Synthesis Of Polysubstituted Pyridines 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.

Synthesis of Polysubstituted Pyridines and Pyrazines via Truce-Smiles Rearrangement of Amino Acid-Based 4-Nitrobenzenesulfonamides.

Immobilized l-glutamic acid β-methyl ester was sulfonylated with 4-nitrobenzenesulfonyl chloride and alkylated with various α-haloketones. The resulting sulfonamides were reacted with potassium trimethylsilanolate. Then, upon cleavage from the polymer support, tetrasubstituted pyridines were produced as the result of one-step C-arylation, aldol condensation, and oxidation. When cleavage from the resin occurred before the trimethylsilanolate treatment, C-arylation was followed by enamination, which yielded trisubstituted pyrazines. Through the developed protocols, targeted synthesis of novel heterocyclic derivatives was performed using mild reaction conditions and a number of readily available starting materials.

Recent developments in the synthesis of polysubstituted pyridinesviamulticomponent reactions using nanocatalysts

This review describes the evolution and application of active metal-based and heterometallic NPs as efficient heterogeneous catalysts for the synthesis of pyridine derivatives by multicomponent reactions in the last decade (2010–2020).

MgO NPs Catalyzed Eco‐friendly Reaction: A Highly Effective and Green Approach for the Multicomponent One‐pot Synthesis of Polysubstituted Pyridines using 2‐Aminobenzothiazole

A one‐pot multicomponent green and environmentally friendly synthesis of 5‐amino‐3‐benzothiazol‐2‐yl‐7‐(phenyl)‐2‐phenyl‐2,3‐dihydro‐thiazolo[4,5‐b]pyridine‐6‐carbonitrile via Knoevenagel condensation followed by Michael addition has been described in the presence of a green, low‐cost, mild, and efficient magnesium oxide as the heterogeneous base catalyst. The present methodology has attractive features such as excellent product yields, environmentally benign milder reaction conditions, use of nontoxic organic solvents, and easily recoverable and reusable nanocatalyst. The synthesized compounds have been confirmed by spectral analysis (Fourier transform infrared, 1H‐NMR, 13C‐NMR, and mass spectrometry).

Synthesis of Polysubstituted Pyridines and Indoles by a Palladium‐Catalyzed Catellani‐type Alkylation‐Alkenylation Sequence

AbstractThe C−H functionalization of heterocycles has attracted extensive attention recently due to the ubiquity of substituted heterocycles in natural products, drugs, and other bioactive molecules. The Catellani‐type C−H functionalization, which is a palladium‐catalyzed and norbornene‐mediated coupling process, can properly overcome the metal poisoning between hetero atoms and metal catalyst. Based on this fact, we developed a method to efficiently build multiple C−C bonds on the pyridine and indole substrates by one‐pot process and finally achieved ortho‐alkylation/ipso‐alkenylation in moderate to good yields.

Dual functional novel catalytic Cu1−xZrxFe2O4 (x=0, 0.5, 1) nanoparticles for synthesis of polysubstituted pyridines and sunlight‐driven degradation of methylene blue

The effect of varied zirconium content on the structural, morphological, magnetic, optical, thermal and catalytic properties of nanoparticles of the ferrite Cu1 − xZrxFe2O4 (x = 0, 0.5, 1) was investigated. The mixed ferrite was synthesized by the auto‐combustion method using nitrates of respective metals and citric acid as a chelating agent. The as‐prepared nanoparticles showed dual benefits. They were employed as a heterogeneous catalyst for one‐pot synthesis of polysubstituted pyridine derivatives as well as for catalytic degradation of industrial waste dyes such as methylene blue (MB). The highlight of the research reported is the catalytic degradation of industrial waste (MB) with high efficiency in eluent of a wide range of pH (3–13). The proposed nanoparticles arguably offer certain great advantages that include: low cost, facile nature, anti‐leaching property, magnetic recoverability and recyclability. The characterization of the as‐synthesized nanoparticles was done using various techniques. The leaching study was carried out using inductively coupled plasma optical emission spectroscopy. The formation of organic products was confirmed using Fourier transform infrared and 1H NMR spectroscopies and examination of degradation products of MB dye was carried out using mass spectrometry and UV–visible spectroscopy.

Investigating the Catalytic Performance of Graphene Oxide –Polyaniline –Lignosulfonate Nanocomposite in the Synthesis of Polysubstituted Pyridines via a Four‐Component Reaction

AbstractIn this research, graphene oxide –polyaniline −lignosulfonate (GO‐PANI‐LS) nanocomposite was synthesized successfully and it was used as an effective recyclable catalyst for the synthesis of polysubstituted pyridines. Characterization of the prepared nanocomposite was carried out by Fourier transform infrared radiation (FT‐IR), X‐ray diffraction patterns (XRD), Energy‐dispersive x‐ray spectroscopy (EDX), Field‐emission scanning electron microscopy (FE‐SEM) and Thermogravimetric analysis (TGA). The first report of using this nanocomposite as a heterogeneous catalyst in synthesis of polysubstituted pyridines, Eco‐friendly, high catalytic activity of catalyst, simplicity of procedure, mild reaction conditions, easy recovery and considerable reusability without significant loss of performance are advantages of this method.

Synthesis of polysubstituted pyridines from oxime acetates using NH4I as a dual-function promoter.

Pyridine formation with oxime acetates as the building blocks under metal-free conditions is described. Ammonium iodide has proved to be a highly efficient promoter for oxime N-O bond reduction and subsequent condensation reactions, whereby it played a dual-function role in the transformation. While the three-component reaction of oxime acetates, benzaldehydes, and 1,3-dicarbonyls proceeded well with the assistance of a stoichiometric amount of ammonium iodide, the condensation of oximes and acroleins was enabled by using a catalytic initiator to afford substituted pyridines. By this protocol, substituted pyridine products were generated in moderate to excellent yields with tolerance towards a broad range of functional groups.

Synthesis of Some Polysubstituted Nicotinonitriles and Derived Pyrido[2,3-d]pyrimidines asIn VitroCytotoxic and Antimicrobial Candidates

The synthesis of polysubstituted pyridines, in addition to some derived pyrido[2,3-d]pyrimidine ring systems supported with chemotherapeutically active functionalities, is described. They were evaluated for theirin vitrocytotoxic effects against three different human tumor cell lines (human colon carcinoma HT29, hepatocellular carcinoma Hep-G2, and Caucasian breast adenocarcinoma MCF7). Nine compounds displayed variable cytotoxic potential, among which alkylthio analogs33,34, and37emerged as the most active members, being almost twice as active as doxorubicin against the colon carcinoma HT29 cell line. In addition, the same three analogs showed a clear differential cytotoxic profile as they exhibited a marginal inhibitory effect on the growth of the normal nontransformed human foreskin fibroblast Hs27 cell line. Meanwhile, nineteen compounds were able to exhibit significant antibacterial activity against both Gram-positive and Gram-negative bacteria, together with moderate antifungal activities. The pyrido[2,3-d]pyrimidine-2(1H)-thione30together with its alkylthio derivatives33and34stemmed as the most active antimicrobial members being equipotent to ampicillin againstS. aureus,E. coli,andP. aeruginosa,together with a noticeable antifungal activity againstC. albicans.Compounds33and34could be considered as a promising template for possible dual antimicrobial-anticancer candidates.

Synthesis of polysubstituted pyridines as potential multidrug resistance modulators

Abstract Polysubstituted pyridines 4 bearing methoxyphenyl groups at different positions of the ring have been prepared by the alkylation of 6-thioxo-1,6-dihydropyridines 1 or by the oxidation of 1,4-dihydropyridine 6 with manganese triacetate. The multidrug resistance–modulating (P-glycoprotein inhibition) activity of pyridine derivatives 4 comparable with that of verapamil has been revealed.

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.

ChemInform Abstract: Synthesis of Polysubstituted Pyridines under Combined Microwave and Ultrasound Irradiation: K2CO3‐Promoted Tandem Addition/Cyclization/Hydrogen Shift Process.

AbstractThe multicomponent reaction, efficiently achieved under optimized conditions A), allows an interesting access to pyridine structures of type (IV).

Regiospecific Synthesis of Polysubstituted Pyridines

Regiospecific Synthesis of Polysubstituted Pyridines

Synthesis of polysubstituted pyridines under combined microwave and ultrasound irradiation: K2CO3-promoted tandem addition/cyclization/hydrogen shift process

A convenient and efficient K2CO3-promoted tandem reaction of chalcone, malononitrile, and methanol for the synthesis of highly functionalized pyridines has been developed. This multi-component reaction employing the weak nucleophilic agent methanol proceeded smoothly under combined microwave and ultrasound irradiation (CMUI). The reaction mechanism was proposed to consist of a Michael addition, a methoxylation of CN bond, a cyclization to a 1,4-dihydropyridine and an intermolecular hydrogen shift between 1,4-dihydropyridine and initial chalcone.

Dimethylformamide Dimethyl Acetal (DMFDMA) in Heterocyclic Synthesis: Synthesis of Polysubstituted Pyridines, Pyrimidines, Pyridazine and Their Fused Derivatives

Reaction of N,N’-dimethylformamide dimethyl acetal (DMFDMA) with malononitrile dimer 8 (1:1) mole afforded 9 while, this reaction when carried out in (2:1) mole to give amidine 11 which can be used for the preparation of pyrimidine 13, amidine 14 and pyridine 19 when reacted with 4-nitroaniline, 4-methylaniline and alkoxide respectively. Malononitrile dimer reacted with diazonium chloride to give pyridazine 21, which can be reacted with DMFDMA, AcOH/HCl and cyanoacetamide to give pyridazine 22, 23 and pyrido[4,3-c] pyridazine 24 respectively. The latter reacted with DMFDMA to afford tricyclic compound 25.

β-Aminocrotononitrile in heterocyclic synthesis: Synthesis of polysubstituted pyridines as precursors to bicycles and polycycles

β-aminocrotononitrile (1) reacted with either cyanothioacetamide to give (3) or malononitrile to afford an anion (5). Pyridine-2(1H)-thione (4) was obtained by boiling of (3) in ethanol and Et 3N or treatment of (5) with H 2S, respectively. The reaction of anion 5 with isothiocyanates (6) gave N-substituted pyridine-2(1H)-thiones (7). N-Substituted pyridine-2(1H)-thiones (7) can be used for the preparation of pyrido[2,3-d]pyrimidines (8a–e) and (10a–e), or the preparation of pyrido[1,2-a]pyrimidines (12a–d). 1,8-Naphthyridine derivatives (14a–d) and (16a–e) can also be obtained from pyridine-2(1H)-thione (7). Finally, 1,8-naphthyridine derivatives (16a–e) can be used for the preparation of tetracyclic compounds 17a–c and 18a,b.

Sulfone‐Mediated Synthesis of Polysubstituted Pyridines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

ChemInform Abstract: Reactions of Sodium Salts of 3‐(Hydroxymethylene)alkan‐2‐ones with Enamines: Synthesis of Polysubstituted Pyridines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: A “One‐Pot” Synthesis of Polysubstituted Pyridines from Metalated Alkylphosphonates, Nitriles, and α,β‐Unsaturated Ketones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

α,α-Dioxoketene dithioacetals as starting materials for the synthesis of polysubstituted pyridines

Reactions of 3-acetyl-4,4-bis(methylthio)but-3-en-2-one 2e and methyl 2-acetyl-3,3-bis(methylthio)prop-2-enoate 2f with cyanothioacetamide, cyanoacetamide, or 2-amino-1,3,3-tricyanoprop-1-ene and base, followed by treatment with acid, give polysubstituted pyridines such as 8,10,11,13,15 and 16. Further elaboration of these products leads to bicyclic systems such as thieno[2,3-b]pyridines 17 and 18 and pyrazolo[3,4-c]pyridine 21 and then to tricyclic systems including pyrazolo[3,4-d]thieno[2,3-b]pyridine 19 and dipyrazolo[3,4-b:3′4′-d] pyridine 22.