【作者】 王静；

【导师】 羊晓东；

【作者基本信息】 云南大学 ， 药物化学， 2020， 硕士

【摘要】 有机膦化合物(例如氧化膦)在合成化学中作为催化剂和配体被广泛应用,其中α-氨基膦氧化物具有重要的生物学和药理特性,例如抗肿瘤、抗HIV、抗菌和抗结核活性等,它们还广泛用于农用化学品中,例如除草剂和植物杀病毒剂等。目前对于构建α-氨基膦氧化物主要是基于各种过渡金属催化剂或超声辐射、电化学、光催化的方法,但是这些方法通常会受到苛刻的反应条件、贵金属催化剂的添加以及化学计量的氧化剂添加的限制。本论文基于课题组前期关于亚胺的研究工作,通过KHMDS来介导的无过渡金属催化的自由基偶联反应,使用二苯基次膦酰氯与亚胺作底物,发展了一种高效的绿色合成方法,合成了一系列α-氨基膦氧化物。本论文分为三个章节。第一章简述了有机膦化合物与α-氨基膦氧化物的应用以及生物活性、α-氨基膦氧化物的合成研究进展,并在此基础上提出了本论文的研究课题。第二章主要对α-氨基膦氧化物的合成方法进行了探索研究。N-苄基亚胺去质子化可产生超电子给体(SED)2-氮杂烯丙基阴离子,之后2-氮杂烯丙基阴离子与二苯基次膦酰氯之间发生单电子转移(SET)分别得到2-氮杂烯丙基自由基与膦自由基,两分子自由基间进行自由基偶联即可得到目标产物α-氨基膦氧化物。通过对反应所使用的碱、溶剂、温度、时间、浓度等反应条件进行筛选,最终确定了一种简单高效的反应条件。紧接着,对这一反应条件的底物适用性进行了研究,分别选用不同的亚胺底物、不同的次膦酰氯,合成了24个不同取代类型的α-氨基膦氧化物,并进行了反应机理初步研究。第三章为实验部分,主要记录了论文中相关化合物的合成实验操作及谱图数据。更多还原

【Abstract】 Organophosphorus compounds(such as phosphine oxides)are widely used as catalysts and ligands in synthetic chemistry.α-Aminophosphine oxides have important biological and pharmacological properties,such as antitumor,anti-HIV,antibacterial and antituberculous activities,etc.They are also widely used in agrochemicals such as herbicides and plant virus killers.At present,the construction of α-aminophosphine oxide mainly used various transition-metal catalysts or ultrasonic radiation,electrochemical,and photocatalytic methods.However,these methods are usually limited by the harsh reaction conditions,addition of toxic metal catalysts,and stoichiometric oxidants.Based on the previous works of our group on imines,using diphenylphosphite chloride and imine as substrates,a new KHMDS mediated metal-free-catalyzed radical coupling reaction to α-aminophosphine oxides was developed in this thesis.This thesis is divided into three chapters.In the first chapter,the application and biological activity of organic phosphorus compounds and α-aminophosphine oxides,and the research progress in the synthesis of α-aminophosphine oxides were briefly reviewed.Based on this,the research topics of this thesis were proposed.In the second chapter,a new synthesis method of α-aminophosphine oxide was developed.Deprotonation of N-benzyl imines may generate super-electrondonor(SED)2-azaallyl anions that reduced chlorodiphenylphosphine oxides to phosphine oxide radicals.Single-electron transfer(SET)process transformed the 2-azaallyl anions into 2-azaallyl radicals,which may couple with phosphine oxide radicals to construct C-P bonds.By screening the reaction conditions such as base,solvent,temperature,time and concentration,a simple and efficient reaction condition was finally established.Then,the substrate scope of this reaction was studied.Different imine substrates and different chlorodiarylphosphine oxides were applied to synthesize 23 different types of α-aminophosphine oxides.The reaction mechanism was also studied.In the third chapter,the experimental partincluding synthetic experimental procedure and spectrum data of related compounds in the thesis was described.更多还原