1、Derivatives of Carboxylic Acids 第十五章 羧酸衍生物,Organic Chemistry A (2) By Prof. Li Yan-Mei Tsinghua University,15.1 Structure & Nomenclature15.2 Physical Properties & Spectrum Data15.3 Chemical Reactions15.4 Fats, Was and Synthetic detergent (learn by yourself)15.5 Preparation15.6 Derivatives of carboni
2、c Acid 15.7 Derivatives of Ortho-Acid15.8 peroxy acid15.9 Isonitrile15.10 Sources and Usages of important Carboxylic Acid Derivatives,Content,15.1 羧酸衍生物的结构与命名15.2 羧酸衍生物物理性质和波谱学性质15.3 化学性质15.4 油脂、蜡和合成洗涤剂15.5 羧酸衍生物的制备15.6 碳酸衍生物 15.7 原酸衍生物15.8 过酸和二酰基过酸15.9 异腈15.10 重要的羧酸衍生物及羧酸衍生物的来源与用途,Content,Carboxyli
3、c Acid Derivatives 羧酸衍生物,羧酸衍生物在结构上的共同特点是都含有酰基。,15.1 Structure & Nomenclature,15.1.1 Structure 15.1.2 Nomenclature,15.1.1 Structure 结构,酰基与其所连的基团都能形成p-共轭体系。C-L 具有部分双键性质，双键的程度取决于C的稳定性，C的稳定性随L的变化而不同。,Acyl halide: L=Cl 电负性大 Anhydride:Ester: L=O 电负性略小 Amide: L=N 电负性更小,15.1.2 Nomenclature,15.1.2.1 Acyl Hal
4、ide and Amide 15.1.2.2 Anhydride and Nitrile15.1.2.3 Ester,15.1.2.1 Acyl Halide and Amide 酰卤与酰胺,中文命名根据分子中酰基所含的碳原子数命名为“某酰卤”或“某酰胺”。,环状酰胺：内酰胺,己内酰胺,5-甲基己内酰胺,注意：编号沿用羧酸的编号,15.1.2.2 Anhydride and Nitrile 酸酐与腈,中文命名 根据水解所得的酸命名为“某酸酐”或“某腈”。,若-CN作为取代基，则称为“氰基”。,间氰基苯甲酸,3-氰基丁磺酸,中文命名 根据水解所得的酸、醇，命名为“某酸某酯”。,15.1.2.3
5、Ester 酯,15.2 Physical Properties and Spectrum Data,15.2.1 Physical Properties 15.2.2 Spectrum Data,Boiling Points 熔点,Even 3 amides have strong attractions.,15.2.1 Physical Properties 物理性质,Melting Points 熔点,Amides have very high melting points. Melting points increase with increasing number of N-H bo
6、nds.,m.p. -61C,m.p. 28C,m.p. 79C,胺的熔点很高, 且随着N-H键的增多而上升.,Acyl HalideTo be irritating and decompose in water strongly.具有刺激性，遇水剧烈分解。AnhydrideTo decompose in water. 遇水分解。,Nitrile,Highly polarized High dipole moment and high boiling point. 高度极化，高的偶极矩与沸点,其它性质：,Esters 酯Esters tend to have sweet smells. 酯一般
7、有芬芳的气息。,Amides 胺,Many amides can form intermolecular hydrogen bond.,许多胺类化合物可以形成分子间氢键。,15.2.2 Spectrum Data (Learn on your own),15.2.2.1 IR Spectroscopy 15.2.2.2 1H NMR Spectroscopy 15.2.2.3 13C NMR Spectroscopy,15.2.2.1 IR Spectroscopy 红外光谱,=,15.2.2.2 1H NMR Spectroscopy 1H NMR 谱,15.2.2.3 13C NMR Sp
8、ectroscopy 13C NMR 谱,15.3 Chemical Reactions,15.3.1 Hydrolysis of Derivatives of Carboxyl Acid 15.3.2 Alcoholysis of Derivatives of Carboxyl Acid 15.3.3 Ammonolysis of Derivatives of Carboxyl Acid 15.3.4 Acidolysis of Derivatives of Carboxyl Acid 15.3.5 Reactions with Organometallic Compounds 15.3.6
9、 Reduction of Carboxyl Acid Derivatives 15.3.7 Other Reactions,15.3.1 羧酸衍生物的水解 15.3.2 羧酸衍生物的醇解 15.3.3 羧酸衍生物的氨解 15.3.4 羧酸衍生物的酸解 15.3.5 与金属有机化合物的反应 15.3.6 与羧酸衍生物的反应 15.3.7 其它反应,水解、氨解、醇解和酸解反应总论：,Nu- = -OH, H2O 水解反应 Nu- = HOR 醇解反应 Nu- = NH3 氨解反应 Nu- = RCOOH 酸解反应,含 义,Acyl halide: L=Cl 电负性大 Anhydride:Este
10、r: L=O 电负性略小 Amide: L=N 电负性更小,反应性,1011 107 1.0 10-2,哪个是更好的离去基团？,一般反应过程,Reactivity decreases as leaving group becomes more basic.随着离去基团碱性增大，离去能力降低，反应活性降低。,氨解反应：,L = X L = OCOR L = OR L = NH2,离去能力均强于NH2,平衡混合物,醇解反应：,L = X L = OCOR L = OR L = NH2,离去能力均强于OR,平衡混合物,离去能力弱于OR,水解反应：,L = X L = OCOR L = OR L =
11、NH2,离去能力均强于OH,离去能力弱于OH,离去能力类似于OH,15.3.1 Hydrolysis of Derivatives of Carboxyl Acid 羧酸衍生物的水解,All carboxylic acid derivatives can be hydrolysed to the parent acid and another product with water.,所以羧酸衍生物都可以水解成相应的羧酸和另外一种产物。,Rates of Hydrolysis (for the same R group),L = X, OCOR, OR, NH2,Acyl Halides 酰卤,
12、Hydrolysis of acyl halides with low molecular weight occurs quickly, even in moist air with no acid or base catalyst. Reagents must be protected from moisture. Rate of the reaction slows down with the increase of molecular weight of acyl halides.,Mechanism: Nucleophilic acyl substitution 机理：酰基的亲核取代,
13、Anhydrides 酸酐,Reacts faster than esters but more slowly than halides. Hydrolysis occurs in neutral, acidic and alkaline solutions. Under room temperature hydrolysis rate is slow.,Esters 酯,Reverse of Fischer esterification.Reaches equilibrium.Reacts more slowly than acyl halides and anhydrides.Genera
14、lly needs catalysis: H+, OH-“皂化”,Hydrolysis Mechanisms (In Alkaline Solution) of Ester 酯的水解机理（碱性溶液中）,QUESTIONS TO BE ANSWERED: Cleave at acyl-oxygen bond or at oxygen-alkyl bond. “酰氧” ？ “烷氧”？ Single molecular mechanism or double molecular mechanism? 单分子？ 双分子？ SN2 mechanism or addition-elimination me
15、chanism?SN2？ 加成消去？,Evidence 1:,Evidence 2:,Evidence 3:,18O-labeling experiments 18O同位素标记,Possible Mechanism 可能机理,Proton Exchange,质子交换,ANSWERS TO THOSE QUESTIONS: Cleave at acyl-oxygen bond. Bimolecular mechanism. Addition-elimination mechanism.,BAc2,碱催化,酰氧键断裂,双分子历程,Hydrolysis Mechanisms (In Acidic S
16、olution) of Ester: 酯的水解机理（酸性溶液中）,Three possible mechanisms are involved in acid-induced ester hydrolysis.,酸催化酯的水解有三种可能的机理：,AAc2 （酸催化的双分子酰氧断裂） 适用于一般的一元羧酸与伯醇或仲醇形成的酯,AAc1 （酸催化的单分子酰氧断裂） 适用于羰基附近有空阻因素的情况,AAl1 （酸催化的单分子烷氧断裂） 适用于三级醇形成的酯。,Amides 酰胺,Reacts more slowly than acyl halides, anhydrides and esters.S
17、trong acid or strong base is required.Prolonged heating is required.,Nitriles 腈,Heating with aqueous acid or base will hydrolyze a nitrile to an acid. Under mild conditions, nitriles hydrolyze to an amide.,15.3.2 Alcoholysis of Derivatives of Carboxyl Acid羧酸衍生物的醇解,15.3.2.1 Alcoholysis of Acyl Halide
18、 15.3.2.2 Alcoholysis of Anhydride 15.3.2.3 Alcoholysis of Ester 15.3.2.4 Alcoholysis of Amide 15.3.2.5 Alcoholysis of Nitrile,Reaction 反应,15.3.2.1 Alcoholysis of Acyl Halide 酰卤的醇解,Application: To prepare esters.,15.3.2.2 Alcoholysis of Anhydride 酸酐的醇解,分步! 两类不同的反应,15.3.2.3. Alcoholysis of Ester 酯的醇解
19、,Cat. : HCl H2SO4 TosH etc Note: Reversible reactions,酯交换反应,1. 合成难以合成或者不能直接酯化合成的酯。,酯交换的结果产物不变,2. 二酯化合物的选择性水解,Applications 应用:,3.工业用途,先酯交换，再聚合。,eg: 涤纶的合成,15.3.2.4. Alcoholysis of Amide 酰胺的醇解,Catalyzed by acidic catalysts.Heating to high temperature is required.,15.3.2.5. Alcoholysis of Nitrile 腈的醇解,A
20、cidic condition. (eg, HCl, H2SO4),无合成应用价值,亚胺酯盐酸盐 （无水时可分离得到）,有水时可直接得到酯,15.3.3.1 Ammonolysis of Acyl Halide 15.3.3.2 Ammonolysis of Anhydride 15.3.3.3 Ammonolysis of Ester 15.3.3.4 Ammonolysis of Amide 15.3.3.5 Ammonolysis of Nitrile,15.3.3 Ammonolysis of Derivatives of Carboxyl Acid羧酸衍生物的氨解,Reaction
21、反应,15.3.3.1 Ammonolysis of Acyl Halide 酰卤的氨解,Eg.,15.3.3.2. Ammonolysis of Anhydride 酸酐的氨解,Eg.,15.3.3.3. Ammonolysis of Ester 酯的氨解,Eg.,肼、羟氨亦可反应,A strong base is not usually a leaving group unless its in an exothermic step （放热过程）.,15.3.3.4 Ammonolysis of Amide 酰胺的氨解,N-acylimidazole is always used as a
22、cylation reagent. N酰基咪唑为优良的酰化剂。,15.3.3.5. Ammonolysis of Nitrile 腈的胺解,高压釜中,咪 盐,15.3.4 Acidolysis of Derivatives of Carboxyl Acid 羧酸衍生物的酸解,15.3.4.1 Acidolysis of Acyl Halide 15.3.4.2 Acidolysis of Anhydride 15.3.4.3 Acidolysis of Ester 15.3.4.4 Acidolysis of Amide,Reactions 反应,酰基转移反应,一般均需采取一定 的手段使平衡右
23、移,15.3.4.1 Acidolysis of Acyl Halide 酰卤的酸解得到平衡混和物，生成新的酸及酰卤,15.3.4.2 Acidolysis of Anhydride 酐的酸解制备混酐,15.3.4.3 Acidolysis of Ester 酯的酸解得到平衡混和物，生成新的酸及酯,15.3.4.4 Acidolysis of Amide 酰胺的酸解得到平衡混和物，生成新的酸及酰胺,Reactivity,For a carboxylic acid derivative to undergo a nucleophilicacyl substitution reaction, th
24、e incoming nucleophilemust not be a much weaker base than the group that is to be replaced. A carboxylic acid derivative can be converted into a less reactive carboxylic acid derivative, but not into one that is more reactive. Only esters and amides are commonly found in nature. Acid halides and aci
25、d anhydrides undergo nucleophilic attack by water such that they cannot exist in living organisms.,15.3.5 Reactions with Organometallic Compounds 与金属有机化合物的反应,15.3.5.1 Reactions with Grignard Reagents and Lithium Alkyl与格氏试剂和烷基锂的反应 15.3.5.2 Reactions with Lithium Dialkylcuprate与二烷基铜锂的反应,15.3.5.1 React
26、ions with Grignard Reagents and Lithium Alkyl 与格氏试剂、烷基锂反应,Acyl Halides 酰卤,Step 1,Step 2,Step 1 Equal molar RMgX Anhydrous FeCl3 Low temperature,Step 2For R and R with large space hindrance, reaction may stop at step 1.,Anhydrides 酸酐,Esters 酯,For R and R with large space hindrance, reaction may stop
27、here.,合成上用处不大,Amides 酰胺,NO H is allowed in N atom,合成上用处不大,Nitriles 腈,亚 胺,15.3.5.2. Reactions with Lithium Dialkylcuprate 只与活泼的酰卤反应，生成酮，产率很高,15.3.6 Reduction of Carboxyl Acid Derivatives 羧酸衍生物的还原,15.3.6.1 Reduction of Acyl Halide 15.3.6.2 Reduction of Anhydride 15.3.6.3 Reduction of Ester 15.3.6.4 Re
28、duction of Amide 15.3.6.5 Reduction of Nitrile,15.3.6.1 Reduction of Acyl Halide 酰卤的还原,LiAlH4,AlLi(t-BuO)3H,Rosenmund Reduction,Acyl Halide Can be reduced to alcohols or aldehydes.,15.3.6.2 Reduction of Anhydride 酸酐的还原,二元酸的环酐可还原成内酯,15.3.6.3. Reduction of Ester 酯的还原,Mechanism 机理,Bouveault-Blanc React
29、ion 玻沃布兰反应,可用于大量制备,15.3.6.4. Reduction of Amide 酰胺的还原,过量N,N-二烃基取代酰胺与还原剂反应可得醛,15.3.6.5 Reduction of Nitrile 腈的还原,Short Review：Reactions of Acyl Halides,Short Review：Reactions of Anhydride,Short Review：Reactions of Ester,15.3.7 Other Reactions 羧酸衍生物的其它反应,15.3.7.1 Halogenation of Acyl Halide on -H酰卤的-H
30、卤化 15.3.7.2 Other Reactions of Ester酯的其它反应 15.3.7.3 Other Reactions of Acyl Amide酰胺的其它反应 15.3.7.4 Hydrolysis of Nitrile腈的水解,Acyl Halide Undergoes Halogenations on -H easier than carboxyl acids. -H卤化比羧酸容易的多。,15.3.7.1 Halogenation of Acyl Halide on -H 酰卤的-H卤化,15.3.7.2. Other Reactions of Ester 酯的其它反应,
31、1. Claisen Condensation Claisen酯缩合反应,Cross Clasien condensation 交叉Clasien酯缩合,解决方法之一：无-H的酯,四个可能产物,Carbonyl group conjugates with the aromatic ring, making this substrate less active. Often stronger base is required (e.g. NaH).,羰基与苯环共轭，不太活泼， 缩合时需要较强的碱。,Induction effect activates one of the carbonyl gr
32、oups, and this reaction is relatively easier.,+,诱导效应使得羰基活泼，容易反应。,Which one is easier to lose its -H ?,解决方法之二：酯与酮的缩合,酮的-H 酸性更强,Dieckmann Reaction 狄克曼反应：分子内酯缩合，生成环酯合成五、六元环的方法,2. Acyloin Condensation 酮醇缩合,Reaction,Mechanism,Bimolecular reduction 双分子还原,-羟基酮,Applications 应用,Synthesis of catenane,Synthesi
33、s of Micro-reactor,索 烃,Synthesis of catenane 索烃的合成,Product of a random cross,成环反应的策略！,p- conjugation p-共轭,Higher acidity 强酸性,15.3.7.3. Other Reactions of Acyl Amide 酰胺的其它反应,Lower alkalescency 弱碱性,Acidity 酸性,Alkalescency 微碱性,Shows no acidity,React with NaOEt,React with NaOH or KOH,1. Acidic and Alkal
34、ine Properties 酸碱性,2. Dehydration 脱水,3. Hoffmann degradation of amides 霍夫曼降级反应,Often used when synthesizing a primary amine which contain 1 carbon less than the reactant.,用于制备少一个碳的一级胺,15.3.7.4 Hydrolysis of Nitrile 腈的水解,Nu： 接受亲核试剂的进攻,Strong Electrophilic reagents 接受强亲电试剂进攻,+ Acid,+ Base,酸性条件下,碱性条件下,
35、Ritter Reaction 里特反应,用途：特殊胺的制备,强酸性溶液中，由叔醇生成的碳正离子类似于质子，可进攻氰基氮原子。,15.4 Fats、 Wax and Synthetic Detergents 油脂、蜡和合成洗涤剂 （Learn on your own）,15.4.1 油脂 （一）分类（二）化学性质 15.4.2 肥皂与合成洗涤剂 （一）结构特点（二）洗涤原理 15.4.3 磷脂与生物膜 15.4.4 蜡,油脂 油 脂 皂化 油的干性 碘值 酸败 肥皂 合成洗涤剂 磷脂 蜡,15.5 Preparation 羧酸衍生物的制备 （Learn on your own）,15.6 De
36、rivatives of Carbonic Acid 碳酸衍生物,15.6.1 Acyl Halide of Carbonic Acids 15.6.2 Amide of Carbonate Acid 15.6.3 Ester of Carbonate Acid,Carbonic Acid H2CO3,Stable稳定,Unstable不稳定,羟基甲酸,共用一个羰基的二元酸,15.6.1 Acyl Halide of Carbonic Acids 碳酸的酰氯,15.6.1.1 Carbonic Acid Monochloride 单酰氯,Unstable 不稳定,15.6.1.2 Carbon
37、ic Acid Dichloride 二酰氯,Phosgene 光气,6/15/2004 Fujian Institute of Research on the Structure of Matter Phosgene leaking caused 1 death and 260 injury.,氯代甲酸,窒息性，剧毒，引起肺水肿,Preparation 制备,Lab：CCl4与80发烟H2SO4（发烟H2SO4中含80游离的SO3）,Industrial 工业方法,Phosgene generator,性质：类似于羧酸的酰氯，可水解、氨解及醇解,Usage 用途,It often works
38、 as an active reagent, or starting material in organic synthesis. 是一种活泼试剂，也是有机合成中的起始原料。,15.6.2 Amide of Carbonate Acid 碳酸的酰胺,15.6.2.1 Carbonate Acid Monoamides 单酰胺,“灭菌灵”,氨基甲酸 Unstable,氨基甲酸盐,氨基甲酸酰氯,氨基甲酸酯,Preparation 制备,15.6.2.2 Carbonate Acid Diamides 二酰胺（尿素）,Carbamide(urea), is one of the final prod
39、ucts of protein metabolizm. About 30g of Carbamide per day is discharged from a healthy adult.,Whls Reaction,Industrial 工业上,Properties 性质,In microorganism土壤中,In organism 生物体系中,In Lab 实验室,1. Hydrolysis 水解,2. Nitrogen releasing reaction 放氮反应,This reaction is often used to measure the carbamide content
40、 in urea by measuring the volume of N2 produced. 测氮气的体积可知尿液中尿素的含量。,This reaction is often used to destroy oxides of nitrous acid, and nitrogen oxides. 用于破坏亚硝酸及氮的氧化物。,3. Biuret Reaction 双缩脲反应,碱,CuSO4溶液,紫红色溶液,凡化合物中含不止一个酰胺片段NHCO ，均发生此反应。这个反应因此也用来进行多肽的鉴别。,Ala-His-Ser,双缩脲,15.6.3 Ester of Carbonate Acid 碳
41、酸的酯,15.6.3.1 Carbonate Acid Monoester 碳酸一酯,Preparation 制备,碳酸甲酯钠,15.6.3.2 Carbonate Acid Diester 碳酸二酯,Preparation 制备,Properties 性质,碳酸二酯主要用于聚碳酸酯的合成,酯基转移反应,15.7 Derivatives of Ortho-Acid 原酸衍生物,15.7.1 原碳酸衍生物15.7.2 原酸衍生物原酸酯,原酸,Very stable 非常稳定,游离状态下亦稳定,Does not exist 不存在,胍,15.7.1 原碳酸衍生物,Preparation 制备,Or
42、tho-Acid is not stable, while its ester, especially its aromatic derivatives, shows some stability.原酸不稳定，但是它的酯，尤其芳香衍生物物却表现出一定的稳定性。,原甲酸三乙酯,15.7.2 原酸衍生物原酸酯,Chemical Reactions 化学性质, 碱性溶液中稳定，在酸性溶液中极易水解成羧酸酯。, 和醛酮反应生成缩醛或缩酮。,类似于缩醛（酮）,用于制备缩醛（酮）,15.8.1 Peroxy Acid （peracid） 15.8.2 Acyl peracid,15.8 Peracid a
43、nd acyl peraacid过酸与二酰基过氧,过氧化氢 过酸 二酰基过氧,15.8.1 Peroxy Acid （peracid） 过酸,15.8.1.1 Structure and Properties 结构与性质,固态下，强的分子内氢键，同时分子间也可以以氢键相连：,溶液中，分子内氢键仍保持不变。, Explosive 极易爆炸, Hydrogen bond 氢健,15.8.1.2 Chemical Reactions 化学反应,1. 酸性比相应的羧酸弱,Baeyer-Villiger Reaction,原因之一： 分子内氢键 原因之二：生成稳定性较小的过酸根,2.氧化烯烃生成环氧化物
44、 3.氧化醛酮,15.8.2 Acyl peracid 二酰基过氧,Often used as free radical initiator 常用作自由基引发剂,15.9 Isonitrile 异腈,15.9.1 Structure and Properties 15.9.2 Reactions of isonitrile,15.9.1 Structure and Properties 结构与性质,结构：,制备：,较稳定的含两价碳的化合物,15.9.2 Reactions of isonitrile 异腈的反应,1、酸、碱稳定性,对碱稳定，对酸不稳定，用稀酸可使其水解为N-烃基甲酰胺。,2、催化加氢,3、与卤素加成,4、与氧化汞及硫反应,Isocyanate 异氰酸酯,Isothiocyanates 异硫氰酸酯,15.10 Important carboxyl acid derivatives、 their source and use,( Learn on your own ),Thank you!,
