Kinetics and mechanism of hydrolysis of N‐(2′‐hydroxyphenyl)phthalamic acid (1) and N‐(2′‐methoxyphenyl)phthalamic Acid (2) in a highly alkaline medium

Abstract

A kinetic study on hydrolysis of N-(2 -hydroxyphenyl)phthalamic acid (1), N-(2 -methoxyphenyl)phthalamic acid (2), and N-(2 -methoxyphenyl)benzamide (3) under a highly alkaline medium gives second-order rate constants, k OH , for the reactions of HO − with 1, 2, and 3 as (4.73 ± 0.36) × 10 −8 at 35 • C, (2.42 ± 0.28) × 10 −6 and (5.94 ± 0.23) × 10 −5 M −1 s −1 at 65 • C, respectively. Similar values of k OH for 3, N-methylbenzanilide, N-methylbenzamide, and N,N-dimethylbenzamide despite the difference between pK a values of aniline and ammonia of ∼10 pK units are qualitatively explained.

Experimental versus theoretical evidence for the rate‐limiting steps in uncatalyzed and H+‐ and HO−‐catalyzed hydrolysis of the amide bond

“…Perhaps the most careful experimentally determined values of k unc are only for N ‐ n ‐butylacetamide 4, formamide 5,6, and a few dipeptides 7–9 as shown in Table III. The reported values of k H for acetamide 35 and k OH for acetamide 35 and N ‐(2′‐methoxyphenyl)benzamide 36, within the respective temperature ranges 25–50 and 35–65°C show that the empirical factors by which the rate constant changes with the change of every 10 K of temperature are 2.1–2.2 for k OH and 2.7 for k H . Thus, an average value of empirical factor of 2.4 is used to estimate k 0 at a desired temperature from the experimentally deduced k 0 value at a different temperature.…”

“… u C 6 H 5 CON(OMet) represents N ‐(2′‐methoxyphenyl)benzamide, and the values of k H and k OH were obtained from 36. …”