Terminal Oxidant Research Articles

Gold Catalyzed [3+2] Oxidative Annulation of 1,3‐Enynes with Indoles

AbstractAn efficient new method has been developed for the synthesis of ketone‐integrated cyclopentene‐fused indoline derivatives with a high regioselectivity through gold‐catalyzed oxidative cyclo‐coupling of 1,3‐enynes with indoles by using 2,6‐dichloropyridine N‐oxide as the terminal oxidant. A plausible mechanism has been proposed, in which, a cascade process of nucleophilic trapping of the vinyl gold carbene surrogate with indole followed by the subsequent intramolecular cyclization provides the dearomative formal [3+2] cycloaddition product. In addition, a scale‐up reaction and further derivation via cyclopentene's epoxidation & hydrazone derivative's 1,5‐ electrocyclization have been performed.

Jasmonate-mediated polyamine oxidase 6 drives herbivore-induced polyamine catabolism in rice.

Polyamines (PAs) along with their conjugated forms, are important mediators of plant defense mechanisms against both biotic and abiotic stresses. Flavin-containing polyamine oxidases (PAOs) regulate PA levels through terminal oxidation. To date, the role of PAOs in plant-herbivore interaction remains poorly understood. We discovered that infestation by the brown planthopper (BPH) disrupts PA homeostasis within the leaf sheaths of rice plants, which co-occurs with the upregulation of OsPAO6, a tissue-specific inducible, apoplast-localized enzyme that regulates the terminal catabolism of spermidine (Spd) and spermine. Functional analysis using CRISPR-Cas9 genome-edited plants revealed that pao6 mutants accumulated significantly higher levels of Spd and phenylpropanoid-conjugated Spd in response to BPH infestation compared to wild-type controls. In addition, BPH feeding on pao6 mutants led to increased honeydew excretion and plant damage by female adults, consistent with in vitro experiments in which Spd enhanced BPH feeding. Furthermore, OsPAO6 transcription is regulated by jasmonate (JA) signaling, and it is dependent on MYC2, which directly binds to the G-box-like motif in the OsPAO6 promoter. Our findings reveal an important role of OsPAO6 in regulating polyamine catabolism in JA-induced responses triggered by herbivore attacks in rice.

The Azobis(isobutyronitrile)-Promoted Oxidative Radical α-Cyanation of Imine under Atmospheric O2.

Herein, we report an azobis(isobutyronitrile) (AIBN)-promoted radical α-cyanation of in situ formed imine under atmospheric O2. This oxidative radical addition (ORA) procedure proceeds with the sequential homocleavage of AIBN, extrusion of N2, and capture of O2 toward an O-centered radical, which is converted to a cyano radical by β-scission. Then, the insertion of the cyano radical into the imine C═N bond forms an aminyl radical, leading to α-cyano imine after 1,2-hydrogen atom transfer (HAT) and H abstraction. Such a transition-metal-free procedure features mild reaction conditions and a broad substrate scope, employing molecular O2 as a clean terminal oxidant.

Oxoammonium salts exert antiviral effects against coronavirus via denaturation of their spike proteins

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2) infection has forced social changes worldwide. Development of potent antiviral agents is necessary to prevent future pandemics. Titanium oxide, a photocatalyst, is a long-acting antiviral agent; however, its effects are weakened in the dark. Therefore, new antiviral substances that can be used in the dark are needed. Two types of nitroxyl radicals, 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) and 2-azaadamantane N-oxyl (AZADO), are commonly used as oxidation catalysts utilizing oxygen in the air as the terminal oxidant. Therefore, in this study, we aimed to evaluate the potential of these radicals as antiviral compounds with sustained activity even in the dark. We evaluated the antiviral effects of oxoammonium salts corresponding to TEMPO and AZADO (TEMPO-Oxo and AZADO-Oxo, respectively), which are the active forms of nitroxyl radicals in oxidation reactions. TEMPO-Oxo and AZADO-Oxo inhibited the binding of SARS-CoV2 spike protein receptor-binding domain (S-RBD) to angiotensin-converting enzyme 2. Notably, AZADO-Oxo exhibited a 10-fold stronger inhibitory effect than TEMPO-Oxo. TEMPO-Oxo and AZADO-Oxo also denatured S-RBD; however, effects of AZADO-Oxo were 10-fold stronger than those of TEMPO-Oxo and did not change in the dark. Some S-RBD peptides treated with AZADO-Oxo were cleaved at the N-terminal side of tyrosine residues. TEMPO-Oxo and AZADO-Oxo exhibited concentration-dependent antiviral effects against feline coronavirus. In conclusion, active forms of the nitroxyl radicals, TEMPO-Oxo and AZADO-Oxo, exerted antiviral effects by denaturing S-RBD, regardless of the presence or absence of light, suggesting their potential as novel antiviral agents.

Mn-Catalyzed Aerobic Oxidative α-Cyanation of Tertiary Amines Using Azo/Hydrazide Redox.

Azo compounds such as diethyl azodicarboxylate have been used in oxidative coupling reactions to generate iminium ions from tertiary amines. However, the requirement of stoichiometric amounts of azo compounds limits their large-scale applications. Herein, we present an aerobic oxidative α-cyanation of tertiary amines using catalytic amounts of an azo compound or hydrazine. The developed protocol provides a practical and ecofriendly route for α-cyanated tertiary amines, using molecular oxygen as the terminal oxidant.

Mapping the heterogeneous removal landscape of wastewater virome in effluents of different advanced wastewater treatment systems of swine farm

In advanced wastewater treatment plants on pig farms, meticulous design aims to eliminate intrinsic pollutants such as organic matter, heavy metals, and biological contaminants. In our field survey across Southern China, a notable disparity in wastewater treatment procedures among various farming facilities lies in the utilization of terminal chemical oxidation post-sedimentation tank. However, recent focus in wastewater surveillance has predominantly centered on antibiotic resistance genes, leaving the efficacy of virus removal in different effluent systems largely unexplored. To profile virus composition at the effluent, assess the virus elimination efficiency of chemical oxidation at the effluent end, and the potential environmental driver of virus abundance, we deployed a meta-transcriptomics approach to first determine the total virome in effluent specimens of terminal clean water tank system (CWT) and terminal chemical oxidation system (TCO) in Southern China pig farms, respectively. From these data, 172 viruses were identified, with a median reads per million (RPM) of 27,789 in CWT and 19,982 in TCO. Through the integration of analyses encompassing the co-occurrence patterns within viral communities, the ecology of viral diversity, and a comparative assessment of average variation degrees, we have empirically demonstrated that the procedure of TCO may perturb viral communities and diminish their abundance, particularly impacting RNA viral communities. However, despite the diminished abundance, pathogenic viruses such as PEDV and PRRSV persisted in the effluent following chemical deoxidation at a moderate RPM value, indicating a substantial in situ presence at effluent. Our environmental driver modeling, employing GLM and mantel tests, substantiated the intricate nature of virus community variation within the effluent, influenced heterogeneously by diverse factors. Notably, pond temperature emerged as the foremost determinant, while fishing farming exhibited a positive correlation with virus diversity (p < 0.05). This revelation of the cryptic persistence of virus communities in wastewater effluent expands our understanding of the varied responses of different virus categories to oxidation. Such insights transcend mere virus characterization, offering valuable implications for enhancing biosafety measures in farming practices and informing wastewater-based epidemiological surveillance.

Recent Advances in the Biosynthesis of Mid- and Long-Chain Dicarboxylic Acids Using Terminally Oxidizing Unconventional Yeasts.

As high-performance monomers for the manufacture of polyamide materials, mid- and long-chain dicarboxylic acids (DCAi, i ≥ 6) have received extensive attention from researchers. Biosynthesis is gradually replacing chemical synthesis due to its outstanding advantages in the industrial production of mid- and long-chain dicarboxylic acids, which is mostly achieved by using the strong terminal oxidation ability of nonmodel microorganisms such as Candida tropicalis to oxidize hydrophobic substrates such as alkanes. Here, we first summarize the metabolic pathways of oxidative alkane conversion into dicarboxylic acid by terminally oxidizing unconventional yeasts and the corresponding metabolic engineering strategies. Then, we summarize the research progress on new dicarboxylic acid production processes. Finally, the future development directions in the biosynthesis of mid- and long-chain dicarboxylic acids are prospected from synthetic biology and bioprocess engineering, which can also provide a reference for the synthesis of other biobased chemicals and biomaterials.

Visible-Light-Mediated, Organophotocatalytic C-H Thiocyanation of Pyrazolo[1,5-a]pyrimidines.

Herein, we report a metal-free, organophotoredox-catalyzed sustainable C-H thiocyanation of a biologically active class of N-heterocycles, pyrazolo[1,5-a]pyrimidines, with potassium thiocyanate (KSCN) using 9-mesityl-10-methylacridinium perchlorate as the photocatalyst (PC) and molecular oxygen as the terminal oxidant under blue-light-emitting diode irradiation at room temperature. The developed catalytic protocol features mild reaction conditions, a broad substrate scope, a high yield of products, and a straightforward scalability. Mechanistic studies revealed a radical pathway involving reductive quenching of the PC by KSCN.

Aerobic Copper-Catalyzed Oxysulfonylation of Vinylarenes with Sodium Sulfinates under Mild Conditions: A Modular Synthesis of β-Ketosulfones.

An aerobic copper-catalyzed oxysulfonylation of vinylarenes with sodium sulfinates is described. This protocol features mild reaction conditions, convenient operation, and broad substrate scope with respect to vinylarenes and sodium sulfinates. Notably, the protocol demonstrates excellent tolerance of functional groups such as chloro, bromo, ester, cyano, and nitro groups. Mechanistic investigations indicated that the reaction should undergo radical cascades involving a sulfonyl radical generated from sodium sulfinate with air as the terminal oxidant, addition across alkene to deliver a benzylic radical, and subsequent cross-coupling with air.

Tandem Synthesis of Benzylidenemalononitrile Derivatives in/on Water under Visible Light

AbstractTandem processes are valuable tools that allow to build molecular complexity while reducing waste production and the number of steps of synthetic routes. In this work, the in situ photooxidation of benzyl alcohols to the corresponding benzaldehydes is coupled with a Knoevenagel condensation for the preparation of benzylidenemalononitrile derivatives. In this rapid one‐pot tandem process, sodium anthraquinone‐1,5‐disulfonate (SAS) and β‐alanine are employed as safe and inexpensive catalysts, while air is used as a terminal oxidant. Moreover, using water as reaction medium results in most cases in the precipitation of the target products, thus facilitating their isolation.

Mn‐Catalyzed Three‐Component Coupling Reactions of Carboxylic Acids, Diazo Compounds, and Tertiary Amines for the Synthesis of β‐Amino Esters

ABSTRACTA simple and efficient three‐component coupling reaction of carboxylic acids, diazo compounds, and tertiary amines catalyzed by manganese has been described. This reaction proceeds smoothly under mild conditions to afford various β‐amino esters in moderate to good yields by using O2 as the terminal oxidant. In this process, Mn‐based carbene radical, single‐electron transfer, and nucleophilic attack were fused into a reaction system.

Aerobic Oxidative Synthesis of N‐Containing Heterocycles from o‐Substituted Aniline Derivatives and Primary Amines by Perylene Diimide Catalysis

The commercially available 3,4,9,10‐perylenetetracarboxylic diimide (PTCDI) acted as a heterogeneous catalyst to catalyze aerobic oxidative synthesis of benzimidazoles, benzothiazoles, and quinoxalines from o‐substituted aniline derivatives and primary amines in high yields with oxygen as the terminal oxidant. The gram scale reaction and reusability (up to six cycles) of the PTCDI catalyst were also successful and would greatly benefit industrial applications.

Ligand Oxidation Activates a Ruthenium(II) Precatalyst for C-H Hydroxylation.

A new class of Ru-sulfonamidate precatalysts for sp3 C-H hydroxylation is described along with a versatile process for assembling unique heteroleptic Ru(II) complexes. The latter has enabled structure-performance studies to identify an optimal precatalyst, 2h, bearing one 4,4'-di-tert-butylbipyridine (dtbpy) and one pyridylsulfonamidate ligand. Single-crystal X-ray analysis confirmed the structure and stereochemistry of this adduct. Catalytic hydroxylation reactions are conveniently performed in an aqueous, biphasic solvent mixture with 1 mol % 2h and ceric ammonium nitrate as the terminal oxidant and deliver oxidized products in yields ranging from 37 to 90%. A comparative mechanistic investigation of 2h against a related homoleptic precatalyst, [Ru(dtbpy)2(MeCN)2](OTf)2, convincingly establishes that the former generates one or more surprisingly long-lived active species under the reaction conditions, thus accounting for the high turnover numbers. Structure-performance, kinetics, mass spectrometric, and electrochemical analyses reveal that ligand oxidation is a prerequisite for catalyst activation. Our findings sharply contrast a large body of prior art showing that ligand oxidation is detrimental to catalyst function. We expect these results to stimulate future innovations in C-H oxidation research.

Photocatalytic Pyridine Synthesis with Enaminones and TMEDA under Metal-Free Conditions.

Reported herein is a new photocatalytic annulation for the synthesis of 2,3,4,6-tetrasubstituted pyridines with enaminones and N,N,N',N'-tetramethyl ethylenediamine (TMEDA). The photocatalytic reactions take place without requiring a transition metal reagent and provide products with broad scope. The methyl in TMEDA acts as the carbon source in pyridine ring construction, and BrCF2CO2Et plays the role of the terminal oxidant for free radical quenching.

HCl/DMSO/HFIP-Mediated Chlorination of Pyrrolo[2,1-a]isoquinolines and Other Electron-Rich Heteroarenes.

An efficient oxidative chlorination of pyrrolo[2,1-a]isoquinolines has been established using HCl (aq) as the chlorine source and DMSO as the terminal oxidant in HFIP at ambient temperature. A variety of chlorinated pyrrolo[2,1-a]isoquinoline derivatives have been prepared readily in 23 to 99% yields. This chlorination strategy can be expanded to the functionalization of other electron-rich heteroarenes including substituted pyrroles, indoles, and naphthols.

Iron-Mediated Bromocyclization of Olefinic Amides for the Synthesis of Bromobenzoxazines

AbstractAn iron-mediated bromination/cyclization for the synthesis of bromobenzoxazines from olefinic amides has been successfully developed. In this protocol, the simple iron salt FeBr3 was employed as a bromination reagent, giving the bromobenzoxazine products in moderate to excellent yields. This methodology features good functional group tolerance, gram-scale synthesis, and green reaction conditions by the use of air as the terminal oxidant. Preliminary mechanistic studies suggest that a free radical pathway is involved.

Thermal and Photoinduced Radical Cascade Annulation using Aryl Isonitriles: An Approach to Quinoline-Derived Benzophosphole Oxides.

Herein, we present a radical cascade addition cyclization sequence to access quinoline-based benzophosphole oxides from ortho-alkynylated aromatic phosphine oxides using various aryl isonitriles as radical acceptors and inexpensive tert-butyl-hydroperoxide (TBHP) as a terminal oxidant in the presence of a catalytic amount of silver acetate. Alternatively, the same cascade can be realized through a sustainable photochemical approach utilizing 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) as an organic photocatalyst at room temperature. The introduced modular approach shows broad functional group tolerance and offers straightforward access to complex P,N-containing polyheterocyclic arenes. These novel π-extended benzophosphole oxides exhibit interesting photophysical and electrochemical properties such as absorption in the visible region, emission and reversible reduction at low potentials, which makes them promising for potential materials science applications. The photophysical properties can further be tuned by the addition of external Lewis and Brønsted acids.

Thermische und photoinduzierte Anellierungen über radikalische Kaskaden mit Arylisonitrilen: Ein Zugang zu Chinolin‐abgeleiteten Benzophospholoxiden

AbstractIn diesem Artikel stellen wir eine Kaskade bestehend aus einer radikalischen Addition und Zyklisierung vor, um Chinolin‐basierte Benzophospholoxide aus ortho‐alkinylierten aromatischen Phosphanoxiden zu erhalten. Dabei werden verschiedene Arylisonitrile als Radikalakzeptoren und kostengünstiges tert‐Butylhydroperoxid (TBHP) als terminales Oxidationsmittel in Gegenwart einer katalytischen Menge Silberacetat verwendet. Alternativ kann die Kaskade auch über einen nachhaltigen photochemischen Ansatz unter Verwendung von 1,2,3,5‐Tetrakis(carbazol‐9‐yl)‐4,6‐dicyanobenzol (4CzIPN) als organischem Photokatalysator bei Raumtemperatur realisiert werden. Der vorgestellte modulare Ansatz zeigt eine breite Toleranz gegenüber funktionellen Gruppen und bietet einen einfachen Zugang zu komplexen P,N‐haltigen polyheterozyklischen Arenen. Diese neuartigen π‐erweiterten Benzophospholoxide besitzen interessante photophysikalische und elektrochemische Eigenschaften wie Absorption im sichtbaren Bereich, Emission und eine reversible Reduktion bei niedrigen Potentialen, weswegen sie vielversprechend für potenzielle materialwissenschaftliche Anwendungen sind. Die photophysikalischen Eigenschaften können weiterhin durch Zugabe externer Lewis‐ und Brønsted‐Säuren beeinflusst werden.

Reusable Magnetite Nanoparticle (Fe3O4 NP) Catalyst for Selective Oxidation of Alcohols under Microwave Irradiation.

Iron oxide nanoparticles (NPs) are nontoxic and abundant materials which have long been investigated as reusable catalysts in oxidation reactions, but their use so far has been hampered by a low selectivity. Here, unsupported iron oxide NPs have been found to successfully catalyze the microwave-assisted oxidation of primary and secondary alcohols to their respective aldehydes and ketones with a high selectivity when N-methylmorpholine N-oxide was used as the terminal oxidant. The crystalline phase and size of the iron-based catalyst have a drastic effect on its activity, with small magnetite (Fe3O4) NPs being the optimal catalyst for this reaction. The nanocatalyst could be easily recovered by magnetoseparation and successfully recycled four times without any need for special pretreatment or reactivation step and with a minimal loss of activity. The subsequent loss of activity was attributed to the transition from magnetite (Fe3O4) to maghemite (γ-Fe2O3), as confirmed by X-ray diffraction, Fourier transform infrared, and X-ray absorption near-edge spectroscopy. The nanocatalyst could then be reactivated by the high-temperature microwave treatment and used again for the microwave-assisted oxidation reaction.

A Low-Cost Ecofriendly Oxidation Process to Manufacture High-Performance Polymeric Biosurfactants Derived from Municipal Biowaste.

Biosurfactants account for about 12% of the global value of the surfactant market, which is currently dominated by synthetic surfactants obtained from fossil sources. Yet, the production of biosurfactants from renewable feedstock is bound to increase, driven by the increasing pressure from both society and governments for chemistry-based industries to become more ecofriendly and economically sustainable. A photo-chemical oxidation process is reported here, yielding new biosurfactants from urban biowaste in water that perform as a solvent and terminal oxidant reagent at room temperature without the addition of conventional oxidants and catalysts. Products with 200-500 kDa molecular weight are obtained. They lower the surface tension of water down to 34 mN/m at 0.5-2 g/L concentration. The estimated cost is rather low (0.1-1.5 EUR/kg), which is competitive with the cost of synthetic surfactants but much lower than the cost of the best-performing bacterial surfactants. For the implementation of the photo-chemical oxidation process at the industrial level, the results suggest that the new biosurfactants obtained in the present work may not reach the performance level of the best-performing bacterial surfactants capable of lowering the surface tension of water down to 28 mN/m. Yet, the biosurfactants produced by the photo-chemical process have a greater chance of being marketed on large scales.