【作者】 郭静；

【导师】 于艳敏；

【作者基本信息】 北京工业大学 ， 化学工程与技术， 2022， 硕士

【摘要】 芳烃化合物的氧化反应因其产物具有重要的工业价值而引起了广泛的关注。芳烃可以选择性氧化侧链上的α-C-H键生成芳醇,也可以选择性氧化苯环上的C-H键生成酚。细胞色素P450能在温和条件下实现芳烃C-H键的选择性催化氧化。目前实验及理论上已经对P450催化氧化芳烃C-H键进行了报道,但芳烃结构和P450活性中心的结构对反应活性的影响尚有待于进一步深入研究。本论文采用密度泛函理论方法研究了P450活性中心催化氧化芳烃侧链α-C-H键和苯环C-H键的反应,深入探讨了芳烃上的取代基以及P450活性中心上的轴向配体对芳烃C-H键氧化反应活性的影响,阐明了影响反应活性的本质因素。研究内容及结论主要分为以下三个方面:1.采用密度泛函理论方法对P450活性中心催化氧化邻、对硝基取代芳烃α-C-H键的反应进行研究,通过计算邻、对硝基取代芳烃α-C-H键的键解离能及高价铁-氧卟啉氧化芳烃α-C-H键的反应活化能考察邻、对硝基取代芳烃α-C-H键发生氧化反应的活性差异。研究结果表明,对硝基取代芳烃由于硝基与苯环的共轭效应使得芳烃α-C-H键的键解离能较小,高价铁-氧卟啉氧化对硝基取代芳烃α-C-H键反应的活化能较低。邻硝基取代芳烃除共轭效应外还存在空间位阻效应。空间位阻效应占主导作用,使得芳烃α-C-H键的解离能增大,高价铁-氧卟啉氧化邻硝基取代芳烃α-C-H键反应的活化能较高。芳烃分子的形变能是影响反应活化能的主要因素。2.采用密度泛函理论方法对P450活性中心催化苯甲醚和硝基苯的邻位羟基化反应进行研究,通过计算整个反应的势能曲线以及对反应中间体和过渡态结构进行几何结构和电子性质分析来探究甲氧基和硝基对邻位苯环C-H键羟基化的影响。研究结果表明,苯环C-H键的活化是整个反应的速控步骤。硝基苯发生苯环C-H键活化的能垒高于苯甲醚,且活化能的差异主要来自于硝基苯分子较大的形变能。质子穿梭和质子回弹步骤没有反应能垒或具有较低的反应能垒。且苯甲醚所生成的中间体由于具有更强的静电相互作用而更利于发生质子穿梭和质子回弹过程,并最终生成酚类化合物。3.采用密度泛函理论方法对具有不同轴向配体（SH^-、Cl^-、F^-、CH₃CN）的高价铁-氧卟啉氧化对二甲苯的反应进行研究。通过分析高价铁-氧卟啉的结构特性以及高价铁-氧卟啉氧化对二甲苯发生α-C-H键羟基化和苯环C-H键羟基化的反应活化能,考察轴向配体对P450活性中心催化氧化对二甲苯C-H键的影响。相较于阴离子轴向配体SH^-、Cl^-和F^-,中性轴向配体CH₃CN可以更好的增强高价铁-氧卟啉上活性氧原子的自由基特征,提高其得电子能力,并进一步增大对二甲苯发生α-C-H键羟基化和苯环C-H键羟基化的反应活性。更多还原

【Abstract】 The oxidation reaction of arenes has attracted extensive attention because the products have important industrial value.Theα-C-H bond in the arene side chain can be selectively oxidized to generate aromatic alcohol,and aromatic C-H bond in the benzene ring can also be selectively oxidized to produce phenol.Cytochrome P450can realize the selective catalytic oxidation of C-H bond in arenes under mild conditions.At present,the oxidation of C-H bond in arenes catalyzed by P450 has been studied using experimental and theoretical methods.But the effects of arenes structure and P450 active center structure on the reactivity need to be further studied.In this dissertation,the oxidation reaction of theα-C-H bond in the arene side chain and the aromatic C-H bond in the benzene ring catalyzed by P450 active center were studied using density functional theory.The effects of arenes substituents and P450axial ligand on the reactivity were discussed and the essential factors affecting the reactivity were clarified.The research contents and conclusions are mainly divided into the following three parts:1.The oxidations of theα-C-H bond in o-and p-nitro-substituted arenes catalyzed by P450 active center were studied using density functional theory.By calculating the bond dissociation energy of theα-C-H bond and the activation energy of theα-C-H bond oxidation in arenes by high-valent iron-oxo porphyrin,the reactivity difference between o-nitro-substituted arenes and p-nitro-substituted arenes was investigated.The results show that the conjugation effect between nitro and benzene ring in p-nitro-substituted arenes reduces the bond dissociation energy of theα-C-H bond and the activation energy of theα-C-H bond oxidation by high-valent iron-oxo porphyrin is low.In o-nitro-substituted arenes,there are not only conjugation effect,but also steric hindrance effect.The steric hindrance effect is dominant in o-nitro-substituted arenes.The bond dissociation energy of theα-C-H bond and the activation energy of theα-C-H bond oxidation by high-valent iron-oxo porphyrin increase due to the steric hindrance effect.The distortion of the arene molecule is the main factor affecting the reactivity of theα-C-H bond oxidation of arenes.2.The o-hydroxylation of anisole and nitrobenzene catalyzed by P450 active center were studied using density functional theory.The effect of methoxy and nitro groups on the o-hydroxylation were investigated by calculating the potential energy profile of the whole reaction and analyzing the geometric and electronic properties of the intermediates and transition structures in the reaction.The results show that the activation of aromatic C-H bond in benzene ring is the rate determining step of the whole reaction.The energy barrier of aromatic C-H bond activation in nitrobenzene is higher than that of anisole,and the difference of activation energy mainly comes from the higher distortion energy of nitrobenzene molecule.There is free energy barrier or have lower energy barrier in the process of proton shuttle and proton rebound.The intermediates produced by anisole is more conducive to performing proton shuttle and proton rebound reaction and finally producing phenolic compounds because of the stronger electrostatic interaction.3.The oxidation of p-xylene by high-valent iron-oxo porphyrins with different axial ligands（SH^-,Cl^-,F^-,CH₃CN）were studied using density functional theory.The effects of axial ligands on the hydroxylation of p-xylene catalyzed by P450 active center were investigated by analyzing the structure properties of high-valent iron-oxo porphyrins with different axial ligands and the reaction activation energy of theα-C-H bond hydroxylation and aromatic C-H bond hydroxylation of p-xylene.Compared with anionic axial ligands（SH^-,Cl^-and F^-）,neutral axial ligand CH₃CN can better enhance the radical characteristics of active oxygen atom and electronic capability of high-valent iron-oxo porphyrin,and further improve the oxidation reactivity of theα-C-H bond hydroxylation and aromatic C-H bond hydroxylation of p-xylene by high-valent iron-oxo porphyrins.更多还原