教学课件：第四章-消除反应

中级有机化学中级有机化学第四章消除四：消除反应-消除反应：消除反应：-消除反应：-消除反应：NCH3LiCH2Cl2HNClNHHCH3-重氮酮的光解或热解：4.1慨念4.2E2消除4.3E1消除4.4E1CB消除4.5E1和E2比较4.6消除和取代竞争41慨念4.1慨念消除和亲核的定义：HHBrH2CEtO-H+EtOH+Br-eliminationsubstitution亲核试剂和碱的不同：亲核试剂进攻碳正离子；碱夺质子亲核试剂和碱的共性：富电子碎片或物种HEtOHH2CH+Br-消除和亲核的竞争和控制（通过试剂的控制）：HZaitsev’s规则：生成取代基多的烯烃Zaitsev烯烃Hofmann 烯烃Br+NaOEtEtOH19%+81%19%BrNaOEtCH3EtOH70%30%+CH36个质子的贡献反应具有区域选择性！Zit’规则的解释Zaitsev’s规则的解释“类”烯烃的过渡态“类”烯烃的过渡态Alkene-liketransitionstate烯烃和烯烃的控制Zaitsev烯烃和Hofmann烯烃的控制碱体积越大，越有利于Hofmann烯烃的生成！离去基团的离去能力越弱，越有利于Hofmann烯烃的生成33333三种经典的消除机理三种经典的消除机理•E1cB:质子先离去，生成碳负离子E1cB:质子先离去，生成碳负离子•E1:离去基团先离去，生成碳正离子•E2:质子和离去基团同时离去•E2:质子和离去基团同时离去种消除机的过渡态三种消除机理的过渡态42E2elimination4.2E2eliminationTheE2ReactionMechanismTheE2ReactionMechanismTheE2ReactionkineticsSubstratesR3CXR2CHXRCH2XSubstratesR3CXR2CHXRCH2XLeavingability:RIRBrRClTheE2ReactionStereochemistryCharacteristicsoftheE2Reaction——TheE2ReactionMechanism•质子和离去基团同时离去CharacteristicsoftheE2Reaction——TheE2Reactionkinetics•反应一步发生•V=k[R-X][B]动力学同位素效应KineticIsotopeEffectKHKD反应的决速步骤包括C-H键的解离CharacteristicsoftheE2Reaction——Substrates类烯烃过渡态Alkene-liketransitionstateRelativereactivity:R3CXR2CHXRCH2XRelativereactivity:R3CXR2CHXRCH2Xtrans:cis=6:1类烯烃过渡态不仅决定了底物的相对反应速度，还决定了产物的构型。ChtitifthE2Rti反式共平面！CharacteristicsoftheE2Reaction——TheE2ReactionStereochemistry反式共平面！立体专一性的反应！•质子和离去基团处于反式共平面，允许轨道重叠CharacteristicsoftheE2Reaction——TheE2ReactionStereochemistry预测产物烯烃的构型PhHBHPhPhPhBrHBrHPhHBrHBrPhPhBrHBrPhBrHPhKOHPhPhBrCharacteristicsoftheE2Reaction——TheE2ReactionStereochemistryegKOHorKOC4H9Bredt'sRulee.g.KOHorKOC4H96-hydrogensNewmanprojection*MustbeparallelporbitalsnottwistedMustbeparallelp-orbitals,nottwisted.Bredt’srule：消除反应产生的烯烃要远离桥头碳OH环足够大时：环足够大时：KnownKnownUnknownDimerizedbeforeisolation卤代环己烷的消除•首先满足反式共平面；满足反式共平面的前提下考虑生成取代基多的烯烃（Zit烯烃）卤代环己烷的消除：•满足反式共平面的前提下，考虑生成取代基多的烯烃（Zaitsev烯烃）BrBrfasteliminationHbHaBu-tverysloweliminationHbBrBBu-teliminationBrBr邻二卤的消除：反式共平面BrBrH3CHI-H3CHHCH3CH3HmesoHCH3trans-BrHCH3I-H3CH+BrH3CHI-CH3HBrH3CH+HH3CBrdlcis-syn-elimination反式共平面不能满足的时候取顺式共平面：反式共平面不能满足的时候，取顺式共平面：C消除Cope消除：NSNNONR1SNNOOO1.mCPBANHNNHR2NHNNH2.R1R2NH2.R1R2NH1.mCPBAOxidationN-MichealNSNNOOOSNNOOOCHNHNNHONHNNHCopeeliminationHCope消除：顺式共平面消除——立体选择性！仲羟胺的制备:COOHCNCOOHMCPBANCOOHCOOHNHKOHMeOH93%NCNN-MichealOxidationMeOHNCNOHNOHheatacetone96%CopeNMichealCopeelimination经过分子内五元环状过渡态的热消除N(CH3)2H2O2N(CH3)2O110oC140oC经过分子内五元环状过渡态的热消除：110oC-140oCCopeeliminationOOtolueneOSPhtoluenerefluxCaCO3+PhSOHCOOEtCOOEtHofmann消除Hofmann消除：HofmannRule——区域选择性！Hofmann消除的区域选择性解释：反式共平面Hofmann消除的区域选择性解释：反式共平面反式共平面！反式共平面R3R3BrNR21Br-Et3N:DCM(1:19)18hrtSOONR21+HBaseSOONR118h,rtNR1Hofmann消除CharacteristicsoftheE2Reaction•ReactionKinetics-bimolecular•ReactionDiagram–inasinglestep•Stereochemistry–stereoselectivereaction•Substrates–R3CXR2CHXRCH2X322•LeavingGroups–dependingontheleavinggroupBredt规则Cope消除Cope消除Hofmann消除E2vsS2E2vsSN2•强的亲核试剂有利于取代，强的碱有利于消除。Stericbulkfavorselimination•SN2:RCH2XR2CHXR3CXE2RCXRCHXRCHX•E2:R3CXR2CHXRCH2X4.3E1eliminationCharacteristicsoftheE1Reaction——TheE1ReactionMechanismRateDeterminingstep!反应分步进行！碳正离子——无立体选择性！ZitRl区域选择性！ZaitsevRule——区域选择性！CharacteristicsoftheE1Reaction——TheE1ReactionMechanism•CompeteswithSN1andE2at3°centers•V=k[RX]32323232碱性增强消除产物增多！碱性增强，消除产物增多！卤代烃碱性条件下的消除：醇在酸性条件下的消除：邻基参与的分子内热销除：4.4E1cBEliminationsE1cB Mechanism42有个差的离去基团有一个差的离去基团NFNFNFNE1cBHaHCH3IOH-ANFB有一个活泼氢Boord烯烃合成E1cBReaction有个活泼氢E1cB Reaction 有一个活泼氢BiologicalElimination:3RSSRSR46EliminationReactions1.E2Elimination1.E2EliminationCharacteristicsoftheE2Reaction2.E1Elimination2.E1EliminationCharacteristicsoftheE1Reaction3.E1CBElimination3.E1CBElimination45ComparingE1andE24.5ComparingE1andE2•强碱有利于E2消除E2具有立体专性•E2具有立体专一性•E1给出Zaitsev烯烃HHCH(CH3)2H3CCH(CH3)2ClClCH3Cl1MNaOCH2CH3CHCHOHE2condition0.01MNaOCH2CH380%thlE1conditionH3CPr-iCH3CH2OH100oCE2condition80%aqueousethanol160oCE1conditionPr-iH3C100%Pr-iH3C32%Pr-iH3C68%+Substrate:4.5取代和亲核的竞争SN2Substrate:3°＞2°＞1°＞CHLSN23＞2＞1＞CH3LSN1,ESummaryofReactivity:SN1,SN2,E1,E2HalidetypeRCH2XSN1SN2E1E2DonotoccurDonotoccurHighlyfavoredOccurswhenstrongbaseusedgR2CHXCanoccurwithbenzylicandallylicOccursincompetitionwithE2CanoccurwithbenzylicandallylicFavoredwhenstrongbaseusedR3CXFavoredinhydroxylicsolventsDonotoccurFavoredwhenbaseusedOccursincompetitionwithSN1PL摄于2011年3月18日