The Hell–Volhard–Zelinsky halogenation reaction is a chemical transformation that transforms an alkyl carboxylic acid to the α-bromo derivative. It is a specialized and rare kind of halogenation.^[1][2]

An example of the Hell–Volhard–Zelinsky reaction can be seen in the preparation of alanine from propionic acid. In the first step, a combination of bromine and phosphorus tribromide (catalyst) is used in the Hell–Volhard–Zelinsky reaction to prepare 2-bromopropionic acid,^[3] which in the second step is converted to a racemic mixture of the amino acid product by ammonolysis.^[4][5]

The reaction is initiated by addition of a catalytic amount of PBr₃, after which one molar equivalent of Br₂ is added. PBr₃ converts the carboxylic OH to the acyl bromide. The acyl bromide tautomerizes to an enol, which reacts with the Br₂ to brominate at the α position.In neutral to slightly acidic aqueous solution, hydrolysis of the α-bromo acyl bromide occurs spontaneously, yielding the α-bromo carboxylic acid. If an aqueous solution is desirable, a full molar equivalent of PBr₃ must be used as the catalytic chain is disrupted.

If little nucleophilic solvent is present, reaction of the α-bromo acyl bromide with the carboxylic acid yields the α-bromo carboxylic acid and regenerates the acyl bromide intermediate. In practice a molar equivalent of PBr₃ is often used anyway to overcome the slow reaction kinetics.

The mechanism for the exchange between an alkanoyl bromide and a carboxylic acid is below. The α-bromoalkanoyl bromide has a strongly electrophilic carbonyl carbon because of the electron-withdrawing effects of the two bromides.

By quenching the reaction with an alcohol, instead of water, the α-bromo ester can be obtained.

The reaction is named after the German chemists Carl Magnus von Hell (1849–1926) and Jacob Volhard (1834–1910) and the Russian chemist Nikolay Zelinsky (1861–1953).^[6][7][8]

• Reformatsky reaction