von Braun cyanogen bromide reaction

What is von Braun cyanogen bromide reaction?

In 1900, Scholl and von Braun independently reported the dealkylation of tertiary amines using cyanogen bromide, resulting in disubstituted cyanamides and alkyl bromides. This reaction is commonly referred to as the von Braun cyanogen bromide reaction or von Braun reaction, with cyanogen bromide BrCN being known as the von Braun reagent.

von Braun cyanogen bromide reaction - general reaction scheme
von Braun cyanogen bromide reaction

The resulting cyanamides can be hydrolyzed to carbamates or converted into isoureas by prolonged treatment with alcohol in the presence of an acid. Although the reaction is not highly selective, the reactivity of the three alkyl groups on the nitrogen atoms of the tertiary amines follows the general order in nucleophilic substitution. However, a cyclopropyl ring will not be cleaved as cyclopropyl bromide. In cyclic amines, both cyclic cyanamides and ω-bromoalkyl cyanamides may form, depending on the reactivity of the individual alkyl groups.

The reactivity towards cyanogen bromide BrCN is retarded to a certain level when the nitrogen atom is attached to an aromatic nucleus due to the decreasing basicity of the nitrogen atom. If the aryl component is activated by an electron-donating group, the reaction may lead to the bromination or cyanation of the aromatic nucleus, instead of dealkylation, depending on the solvents used. In a special case, the hydrolysis of acetyldemissidine bromo-cyanamide undergoes a reversible reaction to form an initial alkaloid.

The von Braun reaction can be accelerated by the addition of a Lewis acid such as FeCl3 or SnCl4. However, this reaction is limited to small-scale preparation due to low yields and the toxicity of cyanogen bromide.

The degradation of alkaloids for early structural elucidation and the preparation of alkaloid derivatives frequently employ von Braun reaction. It can also be utilized for the protection of secondary amines.

References

  • Scholl, C. F. and Norr, W., Ber., 1900, 33, 1550
  • von Braun, J., Ber., 1900, 33, 1938
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