The Hofmann elimination is useful synthetically for preparing alkenes since it gives the least substituted alkene. The reaction involves thermal elimination of a tertiary amine from a quatenary ammonium hydroxide; these are often formed from alkylation of a primary amine with methyl iodide followed by reaction with silver oxide.
Hofmann elimination reactions from bi- and tri-cyclic systems can, however be used to create 'internal' unsaturation without loss of a trialkyl amine for the synthesis of the hexahydrothieno azecine.
ReactionBack to Top
Because the leaving group of a quaternary ammonium ion has about the same leaving tendency as a protonated amino group but does not have an acidic hydrogen, a quaternary ammonium ion can undergo reaction with a strong base. The reaction of a quaternary ammonium ion with hydroxide ion is known as a Hofmann elimination reaction.The leaving group in a Hofmann elimination reaction is a tertiary amine.
Because a tertiary amine is only a moderately good leaving group, the reaction requires heat. It is an E2 reaction.
MechanismBack to Top
The Hofmann elimination is frequently used o determine the structures of complex amines by converting them to simpler amines. The direction of elimination is usually predictable, giving the least substituted alkene. The Hofmann elimination converts an amine into an alkene. The process begins by converting an amine to a quaternary ammonium salt. The general mechanism for the elimination step is shown below. This mechanism illustrates a sample reaction scheme for the Hofmann elimination.
The general mechanism for the elimination in the Hofmann elimination is
Hofmann elimination has been used in the synthesis of dienes and trienes. The use of the Hofmann eliminaion in the synthesis of 2-vinyltryptamines, higher yields were obtained by use of sodium hydroxide rather than with silver oxide.