The rates of alkaline hydrolysis of several metaand para-substituted formanilides are nearly independent of the nature of the substituent. pH-reaction rate profiles and entropies of activation are consistent with a mechanism involving rate-limiting general acid-general base catalyzed elimination of arylamine from the tetrahedral adduct of hydroxide ion and the anilide. p-Nitro-and p-cyanoformanilides, which are partially dissociated to unreactive conjugate bases at high pH, are anomalously reactive toward alkaline hydrolysis. The enhanced reactivity of these compounds is attributed to their hydrolysis by a mechanism involving dissociation of a dinegatively charged tetrahedral intermediate into formate ion and arylamide ion. p-Nitroa cetanilide and Nmethyl-p-nitroformanilide are also anomalously reactive, probably for the same reason.Carbonyl-lsO isotope exchange experiments and pH-rate profiles reveal that p-nitroacetanilide hydrolyzes by two processes, one first order in hydroxide ion and the other second order in hydroxide ion. The kinetics of hydrolysis of several N-methyIformanilides suggest that these reactions are mechanistically similar to hydrolyses of the corresponding formanilides.Prior to 1950, little was known about the kinetics of carboxamide saponification; Reid2•3 had investigated the effects of aryl substituents on the rate of alkaline hydrolysis of benzamides, and Crocker4 and Calvet5 had studied the influence of acyl substituents on alkaline hydrolytic reactivity of aliphatic amides.More recently, the effects of amide structure, hydroxide ion concentration, weak acids and bases, solvent composition, temperature, and other variables on the kinetics of alkaline hydrolysis of amides have been the subjects of a number of investigations. These include studies of hydrolyses of aliphatic amides,6-6 chloroacetamides,10 aliphatic and aromatic diamides,11-16 benzamides,9'16-18 glycinamide,19 and urea.20 Kinetic studies of alkaline hydrolysis of a number of N-substituted amides have also been reported. Most of these investigations concerned acetanilides,21-23 acyl-substituted acetanilides,23-32 and N-methylanilides.24,29,33-35 Sa-(1) Submitted by R. C. N. in partial fulfillment of the requirements for the M.A. (1965) and Ph.D. (1971) degrees at the University of California at Santa Barbara.(2) E. E.

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