Unlike aldehydes and ketones, carboxylic acid derivatives have a leaving group attached to the carbonyl carbon. The tetrahedral intermediate formed by nucleophilic attack collapses by ejecting that leaving group and reforming the C=O — substitution, not addition. This is the central distinction developed in Chapter 13.

Relative reactivity: Acid chlorides → Anhydrides → Esters → Amides (most to least reactive), tracking how good a leaving group each derivative provides.

Starting Material	Typical Reagents/Conditions	Product	Common Pitfall
Carboxylic acid	SOCl₂	Acid chloride	Forgetting this is usually the first step needed before making an anhydride, ester, or amide from a carboxylic acid directly
Carboxylic acid	Alcohol (ROH), acid catalyst (Fischer esterification)	Ester	Assuming this reaction goes to completion — Fischer esterification is an equilibrium and usually needs excess alcohol or water removal to favor the ester
Acid chloride or anhydride	H₂O	Carboxylic acid	—
Acid chloride or anhydride	Alcohol (ROH)	Ester	—
Acid chloride or anhydride	Amine (R₂NH)	Amide	—
Ester	H₃O⁺ or NaOH (saponification), H₂O	Carboxylic acid (or carboxylate, if base)	Confusing acid- and base-mediated hydrolysis — base-mediated hydrolysis (saponification) is irreversible because the carboxylate product is unreactive toward further attack
Ester	Amine (R₂NH)	Amide	Requires more forcing conditions than starting from an acid chloride, since alkoxide is a worse leaving group than chloride

Reading this table as a cascade: acid chlorides and anhydrides are reactive enough to be converted directly into acids, esters, or amides by choosing the nucleophile (water, alcohol, or amine, respectively) — the same substitution mechanism, three different nucleophiles.

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