Benzylation Reaction Research Articles

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.

Chiral Bismuth-Rhodium Paddlewheel Complexes Empowered by London Dispersion: The C-H Functionalization Nexus.

Heterobimetallic [BiRh] tetracarboxylate catalysts endowed with 1,3-disilylated phenylglycine paddlewheels benefit from interligand London dispersion. They were originally designed for asymmetric cyclopropanation but are now shown to perform very well in asymmetric C-H functionalization reactions too. Because of the confined ligand sphere about the derived donor/acceptor carbenes, insertions into unhindered methyl groups are kinetically favored, although methylene units also react with excellent levels of asymmetric induction; even gaseous ethane is a suitable substrate. Moreover, many functional groups in both partners are tolerated. The resulting products are synthetically equivalent to the outcome of traditional asymmetric ester alkylation, allylation, benzylation, propargylation and aldol reactions and therefore constitute a valuable nexus to more conventional chemical logic.

Chiral Bismuth‐Rhodium Paddlewheel Complexes Empowered by London Dispersion: The C−H Functionalization Nexus

AbstractHeterobimetallic [BiRh] tetracarboxylate catalysts endowed with 1,3‐disilylated phenylglycine paddlewheels benefit from interligand London dispersion. They were originally designed for asymmetric cyclopropanation but are now shown to perform very well in asymmetric C−H functionalization reactions too. Because of the confined ligand sphere about the derived donor/acceptor carbenes, insertions into unhindered methyl groups are kinetically favored, although methylene units also react with excellent levels of asymmetric induction; even gaseous ethane is a suitable substrate. Moreover, many functional groups in both partners are tolerated. The resulting products are synthetically equivalent to the outcome of traditional asymmetric ester alkylation, allylation, benzylation, propargylation and aldol reactions and therefore constitute a valuable nexus to more conventional chemical logic.

Reactions of Benzyl- and Hydroxyethyl Radicals with Nitric Oxide

Reactions of Benzyl- and Hydroxyethyl Radicals with Nitric Oxide

Kinetic model, recycling, regeneration, and reusing of tri-phase catalytic nucleophilic substitution esterification

This research aims to develop a liquid–solid–liquid phase-transfer catalyst (PTC) catalytic kinetic model of carboxylate esterification unpublished previously. The bimolecular nucleophilic substitution reaction of sodium benzoate with benzyl bromide has been experimented with the immobilized solid PTC to propose the kinetic model and calculate the apparent reaction rate constant and activation energy. We proposed the proper kinetic model of the esterification successfully. In addition, the experimental results comprehensively matched the pseudo-first-order reaction formula. Under the multiple steps of recovery, reuse, and regeneration, the structure of tri-phase PTC support remains well, nor will it destroy the activated site immobilized on the support. Comparing the reactivity of the fresh PTC with PTCs recovered four times, the reactivity does not decrease with the continued recovery, indicating excellent catalytic reactivity. Besides, the esterification, etherification, and benzylation reactions catalyzed by regenerated PTCs and their yields are not much different from those of the original fresh PTCs. It shows that the catalytic activity of regenerated PTC is quite excellent. In our opinion, exploring the regeneration and reduction of PTC can reduce cost, save resources, possesses the potential to apply to other reaction systems, and improve conventional production.

Multifunctional porous β-cyclodextrin polymer for water purification

Keeping water clean is of vital significance for human health and environmental protection. In order to remove organic micro-pollutants and natural organic substances in water bodies and kill pathogenic microorganisms simultaneously, this study synthesized a multifunctional porous β-cyclodextrin polymer with a high specific surface area by introducing quaternary ammonium groups and rigid benzene rings, respectively, which was then polymerized with crosslinking agent-4,4′-bis (chloromethyl)-1,1′-biphenyl (BCMBP) in an ionic liquid system. The grafting of quaternary ammonium groups was beneficial for the removal of negative-charged humic acid (HA) and sterilization. The introduction of numerous rigid structures during benzylation and Friedel-Crafts alkylation reaction could significantly improve the porosity and specific surface area of the polymer, conducive to the exposure of cyclodextrin binding sites and contaminant adsorption. By changing the proportions of quaternization and benzylation, the structure and surface properties of the polymer could be adjusted, thus further regulating the adsorption performance. Compared with activated carbon, the polymer named BQCD-BP with a huge surface area of 1133 m2 g−1 prepared under optimized conditions showed outstanding adsorption performance and sterilization ability. The pseudo-second-order kinetic constant of BQCD-BP reached 1.2058 g·mg−1·min−1, which was approximately 50 times greater than that of activated carbon (0.0256 g·mg−1·min−1) under the same experimental condition. The adsorption capacity of BQCD-BP to HA was twice as high as that to AC, and the antibacterial ability of BQCD-BP was significant, achieving 90% at the dosage of 1g L−1. Moreover, the adsorption process was hardly affected by the hydrochemical conditions, and the polymer was easy to regenerate. In addition, the excellent adsorption and antibacterial performance of the polymer were also identified by natural water treatment. COD was almost completely removed, and the removal efficiency of TP reached 92% after contact with BQCD-BP. The sterilization rate of BQCD-BP to viable bacteria in complex water bodies reached 82%. Undoubtedly, BQCD-BP is a potential multifunctional water treatment material with reasonable design in the actual water purification.

Rhodium‐Catalyzed Benzylic Addition Reactions of Alkylarenes to Michael Acceptors

The use of alkylarenes as nucleophile precursors in benzylic addition is challenging because the benzylic hydrogen atoms of these compounds are inert to deprotonation. Herein, we report Rh-catalyzed benzylic addition of alkylarenes to Michael acceptors for the formation of C(sp3 )-C(sp3 ) bonds. The catalyst is proposed to activate the aromatic ring via η6 -coordination, dramatically facilitating deprotonation of the unactivated benzylic C-H bond and addition of the resulting carbanion to the α,β-unsaturated double bond in the absence of bases. Notably, this byproduct-free method provides an access to all-carbon quaternary centers through the development of ligands.

Rhodium‐Catalyzed Benzylic Addition Reactions of Alkylarenes to Michael Acceptors

AbstractThe use of alkylarenes as nucleophile precursors in benzylic addition is challenging because the benzylic hydrogen atoms of these compounds are inert to deprotonation. Herein, we report Rh‐catalyzed benzylic addition of alkylarenes to Michael acceptors for the formation of C(sp3)−C(sp3) bonds. The catalyst is proposed to activate the aromatic ring via η6‐coordination, dramatically facilitating deprotonation of the unactivated benzylic C−H bond and addition of the resulting carbanion to the α,β‐unsaturated double bond in the absence of bases. Notably, this byproduct‐free method provides an access to all‐carbon quaternary centers through the development of ligands.

Chemoselective Oxyfunctionalization of Functionalized Benzylic Compounds with a Manganese Catalyst.

Whilst allowing for easy access to synthetically versatile motifs and for modification of bioactive molecules, the chemoselective benzylic oxidation reactions of functionalized alkyl arenes remain challenging. Reported in this study is a new non‐heme Mn catalyst stabilized by a bipiperidine‐based tetradentate ligand, which enables methylene oxidation of benzylic compounds by H2O2, showing high activity and excellent chemoselectivity under mild conditions. The protocol tolerates an unprecedentedly wide range of functional groups, including carboxylic acid and derivatives, ketone, cyano, azide, acetate, sulfonate, alkyne, amino acid, and amine units, thus providing a low‐cost, more sustainable and robust pathway for the facile synthesis of ketones, increase of complexity of organic molecules, and late‐stage modification of drugs.

Chemoselective Oxyfunctionalization of Functionalized Benzylic Compounds with a Manganese Catalyst

AbstractWhilst allowing for easy access to synthetically versatile motifs and for modification of bioactive molecules, the chemoselective benzylic oxidation reactions of functionalized alkyl arenes remain challenging. Reported in this study is a new non‐heme Mn catalyst stabilized by a bipiperidine‐based tetradentate ligand, which enables methylene oxidation of benzylic compounds by H2O2, showing high activity and excellent chemoselectivity under mild conditions. The protocol tolerates an unprecedentedly wide range of functional groups, including carboxylic acid and derivatives, ketone, cyano, azide, acetate, sulfonate, alkyne, amino acid, and amine units, thus providing a low‐cost, more sustainable and robust pathway for the facile synthesis of ketones, increase of complexity of organic molecules, and late‐stage modification of drugs.

Catalytic asymmetric Tsuji-Trost α-benzylation reaction of N-unprotected amino acids and benzyl alcohol derivatives.

Catalytic asymmetric Tsuji–Trost benzylation is a promising strategy for the preparation of chiral benzylic compounds. However, only a few such transformations with both good yields and enantioselectivities have been achieved since this reaction was first reported in 1992, and its use in current organic synthesis is restricted. In this work, we use N-unprotected amino acid esters as nucleophiles in reactions with benzyl alcohol derivatives. A ternary catalyst comprising a chiral aldehyde, a palladium species, and a Lewis acid is used to promote the reaction. Both mono- and polycyclic benzyl alcohols are excellent benzylation reagents. Various unnatural optically active α-benzyl amino acids are produced in good-to-excellent yields and with good-to-excellent enantioselectivities. This catalytic asymmetric method is used for the formal synthesis of two somatostatin mimetics and the proposed structure of natural product hypoestestatin 1. A mechanism that plausibly explains the stereoselective control is proposed.

Synthesis of fluoro and trifluoromethyl substituents containing novel tetracyclic N-benzylated benzopiperazine fused acridone regioisomers using a greener solvent 2-MeTHF and their DFT studies

The current work reports the synthesis of novel tetracyclic N-benzylated benzopiperazine fused acridone regioisomers tagged with three trifluoromethyl and three fluoride substituents. The novelty of this work is based on the execution of green chemical principles, 2-MeTHF (2-Methyl Tetrahydrofuran) was employed as renewable solvent during this benzylation reaction (carried out at room temperature) resulting higher yields (87-94%) under halogenated solvent free methodology. The optimized reaction consists of 1.0 equivalent of compound benzopiperazine fused acridone, 1.5 equivalents of compound appropriate benzyl bromide, 2.0 equivalents of KH, 2-MeTHF solvent (5ml with respect to 1mmol of compound 1).

Silylium‐Catalyzed Alkynylation and Etherification Reactions of Benzylic Acetates

AbstractAddition of catalytic amounts of bistriflimide triggers useful coupling reactions of benzyl acetates with trimethyl(alkynyl)silanes and trimethyl(alkoxy)silanes to afford propargyl arenes and benzyl alkyl ethers, respectively. The added acid assists the release of reactive trimethylsilylium ion into the reaction media, which were found to act as the ultimate catalytic species responsible for the C−C and the C−O forming steps. The cationic nature of these coupling processes is documented.

Direct benzylation reactions from benzyl halides enabled by transition-metal-free photocatalysis

An SN2-based photochemical strategy using dithiocarbamate anion as catalyst was developed for the activation of benzyl halides, which are extremely challenging to be applied as radical precursors in visible light photocatalysis. With this transition-metal-free and oxidant-free protocol, the benzylation (or cyanomethylation) of various heterocycles including quinoxalin-2(1H)-ones, coumarin, 2-phenyl-2H-indazole, 1-methyl-5-phenylpyrazin-2(1H)-one, 1-(fluoromethyl)cinnolin-4(1H)-one, and 2,4-dibenzyl-1,2,4-triazine-3,5(2H,4H)‑dione could be realized (46 examples, up to 98% yield). Importantly, some biologically relevant 3-benzylquinoxalin-2(1H)-ones were also be synthesized under mild conditions.

Transforming Waste Clamshell into Highly Selective Nanostructured Catalysts for Solvent Free Liquid Phase Oxidation of Benzyl Alcohol

High yield production of benzaldehyde in the solvent-free oxidation of benzyl alcohol by using green catalysts is highly desirable. In this work, calcium hydroxide derived from waste clamshell was used as low-cost and environmentally friendly catalyst support (CaSUP) for Pd and V nanoparticles. The physicochemical properties of the catalysts were analyzed using X-ray diffraction spectroscopy (XRD), Fourier transform infrared spectroscopy (FTIR), Brunauer–Emmett–Teller (BET) technique, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The catalytic oxidation of benzyl alcohol to benzaldehyde was studied in a liquid phase reaction by using H2O2 as an oxidizing agent. The effects of catalyst loading, the molar ratio of hydrogen peroxide to benzyl alcohol, temperature and reaction duration were investigated. In the optimized conditions, Pd nanoparticles supported on clamshell-derived supports displayed excellent catalytic conversion (88%) and selectivity to benzaldehyde (89%). Furthermore, the catalyst can be effectively reused without a significant loss in its activity and selectivity. The high yield and stability can be related to the structural and basic properties of the catalyst. These results provide important insights into the benzyl alcohol oxidation process for industrial applications.

Molecular docking and antimicrobial analyses of synthesized imidazole derivatives in solvent less condition, adjacent to human pathogenic bacterial strains

In the present study, we have been achieved effortless, highly adaptable multi-component synthesis of several biologically active imidazoles derivatives in single pot three components via means of the reaction of ammonium acetate, substituted aldehydes and benzyl using tartaric acid as an effective, highly efficient organocatalyst. The synthesis of all the compounds has been confirmed through elemental analysis, FTIR, 1HNMR, and 13C NMR. All of the produced imidazole derivatives were docked against a bacterial protein [glucosamine-6-phosphate synthase (GlcN-6-P)] which were obtained as of [RCSB protein data bank (PDB ID: 2VF5)] using Autodock-vina and obtained conformations of ligand complexes and proteins (PDB ID: 2VF5) were examined for binding energy and interactions of the docked arrangement via [Molegro Molecular Viewer 2.5 and Ligplot v.1.4.5]. The synthesized compounds were also checked for antimicrobial activities beside human pathogenic bacterial strains “Escherichia coli, Bacillus subtilis, Salmonella typhi, and Pseudomonas aeruginosa”by disk diffusion method by gentamicine reference and a negative control “DMSO”. Some of the Imidazole derivatives were found to have high antibacterial action against “Escherichia coli, Salmonella typhi, Bacillus subtilis”, and moderate activity against “Pseudomonas aeruginosa”.

Pyromellitic diamide-diacid bridged mesoporous organosilica nanospheres with controllable morphologies: a novel PMO for the facile and expeditious synthesis of imidazole derivatives.

In this work, novel pyromellitic diamide–diacid bridged mesoporous organosilica (PMAMOS) nanospheres with controllable morphologies and Brønsted acid catalytic centers were designed and prepared through a convenient method by altering the addition sequence of precursors, solvent, and aging time. The obtained PMAMOSs demonstrate high surface areas and uniform pore sizes. FESEM, HRTEM, BET, EDX, XRD, FTIR and TGA analyses were performed to characterize and examine the effective factors for the preparation of PMAMOS nanospheres. Due to the appropriate physicochemical properties including Brønsted acid centers, suitable surface area and thermal stability of the PMAMOS nanosphere material, it was explored in the three-component reaction of benzyl or benzoin, ammonium acetate, and different aldehyde derivatives as a case study of multicomponent reactions. Corresponding imidazole derivatives were obtained in EtOH under reflux conditions in high to quantitative yields and short reaction times. It was also shown that the heterogeneous solid acid can be reused at least five times with negligible loss of its catalytic activity, indicating the appropriate stability and high activity of the newly introduced mesoporous organosilica.

Experimental Observation of Hydrocarbon Growth by Resonance-Stabilized Radical-Radical Chain Reaction.

Rapid molecular-weight growth of hydrocarbons occurs in flames, in industrial synthesis, and potentially in cold astrochemical environments. A variety of high- and low-temperature chemical mechanisms have been proposed and confirmed, but more facile pathways may be needed to explain observations. We provide laboratory confirmation in a controlled pyrolysis environment of a recently proposed mechanism, radical-radical chain reactions of resonance-stabilized species. The recombination reaction of phenyl (c-C6 H5 ) and benzyl (c-C6 H5 CH2 ) radicals produces both diphenylmethane and diphenylmethyl radicals, the concentration of the latter increasing with rising temperature. A second phenyl addition to the product radical forms both triphenylmethane and triphenylmethyl radicals, confirming the propagation of radical-radical chain reactions under the experimental conditions of high temperature (1100-1600 K) and low pressure (ca. 3 kPa). Similar chain reactions may contribute to particle growth in flames, the interstellar medium, and industrial reactors.

Experimental Observation of Hydrocarbon Growth by Resonance‐Stabilized Radical–Radical Chain Reaction

AbstractRapid molecular‐weight growth of hydrocarbons occurs in flames, in industrial synthesis, and potentially in cold astrochemical environments. A variety of high‐ and low‐temperature chemical mechanisms have been proposed and confirmed, but more facile pathways may be needed to explain observations. We provide laboratory confirmation in a controlled pyrolysis environment of a recently proposed mechanism, radical–radical chain reactions of resonance‐stabilized species. The recombination reaction of phenyl (c‐C6H5) and benzyl (c‐C6H5CH2) radicals produces both diphenylmethane and diphenylmethyl radicals, the concentration of the latter increasing with rising temperature. A second phenyl addition to the product radical forms both triphenylmethane and triphenylmethyl radicals, confirming the propagation of radical–radical chain reactions under the experimental conditions of high temperature (1100–1600 K) and low pressure (ca. 3 kPa). Similar chain reactions may contribute to particle growth in flames, the interstellar medium, and industrial reactors.

One-Pot Multicomponent Coupling Reaction of Catechols, Benzyl Alcohols/Benzyl Methyl Ethers, and Ammonium Acetate toward Synthesis of Benzoxazoles.

The multicomponent coupling reaction of catechol, ammonium acetate, and benzyl alcohol/benzyl methyl ether in the presence of a Fe(III) catalyst precursor afforded benzoxazole derivatives in good to excellent yields. The notable features of this protocol are abundant availability of the catalyst system, large-scale synthesis, high diversity, and high yields of products.