Amide Synthesis: Nucleophilic Acyl Substitution with Amines

Learn how to make amides via nucleophilic acyl substitution: acid chlorides/anhydrides/esters + amines. Understand why direct acid + amine gives salts, and see common pitfalls + practice.

  • Best acyl sources: Acid chlorides/anhydrides (fast); esters (slower)
  • Nucleophile: 1°/2° amines (NH3, RNH2, R2NH)
  • Key pitfall: Carboxylic acid + amine → salt (no amide) without activation
  • Base role: Scavenge acid byproducts (e.g., HCl) and keep amine nucleophilic
  • Exam type: Predict the major product
  • Exam type: Synthesis / retrosynthesis
  • Exam type: Choose conditions

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