Chemistry of Aromatic Compounds Electrophilic Aromatic Substitution Directing Effects Side-chain Reactions Synthesis Nucleophilic Aromatic Substitution
Electrophilic Aromatic Substitution
EAS Reactions of Benzene
Bromination / Chlorination
Bromination Mechanism
Reaction Profile
Nitration
Nitration Mechanism
Nitration of Toluene
Sulfonation is Reversible
Desulfonation
Friedel-Crafts Acylation
1st, Formaton of Electrophile
Acylation Mechanism
Intermediate is Resonance-Stabilized
An Acylation
Friedel-Crafts Alkylation many more limitations
Mechanism
Carbocation Generated From Alkene
Unexpected Product?
Carbocations Rearrange…
1o RX Typically Undergoes Shift
Side Chain Reactions 1) Reduction of Aromatic Ketones
Straight-chain Alkylation can be Accomplished in 2 steps: Acylation, then Reduction
2) Oxidation of Alkyl Substituents
3) Benzylic Bromination with NBS
4) Alkali Fusion of Sulfonic Acids
5) Reduction of Nitro Groups
Directing Effects
ortho/para-Directing Activating Groups
Nitration of Anisole
Nitration Affords ortho and para Products
Activating ortho/para directors
Nitration of Toluene
meta-Directing Deactivating Groups
Electron-Withdrawing Nitro Group Directs meta
meta Directors
Comparison
More Limitations with Friedel Crafts Reactions
Substituent Summary
Halogens are the Anomoly Deactivators and o,p-Directors
Reactions of Rings With Two or More Substituents
The (More) Activated Ring Reacts
Mixtures with Conflicting Directing Effects
Provide the Reagents
Must Acylate First
Sulfonic Acid Blocks para Position
Give the Reagents
Provide the Reagents
Provide the Reagents
Nucleophlic Aromatic Substitution
Not an SN1
Not an SN2
“SNA” criteria: Strongly deactivated ring Leaving group Deactivating group(s) ortho &/or para to leaving group (preferably) Strong base (nucleophile) such as RO-, NH2-
Methoxide as a nucleophile
Mechanism
With no EWG, reaction conditions are more extreme Elimination/Addition Mechanism
“Benzyne” Intermediate
Carbons are sp2 (not a second p bond)
Benzyne can be trapped by a Diene: Undergoes a Diels-Alder rxn
Benzyne intermediate has 2 reactive sites
Mixture of Regioisomers