Mechanistic investigation of synthesizing quinoxaline through intramolecular N-arylation from N-aryl β- keto oximes by DFT Study

使用密度泛函理論的方法研究從氮-芳基β-酮肟合成喹喔啉的反應機制。發現反應機制主要包含三個部分:一致性酸鹼反應，一致性合環且二氯化磷酸陰離子作為離去基，用二氯化磷酸陰離子作為鹼的消去反應形成喹喔啉。第一個步驟的吉布士自由能為最高，28.36千卡/摩耳為反應速率決定步驟。使用QST2和IRC計算過渡態能量和反應機制，發現整個反應是屬於一致性反應。除此之外，為了瞭解取代基效應是如何影響整體反應，不同的官能基列入考慮並加以計算。結果發現反應活化能會隨著官能基團從拉電子基團變為推電子基團，反應活化能呈現遞減，-NO2是33.23千卡/摩耳，-Cl是31.43千卡/摩耳，-CH3是22.33千卡/摩耳，這些計算都是在B3LYP/6-31G(d)基底函數下得到的結果。The mechanism of formation of quinoxaline from N-aryl β-keto oximes has been investigated using DFT methods. It is found that the reaction mechanism actually consists of three steps which are concerted acid-baes reaction, concerted cyclization and removal of the phosphoryl Group, elimination with chlorophosphite as base to form quinoxaline.The first step is rate-determining step because it has the highest energy barrier in gas phase, with relative Gibbs free energy values of 28.36 kcal/mol. QST2 and IRC were used to calculate the transition state and mechanism, and find out the overall reaction is concerted reaction. Furthermore, In order to understand how the substituent group affects the overall reaction, different substituent groups are considered. It is found that the reaction energy barrier will decay if the substitutional group go from electron-withdrawing group to electron-donating group. -NO2 is 33.23 kcal/mol, -Cl is 31.43 kcal/mol, -CH3 is 22.33 kcal/mol at B3LYP/6-31G(d) level in gas phase.中文摘要…………………………………………………..…………….i Abstract ……………………………………………………..…………..ii Content of Schemes……………………………………………………..v Content of Tables…………………………………………………………vi Content of Figures……………………………………………………….viii Chapters 1. Introduction………………………………………………….1 1.1 Motivation………………………………………………………….1 1.2 History………………………………………………………………1 1.3 Goal…………………………………………………………………3 Chapter 2. Computational Methods……………………………..………5 2-1. Computational Methods in Details…………………….…………5 2-2.Density Functional Theory…………………………………..……5 2-2-1. B3LYP (Becke, three-parameter, Lee-Yang-Parr)……………7 2-3. Basis Functions…………………………………………………8 2-3-1. Split-valence Basis Set………………………………………..9 2-3-2. Polarization Function……………………………………10 2-3-3. Diffuse Function……………………………………..…10 2-4. Transition State Optimizations with Opt=QST2…………..10 2-5 Polarizable Continuum Model……………………………………11 Chapter 3. Results and Discussions……………………………………..13 3-1 Formation of quinoxaline in gas phase………………………….13 3-1-1. Concerted Acid-Base Reaction in Gas Phase………………13 3-1-2. Concerted Cyclization and Removal of the Phosphoryl Group in Gas Phase…………………………………………………………..17 3-1-3. Elimination with Chlorophosphite as Base to Form Quinoxaline in Gas Phase……………………………………………………..…...21 3-2. Substituents Effect……………………………………….….25 3-2-1. Concerted Acid-Base Reaction in Gas Phase………………….25 3-2-2. Concerted Cyclization and Removal of the Phosphoryl Group in Gas Phase………………………………………………………28 3-2-3. Elimination with Chlorophosphite as Base to Form Quinoxaline in Gas Phase……………………………………………..32 3-3-1. Concerted Acid-Base Reaction in Gas Phase…………………..36 3-3-2. Concerted Cyclization and Removal of the Phosphoryl Group in Gas Phase………………………………………………………..39 3-3-3. Elimination with Chlorophosphite as Base to Form Quinoxaline in Gas Phase……………………………………………………………….43 3-4-1. Concerted Acid-Base Reaction in Gas Phase………………….47 3-4-2. Concerted Cyclization and Removal of the Phosphoryl Group in Gas Phase…………………………………………………………….50 3-4-3. Elimination with Chlorophosphite as Base to Form Quinoxaline in Gas Phase………………………………………………………..54 3-5-1 Substitutional Effect……………………………………….58 3-5-2 Charge Distribution…………………………………….63 3-5-3 Rate Constant and Tunneling Effects………………………67 Chapter 4. Conclusion………………………………………..70 References………………………………………………………..7