Alkylation Reactions Research Articles

Exploring Antimicrobial Features for New Imidazo[4,5-b]pyridine Derivatives Based on Experimental and Theoretical Study

5-bromopyridine-2,3-diamine reacted with benzaldehyde to afford the corresponding 6-Bromo-2-phenyl-3H-imidazo[4,5-b]pyridine (1). The reaction of the latter compound (1) with a series of halogenated derivatives under conditions of phase transfer catalysis solid-liquid (CTP) allows the isolation of the expected regioisomers compounds (2-8). The alkylation reaction of (1) gives, each time, two regioisomers, N3 and N4; in the case of ethyl bromoactate, the reaction gives, at the same time, the three N1, N3 and N4 regioisomers. The structures of synthesized compounds were elucidated on the basis of different spectral data (1H NMR, 13C NMR), X-Ray diffraction and theoretical study using the DFT method, and confirmed for each compound. Hirshfeld surface analysis was used to determine the intermolecular interactions responsible for the stabilization of the molecule. Density functional theory was used to optimize the compounds, and the HOMO-LUMO energy gap was calculated, which was used to examine the inter/intra molecular charge transfer. The molecular electrostatic potential map was calculated to investigate the reactive sites that were present in the molecule. In order to determine the potential mode of interactions with DHFR active sites, the three N1, N3 and N4 regioisomers were further subjected to molecular docking study. The results confirmed that these analogs adopted numerous important interactions, with the amino acid of the enzyme being targeted. Thus, the most docking efficient molecules, 2 and 4, were tested in vitro for their antibacterial activity against Gram-positive bacteria (Bacillus cereus) and Gram-negative bacteria (Escherichia coli). Gram-positive bacteria were more sensitive to the action of these compounds compared to the Gram-negative, which were much more resistant.

Design, synthesis, docking, and antidepressant activity evaluation of isatin derivatives bearing Schiff bases.

Depression is a prevalent psychiatric disorder. Treatment of depression is still a challenge due to the lack of response of some patients to a variety of available medications and side effects. Isatin is an interesting molecule with diversified biological effects. It also participates in many synthetic reactions, as a precursor molecule. In this study, a new series of N-alkyl and N-benzyl isatin derivatives bearing Schiff bases were synthesized and screened for antidepressant activities in mice. The synthesis was initiated by N-alkylation and N-benzylation of isatin by an alkylation reaction to give N-substituted isatins. 2-(Benzyloxy) benzohydrazide derivatives were synthesized by treating methyl2-hydroxybenzoate with benzyl bromide or 4-chlorobenzyl bromide which was followed by a reaction with hydrazine hydrate to provide acid hydrazide derivatives. The final compounds were obtained by condensation of N-substituted isatins with 2-(benzyloxy) benzohydrazide derivatives as Shiff-base products. Compounds were evaluated for antidepressant activities in mice by the locomotor activity, marble burying test, and forced swimming test. Monoamine oxidase-A (MAO-A) enzyme has been used for molecular docking studies. Compounds 8b and 8e in both doses, and 8 c in the lower dose, reduced immobility time during the forced swimming test relative to the control group. All preparations reduced the number of marbles buried compared with the control group. The highest docking score was -11.01 kcal/mol for compound 8e. N-Benzylated-isatin (8b, 8e) and N- acetic acid ethyl ester -isatin derivatives (8c) showed more effective antidepressant activity compared with N-phenyl acetamide isatin derivatives. Docking results relatively confirm the pharmacological results.

Palladium-catalyzed annulative allylic alkylation for regioselective construction of indole-fused medium-sized cyclic ethers

A new palladium-catalyzed annulative allylic alkylation (AAA) reaction of 2-(indol-2-yl)phenols with dual allylic electrophiles such as isobutylene dicarbonate and butene dicarbonate is described, leading to the regioselective synthesis of tetracyclic medium-sized cyclic ethers possessing a bridged aryl-indole scaffold, namely, benzo[2,3]oxocino[4,5-b]indoles and benzo[2,3]oxepino[4,5-b]indoles, in good to excellent yields. This protocol demonstrates a broad substrate scope, good compatibility with substituents and high regioselectivity, providing a catalytic and flexible method for creating bridged aryl-indole skeletons.

A red light-triggered chemical tool for sequence-specific alkylation of G-quadruplex and I-motif DNA.

The importance of non-canonical DNA structures such as G-quadruplexes (G4) and intercalating-motifs (iMs) in the fine regulation of a variety of cellular processes has been recently demonstrated. As the crucial roles of these structures are being unravelled, it is becoming more and more important to develop tools that allow targeting these structures with the highest possible specificity. While targeting methodologies have been reported for G4s, this is not the case for iMs, as evidenced by the limited number of specific ligands able to bind the latter and the total absence of selective alkylating agents for their covalent targeting. Furthermore, strategies for the sequence-specific covalent targeting of G4s and iMs have not been reported thus far. Herein, we describe a simple methodology to achieve sequence-specific covalent targeting of G4 and iM DNA structures based on the combination of (i) a peptide nucleic acid (PNA) recognizing a specific sequence of interest, (ii) a pro-reactive moiety enabling a controlled alkylation reaction, and (iii) a G4 or iM ligand orienting the alkylating warhead to the reactive residues. This multi-component system allows for the targeting of specific G4 or iM sequences of interest in the presence of competing DNA sequences and under biologically relevant conditions.

Co2+ to Al3+ Substitution Induced Dual-Site Synergistic Catalysis to Friedel-Crafts Alkylation Reactions.

The dual-site synergistic effect in heterogeneous catalysis is quite interesting, and also complex because at least two substrate molecules are adsorbed or activated on the catalyst surface, which apparently needs two spatially separated and functionally independent active sites. It would become more difficult when the substrate molecules are large ones. The replacement of Al3+ in Al4 B6 O15 lattice with Co2+ leads to the formation of unsaturated Co2+ (4-fold coordination) along with oxygen vacancies (Ov ). The former one behaves as a medium-strength Lewis acid site, and can adsorb and activate molecules with a nitro group (e. g., β-nitrostyrene). The latter one can adsorb and activate oxygen species, which further activates the indole derivatives. Next, the spatially separated dual sites on the catalyst surface can synergistically and efficiently catalyze their Friedel-Crafts alkylation reactions under mild conditions. The high durability can be proved by the as-maintained high yields, that is, 98, 93, 96, 92 and 90 % for 5 runs, respectively. The reaction kinetics obey the second-order characteristic. Annealing under hydrogen condition can further generate more surficial Ov , leading to an improvement to the catalytic activity. A simple and probably routine aliovalent doping endows such a complex synergistic catalysis involving two large substrate molecules, providing an inspired perspective of developing dual-site catalysts.

One-Step Synthesis of Self-Stratification Core-Shell Latex for Antimicrobial Coating

Herein, we describe a one-step method for synthesizing cationic acrylate-based core-shell latex (CACS latex), which is used to prepare architectural coatings with excellent antimicrobial properties. Firstly, a polymerizable water-soluble quaternary ammonium salt (QAS-BN) was synthesized using 2-(Dimethylamine) ethyl methacrylate (DMAEMA) and benzyl bromide by the Hoffman alkylation reaction. Then QAS-BN, butyl acrylate (BA), methyl methacrylate (MMA), and vinyltriethoxysilane (VTES) as reactants and 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AIBA) as a water-soluble initiator were used to synthesize the CACS latex. The effect of the QAS-BN dosage on the properties of the emulsion and latex film was systematically investigated. The TGA results showed that using QAS-BN reduced the latex film's initial degradation temperature but improved its thermal stability. In the transmission electron microscopy (TEM) photographs, the self-stratification of latex particles with a high dosage of QAS-BN was observed, forming a core-shell structure of latex particles. The DSC, TGA, XPS, SEM, and performance tests confirmed the core-shell structure of the latex particles. The relationship between the formation of the core-shell structure and the content of QAS-BN was proved. The formation of the core-shell structure was due to the preferential reaction of water-soluble monomers in the aqueous phase, which led to the aggregation of hydrophilic groups, resulting in the formation of soft-core and hard-shell latex particles. However, the water resistance of the films formed by CACS latex was greatly reduced. We introduced a p-chloromethyl styrene and n-hexane diamine (p-CMS/EDA) crosslinking system, effectively improving the water resistance in this study. Finally, the antimicrobial coating was prepared with a CACS emulsion of 7 wt.% QAS-BN and 2 wt.% p-CMS/EDA. The antibacterial activity rates of this antimicrobial coating against E. coli and S. aureus were 99.99%. The antiviral activity rates against H3N2, HCoV-229E, and EV71 were 99.4%, 99.2%, and 97.9%, respectively. This study provides a novel idea for the morphological design of latex particles. A new architectural coating with broad-spectrum antimicrobial properties was obtained, which has important public health and safety applications.

Stereochemistry of the Reactions between Palladacycle Complexes and Primary Alkyl Iodides

As an important elementary step in organometallic chemistry, the alkylation reaction of palladacycle complexes and alkyl halides has attracted much attention in recent years due to their presence as a key step in palladium-catalyzed C–H alkylation reactions. In principle, several alkylation mechanisms, such as the stereoinvertive SN2-type mechanism and the stereoretentive oxidative addition mechanism, can be operative, and mechanistic insights can be obtained from the stereochemical outcomes of these alkylation reactions. Previous stereochemical investigations on the alkylation reaction of palladacycle complexes mainly focused on the use of chiral secondary alkyl halides as stereochemical probes, leaving more synthetically relevant primary alkyl iodides untouched. In this work, deuterium-labeled primary alkyl iodides were selected as a stereochemical probe, and their reaction with C,C- and C,N-type palladacycle complexes, namely, Catellani-type palladacycle intermediates and directing group (DG)-coordinated palladacycle complexes, were investigated both experimentally and computationally to elucidate the alkylation mechanism. We found that the C,C-ligated palladacycle intermediates undergo alkylation through the SN2-type mechanism, while the C,N-ligated 8-aminoquinoline-derived palladacycle complex favors a stereoretentive oxidative addition mechanism. In addition, the 2-phenylpyridine-derived C,N-type palladacycle dimer complex was found to react through the SN2-type mechanism due to its stable dimer structure and the d8–d8 interaction between two palladium atoms.

Activation, Transportation, and Reaction of Alkyl Radicals on a Si(111)-B Surface by a Scanning Tunneling Microscope Tip

Activation, Transportation, and Reaction of Alkyl Radicals on a Si(111)-B Surface by a Scanning Tunneling Microscope Tip

Intensified shape selectivity and alkylation reaction for the two-step conversion of methanol aromatization to p-xylene

Two-step conversion of methanol to aromatics via light hydrocarbons can significantly improve the conversion stability compared with direct aromatization of methanol, but it remains a challenge to achieve a high p-xylene (PX) selectivity. Herein, silica coating was firstly used to passivate external acid sites of ZSM-5 catalyst for the aromatization of light hydrocarbons by the chemical liquid deposition method. With the increase of SiO2 deposition, the density of the external acid sites of the catalyst was decreased from 0.1 to 0.03 mmol·g−1, which inhibited the surface secondary reactions and increased the PX/X from 34.6% to 60.0%. In view of the fact that the aromatization process in the second step was partly inhibited as methanol was consumed in advance in the upper methanol-to-light hydrocarbons catalyst layer, part of methanol was directly introduced into the lower aromatization catalyst layer to promote the alkylation process during the aromatization, which decreased the toluene selectivity from 34.5% to 14.3% but increased the xylene selectivity from 40.0% to 55.3%. It was also found that an appropriate external acid density was needed for aromatization catalyst to strengthen the alkylation process and improve the selectivity of xylene under the conditions of methanol introduction.

Soft QPCs: Biscationic Quaternary Phosphonium Compounds as Soft Antimicrobial Agents.

Quaternary ammonium compounds (QACs) serve as a first line of defense against infectious pathogens. As resistance to QACs emerges in the environment, the development of next-generation disinfectants is of utmost priority for human health. Balancing antibacterial potency with environmental considerations is required to effectively counter the development of bacterial resistance. To address this challenge, a series of 14 novel biscationic quaternary phosphonium compounds (bisQPCs) have been prepared as amphiphilic disinfectants through straightforward, high-yielding alkylation reactions. These compounds feature decomposable or "soft" amide moieties in their side chains, anticipated to promote decomposition under environmental conditions. Strong bioactivity against a panel of seven bacterial pathogens was observed, highlighted by single-digit micromolar activity for compounds P6P-12A,12A and P3P-12A,12A. Hydrolysis experiments in pure water and in buffers of varying pH revealed surprising decomposition of the soft QPCs under basic conditions at the phosphonium center, leading to inactive phosphine oxide products; QPC stability (>24 h) was maintained in neutral solutions. The results of this work unveil soft QPCs as a potent and environmentally conscious new class of bisQPC disinfectants.

CO2 capture by benzene‐based hypercrosslinked polymer adsorbent: Artificial neural network and response surface methodology

AbstractIn this research, porous benzene‐based hypercrosslinked polymeric adsorbents with different morphological properties were synthesized through Friedel–Crafts alkylation reaction. The resulting samples were applied for CO2 capture at different operational conditions. Two modelling approaches, including artificial neural network (radial basis function [RBF] and multi layer perceptron [MLP]) and response surface methodology (RSM), were employed to investigate the effect of independent parameters on adsorption capacity. A semi‐empirical quadratic model for adsorption capacity was presented based on RSM‐central composite design technique. Additionally, the optimal structure of RBF was determined with 200 neurons, and the optimal structure of MLP was determined with three hidden layers and 10, 8, and 7 neurons. The modelling results demonstrate the better prediction of MLP and RBF approaches than the RSM method with correlation coefficient values of 0.999, 0.989, and 0.931, respectively. Finally, process optimization was carried out using RSM optimization module and the optimized values of synthesis time, crosslinker ratio (formaldehyde dimethyl acetal [FDA]/benzene), adsorption time, pressure, and temperature were obtained at 10.11 h, 1, 220 s, 9 bar, and 55°C, respectively. The optimum value of CO2 uptake capacity was obtained around 167 (mg/g).

Visible Light Induced C2 Alkylation of 2H‐Benzoxazoles with Cycloalkanes and Ethers via Selectfluor‐Mediated Oxidation

AbstractAn efficient selectfluor‐oxidative protocol was developed for the direct C2‐alkylation of 2H‐benzoxazoles with cycloalkanes and ethers. Selectfluor can effectively promote the oxidative cross‐coupling without an external catalyst under the visible light irradiation at room temperature. This alkylation reaction tolerates a wide range of functional groups affording 48 examples of the C2‐alkylated 2H‐benzoxazoles in moderate to good yields.

Divergent Synthesis of 3-Pyrrolidin-2-yl-1H-indoles, Symmetric and Unsymmetric Bis(Indolyl)Methanes (BIMs) through Photocatalyzed Decarboxylative Coupling/Friedel–Crafts Alkylation Reaction

This paper reports the acid-controlled divergent synthesis of 3-pyrrolidin-2-yl-1H-indoles and symmetric and unsymmetrical bis(indolyl)methanes (BIMs) through photocatalyzed decarboxylative coupling and Friedel-Crafts alkylation reactions, respectively. The protocol involves C-H functionalization, switching formation of two products, room-temperature conditions, low photocatalyst loadings, without strong oxidant, and moderate to excellent yields. This method has been applied for the synthesis of natural product vibrindole A and 1,1-bis(1H-indol-3-yl)-2-phenylethane.

Modulating the acidity and accessibility of HZSM-5@Al-KIT-6 catalysts for the tandem catalytic upgrading of lignin pyrolysis vapors

In this paper, a surface encapsulation method has been developed to synthesize the HZSM-5 @Al-KIT-6 hierarchical zeolites, due to the poor mono-aromatic hydrocarbons (MAHs) selectivity and rapid coke deactivation during the catalytic upgrading lignin pyrolysis vapors. Results showed that the acidity and accessibility of HZSM-5 @Al-KIT-6 hierarchical zeolite can be modulated by changing the TEOS/HZSM-5 mass ratio during catalyst synthesis. The three-dimensional (3-D) cubic mesoporous shell can capture the bulky phenolic oligomers and pre-crack for further reforming. The highest MAH content (44.03%) and lower polycyclic aromatic hydrocarbons (PAHs) (23.79%) were produced when the TEOS/HZSM-5 mass ratio was 1.0. The hierarchical zeolites improved the yield of xylenes due to the enhanced alkylation reaction. In addition, the micro-mesoporous highway reduced the formation of coke deposition. The catalytic mechanism of hierarchical zeolites was then proposed based on the obtained results. This study provides a reference for pilot-scale experiments for the catalytic upgrading lignin pyrolysis vapors.

SYNTHESIS AND SIMPLE METHOD OF CHARACTERIZATION OF ALDEHYDE-SILICA GEL

Two approaches to the functionalization of the silica gel surface have been proposed, which make it possible to obtain materials with covalently immobilized highly reactive aldehyde groups. Immobilization of aldehyde groups in the first case is achieved by the click-reaction of azido-alkyne cycloaddition of 4-(prop-2-in-1-yloxy)benzaldehyde and 3-azidopropyl silica gel. In the second case, surface modification is performed by the alkylation reaction of hydroxybenzaldehydes with 3-chloropropyl silica gel. The obtained silica gel samples were characterized by infrared spectroscopy and thermogravimetric analysis data. In IR spectra absorption bands determination of aldehyde groups on the silica gel surface using 2.4 -dinitrophenylhydrazine has been proposed. The proposed method is based on the condensation reaction between the aldehyde groups grafted on the surface and 2.4 -dinitrophenylhydrazine. The quantitative estimation of the grafted aldehyde groups is suggested to be calculated by the difference between the initial amount of 2.4-dinitrophenylhydrazine and the amount remaining in the solution after the reaction. The necessity of maintaining a constant acidity of the medium by adding H2SO4 was established. It is shown that at λ = 315 nm the Bouguer-Beer-Lambert Law is satisfied in the concentration range 2.5∙10-5 to 12.5∙10-5 M. The correctness of the proposed method was checked using the procedure of operative control of the correctness of the results of chemical analysis. This procedure provides the determination of aldehyde groups in the modified material by multiply varying the silica gel weight and using the root-mean-square deviation of the repeatability of measurement results as an error characteristic. The proposed method for determining the aldehyde groups was tested on all silica gel samples. It was shown that by varying the conditions of surface modification it is possible to obtain materials with different functional capacity for aldehyde groups.

B-Axis-Oriented ZSM-5 Nanosheets for Efficient Alkylation of Benzene with Methanol: Synergy of Acid Sites and Diffusion

ZSM-5 nanosheets are promising catalysts for the catalytic reactions controlled by diffusion limitations. This study reveals its significant application in the alkylation of benzene with methanol. The b-axis-oriented ZSM-5 nanosheets with similar acid property but varied thicknesses of about 30, 90, and 300 nm were prepared to investigate the effect of thickness on their catalytic properties for alkylation reactions. Comparative results demonstrate that the sample with a thickness of 30 nm exhibits higher benzene conversion, xylene selectivity, and methyl selectivity (up to 97%), accompanied by an ultralong lifetime (up to 1000 h, 10 times longer than that of the sample with a thickness of 300 nm) and lower byproduct ethylbenzene selectivity. This is ascribed to the shortened straight channel length, increased specific surface area, and enlarged mesopore volume that significantly facilitate the diffusion of reactants and products, increase the accessibility of acid sites, and decrease the coke formation. Moreover, compared with conventional ZSM-5 nanocrystals, ZSM-5 nanosheets deliver a substantially extended lifetime due to fewer framework defects. Most significantly, this study unravels the diffusion effect on ethylbenzene selectivity over ZSM-5 nanosheets with different thicknesses and illustrates the role of strong Brønsted acid sites in the dynamic changes of ethylbenzene selectivity. In light of the above analysis, we developed a precoking strategy and an introducing-heteroatom strategy to precisely tailor the catalyst acidity, further suppressing the ethylbenzene formation (<0.3%) while maintaining long-term stable operation (>300 h).

Enantioselective Alkylation of Unactivated C–O Bond: Solvent Molecule Affects Competing β-H Elimination and Reductive Elimination Dynamics

Despite the fact that metal-catalyzed asymmetric alkylative cross-couplings have been well-established, enantioselective alkylative substitution of an unactivated C–O bond remains a challenge due to the lack of strategies to cleave the C–O bond and suppress β-H elimination as well as control stereochemistry simultaneously. Herein, the enantioselective alkylative activation of an unactivated C–O bond with β-H-containing alkylating reagents was described using a chiral nickel catalyst, and versatile axially chiral biaryls bearing alkyl moieties with different chain lengths were delivered in good yields and with high ee. Control experiments demonstrated the significant role of the solvent tetrahydrofuran to facilitate this transformation. DFT calculations revealed that the coordination of THF to Mg(II) is pivotal for suppressing β-H elimination during reductive elimination, thus unlocking how the solvent molecule affects the competing β-H elimination and reductive elimination dynamics in transition-metal-catalyzed alkylative cross-coupling reactions.

Synthesis of 2-(2-Nitroalkyl)indoles by Rhodium(III)-Catalyzed C-H Alkylation.

The Rh(III)-catalyzed addition of the indole C2-H bond to nitroalkenes under an ambient atmosphere is disclosed, providing direct access to a wide range of 2-(2-nitroalkyl)indoles (33 examples) with excellent chemo- and regioselectivity. In addition, pyrrole derivatives also successfully participated in this Friedel-Crafts alkylation reaction. Representative nitroalkane products could be converted into structurally diverse and valuable indole derivatives. Furthermore, a series of control experiments were conducted, and a plausible mechanism was proposed.

Low-temperature upcycling of polyolefins into liquid alkanes via tandem cracking-alkylation.

Selective upcycling of polyolefin waste has been hampered by the relatively high temperatures that are required to cleave the carbon-carbon (C-C) bonds at reasonably high rates. We present a distinctive approach that uses a highly ionic reaction environment to increase the polymer reactivity and lower the energy of ionic transition states. Combining endothermic cleavage of the polymer C-C bonds with exothermic alkylation reactions of the cracking products enables full conversion of polyethylene and polypropylene to liquid isoalkanes (C6 to C10) at temperatures below 100°C. Both reactions are catalyzed by a Lewis acidic species that is generated in a chloroaluminate ionic liquid. The alkylate product forms a separate phase and is easily separated from the reactant catalyst mixture. The process can convert unprocessed postconsumer items to high-quality liquid alkanes with high yields.

Perylene Diimide-Containing Dynamic Hyper-crosslinked Ionic Porous Organic Polymers: Modulation of Assembly and Gas Storage

A strategy to synthesize hyper-crosslinked polymers with strong visible-light absorption and abundant ionic sites is discussed. This is achieved in a one-pot reaction via the simultaneous Friedel–Crafts alkylation and quaternization reaction between α,α′-dibromo-p-xylene (DBX) and perylene diimide (PDI) substituted with N,N-dimethyl ethylene to result in hyper-crosslinked ionic polymers (HIPs). These HIPs display good surface areas with strong visible-light absorption (400–650 nm) and dispersibility in polar solvents like water and DMSO. Importantly, our experimental and theoretical studies indicate that PDI-HIPs possess a dynamic network with good uptake of water up to seven times their weight. Notably, PDI in PDI-HIPs is not only responsible for visible-light absorption but also acts as a probe to study their dynamic nature. Moreover, the presence of ultramicropores and CO2-philic functional groups in PDI-HIPs renders good CO2 uptake up to 2.11 mmol/g at 273 K despite their relatively low surface area.