Pyridone Research Articles

Synthesis and reactivity of isomeric Ru complexes with hydroxypyridyl fragment: Active catalysts for β‑alkylation of secondary alcohols with primary alcohols

When the ligand LOH, containing a 2-hydroxy pyridine group, reacts with an equimolar amount of the precursor Ru(DMSO)4Cl2, two isomeric ruthenium complexes are formed. These isomers are termed cis-1 and trans-1, based on the relative positions of the N atom in N-(2-(6-hydroxy pyridin-2-yl)phenyl)acetamide and the pyridine groups of bis((1,4-pyridin-2-yl)methyl)amine. Treatment of these isomers with equimolar amounts of NaH results in deprotonation of the uncoordinated hydroxy pyridine groups, leading to the formation of complex 2 with newly coordinated pyridine groups. The catalytic activity of these three ruthenium complexes in the β-alkylation reaction of primary alcohols and secondary alcohols was evaluated, with complex 2 displaying the highest activity and selectivity. Complex 2 may be seen as an intermediate in the catalysis of the β-alkylation reaction by the isomers (cis-1 and trans-1). These findings are valuable for the development of more effective bifunctional catalysts.

Unleashing potential of Pseudomonas aeruginosa RNC3 and Stenotrophomonas maltophilia RNC7 for chlorpyrifos biodegradation by genome analysis and kinetic studies

Chlorpyrifos (CP) is an extensively used organophosphate (OP) pesticide that inhibits the biogeochemical cycle with subsequent loss of soil fertility. In this view, indigenous soil bacteria with significant CP degradation capacity were identified as Pseudomonas aeruginosa RNC3 and Stenotrophomonas maltophilia RNC7 through 16 S rRNA. The optimum values of independent variables for CP degradation were found to be 30 ℃, pH 7, 100 mgL−1 of CP, and 1 OD600 cell culture. RNC3 and RNC7 showed 82.5 mgL−1 and 77.1 mgL−1 CP degradation within 5 days. A Michaelis-Menten kinetic model estimated the degradation rate (Vmax) and substrate binding affinity (Ks) for RNC3 were 1.23 mgL−1h−1 and 123 mgL−1 whereas for RNC7 as 1.19 mgL−1h −1 and 124.3 mgL−1, respectively. The major metabolites 3,5,6-trichloro-2-pyridinol (TCP) and 2-hydroxy pyridine were identified during CP degradation by RNC3 whereas, only TCP by RNC7 using GC-MS. Key enzymes encoded by opd and opch2 genes were annotated in the genomes of RNC3 and RNC7 along with the set of putative degradation genes (tcp, yieH, pho, prp). Protein-ligand docking between OPCH2 and CP found − 7.9 kcal mol −1 as a high binding affinity with the conserved catalytic triad (Ser155-Asp251-His281) in the active site. The study suggests that RNC3 can completely mineralize CP, whereas both strains have shown robust degradation ability of OP group of pesticides. The potential of rapid acclimatization to natural soil environment and non-virulent nature of the selected strains are beneficial for in situ application. Thus, selected indigenous strains can be applied for the bioremediation of OP-contaminated soil.

2-Pyridone-based stilbazoles containing cyano and trifluoromethyl acceptors: Synthesis and fluorescence properties in solutions and in solid state

A novel simple and efficient stilbazole-based D-π-А system containing cyano and trifluoromethyl acceptors was designed. The developed system demonstrated pronounced (fluoro)solvatochromic properties. The behavior of compound in solution was studied and three forms were identified, namely pyridone (PY), hydroxypyridine (HP), and anionic form (AN). Synthetic equivalents of these forms were prepared and their photophysical characteristics were investigated. It was shown that fluorescence of the stilbazole-based D-π-А chromophore is originated exclusively from hydroxypyridine form, while the pyridone form makes a significant contribution to the absorption properties of the compound. Basing on the obtained 6-(4-(dimethylamino)styryl)-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile a three position solid-state fluorescent acid-base switch was developed.

Novel Urea-Functionalized Magnetic Nanoparticles as a Heterogeneous Hydrogen Bonding Catalyst for the Synthesis of New 2-Hydroxy Pyridines

A novel urea-functionalized silica-coated magnetic nanoparticle namely Fe3O4@SiO2@UBL was described as a reusable and recoverable heterogeneous hydrogen bonding catalyst. For characterization of the catalyst, varied techniques including Fourier-transform infrared (FT‐IR) spectroscopy, energy dispersive X‐ray (EDX) analysis, elemental mapping analysis, thermo gravimetric analysis/differential thermal analysis (TGA/DTG), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and vibrating sample magnetometer (VSM) were applied. Then, its catalytic performance was screened for the synthesis of new 2-hydroxy pyridine derivatives bearing sulfonate or sulfonamide moiety. Also, in a plausible mechanistic route, the stereoelectronic role of a cooperative vinylogous anomeric-based oxidation is suggested for the aromatization of targeted molecules.

RECENT ADVANCES IN THE SYNTHETIC APPROACHES TO 2-PYRIDONES

This microreview focuses on the methodologies for the synthesis of 2-pyridones and their biological applications. Various types of synthetic methods reported in the last 6 years (starting from the year 2014 and onward) have been discussed. Functionalization reactions of 2-pyridones have not been taken into account.

Synthesis, physicochemical and vibrational spectral properties of 2–pyridone and 2–aminopyridine derivatives: An experimental and theoretical study

A convenient and efficient one–pot three–component reaction of acetyl acetone, malononitrile and ammonium acetate was investigated for the synthesis of 3–cyano–4,6–dimethyl–2–pyridone (PI) and 2–amino–3–cyano–4,6–dimethylpyridine (PII). The products were achieved with high purity, high yields and short reaction time. The yields of the two products depend on the concentration of ammonium acetate, reaction time and the solvent used. The structures of the isolated products were confirmed by elemental analysis and spectral data, supported by quantum chemical (MP2) calculations, both in gas phase and solvents (water and ethanol), that were also employed to track the reaction mechanisms and model vibrational spectral properties for final characterization and interpretation of spectral data. A remarkable matching between theoretical predictions and experiments was attained both for the geometrical parameters, as compared to X-Ray data available in the literature, and for vibrational frequencies, leading to a correlation coefficient (R2) of 0.99. Molecular docking was further studied to predict the docking binding energy of the synthesized compounds with the target proteins.

Favipiravir tautomerism: a theoretical insight.

There is no experimental information about the tautomerism of Favipiravir (T-705). Therefore, its tautomeric state was predicted by using density functional theory in gas phase and in solution (toluene, acetonitrile and water). The results have shown that, in neutral state, the enol form is strongly dominating in both gas phase and solution. The carboxamide group is easily protonated in the presence of acid, which leads to shift of the tautomeric equilibrium toward the keto tautomer. In order to validate the theoretical predictions, 2-hydroxy pyridine and 2-hydroxy pyrazine were also included in the set of studied compounds. The available experimental data about their tautomerism are in very good agreement with the theoretical predictions, which validate the conclusions made for T-705.

Pyridine-Directed Rh-Catalyzed C6-Selective C–H Acetoxylation of 2-Pyridones

Pyridine-Directed Rh-Catalyzed C6-Selective C–H Acetoxylation of 2-Pyridones

Cocrystals, Salts, and Supramolecular Gels of Nonsteroidal Anti-Inflammatory Drug Niflumic Acid

Niflumic acid (NFA) is a nonsteroidal anti-inflammatory drug (NSAID) classified under the BCS (Biopharmaceutical Classification System) Class II category of poor aqueous solubility and high permeability. In an attempt to improve the physicochemical properties of NFA, particularly solubility and dissolution rate by cocrystallization and salt formation, cocrystals of NFA were prepared with caprolactam (CPR, 1:1) and 2-hydroxy pyridine (2HP, 1:1) as well as salts with piperazine (PIP, 1:0.5), benzenesulfonic acid (BSA, 1:1), benzyl amine (BZA, 1:1 and 2:2), and tyramine (TYA, 1:1). The new solid forms were characterized by powder X-ray diffraction, infrared spectroscopy, and differential scanning calorimetry and confirmed by single crystal X-ray diffraction. In the cocrystals NFA–CPR and NFA–2HP, the cyclic amide of the coformer forms a dimer synthon through N–H···O hydrogen bonds and such dimers extend through O–H···O hydrogen bonds. In piperazine, benzyl amine, and tyramine salts, proton transfer occurs fr...

Nickel-Catalyzed Asymmetric C–H Functionalization of Pyridones

Key words nickel catalysis - C–H functionalization - pyridones - N-heterocyclic carbenes

Borylation of 2-Pyridones

Borylation of 2-Pyridones

Double hydrogen bond interaction in 7-azaindole complexes with protic solvents

The double hydrogen bond interaction between 7-azaindole (7AI) and protic solvents including methanol (MeOH), formamide (FM), formic acid (FA), pyridone (PY) and 7AI has been investigated as a proper model of mutations generated by tautomeric shifts in hydrogen-bonded bases of DNA. The results confirm electrostatic nature for all considered hydrogen bonds except for NH hydrogen bond in 7AI-FA. The largest interaction and polarization energies are obtained for 7AI-FA by means of energy decomposition analyses (EDA). The EDA results show an inverse competitive correlation between polarization and electrostatic components of attraction energy to determine the nature of hydrogen bond. The red-shifted hydrogen bonds are identified for all complexes as a result of hyperconjugation, except for 7AI-MeOH, which its blue-shift effect is attributed to the rehybridization dominating of CH bond. Investigation of aromaticity indices for 7AI complexes represents an increase in aromaticity of pentagonal ring and a decrease in hexagonal ring. Finally, the double hydrogen bond between 7AI and FA is identified as dominant interaction to achieve the tautomerization of 7AI in all applied approaches.

Thermolysis of some N-arylbenzamidoximes: Mechanistic studies for formation of anilide, oxazole and imidazole derivatives

The thermolysis of N-2-pyridylbenzamidoxime I under nitrogen atmosphere for 5 hours gives rise to 2-phenyl-1H-imidazo[4,5-b]pyridine and N-(pyridin-2-yl)benzamide as the major products (52.4 and 18.11%, respectively), in addition to 2-hydroxy pyridine, benzonitrile, benzoic acid, 2-aminopyridine, 2-phenyloxazolo[4,5-b]pyridine, 9H-pyrrolo[2,3-b:5,4-b’]dipyridine and 2,4,6-triphenyl-1,3,5-triazine. Also, heating N- α-naphthylbenzamidoxime II under the same conditions gave N-(α-Naphthyl)benzamide, 2-Phenyl-3H-naphtho[2,1-d] imidazole as the major products besides benzonitrile, benzoic acid, α-naphthylamine and 2-phenylnaphtho[1,2-d]oxazole. In the presence of tetralin, I gave 1-hydroxytetralin, α-tetralone and 1,1’-bitetrayl besides the previous products. The reaction and isolated products have been interpreted in terms of a free radical mechanism involving the homolysis of N-O and/or C-N bonds. Thermolysis of N-arylbenzamidoximes I and II gives rise to 2-phenyl-1H-imidazo [4,5-b]pyridine, N-arylbenzamides and 2-Phenyl-3H-naphtho[2,1-d]imidazole as the major products besides other acyclic and cyclic products. The isolated products have been interpreted in terms of a free radical mechanism involving the homolysis of N-O and/or C-N bonds.

ChemInform Abstract: Four‐Component Assembly of Natural‐Product‐Like Ring‐Fused Isoquinuclidines.

AbstractCoupling of 2‐pyridones with aldehydes, amines, and activated alkenes is found to allow access to pharmacologically interesting ring‐fused isoquinuclidines.

Computation of polarizability, hyper-polarizability and hardness as descriptor for enol–keto tautomerizations of 2-hydroxy pyridines

Abstracts Density functional theory (DFT) based calculations on a series of intra-molecular proton-transfer reactions e.g. 2-hydroxy pyridine (2HP), 5-methyl-2-hydroxy pyridine (5Me2HP) and 5-fluoro-2-hydroxy pyridine (5F2HP) are performed to understand the variation of the quantum chemical reactivity parameters e.g. polarizability, hardness, ionization potential along the proton transfer co-ordinate. Variations in optical gap and first hyper-polarizability which are measures of non-linear optical parameters are also computed along the proton transfer co-ordinate of the species. The average polarizability ( α av ), first hyper-polarizability ( β ), chemical hardness ( η ), ionization potential (I.P) and optical gap (Δ E ) show their optimum value at the same IRC point which corresponds to the transition state (TS) for all the three titled intra-molecular proton transfer systems. The maximum polarizability and minimum chemical hardness at the transition state (TS) are due to greater extents of charge transfer which arise from smaller optical gap.

ChemInform Abstract: Rhodium‐Catalyzed [2 + 2 + 2] Cycloaddition for the Synthesis of Substituted Pyridines, Pyridones, and Thiopyranimines

AbstractReview: 111 refs.

Rhodium-Catalyzed [2+2+2] Cycloaddition for the Synthesis of Substituted Pyridines, Pyridones, and Thiopyranimines

Rhodium-Catalyzed [2+2+2] Cycloaddition for the Synthesis of Substituted Pyridines, Pyridones, and Thiopyranimines

The Third Hydrogenase: A Ferracyclic Carbamoyl with Close Structural Analogy to the Active Site of Hmd

The synthesis of a close structural analogue of the active site of [Fe]-hydrogenase is described (see structure; C gray, H dark blue, Fe green, N light blue, O red, S yellow). Nature most probably constructs the five membered ferracyclic ring to poise the 2-hydroxy pyridine substituent in a position to assist the heterolytic cleavage of dihydrogen, and the accessibility of the analogue should now provide opportunities for probing this.

Carbon monoxide as intrinsic ligand to iron in the active site of [fe]-hydrogenase.

Structural and spectroscopic studies on [Fe]-hydrogenase revealed an active site mononuclear low spin iron coordinated by the Cys176 sulfur, two CO, and the sp(2) hybridized nitrogen of a 2-pyridinol compound with back bonding properties similar to those of cyanide. Thus, [Fe]-hydrogenases are endowed with an iron-ligation pattern related to that found in the active site of [NiFe]- and [FeFe]-hydrogenases although the three hydrogenases and the enzymes involved in their posttranslational maturation have evolved independently and although CO and cyanide ligands are not found in any other metallo-enzymes. Obviously, low-spin iron complexed with thiolate(s), CO, and cyanide or a cyanide functional analogue plays an essential role in H(2) activation.

Synthesis of 4-Pyridone-3-sulfate and an improved synthesis of 3-Hydroxy-4-Pyridone

An improved synthesis of 3-hydroxy-4-pyridone via an Elbs oxidation of 4-pyridone and isolation of 4-pyridone-3-sulfate is described.