Amidates as Leaving Groups:  Structure/Reactivity Correlation of the Hydroxide-Dependent E1cB-like Breakdown of Carbinolamides in Aqueous Solution

The kinetic study of the aqueous reaction, between pH 10 and 14, of eight N-(hydroxymethyl)benzamide derivatives in water at 25 °C, I = 1.0 M (KCl), has been performed. In all cases, the reaction proceeds via a specific-base-catalyzed deprotonation of the hydroxyl group followed by rate-limiting breakdown of the alkoxide to form aldehyde and amidate (E1cB-like). Such a mechanism was supported by the lack of general buffer catalysis and the first-order dependence of the rate of reaction at low hydroxide concentrations and the transition to zero-order dependence on hydroxide at high concentration. A ρ-value of 0.67 was found for the Hammett correlation between the maximum rate for the hydroxide independent breakdown of the deprotonated carbinolamide (k 1) and the substituent on the aromatic ring of the title compounds. Conversely, the substituents on the aromatic ring of the amide portion of the carbinolamide had only a small effect on the K a of the hydroxyl group indicating that the amide group does not strongly transmit the electronic information of the substituents. These observations led to the conclusion that the major effect of electronic changes on the amide of carbinolamides is reflected in the nucleofugality of the amidate once the alkoxide is formed and not in the pK a of the hydroxyl group of the carbinolamide.