Polysubstituted Pyridine Derivatives Research Articles

Synthesis of Polysubstituted Pyridines via Nitrogen-doped Graphene Catalyzed One-Pot Multicomponent Reaction under Solvent-Free Conditions

Abstract: Polysubstituted pyridine derivatives were produced with high to excellent yields in the presence of nitrogen-doped graphene (NDG) as a dual acid-based catalyst. NDG efficiently catalyzes the multicomponent reaction between arylaldehydes, diethyl-acetylene dicarboxylates, malononitrile, and ammonium acetate under solvent-free conditions at 80°C to afford the polysubstituted pyridines in short reaction times. The structures of the synthesized pyridines were established by Ft-IR, 1H, and 13C NMR spectroscopic analysis. The advantages of this method include the in-situ oxidation of prepared 1,4-dihydropyridines, one-pot procedure, solventless system, operational simplicity, and no column chromatography. Additionally, neither toxic solvents nor catalysts are needed, and the procedure can be very reliable among the reported methodologies. The yields and reaction times in the presence of four times recycled catalyst are in comparable to the fresh catalyst.

L-Proline catalyzed multi-component synthesis of N-pyridyl-tetrahydroisoquinolines and their α-C(sp3)-H oxygenation.

Herein, we report an effective multi-component synthesis that starts with readily available starting materials and accesses poly-substituted pyridine derivatives by using L-proline as a benign catalyst. This process uses cyclic amines, aldehydes, and malononitrile in a condensation reaction to produce a variety of pyridine derivatives under mild conditions. Furthermore, depending on the catalysts used, the selective synthesis of an amide and/or an aldehyde functionality is achieved through α-C(sp3)-H oxygenation of the tertiary amine moiety in the resultant pyridine derivatives. The pyridine ring's nitrogen atom plays a crucial role in accelerating C-H oxygenation at the α-position of the tertiary amine, highlighting the synthetic versatility and usefulness of this method.

One-Pot Multi-Component Synthesis of Polysubstituted Pyridines Using DBU-SiO2 as a Robust Recyclable Catalyst

We report an efficient novel route for the synthesis of polysubstituted pyridine derivatives with DBU-SiO2 catalyzed one-pot four-component reaction. This protocol offers a mild condition that which affords a series of new polysubstituted pyridine derivatives with good yields. A plausible mechanism for this process is proposed.

A novel CDK8 inhibitor with poly-substituted pyridine core: Discovery and anti-inflammatory activity evaluation in vivo

As an ideal anti-inflammatory target, cyclin-dependent kinase 8 (CDK8) has gradually attracted the attention of researchers. CDK8 inhibition up-regulates Interleukin-10 (IL-10) expression by enhancing the transcriptional activity of activator protein-1 (AP-1), and augmenting IL-10 abundance is a viable strategy for the treatment of inflammatory bowel disease (IBD). In this research, through structure-based drug design and dominant fragment hybridization, a series of poly-substituted pyridine derivatives were designed and synthesized as CDK8 inhibitors. Ultimately, compound CR16 was identified as the best one, which exhibited good inhibitory activity against CDK8 (IC50 = 74.4 nM). In vitro and in vivo studies indicated that CR16 could enhance the transcriptional activity of AP-1, augment the abundance of IL-10, and affect CDK8-related signaling pathways including TLR7/NF-κB/MAPK and IL-10-JAK1-STAT3 pathways. In addition, CR16 showed potent therapeutic effect in an animal model of IBD.

Synthesis of Polysubstituted Pyridine Derivatives via Sequential AlCl3‐Catalyzed Condensation/Aza‐Wittig/Isomerization Reactions and a Study of their Antifungal Activities

AbstractA facile approach to access polysubstituted pyridine derivatives starting from Baylis‐Hillman adducts is disclosed. The reactions proceeded smoothly by sequential AlCl3‐catalyzed condensation/aza‐Wittig/isomerization reactions, leading to the target products at room temperature within 24 h in moderate to good yields. Furthermore, the final products were evaluated in mycelial growth tests against Pythium dissimile, Botryotinia fuckeliana and Zymoseptoria tritici and showed potential activities.

Synthesis and Characterization of Nanorod Magnetic Co–Fe Mixed Oxides and its Catalytic Behavior Towards One-Pot Synthesis of Polysubstituted Pyridine Derivatives

ABSTRACTThe nanorod magnetic Fe2O3@Fe3O4@Co3O4 composite as a novel catalyst was synthesized and fully characterized using X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), and transmission electron microscopy. Moreover, the prepared nanorod magnetic Fe2O3@Fe3O4@Co3O4 composites were used as an efficient, cheap, and eco-friendly catalyst for the one-pot synthesis of polysubstituted pyridine derivatives. The catalyst is magnetically separable and recyclable up to the fourth run without significant loss of activity. The products were obtained in high yields (78%-97%) and purities via an easy workup procedure.

Design, Synthesis, and Antimicrobial Evaluation of some Novel Pyridine, Coumarin, and Thiazole Derivatives

Treatment of 2‐cyano‐N′‐(1‐(pyridin‐2‐yl)ethylidene)acetohydrazide 1 with aromatic/heterocyclic aldehydes 2a–f gave arylidene derivatives 3a–f. Polysubstituted pyridine derivatives 4a,b were prepared either from reaction of arylidene 3a,b with malononitrile or from reaction of acetohydrazide 1 with arylidenemalononitrile 5a,b. Cyclocondensation of acetohydrazide 1 with salicylaldehyde derivatives and acetylacetone furnished pyrido‐coumarins 6,7 and 2‐pyridone‐3‐carbonitrile 8, respectively. In addition, pyrido‐thiazoles 13 and 15 were obtained through reaction of 2‐(1‐(pyridin‐2‐yl)ethylidene)hydrazinecarbothioamide 11 with hydrazonyl chlorides and α‐haloketones, respectively. The structures of synthesized compounds were elucidated with spectral and elemental data. The antimicrobial activity of the synthesized compounds was studied.

One-pot facile synthesis of polysubstituted pyridines via tandem reaction of the Blaise reaction intermediates and 3-formylchromones

A novel tandem one-pot method for the synthesis of polysubstituted pyridine derivatives has been developed via Knoevenagel-type reaction and subsequent 6π electrocyclization of the Blaise reaction intermediates and 3-formylchromones. Short reaction time, moderate to good yields and excellent functional group tolerance have been accomplished in this protocol.

ChemInform Abstract: FeCl3‐Catalyzed Four‐Component Nucleophilic Addition/Intermolecular Cyclization Yielding Polysubstituted Pyridine Derivatives.

We report an efficient route to pyridine derivatives via an FeCl3-catalyzed four-component nucleophilic addition/intermolecular cyclization. This simple fragment assembly strategy uses mild conditions and affords a broad range of polysubstituted pyridines in moderate to good yield from simple and readily available starting materials. A plausible mechanism for this process is proposed.

FeCl₃-catalyzed four-component nucleophilic addition/intermolecular cyclization yielding polysubstituted pyridine derivatives.

We report an efficient route to pyridine derivatives via an FeCl3-catalyzed four-component nucleophilic addition/intermolecular cyclization. This simple fragment assembly strategy uses mild conditions and affords a broad range of polysubstituted pyridines in moderate to good yield from simple and readily available starting materials. A plausible mechanism for this process is proposed.

Synthesis of polysubstituted pyridines via reactions of chalcones and malononitrile in alcohols using Amberlite IRA-400 (OH−)

Polysubstituted pyridine derivatives were synthesized through economical one-pot multicomponent reactions of different α,β-unsaturated ketones, malononitrile, and ethanol or methanol in the presence of Amberlite IRA-400 (OH−) at room temperature. The catalyst is recyclable several times without substantial loss of activity. Other valuable features include the wide range of functional group tolerance, easy and clean synthesis with a simple work-up procedure, and excellent yields under mild conditions.

Regioselective synthesis of polysubstituted pyridines via hetero-Diels–Alder reaction of isotellurazoles with acetylenic dienophiles

Treatment of substituted isotellurazoles or their Te-oxides with acetylenic dienophiles efficiently afforded polysubstituted pyridine derivatives through a pathway involving hetero-Diels–Alder reaction of isotellurazoles and the subsequent tellurium extrusion from the intermediary cycloadducts.

One‐Pot Synthesis of Polysubstituted Pyridine Derivatives Using Ketene Dithioacetals.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

One-pot synthesis of polysubstituted pyridine derivatives using ketene dithioacetals

Polysubstituted pyridine derivatives were synthesized by the reaction of ketene dithioacetal, 3,3-bis(methylsulfanyl)methylenemalononitrile 1b, with a variety of active methylene compounds in the presence of either sodium hydroxide or potassium hydroxide as a base in DMSO. This reaction was carried out under economical one-pot reaction conditions (cheap catalyst and solvent) and solved the problem of the odor of methanethiol, commonly derived from reactions of ketene dithioacetals. This is a significant enhancement of GSC (green and sustainable chemistry) in the field of ketene dithioacetal chemistry.

Synthesis of 3,4-Disubstituted Pyridines Starting from Baylis-Hillman Adducts Using Schweizer Reaction

Recently, we have reported the facile synthesis of polysubstituted pyridine derivatives from the Baylis-Hillman adducts. As shown in Scheme 1, the Baylis-Hillman adducts of alkyl vinyl ketone 1a could be converted easily into their tosylamide derivatives 2a. Sequential Michael addition of 2a to the appropriate Michael acceptor, aldol type cyclization, dehydration, elimination of p-toluenesulfinic acid, and the final isomerization afforded polysubstituted pyridines. In the reaction, compound 2a served threecarbons and one-nitrogen atom for the final pyridine while the Michael acceptor served two-carbon atoms. In this paper we wish to report the application of another two-carbon unit, vinyltriphenylphosphonium bromide (3a, Schweizer reagent), for the synthesis of 3,4-disubstituted pyridines. Extensive efforts have been devoted to the synthesis of 3,4-disubstituted pyridine derivatives due to their biological importance and the usefulness as synthetic intermediates. As shown in Scheme 2 and in Table 1, the reaction of 2a and 3a in CH3CN in the presence of DBU at 40-50 C for 16 h afforded 5a in 72% yield. Benzylidene derivative 5a must be formed via the successive Michael-Wittig reaction (Schweizer reaction). We could prepare 3-benzyl-4-methylpyridine (6a) from the reaction of 5a under K2CO3/DMF

Regioselective construction of polysubstituted pyridine ring from Baylis–Hillman adducts via sequential introduction of tosylamide, Michael reaction, aldol condensation, and elimination of TsH

Facile synthetic method of polysubstituted pyridine derivatives was developed starting from the Baylis–Hillman adducts. The reaction involved sequential introduction of tosylamide, Michael addition, aldol condensation, elimination of p-toluenesulfinic acid, and isomerization process.

ChemInform Abstract: Cycloadditions of Vinyl Isocyanate and Isothiocyanate with Oxovinylidene‐ and Phenyliminovinylidenetriphenylphosphoranes. New Synthesis and Crystal Structure of Polysubstituted Pyridine Derivatives.

ChemInformVolume 19, Issue 21 Organoelement Compounds ChemInform Abstract: Cycloadditions of Vinyl Isocyanate and Isothiocyanate with Oxovinylidene- and Phenyliminovinylidenetriphenylphosphoranes. New Synthesis and Crystal Structure of Polysubstituted Pyridine Derivatives. L. KNIEZO, L. KNIEZO Dep. Org. Chem., P. J. Safarik's Univ., 041 67 Kosice, Czech.Search for more papers by this authorP. KRISTIAN, P. KRISTIAN Dep. Org. Chem., P. J. Safarik's Univ., 041 67 Kosice, Czech.Search for more papers by this authorJ. IMRICH, J. IMRICH Dep. Org. Chem., P. J. Safarik's Univ., 041 67 Kosice, Czech.Search for more papers by this authorF. UGOZZOLI, F. UGOZZOLI Dep. Org. Chem., P. J. Safarik's Univ., 041 67 Kosice, Czech.Search for more papers by this authorG. D. ANDREETTI, G. D. ANDREETTI Dep. Org. Chem., P. J. Safarik's Univ., 041 67 Kosice, Czech.Search for more papers by this author L. KNIEZO, L. KNIEZO Dep. Org. Chem., P. J. Safarik's Univ., 041 67 Kosice, Czech.Search for more papers by this authorP. KRISTIAN, P. KRISTIAN Dep. Org. Chem., P. J. Safarik's Univ., 041 67 Kosice, Czech.Search for more papers by this authorJ. IMRICH, J. IMRICH Dep. Org. Chem., P. J. Safarik's Univ., 041 67 Kosice, Czech.Search for more papers by this authorF. UGOZZOLI, F. UGOZZOLI Dep. Org. Chem., P. J. Safarik's Univ., 041 67 Kosice, Czech.Search for more papers by this authorG. D. ANDREETTI, G. D. ANDREETTI Dep. Org. Chem., P. J. Safarik's Univ., 041 67 Kosice, Czech.Search for more papers by this author First published: May 24, 1988 https://doi.org/10.1002/chin.198821249Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume19, Issue21May 24, 1988 RelatedInformation