Ketone halogenation

In organic chemistry α-keto halogenation is a special type of halogenation. The reaction may be carried out under either acidic or basic conditions in an aqueous medium with the corresponding elemental halogen. In this way, chloride, bromide, and iodide (but notably not fluoride) functionality can be installed selectively in the alpha position of a ketone.

The position alpha to the carbonyl group in a ketone is easily halogenated, due to the ability to form an enolate in basic solution, or an enol in acidic solution. An example of alpha halogenation is the mono-bromination of acetone, carried out under either acidic or basic conditions, to give bromoacetone:

Acidic (in acetic acid):

Reaction mechanism for the bromination of acetone while in the presence of acetic acid.

Basic (in aqueous NaOH):

Reaction mechanism for the bromination of acetone while in the presence of aqueous NaOH.

In acidic solution, usually only one alpha hydrogen is replaced by a halogen, because each successive halogenation is slower than the first. The halogen decreases the basicity of the carbonyl oxygen, thus making protonation less favorable. However, in basic solution successive halogenations are more rapid due to inductive electron withdrawal by the halogen, making the remaining hydrogens more acidic. In the case of methyl ketones, this reaction often occurs a third time to form a ketone trihalide, which can undergo rapid substitution with water to form a carboxylate in what is known as the haloform reaction.

The regioselectivity also differs: The halogenation of an unsymmetrical ketone in acid results in the more substituted alkyl group being halogenated. A second equivalent of halogen results in the halogenation of the other alkyl substituent (without the halogen). In contrast, in base, an unsymmetrical ketone halogenates at the less substituted alkyl group. Subsequent halogenation (which usually cannot be stopped by control of stoichiometry) occurs at the position which already has a halogen substituent, until all hydrogens have been replaced by halogen atoms. For methyl alkyl ketones (2-alkanones), the haloform reaction proceeds to give the carboxylic acid selectively.