Lesson 5: Carboxylic Acids, Anhydrides, Amides, and the Hofmann Rearrangement Mechanism — PACE The PANCE

Lesson 5: Carboxylic Acids, Anhydrides, Amides, and the Hofmann Rearrangement Mechanism

How to Understand Carboxylic Acids

Structure and Properties:
- Identify the functional group: -COOH.
- Understand the acidity due to the carboxyl group.
- Recognize common examples (e.g., acetic acid, benzoic acid).
Reactions:
- Know the common reactions, such as esterification and reduction.
- Understand the formation of derivatives (e.g., esters, amides).

How to Understand Anhydrides

Structure and Properties:
- Identify the functional group: R(C=O)O(C=O)R.
- Understand the reactivity due to the presence of two acyl groups.
Reactions:
- Learn the synthesis from carboxylic acids.
- Know common reactions, such as hydrolysis to form carboxylic acids.

How to Understand Amides

Structure and Properties:
- Identify the functional group: -CONH2, -CONHR, -CONR2.
- Understand the resonance stabilization and reduced basicity.
Reactions:
- Learn the synthesis from carboxylic acids or esters.
- Understand hydrolysis to carboxylic acids and amines.

How to Understand the Hofmann Rearrangement Mechanism

Overview:
- Recognize the transformation of primary amides to primary amines with the loss of one carbon atom.
Mechanism Steps:
1. Formation of the Bromamide Intermediate:
  - React the amide with bromine (Br2) in the presence of a strong base (usually NaOH).
2. Formation of the Nitrene Intermediate:
  - The bromamide intermediate undergoes deprotonation to form an isocyanate.
3. Rearrangement:
  - The isocyanate rearranges to form an amine with the loss of a carbon dioxide (CO2) molecule.
4. Hydrolysis:
  - The resulting amine can be hydrolyzed to form the primary amine.