Oxidative Coupling Research Articles

Iodine-Promoted Thioylation and Dicarbonylation of Enaminone α-C Sites: Synthesis of Fully Substituted Thiazoles via C═C Bond Cleavage.

A novel iodine-promoted difunctionalization of α-C sites in enaminones was demonstrated as a means of synthesizing a variety of fully substituted thiazoles by constructing C-C(CO), C-S, and C-N bonds. This transformation allows the realization of enaminones as unusual aryl C2 synthons and simultaneously allows the thioylation and dicarbonylation of α-C sites. A preliminary mechanistic study was performed and indicated that the cleavage of C═C bonds in enaminones involves a bicyclization/ring-opening and oxidative coupling sequence.

Cyclo[2]pyridine[8]pyrrole: An Expanded Porphyrinoid with Three Closed-Shell Oxidation States.

We report here an expanded porphyrinoid, cyclo[2]pyridine[8]pyrrole, 1, that can exist at three closed-shell oxidation levels. Macrocycle 1 was synthesized via the oxidative coupling of two open chain precursors and fully characterized by means of NMR and UV-vis spectroscopies, MS, and X-ray crystallography. Reduction of the fully oxidized form (1, blue) with NaBH4 produced either the half-oxidized (2, teal) or fully reduced forms (3, pale yellow), depending on the amount of reducing agent used and the presence or absence of air. Reduced products 2 or 3 can be oxidized to 1 by various oxidants (quinones, FeCl3, and AgPF6). Macrocycle 1 also undergoes proton-coupled reductions with I-, Br-, Cl-, SO32-, or S2O32- in the presence of an acid. Certain thiol-containing compounds likewise reduce 1 to 2 or 3. This conversion is accompanied by a readily discernible color change, making cyclo[2]pyridine[8]pyrrole 1 able to differentiate biothiols, such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH).

Determination of Micro Amounts of Promethazine Hydrochloride in Pure and Pharmaceutical Samples Using UV- Visible Spectrophotometry

This study presents the development of a novel, facile, and overly sensitive spectrophotometric approach for quantifying promethazine hydrochloride (PRO) within its pharmaceutical formulations. The method capitalizes on an oxidative coupling reaction, achieved through the oxidation of the compound in an acidic milieu utilizing ammonium cerium (IV) sulfate dehydrate (Ce+4) solution. This process leads to the creation of a green-colored solution, which, upon conjugation with 5-aminosalicylic acid, exhibits maximum absorption at a wavelength of 598 nm. The methodology investigated several parameters, encompassing oxidation duration, temperature, quantities of oxidizing agent and coupling reagent, and determining the stoichiometric ratio between promethazine hydrochloride and 5-aminosalicylic acid. The established ratio was confirmed to be 1:1. Numerous organic solvents were evaluated, with water emerging as the optimal choice due to its pronounced absorption characteristics at the 598 nm wavelength. The applicability of Beer's law was verified over a concentration range of 2 - 28 μg/mL of promethazine hydrochloride, with a calculated molar absorption coefficient of 1.9606 x 104 L/mol∙cm. The Sandell sensitivity index was determined as 0.0164 μg/cm2, while the relative standard deviation (RSD) ranged from 0.8553- 1.2671%. Notably, recovery percentages were also within the 99.88 – 100.34% range. The efficacy of this technique was effectively demonstrated through its successful application in the analysis of pharmaceutical formulations containing promethazine hydrochloride, employing the standard method as a benchmark.

Mn(II) Promoted Divergent-Convergent Domino Reaction Giving Dinuclear Tetrasubstituted Pyrrole Complex.

Domino reaction of benzo[d]thiazole-2-methylamine (S1) has been developed in the presence of MnCl2 ⋅ 4H2O, leading to tetrasubstituted pyrrole coordinated dinuclear Mn(II) complex 1 ([MnClP]2, P-=2,3,4,5-tetrakis(benzo[d]thiazol-2-yl)pyrrol-1-ide). The reaction process has been studied by assigning a series of intermediates based on time-dependent mass spectrometry, control experiments, crystallography, and density functional theory (DFT) theoretical calculation. A plausible mechanism involving an unprecedented divergent-convergent domino sequence has been proposed. Compound S1 could be activated by MnCl2 ⋅ 4H2O via coordination, which divergently produces two intermediates imine II (1-(benzo[d]thiazol-2-yl)-N-(benzo[d]thiazol-2-ylmethyl)methanimine) and alkene C (1,2-bis(benzo[d]thiazol-2-yl)ethene) through oxidative self-condensation and free radical coupling followed by elimination, respectively. They could then react with each other convergently via formal [3+2] cycloaddition to give deprotonated tetrasubstituted pyrrole coordinated intermediate [MnClP] after aromatization. Dimerization of [MnClP] produces the final product 1. Three C-C bonds and one C-N bond are formed through this six-step domino sequence. The corresponding organic skeleton (HP: 2,2',2'',2'''-(1H-pyrrole-2,3,4,5-tetrayl)tetrakis(benzo[d]thiazole)) has been obtained from 1 and shows a higher fluorescent quantum yield (52 %) than the reported 3,4-diphenyl substituted analogue 2,2'-(3,4-diphenyl-1H-pyrrole-2,5-diyl)bis(benzo[d]thiazole) (DPB) (42 %).

A review of carbon-based catalysts and catalyst supports for simultaneous organic electro-oxidation and hydrogen evolution reactions

Producing organic electro-oxidation and hydrogen evolution reactions (HER) simultaneously in an electrolytic cell is an appealing method for generating valuable chemicals at the anode while also producing H2 at the cathode. Within this framework, the task of designing energy-saving electrocatalysts with high selectivity and stability is a considerable challenge. Carbon-based catalysts, along with their supports, have emerged as promising candidates due to their diverse sources, large specific surface area, high porosity and multidimensional characteristics. This review summarizes progress from 2012 to 2022, in the use of carbon-based catalysts and their supports for organic electrooxidation and HER. It delves into outer-sphere electrooxidation mechanisms involving molecule-mediated oxidation and oxidative radical coupling reactions, as well as inner-sphere electrooxidation mechanisms, encompassing both acidic and alkaline electrolytes. The review also explores prospective research directions within this domain, addressing various aspects such as the design of electrocatalytic materials, the study of the relationship between the structure and properties of electrocatalysts, as well as examining their potential industrial applications.

Polyoxometalate-dependent Photocatalytic Activity of Radical-doped Perylenediimide-based Hybrid Materials.

Inorganic-organic hybrid materials are a kind of multiduty materials with high crystallinity and definite structures, built from functional inorganic and organic components with highly tunable photochemical properties. Perylenediimides (PDIs) are a kind of strong visible light-absorbing organic dyes with π-electron-deficient planes and photochemical properties depending on their micro-environment, which provides a platform for designing tunable and efficient hybrid photocatalytic materials. Herein, four radical-doped PDI-based crystalline hybrid materials, Cl4-PDI⋅SiW12O40 (1), Cl4-PDI⋅SiMo12O40 (2), Cl4-PDI⋅PW12O40 (3), and Cl4-PDI⋅PMo12O40 (4), were attained by slow diffusion of polyoxometalates (POMs) into acidified Cl4-PDI solutions. The obtained PDI-based crystalline hybrid materials not only exhibited prominent photochromism, but also possessed reactive organic radicals under ambient conditions. Furthermore, all hybrid materials could be easily photoreduced to their radical anions (Cl4-PDI⋅-), and then underwent a second photoexcitation to form energetic excited state radical anions (Cl4-PDI⋅-*). However, experiments and theoretical calculations demonstrated that the formed energetic Cl4-PDI⋅-* showed unusual POM-dependent photocatalytic efficiencies toward the oxidative coupling of amines and the iodoperfluoroalkylation of alkenes; higher photocatalytic efficiencies were found for hybrid materials 1 (anion: SiW12O40 4-) and 2 (anion: SiMo12O40 4-) compared to 3 (anion: PW12O40 3-) and 4 (anion: PMo12O40 3-). The photocatalytic efficiencies of these hybrid materials are mainly controlled by the energy differences between the SOMO-2 level of Cl4-PDI⋅-* and the LUMO level of the POMs. The structure-photocatalytic activity relationships established in present work provide new research directions to both the photocatalysis and hybrid material fields, and will promote the integration of these areas to explore new materials with interesting properties.

Selective oxidative coupling of amines through light‐activated bismuth halide perovskites

AbstractBismuth halide perovskites have emerged as promising alternatives for sustainable and efficient photocatalysts for light‐induced organic transformations. Caesium bismuth halide perovskites (Cs3Bi2(ClxBr1‐x)9) with different ratios of chloride and bromide were synthesised using a one‐step solution process. These perovskites were then employed as photocatalysts for the photocatalytic oxidative coupling of benzylamine (BZA) to produce N‐benzylidenebenzylamine (BZI) under ultraviolet‐visible light radiation at ambient conditions. The incorporation of bromide ions into the chloride‐based perovskite resulted in a noticeable reduction in the bandgap, leading to an enhancement in the photocatalytic activity. Conversely, the addition of chloride ions within the bromide‐based perovskite was found to be beneficial for the material's photostability while simultaneously maintaining its high photocatalytic activity. The optimal compromise between the stability and photocatalytic activity for the BZI production was achieved using Cs3Bi2(Cl0.8Br0.2)9, being attained a total BZA conversion and the maximum BZI production with 100 % of selectivity after 6 hours of irradiation. The efficiency of this photocatalyst was ascribed to the highest current density observed during the photocurrent experiments, which improves the charge carrier mobility of the resulting material.

Oxidative coupling of methane using oxidant mixtures of CO2 and O2 over Sr/La2O3

Oxidative coupling of methane with CO2 (CO2-OCM) is beneficial because it avoids complete oxidation, an undesired reaction that occurs during O2-oxidative coupling of methane. Previous literature has sparsely considered the respective roles of CO2 and O2 as reactants at CO2-OCM reaction conditions. This work explores the roles of CO2 and O2 in OCM over Sr/La2O3 with different reactant oxidant mixtures. While CO2 alone did not significantly activate methane at 875 °C, a tenfold increase in C2 yield resulted from adding 2 % O2. The role of CO2 in heterogeneous reactions was supported by XPS and XRD, which showed presence of carbonate species on the catalyst surface while the bulk phase remained La2O3. The work shows that a small amount of gaseous oxygen in the reactants can greatly improve methane conversion, and while oxygen is crucial in converting methane, CO2 plays an important role during ethane dehydrogenation.

Divergent Bimetallic Mechanisms in Copper(II)-Mediated C-C, N-N, and O-O Oxidative Coupling Reactions.

Copper-catalyzed aerobic oxidative coupling of diaryl imines provides a route for conversion of ammonia to hydrazine. The present study uses experimental and density functional theory computational methods to investigate the mechanism of N-N bond formation, and the data support a mechanism involving bimolecular coupling of Cu-coordinated iminyl radicals. Computational analysis is extended to CuII-mediated C-C, N-N, and O-O coupling reactions involved in the formation of cyanogen (NC-CN) from HCN, 1,3-butadiyne from ethyne (i.e., Glaser coupling), hydrazine from ammonia, and hydrogen peroxide from water. The results reveal two different mechanistic pathways. Heteroatom ligands with an uncoordinated lone pair (iminyl, NH2, OH) undergo charge transfer to CuII, generating ligand-centered radicals that undergo facile bimolecular radical-radical coupling. Ligands lacking a lone pair (CN and CCH) form bridged binuclear diamond-core structures that undergo C-C coupling. This mechanistic bifurcation is rationalized by analysis of spin densities in key intermediates and transition states, as well as multiconfigurational calculations. Radical-radical coupling is especially favorable for N-N coupling owing to energetically favorable charge transfer in the intermediate and thermodynamically favorable product formation.

N1-methylation of adenosine (m1A) in ND5 mRNA leads to complex I dysfunction in Alzheimer's disease.

One mechanism of particular interest to regulate mRNA fate post-transcriptionally is mRNA modification. Especially the extent of m1A mRNA methylation is highly discussed due to methodological differences. However, one single m1A site in mitochondrial ND5 mRNA was unanimously reported by different groups. ND5 is a subunit of complex I of the respiratory chain. It is considered essential for the coupling of oxidation and proton transport. Here we demonstrate that this m1A site might be involved in the pathophysiology of Alzheimer's disease (AD). One of the pathological hallmarks of this neurodegenerative disease is mitochondrial dysfunction, mainly induced by Amyloid β (Aβ). Aβ mainly disturbs functions of complex I and IV of the respiratory chain. However, the molecular mechanism of complex I dysfunction is still not fully understood. We found enhanced m1A methylation of ND5 mRNA in an AD cell model as well as in AD patients. Formation of this m1A methylation is catalyzed by increased TRMT10C protein levels, leading to translation repression of ND5. As a consequence, here demonstrated for the first time, TRMT10C induced m1A methylation of ND5 mRNA leads to mitochondrial dysfunction. Our findings suggest that this newly identified mechanism might be involved in Aβ-induced mitochondrial dysfunction.

Structural Conjugation Tuning in Covalent Organic Frameworks Boosts Charge Transfer and Photocatalysis Performances.

Structural conjugation greatly affects the optical and electronic properties of the COF photocatalyst. Herein, we show that 2D hydrazone COFs with either π-extended biphenyl (BPh-COF) or acetylene (AC-COF) frameworks demonstrated distinct charge transfer and photocatalytic performances. The two COFs show good crystallinity and decent porosity as their frameworks are enforced by intra/interlayers hydrogen bonding. However, computational and experimental data reveal that AC-COF managed broader visible-light absorption and narrower optical bandgaps and performed efficient photoinduced charge separation and transfer in comparison with BPh-COF, meaning that the ethynyl skeleton with enhanced planarity better improves the π-conjugation of the whole structure. As a result, AC-COF exhibited an ideal bandgap for rapid oxidative coupling of amines under visible-light irradiation. Furthermore, taking advantage of its better charge transfer properties, AC-COF demonstrated considerable enhanced product conversion and notable functional tolerance for metallaphotocatalytic C-O cross-coupling of a wide range of both aryl bromides and chlorides with alcohols. More importantly, besides being recoverable, AC-COF showcased the previously inaccessible etherification of dihaloarene. This report shows a facile approach for manipulating the structure-activity relationship and paves the way for the development of a COF photocatalyst for solar-to-chemical energy conversion.

Oxidative Nickel-Catalyzed ortho-C-H Amination of (Iso)quinolines with Alicyclic Amines Directed by a Sacrificial N-Oxide Group.

Transition metal (TM)-catalyzed direct amination of C-H bonds on free or fused pyridine (Py) rings with free amines still remains scarce because amines and the Py ring tend to adopt a nonproductive N-bound coordination with many TMs, leading to a significant decrease of catalytic reactivity. We herein disclose a nickel-catalyzed and a sacrificial N-oxide group directed oxidative coupling of (iso)quinolyl C-H bonds and alicyclic amines, which furnishes bioimportant amino(iso)quinolines efficiently and selectively in a single step. Noteworthy, this protocol avoids the use of aggressive reactants and very strong bases usually required when aminating on nonoxidized Py rings.

Theoretical Insights into the Regiodivergence in Ni-Catalyzed [2+2+2] Cycloaddition of Unsymmetric Diynes and CO2

To achieve the peak of carbon dioxide emission and carbon neutrality, utilizing it as a renewable carbon unit in organic synthesis presents an effective chemical solution for sustainable development. In this study, we report a theoretical investigation into the reaction mechanism and the regiodivergence of the Ni-catalyzed [2+2+2] cycloaddition of unsymmetric diynes and CO2 by using DFT calculations. The reaction mechanisms can be classified into two types: one is related to the oxidative coupling of the C≡C moiety with CO2, and the other is related to the oxidative coupling of the two C≡C moieties of diyne. In each type, two possible paths were proposed depending upon the positions of the substituents (H and silyl). Our calculation results indicate that the oxidative coupling of the C≡C moiety and CO2 favors the positions of H-substituent, while the oxidative coupling of the two C≡C moieties is beneficial for inserting CO2 at the positions of silyl-substituent. The regiodivergence is controlled by substrate chain-length and ligand in the different reaction mechanisms.

Open Air Direct Oxidative Coupling of Alcohols and Amines to Imines Catalyzed by Ruthenium Nanoclusters Supported on a Mesoporous Carbon (CMK-8) in/on Water

Open Air Direct Oxidative Coupling of Alcohols and Amines to Imines Catalyzed by Ruthenium Nanoclusters Supported on a Mesoporous Carbon (CMK-8) in/on Water

P450‐Modified Multicyclic Cyclophane‐Containing Ribosomally Synthesized and Post‐Translationally Modified Peptides

AbstractCyclic peptides with cyclophane linkers are an attractive compound type owing to the fine‐tuned rigid three‐dimensional structures and unusual biophysical features. Cytochrome P450 enzymes are capable of catalyzing not only the C−C and C−O oxidative coupling reactions found in vancomycin and other nonribosomal peptides (NRPs), but they also exhibit novel catalytic activities to generate cyclic ribosomally synthesized and post‐translationally modified peptides (RiPPs) through cyclophane linkage. To discover more P450‐modified multicyclic RiPPs, we set out to find cryptic and unknown P450‐modified RiPP biosynthetic gene clusters (BGCs) through genome mining. Synergized bioinformatic analysis reveals that P450‐modified RiPP BGCs are broadly distributed in bacteria and can be classified into 11 classes. Focusing on two classes of P450‐modified RiPP BGCs where precursor peptides contain multiple conserved aromatic amino acid residues, we characterized 11 novel P450‐modified multicyclic RiPPs with different cyclophane linkers through heterologous expression. Further mutation of the key ring‐forming residues and combinatorial biosynthesis study revealed the order of bond formation and the specificity of P450s. This study reveals the functional diversity of P450 enzymes involved in the cyclophane‐containing RiPPs and indicates that P450 enzymes are promising tools for rapidly obtaining structurally diverse cyclic peptide derivatives.

P450-Modified Multicyclic Cyclophane-Containing Ribosomally Synthesized and Post-Translationally Modified Peptides.

Cyclic peptides with cyclophane linkers are an attractive compound type owing to the fine-tuned rigid three-dimensional structures and unusual biophysical features. Cytochrome P450 enzymes are capable of catalyzing not only the C-C and C-O oxidative coupling reactions found in vancomycin and other nonribosomal peptides (NRPs), but they also exhibit novel catalytic activities to generate cyclic ribosomally synthesized and post-translationally modified peptides (RiPPs) through cyclophane linkage. To discover more P450-modified multicyclic RiPPs, we set out to find cryptic and unknown P450-modified RiPP biosynthetic gene clusters (BGCs) through genome mining. Synergized bioinformatic analysis reveals that P450-modified RiPP BGCs are broadly distributed in bacteria and can be classified into 11 classes. Focusing on two classes of P450-modified RiPP BGCs where precursor peptides contain multiple conserved aromatic amino acid residues, we characterized 11 novel P450-modified multicyclic RiPPs with different cyclophane linkers through heterologous expression. Further mutation of the key ring-forming residues and combinatorial biosynthesis study revealed the order of bond formation and the specificity of P450s. This study reveals the functional diversity of P450 enzymes involved in the cyclophane-containing RiPPs and indicates that P450 enzymes are promising tools for rapidly obtaining structurally diverse cyclic peptide derivatives.

Synthesis and Characterization of DOPO-Containing Poly(2,6-dimethyl-1,4-phenylene oxide)s by Oxidative Coupling Polymerization.

A set of polyphenylene oxides incorporating DOPO (9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide) functionality, denoted as DOPO-R-PPO, was synthesized by copolymerization of 2,6-dimethylphenol (2,6-DMP) with various DOPO-substituted tetramethyl bisphenol monomers. In the initial step, a Friedel-Crafts acylation reaction was employed to react 2,6-DMP with different acyl chlorides, leading to the formation of ketone derivatives substituted with 2,6-dimethylphenyl groups. Subsequently, the ketones, along with DOPO and 2,6-DMP, underwent a condensation reaction to yield a series of DOPO-substituted bisphenol derivatives. Finally, polymerizations of 2,6-dimethylphenol with these DOPO-substituted bisphenols were carried out in organic solvents using copper(I) bromide/N-butyldimethylamine catalysts (CuBr/DMBA) under a continuous flow of oxygen, yielding telechelic PPO oligomers with DOPO moieties incorporated into the polymer backbone. The chemical structures of the synthesized compounds were characterized using various analytical techniques, including Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR), phosphorus nuclear magnetic resonance (31P NMR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). When compared to conventional poly(2,6-dimethyl-1,4-phenylene oxide)s with a similar molecular weight range, all DOPO-PPOs exhibited higher glass transition temperatures, enhanced thermal degradability, and increased char yield formation at 800 °C without compromising solubility in organic solvents.

Pd-Catalyzed Oxidative Functionalization of Alkenes, Arenes, and 1,3-Dienes Using Molecular Oxygen as the Terminal Oxidant

AbstractThis Account presents palladium-complex-catalyzed oxidative couplings mainly developed by the author’s group, including oxidative amination and silylation of terminal alkenes, direct oxidative arylation of aromatic compounds, and oxidative difunctionalization of 1,3-dienes. The catalytic cycles in these representative reactions feature re-oxidation of the palladium species with molecular oxygen as the terminal oxidant. Varying the combination of palladium catalyst and re-oxidant enables the formation of a variety of bonds through dehydrogenative cross-coupling reactions.1 Introduction2 Oxidative Amination of Terminal Alkenes3 Direct Oxidative Arylation of Aromatic Compounds4 Oxidative Silylation of Terminal Alkenes5 Oxidative Difunctionalization of 1,3-Dienes6 Conclusions and Perspectives

Natural bentonite/cellulose/vanadium novel complex nanopolymer complex catalyst: Synthesis, characterization, and oxidation activity of several organic compounds

The first bentonite catalyst for oxidation of sulfides and oxidative coupling of thiols was fabricated. This novel catalyst was included natural bentonite, extracted cellulose from wheat wastes, and vanadium complex (Cell/Bent@V nanocomposite). It was characterized using SEM, TEM, ICP, AFM, XRD, XPS, and FT-IR. Further, oxidation of primary and secondary of alcohols were considered to show its catalytic potential for the various substrates. High yield, excellent conversion, and selectivity were observed for oxidation reactions catalyzed by Cell/Bent@V nanocomposite. Cel/Ben/V nanocomposite was shown the excellent stability and activity confirming by SEM, XRD, and FT-IR of recycled catalyst. Finally, the effect of ultrasonic irradiation instead of stirring on the oxidation reaction was evaluated. The high yields and conversions in the less times were observed.

Continuous Flow System for Highly Efficient and Durable Photocatalytic Oxidative Coupling of Methane.

Photocatalytic oxidative coupling of methane (OCM) into value-added industrial chemicals offers an appealing green technique for achieving sustainable development, whereas it encounters double bottlenecks in relatively low methane conversion rate and severe overoxidation. Herein, we engineer a continuous gas flow system to achieve efficient photocatalytic OCM while suppressing overoxidation by synergizing the moderate active oxygen species, surface plasmon-mediated polarization, and multipoint gas intake flow reactor. Particularly, a remarkable CH4 conversion rate of 218.2 μmol h-1 with an excellent selectivity of ∼90% toward C2+ hydrocarbons and a remarkable stability over 240 h is achieved over a designed Au/TiO2 photocatalyst in our continuous gas flow system with a homemade three-dimensional (3D) printed flow reactor. This work provides an informative concept to engineer a high-performance flow system for photocatalytic OCM by synergizing the design of the reactor and photocatalyst to synchronously regulate the mass transfer, activation of reactants, and inhibition of overoxidation.