Kinetics and mechanism of cyclisation of N-(methylaminocarbonyl)glycine to 3-methylimidazolidine-2,4-dione

Abstract

The dependence of rate coefficients for cyclisation upon acidity, solvent isotope effects, and the kinetics of oxygen exchange of the product, support the view that in the acid catalysed cyclisation there is rate-determining ring closure of the neutral substrate synchronous with protonation of the carboxy oxygen. This is contrary to what current views of the mechanism of acid-catalysed amide hydrolysis would lead one to expect; reasons for this are discussed. The kinetics of the uncatalysed cyclisation and of the reverse ring opening reaction in alkali are reported, and a mechanistic scheme for the whole pH range is presented. The equilibrium constant of the title reaction in water at 25 °C is shown to lie between 10³ and 10⁶; the slowness of the reaction at central values of pH prevents a closer estimate.