| Hofmann elimination | |
|---|---|
| Named after | August Wilhelm von Hofmann |
| Reaction type | Elimination reaction |
| Identifiers | |
| Organic Chemistry Portal | hofmann-elimination |
| RSC ontology ID | RXNO:0000166 |
Hofmann elimination is anelimination reaction of anamine to formalkenes. The least stable alkene (the one with the fewest substituents on the carbons of the double bond), called theHofmann product, is formed. This tendency, known as theHofmann alkene synthesis rule, is in contrast to usual elimination reactions, whereZaitsev's rule predicts the formation of the most stable alkene. It is named after its discoverer,August Wilhelm von Hofmann.[1][2]
The reaction starts with the formation of aquaternary ammonium iodide salt by treatment of the amine with excessmethyl iodide (exhaustive methylation), followed by treatment withsilver oxide andwater to form a quaternary ammonium hydroxide. When this salt is decomposed by heat, the Hofmann product is preferentially formed due to thesteric bulk of theleaving group causing the hydroxide to abstract the more easily accessible hydrogen.
In the Hofmann elimination, the least substituted alkene is typically favored due to intramolecular steric interactions. The quaternary ammonium group is large, and interactions with alkyl groups on the rest of the molecule are undesirable. As a result, the conformation necessary for the formation of the Zaitsev product is less energetically favorable than the conformation required for the formation of the Hofmann product. As a result, the Hofmann product is formed preferentially. TheCope elimination is very similar to the Hofmann elimination in principle, but occurs under milder conditions. It also favors the formation of the Hofmann product, and for the same reasons.[3]
An example of a Hofmann elimination (not involving a contrast between a Zaitsev product and a Hofmann product) is the synthesis oftrans-cyclooctene.[4] Thetrans isomer is selectivelytrapped as acomplex withsilver nitrate (in this diagram thetrans form looks like acis form, but see thetrans-cyclooctene article for better images):
In a relatedchemical test, known as theHerzig–Meyer alkimide group determination, a tertiary amine with at least one methyl group and lacking a beta-proton is allowed to react withhydrogen iodide to the quaternary ammonium salt which when heated degrades to methyl iodide and the secondary amine.[5]
