Theoretical Chemists on the Cover of the 1000th Issue of Chemistry – A European Journal

A team of theoretical chemists led by Trevor A Hamlin and Matthias Bickelhaupt from AIMMS (Vrije Universiteit Amsterdam) have published a unified model to understand and rationalize the inherent competition between bimolecular nucleophilic substitution (SN2) and base-induced elimination (E2)

12/14/2020 | 2:35 PM

The work by Pascal Vermeeren, Thomas Hansen, Trevor A. Hamlin, Matthias Bickelhaupt of the Department of Theoretical Chemistry and their European collaborators has been published in the 1000th issue of Chemistry – A European Journal, the flagship journal of Chemistry Europe, where it was awarded with an appearance on the cover.

SN2/E2 Competition
The ability to rationally design chemical reactions is one of the fundamental challenges in chemistry. It is, therefore, essential to understand how reactants react with each other. The bimolecular nucleophilic substitution (SN2) and base-induced elimination (E2) reactions are two of the most fundamental reactions in organic chemistry and are in principle always in competition (see the scheme below). Thus, it is vital to have the ability to tune the reactivity of these reactions towards the desired pathway (either SN2 or E2) to improve the yield of the desired product and to minimize the formation of unwanted side products.
A Unified Framework
The team lead by Hamlin and Bickelhaupt have proposed a transparent and physically sound model to explain when an electron-rich Lewis base acts as a nucleophile or a protophile, following the SN2 or E2 reaction pathway, respectively. The authors propose the novel, easy to understand concepts of “characteristic distortivity”, “intrinsic and apparent nucleophilicity”, and “transition state acidity”, which not only have the potential to enable chemists to better understand and design reactions, but will also help to teach the SN2/E2 competition to bachelor and master students.