1. 8.3 The S N 2 Mechanism of Nucleophilic Substitution

2. Many nucleophilic substitutions follow a second-order rate law. CH 3 Br + HO –  CH 3 OH + Br – rate = k[CH 3 Br][HO – ] inference: rate-determining step is bimolecular Kinetics

3. HO – CH 3 Br + HOCH 3 Br – + one step concerted Bimolecular mechanism

4. HO – CH 3 Br + HOCH 3 Br – + one step concerted Bimolecular mechanism

5. HO – CH 3 Br + HOCH 3 Br – + one step concerted HO CH 3 Br  transition state Bimolecular mechanism

6. 8.4 Stereochemistry of S N 2 Reactions

7. Nucleophilic substitutions that exhibit second-order kinetic behavior are stereospecific and proceed with inversion of configuration. Generalization

8. nucleophile attacks carbon from side opposite bond to the leaving group Inversion of Configuration

9. nucleophile attacks carbon from side opposite bond to the leaving group three-dimensional arrangement of bonds in product is opposite to that of reactant Inversion of Configuration

10. A stereospecific reaction is one in which stereoisomeric starting materials give stereoisomeric products. The reaction of 2-bromooctane with NaOH (in ethanol-water) is stereospecific. (+)-2-Bromooctane  (–)-2-Octanol (–)-2-Bromooctane  (+)-2-Octanol Stereospecific Reaction

11. CH CH 3 Br CH 3 (CH 2 ) 5 CH CH 3 HO (CH 2 ) 5 CH 3 NaOH (S)-(+)-2-Bromooctane (R)-(–)-2-Octanol Stereospecific Reaction

12. The Fischer projection formula for (+)-2-bromooctane is shown. Write the Fischer projection of the (–)-2-octanol formed from it by nucleophilic substitution with inversion of configuration. Problem 8.4

13. H Br CH 3 CH 2 (CH 2 ) 4 CH 3 The Fischer projection formula for (+)-2-bromooctane is shown. Write the Fischer projection of the (–)-2-octanol formed from it by nucleophilic substitution with inversion of configuration. HOH CH 3 CH 2 (CH 2 ) 4 CH 3 Problem 8.4

14. 8.5 How S N 2 Reactions Occur

15. : Br C H.... –.... HO CH 3 (CH 2 ) 5 H3CH3CH3CH3C

16. : Br C H.... –.... HO C H Br  –.... HO :.... CH 3 (CH 2 ) 5 H3CH3CH3CH3C CH 3

17. : Br C H.... –.... HO C H Br  –.... HO :.... C H HO.... –.... : Br CH 3 (CH 2 ) 5 H3CH3CH3CH3C (CH 2 ) 5 CH 3 CH 3 (CH 2 ) 5 CH 3

18. 8.6 Steric Effects in S N 2 Reactions

19. The rate of nucleophilic substitution by the S N 2 mechanism is governed by steric effects. Crowding at the carbon that bears the leaving group slows the rate of bimolecular nucleophilic substitution. Crowding at the Reaction Site

20. RBr + LiI  RI + LiBr AlkylClassRelative bromiderate CH 3 BrMethyl221,000 CH 3 CH 2 BrPrimary1,350 (CH 3 ) 2 CHBrSecondary1 (CH 3 ) 3 CBrTertiarytoo small to measure Table 8.2 Reactivity toward substitution by the S N 2 mechanism

21. CH 3 Br CH 3 CH 2 Br (CH 3 ) 2 CHBr (CH 3 ) 3 CBr Decreasing S N 2 Reactivity

22. CH 3 Br CH 3 CH 2 Br (CH 3 ) 2 CHBr (CH 3 ) 3 CBr Decreasing S N 2 Reactivity

23. The rate of nucleophilic substitution by the S N 2 mechanism is governed by steric effects. Crowding at the carbon adjacent to the one that bears the leaving group also slows the rate of bimolecular nucleophilic substitution, but the effect is smaller. Crowding Adjacent to the Reaction Site

24. RBr + LiI  RI + LiBr AlkylStructureRelative bromiderate EthylCH 3 CH 2 Br1.0 PropylCH 3 CH 2 CH 2 Br0.8 Isobutyl(CH 3 ) 2 CHCH 2 Br0.036 Neopentyl(CH 3 ) 3 CCH 2 Br0.00002 Table 8.3 Effect of chain branching on rate of S N 2 substitution