1、.,Derivatives of Carboxylic Acids 第十五章 羧酸衍生物,Organic Chemistry A (2),.,15.1 Structure & Nomenclature 15.2 Physical Properties & Spectrum Data 15.3 Chemical Reactions 15.4 Fats, Was and Synthetic detergent (learn by yourself) 15.5 Preparation 15.6 Derivatives of carbonic Acid 15.7 Derivatives of Orth

2、o-Acid 15.8 peroxy acid 15.9 Isonitrile 15.10 Sources and Usages of important Carboxylic Acid Derivatives,Content,.,15.1 羧酸衍生物的結(jié)構(gòu)與命名 15.2 羧酸衍生物物理性質(zhì)和波譜學(xué)性質(zhì) 15.3 化學(xué)性質(zhì) 15.4 油脂、蠟和合成洗滌劑 15.5 羧酸衍生物的制備 15.6 碳酸衍生物 15.7 原酸衍生物 15.8 過酸和二酰基過酸 15.9 異腈 15.10 重要的羧酸衍生物及羧酸衍生物的來源與用途,Content,.,Carboxylic Acid Derivativ

3、es 羧酸衍生物,羧酸衍生物在結(jié)構(gòu)上的共同特點(diǎn)是都含有酰基。,.,15.1 Structure & Nomenclature,15.1.1 Structure 15.1.2 Nomenclature,.,15.1.1 Structure 結(jié)構(gòu),?；c其所連的基團(tuán)都能形成p-共軛體系。C-L 具有部分雙鍵性質(zhì)，雙鍵的程度取決于C的穩(wěn)定性，C的穩(wěn)定性隨L的變化而不同。,.,Acyl halide: L=Cl 電負(fù)性大 Anhydride: Ester: L=O 電負(fù)性略小 Amide: L=N 電負(fù)性更小,.,15.1.2 Nomenclature,15.1.2.1 Acyl Halide and

4、 Amide 15.1.2.2 Anhydride and Nitrile 15.1.2.3 Ester,.,15.1.2.1 Acyl Halide and Amide 酰鹵與酰胺,中文命名 根據(jù)分子中?；奶荚訑?shù)命名為“某酰鹵”或“某酰胺”。,.,環(huán)狀酰胺：內(nèi)酰胺,己內(nèi)酰胺,5-甲基己內(nèi)酰胺,注意：編號沿用羧酸的編號,.,.,.,15.1.2.2 Anhydride and Nitrile 酸酐與腈,中文命名 根據(jù)水解所得的酸命名為“某酸酐”或“某腈”。,.,若-CN作為取代基，則稱為“氰基”。,間氰基苯甲酸,3-氰基丁磺酸,.,.,中文命名 根據(jù)水解所得的酸、醇，命名為“某酸某酯”

5、。,15.1.2.3 Ester 酯,.,.,15.2 Physical Properties and Spectrum Data,15.2.1 Physical Properties 15.2.2 Spectrum Data,.,Boiling Points 熔點(diǎn),Even 3 amides have strong attractions.,15.2.1 Physical Properties 物理性質(zhì),.,Melting Points 熔點(diǎn),Amides have very high melting points. Melting points increase with increasi

6、ng number of N-H bonds.,m.p. -61C,m.p. 28C,m.p. 79C,胺的熔點(diǎn)很高, 且隨著N-H鍵的增多而上升.,.,Acyl Halide To be irritating and decompose in water strongly. 具有刺激性，遇水劇烈分解。 Anhydride To decompose in water. 遇水分解。,Nitrile,Highly polarized High dipole moment and high boiling point. 高度極化，高的偶極矩與沸點(diǎn),其它性質(zhì)：,.,Esters 酯 Esters te

7、nd to have sweet smells. 酯一般有芬芳的氣息。,.,Amides 胺,Many amides can form intermolecular hydrogen bond.,許多胺類化合物可以形成分子間氫鍵。,.,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 紅外光譜,=,.,15.2.2.2 1H NMR Spect

8、roscopy 1H NMR 譜,.,15.2.2.3 13C NMR Spectroscopy 13C NMR 譜,.,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 Reacti

9、ons with Organometallic Compounds 15.3.6 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 與金屬有機(jī)化合物的反應(yīng) 15.3.6 與羧酸衍生物的反應(yīng) 15.3.7 其它反應(yīng),.,水解、氨解、醇解和酸解反應(yīng)總論：,Nu- = -OH, H2O 水解反應(yīng) Nu- = HOR 醇解反應(yīng) Nu- = NH3 氨解反應(yīng) Nu- = RCOOH 酸解

10、反應(yīng),含 義,.,Acyl halide: L=Cl 電負(fù)性大 Anhydride: Ester: L=O 電負(fù)性略小 Amide: L=N 電負(fù)性更小,反應(yīng)性,1011 107 1.0 10-2,.,哪個(gè)是更好的離去基團(tuán)？,一般反應(yīng)過程,.,Reactivity decreases as leaving group becomes more basic. 隨著離去基團(tuán)堿性增大，離去能力降低，反應(yīng)活性降低。,.,氨解反應(yīng)：,L = X L = OCOR L = OR L = NH2,離去能力均強(qiáng)于NH2,平衡混合物,.,醇解反應(yīng)：,L = X L = OCOR L = OR L = NH2,離

11、去能力均強(qiáng)于OR,平衡混合物,離去能力弱于OR,.,水解反應(yīng)：,L = X L = OCOR L = OR L = NH2,離去能力均強(qiáng)于OH,離去能力弱于OH,離去能力類似于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應(yīng)的羧酸和另外一種產(chǎn)物。,.,Rates of Hydrolysi

12、s (for the same R group),L = X, OCOR, OR, NH2,.,Acyl Halides 酰鹵,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 acy

13、l halides.,.,Mechanism: Nucleophilic acyl substitution 機(jī)理：?；挠H核取代,.,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

14、 equilibrium. Reacts more slowly than acyl halides and anhydrides. Generally needs catalysis: H+, OH- “皂化”,.,Hydrolysis Mechanisms (In Alkaline Solution) of Ester 酯的水解機(jī)理（堿性溶液中）,QUESTIONS TO BE ANSWERED: Cleave at acyl-oxygen bond or at oxygen-alkyl bond. “酰氧” ？ “烷氧”？ Single molecular mechanism or do

15、uble molecular mechanism? 單分子？ 雙分子？ SN2 mechanism or addition-elimination mechanism? SN2？ 加成消去？,.,Evidence 1:,Evidence 2:,Evidence 3:,18O-labeling experiments 18O同位素標(biāo)記,.,Possible Mechanism 可能機(jī)理,Proton Exchange,質(zhì)子交換,.,ANSWERS TO THOSE QUESTIONS: Cleave at acyl-oxygen bond. Bimolecular mechanism. Addi

16、tion-elimination mechanism.,BAc2,堿催化,酰氧鍵斷裂,雙分子歷程,.,Hydrolysis Mechanisms (In Acidic Solution) of Ester: 酯的水解機(jī)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種可能的機(jī)理：,.,AAc2 （酸催化的雙分子酰氧斷裂） 適用于一般的一元羧酸與伯醇或仲醇形成的酯,.,AAc1 （酸催化的單分子酰氧斷裂） 適用于羰基附近有空阻因素的情況,.,AAl1 （酸催化的單

17、分子烷氧斷裂） 適用于三級醇形成的酯。,.,Amides 酰胺,Reacts more slowly than acyl halides, anhydrides and esters. Strong 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 amid

18、e.,.,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 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 反應(yīng),.,15.3.2.1 Alcoholysis of Acyl Halide 酰鹵的醇解,Application: To

19、 prepare esters.,.,15.3.2.2 Alcoholysis of Anhydride 酸酐的醇解,分步! 兩類不同的反應(yīng),.,15.3.2.3. Alcoholysis of Ester 酯的醇解,Cat. : HCl H2SO4 TosH etc Note: Reversible reactions,酯交換反應(yīng),.,1. 合成難以合成或者不能直接酯化合成的酯。,酯交換的結(jié)果產(chǎn)物不變,2. 二酯化合物的選擇性水解,Applications 應(yīng)用:,.,3.工業(yè)用途,先酯交換，再聚合。,eg: 滌綸的合成,.,15.3.2.4. Alcoholysis of Amide 酰胺

20、的醇解,Catalyzed by acidic catalysts. Heating to high temperature is required.,15.3.2.5. Alcoholysis of Nitrile 腈的醇解,Acidic condition. (eg, HCl, H2SO4),無合成應(yīng)用價(jià)值,亞胺酯鹽酸鹽 （無水時(shí)可分離得到）,有水時(shí)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 Ammo

21、nolysis 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 反應(yīng),.,15.3.3.1 Ammonolysis of Acyl Halide 酰鹵的氨解,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、羥氨亦可反應(yīng),.,.,A strong base is not usuall

22、y a leaving group unless its in an exothermic step （放熱過程）.,.,15.3.3.4 Ammonolysis of Amide 酰胺的氨解,N-acylimidazole is always used as acylation reagent. N酰基咪唑?yàn)閮?yōu)良的?；瘎?.,15.3.3.5. Ammonolysis of Nitrile 腈的胺解,高壓釜中,咪 鹽,.,15.3.4 Acidolysis of Derivatives of Carboxyl Acid 羧酸衍生物的酸解,15.3.4.1 Acidolysis of Acy

23、l Halide 15.3.4.2 Acidolysis of Anhydride 15.3.4.3 Acidolysis of Ester 15.3.4.4 Acidolysis of Amide,.,Reactions 反應(yīng),酰基轉(zhuǎn)移反應(yīng),一般均需采取一定 的手段使平衡右移,.,15.3.4.1 Acidolysis of Acyl Halide 酰鹵的酸解 得到平衡混和物，生成新的酸及酰鹵,15.3.4.2 Acidolysis of Anhydride 酐的酸解 制備混酐,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.

24、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, the 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 re

25、active carboxylic acid derivative, but not into one that is more reactive. Only esters and amides are commonly found in nature. Acid halides and acid anhydrides undergo nucleophilic attack by water such that they cannot exist in living organisms.,.,15.3.5 Reactions with Organometallic Compounds 與金屬有

26、機(jī)化合物的反應(yīng),15.3.5.1 Reactions with Grignard Reagents and Lithium Alkyl 與格氏試劑和烷基鋰的反應(yīng) 15.3.5.2 Reactions with Lithium Dialkylcuprate 與二烷基銅鋰的反應(yīng),.,15.3.5.1 Reactions with Grignard Reagents and Lithium Alkyl 與格氏試劑、烷基鋰反應(yīng),Acyl Halides 酰鹵,Step 1,Step 2,Step 1 Equal molar RMgX Anhydrous FeCl3 Low temperature,St

27、ep 2 For 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 here.,合成上用處不大,.,Amides 酰胺,NO H is allowed in N atom,合成上用處不大,Nitriles 腈,亞 胺,.,.,15.3.5.2. Reactions with Lithium Dialkylcuprate 只與活潑的酰鹵反應(yīng)，生成酮，產(chǎn)率

28、很高,.,15.3.6 Reduction of Carboxyl Acid Derivatives 羧酸衍生物的還原,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 Reduction of Amide 15.3.6.5 Reduction of Nitrile,.,15.3.6.1 Reduction of Acyl Halide 酰鹵的還原,LiAlH4,AlLi(t-BuO)3H,Rosenmund Reduction,Acyl

29、Halide Can be reduced to alcohols or aldehydes.,.,15.3.6.2 Reduction of Anhydride 酸酐的還原,二元酸的環(huán)酐可還原成內(nèi)酯,.,15.3.6.3. Reduction of Ester 酯的還原,Mechanism 機(jī)理,.,Bouveault-Blanc Reaction 玻沃布蘭反應(yīng),可用于大量制備,.,15.3.6.4. Reduction of Amide 酰胺的還原,過量N,N-二烴基取代酰胺與還原劑反應(yīng)可得醛,.,15.3.6.5 Reduction of Nitrile 腈的還原,.,Short Rev

30、iew：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應(yīng),15.3.7.1 Halogenation of Acyl Halide on -H 酰鹵的-H鹵化 15.3.7.2 Other Reactions of Ester 酯的其它反應(yīng) 15.3.7.3 Other Reactions of Acyl Amide 酰胺的其它反應(yīng) 15.3.7.4 Hydrolysis o

31、f Nitrile 腈的水解,.,Acyl Halide Undergoes Halogenations on -H easier than carboxyl acids. -H鹵化比羧酸容易的多。,15.3.7.1 Halogenation of Acyl Halide on -H 酰鹵的-H鹵化,.,15.3.7.2. Other Reactions of Ester 酯的其它反應(yīng),1. Claisen Condensation Claisen酯縮合反應(yīng),.,.,.,Cross Clasien condensation 交叉Clasien酯縮合,解決方法之一：無-H的酯,四個(gè)可能產(chǎn)物,.,

32、Carbonyl group conjugates with the aromatic ring, making this substrate less active. Often stronger base is required (e.g. NaH).,羰基與苯環(huán)共軛，不太活潑， 縮合時(shí)需要較強(qiáng)的堿。,.,Induction effect activates one of the carbonyl groups, and this reaction is relatively easier.,+,誘導(dǎo)效應(yīng)使得羰基活潑，容易反應(yīng)。,.,.,Which one is easier to los

33、e its -H ?,解決方法之二：酯與酮的縮合,酮的-H 酸性更強(qiáng),.,Dieckmann Reaction 狄克曼反應(yīng)： 分子內(nèi)酯縮合，生成環(huán)酯合成五、六元環(huán)的方法,.,2. Acyloin Condensation 酮醇縮合,Reaction,Mechanism,Bimolecular reduction 雙分子還原,-羥基酮,.,Applications 應(yīng)用,Synthesis of catenane,Synthesis of Micro-reactor,索 烴,.,Synthesis of catenane 索烴的合成,Product of a random cross,成環(huán)反應(yīng)的

34、策略！,.,p- conjugation p-共軛,Higher acidity 強(qiáng)酸性,15.3.7.3. Other Reactions of Acyl Amide 酰胺的其它反應(yīng),Lower alkalescency 弱堿性,.,Acidity 酸性,Alkalescency 微堿性,Shows no acidity,React with NaOEt,React with NaOH or KOH,1. Acidic and Alkaline Properties 酸堿性,.,2. Dehydration 脫水,.,3. Hoffmann degradation of amides 霍夫曼

35、降級反應(yīng),Often used when synthesizing a primary amine which contain 1 carbon less than the reactant.,用于制備少一個(gè)碳的一級胺,.,15.3.7.4 Hydrolysis of Nitrile 腈的水解,Nu： 接受親核試劑的進(jìn)攻,Strong Electrophilic reagents 接受強(qiáng)親電試劑進(jìn)攻,.,+ Acid,+ Base,酸性條件下,堿性條件下,.,Ritter Reaction 里特反應(yīng),用途：特殊胺的制備,強(qiáng)酸性溶液中，由叔醇生成的碳正離子類似于質(zhì)子，可進(jìn)攻氰基氮原子。,.,15

36、.4 Fats、 Wax and Synthetic Detergents 油脂、蠟和合成洗滌劑 （Learn on your own）,.,15.4.1 油脂 （一）分類 （二）化學(xué)性質(zhì) 15.4.2 肥皂與合成洗滌劑 （一）結(jié)構(gòu)特點(diǎn) （二）洗滌原理 15.4.3 磷脂與生物膜 15.4.4 蠟,油脂 油 脂 皂化 油的干性 碘值 酸敗 肥皂 合成洗滌劑 磷脂 蠟,.,15.5 Preparation 羧酸衍生物的制備 （Learn on your own）,.,15.6 Derivatives of Carbonic Acid 碳酸衍生物,15.6.1 Acyl Halide of Car

37、bonic Acids 15.6.2 Amide of Carbonate Acid 15.6.3 Ester of Carbonate Acid,.,Carbonic Acid H2CO3,Stable穩(wěn)定,Unstable不穩(wěn)定,羥基甲酸,共用一個(gè)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 單酰氯,Unstable 不穩(wěn)定,15.6.1.2 Carbonic Acid Dichloride 二酰氯,Phosgene 光氣,6/15/2004 Fujian In

38、stitute of Research on the Structure of Matter Phosgene leaking caused 1 death and 260 injury.,氯代甲酸,窒息性，劇毒，引起肺水腫,.,Preparation 制備,Lab：CCl4與80發(fā)煙H2SO4（發(fā)煙H2SO4中含80游離的SO3）,Industrial 工業(yè)方法,Phosgene generator,.,性質(zhì)：類似于羧酸的酰氯，可水解、氨解及醇解,.,Usage 用途,It often works as an active reagent, or starting material in o

39、rganic synthesis. 是一種活潑試劑，也是有機(jī)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 單酰胺,“滅菌靈”,氨基甲酸 Unstable,氨基甲酸鹽,氨基甲酸酰氯,氨基甲酸酯,.,Preparation 制備,15.6.2.2 Carbonate Acid Diamides 二酰胺（尿素）,Carbamide(urea), is one of the final products of protein metabolizm. About 30g of Car

40、bamide per day is discharged from a healthy adult.,Whls Reaction,Industrial 工業(yè)上,.,Properties 性質(zhì),In microorganism土壤中,In organism 生物體系中,In Lab 實(shí)驗(yàn)室,1. Hydrolysis 水解,.,2. Nitrogen releasing reaction 放氮反應(yīng),This reaction is often used to measure the carbamide content in urea by measuring the volume of N2 produced. 測氮?dú)獾捏w積可知尿液中尿素的含量。,This reaction is often used to destroy oxides of nitrous acid, and nitrogen oxides. 用于破壞亞硝酸及氮的氧化物。,.,3. Biuret Reaction 雙縮脲反應(yīng),堿,CuSO4溶液,紫紅色溶液,凡化合物中含不止一個(gè)酰胺片段NHCO ，均發(fā)生此反應(yīng)。這個(gè)反應(yīng)因此也用來進(jìn)行多肽的鑒別。,Ala-His-Ser,雙縮脲,.,15.6.3 Ester of Carbonate Acid 碳酸的酯,15.6.3.1 Carbonate Acid Mo