Nucleophilic Acyl Substitution: The Core Mechanism of Carboxylic Acid Derivatives

Learn nucleophilic acyl substitution step-by-step: addition to carbonyl, tetrahedral intermediate, and leaving group departure. Includes reactivity order (acid chlorides → amides) and practice.

• Two-step pattern: Addition → tetrahedral intermediate → elimination
• Key comparison: Leaving group ability controls reactivity
• Reactivity order: Acid chloride > anhydride > ester ≈ acid (activated) > amide
• Acid/base note: Conditions (acidic vs basic) change which species is nucleophile/leaving group
• Exam type: Choose the mechanism
• Exam type: Predict the major product
• Exam type: Synthesis / retrosynthesis