Quinolinium Salts Research Articles

Iodine‐Mediated Oxidative C=C Double‐Bond Formation toward Fused Quinolinones and Quinolinium Salts

An iodine‐mediated C=C double bond‐forming reaction has been established to access various fused quinolinone derivatives under transition metal‐free conditions. The present reaction is also applicable to the synthesis of fused quinolinium frameworks from the corresponding precursors and can be conducted on a gram scale.

Ruthenium-Catalyzed Interrupted Transfer Hydrogenation: An Approach for Reductive Functionalization of Quinolinium and Napthyridinium Salts.

Until now, a myriad of effective approaches have emerged for the functionalization of N-heteroaryl C-H bonds. In contrast, dearomatization and construction of fused heterocycles from activated heteroarenes is still a subject to explore. In this work, we present a refined approach for both dearomatization of N-heteroarenes and the synthesis of fused heterocycles from activated heteroarenes ruthenium catalysis using paraformaldehyde along with additive and base. Notably, quinolinium salts with a hydrogen at the C-4 position yield a methoxymethyl-substituted fused cyclic product through the Thorpe Ingold effect. An innovative aspect of this research is the dual functionality of paraformaldehyde as both a hydride donor and electrophile, utilizing readily available feedstock chemicals. A broad range of electron withdrawing and donating substituents was tolerable under standardized reaction conditions.

A Regiodivergent Dearomative Trifunctionalization of Quinolinium Salts to Access Fused Tetrahydroquinoline Polycycles.

Dearomative trifunctionalization of quinolinium salts is one of the most straightforward approaches to access biologically relevant multisubstituted tetrahydroquinolines. However, research in this field is still in its infancy. Here, we report a base-controlled regiodivergent dearomative trifunctionalization strategy for transforming quinoliniums into two kinds of structurally intriguing tetrahydroquinoline polycycles through a one-pot three-component cascade annulation. The key is the in situ generation of a "Nu-E-Nu" trifunctional reagent that can precisely identify the matched reactive sites of quinoliniums.

Dearomative Functionalization of Activated Quinolines: Transfer Hydrogenation/Cycloaddition Cascade to Construct α‐Tertiary Amines

Cascade dearomative functionalization is a robust protocol to convert flat arenes into medicinally relevant three‐dimensional architectures with added new functionality. Herein, a dearomative cycloaddition protocol for synthesizing tetrahydroquinoline‐embedded α‐tertiary amine scaffolds has been developed employing quinolinium salts and sulfonyl azides under metal‐free conditions. An underexplored and mechanistically distinct pathway is unveiled, creating quaternary‐center‐bearing amine skeletons by an amine group migration during the transfer hydrogenation and cycloaddition cascade reaction. This approach provided a broad substrate scope of α‐tertiary amine scaffolds from a plethora of C3‐substituted quinolinium and sulfonyl azides. The post‐synthetic modifications have further diversified the α‐tertiary amine core into interesting scaffolds. Preliminary mechanistic studies suggested the involvement of aziridine ring formation for the amine migration to the C‐3 position of quinoline to generate the α‐tertiary amine core.

Streamlined Synthesis of Varied Heteroarene-Condensed Benzofuran Derivatives via [4 + 2] Annulation of Benzofuran-Derived Azadienes and N-Alkyl Quinolinium Salts.

Herein we have pioneered an innovative synthetic strategy for the efficient assembly of various heteroarene-condensed benzofuran derivatives, utilizing benzofuran-derived azadienes (BDAs) and quinolines as the starting materials. This method functions with transition-metal catalysis and uses cost-effective formic acid as the reducing agent. Mechanistic investigations indicate that this transformation would involve a [4 + 2] annulation cascade process. This approach demonstrates a high tolerance to various functional groups and yields excellent results.

Divergent Synthesis of Cyclopropanated Tetrahydroquinolines by Tandem Functionalization of Quinoline Derivatives.

Here, reported is a new method for divergent synthesis of functionalized tetrahydroquinolines (THQs), featuring a biomedically interesting azabicyclo[4.1.0]heptane core, proceeding with mild conditions, good substrate and functionality tolerance, and operational simplicity. Mechanistic studies suggest that the products are formed via carbonucleophilic 1,4-addition-induced dearomatization of quinolinium salts and intramolecular cyclopropanation with α-halo ketones followed by α-nucleophilic addition with different nucleophiles. The present work lays a foundation to access new N-heterocycles via the dearomative tandem functionalization of azaarenes.

A highly sensitive ratiometric fluorescent probe for detecting HSO3−/SO32− and viscosity change based on FRET/TICT mechanism

BackgroundSulfur dioxide (SO2) is a significant gas signaling molecule in organisms, and viscosity is a crucial parameter of the cellular microenvironment. They are both involved in regulating many physiological processes in the human body. However, abnormalities in SO2 and viscosity levels are associated with various diseases, such as cardiovascular disease, lung cancer, respiratory diseases, neurological disorders, diabetes and Alzheimer's disease. Hence, it is essential to explore novel and efficient fluorescent probes for simultaneously monitoring SO2 and viscosity in organisms. ResultsWe selected quinolinium salt with good stability, high fluorescence intensity, good solubility and low cytotoxicity as the fluorophore and developed a highly sensitive ratiometric probe QQD to identify SO2 and viscosity changes based on Förster resonance energy transfer/twisted intramolecular charge transfer (FRET/TICT) mechanism. Excitingly, compared with other probes for SO2 detection, QQD not only identified HSO3−/SO32− with a large Stokes shift (218 nm), low detection limit (1.87 μM), good selectivity, high energy transfer efficiency (92 %) and wide recognition range (1.87–200 μM), but also identified viscosity with a 26-fold fluorescence enhancement and good linearity. Crucially, QQD was applied to detect HSO3−/SO32− and viscosity in actual water and food samples. In addition, QQD had low toxicity and good photostability for imaging HSO3−/SO32− and viscosity in cells. These results confirmed the feasibility and reliability of QQD for HSO3−/SO32− and viscosity imaging and environmental detection. SignificanceWe reported a unique ratiometric probe QQD for detecting HSO3−/SO32− and viscosity based on the quinolinium skeleton. In addition to detecting HSO3−/SO32− and viscosity change in actual water and food samples, QQD could also monitor the variations of HSO3−/SO32− and viscosity in cells, which provided an experimental basis for further exploration of the role of SO2 derivatives and viscosity in biological systems.

Iridium-catalyzed reductive β-alkylation of (iso)quinoline derivatives by an in situ enone-trapping strategy.

By employing [IrCp*Cl2]2/Mg(OMe)2/(CH2O)n as an applicable catalyst system, we report a reductive β-alkylation of (iso)quinolinium salts with cost-effective and readily available β-chloro ketones, proceeding with good chemoselectivity, mild reaction conditions, and without the need for introduction of a substituent at position-3 of the quinolyl skeleton. Mechanistic investigations suggest that the reaction proceeds via a sequence of hydride transfer-initiated dearomatization of (iso)quinolinium salts, in situ enamine-trapping of enone and a second round of hydride transfer to the coupling adducts. The present work offers an important complement to the synthesis of functionalized (iso)tetrahydroquinolines.

Phototherapeutic applications of benzophenone-containing NIR-emitting photosensitizers based on different receptor modulations.

Photodynamic therapy (PDT) plays a crucial role in treating cancer and major infectious diseases. However, the hypoxic microenvironment and deep-seated tumors often compromise the effectiveness of photosensitizers (PSs). PSs primarily generate type-II reactive oxygen species (ROS), which are limited under hypoxic conditions. Pyridinium salts frequently exhibit critical dark toxicity in vitro. Moreover, PDT alone often fails to achieve optimal anti-tumor effects compared to its combined application with photothermal therapy (PTT). To address these issues, we replaced pyridinium with quinolinium, significantly reducing dark toxicity. Additionally, the incorporation of benzophenone enhanced ROS generation, achieving a synergistic effect of type-I and type-II PDT. Fine-tuning the conjugated structure enhanced the donor-acceptor (D-A) intensity, while the stretching vibrations of carbon-carbon double bonds and carbon-nitrogen triple bonds red-shifted the excitation wavelength to the near-infrared (NIR) region and improved the photothermal conversion efficiency (PCE). This strategy provides a molecular design approach for achieving synergy between PDT and PTT. The synthesized four NIR-emitting aggregation-induced emission quinolinium salts exhibited mitochondrial targeting ability and low dark toxicity. Among them, FCN-TPAQ-BP showed excellent ROS generation capability, a PCE of 39.2%, good biocompatibility, and low dark toxicity, making it an ideal candidate for enhancing PDT's antitumor efficacy.

Facile one-pot synthesis of novel imidates as multifunctional organic fluorescent materials

A novel one-pot synthesis of multifunctional organic fluorescent imidates from quinolinium salt derivatives, nitrosoarenes and alcohols was presented. This method had a wide substrate scope and excellent isolated yields.

A ratiometric fluorescent probe based on the FRET platform for the detection of sulfur dioxide derivatives and viscosity

BackgroundSulfur dioxide (SO2) is a common gaseous pollutant that significantly threatens environmental pollution and human health. Meanwhile, viscosity is an essential parameter of the intracellular microenvironment, manipulating many physiological roles such as nutrient transport, metabolism, signaling regulation and apoptosis. Currently, most of the fluorescent probes used for detecting SO2 derivatives and viscosity are single-emission probes or probes based on the ICT mechanism, which suffer from short emission wavelengths, small Stokes shifts or susceptibility to environmental background. Therefore, the development of powerful high-performance probes for real-time monitoring of sulfur dioxide derivatives and viscosity is of great significance for human health. ResultsIn this research, we designed the fluorescent probe QQC to detect SO2 derivatives and viscosity based on FRET platform with quinolinium salt as donor and quinolinium-carbazole as acceptor. QQC exhibited a ratiometric fluorescence response to SO2 with a low detection limit (0.09 μM), large Stokes shift (186 nm) and high energy transfer efficiency (95 %), indicating that probe QQC had good sensitivity and specificity. In addition, QQC was sensitive to viscosity, with an 9.10-folds enhancement of orange fluorescence and an excellent linear relationship (R2 = 0.98) between the logarithm of fluorescence intensity at 592 nm and viscosity. Importantly, QQC could not only recognize SO2 derivatives in real water samples and food, but also detect viscosity changes caused by food thickeners and thereby had broad market application prospects. SignificanceWe have developed a ratiometric fluorescent probe based on the FRET platform for detecting sulfur dioxide derivatives and viscosity. QQC could not only successfully detect SO2 derivatives in food and water samples, but also be made into test strips for detecting HSO3−/SO32− solution. In addition, the probe was also used to detect viscosity changes caused by food thickeners. Therefore, this novel probe had significant value in food and environmental detection applications.

N-Vinylthio Phthalimides (N-VTPs): Modular Reagents for Vinylthio AIEgen Transfer.

Novel sulfur reagents N-vinylthio phthalimides (N-VTPs) have been employed as modular reagents for vinylthiolation, enabling the construction of aggregation-induced emission (AIE)-active tetraaryldivinyl sulfides (TADVSs) and diarylvinyl sulfides (DAVSs). Notably, TADVSs with sulfur insertion to ethene stators are reported as AIE luminogens (AIEgens) for the first time, and the corresponding photophysical properties and aggregated confirmation have been detailed for the demonstration of the AIE effect. A water-soluble TADVS with a quinolinium salt was prepared for cell imaging.

Diastereoselective Dearomatization of Chalcone‐Based Quinolinium Salts to Assemble Bridged Quinobenzazepine Polycycles

AbstractQuinobenzazepines are useful in medicinal chemistry, but their synthesis is very challenging. Herein, we designed and synthesized a range of multi‐functional chalcone‐based quinolinium salts; their synthetic application in the rapid and straightforward construction of quinobenzazepines was successfully explored. A wide range of oxa‐bridged quinobenzazepine polycycles were afforded serendipitously through a dearomative cascade reaction of our newly developed quinolinium salts and acetylacetone. This synthetic strategy features high bond‐ and ring‐forming efficiency and complete regio‐ and diastereoselective control.

Liquid–Vapor Equilibrium in a Toluene–Methanol–N-Octylquinolinium Bromide System

The liquid–vapor equilibrium in the toluene–methanol–N-octylquinolinium bromide system has been studied at 101.3 kPa and various concentrations of the organic salt. It was shown that the quinolinium salt can be used as a separating agent for a toluene–methanol azeotrope mixture. For breaking the azeotrope and separating the mixed solvent into components, the N-octylquinolinium bromide concentration (in mole fractions) should be 0.55 or higher.

Photochemically Mediated Ring Expansion of Indoles and Pyrroles with Chlorodiazirines: Synthetic Methodology and Thermal Hazard Assessment

AbstractWe demonstrate that arylchlorodiazirines serve as photo‐activated halocarbene precursors for the selective one‐carbon ring expansion of N‐substituted pyrroles and indoles to the corresponding pyridinium and quinolinium salts. Preliminary investigations indicate that the same strategy also enables the conversion of N‐substituted pyrazoles to pyrimidinium salts. The N‐substituent of the substrate plays an essential role in: (1) increasing substrate scope by preventing product degradation, (2) enhancing yields by suppressing co‐product inhibition, and (3) activating the azinium products towards subsequent synthetic manipulations. This latter point is illustrated by subjecting the quinolinium salts to four complementary partial reductions, which provide concise access to ring‐expanded products with different degrees of increased C(sp3) character. Thermal analysis of the diazirines by differential scanning calorimetry (DSC) provides detailed insight into their energetic properties, and highlights the safety benefits of photolyzing—rather than thermolyzing—these reagents.

Photochemically Mediated Ring Expansion of Indoles and Pyrroles with Chlorodiazirines: Synthetic Methodology and Thermal Hazard Assessment.

We demonstrate that arylchlorodiazirines serve as photo-activated halocarbene precursors for the selective one-carbon ring expansion of N-substituted pyrroles and indoles to the corresponding pyridinium and quinolinium salts. Preliminary investigations indicate that the same strategy also enables the conversion of N-substituted pyrazoles to pyrimidinium salts. The N-substituent of the substrate plays an essential role in: (1) increasing substrate scope by preventing product degradation, (2) enhancing yields by suppressing co-product inhibition, and (3) activating the azinium products towards subsequent synthetic manipulations. This latter point is illustrated by subjecting the quinolinium salts to four complementary partial reductions, which provide concise access to ring-expanded products with different degrees of increased C(sp3 ) character. Thermal analysis of the diazirines by differential scanning calorimetry (DSC) provides detailed insight into their energetic properties, and highlights the safety benefits of photolyzing-rather than thermolyzing-these reagents.

Eco-friendly, Fact and Green Synthesis of Methanobenzo[d]naphtho[1,2- g][1,3]Oxazocines using 1-Butyl-3-methylimidazolium Hydroxide under Solvent-free Ball Milling

Abstract: A green, solvent-free, and efficient strategy for the assembly of methanobenzo[ d]naphtho[1,2-g][1,3]oxazocine heterocycles using 1‑butyl‑3‑methylimidazolium hydroxide ([bmim]OH) ionic liquid under ball-milling solvent-free condition has been developed. For this purpose, the synthesis of methanobenzo[d]naphtho[1,2-g][1,3]oxazocine derivatives was carried out in a single step and one-pot reaction using 2-naphthol and quinolinium salts with the catalyst, 1‑butyl‑3‑ methylimidazolium hydroxide ([bmim]OH), at room temperature. This protocol's specific advantages are environmentally benign media, high yield, easy purification and short experimental time.

Oxidation of N-Alkyl(iso)quinolinium Salts Over TEMPO@Metal-Organic Framework Heterogeneous Photocatalyst†.

Quinolones and isoquinolones are of particular importance to pharmaceutical industry due to their diverse biological activities. However, their synthetic protocols were limited by high toxicity, high energy consumption, poor functional group tolerance and noble metal catalyst. This study concerns the development of a series of TEMPO@PCN-222 (TEMPO: 2,2,6,6-tetramethylpiperidinyl-1-oxy; PCN: porous coordination network) composite photocatalysts by coordinating different amount of 4-carboxy-TEMPO with the secondary building units of PCN-222. Upon visible-light irradiation, photogenerated holes in the highest occupied molecular orbital of PCN-222 can smoothly transfer to TEMPO, which can significantly boost the photosynthesis of bioactive (iso)quinolones from readily available N-alkyl(iso)quinolinium salts. TEMPO@PCN-222 exhibits an outstanding catalytic stability and substrate tolerance with a 1-methyl-2-quinolinone yield of 86.7 %, over four times that with PCN-222 (21.4 %). This work provides a new route to construct composite photocatalysts from abundant starting materials for efficient photosynthesis of high value-added chemicals.

Phenyl pyrrolo [1,2-a] quinolines- finding of a key by-product during quinolinium salt preparation

A key by-product, 2-phenylpyrrolo [1,2-a] quinoline, is isolated and characterized during the preparation of bioactive Pyridinium and quinolinium salts at ambient temperature. This protocol turned out to be an efficient approach for the one-pot synthesis of a series of 2-phenylpyrrolo [1,2-a] quinoline derivatives from 2-methyl quinoline and substituted phenacyl bromides. This method implicates a transition metal-based catalyst and base-free, environment-friendly solvent-free reaction conditions. All the newly synthesized derivatives have been characterized by 1H-NMR, 13C-NMR, and HRMS.

Mechanochemical Synthesis of 1,2,4‐Triazoles via a [3+2] Cycloaddition of Azinium‐N‐Imines and Nitriles

AbstractWe report here a mechanochemical Cu‐catalyzed [3+2] cycloaddition of azinium‐N‐imines with nitriles under solventless grinding conditions. Various 1,2,4‐triazolos derivatives were obtained in 51–80% yields. The developed protocol offers advantages in functional‐group compatibility, scalability, no use of solvents, shorter reaction time, and without external heating. In addition, heterocyclic N‐imines such as quinolinium and isoquinolinium salts are also suitable substrates, resulting in the production of 1,2,4‐triazolo[1,5‐a]quinoline and 1,2,4‐triazolo[5,1‐a]isoquinoline derivatives under mechanochemical conditions.magnified image