加州大学伯克利分校有机化学第七章.ppt

Relative rates of4arrowsdiffer C H C L B Nu Chapter7 SN1 E1 E2 notjustSN2 E1 E2 SN2 SN1 E1 E2 E1 E2 SN2 SN1 Lingo position position furtheraway andsoon SolventMeOH SolventDMF CH3Br H2O But CH3 3CBr CH3 2CHBr or react HOH Acetone HBr WeakNu Despitebeing branched Hydrolysis CH3 2CHBr HOCH3 CH3 2CHOCH3 DMF HBr Methanolysis Generally Solvolysis Recall SN2slowswithweakNu andbranching Forexample Mechanism 1 Rate k R L 1storderunimolecular onlyR Linrate determiningTS bottleneck 2 Stereochemistry Racemization extensive althoughoftennotcomplete BothobservationsinconsistentwithSN2mechanism 3 Accelerateswithpolar bestwithprotic incontrasttoSN2 solvents Hexane CHCl3 CH3CCH3 CH3OH O 4 AccelerateswithbetterL 5 Productdeterminingstepsafter bottleneck CompetitionbetweenNu s CH3 3CCl CH3OH NaN3 Intermediate N N N k2 k3 CH3OH CH3 3CN3 wins Mechanism 1 Electrondeficient 2 3 Unimolecularnucleophilicsubstitution 1stOrderratelawRacemizationAccelerationinpolarsolvents AccelerationwithbetterLFastproductdeterminingstep Mechanismexplainsdata SN1 SN1 SN1PE Bottleneck Bottleneck IncompleteRacemization Maystayclosetoformanionpair Planarandachiral butbothsidesnotequallyaccessibleinionpairwithBr Ideally inpractice Slightenantiomerexcess SN1Racem TheStrongEffectofPolarSolventsontheSN1Reaction Increasingsolventpolarityspeedsreaction Increasingsolventpolarityretardsreaction C H C CH3 CH3CH2 CH3 2CH CH3 3C ofneighboringCHbondinteractswithempty2porbital Stabilizing 2e Betterthanradical 3e 2p BondingMO E Toounstable Theonlycationsfeasibleinsolution WhatmakesSN1possible 1 SN2isslow 2 Branchedcarbocationsarestabilizedbyhyperconjugation Hyperconjugation X RayStructureofthe1 1 DimethylethylCation Laube 1993 LipshutzSN1 Django Summary Rprim L noSN1 onlySN2 Rtert L onlySN1 noSN2 Rsec L both SN2 SN1ratiosdifficulttopredict exceptin extreme cases suchas CH3 2CHCl CH3 2CHOH CF3SO3H SN1 Solvent CH3 2CHSCH3 CH3S SN2 DMF ReactivityofR X Problem SN2orSN1 CH3 2S Therefore EliminationE1 asidereactionofSN1 Samefirstdissociationsteptocation CH3 3CL C C H C C Thenprotonlosstobase solvent NormallyBactsasNutogiveSN1 WhenNuactsasB Cationsaredeprotonated Elimination E1andE2 MechanismoftheE1Reaction Weusuallyomitthebaseindeprotonationsandsimplywrite H E1Lipshutz Caruso RatiosofSN1toE1productsareindependentofL E1GivesMixtures AllCHat positionsincationareacidic CH3 Cl Cl CH3O H H Mixture Regio andstereoisomers cis trans E1 SN1ratiosaredifficulttopredict Generally IncreasingamountsofE1productsareformedwith 1 HigherT becauseentropyofeliminationispositive RXisconvertedtoalkeneplusHX Recall G H T S hencepositive S makes G morenegative 2 Verypoorlynucleophilicmedium slowsSN1 e g Acetonesolvent Whynotbase Base unlessveryweak changesthemechanismonceagain BimolecularEliminationE2 Withstrongbase Mechanismchanges baseattacksR Ldirectlyat H E2 fasterthanSN1 E1 Mechanism 1 Rate k R L B 2ndorderbimolecularTS 2 LleavesinTS RClRBrRI effectkH kD 7 4 Stereochemistry C C H L B Anti TS OnediastereomerofRX e g R R S Sbelow givesonlyonestereoisomerofalkeneproduct TheE2ReactionisStereospecific OrtheS R R Spair MechanismoftheE2Reaction TS staggered bestoverlap leaste repulsion E2 Walba Lipshutz Cream Ray E2inCyclicSystems HinderedBaseEnsuresE2 Summary Factor1 Basestrengthofthenucleophile WeakBases Substitutionmorelikely StrongBases Likelihoodofeliminationincreased Factor2 Sterichindrancearoundthereactingcarbon Stericallyhindered Likelihoodofeliminationincreased Branchedprim orsecandterthaloalkanes H2O ROH PR3 halides N3 RCOO RS NC H2O ROH FactorsthatAffecttheCompetitionbetweenSNandE Factor3 Sterichindranceinnucleophile strongbase Stericallyunhindered Stericallyhindered Substitutionmayoccur Eliminationstronglyfavored Analkene 1 Mechanism SN2SN1E2E1 2 Atlowertemperaturesoneofthefollowingratioswillincrease SN2 SN1SN1 E1E2 E1SN2 E2 Problem No orexceedinglyslow reactionwithpoornucleophiles ReactivityofPrimHaloalkanesR XwithNucleophiles Bases CH3CH2CH2Br CH3CH2CH2CN Acetone CH3CH2CH2Br CH3CH2CH2OCH3 CH3OH SN2withgoodnucleophilesthatarenotstronglybasic SN2withgoodnucleophilesthatarealsostrongbases ButE2withstrong hinderedbases CH3CH2CH2Br CH3CO CH3 CH3 CH3 3COH HBr ForunhinderedprimaryRX CH3OH CH3CCH2Br CH3 H I CH3CCH2I CH3 H Acetone SN2withgoodnucleophiles althoughslowcomparedwithunhinderedRX ForbranchedprimaryRX No orexceedinglyslow reactionwithpoornucleophilesorneopentylsystems inwhichEisnotpossible CH3CCH2Br HBr CH3 H E2withstrongbase notnecessarilyhindered ReactivityofSecHaloalkanesR XwithNucleophiles Bases CH3CBr CH3 H CH3CH2OH HBr Major Minor moreonincreasingT SN1andE1 whenXisagoodleavinggroupinahighlypolarmediumwithweaknucleophiles E2withhighconcentrationsofstrongbase forexample HOorROinalcoholsolvent CH3CBr CH3 H CH3CSCH3 CH3 H SN2withhighconcentrationsofgood weaklybasicnucleophiles CH3CBr CH3 H CH3CH2O CH3CH2OH HBr ReactivityofTertHaloalkanesR XwithN