Hofmann's Rule

Definition

Hofmann's rule, also known as the Hofmann elimination, is a principle that predicts the major product in an elimination reaction involving a quaternary ammonium salt. It states that the elimination reaction will favor the formation of the alkene with the least substituted (most terminal) double bond.

5 Must Know Facts For Your Next Test

1. Hofmann's rule is particularly relevant in the context of E1 and E1cB elimination reactions, as well as in the reactions of amines.
2. The rule states that the major product of an elimination reaction involving a quaternary ammonium salt will be the alkene with the least substituted (most terminal) double bond.
3. This is because the formation of the more substituted alkene would result in a more stable, but less reactive, carbocation intermediate in an E1 reaction.
4. In an E1cB reaction, the formation of the less substituted alkene is favored because it requires the removal of a less hindered proton.
5. Hofmann's rule is a useful tool for predicting the major product in elimination reactions involving quaternary ammonium salts, which are common intermediates in the reactions of amines.

Review Questions

• Explain how Hofmann's rule applies to the E1 reaction mechanism.
  • In an E1 reaction, the formation of the carbocation intermediate is the rate-determining step. According to Hofmann's rule, the major product of the elimination will be the alkene with the least substituted (most terminal) double bond. This is because the formation of the more substituted alkene would result in a more stable, but less reactive, carbocation intermediate. The less substituted alkene is therefore the kinetically favored product in an E1 elimination reaction.
• Describe how Hofmann's rule influences the outcome of E1cB reactions involving quaternary ammonium salts.
  • In an E1cB reaction, the rate-determining step is the removal of a proton to form a carbanion intermediate. Hofmann's rule states that the major product will be the alkene with the least substituted (most terminal) double bond. This is because the formation of the less substituted alkene requires the removal of a less hindered proton, which is kinetically favored over the removal of a more hindered proton to form the more substituted alkene. Therefore, Hofmann's rule helps predict the major product in E1cB eliminations of quaternary ammonium salts.
• Analyze how Hofmann's rule can be used to predict the outcome of amine reactions, particularly in the context of the formation of quaternary ammonium salts.
  • Hofmann's rule is particularly relevant in the reactions of amines, as these often involve the formation of quaternary ammonium salts as intermediates. When these quaternary ammonium salts undergo elimination reactions, Hofmann's rule can be used to predict the major product. The rule states that the alkene with the least substituted (most terminal) double bond will be the kinetically favored elimination product. This is because the formation of the less substituted alkene is more favorable, either through the stabilization of a carbocation intermediate in an E1 reaction or the removal of a less hindered proton in an E1cB reaction. By understanding Hofmann's rule, one can better anticipate the outcomes of amine reactions involving quaternary ammonium salt intermediates.

Related terms

E1 Reaction:

An elimination reaction in which the rate-determining step involves the formation of a carbocation intermediate.

E1cB Reaction:

An elimination reaction that proceeds through a carbanion intermediate, with the rate-determining step being the removal of a proton.

Quaternary Ammonium Salt: A positively charged nitrogen atom bonded to four alkyl or aryl groups, forming a salt with a counterion.