The Catalytic Potential of Substituted Pyridines in Acylation Reactions: Theoretical Prediction and Experimental Validation

A larger number of catalysts based on the 3,4-diaminopyridine motif have been synthesized and tested in the acetylation of tertiary alcohols. The rate data determined in these reactions together with results from previous studies were compared with theoretical data describing the ground and transition state properties of the respective catalysts. Surprisingly, it was found that the ground state data provided a better overall description of the catalytic activity than the transition state models. The latter approach clearly showed the presence of separate correlations for catalysts with small, but significant topological differences. Full analysis of the potential energy surface revealed that this owes to changes in the rate limiting step in the catalytic cycle.