12章羧酸衍生物教学课件.ppt

1、Chapter12CarboxylicAcidDerivativeRCOXRCONH2(R)RCOORRCOO CORRCNacylhalideamideesteranhydridenitrile一一.StructureandNomenclature (一)Structure RCOLthe general formulaP-conjugationSP2 hybridizationresonancehybride RCOLSP hybridizationRCOLRCOLHCONHHHCONHHHCONHHRC NRC N(二)、NomenclatureacylhalideamideHCCOBr

2、邻苯二甲酰亚胺HCONCH3CH3DMFHCH3CNHOON,N-二甲甲酰胺3-对甲苯基烯丙酰溴anhydridenitrileO COH3C CN乙腈C乙（酸）丙（酸）酐苯甲酸酐OO COCH3COCH3甲氧甲酰基CN氰基乙酰氧基O CH3COO COCH3CONH2COCl氨甲酰基氯甲酰基H3COOC邻苯二甲酸二乙酯O COCH3H2C乙二醇二乙酸酯-甲甲基基-戊戊内内酯酯COOCH3OOCH3O COCH3H2COHCORSO3HROCORORCORXCORNR2CORCNRHCORRCOROHROHArNR2RRORester2二二.PhysicalProperties 低级酰卤、酸酐

3、：刺激性气味，气体低级酰卤、酸酐：刺激性气味，气体 低级酯：易挥发、香味低级酯：易挥发、香味 酰胺：固体（甲酰胺、酰胺：固体（甲酰胺、N-取代酰胺液体）取代酰胺液体）酰卤、酯、酸酐酰卤、酯、酸酐:b.p.(nohydrogenbond)NH酰胺：酰胺：bp.,mp.COOH(hydrogenbond)N取代酰胺：液体，取代酰胺：液体，bp.,mp.(nohydrogenbond)DMF 腈：极性大，腈：极性大，mp.,bp.(nohydrogenbond)IR C=O:18501630cm-1 1H-NMR-H:23COO-CH2-:3.74.1CON-H:58三、三、ChemicalProp

4、erties(一）一）NucleophilicreactionLLCORNu+NuCORNu=H2O,ROH,NH3,RNH2L=-X,-OOCR,-OR,-NH2(R)H3CCOCl+HClC19H39COClH2On-H3CCOOHH2OdioxaneC19H39COOHn-+HCl(1)The hydrolysis of the acyl halides HLLCOR+OHCORH2O+1.Hydrolysis+H2OOH3CHOOOHH3CHOOOH(2).Acid Anhydrides(3)ThehydrolysisofesterOCOR酰氧断裂ROCORR烷氧断裂acidorbas

5、econditionBaseCondition(亲核加成亲核加成消除消除)OCCOH3C(R)-(+)-1-苯乙醇EtOH-H2O+KOHOKCOH3CCH3HC6H5CHOCH3HC6H5(R)-(+)-乙酸-1-苯乙醇酯C-O断裂途径(两条）AcidCondition 1o,2o-酰氧键断裂酰氧键断裂RCOORHRCOHORHOHRCOHOROH2RCOHOROHH-ROHRCOHOHRCOOHH+Mechanism叔醇酯：烷氧键断裂acidity,mechanism+NH3H2ORCOOHfastRCONH2+HRCOHNH2RCOHNH2OH2RCOHOHRCOHNH3OH+NH4+K

6、OHH2OH3CCOOK100oCNHCO2NOCH3OCH3NH2O2NOCH3base,mechanism(4).Amides(5).Nitrile-COOH OHH3OMechanismR C NOHH orH2OR CONH2OHH3OorR COOH活性顺序：R COCl1011R COO CORR COORR CONH2R CONR2R COL10-21071.0NH2RORCOOCl醛、酮：亲核加成 羧酸衍生物：亲核取代(二二)AlcoholysisR COLHLHOR+R COOR（1）.AcylHalides Schotton-BaumannHClEt2O+(H3C)3CCO

7、Cl+Py+H3CCOClOH(H3C)3CCOON(H3C)3COHC6H5N(CH3)2H3CCOOC(CH3)3+C6H5N(CH3)2HClH3CCOO+H2SO4+H3CCOOHOHH3CCOO2SO3H+C2H5OHOOOOC2H5OOOC2H5(2).AcidAnhydrides(3).Alcohols+PTSH3C COOCH3OHOH3C CO+HOCH3(4).Nitrile+HClH3CC N+HOC2H5CH3C(OC2H5)3NH4ClH2CCOClOHbNaCNaNa2CO3H2CCOCNONaH2SO4C2H5OHH2CCOCO2C2H5OC2H5+3、Ammon

8、lysis(1).Acylhalides+NaCl+H2OC6H5COClbNaCNNaOHHN+C6H5CON(2).AcidAnhydridesOOONH3ONH4OONH2H300oCOHOONH2NHOO+(3).EsterOHOC2H5OHNH2CH3OC2H5OHOHNH3C+H2NNH2OC2H5CH3CH2CO+C2H5OHNHNH2CH3CH2CO+H2NOHOC2H5CH3CH2CO+C2H5OHNHOHCH3CH2CO(4).AmindesCH3NH2NH2H3CCONH3NHCH3H3CCO+(二二)、ReactionwithMetalAgents 1.Grignard

9、ReagentsH3CCOCl+CH3MgIFeCl3-15oCH3CCOCH3CH3MgIH3CCOHCH3CH3CN-CORMgXCNRbH2OaC6H5MgBrCNMgXRRH2OCORRCNCO酰胺、酸酐R2CuLiketonen-X-CNCORORCORXCORNH2(R2)R2CuLiCOC4H9O(CH2)4COCl(CH3)2CuLin-COC4H9O(CH2)4COCH32.R2CuLiLiAlH4Hx+CORXCOROCCH2OHRORLiAlH4RCH2OH+CH2OHRCORORLiAlH4ROH+CH2OHRCNRLiAlH4CH2NH2RCORNH2LiAlH4CH

10、2NH2R(三三)、Reduction1.LiAlH42.RosenmundReactionPd/BaSO4H2,Pd-BaSO4CORXR=aliphaticoraromaticCORHquinoline3.CatalyticHydrogenationorChemicalAgentsBouveault-Blancref.Na+EtOHCOC2H5OCH2CH=CHCH3+CH3CH2CH2OHH2/CuO.CuCrO4125oC/加压COCH2CH=CH2OCH2OHHOH2C CH2CH=CHCH3(四四)ClaisenCondensation 21.NaOC2H5COOC2H5H3C2.

11、H3OCOOC2H5CCH2OH3CMechanismverystrongbase(C6H5)3CNa-Handno-HC2H5ONa+H COOC2H5HC CH2CC6H5CH(COO C2H5)2H3C COOC2H52.H3O1.OOOC2H5C2H5O COOC2H5C6H5CH2COOC2H5C2H5ONa2.H3O1.+DickmanCondensationC2H5ONa2.H3O1.CO2C2H5CO2C2H5OCO2C2H5intramolecularC2H5ONa2.H3O1.CO2C2H5CO2C2H5+C2H5O2CC2H5O2CC2H5ONa2.H3O1.OOCO2C

12、2H5C2H5O2CCO2C2H5CO2C2H5CO2C2H5CO2C2H5OOC2H5O2CC2H5O2C+intermolecularketoneandesteC2H5ONa2.H3O1.C2H5CO2C2H5+C2H5ONa2.H3O1.CH3CC6H5OC6H5CCH2CC6H5OOCO2C2H5COCH3OO1.acidandbaseKOH+NaOHR CONH2NHOO+H2ONNaOONHOONKOO+H2OpKa 9.6pKa7.4P-conjugationpH=7酰亚胺NOOBrNBS(五)、Properties of Amide2.HofmanDegradation+Br2

13、RCONH2CO32-OHRNH2Mechanism制备：伯胺和氨基酸重排，迁移基团构型不变Br2CCONH2OHrea.-SN2(S)-(+)C6H5H3CHCNH2C6H5H3CH(S)-(-)3.Dehydration/Dehydrolysisdehydrolyzingagent:P2O5,POCl3,SOCl2+H2ORCOONH4-H2OSOCl2RCNCH3(CH2)4CNRCONH2+H2O-H2OH3C(H2C)4CONH2CONH2ClP2O5CNCl(六六)、DarzenReaction C2H5ONa+ClCH2CO2C2H5RCR(H)OOR(H)RCO2C2H5OKO

14、C(CH3)3+ClCH2CO2C2H5OCO2C2H5MechanismClCHCO2C2H5ROOR(H)RCO2C2H5HClCHCO2C2H5OCHCR(H)RCO2C2H5RCOR(H)ClUsingCH2CO2C2H5+OC6H5H3CCO2C2H5BrNaOC2H5C6H5COCH3OC6H5H3CCOOHC6H5CCHCH3OHC6H5HCCHCH3Oa.OH/H2Ob.H四、四、Preparation(一一)、由羧酸制备、由羧酸制备 Chapter11(二二)、由羧酸衍生物间互相转化制备、由羧酸衍生物间互相转化制备 NH3/RCONH2RCOCl(RCO)2ORCO2NaNa

15、OHH2OH2ONH3NH3RCNP2O5/NH3RCO2Ha.OH/H2Ob.HH/ROHHorOH/H2ORCO2RROHP2O5SOCl2orPCl5RClROHHorOH/H2O（三）酮肟重排制备（三）酮肟重排制备N-取代酰胺取代酰胺 BeckmanRea.CRRNOHHCRNHRORea.Catalyst:H2SO4,HCl,PPA,PCl5,PhSO2Cl,CH3COClCRRNOHHCRNCRRNOH2-H2ORCRN RH2OCH2ORNRHCHORNRCORNHRMechanism:异构体（EZ）CC6H5H3CNOHH2NOH+ZECOC6H5CH3CC6H5H3CNOHC

16、H3OH2NOHCH3NOH优先基团：芳基烷基CC6H5H3CN OH75100%+PCl5CC6H5H3CNHOCCH3C6H5NHO构型CCH3CNOHH2SO4CH3C6H5HHNCCH3CCH3C6H5HO五、五、AcetoactaticEster(一一)KetoForm-EnolFormTautomerism ketoform92.5%CH3CCH2CO2C2H5Oenolform7.5%CHCCH3COOC2H5OH双重特性ketone:HCN,NaHS O3,NH2OH,C6H5NHNH2enolform:Br2/CCl4,F eCl3tautomerismCHCOCHNOCNO

17、HCHCNCCNHCHNOONHCOC NOHON C OH（二）酮式分解和酸式分解（二）酮式分解和酸式分解 H3CCOH2CCOOC2H5H3CCOCH3H3CCOOHdil.NaOHcon.NaOHMechanism（三）合成应用（三）合成应用 H3CCOH2CCOOC2H5HC COCH3NaOC2H5H3CCOCHCO2C2H5R-Xa.OH/H2Ob.H3OH3C COCHCO2C2H5RNaOC2H5H3C COCCO2C2H5RH3C COCH2RR-XH3C COCCO2C2H5RRa.OH/H2Ob.H3OH3C COCHRR+CH3CCH2CO2C2H5Oa.C2H5ONa

18、b.n-C4H9BrCH3CCHCO2C2H5OC4H9-na.NaOH/H2Ob.H3OCH3CCH2OC4H9-n制备二酮制备二酮 CH3CCH2CO2C2H5OCH3CCHCO2C2H5OClCH2ClCH3CCHOCO2C2H5H2CCHCCH3CO2C2H5OCH3CCH2OCH2CCH3OCH2C2H5ONaa.OH/H2Ob.H3O2环酮CH2CH2CO2C2H5CH2CH2CO2C2H5CO2C2H5OCO2C2H5OC2H5OC2H5a.C2H5ONaa.OH/H2Ob.H3Oa.C2H5ONab.C2H5Brb.H3O/-烃化烃化或或酰化酰化 dil.OHcon.OHRXC

19、H3CCHORCO2C2H5HOCCH2ORCH3CCH2ORdil.OHcon.OHCH3CCHOCCO2C2H5CH3CCH2OCORORHOCCH2OCORX COR六、丙二酸二乙酯合成应用六、丙二酸二乙酯合成应用 H5C2OCCH2OCOOC2H5H2CCO2C2H5CO2C2H5NaOC2H5HCCO2C2H5CO2C2H5RXCHCO2C2H5CO2C2H5Ra.OH/H2Ob.H3O/CH2CO2HRNaOC2H5CCO2C2H5CO2C2H5RRXCCO2C2H5CO2C2H5RRa.OH/H2Ob.H3O/HCCO2HRR羧酸制备方法羧酸制备方法 1.取代乙酸取代乙酸 H2C

20、CO2C2H5CO2C2H5a.NaOC2H5a.OH/H2Ob.H3O/b.CH3(CH2)2BrCH2COOHCH3(CH2)2CH3(CH2)2CH(CO2C2H5)22.二元羧酸H2CCO2C2H5CO2C2H5NaOC2H5a.OH/H2Ob.H3O/BrCH2CH2BrHCCO2C2H5CO2C2H5CH(CO2C2H5)2(CH2)2CH(CO2C2H5)2CH2COOH(CH2)2CH2COOH22H2CCO2C2H5CO2C2H5a.NaOC2H5a.OH/H2Ob.H3O/b.H5C2O2CCHBrCH3CH(CO2C2H5)2CHCO2C2H5H3CCH2COOHCHCO

21、OHH3C3环烷酸H2CCO2C2H5CO2C2H5a.NaOC2H5a.OH/H2Ob.H3O/b.Br(CH2)3BrCO2C2H5CO2C2H5COOH七、碳酸衍生物COOHureaphosgenethioureaguanidineHOCOLHOCOLLCOClClCONH2H2NCNHNH2H2NCSNH2H2Nhydrolysis,alcohlysis,aminolysisCOClROHH2O-HCl2NH3ROCONH2H2NCOClClCOORROCONH2ROHClCO2+HCl+NH3ROHNaOH/H2OROHNH3Na2CO3CONH2H2NCONH2RO+CO2HClN

22、aOHNH3Na2CO3+NH4Cl+(一)UreaweakbaseCONH2H2NHNO3CONH2H2NHNO3酰氯、酸酐、酯作用NaOC2H5C2H5OHCOH2NH2NH2CCO2C2H5CO2C2H5+H2CCNHCNHCOOOtautomerismenolformpKaHAc3.98ketoformH2CC NHCNHCOOOHCC NCNCHOHOOHpKa:4.76CONH2H2NCONH2NHHCOH2NCONH2HN(二二)、Guanidine 胍基CNHNH2H2N胍CNHH2NCNHNHH2N脒基pKa:13.8有机强碱H2OCNHNH2H2N2CO22CNHNH2H2NH2CO3HCNHNH2H2NCNH2NH2H2NCNH2NH2H2NCNH2NH2H2N易水解CNHNH2H2N+H2OBa(OH)2CONH2H2N保存：盐八、油脂、原酸酯八、油脂、原酸酯 （一）、油脂（一）、油脂 CHOCH2OCCH2OCCOROROR（二）原酸酯（ortho-esters）CORORRORpreparation+HCCl33NaCl3C2H5CONaHC(OC2H5)3UsingCORR+H2OHHC(OC2H5)3COC2H5RROC2H5MgBrH3CHC(OC2H5)3CH(OC2H5)2H3CCHOH3C谢谢