Kinetics of electrophilic bromine transfer from N-bromosuccinimide to amines and amino acids

Abstract

The kinetics of the reactions of glycine, sarcosine, 2-aminoisobutyric acid, proline and pyrrolidine with N-bromosuccinimide (NBS) have been studied and it has been found that the rates of formation of the N-bromoamino products are proportional to the NBS and amino substrate concentrations; that they decrease linearly with increasing H⁺ concentration in the –log [H⁺] interval 8.50 to 4.00; and that they are independent of ionic strength and the concentration and nature of the buffer. The second order reaction rate constant increases with the basicity of the amino substrate, ranging from 2.7 × 10⁶ dm³ mol^–1 s^–1 for the formation of N-bromoglycine to 4.74 × 10⁶ dm³ mol^–1 s^–1 for the formation of N-bromopyrrolidine (I= 0.1 mol dm^–3). The activation enthalpies measured for these reactions are small and typical of fast processes while the activation entropies are large and negative and indicative of a highly solvated transition state.

On the basis of these observations, we propose that the N-bromo compounds form via a concerted reaction in which the unprotonated amino group of the substrate attacks the NBS bromine, the overall result being ‘Br⁺’ transfer from the nitrogen atom of NBS to the nitrogen atom of the substrate.