吉林大学有机化学课件——12.doc

第十二章羧酸衍生物概述RCOX 酰卤(RCO)2O 酸酐RCOOR酯RCONH2酰胺RCN 腈水解均生成羧酸12.1 羧酸衍生物的结构、命名和物理性质一、羧酸衍生物的结构RCLO结构与羧酸类似：p-共轭HCNH2 CH3NH2OCN键长 0.1376nm 0.1474nmHCOCH3 CH3OHOCO键长0.1334nm 0.143nm二、羧酸衍生物的命名1. 酰卤的命名CH3COCl 乙酰氯ClCOCOCl 乙二酰二氯 (草酰氯)PhCOCl 苯甲酰氯HOOCCOCl对氯甲酰苯甲酸CH3CH2CH2COBr丁酰溴2. 酸酐的命名OOO丁二酸酐(琥珀酸酐)(CH3CO)2O乙酸酐(醋酸酐)CH3COOCOC2H5 乙丙酐OOO顺-丁烯二酸酐(马来酸酐)3. 酯的命名CH3COOC2H5 乙酸乙酯CH3COOCH=CH2 乙酸乙烯酯OOOO-(丁)内酯-内酯PhCH=CHCOOC2H5 3-苯丙烯酸乙酯CH3OOCCH2COOCH3 丙二酸二甲酯4. 酰胺的命名CH3CONH2 乙酰胺CH3CONHCH3 N-甲基乙酰胺HCONMe2 N,N-二甲基甲酰胺（DMF）NHO己内酰胺NHOO丁二酰亚胺COOHNHCOCH34-乙酰氨基-1-萘甲酸5. 腈的命名CH3CN乙睛CH2CHCN 丙烯睛CH3CH2CHCOOHCN2-氰基丁酸三、羧酸衍生物的物理性质1. 气味低级酰卤、酸酐：刺鼻气味低级酯：香味（香料）乙酸异戊酯：香蕉味戊酸异戊酯：苹果味丁酸丁酯：菠萝味2. 沸点酰卤、酸酐、酯的沸点低于分子量相近的羧酸和酰胺（氢键）CH3CH2CH2CONH2 CH3CH2CH2CH2COOH (CH3CO)2O CH3COOC3H7-n CH3CH2COClb.p.(C)216 186 140 102 803. 溶解度酰卤、酸酐不溶于水，低级酰卤、酸酐遇水分解酯在水中溶解度小低级酰胺溶于水如：N,N-二甲基甲酰胺、N,N-二甲基乙酰胺与水互溶CLRO碱性还原、亲核反应取代12.1 羧酸衍生物的化学性质一、亲核取代反应碱催化CLRO B-CO-RBLCBRO L-酸催化CLROCBROH+CLROHCOHRBLCBROHH+B-反应活性：RCOX(RCO)2ORCOORRCONH2原因：A. 电子效应：CLROL：C、I+C : -N-O-X I: -X-O-N吸电子能力：-X-OCOR-OR-NH2-L吸电子能力越强,亲核取代反应越快B. 离去基团的离去能力：X-RCOO-RO-NH2-1. 水解反应A. 酰卤的水解CH3COCl+H2OCH3COOH+HCl反应迅速，室温空气中冒烟B. 酸酐的水解中性、酸性、碱性介质中均可水解O H2OOOH3COOH3COHOH94C. 酯的水解RCOOR + H2ORCOOH + ROH 可逆RCOOR + H2ORCOO- + ROH 不可逆H+OH-a) 碱催化RCOO- ROHCORRO OH-CO-ROHORCOHRO RO-影响酯水解的因素（碱性条件下）：电子效应：RCOOC2H5 + OH-RCOO- + C2H5OHR： CH3 CH2Cl CHCl2 CCl3相对速率：1290 613023150空间效应：RCOOC2H5 + OH-RCOO- + C2H5OHR： CH3 C2H5 CH(CH3)2 C(CH3)3相对速率：10.47 0.100.01CH3COOR + OH-CH3COO- + ROHR： CH3 C2H5 CH(CH3)2 C(CH3)3相对速率：10.431 0.0650.002油脂的水解皂化反应CH3(CH2)16COONa 硬脂酸钠（肥皂主要成分）CH2OCORCHOCORCH2OCORNaOHCH2OHCHOH +CH2OHRCOONaRCOONaRCOONab) 酸催化酰氧断键R: 1、2CORROH+CORROHCOHROH2ORH2OCOHROHORH-ROHCOHROHH+COHRO烷氧断键R: 3、苄基COC(CH3)3ROH+H2OCOC(CH3)3ROHRCOOH + (CH3)3C(CH3)3COH2H+(CH3)3COHD. 酰胺的水解强酸、强碱、长时间加热PhCH2CONH235%HCl回流PhCH2COOH NH4+ Cl-80%E. 腈的水解PhCH2CN35%HCl4050 CPhCH2CONH2 80%CH3CNOH-CH3COO- NH3CH2=CHCN + H2O骨架铜CH2CHCONH2CH2CHCONH2n水的絮凝剂2. 醇解反应A. 酰卤的醇解苯酚、高空阻醇不能用羧酸酯化，需用酰卤酯化(CH3)3COH + PhCOClPhCOOC(CH3)3 +NN+HCl-(CH3)3CCOCl + PhOH(CH3)3CCOOPh +NN+HCl-80%B. 酸酐的醇解OOO+ n-C4H7OHCOOHCOOC4H7-nH2SO4 n-C4H7OHCOOC4H7-nCOOC4H7-n(CH3CO)2O + PhCH2OHCH3COOCH2Ph+CH3COOHC. 酯的醇解酯交换反应CH2CHCOOCH3 n-C4H7OHH3CSO3HCH2CHCOOC4H7-n + CH3OH由低沸点醇酯制备高沸点醇酯n CH3COOCH=CH2偶氮二异丁睛CH2CHOOCCH3n100。CCH3OHOH-CH2CHOHnCH3COOCH3 +D. 酰胺的醇解H+CH2=CHCOOC2H5 + NH4+CH2=CHCONH2C2H5OHE. 腈的醇解CH3CN + C2H5OHHClCOC2H5H3CNH2ClH3OCH3COOC2H53. 氨(胺)解反应A. 酰卤的氨(胺)解(CH3)2CHCOCl + NH3 H2O(冷)(CH3)2CHCONH2 + NH4Cl83%PhCOCl +NHNaOHNCOPh + NaCl + H2O81%.H2OOOOCOONH4CONH2+ NH3H +COOHCONH2温热300 CNHOOB. 酸酐的氨(胺)解C. 酯的氨(胺)解COOC2H5OHNH2CH3CONHOHCH377CH3CH2COOC2H5 NH2NH2CH3CH2CONHNH2 C2H5OHD. 酰胺的氨(胺)解CH3CONH2 CH3NH2HClCH3CONHCH3 NH4Cl75%E. 腈的氨(胺)解CNH2RNHRCN + NH3NH4Cl加压脒二、与金属有机化合物的反应1. 酰卤A. 与RMgX反应（酰卤活性高于酮）RMgXRCOX低温RCOR1 ： 1RMgX RCOX高温2 ： 1H2OCOHRRR高空阻反应物（RCOX、RMgX）生成酮CH3COCl CH3(CH2)3MgCl70C 乙醚 FeCl3CH3CO(CH2)3CH372%PhCOBr PhMgBr乙醚PhCOPh回流2h1)PhMgBr2)H2OCOHPhPhPh93%(CH3)2CHCOCl + CH3CH2CMgClCH3CH3 乙醚1618 C 5dCCH3C2H5CH3COCH(CH3)2B. 与R2Cd反应R2Cd活性低于RMgX，不与RBr、RCHO、RCOR、RCOOR、RCONH2、RCN、RNO2反应2 RMgBr+ CdCl2R2Cd + MgBr2 + MgCl22 PhCOCl (CH3CH2)2Cd2 PhCOC2H5 + CdCl2C2H5OOCCH2CH2COCl + (C2H5)2CdC2H5OOCCH2CH2COC2H5丙酰基丙酸乙酯4羰基己酸乙酯84%C. 与R2CuLi反应83%n-C4H9-CO-(CH2)4COCl(n-C4H9)2CuLi78 C 乙醚n-C4H9-CO-(CH2)4CO-C4H9-nD. 与RLi反应CH3COCl CH3CH2LiCOHH3CC2H5C2H5H2OR2Cd活性低于RMgX，与RCHO、RCOX反应，与RCOR反应慢，不与RBr、RCOOR、RCN反应2. 酸酐与RMgX反应与酰卤类似(CH3CO)2O + CH3CH2MgCl70C 乙醚H2OCH3COC2H53. 酯与RMgX反应PhCOOEt1)CH3MgX2) H3O+CCH3PhCH3OH87HCOOEt1)CH3MgX2) H3O+(CH3)2CHOH4. 酰胺与RMgX反应2 RH + RCON(MgX)2COMgXRRN(MgX)2RCORRCONH22 RMgXRMgXH2ORMgXH3+OCRRROH5. 腈与RMgX反应RCORRCN + RMgXH3+OCRRNMgX三、还原反应1. 酰卤的还原羧酸衍生物比羧酸易还原A. Rosenmund(罗森孟)还原COClCHO7481%73%COClClCHOClPd/BaSO4喹啉SPd/BaSO4喹啉S+ H2+ H2B. LiAlH4还原RCOXLiAlH4H3+ORCH2OHC. LiAlHOC(CH3)33还原H3+OCOClNC 80%LiAlHOC(CH3)33CHONC2. 酯的还原A. 催化加氢PhCOOC2H5 + H2CuO,CuCrO4125 C, 30MPaPhCH2OH 65%B. Na/ROH还原NaHH3C(H2C)7(CH2)7COOC2H5HC2H5OHHH3C(H2C)7(CH2)7CH2OHH油酸乙酯C. LiAlH4还原PhCOOC2H5LiAlH4H2OPhCH2OH C2H5OH 90D. 酮醇缩合酯的双分子还原2 (CH3)2CHCOOCH3Na, N2H2O甲苯,(CH3)2CHCHCCH(CH3)2OHOCOOC2H5COOC2H5Na, N2H2O二甲苯OHO反应机理CROORCROOR+ 2NaCROORCROORCROORCROORCROCRO2NaCROCROH2OCROHCROHCROCHROH3. 酰胺的还原A. 催化加氢B. LiAlH4还原CH3(CH2)9CH2CONH2 + H2CuCrO4250 C, 30MPaCH3(CH2)10CH2NH2PhOCH2CONH2LiAlH4H2OPhOCH2CH2NH2 80CH3CONHPhLiAlH4H2OCH3CH2NHPh 60CON(CH3)2LiAlH4H2OCH2N(CH3)2 88%C. LiAlH(OC2H5)3还原3胺4. 腈的还原PhCNLiAlH4H2OPhCH2NH2 85CH3CH2CH2CON(CH3)2LiAlH(OC2H5)3H2OCH3CH2CH2CHO + (CH3)2NHRCNSnCl2.HCl 乙醚RCHO四、酰胺的特殊反应1.酰化反应及Grabriel(盖布瑞尔)法合成伯胺A. 酰化反应RCONH2RCOClRCONHCORRCONH2(RCO)2ORCONHCORpKa: 16 9B. Grabriel法合成伯胺OOO+ NH3NHOO300 CKOHNKOORXNROOCOOKCOOKRNH2KOHNK + ClCH2COOC2H5OODMFH2NCH2COOH 85%KOHNCH2COOC2H5OO氨基乙酸2. 脱水反应CONH2ClRCONH2RCN或SOCl2P2O5P2O5CNCl95(CH3)3CCONH2SOCl2(CH3)3CCN3. Hofmann(霍夫曼)降解反应RCONH2Br2NaOHRNH2制备较少C1的伯胺PhCONH2Br2(CH3)2CHCONH2NaOHPhNH2Br2NaOH(CH3)2CHNH2 94%CCH3CONH2PhC2H5Br2NaOHCCH3NH2PhC2H5反应机理RCONH2 + Br2RCONHBrOH -OCNRH2OCO2RNH2RCNBrOBr-RNHCOOH五、乙烯酮的反应CH3COOHAlPO4CH2CO 乙烯酮CH3COOHCH2COH2OCH3COORROH(CH3CO)2OCH3COOHCH3CONH2NH3CH3COBrHBr六、酯的特殊反应1. 酯的热消除RCOOCH2CH2R300500 CRCH=CH2+RCOOH500CCH3CH2CH=CH2 + CH3COOHCH3COOCH2CH2CH2CH3OH2CCHHOCC2H5CH3CH3HHOAcHCH3HCH3H3CDPhAcOPhHHPhDPhHOAcHPhHPhDOAcHPhDHPh前者比后者稳定反应特点：A. 顺式消除B. Hofmann消除为主500 CCH2=CHCH2CH2CH3 + CH3CH=CHCH2CH3 57% 43%CH3COOCHCH2CH2CH3CH3消除酸性大、空阻小的-H为主C. 反式烯烃为主500 CCH3COOCHCH2PhPhHPhHPh应用：合成烯烃CH2OHCH2CH2OCOCH3H+CH32. 酯的Claisen(克莱森)缩合A. 含-H酯制备-羰基酯2 CH3COOEtEtONaEtOHH+CH3COCH2COOEt + EtOH乙酰乙酸乙酯2 CH3CH2COOEtEtONaEtOHCH3CH2COCHCOOEt + EtOHCH3H+反应机理CH3COOC2H5C2H5OCH3COC2H5 CH3COCH2COOC2H5OC2H5CH3COCH2COOEtCH2COOC2H5CH2COC2H5OOCH2COOC2H5C2H5O-CH3COCHCOOC2H5H+CH3COCH2COOEtC2H5OB. 含-H酯与不含-H酯HCOOC2H5 PhCH2COOC2H570EtONaEtOHH+HCCHCOOC2H5PhOPhCOOC2H5 CH3CH2COOC2H556H+PhCCHCOOC2H5CH3ONaHCOOC2H5COOC2H5 CH3(CH2)16COOC2H51)NaOEt 2)H+COOC2H5COCHCOOC2H5(CH2)15CH371C. 酮酯缩合制备1,3-二酮CH3COOEt + CH3COCH31)EtONa2)H3+OCH3COCH2COCH3 + C2H5OH3845%PhCOOEt + CH3COPh1)EtONa2)H3+OPhCOCH2COPh + C2H5OH6271%PhCOOEt OOCOPh C2H5OH1)EtONa2)H3+OD. 分子内酯缩合：Dieckmann(狄克曼)反应H+EtONaEtOHCOOEtCOOEtOCOOEt EtOHCOOC2H5COOC2H5H+EtONaEtOHOCH3COOC2H5 EtOHCH2COOEtCH2COOEtH+NaHOCOOEt7090%COOC2H5COOC2H51)NaOEt 2)H+EtOOCCH2CHCH2COOEtCH3H3CCOOEtEtOOCOO100%E. 酯缩合在合成中的应用例1PhCCHCOOEtCH3OaPhCOOEt +CH3CH2COOEtbPhCOCH2CH3 + C2H5OCOC2H5O例2CHCOOEtOOCOOEtCOCH2COOEtCOOEtCOOEt CH3COOEt例3OOOOCOOEtEtOOCCH2CH2COOEtOEtOOEtOOC2 EtOOCCH2CH2COOEt七、乙酰乙酸乙酯和丙二酸二乙酯在合成中的应用1. 乙酰乙酸乙酯A. 结构CH3CCH2COC2H5OOOH2CH3CC2H5OOCHCOHOC2H5OH3C92.5% 7.5%B. 分解反应CH3CCH2COC2H5OOCH3COCH3 + CO2 10%NaOHCH3CCH2CO-OOH3+O酮式分解酸式分解CH3CCH2COC2H5OO2CH3COOH + C2H5OH浓NaOHH3+OCH3CCH2COC2H5OO40%NaOHCH3CCH2COC2H5OHOO-CH3COOH + CH2COOC2H5CH3COO- + CH3COOC2H5OH-CH3COO- + C2H5OHH3+OH3+O2CH3COOHC. 烷基化及酰基化反应CH3CCH2COC2H5OORXC2H5O-CH3CCHCOC2H5OOCH3CCHCOC2H5OORCH3CCHCOC2H5OORCH3CCHCOC2H5OO1)稀OH-2)H3+OCH3COCH2R1)浓OH-2)H3+OCH3COOH RCH2COOH制备甲基酮类化合物制备取代乙酸NaOC2H5RXRCH3CCCOC2H5OOR1)稀OH-2)H3+OCH3COCHR1)浓OH-2)H3+OCH3COOH RCHCOOH制备甲基酮类化合物制备取代乙酸RRRX：a)卤代烷1RX较好、2产率低、3RX、PhX、CH2CHX不可用b)多卤代物X(CH2)nXc) -卤代酮XCH2COCH3d)卤代酯X(CH2)nCOOEte) 酰卤RCOX、PhCOXD. 在合成中应用合成甲基酮衍生物CH3CCH CH2CH3OCH3例1CH3COCH2COOEt1)C2H5O-2)C2H5Br1)C2H5O-2)CH3I稀OH-T.M.H3+OCH3CCH COOC2H5OC2H5CH3CC COOC2H5OCH3C2H5例2：CH3COCH2CH2COCH3例3：CH3COCH2COPhC2H5O-CH3COCH2COOEtPhCOCl稀OH-T.M.H3+OCH3COCH2COOEt稀OH-T.M.BrCH2COCH3C2H5O-H3+OCH3COCH2COOEtCH3COCHCOOC2H5CH3COCHCOOC2H5C2H5O-I2稀OH-T.M.H3+O例4：CH3CO(CH2)6COCH3C2H5O-CH3COCH2COOEtCl(CH2)4Cl稀OH-T.M.H3+O过量例5CO