Dissociation of Hydroxamic Acids: Solvent Effects

Abstract

The dissociation constants of benzohydroxamic, 4-chlorobenzohydroxamic, and 4-nitrobenzohydroxamic acids, and their N-methyl and O-methyl derivatives, were measured spectrophotometrically or potentiometrically in mixtures of 2-propanol and water. The results were extrapolated to zero ionic strength. The ratio of dissociation constants of the N-methyl and O-methyl derivatives can be taken to represent - with some approximation - the ratio of NH and OH acidities of the parent acid. This ratio increases with substitution by electron-attracting substituents, and decreases with solvent permittivity: some irregularities might be attributable to the effects of mixed solvents, It follows that 4-nitrobenzohydroxamic acid behaves essentially as N-acid in all solvents, 4-chlorobenzohydroxamic acid only in 90% 2-propanol or 80% methyl cellosolve. In benzohydroxamic acid the NH and OH acidities are comparable, the latter prevails slightly in water, the former in less polar solvents. Some apparent discrepancies in the literature can be explained in the same terms, only a few results have not yet been explained.

Site of Protonation of Carboxylic and Non-Carboxylic Amides in the Gas Phase and in Water

“…There is also no guarantee that the spectroscopic behavior of alkylated models is exactly the same as that of the compound under study, especially when we are dealing with small changes. [7] We have recently shown that a powerful means to solve this problem is the analysis of the changes in the NMR relaxation time (T 1 ) of all the nuclei which may be ionization sites. [8±10] This is because the NMR relaxation rate of quadrupolar nuclei (e.g.…”

Hydroxamates as Substrates and Inhibitors for FMN-Dependent 2-Hydroxy Acid Dehydrogenases

“…Its K i value at pH 7.5 is nearly two orders of magnitude higher than the substrate K M value; the pK a of the free compound is 8.7 (73), not very different from that of HYPAH. Pending further binding studies as a function of pH, it seems that benzohydroxamate has much less affinity for HAO than the substrate and its product, benzoylformic acid (Table 4), and an affinity similar to that of HYPAH.…”

Ring‐substituted benzohydroxamic acids: 1H, 13C and 15N NMR spectra and NHOH proton exchange

“…2,50,51 The extent and accuracy of our exchange data do not allow tests of more sophisticated models including dimerization and/or conformational changes. 52 -54 Our experiments and calculations may also contribute to the long-debated problem of hydroxamic acid protonation and subsequent hydrolysis.…”

“…Correlations of 44 about half of that in silylated benzohydroximic acids, R-C 6 H 4 -C(OSi) 15 N-OSi (7.7-7.9 ppm) 45 or benzamidoximes, R-C 6 H 4 -C NH 2 15 N-OH (8.6 ppm) 46 and about one-fifth of that in benzaldoximes, R-C 6 H 4 -CH 15 N-OH (15.1 ppm). 47 The 2-chloro derivative is anomalous in several respects.…”

“…2 Although much attention has been given to the above equilibrium, 2 the kinetics of proton exchange between NH and OH groups has not yet been studied (with the exception of oxalohydroxamic acid 3 ), even though it is of key importance to our understanding of the 1 H NMR spectra of HAs. Indeed, such proton exchange dominates the appearance of the spectra in the region υ 8-13 and may be accompanied by a change in conformation.…”