Models of Water-Assisted Hydrolyses of Methyl Formate, Formamide, and Urea from Combined DFT-SCRF Calculations

Abstract

In this work we present theoretical studies of the hydrolytic reaction of methyl formate, formamide and urea with one water molecule. The studied systems contain two additional water molecules which can act as bifunctional acid-base catalysts. These water molecules catalyze proton transfers between the primary reacting species. Our models describe the concerted transfer of two protons in every reaction step. The calculations have been carried out with the Becke3LYP/6-31G* method. Unspecific solvation effects have been included by means of a polarizable continuum model. Substrate reactivity differences as well as preferences for different reaction pathways can be discussed with the aid of these molecular systems. The studied alternative mechanisms include the common addition-elimination mechanism via a tetrahedral intermediate, and a concerted S_N-like mechanism without a reaction intermediate. Our results suggest that the proved decreasing substrate reactivity in the order ester, amide, urea is caused by a rising resonance stabilization of the reaction centre, and not by a different positive partial charge of the carbonyl carbon. It is also concluded, that the probability of a concerted addition of a nucleophile and elimination of a leaving group without a tetrahedral intermediate rises in the order ester, amide, urea. The ordering of reactivity is not influenced by this behaviour.