A fragment based analysis of the S_N2 substitution mechanism for the benzylation of adenine

Presented by: Dominique Buyens

Department of Chemistry, University of Pretoria, E-mail: [email protected]

The S_N2 mechanism for the benzylation of adenine was simulated computationally, using DMSO as the implicit solvent model.  Four paths were computed to investigate reaction at each of the four N-atoms of the purine ring, the N1, N3, N7 and N9 atoms. The results were ambiguous when considering the electronic energies along each reaction path alone.  An approach was developed (employing IQA-defined energy terms and the hardly used concept of interacting quantum fragments, IQF) to study fragment interactions along each reaction path to allow comparison of dominant energy contributors which determine the regio-selectivity of the benzylation.  Although the electronic energies of the reactions paths are similar, the N1/N7 pathways show highly stabilizing interactions arising from the bromine atom with the purine ring.  Such interactions would disadvantage or obstruct these routes.  By contrast, the purine-bromine stabilizing interactions are absent in the N9/N3 pathways and their preference is solely attributed to the formation of the N-C bond. The energetically favoured N9/N3 substitution sites of benzylation occurs after the transition state whereas the N1/N7 reaction paths fail to proceed to the benzylated product due to interference coming from the leaving bromine.  The N9-pathway dominates the N3-pathway at the product formation step, which corresponds to experimental observation having N9-benzyladenine as the major product and N3-benzyladenine being the minor product from the benzylation of adenine.

Date: Friday, 24 July 2015

Time: 11:30

Venue: The Avogadro, Chemistry Building

Enquiries: Dr Lynne Pilcher, [email protected], Prof Ignacy Cukrowski, [email protected]