Question

Which of the following is the most reactive towards ring nitration? (1) Benzene (2) Toluene (3) m-Xylene (4) Mesitylene

Short answer

Mesitylene (option 4)

Step-by-step solution

- Understand the Effect of Substituents

Nitration is an electrophilic aromatic substitution reaction. For such reactions, electron-donating groups (EDGs) activate the benzene ring and make it more reactive towards nitration, while electron-withdrawing groups (EWGs) deactivate the ring.

- Analyze Each Compound

Benzene (option 1) has no substituents, so it is our baseline. Toluene (option 2) has a methyl group, which is an electron-donating group. m-Xylene (option 3) has two methyl groups at the meta positions, and Mesitylene (option 4) has three methyl groups at 1,3,5 positions.

- Compare the Activation Effects

Electron-donating groups increase the electron density of the benzene ring, thus increasing its reactivity towards nitration. Since methyl groups are electron-donating, increasing the number of methyl groups should increase the reactivity.

- Determine the Compound with Most EDGs

Among the given options, Mesitylene (option 4) has three methyl groups. More methyl groups mean a higher level of activation, making the ring more reactive towards nitration.

- Conclude the Most Reactive Compound

Based on the number of electron-donating groups, Mesitylene (option 4) is the most reactive towards ring nitration because it has three methyl groups.

Key concepts

Nitration reaction

Nitration is a key example of an electrophilic aromatic substitution reaction. It introduces a nitro group (O2) into an aromatic ring, like benzene. The reaction typically uses a mixture of concentrated nitric acid (HNO3) and sulfuric acid (H2SO4) as reagents. These acids work together to produce the nitronium ion (NO2+), which acts as the electrophile. During the reaction, the aromatic ring temporarily loses its aromaticity when it forms a sigma complex or arenium ion. Finally, it regains aromaticity by eliminating a proton, resulting in the nitrated aromatic product.
Understanding the nitration mechanism helps in predicting how different substituents will affect the reactivity of the aromatic ring during the reaction.

Electron-donating groups

Electron-donating groups (EDGs) are groups that push electrons towards the aromatic ring, increasing its electron density. These groups make the ring more reactive towards electrophilic substitution reactions, like nitration.
Common EDGs include alkyl groups (e.g., methyl), hydroxyl groups (e.g., -OH), and amino groups (e.g., -NH2). Their effect is opposite to that of electron-withdrawing groups, which pull electron density away from the ring.
Here’s why EDGs increase reactivity:

• They stabilize the positively charged intermediates (sigma complex) formed during the reaction.
• They make the ring more nucleophilic, meaning it can better attract the positively charged electrophile, such as the nitronium ion.
  For instance, a methyl group is a typical EDG. It activates the benzene ring by hyperconjugation and inductive effect, making toluene more reactive towards nitration than benzene.

Substituent effects

Substituent effects describe how different groups attached to the benzene ring influence its reactivity towards electrophilic substitution reactions. This is crucial in understanding which compound will react the fastest in nitration.
We can categorize these effects into two types:

• Activating: Substituents that donate electrons increase the ring's reactivity. Examples include -CH3 (methyl), -OH (hydroxyl), and -NH2 (amino). These groups make the ring more reactive by stabilizing the intermediate formed during the reaction.
• Deactivating: Substituents that withdraw electrons decrease the ring's reactivity. Examples include -NO2 (nitro), -COOH (carboxyl), and -CF3 (trifluoromethyl). These groups make the ring less reactive by destabilizing the intermediate.
  The strength of activation or deactivation also varies. A strong EDG, like an amino group, significantly increases reactivity, while a weak EDG, like an alkyl group, has a moderate effect.
  In the given exercise, we saw that mesitylene, with three electron-donating methyl groups, is more reactive towards nitration compared to benzene, toluene, or m-xylene. The reactivity increases as we add more EDGs to the ring, due to the greater electron density and stability provided to the transition state.