第十章 羧酸衍生物-2

1、Chapter 10 Chapter 10 羧酸衍生物羧酸衍生物 羧酸衍生物指羧酸分子中，羧基上的羟基被其它原子羧酸衍生物指羧酸分子中，羧基上的羟基被其它原子或原子团取代后生成的化合物。或原子团取代后生成的化合物。OCROHOCRXOCROCOROCROROCRNH2C NR羧酸酰卤酸酐酯酰胺腈10.1 10.1 命名命名酰卤的命名酰卤的命名: : 将羧酸分子中的将羧酸分子中的“酸酸”字改为酰卤即可。字改为酰卤即可。乙酰氯 苯甲酰溴 环己烷甲酰氯COClCH3CClOCOBr酸酐的命名酸酐的命名: : 在羧酸名称的后面加上酐字。在羧酸名称的后面加上酐字。OCH3COCOCH3OOOAcetic

2、 anhydrideBenzoic anhydrideSuccinic anhydrideCOOCO乙酸酐 苯甲酸酐 丁二酸酐OCClH2COCOCH2ClBis(chloroacetic) anhydrideOCH3COCOAcetic benzoic anhydride双氯乙酸酐乙酸苯甲酸酐酰胺的命名酰胺的命名: : 将羧酸名称中的酸字改为酰胺。将羧酸名称中的酸字改为酰胺。CNH2OAcetamide(from acetic acid)Hexanamide(from hexanoic acid)Cyclopentanecarboxamide(from cyclopentanecarboxy

3、lic acid)CH3CNH2OCH3(CH2)4CNH2O乙酰胺 己酰胺 环戊烷甲酰胺酰胺的命名 N-甲基丙酰胺 N,N-二乙基环己烷甲酰胺CON(CH2CH3)2CH3CH2CNHCH3O酯的命名酯的命名在羧酸的名称后面加上醇或酚中的在羧酸的名称后面加上醇或酚中的烃基名称烃基名称和和酯酯字。字。CH3COCH2CH3OCH3OCCH2COCH3OOCOOC(CH3)3Ethyl acetateDimetyl malonatetert-Butylcyclohexanecarboxylate(the ethyl ester of acetic acid)(the dimethyl ester

4、 of malonic acid)(the tert-butyl ester ofcyclohexanecarboxylic acid) 乙酸乙酯丙二酸二甲酯环己甲酸叔丁酯腈的命名腈的命名: :根据母体链碳原子数叫某腈。根据母体链碳原子数叫某腈。4甲基戊腈 乙腈CH3CHCH2CH2CNCH354321CH3C NC NCNCH3CH3123456苯甲腈2,2-二甲基环己甲腈10.2 10.2 羧酸衍生物的取代反应羧酸衍生物的取代反应COXRCH2COOCOORCONH2(R)CRORCH2RCH2RCH2RCHCOLHRCOLNuRCONu+Lor HNuHLorRCOLRCOOHH2OH

5、or OHROHRNH2RCOORRCONHRH or OHRCOLNuRCONu+ LRCONuL亲亲核核加加成成消消除除RCOHLHNuRCOHNu+RCOHNuL亲亲核核加加成成消消除除HRCOHNuLHLHOCYRA leaving groupA carbonxylic acid derivativeOCRHOCRRAn aldehydeA ketoneNot a leaving group羧酸衍生物与醛酮亲核取代反应比较提问：提问： 醛、酮和羧酸衍生物分子中都含有羰基，羧酸醛、酮和羧酸衍生物分子中都含有羰基，羧酸衍生物可发生亲核取代反应，但醛、酮只发生亲核加衍生物可发生亲核取代反应，

6、但醛、酮只发生亲核加成而不发生亲核取代。为什么？成而不发生亲核取代。为什么？ 解答解答: 醛、酮和羧酸衍生物均接受亲核试剂的进攻，第一步醛、酮和羧酸衍生物均接受亲核试剂的进攻，第一步发生亲核加成，形成四面体的氧负离子中间体；而在发生亲核加成，形成四面体的氧负离子中间体；而在第二步消除反应中，由于第二步消除反应中，由于 H H- - 或或 R R- - 的碱性极强，很的碱性极强，很难于离去，因此中间体氧负离子结合一个质子得到加难于离去，因此中间体氧负离子结合一个质子得到加成产物。成产物。 RCONuLRCOHNuLHor该反应的反应机理？CClONa+ -OCH3CH3OHCOOCH3羧酸衍生物

7、的相对反应活性羧酸衍生物的相对反应活性RCOClRCOORCOORRCONH2(R)CRORCOL XOORNH2(R)CRO反应活性是两方面因素共同作用的结果羧酸衍生物取代反应的种类羧酸衍生物取代反应的种类CORY羧酸衍生物COROHH2O水解CORORROH醇解CORNH2NH3氨解CORHCROHHHHH还原1 alcoholCORRCROHRRRMgXRMgXKetone3 alcohol预测产物:COClCH3CHCH3OH?Benzoyl chlorideCOClCH3CHCH3OHCOOCHCH3CH3Benzoyl chlorideIsopropyl benzoateLeavi

8、ng groupNucleophile预测下列反应的产物:OCOCH3COCH3H3COCOCH3(a)(c)NaOHH2OCH3OH?COH3CCl?NH3(b)Na+ -OCH310.3 酰卤酰卤的反应酰卤的水解RClO+H2OROHO乙酰氯遇水强烈水解，但随着酰氯分子量的增大，水解速度减慢，可能是由于酰氯在水中的溶解度减小所致。芳香族酰氯水解速度很慢，加热或加碱能使水解迅速进行。CORCl+ OH2COORClHHCOROHHCOROHAn acid chlorideA carboxylic acidCl-+Cl-酰卤的醇解COCl+OHCOOPyridineBenzoyl chlori

9、deCyclohexanolCyclohexyl benzoate (97%)CH2OHHO+H3CCOClPyridine位阻小位阻大HOOCOCH3酰氯与酚酯化反应吡啶与NaOH中和产生的HClClO+OHOOOCl+OHNaOH/H2OOO吡啶酰卤的氨解(CH3)2CHCClO+ 2 NH3(CH3)2CHCNH2O+ NH4 Cl2-Methylpropanoyl chloride2-Methylpropanamide (83%)COCl+ 2 NH(CH3)2CON(CH3)2+ NH2(CH3)2 ClBenzoyl chlorideN,N-Dimethylbenzamide (9

10、2%)酰卤的氨解CH3OCH3OCH3OCOCl +NOHNaOHH2OCH3OCH3OCH3OCONO + NaCl3,4,5-Trimethoxybenzoyl chlorideMorpholineTrimetozine (an amide)上述反应的反应机理？上述反应的反应机理？OCH3CH3OCH3OCOClNOHOCH3CH3OCH3OCOClNOHOHOCH3CH3OCH3OCOClNO+ H2OOCH3CH3OCH3OCNOO+ NaOHnucleophilicaddition ofmorpholinedeprotonationby hydroxideeliminationof

11、chlorideTrimetozine酰卤的还原COClCH2OH1.LiAlH4,etherBenzoyl chlorideBenzyl alcohol (96%)2.H3OCORCl+ HLiAlH4EtherCOHRClCORHCOHHRHAn acidchlorideA primary alcoholAn aldehyde(NOT isolated)1.LiAlH42.H3O如果使用还原能力较小的还原剂三叔丁氧基氢三叔丁氧基氢化铝锂化铝锂，酰卤可以被还原为醛。3(CH3)3COH + LiAlH4Li AlHOC(CH3)33+ 3H2Lithium tri-tert-butoxyal

12、uminum hydrideCO2NOClCO2NOH1.LiAlHOC(CH3)33,etherp-Nitrobenzoyl chloridep-Nitrobenzaldehyde (81%)2.H3OOClOH+ H2Pd-BaSO474-81%酰氯用活性较小的Pd-BaSO4 催化氢化，也得到醛叫 Rosenmund 还原。例如：酰卤的与格氏试剂的反应：酰卤的与格氏试剂的反应：CORCl+ 2RMgXCROHRR1.Ether solvent2.H3OAn acidchlorideA 3 alcoholCOClCOCH3COHH3CCH3CH3MgBrEther1.CH3MgBr2.H3

13、OBenzoyl chlorideAcetophenone(NOT isolated)2-Phenyl-2-propanol (92%)酰卤与二烃基铜锂的反应：CORClAn acidchloride+ R2Cu LiCORRA ketoneA Gilman reagentEthersolventC CHCCH3OClCH3CH2CHCH3C CHCCH3OCH2CH3CH3CH2CHCH3(CH3CH2)2CuLiEther, -78 CManicone(92%)2,4-Dimethyl-2-Hexenoyl chlorideOCl(CH3)2CuLi-78oCOCH381%CCH(CH3)

14、2O(a)CHCCH2CH2CH3OH2C(b)如何以酰卤与二烃基铜锂反应制备下列产物？10.4 酸酐酸酐的制法COHO+COClCH3NaCOHOCOCH3Ether25 CROOHROORO脱水剂脱水剂：P2O5, 乙酸酐酸酐的反应COHOOH+CH3COCCH3O OCOHOOCOCH3+CH3COONaOHH2OAspirin (an ester)AceticanhydrideSalicyclic acid(o-Hydroxybenzoic acid)NH2HO+CH3COCCH3O ONaOHH2ONHOHCCH3O+CH3COOAceticanhydridep-Hydroxyani

15、lineAcetaminophen镇痛解热试推测甲醇和邻苯二甲酸酐（环状酸酐）反应的产物。 COCOO+CH3OHCCOOOCH3OH邻苯二甲酸酐ArNH2CH3COClor (CH3CO)2OArNHCCH3NH2COOHRCl COCH2PhOBoc2ONHCOOCH2PhCOOHRNHCOOBu-tCOOHR碱碱碱碱H2, PdHClOH2O, OHOOONH3OHOONH2300oCNHOOBr2NaOHNOONOOBrNaOOONH3NHOOKOHor K2CO3NOOKR XNOORNH2NH2OOH2NRNHNH+肼肼解解10.5 羧酸酯CH3CH2CH2COCH3OCH3COC

16、H2CH2CHCH3OCH3CH2OCRCHOCRCH2OCROOOCOCH2CH2CH2CH3COCH2CH2CH2CH3OO丁酸甲酯（菠萝）乙酸异戊酯（香蕉）三羧酸甘油酯（油脂）增塑剂酯的制备方法酯的制备方法CORClCOROHCORORCORORCORORSOCl2ROHHClROHPyridine2.RX1.NaOH局限于伯烷基卤代物局限于简单羧酸制备适用范围广酯的反应酯的反应酯的水解酯的水解（在酸或碱的存在下，酯水解生成羧酸和醇。CORORCOROH+ROHEsterH2O,NaOHor H3OAcid碱催化的酯的水解机理：COROROHCOOHRROCOROH+ORCORO+HOR

17、COROHH3O酸催化的酯的水解机理：酸催化的酯的水解机理：H2ORCOHORH2ORCOHORRCOHOH HORRCOOHRCOORHHORCOHORH HHOR烯烯烃烃H2O HRCOHORCOOHRCOORHRR+机理II适用于能形成较为稳定碳正离子的酯，其它为机理ICOOCH2CH3COOHCH3CH2CH3CH2+HOCH2CH3*1.NaOH,H2OThis bond is broken2.H3O酯的酯的碱性水解碱性水解和和酸性水解酸性水解，一般为酰氧键断裂。，一般为酰氧键断裂。酯的醇解酯交换反应酯的醇解酯交换反应: : RCOORRCOORROHHorRO+ROH+H2CCHC

18、OOCH3n-BuOHTsOHH2CCHCOOBun+ CH3OHOCOHOCH3NaOCH3CH3OOHCOCH3OCH3COCH3+CHCH2CHCH2OAcOAcnCH3OHOHCHCH2CHCH2OHOHnCCH3OO+CH3COCH3OCO2CH3CO2CH3+2 HOCH2CH2OHRONa190oCCO2CH2CH2OHCO2CH2CH2OH+ 2 CH3OH（合成涤纶的原料）酯的氨解酯的氨解COOCH3NH3EtherCONH2+CH3OHMethyl benzoateBenzamideCO2EtOCH3+NH2NaHDMSOCONHOCH3酯的还原酯的还原CH3CH2CHCH

19、COCH2CH3O1.LiAlH4,etherCH3CH2CH CHCH2OH +CH3CH2OHEthyl 2-pentenoate2-Penten-1-ol (91%)2.H3OOOCH31.LiAlH4,etherHOCH2CH2CH2CHCH3OHA lactone1,4-Pentanediol (86%)2.H3O酯的还原酯的还原CROOR+HEtherCOHRROCROH+RO2.H3OCOHHRHA primary alcoholLiAlH41.LiAlH4+CH3(CH2)10COCH2CH3O1.DIBAH in tolueneCH3(CH2)10CHOCH3CH2OHEth

20、yl dodecanoateDodecanal (88%) DIBALH=(CH3)2CHCH22AlH2.H3ODIBALH还原性较弱，反应可停留在醛阶段写出下列反应产物OO1) DIBALH-78oC2) H3O+CH3CH2CH2CHCOCH3OH3C1.LiAlH4,ether2.H3OCOO1.LiAlH4,ether2.H3OCH3CH2CH2CHCH2OHH3COOHOHHO+RCOORRCH2OHNaROHNa, N2乙乙醚醚 or 甲甲苯苯RCORCHOHRCOOR2RCOORRCH2OHNaROHRCOORNaRCOORRCOORRCOHORRCOHeNaeNaNaNaHe

21、NaNaeRCOHNaROHRCOHNaHH2ORCOORNaRCORCHOHRCOOR自自由由基基偶偶合合RCOORRCOORRCORCONaRCORCORCORCORCOHRCOHH2O2222e2Na2 ORNaNaNaNa互互变变异异构构(CH2)nCO2RCO2RNa二二甲甲苯苯(CH2)nH2OCCHOHO酯与格式试剂的反应酯与格式试剂的反应COCH3O1. 2MgBrCOHMethyl benzoateTriphenylmethanol (96%)OO1. 2 CH3MgBr,etherCH3CCH2CH2CH2CH2OHOHCH3Valerolactone5-Methyl-1,

22、5-hexanediol2.H3O2.H3O为什么酯与格氏试剂的反应不能停留在生成酮的阶段？反应活性： 酮大于酯10.6 10.6 酰胺酰胺酰胺的制备COClRCONH2RCONHRRCONR2RNH3RNH2R2NHCHRH2NC OHOHN CHRCHNOCHRCHNOCHCORAmino acidA protein (polyamide)酰胺的水解酰胺的水解酰胺难以水解，一般来说，酰胺的水解需要在酸或碱的存在下加热进行。CONH2H2SO4/H2OCO2H+ NH4HSO4CONH2RCONH2RH+OH2H3OCOORH2NHHHCOORH3NHHCOROH+NH4酸催化水解碱催化水解

23、CONH2ROHCOORH2NHOHCOORH2NCORO+NH2CH3(CH2)10CNHCH3O2. H2O1. LiAlH4,etherCH3(CH2)3CH2NHCH3N-MethyldodecanamideDodecylmethylamine (95%)酰胺的还原酰胺的还原NH3CH3CHONH3CH3CHHH2. H2O1. LiAlH4,etherA lactamA cyclic amine (80%)CONH2R+HLiAlH4EtherCOHRH2NAlH3CNRHHHCNH2HRHAmideIminium ionH四氢铝锂（LiAlH4）还原酰胺可用于制备胺如何通过多步反应

24、制备该三级胺？Br?CH2N(CH3)2(N,N-Dimethylaminomethyl)cyclohexaneBrMg,etherMgBrCOHO1. CO2,ether2. H3O+CClOSOCl2CN(CH3)2OCH2N(CH3)2(CH3)2NHNaOH1. LiAlH42. H2OHofmann Hofmann 降级反应降级反应HofmannHofmann重排：重排：酰胺与溴或氯在碱性溶液中反应，生成少一个碳原子（羰基碳原子）的伯胺 Hofmann 降级反应。RNH2O+ Br2 + NaOHRNH2 + Na2CO3 + Br-NH2OBr2/KOHH2OBrNH2Br87%N

25、H2OBr2/NaOHH2ONH294%反应机理：反应机理：RNH2OH2OOH-RNH-O Br2RNHBrOOH-RNOBr-R N C OR N COOHH-CO2RNH210.7 腈腈的制法：RCH2Br+Na CNSN2reactionRCH2CN+NaBrCH3CH2CH2CH2CHCONH2CH2CH3CH3CH2CH2CH2CHCCH2CH3NSOCl2,benzene80 CCONH2RCORNHHSOClCORNHSOClR C N+ SO2SOClClCl-Cl-腈的反应腈的反应腈的水解R C NCOROH+NH3H3Oor NaOH,H2O反应机理？碱催化的腈的水解：R

26、 C N +OHCOHRNCOHRNHCORNHHH2OAmideNitrileHydroxy imineR C C HCOHCRHHCORCHH HH3OH2SO4TautomerizationAn enolA ketone酸催化的腈的水解：R C NR C NHCOH2RNHCOHRNH2CORNH2HCORNH2OH2H+H3OH2OOH2Amideprotonationloss ofprotonaddition of waterprotontransferCONH2RCONH2RH+OH2H3OCOORH2NHHHCOORH3NHHCOROH+NH4酸催化水解碱催化水解CONH2ROH

27、COORH2NHOHCOORH2NCORO+NH2酰胺进一步水解为羧酸腈的还原腈的还原CCH2NH2CH3CH3N1. LiAlH4,ether2. H2Oo-Methylbenzonitrileo-MethylbenzylamineR C NCNRHImine anionCNRHImine anionCRHNH2HPrimary amineCORH+NH3AldehydeNitrileLiAlH4EtherDIBAHToluene1. LiAlH42. H2OH2OHDIBAH = 二异丁基氢化铝CHCH2CCCHCH2CHCCH3CH3CH2CH2CH3CH3NO2. H2O1. DIBA

28、H,toluene,-78 C96%腈与格氏试剂的反应R C NCNRRCORR+NH3Imine anionNitrileKetoneH2OR MgXCC CH2CH3ON1. CH3CH2MgBr,ether2.H3OBenzonitrilePropiophenone (89%)腈与格氏试剂反应应用以腈为原料如何制备2甲基3戊酮?CH3CH2CCHCH3OCH32-Methyl-3-pentanoneThere are two possibilities:CH3CH2CCHCH3OCH3CH3CH2C N+(CH3)2CHMgBrCH3CHCCH3N+CH3CH2MgBr2-Methyl-

29、3-pentanone1. Grignard2. H3O1. Grignard2. H3O写出下列反应产物?(a)CH3CH2CN1. CH3CH2MgBr2. H2O(b)(CH3)2CHCN1. DIBAH2. H2O(c)CN1. CH3MgBr2. H2OorCH3CN1. C6H5MgBr2. H2OCH3CH2CCH2CH3O(CH3)2CHCHOCCH3O以苄溴为原料制备1苯基2丁酮：CH2BrCH2CCH2CH3OCH2BrCH2CNCH2CCH2CH3ONaCN1. CH3CH2MgBr2. H2ORCOOHRCOORRCONHRRCOClRCOOCROH2OSOCl2RCO

30、OHROHP2O5H2ORNH2ROHNH2RRNH2,H2O, H+ or OH-ROH, H+RNH2ROHH2O, H+ or OH-10.8 10.8 酯缩合反应酯缩合反应 ClaisenClaisen 缩合缩合醛、酮分子中的H 表现出一定的酸性，在碱作用下，可以发生羟醛缩合反应。同样，其它含有吸电子基团的有机物中的H 也表现出一定的酸性，与碱作用生成碳负离子，发生一系列的反应。H2COEtCOH3CCORH2CORCOH2COEtCOOCOEtH2COEtCORCORCH2CN RCH2NO2在醇钠作用下，具有在醇钠作用下，具有H H 的酯发生分子间的缩合反的酯发生分子间的缩合反应，

31、生成应，生成酮酸酯称为酮酸酯称为ClaisenClaisen 缩合。缩合。RCH2CORORCH CORORCH2COCH CORORH+ HORORCH3COCH2CH3O21.Na OEt, ethanol2.H3OCH3COCH2COCH2CH3OCH3CH2OHEthyl acetoacetate-keto ester (75%)aEthyl acetateCH3CH2COCH2CH3O1. NaOEt, ethanol2.H3OCH3CH2OHEthyl acetateCH3CHCOCH2CH3OCCH2CH3O81%CH3COEtOOEtCH2COEtOEtOHCH3COEtONu

32、cleophilic donorElectrophilic acceptorCH3COEtOCH2COEtCH3CCH2COEtOOCH3CCHCOEtOOEtOHH3OCH3CCH2COEtOOH2OEtOClaisen 缩合是可逆反应， -酮酸酯在碱作用下能够裂解。例如：CCOEtOOOHaddition ofhydroxideCCOEtOOOHelimination of acetateOHOOH2COEtH3OneutralizationCOHOOH3COEtCCOEtOO1.equiv NaOH2.EthanolCOOCH3COEtO10.9 10.9 交叉酯缩合反应交叉酯缩合反应用

33、一个无H 的酯和一个有H 的酯缩合，可以得到较单一产物，有合成价值。 COEtOCH3COEtO1.NaH/THFCOCH2COEtOEtOH2.H3OEthyl benzoateacceptorEthyl acetatedonorEthyl benzoylacetateH3O+heatCH3O10.1010.10 分子内的酯缩合反应分子内的酯缩合反应 DieckmannDieckmann 缩合缩合己二酸酯和庚二酸酯在醇钠作用下，发生分子内的酯缩合反应，生成环状的-酮酸酯，这种分子内的酯缩合反应称为Dieckmann 缩合。OEtOOEtO1.Na OEt, ethanol2.H3OOCOEt

34、OEtOHEthyl 2-oxocyclopentanecarboxylate82%Diethyl hexanedioate a 1,6-diesterOEtOOEtO1.Na OEt, ethanol2.H3OCOEtOOEtOHDiethyl heptanedioate a 1,7-diesterEthyl 2-oxocyclohexanecarboxylateDieckmann 缩合机理缩合机理：OEtOHHCOOEtOEtOHCOOEtNa OEtEtOHHCOOEtOOEtOHCOOEtOEtOHCOOEtOEtOCOOEtEtOHH3OOHCOOEtH2O试推测3-甲基庚二酸酯进行

35、Dieckmann酯缩合的产物并描述其反应过程。OEtCH3CCOEtOO1234567OEtCH3CCOEtOONa OEtEtOHCH3CCOOEtOOEtH3OOH3CCOOEtEtOHC1-C6 bond formationNa OEtEtOHOEtCH3CCOEtOOCH3COOEtEtOOCOEtOOCEtOHH3CH3OC2-C7 bond formation丁二酸二乙酯发生分子间的缩合反应，辛二酸二乙酯只得到少量的含七元环的-酮酸酯。因此， Dieckmann 缩合主要用于合成含五元环或六元环的化合物。CO2EtCO2Et21. NaOEt/EtOH2. H3O+CO2EtEt

36、O2COO65%Dieckmann 缩合产物在强碱作用下可以发生烷基化反应。OCO2EtH1.Na OEt,H2CCHCH2Br2.OCO2EtCH2CH CH2H3OheatOHCH2CH CH2EtOHCO22-Allycyclohexanone83%Ethyl 2-oxocyclo-hexanecarboxylate有H 酮与酯在强碱作用下，也可以发生交叉酯缩合反应。当然，有H 酮与无H的酯缩合产物更单一。例如：COEtOOHHH3CH3CCOHOEt2,2-dimethylcyclohexanoneEthyl formatedonoracceptor2.H3OOHCH3CH3COH-k

37、eto aldehydeA91%CH3O+1. NaOEt, ethanol1.NaOEt, ethanol2.H3OOO70%NaHO+OCO2C2H5H5C2OCOC2H5OCH3CCH3OCH3COC2H5O+NaOC2H5CCH2OH3CCOCH3O+HCOC2H5ONaHOCHOCH2COC2H5OHCH2CCH3OHpKa2024C2H5OCCH2OCH3HCCH2OOC2H5HCCH2OCH3CH3COC2H5OCCH2OCH3COH3CC2H5OCCH2OCH3COH3COC2H5H3CCOCH2COC2H5O 羰羰基基酯酯H3CCOCH2CCH3OC2H5OCOCH2COC2

38、H5O 二二酮酮 二二酯酯H3CCOHCCH3OCHRCOHCOC2H5OCHC2H5OCOHCOC2H5OCH76%7.5%很很少少COCOCHH原因：原因：1 1、两个羰基使亚甲基活化；、两个羰基使亚甲基活化；2 2、分子内氢键，、分子内氢键，形成六元闭环，使体系能量降低。形成六元闭环，使体系能量降低。成酮分解和成酸分解H3CCOCH2COC2H5OH3CCOCH2COC2H5O成酮分解成酸分解CH3C-CH2COEtOONaOHCH3C-CH2CONaOOH+CH3C-CH2COHOOCH3C-CH3OCH3C-CH2COEtOONaOHCH3COHOH+EtOH稀碱作用稀碱作用浓碱作用

39、浓碱作用成酮成酸CH3C-CH2COEtOOOH-CH3C-CH2COEtOOOHCH3COHOCH2COEtOCH3COOCH3COEtOOH-H+CH3COHOEtOHCH3C-CH2COEtOOEtONaCH3C-CH2-ROOH-H+H2O- CO2RCH3C-CH-COEtOORX注：注： R R最好用最好用1 1，2 2产量低，不能用产量低，不能用3 3和乙烯式卤代烃。和乙烯式卤代烃。 RX RX也可是卤代酸酯和卤代酮。也可是卤代酸酯和卤代酮。CH3C-CH2COEtOOEtONaCH3C-CH-ROROH-H+H2O- CO2RCH3C-CH-COEtOOEtONaRCH3C-C

40、-COEtOORRXRXCH3C-CH2COEtOOEtONaCH3C-ClCH3C-CH2-C-CH3OOH-H+H2O- CO2COCH3CH3C-CH-COEtOOOOCH3C-CH2COEtOOEtONaCH3C-CH2ClOCH3C-CH2-CH2C-CH3OOOH-H+H2O- CO2CH2COCH3CH3C-CH-COEtOOCH3C-CH2COEtOOEtONaCl-CH2COEtOCH3C-CH2CH2COOHOOH-H+H2O- CO2CH2COOC2H5CH3C-CH-COEtOOCH3C CH2CH2OCH2经结构分析，需引入原引CH3C CHCH2CH=CH2OCH3

41、引原要分两次引入，先引入再引入CH3CH2CH=CH2CH3C CH2OCOC CH3O引引原原 说明：乙酰乙酸乙酯合成法主要用其酮式分解制取酮，说明：乙酰乙酸乙酯合成法主要用其酮式分解制取酮，酸式分解制酸很少，制酸一般用丙二酸二乙酯合成法。酸式分解制酸很少，制酸一般用丙二酸二乙酯合成法。CH3CH2CH2CH2CH2CCH3O以乙酰乙酸乙酯合成法制备：CH3CH2CH2CH2CH2CCH3OCH3CH2CH2CH2BrEtOCCH2CCH3NaEtOHOEtOOCH3CH2CH2CH2CHCCH3CO2EtOH3OHeatCH3CH2CH2CH2CH2CCH3O以乙酰乙酸乙酯合成法制备：CH

42、3CH2CH2CH2CHCCH3OCH3CH3CH2CH2CH2CHCCH3CO2EtNaOEt1.CH3CH2CH2CH2CCH3H3OHeatCH3CH2CH2CH2CHCCH3OCH3OCO2EtCCH3O2.CH3I见上页如何用乙酰乙酸乙酯合成法制备甲基环戊酮如何用乙酰乙酸乙酯合成法制备甲基环戊酮? ?CH2CCH3OCOOEtNaOEt1. 22.BrCH2CH2CH2CH2BrCCOOEtOH3C2NaBrH3OHeat,CH3COCO2EtOHCH3COCOOC2H5COOC2H5CH2NaOC2H5NaCOOC2H5COOC2H5CHRX-NaXNaOHHNaCOOHCH2RC

43、OOC2H5CHCOOC2H5COOC2H5COOC2H5CHRpKa = 13H2OCH3COOHCH2COOHClNaCNNaOHCH2COONaCNC2H5OHH2SO4COOC2H5COOC2H5P / Cl2CH2NaCOOC2H5COOC2H5CHRX-NaXCOOC2H5COOC2H5CHRCOOC2H5COOC2H5CH2NaOC2H5NaCOOC2H5COOC2H5CHCOOC2H5COOC2H5CHRNaOC2H5NaOHHCOOC2H5COOC2H5CRCOOHCHRRNa-NaXRXCOOC2H5COOC2H5CRRH2ONaCOOC2H5COOC2H5CH2COOC2

44、H5COOC2H5CHNaOC2H5COOC2H5CH2XNaNaOHHH2OCOOHCH2CH2COOHCOOC2H5CHCOOC2H5COOC2H5COOC2H5CHCH2C2H5OOCpKa = 13NaCOOC2H5COOC2H5CHCH2CH2XXNaOHHH2OCH2COOHCH2CH2CH2COOHCH(COOC2H5)2CH2CH2CH(COOC2H5)22CH2(COOC2H5)22 NaOC2H5(CH2)nC(COOC2H5)2C(COOC2H5)2CH2NaOHH(CH2)nCH(COOC2H5)2CH(COOC2H5)2(CH2)nC-COOHC-COOHCH2CH2

45、I2NaOC2H52X(CH2)nXn = 37H2OCH2(COOC2H5)2NaOC2H5Br(CH2)4BrNaOHHH2ONaOC2H5COOHCOOC2H5COOC2H5(1)(2)CCO2EtRHCO2EtNa1.2. R XCCO2EtRRCO2EtAn alkylatedmalonic esterA dialkylatedmalonic esterOEt丙二酸二乙酯的单烷基化产物或二烷基化产物与盐酸水溶液一起加热，发生水解和脱羧反应，生成取代的羧酸。CCO2EtRHCO2EtH3OHeatCHRHCOOHCO22EtOHOCCCOHOR HOHA diacid-CO2RCCOH

46、HOHAn acid enolRCCOHHOHA carboxylic acidOCCCOHOR HRA -keto acid-CO2RCCRHOHAn enolRCCRHOHA ketoneCH3CH2CH2CH2Br1-BromobutaneCH2(CO2Et)2Diethyl malonateNaEtOHOEtCH3CH2CH2CH2CCO2EtCO2EtHH3OHeatCH3CH2CH2CH2CH2COHOCO22EtOHHexanoic acid (75%)以丙二酸二乙酯合成法制备正己酸：CH3CH2CH2CH2CH2COHOCH3CH2CH2CH2CCO2EtCO2EtHNaOEt

47、1.CH3CH2CH2CH2CCO2EtCO2EtCH3H3OHeatCH3CH2CH2CH2CHCOHOCO22EtOHCH32-Methylhexanoic acid (74%)2.CH3I以丙二酸二乙酯合成法制备2甲基正己酸：CH3CH2CH2CH2CHCOHOCH3为什么要先上正丁基？（见上页）如果用1mol 的丙二酸二乙酯、2mol的乙醇钠和2mol的卤代烷反应，可以同时加上两个相同的烷基。CH2(COOEt)22NaOEt1.2. 2CH3CH2BrCH3CH2CH(COOEt)2NaBrCH2CH386%1. NaOH/H2O2. HCl, heatCH3CH2CHCOOHCH2

48、CH3如果用2mol 的丙二酸二乙酯、2mol的乙醇钠和1mol的二卤代烷反应，可以得到二元羧酸。H2CCO2EtCO2EtH3OHeat1. NaOEt/EtOH2. BrCH2CH2Br(EtO2C)2CHCH2CH2CH(CO2Et)2HO2CCH2CH2CH2CH2CO2H2如果用1mol 的丙二酸二乙酯、2mol的乙醇钠和1mol的适当的二卤代烷反应，可以合成脂环族羧酸。H2CH2CCH2CH2BrBrHCCO2EtCO2EtNaEtOHOEtH2CH2CCH2H2CBrCHCO2EtCO2EtNaEtOHOEtH2CH2CCH2H2CBrCCO2EtCO2Et1,4-DibromobutaneH2CH2CCH2CH2CCO2EtCO2EtH3OHeatCOHOCO22EtOHCyclopentane-carboxylic acid以丙二酸二乙酯合成法制备下列化合物： (a) 3苯基丙酸 (b) 2甲基戊酸(c) 4甲基戊酸 (d) 环丁烷甲酸乙酯PhH2C CH2COOHfrom malonic esterfrom halide(a)CH2(COOEt)2NaOEt1.2. PhCH2BrPhCH2CH(COOEt)2NaBrH3OHeatPhCH2CH2COOHCO22EtOH3-Phenylpropan