Organic Chemistry by Brown, Iverson, Anslyn, Foote | Mayya's Study Guide

Chapter 22:Reactions of Benzene and Its Derivatives

Table of Contents:

Electrophilic Aromatic Substitution
Disubstitution and Polysubstitution
Nucleophilic Aromatic Substitution

Electrophilic Aromatic Substitution

During electrophilic aromatic substitution reactions, a hydrogen on the benzene ring gets replaced by another group.

1. Chlorination and Bromination

Chlorination Mechanism

2. Nitration

Nitration Mechanism

Formation of the Nitronium Ion

Nitration of Benzene

3. Sulfonation

4. Friedel-Crafts Alkylation

Friedel-Crafts Alkylation Mechanism

Friedel-Crafts Alkylation Limitation 1: Rearrangements can happen in Friedel-Crafts Alkylation. Rearrangement will happen if there is a carbon on the alkyl chain more substituted than the carbon attached to the chlorine.

Let's take a look at the example above. While we would predict the top product, it is actually wrong. The bottom product is correct due to a rearrangement. Let's take a look at how it happens.

As we can see in the mechanism the carbon attached to chlorine is primary (attached to one carbon only). The carbon neighboring the carbon with the chlorine group is tertiary and is more substituted. In this case a hydride shift occurs which results in a tertiary carbocation.

Limitation 2: Friedel-Crafts alkylation can NOT happen if there are electron withdrawing groups already present on the benzene ring. These include: SO3H, CN, NO2, COOR, COOH, CF3.

Limitation 3: It is hard to stop the reaction after one alkyl group is added. The reaction may result in more than one alkyl group being added.

5. Friedel-Crafts Acylation

Friedel-Crafts Acylation Mechanism: Generation of an Acylium Ion

Disubstitution and Polysubstitution

So far we have learned the reactions where we put one group on a benzene ring. What happens, though, when there is already a group on it? Where would the next group go? Substituent that is already attached to the benzene ring will dictate where the new group attaches. Positions can be ortho, para or meta.

The chart below needs to be memorized in order to predict the products and do synthesis correctly for this chapter.

How do we read this chart? For example, if there is an NO2 group on the benzene ring, where would the next group go? It should go meta to the NO2 group. Groups that direct ortho also direct para. We usually show both products but para is usually major since it is less sterically hindered.

Common Mistake: Students often think that the group that is being added is the one that directs. Please do not make this mistake. It is the group that is on the benzene ring that directs where the next group goes.

Bromine is ortho/para directing. Therefore, nitrate group will go ortho and para to the bromine, giving two products.

Note: Please note that the chart above also shows which groups are activating (make the benne ring more reactive)and which ones are deactivating (make the benzene ring less reactive).

Theory of Directing Effects

Why do some groups direct ortho/para while others direct meta? We can account for these patterns once we look at the mechanisms and intermediates.

Nitration of Anisole

There is an extra! resonance form in the PARA substitution of anisole.

Nitration of Benzoic Acid

In para, there is one resonance form that is not stable!

What happens if there are two or more groups on the benzene ring? How do you know where the next group goes?

The group that is most activating will direct where the next group will be added. Find the most activating group on the benzene ring and use it solely for the direction of the next group.

Nucleophilic Aromatic Substitution

In a nucleophilic aromatic substitution reaction, instead of adding a group to the ring, one of the groups on the ring (halogen) is replaced by a nucleophile.

Nucleophilic Aromatic Substitution: A Benzyne Intermediate