The gem-disubstituent effect—a computational study that exposes the relevance of existing theoretical models

Abstract

The DFT B3LYP/6-31G (d, p) and HF/6-31G calculation results for the cyclization reactions of six different di-substituted 4-bromobutylamines (Brown’s system) reveal that the driving force for accelerations in the rate for intramolecular cyclization compared to the linear unsubstituted compound is due to strain effects (difference in strain energy in the ground state and in the transition state) and not to proximity in the ground state stemming from the distribution of rotational conformations ‘near attack conformation’ (time of residence at a reactive distance). Further, the results indicate that the reaction rate (log k rel) for the intramolecular cyclization process is strongly correlated with the distance between the two reacting centers ( r) and the attack angle ( α). The latter result is the first to correlate strain and reaction rate with geometrical parameters ( r and α).