16.S: Chemistry of Benzene - Electrophilic Aromatic Substitution (Summary)
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Concepts & Vocabulary
- Aromatic compounds don't typically undergo addition reactions.
- Aromatic compounds typically undergo substitution reactions.
16.1 Electrophilic Aromatic Substitution Reactions: Bromination
- Aromatic molecules only react with strong electrophiles.
- The first step in many electrophilic aromatic substitution mechanisms is activation or formation of the electrophile.
- The electrophilic aromatic substitution mechanism occurs in two steps. The first is addition of the electrophile to the ring and the second is elimination of a hydrogen from the ring to re-form the pi bond and restore aromaticity.
- In bromination of an aromatic ring, molecular bromine (Br 2 ) is reacted with iron tribromide (FeBr 3 ) to form the strongly electrophilic bromine cation and FeBr 4 . Following this, the aromatic ring is reacted with the bromine cation and adds to the ring to form a benzenonium cation. This molecule then reacts with one of the bromine atoms from FeBr 4 to lose a hydrogen forming the product and HBr as well as reforming the iron tribromide.
16.2 Other Aromatic Substitutions
- Aluminum bromide (AlBr 3 ) can be used in place of FeBr 3 to create the bromine cation. Also the chlorides of alumnium and iron can also be used to create a chlorine cation which will also undergo electrophilic aromatic substitution.
- Reacting nitric acid and sulfuric acid forms nitronium (NO 2 + ), which will react with aromatics for form nitro compounds.
- Sulfonation of aromatics can be accomplished by reacting with sulfur trioxide and sulfuric acid to yield sulfonic acids.
16.3 Alkylation and Acylation of Aromatic Rings - The Friedel-Crafts Reaction
- Friedel-Crafts reactions incorporate activation of alkyl and acyl halides by reacting them with a Lewis Acid catalyst, AlCl 3 .
- Friedel-Crafts alkylations allow for adding alkyl chains to aromatic rings.
- After activation with aluminum chloride, alkyl carbocations can undergo rearrangement if it leads to a more stable intermediate.
- Friedel-Crafts acylations add alkyl ketones to aromatic rings.
16.4 Substituent Effects in Substituted Aromatic Rings
- Aromatic inductive effects are caused by differences in electronegativity between atoms bonded to the ring and the ring carbons.
- Most common heteroatoms (N, O, halogens) donate electron density toward the ring inductively.
- Aromatic resonance effects are caused by conjugation of substituents with the pi bonds of the ring.
- Substituents that increase the electron density of the ring activate the ring (make more reactive) toward electrophilic substitution.
- Substituents that decrease the electron density of the ring deactivate the ring (make less reactive) toward electrophilic substitution.
16.4b An Explanation of Substituent Effects
- Steric effects can increase para substitution as ortho/para directors become larger.
- Activating groups are ortho/para (o, p) directors.
- Deactivating groups are meta directors.
- Alkyl groups inductively donate electron density to the ring making them o, p directors.
- Groups with an O or N attached to the aromatic ring are activators and o, p directors due to resonance.
- Groups with a pi bond attached to the aromatic ring are deactivators and m directors due to resonance.
- Halogens are o, p directors, but are deactivators.
16.5 Trisubstituted Benzenes: Additivity of Effects
- When there is more than one group attached to an aromatic ring, these groups may reinforce directing effects (cooperative) or have opposing directing effects (non-cooperative).
16.6 Nucleophilic Aromatic Substitution
- Highly activated aromatic rings can react with strong nucleophiles through a substitution mechanism.
- The mechanism typically begins with addition of a nucleophile followed by elimination of a leaving group.
- Under highly reactive conditions, a mechanism that begins with elimination for form a benzyne molecule intermediate followed by addition of a nucleophile resulting in nucleophilic aromatic substitution.
16.8 Oxidation of Aromatic Compounds
- Alkyl side-chains can be oxidized to benzoic acid (or a benzoic acid derivative if there are other groups present on the ring) by potassium permanganate (KMnO 4 ) as long as the benzylic carbon has at least one hydrogen attached.
- Radical halogenation will occur at the benzylic carbon, due to stabilization of radical intermediates.
16.9 Reduction of Aromatic Compounds
- Catalytic hydrogenation (H 2 and a catalyst) can be used to reduce many aromatic side-chains.
- Nitro groups can be selectively reduced to amines with SnCl 2 and HCl or with Fe and HCl.
- Carbonyls adjacent to the ring can be reduced by either Clemmensen reduction (Zn(Hg) and HCl.
- Birch reductions can reduce aromatic rings.
16.10 Synthesis of Polysubstituted Benzenes
- Multistep synthesis requires a combination of forward (from the starting material) and backward (from the target compound) thinking.
Skills to Master
- Skill 16.1 Write detailed electrophilic aromatic substitution mechanisms (halogentation, nitration, sulfonation, Friedel-Crafts alkyation and acylation).
- Skill 16.2 Write detailed mechanisms for formation of reactive electrophiles.
- Skill 16.3 Predict and explain rearrangements that can occur during Friedel-Crafts alkylation.
- Skill 16.4 Explain activation and deactivation of aromatic rings toward electrophilic aromatic substitution.
- Skill 16.5 Explain ortho, para vs. meta directing during electrophilic aromatic substitution reactions.
- Skill 16.6 Combine activation and deactivation and directing effects to predict products of reactions of substituted aromatic molecules.
- Skill 16.7 Write detailed nucleophilic aromatic substitution mechanisms through addition-elimination.
- Skill 16.8 Write detailed nucleophilic aromatic substitution mechanisms through benzyne elimination-addition.
- Skill 16.9 Draw products of oxidation of aromatic molecules.
- Skill 16.10 Draw products of reduction of aromatic side-chains.
- Skill 16.11 Draw mechanisms for reduction of aromatic rings.
- Skill 16.12 Solve multistep synthesis problems incorporating directing effects and side-chain reactions.