Friedel-Crafts Benzylation Research Articles

Organocatalytic Friedel–Crafts Benzylation of Heteroaromatic and Aromatic Compounds via an SN1 Pathway

The Friedel–Crafts-type benzylation of various π-excessive heteroaromatic and aromatic compounds with trityl or benzhydryl halides was efficiently promoted by a thiourea catalyst. This is a novel example of thiourea catalysis of aromatic alkylation by way of an S_N1 pathway.

Iron‐Catalyzed Friedel–Crafts Benzylation with Benzyl TMS Ethers at Room Temperature

Friedel-Crafts benzylations between unactivated arenes and benzyl alcohol derivatives are clean and straightforward processes to construct biologically useful di- and tri-arylmethanes. We have established an efficient iron-catalyzed Friedel-Crafts benzylation method at room temperature that uses benzyl TMS ethers as substrates, which are poorly reactive under common nucleophilic substitution conditions. The reaction seems to progress through iron-catalyzed self-condensation of the benzyl TMS ether to the corresponding dibenzylic ether. The use of excess arene relative to benzyl TMS ether produced mono-benzylated arene (di- and tri-arylmethane products), whereas the use of excess benzyl TMS ether versus arene provided bis-benzylated arene (polyarylated products) in high yields and regioselectivities. In previous methods, the latter double Friedel-Crafts benzylations hardly proceed.

TUD‐1‐Encapsulated HY Zeolite: A New Hierarchical Microporous/Mesoporous Composite with Extraordinary Performance in Benzylation Reactions

AbstractA new composite material consisting of amorphous TUD‐1 encapsulating crystalline zeolite Y was synthesized. Samples with different HY zeolite loadings (10, 20, 40, and 60 wt %) were prepared, and the resulting solid products were characterized with elemental analysis, XRD, N2 physisorption, 27Al MAS NMR, IR, pyridine adsorption in combination with FTIR, temperature‐programmed desorption of ammonia, HRSEM, and HRTEM. Characterization data confirm the presence of a thin layer of the mesoporous TUD‐1 phase with a thickness of 30–100 nm surrounding the zeolite crystals. The catalytic performance of the composite was studied in the Friedel–Crafts benzylation of benzene with benzyl alcohol at 353 K. The catalytic activity of the HY/TUD‐1 composite was higher than that of HY zeolite, whereas the composite showed a much slower rate of deactivation. The improved performance of the composite is related to beneficial changes in the acidity of the HY crystal through chemical interactions with TUD‐1.

Environmentally benign Friedel-Crafts benzylation over nano-TiO2/SO42-

During the past decade, much attention has been paid to the replacement of homogeneous catalysts by solid acid catalysts. Friedel-Crafts benzylation of toluene with benzyl chloride (BC) in liquid phase was carried out over highly active, nano-crystalline sulfated titania systems. These catalysts were prepared using the sol gel method. Modification was done by loading 3% of transition metal oxides over sulfated titania. Reaction parameters such as catalyst mass, molar ratio, temperature, and time have been studied. More than 80% conversion of benzyl chloride and 100% selectivity are shown by all the catalysts under optimum conditions. Catalytic activity is correlated with Lewis acidity obtained from perylene adsorption studies. The reaction appears to proceed by an electrophile, which involves the reaction of BC with the acidic titania catalyst. The catalyst was regenerated and reused up to four reaction cycles with equal efficiency as in the first run. The prepared systems are environmentally friendly and are easy to handle.

ChemInform Abstract: Synthesis of Diarylmethanes via a Friedel—Crafts Benzylation Using Arenes and Benzyl Alcohols in the Presence of Triphenylphosphine Ditriflate.

AbstractA mixture of triphenylphosphine oxide and triflic anhydride generates the title reagent, which is demonstrated to be an efficient promotor for the procedure.

Cage type mesoporous ferrosilicate catalysts with 3D structure for benzylation of aromatics

The Friedel–Crafts benzylation of benzene and various substituted benzenes employing benzyl chloride as an alkylating agent over a series of three-dimensional cage type mesoporous ferrosilicate (FeKIT-5) catalysts was investigated. These FeKIT-5 materials with different nSi/nFe and ratios were synthesized hydrothermally using polymeric pluronic F127 surfactant in a highly acidic medium and characterized using various physicochemical techniques. The characterization results confirmed that the prepared materials exhibit a well-ordered 3D porous structure with cage type pores and excellent textural characteristics such as high surface areas (935–1130m2g−1) and large pore volumes (0.57–0.76cm3g−1). The unit cell constant of the samples increased with increasing the iron content of the samples, confirming the incorporation of iron in the silica framework structure of KIT-5. UV–vis results revealed that most of the Fe atoms in FeKIT-5 are in tetrahedral coordination and occupy framework position. It was found that the iron incorporated mesoporous silica materials exhibited a high conversion and selectivity for benzylation under liquid phase condition. The influence of various parameters such as temperature, time on stream, nBenzene/nBC ratio and the nSi/nFe ratio of the catalyst affecting the activity of the catalyst on the benzylation of benzene using benzyl chloride was investigated. The study was also extended to the benzylation of toluene, p-xylene, mesitylene and anisole in order to check the catalytic performance of the catalyst over different electron donating substituents. The reaction kinetics of benzene benzylation over FeKIT-5 catalyst was also investigated. The catalytic activity of FeKIT-5 catalyst was also compared with AlSBA-15, FeHMS and pure mesoporous silica KIT-5. Among the catalysts studied, FeKIT-5(7) showed the highest activity with a complete conversion of benzyl chloride and 100% selectivity to diphenylmethane in 35min under the optimized reaction condition.

Synthesis of diarylmethanes via a Friedel–Crafts benzylation using arenes and benzyl alcohols in the presence of triphenylphosphine ditriflate

Triphenylphosphine ditriflate (TPPD) was found to be an efficient promoter for the Friedel–Crafts benzylation of arenes with benzyl alcohols in CH2Cl2 at room temperature. The good yields, the 1:1 molar ratio of arene and benzyl alcohol, the benzylation of chlorobenzene as a nonactivated aromatic compound at room temperature, and no by-product formation are the main advantages of this procedure.

Liquid Phase Benzylation of Toluene over Modified Titania Catalysts

Titania, sulfated titania and a series of iron loaded sulfated titania catalyst with different iron loadings (39 %) are prepared by sol-gel method and calcined at 500°C. Anatase is found to be the active phase with crystallite size in the nano range. All the prepared catalysts are found to be stable up to 700°C. Acidity is measured using spectrophotometric monitoring of adsorption of perylene, thermogravimetric desorption of 2,6-dimethylpyridine and temperature programmed desorption of ammonia. The activities of the catalysts were tested for liquid phase Friedel-Crafts benzylation of toluene with benzyl chloride. It has been concluded that Lewis acid sites are responsible for the reaction.

Friedel-Crafts Alkylation of o-xylene over V2O5 / ZrO2 Catalysts

The present study has undertaken the Friedel-Crafts benzylation of aromatics over the V2O5/ZrO2 catalysts systems. Catalysts with different V2O5 content (0-15wt %) was prepared by wet impregnation method and characterized by XRD, BET surface area, FTIR and 5’V NMR techniques. The surface acidic properties were determined by temperature programmed desorption of NH3, cumene cracking and perylene adsorption. Under the optimized reaction conditions, these catalysts are found to be very effective and considerably more selective than the conventional homogeneous Lewis acid catalysts. The investigation of vanadia systems-catalyzed benzylation of o-xylene with benzyl chloride revealed that the catalytic activity and product selectivity are sensitive to the precise reaction parameters and can be related to the Lewis acidity of the systems. The reaction is found to be very clean and produces the desired monoalkylated product with high yield.

ChemInform Abstract: Friedel—Crafts Benzylation of Activated and Deactivated Arenes.

AbstractThe hydroxamate leaving group is described as a novel efficient option to achieve simple transformations.

On the rational design of microwave-actuated organic reactions

Microwave-actuated organic reactions are defined herein as chemical reaction systems for which microwave irradiation provides a clear benefit over conventional heating to the same temperature. This study is focused on a rationally designed, microwave-actuated reaction (thermal Friedel–Crafts benzylation), in which a microwave-absorbing ionic solute reacts in a non-polar and largely microwave-transparent solvent. Steady-state microwave irradiation (ssMWi) induces observed levels of reactivity from the solute that cannot be duplicated by conventional heating of the homogeneous solution to similar temperatures. This observation is qualitatively consistent with the Arrhenius [k = Ae(−Ea/RT)] relationship between rate and molecular collisions (k ∝ A at constant T). A new paradigm for designing microwave-actuated organic reactions for microwave-assisted organic synthesis emerges from this study.

Friedel–Crafts Benzylation of Activated and Deactivated Arenes

Friedel–Crafts Benzylation of Activated and Deactivated Arenes

Friedel-Crafts Benzylation of Activated and Deactivated Arenes

Eine experimentell einfache, neuartige Friedel-Crafts-Benzylierung verläuft bei moderaten Temperaturen und hat ein verbreitertes Substratspektrum für die Bildung präparativ nützlicher Diarylmethane (siehe Schema). Bei Komplexierung mit BF3⋅OEt2 wirken Hydroxamate als reversible Abgangsgruppen, die hoch reaktive Carbokationen stabilisieren. Selbst desaktivierte Arene und elektronenarme Benzylhydroxamate reagieren glatt unter diesen Bedingungen. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Synthesis of Isoreticular Zinc(II)‐Phosphonocarboxylate Frameworks and Their Application in the Friedel–Crafts Benzylation Reaction

Three isoreticular zinc(II)-phosphonocarboxylate frameworks, namely {[Zn(3)(pbdc)(2)]·2H(3)O}(n) (ZnPC-2), {[Zn(3)(pbdc)(2)]·Hpd·H(3)O·4H(2)O}(n) (Hpd@ZnPC-2) and {[Co(1.5)Zn(1.5)(pbdc)(2)]·2H(3)O}(n) (CoZnPC-2) (H(4)pbdc=5-phosphonobenzene-1,3-dicarboxylic acid, pd=pyrrolidine), were solvothermally synthesized. ZnPC-2 has a 3D structure based on trinuclear Zn(II) clusters (Zn(3)-SBU) showing 3D interconnected channels. Hpd@ZnPC-2 contains an isoreticular framework of ZnPC-2 with small channels blocked by Hpd molecules. In CoZnPC-2, Zn(II) ions in ZnPC-2 are partially substituted by Co(II) ions. The Friedel-Crafts benzylation reactions were carried out over these isoreticular porous materials. The catalytic results reveal that ZnPC-2 is an excellent heterogeneous Lewis acid catalyst with a high selectivity (>90%) towards less bulky para-oriented products. The catalytic reaction has been proved to occur inside the pore of ZnPC-2, and the immobilized Zn(3)-SBUs are the active sites.

Synergistic catalysis of isolated Fe3+ and Fe2O3 on FeO /HZSM-5 catalysts for Friedel–Crafts benzylation of benzene

Abstract FeO x /HZSM-5 catalyst with 8 wt.% Fe-loading (8-FeZ) exhibited significantly higher reactivity in the benzylation of benzene with benzyl chloride than FeO x /HZSM-5 catalyst with 2.5 wt.% Fe-loading (2.5-FeZ) because the synergistic catalysis between isolated Fe 3+ and superfine Fe 2 O 3 occurred on 8-FeZ in the reaction.

Mesoporous MFI zeolite material from silica–alumina/epoxy-resin composite material and its catalytic activity

Although the versatilities of zeolitic materials are widely known to chemists and materials scientists, their exclusive microporosity sometimes causes various defections especially in the diffusion of reactant and product molecules in catalytic reactions. Silica–alumina/epoxy-resin composite materials were obtained from TMOS (tetramethoxysilane), aluminum acetylacetonate and bisphenol A diglycidyl ether with a cyclic acid anhydride as both condensation and curing reagents. Hydrothermal treatment of the composite materials with TPAOH (tetra- n-propylammonium hydroxide) crystallized the amorphous silica–alumina part to the MFI zeolite crystalline phase and induced the phase separation of epoxy-resin domain from the zeolite phase at the same time, forming both zeolite microporosity and mesoporosity in the solid catalyst after calcination. The mesoporous MFI zeolite thus prepared had a good catalytic activity in liquid phase Friedel–Crafts benzylation reaction. The mesoporous channels fabricated in the MFI zeolite material enhanced the diffusion of reactants and products in the solid matrix, and thus it showed a better catalytic activity in the benzylation of toluene together with the high selectivity of the mono-substituted para-isomer. The new methodology reported in this paper to produce the mesoporous zeolite materials will promote the chemistry and the applications of zeolite catalysts and related materials.

DFT calculations on the Friedel-Crafts benzylation of 1,4-dimethoxybenzene using ZnCl2 impregnated montmorillonite K10 — inversion of relative selectivities and reactivities of aryl halides

AbstractZinc was bound on montmorillonite K10 by cation exchange to obtain a catalyst named clayzic. In the Friedel-Crafts benzylation of 1,4-dimethoxybenzene, this catalyst was used for the synthesis of substituted diphenylmethanes using 4-chlorobenzyl chloride and 4-bromobenzyl bromide. During the reaction, sub-products from a second benzylation reaction process were observed. For a better understanding of their formation, reactions were carried out at different times to obtain data on the progress of benzylation and the relative ratio of each product was calculated using two different analytical methods. It was shown that the selectivity and reactivity of both aryl halides were reversed under these experimental conditions contrary to those obtained using the more conventional catalyst, zinc dichloride. These results were explained by geometrical and electronic considerations. It was found that the formation of transition states and Wheland intermediates from aryl bromide and chloride in the presence of clayzic can be explained in terms of preferential absorption. Moreover, the high percentage of 4-chlorobenzyl chloride conversion was attributed to its covalent radius, which is smaller than that of Br. At the same time it was shown that the presence of a Brönsted acid, due to the liberation of HCl during the benzylation, is responsible for the poisoning of the clayzic catalyst. Moreover, poisoning effect of the bromine anion could not be excluded.

ChemInform Abstract: Synthesis and Structures of 8‐Benzyl[2.2]metaparacyclophanes.

AbstractThe title compounds (III) are prepared via a Friedel—Crafts benzylation.

New mesoporous perovskite ZnTiO 3 and its excellent catalytic activity in liquid phase organic transformations

A new mesoporous perovskite ZnTiO 3 material has been synthesized by the evaporation-induced self-assembly (EISA) method using non-ionic surfactant Pluronic P123 as template. After calcination of the dried gel of equimolar concentrations of Zn(II) and Ti(IV) at 673 K, a new perovskite mesophase of ZnTiO 3 (MZT-11) formed, having highly crystalline cubic ZnTiO 3 pore wall. Interestingly, in the absence of P123 but otherwise identical synthesis conditions showed no cubic structure and a mixed phase consisting of ZnO and TiO 2 phases (ZT-11). The BET surface area of the mesoporous perovskite materials (MZT-11) was 136 m 2 g −1 and the average dimension of the pores was ca. 5.1 nm. The material was thoroughly characterized by different analytical methods including small and wide angle powder XRD, FE SEM, TEM, FT IR, UV–visible, photoluminescence (PL) and X-ray fluorescence (XRF) analysis. This new mesoporous perovskite material showed excellent catalytic activity in the Friedel-Crafts (FC) benzylation of aromatics and in the Fischer esterification of different long chain carboxylic acids in the presence of methanol under solvent-free conditions.

Synthesis of a Prostaglandin EP4 Receptor Antagonist

EP4 Receptor antagonists are candidates for the treatment of inflammatory disorders associated with arachidonic acid metabolism. Noteworthy steps in the synthesis shown were (1) a large-scale Kulinkovich cyclopropanation (A → B), (2) an FeCl3-catalyzed Friedel-Crafts benzylation of 2,5-dimethylthiophene (E) using 4-trifluoromethylbenzyl alcohol (D) as the electrophile and (3) an FeCl3-catalyzed Friedel-Crafts acylation of thiophene F using isocyanate C as the electrophile.