction of aniline or cycloaddition of azide compounds. These methods typically require highly toxic or unstable reagents, such as callosal, nitro, diazo or azide compounds, and require very harsh reaction conditions. One of the most effective methods for the preparation of indazole is the catalytic cyclization of o-haloaryl N-sulfonyl Hydrazone. At present, some research groups have reported the synthesis of 1H-indazole compounds from 2-haloaryl N-sulfonyl hydrazone, but the E configuration has been reported. O-haloaryl N-sulfonyl Hydrazone is still not applicable. The isomerization of Con N double bonds in Hydrazone has wide application potential in chemical transformation, so it has attracted considerable attention. In general, this double bond isomerization can be achieved by photochemistry or heating. In this work, we propose a new isomerization method. Under mild conditions, the isomerization of Con N double bonds in Hydrazone was realized using copper acetate monohydrate as catalyst, and then the coupling reaction of intramolecular high efficiency C-N bond was carried out. A new method for the convenient preparation of 1H-indazole by O-haloaryl N-sulfonyl hydrazone with E- / Z mixed configuration is presented. Compared with some methods reported before, this new method has the advantages of low reagent cost, convenient operation, high yield and wide substrate range. The method has been proved to be suitable for the reaction of Yu Ke's quantity level, so it has good application value. The method is convenient for the synthesis of this kind of compounds.
【学位授予单位】：西北大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626

【相似文献】