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Alpha Halogenation

The α-halogenation of carboxylic acids is achieved with red phosphorus and an excess of molecular bromine.

α-Halogenation of carboxylic acids▶ Watch the video on YouTube
Bromination of butanoic acid with Br₂ and red phosphorus followed by hydrolysis: 2-bromobutanoic acid

The α position of a carboxylic acid is thus functionalized and activated for further reactions.

The reaction was named after its discoverers and developers: Hell-Volhard-Zelinsky (click on each name to read a short biography).

Mechanism

Phosphorus reacts with bromine to form PBr₃

Phosphorus gives electrons to molecular bromine and forms phosphorus tribromide (PBr3).

Click here to revisit other uses of phosphorus tribromide.

Three acid molecules attack the phosphorus of PBr₃ to form a protonated triple anhydride

The central phosphorus of PBr3 is quite electrophilic because it is bonded to three electronegative bromine atoms. It is thus easily attacked even by a weak base such as the oxygen of the carboxyl group.

A triple anhydride is then formed. The oxygen bonded to phosphorus becomes an excellent leaving group. The by-product HBr protonates the C=O group and makes it ready for the bromide nucleophilic addition.

Bromide attacks the carbonyl group, H₃PO₃ is lost and the acid bromide forms, in equilibrium with its enol

The nucleophilic bromide attack leads to an acid bromide. The reaction is quite similar to that of thionyl chloride.

The acid bromide with α-hydrogens is in equilibrium with a few enol molecules.

The bromide reaction produces an intermediate where the attacked carbon turns to sp3 hybridization. From that intermediate phosphorous acid (H3PO3) is lost and the carbon recovers its sp2 hybridization. The few enol molecules in equilibrium react with the excess Br2.

The acid bromide enol reacts with Br₂ to give the α-bromo acid bromide, whose hydrolysis releases the α-bromo acid

Enol molecules break up the bromine molecules in excess. A bromine atom is then added to the double bond ending up at the α position. At this point, the reaction leads to an α-bromo acid bromide. Its mild hydrolysis finally gives the α-bromo carboxylic acid.

α-Halogenation of carboxylic acids is a very useful reaction that allows us to activate the neighboring position to a carboxylic acid function and obtain interesting products such as α-hydroxy and α-amino acids.

α-Bromophenylacetic acid: with water and base it gives an α-hydroxy acid and with ammonia an α-amino acid