Friedel-Crafts Benzylation Research Articles

Access to Substituted 1,1-Diarylalkanes by Friedel-Crafts Benzylations Mediated by FeCl3-based Deep Eutectic Solvents.

The development of new, more efficient Friedel-Crafts benzylation methodologies that provide access to 1,1-diarylalkanes is an important objective of interest for the production of pharmaceuticals and fine chemical products. In this regard, this study introduces a novel synthetic route to 1,1-diarylalkanes conducted in the Deep Eutectic Solvent (DES) 3 FeCl3 ⋅ 6 H2O/Gly, which serves as both a reaction medium and promoter. Under these conditions, Friedel-Crafts benzylations of various arenes bearing activating and deactivating ortho-/para-directing groups, can be performed using diverse benzylating reagents such as styrenes, alcohols, acetates, ethers, and chlorides. Importantly, highly electronically deactivated electrophiles, including those with CF3 and NO2 groups, are suitable substrates. This methodology provides a wide range of asymmetric 1,1-diarylalkanes (up to 132 examples) with generally good yields and high regioselectivities. The efficiency of this approach was demonstrated with the multigram-scale synthesis (10 mmol) of 1-phenyl-1-xylyl ethane (PXE), a liquid with great industrial applicability. Moreover, the Fe(III)-based DES could be reused for 20 consecutive cycles with no appreciable erosion of the yields.

Au(III)/TPPMS-catalyzed Friedel-Crafts benzylation of deactivated N-alkylanilines in water.

The Friedel-Crafts reaction of electronically deactivated anilines including those with strong electron-withdrawing NO2, CN or CO2H groups is challenging due to the reduced electron density of the aromatic ring. Here, we demonstrate the Au(III)/TPPMS-catalyzed Friedel-Crafts benzylation of deactivated anilines in water. This reaction exhibits operational simplicity and a broad substrate scope with high regioselectivity, enabling rapid access to 2-benzylanilines.

Aryl carbonyls and carbinols as proelectrophiles for Friedel-Crafts benzylation and alkylation.

Friedel-Crafts benzylation/alkylation using benzylic, tertiary, and homobenzylic alcohols; aryl aldehydes, aryl ketones, and the highly challenging aryl carboxylic acids and esters as proelectrophiles has been achieved using borane-ammonia and TiCl4, greatly broadening the scope of useable substrates. Incorporation of deactivated aromatic proelectrophiles and specificity for substitution at the benzylic position are demonstrated in the synthesis of various di- and triarylalkane products. Dual protocols allow for the use of standard nucleophilic solvents (benzene, toluene, etc.) or for stoichiometric addition of more valuable nucleophiles including furans, thiophenes, and benzodioxoles.

Reactivity in Friedel-Crafts aromatic benzylation: the role of the electrophilic reactant.

Density functional theory is employed in understanding the reactivity in the TiCl4 catalyzed Friedel-Crafts benzylation of benzene with substituted benzyl chlorides in nitromethane solvent. A series of ten substituted (in the aromatic ring) benzyl chlorides are characterized by theoretical reactivity indices. The theoretical parameters are juxtaposed to experimental relative rates of benzylation. It is established that the carbon-chlorine ionic bond dissociation energy and the Hirshfeld charge at the chlorine atom for the benzyl chlorides reactants - describe quite satisfactorily the reactivity trends. These results provide further insights into the factors governing reactivity in EAS reactions, which so far have been mostly focused on rate variations induced by changes in the structure of the aromatic substrate. The EAS benzylation investigated is quite unusual since, in contrast to most EAS reactions, the latest experimental kinetic results suggest that the aromatic substrate does not participate in the kinetic equation of the process. To shed more light on this unexpected result, we also conducted a theoretical study on the mechanistic pathway by applying M06-2X density functional computations combined with several basis sets: 6-311+G(d,p), 6-311+G(2df,2p), and def2-TZVPP. Because of the well-known difficulties in evaluating realistic free energy barriers for organic reactions, we tested two solvent models in determining the barrier for the TiCl4-catalyzed Friedel-Crafts benzylation of benzene by benzyl chloride. Since all methods employed did not provide satisfactory results for the free energy barriers, we used a combination of theoretically estimated enthalpy barriers and the available (from kinetic experiments) entropy contribution. This approach enabled us to verify that indeed the rate of this EAS reaction does not depend on the nature of the aromatic substrate. The computations revealed the structure and relative energies of the critical structures along the mechanistic pathway. Four intermediates were established along the reaction route.

Friedel-Crafts Benzylation of Unprotected Anilines with Indole-3- carbinols to Access Trifluoro-methyl(indolyl)phenylmethanes

:An unprecedented protocol for the efficient and highly chemoselective alkylation of unprotected anilines with deactivated CF3-indole-3-carbinols promoted by In(OTf)3 has been developed. A series of diversified trifluoromethylated (indolyl)phenylmethanes were produced featuring the C-alkylation in moderate to high chemical yields and with high regioselectivities.

Lignin-based sulfonated carbon as an efficient biomass catalyst for clean benzylation of benzene ring compounds

Low-temperature carbonization–sulfonation two-step process or one-step sulfonation process was employed to draft sodium lignosulfonate (SLS), the primary biological macromolecule ingredient of papermaking black liquor, into lignin-based sulfonated carbon. The two-step lignin-based sulfonated carbon named SLC400,1S was found to be an efficient catalyst for clean Benzyl-alcohol (BA) route Friedel-Crafts (F-C) benzylation of benzene ring compounds. FT-IR, XRD, Raman spectra, XPS, SEM with EDX-mapping, TGA-DSC, acid-base titration, and n-butylamine–acetonitrile titration characterizations demonstrated that the specific two-step process could introduce porous properties and a large number of surface sulfonic, hydroxyl, and carboxyl active groups into the structure of the prepared material, which was found to account for the good catalytic performance for benzylation. Similar to that of hierarchical mesoporous ZSM-5 under optimal conditions, the apparent activation energy for benzylation of paraxylene (PX) with BA over SLC400,1S was estimated to be 119 kJ·mol−1. The common by-product of BA route benzylation, dibenzyl ether (DBE), was almost inhibited because of the extraordinary activity of SLC400,1S and the optimized reaction conditions. A 12-run recycling test demonstrated easy recovery and steady reusability of the above lignin-based sulfonated carbon catalyst.

In Situ Anodically Oxidized BMIm-BF4: A Safe and Recyclable BF3 Source.

The anodic oxidation of 1-butyl-3-methylimidazolium tetrafluoroborate (BMIm-BF4) efficiently generates BF3 from BF4–. This Lewis acid, strongly bound to the ionic liquids, can be efficiently used in classical BF3-catalyzed reactions. We demonstrated the BF3/BMIm-BF4 reactivity in four reactions, namely, a domino Friedel–Crafts/lactonization of phenols, the Povarov reaction, the Friedel–Crafts benzylation of anisole, and the multicomponent synthesis of tetrahydro-11H-benzo[a]xanthen-11-ones. In comparison with literature data using BF3-Et2O in organic solvents, in all the presented cases, analogous or improved results were obtained. Moreover, the noteworthy advantages of the developed method are the in situ generation of BF3 (no storing necessity) in the required amount, using only the electron as redox reagent, and the recycling of BMIm-BF4 for multiple subsequent runs.

Enhanced Friedel-Crafts benzylation activity of bimetallic WSn-KIT-6 catalysts

A series of W and Sn-containing KIT-6 mesoporous silicates (designated as WxSn5) with similar Sn (~5 wt%) and varying W (x = 3–23 wt%) loadings were prepared by a one-pot hydrothermal synthesis method. No detectable bulk WO3 species were observed for W loading up to 14 wt% with preferential dispersion of WOx species near SnO2 sites. The WxSn5 materials exhibited superior performance for Friedel-Crafts anisole benzylation with intrinsic rate constants for all WxSn5 catalysts being greater than those without Sn. Based on results from DR-UV–Vis, XRD, XPS, EXAFS techniques, we postulate that the WxSn5 materials contain both isolated [WO4]2-/SnO2 and isolated [WO4]2-/SiO2 as active species, with the former being more active. The relative populations of these two highly dispersed species dictate the overall catalyst activity. The intrinsic activities of the WxSn5 catalysts are found to scale linearly with total acidity but are mainly dictated by the Lewis acid sites.

Friedel–Crafts benzylation of toluene catalyzed by ZnCl2/SiO2 heterogeneous catalyst to para- and ortho-mono-benzylated toluene

A series of catalysts was prepared for the liquid-phase Friedel–Crafts benzylation of toluene with benzyl chloride (BC) by impregnating rice husk ash silica with ZnCl2 (3 wt%, 6 wt%, 9 wt%, and 12 wt%) via a wet impregnation method. The XRD analysis indicates that the catalysts were amorphous with ill-defined pore systems. The XPS analysis detected the coexistence of ZnO nanoparticles together with ZnCl2 on the catalyst surface, whereas the 29Si NMR analysis indicates the formation of Si–O–Zn bond. Quantitative conversion of benzyl chloride (100%) was achieved within 3 h at 353 K when a catalyst with 9 wt% ZnCl2 was used due to its narrow pore size and high surface area (635 m2 g−1). Para- and ortho-mono-benzylated toluene was obtained as the products. The reaction is proposed to take place via weak attraction between benzyl chloride and the Zn through its chlorine atom. The catalyst was recycled four times with minimum loss (8%) in activity. The benzylation of benzene, toluene, p-xylene, and anisole followed the classical mechanism of Friedel–Craft-type acid-catalyzed benzylation reaction. The BC conversion increased in the order of toluene = p-xylene > anisole > benzene. The catalyst was also screened to be active in the benzoylation of toluene with benzoyl chloride (BOC). The conversion of BOC was 45% with selectivity toward 2-methylbenzophenone (50%) and 3-methylbenzophenone (50%).

Single-step synthesis of novel chloroaluminate ionic liquid for green Friedel–Crafts alkylation reaction

Friedel–Crafts alkylation reactions constitute a very important class of reactions which are usually catalysed in the liquid phase using Lewis acids at the industrial scale. Diphenyl methane synthesised by Friedel–Crafts alkylation from benzene with benzyl chloride has been interesting in organic synthesis, perfumes and dyes. The new environmental legislation recommends a green and reusable catalyst system that is environmentally benign which leads to minimal pollution and waste generation. Chloroaluminate ionic liquids (ILs) have been used immensely as homogeneous catalyst in the organic synthetic processes. Though these ILs have multiple advantages, their synthesis process involves certain disadvantages like multiple step synthesis, viz. use of solvents and its removal after reaction, removal of precursors, solvent washing for removal of trace impurities and drying of salt/adduct. We have established a novel single-step synthesis method of chloroaluminates from tributylamine and aluminium chloride via amine–aluminium chloride adduction using suitable solvent or one of the reactants as reaction medium. The process improved the atom economy, reduced the use of volatile organic chemicals and drastically minimised the generation of wastes. Formation of chloroaluminate ILs was confirmed by FTIR, 27Al NMR and mass spectroscopy (ESI–MS), and other physicochemical properties were also determined. The chloroaluminate IL was used as catalyst for Friedel–Crafts benzylation of benzene. The performance of the ILs as catalyst showed higher catalytic activity and could be recycled twice for benzylation reaction. Reaction parameters were also optimised to achieve higher yields of diphenyl methane. Tributylamine can be easily recovered by hydrolysis of spent IL which would moderate the chemical oxygen demand in generated effluent.

Green, Mild, and Efficient Friedel-Crafts Benzylation of Scarcely Reactive Arenes and Heteroarenes under On-Water Conditions.

Metal-free Friedel-Crafts benzylation (FCB) of scarcely reactive arenes and heteroarenes was performed under on-water conditions by an environmentally sustainable procedure. The catalytic strategy exploits the hydrophobicity of the resorcinarene macrocycle 1 a. The proposed mechanism is based on the activation of benzyl chloride by H-bonding interactions with catalyst 1 a. In fact, under on-water conditions the hydrophobic amplification of the strength of the H-bonding interactions between the OH groups of the resorcinarene catalyst and the chlorine atom of benzyl chloride leads to polarization of the C-Cl bond, which consequently promotes electrophilic attack of the π nucleophile. Thus, many arenes and heteroarenes were efficiently benzylated under mild on-water conditions by using resorcinarene 1 a as catalyst. The FCB of benzene is industrially relevant for the synthesis of diphenylmethane, and hence the on-water procedure was extended to the gram-scale synthesis of diphenylmethane, starting from benzene and benzyl chloride in the presence of resorcinarene catalyst 1 a.

9-Borabicyclo[3.3.l]nonane-induced Friedel–Crafts benzylation of arenes with benzyl fluorides

Friedel-Crafts benzylation of arenes with benzyl fluorides using 9-borabicyclo[3.3.l]nonane (9-BBN) as a mediator has been developed. This provides a simple and cheap route to the activation of C-F bonds to synthesize 1,1-diarylmethanes in good to excellent yields (up to 98%) under mild conditions. Functional group tolerance and the mechanism are considered.

Spectroscopic Evidence for the Involvement of a Radical Intermediate in the Friedel-Crafts Benzylation Using Ion-Exchanged K10 Catalysts

For Friedel-Crafts alkylation of aromatic hydrocarbons an ionic reaction path is considered as classical reaction mechanism. The alkylation with benzyl chloride in the presence of ion-exchanged K10 montmorillonite catalysts containing multivalent, reducible cations had an outstanding activity, therefore a radical initial step as a supplement to the ionic mechanism was proposed earlier. We made ESR investigations to clarify the existence and the nature of the suggested radical species. The ESR experiments verified that the reaction involves a radical step.

Bisulfate Salt-Catalyzed Friedel-Crafts Benzylation of Arenes with Benzylic Alcohols.

We report here a method of direct Friedel-Crafts benzylation of arenes with benzylic alcohols using cheap and readily available bisulfate salt as the catalyst in hexafluoroisopropanol. The catalytic system is powerful with a quite diverse group of functionalized arenes and benzylic alcohols. These mild conditions provide a straightforward synthesis of a variety of unsymmetrical diarylmethanes in high yield with good to high regioselectivity. An SN1 mechanism involving activation of the hydroxy group through a hydrogen bond is proposed.

Stereoarrayed 2,3-Disubstituted 1-Indanols via Ruthenium(II)-Catalyzed Dynamic Kinetic Resolution-Asymmetric Transfer Hydrogenation.

Activated racemic 2,3-disubstituted 1-indanones 1 possessing two stereolabile centers were stereoselectively reduced to the corresponding chiral 2,3-disubstituted-1-indanols 2 by ruthenium(II)-catalyzed dynamic kinetic resolution-asymmetric transfer hydrogenation. In particular, this route offers a practical access to a new class of conformationally rigid enantiopure 1,4-diols 2k-m having four contiguous chiral centers. Transformation of ent-2k into a Pallidol analogue via a highly diastereo- and regioselective Friedel-Crafts benzylation of o-chloroanisole is presented.

Mild Friedel-Crafts Reactions inside a Hexameric Resorcinarene Capsule: C-Cl Bond Activation through Hydrogen Bonding to Bridging Water Molecules.

A novel catalytic feature of a hexameric resorcinarene capsule is highlighted. The self-assembled cage was exploited to promote the Friedel-Crafts benzylation of several arenes and heteroarenes with benzyl chloride under mild conditions. Calculations showed that there are catalytically relevant hydrogen-bonding interactions between the bridging water molecules of the capsule and benzyl chloride, which is fundamental for the activation of the C-Cl bond. The capsule controls the reaction outcome. Inside the inner cavity of the capsule, N-methylpyrrole is preferentially benzylated in the unusual β-position while mesitylene reacts faster than 1,3-dimethoxybenzene despite the greater π-nucleophilicity of the latter compound.

Mild Friedel–Crafts Reactions inside a Hexameric Resorcinarene Capsule: C−Cl Bond Activation through Hydrogen Bonding to Bridging Water Molecules

AbstractA novel catalytic feature of a hexameric resorcinarene capsule is highlighted. The self‐assembled cage was exploited to promote the Friedel–Crafts benzylation of several arenes and heteroarenes with benzyl chloride under mild conditions. Calculations showed that there are catalytically relevant hydrogen‐bonding interactions between the bridging water molecules of the capsule and benzyl chloride, which is fundamental for the activation of the C−Cl bond. The capsule controls the reaction outcome. Inside the inner cavity of the capsule, N‐methylpyrrole is preferentially benzylated in the unusual β‐position while mesitylene reacts faster than 1,3‐dimethoxybenzene despite the greater π‐nucleophilicity of the latter compound.

Synthesis and Catalytic Properties of New Sustainable Aluminosilicate Heterogeneous Catalysts Derived from Fly Ash

The field of heterogeneous catalysis has recently become increasingly interested in the utilization of industrial wastes as inexpensive precursors for active catalysts. Here we report a facile synthesis of fly-ash-based geopolymers as new highly reactive sustainable porous aluminosilicate heterogeneous catalysts for acidic and/or redox applications. The catalytic properties of these catalysts for Friedel–Crafts benzylation reactions of benzene and other substituted aromatics were thoroughly investigated. Fly ashes were collected from various sources were investigated, and the impact of the variation of their chemical and physical properties on the resulting catalysts was studied. The catalysts demonstrated excellent catalytic reactivity superior to other commonly used aluminosilicate catalysts such as M-zeolite, mesoporous molecular sieves, mixed oxides, and ionic liquids. This study not only highlights the feasibility of synthesizing active heterogeneous catalysts with predictable features from several different fly ash precursors but also suggests a new and very useful means for effectively utilizing fly ash.

Friedel–Crafts Benzylation of Deactivated Benzylic Alcohols

Key words Friedel-Crafts reaction - strongly deactivated benzylic alcohols - hexafluoro-isopropanol

Synthesis of hierarchical ZSM-5 zeolites by solid-state crystallization and their catalytic properties

Hierarchically porous structure is important to promote mass transport and active site utilization of zeolites for many petrochemical reactions involving bulky molecules. Their conventional hydrothermal synthesis with meso-template materials is often complicated and expensive, and produces a large amount of aqueous pollute. We demonstrate here successful synthesis of mesoporous zeolites of MFI structure by solid-state crystallization without meso-template. Aluminosilicate nanogels are produced with only precursors and the dried nanoparticles are then transformed into nanocrystals in solid state using only their intrinsic water storage. After orientating with each other at edges, these nanocrystals join into monolithic zeolites with connecting inter-lattice mesopores. The produced hierarchical ZSM-5 zeolites exhibit superior stability and excellent catalytic performance in reactions such as Friedel-Crafts benzylation, lignin ethanolysis, and naphthalene hydrogenation. Compared with conventional synthesis routes, this new solid crystallization approach simplifies zeolite production, lowers the cost, and avoids toxic liquid waste, which may greatly benefit many energy applications.