O-phenylenediamine Derivatives Research Articles

Sodium fluoride-assisted, solvent-controlled regioselective synthesis of 2-substituted and 1,2-disubstituted benzimidazoles with diverse substituents, and unveiling mechanistic insights

The regioselective formation of 2-substituted benzimidazoles and 1,2-disubstituted benzimidazoles with similar substituents at N1 and C2-positions has been achieved by the reaction of o-phenylenediamine derivatives with different aldehydes in the presence of sodium fluoride (NaF) in two different polar solvents. This method is simple, economical, and applicable to a wide range of aldehydes. The method aids in forming 2-substituted benzimidazoles in anhydrous dimethylformamide and 1,2-disubstituted benzimidazoles with similar substituents in glacial acetic acid in excellent yields when using 4.76 mol% of NaF as the catalyst. Furthermore, we have demonstrated the synthesis of 1,2-disubstituted benzimidazoles with dissimilar substitutions at N1 and C2-positions utilizing a one-pot method that eliminates the need to isolate the intermediate 2-substituted benzimidazole. The structure of 1,2-disubstituted benzimidazole (11p) was confirmed using single crystal X-ray diffraction analysis in addition to the spectral studies. These findings emphasize the practical feasibility of our approach to the production of benzimidazole-based drug molecules.

Synthesis, topology, molecular docking and dynamics studies of o-phenylenediamine derivative

The N, N’-(1,2-phenylene) bis (1- (4- chlorophenyl) methanimine) (CS4) was synthesized and characterized by infrared (IR), absorption (UV-vis) and NMR (1H and 13C) spectral analyses. The structural parameters, vibrational frequencies, potential energy and the distribution analysis (PED) were calculated by using DFT with the basis set of B3LYP/cc-pVDZ and these spectral values were compared to the experimental values. HOMO and LUMO studied were performed in order to understand the stability and biological activity of the compound. The most reactive sites on the compound were investigated by utilizing MEP energy surface and Fukui function descriptor with the natural population analysis (NPA) of the charges. The study of the natural bond orbitals (NBO) reveals the delocalization of the intramolecular interaction of the charges in the compound. Additionally, topological investigations (ELF, LOL), determination of thermodynamic parameters and noncovalent interaction (NCI) study by using topology (RDG) analysis were also carried out. Finally, the molecular docking and molecular dynamics simulations was carried out by examining against glycosylphosphatidylinositol phospholipase D inhibitor receptor for distinct protein targets (3MZG). Communicated by Ramaswamy H. Sarma

Simultaneous determination of carbonyl compounds related to thermal treatment and oxidative stability of infant formulas by gas-diffusion microextraction and high-performance liquid chromatography with ultraviolet detection

Infant formulae are the only possible alternative to breastfeeding during the first year of life, so it is crucial to assure their innocuousness. Infant formula undergoes heat treatments to ensure safety and shelf life. However, such processes impact health as they lead to the formation of malondialdehyde, acrolein, and α-dicarbonyl compounds, related to Maillard reaction. Thus, there is a need for improved analytical methods to ensure the safety, quality, and nutritional value of infant formulae, and also exploring the potential of specific compounds as indicators for quality control and monitoring purposes.We developed and validated a novel, efficient, and cost-effective method using gas-diffusion microextraction for the simultaneous quantification of carbonyl compounds in infant formula. Malondialdehyde, acrolein, glyoxal, methylglyoxal, and diacetyl were detected as o-phenylenediamine derivatives using HPLC with UV detection. Parameters influencing extraction efficiency were studied using an asymmetric screening design. The validated method has shown excellent linearity, sensitivity, accuracy, and precision. It was applied to analyze 26 infant formula samples, including starter, follow-up, and special formulated powdered infant formula. Methylglyoxal was found in all samples (0.201–3.153 μg mL−1), while malondialdehyde was present only in certain starter formulas (1.033–1.802 μg mL−1). Acrolein (0.510–3.246 μg mL−1), glyoxal (0.109–1.253 μg mL−1), and diacetyl (0.119–2.001 μg mL−1) were detected in various sample types. Principal components and hierarchical cluster analyses have showcased distinct sample clustering based on analyte contents.This study presents a novel methodology for the analysis of markers of thermal treatment and oxidative stability in infant formula. It contributes to the characterization of the products’ composition and quality control of infant formulae, thereby enhancing their safety and nutritional adequacy. This study also presents the first reported quantification of acrolein in infant formula and introduces the application of the acrolein-o-phenylenediamine derivative for food analysis.

Electronic Effect Promoted Visible-Light-Driven CO2-to-CO Conversion in a Water-Containing System.

The design of unsaturated nonprecious metal complexes with high catalytic performance for photochemical CO2 reduction is still an important challenge. In this paper, four coordinatively unsaturated Co-salen complexes 1-4 were explored in situ using o-phenylenediamine derivatives and 5-methylsalicylaldehyde as precursors of the ligands in 1-4. It was found that complex 4, bearing a nitro substituent (-NO2) on the aromatic ring of the salen ligand, exhibits the highest photochemical performance for visible-light-driven CO2-to-CO conversion in a water-containing system, with TONCO and CO selectivity values of 5300 and 96%, respectively. DFT calculations and experimental results revealed that the promoted photocatalytic activity of 4 is ascribed to the electron-withdrawing effect of the nitro group in 4 compared to 1-3 (with -CH3, -F, and -H groups, respectively), resulting in a lower reduction potential of active metal centers CoII and lower barriers for CO2 coordination and C-O cleavage steps for 4 than those for catalysts 1-3.

Exploiting and Engineering Neuroglobin for Catalyzing Carbene N-H Insertions and the Formation of Quinoxalinones.

It is desired to design and construct more efficient enzymes with better performance to catalyze carbene N-H insertions for the synthesis of bioactive molecules. To this end, we exploited and designed a series of human neuroglobin (Ngb) mutants. As shown in this study, a double mutant, A15C/H64G Ngb, with an additional disulfide bond and a modified heme active site, exhibited yields up to >99% and total turnover numbers up to 33000 in catalyzing the carbene N-H insertions for aromatic amine derivatives, including those with a large size such as 1-aminopyrene. Moreover, for o-phenylenediamine derivatives, they underwent two cycles of N-H insertions, followed by cyclization to form quinoxalinones, as confirmed by the X-ray crystal structures. This study suggests that Ngb can be designed into a functional carbene transferase for efficiently catalyzing carbene N-H insertion reactions with a range of substrates. It also represents the first example of the formation of quinoxalinones catalyzed by an engineered heme enzyme.

Synthesis of benzimidazole derivatives via reaction between aromatic amines and aldehydes: Structure determination and theoretical insights

The condensation reaction between primary amine and aromatic aldehyde or ketone ubiquitously synthesizes –C=N- function that appears in the Schiff bases. Presence of ortho –NH/NH2 group may form a cyclic product which is further oxidized to generate –C=N- function. Herein, two quinoline based cyclic benzimidazole compounds, namely, 2-[1-(Phenyl-pyridin-2-yl-methyl)-1H-benzoimidazol-2-yl]-quinoline (L5) and 2-[1-(Phenyl-pyridin-2-yl-methyl)-1H-benzoimidazol-2-yl]-quinolin-8-ol (L6) are synthesized from o-phenylenediamine derivative [N1-(phenyl(pyridin-2-yl)methyl)benzene-1,2-diamine] (L) via condensation followed by in-situ dehydrogenation. The structures of the products have been confirmed by the single crystal X-ray diffraction measurement and other physicochemical data. The intra- and intermolecular H-bonding, C–H … π interactions in the structures instigate supramolecular self-assembly. The DFT computation has been attempted to explain the formation of energy minimized cyclic product out of acyclic counterpart; the meticulous comparison of the present theoretical outcomes with that of previously reported o-phenylenediamine derivatives, further supports the formation of energy minimized products.

Controlling the Nucleation Process to Prepare a Family of Crystalline Tribenzimidazole-Based Covalent Organic Frameworks

Covalent organic frameworks (COFs) are at the forefront of porous material research due to their crystallinity and topological diversity. However, most COFs are connected by reversible chemical bonds, which limit their applications under harsh conditions. Herein, we develop a novel synthetic method to lock the imine bond using amino groups via a precursor-involved cascade reaction. We experimentally demonstrated that the nucleation process of COFs can be controlled by precursor hydrolysis. A family of crystalline two-dimensional tribenzimidazole-based COFs (2D BI-COFs) was prepared by the condensation of o-phenylenediamine derivative and aryl aldehydes. Their structures were confirmed by powder X-ray diffraction, Fourier-transform infrared spectroscopy, and solid-state 13C cross-polarization magic angle spinning nuclear magnetic resonance (CP/MAS NMR) spectroscopy. They showed high surface areas, good CO2 uptake capacities, excellent CO2/N2 selectivities, and high chemical stabilities. Of these materials, BI-COF-1 was an efficient photocatalyst for the visible-light-driven photocatalytic oxidation of sulfides, which displayed high conversion (∼100%) and excellent selectivity (>90%). We believe that our study can provide new insights into the synthesis of 2D chemical-stable COFs.

Carbonyl flavor compound-targeted colorimetric sensor array based on silver nitrate and o-phenylenediamine derivatives for the discrimination of Chinese Baijiu

Baijiu is a distilled liquor of great importance in the food industry. Various aroma types, brands, and grades of Baijiu have filled the market; thus, discrimination for quality control is required. Herein, we constructed a novel colorimetric sensor array based on the redox reaction between silver nitrate and o-phenylenediamine or its derivatives for the discrimination of carbonyl flavor compounds (CFCs) and Baijius. The specific colored products were changed by CFCs depending on the influence of silver nanoparticle aggregation and chemical reactions. The array was used to qualitatively and quantitatively identify 21 CFCs with fast response (<14 min), wide linear range (0.025–25 mmol/L), and low detection limits (<60 μmol/L, 29 nmol/L for carboxylic acids). Finally, the array was successfully applied to the discrimination of 56 Baijius. The method proposed in this study is simple, fast, reliable, and has good application potential for the visual determination of Chinese Baijiu.

Composition and distribution of α-dicarbonyl compounds in propolis from different plant origins and extraction processing

α-Dicarbonyl compounds (α-DCs), mainly produced during thermal treatment and storage of sugary foods, are routinely measured to evaluate food quality. Propolis is a functional food that has gained wide usage; thus, its quality control is an emerging concern. There are no reports on distribution of α-DCs in propolis. In this study, 10 main α-DCs standards of o-phenylenediamine (OPD) derivatives were prepared and confirmed by high resolution mass spectrometry. Based on these standards, an ultra-high performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS) was established and validated to determine the α-DCs in different propolis samples. Nine α-DCs were detected, ranging from 0.006 to 44.936 mg/kg. Methyl glyoxal (MGO), 2,3-butanedione and glucosone are rich in content, with the highest content of MGO. The level of 3-deoxypentosulose (3-DG) increased sharply with long-term storage of propolis extracts. The comparison revealed 20-fold lower levels of MGO when supercritical CO2 extraction and ethanol extraction were used, highlighting the importance of extraction techniques used in processing raw propolis. The investigation of commercially available propolis products found that α-DCs were in the range of 0.013–16.181 mg/kg. The results indicated that α-DCs can be the potential index to control propolis quality.

Synthesis, structural characterization and antimicrobial activity of Schiff bases and benzimidazole derivatives and their complexes with CoCl2, PdCl2, CuCl2 and ZnCl2

In this study, new Schiff bases (H2L1 and H2L2) and benzimidazolylphenol derivatives (HL3 − HL5) derived from 5-chlorosalicylaldehyde and appropriate aminophenol and o-phenylenediamine derivatives including 4-methyl/4,5-dimethyl/4-chloro‑5-nitro groups were synthesized and characterized. CoCl2, PdCl2, CuCl2 and ZnCl2 complexes of the ligands were synthesized and characterized by using elemental analysis, molar conductivity, magnetic moment, FT-IR and NMR spectroscopy. In addition, the crystal structure of H2L1 and [Pd(L1)(CH3CN)]·H2O were determined by X-ray diffraction spectroscopy. Keto-enol tautomerism is observed in the Schiff base compounds according to spectral data. Antimicrobial activities of the compounds were tested toward six bacteria and three fungi. Some metal complexes (e.g. Co(II) complexes of the benzimidazole derivatives) showed higher activity towards the test microorganisms than the ligands. In addition, it is observed that the Co(II) complexes show in a wide range antimicrobial activity compared to the other complexes.

P-Toluenesulfonic Acid Coated Natural Phosphate as an Efficient Catalyst for the Synthesis of 2-Substituted Benzimidazole

2-Substituted benzimidazoles are selectively synthesised in high yields via the condensation of o-phenylenediamine derivatives with aldehyde derivatives using catalytic amount of p-toluenesulfonic acid coated natural phosphate (NP/PTSA) under mild conditions. The use of NP/PTSA as a reusable catalyst makes this process simple, convenient, and environmentally friendly.

Regioselective transmonocyanoacetylation of o-phenylenediamine derivatives: simple and efficient synthesis of 2-cyanomethylbenzimidazole derivatives

A simple and efficient method for the regioselective transmonocyanoacetylation of o-phenylenediamine derivatives was developed using 1-cyanoacetyl-3,5-dimethylpyrazole as a cyanoacetylating agent. This method provided operationally simple and efficient access to a series of N-(2-aminophenyl)-2-cyanoacetamide derivatives under mild conditions with short reaction time. Also, 2-cyanomethylbenzimidazole derivatives have been synthesized through the cyclocondensation of N-(2-aminophenyl)-2-cyanoacetamide derivatives. In all cases, high yield of products was obtained and reaction times were significantly reduced with relation to similar reactions.

SYNTHESIS OF NEW HETEROCYCLIC SYSTEMS CONTAINING QUINOXALINE MOIETY

The synthesis of a new brick heterocyclic system of quinoxaline was developed by a cyclocondensation reaction starting from o-phenylenediamine derivatives. Thus 6-chloroquinoxaline-2,3(1H,4H)–dione was obtainedin excellent yield by condensation of 4-Chloro-o-phenylenediamine with oxalic acid at reflux in a hydrochloric acid solution. Thealkylationreactions werethen carried out and optimized by using monohalogenated agents under phase transfer catalysis conditions. The reaction studied lead to the expected products in good yields and the structures of various obtained compounds are easilydetermined by the usual spectroscopic methods. This kind of products can show a potent pharmacological and therapeutic activitiesas given in the studies reported in the literature.

Theoretical Design of a Two-Photon Fluorescent Probe for Nitric Oxide with Enhanced Emission Induced by Photoninduced Electron Transfer.

In the present work, we systematically investigate the sensing abilities of two recently literature-reported two-photon fluorescent NO probes, i.e., the o-phenylenediamine derivative of Nile Red and the p-phenylenediamine derivative of coumarin. The recognition mechanisms of these probes are studied by using the molecular orbital classifying method, which demonstrates the photoinduced electron transfer process. In addition, we have designed two new probes by swapping receptor units present on fluorophores, i.e., the p-phenylenediamine derivative of Nile Red and the o-phenylenediamine derivative of coumarin. However, it illustrates that only the latter has ability to function as off-on typed fluorescent probe for NO. More importantly, calculations on the two-photon absorption properties of the probes demonstrate that both receptor derivatives of coumarin possess larger TPA cross-sections than Nile Red derivatives, which makes a better two photon fluorescent probe. Our theoretical investigations reveal that the underlying mechanism satisfactorily explain the experimental results, providing a theoretical basis on the structure-property relationships which is beneficial to developing new two-photon fluorescent probes for NO.

A novel catalytic one-pot three-component reaction of aldehydes, o-phenylenediamine derivatives and isocyanides for synthesis of 3,4-dihydroquinoxalin-2-amine derivatives in the presence of zirconium tetrachloride

A simple and efficient one-pot procedure for the synthesis of biologically interesting 3,4-dihydroquinoxalin-2-amine derivatives through a three-component condensation reaction of o-phenylenediamines, carbonyl compounds and isocyanides in ethanol at room temperature is described. In this work, unlike the other methods, aldehydes reacted as well as ketones in the presence of 10 mol% of zirconium tetrachloride as catalyst to afford good to excellent yields of products. This methodology is of great value because of its environmentally benign character, high yields, ease of handling and reliable for both aldehydes and ketones. The newly synthesized compounds were systematically characterized by IR, 1H NMR, 13C NMR and elemental analysis. A novel catalytic one-pot three-component reaction of aldehydes, o-phenylenediamine derivatives and isocyanides for synthesis of 3,4-dihydroquinoxalin-2-amine derivatives in the presence of zirconium tetrachloride .

Strong Electronic Coupling of Molecular Sites to Graphitic Electrodes via Pyrazine Conjugation.

Glassy carbon electrodes were functionalized with redox-active moieties by condensation of o-phenylenediamine derivatives with o-quinone sites native to graphitic carbon surfaces. Electrochemical and spectroscopic investigations establish that these graphite-conjugated catalysts (GCCs) exhibit strong electronic coupling to the electrode, leading to electron transfer (ET) behavior that diverges fundamentally from that of solution-phase or surface-tethered analogues. We find that (1) ET is not observed between the electrode and a redox-active GCC moiety regardless of applied potential. (2) ET is observed at GCCs only if the interfacial reaction is ion-coupled. (3) Even when ET is observed, the oxidation state of a transition metal GCC site remains unchanged. From these observations, we construct a mechanistic model for GCC sites in which ET behavior is identical to that of catalytically active metal surfaces rather than to that of molecules in solution. These results suggest that GCCs provide a versatile platform for bridging molecular and heterogeneous electrocatalysis.

An efficient NaHSO3-promoted protocol for chemoselective synthesis of 2-substituted benzimidazoles in water

An efficient protocol for chemoselective synthesis of 2-substituted benzimidazoles from a variety of aliphatic/aromatic/heteroaryl aldehydes and o-phenylenediamine derivatives promoted by NaHSO3 in water had been developed. The amount of NaHSO3 had a great effect on the reaction selectivity of 2-substituted benzimidazole and 1,2-disubstituted benzimidazole when the reaction was carried out in water. When the amount of the NaHSO3 was more than 11 equivalents, the 2-substituted benzimidazole could be highly selectively formed as the sole product. NaHSO3 was firstly reacted with aldehyde to form the aldehyde sodium bisulfite, which reacted with o-phenylenediamine to form the 2-substituted benzimidazole and inhibited the formation of 1,2-disubstituted benzimidazole. This protocol solved the poor selectivity problem appearing in traditional method when cyclocondensation between o-phenylenediamine and aldehydes. The method also had advantage of simple work up by filtrating the single 2-substituted benzimidazole precipitates from reaction mixture at the end of the reaction without further purification. In addition, the method was applicable to both electron-rich and electron-poor starting materials, which was successfully used for synthesizing nine novel 2-substituted benzimidazole derivatives containing a 1,2,3-triazole moiety. They were characterized by NMR, IR and HRMS spectrum. Moreover, this method had been applied to a large scale synthesis of 2-substituted benzimidazole derivatives.

I2-Mediated Intramolecular C–H Amidation for the Synthesis of N-Substituted Benzimidazoles

A practical intramolecular C-H amidation methodology has been developed using molecular iodine under basic conditions. The required imine substrates were readily obtained by condensation of simple o-phenylenediamine derivatives and aldehydes. The transition-metal-free cyclization reaction described here works well with crude imines and allows for the sequential synthesis of N-protected benzimidazoles without purification of the less stable condensation intermediates. This operationally simple synthetic approach is broadly applicable to a variety of aromatic, aliphatic, and cinnamic aldehydes to produce diverse 1,2-disubstituted benzimidazole derivatives in an efficient and scalable fashion.

A redox-flow battery with an alloxazine-based organic electrolyte

Redox-flow batteries (RFBs) can store large amounts of electrical energy from variable sources, such as solar and wind. Recently, redox-active organic molecules in aqueous RFBs have drawn substantial attention due to their rapid kinetics and low membrane crossover rates. Drawing inspiration from nature, here we report a high-performance aqueous RFB utilizing an organic redox compound, alloxazine, which is a tautomer of the isoalloxazine backbone of vitamin B2. It can be synthesized in high yield at room temperature by single-step coupling of inexpensive o-phenylenediamine derivatives and alloxan. The highly alkaline-soluble alloxazine 7/8-carboxylic acid produces a RFB exhibiting open-circuit voltage approaching 1.2 V and current efficiency and capacity retention exceeding 99.7% and 99.98% per cycle, respectively. Theoretical studies indicate that structural modification of alloxazine with electron-donating groups should allow further increases in battery voltage. As an aza-aromatic molecule that undergoes reversible redox cycling in aqueous electrolyte, alloxazine represents a class of radical-free redox-active organics for use in large-scale energy storage. Redox-flow batteries with organic-based electrolytes hold many advantages over conventional-flow batteries. Here the authors report a high-performance flow battery based on alloxazine, an aqueous-stable and soluble redox-active organic molecule resembling the backbone structure of vitamin B2.

Nitric Oxide (NO) Endows Arylamine-Containing Block Copolymers with Unique Photoresponsive and Switchable LCST Properties

The fabrication of materials that are responsive to endogenous gasotransmitter molecules (i.e., nitric oxide, hydrogen sulfide, and carbon monoxide) has emerged as an area of increasing research interest. In the case of nitric oxide (NO), o-phenylenediamine derivatives have traditionally been employed due to their ability to react with NO in the presence of oxygen (O2) with the formation of benzotriazole residues. Herein, we report the synthesis of a novel NO-responsive polymer containing aromatic primary amine groups derived from p-phenylenediamine groups (i.e., isomers of o-phenylenediamine). A new NO-responsive monomer, N-(4-aminophenyl)methacrylamide (p-NAPMA), was first synthesized via the amidation of one of the primary amine groups in the p-phenylenediamine with methacrylic anhydride. Notably, the p-NAPMA monomer can efficiently react with NO in aqueous solution in the presence of O2 with the generation of phenyldiazonium groups rather than benzotriazole moieties. While the resultant phenyldiazoniu...