Mechanism of autoreduction of 2,2,6,6-tetramethyl-1,4-dioxopiperidinium cation in alkaline medium

Abstract

Autoreduction of 2,2,6,6-tetramethyl-1,4-dioxopiperidinium ion to nitroxyl radical in alkaline medium involves a number of parallel and consecutive reactions. The primary products of the reaction of 2,2,6,6-tetramethyl-1,4-dioxopiperidinium with hydroxide ion are three nitroso compounds and N-hydroxy-2,2,6,6-tetramethylpiperidine N-oxide. Isomerization of the nitroso compounds and elimination of acetone from the N-oxide give cyclic hydroxylamines which reduce the initial cation to nitroxyl radical, being oxidized to nitrones.Stable nitroxyl radicals give rise to redox triad consisting of oxoammonium cation R 2 N + =O, nitroxyl radical R 2 N-O · , and hydroxylamine R 2 N-OH (Scheme 1), which possesses a unique set of parameters. Properties of two-electron redox couple R 2 N + =O/R 2 N-OH and one-electron redox couples R 2 N + =O/R 2 N-O · and R 2 N-O · /R 2 N-OH were utilized in such processes as selective oxidation of alcohols [1][2][3][4][5], design of chemical current sources with improved parameters [6,7], suppression of oxidative stress in living organisms [8], and even DNA-mediated signaling by base excision repair enzymes [9]. Oxoammonium derivatives of nitroso ureas were found to exhibit a strong antitumor activity [10,11]. nium salts are the corresponding nitroxyl radicals, it was presumed [12] that hydroxide ion acts as reducing agent in this reaction. Nevertheless, the equilibrium constant calculated from the reduction potentials of 2,2,6,6-tetramethyl-1-oxopiperidinium ion (0.75 V [14]) and hydroxyl radical OH · (1.89 V [15]) is very small, K 1 = k 1 /k -1 ≈ 5 × 10 -20 (Scheme 2).

Effect of the structure of nitroxyl radicals on the kinetics of their acid-catalyzed disproportionation

“…In contrast to them, oxoammonium cation 2o is strongly destabilized by the carbonyl group and the regeneration of the radical 1o after neutralization of its acid solution is negligible. The detailed mechanism of fragmentation of cation 2o is studied in …”

“…The latter is of great importance for usage of nitroxyl radicals as oxidation catalysts, redox mediators in solar cells and batteries active materials. On the other hand, new nitrones or nitroso compounds can be synthesized due to the instability of some oxoammonium cations . Imidazolidine nitroxyl radicals, which can be easily oxidized by RO 2 • radicals to unstable oxoammonium cations, may be used for selective detection of RO 2 • radicals in biological medium …”

Kinetics and thermodynamics of reversible disproportionation–comproportionation in redox triad oxoammonium cations – nitroxyl radicals – hydroxylamines

“…[24] In alkaline medium, the rate of reaction increases, and the composition of the products indicates that the main primary process is an attack of OH À on C-H bonds of the piperidine ring of 2g. [35] K 4 versus pK 3H+…”

Mechanism of autoreduction of bis(4-methoxyphenyl)-oxoammonium perchlorate in aqueous alkali

“…Their catalytic efficiency in aqueous medium is limited by the stability of oxoammonium cations which are converted into nitroxyl radicals and other by-products. The rate of this transformation strongly depends on the structure of oxoammonium ion and pH.For example, autoreduction of 2,2,6,6-tetramethyl-1,4-dioxopiperidinium perchlorate in alkaline medium is determined by the transformation of dioxopiperidinium ion into cyclic hydroxylamines as shown in Scheme 1 [6]. Cyclic hydroxylamines reduce dioxopiperidinium ion to nitroxyl radicals, thus being oxidized to the corresponding cyclic nitrones.…”

“…For example, autoreduction of 2,2,6,6-tetramethyl-1,4-dioxopiperidinium perchlorate in alkaline medium is determined by the transformation of dioxopiperidinium ion into cyclic hydroxylamines as shown in Scheme 1 [6]. Cyclic hydroxylamines reduce dioxopiperidinium ion to nitroxyl radicals, thus being oxidized to the corresponding cyclic nitrones.…”