1. Nucleophilic Substitution

2. Organic Substitution versus Inorganic Single Replacement
Oxidation-reduction, with new ionic bonds, in single replacement
Making and breaking covalent bonds in organic substitution

3. Aromatic and Acyl Substitution
Addition/elimination that reconstitutes aromatic system
Addition/elimination that reconstitutes carbonyl group

4. Radical Substitution

5. Nucleophilic Substitution
Bimolecular Nucleophilic Substitution (SN2)
Second Order with Inversion
Unimolecular Nucleophilic Substitution (SN1)
First Order with Racemization

6. SN2 Inversion versus SN1 Racemization
Stereospecific
SN1 Racemization
Loss of optical purity

7. Kinetics of SN2 versus SN1
Rate = k[Substrate][Nucleophile]
Rate depends on nucleophile conc.
Restrictive collision orientation in RDS
SN1
Rate = k[Substrate]
Rate independent of nucleophile conc.
Net bond dissociation in RDS

8. Kinetic Control versus Thermodynamic Control

9. Steric Hindrance versus Carbocation Stability
Less hindered substrate favors SN2
More stable carbocation favors SN1

10. Protic Solvents for SN2 versus SN1
Nucleophile stabilized in SN2
Charged intermediates stabilized in SN1

11. Protic versus Aprotic Solvents

12. Effect of Nucleophile SN2 could be favored with superior nucleophiles:
Localized, destabilized anion
Low electronegativity atom
Larger, more polarizable atom
High p-character hybrid orbital
Low steric hindrance

13. Factors Favoring SN2 versus SN1
Less hindered substrates favor SN2; substrates with more stable carbocation intermediates favor SN1.
Polar aprotic solvents, which avoid sequestration of nucleophiles, are favored for SN2; protic solvents, which stabilize intermediates, are favored for SN1.
Exceptional nucleophiles may improve the preference for SN2 over SN1.