Oxoammonium Cation Research Articles

Oxidative Cleavage of Aromatic C-O Linkages by Oxoammonium Salts.

Oxidative cleavage of aromatic C(sp2)-O bond is important to the conversion of biomass and plastic wastes into value-added chemicals. Here we put forward the oxidative cleavage of para-C-O bonds in phenolic compounds in use of oxoammonium salts as oxidant and water as the oxygen source. The mechanism is that oxoammonium cation activates water to form hydroxy-oxoammonium adduct and thus realizes the ipso-substitution of 4-alkoxyphenol, which is proved by substituent effect, isotope labelling experiments, and kinetic analysis. Furthermore, this protocol is successfully applied into the depolymerization of both lignin model compounds with α-O-5 and 4-O-5 linkages and polyphenylene oxide (PPO).

Redox factors in the antioxidant activity of nitroxides toward DNA guanyl and 2-deoxyribose-peroxyl radicals

A series of eight nitroxide compounds (four substituted piperidines, three pyrrolidines and one oxo-piperidine) are found to undergo electron transfer to 2’-deoxyribose-peroxyl and the guanyl radical. One-electron oxidation potentials of the nitroxides to oxoammonium cations (oxoammonium reduction potential), E 0’, have been measured against a common redox indicator, chlorpromazine, and found to span the range 751 ± 15 mV to 973 ± 15 mV. Fast chemical reduction of the 2’-deoxyribose-peroxyl radical to the hydroperoxide, generated by • OH radical attack on 2-deoxyribose, dR, in oxygenated aqueous solution, is a redox-dependent reaction, with rate constants of 0.8–3.5 x 107 M−1 s−1.The guanyl radicals, produced upon one-electron oxidation of 2’-deoxyguanosine monophosphate, dG, by the selenite radical, SeO3 • -, react with the nitroxides in a redox-independent reaction with diffusion rate constants of 1–2 x 108 M−1 s−1. These findings represent a possible antioxidant role for nitroxides in the fast chemical repair of DNA radicals, which is supported by an in vitro strand break study using a plasmid.

Harnessing Oxoammonium Salts for Oxidations in Organic Synthesis and Catalysis: Origins and Applications

The oxoammonium cation has been identified as the true oxidant intermediate in many aerobic oxidations promoted by long‐lived nitroxide radicals. Various oxoammonium salts have been synthesized and utilized to perform these oxidation reactions. In addition to alcohol dehydrogenation and oxidative coupling reactions, new types of reactions involving oxoammonium salts have recently been reported. This concept aims to discuss these oxidations from the perspective of reaction mechanisms, with a focus on progress made since 2019. Beyond the electron transfer route for synthesizing oxoammonium salts, four types of reaction mechanisms are included.

Ferrier Glycosylation Mediated by the TEMPO Oxoammonium Cation.

The TEMPO oxoammonium cation has been proven to be both an efficient oxidizing reagent and an electrophilic substrate frequently found in organic reactions. Here, we report that this versatile chemical reagent can also be used as an efficient promoter for C- and N-glycosylation reactions through a Ferrier rearrangement with moderate to high yields. This unprecedented reactivity is explained in terms of a Lewis acid activation of glycal by TEMPO+ forming a type of glycal-TEMPO+ mesomeric structure, which occurs through an extended vinylogous hyperconjugation toward the π*(O═N+) orbital [LP(O1) → π*(C1═C2), π*(C1═C2) → σ*(C3-O3), and LP(O6) → π*(O═N+)]. This enables the formation of the respective Ferrier glycosyl cation, which is trapped by various nucleophiles. The extended hyperconjugation (or double hyperconjugation) toward the π*(O═N+) orbital, which confers the Lewis acid character of the TEMPO cation, was supported by natural bond orbital analysis at the M06-2X/6-311+G** level of theory.

Redox‐Driven Logic Gates Based on Intramolecular Weak Interactions in Pyridyl‐Containing Diarylnitroxides

AbstractA new stable diarylnitroxide with two 2‐pyridyl groups in the ortho‐positions of the phenyl rings, in the close vicinity to the NO fragment, was obtained. Conformational flexibility of the molecule provides stimuli‐responsive reversible on/off switching of the intramolecular interactions, stabilizing the oxidized and reduced states of the nitroxide (due to the n‐π* interaction and the intramolecular H‐bonding, respectively) and giving rise to novel properties. The intrinsic electrofluorochromism of the oxoammonium cation rigidified by the intramolecular N−O bond between the pyridyl lone pair and the O atom was first disclosed. Structural simplicity and facile synthesis of the diarylnitroxide make it promising for creating novel types of redox‐switchable molecular logic gates.

Electrocatalytic Poly(3,4-ethylenedioxythiophene) for Electrochemical Conversion of 5-Hydroxymethylfurfural.

This study investigates the utilization of the conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) as a catalytic material for the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA). PEDOT films doped with different counterions were electrodeposited on graphite foil. In particular, the mobile anion perchlorate and the polymeric ionomers polystyrenesulfonate, Nafion, and Aquivion were used. The electrocatalytic properties of PEDOT films were evaluated toward the TEMPO redox mediator in the absence and the presence of HMF as a substrate for oxidation reactions. The electrocatalytic HMF oxidation was confirmed to occur at PEDOT electrodes, and it was also found that the chemical nature of PEDOT counterions controls the electrocatalytic conversion of HMF by modulating the kinetics of the electrochemical generation of the oxoammonium cation TEMPO(+). Potentiostatic electrolysis experiments showed that both the reference graphite electrode and PEDOT substrates were able to convert HMF to FDCA with an 80% faradaic efficiency (FE) and a >90% yield (FDCA), but, compared to graphite, the complete conversion of HMF to FDCA required a ca. 30% shorter time when using PEDOT electrodes doped with perchlorate or Aquivion, thanks to their ability to sustain a higher current density in the initial phase of the electrolysis. In addition, while all PEDOT films were chemically stable under the electrochemical conditions herein described, only PEDOT films doped with Aquivion were also mechanically robust and stable against delamination. Thus, the new PEDOT/Aquivion composite may represent the best choice for the implementation of PEDOT-based electrodes in TEMPO-mediated electrocatalytic applications.

The Cellular and Organismal Effects of Nitroxides and Nitroxide-Containing Nanoparticles.

Nitroxides are stable free radicals that have antioxidant properties. They react with many types of radicals, including alkyl and peroxyl radicals. They act as mimics of superoxide dismutase and stimulate the catalase activity of hemoproteins. In some situations, they may exhibit pro-oxidant activity, mainly due to the formation of oxoammonium cations as products of their oxidation. In this review, the cellular effects of nitroxides and their effects in animal experiments and clinical trials are discussed, including the beneficial effects in various pathological situations involving oxidative stress, protective effects against UV and ionizing radiation, and prolongation of the life span of cancer-prone mice. Nitroxides were used as active components of various types of nanoparticles. The application of these nanoparticles in cellular and animal experiments is also discussed.

Bifunctional TEMPO-based catalysis boosts luminol electrochemiluminescence for cholesterol sensing

Electrochemiluminesence (ECL) of luminol has been enhanced through the catalysis of various artificial nanomaterials to improve its performance in sensing applications. Herein, we report on a biofunctional-catalytic approach based on a simple organic radical, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), which enhances significantly the ECL emission for both luminol/O2 and luminol/H2O2 systems. The electrochemical studies showed that TEMPO could be oxidized to highly stable oxoammonium cation (TEMPO+) without any interferences of dissolved O2, but was found to improve the oxidation of luminol. On the other hand, TEMPO as an electrocatalyst could make the oxidation of H2O2 more efficient. This bifunctional-catalysis of TEMPO has facilitated the production of L−• in luminol/dissolved O2 system and O2−• in luminol/H2O2 system for ECL generation. Based on the enhanced ECL of luminol/TEMPO/cholesterol oxidase (ChOx)/cholesterol system, an ECL sensor has been designed for the selective and sensitive detection of cholesterol with a linear range between 0.30 μM and 100 μM and a low detection limit of 0.08 μM. Finally, the present work opens new avenues for studying luminol ECL using the bifunctional-catalysis of nitroxyl radicals.

Mechanistic Basis for Oxoammonium Salt‐Mediated Tertiary Alcohol Oxidative Transformation Decoded by Computations and Experiments

AbstractOxoammonium salts have demonstrated superior efficacy as reagents in mediating various reactions involving tertiary alcohols, including the eliminative functionalization of tertiary benzylic alcohols, oxidative rearrangement of tertiary allylic alcohols, and oxidative Nazarov cyclization. These reactions have been believed to be triggered by the addition of alcohols to the N−O double bonds of oxoammonium cations. However, in this work, a combination of density functional theory (DFT) and ab initio molecular dynamics (AIMD) calculations shows that the formation of this adduct is thermodynamically unfavorable. A thorough exploration of the possible mechanisms has shown that the reaction occurs through the ring opening of the oxoammonium cation. The oxoammonium cation acted as a masked tertiary carbocation and triggered the subsequent reactions. The computational results were further supported by control experiments and high‐resolution mass spectroscopy (HRMS) characterization.

PTIO as a redox mediator to enhance organic contaminants oxidation by permanganate

Although permanganate (Mn(VII)) is extensively utilized as a strong oxidizer for the purification of water, the direct reaction rates between some refractory pollutants and Mn(VII) are moderate or relatively low. In this study, we found that 2-phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl (PTIO), could act as a redox mediator to enhance bisphenol A (BPA) degradation by Mn(VII) at pH 5.0 − 9.0, with a removal higher than 80% over 5 min. Moreover, the Mn(VII)/PTIO system is highly efficient toward a broad spectrum of contaminants. Mechanism was elucidated as following: PTIO was oxidized by Mn(VII) to PTIO+, an oxoammonium cation. As a newly generated reactive species, PTIO+ could oxidize organics and be reduced to PTIOH (PTIO hydroxylamine) or PTIO simultaneously. The redox cycle of PTIO in consecutive runs as an electron shuttle proved its stability and reusability in Mn(VII) oxidation. In addition to being an electron shuttle, PTIO also acts as an activator of Mn(VII) to promote the production of MnO2, which plays a vital role in enhancing BPA abatement at the acidic condition. For the purpose of further understanding the interaction between PTIO and target contaminants, three corresponding degradation pathways for BPA were proposed. Notably, the transformation products of BPA coupling with PTIO were detected, indicating PTIO inhibited the self-coupling of BPA and facilitated the ring-opening pathway. In addition, the ubiquitous humic acid has a positive effect on the Mn(VII)/PTIO system, suggesting a high promise of this system for practical application.

Smart superplasticizers based on redox-responsive polymers for rheology control of cementitious materials

A new concept is introduced for active rheology control of cementitious materials using stimuli-responsive polymers. RAFT polymerization of methacrylic acid (MAA) and 2,2,6,6, tetramethyl-4-piperidyl methacrylate (TMPMA) was employed to prepare poly(MAA-co-TMPMA) as precursor for the preparation of poly(MAA-co-TEMPO), a redox-responsive copolymer containing 2,2,6,6-tetramethylpiperidine-1-oxyl group. Poly(MAA-co-TEMPO) is soluble in alkaline water and undergoes a redox switch when electrically triggered, oxidizing the TEMPO group to the oxoammonium cations (TEMPO+). The observed active stiffening control is hypothesized to result from adsorption of the negatively charged copolymer with the TEMPO side chains on cement particles and (partial) desorption of the zwitterionic copolymer with the TEMPO+ side chains. The new chemical admixtures could enhance flowability of cement pastes at low W/C ratio and sharply increase storage modulus when applying an electric potential of 1 V. Poly(MAA-co-TEMPO) acts as smart superplasticizer that can actively alter the rheology of cementitious materials upon applying an electric voltage.

Reducing the Charging Voltage of a Zn–Air Battery to 1.6 V Enabled by Redox Radical-Mediated Biomass Oxidation

Zn–air batteries (ZABs) are one of the promising candidates of future energy storage technology owing to their advantages of high theoretical energy density, high safety, and low cost. However, high voltage polarization and low energy efficiency hinder their practical applications. Herein, we show that the charging voltage of a ZAB can be reduced to ∼1.6 V with a high energy efficiency of ∼70% by adding a redox radical, 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO), and a biomass, glucose, into the electrolyte. Upon charging, the oxidation of TEMPO forming the oxoammonium cation at the cathode catalyzes the oxidation of glucose to generate value-added derivatives. Operando differential electrochemical mass spectrometry, first principle calculations, and ex situ spectroscopic characterizations demonstrate the significant effects of TEMPO and glucose on inhibiting side reactions and dendrite growth of the Zn anode, which endow the TEMPO-mediated ZABs with long-term charging/discharging cycles over 400 h.

On the Reaction Mechanism of the Selective C(sp3)–H Functionalization of N-Benzylpiperidines Mediated by TEMPO Oxoammonium Cation

AbstractThe selective and dual C(sp3)–H oxidation of N-heterocycles to their corresponding 3-alkoxyamino lactams mediated by TEMPO oxoammonium cation (TEMPO+) is turning into a convenient nonmetallic strategy for the rapid functionalization of piperidines and pyrrolidines to bioactive alkaloids. Mechanistic proposal suggests that TEMPO+ prefers to oxidize the endocyclic C–Hα bond of either N-substituted piperidines or pyrrolidines to their corresponding endocyclic iminium intermediates, which are transformed into enamine intermediates, and then trapped by oxoammonium cation. Although the product formation seems to be in concordance with this mechanistic rationale, neither experimental evidence nor theoretical calculations have been reported. Accordingly, the current investigation provides computational findings explaining that the origin of the selective C–Hα oxidation can be attributed to an unprecedented C–H···π interaction between two hydrogen atoms of TEMPO+ with the aromatic ring of the piperidine benzyl group. To prove the existence of the enamine intermediate, we developed an unprecedented transition-metal-free tetra C–H oxidation of two N-benzyl-4-methylenepiperidines. Accordingly, the existence of the elusive enamine intermediate was attained by generating a transitory dienamine intermediate, which was trapped by TEMPO+ and NaClO2­ to give the corresponding 4-(aminooxymethyl)-3,4-epoxy-2-piperidone.

Asymmetric Synthesis of trans-3-Alkoxyamino-4-Oxygenated-2-Piperidones Mediated by Transition-Metal-Free Dual C-H Oxidation and Its CAL-B-Assisted Enzymatic Resolution

A general chemo-enzymatic approach to synthesize both enantioenriched trans-3-alkoxyamino-4-oxy-2-piperidones, which are important scaffold for various naturally occurring alkaloids, is reported. To this end, a selective transition-metal-free dual C−H oxidation of piperidines mediated by the TEMPO oxoammonium cation (TEMPO+) was used, followed by enzymatic resolution of the corresponding alkoxyamino-2-piperidones with Candida antarctica lipase (CAL-B), to yield the title compounds in high enantiomeric excess (ee). The absolute configuration of both enantioenriched compounds was determined using chemical correlation and circular dichroism (CD) spectroscopy. The former method highlights the oxidative ring contraction of the trans-alkoxyamine-2-piperidone ring into its corresponding 2-pyrrolidinone.

Chemoselective oxidation of alcohols in the presence of amines using an oxoammonium salt

The oxidation of alcohols in the presence of reactive amines employing the commercially available oxoammonium cation, “Bobbitt's salt” is described. The oxidation is accomplished under acidic conditions and subsequent treatment with a suitable base affords a convenient one-pot method to access imines in good to excellent isolated yields (74–99%).

Chemoselective Oxidation of Thiols with Oxoammonium Cations.

The oxidation of various aryl and aliphatic thiols with the commercially available and environmentally benign reagent Bobbitt's salt (1) has been investigated. The reaction affords the corresponding disulfide products in good to excellent yields (71-99%) and can be accomplished in water, methanol, or acetonitrile solvent. Moreover, the process is highly chemoselective, tolerating traditionally oxidation-labile groups such as free amines and alcohols. Combined experimental and computational studies reveal that the oxidation takes place via a polar two-electron process with concomitant and unexpected deoxygenation of the oxoammonium cation through homolysis of the weak N-O bond, differing from prototypical radical-based thiol couplings. This unusual consumption of the oxidant has significant implications for the development of new nitroxide-based radical traps for probing S-centered radicals, the advancement of new electrochemical or catalytic processes involving nitroxide/oxoammonium salt redox couples, and applications to biological systems.

Abatement of Organic Contaminants by Mn(VII)/TEMPOs: Effects of TEMPOs Structure, Organic Contaminant Speciation, and Active Oxidizing Species.

In this study, a representative redox mediator, 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), and its para-substituted derivatives (TEMPOs: 4-hydroxyl-TEMPO, 4-acetylamino-TEMPO, and 4-amino-TEMPO) significantly accelerated the abatement of trace organic contaminants (TrOCs, i.e., bisphenol-A (BPA), phenol, amines, and phenylbutazone) by Mn(VII) over a wide pH range of 4.0-9.0. The addition of substituents at para to the > N-O• moiety significantly influenced the degradation kinetics of TrOCs by changing the reduction potentials of TEMPOs and the corresponding oxoammonium cations (TEMPOs+); a linear relationship was observed between the substituents' para Hammett sigma constants and the reduction potentials of TEMPOs and TEMPOs+. Pseudo-first-order reaction rate constants (kobs, min-1) of TrOC degradation by Mn(VII)/TEMPOs were also affected by the pKa of the TrOCs. Generally, the highest kobs values for individual TrOCs were observed at pH near the pKa even for TEMPOs+ with relatively pH-invariant reduction potentials. Overall, TrOC abatement kinetics were related to a combination of reactive species (Mn(VII), in situ formed MnO2, and TEMPOs+). For BPA, the relative contributions (R) of reactive species ranked as R(TEMPOs+) > R(Mn(VII)) > R(in situ formed MnO2) at pH 4.0-8.0, whereas R(Mn(VII)) > R(TEMPOs+) at pH 9.0 mainly owing to a change in BPA speciation as the pH approached the pKa1 value for BPA. The results of this study are useful for the development of heterogeneous TEMPO-based redox mediators and future applications of TEMPO-mediated oxidation systems for accelerated abatement of TrOCs in water.

Stability of TMA-TEMPO-based aqueous electrolytes for redox-flow batteries

The TEMPO scaffold is one of the most prominent used posolyte systems in organic redox flow batteries (RFBs). While the aminoxyl radical is well known for his extraordinary stability, there are only a few studies investigating the stability of the respective oxoammonium cation. In this study, we utilize battery experiments to quantify the fade rate of the oxoammonium cation derived from N,N,N-2,2,6,6-heptamethylpiperidinyloxy-4-ammonium chloride (TMA-TEMPO) in correlation with temperature and time. The observed capacity decay is mostly caused by a deactivation of the oxidized TMA-TEMPO yielding the corresponding hydroxylamine, which can mostly be regenerated by reoxidation. Additionally, unbalanced compositionally symmetric flow cells are used to compare the fade rate at different temperatures combined with varying hold times showing a strong dependency on temperature and residence time in high states of charge. The acquired results are used for a use-oriented cycling program comprising a single cycle per day. Furthermore, GC-HRMS and isotopic labeling are used to analyze the volatile decomposition products of heated and oxidized TMA-TEMPO, identifying key intermediates of the decomposition mechanism and the role of an aqueous environment.

Boron complexes of π-extended nitroxide ligands exhibiting three-state redox processes and near-infrared-II (NIR-II) absorption properties

Persistent radicals have attracted increasing attention owing to their fascinating properties, including multi-step redox and long-wavelength absorption characteristics. In this study, boron complexes with π-extended nitroxide ligands were synthesised via Buchwald-Hartwig amination reactions of the corresponding boron-nitroxide complex and diarylamines. These nitroxide complexes exhibited two-step and reversible one-electron oxidation processes, suggesting stable redox triads involving anionic aminoxide, neutral nitroxide-radical, and cationic oxoammonium ligands. Cationic boron complexes of the nitroxide radical ligands were obtained via chemical oxidation of the aminoxide complexes and structurally characterised. The cationic nitroxide-radical complexes exhibited strong absorptions at approximately 1100 nm, demonstrating their potential as near-infrared (NIR)-II-active functional dyes.

Water oxidation at low potential exploiting a nitroxide/oxoammonium ion redox couple as mediator

Chemical or electrochemical oxidation of a nitroxide radical leads to formation of an oxoammonium cation (OAC). OAC is able, in basic aqueous solution, of water oxidation with the formation of oxygen, while OAC reduces back to the initial radical.