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What is the impact of steric hindrance on nucleophilic aromatic substitution?

Steric hindrance plays an important role in nucleophilic aromatic substitution (NAS) because it can slow down or even prevent the reaction. Here’s a explanation:


1. What is Steric Hindrance?

  • Steric hindrance occurs when large groups around a reactive site physically block a nucleophile from reaching the carbon atom.
  • In NAS, the nucleophile must attack the carbon attached to the leaving group on the aromatic ring.

2. Impact on NAS

  1. Slows down the reaction:
    • Bulky groups near the leaving group make it harder for the nucleophile to approach, reducing the reaction rate.
  2. Reduces yield:
    • If the nucleophile cannot easily reach the carbon, fewer molecules react, leading to lower product formation.
  3. Influences substitution position:
    • Steric hindrance may force the nucleophile to attack a less hindered site, if the ring has multiple reactive positions.

3. Examples

  • A halogen attached to a crowded aromatic ring (like ortho-substituted nitrobenzene) reacts slower in NAS than a halogen on an unsubstituted or less hindered ring.
  • NAS works best when the leaving group is accessible and there are electron-withdrawing groups to stabilize the intermediate.

Summary

  • Bulky groups near the reaction site reduce the rate and efficiency of NAS.
  • Chemists must consider steric effects when designing aromatic substitution reactions in drugs, dyes, or fine chemicals.

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