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Relative “rates” of 4 arrows differ,C,H,C,L,B,Nu,:,-,:,-,Chapter 7: SN1, E1, E2, notjust SN2,E1, E2,SN2, SN1, E1, E2,E1, E2,SN2, SN1,“Lingo”: position, position; further away: , , and so on.,SolventMeOH,SolventDMF,CH3Br,+,H2O,But,(CH3)3CBr,(CH3)2CHBr,or,react!,+,H OH,Acetone,H Br,+,Weak Nu,Despite being -branched,Hydrolysis,+,(CH3)2CH Br,H OCH3,(CH3)2CH OCH3,DMF,H Br,+,Methanolysis,Generally: Solvolysis,Recall: SN2 slows with weak Nu (and branching). For example:,Mechanism:,1. Rate = kR-L, 1st order unimolecular, only R-L in rate-determining TS: “bottleneck”.,2. Stereochemistry: Racemization (extensive, although often not complete).,Both observations inconsistent with SN2 mechanism,3. Accelerates with polar (best with protic, in contrast to SN2) solvents:,Hexane CHCl3 CH3CCH3 CH3OH,O,4. Accelerates with better L,5. Product determining steps after “bottleneck”: Competition between Nus.,(CH3)3CCl,+,CH3OH,+,Na N3,+,-,Intermediate,N,N,N,:,:,:,:,-,-,+,k2,k3,.,CH3OH,(CH3)3CN3,wins,Mechanism,1.,Electron deficient!,2.,3.,Unimolecular nucleophilic substitution:,1st Order rate law Racemization Acceleration in polar solvents,Acceleration with better L Fast product determining step,Mechanism explains data:,SN1,SN1,SN1PE,Bottleneck:,“Bottleneck”,Incomplete Racemization,May stay close to form an ion pair,Planar and achiral, but both sides not equally accessible in ion pair with Br-,Ideally; in practice: Slight enantiomer excess,SN1Racem,The Strong Effect of Polar Solvents on the SN1 Reaction,Increasing solvent polarity speeds reaction,Increasing solvent polarity retards reaction,C,+,H,C,CH3,CH3CH2,(CH3)2CH,(CH3)3C,+,+,+,+,of neighboring C H bond interacts with empty 2p orbital,Stabilizing (2e)! Better than radical (3e).,2p,Bonding MO,E,Too unstable,The only cations feasible in solution,What makes SN1 possible? 1. SN2 is slow. 2. -Branched carbocations are stabilized by hyperconjugation,Hyperconjugation,X-Ray Structure of the 1,1-Dimethylethyl Cation(Laube, 1993),LipshutzSN1,Django,Summary,:,Rprim- L : no SN1, only SN2,Rtert- L : only SN1, no SN2,Rsec- L : both, SN2/SN1 ratios difficult to predict, except in “extreme cases, such as:,+,(CH3)2CH Cl,(CH3)2CHOH,CF3SO3H,SN1,Solvent,+,(CH3)2CHSCH3,+,+,CH3S,-,SN2,DMF,Reactivity of R-X,Problem:,SN2 or SN1 ?,-(CH3)2S,(-),:,Therefore: Elimination E1, a side reaction of SN1. Same first dissociation step to cation:,(CH3)3C L,C,+,C,H,C,C,Then proton loss to base (solvent),Normally B acts as Nu to give SN1.,:,:,When Nu acts as B : Cations are deprotonated,Elimination: E1 and E2,(-),:,Mechanism of the E1 Reaction,We usually omit the base in deprotonations and simply write “-H+ ”.,E1Lipshutz,Caruso,Ratios of SN1 to E1 products are independent of L,E1 Gives Mixtures,All C H at -positions in cation are acidic:,CH3,Cl,Cl,-,+,CH3O,H,H,+,+,+,+,Mixture,“Regio-” and stereoisomers (“cis/trans”),.,+,E1/SN1 ratios are difficult to predict,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 TS, hence positive S makes G more negative.,2. Very poorly nucleophilic medium (slows SN1), e.g: Acetone solvent.,Why not base? Base (unless very weak) changes the mechanism once again.,Bimolecular Elimination E2,With strong base: Mechanism changes, base attacks R-L directly at -H: E2 (faster than SN1/E1),Mechanism:,1. Rate = k R-L B,2nd order bimolecular TS,2. L leaves in TS: RCl RBr RI,effect kH/kD 7,4. Stereochemistry:,C,C,H,L,B,:,-,Anti-TS,*,*,:,-,One diastereomer of RX (e.g. R,R/S,S below) gives only one stereoisomer of alkene product:,The E2 Reaction is Stereospecific,Or the S,R-R,S pair:,Mechanism of the E2 Reaction,TS: staggered, best overlap, least e-repulsion,E2,Walba,Lipshutz,Cream,Ray,E2 in Cyclic Systems,Hindered Base Ensures E2,Summary,Factor 1: Base strength of the nucleophile,Weak Bases,Substitution more likely,Strong Bases,Likelihood of elimination increased,Factor 2: Steric hindrance around the reacting carbon,Sterically hindered,Likelihood of elimination increased,Branched prim, or sec and tert haloalkanes,H2O,ROH,PR3,halides,N3,RCOO,RS,-,NC,-,H2O,ROH,Factors that Affect the Competition between SN and E,-,-,Factor 3: Steric hindrance in nucleophile (strong base),Sterically unhindered,Sterically hindered,Substitution may occur,Elimination strongly favored,-,An alkene,1. 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 Prim Haloalkanes R-X with Nucleophiles (Bases),CH3CH2CH2Br,CH3CH2CH2CN,Acetone,+,+,CH3CH2CH2Br,CH3CH2CH2OCH3,+,+,CH3OH,SN2 with good nucleophiles that are not strongly basic,SN2 with good nucleophiles that are also strong bases,But E2 with strong, hindered bases,CH3CH2CH2Br,+,CH3CO,CH3,CH3,-,(CH3)3COH,HBr,For unhindered primary R X :,(CH3OH),+,CH3CCH2Br,CH3,H,I,-,CH3CCH2I,CH3,H,+,Acetone,SN2 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),CH3CCH2Br,HBr,CH3,H,+,E2 with strong base (not necessarily hindered),Reactivity of Sec Haloalkanes R-X with Nucleophiles (Bases),CH3CBr,CH3,H,CH3CH2OH,HBr,+,Major,Minor (more on increasing T),SN1 and E1, when X is a good leaving group in a highly polar medium with weak nucleophiles,E2 with high concentrations of strong base (for example, HO or RO in alcohol solvent),CH3CBr,CH3,H,+,CH3CSCH3,CH3,H,+,SN2 with high concentrations of good, weakly basic nucleophiles,-,-,CH3CBr,CH3,H,CH3CH2O,-,+,CH3CH2OH,HBr,Reactivity of Tert 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 present,CH3CH2CBr,CH3,CH3,CH3CH2COH,CH3,CH3,+,HBr,alkenes,HOH, acetone,E2 with high concentrations of strong base,CH3CH2CCl,CH2,CH2,CH3CH2C,CH2,CH3O, CH3OH,HCl,H3C,H3C,CHCH3,H3C,-,
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