22.6 Hofmann Elimination

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Hofmann Elimination

The Hofmann Elimination is a reaction of amines from which the term Hofmann Elimination, referring to the formation of the least substituted alkene, gets its name.  Back in the lesson on the Exceptions to Zaitsev's Rule, it was presented that one of the exceptions to Zaitsev's Rule occurs with a poor leaving group.  In that lesson the poor leaving group presented was F-, which being a moderate base was not a good leaving group like the very weak bases Cl-, Br-, and I-.  In the Hofmann Elimination an amine acts as the leaving group, and being a moderate base is also not a good leaving group thus resulting in formation of the least substituted alkene (a.k.a. the Hofmann product) as the major product.

Hofmann Elimination

Hofmann Elimination Mechanism

The Hofmann Elimination occurs in three major steps:

  1. Exhaustive Methylation
  2. Anion Exchange
  3. E2 Elimination

1. Exhaustive Methylation

Excess methyl iodide is added to the reactant amine.  The amine acts as a nucleophile in an SN2 reaction displacing I- as the leaving group (this substitution is referred to as methylation).  For a tertiary amine this would lead directly to a quaternary ammonium ion, but primary and secondary amines undergo subsequent deprotonation followed by successive methylation reactions until a quaternary ammonium ion is produced.  This is what is meant by the term 'exhaustive' methylation.

Hofmann Elimination Mechanism Exhaustive Methylation

2. Anion Exchange

The quaternary ammonion ion is formed as a salt with iodide acting as the counter ion.  The addition of silver oxide (Ag2O) serves two purposes.  First, it precipitates the iodide ion as AgI which is insoluble.  Second, silver oxide is basic and replaces the iodide ion with hydroxide which will act as the strong base in the final step of the mechanism: E2 Elimination.

Hofmann Elimination Mechanism Step 2

3. E2 Elimination

The final step in the Hofmann Elimination is simply E2 Elimination.  With a poor leaving group the transition state is carbanion-like on the beta carbon.  As a less substituted carbanion is more stable, elimination takes place preferentially with the less substituted beta carbon leading to the less substituted alkene (the Hofmann product).

Hofmann Elimination Mechanism E2 step