Density functional study of the Hoffmann elimination of (N-Cl),N-methylethanolamine in gas phase and in aqueous solution

The molecular mechanism of the Hoffmann elimination involving (N-Cl),N-methylethanolamine and HO− to yield 2-methyleneamino-ethanol has been theoretically characterized by using DFT at the B3LYP/6-31++G∗∗ computing level. The role of water as a solvent was analyzed by using both discrete and hybrid discrete-continuum models. The rearrangement proceeds along a water-assisted asynchronous concerted mechanism. The Gibbs free energy reaction barrier decreases when two water molecules are included in the reaction, one of them acting simultaneously as H+ donor/acceptor to/from the nitrogen/oxygen atom of (N-Cl),N-methylethanolamine, although not involved in a proton relay mechanism, it favours the elimination.