The role of water on the acid-promoted E/Z isomerization of oximes in aqueous solution

Acid-promoted E/Z isomerization of oximes in water is studied by means of theoretical calculations at the B3LYP/6-31G(d,p) level. We have considered a simple derivative, acetaldoxime, as a model to discuss the isomerization mechanism in more complex systems. The solvent is represented by a continuum or by a discrete-continuum model. Our calculations suggest that E/Z isomerization in water occurs through the formation of a protonated oxime-water adduct that involves the creation of a C(oxime)-O(water) bond and lies 14.2 kcal/mol above the separated reactants. In this intermediate, there is a single CN bond and rotation around this bond is free. The previously proposed mechanism assumed water addition to the CN double bond of the oxime with formation of a tetrahedral intermediate To. We predict this mechanism to be significantly less favorable than the one proposed in the present work.