140A ch7 lecture

140A ch7 lecture - Chapter 7: SN1, E1, E2, not Chapter just...

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Unformatted text preview: Chapter 7: SN1, E1, E2, not Chapter just SN2 just SN2, SN1 B: E1, E2 H E1, E2 C C L : Nu Relative “rates” of 4 arrows differ SN2, SN1, E1, E2 “Lingo”: ! position, ß position; further away: ", #, and so on. SolventMeOH SolventDMF Recall: SN2 slows with weak Nu Nu (and branching). For example: CH3Br + H2O CH Weak Nu Weak Nu (CH3)3CBr or react! But (CH3)2CHBr Despite being !-branched Despite (CH3)3C Br + H OH Br OH (CH3)2CH Br + H OCH3 Br OCH Acetone Hydrolysis (CH3)3C OH + H Br OH Br (CH3)2CH OCH3 + H Br OCH Br DMF Methanolysis Generally: Solvolysis Generally: Solvolysis Mechanism: Mechanism: 1. Rate = k[R-L], 1st order unimolecular, only 1. unimolecular R-L in rate-determining TS: “bottleneck”. R-L 2. Stereochemistry: Racemization (extensive, 2. Racemization (extensive, although often not complete). Both observations inconsistent with SN2 mechanism 3. Accelerates with polar (best with protic, in Accelerates polar protic contrast to SN2) solvents: O Hexane < CHCl3 < CH3CCH3 < CH3OH Hexane CHCl 4. Accelerates with better L 4. Accelerates better L: Cl < Br < I < OSO2R 5. Product determining steps after 5. Product “bottleneck”: Competition between Nu’s. Competition Nu + - k1 (CH3)3CCl + CH3OH + Na N3 Intermediate .. + - :N N N :CH3OH .. : : : : k3 > k2 > k1 k2 k3 (CH3)3OCH3 wins (CH3)3CN3 Mechanism Mechanism 1. Electron deficient! 2. 2. 3. 3. Mechanism explains data: • 1st Order rate law • Racemization • Acceleration in polar solvents • Acceleration with better L with • Fast product determining step Unimolecular nucleophilic substitution: nucleophilic SN 1 SN1 “Bottleneck” SN1PE Bottleneck: Incomplete Racemization Incomplete May stay close to form an ion pair Planar and achiral, Planar but both sides not not equally accessible in ion pair with Brin Br SN1Racem Ideally; in Ideally; practice: Slight Slight enantiomer excess The Strong Effect of Polar The Solvents on the SN1 Reaction Increasing solvent polarity speeds reaction Increasing solvent polarity retards reaction What makes SN1 possible? 1. SN2 is slow. slow 2. !-Branched carbocations are stabilized 2. carbocations stabilized by hyperconjugation by hyperconjugation + + H + + + C C CH3 < CH CH 3 2 (CH3)2CH (CH3)3C Too unstable The only cations feasible in solution Stabilizing (2e)! Better than Better radical (3e). radical Bonding MO of neighboring C H of bond interacts with empty 2p orbital E 2p Hyperconjugation Hyperconjugation X-Ray Structure of the X-Ray 1,1-Dimethylethyl Cation (Laube, 1993) Django LipshutzSN1 Summary : Rprim- L : no SN1, only SN2 Summary no 1, only Rsec- L : both, both SN2/SN1 ratios difficult to predict, except in “extreme" cases, such as: (CH3)2CH Cl + CH3S CH Cl DMF SN2 Rtert- L : only SN1, no SN2 only 1, no (CH3)2CHSCH3 + Cl (CH3)2CHOH + CF3SO3H (CH3)2CH OSO2CF3 + H2O CH OSO Solvent SN1 Reactivity of R-X Reactivity : When Nu :(-)acts as B (-) : Cations are deprotonated When Nu (-) deprotonated Elimination: E1 and E2 Therefore: Elimination E1, a side reaction of SN1. side Same first dissociation step to cation: dissociation :B + C (CH3)3C L C C –L Then proton Then proton H loss to base (solvent) C Normally B: acts as Nu: to give SN1. Normally Mechanism of the E1 Reaction Mechanism We usually omit the base in deprotonations and We omit and simply write “-H+ ”. simply Caruso E1Lipshutz Ratios of SN1 to E1 products are independent of L E1 Gives Mixtures E1 All C H at $-positions in cation are acidic: All -positions acidic . Cl CH3 CH3OH Cl + :: :: + CH3OH CH3O :: :: +H H Mixture + + + “Regio-” and stereoisomers (“cis/trans”) E1/SN1 ratios are difficult to predict E1/S Generally: Increasing amounts of E1 products Generally: Increasing products are formed with: 1. Higher T, because entropy of elimination is 1. Higher entropy positive: (RX is converted to alkene plus HX). Recall: !G° = !H º– T!Sº, hence positive !Sº Recall: º– hence makes !G° more negative. makes more 2. Very poorly nucleophilic medium (slows SN1), 2. poorly e.g: Acetone solvent. Why not base? Base (unless very weak) changes the mechanism once again. Bimolecular Elimination E2 Bimolecular With strong base: Mechanism changes, base attacks With strong R-L directly at $-H: E2 (faster than SN1/E1) R-L directly -H: (faster Mechanism: 1. Rate = k [R-L][:B] 2nd order 2. L leaves in TS: RCl 2. + bimolecular TS RBr RI RI L 3. H removed in TS: Deuterium isotope effect kH/kD~ 7 effect 4. Stereochemistry: Anti-TS B: C H * C * The E2 Reaction is Stereospecific The Stereospecific One diastereomer of RX (e.g. R,R/S,S below) gives below) only one stereoisomer of alkene product: only stereoisomer Or the S,R-R,S pair: S,R Mechanism of the E2 Reaction Mechanism TS: staggered, best overlap, least e-repulsion E2 Cream Walba Ray Lipshutz E2 in Cyclic Systems E2 Hindered Base Ensures E2 Hindered Summary Summary Factors that Affect the Competition between SN and E Factor 1: Base strength of the nucleophile Factor Base Weak Bases Substitution more likely H2O , ROH , PR3 , halides , RS , N3 , NC , RCOO Strong Bases Likelihood of elimination increased HO , RO , H2N , R2N Factor 2: Steric hindrance around the reacting Steric reacting carbon Sterically unhindered Sterically unhindered Primary haloalkanes Primary haloalkanes Substitution more likely Sterically hindered Sterically hindered Branched prim, or sec and tert haloalkanes Branched haloalkanes Likelihood of elimination increased Factor 3: Steric hindrance in nucleophile Factor Steric nucleophile (strong base) Sterically unhindered Sterically unhindered HO , CH3O , CH3CH2O , H2N Substitution may occur Sterically hindered Sterically hindered (CH3)3CO , [(CH3)3CH]2N Elimination strongly favored Reactivity of Prim Haloalkanes R-X with Nucleophiles (Bases) For unhindered primary R X : SN2 with good nucleophiles that are not strongly basic CH3CH2CH2Br + CN Acetone CH3CH2CH2CN + Br- SN2 with good nucleophiles that are also strong bases CH3CH2CH2Br + CH3O CH3OH CH3CH2CH2OCH3 + Br- But E2 with strong, hindered bases CH3 - (CH3)3COH CH3CH2CH2Br + CH3CO CH3 HBr CH3CH CH2 No (or exceedingly slow) reaction with poor nucleophiles (CH3OH) No For branched primary R X : For SN2 with good nucleophiles (although slow compared with unhindered RX) CH3 CH3CCH2Br + I H Acetone CH3CCH2I + BrBr H CH3 E2 with strong base (not necessarily hindered) CH3CCH2Br + CH3CH2O H CH3 CH3CH2OH HBr CH3 CH3C CH2 No (or exceedingly slow) reaction with poor nucleophiles or neopentyl systems (in which E is not possible) Reactivity of Sec Haloalkanes R-X with Reactivity Nucleophiles (Bases) SN1 and E1, when X is a good leaving group in a highly polar medium with weak nucleophiles CH3 CH3CBr H CH3 CH3COCH2CH3 + CH3CH H Major CH2 CH3CH2OH HBr Minor (more on increasing T) SN2 with high concentrations of good, weakly basic nucleophiles CH3 CH3CBr H + CH3S CH3CH2OH CH3CSCH3 + BrH CH3 E2 with high concentrations of strong base (for example, HO or RO in alcohol solvent) CH3 CH3CBr H + CH3CH2O CH3CH2OH HBr CH3CH CH2 Reactivity of Tert Haloalkanes R-X Reactivity with Nucleophiles (Bases) SN1 and E1 in polar solvents when X is a good leaving group and only dilute or no base is present CH3 CH3 CH3CH2CBr CH3 HOH, acetone acetone HBr CH3CH2COH + alkenes CH3 E2 with high concentrations of strong base H3C CH2 CH3CH2CCl H3C CH2 CH3O, CH3OH HCl H3C CH2 CH3CH2C CHCH3 ...
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