Density-based quantification of steric effects: validation by Taft steric parameters from acid-catalyzed hydrolysis of esters.

Abstract

The steric effect is one of the most widely used concepts for chemical understanding in publications and textbooks, yet a well-accepted formulation of this effect is still elusive. Experimentally, this concept was quantified by the acid-catalyzed hydrolysis of esters, yielding the so-called Taft steric parameter. Theoretically, we recently proposed a density-based scheme to quantify the effect from density functional theory. In this work, we directly compare these two schemes, one from theory and the other from experiment. To this end, we first establish the ester hydrolysis mechanism with multiple water molecules explicitly considered and then apply the energetic span model to represent the hydrolysis barrier height between the two schemes. Our results show that the barrier height of the reaction series is strongly correlated with both Taft steric parameters from experiment and steric quantification from theory. We also obtained strong correlations with steric potential, steric force, and steric charge from our theoretical scheme. Strong correlations with a few information-theoretic quantities are additionally unveiled. To the best of our knowledge, this is the first time in the literature that such a direct comparison between theoretical and experimental results is made. These results also suggest that our proposed two-water three-step mechanism for ester hydrolysis is effective, and our theoretical quantification of the steric effect is valid, robust, and experimentally comparable. In our view, this work should have satisfactorily addressed the issue of how the steric effect can be formulated and quantified, and thus it lays the groundwork for future applications.