Pyridine System Research Articles

ChemInform Abstract: Synthesis of Cycloalkano[b]pyridines by Multicomponent Strategy: Ring‐Size Mediated Product Selectivity, Substitution‐Induced Axial Chirality and Influence of the 14N Quadrupole‐Relaxation.

AbstractEquimolar amounts of cyclooctanone, malononitrile, alkyl amines and aromatic aldehydes react under conditions A) to afford unprecedented fused pyridine systems.

Pyridines and Imidazopyridines with Medicinal Significance.

Pyridine and pyridine-fused ring systems are ubiquitous in medicinal research and demonstrate such diverse pharmacological benefits as anticonvulsant therapies, treatment for fungal and bacterial infections as well as chemotherapy agents. For example, imidazo[1,2-a]pyridines have exhibited a broad range of activity as antiviral, antibacterial, analgesic, antipyretic, and antiinflammatory agents. Indeed many advances in the development of novel synthetic approaches to the pyridines and their fused counterparts are designed around the relevance of these systems to pharmacological research. Moreover, pyridine-based natural products with interesting biological activity continue to be discovered each year. This article highlights recent (2004-2014) discoveries related to the medicinal and pharmacological significance of pyridines, imidazo[1,2-a]pyridines, quinolones and a few other pyridine-fused compounds and is organized around their type of biological activity.

A study of the small-molecule system used to investigate the effect of arginine on antibody elution in hydrophobic charge-induction chromatography

Hydrophobic charge-induction chromatography (HCIC) using 4-mercaptoethylpyridine (4-MEP) as the ligand is used to purify antibodies. The 4-MEP resin ligand has high affinity for antibodies, which makes it difficult to optimize the elution conditions. Recent studies showed that arginine is effective at eluting and purifying antibodies using the HCIC with 4-MEP. In the present study, we investigated the mechanism of the action of arginine on the interaction between butyl gallate (BG) and the 4-MEP resin as a model system for protein–4-MEP interactions. Equilibrium adsorption experiments showed that arginine has a significant effect on the desorption of BG from the 4-MEP resin and, in fact, is found to exhibit a greater effectiveness than guanidine and urea, which are known denaturants. The calculated binding free energy between a BG molecule and a 4-MEP resin ligand molecule using molecular dynamics simulations was qualitatively consistent with the experimental results. A principal component analysis of the simulations showed that arginine molecules intervene in the interaction between the BG and 4-MEP molecules at a distance of 8.5 Å by entering the space between the phenol and pyridine planes. The present results suggest that arginine has a unique mechanism of interaction with the phenol–pyridine system, which should be associated with the effects of arginine on the protein–4-MEP systems.

Ab Initio Atom-Atom Potentials Using CamCASP: Theory and Application to Many-Body Models for the Pyridine Dimer.

Creating accurate, analytic atom-atom potentials for small organic molecules from first principles can be a time-consuming and computationally intensive task, particularly if we also require them to include explicit polarization terms, which are essential in many systems. We describe how the CamCASP suite of programs can be used to generate such potentials using some of the most accurate electronic structure methods currently applicable. We derive the long-range terms from monomer properties and determine the short-range anisotropy parameters by a novel and robust method based on the iterated stockholder atom approach. Using these techniques, we develop distributed multipole models for the electrostatic, polarization, and dispersion interactions in the pyridine dimer and develop a series of many-body potentials for the pyridine system. Even the simplest of these potentials exhibits root mean square errors of only about 0.6 kJ mol(-1) for the low-energy pyridine dimers, significantly surpassing the best empirical potentials. Our best model is shown to support eight stable minima, four of which have not been reported before in the literature. Further, the functional form can be made systematically more elaborate so as to improve the accuracy without a significant increase in the human-time spent in their generation. We investigate the effects of anisotropy, rank of multipoles, and choice of polarizability and dispersion models.

Soft, tough, and flexible curdlan hydrogels and organogels fabricated by covalent cross-linking

Abstract Soft, tough and flexible curdlan (CD) hydrogels were fabricated by covalent cross-linking of CD using ethylene glycol diglycidyl ether (EGDGE) as a cross-linker. The mechanical properties of the gels were investigated by uniaxial compression test. CD hydrogels showed non-linear elastic behavior. The elastic modulus of CD hydrogels was 0.004–0.011 kPa. CD hydrogels were highly tough and did not fracture under compression to 90% strain at the maximum. The gels could retain water during compression, and no water was squeezed out from the gel. In addition, CD hydrogel could recover the original shape and elastic modulus after 90% compression, indicating its high flexibility. Subsequently, hydroxyl groups of CD hydrogels were acetylated in acetic anhydride and pyridine system to give hydrophobic property, and novel CD organogels were obtained. CD organogel were swollen in chloroform and resistant to repeated drying and swelling treatment in chloroform.

Design, synthesis and anti-P. falciparum activity of pyrazolopyridine–sulfonamide derivatives

Ten 1-phenyl-1H-pyrazolo[3,4-b]pyridine derivatives connected by a linker group to benzenesulfonamide moieties with different substituents in the 4-position were synthesized and assayed against Plasmodium falciparum. These ten compounds exhibited activity in vitro against the chloroquine-resistant clone W2 with IC50 values ranging from 3.46 to 9.30μM. The most active derivatives with substituent R2=Cl or CH3 at the benzenesulfonamide moiety exhibited the lowest IC50. Compounds with an R1=CO2Et substituent at the 5-position of the 1H-pyrazolo[3,4-b]pyridine ring presented lower activity than those with a CN substituent. The 1H-pyrazolo[3,4-b]pyridine system appears to be promising for further studies as an antimalarial for overcoming the burden of resistance in P. falciparum.

Orally bioavailable pyridine and pyrimidine-based Factor XIa inhibitors: Discovery of the methyl N-phenyl carbamate P2 prime group

Pyridine-based Factor XIa (FXIa) inhibitor (S)-2 was optimized by modifying the P2 prime, P1, and scaffold regions. This work resulted in the discovery of the methyl N-phenyl carbamate P2 prime group which maintained FXIa activity, reduced the number of H-bond donors, and improved the physicochemical properties compared to the amino indazole P2 prime moiety. Compound (S)-17 was identified as a potent and selective FXIa inhibitor that was orally bioavailable. Replacement of the basic cyclohexyl methyl amine P1 in (S)-17 with the neutral p-chlorophenyltetrazole P1 resulted in the discovery of (S)-24 which showed a significant improvement in oral bioavailability compared to the previously reported imidazole (S)-23. Additional improvements in FXIa binding affinity, while maintaining oral bioavailability, was achieved by replacing the pyridine scaffold with either a regioisomeric pyridine or pyrimidine ring system.

ChemInform Abstract: Reactivity of Dehydroacetic Acid in Organic Synthesis

AbstractReview: 130 refs.

Synthesis of N-alkylated benzo- and pyridothienopyrrolo-[1,2a][1,4]diazepin-6-ones acting as antidotes against the herbicide 2,4-D

We report N-alkylation reactions of pyrrolo[1,2-a][1,4]diazepin-6-ones annulated with a benzene ring or thieno[2,3-b]pyridine system. A range of new N5-substituted pyrrolodiazepines were synthesized, including compounds acting as antidotes against the herbicide 2,4-D.

Intramolecular oxyacetoxylation of N-allylamides: an expeditious synthesis of oxazolines and oxazines by using a PhI(OAc)2/hydrogen fluoride-pyridine system.

The synthesis of oxazolines and oxazines from N-allylamides was accomplished via an unprecedented reaction set. This reaction involved an intramolecular cyclization of N-allylamides resulting from nucleophilic attack of the allylamine on the benzoxazin-4-one. Unlike the previous literature, the isolable N-allylamide could readily be subjected to exo and endo fashion ring-closure under conditions to afford the title compounds.

Copper catalyzed direct aerobic double-oxidative cross-dehydrogenative coupling of imidazoheterocycles with aryl acetaldehydes: an articulate approach for dicarbonylation at C-3 position

Direct aerobic oxidative cross-dehydrogenative coupling of aryl acetaldehydes at C-3 position of imidazoheterocycles via copper catalyzed reaction resulted in the synthesis of dicarbonylated imidazoheterocycles in 55–85% yields. The methodology provides a straightforward, high yielding and one-pot approach towards the synthesis of C-3 dicarbonylated imidazoheterocycles without prior activation of C(sp2)-H or a base. This also reports the first method of coupling of aryl acetaldehydes on imidazo[1,2-a]pyridine system via double-oxidative cross-dehydogenative process.

ChemInform Abstract: Three‐Component Solvent‐Free Synthesis of Fluorine Substituted Bicyclic Pyridines.

AbstractStarting from heterocyclic ketene aminals, methylene‐containing diones, and triethoxymethane a one‐pot preparation of trifluoromethyl‐substituted fused bicyclic pyridine systems is developed.

Pyridine and Pyridinium Electrochemistry on Polycrystalline Gold Electrodes and Implications for CO2 Reduction

We examine the electrochemical behavior of pyridine (py) and pyridinium ion (pyrH+) on gold electrodes in inert nitrogen (N2) and carbon dioxide (CO2) environments to evaluate potential catalytic roles of nitrogen heterocycles in electrochemical CO2 reduction. Analysis of the pyridine and pyridinium systems shows that gold electrodes exhibit unique pyrH+ and CO2 electrochemistry compared with previous work on platinum electrodes or photoelectrode systems. Specifically, analysis of the data shows specific adsorption of pyridine/pyridinium, an irreversible reduction wave at −1.0 V vs Ag/AgCl associated with the one-electron reduction of pyridinium, and an enhanced reductive current when CO2 and pyrH+ are included together in the aqueous solution. Our results show no evidence to support formation of carbon-containing reduction products and implicate CO2 as a possible weak acid catalyst for production of dihydrogen.

Design and Efficient Synthesis of Some Azole and Thiazole Systems Based 3-(1,3-Dioxoisoindolin-2-yl)-3-oxopropanenitrile

A variety of pyrazoles, thiazoles, thiadiazoles, thiazolidines, azetidine, thiazolo[3,2-a]pyrimidine and pyrazolo[3,4-b]pyridine systems, based on 3-(1,3-dioxoisoindolin-2-yl)-3-oxopropanenitrile precursor are synthesized in good yields. The mechanistic aspect for the formation of the newly synthesized compounds is discussed and the structure of the synthesized compounds was established based on elemental analysis and spectral data. Keywords: Azole, thiazole, phthalimide, pyrazole, enaminonitrile, 1, 3-dioxoisoindoline.

ChemInform Abstract: A Heavy Metal‐ and Oxidant‐Free, One‐Pot Synthesis of Pyridines and Fused Pyridines Based on a Lewis Acid‐Catalyzed Multicomponent Reaction.

The InCl3-catalyzed sequential multicomponent reaction between 2-furfurylamine, β-dicarbonyl compounds and α,β-unsaturated aldehydes in ethanol, followed by microwave irradiation in solvent-free conditions, afforded good to excellent yields of highly substituted pyridines, with loss of a 2-furylmethyl side chain. The method was also adapted to the synthesis of quinolones, isoquinolines, phenanthridines and more complex fused pyridine systems.

Synthesis, Structure Elucidation, Antioxidant and Antimicrobial Activity of Novel 2-(5-Trifluoromethyl-1H-pyrazol-1-yl)-5-(5-trihalomethyl-1H-pyrazol-1-yl-1-carbonyl)pyridines

This paper describes an efficient approach for the synthesis of a novel series of sixteen 2-(5-trifluoromethyl-1H-pyrazol-1-yl)-5-(5-trihalomethyl-1H-pyrazol-1-yl-1-carbonyl) pyridines, for the first time with non-identical substituents in both pyrazole rings, through the cyclocondensation reaction of 4-methoxy-4-alkyl(aryl/heteroaryl-1,1,1-trihaloalk-3-en-2-ones [CX3C(O)CH=CR1OCH3, in which R1 = CH3, C6H5, 4-CH3C6H4, 4-OCH3C6H4, 2-furyl and X = F, Cl] or acetylacetone with some 6-[3-alkyl(aryl)-5-trifluoromethyl-1H-pyrazol-1-yl]nicotinohydrazides. Optimized yields of 67-91% were obtained when the reactions were performed in ethanol (green solvent) at reflux for 16 h. Subsequent antioxidant and antimicrobial evaluation revealed promising 1,1-diphenyl-2-picrylhydrazyl (DPPH) inhibition percentage and exhibited fungiostatic and fungicidal activities against yeasts, dermatophytes and filamentous, especially for the pyridine systems, when the both pyrazole rings attached to a pyridine ring contain CX3 groups (X = H, F, Cl) of different kinds. It is also observed the trichloromethyl substituted compounds presented higher antioxidant activity in comparison to their fluorinated analogous.

Study on the synthesis of novel 5-substituted 2-[2-(pyridyl)ethenyl]-1,3,4-oxadiazoles and their acid-base interactions.

A series of novel 5-substituted 2-[2-(pyridyl)ethenyl]-1,3,4-oxadiazoles were efficiently synthesized by cyclocondensation of the appropriate 3-(pyridyl)acrylohydrazides with triethyl orthoesters in the presence of glacial acetic acid. The products were identified by means of spectroscopic methods and their pK A ionization constants were determined. The influence of substituents on the basicity of the pyridine system has been discussed.Graphical

A new, efficient and highly-regioselective approach to synthesis of 6-O-propionyl-d-glucose by using whole-cell biocatalysts

For the first time, whole microbial-cell biocatalysis method was successfully applied by us to the production of glucose esters by transesterification of glucose with vinyl propionate. Among ten bacterial and fungal strains tested, lyophilized cells of Pseudomonasstutzeri strain GIM 1.273 efficiently catalyzed the reaction with the highest conversion and initial rate. 13C NMR analysis showed that the reaction catalyzed by P. stutzeri yielded 6-O regiomer predominantly (>99%), clearly indicating high regioselectivity of the biocatalyst toward the 6-O-hydroxy group of glucose. Efficiency of the reaction catalyzed by lyophilized cells was evidently solvent-dependent. With the exception of acetonitrile-pyridine and tetrahydrofuran-pyridine systems, the substrate conversion rate clearly increased with increasing hydrophobicity of the organic solvent media used. The best results were obtained in isooctane–pyridine (3:7 v/v) system. Other optimal conditions were: water content 2% (v/v), molar ratio of the acyl donor to glucose 10:1, biocatalyst dosage 80mg/mL and reaction temperature 35°C, under which glucose conversion and reaction rate were 97.2% and 29.7mmol/Lh over the duration of 24h. A tenfold scale-up production of the 6-O-glucose ester further demonstrated that whole-cell P.stutzeri was an efficient and highly-regioselective alternative to purified enzymes for synthesis of glucose esters.

Employment of the TiCl4–Anisole–Pyridine System in the Condensation of Amides with Aromatic Amines

Employment of the TiCl4–Anisole–Pyridine System in the Condensation of Amides with Aromatic Amines

ChemInform Abstract: Functionalization of Imidazo[1,2‐a]pyridines by Means of Metal‐Catalyzed Cross‐Coupling Reactions

AbstractReview: [101 refs.