Ch. 18 - Reactions of Aromatics: EAS and BeyondSee all chapters
All Chapters
Ch. 1 - A Review of General Chemistry
Ch. 2 - Molecular Representations
Ch. 3 - Acids and Bases
Ch. 4 - Alkanes and Cycloalkanes
Ch. 5 - Chirality
Ch. 6 - Thermodynamics and Kinetics
Ch. 7 - Substitution Reactions
Ch. 8 - Elimination Reactions
Ch. 9 - Alkenes and Alkynes
Ch. 10 - Addition Reactions
Ch. 11 - Radical Reactions
Ch. 12 - Alcohols, Ethers, Epoxides and Thiols
Ch. 13 - Alcohols and Carbonyl Compounds
Ch. 14 - Synthetic Techniques
Ch. 15 - Analytical Techniques: IR, NMR, Mass Spect
Ch. 16 - Conjugated Systems
Ch. 17 - Aromaticity
Ch. 18 - Reactions of Aromatics: EAS and Beyond
Ch. 19 - Aldehydes and Ketones: Nucleophilic Addition
Ch. 20 - Carboxylic Acid Derivatives: NAS
Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon
Ch. 22 - Condensation Chemistry
Ch. 23 - Amines
Ch. 24 - Carbohydrates
Ch. 25 - Phenols
Ch. 26 - Amino Acids, Peptides, and Proteins

Electrophilic Aromatic Substitution

See all sections
Sections
Electrophilic Aromatic Substitution
Benzene Reactions
EAS: Halogenation Mechanism
EAS: Nitration Mechanism
EAS: Friedel-Crafts Alkylation Mechanism
EAS: Friedel-Crafts Acylation Mechanism
EAS: Any Carbocation Mechanism
Electron Withdrawing Groups
EAS: Ortho vs. Para Positions
Acylation of Aniline
Limitations of Friedel-Crafts Alkyation
Advantages of Friedel-Crafts Acylation
Blocking Groups - Sulfonic Acid
EAS: Synergistic and Competitive Groups
Side-Chain Halogenation
Side-Chain Oxidation
Birch Reduction
EAS: Sequence Groups
EAS: Retrosynthesis
Diazo Replacement Reactions
Diazo Sequence Groups
Diazo Retrosynthesis
Nucleophilic Aromatic Substitution
Benzyne
Additional Practice
EAS: Sulfonation Mechanism
EAS: Gatterman–Koch Reaction
EAS: Total Benzene Isomers
EAS: Polycyclic Aromatic Hydrocarbons
EAS: Directing Effects
Resonance Theory of EAS Directing Effects
Activated Benzene and Polysubstitutions
Clemmensen Reduction
EAS: Dueling Benzenes
Hydrogenation of Benzene
EAS: Missing Reagent
EAS: Synthesis
Diazonization of Aniline
Diazo Coupling Reactions
SNAr vs. Benzyne
Aromatic Missing Reagent
Aromatic Synthesis
Aromatic Retrosynthesis
EAS on 5-membered Heterocycles
Johnny Betancourt

Electrophilic aromatic substitution (EAS) is the primary method used to add substituents to benzene. Aromatic molecules like benzene don’t react like regular alkenes, so catalysts or special conditions are required. 


Mechanisms

Halogenation 


EAS-halogenation-mechanism-using-FeX3

EAS halogenation mechanism using FeX3

The benzene won’t react like an alkene in a standard halogenation reaction; instead, a Lewis acid catalyst with the formula AlX3 or FeX3 must be used. The X in the reagents X2 and represents bromine or chlorine since the mechanisms are the same. 

The iron has an empty p-orbital, so one of the halogens bonds to it. This creates a good leaving group, so the benzene attacks the neutral halogen and the bond to the cationic halogen is broken. From there, the bond between the halogen and the iron breaks to pull off a hydrogen and restore aromaticity to the ring. 

So, you know, the generic name of this reaction is EAS halogenation. If we’re adding a chlorine, it’s EAS chlorination; if we’re adding a bromine, it’s EAS bromination. 

Nitration

EAS-nitration-mechanism

EAS nitration mechanism

To get the benzene to react, we need to create an even stronger electrophile than the cationic nitrogen in nitric acid. To do that, we add a strong acid like H2SO4. The hydroxyl group on nitric acid deprotonates the sulfuric acid to become a good leaving group, and the anionic oxygen kicks it off as water to form a nitronium cation (NO2+). Now the benzene attacks the nitrogen, and the conjugate base of sulfuric acid restores aromaticity to the ring. 

Sulfonation

EAS-sulfonation-mechanism

EAS Sulfonation Mechanism

Just like in nitration, benzene will not attack the central atom in SO3 without modification. To make the sulfur even more electrophilic, we use sulfuric acid to protonate one of the oxygens. Sometimes you might see it as just SO3 (fuming), and that decomposes to H2SO4

Now that the sulfur shares that positive charge with the oxygen, it’s electrophilic enough for the benzene to attack. Once the SO3H is attached, the conjugate base of sulfuric acid pulls off a hydrogen to restore aromaticity to the ring. 

Friedel-Crafts Alkylation

Friedel-Crafts-alkylation-mechanism-using-AlCl3

Friedel-Crafts alkylation mechanism using AlCl3

Just like in the halogenation mechanism, a Lewis acid catalyst is needed. Chlorine or bromine can be used as the halogen in our alkyl halide. The halogen dissociates to form a complex with the Lewis acid catalyst, and a carbocation is produced. 

REMEMBER: carbocations are subject to rearrangement, so hydride shifts, methyl shifts, and ring expansions are possible. The benzene is then “tempted” enough to attack, and then it’s the same old story: the halide dissociates from its complex with the Lewis acid catalyst to remove a proton and restore aromaticity

Friedel-Crafts Acylation

Friedel-Crafts-acylation-mechanism

Friedel-Crafts acylation mechanism

This mechanism is very similar to Friedel-Crafts alkylation, but it uses an acyl halide (aka acid halide) instead of an alkyl halide. Again, chlorine or bromine can be used. There are two variations to the first step, but each result in the exact same thing: the halogen bonds to the Lewis acid catalyst to form the blue molecule or it completely dissociates form the carbonyl to form the purple molecule.

Acylium cations like the one in purple are resonance-stabilized by the oxygen and are incapable of rearrangement. The benzene then attacks the cation. If using the blue molecule, the benzene acts as a nucleophile in a nucleophilic acyl substitution mechanism, kicking off the Lewis acid catalyst-halogen complex.  In both cases, the last step involves the halogen dissociating from the catalyst to remove a hydrogen and restore aromaticity.

Any Carbocation (two types)

Bronsted acid

Any-carbocation-Bronsted-mechanism

Any carbocation Bronsted mechanism

If there’s a carbocation, benzene can attack! A common version of this reaction is to use an alkene and hydrofluoric acid to form the carbocation. REMEMBER: carbocations are subject to rearrangement, so hydride shifts, methyl shifts, and ring expansions are possible. 

We usually use HF because is a pretty poor nucleophile and preventing side reactions is a big plus. After any carbocation rearrangement, benzene will attack, and the fluoride anion will remove a proton and restore aromaticity

Lewis acid

Any-carbocation-Lewis-mechanism

Any carbocation Lewis mechanism

In the Lewis acid version of the “any carbocation” mechanism, an alcohol is used instead of an alkene. Boron’s empty p-orbital accepts the electrons from the dissociating alcohol’s bond to carbon, and a carbocation is produced. The benzene attacks the carbocation, and one of the fluorines dissociates from the Lewis acid catalyst-hydroxyl group complex to remove a hydrogen and restore aromaticity

This is considered an acid-promoted mechanism instead of an acid-catalyzed mechanism, since the BF3 lewis acid is consumed in the reaction (it becomes BF2OH). 

Ortho, Meta, and Para Positions

When there are two substituents on a benzene, we can denote their positions in a couple of ways: we can use numbers (e.g. 1,3 dichlorobenzene) or we can use the ortho, meta, and para designations (e.g. meta-dichlorobenzene or m-dichlorobenzene). 

ortho-meta-and-para-dichlorobenzene

Ortho, meta, and para dichlorobenzene

Activation and Directing Effects

Electron-withdrawing groups (EWGs) pull electron density out of the ring, reducing benzene’s reactivity. Electron-donating groups (EDGs) push electron density into the ring, increasing benzene’s reactivity.  

In EAS reactions with a substituent already on benzene, regioselectivity is something that needs to be considered! EWGs will generally direct the next substituent added through EAS to the meta position. EDGs will generally direct to the ortho or para positions (preferably para due to sterics). 

Activation-and-directing-effects

Activation and directing effects

Notice that not all deactivators (EWGs) are meta directors! Halogens, denoted as X, are actually ortho, para directors. 



Johnny Betancourt

Johnny got his start tutoring Organic in 2006 when he was a Teaching Assistant. He graduated in Chemistry from FIU and finished up his UF Doctor of Pharmacy last year. He now enjoys helping thousands of students crush mechanisms, while moonlighting as a clinical pharmacist on weekends.