The HellâÂÂVolhardâÂÂZelinsky halogenation reaction is a chemical transformation that transforms an alkyl carboxylic acid to the ñ-bromo derivative. It is a specialized and rare kind of halogenation.
An example of the HellâÂÂVolhardâÂÂZelinsky 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 HellâÂÂVolhardâÂÂZelinsky reaction to prepare 2-bromopropionic acid, which in the second step is converted to a racemic mixture of the amino acid product by ammonolysis.
The reaction is initiated by addition of a catalytic amount of PBr<sub>3</sub>, after which one molar equivalent of Br<sub>2</sub> is added. PBr<sub>3</sub> converts the carboxylic OH to the acyl bromide. The acyl bromide tautomerizes to an enol, which reacts with the Br<sub>2</sub> to brominate at the ñ position. In neutral to slightly acidic aqueous solution, hydrolysis of the ñ-bromo acyl bromide occurs spontaneously, yielding the ñ-bromo carboxylic acid. If an aqueous solution is desirable, a full molar equivalent of PBr<sub>3</sub> must be used as the catalytic chain is disrupted.
If little nucleophilic solvent is present, reaction of the ñ-bromo acyl bromide with the carboxylic acid yields the ñ-bromo carboxylic acid and regenerates the acyl bromide intermediate. In practice a molar equivalent of PBr<sub>3</sub> 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 ñ-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 ñ-bromo ester can be obtained.
The reaction is named after the German chemists Carl Magnus von Hell (1849âÂÂ1926) and Jacob Volhard (1834âÂÂ1910) and the Russian chemist Nikolay Zelinsky (1861âÂÂ1953).