Kinetics of acid-catalyzed cyclization of substituted hydantoinamides to substituted hydantoins

Abstract

The kinetics of acid-catalyzed cyclization of the hydantoinamides type R3-N(5)H-CO-N(3)R2-CH2-CO-N(1)HR1 (R1, R2, R3 = H and/or CH3) has been studied in 0·5 to 5 mol l-1 hydrochloric acid. The cyclization rate is limited by the rate of the attack of nitrogen atom N(5) on the carbon atom of the protonated amide group. The dissociation constants of the protonated hydantoinamides and rate constants of their cyclizations have been determined. Replacement of hydrogen atom by methyl group at the N(5) nitrogen atom accelerates the cyclization about two times., the same substitution at N(3) accelerates about 50x, whereas at N(1) it results in a 300 fold retardation. With the hydantoinamides having R3 = CH3, the cyclization rate of the protonated hydantoinamide increases with increasing concentration of hydrochloric acid, whereas with the other derivatives this value is independent of the acid concentration.