15.9 : Multiple Halogenation of Methyl Ketones: Haloform Reaction

The haloform reaction is a method to obtain carboxylic acids from methyl ketones in the presence of an excess of base and halogen. It is named after the by-product of the reaction—haloform.

The reaction commences with generation of an enolate, followed by halogenation to give an α-halo ketone.

This continues until all α protons are replaced by halogens to form a trihalomethyl ketone.

The resulting molecule is unstable and undergoes a nucleophilic acyl substitution reaction with a hydroxide base to expel trihalomethyl carbanion—a good leaving group—and form carboxylic acid.

The carbanion is stabilized by the electron-withdrawing effect of the three halogens, which irreversibly deprotonates the carboxylic acid to produce carboxylate ion and haloform.

This step drives the haloform reaction to completion. Further, acidification of the carboxylate generates carboxylic acid.

With chlorine and bromine, the by-products are chloroform and bromoform which are liquids and immiscible in the reaction mixture.

The use of iodine forms iodoform—a yellow precipitate. This forms the basis of the iodoform test for the qualitative detection of methyl ketones.