炔丙醇衍生物参与的吡唑和稠合吡啶衍生物的合成

发布时间：2018-06-06 01:48

本文选题：炔丙醇衍生物 + 吡唑衍生物　；参考：《江苏师范大学》2017年硕士论文

【摘要】：串联反应是近年来有机化学研究的热门领域,是合成多种复杂有机化合物的有效方法之一,因此,串联反应已经被广泛地应用于有机化合物的合成中,尤其是一些天然有机产物的合成中。本论文主要研究了利用炔丙醇衍生物参与的串联反应,合成了三个系列氮杂环化合物。在研究这些反应的过程中,将布朗斯特酸的催化作用与微波加热相结合,使反应底物能迅速地转化为目标产物,有效地避免了反应过程中的中间体的分离,提高了反应的原子利用率,降低废弃物的排放,体现了现代化学所提倡的高效性与环境友好性。本论文的主要研究内容总结如下:第一部分内容介绍了炔丙醇衍生物作为有效的合成子在氮杂环骨架构建中的应用。综合文献中炔丙醇衍生物参与的串联反应的讨论,提出了本论文的选题依据与创新点。第二部分发展了一类新的微波辐射下炔丙醇参与的吡唑类衍生物的合成。该反应以结构不同的炔丙醇衍生物与芳基肼为起始原料,以醋酸为溶剂,在微波辐射下经历去羟基的[3+2]环化反应,区域选择性地合成了一系列官能化的吡唑衍生物,产率优良。反应过程中发现当芳基肼苯环上的取代基为供电子基时,提供的目标产物产率较高而吸电子基时降低了反应效率,转化较低。此外,与吸电子基团相比,炔丙醇苯环上的取代基为供电子基时有利于该反应的转化,能提供更高产率的目标产物。基于文献报道,我们提出该反应的可能反应机理。第三部分描述了一类新的炔丙醇衍生物与烯胺酮的去羟基[3+3]环化反应。用自制的环状烯胺酮为1,3-双亲核试剂与具有1,3-双亲电的炔丙醇衍生物在微波辐射下进行反应,高区域选择性地合成多取代氢化喹啉衍生物,产率优良。该反应需要用对甲基苯磺酸为布朗斯特酸促进剂,且在醋酸溶剂中进行。为了进一步拓展此反应的适用范围,用季酮酸衍生的烯胺酯作为烯胺酮取代物,将其与炔丙醇衍生物在微波辐射下进行反应。反应能顺利进行,提供相应的的氢化呋喃并[3,4-b]吡啶衍生物,产率优良。该反应具有原料易得、底物适用范围宽、反应条件温和和反应时间短等优点,为此类稠合吡啶的合成提供了新的快速有效的合成方法。第四部分介绍了一类新的炔丙醇衍生物与5-氨基吡唑衍生物发生的[3+3]环化反应。利用廉价易得的5-氨基吡唑衍生物为1,3-双亲核试剂,将其与炔丙醇衍生物进行两组分串联反应,高效地合成了一系列吡唑并[3,4-b]吡啶衍生物。在此反应中,布朗斯特酸首先活化炔丙醇的羟基,使其离去转化为联烯正离子,与5-氨基吡唑发生亲核加成以及随后的环化,转化为目标产物。上述发展的三类反应都具有反应时间短,操作简便,收率高,且中间体不需要纯化等优点。利用炔丙醇衍生物为核心反应底物分别合成了吡唑、呋喃并吡啶以及吡唑并吡啶衍生物。所合成的目标化合物的结构均经NMR,IR和HRMS确证,部分化合物的结构经X-单晶衍射进一步证实。
[Abstract]:Series reaction is a hot field in organic chemistry in recent years. It is one of the effective methods to synthesize complex organic compounds. Therefore, series reaction has been widely used in the synthesis of organic compounds, especially in the synthesis of some natural organic products. This paper mainly deals with the use of propargyl alcohol derivatives in series. Three series of nitrogen heterocyclic compounds were synthesized. In the process of studying these reactions, the catalytic action of Blans Te Um was combined with microwave heating to quickly convert the reaction substrate into the target product. It effectively avoided the separation of intermediates during the reaction process, improved the atomic utilization rate of the reaction, and reduced the waste discharge. The main contents of this paper are summarized as follows: the first part of this paper is summarized as follows: the first part introduces the application of propargyl alcohol derivatives in the construction of nitrogen heterocyclic cytoskeleton as an effective syntheser. The second part developed a new type of synthesis of pyrazole derivatives with the participation of propargyl alcohol under microwave radiation. This reaction takes the structure of different alkynyl alcohol derivatives and aryl hydrazine as starting materials, acetic acid as solvent and [3+2] cyclization reaction under microwave irradiation, and a series of selective synthesis is made. In the reaction process, it is found that when the substituent on the phenyl ring of aryl hydrazine is the electron donor base, the yield of the target product is higher and the electron base absorption reduces the reaction efficiency and the conversion is low. In addition, the substituent on the benzene ring of propargyl alcohol is beneficial to the reaction compared with the electron group. In the third part, we describe a new class of propargyl alcohol derivatives and the de hydroxyl [3+3] cyclization of alkenamines. Using homemade cyclic alkenone as a 1,3- nucleated test agent and a propargyl alcohol derivative with 1,3- amphiphilic electricity The synthesis of multi substituted hydroquinoline derivatives under microwave irradiation is excellent. The reaction needs to be used as a Bronchos acid promoter and in the acetic acid solvent. In order to further expand the scope of the reaction, the alkenamines derived from Quaternary ketone acid are used as the substituents of enaminone. The reaction can be carried out with the propargyl alcohol derivative under microwave radiation. The reaction can be carried out smoothly, providing the corresponding hydrogenated furan and [3,4-b] pyridine derivative with excellent yield. The reaction has the advantages of easy raw material, wide application range, mild reaction conditions and short reaction time, which provides a new fast and effective synthesis for the synthesis of this kind of fused pyridine. The fourth part introduces the [3+3] cyclization of a new class of propargyl alcohol derivatives and 5- amino pyrazole derivatives. By using the cheap and easily available 5- amino pyrazole derivatives as 1,3- double nucleophilic reagents, they are connected in series with the propargyl alcohol derivatives in series, and a series of pyrazole and [3,4-b] pyridine derivatives are synthesized efficiently. In this reaction, branct acid first activates the hydroxyl hydroxyl of propargyl alcohol, and makes its departure into a positive ion of allene, nucleophilic addition of 5- amino pyrazole, and subsequent cyclization to be the target product. The three kinds of reactions mentioned above have the advantages of short reaction time, high yield, and no need to purify the intermediate. Pyrazole, furazolidopridine and pyrazolyl pyridine derivatives were synthesized with propargyl alcohol derivatives as the core reaction substrates. The structure of the synthesized target compounds were confirmed by NMR, IR and HRMS, and the structure of some compounds was further confirmed by X- single crystal diffraction.
【学位授予单位】：江苏师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626

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