【作者】 赵治刚；

【导师】 高文涛；

【作者基本信息】 渤海大学 ， 有机化学， 2012， 硕士

【摘要】 吲哚类化合物是一类非常重要的杂环化合物，许多具有良好的药理活性的药物分子中都存在有吲哚结构。乙酰基吲哚类衍生物就是一类含有吲哚结构的化合物，此类化合物具有广泛的药理活性，如抗癌、抗病毒、杀菌、消炎、心血管疾病等药物活性。因此对含有乙酰基吲哚结构的杂环化合物的合成及反应研究具有特殊的意义。我们着力于研究此类化合物的目的在于希望通过对乙酰基吲哚的结构修饰为医药行业提供丰富的医药中间体。本论文分为四部分，论文主要研究的是基于乙酰基吲哚为骨架的新型杂环化合物的合成及其反应研究。第一部分，在对以往文献大量检索的基础上对吲哚及其衍生物的应用、合成方法、及研究现状进行了文献综述。第二部分，以3-乙酰基-1-苄基-2-氯吲哚(1)为底物与芳醛在KOH作催化剂、无水KCO3作吸水剂，应用无溶剂有机合成法在常温条件下经研磨完成Aldol反应。以52.3-70.1%的产率生成11种结构新颖的肉桂酰基取代的吲哚类杂环化合物(3a-3k)，并对所合成的新化合物结构进行了红外、核磁、质谱等表征。第三部分，我们以2-吲哚酮和氯化苄为原料，以N,N-二甲基甲酰胺(DMF)作溶剂、无水碳酸钾和少量碘化钾作催化剂的条件下，2-吲哚酮发生非正常的亲核取代反应，意外的合成了3,3-二苄基吲哚酮(6)和1,3,3-三苄基吲哚酮(7)。以化合物(6)为底物与乙酸酐、氯乙酰氯在DMAP作催化剂，加热回流的条件下分别以86.0%和61.5%的收率合成了1-乙酰基-3,3-二苄基吲哚酮(9)和3,3-二苄基-1-氯乙酰基-2-酮吲哚(11)。3,3-二苄基吲哚酮(6)经x射线衍射对单晶结构分析予以确认。第四部分，首先以靛红为原料合成N-苄基吲哚酮(13)。 N-苄基吲哚酮(13)与乙酸酐为原料，在DMAP催化作用下以62.4%的收率合成了中间体3-乙酰基-2-乙酰氧基-1-苄基吲哚。中间体经水解以79.9%的收率生成了3-乙酰基-1-苄基-2-羟基吲哚(14)，化合物14与碘甲烷为原料在碱性条件下，没有得到3-乙酰基-1-苄基-2-甲氧基吲哚而是得到了3-乙酰基-1-苄基-3-甲基-2-吲哚酮(17)，所有合成的化合物做了结构表征。更多还原

【Abstract】 Indoles are important heterocyclic compounds and many drug molecules with goodpharmacological activity containing indole structure. For example, acetyl-substituted indolederivatives have a wide range of pharmacological activity, such as anticancer, antiviral,sterilization, anti-inflammatory and cardiovascular inhibitory activities. Thus, the synthesisand further reactions of heterocyclic compounds containing acetylindole moiety would beinteresting. So, in continuation of our previous work on the synthesis of biologically activeheterocycles and in view of the wide application of indole compounds in medicineintermediates industry，the thesis mainly focused on the synthesis and study of novel acetylindole heterocyclic compounds. This thesis is mainly divided into four parts.In the first part, the recent advance on the synthesis and application of indole and itsderivatives was reviewed.In the second part, eleven novel cinnamoyl substituted indole derivatives (3a-3k) weresynthesized in52.3-70.1%yields through the Aldol-Condensated reactions of1-(1-benzyl-2-chloro-1H-indol-3-yl)ethanone and benzaldehyde and substituted benzaldehydes using KCO3as catalyst under solvent-free condition. The structures of all the novel compounds wereconfirmed by IR, MS, and1H NMR.In the third part,3,3-dibenzylindolin-2-one (6) and1,3,3-tribenzylindolin-2-one (7) weresynthesized by unexpected nucleophilic substitution reaction of indolin-2-one and (chloromethyl)benzene in refluxing acetone in the presence of anhydrous K2CO3and KI as catalyst.Subsequently, the resulting ether6was further reacted with acetic anhydride or chloroacetylchloride using DMAP as catalyst to give the corresponding compounds9and11. Thestructure of3,3-dibenzylindolin-2-one (6) was confirmed by the X-ray crystal structure.In the fourth part,1-benzylindolin-2-one (13) was first synthesized from isatin, whichwas further reacted with acetic anhydride using DMAP as catalyst to give the intermediate3-acetyl-1-benzyl-1H-indol-2-yl-acetate in62.4%yield. The resulting intermediate wasfurther hydrolyzed to afford the corresponding1-(1-benzyl-2-hydroxy-1H-indol-3-yl)ethanone (14) in79.9%yields. The reaction of compound14with iodomethane did not givethe corresponding1-(1-benzyl-2-methoxy-1H-indol-3-yl)ethanone but afford3-acetyl-1- benzyl-3-methylindolin-2-one (17) as main product, which was characterized by spectraldata.更多还原