Chemistry-of-Benzene-Electrophilic-Aromatic-Substi

Chapter16.ChemistryofBenzene:ElectrophilicAromaticSubstitutionBasedonMcMurry’sOrganicChemistry,Chapter16SubstitutionReactionsofBenzeneandItsDerivativesBenzeneisaromatic:acyclicconjugatedcompoundwith6electronsReactionsofbenzeneleadtotheretentionofthearomaticcoreElectrophilicaromaticsubstitutionreplacesaprotononbenzenewithanotherelectrophile16.1BrominationofAromaticRingsBenzene’selectronsparticipateasaLewisbaseinreactionswithLewisacidsTheproductisformedbylossofaproton,whichisreplacedbybromineFeBr3isaddedasacatalysttopolarizethebrominereagentAdditionIntermediateinBrominationTheadditionofbromineoccursintwostepsInthefirststeptheelectronsactasanucleophiletowardBr2(inacomplexwithFeBr3)ThisformsacationicadditionintermediatefrombenzeneandabrominecationTheintermediateisnotaromaticandthereforehighinenergy(seeFigure16.2)FormationofProductfromIntermediateThecationicadditionintermediatetransfersaprotontoFeBr4-(fromBr-andFeBr3)Thisrestoresaromaticity(incontrastwithadditioninalkenes)AromaticChlorinationandIodinationChlorineandiodine(butnotfluorine,whichistooreactive)canproducearomaticsubstitutionwiththeadditionofotherreagentstopromotethereactionChlorinationrequiresFeCl3IodinemustbeoxidizedtoformamorepowerfulI+species(withCu+orperoxide)AromaticNitrationThecombinationofnitricacidandsulfuricacidproducesNO2+(nitroniumion)ThereactionwithbenzeneproducesnitrobenzeneAromaticSulfonationSubstitutionofHbySO3(sulfonation)ReactionwithamixtureofsulfuricacidandSO3ReactivespeciesissulfurtrioxideoritsconjugateacidReactionoccursviaWhelandintermediateandisreversibleAlkaliFusionofAromaticSulfonicAcidsSulfonicacidsareusefulasintermediatesHeatingwithNaOHat300ºCfollowedbyneutralizationwithacidreplacestheSO3HgroupwithanOHExampleisthesynthesisofp-cresol16.3AlkylationofAromaticRings:TheFriedel–CraftsReaction(傅克反应)AromaticsubstitutionofaR+forHAluminumchloridepromotestheformationofthecarbocationWhelandintermediateformsLimitationsoftheFriedel-CraftsAlkylation（傅克烷基化）Onlyalkylhalidescanbeused(F,Cl,I,Br)Arylhalidesandvinylichalidesdonotreact(theircarbocationsaretoohardtoform)Willnotworkwithringscontaininganaminogroupsubstituentorastronglyelectron-withdrawinggroupControlProblemsMultiplealkylationscanoccurbecausethefirstalkylationisactivatingCarbocationRearrangementsDuringAlkylationSimilartothosethatoccurduringelectrophilicadditionstoalkenesCaninvolveHoralkylshiftsHowmanythesubstitutedbenzenesbelowcanbesubjectedtoFriedel-Craftsalkylation?161.Onlyone2.Twoofthem3.Allofthem4.NoneofthemNH2COOHOCH3AcylationofAromaticRings:Friedel-CraftsAcylation(傅克酰基化)Reactionofanacidchloride(RCOCl)andanaromaticringinthepresenceofAlCl3introducesacylgroup,CORBenzenewithacetylchlorideyieldsacetophenoneMechanismofFriedel-CraftsAcylationSimilartoalkylationReactiveelectrophile:resonance-stabilizedacylcationAnacylcationdoesnotrearrange16.4SubstituentEffectsinAromaticRingsSubstituentscancauseacompoundtobe(much)moreor(much)lessreactivethanbenzeneSubstituentsaffecttheorientationofthereaction–thepositionalrelationshipiscontrolledortho-andpara-directingactivators,ortho-andpara-directingdeactivators,andmeta-directingdeactivatorsOriginsofSubstituentEffectsAninterplayofinductiveeffectsandresonanceeffectsInductiveeffect-withdrawalordonationofelectronsthroughasbondResonanceeffect-withdrawalordonationofelectronsthroughabondduetotheoverlapofaporbitalonthesubstituentwithaporbitalonthearomaticringInductiveEffects（诱导效应）ControlledbyelectronegativityandthepolarityofbondsinfunctionalgroupsHalogens,C=O,CN,andNO2withdrawelectronsthroughsbondconnectedtoring（PolarCovalentBonds）AlkylgroupsdonateelectronsResonanceEffects（共振效应）–ElectronWithdrawalC=O,CN,NO2substituentswithdrawelectronsfromthearomaticringbyresonance(throughabond)electronsflowfromtheringstothesubstituentsResonanceEffects–ElectronDonationHalogen,OH,alkoxyl(OR),andaminosubstituentsdonateelectronselectronsflowfromthesubstituentstotheringEffectisgreatestatorthoandpara16.5AnExplanationofSubstituentEffectsActivatinggroupsdonateelectronstothering,stabilizingthecarbocationintermediateDeactivatinggroupswithdrawelectronsfromthering,destabilizingthecarbocationintermediateOrtho-andPara-DirectingActivators:AlkylGroupsAlkylgroupsactivate:directfurthersubstitutiontopositionsorthoandparatothemselvesAlkylgroupismosteffectiveintheorthoandparapositionsOrtho-andPara-DirectingActivators:OHandNH2Alkoxyl,andaminogroupshaveastrong,electron-donatingresonanceeffectMostpronouncedattheorthoandparapositionsOrtho-andPara-DirectingDeactivators:HalogensElectron-withdrawinginductiveeffectoutweighsweakerelectron-donatingresonanceeffectResonanceeffectisonlyattheorthoandparapositions,stabilizingcarbocationintermediateMeta-DirectingDeactivatorsInductiveandresonanceeffectsreinforceeachotherOrthoandparaintermediatesdestabilizedbydeactivationfromcarbocationintermediateResonancecannotproducestabilizationSummaryTable:EffectofSubstituentsinAromaticSubstitutionHomework:P591:16.30,16.31,16.32P592:16.33,16.3716.6Trisu