Theoretical investigation of von Braun and von Braun-like reactions

The von Braun reaction, discovered at the dawn of the past century, consists of the reaction between a tertiary amine and cyanogen bromide. It leads to the cleavage of a CN bond with the formation of an N-dialkylcyanamide and an alkyl bromide and has been extensively used in organic synthesis. A detailed in silico study (PCM/density functional theory [DFT]/B3LYP/6-31++G(d,p) calculations) of this venerable reaction has shown that in the first stage a zwitterionic adduct with a multibonded bromine atom is formed. The widely accepted mechanism involving an S(N)2 reaction occurs in the second step, thus accounting for its selectivity. Quantum chemical calculations were performed for the von Braun-like reactions in systems formed by cyclic tertiary amines (N-alkyl azetidines). In these cases, the first stage is almost the same as in the classical von Braun processes, and selective S(N)2 mechanisms can occur in the second step.