北大有机课件第十三章-有机含氮化合物.ppt

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1、2023/9/24,有机,Chapter 13 Organic Compounds Containing Nitrogen有机含氮化合物,硝基化合物,酰胺,腈,肟,胺,重氮和偶氮化合物,2023/9/24,有机,含氮有机物,硝基化合物 Nitro Compunds,酰胺 Amides,腈 Nitriles,肟 Oximes,胺 Amines,重氮和偶氮化合物 Diazonium Salts&Azo compounds,2023/9/24,有机,Amine(胺),NH3,胺(Amine),铵 铵盐(Ammonium Salt),氨(Ammonia),季胺盐(Quaternary Ammonium

2、 Salt),2023/9/24,有机,根据N上所连烃基的种类,脂肪胺,芳香胺,芳脂胺,CH3NH2,一.Classification&Naming:,2023/9/24,有机,根据N上所连烃基的数目,RNH2,R2NH,R3N,R4N+,1胺（伯胺）Primary Amines,2胺（仲胺）Secondary Amines,3胺（叔胺）Tertiary Amines,4胺（季铵盐)Quaternary Ammonium Salt,Classification&Naming,2023/9/24,有机,根据分子中胺基的数目,一元胺,多元胺,胺的分级与卤代烃、醇不同！,(CH3)3C-OH,3醇,

3、(CH3)3C-NH2,1胺,Classification&Naming,3o卤代烃,2023/9/24,有机,(CH3)2NH,dimethyl amine,aniline 苯胺,N-methyl aniline,CH3-NH2,methyl amine 甲（基）胺,CH3CH2NH2,ethyl amine 乙胺,Classification&Naming,2023/9/24,有机,3-胺甲基-2-N,N-二甲胺基己烷,C6H5NH3+Cl-,氯化苯铵,Classification&Naming,3-(N-乙胺基)庚烷,2-氨基乙醇,-(N-甲胺基)丙酸,对氨基苯磺酸,氯化四甲铵,硫酸乙铵

4、,2023/9/24,有机,二.Structure&Isomerism:,SP3,2023/9/24,有机,SP3,SP3,“SP2”,Structure&Isomerism,2023/9/24,有机,胺的对映体的转变,构型翻转，能垒较低，翻转速度较快,N上不同的取代,手性氮,对映异构体？,自动外消旋化，不可拆分,Structure&Isomerism,2023/9/24,有机,氮在环内，翻转受阻,季铵盐 不能进行氮的翻转,可分离出稳定的旋光异构体,胺的对映体的转变,Structure&Isomerism,Troger 碱,S-,R-,形成N氧化物，不能翻转,2023/9/24,有机,三.Pr

5、eparation of Aamines,Preparation by Nucleolic Substitution,1、胺的烷基化,1 胺,2胺,3胺,4胺,反应产物复杂,如何控制产物在1 胺？,采用该法合成胺，哪一种卤代烷不适用？,芳香胺,2023/9/24,有机,Preparation of Aamines,3、Gabriel 合成法制备1胺,2、芳香卤代烃的胺解,2023/9/24,有机,Preparation of Aamines,Preparation by Reduction,1.硝基化合物,1 胺,2.腈,3.酰胺,4.肟,5.Alkyl Azide 叠氮物,2023/9/24

6、,有机,Preparation of Aamines,6、羰基化合物的还原胺化(Reductive Amination),NH3,1 胺,1 胺,2 胺,2 胺,3 胺,1 胺的二甲基化,2023/9/24,有机,Preparation of Aamines,Preparation by Rearrangements,1、Hofmann Rearrangements（Hofmann 重排，降解）,异氰酸酯,机理,2023/9/24,有机,Preparation of Aamines,R-2-甲基丁酰胺,R-2-甲基丁胺,三元环过渡态,构型保持,SN2,Stereochemistry,2023/

7、9/24,有机,Preparation of Aamines,2、Curtius&Schmidt Rearrangements,酰叠氮化合物,Curtius,Schmidt,2023/9/24,有机,Preparation by Mannich reaction,Preparation of Aamines,-胺基酮,-H 酮,甲醛,胺盐,酸性水、醇溶液,胺甲基化反应,2023/9/24,有机,机理,Preparation of Aamines,Mannich Base,2023/9/24,有机,四.Reaction,SP3,Long electron pair,Basicity碱性，成盐,N

8、ucleophlicity亲核性，烷基化,Resonance Activition to the Aromatic ringElectophilic Substitution芳香环的亲电取代反应,2023/9/24,有机,(一)Basicity and Formation of Ammonium Salts：,氮上的孤对电子,不溶,溶解,Lewis Base,pKb=-lgKb,实验测定,接受质子或提供电子,2023/9/24,有机,试验测定的胺的pKb,Basicity and Formation of Ammonium Salts,2023/9/24,有机,脂肪胺氨苯胺,脂肪胺:2胺1胺3

9、胺,芳香胺：对甲氧基苯胺苯胺对硝基苯胺,Basicity and Formation of Ammonium Salts,2023/9/24,有机,脂肪胺的碱性,2o 1o 3o,脂肪胺的碱性都大于氨；烷基相同，仲胺碱性最强，伯、叔胺次之,电子(诱导、共轭）效应,溶剂化效应,位阻效应,3o 2o 1o,1o 2o 3 o,1o 2o 3 o,胺的碱性强度,决定于氮上电子云密度,增高N上电子云密度,降低N上电子云密度,Basicity and Formation of Ammonium Salts,pKb 3.01,pKb 2.73,2023/9/24,有机,芳香胺的碱性,苯胺的结构,p-共轭,

10、N上电子云密度下降,芳香胺碱性比氨弱,芳香胺氮上氢被推电子基团取代,芳香胺氮上氢被吸电子基团取代,芳香胺苯环上氢被基团取代，对碱性影响-取代基的结构与位置,致活基团(-NH2,-OCH3,-CH3),致钝基团(-NO2,-SO3H,-CO2H,-X,-NH3+),Basicity and Formation of Ammonium Salts,诱导与共轭,2023/9/24,有机,季胺碱,离子化合物,碱性顺序：,季胺碱 脂肪氨 氨 芳香胺酰胺 磺酰胺 酰亚胺,Basicity and Formation of Ammonium Salts,2023/9/24,有机,胺的成盐反应,Basicit

11、y and Formation of Ammonium Salts,水溶性,铵盐：无臭，不挥发的固体，溶于水，但不溶于有机溶剂。,分离，纯化植物中生物碱的提取,利于吸收和保存,盐酸普鲁卡因,乌头碱/附子,2023/9/24,有机,手性羧酸的拆分,Basicity and Formation of Ammonium Salts,非对映异构体,番木鳖碱(strychnine),马钱子碱(brucine),辛可宁(cinchonine),奎宁(quinine),2023/9/24,有机,(二)Alkylation and Quaternary Ammonium Salts,Alkylation,碱性

12、,亲核性,烷基化,季铵碱Quaternary Ammonium Base,2023/9/24,有机,Alkylation and Quaternary Ammonium Salts,Quaternary Ammonium Compounds,胆碱(choline),溴化乙酰胆碱(acetylcholine bromide),乙酰胆碱(acetylcholine,ACh),磷脂,2023/9/24,有机,Quaternary Ammonium Salts,两溶性,相转移催化剂(Phase-transfer Catalyst),2023/9/24,有机,Phase-transfer Catalys

13、t,2023/9/24,有机,(三)Methylation and Hofmann Elimination,Hofmann Elimination,E2elinmination,Mechanism of the Hofmann elimination,2023/9/24,有机,Methylation and Hofmann Elimination,Hofmanns rule:The less substituted alkene is preferred,minor,major,2023/9/24,有机,Methylation and Hofmann Elimination,Stereoche

14、mistry of Hofmann elimination,E2,Trans elimination,2023/9/24,有机,Methylation and Hofmann Elimination,2023/9/24,有机,Methylation and Hofmann Elimination,Application,胺结构的分析,完全甲基化,Hofmann消除,第一次完全甲基化生成的季铵盐甲基增加个数,胺的级别,消除的次数,产生烯烃及胺的结构,原胺的结构,有几个含-H的烃基,2023/9/24,有机,(四)Acylation and Sulfonylation,Reaction,or,缚酸

15、剂除酸剂,苯磺酰氯,苯磺酰胺,Acylation,Sulfonylation,2023/9/24,有机,Acylation and Sulfonylation,Applications,药物合成中的应用,扑热息痛(paraspen),非那西丁(phenacetin),磺胺药(抗菌剂，利尿药，降糖药),2023/9/24,有机,Acylation and Sulfonylation,2023/9/24,有机,氨基的保护,芳胺的易氧化性,乙酰氨基的定位规律,胺的分离、鉴定,Hinsberg Reaction,溶解,不溶,不反应,Acylation and Sulfonylation,2023/9/

16、24,有机,(五)Reaction with Nitrous Acid,HNO2,亚硝酸,NaNO2/HCl,NaNO2/H2SO4,芳香伯胺,氯化重氮苯,Diazonium Salt重氮盐,重氮化反应Diazotization,Mechanism,2023/9/24,有机,脂肪伯胺,e.g.,Reaction with Nitrous Acid,2023/9/24,有机,仲胺,N-亚硝基胺黄色油状物，难溶于水和稀酸,Reaction with Nitrous Acid,2023/9/24,有机,脂肪叔胺,芳香叔胺,成盐,苯环上取代,Reaction with Nitrous Acid,202

17、3/9/24,有机,(六)Schiffs base&Enamine(Schiff 碱和烯醇),Schiffs Base,Imine,Schiffs base,Imine&Enamine,Imine,Enamine,2023/9/24,有机,Enamine(烯胺),Formation,酸催化,除水,环状仲胺,2023/9/24,有机,Enamine(烯胺),Reactions,亲核能力弱;活泼卤代烃、酰氯反应,2023/9/24,有机,Enamine(烯胺),Question:,2023/9/24,有机,(七)Electrophilic aromatic substitution,A stron

18、gly activiting group,Ortho-&Para-position,2023/9/24,有机,Electrophilic aromatic substitution,Nitrated 硝化,Sulfonated 磺化,2023/9/24,有机,(八)Diazotization&Diazonium Salts 重氮化反应和重氮盐,取代基对稳定性的影响,2023/9/24,有机,Diazotization&Diazonium Salts,ArN2+X-,易分解-取代反应,重氮正离子-亲电试剂-偶联反应,性质:离子型化合物,水溶性好,稳定性差(光、热、振动)中性或碱性不稳定,2023

19、/9/24,有机,Substitution&Applications,被卤素和氰基取代,Sandmeyer Reaction,Diazotization,重氮盐不分离、强酸、低温,试验操作,Diazotization&Diazonium Salts,2023/9/24,有机,Question?,Diazotization&Diazonium Salts,2023/9/24,有机,Diazotization&Diazonium Salts,被羟基和氢取代,反应条件,2023/9/24,有机,Diazotization&Diazonium Salts,被硝基取代,取代反应在合成上的应用,活化、定位

20、作用活化能力的控制,转换、占位作用,胺基的占位作用-可以制备两个或三个邻对位定位基处于间位的苯衍生物,2023/9/24,有机,Diazotization&Diazonium Salts,Coupling Reaction 偶合反应,对羟基偶氮苯,对(N,N-二甲氨基)偶氮苯,弱亲电试剂，进攻活泼的芳香环；定位效应-先对位，后邻位,2023/9/24,有机,Diazotization&Diazonium Salts,偶合位置,Azo Compounds 偶氮化合物,几何异构,还原反应,颜色,2023/9/24,有机,(九)Diazomethane 重氮甲烷,性质：有毒，易挥发，易爆,2023/9/24,有机,Diazomethane 重氮甲烷,甲基化成酯、醚,与醛酮反应,分解成卡宾,Carben,