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Carbonyl Chemistry Chapter 13: Carboxylic Acids and Their Derivatives

Chapter 13: Carboxylic Acids and Their Derivatives

Substitution at the Carbonyl

Estimated reading time: 2 min

In this chapter

Introduction

Carboxylic acids and their derivatives represent another major family of carbonyl compounds.

These include:

  • carboxylic acids,
  • esters,
  • amides,
  • acid chlorides,
  • and anhydrides.

Although these compounds differ in structure and reactivity, they share many common features.

Relative Reactivity

Some carbonyl compounds are more reactive than others.

In general:

Acid chlorides → Anhydrides → Esters → Amides

Understanding this trend helps explain many reaction pathways.

Nucleophilic Acyl Substitution

Unlike aldehydes and ketones, many carboxylic acid derivatives undergo substitution rather than simple addition.

The general pattern is:

  1. Nucleophilic attack.
  2. Formation of a tetrahedral intermediate.
  3. Departure of a leaving group.

This mechanism appears repeatedly throughout Organic Chemistry II.

Figure 13.1. Nucleophilic acyl substitution: the same first step as Ch.12's addition mechanism — a nucleophile attacks the carbonyl carbon to give a tetrahedral intermediate — but here a leaving group (L) is present, so the intermediate collapses by re-forming the C=O and ejecting L⁻ rather than being protonated. ("Nucleophilic acyl substitution" by V8rik, public domain, via Wikimedia Commons.)
Figure 13.1. Nucleophilic acyl substitution: the same first step as Ch.12's addition mechanism — a nucleophile attacks the carbonyl carbon to give a tetrahedral intermediate — but here a leaving group (L) is present, so the intermediate collapses by re-forming the C=O and ejecting L⁻ rather than being protonated. ("Nucleophilic acyl substitution" by V8rik, public domain, via Wikimedia Commons.)

Biological Importance

These functional groups are widespread:

Esters

Lipids and fats.

Amides

Proteins and peptides.

Carboxylic Acids

Fatty acids and metabolism.

Thinking About Reactivity

Helpful questions include:

  • How good is the leaving group?
  • Which derivative is more reactive?
  • Which pathway is favored?

Self-Assessment

I can:

☐ Rank acid chlorides, anhydrides, esters, and amides by relative reactivity.

☐ Distinguish nucleophilic acyl substitution from nucleophilic addition.

☐ Describe the tetrahedral intermediate and leaving-group departure.

☐ Connect carboxylic acid derivatives to biological roles (esters in lipids, amides in proteins).

Looking Ahead

Carbonyl chemistry becomes even richer when reactions occur adjacent to the carbonyl group.

This introduces the chemistry of enols and enolates.

Common Mistake — Treating All Carbonyl Compounds Equally

Better approach: Recognize differences in reactivity.

Common Mistake — Ignoring Leaving Groups

Better approach: Think mechanistically.