Organic 2: The Hell-Volhard-Zelinsky halogenation reaction

The Hell-Volhard-Zelinsky halogenation reaction, shown in Figure 1, halogenates carboxylic acids at the α carbon.¹

Figure 1.

A carboxylic acid is first reacted with PBr₃ and Br₂. The PBr₃ replaces the OH group of the carboxylic acid with bromine, resulting in a carboxylic acid bromide. The acid bromide can then tautomerize to an enol, which will readily react with the Br₂ to brominate the molecule a second time at the α position. The first step results in a carboxylic acid bromide which is also brominated at the α position.

In a second step, the carboxylic acid may be recovered by reacting the carboxylic acid bromide with water or a weak aqueous acid. This results in the hydrolysis of the acid bromide, which is the displacement of the bromine directly bound to the carbonyl group by an OH group. (The hydrolysis is an example of a nucleophilic acyl substitution.) The final product is the original carboxylic acid brominated at the α position. This is shown in Figure 2 and Figure 3.¹³

Figure 2

Figure 3

The mechanism for the exchange between an alkanoyl bromide and a carboxylic acid is shown in Figure 4.¹ The α-bromoalkanoyl bromide has a strongly electrophilic 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.¹

Figure 4

The formation of dimethylketene is an example of Hell-Volhard-Zelinsky mechanism. The starting reactant is isobutyric acid and forms propanoyl bromide using PBr_2.Dimethylketene is also been prepared by the treatment of α-bromoisobutyryl bromide with zinc and by the pyrolysis of isobutyrylphthalimide, dimethylmalonic anhydride, or α-carbomethoxy-α, β-dimethyl-β-butyrolactone. Dimethylketene dimer has been prepared by heating isobutyryl chloride with a tertiary amine. Pyrolysis of the dimer yields dimethylketene. These steps are shown in Figure 5.⁴