含氮杂环芳基氟化物的合成研究
发布时间：2018-08-17 19:04
【摘要】：含氮杂环芳基化合物广泛的应用于医药及光电材料领域,向其结构中引入氟原子或含氟基团后,能够显著的改变其物理、化学及生理活性。由于氟化试剂的高反应活性及C-F键极大的化学键能,已合成的杂环芳基氟化物种类并不丰富,且在合成方法中也存在着步骤繁杂、成本较高的不足。因此,探索高效实用的含氮杂环芳基氟化物合成方法,并通过C-F键选择性活化的方法对其结构进行修饰,可以完善有机氟化物的制备方案,并丰富产物的种类。此外,对C-F键选择性活化的机理进行研究,有助于加深对C-F键活化的理解,具有重要的理论价值。本文的主要研究内容如下:本文以2-羟基喹啉/喹喔啉衍生物为原料,通过对溴化方法进行筛选,以中等到良好的产率得到了对应的2-溴喹啉/喹喔啉衍生物。然后通过对催化剂、配体、键及溶剂进行筛选,实现了2-溴喹啉/喹喔啉衍生物与贫电子型多氟芳烃的偶联反应,反应具有很好的底物适用性。获得的最优反应条件为:n(2-溴喹啉/喹喔啉衍生物):n(多氟芳烃):n(碘化亚铜):n(1,10-菲Up啉):n(磷酸钾)=1.0:1.5:0.1:0.1:2.0,以二甲基甲酰胺-二甲苯(1/1,V/V)为溶剂,110 oC下反应12 h。在该反应条件的基础上,进行了放大量合成,研究了该体系在规模化制备时的实用性。本文开展了C-F键活化法对含氮杂环芳基氟化物进行结构修饰的研究。以氟代苯甲酸为原料,经缩合反应、关环反应制备了一系列含有导向基团的氟代苯基VA唑啉,然后以之为底物,通过C-F键活化的方法实现了与苯胺衍生物的偶联反应,能够在不使用过渡金属催化剂的条件下以优秀的产率获得一系列含VA唑啉环的氟代二苯胺衍生物,并对产物进行了核磁氢谱、碳谱、氟谱及高分辨质谱表征。该反应体系可以对VA唑啉环邻位的单个C-F键进行活化,对含不同取代基团(-F,-Cl,-CH3,-OCH3等)的苯胺衍生物均具有很好的实用性,且适用于含有较少氟原子的氟代芳基VA唑啉。研究了反应时间及投料比例对C-F键活化选择性的影响,延长反应时间及增加偶联试剂的投料比例后,并没有其他位点的C-F键发生活化,产物结构具有很好的可控性。本文对多氟苯基VA唑啉C-F键选择性活化的反应机理进行了研究。通过合成含有不同杂环结构的氟代苯基化合物,对导向基团的导向作用进行研究;通过对照实验与理论计算结合的方法,获得了配位中间体的最优几何构型,研究了配位效应对C-F键活化的影响;通过对分子内氢键作用进行研究,探索其在C-F键选择性活化中对C-F键活化数目的影响。综合分析导向基团、配位效应及分子内氢键作用,提出了该体系中C-F键选择性活化的反应机理。
[Abstract]:Nitrogen-containing heterocyclic aryl compounds are widely used in the field of medicine and optoelectronic materials. When fluorine atoms or fluorine groups are introduced into their structures, the physical, chemical and physiological activities of nitrogen-containing heterocyclic aryl compounds can be significantly changed. Due to the high reactivity of fluorinated reagents and the great chemical bond energy of C-F bond, the kinds of heterocyclic aryl fluoride synthesized are not abundant, and there are many complicated steps and high cost in the synthesis method. Therefore, to explore an efficient and practical method for the synthesis of nitrogen-containing heterocyclic aryl fluoride, and to modify its structure by C-F bond selective activation, can improve the preparation of organic fluorides and enrich the kinds of products. In addition, the study on the mechanism of selective activation of C-F bond is helpful to further understand the activation of C-F bond and has important theoretical value. The main contents of this paper are as follows: in this paper, 2-hydroxyquinoline / quinoxaline derivatives were used as raw materials, and the corresponding 2-bromoquinoline / quinoxaline derivatives were obtained by bromination method. Then the coupling reaction of 2-bromoquinoline / quinoxaline derivatives with electron-poor polyfluorinated aromatic hydrocarbons was realized by screening catalysts ligands bonds and solvents. The optimal reaction conditions were obtained as follows: 1: n (2-bromoquinoline / quinoxaline derivative): n (polyfluorinated aromatic hydrocarbon): n (cuprous iodide): n (1n (1-10 -phenanthroline): n (potassium phosphate) 1.0: 1.5: 0.1: 0.1: 0.12.0The reaction was carried out at 110oC with dimethylformamide / xylene (1 / 1 V / V) as solvent for 12 h. On the basis of the reaction conditions, a large amount of synthesis was carried out, and the practicability of the system in large-scale preparation was studied. In this paper, the structure modification of nitrogen-containing heterocyclic aryl fluoride by C-F bond activation method has been studied. Using fluorobenzoic acid as raw material, a series of fluorophenyl VA azoline containing guiding groups were prepared by condensation reaction and closed ring reaction. Then the coupling reaction with aniline derivatives was realized by C-F bond activation with fluorobenzoic acid as substrate. A series of fluorinated diphenylamine derivatives containing VA azoline ring can be obtained in excellent yield without using transition metal catalyst. The products were characterized by NMR, carbon, fluorine and high resolution mass spectrometry. The reaction system can activate a single C-F bond at the ortho position of VAZoline ring, and has good practicability for aniline derivatives containing different substituents (-FF- Cl-Cl-CH3-OCH3, etc.) and is suitable for fluoroarylVA azoline containing less fluorine atoms. The effects of reaction time and feed ratio on the activation selectivity of C-F bond were studied. When the reaction time was prolonged and the ratio of coupling reagent was increased, there was no activation of C-F bond at other sites, and the structure of the product had good controllability. The mechanism of selective activation of polyfluorophenyl Vazoline C-F bond was studied. Through the synthesis of fluorophenyl compounds with different heterocyclic structures, the orientation of the guiding groups was studied, and the optimal geometric configuration of the coordination intermediates was obtained by combining the experimental results with the theoretical calculations. The effect of coordination effect on the activation of C-F bond was studied, and the effect of coordination effect on the number of C-F bond activation in selective activation of C-F bond was investigated. The mechanism of selective activation of C-F bonds in the system was proposed by synthetically analyzing the guiding group, the coordination effect and the intramolecular hydrogen bond interaction.
【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】：O626
本文编号：2188595
[Abstract]:Nitrogen-containing heterocyclic aryl compounds are widely used in the field of medicine and optoelectronic materials. When fluorine atoms or fluorine groups are introduced into their structures, the physical, chemical and physiological activities of nitrogen-containing heterocyclic aryl compounds can be significantly changed. Due to the high reactivity of fluorinated reagents and the great chemical bond energy of C-F bond, the kinds of heterocyclic aryl fluoride synthesized are not abundant, and there are many complicated steps and high cost in the synthesis method. Therefore, to explore an efficient and practical method for the synthesis of nitrogen-containing heterocyclic aryl fluoride, and to modify its structure by C-F bond selective activation, can improve the preparation of organic fluorides and enrich the kinds of products. In addition, the study on the mechanism of selective activation of C-F bond is helpful to further understand the activation of C-F bond and has important theoretical value. The main contents of this paper are as follows: in this paper, 2-hydroxyquinoline / quinoxaline derivatives were used as raw materials, and the corresponding 2-bromoquinoline / quinoxaline derivatives were obtained by bromination method. Then the coupling reaction of 2-bromoquinoline / quinoxaline derivatives with electron-poor polyfluorinated aromatic hydrocarbons was realized by screening catalysts ligands bonds and solvents. The optimal reaction conditions were obtained as follows: 1: n (2-bromoquinoline / quinoxaline derivative): n (polyfluorinated aromatic hydrocarbon): n (cuprous iodide): n (1n (1-10 -phenanthroline): n (potassium phosphate) 1.0: 1.5: 0.1: 0.1: 0.12.0The reaction was carried out at 110oC with dimethylformamide / xylene (1 / 1 V / V) as solvent for 12 h. On the basis of the reaction conditions, a large amount of synthesis was carried out, and the practicability of the system in large-scale preparation was studied. In this paper, the structure modification of nitrogen-containing heterocyclic aryl fluoride by C-F bond activation method has been studied. Using fluorobenzoic acid as raw material, a series of fluorophenyl VA azoline containing guiding groups were prepared by condensation reaction and closed ring reaction. Then the coupling reaction with aniline derivatives was realized by C-F bond activation with fluorobenzoic acid as substrate. A series of fluorinated diphenylamine derivatives containing VA azoline ring can be obtained in excellent yield without using transition metal catalyst. The products were characterized by NMR, carbon, fluorine and high resolution mass spectrometry. The reaction system can activate a single C-F bond at the ortho position of VAZoline ring, and has good practicability for aniline derivatives containing different substituents (-FF- Cl-Cl-CH3-OCH3, etc.) and is suitable for fluoroarylVA azoline containing less fluorine atoms. The effects of reaction time and feed ratio on the activation selectivity of C-F bond were studied. When the reaction time was prolonged and the ratio of coupling reagent was increased, there was no activation of C-F bond at other sites, and the structure of the product had good controllability. The mechanism of selective activation of polyfluorophenyl Vazoline C-F bond was studied. Through the synthesis of fluorophenyl compounds with different heterocyclic structures, the orientation of the guiding groups was studied, and the optimal geometric configuration of the coordination intermediates was obtained by combining the experimental results with the theoretical calculations. The effect of coordination effect on the activation of C-F bond was studied, and the effect of coordination effect on the number of C-F bond activation in selective activation of C-F bond was investigated. The mechanism of selective activation of C-F bonds in the system was proposed by synthetically analyzing the guiding group, the coordination effect and the intramolecular hydrogen bond interaction.
【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】：O626
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