Hydrolysis of 4-imino-imidazolidin-2-ones in acid and the mechanism of cyclization of hydantoic acid amides

Abstract

The hydrolysis of iminohydantoins generates the same tetrahedral intermediate T as that obtained in the cyclization of hydantoic acid amides to hydantoins. The ratio of the products of imine hydrolysis under kinetic control is determined by the relative height of the barriers of the breakdown of T to amide or to hydantoin. Thus the partitioning of products unequivocally proves which is the rate determining step in the cyclization reaction—formation or breakdown of T. UV and ¹H NMR monitoring of the acid catalyzed hydrolysis of four 5-substituted 4-imino-1-methyl-3-(4-nitrophenyl)imidazolidin-2-ones 1 found hydantoins 3 as the only products. The kinetics of hydrolysis of imines were measured in 0.001–1 M HCl. Contrary to the remaining imines, 1,5-dimethyl-4-imino-3-(4-nitrophenyl)imidazolidin-2-one1b is readily oxidized as stock solution in THF containing peroxides to 1,5-dimethyl-5-hydroxy-4-imino-3-(4-nitrophenyl)imidazolidin-2-one1d. In all cases, hydrolysis was found to be zero order with respect to [H⁺]. As imines are fully protonated under the acidity studied, this is evidence of a transition state of a single positive charge. Comparison of imine hydrolysis rates with previous data on rates of cyclization of the corresponding amides of hydantoic acids allowed conditions (acid concentration, substitution pattern—gem-dimethyl effect) to be found that guaranteed kinetic control of the products obtained. Thus it was unequivocally proven that formation of the tetrahedral intermediate is rate determining in the cyclization of hydantoic acid amides. The small steric effects upon methyl substitution at 5-C and a solvent kinetic isotope effect k_H/k_D of 1.72 favour a mechanism for imine hydrolysis whereby the rate is limited by water attack on the protonated imine concerted with proton transfer from attacking water to a second water molecule.