Write a mechanism for nitration of acetanilide to p-nitroacetanilide.
The Correct Answer and Explanation is:
Mechanism for the Nitration of Acetanilide to p-Nitroacetanilide
Step 1: Generation of the Electrophile
The nitration reaction begins with the generation of the nitronium ion (NO₂⁺), which acts as the electrophile. This occurs when concentrated nitric acid reacts with concentrated sulfuric acid:
HNO₃ + H₂SO₄ → NO₂⁺ + HSO₄⁻ + H₂O
Step 2: Activation of Acetanilide
Acetanilide contains an amide group (-NHCOCH₃) attached to the benzene ring. The nitrogen donates electron density through resonance into the ring, activating it toward electrophilic substitution, particularly at the ortho and para positions. However, the acetyl group (COCH₃) on the nitrogen moderates the activation, making it less reactive than aniline but still significantly activated.
Step 3: Electrophilic Attack
The nitronium ion attacks the aromatic ring of acetanilide, and due to steric hindrance at the ortho positions and electronic preference, substitution predominantly occurs at the para position relative to the acetamido group. The intermediate formed is a resonance-stabilized sigma complex (also known as the arenium ion).
Step 4: Restoration of Aromaticity
The sigma complex loses a proton from the carbon where substitution occurred, restoring aromaticity and yielding p-nitroacetanilide.
Explanation
The nitration of acetanilide to form p-nitroacetanilide is a classic example of electrophilic aromatic substitution. Acetanilide serves as the substrate, and its aromatic ring is activated by the electron-donating nature of the acetamido group. This group donates electron density to the ring via resonance and inductive effects, making the ortho and para positions more reactive toward electrophiles.
The nitrating agent in this reaction is the nitronium ion, which is a strong electrophile. It is produced in situ by mixing concentrated nitric acid and sulfuric acid. Sulfuric acid acts as a proton donor and helps in protonating nitric acid, facilitating the generation of NO₂⁺.
Once formed, the nitronium ion attacks the benzene ring of acetanilide. The para position is favored over the ortho position for two primary reasons. First, steric hindrance from the bulky acetamido group makes the ortho positions less accessible. Second, the para product is more stable due to better resonance stabilization and less steric crowding.
The attack of the nitronium ion forms a high-energy intermediate called the sigma complex, which temporarily disrupts the aromaticity of the ring. This complex then loses a proton, allowing the ring to regain its aromatic character and forming the final product, p-nitroacetanilide.
This reaction is highly regioselective and demonstrates how functional groups influence the reactivity and orientation of electrophilic substitution on aromatic systems. The acetyl group on the amine nitrogen serves a protective role, reducing the reactivity of the nitrogen and improving the yield of the para product by minimizing polysubstitution.
