丙烯酰胺衍生物参与的C-H官能化反应的研究

发布时间：2018-03-25 10:22

本文选题：C-H官能化　切入点：杂环化合物　出处：《江南大学》2017年硕士论文

【摘要】：作为当代有机合成的重要手段之一,C-H官能化反应无需对底物进行预官能化,降低了卤化物以及无机盐等废弃物的排放,简化了反应步骤,且具有较高的原子经济性。因此,对于可持续发展绿色化学来说,研究C-H官能化反应具有非常重要的意义。氧化吲哚和异喹啉酮骨架广泛存在于天然产物、生物碱和药物活性分子中,关于该类化合物的合成方法大都存在反应条件苛刻、使用昂贵或毒性较大的试剂、反应底物适用范围窄和操作复杂等问题,因此,利用C-H官能化反应构建含氮杂环化合物具有重要的研究价值。本论文重点研究了基于丙烯酰胺衍生物参与的C-H官能化反应,构建氧化吲哚类和异喹啉酮类的含氮杂环化合物,具体研究内容如下:1.在布朗斯特酸催化下,N-芳基丙烯酰胺与酮发生串联自由基加成/环化反应,生成相应的氧化吲哚衍生物。另外,在相同的酸催化条件下使用N-芳基磺酰基丙烯酰胺作为底物可以制备γ-过氧化酮衍生物。2.在催化剂甲烷磺酸和氧化剂TBHP存在条件下,丙烯酰胺衍生物与酮或醇发生自由基加成/环化反应,提供了一种有效的途径合成4-取代-1,3-异喹啉二酮衍生物。此外,丙烯酰胺与醇生成的产物还可以转化为四氢呋喃并异喹啉酮衍生物。3.在催化剂Cu(OAc)_2和配体1,10-phen存在条件下,丙烯酰胺衍生物与NFSI发生自由基加成/环化反应,报道了一种合成磺酰胺取代的1,3-异喹啉二酮衍生物的新方法。4.在催化剂Pd(OAc)_2和配体DPE-phos存在条件下,丙烯酰胺衍生物与BrCF_2CO_2Et发生自由基串联的二氟烷基化/环化反应,发展了一种合成含有酯基的1,3-异喹啉二酮衍生物的新方法。其中,该反应的产物可以通过NaBH_4还原得到含有羟基的1,3-异喹啉二酮衍生物,并且氟代试剂可以扩展到全氟代烷基碘化物和溴二氟甲基膦酸酯。5.在催化剂AgNO_3或Ru(bpy)_3Cl_2·6H_2O存在条件下,丙烯酰胺衍生物与硫化物或磺酰氯发生自由基加成/环化反应,发展了一种合成含砜基的1,3-异喹啉二酮衍生物的新方法。以上研究的内容主要使用了以下的研究方法:1.分别以各部分的反应底物为原料,对反应的影响因素进行筛选,最终得到最佳反应条件,并探究了反应底物的适用性。其中,筛选的影响因素包括催化剂的种类及用量、添加剂的种类及用量、反应温度、反应时间、反应气氛、反应溶剂的种类和原料的摩尔比等。2.利用核磁共振仪、质谱仪、红外光谱仪、熔点仪等仪器对目标产物进行鉴定和表征,确认目标产物的结构。3.通过设计控制实验、自由基捕获实验和动力学实验等,对反应进程进行跟踪检测,从而推测出可能的反应机理。
[Abstract]:As one of the most important methods of organic synthesis, C-H functionalization does not need to prefunctionalize the substrate, reduce the discharge of wastes such as halides and inorganic salts, simplify the reaction steps, and have high atomic economy. For the sustainable development of green chemistry, the study of C-H functionalization is of great significance. Indoles and isoquinolones are widely present in natural products, alkaloids and drug active molecules. There are many problems in the synthesis of these compounds, such as harsh reaction conditions, expensive or toxic reagents, narrow range of application and complex operation of the reaction substrates, and so on. It is of great value to construct nitrogen-containing heterocyclic compounds by C-H functionalization reaction. In this paper, the C-H functionalization reaction based on acrylamide derivatives was studied to construct nitrogen-containing heterocyclic compounds of indoles and isoquinolones. The specific contents of the study are as follows: 1. In the presence of Brownstearic acid, N-aryl acrylamide and ketone undergo series radical addition / cyclization to form corresponding oxindole-derived derivatives. In the presence of methanesulfonic acid and oxidant TBHP, 纬 -ketone derivatives can be prepared by using N-aryl sulfonyl acrylamide as substrate under the same acid catalytic conditions. The free radical addition / cyclization of acrylamide derivatives with ketones or alcohols provides an effective way to synthesize 4- substituted-1-3-isoquinolinedione derivatives. The product of acrylamide and alcohol can also be transformed into tetrahydrofuran isoquinolinone derivatives. In the presence of catalyst Cu(OAc)_2 and ligands 1 ~ (10 ~ (-phen)), acrylamide derivatives react with NFSI by radical addition / cyclization. A new method for the synthesis of sulfonamide-substituted 1 / 3-isoquinolinedione derivatives was reported. In the presence of catalyst Pd(OAc)_2 and ligands DPE-phos, acrylamide derivatives reacted with BrCF_2CO_2Et in series of difluoroalkylation / cyclization. A new method for the synthesis of 1,4-isoquinolinedione derivatives containing ester groups has been developed, in which the products of the reaction can be reduced by NaBH_4 to obtain 1H 3-isoquinolinone derivatives containing hydroxyl groups. And fluorinated reagents can be extended to perfluoroalkyl iodides and bromodifluoromethyl phosphonates. In the presence of catalyst AgNO_3 or Ru(bpy)_3Cl_2 6H_2O, acrylamide derivatives react with sulfides or sulfonyl chloride by free radical addition / cyclization. A new method for the synthesis of sulfo-containing 1 / 3-isoquinolinedione derivatives was developed. The following research methods were used in the above studies: 1. The factors affecting the reaction were screened using each part of the reaction substrate as the raw material, respectively. Finally, the optimum reaction conditions were obtained, and the applicability of the reaction substrate was explored. Among them, the factors affecting the selection included the type and amount of catalyst, the type and amount of additives, the reaction temperature, the reaction time, the reaction atmosphere, The kind of solvent and the molar ratio of raw material etc. 2. The target product was identified and characterized by NMR, mass spectrometer, infrared spectrometer, melting point instrument, etc. The structure of the target product was confirmed by designing and controlling experiment. The free radical trapping experiment and kinetic experiment were used to track and detect the reaction process, and the possible reaction mechanism was deduced.
【学位授予单位】：江南大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.25

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