8.3The SN2 Mechanism of Nucleophilic Substitution,Many nucleophilic substitutions follow asecond-order rate law.CH3Br + HO CH3OH + Br rate = kCH3BrHO inference: rate-determining step is bimolecular,Kinetics,one stepconcerted,Bimolecular mechanism,one stepconcerted,Bimolecular mechanism,one stepconcerted,Bimolecular mechanism,8.4Stereochemistry of SN2 Reactions,Nucleophilic substitutions that exhibitsecond-order kinetic behavior are stereospecific and proceed withinversion of configuration.,Generalization,nucleophile attacks carbonfrom side opposite bondto the leaving group,Inversion of Configuration,nucleophile attacks carbonfrom side opposite bondto the leaving group,three-dimensionalarrangement of bonds inproduct is opposite to that of reactant,Inversion of Configuration,A stereospecific reaction is one in whichstereoisomeric starting materials givestereoisomeric products. The reaction of 2-bromooctane with NaOH (in ethanol-water) is stereospecific. (+)-2-Bromooctane ()-2-Octanol ()-2-Bromooctane (+)-2-Octanol,Stereospecific Reaction,(CH2)5CH3,NaOH,(S)-(+)-2-Bromooctane,(R)-()-2-Octanol,Stereospecific Reaction,The Fischer projection formula for (+)-2-bromooctaneis shown. Write the Fischer projection of the()-2-octanol formed from it by nucleophilic substitution with inversion of configuration.,Problem 8.4,The Fischer projection formula for (+)-2-bromooctaneis shown. Write the Fischer projection of the()-2-octanol formed from it by nucleophilic substitution with inversion of configuration.,Problem 8.4,8.5How SN2 Reactions Occur,:,Br,C,H,.,.,.,.,HO,CH3(CH2)5,H3C,:,Br,C,H,.,.,.,.,HO,C,H,Br,d ,.,.,HO,:,.,.,d ,CH3(CH2)5,H3C,CH3(CH2)5,CH3,:,Br,C,H,.,.,.,.,HO,C,H,Br,d ,.,.,HO,:,.,.,d ,C,H,HO,.,.,CH3(CH2)5,H3C,(CH2)5 CH3,CH3(CH2)5,CH3,CH3,8.6Steric Effects in SN2 Reactions,The rate of nucleophilic substitutionby the SN2 mechanism is governedby steric effects. Crowding at the carbon that bears the leaving group slows the rate ofbimolecular nucleophilic substitution.,Crowding at the Reaction Site,RBr + LiI RI + LiBr,AlkylClassRelativebromiderate CH3BrMethyl221,000 CH3CH2BrPrimary1,350 (CH3)2CHBrSecondary1 (CH3)3CBrTertiarytoo smallto measure,Table 8.2 Reactivity toward substitution by the SN2 mechanism,CH3Br,CH3CH2Br,(CH3)2CHBr,(CH3)3CBr,Decreasing SN2 Reactivity,CH3Br,CH3CH2Br,(CH3)2CHBr,(CH3)3CBr,Decreasing SN2 Reactivity,The rate of nucleophilic substitutionby the SN2 mechanism is governedby steric effects. Crowding at the carbon adjacentto the one that bears the leaving groupalso slows the rate of bimolecularnucleophilic substitution, but the effect is smaller.,Crowding Adjacent to the Reaction Site,RBr + LiI RI + LiBr,AlkylStructureRelativebromiderate EthylCH3CH2Br1.0 PropylCH3CH2CH2Br0.8 Isobutyl(CH3)2CHCH2Br0.036 Neopentyl(CH3)3CCH2Br0.00002,Table 8.3 Effect of chain branching on rate of SN2 substitution,