Hydroxylamine Derivatives Research Articles

Hydroxylamine-induced activation of permanganate for enhanced oxidation of sulfamethoxazole: Mechanism and products

Recently, many reagents have been introduced to accelerate the formation of highly reactive intermediate Mn species from permanganate (KMnO4), thereby improving the oxidation activity of KMnO4 towards pollutants. However, most studies have mainly focused on sulfur-containing reducing agents (e.g., bisulfite and sodium sulfite), with little attention paid to nitrogen-containing reducing agents. This study found that hydroxylamine (HA) and hydroxylamine derivatives (HAs) can facilitate KMnO4 in pollutant removal. Taking sulfamethoxazole (SMX) as a target contaminant, the effect of pH, SMX concentration, KMnO4 and HA dosages, and the molar ratio of HA and KMnO4 on the degradation of SMX in the KMnO4/HA process was systematically investigated. Quenching experiments and probe analysis revealed MnO2-catalyzed KMnO4 oxidation, Mn(III) and reactive nitrogen species as the primary active species responsible for SMX oxidation in the KMnO4/HA system. Proposed transformation pathways of SMX in the KMnO4/HA system mainly involve hydroxylation and cleavage reactions. The KMnO4/HA system was more conducive to selective oxidation of SMX, 2,4-dichlorophenol, and several other pollutants, but reluctant to bisphenol S (BPS). Overall, this study proposed an effective system for eliminating pollutants, while providing mechanistic insight into HA-driven KMnO4 activation for environmental remediation.

Exploring Multifaceted Roles of Nitroreductases in Bacterial, Animal and Plant Biosystems and their Detection using Fluorescent Probes

AbstractNitroreductases are the enzymes that can convert nitroaromatic substances including explosives like TNT to their corresponding nitrite, hydroxylamine or amino derivatives with reduced NADH or NADPH as an electron donor. A wide range of nitroreductases are known to present in bacterial genomes that are explored for their potential in the reduction of nitroaromatic compounds and they are used in converting prodrugs to toxic hydroxylamine derivatives causing tumor cell killing. Likewise, in cancer cells, the low oxygen condition called hypoxia is a characteristic of solid tumors and during hypoxia nitroreductase gene expression occurs. Moreover, due to the ability of nitroreductases to reduce nitroaromatic compounds, phytoremediation potential of plants was inspected by expressing bacterial nitroreductase genes in plants through genetic engineering. Due to its diversity and widespread applications in different biosystems, its detection has gained momentum among the scientific community. Designing fluorescent probes for detecting nitroreductases has emerged as a beneficial tool compared to conventional monitoring approaches due to their high sensitivity, selectivity, and real‐time monitoring ability. This review aims to provide an understanding of the activity and the status of nitroreductases in bacteria, plants and animal cells as well as the significance of fluorescent imaging‐related studies by employing recently designed probes.

Nickel-Catalyzed Electrophilic Amination of the Biphenylene C-C σ-Bond.

A nickel-catalyzed three-component carboamination of the biphenylene C-C σ-bond has been developed. Arylboronates and hydroxylamine derivatives work as carbon nucleophiles and nitrogen electrophiles, respectively, and the corresponding difunctionalized ring-opening products are obtained in good yields. The arylboronate nucleophile can be replaced with B2pin2 (boron nucleophile) and H-Si(OMe)3 (hydride nucleophile), thus allowing for the aminoboration and hydroamination of the biphenylene C-C σ-bond under similar nickel catalysis.

The most Recent Compilation of Reactions of Enaminone Derivatives with various Amine Derivatives to Generate Biologically Active Compounds.

Heterocyclic derivatives serve as the fundamental components of both natural and synthetic drugs. Enaminones play a crucial role as foundational units in the synthesis of numerous bioactive heterocyclic compounds, including pyrazoles, pyridines, oxazoles, isoxazoles, as well as fused heterocyclic structures like indoles, carbazoles, quinolines, acridines, and phenanthridines. These diverse heterocyclic rings are well-known for their various therapeutic activities, encompassing anticancer, anti-inflammatory, antimicrobial, antidepressant, and antiviral properties. By reacting with nitrogenbased nucleophiles, enaminones can generate bioactive azoles, azines, and their fused systems. This study focuses on the recent advancements in enaminone reactions with (a) nitrogen-based nucleophiles, such as aliphatic amines, derivatives of aniline, heterocyclic amines, hydroxylamine, hydrazine derivatives, guanidine derivatives, urea, and thiourea derivatives, and (b) nitrogen-based electrophiles, such as diazonium salts. These reactions have led to the synthesis of a wide range of bioactive fused heterocyclic compounds from 2010 to the end of 2022.

Inhibition of kynurenine production by N,O-substituted hydroxylamine derivatives

The inhibition of kynurenine production is considered a promising target for cancer immunotherapy. In this study, an amino acid derivative, compound 1 was discovered using a cell-based assay with our screening library. Compound 1 suppressed kynurenine production without inhibiting indoleamine 2,3-dioxygenase 1 (IDO1) activity. The activity of 1 was derived from the inhibition of IDO1 by a metabolite of 1, O-benzylhydroxylamine (OBHA, 2a). A series of N-substituted 2a derivatives that exhibit potent activity in cell-based assays may represent effective prodrugs. Therefore, we synthesized and evaluated novel N,O-substituted hydroxylamine derivatives. The structure–activity relationships revealed that N,O-substituted hydroxylamine 2c inhibits kynurenine production in a cell-based assay. We conducted an in vivo experiment with 2c, although the effectiveness of O-substituted hydroxylamine derivatives in vivo has not been previously reported. The results indicate that N,O-substituted hydroxylamine derivatives are promising IDO1 inhibitors.

Meta-C-H functionalization of phenylethyl and benzylic alcohol derivatives via Pd/NBE relay catalysis.

The transition metal-catalyzed meta-C-H functionalization of alcohols and their hydroxylamine derivatives remains underdeveloped. Herein, we report an efficient meta-C-H arylation of both phenylethyl and benzylic alcohols and their hydroxylamine derivatives using a readily removable oxime ether directing group. Using electronically activated 2-carbomethoxynorbornene as the transient mediator and 3-trifluoromethyl-2-pyridone as the enabling ligand, this reaction features a broad substrate scope and good functional group tolerance. More importantly, with this oxime-directed meta-C-H functionalization, this method provides a dual approach for efficient access to both meta-substituted alcohols and hydroxylamines using two sets of simple deprotection conditions. This protocol leads to the efficient synthesis of bioactive compounds possessing promising reactivities for the treatment of pulmonary fibrosis.

γ-Lactam synthesis from cyclobutanone via transoximation and the Beckmann rearrangement.

This manuscript describes the synthesis of γ-lactam from the nitrogen insertion reaction of cyclobutanones using an oxime as an aminating reagent with a catalytic amount of Brønsted acid. This method was employed with a more stable oxime reagent, which is a precursor analog of hydroxylamine derivatives with explosive properties. The reaction was tolerated by various substituted cyclobutanones and less strained five- or six-membered ketones. The obtained γ-lactam products could be transformed into γ-aminobutyric acid derivatives via ring-opening hydrolysis. The reaction mechanism is discussed from the perspective of the isotope effect, etc.

Improving the Photovoltaic Properties and Stability of Inverted Perovskite Solar Cells with Hydroxylamine‐Based Additives

AbstractOrganic–inorganic halide perovskite solar cells (PVSCs) are considered a promising emerging photovoltaic technology that offer exceptional optoelectronic properties and the potential for economic solar energy conversion. Additive engineering‐based fabrication processes can achieve highly efficient and stable PVSCs that feature well‐controlled perovskite layers with a dense, uniform, “black” α‐phase crystal structure, as well as large grains and few defects. In this study, several hydroxylamine derivatives are introduced as additives to FAPbI3 precursor solutions to investigate their effects on the performance of PVSCs. The addition of hydroxylamine derivatives suppresses the formation of the unwanted δ‐phase and lead iodide, while the α‐phase cubic structure is preferentially formed without changing the bandgap of FAPbI3. Additionally, the additive‐treated perovskite films show improved stability compared with those without additives. Moreover, using X‐ray diffraction and X‐ray photoelectron spectroscopy analyses, it is discovered that the hydroxylamine‐based additives are not incorporated in the crystal lattices but rather resided on the surface or grain boundaries. Notably, the inverted PVSCs added with N‐methylhydroxylamine exhibit an improved power conversion efficiency, higher stability, and minimal hysteresis.

Theoretical Analysis of a Three-Component Reaction between Two Diazo Compounds and a Hydroxylamine Derivative: Mechanism, Enantioselectivity, and Effect of Cooperative Catalysis.

The mechanism, enantioselectivity, and effect of chiral phosphoric acid (CPA) cocatalyst were investigated by the density functional theory (DFT) for the three-component asymmetric aminohydroxylation between two diazo compounds and a hydroxylamine derivative. This type of cascade process is cooperatively catalyzed by Rh2(OAc)4 and CPA. The obtained results clearly indicate that the first step of the global reaction involves a nucleophilic attack at the nitrogen center of N-hydroxyaniline by rhodium-carbene intermediates producing imines. Subsequently, an enolate intermediate was recognized as the key species generated from the second diazo compound and the leaving benzyl alcohol (BnOH) fragment of the first step and in the presence of the same dirhodium catalyst. Then, the reaction is terminated by the asymmetric Mannich-type addition, delivering the aminohydroxylation products of an S-R conformation with the assistance of chiral phosphoric acid. The distortion/interaction analysis shows that the relative distortions of CPA and the enol play a vital role in the energy ordering of the stereocontrolling transition states (TSs). Furthermore, the influence of different substituents in CPA was fully rationalized by distortion/interaction analysis. This study opens up novel synthetic possibilities and improves the reaction predictability when exploring the related types of cooperatively catalyzed organic transformations.

A Scalable and Metal-Free Synthesis of Indazoles from 2-Aminophenones and In Situ Generated De-Boc-Protected O-Mesitylsulfonyl Hydroxylamine Derivatives.

A one-pot metal-free protocol to access indazoles from easily available 2-aminophenones and hydroxylamine derivatives has been achieved. The reaction is operationally simple, mild, and insensitive to air and moisture. A broad range of indazoles were prepared in good to excellent yield (up to 97% yield), and the reaction displayed a broad functional group tolerance. The reaction was performed at gram scale, and its synthetic application was exhibited through the rapid and efficient preparation of bioactive molecule YC-3 and FDA-approved drug axitinib.

Copper-catalyzed primary amination of arene C[sbnd]H bond with hydroxylamine derivative

A novel methodology for the primary amination of aromatic C(sp2)-H bond utilizing hydroxylamine derivative as ammonia surrogates has been developed. With a cost-effective and convenient copper oxide, a variety of aromatic primary amines were synthesized without external oxidant with moderate to good yields under the mild conditions. This amination exhibits excellent functional group tolerance, wide substrate scope, the use of readily available substrates, and a facile work-up procedure. Furthermore, the late-stage modification of drug-like small molecules with complex structures was also allowed.

Photoredox-Catalyzed Three-Component Amidoheteroarylation of Unactivated Alkenes.

A photoredox-catalyzed 1,2-amidoheteroarylation of unactivated alkenes with O-acyl hydroxylamine derivatives and heterocycles is presented. A range of heterocycles, including quinoxaline-2(1H)-ones, azauracils, chromones, and quinolones, are capable for this process, allowing the direct synthesis of valuable heteroarylethylamine derivatives. Structurally diverse reaction substrates, including drug-based scaffolds, were successfully applied, demonstrating the practicality of this method.

Application of multi-walled carbon nanotubes functionalized with hemin to evaluate the electrochemical behavior of nitrofurazone in aqueous media

A sensor based on a carbon glassy electrode modified with hemin complex and multi-walled carbon nanotubes (MWCNT) was developed as an alternative technique to evaluate the behavior electrochemical of nitrofurazone (NF). This modified electrode showed only one irreversible diffusion-controlled cathodic process in acidic medium, involving four electrons for the hydroxylamine derivative formation with 90 mV potential anticipation and current peak 45 times higher when compared to the bare glassy carbon electrode, GCE. From pH > 9, the NF reduction to hydroxylamine derivative occurred in two steps, being the first one associated to the nitro-anion radical formation in one-electron reversible process. In this case, the reduction potential referring to the radical was anticipated in 250 mV and the peak currents were approximately 13 times higher for sensor modified than those for GCE. The molecular O2 was confirmed as the best radical scavengers against the glutathione and cysteine and it was 4 times more stable on modified sensor than on the GCE.

Chiral-at-Ruthenium Catalysts for Nitrene-Mediated Asymmetric C–H Functionalizations

ConspectusAsymmetric transition metal catalysis is an indispensable tool used both in academia and industry for forging chiral molecules in an enantioselective fashion. Its advancement relies in large part on the design and discovery of new chiral catalysts. In contrast to conventional endeavors of generating chiral transition metal catalysts from carefully tailored chiral ligands, the development of chiral transition metal catalysts containing solely achiral ligands (chiral-at-metal catalysts) has been neglected. This Account presents our recent work on the synthesis and catalytic applications of a new class of C2-symmetric chiral-at-ruthenium catalysts. These octahedral ruthenium(II) complexes are constructed from two achiral bidentate N-(2-pyridyl)-substituted N-heterocyclic carbene (PyNHC) ligands and two monodentate acetonitriles, and the dicationic complexes are typically complemented with two hexafluorophosphate anions. The chirality of these complexes originates from the helical cis-arrangement of the bidentate ligands, thereby generating a stereogenic metal center as the exclusive stereocenter in these complexes. The strong σ donor and π acceptor properties of the PyNHC ligands provide a strong ligand field that ensures a high constitutional and configurational inertness of the helical Ru(PyNHC)2 core, while at the same time, the trans-effect exerted by the σ-donating NHC ligands results in high lability of the MeCN ligands and, therefore, provides high catalytic activity. As a result, this chiral-at-ruthenium catalyst scaffold combines formidable structural robustness with high catalytic activity in a unique fashion. Asymmetric nitrene C-H insertion constitutes an efficient strategy for accessing chiral amines. The direct conversion of C(sp3)-H bonds into amine functionality circumvents the need for using functionalized starting materials. Our C2-symmetric chiral-at-ruthenium complexes display exceptionally high catalytic activity and excellent stereocontrol for various asymmetric nitrene C(sp3)-H insertion reactions. The ruthenium nitrene species can be generated from nitrene precursors, such as organic azides and hydroxylamine derivatives, which undergo ring-closing C-H aminations to afford chiral cyclic pyrrolidines, ureas, and carbamates in high yields and with excellent enantioselectivities at low catalyst loadings. Mechanistically, the turnover-determining C-H insertion is proposed to proceed in a concerted or stepwise fashion, depending on the nature of intermediate ruthenium nitrenes (singlet or triplet). Computational studies revealed that the stereocontrol originates from a better steric fit in combination with favorable catalyst/substrate π-π stacking effects for aminations at benzylic C-H bonds. In addition, we also present our research for exploring novel reaction patterns and reactivities of intermediate transition metal nitrenes. First, we discovered a novel chiral-at-ruthenium-catalyzed 1,3-migratory nitrene C(sp3)-H insertion to convert azanyl esters into nonracemic α-amino acids. Second, we found a chiral-at-ruthenium-catalyzed intramolecular C(sp3)-H oxygenation, thereby allowing for the construction of chiral cyclic carbonates and lactones via nitrene chemistry. We expect that our research program on catalyst development and reaction discovery will inspire the creation of novel types of chiral-at-metal catalysts and drive the development of new applications for nitrene-mediated asymmetric C-H functionalization reactions.

High-Temperature, Solid-Phase Reaction of α-Amino Groups in Peptides with Lactose and Glucose: An Alternative Mechanism Leading to an α-Ketoacyl Derivative.

The reaction of proteins with reducing sugars results in the formation of Amadori products, which involves the N-terminal group and/or ε-amino group of the lysine side chain. However, less attention has been given to the reactivity of the N-terminus of a peptide chain under similar conditions. In our work, we focused on the reaction of the α-amino group of peptides in the presence of a reducing sugar, specifically lactose. We optimized the reaction conditions of model peptides with lactose in the solid phase and showed that temperatures above 120 °C lead to the deamination of the N-terminal amino acid moiety, ultimately resulting in α-ketoacids. We carried out detailed studies to confirm the structure of the deaminated product using analytical methods such as ESI-MS and LC-MS/MS, as well as chemical methods that involved the reduction of the carbonyl group combined with isotopic exchange and the reactivity of the carbonyl group with the hydroxylamine derivative. The structure of the reaction product was also confirmed by chemical synthesis. We suggested plausible mechanisms for the formation of the deaminated product and considered the probable path of its formation. Our aim was to determine whether the reaction proceeds according to the Strecker-based mechanism and direct imine isomerization by carrying out reactions of model peptides in the presence of lactose under aerobic and anaerobic conditions and comparing the results obtained.

Iron-Catalyzed Intermolecular Oxyamination of Terminal Alkenes Promoted by HFIP Using Hydroxylamine Derivatives

An atom-economical intermolecular iron-catalyzed oxyamination of alkenes is described herein. The insertion of oxygenated and nitrogenated moieties from the hydroxylamine substrate was observed with full regio- and chemo-selectivity for terminal alkenes in good yields. HFIP as a solvent appeared to have a synergistic effect with the iron catalyst to promote the formation of the oxyaminated products. Preliminary mechanistic studies suggest a pathway going through an aziridination reaction followed by an in situ ring opening.

Azide-Free Synthesis of N-Alkyliminophosphoranes from Phosphines and Hydroxylamine Derivatives.

A broadly applicable and efficient method for the synthesis of N-alkyliminophosphoranes from phosphines that does not use potentially hazardous alkyl azides is reported. Under iron catalysis, a hydroxylamine-derived triflic acid salt oxidizes phosphines to a wide range of iminophosphorane triflic acid salts. Diphosphines afford phosphine-iminophosphoranes that can serve as ligands in transition metal complexes. The developed method can be employed in the synthesis of mixed diiminophosphoranes and in a traceless Staudinger ligation.

Synthesis of α-Aminophosphonates by Umpolung-Enabled Cu-Catalyzed Regioselective Hydroamination

A copper-catalyzed regioselective hydroamination of α,β-unsaturated phosphonates has been developed to form corresponding α-aminophosphonates of interest in medicinal chemistry. The introduction of an umpolung, electrophilic amination strategy with the hydroxylamine derivative is the key to achieving the α-amination regioselectivity, which is otherwise difficult under the conventional nucleophilic hydroamination conditions with the parent amine. Asymmetric synthesis with a chiral bisphosphine ligand and application to a related silylamination reaction are also described.

Nitrene transfer reaction with hydroxylamine derivatives.

Recent progress on catalytic nitrene transfer reactions with hydroxylamine derivatives as prevalent precursors is summarized in this highlight. The salient features of these N-O derived nitrene transfer reagents are that they are readily available, bench-stable, and can be facilely activated by a range of transition metal-catalysts under mild conditions. The application of these reagents in transition metal-catalysis has led to many new amidation or amination reactions, such as C-H insertions and aziridination of olefins. These reagents have also been applied in difunctionalisation of unsaturated bonds, dearomative amination of indoles, and formation of N-X bonds. Moreover, the recent achievements in photocatalysis and enzyme catalysis further emphasize the importance of these appealing reagents. This highlight provides an overview of these reactions reported in recent years. Challenges and potential opportunities for future developments are also discussed.

Multi-Walled Carbon Nanotubes Functionalized with Hydroxamic Acid Derivatives for the Removal of Lead from Wastewater: Kinetics, Isotherm, and Thermodynamic Studies.

Hydroxamic acids are recognized chelators for various metals; however, using them as functional groups on carbon nanotubes (CNTs) is rare. In this study, novel multi-walled carbon nanotubes (MWCNTs) functionalized with hydroxamic acid derivatives were developed. The MWCNTs were first oxidized, and the resulting product, MWCNT-COOH (A), was treated with oxalyl chloride to yield MWCNT-COCl. The functionalized MWCNTs were susceptible to reacting with the hydroxylamine derivatives of type R–NHOH and produced MWCNTs functionalized with the following hydroxamic acid derivatives (MWCNT-HA): MWCNT-CONOHMe (B), MWCNT-CONOHCOMe(C), and MWCNT-CONOHPh (D). The synthesized derivatives were confirmed by various techniques such as scanning electron microscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy. In order to examine their chelation ability, these materials were examined as possible new adsorbents for harmful Pb(II) particles. The adsorption efficiency of the functionalized MWCNT adsorbents toward Pb(II) was investigated. The effects of the adsorbent dose, temperature, pH, and time on adsorption efficiency were considered, and adsorption boundaries that resulted in enhanced effectiveness were obtained. The developed materials were found to have extraordinary coordination sites, such as amine, hydroxyl, and carboxyl groups, which served as excellent chelating specialists for the Pb(II) particles. Thermodynamic and kinetic investigations revealed the unconstrained nature of the adsorption of Pb(II) by the developed MWCNT adsorbents at room temperature. The adsorption was noted to follow the pseudo-second-order and Langmuir isotherm models.