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，羧基上的羥基被其它原子羧酸衍生物指羧酸分子中，羧基上的羥基被其它原子或原子團(tuán)取代后生成的化合物?；蛟訄F(tuán)取代后生成的化合物。OCROHOCRXOCROCOROCROROCRNH2C NR羧酸酰鹵酸酐酯酰胺腈10.1 10.1 命名命名酰鹵的命名酰鹵的命名: : 將羧酸分子中的將羧酸分子中的“酸酸”字改為酰鹵即可。字改為酰鹵即可。乙酰氯 苯甲酰溴 環(huán)己烷甲酰氯COClCH3CClOCOBr酸酐的命名酸酐的命名: : 在羧酸名稱的后面加上酐字。在羧酸名稱的后面加上酐字。OCH3COCOCH3OOOAcetic

2、 anhydrideBenzoic anhydrideSuccinic anhydrideCOOCO乙酸酐 苯甲酸酐 丁二酸酐OCClH2COCOCH2ClBis(chloroacetic) anhydrideOCH3COCOAcetic benzoic anhydride雙氯乙酸酐乙酸苯甲酸酐酰胺的命名酰胺的命名: : 將羧酸名稱中的酸字改為酰胺。將羧酸名稱中的酸字改為酰胺。CNH2OAcetamide(from acetic acid)Hexanamide(from hexanoic acid)Cyclopentanecarboxamide(from cyclopentanecarboxy

3、lic acid)CH3CNH2OCH3(CH2)4CNH2O乙酰胺 己酰胺 環(huán)戊烷甲酰胺酰胺的命名 N-甲基丙酰胺 N,N-二乙基環(huán)己烷甲酰胺CON(CH2CH3)2CH3CH2CNHCH3O酯的命名酯的命名在羧酸的名稱后面加上醇或酚中的在羧酸的名稱后面加上醇或酚中的烴基名稱烴基名稱和和酯酯字。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環(huán)己甲酸叔丁酯腈的命名腈的命名: :根據(jù)母體鏈碳原子數(shù)叫某腈。根據(jù)母體鏈碳原子數(shù)叫某腈。4甲基戊腈 乙腈CH3CHCH2CH2CNCH354321CH3C NC NCNCH3CH3123456苯甲腈2,2-二甲基環(huán)己甲腈10.2 10.2 羧酸衍生物的取代反應(yīng)羧酸衍生物的取代反應(yīng)COXRCH2COOCOORCONH2(R)CRORCH2RCH2RCH2RCHCOLHRCOLNuRCONu+Lor HNuHLorRCOLRCOOHH2OH

5、or OHROHRNH2RCOORRCONHRH or OHRCOLNuRCONu+ LRCONuL親親核核加加成成消消除除RCOHLHNuRCOHNu+RCOHNuL親親核核加加成成消消除除HRCOHNuLHLHOCYRA leaving groupA carbonxylic acid derivativeOCRHOCRRAn aldehydeA ketoneNot a leaving group羧酸衍生物與醛酮親核取代反應(yīng)比較提問：提問： 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，羧酸衍生物可發(fā)生親核取代反應(yīng)，但醛、酮只發(fā)生親核加衍生物可發(fā)生親核取代反應(yīng)，

6、但醛、酮只發(fā)生親核加成而不發(fā)生親核取代。為什么？成而不發(fā)生親核取代。為什么？ 解答解答: 醛、酮和羧酸衍生物均接受親核試劑的進(jìn)攻，第一步醛、酮和羧酸衍生物均接受親核試劑的進(jìn)攻，第一步發(fā)生親核加成，形成四面體的氧負(fù)離子中間體；而在發(fā)生親核加成，形成四面體的氧負(fù)離子中間體；而在第二步消除反應(yīng)中，由于第二步消除反應(yīng)中，由于 H H- - 或或 R R- - 的堿性極強，很的堿性極強，很難于離去，因此中間體氧負(fù)離子結(jié)合一個質(zhì)子得到加難于離去，因此中間體氧負(fù)離子結(jié)合一個質(zhì)子得到加成產(chǎn)物。成產(chǎn)物。 RCONuLRCOHNuLHor該反應(yīng)的反應(yīng)機理？CClONa+ -OCH3CH3OHCOOCH3羧酸衍生物

7、的相對反應(yīng)活性羧酸衍生物的相對反應(yīng)活性RCOClRCOORCOORRCONH2(R)CRORCOL XOORNH2(R)CRO反應(yīng)活性是兩方面因素共同作用的結(jié)果羧酸衍生物取代反應(yīng)的種類羧酸衍生物取代反應(yīng)的種類CORY羧酸衍生物COROHH2O水解CORORROH醇解CORNH2NH3氨解CORHCROHHHHH還原1 alcoholCORRCROHRRRMgXRMgXKetone3 alcohol預(yù)測產(chǎn)物:COClCH3CHCH3OH?Benzoyl chlorideCOClCH3CHCH3OHCOOCHCH3CH3Benzoyl chlorideIsopropyl benzoateLeavi

8、ng groupNucleophile預(yù)測下列反應(yīng)的產(chǎn)物:OCOCH3COCH3H3COCOCH3(a)(c)NaOHH2OCH3OH?COH3CCl?NH3(b)Na+ -OCH310.3 酰鹵酰鹵的反應(yīng)酰鹵的水解RClO+H2OROHO乙酰氯遇水強烈水解，但隨著酰氯分子量的增大，水解速度減慢，可能是由于酰氯在水中的溶解度減小所致。芳香族酰氯水解速度很慢，加熱或加堿能使水解迅速進(jìn)行。CORCl+ OH2COORClHHCOROHHCOROHAn acid chlorideA carboxylic acidCl-+Cl-酰鹵的醇解COCl+OHCOOPyridineBenzoyl chlori

9、deCyclohexanolCyclohexyl benzoate (97%)CH2OHHO+H3CCOClPyridine位阻小位阻大HOOCOCH3酰氯與酚酯化反應(yīng)吡啶與NaOH中和產(chǎn)生的HClClO+OHOOOCl+OHNaOH/H2OOO吡啶酰鹵的氨解(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%)酰鹵的氨解CH3OCH3OCH3OCOCl +NOHNaOHH2OCH3OCH3OCH3OCONO + NaCl3,4,5-Trimethoxybenzoyl chlorideMorpholineTrimetozine (an amide)上述反應(yīng)的反應(yīng)機理？上述反應(yīng)的反應(yīng)機理？OCH3CH3OCH3OCOClNOHOCH3CH3OCH3OCOClNOHOHOCH3CH3OCH3OCOClNO+ H2OOCH3CH3OCH3OCNOO+ NaOHnucleophilicaddition ofmorpholinedeprotonationby hydroxideeliminationof

11、chlorideTrimetozine酰鹵的還原COClCH2OH1.LiAlH4,etherBenzoyl chlorideBenzyl alcohol (96%)2.H3OCORCl+ HLiAlH4EtherCOHRClCORHCOHHRHAn acidchlorideA primary alcoholAn aldehyde(NOT isolated)1.LiAlH42.H3O如果使用還原能力較小的還原劑三叔丁氧基氫三叔丁氧基氫化鋁鋰化鋁鋰，酰鹵可以被還原為醛。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%酰氯用活性較小的Pd-BaSO4 催化氫化，也得到醛叫 Rosenmund 還原。例如：酰鹵的與格氏試劑的反應(yīng)：酰鹵的與格氏試劑的反應(yīng)：CORCl+ 2RMgXCROHRR1.Ether solvent2.H3OAn acidchlorideA 3 alcoholCOClCOCH3COHH3CCH3CH3MgBrEther1.CH3MgBr2.H3

13、OBenzoyl chlorideAcetophenone(NOT isolated)2-Phenyl-2-propanol (92%)酰鹵與二烴基銅鋰的反應(yīng)：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)如何以酰鹵與二烴基銅鋰反應(yīng)制備下列產(chǎn)物？10.4 酸酐酸酐的制法COHO+COClCH3NaCOHOCOCH3Ether25 CROOHROORO脫水劑脫水劑：P2O5, 乙酸酐酸酐的反應(yīng)COHOOH+CH3COCCH3O OCOHOOCOCH3+CH3COONaOHH2OAspirin (an ester)AceticanhydrideSalicyclic acid(o-Hydroxybenzoic acid)NH2HO+CH3COCCH3O ONaOHH2ONHOHCCH3O+CH3COOAceticanhydridep-Hydroxyani

15、lineAcetaminophen鎮(zhèn)痛解熱試推測甲醇和鄰苯二甲酸酐（環(huán)狀酸酐）反應(yīng)的產(chǎn)物。 COCOO+CH3OHCCOOOCH3OH鄰苯二甲酸酐ArNH2CH3COClor (CH3CO)2OArNHCCH3NH2COOHRCl COCH2PhOBoc2ONHCOOCH2PhCOOHRNHCOOBu-tCOOHR堿堿堿堿H2, PdHClOH2O, OHOOONH3OHOONH2300oCNHOOBr2NaOHNOONOOBrNaOOONH3NHOOKOHor K2CO3NOOKR XNOORNH2NH2OOH2NRNHNH+肼肼解解10.5 羧酸酯CH3CH2CH2COCH3OCH3COC

16、H2CH2CHCH3OCH3CH2OCRCHOCRCH2OCROOOCOCH2CH2CH2CH3COCH2CH2CH2CH3OO丁酸甲酯（菠蘿）乙酸異戊酯（香蕉）三羧酸甘油酯（油脂）增塑劑酯的制備方法酯的制備方法CORClCOROHCORORCORORCORORSOCl2ROHHClROHPyridine2.RX1.NaOH局限于伯烷基鹵代物局限于簡單羧酸制備適用范圍廣酯的反應(yīng)酯的反應(yīng)酯的水解酯的水解（在酸或堿的存在下，酯水解生成羧酸和醇。CORORCOROH+ROHEsterH2O,NaOHor H3OAcid堿催化的酯的水解機理：COROROHCOOHRROCOROH+ORCORO+HOR

17、COROHH3O酸催化的酯的水解機理：酸催化的酯的水解機理：H2ORCOHORH2ORCOHORRCOHOH HORRCOOHRCOORHHORCOHORH HHOR烯烯烴烴H2O HRCOHORCOOHRCOORHRR+機理II適用于能形成較為穩(wěn)定碳正離子的酯，其它為機理ICOOCH2CH3COOHCH3CH2CH3CH2+HOCH2CH3*1.NaOH,H2OThis bond is broken2.H3O酯的酯的堿性水解堿性水解和和酸性水解酸性水解，一般為酰氧鍵斷裂。，一般為酰氧鍵斷裂。酯的醇解酯交換反應(yīng)酯的醇解酯交換反應(yīng): : RCOORRCOORROHHorRO+ROH+H2CCHC

18、OOCH3n-BuOHTsOHH2CCHCOOBun+ CH3OHOCOHOCH3NaOCH3CH3OOHCOCH3OCH3COCH3+CHCH2CHCH2OAcOAcnCH3OHOHCHCH2CHCH2OHOHnCCH3OO+CH3COCH3OCO2CH3CO2CH3+2 HOCH2CH2OHRONa190oCCO2CH2CH2OHCO2CH2CH2OH+ 2 CH3OH（合成滌綸的原料）酯的氨解酯的氨解COOCH3NH3EtherCONH2+CH3OHMethyl benzoateBenzamideCO2EtOCH3+NH2NaHDMSOCONHOCH3酯的還原酯的還原CH3CH2CHCH

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

20、yl dodecanoateDodecanal (88%) DIBALH=(CH3)2CHCH22AlH2.H3ODIBALH還原性較弱，反應(yīng)可停留在醛階段寫出下列反應(yīng)產(chǎn)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互互變變異異構(gòu)構(gòu)(CH2)nCO2RCO2RNa二二甲甲苯苯(CH2)nH2OCCHOHO酯與格式試劑的反應(yīng)酯與格式試劑的反應(yīng)COCH3O1. 2MgBrCOHMethyl benzoateTriphenylmethanol (96%)OO1. 2 CH3MgBr,etherCH3CCH2CH2CH2CH2OHOHCH3Valerolactone5-Methyl-1,

22、5-hexanediol2.H3O2.H3O為什么酯與格氏試劑的反應(yīng)不能停留在生成酮的階段？反應(yīng)活性： 酮大于酯10.6 10.6 酰胺酰胺酰胺的制備COClRCONH2RCONHRRCONR2RNH3RNH2R2NHCHRH2NC OHOHN CHRCHNOCHRCHNOCHCORAmino acidA protein (polyamide)酰胺的水解酰胺的水解酰胺難以水解，一般來說，酰胺的水解需要在酸或堿的存在下加熱進(jìn)行。CONH2H2SO4/H2OCO2H+ NH4HSO4CONH2RCONH2RH+OH2H3OCOORH2NHHHCOORH3NHHCOROH+NH4酸催化水解堿催化水解

23、CONH2ROHCOORH2NHOHCOORH2NCORO+NH2CH3(CH2)10CNHCH3O2. H2O1. LiAlH4,etherCH3(CH2)3CH2NHCH3N-MethyldodecanamideDodecylmethylamine (95%)酰胺的還原酰胺的還原NH3CH3CHONH3CH3CHHH2. H2O1. LiAlH4,etherA lactamA cyclic amine (80%)CONH2R+HLiAlH4EtherCOHRH2NAlH3CNRHHHCNH2HRHAmideIminium ionH四氫鋁鋰（LiAlH4）還原酰胺可用于制備胺如何通過多步反應(yīng)

24、制備該三級胺？Br?CH2N(CH3)2(N,N-Dimethylaminomethyl)cyclohexaneBrMg,etherMgBrCOHO1. CO2,ether2. H3O+CClOSOCl2CN(CH3)2OCH2N(CH3)2(CH3)2NHNaOH1. LiAlH42. H2OHofmann Hofmann 降級反應(yīng)降級反應(yīng)HofmannHofmann重排：重排：酰胺與溴或氯在堿性溶液中反應(yīng)，生成少一個碳原子（羰基碳原子）的伯胺 Hofmann 降級反應(yīng)。RNH2O+ Br2 + NaOHRNH2 + Na2CO3 + Br-NH2OBr2/KOHH2OBrNH2Br87%N

25、H2OBr2/NaOHH2ONH294%反應(yīng)機理：反應(yīng)機理：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-腈的反應(yīng)腈的反應(yīng)腈的水解R C NCOROH+NH3H3Oor NaOH,H2O反應(yīng)機理？堿催化的腈的水解：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酸催化水解堿催化水解CONH2ROH

27、COORH2NHOHCOORH2NCORO+NH2酰胺進(jìn)一步水解為羧酸腈的還原腈的還原CCH2NH2CH3CH3N1. LiAlH4,ether2. H2Oo-Methylbenzonitrileo-MethylbenzylamineR C NCNRHImine anionCNRHImine anionCRHNH2HPrimary amineCORH+NH3AldehydeNitrileLiAlH4EtherDIBAHToluene1. LiAlH42. H2OH2OHDIBAH = 二異丁基氫化鋁CHCH2CCCHCH2CHCCH3CH3CH2CH2CH3CH3NO2. H2O1. DIBA

28、H,toluene,-78 C96%腈與格氏試劑的反應(yīng)R C NCNRRCORR+NH3Imine anionNitrileKetoneH2OR MgXCC CH2CH3ON1. CH3CH2MgBr,ether2.H3OBenzonitrilePropiophenone (89%)腈與格氏試劑反應(yīng)應(yīng)用以腈為原料如何制備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寫出下列反應(yīng)產(chǎn)物?(a)CH3CH2CN1. CH3CH2MgBr2. H2O(b)(CH3)2CHCN1. DIBAH2. H2O(c)CN1. CH3MgBr2. H2OorCH3CN1. C6H5MgBr2. H2OCH3CH2CCH2CH3O(CH3)2CHCHOCCH3O以芐溴為原料制備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 酯縮合反應(yīng)酯縮合反應(yīng) ClaisenClaisen 縮合縮合醛、酮分子中的H 表現(xiàn)出一定的酸性，在堿作用下，可以發(fā)生羥醛縮合反應(yīng)。同樣，其它含有吸電子基團(tuán)的有機物中的H 也表現(xiàn)出一定的酸性，與堿作用生成碳負(fù)離子，發(fā)生一系列的反應(yīng)。H2COEtCOH3CCORH2CORCOH2COEtCOOCOEtH2COEtCORCORCH2CN RCH2NO2在醇鈉作用下，具有在醇鈉作用下，具有H H 的酯發(fā)生分子間的縮合反的酯發(fā)生分子間的縮合反應(yīng)，

31、生成應(yīng)，生成酮酸酯稱為酮酸酯稱為ClaisenClaisen 縮合?？s合。RCH2CORORCH CORORCH2COCH CORORH+ HORORCH3COCH2CH3O21.Na OEt, ethanol2.H3OCH3COCH2COCH2CH3OCH3CH2OHEthyl acetoacetate-keto ester (75%)aEthyl acetateCH3CH2COCH2CH3O1. NaOEt, ethanol2.H3OCH3CH2OHEthyl acetateCH3CHCOCH2CH3OCCH2CH3O81%CH3COEtOOEtCH2COEtOEtOHCH3COEtONu

32、cleophilic donorElectrophilic acceptorCH3COEtOCH2COEtCH3CCH2COEtOOCH3CCHCOEtOOEtOHH3OCH3CCH2COEtOOH2OEtOClaisen 縮合是可逆反應(yīng)， -酮酸酯在堿作用下能夠裂解。例如：CCOEtOOOHaddition ofhydroxideCCOEtOOOHelimination of acetateOHOOH2COEtH3OneutralizationCOHOOH3COEtCCOEtOO1.equiv NaOH2.EthanolCOOCH3COEtO10.9 10.9 交叉酯縮合反應(yīng)交叉酯縮合反應(yīng)用

33、一個無H 的酯和一個有H 的酯縮合，可以得到較單一產(chǎn)物，有合成價值。 COEtOCH3COEtO1.NaH/THFCOCH2COEtOEtOH2.H3OEthyl benzoateacceptorEthyl acetatedonorEthyl benzoylacetateH3O+heatCH3O10.1010.10 分子內(nèi)的酯縮合反應(yīng)分子內(nèi)的酯縮合反應(yīng) DieckmannDieckmann 縮合縮合己二酸酯和庚二酸酯在醇鈉作用下，發(fā)生分子內(nèi)的酯縮合反應(yīng)，生成環(huán)狀的-酮酸酯，這種分子內(nèi)的酯縮合反應(yīng)稱為Dieckmann 縮合。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 縮合機理縮合機理：OEtOHHCOOEtOEtOHCOOEtNa OEtEtOHHCOOEtOOEtOHCOOEtOEtOHCOOEtOEtOCOOEtEtOHH3OOHCOOEtH2O試推測3-甲基庚二酸酯進(jìn)行

35、Dieckmann酯縮合的產(chǎn)物并描述其反應(yīng)過程。OEtCH3CCOEtOO1234567OEtCH3CCOEtOONa OEtEtOHCH3CCOOEtOOEtH3OOH3CCOOEtEtOHC1-C6 bond formationNa OEtEtOHOEtCH3CCOEtOOCH3COOEtEtOOCOEtOOCEtOHH3CH3OC2-C7 bond formation丁二酸二乙酯發(fā)生分子間的縮合反應(yīng)，辛二酸二乙酯只得到少量的含七元環(huán)的-酮酸酯。因此， Dieckmann 縮合主要用于合成含五元環(huán)或六元環(huán)的化合物。CO2EtCO2Et21. NaOEt/EtOH2. H3O+CO2EtEt

36、O2COO65%Dieckmann 縮合產(chǎn)物在強堿作用下可以發(fā)生烷基化反應(yīng)。OCO2EtH1.Na OEt,H2CCHCH2Br2.OCO2EtCH2CH CH2H3OheatOHCH2CH CH2EtOHCO22-Allycyclohexanone83%Ethyl 2-oxocyclo-hexanecarboxylate有H 酮與酯在強堿作用下，也可以發(fā)生交叉酯縮合反應(yīng)。當(dāng)然，有H 酮與無H的酯縮合產(chǎn)物更單一。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、兩個羰基使亞甲基活化；、兩個羰基使亞甲基活化；2 2、分子內(nèi)氫鍵，、分子內(nèi)氫鍵，形成六元閉環(huán)，使體系能量降低。形成六元閉環(huán)，使體系能量降低。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稀堿作用稀堿作用濃堿作用

39、濃堿作用成酮成酸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產(chǎn)量低，不能用產(chǎn)量低，不能用3 3和乙烯式鹵代烴。和乙烯式鹵代烴。 RX RX也可是鹵代酸酯和鹵代酮。也可是鹵代酸酯和鹵代酮。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經(jīng)結(jié)構(gòu)分析，需引入原引CH3C CHCH2CH=CH2OCH3

41、引原要分兩次引入，先引入再引入CH3CH2CH=CH2CH3C CH2OCOC CH3O引引原原 說明：乙酰乙酸乙酯合成法主要用其酮式分解制取酮，說明：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備：CH3CH2CH2CH2CH2CCH3OCH3CH2CH2CH2BrEtOCCH2CCH3NaEtOHOEtOOCH3CH2CH2CH2CHCCH3CO2EtOH3OHeatCH3CH2CH2CH2CH2CCH3O以乙酰乙酸乙酯合成法制備：CH

42、3CH2CH2CH2CHCCH3OCH3CH3CH2CH2CH2CHCCH3CO2EtNaOEt1.CH3CH2CH2CH2CCH3H3OHeatCH3CH2CH2CH2CHCCH3OCH3OCO2EtCCH3O2.CH3I見上頁如何用乙酰乙酸乙酯合成法制備甲基環(huán)戊酮如何用乙酰乙酸乙酯合成法制備甲基環(huán)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丙二酸二乙酯的單烷基化產(chǎn)物或二烷基化產(chǎn)物與鹽酸水溶液一起加熱，發(fā)生水解和脫羧反應(yīng)，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備正己酸：CH3CH2CH2CH2CH2COHOCH3CH2CH2CH2CCO2EtCO2EtHNaOEt

47、1.CH3CH2CH2CH2CCO2EtCO2EtCH3H3OHeatCH3CH2CH2CH2CHCOHOCO22EtOHCH32-Methylhexanoic acid (74%)2.CH3I以丙二酸二乙酯合成法制備2甲基正己酸：CH3CH2CH2CH2CHCOHOCH3為什么要先上正丁基？（見上頁）如果用1mol 的丙二酸二乙酯、2mol的乙醇鈉和2mol的鹵代烷反應(yīng)，可以同時加上兩個相同的烷基。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的乙醇鈉和1mol的二鹵代烷反應(yīng)，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的乙醇鈉和1mol的適當(dāng)?shù)亩u代烷反應(yīng)，可以合成脂環(huán)族羧酸。H2CH2CCH2CH2BrBrHCCO2EtCO2EtNaEtOHOEtH2CH2CCH2H2CBrCHCO2EtCO2EtNaEtOHOEtH2CH2CCH2H2CBrCCO2EtCO2Et1,4-DibromobutaneH2CH2CCH2CH2CCO2EtCO2EtH3OHeatCOHOCO22EtOHCyclopentane-carboxylic acid以丙二酸二乙酯合成法制備下列化合物： (a) 3苯基丙酸 (b) 2甲基戊酸(c) 4甲基戊酸 (d) 環(huán)丁烷甲酸乙酯PhH2C CH2COOHfrom malonic esterfrom halide(a)CH2(COOEt)2NaOEt1.2. PhCH2BrPhCH2CH(COOEt)2NaBrH3OHeatPhCH2CH2COOHCO22EtOH3-Phenylpropan