Kinetics and Mechanisms of Cyclization in Acidic Media of N-N-glycine to Hydantoins: Iprodione and Its Isomer

Article abstract of DOI:10.1021/jo00278a037

N-<(3,5-dichloroanilino)carbonyl>-N-<(isopropylamino)carbonyl>glycine (1) cyclizes quantitatively and irreversibly at 50 deg C in the pH range 0.5-6 by two parallel paths to give iprodione (2) and its isomer 3.Formation of the antifungal agent 2 is characterized by a general base catalysis with carboxylate anions, water, and hydroxide ion (β = 0.38) and a solvent isotope effect of 2.90.These results are consistent with a specific base catalyzed addition of the enolate anion of the ureido group to the carboxylic function of hydantoic acid (pK_a1 = 4.25) to givetetrahedral intermediate T^- whose general acid catalyzed decomposition is rate limiting.Formation of isomer 3 occurs by a specific base catalyzed cyclization of 1 compatible with a nucleophilic attack of the enolate anion of the ureido moiety on the carboxylic group in the pH range 2-6.Below pH 2 hydantoic acid undergoes a specific acid catalysed and spontaneous hydrolysis involving a nucleophilic attack of the ureido enol on the carboxylic function, protonated or not, respectively.Formation of iprodione is general base catalysed while that of its isomer is not: this can be explained by the change in basicity of the leaving groups from the tetrahedral intermediate, i.e., the N-<(3,5-dichlorophenyl)ureido> (pK_a2 = 11.7) and the N-isopropylureido (pK_a3 ca. 18) anions, respectively.