Synthesis Of Quinolines Research Articles

Potassium Phosphate-Mediated Synthesis of C4-Phosphorylated Quinolines via Cascade Cycloisomerization of Ynones.

A cascade phosphorylation cycloisomerization of readily accessible ynones and diphenylphosphine oxides facilitated by potassium phosphate is described, allowing for the straightforward synthesis of C4-phosphorylated quinoline scaffolds. The formation of a C-P bond and a C-N bond is achieved in a single procedure without the need for pre-assembled quinoline cores prior to phosphorylation. This transformation operates without the requirement for metals or oxidants and exhibits excellent compatibility with various functional groups. Furthermore, antimicrobial activity evaluation demonstrated that the synthesized C4 phosphorylated quinoline derivatives exhibited potent inhibitory activity against Staphylococcus aureus.

Co(II) and Cu(II) Porphyrins Catalysed the Synthesis of Quinoline and Naphthoxazine via Dehydrogenative Reactions

: In this study, we developed a facile Co (II) and Cu (II)-porphyrin catalytic system for dehydrogenative coupling reaction of benzyl alcohol with acetophenone derivatives for quinoline synthesis and intramolecular cyclisation of Betti base for naphthoxazine synthesis. Functionalized porphyrins containing ester and quinoline ring (CoTPPBenzo(NPh)) and (CuTPPBenzo(NPh)) were synthesized and confirmed via various analytical techniques. These cobalt (II) and copper (II) porphyrins were tested for the synthesis of quinolines and naphthoxazines via a dehydrogenative coupling reaction. These cobalt and copper porphyrins showed excellent catalytic activity with broad substrate scope. Additionally, a series of controlled experiments were performed to support this work.

Quinoline Synthesis: Nanocatalyzed Green Protocols-An Overview.

Heterocyclic compounds are of great interest in our daily lives. They are widely distributed in nature and are synthesized in laboratories. Heterocycles play an important role in the metabolism of all living cells, including vitamins and coenzyme precursors like thiamine and riboflavin. Furthermore, heterocyclic systems are essential building blocks for creating innovative materials with intriguing electrical, mechanical, and biological properties. Also, more than 85% of all biologically active chemical entities comprise a heterocycle. As a result, heterocycle synthesis piqued researchers' curiosity, and in recent decades, chemists have concentrated more on nitrogen-containing cyclic nuclei in structures. Quinoline and its derivatives exhibit several biological functions, including antimicrobial, anticancer, antimalarial, anti-inflammatory, antihypertensive, and antiasthmatic effects. In addition, over a hundred quinoline-based drugs are available to treat a variety of disorders. Because of its biological importance, researchers developed one-pot synthetic methods employing effective acid/base catalysts (Lewis acids, Brønsted acids, and ionic liquids), reagents, and transition-metal-based catalysts. These methods have some downsides, including longer reaction times, harsher reaction conditions, creation of byproducts, costly catalysts, use of hazardous solvents, an unacceptable economic yield, and catalyst recovery. Researchers' focus has switched to creating environmentally friendly and effective methods for the synthesis of quinoline derivatives as a result of these methodologic shortcomings. Because of its special qualities, the use of nanocatalysts or nanocomposites offers an option for the effective synthesis of quinolines. This review focuses on the published research articles on nanocatalysts to synthesize substituted quinoline derivatives. This review covers all contributions until May 2024, focusing on quinoline ring building and mechanistic issues. With the aid of this review, we anticipate that synthetic chemists will be able to develop more effective methods of synthesizing quinolines.

Promising metal-free green heterogeneous catalyst for quinoline synthesis using Brønsted acid functionalized g-C3N4

Rationally designing distinct acidic and basic sites can greatly enhance performance and deepen our understanding of reaction mechanisms. In our current investigation, we studied the utilization of Brønsted acid sites within layered graphitic carbon nitride (g-C3N4) for the first time to enhance the rate of the Friedländer synthesis. The structural and surface analyses confirm the effective integration of -COOH and -SO3H groups into the g-C3N4 lattice. The surface-functionalized g-C3N4-CO-(CH2)3-SO3H exhibits a remarkable acceleration in quinoline formation, surpassing previously mentioned catalysts, and demonstrating notable recyclability under optimized mild reaction conditions. The heightened reaction rate observed over g-C3N4-CO-(CH2)3-SO3H is attributed to its elevated surface acidity. By probing the Friedländer reaction mechanism through surface characterization, examination of reaction intermediates, and investigation of substrate scope, we elucidate the pivotal role of Brønsted acid sites. This study constitutes a comprehensive exploration of metal-free heterogeneous catalysts for the Friedländer reaction, offering a unique contribution to the field.

Synthesis of Quinolines Catalyzed by Bidentate Terpyridine Mn(I) Complex

ABSTRACTA method for efficient synthesis of quinolines via acceptorless dehydrogenative condensation is presented. A series of quinolines are obtained by the coupling reaction of 2‐aminobenzyl alcohols with secondary alcohols in the presence of bidentate terpyridine Mn(I) complex in good to excellent yields. Pleasantly, various substituted secondary alcohols and substituted aminobenzyl alcohols all provide quinolines with good functional group tolerance. Importantly, this investigation also provides a green and environmentally friendly protocol for constructing heterocyclic compounds.

Total synthesis of natural benzoazepinoquinolinone alkaloid irrepairzepine via Au(I)-catalyzed cycloisomerization and regioselective functionalization

Irrepairzepine (1), a unique benzoazepinoquinolinone alkaloid isolated from an endophytic fungus, exhibits synthetic lethality targeting in PTEN-deficient glioblastoma cells. Herein, the first synthesis of irrepairzepine was achieved through a series of high-yielding reactions. The key steps include the synthesis of quinoline via the Au(I)-catalyzed cycloisomerization of N-propargyl aniline and construction of the azepinone core through the acid-catalyzed lactamization of an aminophenyl cyanoquinoline precursor, which was prepared using a simple umpolung approach that involves regioselective bromination followed by the Rosenmund-von Braun reaction.

Electrochemical Synthesis of Quinolines

AbstractThis report outlines an intramolecular oxidative annulation process involving N-substituted o-amino phenylacetylene, performed under electrochemical conditions, which yields substituted quinoline in an undivided cell at room temperature. The reaction features mild conditions, requiring neither external oxidants nor metals, and achieves yields that range from good to excellent. Moreover, the synthetic potential of quinoline has been demonstrated resulting in the synthesis of substituted polycyclic isoindolinone and (aza-)isoindolinone compounds.

Design, synthesis and molecular docking study of novel quinoline–triazole molecular hybrids as anticancer agents

A series of novel thirty-three quinoline-triazole molecular hybrids were designed and synthesized via Copper catalyzed azide-alkyne cycloaddition (CuAAC) strategy. The in-vitro anticancer activity of the synthesized compounds was screened against human breast cancer MCF-7 cell line. Among these, compounds 6h, 8i, 8l and 8n have displayed superior anticancer activity (IC50 values 0.39–3.65 μg/mL) than standard drug Doxorubicin (IC50 value 3.69 μg/mL). Whereas, compounds 6b, 8d, 8f, 8h, 8m and 8o have displayed moderate anticancer activity with IC50 values ranging from 5.52 to 11.49 μg/mL. Drug-likeness and ADMET profiling revealed favorable properties, and DFT studies confirmed promising electronic characteristics. Molecular docking indicated strong binding to CDK2 with affinities of -9.7 to -10 kcal/mol, supporting their potential as therapeutic candidates.

Synthesis of quinoline fused 1,2,3-triazole derivatives via continuous CuAAC and C[sbnd]H arylation; anti-breast cancer, anti-EGFR and HER2 activities, computational studies

Some new quinoline linked fused 1,2,3-triazole hybrids (5a-5o) were synthesized via Cu(I) catalyzed azide-alkyne cycloaddition followed by intramolecular CH arylation in one pot. Further, these derivatives were screened for their anti-breast cancer activity against MCF-7, MDA-MB-468 and MDA-MB-231 cell lines and results were compared with the 5-fluorouracil (5-FU). Out of all, compounds 5a, 5c, 5f, 5g and 5j displayed higher activity than the 5-FU against three cancer cell lines. Compound 5a was more effective in inhibiting both tyrosine kinase EGFR and HER2 enzymes than the Erlotinib and Lapatinib. Furthermore, compound 5j demonstrated greater potency than the Erlotinib against EGFR. Molecular docking studies revealed the important binding features of most potent compounds 5a, 5c, 5f, 5g and 5j with EGFR (PDB ID-4HJO) and HER2 (PDB ID-3RCD) and results were found to be supportive with corresponding IC50 data. Finally, in silico pharmacokinetic studies revealed that compounds 5a, 5c, 5f, 5g and 5j followed Ghose, Egan, Muegge, Lipinski and Veber rules without any deviation.

Dehydrogenative N−N Coupling and Facile Synthesis of Cobalt Complexes Supported by Tetrazene Based Ligand: Synthesis of Quinolines and Quinazolinones via Activation of Alcohols

AbstractHerein we first report the unprecedented synthesis of tetrazene‐based cobalt complexes using unusual coupling of amines via dehydrogenation. These cobalt complexes were employed for dehydrogenative coupling reactions to synthesize N‐heterocycles (quinoline, and quinazolinone). Based on control experiments and IR identification of intermediates, we proposed a plausible reaction mechanism. Synthesis protocols were utilized for preparative scale synthesis and biologically active molecule (±)‐galipinine synthesis.

Insight into the Various Approaches Undertaken for the Synthesis of Quinoline Hybrids Imparting Diverse Therapeutic Activities

Abstract: Quinoline is one of the promising and prominent biologically active N-based heterocyclic compounds. This review paper aims to discuss the synthetic approaches, summarized from various research articles on the preparation of quinoline derivatives intended for different therapeutic activities like antifungal activity, anticancer activity, anticonvulsant activity, antitubercular activity, antimalarial activity, anti-Alzheimer activity and so on. The comprehensive study complies with all related publications and trademark publications demonstrating the synthesis and biological aspects of quinoline derivatives. Various types of quinoline hybrids were synthesized and treated for therapeutic activity, including anticancer, antitubercular, anti-Alzheimer, antioxidant, and antifungal activity, which have been analyzed. Quinoline is a planner hetero-aromatic compound with the chemical formula C9H7N. Several wellknown synthetic routes to the quinoline skeleton include Friedlander synthesis, Knorr quinoline synthesis, and Skraup reaction. Researchers may use other techniques or alter current strategies to reach their objectives, depending on what exact structure and therapeutic action they are investigating. The availability of starting materials, reaction conditions, scalability, desired regioselectivity, and functionalization of the quinoline core all have a role in the choice of synthetic method. This review covers the latest literature and knowledge on the synthetic procedures for numerous quinoline and its derivatives and their biological and pharmacological application.

Recent Innovations in Synthetic Methodologies and Patent Landscape of Quinoline Analogues: A Comprehensive Review

: Quinoline is a general group of heterocyclic compounds that have garnered much interest in medicinal chemistry and drug development due to their wide range of pharmacological effects. Pyridine ring fused with benzene defines the class of chemical compounds known as quinolines. Quinoline is a weak tertiary base, also known as 1-aza-naphthalene. Numerous patents have been filed for the synthesis of quinoline-based compounds, discussing about their derivatives and uses. Here, we have discussed the methods of quinoline synthesis, structural alterations, and patents showing its importance in various industries. Quinolines have been investigated as antimalarial substances, with substances, like quinine and chloroquine, serving as notable examples, and they have also been investigated to possess anti-inflammatory, anti-tumor, and CNS activity. The synthesis of quinoline is also subjected to several recognized procedures. The variations in the ring system and various synthetic approaches are the key highlights of the article, and it includes the various catalysts that could be recycled and reused by the assisted technique, which increases the yield and requires less time for the synthesis (ultrasound-promoted synthesis, one-pot reaction, and microwave and photocatalytic reactions). The development of synthetic procedures can help in the sustainable synthesis of quinoline derivatives.

Metal–Organic Frameworks Based on Copper and Dicarboxy‐Functionalized Imidazole Modified With Halides: Enhancement of Catalysis in Organic Synthesis

ABSTRACTNew chloride‐ and bromide‐modified metal–organic frameworks (MOFs) based on copper and 1,3‐bis (carboxymethyl)imidazole (bcmim) derivatives have been prepared via post–synthetic modification (PSM) or by a direct route, following a simple, effective, and sustainable protocol. These materials have been characterized, and their catalytic activity has been studied. Cu‐bcmim‐Cl and Cu‐bcmim‐Br materials have been shown to be more efficient acidic catalytic systems than nonmodified materials. The catalytic activity has been tested as a Lewis acid catalyst in the methanolysis of styrene oxide and in the synthesis of quinolines and acridines, with the recovery and recyclability of the catalysts being possible. Furthermore, the catalytic activity of the catalysts has been tested in the oxidative coupling of formamides and carboxylic acids.

Marine Actinobacteria Mediated Titanium Dioxide Nanoparticle Synthesis and Its Application Towards Synthesis of Quinolines

Marine Actinobacteria Mediated Titanium Dioxide Nanoparticle Synthesis and Its Application Towards Synthesis of Quinolines

Single-Atom Fe-Catalyzed Acceptorless Dehydrogenative Coupling to Quinolines.

A single-atom iron catalyst was found to exhibit exceptional reactivity in acceptorless dehydrogenative coupling for quinoline synthesis, outperforming known homogeneous and nanocatalyst systems. Detailed characterizations, including aberration-corrected HAADF-STEM, XANES, and EXAFS, jointly confirmed the presence of atomically dispersed iron centers. Various functionalized quinolines were efficiently synthesized from different amino alcohols and a range of ketones or alcohols. The iron single-atom catalyst achieved a turnover number (TON) of up to 105, far exceeding the results of current homogeneous and nanocatalyst systems. Detailed mechanistic studies verified the significance of single-atom Fe sites in the dehydrogenation process.

Design, Synthesis, and Biological Evaluation of Quinoline (Quinolinone) Derivatives as NADPH Oxidase (NOX) Inhibitors.

NADPH oxidases (NOXs) are the sole enzyme in the human body that can directly produce reactive oxygen species. Recent studies have shown that NOXs is a very promising target for the treatment of diabetic nephropathy (DN). Here, a series of quinoline(quinolinone) derivatives have been designed based on pharmacophore strategy, synthesized and evaluated. Among them, 19d exhibits potent antiproliferative and NOXs inhibitory activities, and is worthy for further investigation.

Synthesis of a CCC-NHC pincer Mn complex: An earth abundant catalyst for synthesis of α-alkylated ketones, 2-oxindole derivatives via borrowing hydrogen and one-pot synthesis of quinolines

A CCC-NHC pincer Mn complex was prepared and was characterized by 1H and 13C NMR spectroscopy, mass spectroscopy, elemental analysis, and single crystal X-ray crystallography. Its catalytic activities were demonstrated through diverse chemical transformations including cross-coupling borrowing hydrogen reactions and dehydrogenative cyclization reactions, which resulted in the formation of both C–C and C–N bonds. These cascade reactions involved multiple processes, including dehydrogenation, condensation, and hydrogenation. Under optimized conditions, Mn catalyst affectively converted a broad substrate scope. The different reactions yielded saturated ketones (isolated yields, 42 %–92 %), 2-oxindole derivatives (isolated yields, 70 %–83 %), and quinoline derivatives (isolated yields, 70 %–89 %). These atom economical transformations produce only water molecules as by-products enhancing their environmental friendliness. The catalyst utilized earth-abundant Mn potentially reduce costs. Catalytic cycles were proposed for borrowing hydrogen and acceptorless dehydrogenative cyclization reactions based on control experiments. These included oxidation, aldol condensation, and hydrogenation reactions.

Exploiting Nitroreductases for the Tailored Photoenzymatic Synthesis of Structurally Diverse Heterocyclic Compounds.

N-heterocyclic compounds have a broad range of applications and their selective synthesis is very appealing for the pharmaceutical and agrochemical industries. Herein we report the usage of the flavin-dependent nitroreductase BaNTR1 for the photoenzymatic synthesis of various anthranils and quinolines from retro-synthetically designed o-nitrophenyl-substituted carbonyl substrates, achieving high conversions (up to >99 %) and good product yields (up to 96 %). Whereas the effective production of anthranils required the inclusion of H2O2 in the reaction mixtures to accumulate the needed hydroxylamine intermediates, the formation of quinolines required the use of anaerobic or reducing conditions to efficiently generate the essential amine intermediates. Critical to our success was the high chemoselectivity of BaNTR1, performing selective reduction of the nitro group without reduction of the carbonyl moiety or the activated carbon-carbon double bond. The results highlight the usefulness of an innocuous chlorophyll- and nitroreductase-based photoenzymatic system for the tailored synthesis of diverse N-heterocycles from simple nitro compounds.

Gold catalysis in quinoline synthesis.

Quinolines are biologically and pharmaceutically important N-heterocyclic aromatic compounds, which have broad applications in medicinal chemistry. Thus, their efficient synthesis has attracted extensive attention, and a broad range of synthetic strategies have been established. Of note, gold-catalyzed methodologies for the synthesis of quinolines have greatly advanced this field. Various gold-catalyzed intermolecular annulation reactions, such as annulations of aniline derivatives with carbonyl compounds or alkynes, annulations of anthranils with alkynes, and annulations based on A3-coupling reactions, as well as intramolecular cyclization reactions of azide-tethered alkynes, 1,2-diphenylethynes, and 2-ethynyl N-aryl indoles, have been developed. This review provides an overview of this exciting research area. Typical achievements in reaction methodologies and plausible reaction mechanisms are summarized.

Lewis Acid‐Promoted Domino Processes for the Synthesis of Homoallylic Amines, Quinolines and Tetrahydroquinolines

AbstractHerein, the synthesis of homoallylic amines, quinolines, and tetrahydroquinolines has been demonstrated. The domino one‐pot multi‐component approach has been accomplished using Lewis acid‐catalyzed conditions. A useful scaffold construction strategy can be achieved by controlling the electronic effect of aniline rather than relying on reaction conditions. The described method applies to a wide variety of substrates embedded with diverse functional groups and can be extended toward the synthesis of natural products. Suitable control experiments, real‐time NMR studies, and DFT calculations have validated the reported process. The protocol outlines a strategy for synthesizing homoallylic amines and quinolines, controlled by the electronic properties of anilines.