Benzyl Bromide Research Articles

Dess-Martin Periodinane-Mediated Oxidative Coupling Reaction of Isoquinoline with Benzyl Bromide.

Dess-Martin periodinane (DMP) is a broadly applicable oxidant in chemical synthesis. In this work, an efficient and convenient synthesis of N-substituted isoquinolinone derivatives mediated by DMP was achieved through the oxidative coupling reaction of functionalized isoquinoline with readily available benzyl bromide, which is a metal-free, mild, and practical method for synthesizing isoquinoline-1,3-dione or isoquinoline-1,3,4-trione derivatives in excellent yields. The H2O18-labeling experiment was performed to gain insight into the possible mechanism for this reaction.

Transition-metal-mediated benzylation of C60 with benzyl chlorides.

Benzyl bromides have been widely used for fullerene functionalization. However, the use of benzyl chlorides, a more affordable but less reactive counterpart of benzyl bromides, has been rarely reported. Herein, a new metal-mediated benzylation of C60 with benzyl chlorides is presented. In this method, with the combinatorial use of Mn powder and Cu(OAc)2, various benzyl chloride derivatives could react with C60 to afford 1,4-dibenzylated products in 12-53% yields. A mechanistic study by in situ visible near infrared (vis-NIR) spectroscopy and various control experiments suggests that, unlike the conventional anionic pathway that uses benzyl bromides, the transition-metal-mediated benzylation of C60 with benzyl chlorides proceeds via a metal-mediated iterative single electron transfer process.

In situ spatiotemporal characterization and analysis of chemical reactions using an ATR-integrated microfluidic reactor.

Determining kinetic reaction parameters with great detail has been of utmost importance in the field of chemical reaction engineering. However, commonly used experimental and computational methods however are unable to provide sufficiently resolved spatiotemporal information that can aid in the process of understanding these chemical reactions. With our work, we demonstrate the use of a custom designed single-bounce ATR-integrated microfluidic reactor to obtain spatiotemporal resolution for in situ monitoring of chemical reactions. Having a single-bounce ATR accessory allows us to individually address different sensing areas, thereby providing the ability to obtain spatially and temporally resolved information. To further enhance the spatial resolution, we utilize the benefits of synchrotron IR radiation with the smallest beam spot-size ∼150 μm. An on-flow modular microreactor additionally allows us to monitor the chemical reaction in situ, where the temporal characterization can be controlled with the operational flowrate. With a unique combination of experimental measurements and numerical simulations, we characterize and analyse a model SN2 reaction. For a chemical reaction between benzyl bromide (BB) and sodium azide (SA) to produce benzyl azide (BA), we successfully show the capability of our device to determine the diffusion coefficients of BB and SA as 0.367 ± 0.115 10-9 m2 s-1 and 1.17 ± 0.723 10-9 m2 s-1, respectively. Finally, with the above characteristics of our device, we also calculate a reaction rate of k = 0.0005 (m3s-1mol-1) for the given chemical reaction.

Regioselective synergic catalytic C-H activation: Unprecedented formation of sporadic 4-substituted (oxo-diaryl alkyl) isoquinolinium salts using SA-NEt2 catalyst

First regioselective synergic CH bond activation at C-4 position of isoquinoline has been developed using isoquinoline, benzyl bromides and chalcones. An economic, efficient and one pot, synergically catalysed, aziridine intermediated synthesis of rare 4-substituted (oxo-diaryl alkyl) isoquinolinium salt has been performed using recyclable heterogeneous bifunctional catalyst Silica-Alumina supported 3-(diethylamino)propyl functional group (SA-NEt2) in good to moderate yield (82–71%).

Asymmetric construction of phosphono dihydropyranones from α-ketophosphonates enabled by Pd/chiral isothiourea relay catalysis.

A highly enantio- and diastereoselective approach has been developed for the synthesis of chiral phosphono dihydropyranones. This approach is enabled by Pd/chiral isothiourea relay catalysis under mild reaction conditions, starting from readily available benzyl bromides, CO, and α-ketophosphonates. The cascade reaction involves the generation of a ketene intermediate from Pd-catalyzed carbonylation of benzyl bromide and subsequent chiral Lewis base catalyzed formal [4 + 2] reaction. Phosphono lactone products can also be transformed to chiral 1,5-diester products in good yield and high stereoselectivity.

Electroorganic synthesis in aqueous solution via generation of strongly oxidizing and reducing intermediates.

Water is the ideal green solvent for organic electrosynthesis. However, a majority of electroorganic processes require potentials that lie beyond the electrochemical window for water. In general, water oxidation and reduction lead to poor synthetic yields and selectivity or altogether prohibit carrying out a desired reaction. Herein, we report several electroorganic reactions in water using synthetic strategies referred to as reductive oxidation and oxidative reduction. Reductive oxidation involves the homogeneous reduction of peroxydisulfate (S2O82-) via electrogenerated Ru(NH3)62+ at potential of -0.2 V vs. Ag/AgCl (3.5 M KCl) to form the highly oxidizing sulfate radical anion (E0' (SO4˙-/SO42-) = 2.21 V vs. Ag/AgCl), which is capable of oxidizing species beyond the water oxidation potential. Electrochemically generated SO4˙- then efficiently abstracts a hydrogen atom from a variety of organic compounds such as benzyl alcohol and toluene to yield product in water. The reverse analogue of reductive oxidation is oxidative reduction. In this case, the homogeneous oxidation of oxalate (C2O42-) by electrochemically generated Ru(bpy)33+ produces the strongly reducing carbon dioxide radical anion (E0' (CO2˙-/CO2) = -2.1 V vs. Ag/AgCl), which can reduce species at potential beyond the water or proton reduction potential. In preliminary studies, the CO2˙- has been used to homogeneously reduce the C-Br moiety belonging to benzyl bromide at an oxidizing potential in aqueous solution.

Bifunctional diazirine reagent for covalent dyeing of Kevlar and inert polymer materials

A bifunctional reagent containing a diazirine carbene precursor and a benzyl bromide electrophile can be used to photofunctionalize Kevlar and other inert polymers, providing sites for covalent attachment of dyes.

Indium chloride catalysed benzyl bromination using continuous flow technology.

This report describes the development of a water-tolerant green catalyst for benzyl bromination. The catalyst, indium chloride, exhibits high catalytic activity with a variety of toluene derivatives in continuous flow. Good yields (59-77%) were obtained in all the cases. Improved selectivity was observed under flow conditions, when compared to batch operation.

Base-promoted tandem synthesis of 2-azaaryl indoline.

A novel tandem method to synthesize 2-azaaryl indoline promoted by LiN(SiMe3)2 from 2-azaaryl methyl amine and 2-fluoro benzyl bromides was developed. Mechanistic investigation indicated that this tandem cyclization was initiated by selective benzyl C-SN2 substitution followed by an intramolecular SNAr reaction. Diverse 2-azaaryl indoles could also be obtained via simple functional transformations.

From cyclic (alkyl)(amino)carbene (CAAC) precursors to fluorinating reagents. Experimental and theoretical study.

Addition of anhydrous HF to the hydrochloride [MeCAACH][Cl(HCl)0.5] resulted in the formation of salts with high HF content. By stepwise removal of HF in vacuo, we selectively prepared [MeCAACH][F(HF)2] (3) and [MeCAACH][F(HF)3] (4). We also characterised a salt with [F(HF)4]- anions within the structure of [MeCAACH][F(HF)3.5] (5). Compounds with a lower content of HF were not accessible under vacuum conditions. MeCAAC(H)F (1) was selectively prepared by abstraction of HF from 3 with CsF or KF, while [MeCAACH][F(HF)] (2) was prepared by mixing 3 and 1 in a 1 : 1 ratio. Compound 2 proved to be quite unstable as it tends to disproportionate into 1 and 3. This observation triggered our computational study, in which the structural relationships between CAAC-based fluoropyrrolidines and dihydropyrrolium fluorides were investigated using different DFT methods. The study showed that the results were very sensitive to the computational method used. For a correct description, the quality of the triple-ζ basis set was crucial. Surprisingly, the isodesmic reaction of [MeCAACH][F] + [MeCAACH][F(HF)2] → [MeCAACH][F(HF)] + [MeCAACH][F(HF)] did not confirm the low thermodynamic stability of 2. Furthermore, the use of 3 as a nucleophilic fluorinating reagent was tested on a range of organic substrates, as it is the most stable compound in this series. It was found to have the potential to fluorinate benzyl bromides, 1- and 2-alkyl bromides, silanes and sulfonyls with good to excellent yields of the target fluorides.

Synthesis and Evaluation of Novel S-alkyl Phthalimide- and S-benzyl-oxadiazole-quinoline Hybrids as Inhibitors of Monoamine Oxidase and Acetylcholinesterase.

New S-alkyl phthalimide 5a-f and S-benzyl 6a-d analogs of 5-(2-phenylquinolin-4-yl)-1,3,4-oxadiazole-2-thiol (4) were prepared by reacting 4 with N-bromoalkylphthalimide and CF3-substituted benzyl bromides in excellent yields. Spectroscopic techniques were employed to elucidate the structures of the synthesized molecules. The inhibition activity of newly synthesized molecules toward MAO-A, MAO-B, and AChE enzymes, was also assessed. All these compounds showed activity in the submicromolar range against all enzymes. Compounds 5a and 5f were found to be the most potent compounds against MAO-A (IC50 = 0.91 ± 0.15 nM) and MAO-B (IC50 = 0.84 ± 0.06 nM), while compound 5c showed the most efficient acetylcholinesterase inhibition (IC50 = 1.02± 0.65 μM). Docking predictions disclosed the docking poses of the synthesized molecules with all enzymes and demonstrated the outstanding potency of compounds 5a, 5f, and 5c (docking scores = -11.6, -15.3, and -14.0 kcal/mol against MAO-A, MAO-B, and AChE, respectively). These newly synthesized analogs act as up-and-coming candidates for the creation of safer curative use against Alzheimer's illness.

Engineered Phage with Aggregation-Induced Emission Photosensitizer in Cocktail Therapy against Sepsis.

Sepsis, a widely recognized disease, is characterized by multiple pathogen infections. Therefore, it is imperative to develop methods that can efficiently identify and neutralize pathogen species. Phage cocktail therapy utilizes the host specificity of phages to adapt to infect resistant bacteria. However, its low sterilization stability efficiency and lack of imaging units seriously restrict its application. Here, a novel strategy combining the aggregation-induced emission photosensitizer (AIE-PS) TBTCP-PMB with phages through a nucleophilic substitution reaction between benzyl bromide and sulfhydryl groups to remove pathogenic bacteria for sepsis treatment is proposed. This strategy retains the phage's host specificity while possessing AIE-PS characteristics with a fluorescence imaging function and reactiveoxygenspecies (ROS) for detecting and sterilizing bacteria. This synergetic strategy combining phage cocktail therapy and photodynamic therapy (PDT) shows a strong "1+1>2" bactericidal efficacy and superior performance in sepsis mouse models with good biocompatibility. Furthermore, the strategy can quickly diagnose blood infections of clinical blood samples. This simple and accurate strategy provides a promising therapeutic platform for rapid pathogen detection and point-of-care diagnosis. Moreover, it presents a new method for expanding the library of antibacterial drugs to develop new strain identification and improve infectious disease treatment, thereby demonstrating strong translational potential.

Varying the hydrophobicity of humic matter by a phase-transfer-catalyzed O-alkylation reaction

An O-alkylation reaction catalyzed by tetrabutylammonium hydroxide (TBAH) as a phase-transfer agent was applied to a humic acid (HA) to modify its hydrophobic properties. The carboxyl and hydroxyl functional groups of HA acted as nucleophiles in substitution reactions (Sn2) with methyl iodide, pentyl bromide and benzyl bromide added in amounts equimolar to 20, 60 and 80% of HA total nucleophilic sites. The occurrence of O-alkylation was shown by DRIFT spectrometry, NMR spectroscopy, High Performance Size Exclusion Chromatography (HPSEC) and elemental analysis of reaction products. DRIFT spectra showed changes in C–H stretching and bending regions following the insertion of methyl and pentyl groups, while the incorporation of benzyl groups revealed the characteristics aromatic C–H stretching bands. Both liquid- and solid-state NMR spectra revealed characteristic signals for alkyl/aryl esters and ethers. HPSEC chromatograms of alkylated materials invariably displayed an increase in hydrodynamic volume in respect to the original HA, thereby suggesting that the enhanced hydrophobicity conveyed further associations among humic molecules. Analytical, HPSEC and spectroscopic results suggest that benzylation was the most effective reaction at all percentages of HA total nucleophilicity, followed, in the order, by pentylation and methylation, The benzylation reaction was used to improve reaction and work-up conditions and show that HA could be efficiently alkylated also with substantial reduction of TBAH amount, with no THF addition, increase of reaction time and of washing cycles to remove catalyst impurities. These findings indicate that the hydrophobicity of humic substances can be modulated through a mild O-alkylation reaction under a phase-transfer catalysis according to the extent of exposed HA nucleophilic sites. Such a structural modification of humic matter may have multiple chemical, environmental and biological applications.

Asymmetric Cascade Carbonylation/Annulation of Benzyl Bromides, CO, and Vinyl Benzoxazinanones Enabled by Pd/Chiral Lewis-Base Relay Catalysis.

A highly enantioselective cascade carbonylation/annulation of benzyl bromides, CO, and vinyl benzoxazinanones under mild conditions has been established by Pd/chiral Lewis base relay catalysis, providing an efficient method to assemble chiral quinolinones from readily available starting materials in good yields with excellent diastereo- and enantioselectivities. The palladium catalyst plays two roles in this reaction, enabling both the carbonylation process and the generation of the zwitterionic π-allyl palladium intermediate.

Stoichiometric metal nitration based novel green synthesis of mesoporous metal oxides and their enhanced heterogeneity

In this work, a general and novel method for the green synthesis of mesoporous metal oxides via stoichiometric metal nitration has been demonstrated. Pluronic surfactants and their effect on synthesis procedures in terms of surface area have been experimentally studied in detail. Contrary to the traditional synthesis procedure, water has been utilized as the solvent and in several cases, such as tin oxide, manganese oxide, aluminum oxide, antimony oxide, zinc oxide, cobalt oxide, copper oxide, yttrium oxide, lanthanum oxide, and silver either the highest or comparable surface areas have been successfully synthesized. Through XRD, and TEM, all materials were observed to be crystalline except silver and magnesium oxide. SEM shows that with an increase in surfactant molar mass agglomeration decreases. Ammonia chemisorption on acidic materials gives quantitative amounts of ammonia chemical bonding with catalysts, whereas carbon dioxide chemisorption gives a quantitative value of CO2 chemical binding with basic sites. As high as 1901.8 μmol/g and 994.6 μmol/g ammonia chemisorption values for oxides of vanadium and tin were achieved. Amphoteric materials give both acidic and basic enhanced adsorption. Finally, all synthesized materials are studied under organic catalytic transformations. Benzyl bromide is theoretically more active compared with benzylamine and benzyl alcohol which was also experimentally shown through the conversion.

Metal-free C(sp3)-H Bromination: Synthesis of Phenacyl bromide and Benzyl bromide derivatives

Metal-free C(sp3)-H Bromination: Synthesis of Phenacyl bromide and Benzyl bromide derivatives

Novel Phthalazin-1(2H)-One Derivatives Displaying a Dithiocarbamate Moiety as Potential Anticancer Agents

Nowadays, cancer disease seems to be the second most common cause of death worldwide. Molecular hybridization is a drug design strategy that has provided promising results against multifactorial diseases, including cancer. In this work, two series of phthalazinone-dithiocarbamate hybrids were described, compounds 6-8, which display the dithiocarbamate scaffold at N2, and compounds 9, in which this moiety was placed at C4. The proposed compounds were successfully synthesized via the corresponding aminoalkyl phthalazinone derivatives and using a one-pot reaction with carbon disulfide, anhydrous H3PO4, and different benzyl or propargyl bromides. The antiproliferative effects of the titled compounds were explored against three human cancer cell lines (A2780, NCI-H460, and MCF-7). The preliminary results revealed significant differences in activity and selectivity depending on the dithiocarbamate moiety location. Thus, in general terms, compounds 6-8 displayed better activity against the A-2780 and MCF-7 cell lines, while most of the analogues of the 9 group were selective toward the NCI-H460 cell line. Compounds 6e, 8e, 6g, 9a-b, 9d, and 9g with IC50 values less than 10 µM were the most promising. The drug-likeness and toxicity properties of the novel phthalazinone-dithiocarbamate hybrids were predicted using Swiss-ADME and ProTox web servers, respectively.

Radical-Polar Crossover Catalysis with a d0 Metal Enabled by a Redox-Active Ligand.

Radical-polar crossover mechanisms are invoked in numerous late transition metal and photocatalyzed reactions. To the best of our knowledge, reductive radical-polar crossover mechanisms are not invoked for group 3 early transition metals due to their propensity to exist in high oxidation states. Through use of a redox-active (tris)amido ligand we have accessed this mechanism for use with early transition metals. This mechanism is showcased through enabling product formation for a wide variety of elimination products from α-halo substituted benzylic bromides. The mechanism of this new type of reactivity with Sc is explored, and Hammett analysis reveals an anionic intermediate. The wide functional group tolerance of this reaction is also demonstrated.

Highly Reactive Palladium-Catalyzed and Acetonitrile-Mediated Three-Component Reactions for Arylsulfone Synthesis.

Arylsulfone groups play an important role in the synthesis of functionalized molecules. The acetonitrile-mediated three-component reactions for arylsulfone synthesis were developed in the presence of a 0.00025 mol % palladium catalyst. Arylboronic acids reacted with potassium metabisulfite (K2S2O5) and benzyl bromide in the presence of LiF and a very low concentration of PdCl2 in acetonitrile solvents to produce the corresponding benzyl arylsulfones in moderate to good yields. Various arylboronic acids reacted with K2S2O5 and carbon electrophiles to produce the desired arylsulfones under the optimized conditions. It was proposed that acetonitrile accelerated the generation of aryl anion species from the reaction of arylboronic acids and LiF.

Synthesis, characterization, theoretical studies and antioxidant and cytotoxic evaluation of a series of Tetrahydrocurcumin (THC)-benzylated derivatives

The benzylation reaction of curcumin and tetrahydrocurcumin (THC) with benzyl bromide and potassium carbonate in acetone was investigated. It was found that curcumin undergoes O-alkylation first, followed by C-1 substitution. In contrast, THC undergoes these reactions in reverse order, which was further explained by DFT calculations showing a clear energetic preference (19.5 Kcal/mol) for the C-1 versus the O-alkylation reaction of THC. In addition, the antioxidant activities on lipid peroxidation and cytotoxic activities of both benzylated derivatives were studied, showing that the C-dibenzylated curcuminoid (C-DiBn, 2b), exerts a superior activity than both tribenzylated (TriBn, 2c) and tetrabenzylated (TetraBn, 2d) curcuminoid derivatives in both essays. A DFT theoretical study to explain the experimental results and the preferences for the nucleophilic attack between the phenolic oxygen or C-1 anions was conducted. Furthermore, docking calculations on a DNA fragment shed light on the potential factors affecting the biological activity of these benzylated curcuminoids.