Aromatic electrophilic substitution (ArES)

This should not be viewed as markedly different behaviour from alkenes, but merely as an obvious consequence of aromatic stabilization dictating the fate of the initial carbocation. However, there are of course differences, as discussed earlier in the introduction.

In general, electrophilic substitution of aromatic compounds requires much stronger electrophiles or conditions for the reaction to take place due to the loss of aromatic stabilisation in the initial attack and the formation of the carbocation.

Overall equation for ArES:

Mechanism for ArES:

1. Formation of the reactive electrophile, E⁺

Benzene ring is a weaker nucleophile compared to other aliphatic compounds such as alkene, due to the more stable π-electrons system present in benzene. Therefore, moderate electrophile like bromine, while sufficient for reaction with alkene, fails to react with benzene on its own. Presence of a catalyst  as well as heating is required for the reaction with benzene to occur.

 

Bromine cation generated is a stronger electrophile, capable of reacting with benzene. This is an example of  generation of reactive electrophile, E⁺

2. Attacking of Electrophile

An electrophile attacks the pi electrons of the aromatic benzene ring which results in the formation of a resonance stabilized carbocation. This carbocation is called the arenium ion and has three resonance contributors. Electrophilic attack is a very slow process. It is endergonic and has high activation energy due to the loss of aromaticity.

3. Attacking of Carbocation by Base

Finally, the carbocation intermediate is attacked by a base and loses a proton. These electrons are used to reform a pi bond and restore aromaticity. As opposed to the first step, this step is fast and exergonic because aromaticity is regained. It is important to note that the carbocation loses a proton where the electrophile attacked the benzene ring.

Similar to SN1 and E1 reactions, the rate-determining step for electrophilic substitution is step which involves the formation of the carbocation because energy required for step 2, which is the formation of the carbocation is the greatest, as shown from the energy profile diagram of the reaction.

Hence, Rate = k[Aromatic Compound] [Electrophile], where k is the rate constant.

5 Most Common Electrophilic Substitution Reactions

The following are the 5 most common electrophilic substitution and their mechanism will also be shown below.

1. Halogenation

Functional groups are halides (E.g: Cl, Br, I).

C-C bond is formed in this reaction, where alkyl chain is attached onto benzene ring. The alkyl halides generate C + as electrophile and FeBr₃ or AlBr₃ promotes the formation of carbocation (C+ ).

 

2. Sulfonation

With SO₃ or SO₃H⁺                       

Note: This is the only reversible Electrophilic Substitution reaction.

3. Nitration

Functional group: ⁺NO₂

4. Friedel-Crafts alkylation (alkyl group, R)

 

5. Friedel-Crafts Acylation ( + O C–R, acylium ion)

 

 

Effects of Substitution on Electrophilic Substitution

Generally, electrophilic substitution can form 3 products. Substituent can be formed on the ortho-positions, meta-positions and para-positions. The preferred product depends on one of three factors: sterics, probability, or the mechanism itself which are determined by the properties of the substituent. The stability of the carbocation is what matters the most. In general, the factors are ranked: Mechanism>probability>sterics (only when sterics aren’t severe).

Electron Donating Groups (EDG)

Alkyl groups, aryl, vinyl, alkynyl, hydroxyl, ether and amine are examples of electron donating groups. These groups donate electron density by inductive electron donation and through donation by resonance. Substituents that donate electron density stabilize the carbocation  increases the rate of EAS. Electron donating groups are also called activators and they increase the EAS reaction rate by making the benzene ring more reactive. EDG are ortho/para directors meaning electrophilic attack will result in the new atom forming a bond in the ortho or para position.

 

Electron Withdrawing Groups (EWG)

Example of electron withdrawing groups are Nitro carbonyl, trifluormethyl, ammonium and any groups with a positive charge. These substituents remove electron density from the aromatic ring, hence reducing benzene’s nucleophilicity and slowing the rate of electrophilic attack. Electron withdrawing groups are also known as deactivators and are meta directors.

Halogens are a special case. They provide a small resonance contribution making them ortho/para directors but, due to a significant inductive effect, halogens are also deactivators.

What happens if there are two substituents?

• Case 1. If the substituents direct to the same position, then the electrophile will attach there.
• Case 2. If the substituents direct to the different position, the activating substituent “will win out.”

We also need to consider the steric effects of the two substituents attached to the aromatic ring.

• Substitution between two groups in a meta- bi-substituted molecule rarely occurs due to steric hinderance

• Adjacent tri-substituted benzene compounds must start with ortho- bi-substituted substrates

Industrial Application of Electrophilic Substitution 

Synthesis of Allura Red AC and Azo Dye

Azo dyes are reds, yellows and oranges. They are highly soluble in water and were discovered to be carcinogens. They are synthesized in a process called diazo coupling. This reaction is very sensitive to sterics and results in the formation of N=N. Due to sterics, there is often a cis and trans product with the trans being more stable.