Nucleophilic Reaction Research Articles

Moisture-Assisted Hydroboration of Nitriles and Conversion Thereof to N-Heterocyles and N-Containing Derivatives.

The recent revelation of hidden-borane catalysis has revolutionized the field of catalytic hydroboration in organic synthesis. Many nucleophilic reaction promoters, previously believed to be the catalysts, in fact primarily facilitated the formation of borane (BH3), which subsequently acted as the true catalyst. This revelation prompted us to explore the untapped potential of these unexpected transformations, with a view to simplify hydroboration using more cost-effective and environmentally friendly nucleophilic precatalysts. Via computational studies, we were able to identify that water can actually undertake that role. Herein, we report a study on the simple hydroboration of nitriles, a notoriously challenging yet synthetically valuable class of substrates, using nothing more than moisture as an activating agent. This moisture-assisted nitrile hydroboration process can seamlessly integrate with a range of downstream transformations in a one-pot fashion to produce valuable N-containing products such as symmetrical imines, thioureas, and bis(alcohol)amines as well as N-heterocycles such as pyrroles, pyridines, pyridinium salts, 2-iminothiazolines, and carbazoles.

Carbazole-based mitochondria-targeted fluorescent probes for in vivo viscosity and cyanide detection in cells and zebrafish

Cells of most eukaryotic species contain mitochondria, which play a role in physiological processes such as cellular senescence, metabolism, and autophagy. Viscosity is considered a key marker for many illnesses and is involved in several crucial physiological processes. Cyanide (CN−) can target cytochrome-c oxidase, disrupting the mitochondrial electron transport chain and causing cell death through asphyxiation. In this study, a fluorescent probe named HL-1, which targets mitochondria and measures viscosity and CN− levels, was designed and synthesized. HL-1 is viscosity-sensitive, with a linear correlation coefficient of up to 0.992. In addition, HL-1 was found to change color substantially during a nucleophilic addition reaction with CN−, which has a low detection limit of 47 nM. HL-1 not only detects viscosity and exogenous CN− in SKOV-3 cells and zebrafish but also monitors viscosity changes during mitochondrial autophagy in real time. Furthermore, HL-1 has been used successfully to monitor changes in mitochondrial membrane potential during apoptosis. Endogenous CN− in plant samples was quantified. HL-1 provides new ideas for studying viscosity and CN−.

Recent Advances in Nucleophilic Lewis Base‐Catalyzed Cycloadditions for Synthesis of Spirooxindoles

AbstractSpirooxindoles are privileged scaffolds in diverse bioactive natural products and pharmaceuticals, significant achievements for the construction of these molecules have thus been made in the past years. Among them, organocatalysis, in particular, nucleophilic Lewis base catalysis, has recently emerged as an efficient and reliable method for the preparation of diverse and valuable functionalized spirooxindoles. According to different kinds of nucleophilic catalysts, we summarize and classify three catalytic strategies; these are tertiary amine‐catalyzed cycloadditions, NHC‐catalyzed cycloadditions, and tertiary phosphine‐catalyzed cycloadditions, respectively. Through these methods, potential bioactive spirooxindole skeletons owning various functional groups can be produced to enrich the small organic molecule library. In this review, we describe a comprehensive and updated advances of nucleophilic Lewis base catalytic cycloaddition reactions for the construction of spirooxindoles. Meanwhile, the related mechanism and the application of these annulation strategies in natural product total synthesis will be highlighted in detail.

Elucidating the corrosion inhibition mechanisms: A computational and statistical exploration of the molecular structure-efficiency relationship for phenolic Schiff bases in acidic medium on the mild steel surface

This study investigated mild steel corrosion inhibition using four Schiff bases in a theoretical framework. The study used statistical analysis to relate the experimental inhibitor's efficacy to theoretical data, revealing the corrosion inhibition process. Density functional theory (DFT) was used to assess the global reactivity of the four inhibitors' neutral, protonated, and complex forms. Where, Fukui functions were used for local reactivity study of the four inhibitors in neutral and protonated forms. To study system dynamics at the inhibitor-steel contact, a Monte Carlo simulation was performed. The experimental and quantum results are strongly correlated when the global quantum features of the neutral and protonated forms, such as the dipole moment μ, EHOMO, and ELUMO, are examined. The PA and pKa protonation parameters demonstrate that the protonation of the compounds strongly influences the inhibition efficiency. According to Fukui functions, the amine function (N) is the highest nucleophilic reactivity, making it highly sensitive to electrophilic attack, for all four inhibitors. The stability and predominance of complex forms in the medium were interpreted using thermodynamic characteristics of PSBi-FeCl2 complexes. Monte Carlo simulation yielded the most stable adsorption configurations, which were geometrically and energetically examined to explain experimental data. QSAR shows a significant linearity between theoretical parameters and experimental inhibitory efficiency.

Mechanistic Insights into Amphoteric Reactivity of an Iron-Bispidine Complex.

The reactivity of FeIII -alkylperoxido complexes has remained a riddle to inorganic chemists owing to their thermal instability and impotency towards organic substrates. These iron-oxygen adducts have been known as sluggish oxidants towards oxidative electrophilic and nucleophilic reactions. Herein, we report the synthesis and spectroscopic characterization of a relatively stable mononuclear high-spin FeIII -alkylperoxido complex supported by an engineered bispidine framework. Against the notion, this FeIII -alkylperoxido complex serves as a rare example of versatile reactivity in both electrophilic and nucleophilic reactions. Detailed mechanistic studies and computational calculations reveal a novel reaction mechanism, where a putative superoxido intermediate orchestrates the amphoteric property of the oxidant. The design of the backbone is pivotal to convey stability and reactivity to alkylperoxido and superoxido intermediates. Contrary to the well-known O-O bond cleavage that generates an FeIV -oxido species, the FeIII -alkylperoxido complex reported here undergoes O-C bond scission to generate a superoxido moiety that is responsible for the amphiphilic reactivity.

Origin of Ligand and Acid Effects on the Pd-Catalyzed Regiodivergent Coupling Reaction of Indazoles and Isoprene: A DFT Study.

Comprehensive computational studies were carried out to explore the mechanisms and origin of regioselectivity in the Pd-catalyzed regiodivergent coupling reaction of indazoles and isoprene. Three different insertion models were investigated for regioselectivity 1,2- or 4,3-insertion with respect to the electrophilic sites on isoprene under two different ligands (L1 and L2) and acids ((PhO)2PO2H, (nBuO)2PO2H) via PdII-H species, allyl-π-PdII-O, and indazoles-acid-assisted PdII-π-allyl. The calculated results show that the PdII-π-allyl coordinated mechanism is the most preferred one. The noncovalent interactions between the less bulky ligand L1, substrates, and (PhO)2PO2- are found to be key factors for 1,2-insertion. The 4,3-insertion selectivity is primarily controlled by the steric repulsion of the t-Bu group of bulky ligand L2 and substrate, as well as the geometry distortion. Therefore, the regioselectivity difference of the 1,2- and 4,3-insertion on electrophilic sites is controlled by the synergistic effect of ligands and acids instead of the size of the ligand. Similarly, nucleophilic site selectivity at N1 or N2 of indazoles is governed by cooperative acid BF3 and solvent iPrOH rather than BF3 alone. Overall, our findings might open a new avenue for designing more efficient regioselective 1,2- or 4,3-addition or N1-/N2-selective nucleophilic reactions.

Amphiphilic HZSM-5 for Cyclopentene Hydration at the Liquid-Liquid Interface in Pickering Emulsion.

Zeolite is considered an ideal catalyst for olefin hydration due to its high specific surface area and abundant acid sites. However, the immiscibility of the water-oil two phases in olefin hydration limits mass transfer, and the side reaction of etherification occurs acutely, resulting in a low yield of alcohol. Thus, water-oil amphiphilic HZSM-5 was prepared by sulfonating silanized zeolite. The successful introduction of organic and sulfonic acid groups is demonstrated by FT-IR, TG, and water contact angles. Amphiphilic HZSM-5 can stabilize the Pickering emulsion and catalyze cyclopentene hydration at the phase interface. In addition, NH3-TPD and Py-IR show that the amount of strong Bro̷nsted acid sites of zeolites increases significantly after sulfonation. This facilitates the rate-determining step of cyclopentene activation by H+ to form carbocation. Moreover, the nucleophilic side reactions are inhibited by a high concentration of H+. Finally, under the optimized reaction condition, the conversion of cyclopentene can achieve 5.066% with a selectivity of 85.37% to cyclopentanol, which almost reaches the reaction equilibrium.

Palladium-Catalyzed Tandem Cyclization of Bromoalkynes, Anilines and CO: Access to 1,3-Substituted Maleimides.

A novel palladium-catalyzed three-component carbonylation reaction for the assembly of various 1,3-substituted maleimide derivatives from haloalkynes and simple anilines. The nucleophilic addition reaction of haloalkynes, anilines and CO, and insertion of carbonyl have been achieved sequentially in this reaction. The high chemo- and regioselectivities, as well as no need of expensive ligands or additives further illustrate the synthetic value of this approach.

Nucleophilicity of 4-(Alkylthio)-3-imidazoline Derived Enamines.

Imidazolidine-4-thiones (ITOs) are cyclic, secondary amines that were considered as potential prebiotic organocatalysts for light-driven α-alkylations of aldehydes by bromoacetonitrile (BAN). Recent studies showed that the initially supplied ITOs represent the pre-catalyst because they undergo S-alkylation with BAN to give 4-(alkylthio)-3-imidazolines (TIMs). Given that the same reagent mix that undergoes light-driven α-alkylations is also effective in the dark, we synthesized ten ITO- or TIM-derived enamines of aldehydes and characterized their nucleophilic reactivities by kinetic studies in acetonitrile. The experimental second-order rate constants k2 for reactions of enamines with benzhydrylium ions (reference electrophiles) were evaluated by the Mayr-Patz equation, lg k2 (20 °C)=sN (N+E). The determined nucleophilicities N (and sN ) reveal the reactivity profiles of these enamines under prebiotically relevant conditions as well as their potential for use in organocatalytic synthesis.

Catalytic Enantioselective Nucleophilic Addition to Arynes by a New Quaternary Guanidinium Salt-Based Phase-Transfer Catalyst.

Owing to the mild generation methods, arynes have been widely used in synthetic chemistry. However, achieving asymmetric organocatalytic reactions with arynes remains a formidable and infrequent challenge, primarily because these neutral and transient species tend to spontaneously quench. To address this issue, a solid-liquid phase-transfer strategy is devised in which the generation speed of arynes could be controlled by the in situ generated fluoride-based chiral phase-transfer catalyst. In this study, we present a catalytic enantioselective nucleophilic addition reaction involving arynes, utilizing an amino amide-based guanidinium salt QG•X. Furthermore, we demonstrate the broad compatibility of this reaction with various arynes and cyclic/acyclic β-keto amides, leading to the creation of diverse α-aryl quaternary stereocenters with good stereoselectivity. Mechanistic investigations have uncovered the potential involvement of a chiral intramolecular cationic-anionic pair and HF during the ion exchange between QG•X and CsF for nucleophile activation and aryne generation. Additionally, DFT calculations suggested that the observed high levels of enantioselectivity can be attributed to steric repulsion and the cumulative noncovalent interactions between the catalysts and substrates.

Enabling Nucleophilic Reactivity in High-Spin Fe(II) Imido Complexes: From Elementary Steps to Cooperative Catalysis.

ConspectusTransition metal complexes featuring an M═NR bond have received great attention as critical intermediates in the synthesis of nitrogen-containing compounds. In general, the properties of the imido ligand in these complexes are dependent on the nature of the metal center. Thus, the imido ligand tends to be nucleophilic in early transition metal complexes and electrophilic in late transition metal complexes. Nonetheless, the supporting ligand can have a dramatic effect on its reactivity. For example, there are sporadic examples of nucleophilic late transition metal imido complexes, often based on strongly donating supporting ligands. Building on these earlier works, in this Article, we show that the imido ligand in a low-coordinate high-spin bis(carbene)borate Fe(II) complex is able to access previously unknown reaction pathways, ultimately leading to new catalytic transformations. We first focus on the synthesis, characterization, and stoichiometric reactivity of a highly nucleophilic Fe(II) imido complex. The entry point for this system is the intermediate-spin three-coordinate Fe(III) imido complex, which is generated from the reaction of an Fe(I) synthon with an organic azide. Alkali metal reduction leads to a series of M+ (M = Li, Na, K) coordinated and charge-separated (M = K(18-C-6)) high-spin Fe(II) imido complexes, all of which have been isolated and fully characterized. Combined with the electronic structure calculations, these results reveal that the alkali ions moderately polarize the Fe═N bond according to K+ ≈ Na+ < Li+. As a result, the basicity of the imido ligand increases from the charged separated complex to K+, Na+, and Li+ coordinated complexes, as validated by intermolecular proton transfer equilibria. The impact of the counterion on imido ligand reactivity is demonstrated through protonation, alkylation, and hydrogen atom abstraction reactions. The counterion also directs the outcome of [2 + 2] reactions with benzophenone, where alkali coordination facilitates double bond metathesis. Building from here, we describe how the unusual nucleophilicity of the high-spin Fe(II) imido complex revealed in stoichiometric reactions can be extended to new catalytic transformations. For example, a [2 + 2] cycloaddition reaction serves as the basis for the catalytic guanylation of carbodiimides under mild conditions. More interestingly, this complex also exhibits the first ene-like reactivity of an M═NR bond in reactions with alkynes, nitriles, and alkenes. These transformations form the basis of catalytic alkyne and nitrile α-deuteration and pKa-dictated alkene transposition reactions, respectively. Mechanistic studies reveal the critical role of metal-ligand cooperativity in facilitating these catalytic transformations and suggest the new avenues for transition metal imido complexes in catalysis that extend beyond classical nitrene transfer chemistry.

Transforming Hetera-Buckybowls into Chiral Conjugated Polycycles Incorporating Epoxycyclooctadiene: a Two-Step Approach.

Chiral π-conjugated polycycles have garnered increasing attention due to versatile applications in optoelectronic materials and biological sciences. In this study, we report the synthesis of chiral π-conjugated polycycles incorporating a chiral epoxycyclooctadiene moiety. Our synthetic strategy capitalizes on the novel reactions of hetera-buckybowl triselenasumanene (TSS) and is achieved in two-step manner. Firstly, the TSS is regio-selectively transformed into its ortho-quinone form. Subsequently, the nucleophilic addition reactions of TSS ortho-quinone by phenylethynides are metal ion-dependent. When utilizing (phenylethynyl)magnesium bromide as the nucleophile, two phenylethynyls are furnished onto the edged benzene ring of TSS. When the nucleophile is (phenylethynyl)lithium, a cascade of nucleophilic addition, intermolecular electron-transfer, ring-opening, and tetradehydro-Diels-Alder (TDDA) reactions occur sequentially in one-pot, ultimately affording chiral π-conjugated polycycles featuring the epoxycyclooctadiene moiety as an integral part of their backbones. This work represents a step forward in the synthesis of chiral π-conjugated polycycles using TSS as synthon.

A Mitochondria‐Targeted Fluorescent and Colorimetric Probe for Sulfur Dioxide Derivatives and Hydrogen Peroxide in Live Cells

AbstractThe abnormal fluctuations of sulfur dioxide (SO2) and its derivatives are closely associated with various physiological and pathological progresses in biological systems. Herein, we have developed two fluorescent and colorimetric probes based on a hemicyanine dye for the detection of SO2 derivatives and hydrogen peroxide (H2O2) in vitro and live cells. The response mechanisms involve an SO2‐derivative‐mediated nucleophilic addition reaction to the double bond and subsequent H2O2‐promoted elimination of bisulfite. As well as having excellent photophysical properties, the probe with higher fluorescence efficiency is further applied for live cell imaging, and it is found that it can solely accumulate in mitochondria and track SO2 derivatives and H2O2 in live cells.

Amorphous Poly (Aryl Ether Ketones) Containing Methylene Groups with Excellent Thermal Resistance, Dielectric Properties and Mechanical Performance

Low-dielectric constant polymers are widely used in various microelectronic materials. With the development of 5G communication technology, there is an urgent need for polymer materials with low dielectric constant at high frequency, good thermal resistance, and mechanical properties. In this study, four novel poly (aryl ether ketone) (PAEK) containing different numbers of methylene groups were synthesized via nucleophilic polycondensation reaction. At 10 GHz, these polymer films exhibit excellent dielectric properties with dielectric constants as low as 2.76. The relationship between the dielectric constant and the number of methylene groups is illustrated by constructing the amorphous accumulation cell model. In addition, methylene groups provided the polymer with favorable mechanical performance, including Young’s modulus in the range of 2.17–2.21 GPa, the tensile strength from 82.0 to 88.5 MPa and the elongation at the break achieved 7.94%, respectively. Simultaneously, the polymer maintains good thermal resistance with a glass transition temperature (Tg) reaching 216 °C. The result indicates that the obtained novel PAEK is potentially valuable in the field of high-frequency communications.

Convergent Paired Electrolysis for the Synthesis of Pyrazolyl‐Substituted Tetrahydroisoquinolines

AbstractA convergent paired electrolysis method for the synthesis of 1‐pyrazolyl‐substituted tetrahydroisoquinolines has been developed. The reaction proceeded without any transition metal catalyst and chemical oxidant. The desired products could be isolated in high yields (80–99%) in 60–80 minutes. The Faradaic efficiency was 108% and gram‐scale synthesis (84%) could be carried out. Mechanistic studies revealed that the C−N bond formation process might mainly involve a nucleophilic addition reaction.

Quaternized hollow TiO2-enhanced the dye adsorption capacity and photogenerated carrier separation for efficient reactive dye removal

Currently, titanium dioxide (TiO2) has been demonstrated as a significant photocatalyst for the efficient removal of reactive dyes in dyeing effluents. However, due to the easy recombination of photogenerated carriers and electrostatic repulsion with reactive dye, single TiO2 cannot achieve satisfactory removal efficiency to reactive dye which is commonly used in cellulose fibers dyeing. Therefore, we prepared hollow titanium dioxide (H-TiO2) by alkaline treatment etching method and introduced quaternary ammonium groups on the surface of H-TiO2 photocatalyst (QAS-H-TiO2) by nucleophilic addition reaction. Improving the adsorption capabilities of C. I. reactive red 2 (RR2) and simultaneously separating the photogenerated carriers via the nitrogen cation of the quaternary ammonium groups facilitated the enhancement of its RR2 removal. The experimental results indicated that the utilization of QAS-H-TiO2 substantially bolstered the removal efficiency of RR2. The impact of molecular structure of quaternary ammonium salts on the adsorption ability of RR2, and the mechanism of regulation for photogenerated carriers, were investigated. It was found that the grafting of the quaternary ammonium group enabled mass and electron transfer channels, resulting in faster adsorption of dyes and separation of photogenerated carriers. This study presents a novel approach for preparing efficient QAS-H-TiO2 for high-performance organic dye removal.

Deep eutectic solvents for effective removal of indoor formaldehyde: Theoretical design, experiment, and adsorption mechanism study

Formaldehyde (HCHO) represents a prevalent indoor air pollutant, and its efficient removal continues to be an area of significant concern. Adsorption is a typical technique to capture this pollutant gas. In this work, the COSMO-RS theoretical framework guided the selection of three deep eutectic solvents (DES): L-arginine/glycerol, L-lysine/glycerol, and L-proline/glycerol, from a pool of 416 combinations involving 16 amino acids and 26 alcohols. These DES were used for the first time to adsorb HCHO. The adsorption experiments of HCHO illustrated that the DES system had a higher HCHO adsorption capacity than the pure fraction. Among them, L-arginine-glycerol-1:5 (A-G-DES) had the highest adsorption efficiency, requiring only 0.1 g to remove 92.7% HCHO in 6 h, which is consistent with the predicted results. The nucleophilic addition reaction between amino acids and HCHO during the adsorption was revealed by FT-IR and 13C NMR. DFT calculations analyzed the interaction strength of HCHO at different adsorption sites, and the formation of DES system was demonstrated to produce more favorable HCHO adsorption behavior through the interaction energy calculation. The molecular dynamics simulations (MD) verified that the main mode of HCHO adsorption was the non-covalent interaction between polar functional groups (such as −COOH, −NH and −OH) in DES system and O and/or C atoms in the HCHO molecules.

Design and synthesis of a novel fluorescent probe for the detection of bisulfite in plant and zebrafish

Sulfur dioxide (SO2) and its derivative bisulfite (SO32−/HSO3−) have a serious impact on the human health and environment. Therefore, the development of highly sensitive and specific detection methods for SO2 and its derivative is of great significance for environmental monitoring, food safety, and related disease research. In this paper, probe TPN-DP based on the triphenylamine fluorophore was developed to enable the imaging and detection of HSO3− in plant and zebrafish. In PBS buffer solution, the designed probe TPN-DP can react with HSO3− by highly selective nucleophilic addition reaction, leading to a sensitive change in the color of probe TPN-DP solution from pink to colorless. The changes in fluorescence and color can be easily recognized by the naked eye. Moreover, probe TPN-DP exhibited a fast response time of 8 min, high sensitivity of 19.4 nM, and excellent selectivity for sensing HSO3−. With the help of probe TPN-DP, the detection of HSO3− was successfully achieved in water sample and various biological systems, including onion epidermal cells, tobacco seedling roots, and zebrafish. These findings not only provide valuable insights into the biological role of HSO3− but also offer a promising analytical method for efficient HSO3− recognition.

Highly aqueously stable C60-polymer nanoparticles with excellent photodynamic property for potential cancer treatment.

Fullerenes are a class of carbon nanomaterials that find a wide range of applications in biomedical fields, especially for photodynamic cancer therapy because of its photosensitive effect. However, hydrophobic fullerenes can only be dispersed in organic solvents which hinders their biomedical applications. Here, we report a facile method to prepare highly water-dispersible fullerene (C60)-polymer nanoparticles with hydrodynamic sizes of 50-70nm. Hydrophilic random copolymers containing different ratios of polyethylene glycol methyl ether methacrylate and 2-aminoethylmethacrylamide were synthesized for conjugating with C60 molecules through efficient nucleophilic Michael addition reaction between amine groups from hydrophilic polymer and carbon-carbon double bonds from C60. As a result, the amphiphilic C60-polymer conjugates could be well dispersed and nano-assembled in water with a C60 concentration as high as 7.8mg/mL, demonstrating a significant improvement for the solubility of C60 in an aqueous system. Owing to the high C60 content, the C60-polymer nanoparticles showed a strong photodynamic therapy effect on human lung cancer cells (A549) under light irradiation (450nm) in both 2D cell culture and 3D spheroid culture, while demonstrating ignorable cytotoxicity under dark. This highly efficient and convenient method to prepare water-dispersible C60-polymer conjugates may have a great impact on the future biomedical applications of fullerenes.

Investigation on DOPO as reactive fumes suppressant to reduce the fumes emission of asphalt

Asphalt fumes released during pavement construction posed a threat to human health and environment. In this study, 9,10-dihydro-9-oxa-10-phosphorophenanthrene-10-oxide (DOPO) was used as a reactive fumes suppressant to reduce the asphalt fumes emission. The volatilization behavior of DOPO modified asphalt (DOPO-Asphalt) was investigated through thermogravimetric analysis, volatility test and thermal destruction gas chromatography mass spectrometry, and effect of DOPO on the chemical structure and composition of asphalt was explored through nuclear magnetic resonance hydrogen spectroscopy, Fourier transform infrared spectroscopy, and asphalt component testing. The results indicated that 1.0 wt% DOPO reduced the fume content of control asphalt by 1.1% from 120 ℃ − 200 ℃ and the H2S and VOC content by 96.9% and 84.2%, respectively, at 180 ℃. Moreover, 1.0 wt% DOPO reduced the content of aliphatic hydrocarbons, hydrocarbon derivatives, aromatics, and sulfides in control asphalt fumes by 86.8%, 89.7%, 90.7%, and 93.5%, respectively, which may be attributed to electrophilic and nucleophilic reactions between DOPO and volatile substances in asphalt. Chemical structure and composition changing of DOPO-Asphalt confirmed that P-H bond in DOPO was chemically reacted with components in asphalt, generating stable aromatic hydrocarbons and resins. The results provided a novel method for inhibiting the volatilization of harmful substances in asphalt.