Synthesis Of Pyridine Derivatives Research Articles

Synthesis, crystallographic, quantum chemical and molecular docking studies of 4-benzoyl-1,2,3,11a-tetrahydro-6H-chromeno[3,2-e]imidazo[1,2-a]pyridin-6-one

The synthesis of pyridine derivatives is an active area of research in the development of new drugs. In view of the above importance, a novel compound with fused rings of derivatives of biologically active imidazole, pyridine and chromanone was synthesized. The crystal structure was analysed by single crystal X-ray diffraction method. The quantum chemical parameters of the molecule in the gaseous state were calculated by semi-empirical method using restricted Hartree-Fock wavefunction. The physicochemical properties such as druglikeness and bioactive scores were predicted to understand the drug transport and receptor interactions. Molecular docking studies were performed to analyze the binding of this compound with various bacterial and fungal pathogens. This study points out the potential of this compound to act as an antimicrobial agent. Comparison with related compounds shows that the addition of more number of biologically active groups enhances the activity.

Alkyl/Glycosyl Sulfoxides as Radical Precursors and Their Use in the Synthesis of Pyridine Derivatives.

We report here the use of simple and readily available alkyl sulfoxides as precursors to radicals and their application in the preparation of pyridine derivatives. We show that alkyl sulfoxides, N-methoxy pyridinium salts and fluoride anions form electron donor-acceptor (EDA) complexes in solution, which, upon visible light irradiation, undergo a radical chain process to afford various pyridine derivatives smoothly. This reaction displays broad scope with respect to both sulfoxides and N-methoxy pyridiniums. The synthetic versatility of sulfoxides as a handle in chemistry adds to their power as radical precursors. Glycosyl sulfoxides are converted to the corresponding pyridyl C-glycosides with high stereoselectivities. Computational and experimental studies provide insights into the reaction mechanism.

Alkyl/Glycosyl Sulfoxides as Radical Precursors and Their Use in the Synthesis of Pyridine Derivatives**

AbstractWe report here the use of simple and readily available alkyl sulfoxides as precursors to radicals and their application in the preparation of pyridine derivatives. We show that alkyl sulfoxides,N‐methoxy pyridinium salts and fluoride anions form electron donor–acceptor (EDA) complexes in solution, which, upon visible light irradiation, undergo a radical chain process to afford various pyridine derivatives smoothly. This reaction displays broad scope with respect to both sulfoxides andN‐methoxy pyridiniums. The synthetic versatility of sulfoxides as a handle in chemistry adds to their power as radical precursors. Glycosyl sulfoxides are converted to the corresponding pyridylC‐glycosides with high stereoselectivities. Computational and experimental studies provide insights into the reaction mechanism.

Base-Promoted One-Pot Synthesis of Pyridine Derivatives via Aromatic Alkyne Annulation Using Benzamides as Nitrogen Source.

In the presence of Cs2CO3, the first simple, efficient, and one-pot procedure for the synthesis of 3,5-diaryl pyridines via a variety of aromatic terminal alkynes with benzamides as the nitrogen source in sulfolane is described. The formation of pyridine derivatives accompanies the outcome of 1,3-diaryl propenes, which are also useful intermediates in organic synthesis. Thus, pyridine ring results from a formal [2+2+1+1] cyclocondensation of three alkynes with benzamides, and one of the alkynes provides one carbon, whilst benzamides provide a nitrogen source only. A new transformation of alkynes as well as new utility of benzamide are found in this work.

Selective VEGFR-2 inhibitors: Synthesis of pyridine derivatives, cytotoxicity and apoptosis induction profiling

VEGFR-2 is a key regulator in cancer angiogenesis. This research displays the design and synthesis of novel 3-cyano-6-naphthylpyridine scaffold-based derivatives as selective VEGFR-2 inhibitors and cytotoxic agents. In vitro percent kinase activity inhibition screening against a panel of 23 kinases at a single high dose (30 nM) affirmed that VEGFR-2 was selectively the most responsive to inhibition by the investigated chemotypes. IC50 values determination demonstrated kinase inhibitory activities of the test compounds at the sub-nanomolar level. In vitro testing of the new compounds against two prostate cancer cell lines namely PC3 and DU145 and two breast cancer cell lines namely MCF-7 and MDA-MB435 confirmed their potent cytotoxic activity with IC50s at the nanomolar level. The most active compound against MCF-7 viz.11d was subjected to an in vivo examination against a xenograft mouse model and was found effective. Studying the tissue mRNA expression levels of various cell cycle controlling biomolecules in 11d-treated MCF-7 cells demonstrated (i) upregulation of p53, p21 and p27, (ii) cleavage of PARP protein, (iii) activation of caspase-3, −8 and −9, (iv) downregulation of the anti-apoptotic protein Bcl, (v) upregulation of the pro-apoptotic protein Bax, and (vi) decreased expression of Cdks 2, 4, 6 and cyclin D1. Additionally, 11d affected a cell cycle arrest at the G1 phase in treated MCF-7 cells and an S phase arrest in MCF-7 p53 knockdown cells. Additionally, molecular docking was performed to predict how 11d might bind to its biological target VEGFR-2. Finally, in-silico ADME and drug-likeness profiling of these derivatives demonstrated favorable properties thereof.

NH4I-Triggered [4 + 2] Annulation of α,β-Unsaturated Ketoxime Acetates with N-Acetyl Enamides for the Synthesis of Pyridines.

The NH4I-triggered formal [4 + 2] annulation of α,β-unsaturated ketoxime acetates with N-acetyl enamides has been developed. The current protocol employs electron-rich enamides as C2 synthons and enables the efficient and straightforward construction of polysubstituted pyridines in moderate to good yields based on metal-free systems. The reaction tolerates a wide range of functional groups and represents an alternate route toward the synthesis of pyridine derivatives.

Transition-Metal-Free Synthesis of Pyridine Derivatives by Thermal Cyclization of N-Propargyl Enamines

A transition-metal-free synthesis of pyridine derivatives by 6-endo-dig cyclization of N-propargyl enamines was developed. This method is environmentally friendly and is a high atom economy reaction that is easily accessed to provide pyridine derivatives in moderate to good yield by heating N-propargyl enamines in solvent without additives. The total synthesis of onychine was achieved in 51% yield in only two steps by using this method.

Synthesis of Pyridine Derivatives from Acetophenone and Ammonium Acetate by Releasing CH4

AbstractAn efficient copper‐catalyzed cyclization of acetophenone and ammonium acetate with release of methane has been developed for the synthesis of polysubstituted pyridines. A series of 2,4,6‐triphenyl‐pyridines has been produced in good yields. This synthetic method is sustainable, simple, and environment‐friendly.

Synthesis and characterization of 2-(4-aryl-3-cyano-6-methylpyridin-2(1H)-ylidene)malononitriles

The synthesis of pyridine derivatives containing a buta-1,3-diene-1,1,3-tricarbonitrile fragment via the base-promoted reaction of benzalacetones and malononitrile dimer with subsequent oxidation is described. The influence of the substituents on the spectral-luminescent and electrochemical properties was also investigated.

ChemInform Abstract: Dihydropyridine Preparation and Application in the Synthesis of Pyridine Derivatives

AbstractReview: 236 refs.

Synthesis of pyridine derivatives as potential antagonists of chemokine receptor type 4.

A series of pyridine derivatives were synthesized as potential inhibitors of chemokine receptor type 4. This chemokine receptor has been linked to various disease pathways including HIV-1 proliferation, autoimmune disorders, inflammatory diseases, and cancer metastasis. The compounds were tested for activity using an affinity binding assay and an assay that tests the ability to inhibit cell invasion. Two hit compounds (2b and 2j) have been identified for further evaluation that inhibit cell invasion by at least 50% and have an effective concentration of less than 100 nM in the binding affinity assay. The structures of the synthesized compounds were confirmed by spectral data.

ChemInform Abstract: Application of Benzoylacetonitrile in the Synthesis of Pyridine Derivatives

AbstractReview: 92 refs.

Application of Benzoylaceteonitrile in the Synthesis of Pyridines Derivatives

This review deals with synthetic potential and utility of benzoylacetonitrile in the synthesis of pyridine derivatives. The reactions are subdivided into groups that cover the synthetic methods of pyridine derivatives from benzoylacetonitrile e.g. self condensation, Friedlander reaction, Michael Addition reaction, addition to enaminones, reaction with enamino-nitriles or enamino-esters, and one-pot three component reactions. A brief account on the synthesis of benzoylacetonitrile was also displayed. Keywords: Benzoylacetonitrile, Pyridines, Quinolines, Naphthyridines, Enaminones, Benzonitrile, Acetophenone, Haloacetophenone, bis(trifluoromethylsulfonyl)imide (PNIPAM), Electrosteric stabilisation

ChemInform Abstract: Recent Advances in Transition‐Metal‐Catalyzed [2 + 2 + 2]‐Cyclo(co)trimerization Reactions

AbstractReview: ca. 120 refs.

Recent Advances in Transition-Metal-Catalyzed [2+2+2]-Cyclo(co)trimerization Reactions

Transition-metal-catalyzed [2+2+2] cyclo(co)trimerization reactions are a powerful methodology to synthesize various complex multi-substituted (poly)cyclic molecules in a single step with optimal atom efficiency. Ever since the discovery, the reaction has been plagued by issues concerning regio- and chemoselectivity. Over the last decades many advances have been made to overcome these issues by, for example, employing regio-directing groups or tethering the reaction partners together in an intramolecular approach. These solutions, however, have certain limitations. Nowadays, it is also possible to synthesize chiral molecules by performing an asymmetric transition-metal-catalyzed [2+2+2]-cyclo(co)trimerization reaction. This review focuses on the recent advances in mechanistic insight, solving the regioselectivity issue, synthesis of chiral molecules and alternative approaches for the synthesis of substituted benzenes, pyridines and 2-pyridones. In addition, recent applications in areas such as total synthesis of natural products are also described, demonstrating that the transition-metal-catalyzed [2+2+2]-cyclo(co)trimerization reaction is a powerful tool and a welcome addition to the chemist’s ‘synthetic toolbox’. 1 Introduction 2 Synthesis of Benzene Derivatives 2.1 Mechanistic Insight 2.2 Regioselectivity 2.3 Synthesis of Chiral Systems 2.4 Other [2+2+2] Approaches 2.5 Synthesis of (Iso)quinolines 3 Synthesis of Pyridine Derivatives 3.1 Mechanistic Insight 3.2 Regioselectivity 3.3 Synthesis of Chiral Systems 4 Synthesis of Pyridone Derivatives 4.1 Mechanistic Insight 4.2 Regioselectivity 4.3 Synthesis of Chiral Systems 5 Applications 6 Future Directions 7 Conclusion

ChemInform Abstract: Synthesis of Pyridine Derivatives by the Three-Component Condensation of a β-Dicarbonyl Compound, β-Enaminocarbonyl Compound, and Ethyl Orthoformate.

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Developing state-of-the-art antiseptics based on pyridine derivatives

Research and design in the synthesis of pyridine derivatives with antiseptic properties, a pilot plant, and the organization of commercial production of state-of-the-art domestic antiseptics that reliably protect against dangerous infections are discussed, stressing that these project tasks were solved thanks to the RAS target program Innovation Support.

Heterogeneous Catalyzed Pyridine Synthesis using Montmorillionite and Nanoparticle‐Impregnated Alumina in a Continuous Micro Flow System

AbstractThe synthesis of pyridine derivatives was investigated using a combined micro flow‐through system. Therefore, two different heterogeneous catalyst assemblies were used subsequently under different temperature conditions. The investigated pyridine synthesis method includes three reaction steps: at first, an enamine has to be formed by a condensation reaction of methyl ketone and propargylamine. Secondly, a pericyclic reaction of the enamine is needed to form dihydropyridine derivatives. Finally, the dihydropyrimidines received have to be oxidized to yield the desired pyridine derivative. The propargylamine used tends towards side reactions even if activating catalysts are present at elevated temperatures. To reach high yields for the overall process, each reaction step demands for a specific catalyst and suited reaction conditions. Hence, the reaction sequence was separated into two consecutive steps. For the initial condensation reaction, montmorillionite was investigated as heterogeneous catalyst. For the subsequent reaction steps, different types of nanoparticles impregnated on alumina were investigated as oxidation catalyst, using air as oxidation agent. Here, the results and optimized process conditions for the conversion of aliphatic and aromatic methyl ketones are presented. As a result, the separation of the reaction steps by application of the two‐step microreactor system leads to a significant improvement of the process performance. The reaction time was reduced significantly to about 20 minutes without reduction of the product turnover in several cases.

Synthesis of pyridine derivatives and their influence as additives on the photocurrent of dye-sensitized solar cells

New kinds of additive, 4-alkyloxypyridne derivatives, were synthesized by introducing an alkyloxy group into the 4-position of 2-methylpyridine. The influence of these electrolyte additives on the short-circuit photocurrent (J sc) of dye sensitized solar cells was investigated by combining electrochemical and spectral techniques. With the addition of pyridine derivatives to the electrolyte, a decrease in the rate of dye regeneration was observed by laser flash photolysis measurements and cyclic voltammetry, whereas, measurement of electrochemical impedence spectra showed an increase in the charge transfer resistance due to the formation of a complex between the pyridine derivatives and iodine, as identified by an absorption peak around 378 nm in the UV–Vis spectra. This leads to a decrease in J sc of dye-sensitized solar cells. This adverse effect on the J sc can be attributed to reaction or coordination between the dye cations and the iodine in the electrolyte.

One‐Pot Synthesis of Pyridine Derivatives via Diels—Alder Reactions of 2,4‐Dimethyl‐5‐methoxyoxazole.

AbstractFor Abstract see ChemInform Abstract in Full Text.