von Braun amide degradation

What is von Braun amide degradation?

The von Braun amide degradation is a chemical reaction that is used to break down amides – organic compounds made up of a nitrogen atom bonded to a carbon atom.

The von Braun amide degradation involving N-alkylbenzamide and phosphorus pentahalide to produce benzonitrile, alkyl halide (or alkylene dihalide), phosphorus oxyhalide, and hydrogen halide is commonly known as the von Braun degradation. The von Braun amide degradation was first reported by von Pechmann in 1895 and confirmed by Ley and Holzweissig in 1903 before it was extensively studied by von Braun in the 1910s.

von Braun amide degradation - general reaction scheme - von Braun degradation
von Braun amide degradation

While it is occasionally referred to as the von Braun reaction, the term von Braun reaction should not be used to avoid confusion with another reaction also named after von Braun (von Braun cyanogen bromide reaction).

von Braun amide degradation - general reaction scheme
von Braun amide degradation

This reaction is generally applicable to amides of aromatic acids and aliphatic acids without α-proton(s). The electronic effect and steric hindrance can influence the reactivity of benzamides with phosphorus pentahalides. The yield of this reaction is proportional to the accessibility of the αN-carbon for nucleophilic attack, which will result in the inversion of configuration for an asymmetric αN-carbon. For instance, the degradation of N-benzoylpiperidine, N-benzoyl-α,α-dimethylpiperidine, and N-benzoyl-α,α,α,α-tetramethylpiperidine with phosphorus pentabromide produces 78%, 19%, and 0% of the corresponding 1,5-dibromopentane, 2,6-dibromoheptane, and 2,6-dimethyl-2,6-dibromoheptane, respectively. The yields of the product in the von Braun degradation for the amides of benzylamines of a given acyl component are found to parallel the relative stabilities of the corresponding benzyl carbonium ions. In contrast, the yields depend on the group in the acyl moiety, particularly on its ability to stabilize a positive charge on the acyl carbon, for the amide of a given benzyl group. Although the steric hindrance from the acyl moiety is negligible, the preparation of alkyl halides with boiling points out of the range of POCl3 and benzonitrile, and the disposal problem of POCl3 are drawbacks of this reaction.