Benzyl Chloride Research Articles

Synthetic Benzylic Diselenides and Disulfides: Potential Anticancer Activities via Modulation of the ROS-dependent Akt/β-Catenin Signaling Pathway.

The natural and synthetic organodiselenides have garnered much research attention due to their chemotherapeutic and chemopreventive activities. Herein, we describe the synthesis of a series of benzylic diselenides, which were synthesized by coupling the in situ generated disodium diselenide with the corresponding benzylic halides. The diselenides were evaluated for their anticancer activities in the highly aggressive triple-negative breast cancer cells. Preliminary anti-proliferative activities indicated 4-cyano-substituted diselenide 7 to be most potent with an IC50 value of 1.9 ± 0.3 μM. Detailed mechanistic investigations showed that diselenide 7 induces apoptosis and causes G1 phase arrest of the cell cycle. It exhibits anticancer activity by suppressing the Akt/β-catenin signaling pathway. Further control experiments with LiCl (inhibitor of GSK-3β) revealed that down-regulation of β-catenin was promoted by GSK-3β-induced phosphorylation of β-catenin and its subsequent proteasomal degradation. Moreover, the intracellular ROS was found to act as an upstream mediator for the inactivation of the Akt/β-catenin signaling pathway. The present study describing the efficient anticancer activity of a synthetic benzylic diselenide towards triple-negative breast cancer cells through the modulation of ROS-dependent Akt/β-catenin signaling pathway would certainly be helpful in the future towards the development of small-molecule organoselenium compounds for the treatment of cancer.

Structure-Functional Activity of Pyrone Derivatives for Inhibition of Barnacle Settlement and Biofilm Formation.

Naturally occurring 6-pentyl-2H-pyran-2-one and its synthetic analogues greatly inhibit the settlement of Amphibalanus amphitrite cyprids and the growth and biofilm formation of marine bacteria. To optimize the antifouling activities of pyrone derivatives, this study designed pyrone analogues by modifying functional groups, such as the benzyl group, cyclopentane, and halides, substituted on both sides of a pyrone. The antifouling effects of the synthesized pyrone derivatives were subsequently evaluated against five marine biofilm-forming bacteria, Loktanella hongkongensis, Staphylococcus cohnii, S. saprophyticus, Photobacterium angustum, and Alteromonas macleodii, along with barnacle cyprids of Amphibalanus amphitrite. Substituting nonpolar parts-such as the aliphatic, cyclopentyl, or phenyl moieties on C-5 or the furan moieties on C-3-not only increased antibacterial activity and inhibited biofilm formation but also inhibited barnacle cyprid settlement when compared to 6-pentyl-2H-pyran-2-one.

Synthesis and Characterization of Novel Selenium N,S-heterocyclic carbene compounds

Two novel benzothiazolium salts, N-(4-methoxybenzyl)benzothiazolium chloride (1a) and N-(4-tert-butylbenzyl)benzothiazolium bromide (1b), were prepared by using benzothiazole and related benzyl halides. Selenourea N,S-heterocyclic-based derivatives (2a and 2b) were obtained by the reaction of the salts with selenium in the presence of KOBut base. 1H NMR, 13C NMR and elemental analysis were used for characterization of the synthesized compounds. Also, molecular weights of the selenium adducts were validated by LC-MS/MS analysis.

Chloroimidazolium Deoxyfluorination Reagent with H2F3- Anion as a Sole Fluoride Source.

In the study, we introduce an air-stable NHC-based deoxyfluorination reagent ImCl[H2F3], offering a promising avenue for deoxyfluorination across various substrates. Reagent efficiently fluorinates benzyl alcohols, carboxylic acids, and P(V) compounds without external fluoride sources. A mechanistic study reveals a two-step process involving benzyl chloride as an intermediate, shedding light on the two-step reaction pathway. The Hammet plot provides insights into reaction mechanisms with different substrates, enhancing our understanding of this versatile deoxyfluorination method.

Visible-Light-Promoted Thiolation of Benzyl Chlorides with Thiosulfonates via a Photoactive Electron Donor-Acceptor Complex.

Visible-light-promoted thiolation of benzyl chlorides with thiosulfonates is disclosed via an electron donor-acceptor complex strategy. In addition to efficiently delivering a series of arylbenzylsulfide compounds, versatile thioglycosides were also successfully constructed by applying the metal- and photocatalyst-free protocol. Preliminary mechanistic studies suggest that a radical-radical coupling process was involved in this transformation.

Efficient electrochemical synthesis of phenylacetic acid derivatives: Utilizing CO2 for sustainable production

Phenylacetic acid derivatives, including 1-naphthaleneacetic acid, hold crucial applications in various domains. Traditional synthesis methods often involve intricate steps or the use of expensive and polluting heavy metal catalysts. This paper presents an electrochemical approach for efficiently producing valuable compounds like 1-naphthaleneacetic acid and other phenylacetic acid analogs through the reduction of benzyl halides, such as 1-chloromethyl naphthalene, in the presence of CO2. At the same time as preparing phenylacetic acid, the resource utilization of CO2 is realized. Six kinds of carboxy analogs were synthesized by potentiostatic electrolysis of benzyl halides in acetonitrile with CO2 as a co-reactant and tetraethyl ammonium tetrafluoroborate as an electrolyte. The electrochemical reduction products were confirmed structurally through NMR, mass spectrometry, and other techniques. The Faraday electrolysis efficiencies ranged from 82 % to 94 %, with 72.5–92.9 % conversions. The study delves into the electron transfer mechanism using cyclic voltammetry and in situ FT-IR spectroelectrochemistry. The reduction process on silver electrodes under a CO2 atmosphere was identified as an irreversible two-electron process, generating a monovalent anion that attacks CO2 to yield the respective carboxyl analogs.

Palladium‐catalyzed sequential Heck/Suzuki coupling reaction and the synthesis of diarylmethanes in aqueous media using indole‐based N‐heterocyclic carbene precursors

AbstractThis study introduced a versatile class of indole‐based benzimidazolium salts, offering distinct advantages: (1) the utilization of affordable and easily accessible starting materials; (2) a straightforward and uncomplicated synthesis process; (3) the diversity of the salt should provide fine‐tunability of steric and electronic properties. These salts, employed as N‐heterocyclic carbene (NHC) precursors, were effectively utilized in the Pd‐catalyzed C–C bond formation reactions involving aryl or benzyl halide. The catalytic system, arising from the in situ generation of Pd(OAc)2 and indole‐based benzimidazolium salts, demonstrated remarkable efficiency. It accomplished the synthesis of diarylmethanes via the Suzuki coupling of benzyl chlorides and arylboronic acids in aqueous media with a Pd loading of 0.5 mol%. Furthermore, it successfully achieved the one‐pot sequential Heck/Suzuki coupling reactions with a Pd loading of as low as 0.25 mol%.

Cooperative Catalytic Coupling of Benzyl Chlorides and Bromides with Electron-Deficient Alkenes.

Benzyl radicals are an important class of intermediate. The use of visible light to generate them directly from their respective halides is an ideal synthetic strategy. The central impediment associated with their direct single-electron reduction (photo- or electro-) lies in their highly variable and structurally dependent reduction potential, which combine to make the identification of a general set of conditions difficult. Herein, we have employed a strategy of nucleophilic cooperative catalysis in which catalytic lutidine undergoes halide substitution, which decreases and levels the reduction potential. This allows a general set of photocatalytic conditions to transform a broad range of benzyl halides into radicals that can be used in the synthesis of more complex molecules, exemplified here by Giese coupling with electron-deficient alkenes.

A thiol-anchored solvatochromic and fluorogenic molecular rotor for covalent protein labeling in SDS-PAGE and mitochondria specific fluorescence imaging.

Fluorescent labeling is a widely used method for protein detection and fluorescence imaging. A solvatochromic and fluorogenic molecular rotor DASPBCl was developed for covalent protein labeling in solution and SDS-PAGE, and also for stable mitochondria labeling and fluorescence imaging. The dye DASPBCl consisted of a 4-(N,N-dimethylamino)phenyl moiety as the electron donor and a positively charged N-benzylpyridinium moiety as the electron acceptor. A benzyl chloride group was introduced into the pyridine moiety for covalent labeling of thiol in proteins. When the fluorescent dye DASPBCl is covalently labeled to the thiol of proteins, significantly enhanced fluorescence was obtained, which is attributed to the polarity sensitivity caused solvatochromic effect from the hydrophobic protein structure and the viscosity sensitivity caused fluorogenic effect from the restriction of single bond rotation. DASPBCl exhibits high sensitivity and good linear response for protein detection in SDS-PAGE analysis with both the pre-staining method and post-staining method. DASPBCl was also successfully used for covalently protein-anchored fluorescence imaging of mitochondria in living cells.

Modular Synthesis of [6,6]‐Oxaspirolactones Enabled by Palladium‐Catalyzed Carbonylative Spirolactonization

AbstractAn expedient and efficient carbonylative protocol proceeded via palladium‐catalyzed tandem cyclic ketonization and carbonylative spirolactonization has been developed. This carbonylation reaction is compatible with a wide range of hydroxyalkyl ketone tethered benzyl chlorides bearing different functional groups and can be proceeded under comericially available Pd2(dba)3/BINAP catalyst system, providing a straithfowrd and practical approach to a broad range of [6,6]‐oxaspirolactones. The synthesized [6,6]‐oxaspirolactones are commonly found as core structures in natural products and can potentially serve as C2‐symmetric ligand synthons.

Frustrated Lewis pair-mediated hydro-dehalogenation: crucial role of non-covalent interactions.

Organic halides stand as invaluable reagents with diverse applications in synthetic chemistry and various industrial processes. Despite their utility, concerns arise due to their inherent toxicity. Addressing these apprehensions, hydro-dehalogenation has emerged as a promising strategy involving the replacement of halogen atoms with hydrogen atoms to transform toxic organic halides into hydrocarbons. This study delves into the computational exploration of hydro-dehalogenation reactions of benzyl halide, mediated by frustrated Lewis pairs (FLPs), using density functional theory (DFT). The reactions entail the formation of FLP1 or FLP2 in the presence of TMP or lutidine with B(C6F5)3, respectively. This is followed by heterolytic cleavage of dihydrogen and subsequent reaction with benzyl halides. Non-covalent interaction analysis underscores the significance of π-π stacking and CH-π interactions in stabilizing transition states. Additionally, the activation strain model (ASM) dissects activation energies, revealing the substantial impact of strain energy on reaction barriers. Energy decomposition analysis (EDA) offers insights into the contributions of electrostatic, orbital, and dispersion energies to the overall attractive interaction energy. The investigation extends to hydro-dehalogenation reactions of ethyl halides, uncovering distinct mechanisms and activation barriers. This comprehensive analysis illuminates the intricacies of hydro-dehalogenation reactions, providing valuable insights into their mechanisms and paving the way for future studies in this field. Geometry optimizations were carried out at the M06-2X/def2-SVP level of theory, which was performed using the Gaussian 16 program. Solvent-corrected single-point energies were also calculated using the polarizable continuum model (PCM) at the PCM(chloroform)-M06-2X/def2-TZVP//M06-2X/def2-SVP level of theory. The Gibbs free energy correction was determined from computations performed at the M06-2X/def2-SVP level of theory. Principal interacting orbital (PIO) analysis was conducted using the NBO 6.0 software. The nature of bonding in the respective transition state (TS) structures was analyzed using atoms-in-molecules (AIM) analyses. Additionally, the presence of non-covalent interactions (NCI) was exemplified using Multiwfn software.

Synthesis, characterization and antimicrobial evaluation of quaternary ammonium compounds from natural oils

Quaternary ammonium salts refer to any class of salt derived from ammonium in which the nitrogen atom is attached to four organic groups covalently, as in benzalkonium chloride (R4N+). Quaternary ammonium compounds were synthesized from Canola oil (Brasssicanapus) and Coconut oil (Cocos nucifera) extracts by reacting the oils with N,N-diethylethylenediamine in the presence of potassium tertiary butoxide as catalyst. Fourier Transform Infrared (FTIR) Spectrometric analyses of the starting materials, the intermediates and the final products were conducted, the results showed a disappearance of the carbonyl (C=O) stretch of an ester (the oil) at 1744cm-1 and appearance of N-H band of an amide at 3433cm-1, which resulted from the quaternization of benzyl chloride with the intermediates for both oils. Other functional groups such as C=C and C-H stretch of aromatic compound, C=O stretch of an amide were also observed.Mass spectrometric analysis of the final products were conducted and results showed the Molecular Ion peak (M+) which is the molecular weights of the products. Vital fragments such as base peaks were observed for both quats, other fragmented radical cations were observed.Antimicrobial activity of the synthesized Quaternary ammonium compounds (QACs) exhibited excellent anti-bacterial activity covering a diameter of 22 mm and 28 mm of E. coli for QACs from Cocos nucifera and Brassic anapus oils respectively as compared to the standard antibiotic (Ampillicin).

Electric Double Layer Effect on the Outer-Sphere Benzyl Halides Electro-Reduction Mechanism

Electric Double Layer Effect on the Outer-Sphere Benzyl Halides Electro-Reduction Mechanism

Multi-omic integration reveals alterations in nasal mucosal biology that mediate air pollutant effects on allergic rhinitis.

Allergic rhinitis is a common inflammatory condition of the nasal mucosa that imposes a considerable health burden. Air pollution has been observed to increase the risk of developing allergic rhinitis. We addressed the hypotheses that early life exposure to air toxics is associated with developing allergic rhinitis, and that these effects are mediated by DNA methylation and gene expression in the nasal mucosa. In a case-control cohort of 505 participants, we geocoded participants' early life exposure to air toxics using data from the US Environmental Protection Agency, assessed physician diagnosis of allergic rhinitis by questionnaire, and collected nasal brushings for whole-genome DNA methylation and transcriptome profiling. We then performed a series of analyses including differential expression, Mendelian randomization, and causal mediation analyses to characterize relationships between early life air toxics, nasal DNA methylation, nasal gene expression, and allergic rhinitis. Among the 505 participants, 275 had allergic rhinitis. The mean age of the participants was 16.4 years (standard deviation = 9.5 years). Early life exposure to air toxics such as acrylic acid, phosphine, antimony compounds, and benzyl chloride was associated with developing allergic rhinitis. These air toxics exerted their effects by altering the nasal DNA methylation and nasal gene expression levels of genes involved in respiratory ciliary function, mast cell activation, pro-inflammatory TGF-β1 signaling, and the regulation of myeloid immune cell function. Our results expand the range of air pollutants implicated in allergic rhinitis and shed light on their underlying biological mechanisms in nasal mucosa.

Miniature spectrometer based on graded bandgap perovskite filter

Abstract Miniature spectrometer is powerful tool for scientific research and industrial inspection. Here, we report the fabrication of graded perovskite filters with tunable bandgap and their application in constructing miniature spectrometer. The graded perovskite filters were fabricated using a Finkelstein reaction between in-situ formed halogen ion with a preformed MAPbX3 film. The graded bandgap of perovskite films can be well tunned from 400 to 750 nm by controlling the volume ratio between 5,5-dimethyl-1-pyrroline N-oxide and benzyl chloride(bromide). By combining a deep residual network, graded bandgap perovskite film and commercial CMOS sensor chip, a miniature spectrometer is demonstrated, achieving an accurate spectrum reconstruction (PSNR = 40.749) with monochromatic spectral resolution of 1.31 nm.

Reduction of Thorium Tris(amido)arene Complexes: Reversible Double and Single C-C Couplings.

The reduction chemistry of thorium complexes is less explored compared to that of their uranium counterparts. Here, we report the synthesis, characterization, and reduction chemistry of two thorium(IV) complexes, (AdTPBN3)ThCl (1) and (DtbpTPBN3)ThCl(THF) (4) [RTPBN3 = 1,3,5-[2-(RN)C6H4]3C6H3; R = 1-adamantyl (Ad) or 3,5-di-tert-butylphenyl (Dtbp); THF = tetrahydrofuran], supported by tripodal tris(amido)arene ligands with different N-substituents. Reduction of 1 with excessive potassium in n-pentane yielded a double C-C coupling product, [(AdTPBN3)ThK(Et2O)2]2 (3), featuring a unique tetraanionic tricyclic core. On the other hand, reduction of 4 with 1 equiv of KC8 in hexanes/1,2-dimethoxyethane (DME) afforded a single C-C coupling product, [(DtbpTPBN3)Th(DME)]2 (5), with a dianionic bis(cyclohexadienyl) core. The solid- and solution-state structures of dinuclear thorium(IV) complexes 3 and 5 were established by X-ray crystallography and NMR spectroscopy. In addition, reactivity studies show that 3 and 5 can behave as thorium(II) and thorium(III) synthons to reduce organic halides. For instance, 3 and 5 are able to reduce 4 and 2 equiv of benzyl chloride, respectively, to regenerate 1 and 4 with concomitant formation of dibenzyl. Reversible C-C couplings under redox conditions provide an alternative approach to exploiting the potential of thorium arene complexes in redox chemistry.

Nucleophilic Organocatalyst for Photochemical Carbon Radical Generation via SN2 Substitution.

Photochemical generation of radicals is a powerful way to construct various molecules. But most of these methods rely on initiators or the redox properties of radical precursors. Herein, we report a photochemical organic catalyst that reacts with benzyl halide to generate carbon radical via an SN2 pathway. This nucleophilic catalyst can be easily prepared and is bench-stable. The SN2 process does not rely on the redox properties of halides, showing potential synthetic utility. Control experiments and UV-vis spectroscopic analysis indicate that the SN2 substitution adduct is the key intermediate.

An Electrocatalytic Cascade Reaction for the Synthesis of Ketones Using CO2 as a CO Surrogate

AbstractThe construction of carbonyl compounds via carbonylation reactions using safe CO sources remains a long‐standing challenge to synthetic chemists. Herein, we propose a catalyst cascade Scheme in which CO2 is used as a CO surrogate in the carbonylation of benzyl chlorides. Our approach is based on the cooperation between two coexisting catalytic cycles: the CO2‐to‐CO electroreduction cycle promoted by [Fe(TPP)Cl] (TPP=meso‐tetraphenylporphyrin) and an electrochemical carbonylation cycle catalyzed by [Ni(bpy)Br2] (2,2′‐bipyridine). As a proof of concept, this protocol allows for the synthesis of symmetric ketones from good to excellent yields in an undivided cell with non‐sacrificial electrodes. The reaction can be directly scaled up to gram‐scale and operates effectively at a CO2 concentration of 10 %, demonstrating its robustness. Our mechanistic studies based on cyclic voltammetry, IR spectroelectrochemistry and Density Functional Theory calculations suggest a synergistic effect between the two catalysts. The CO produced from CO2 reduction is key in the formation of the [Ni(bpy)(CO)2], which is proposed as the catalytic intermediate responsible for the C−C bond formation in the carbonylation steps.

An Electrocatalytic Cascade Reaction for the Synthesis of Ketones Using CO2 as a CO Surrogate.

The construction of carbonyl compounds via carbonylation reactions using safe CO sources remains a long-standing challenge to synthetic chemists. Herein, we propose a catalyst cascade Scheme in which CO2 is used as a CO surrogate in the carbonylation of benzyl chlorides. Our approach is based on the cooperation between two coexisting catalytic cycles: the CO2-to-CO electroreduction cycle promoted by [Fe(TPP)Cl] (TPP=meso-tetraphenylporphyrin) and an electrochemical carbonylation cycle catalyzed by [Ni(bpy)Br2] (2,2'-bipyridine). As a proof of concept, this protocol allows for the synthesis of symmetric ketones from good to excellent yields in an undivided cell with non-sacrificial electrodes. The reaction can be directly scaled up to gram-scale and operates effectively at a CO2 concentration of 10 %, demonstrating its robustness. Our mechanistic studies based on cyclic voltammetry, IR spectroelectrochemistry and Density Functional Theory calculations suggest a synergistic effect between the two catalysts. The CO produced from CO2 reduction is key in the formation of the [Ni(bpy)(CO)2], which is proposed as the catalytic intermediate responsible for the C-C bond formation in the carbonylation steps.

Copper-Catalyzed Cross-Coupling of Benzyl Halides with (Me4N)SCF3

Copper-Catalyzed Cross-Coupling of Benzyl Halides with (Me4N)SCF3