Substituent effects on ¹⁵N NMR chemical shifts in selected N‐alkylthiohydroxamic acids. A comparative study

Abstract

The 15N NMR spectra of three N-alkyl-delta-carbomethoxyvalerothiohydroxamic acids (2) and six synthesized N-isopropylbenzothiohydroxamic acids (3) were measured and compared with appropriate spectra of structurally similar hydroxylamines (1), benzohydroxamic acids (4), benzamides (5) and thiobenzamides (6). The analysis of the chemical shifts of the thiohydroxamic acids under investigation indicates that the inductive effect of the hydroxyl group rather than steric hindrance is responsible for non-additivity of the effect of substituents. Additionally, N-hydroxyl diminishes the effect of aromatic ring substituents on the 15N chemical shifts in the thiohydroxamic acids 3 which is approximately half that in the respective thiobenzamides 6. The chemical shift values correlate best with Brown's sigma+ parameter.

Mechanism of the Reaction of Lawesson’s Reagent with N‐Alkylhydroxamic Acids

“…However, the 15 N NMR spectrum shows a trace peak due to salt 1a (δ N = -177.5 ppm) in addition to the peak of the adduct 21a salt (δ N = -186.5 ppm). [21] Analysis of the 31 P and 15 N NMR spectra of the reaction mixture rules out the N-O-P (21a) Ǟ N-S-P (21aЈ) isomerisation reaction, which could result in a system with a weak N-S bond. Besides, attempts to capture the product of possible 21aЈ isomerisation by TBDMSCl led to only O-silylated HA 1a (vide supra) (Scheme 8).…”

Cytotoxic and Antioxidant Activities of Benzohydroxamic Acid Analogues

“…In the present study, 20 benzohydroxamic acid analogues, including three new compounds N-isopropyl-benzohydroxamic acids (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13), N-isopropyl-thiobenzohydroxamic acids (14)(15)(16)(17), and N-methyl-benzohydroxamic acids (18)(19)(20) were synthesized and evaluated for their in vitro cytotoxicities against mouse mammary tumor cells as well as antioxidant activities. The aim of this paper was to derive predictive structure-activity relationships for the purpose of improved compound design.…”

“…Analogues (14-17) containing a C=S group exhibited greater cytotoxicities than their corresponding C=O-substituted compounds; especially, in the case of no substituents (14 > 1), 3-methyl (15 > 5), and 3-methoxy substituents (16 > 9), drastic differences were observed. NMethyl-substituted analogues (18)(19)(20) possessed relatively weak activities compared to N-isopropyl derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Among the most active compounds (14)(15)(16)(17), those containing alkoxy groups showed increased cytotoxicity due to the donation of electrons to their aromatic rings, resulting in higher electron density and improved reactivity (16, 17 > 14, 15).…”

“…Interestingly, bulky substituents such as tert-butyl (7), trimethyl (8), and benzyloxy (11) groups increased activity. Antioxidant activities of benzohydroxamic acid analogues (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) were examined for their inhibitory activities against DPPH radical and superoxide anion. As presented in Table 1, all tested compounds dose-dependently scavenged both harmful radicals.…”

“…Among the C=O-substituted compounds, compounds 10 and 11 bearing an electrondonating group at the C-4 position showed strong DPPH radical scavenging properties. Trialkyl substitution within the benzene ring greatly reduced antioxidant activity (8,20). In addition to the cytotoxicity and DPPH scavenging activity results, superoxide anion quenching ability appeared to be most active in compounds 10 and 11 which belong to the C=O series.…”