Bài giảng Organic Chemistry - Chapter 7: Unimolecular Substitution And Elimination

Relative “rates” of the four arrows differ and depend on substrate, reagent, and conditionsCHCLBNu:-:-Chapter 7: Unimolecular Substitution And EliminationE1, E2SN2, SN1, E1, E2E1, E2SN2, SN1(CH3)2CH Br(CH3)3C BrH OCH3+H OH(CH3)3C OCH3H Br+HydrolysisGenerally: “Solvolysis”Some ObservationsRecall from Chapter 6:Indeed:Tertiary!H Br+(CH3)2CH OH+MethanolysisSecondaryLousy NuLousy NuModerate rateFast!1. Rate = k [R-L], 1st order unimolecular, only R-L in rate-determining TS: “bottleneck”.2. Stereochemistry: not stereospecific, i.e. enantiomerically pure starting material leads to (extensively) racemic products; pure cis (or trans) gives cis/trans mixtures, etc..Both observations inconsistent with SN2 mechanismA New Mechanismk1Intermediate3. Accelerates with polar (best with protic, in contrast to SN2) solvents:Hexane >..CH3OH....(CH3)3OCH3..(CH3)3CN3 winsWhat Is The Intermediate? Mechanism1.Electron deficient!2.3.Unimolecular nucleophilic substitution: 1st Order rate law Racemization Acceleration in polar solvents Acceleration with better L Product determining step occurs after rate determining stepSN1SN1The Mechanism Explains The DataSN1PotEBottleneck:SN2 Versus SN1“Bottleneck”RacemizationIn practice: Often, slight inversion is observed, due to “ion pairing”, R+····Br-.SN1RacemThe Strong Effect Of Polar Solvents On The SN1 ReactionIncreasing solvent polarity speeds reactionIncreasing solvent polarity retards reactionAs Expected: Good Leaving Groups Accelerate The SN1 Reaction The Nucleophile Has No Effect On The Rate Of The SN1 Reaction All reactions take place at the same rate k1. But in competition, the better Nu wins.C+HCCH3CH3CH2(CH3)2CH(CH3)3C++++Energetically inaccessible in solutionThe only cations feasible in solution<1. α-Branching slows competing SN2.2. α-Branched carbocations are stabilized by hyperconjugation.What Makes SN1 Possible?HyperconjugationLipDjangoRprim-L : no SN1, only SN2Rtert-L : only SN1, no SN2 Rsec-L : both SN2/SN1 ratios difficult to predict, except in “stacked" cases, such as: +(CH3)2CH Cl(CH3)2CHOHCF3SO3HSN1Solvent(CH3)2CH OSO2CF3H2O+(CH3)2CHSCH3Cl-++CH3S-SN2DMFReactivity Of R-X In SubstitutionsSubstitutions Of R-X OverviewProblem:SN2 or SN1 ? -(CH3)2SHWhen Nu acts as B the intermediate cations of the SN1 reaction are deprotonated: Elimination E1 to alkenes, a competing reaction: (-) :C –L-B-:C+CHCCE1, proton loss to base (solvent in solvolysis)SN2, B:- acts as Nu:-(-):Elimination: E1LC –BHHC NuC Methanolysis Of 2-Bromo-2-Methylpropane The Deprotonation Step We usually omit the base in deprotonations andsimply write “-H+ ”.LipOrbHyperconjugationConsistent with this picture, the ratios of SN1 to E1 products are independent of LMechanism Of E1All neighboring C H in cation are acidic:CH3ClCl-CH3OH::CH3OH::+CH3OHH++++Mixture“Regio-” (constitutional) and stereoisomers (cis/trans).+E1 Gives Mixtures Of Alkenes :Generally: Increasing amounts of E1 products are formed with: 1. Higher T, because entropy of elimination is positive: (RX is converted to alkene plus HX). Recall: ∆G° = ∆H º–T∆Sº, hence positive ∆Sº makes ∆G° more negative. 2. Very poorly nucleophilic medium (slows SN1), e.g: nonhydroxylic solvent, poor nucleophiles (e.g., SO42-, CO32-).Why not strong base? Yes, but changes the mechanism once again.E1/SN1 Ratios Are Difficult To PredictBimolecular Elimination E2Strong base attacks R-L directly at β-H: E2 (faster than SN1/E1 — and SN2 if sterically hindered)Mechanism: 1. Rate = k[R-L][ B]2nd order bimolecular TS3. H removed in TS: deuterium isotope+2. L leaves in TS: RCl RBr RIeffect kH/kD~ 74. Stereochemistry:CCHLB:-Anti-TS**:-One diastereomer of RX gives only one stereoisomer of alkene product:The E2 Reaction is StereospecificR,R/S,S gives only ES,R/R,S gives only ZThe Transition State of the E2 ReactionTS: staggered, best overlap, least e-repulsionE2WalbaCreamAnti Versus Syn E2Hindered Bases Ensure E2Steric hindrance slows or shuts down competing SN2Mechanisms By Which Haloalkanes React With Nucleophiles (Bases)Factor 1: Base strength of the nucleophileHO-RO-R2N-H2N-,,,Weak BasesSubstitution more likelyStrong BasesLikelihood of elimination increasedFactor 2: Steric hindrance around the reacting carbonPrimary haloalkanesSubstitution more likelySterically unhinderedSterically hinderedLikelihood of elimination increasedBranched prim, or sec and tert haloalkanesH2OROHPR3halidesN3RCOORS-NC-,,H2OROH,,,,,,,Factors That Affect The Competition Between SN And E--Factor 3: Steric hindrance in nucleophile (strong base)Sterically unhinderedSterically hinderedSubstitution may occurElimination strongly favoredHO-H2N-CH3O--CH3CH2O,,,(CH3)3CO[(CH3)3CH]2N-,- An alkene1. Mechanism: SN2 SN1 E2 E1? 2. At lower temperatures one of the following ratios will increase: SN2 / SN1 SN1 / E1 E2 / E1 SN2 / E2 Problem:No (or exceedingly slow) reaction with poor nucleophiles Reactivity Of Primary Haloalkanes R-X With Nucleophiles (Bases)CH3CH2CH2BrBr-CN-CH3CH2CH2CNAcetone++CH3CH2CH2BrBr-CH3O-CH3CH2CH2OCH3++CH3OHSN2 with good nucleophiles that are not strongly basicSN2 with good nucleophiles that are also strong basesBut E2 with strong, hindered basesCH3CH2CH2Br+CH3COCH3CH3-(CH3)3COHHBrCH3CHCH2For unhindered primary R X :(CH3OH)Br-+CH3CCH2BrCH3HI-CH3CCH2ICH3H+AcetoneSN2 with good nucleophiles (although slow compared with unhindered RX)For branched primary R X :No (or exceedingly slow) reaction with poor nucleophiles or neopentyl systems (in which E is not possible)CH3CCH2BrCH3CH2O-CH3CH2OHHBrCH3HCH3CCH2CH3+E2 with strong base (not necessarily hindered)Reactivity Of Secondary Haloalkanes R-X With Nucleophiles (Bases)CH3CBrCH3HCH3CH2OHHBr+CH3CHCH2CH3COCH2CH3CH3HMajorMinor (more on increasing T)SN1 and E1 when X is a good leaving group in a highly polar medium with weak nucleophilesE2 with high concentrations of strong base (for example, HO or RO in alcohol solvent)CH3CBrCH3HCH3CH2OH+CH3CSCH3CH3HBr-CH3S-+SN2 with high concentrations of good, weakly basic nucleophiles--CH3CHCH2CH3CBrCH3HCH3CH2O-+CH3CH2OHHBrReactivity Of Tertiary Haloalkanes R-X With Nucleophiles (Bases)SN1 and E1 in polar solvents when X is a good leaving group and only dilute or no base is presentCH3CH2CBrCH3CH3CH3CH2COHCH3CH3+HBralkenesHOH, acetoneE2 with high concentrations of strong baseCH3CH2CClCH2CH2CH3CH2CCH2CH3O, CH3OHHClH3CH3CCHCH3H3C-