Combined use of kinetic and crystallographic data to probe the hydrolysis of a simple amide

Abstract

The base-catalysed hydrolysis of the formyl derivative of a nitromethylene heterocycle is described. A Brønsted plot of the data gives β= 0.56. The point for water falls on the Brønsted line, which indicates that the water-catalysed hydrolysis involves a transition state in which one molecule of water, acting as a base, abstracts a proton from a nucleophilic water molecule. This result is supported by proton inventory studies. We have also analysed the crystal structures of the amide and of its product of hydrolysis and have identified structural features that are thought to be responsible for facile hydrolysis.