Quinolinium Salts Research Articles

Nitrogen-Doped Carbon Supported Nanocobalt Catalyst for Hydrogen-Transfer Dearomative Coupling of Quinolinium Salts and Tetrahydroquinolines.

A nitrogen-doped carbon supported nanocobalt catalyst was developed and successfully applied for the hydrogen-transfer coupling of quinolinium salts and tetrahydroquinoline compounds. The selective coupling of the C6 sites of tetrahydroquinolines (THQs) with the α sites of quinoline salts generated a series of 2-substituted N-alkyl-tetrahydroquinolines. This catalytic conversion method, which can be employed to synthesize various functionalized tetrahydroquinolines, has several advantages that include excellent hydrogen transfer selectivity, a reusable and inexpensive catalyst, and environmental friendliness.

Indolizine quaternary ammonium salt inhibitors: The inhibition and anti-corrosion mechanism of new dimer derivatives from ethyl acetate quinolinium bromide and n-butyl quinolinium bromide

The dimer derivatives of ethyl acetate quinolinium bromide (Di-EAQBr) and n-butyl quinolinium bromide (Di-BuQBr) were synthesized from EAQBr and BuQBr, respectively. The structure of these indolizine dimer derivatives was confirmed by high-resolution mass spectrometry and nuclear magnetic resonance techniques. These compounds were employed as new and highly effective corrosion inhibitors (CIs) for N80 steel in 15 wt% HCl. The corrosion inhibition effectiveness was evaluated using immersion and electrochemical tests. It was shown that both dimers exhibited significantly higher corrosion inhibition effectiveness compared with quinolinium salt precursors and have great potential in oilfield applications. Next, the thermodynamic and adsorption isotherm aspects thereof, as well as the corrosion inhibition mechanism, were investigated using atomic force microscopy, X-ray photoelectron spectroscopy, and density functional theory (DFT) and molecular dynamics (MD) simulations. The results show that both dimers exhibit higher corrosion inhibition effectiveness compared with quinolinium salt precursors, although the dosage of the dimers was only 1% of the quinolinium salts. The dimers show stronger chemisorption as assessed by Gibbs standard free energy.

Evolution of the Dearomative Functionalization of Activated Quinolines and Isoquinolines: Expansion of the Electrophile Scope.

Herein we disclose a mild protocol for the reductive functionalisation of quinolinium and isoquinolinium salts. The reaction proceeds under transition‐metal‐free conditions as well as under rhodium catalysis with very low catalyst loadings (0.01 mol %) and uses inexpensive formic acid as the terminal reductant. A wide range of electrophiles, including enones, imides, unsaturated esters and sulfones, β‐nitro styrenes and aldehydes are intercepted by the in situ formed enamine species forming a large variety of substituted tetrahydro(iso)quinolines. Electrophiles are incorporated at the C‐3 and C‐4 position for quinolines and isoquinolines respectively, providing access to substitution patterns which are not favoured in electrophilic or nucleophilic aromatic substitution. Finally, this reactivity was exploited to facilitate three types of annulation reactions, giving rise to complex polycyclic products of a formal [3+3] or [4+2] cycloaddition.

Evolution of the Dearomative Functionalization of Activated Quinolines and Isoquinolines: Expansion of the Electrophile Scope.

Herein we disclose a mild protocol for the reductive functionalisation of quinolinium and isoquinolinium salts. The reaction proceeds under transition-metal-free conditions as well as under rhodium catalysis with very low catalyst loadings (0.01 mol %) and uses inexpensive formic acid as the terminal reductant. A wide range of electrophiles, including enones, imides, unsaturated esters and sulfones, β-nitro styrenes and aldehydes are intercepted by the in situ formed enamine species forming a large variety of substituted tetrahydro(iso)quinolines. Electrophiles are incorporated at the C-3 and C-4 position for quinolines and isoquinolines respectively, providing access to substitution patterns which are not favoured in electrophilic or nucleophilic aromatic substitution. Finally, this reactivity was exploited to facilitate three types of annulation reactions, giving rise to complex polycyclic products of a formal [3+3] or [4+2] cycloaddition.

Dearomatization of Heteroarenium Salts with ArBpin Reagents. Application to the Total Synthesis of a Nuphar Alkaloid.

Rhodium-catalyzed enantioselective addition of aryl and heteroaryl boron pinacol esters to pyridinium and quinolinium salts is developed for the synthesis of enantioenrichred dihydroheteroarenes. The methodology has enabled the synthesis of 2-heteroaryl-substituted dihydropyridines in high yield and ee, which provided efficient synthetic access to a nuphar alkaloid.

Recent Applications of Quinolinium Salts in the Synthesis of Annulated Heterocycles

AbstractQuinoline derivatives are frequently found in natural products and biologically active compounds; however, construction of quinoline fused polyheterocycles is a challenging goal in synthetic organic chemistry. In this regard, quinolinium salts meet the demand to a great level, as they can be synthesized readily and employed effectively for rapid construction of the condensed heterocyclic core. The present review focuses on recent (2015–2021) applications of different quinolinium salts, which react with suitable partners to access diverse annulated products. Most of the reactions discussed here involve easily available starting materials, are operationally simple, offer high atom-efficiency, and are environmentally benign. Mechanistic aspects of representative transformations have also been highlighted to better understand the reaction pathways.1 Introduction2 Annulation Involving N-Alkyl Quinolinium Salts2.1 Reaction with Alkenes2.2 Reaction with Alkynes/Arynes2.3 Reaction with Phenolic Compounds2.4 Reaction with Cyclic/Acyclic Diketones2.5 Reaction with Amines/Cyclic Amines2.6 Reaction with Enamines2.7 Reaction with Isocyanoacetates2.8 Reaction with Cyclopropanes2.9 Ring Expansion Reactions3 Annulation Involving Quinolinium Zwitterionic Tosylates3.1 Reaction with Alkynes/Arynes3.2 Reaction with Allenes/Ketenes3.3 Reaction with Aldehyde-Amino Acid (Azomethine Ylide)3.4 Reaction with Sulfonium Salts3.5 Reaction with Diazoacetate4 Annulation Involving Quinolinium Zwitterionic Thiolates4.1 Reaction with Sulfonium Salts4.2 Reaction with Sulfenes4.3 Reaction with Arynes5 Annulation Involving Quinoline N-Oxides5.1 Reaction with Diynes and Ynones5.2 Lactonization Involving Acrylate6 Annulation Involving N-Iminoquinolinium Salts6.1 Reaction with Allenoates6.2 Reaction with Hydroxymethylallyl Carbonate7 Miscellaneous Cyclizations8 Conclusions

Organic Cation Transporter-Mediated Accumulation of Quinolinium Salts in the LV Myocardium of Rodents

PurposeQuaternary ammonium salts have demonstrated marked accumulation in the left ventricular (LV) myocardium of rodents and swine. To investigate the mechanism underlying this uptake, the present study examined the interaction of [18F]fluoroethylquinolinium ([18F]FEtQ) with the family of organic cation transporters (OCTs).ProceduresThe cellular uptake of [18F]FEtQ into HEK293 cells, expressing human OCT1, -2, or -3 (HEK293-hOCT), and its inhibition by corticosterone was evaluated in vitro. The inhibitory effect of decynium 22 (D 22) in vivo was also studied, using PET/CT of HEK293-hOCT tumor-bearing mice. Furthermore, the distribution kinetics of [18F]FEtQ were determined in rats, with and without pre-administration of corticosterone, and following administration to a non-human primate (NHP).ResultsThe accumulation of [18F]FEtQ in HEK293-hOCT cells was 15–20-fold higher than in control cells and could be inhibited by corticosterone. in vivo, the uptake of [18F]FEtQ in the LV myocardium of corticosterone-treated rats was significantly reduced compared to that of untreated animals. Similarly, following administration of D 22 to HEK293-hOCT tumor-bearing mice, the peak tumor uptake of [18F]FEtQ was reduced by 40–45 % compared to baseline. Contrary to the distinct accumulation of [18F]FEtQ in the LV myocardium of rats, no cardiac uptake was observed following its administration to a NHP.ConclusionsThe quinolinium salt derivative [18F]FEtQ interacts with the family of OCTs, and this interaction could account, at least in part, for the increased uptake in the LV myocardium of rodents. Nonetheless, its low affinity for hOCT3 and the results of PET/CT imaging in a NHP indicate a limited clinical applicability as a radiopharmaceutical for cardiac and/or OCT imaging.

Construction of Fused Tetrahydroquinolines by Catalytic Hydride-Transfer-Initiated Tandem Functionalization of Quinolines

Herein, we present a new annulation reaction of quinolinium salts with indoles and paraformaldehyde, which enables syn-diastereoselective construction of a vast range of fused tetrahydroquinolines via ruthenium-catalyzed hydride-transfer-initiated tandem functionalization of the quinoline skeleton. The developed transformation proceeds with mild reaction conditions, good substrate and functional group compatibility, readily available feedstocks, and operational simplicity.

Dearomative Periphery Modification of Quinolinium Salts to Assemble Ring-Encumbered Pyrrolidine-Tetrahydroquinoline Polycycles.

We report an unexpected dearomative periphery modification strategy for transforming quinolinium salts into structurally crowded pyrrolidine-tetrahydroquinoline polycyclic systems with complete regio- and diastereoselectivity. Importantly, the reaction pathway was regulated by simply tuning the substituents, achieving substituent-directed divergent synthesis. The notable features of this transformation include readily available starting materials, green conditions, a simple workup procedure, high bond- and ring-forming efficiency, and substituent-directed diverse synthesis.

Efficient Synthesis of 7H‐Chromeno[3,2‐c]quinolin‐5‐ium Salts and Quinolin‐4‐ones through Acid‐Promoted Cascade Reaction of 3‐Formylchromones and Anilines

AbstractWe report an efficient and environment‐friendly approach for the synthesis of multisubstituted 7‐oxo‐7H‐chromeno[3,2‐c]quinolin‐5‐ium salts using ambient air as a green sole oxidant. The chromeno[3,2‐c]quinolin‐5‐ium salts were prepared through metal‐free cascade intermolecular cycloaddition/oxidation reaction of 3‐formylchromones and N‐substituted anilines using HClO4 as the reagent and promoter under concise one‐pot conditions. In the applied research, the resulting quinolinium salts could serve as synthons and could be further transformed to diverse synthetically useful 3‐(2‐hydroxy‐benzoyl)quinolin‐4‐ones in water. This protocol offers a simple cascade strategy to synthesize a wide variety of natural‐like chromeno[3,2‐c]quinolin‐5‐ium salts and quinolin‐4‐ones, and shows some academic research potential as well as industrial applications.

Directly arylated oligonucleotides as fluorescent molecular rotors for probing DNA single-nucleotide polymorphisms

We developed direct arylated oligonucleotide based molecular rotor (AOMR) to discriminate perfect matched DNA sequence from one base mismatched sequences. Quinolinium salts attached to vinyl aniline would be excellent fluorescent analogs with molecular rotor properties and are suitable for the detection of microenvironment change arising from dynamic motions with match-mismatch DNA base pairs. We applied direct N6 arylation of the adenosine located in natural oligonucleotide as a tool to incorporate the molecular rotor (Quinolinium salts attached vinyl aniline) and used it to discriminate perfect matched DNA sequence from one base mismatch sequences. The fluorescence and quantum yield of arylated oligonucleotide based molecular rotor (AOMR), particulary, RMAQn reveals 28.3 times higher discrimination factor with perfect matched sequence (RMAQn:T) (QY = 0.17) compare to single strand RMAQn (QY = 0.006) and one base mismatched sequence (RMAQn:G, RMAQn:A, and RMAQn:C) at λmax = 600 nm (orange emission), which would be useful for in vivo application. RMAQn:T duplex also showed high brightness (6068), 32.9 times higher than single strand RMAQn (192), as a result of restricted rotation of the Quinolinium salts attached vinyl aniline on adenosine moiety with perfect matched sequence compare to the mismatch sequences. Arylated oligonucleotide based molecular rotor (AOMR) proves to be an unprecedented sensitivity in detecting local dynamics of nucleic acids and also would be simple and cost-effective method to prepare SNP probe.

Facile and Selective Methylation of N-Heterocycles: The Base-Free Synthesis of Quinolinium and Pyridinium Salts at Room Temperature

Facile and Selective Methylation of N-Heterocycles: The Base-Free Synthesis of Quinolinium and Pyridinium Salts at Room Temperature

Organocatalysis: A Tool of Choice for the Enantioselective Nucleophilic Dearomatization of Electron-Deficient Six-Membered Ring Azaarenium Salts

Nucleophilic dearomatization of azaarenium salts is a powerful strategy to access 3D scaffolds of interest from easily accessible planar aromatic azaarene compounds. Moreover, this approach yields complex dihydroazaarenes by allowing the functionalization of the scaffold simultaneously to the dearomatization step. On the other side, organocatalysis is nowadays recognized as one of the pillars of the asymmetric catalysis field of research and is well-known to afford a high level of enantioselectivity for a myriad of transformations thanks to well-organized transition states resulting from low-energy interactions (electrostatic and/or H-bonding interactions…). Consequently, in the last fifteen years, organocatalysis has met great success in nucleophilic dearomatization of azaarenium salts. This review summarizes the work achieved up to date in the field of organocatalyzed nucleophilic dearomatization of azaarenium salts (mainly pyridinium, quinolinium, quinolinium and acridinium salts). A classification by organocatalytic mode of activation will be disclosed by shedding light on their related advantages and drawbacks. The versatility of the dearomatization approach will also be demonstrated by discussing several chemical transformations of the resulting dihydroazaarenes towards the synthesis of structurally complex compounds.

Development and preclinical evaluation of novel fluorinated ammonium salts for PET myocardial perfusion imaging

We previously presented the radiolabeled ammonium salt [11C]-dimethyl diphenylammonium trifluoromethanesulfonate ([11C]DMDPA) as a potential novel PET-MPI agent. The current study aimed to increase the clinical applicability of PET-MPI by designing and synthesizing fluorinated ammonium salt derivatives. Four fluorinated DMDPA derivatives and two quinolinium salt analogs were radiolabeled. The dynamic distribution in vivo, following injection of each derivative into male SD rats, was evaluated using small-animal dedicated PET/CT. Organ uptake after injection of [18F]fluoroethylquinolinium acetate ([18F]FEtQ) was examined ex vivo. Four fluorinated DMDPA derivatives were synthesized, two were labeled with fluorine-18: [18F]fluoroethyl-methyldiphenylammonium trifluoromethanesulfonate ([18F]FEMDPA) and [18F]fluorobuthyl-methyldiphenylammonium trifluoromethanesulfonate ([18F]FBMDPA). The other two were labeled using carbon-11: [11C]methyl-(3-fluorophenyl)-methylphenylammonium trifluoromethanesulfonate ([11C]3-F-DMDPA) and [11C]methyl-(4-fluorophenyl)-methylphenylammonium trifluoromethanesulfonate ([11C]4-F-DMDPA). All four DMDPA derivatives exhibited significantly lower heart/liver radioactivity uptake ratios (0.6, 0.4, 0.7 and 0.6, respectively) compared to that of [11C]DMDPA (1.2). Conversely, the two radiolabeled quinolinium salt derivatives, [11C]methylquinolinium iodide ([11C]MeQ) and [18F]FEtQ demonstrated improved heart/liver ratios (2.0 and 1.3, respectively) with clear visualization of the left ventricle myocardium. Renal clearance was the major route of elimination. Among the fluorinated quaternary ammonium salts tested, [18F]FEtQ yielded the best images. Further studies are in progress to elucidate the underlying mechanism of its cardiac uptake.

Technology Focus: Acidizing (June 2021)

Hydraulic fracturing technologies propagated from North America outward to other oil- and gas-producing regions in the world. In earlier days, the main technology developments were mostly related to the materials, such as fluids and proppants, and their characterizations. In recent years, more advancements have been made in tools, engineering processes, and analyses. In a cased-hole fracturing treatment, perforating plays a critical role to the success of the job, though it is often overlooked because perforations are visualized as holes with empty tunnel behind the pipe. Any damage is irrelevant because fracturing will simply bypass the damage. In fact, a shaped charge is made of metal liner and case with explosive loaded in between. The metal material is pushed into the formation under extremely high pressure from the detonation of the explosive. Without backflow of reservoir fluid to flush out the debris, the perforation tunnels are very likely plugged. In tight formations, the backflow is not efficient because the permeability is too low and the time scale of the surge is very short. Obtaining information about perforation before pumping the fracture treatment allows the engineers to adjust the job design, adding perforations or other means to deliver a more-desirable outcome for the fracturing treatment. Not all the wells or zones are suitable for hydraulic fracturing. Concerns over the well completion rating, nearby water layers, equipment and water availability, and other environmental and infrastructure constraints can limit the selection of stimulation method. Matrix chemical injection has often been the preferred or sometimes the only option. More-advanced technologies, however, are needed to extend reservoir access beyond the distance of matrix stimulation. Mechanical tunneling tools have been developed in recent years. They can bridge the gap between matrix and fracturing treatment very well. When combined with chemicals, this process can add efficiency in certain carbonate reservoirs. Hydrochloric acid continues to be the most effective and low-cost material for carbonate stimulation. Though exotic chemistries such as chelating agents and organic acids have been promoted for being less corrosive at high temperatures, the cost and dissolving capacity limit their use to large-scale implementation. The ability to inhibit the corrosion tendency of hydrochloric acid can prove to be beneficial in the economics of acidizing. New technologies in corrosion prevention, both in acid stimulation and production processes, should always be beneficial. During the tough year of 2020, and for the foreseeable future, implementation of engineering ingenuity will become more critical to maintain economical energy delivery in our industry. Recommended additional reading at OnePetro: www.onepetro.org. SPE 202369 Novel High-Effective Component for Acidizing Corrosion Inhibitors: Indolizine Derivatives of the Quaternary Quinolinium Salts by Zhen Yang, China University of Petroleum, et al. SPE 203086 First Successful Fishbone Stimulation Completion in Onshore Oil Field in the United Arab Emirates by Fernando Quintero, ADNOC, et al.

Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents.

We report here the design, synthesis, experimental and in silico evaluation of the antibacterial and antifungal activity of some new benzo[f]quinoline derivatives. Two classes of benzo[f]quinolinium derivatives—(benzo[f]quinolinium salts (BQS) and pyrrolobenzo[f]quinolinium cycloadducts (PBQC)—were designed and obtained in two steps via a direct and facile procedure: quaternization followed by a cycloaddition reaction. The synthesized compounds were characterized by elemental and spectral analysis (FT-IR, 1H-NMR, 13C-NMR). The antimicrobial assay reveals that the BQS salts have an excellent quasi-nonselective antifungal activity against the fungus Candida albicans (some of them higher that the control drug nystatin) and very good antibacterial activity against the Gram positive bacterium Staphylococcus aureus. The PBQC compounds are inactive. Analysis of the biological data reveals interesting SAR correlations in the benzo[f]quinolinium series of compounds. The in silico studies furnished important data concerning the pharmacodynamics, pharmacokinetics and ADMET parameters of the BQS salts. Studies of the interaction of each BQS salt 3a–o with ATP synthase in the formed complex, reveal that salts 3j, 3i, and 3n have the best fit in a complex with ATP synthase. Study of the interaction of each BQS salt 3a-o with TOPO II in the formed complex reveals that salts 3j and 3n have the best-fit in complex with TOPO II. The in silico ADMET studies reveal that the BQS salts have excellent drug-like properties, including a low toxicity profile. Overall, the experimental and in silico studies indicate that compounds 3e and 3f (from the aliphatic series), respectively, and 3i, 3j and 3n (from the aromatic series), are promising leading drug candidates.

Synthesis and Biological Screening of New Cyano-Substituted Pyrrole Fused (Iso)Quinoline Derivatives.

Several new cyano-substituted derivatives with pyrrolo[1,2-a]quinoline and pyrrolo[2,1-a]isoquinoline scaffolds were synthesized by the [3 + 2] cycloaddition of (iso)quinolinium ylides to fumaronitrile. The cycloimmonium ylides reacted in situ as 1,3-dipoles with fumaronitrile to selectively form distinct final compounds, depending on the structure of the (iso)quinolinium salt. Eleven compounds were evaluated for their anticancer activity against a panel of 60 human cancer cell lines. The most potent compound 9a showed a broad spectrum of antiproliferative activity against cancer cell lines representing leukemia, melanoma and cancer of lung, colon, central nervous system, ovary, kidney, breast and prostate cancer. In vitro assays and molecular docking revealed tubulin interaction properties of compound 9a.

DABCO-Catalyzed Easy Access to Benzo[d]naphtho[2,3-g][1,3]-oxazocine‑8,13(6H,14H)‑diones in Aqueous Media

An eco-friendly, highly efficient, and tandem reaction between 2-hydroxy-1,4-naphthoquinone and quinolinium salts in the presence of DABCO, 1,4-diazabicyclo[2.2.2]octane, in an aqueous medium is developed for the synthesis of functionalized polycyclic naphthooxazocines. The advantageous features of this operationally simple procedure along with good to excellent yields of products highlighted this method for the preparation of oxazocine. Moreover, the products obtained without the need for column chromatography. In order to reduce the hazards of chemicals and solvents, the reaction was conducted in the green solvent, water. All newly synthesized compounds were characterized by different methods involving IR, 1H NMR, 13C NMR spectroscopy.

Atroposelective Synthesis, Structure and Properties of a Novel Class of Axially Chiral N‐Aryl Quinolinium Salt

AbstractInspired by naturally occurring molecules containing atropisomeric N+‐C axes, we have developed a novel synthetic approach to generate a library of axially chiral N‐aryl quinolinium salts. Enantiopurities up to 93 % ee were obtained via a four‐step route from commercially available precursors. Axial stereochemistry was controlled through an enantioselective ring‐closing Buchwald–Hartwig coupling reaction. The structure and properties of the salts were examined by X‐ray crystallography, DFT, UV‐Vis, and fluorescence spectroscopy, revealing high rotational barriers and solvatochromic behaviour.

1,3-Dipolar cycloaddition of cyanopyridines to heterocyclic N-imines: experimental and theoretical study

Series of 2-pyridyl[1,2,4]triazolo[1,5-a]azines have been synthesized by cycloaddition of cyanopyridines with N-aminoazinium mesitylenesulfonates under basic conditions (KOH/H2O). An improved protocol for pyridyl-substituted [1,2,4]triazolo[1,5-a]pyridines synthesis based on addition of H2O2 as internal oxidant has been suggested. In the case of quinolinium and isoquinolinium salts, only dimerization of the corresponding N-imines has been observed, while pyrazinium-N-imine has not shown any reactivity toward cycloaddition. DFT studies have shown that the cycloaddition proceeds through concerted mechanism.