Alkylation Reactions Research Articles

Toluene Alkylation Reactions over Y-Type Zeolite Catalysts: An Experimental and Kinetic Study

The present study demonstrated an improvement in both 1-heptene conversion and mono-heptyltoluene selectivity. It simultaneously depicted the isomerization reactions of 1-heptene and toluene alkylation over Y zeolite catalysts having a Si/Al of 3.5 and a surface area of 817 m2/g. The physical properties of the fresh zeolite catalyst were characterized using XRD, FTIR, XRF, TPD, and N2 adsorption–desorption spectroscopy. The experimental part was carried out in a 100 mL glass flask connected to a reflux condenser at different reaction temperatures ranging from 70 to 90 °C, toluene:1-heptene ratios of 3–8, and catalyst weights of 0.25–0.4 g. The highest conversion of ~96% was obtained at the highest toluene:1-heptene ratio (i.e., 8:1), 0.25 g of zeolite Y, at 180 min of reaction time and under a reaction temperature of 90 °C. However, the selectivity of 2-heptyltoluene reached its highest value of ~25% under these conditions. Likewise, the kinetic modeling developed in this study helped describe the proposed reaction mechanism by linking the experimental results with the predicted results. The kinetic parameters were determined by nonlinear regression analysis using the MATLAB® package genetic algorithm. The ordinary differential equations were integrated with respect to time using the fourth-order Runge–Kutta method, and the resulting mole fractions were fitted against the experimental data. The mean relative error (MRE) values were calculated from the experimental and predicted results, which showed a reasonable agreement with the average MRE being ~11.7%. The calculated activation energies showed that the reaction rate follows the following order: coking (55.9–362.7 kJ/mol) > alkylation (73.1–332.1 kJ/mol) > isomerization (69.3–120.2 kJ/mol), indicating that isomerization reactions are the fastest compared to other reactions. A residual activity deactivation model was developed to measure the deactivation kinetic parameters, and the deactivation energy value obtained was about 48.2 kJ/mol.

Difluoroenoxysilanes in Catalytic Asymmetric Allylic Alkylation.

An allylic substitution with difluoroenoxysilanes as the nucleophile is accomplished for the enantioselective synthesis of α-allylic α,α-difluoroketones. With racemic branched allylic alcohols as the easily accessible allylic electrophile, this branched-selective and enantioconvergent allylic alkylation reaction is catalyzed by an Ir(I)/(P,olefin) complex and overcomes the low nucleophilicity of difluoroenoxysilanes to furnish β-chiral α,α-difluoroketones in moderate to good yields with high enantioselectivity (up to >99.9:0.1 er).

Synthesis and in vitro/in silico evaluation of the antimalarial activity of potential amino-quinoline derivatives

In this study, a series of N-arylamino-7-chloroquinolines were synthesized via an alkylation reaction involving aniline derivatives (2) and 4,7-dichloroquinoline (1). Additionally, the synthesis of a library of N-aryl-N-benzylamino-7-chloroquinoline analogues, modified on the aniline nitrogen, has also reported. A structure-activity relationship (SAR) study was conducted to evaluate the biological efficacy and safety of these derivatives against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfW2) Plasmodium falciparum strains. Compounds 5i and 5c showed promising efficacy against the Pf3D7 strain with IC50 values of 0.25 μM and 0.54 μM, respectively, while compound 5l demonstrated significant activity against the PfW2 strain with an IC50 of 5.82 μM. The cytotoxicity of these compounds was also evaluated on HUVEC cell lines. Additionally, their pharmacological and pharmacokinetic (ADME) properties were studied to predict their fate and identify promising candidates for further clinical studies.

Highly selective production of 2-methylnaphthalene by CO2 hydrogenation and naphthalene alkylation

Many researchers have extensively studied the alkylation of naphthalene with methanol for the preparation of high-value-added chemicals, especially methylnaphthalenes (MNs). Studies indicated that methanol generates a large number of methanol-to-olefin by-products on zeolites, resulting in low selectivity of the target product and poor stability of the catalyst, limiting its application in the industrial field. In this study, CO2 hydrogenation was coupled with naphthalene alkylation, and the H3CO* active intermediate generated in situ was alkylated with naphthalene by using metal oxide-zeolite (OX-ZEO) bifunctional catalysts, which exhibited the ‘slow release’ phenomenon of the methylation reagent. It improved naphthalene conversion, suppressed deep alkylation and coke deposition side reactions and kept the catalyst stable for up to 500 h. A high-density and medium-strength Brønsted acid center facilitated the efficient migration of H3CO* active intermediates with the desorption of 2-methylnaphthalene (2-MN), which was particularly important for improving naphthalene conversion and 2-MN selectivity. The in situ IR showed that more Brønsted acid sites of Ga-S-1 effectively pulled the migration process of H3CO* species to the zeolitic acid center and increased the efficiency of C-C coupling compared to ZSM-5, which promoted the alkylation of H3CO* species with naphthalene. The results of chemisorption experiments showed that the medium-strength Brønsted acid site, which promoted the desorption of 2-MN, inhibited the deep alkylation reaction. The 2,6-dTBPy-IR results showed that the presence of fewer Brønsted centers on the outer surface of Ga-S-1 further optimized the product distribution and enhanced the selectivity of 2-MN in MNs to more than 90 %. Under optimal conditions, 80.1 % selectivity for MNs was obtained via ZnZrOx&Ga-S-1 bifunctional catalysts, with 97.4 % selectivity for 2-MN in MNs.

Synthesis and marine antifouling properties of carbazole amide derivatives with fluorescent properties and their zinc acrylate resins

Fluorescent antifouling is a method that utilizes substances fluorescent repellent effect to prevent organisms attachment and fouling. It is considered one of the directions for developing environmentally friendly marine antifouling materials. The current fluorescent antifouling materials were characterized by issues such as single functionality, unclear antifouling mechanisms, and suboptimal antifouling performance. In this study, three carbazole derivatives containing carbon–carbon double bonds were synthesized by Friedel-Crafts alkylation reaction, and a series of zinc acrylate resins containing carbazole derivative structures were further synthesized through free radical polymerization. Three carbazole derivatives were tested for their fluorescence and their growth inhibition properties against bacteria and algae. The results showed that the three carbazole derivatives not only had high fluorescence intensity, but also had good inhibitory effects on bacteria and algae, with the highest inhibition rate of 81% on algae. The fluorescence properties, algal inhibition properties and anti-algal adhesion properties of the resin were investigated. The results showed that the fluorescence intensity of the resin was enhanced with the increase of carbazole derivative content. The inhibition rate of the resin against algae was as high as 88.5%, and the anti-algal adhesion rate of the resin was improved under light conditions. Mechanistic studies showed that the resin influenced the cell wall, and the fluorescence caused the algae to prioritize photosynthesis rather than attachment and settlement. Self-polishing performance test results showed that the introduction of carbazole derivatives improved the stability of the resin. The results of the real sea antifouling test show that the resin integrates fluorescence, chemical activity and self-polishing, and has excellent antifouling performance. This provides a theoretical basis for the development of environmentally friendly marine antifouling materials.

Preparation of heteroatom-doped hyper-crosslinked polymers via waste utilization of sulfur-containing petroleum coke: A promising adsorbent for CO2 capture

To overcome the worldwide environmental crisis related to the continuous emission of CO2, the use of porous organic polymers, which are excellent absorbents and conversion materials, to reduce CO2 emission is of great significance. Among them, hyper-crosslinked polymers (HCPs) are porous materials with a high pore density that are synthesized using a simple one-pot method that is economical and can realized at a low temperature, hence they have good application prospects as adsorbents for CO2. In this study, a batch of petroleum coke-based HCPs with different sulfur contents was prepared via the one-pot Friedel-Crafts alkylation reaction using inexpensive and abundant petroleum coke as raw material. Thereafter, the use of the prepared materials for CO2 adsorption revealed that the HCPs with a high sulfur content had a larger specific surface area (825 m2/g) and showed a higher CO2 adsorption capacity (2.1603 mmol/g at 1 bar 298 K) than its counterpart with a lower sulfur content. Thus, the presence of sulfur significantly enhanced the CO2 adsorption performance of the material. Further, the simulation of the heat of adsorption of HCPs with and without sulfur using Material Studio also confirmed the higher CO2 capture efficacy of HCPs with a higher sulfur content.

Total Synthesis of Tipranavir Based on Iridium-Catalyzed Asymmetric Allylic Substitution of Dihydropyranone.

An efficient and highly enantioselective synthesis of tipranavir is realized based on an iridium-catalyzed asymmetric allylic substitution. High yield and diastereoselectivity (>20:1), as well as excellent enantioselectivity (99% ee), were obtained for the key intermediate through direct asymmetric alkylation reaction of dihydropyranone with allylic tert-butyl carbonate. Anti-AIDS drug of tipranavir was finally accomplished in 8 steps and 6 pots starting from commercially available 1-phenyl-3-hexanone in 20.7% overall yield with 99% ee and >20:1 dr.

In Situ Synthesis of Hypercrosslinked Polymer as Stationary Phase for Capillary Gas Chromatography

Hypercrosslinked polymers (HCPs) constructed by the Friedel–Crafts alkylation reaction of aromatic compounds have emerged as a new class of porous materials with unique merit. Herein, a HCP named HCP-TPB was coated onto a capillary column through in situ synthesis. The prepared column exhibited a nonpolar nature, and the column efficiency for n-dodecane was 3003 plates m−1. Moreover, the relative standard deviations of retention time and peak area for six replicate injections of the C3–C6 were lower than 0.1% and 1.5%, respectively. The results of this study showed that it is very promising to utilize HCPs as stationary phases for the separation of C3–C6.

Bipyridyl Functionalized NHC-Sulfenyl, Selenenyl Cations; Potential Species for Alkylation Reactions and Ligands in Copper(I) Catalysis.

Reactions of bipyridyl-functionalized imidazole-thiones and selones with MeX (X = I, OTf) afforded sulfenyl and selenenyl cations [(NNC)EMe]X (2/3, E = S, Se). Further reactions of these main-group cations with [Cu(CH3CN)4]BF4, Cu(OTf) furnished dicationic [{Cu(µ-I)(NNC)EMe}2][Y]2 (5/6, Y = BF4, OTf) and tricationic copper(I) complexes [Cu{(NNC)EMe}2](OTf)2BF4 (7a/7b) when employed [(NNC)EMe]I and [(NNC)EMe]OTf respectively. All these cationic complexes were characterized by various spectroscopic techniques, including X-ray diffraction analysis. The solid-state structures revealed novel bonding modes of the cations. The cationic nature of new complexes was analyzed by the 77Se NMR spectroscopy, which indicated different electronic environments around the selenium centers. The cations [(NNC)EMe]X (X= I, OTf), and (NNC)SMe bearing copper complex [{Cu(µ-I)(NNC)EMe}2][Y]2 proved as potential candidates for alkylation of various Lewis bases and as molecular catalyst in aldehyde-alkyne-amine coupling reactions, respectively. The latter catalytic reactions yielded a range of three-component products in good to excellent yields with low catalyst loading under solvent-free conditions, which demonstrate the potential utility of group-16 cations as ancillary ligands in homogeneous catalysis.

Pnictogen and Chalcogen Salts as Alkylating Agents.

Alkylation reactions and their products are considered crucial in various contexts. Synthetically, the alkylation of a nucleophile is usually promoted using hazardous alkyl halides. Here, we aim to highlight the potential of pnictogen (ammonium or phosphonium) and chalcogen salts (sulfonium, selenonium, and telluronium) to function as alkylating agents. These compounds can be considered as non-volatile electrophilic alkyl reservoirs. We will center our discussion on the strategies developed in recent years to expand the synthetic utility of these salts in terms of transferable alkyl groups, substrate scope, and product selectivity.

Rhodium(III)-Catalyzed Regioselective C-H Alkenylation and Alkylation of Menadione Analogues with β-Trifluoromethyl Enones.

Menadione and its structural analogues are important motifs present in various bioactive natural products and drugs with a wide range of biological activities. In addition, β-trifluoromethyl enone has been employed as an efficient fluorinated building block for the synthesis of CF3-containing organic scaffolds. Herein, we report both C-H alkenylation and C-H alkylation reactions using β-CF3 enones as coupling partners with amino-substituted menadiones under Rh(III) catalysis. While β-CF3 enones have been studied in C-H alkylation reactions, we herein for the first time disclose the Rh (III)-catalyzed C-H alkenylation reaction of β-CF3 enones. The presence of an oxidant was crucial for the alkenylation reaction with β-CF3 enone. Meanwhile, the alkylation reaction proceeds via redox-neutral conditions.

Perylene diimide-based hyper-cross-linked polymers for visible-light-driven selective organic sulfide oxidation

Hyper-cross-linked polymers (HCPs) feature excellent pore structures, ultra-high stability, and ease of preparation, making them promising candidates for visible-light-driven selective organic sulfide oxidation. Developing new HCPs of good performance is of great significance in the endeavor. Perylene diimide (PDI) exhibits excellent visible light absorption properties due to its high planar conjugated structure, showing potential as a monomer for photocatalytic HCP synthesis. In this study, we report the construction of two HCPs, named NUT-18 and NUT-18-Me, employing the Friedel-Crafts alkylation reaction using PDI derivatives as monomers. Both HCPs possess high specific surface area (reaching up to 811 and 828 m2/g) and photoactivity. Consequently, NUT-18 and NUT-18-Me demonstrated photocatalytic efficiency, with conversion and selectivity exceeding 98 % in the various organic sulfides’ photocatalytic oxidation. Notably, the photocatalytic performance is well-maintained even after 5 cycles, indicating good recyclability. Investigation of the catalytic mechanisms revealed that the selective catalytic oxidation of sulfides is based on the synergistic promotion of dual pathways for electron and energy transfer. This research highlights the potential of PDI molecules in designing and synthesizing porous materials as promising photocatalysts.

Aromatics Alkylated with Olefins Utilizing Zeolites as Heterogeneous Catalysts: A Review

The alkylation reaction of aromatic compounds gains considerable attention because of its wide application in bulk and fine chemical production. Aromatics alkylated with olefins is a well-known process, particularly for linear alkylbenzene, phenyloctanes, and heptyltoluene production. As octane boosters and precursors for various petrochemical and bulk chemical products, a wide range of alkylated compounds are in high demand. Numerous unique structures have been proposed in addition to the usual zeolites (Y and beta) utilized in alkylation procedures. The inevitable deactivation of industrial catalysts over time on stream, which is followed by a decrease in catalytic activity and product selectivity, is one of their disadvantages. Therefore, careful consideration of catalyst deactivation regarding the setup and functioning of the process of catalysis is necessary. Although a lot of work has been carried out to date to prevent coke and increase catalyst lifespan, deactivation of the catalyst is still unavoidable. Coke deposition can lead to catalyst deactivation in industrial catalytic processes by obstructing pores and/or covering acid sites. It is very desirable to regenerate inactive catalysts in order to remove the coke and restore catalytic activity at the same time. Depending on the kind of catalyst, the deactivation processes, and the regeneration settings, each regeneration approach has pros and cons. In this comprehensive study, the focus was on discussing the reaction mechanism of 1-octene isomerization and toluene alkylation as an example of isomerization and alkylation reactions that occur simultaneously, shedding light in detail on the catalysts used for this type of complex reaction, taking into account the challenges facing the catalyst deactivation and reactivation procedures.

Synthesis of α-Boryl-α-Substituted Allylboronates from Propyne.

A novel method for the two-step synthesis of α-boryl-α-substituted allylboronates from propyne is described. These allylboronates are prepared by the Co-catalyzed 1,1-diboration reaction of propyne with B2pin2, followed by the base-mediated alkylation reaction of 1,1-di(boryl)propene at the α-position. Computational studies revealed the origins of observed reactivity and selectivity in the base-mediated alkylation reaction. The resulting α-boryl-α-methyl-allylboronate is applied to the allylation of aldehydes, which gives homoallylic alcohols with a trisubstituted alkene moiety.

COSMO-RS prediction, experimental investigation, and mechanism analysis: A new approach to separating the n-hexane - tert-butanol azeotropic system via liquid-liquid extraction with ionic liquids

n-Hexane and tert-Butanol (TBA) are frequently utilized to refine the conditions for Grignard, Wittig, and Friedel-Crafts alkylation reactions. During the synthesis of loratadine, the formation of azeotropic mixtures n-hexane and TBA, which are challenging to separate through conventional distillation, is inevitable. This study utilizes the COSMO-RS model to identify suitable ionic liquids (ILs) for the separation of the n-hexane - TBA azeotropic system. Based on solvent capacity and selectivity, 1-ethyl-3-methylimidazolium trifluoroacetate ([EMIM][TFA]), 1-butyl-3-methylimidazolium trifluoroacetate ([BMIM][TFA]), and 1-hexyl-3-methylimidazolium trifluoroacetate ([HMIM][TFA]) were selected as extractants. The liquid–liquid equilibrium (LLE) data for the n-hexane - TBA - ILs ternary system were measured at 303.15 K and atmospheric pressure. Distribution coefficients and selectivity were calculated to evaluate the performance of the extractants, with the NRTL model used to correlate the experimental LLE data. The consistency of the NRTL model parameters was corroborated through topological analysis associated with the Gibbs tangent principle. Quantum chemical calculations, including interaction energy, ESP analysis, IGMH analysis, and QTAIM topological analysis, were performed to explore the separation mechanism at the molecular level. The results indicated that the interaction energies between the ILs and TBA were higher than those between the ILs and n-hexane, indicating a stronger attraction of ILs to TBA. Consequently, the ILs effectively separated TBA from the n-hexane - TBA azeotropic system, with extraction capacities ranked as [EMIM][TFA] > [BMIM][TFA] > [HMIM][TFA]. The quantum chemical calculations successfully explained the experimental results, aligning with COSMO-RS model predictions and confirming their reliability. IGMH and QTAIM topological analyses systematically explored the types and strengths of interactions, revealing that hydrogen bonds are predominant between the ILs and TBA, with additional contributions from van der Waals forces. Furthermore, the hydrogen bond strengths between TBA and the anions and cations of the ILs are classified as strong and moderate, respectively. This work provides valuable insights into the separation of azeotropic systems using ILs, elucidating the underlying mechanisms behind this process.

Design, synthesis, and anti-breast cancer activity evaluation of novel 3-cyanopyridine derivatives as PIM-1 inhibitors.

A novel series of cyanopyridines 7a-j were synthesized via a one-pot multicomponent reaction of arylidene 4 with ammonium acetate 5 and respective methylaryl/heterylketones 6a-j in ethanol using vanillin as a natural starting material. Moreover, the regioselective alkylation reaction was studied by the treatment of cyanopyridines 7a-f and 7j with CH3I in the presence of K2CO3 in DMF to afford O-methylcyanopyridines 8a-g (major) and N-methylcyanopyridines 9a-g (minor), whereas bipyridine 7h gave bipyridinium iodide salt 10. All of the designed cyanopyridines were evaluated as anti-breast cancer (MCF-7) cell lines via PIM Kinase inhibitory activity, and the results displayed that some of them showed high activities, especially compounds 7h and 8f, which showed excellent activities against MCF-7 with IC50 values of 1.89 and 1.69 μM, respectively, more potent than the reference drug doxorubicin. Mechanistically, compounds 7h and 8f exhibited strong in vitro PIM-1 kinase inhibitory activity with an IC50 of 0.281 and 0.58 μM, respectively, compared to the reference staurosporine. Moreover, compound 7h arrested the tumor cells at the S phase and caused cell death mainly by inducing early and late apoptosis. Molecular docking studies against PIM-1 revealed good binding modes of the synthesized compound and showed agreement with the biological results.

Combining the Nonnatural Activity of Lipase and Electrocatalysis in One Pot: Sustainable and Regioselective Synthesis of C‐3 Alkylated Oxindoles

AbstractIn this study, we report an environment‐friendly protocol by integrating the nonnatural catalytic activity of lipase with electrocatalysis for synthesizing C‐3 alkylated oxindoles, which are part of many natural and pharmaceuticals products. Gratifyingly, Candida antarctica lipase B (CALB) is found to be highly active and regioselective for catalyzing the nonnatural C‐3 alkylation reaction at indole when combined with an electrochemical C‐2 oxidation process in the same vessels. Further, the generality and feasibility of the developed protocol are shown by employing several functional groups on the indole moiety and obtaining the desired products in moderate to good yield. Besides, the control experiments are set up along with the molecular docking studies to substantiate the role of the active site of Candida antarctica lipase B (CALB) in carrying out the regioselective C‐3 alkylation reaction. In addition, control experiments and cyclic voltammetry are performed to get insight into the electrochemical C‐2 oxidation process and as a result, a plausible mechanism for the integrated process is presented.

Chalcogen Bond-Driven Alkylations: Selenoxide-Pillar[5]arene as a Recyclable Catalyst for Displacement Reactions in Water.

A novel strategy to catalyze alkylation reactions through chalcogen bond interaction using a supramolecular structure is presented herein. Utilizing just 1.0 mol % of selenoxide-pillar[5]arene (P[5]SeO) as the catalyst we achieved efficient catalysis in the cyanation of benzyl bromide in water. Our approach demonstrated high efficiency and effectiveness, with the results supported by designed control experiments and theoretical models, highlighting the catalytic effect of the pillar[5]arene through noncovalent interactions. Quantum-chemical calculations (ωB97X-D/def2-TZVP@SMD) pointed out that the catalyzed cyanation reaction followed an SN2-like mechanism, with energy barriers (ΔH≠) ranging from 16.7 to 18.2 kcal mol-1, exhibiting dissociative character depending on the para-substituent. 1H NMR analysis revealed that P[5]SeO acted as a catalyst through inclusion complex formation, facilitating the transfer of the electrophilic substrate to the aqueous solution for nucleophilic displacement. Our reaction protocol proved applicable to various substrates, including aromatic and alpha-carbonyl derivatives. The use of sodium azide as the nucleophile was also feasible. Importantly, our method allowed scalability, and the catalyst P[5]SeO could be recovered and reused effectively for multiple reaction cycles, showcasing sustainability.

Iridium‐Pyrazolato Complex Catalyzed Dehydrogenative Alkylation of Ketones and Arylacetonitriles with Primary Alcohols

AbstractHerein, we report the use of an air‐stable iridium pyrazolato complex as an effective catalyst for the α‐alkylation of ketones and arylacetonitriles with primary alcohols, employing borrowing hydrogen strategy. The alkylation reactions were efficiently conducted at 120 °C in toluene utilizing a very low catalyst loading (0.1 mol %). A broad range of ketones and arylacetonitriles, in combination with various aromatic and aliphatic primary alcohols, were successfully transformed into the corresponding α‐alkylated products. Additionally, quinoline derivatives were synthesized from 2‐aminobenzylalcohol and ketones using dehydrogenative coupling strategy. A mechanistic investigation unveiled that the key step involved alcohol activation via metal‐ligand cooperation.

Artificial Light-Harvesting Systems with a Three-Step Sequential Energy Transfer Mechanism for Efficient Photocatalytic Minisci-Type Late-Stage Functionalization.

The natural process of photosynthesis involves a series of consecutive energy transfers, but achieving more steps of efficient energy transfer and photocatalytic organic conversion in artificial light-harvesting systems (ALHSs) continues to pose a significant challenge. In the present investigation, a range of ALHSs showcasing a sophisticated three-step energy transfer mechanism is designed, which are meticulously crafted using pillar[5]arene (WP[5]) and p-phenylenevinylene derivative (PPTPy), utilizing host-guest interactions as energy donors. Three distinct types of fluorescent dyes, namely Rhodamine B (RhB), Sulforhodamine 101 (SR101), and Cyanine 5 (Cy5), are employed as acceptors of energy. Starting from PPTPy-2WP[5], energy is sequentially transferred to RhB, SR101, and Cy5, successfully constructing a multi-step continuous energy transfer system with high energy transfer efficiency. More interestingly, as energy is progressively transferred, the efficiency of superoxide anion radical (O2 •-) generation gradually increased, while the efficiency of singlet oxygen (1O2) generation decreased, achieving the transformation from type II photosensitizer to type I photosensitizer. Furthermore, in order to fully utilize the energy harvested and reactive oxygen species (ROS) obtained, the ALHSs employ a multi-step sequential energy transfer process to enhance Minisci-type alkylation reactions with aldehydes through photocatalysis for late-stage functionalization in an aqueous environment, achieving a 91% yield.