Proton Inventory Study of the Base-Catalyzed Hydrolysis of Formamide. Consideration of the Nucleophilic and General Base Mechanisms

Abstract

An NMR study of the rates of hydroxide-promoted hydrolysis of formamide in aqueous media of varying mole fraction D(2)O (n) was performed at [LO(-)] = 1.42 M, T = 25 degrees C, to shed light on whether the mechanism involves a nucleophilic attack of HO(-) on the C=O or HO(-) acting as a general base to remove a proton from an attacking water. The solvent deuterium kinetic isotope effect under these conditions is inverse, k(OH)/k(OD) = 0.77 +/- 0.02 or k(OD)/k(OH) = 1.30 +/- 0.03. Proton inventory analysis of the k(n)() versus n data was undertaken through NLLSQ fits to equations representing four possible mechanisms encompassing nucleophilic and general base ones with waters of solvation on the attacking hydroxide, and with or without waters of solvation on the developing amide hydrate oxyanion. Both nucleophilic and general base mechanisms can be accommodated, but there are restraints on each that are discussed. The preferred mechanism is a nucleophilic one proceeding through a transition state having two solvating waters remaining on the attacking hydroxide and three additional waters attached to the developing amide hydrate oxyanion.

Hydrolysis kinetics and mechanism of adipamide in high temperature water

“…Therefore, a noncatalytic, water-assisted mechanism may also be possible for the hydrolysis of ADAM in HTW. Based on the experimental results and the theoretical study on the amide hydrolysis (González and Montané, 2005;Itami et al, 2004;Slebocka-Tilk et al, 2003), we present one possible reaction mechanisms for ADAM hydrolysis in near-neutral HTW to illustrate a possible role for water during the hydrolysis process. Fig.…”

“…Thus this system has relevance for living systems (Marlier et al, 1999;Lebocka-Tilk et al, 2003) and it has been studied extensively near room temperature (Crespo et al, 2005;Brown et al, 1992). Hydrolysis of amides in HTW is very likely to occur during the hydrothermal processing of protein-containing biomass.…”

Presence or absence of a novel charge-transfer complex in the base-catalyzed hydrolysis of N-ethylbenzamide or ethyl benzoate

“…For the base-catalyzed amide hydrolysis, Brown and co-workers made extensive studies of the carbonyl 18 O exchange and D 2 O solvent kinetic isotope effects [21–25]. They suggested intervention of a pair of a zwitterion and OH − as well as that of the anionic tetrahedral intermediate (Scheme 1).…”

The enthalpy and entropy of activation for ethyl acetate saponification

“…A nuclear magnetic resonance study was performed to the rates of hydroxide-promoted hydrolysis regarding formamide within an aqueous media of varying mole fraction D 2 O to shed light on whether this mechanism involves a nucleophilic attack of OH − on the C O or OH − , acting as a general base for removing protons from an attacking water. Both nucleophilic and general base mechanisms can be accommodated, but there are restraints on each mechanism, as discussed in [10].…”