羰基化合物的反应

1第7章羰基化合物的反应7.1羰基的特点烯醇化及互变异构ORCH2R'OHRCHR'ORCHR'+H+-H+-H++H+ORCHR'ketoneformenolform2a.通过在含氘溶剂DS中H-D交换间接测定烯醇形成的速度b.通过测定羰基化合物卤代反应速度，间接测定互变异构速度ROHRRBRO+BHRRRO+DSRRRODRR+SROHRRBRO+BHRRslowRO+X2RRfastROXRR+X3羰基的分子轨道E1=α+1.618β,Ψ1=0.526φC+0.851φOE2=α－0.618β,Ψ2=0.851φC－0.526φO电荷分布：qC=2*0.5262=0.553;qO=2*0.8512=1.448COHHCOHH+0.447e0.448COHHCO4轨道作用:LUMO能量降低，碳原子系数增大，有利于亲核试剂的进攻静电相互作用:碳原子正电荷增加，有利于亲核试剂进攻质子化甲醛COHHH+0.8575e0.1425eCOHECOE未质子化甲醛56羰基亲核加成的一般机理Od+d-:Nu-7羰基的反应性：亲核性，亲核试剂进攻碳原子R'ROslowROHR'YRO-R'Y+H+fastY:-RO-R'Y8R'RO+Y-HROHR'YR/Sracemate9R或R‘=OH,OR,NH2（羧酸衍生物）反应的结果是取代（加成/消除）酸催化加成/消除机理XRO+H+fastXRHO+XRHO+XRHO++Y:slowROHXYROHXYROHCY++XROHCY+YRO+H+107.2与羰基相连基团对其反应性能的影响★+C,+I效应使羰基碳的正电荷量减下，其反应性能减弱★强吸电子基则使羰基碳的正电荷量增加，与亲核试剂的反应性能加强★空间效应也是影响羰基反应性能的重要因素常见的羰基化合物的活泼次序HHORHORROOMeRONHRROORO-11ApproximateEquilibriumConstantsat25CfortheReactionofR1R2C=O+H2OR1R2C(OH)2carbonylcompdsOHHOMeHOMeMeK[H2O]=[R1R2C=O]R1R2C(OH)22*1031.32*103OClCH2HOCl3CHOC2H5HOiPrHOt-BuH372.8*1040.710.430.24OClCH2H3COClCH2ClCH22.9100.0220.11ClOHO2NOH12羰基化合物反应的通式XONu_+_ONuX_X=nucleofugeXONu_NuO(-OR,-NR2,Hal)substitutionXnotanucleofuge(H,R,Ar)/H+OHNuXadditionNuhasα-H-H2OeliminationNuXcondensation13Scopeofthereaction::Nu+R-(C=O)-X→R-(C=O)-Nu+XNu:ORNR2OCORHalSROC6H4NO2(Opnp)estersamidesanhydridesacylthiolp-nitrophenylesterhalidesestersH2O(OH-,√√√√√√H3O+)ROH√√√√√R2NH√√√√√RSH√√√H-(AlH4－)√√√√√√R－√√S2O32－,√√√√RO2－,OCl－147.3羰基加成可能的反应进程图O+:Nu-k1k-1NuO-k2k-2NuOH+H-A+A-NuO-15当受到强亲核试剂进攻时,第一步是决速步无酸催化（k-1k2）O+Nu-+HANu-O+A-NuHO+A-(a)16O+Nu-+HANu-O+A-NuHO+A-(b)当亲核试剂稍弱时，k-1与k2相当。没有决速步，中间体通过酸质子化而捕获，总反应速率显示一般酸催化17O+Nu-+HANu-O+A-NuHO+A-(c)当k-1k2[HA]时，显示一般酸催化，质子转移为决速步18O+Nu-+HANuONuHO+A-(d)HA_Transitionstate当亲核试剂很弱时中间体寿命极短，不能存在。亲核试剂进攻与质子转移同步进行。可观察到一般酸催化19例：羰基化合物的酸/碱催化水合酸催化H2O+C=O+HACOHOH2+A_+COHOH2+A_+fastCOHOH过渡态：COOH2+HAδ－20例：羰基化合物的酸/碱催化水合碱催化H2O+C=O+BCOHOfastCOHOH+Bslow_+BH+COHO_+BH+21例：醛、酮对HCN的加成碱催化O+-CNslowCNO-CNOH+H-A+A-CNO-HCN+A-fastHA+CN-fastacyanhydrin22醛、酮与HCN加成的平衡常数（20C,96%EtOH）OR2R1+HCNOHR1R2CNR1Php-MeC6H4p-MeOC6H4p-NO2C6H4PhR2HHHHMeK23611432.718200.77R1MeMeMeMeR2MeEtiPrtBuK33386532环酮环戊酮环己酮环庚酮环辛酮K4810007.81.17237.4加成的立体化学ORR'Nu:_Nu:_NuR'OR_ROR'Nu_R/S1:1ThetwofacesR’=R,homotopicR’R,enantiotopicRand/orR’=stereogenicdiastereotopic2425构象分析确定产物的立体化学：Cram规则开链模型（S:smallest;M:medium;L:largest）MO作用能量低于LO之间的作用，A/B1MORMR'SLR'MLSRR'HOMAlowenergy(RisgauchetotheSgroup)ORMSLSR'RHOMBLMR'R'MA/B126EtMeOEtMeHCNHHOHH+HCNmainaabbEtMeHCNOHHminoriPrOPhHMeLAHiPrPhHMeHOH+iPrPhHMeOHH51Examples2728MeHHBn2NMeLiOHNBn2MeCHO+MeLi91%MeMeHNBn2HOH+MeMeHNBn2HOH91:9AcOIi.Znii.CuCN.2LiClAcOCu(CN)ZnIOHCPhMeBF3.OEt277%AcOPhOHMesyn:anti83:1729环状模型当α-C上连有-OH,-OR,-NHR等基团时，R‘-MgX等金属化合物在反应瞬间与羰基及OH等基团形成环状中间体，R’由五员环空间阻碍较小的一侧进攻羰基碳原子OHLSRO(M)R'MgXHOLSRO(M)MgR'XLOH(M)SR'RHO30例：当OH为S基团时，如S=OH,M=Me,L=Ph时,开链模型会产生错误，只能用环状模型(S)HO(L)PhMe(M)PhOMeLiHOMePhLiPhOMeOHPhMePhMeHO(S)HO(L)PhMe(M)PhOMeLiOHPhMePhOHMeMeLi开链3132AroundandbeyondCram'sruleMengelA,ReiserOCHEMICALREVIEWS1999,99(5):1191-1223.33Prelog'sMethod:DeterminationoftheabsoluteconfigurationintheprocessoftheasymmetricsynthesisofatrolacticacidS-(+)-苯基乳酸OOOSMLMeMgIOOSMLMeIMgOH2OOHOMeHO稳定性ABCOOOSMLOOOLSMMeMgIAOOOMLSBC34Prelog规律SOHMLHOMeCO2HPh(S)-(+)-苯基乳酸HOSMLMeOHCO2HPh(R)-(－)-苯基乳酸35Prelog规则--应用实例雄甾烷-17β-醇中C(17)构型的确定OOOH(S)(M)(L)HO2CMeOH(S)-(+)-苯基乳酸萜醇中绝对构型的确定(S)(M)(L)HOOOPhMeMgIPhMeHOOROH2OHO2CPhMeOH(R)-(-)-苯基乳酸367.5羧酸酯的反应7.4.1羧酸酯的水解1．酰氧断裂机理R-C-OR'O+H+R-C-OR'OH+R-C-OR'OH++H2OR-C-OR'OHOH2+R-C-OR'OHOH2+R-C-OR'OHOH+HR-CO2H+R'OH+H+EtCOOMeH+,H2OEtCO2H+MeOH1818酸催化:一般为可逆反应，AAc2机理(A:acidic;Ac:acyl-oxygen;2:bimolecular).Rate=k2[ester][H3O+]37碱催化:一般为不可逆反应，酰氧断裂，机理为BAc2(B:basic)Rate=k2[ester][OH－]酰氧键断裂的同位素证据立体化学证据MeOOHEtMeMeCO2H+HOHEtMeCOROR'+OH－COROR'OHCOROH+OR'－CORO+R'OHRCOOR'+H2O18RCOHOR'OH18RCOOR'+H2O382.烷氧断裂机理（Alkyl-oxygencleavage）:TheAAl1mechanism.R-C-OCR'3+H+OOHR-C-O-CR'3+RCO2H++CR'3alkene+H+H2OR'3C-OH例如:当烷基为叔丁基时，由于空间位阻效应及(CH3)3C+较稳定393.分子机理：theAAc1mechanism例如:强而浓度大的酸中（conc.H2SO4），发生酰氧断裂R-C-OR'+H+OOHR-C-O-R'+OR-C-O-R'+HRCO++R'OHH2ORCO2H+H+R=MeMeMe407.4.2酸酸酯的取代反应在较强亲核试剂作用下，能发生取代反应。如OArRO+NNHNNRO+Ar-OHH2ONNHRCO2H+canbeobservedbyitscharacteristicabsorptionat245nm417.5Wittig反应O+CPh3PR'R+RR'+Ph3POphosphorousylideCHPh3PR'R+X_BuLiCHXR'R+Ph3Pphosphorousylide：butaine甜菜碱式化合物一般为醛R,R'不得为-CN,酯基等吸电子基双键的立体异构与碳原子上原有取代基有关，也与反应条件（反应温度、所用溶剂、有无金属盐等）有关。seeareview:J.Am.Chem.Soc.1988,110,3948.SeealsoJ.Am.Chem.Soc.1990,112,3905.4243PhCHOPhCH-PPh3-+PhCH=CHPh70%trans,30%cisPhCH=CHCH313%trans,87%cisCH3CH-PPh3-+例如其它ylide:如锍、砷等P,As,S与C的电负性相当，不形成双键3d或4d轨道为空轨道RCH-SR2-+RCH-AsR3-+44锍Ylide的制备及反应SOMeMe+MeIMe3SO+I-NaHDMSOSMeOCH2Me+-SMeMe+MeIMe3S+I-NaHDMSOMe2S+CH2-与醛、酮化合物的反应：R2C=O+-CH2SMe2O+R2C-CH2SMe2O-O+OCCH2RR+Me2S=OR2C=O+-CH2SMe2+R2C-CH2SMe2O-+OCCH2RR+Me2S45改进的Wittig反应，反应条件温和，亲核性更强，副反应少[Me2N]2PCHR1R2On-BuLi[Me2N]2PCR1R2O_Li+R3R4CO[Me2N]2POCR1R2CR3R4O_H2O[Me2N]2POCR1R2CR3R4OH[Me2N]2POOH+R1R2C=CR3R4PO试剂PCHR1R2OEtOOEtPCHOHOHOR1R2467.6羰基反应的应用Knoevenagel-condensationbenzoincondensationCannizzaroreactionClaisen-condensationNitrolaldolreaction(Henryreaction)Aldolcondensationenaminer