1. Chapter 8 - Nucleophilic Substitution at sp3 C
nucleophile is a Lewis base (electron-pair donor)
often negatively charged and used as Na+ or K+ salt
substrate is usually an alkyl halide
YSU

2. 8.1 Functional Group Transformation by SN2
Table 8.1 Examples of Nucleophilic Substitution
Alkoxide ion as the nucleophile
gives an ether
Referred to as the Williamson ether synthesis
Limited to primary alkyl halides
Run in solvents such as diethyl ether and THF
YSU

3. Carboxylate ion as the nucleophile
gives an ester
Not very useful – carboxylates are poor nucleophiles
Limited to primary alkyl halides
Run in solvents such as diethyl ether and THF
Better ways of forming esters later in 3720
YSU

4. Cyanide as nucleophile
Azide as nucleophile
YSU

5. Halides as Nucleophiles – Finkelstein Reaction
NaI is soluble in acetone, NaCl and NaBr are not
8.2 Relative reactivity of halide leaving groups
Halides are very good leaving groups
I- better than Br- which is better than Cl-
F- is not used as a leaving group
YSU

6. 8.3 The SN2 mechanism of Nucleophilic Substitution
Example: CH3Br + HO – CH3OH + Br –
rate = k[CH3Br][HO – ]
inference: rate-determining step is bimolecular
P.E.
R.C.
YSU

7. Inversion of configuration during SN2 reaction – Figure 8.1
YSU

8. 8.4 Steric effects in substitution (SN2) reactions
Figure 8.2
YSU

9. Table 8.3 - Relative rates of reaction of different primary alkyl bromides
YSU

10. 8.5 – Nucleophiles and Nucleophilicity – Table 8.4
YSU

11. Solvation of a chloride by ion-dipole
Figure 8.3
YSU
Choice of solvent is important for SN2 - polar aprotic used most often

12. 8.6 The SN1 reaction revisited
Tertiary system - favours SN1 - carbocation possible
Carbocation will be the electrophile
Water will be the nucleophile
YSU

13. Solvolysis of t-BuBr with water
Figure 8.5
YSU

14. 8.7 Relative rates of reaction by the SN1 pathway
Table 8.5
YSU

15. 8.8 Stereochemical consequences in SN1 reactions
Figure 8.6
YSU

16. 8.9 Carbocation rearrangements also possible in SN1
Look for change in the product skeleton.
Rearrangement (in this case hydride shift) to generate a more stable carbocation.
YSU

17. 8.10 Choice of solvent for SN1 is important – Table 8.6
More polar solvents (higher dielectric constant) will help stabilize the ionic intermediates.
YSU

18. 8.10 Proper solvent can stabilize transition states
Figure 8.7
YSU

19. 8.10 Choice of solvent important – Table 8.7
YSU

20. 8.11 Substitution vs. Elimination – SN2 vs. E2
YSU

21. 8.11 Substitution vs. Elimination
Figure 8.8
YSU

22. 8.12 Sulfonate ester leaving groups – Table 8.8
YSU