The Hell–Volhard–Zelinsky halogenation reaction halogenates carboxylic acids at the α carbon. The reaction is named after three chemists, the German chemists Carl Magnus von Hell (1849–1926) and Jacob Volhard (1834–1910) and the Russian chemist Nikolay Zelinsky (1861–1953).
Unlike other halogenation reactions, this reaction takes place in the absence of a halogen carrier. The reaction is initiated by addition of a catalytic amount of PBr3, after which one molar equivalent of Br2 is added.
PBr3 replaces the carboxylic OH with a bromide, resulting in a carboxylic acid bromide. The acyl bromide can then tautomerize to an enol, which will readily react with the Br2 to brominate a second time 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 in an example of a nucleophilic acyl substitution. 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 product 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.
- Hell C. (1881). "Ueber eine neue Bromirungsmethode organischer Säuren". Berichte 14: 891–893. doi:10.1002/cber.188101401187.
- Volhard J. (1887). "Ueber Darstellung α-bromirter Säuren". Annalen der Chemie 242: 141–163. doi:10.1002/jlac.18872420107.
- Zelinsky N. (1887). "Ueber eine bequeme Darstellungsweise von α-Brompropionsäureester". Berichte 20: 2026–2026. doi:10.1002/cber.188702001452.
- Allen C. F., Kalm M. J. (1963). "2-Methylenedodecanoic Acid". Org. Synth.; Coll. Vol. 4, p. 616