How A-level chemistry solved the 200-year-old problem with the haloform reaction

The 200-year-old haloform reaction has been given a modern makeover. Using rigorous mechanistic studies to inform their strategy, researchers at the University of Bristol drove this reaction to accept secondary alcohols in stochiometric quantities, something never attempted in the reaction’s history.

First discovered in 1822, the haloform reaction converts methyl ketones into carboxylic acids or esters, forming an insoluble haloform as a byproduct. ‘The methyl protons are acidified by virtue of being next to the carbonyl which essentially means that the methyl group CH₃ can be converted into CX₃, the trihalomethyl, which is a leaving group,’ explains Liam Ball, a physical organic chemist at the University of Nottingham who wasn’t involved with the new work. ‘This CX₃ group can then be substituted by either water or alcohol at the carbonyl to make a new C–OH or C–OR bond.’ Both mild and reliable, the reaction became an industrial staple for the synthesis of carboxylic acids and methyl esters, but the requirement for solvent quantities of alcohol limited its application in the synthesis of more complex products.