Hell-Volhard-Zelinsky halogenation

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 and the Russian chemist Nikolay Zelinsky. [cite journal | author= Hell C. | title=Ueber eine neue Bromirungsmethode organischer Säuren| journal= Berichte| volume= 14| year=1881| pages=891–893| doi = 10.1002/cber.188101401187 | url = http://gallica.bnf.fr/ark:/12148/bpt6k90692z/f893.chemindefer] [cite journal | author= Volhard J. | title=Ueber Darstellung α-bromirter Säuren| journal=Annalen der Chemie | volume=242| year=1887| pages=141–16 | doi = 10.1002/jlac.18872420107] [cite journal | author= Zelinsky N. |title=Ueber eine bequeme Darstellungsweise von α-Brompropionsäureester | journal= Berichte| volume=20| year=1887| pages=2026 | url = http://gallica.bnf.fr/ark:/12148/bpt6k907102/f1212.table| doi = 10.1002/cber.188702001452] [OrgSynth | author= Allen C. F., Kalm M. J. |title= 2-Methylenedodecanoic Acid| collvol = 4 | collvolpages = 616 | year = 1963 | prep = cv4p0616]

Scheme

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 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 at below.The α-bromoalkanoyl bromide has a strongly electrophilic (δ+) carbonyl carbon because of the electron-withdrawing effects of the two bromides. The carboxylic acid will act as a nucleophile that the carbonyl oxygen of the carboxylic acid has a partial negative charge (δ-).

References