Schiff bases have been widely used as protective group of the amino group in organic synthesis [1]. The hydrolysis of these compounds has been extensively investigated by Jencks and others empirically [2]. However, to our knowledge there have been no computational attempts to model this process in detail.

The molecular mechanism of imines hydrolysis at neutral pH has been theoretically characterized by using DFT at the B3LYP/6-31++G** computing level. The geometry and energy of all relevant stationary points for several simple imines derived from aliphatic amines were calculated. The reaction proceeds via a stepwise mechanism, as empirically observed (see scheme) [2]. The attack of a water molecule on the C=N double bond takes place in the first step, subsequently the so-formed hemiaminal collapses, leading to the parent amine and carbonyl compounds.

The role of water as solvent was analyzed by using discrete and hybrid discrete-polarized continuum (PCM) models. Discrete water molecules were added to describe the solute-solvent interaction in the first solvation layer, while the PCM model was used to assess the effect of bulk water.

Explicit water molecules showed catalytic effect, lowering the reaction barrier, either by net charge stabilization, or directly participating in the transition structures. Calculations involving the PCM model improve the description of the studied reaction in water, stabilizing the localized charges, and, therefore, modifying significantly the corresponding free energy profile. Quantum chemical calculations revealed the role of water in the title reaction, and the characteristics of the process obtained with water clusters and PCM should hold in the reaction in bulk solvent.

The present study opens the door to the detailed analysis of the molecular mechanism of the hydrolysis of Schiff bases.

[1] P. Bey, J. P. Vevert, Tetrahedron Lett. 1977, 18, 1455-1458.

[2] E. H. Cordes, W. P. Jencks, J. Am. Chem. Soc. 1963, 85, 2843-2848.

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/8313 must be provided.

1. Photoreactivity of β- and γ-Lactams
2. Mechanisms of Direct and TiO₂-Photocatalysed UV-Photodegradation of Environmentally Relevant N-Phenyl Derivatives
3. How do Biocides Derived from Sym-Triazines Start Their Fate?
4. Reduction of SO₂ on Carbons. Reactivity of the Intermediates and Mechanisms of Insertion of Organic Moities on the Carbon Matrix