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 C─N 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.