Alkaline hydrolysis of hydantoin, 3-methylhydantoin, and 1-acetyl-3-methylurea. Effect of ring size on the cleavage of acylureas

Abstract

The alkaline hydrolysis of hydantoin, 3-methylhydantoin, and 1-acetyl-3-methylurea was found to be mainly second order in OH^– at low basicity changing over to first order at higher values. The reaction proceeds by attack of OH^– on the un-ionized substrate with rate-limiting base catalysed breakdown of the tetrahedral intermediate. At high hydroxide ion concentrations the breakdown becomes fast and addition determines the rate. Some interpretations of hydrolysis of hydantoin derivatives have been revised. The effect of ring size on the pK values for deprotonation at the imide nitrogen and on the rates of formation and breakdown of the tetrahedral intermediate has been examined for the five- and six-membered ring acylureas and the open-chain compound. The acidity decreases strongly in this order. The enhanced acidity of the five-membered ring acylureas is further exhibited in the pK value of 13.06 for ionization at N-1 of 3-methylhydantoin. The k⁶ : k⁵ ratio for formation of the tetrahedral intermediate is uniformly ca. 2–3, while for the partitioning ratio for its breakdown, k⁶ : k⁵ is different for the unsubstituted and N-methylated compounds, 0.08 and 1.6, respectively. The open-chain compound adds OH^– an order of magnitude more slowly than the cyclic derivatives. The nature of the effects is discussed.