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Imidazo[1,2-a]pyridines are privileged aza-fused heterocyclic scaffolds possessing wide range of applications in medicinal chemistry, organometallics and material science. Imidazo[1,2-a]pyridines functionalized with aroyl group are perceived for their therapeutic applications. However, inaccessibility of this aroylated imidazo[1,2-a]pyridine by Friedel-Crafts reaction had left chemists with an alternate of three-steps long and tiresome protocol as the only source. Hence, in this review we have discussed all the rigorous efforts made in last decade for regioselective and straightforward synthesis of 3-aroyl and 2-aroyl imidazo[1,2-a]pyridines from readily accessible precursors in step-economic pathway. Most importantly, it draws our attention towards the challenge of regioselective aroylation at C-2 position of imidazo[1,2-a]pyridines, as only three methods are reported till date. [ABSTRACT FROM AUTHOR]

Cellulose sulfate was synthesized by esterification of α-cellulose with concentrated sulfuric acid at −10°C in ethanol. Cellulose is mainly sulfated on 3-, 6- and 3, 6-positions of the cellulose. It acts as a heterogeneous catalyst for the ring-opening of epoxides with alcohols or anilines and the Friedel-Crafts reaction between N-benzylindole and crotonaldehyde at room temperature. Methanolysis of cyclic epoxides, styrene oxide, terminal aliphatic epoxides, and glycidyl ethers were carried out using the catalyst (0.4–6.8 mg/mmol of epoxide) and afforded the corresponding products in 53–97% isolated yields after 10 min–24 h. Cellulose sulfate was successfully recycled and reused up to 3 catalytic cycles for the ring-opening of styrene oxide with methanol. [ABSTRACT FROM AUTHOR]

An efficient organocatalytic route has been developed to synthesize novel substituted thioxanthenes (2a-2v) starting from diaryl thioether alcohols (1a-1v) using the intramolecular Friedel-Crafts reaction. The starting materials were obtained in two stages via a coupling reaction followed by the Grignard reaction. In this study, we tried for the first time to use some organic Brønsted acids as organocatalysts (3a-3h) in the intramolecular Friedel-Crafts cyclization reaction of thioether alcohols. The synthesis of original substituted thioxanthenes was achieved within 15 minutes by using N-triflylphosphoramide (3h) with quantitative yields in THF at room temperature. [ABSTRACT FROM AUTHOR]

Biologically active phenyl[3-(3,7-dimethyl-2,6-octadienyl)-2,4,6-trihydroxyphenyl]methanone (2) and phenyl[2,4,6-trihydroxy-3-(3-methyl-2-butenyl)phenyl]methanone (3) were synthesized by an efficient and convenient synthetic sequence. The reaction steps of this synthesis included methylation, Friedel-Crafts acylation, demethylation and geranylation steps. [ABSTRACT FROM PUBLISHER]

A facile, SbCl3-catalyzed, one-pot, tandem Friedel–Crafts/lactonization reaction of phenols and mandelic acids has been developed under solvent-free conditions to afford 3-aryl benzofuran-2(3H)-ones in good to high yields (52–90%). Additionally, the utility of 3-aryl benzofuran-2(3H)-ones is demonstrated by using them as precursors in the synthesis of a new class of spirocyclic benzofuran-2-ones using classical synthetic methodologies. [ABSTRACT FROM AUTHOR]

A discovery that the inexpensive Br2can serve as a potent Lewis acid catalyst for bis(2-hydroxy-1-naphthyl)methanes synthesis is presented. Under the catalysis of Br2at room temperature, naphthols reacted smoothly with various aldehydes with high efficiency and broad substrate scope. This reaction used to require highly acidic conditions and/or high temperature and/or pressure, and sometimes featured poor yields. Moreover, theoretical calculations suggested that Br2is a potent Lewis acid to activate the carbonyl group, yet it was not the primary cause for the remarkable activity of Br2in the current communication. [ABSTRACT FROM AUTHOR]

Friedel–Crafts reaction of indoles to aromaticα-ketimino esters was found to be catalyzed by camphorsulfonic acid with good yields (up to 98%) under ambient temperature. This process provides an efficient method for the synthesis of unnatural amino acid derivatives that bear quaternary carbon centers. [ABSTRACT FROM PUBLISHER]

A simple and efficient process for the large-scale preparation of agomelatine (1), an antidepressant drug is, described. Agomelatine was prepared in a linear manner starting from readily available, inexpensive 2-naphthol. Key steps in the synthesis are Friedel–Crafts acylation of 2-naphthyl acetate with chloroacetyl chloride, reduction of keto intermediate, and nucleophilic displacement of chloro intermediate with sodium diformylamide. A systemic approach was described to streamline the process into a robust scalable process by controlling the impurities. [ABSTRACT FROM PUBLISHER]

A simple method to synthesize N-heteropolycyclic quinazolinones was developed including Knoevenagel condensation of quinazolines and aldehydes and Friedel–Craft alkylation as key steps. Knoevenagel reaction of 2-methyl-3-phenylquinazolin-4(3H)-one proceeded smoothly under a basic condition and subsequent Friedel–Craft alkylation with Brønsted acid gave the N-heteropolycyclic quinazolinones in good yields. Furthermore, these new polycyclic compounds were converted into organic molecules having a longπ-conjugation system by treatment of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) to utilize them as organic dyes. [ABSTRACT FROM AUTHOR]

A greener approach for the synthesis of 3-arylmethyl/diarylmethyl indoles has been achieved via a PMA-SiO2-mediated three-component reaction (the aza-Friedel–Crafts reaction) involving indoles, aldehydes, andN,N-disubstituted anilines in PEG-400. A variety of indole derivatives were prepared by using this operationally simple and straightforward methodology in acceptable yields. [ABSTRACT FROM AUTHOR]

An efficient and ecofriendly allylation of O-H, N-H, and C-H groups has been achieved successfully with the reaction of allyl bromide by using sodium perborate as a new catalyst in aqueous media. The advantage of this method is operationally simple, short reaction time, good yield, and simple workup conditions over the previously reported conventional methods such as amination, oxyalkylation reactions of allyl bromide, and Friedel–Crafts allylation chemistry. [ABSTRACT FROM AUTHOR]

The triarylmethane antituberculosis drug CDRI-830 is synthesized. The triarylmethane derivative4is prepared from ether6by a rearrangement process. The total synthesis of the drug CDRI-830 is achieved in a good overall yield of 35% from a simple thiophene derivative8. [ABSTRACT FROM PUBLISHER]

Mild and high-yielding synthesis is described for raloxifene via piperdine nucleophilic substitution of a new raloxifene intermediate 3-aroyl-2-aryl-substituted benzo[b]thiophenes, which is obtained by acylation of para-substituted benzoyl chlorides and 2-arylbenzo[b]thiophenes. The key step is solvent free and offers valuable advantages, such as low cost, and is suitable for industrial production. [ABSTRACT FROM PUBLISHER]

The catalytic activity of metal triflates was investigated in Friedel–Crafts benzoylation under microwave irradiation. Friedel–Crafts benzoylation with benzoyl chloride of a variety of arenes containing electron-rich and electron-poor rings using bismuth triflate under microwave irradiation is described. This method allows the preparation of aryl ketones under solventless conditions in good to excellent yields and short reaction time. Bismuth triflate was easily recovered and reused five times without significant loss of the catalytic activity. [ABSTRACT FROM PUBLISHER]

1,2-Indandione reacts efficiently with arenes to give 2,2-diaryl-1-indanones by the hydroxyalkylation reaction. The Brønsted superacid CF3SO3H (triflic acid) is an effective catalyst for these condensation reactions. The requisite 1,2-indandiones were prepared from the 1-indanones. [ABSTRACT FROM AUTHOR]

Application of Fe3O4nanoparticles (NPs) as a robust, very efficient, and magnetically recoverable catalyst was investigated in Friedel–Crafts acylation (FCA) of ferrocene and aromatic compounds. This reaction was performed with acid chlorides in solvent-free conditions at room temperature. The catalyst was easily separated by an external magnetic field from the reaction mixture. The separated catalyst was recycled for several consecutive runs without appreciable loss of its catalytic activity. Supplemental materials are available for this article. Go to the publisher's online edition ofSynthetic Communications® to view the free supplemental file. [ABSTRACT FROM PUBLISHER]

Friedel–Crafts acetylation at the 4-position of 3-phenylsydnone (1) was achieved via thermal heating overnight in moderate to good yields by employing various metal triflate catalysts (5–20 mol%), lithium perchlorate (0–20 mol%), and acetic anhydride (4 equivalents) using either acetonitrile or acetic anhydride, in excess, as solvent. Six commercially available, homogeneous metal triflate catalysts were investigated, and optimal conditions were determined. The best yields overall were achieved with indium triflate. Supplemental materials are available for this article. Go to the publisher's online edition ofSynthetic Communications®to view the free supplemental file. [ABSTRACT FROM PUBLISHER]

An alternate approach to 2-(substituted phenyl)-3,3a-dihydro-8H-pyrazolo[5,l-a] isoindol-8-ones via chalcone-based N-formyl-pyrazolines is described. N-Formyl-pyrazolines were prepared in excellent yield (81–96%) by the reaction of chalcones with hydrazine hydrate in the presence of formic acid, which undergoes intramolecular Friedel–Crafts acylation in the presence of trifluoroacetic acid (TFA) as a catalyst to afford functionalized 2-(substituted phenyl)-3,3a-dihydro-8H-pyrazolo[5,1-a]isoindol-8-ones in good to excellent yield (74–94%) at reflux in acetonitrile. Our synthetic route avoids expensive reagents and significantly improves yields. [ABSTRACT FROM PUBLISHER]

Friedel–Crafts acylations of various 3-arylsydnones at the C4 position have been achieved in good yields using 4 equivalents of an alkyl anhydride and 25 mol% each of bismuth triflate and lithium perchlorate in anhydrous acetonitrile at 95 °C. Acylations appear to be faster with arylsydnones bearing electron-donating moieties and sterically unencumbered anhydrides. [ABSTRACT FROM AUTHOR]

We report herein the synthesis of zinc oxide (ZnO) nanoparticles incorporating a polyaniline (PANI) matrix in aqueous medium and its catalytic performance toward Friedel–Crafts acylation reactions. The acylation reactions demonstrate that polyaniline/nano-ZnO composites are very active catalysts and are able to activate the reactant at ambient temperature. The obtained nanocatalyst was characterized by Fourier transform–infrared, scanning electron microscopy, transmission electron microscopy, Brunauer–Emmett–Teller, X-ray diffraction, and particle-size analysis techniques. The catalyst was reusable for five cycles without appreciable loss in activity. [ABSTRACT FROM AUTHOR]

The Friedel–Crafts acylation of ferrocene catalyzed by a new type of catalyst of rare-earth solid superacid sulfated zirconia SZR3+ was developed. Comparison of catalytic activities between different solid acid catalysts is presented. The catalyst, sulfated zirconia ytterbium SZNYb3+, showed interesting catalytic properties for preparation of acylferrocenes. Furthermore, the catalyst could be regenerated and reused in succession after simple filtration. [ABSTRACT FROM AUTHOR]

A number of 2-aminobenzophenones have been synthesized by acylation of para-chloroaniline with different 2-, 3-, 4-chloro- or fluorobenzoyl chloride in solid state via the Friedel-Crafts reaction. Synthesized compounds were characterized by 1H and 13C NMR, Fourier transform-infrared, ultraviolet-visible spectroscopy, mass spectrometry, and elemental analysis. Evaluation of biological activity in vitro showed that the selected compounds 9, 10, and 13 have potential anticancer activity. The presence of one chlorine atom in the second aromatic ring of the benzophenone molecule makes it more active.[image omitted] [ABSTRACT FROM AUTHOR]

The TiCl4-catalyzed Friedel-Crafts reaction with trifluoroacetaldehyde ethyl hemiacetal is shown to serve as an efficient route for the synthesis of CF3-substitituted compounds of biological and synthetic importance, producing 2,2,2-trifluoroethyl phenols in good yields under mild conditions. [image omitted] [ABSTRACT FROM AUTHOR]

[image omitted] Fexofenadine is a selective H1-histamine receptor antagonist, which is an attractive alternative treatment for allergy symptoms. An efficient and environmentally friendly synthetic approach for the preparation of fexofenadine was developed from commercially available cumene. The method involves the Friedel-Craft's reaction, substitution, reduction, bromination, and the Grignard reaction. [ABSTRACT FROM AUTHOR]

[image omitted] Friedel-Crafts acylation of aromatic ethers, anisole, 2-methoxynaphthalene, and dimethoxybenzenes with different acid anhydrides is carried out in the presence of an inexpensive and nonhazardous solid acid, Amberlyst 15. The catalyst is reusable, thus making the process environmentally friendly. [ABSTRACT FROM AUTHOR]

An efficient method has been developed for the synthesis of indole 3-derivatives by the Friedel-Crafts alkylation of indole with nitro olefins in presence of boric acid in aqueous medium. [ABSTRACT FROM AUTHOR]

The one-pot reaction of succinic anhydride with 1,2-dimethoxybenzene furnished two structurally complicated polymethoxyarylnaphthalene lignans, polymethoxyarylnaphthol 1 as the minor product and polymethoxynaphtho[1,2-b]oxacycloheptatrienone 2 as the major product, in the presence of a small amount of polyphosphoric acid (PPA) as catalyst at 140°C and yielded 2 as a single product in good yield when a large amount of PPA as solvent was employed at 60-80°C. The novel structures of 1 and 2 were elucidated from 1H NMR, 13C NMR, infrared (IR), and Electrospray ionization-mass spectrometry (ESI-MS) and further confirmed by x-ray diffractions. The possible mechanisms for the formation of 1 and 2 were also proposed. [ABSTRACT FROM AUTHOR]

An efficient and chemoselective method for the Friedel-Crafts acylation of aromatic compounds using P2O5/Al2O3 and carboxylic acids. Both aromatic and aliphatic carboxylic acids reacted easily to afford the corresponding aromatic ketones in good yields. [ABSTRACT FROM AUTHOR]

This section presents graphical abstracts of articles related to chemistry including "Solvent-Free Friedel-Crafts Cyclization With Trichloroacetic Anhydride," by Ben Andrews et al, "Facile Method for Thiocyanation of Activated Arenes Using Ioidic Acid in Combination With Ammonium Thiocyanate," by Ulhas S. Mahajan and Krishnacharya G. Akamanchi, and "Simplified Ketimine Preparation," by Neeranat Thienthong et al.

Friedel-Crafts cyclization products were obtained using 1.1 equivalents of environmentally benign trichloroacetic anhydride as sole reagent and solvent. The resulting ketones included benzothiepins, benzothiopyrans, benzoxepins, dibenzothiepins, dibenzoxepins, and tetralones. [ABSTRACT FROM AUTHOR]

Lewis acid-mediated arylation of N-protected 2/3-bromomethylindoles with different types of arenes is reported. [ABSTRACT FROM AUTHOR]

1,3-Dimesityl-propane-1,3-dione was synthesized in high yield, via a stable intermediate (its aluminum complex) from malonyl dichloride and mesitylene by Friedel-Crafts reaction using anhydrous aluminum chloride as catalyst. The intermediate aluminum complex was isolated and characterized by X-ray diffraction analysis, which decomposed upon reflux in concentrate hydrochloric acid to give the title compound. [ABSTRACT FROM AUTHOR]

A simple and novel bimetallic catalyst, an iron and magnesium complex (Fe-Mg-hexamethylphosphoramide (HMPA)), with dual activation was found to be an effective and promising catalyst for the Michael-type Friedel-Crafts reactions of indoles with chalcones. This novel catalytic system has the advantages of highly efficient, mild reaction conditions and exhibits high reactivity and selectivity, which make it a useful and attractive process for the synthesis of indole derivatives. [ABSTRACT FROM AUTHOR]

An intramolecular cyclization of 17β-acetoxy-3-methoxy-9,11-seco-1,3,5(10)-estratriene-11-oic acid under different Friedel-Crafts reaction conditions is described. [ABSTRACT FROM AUTHOR]

Zn(OTf)2 · 6H2O was used to promote Friedel-Crafts acylation of aromatics. The work describes the high activity and efficiency of Zn(OTf)2 · 6H2O in acylation of aromatics, and the catalyst has surpassed most metal triflates in dispensing when dried at high temperature under vacuum before use. [ABSTRACT FROM AUTHOR]

A series of aryl ferrocenyl ketones were prepared from iodoferrocene, phenylboronic acids, and CO via palladium-catalyzed carbonylation coupling in a short time. The procedure was efficient and convenient and avoided formation of diacylated derivatives compared with currently available Friedel-Crafts acylation methodologies. [ABSTRACT FROM AUTHOR]

An efficient and simple synthesis of substituted 3-phenyl-7-methoxybenzopyrans as pseudo-vitamin-D3 analogs in good yields under mild reaction conditions is described. [ABSTRACT FROM AUTHOR]

Catalytic amount of chlorotrimethylsilane (TMSCl) was found to be an effective silicon Lewis acid catalyst in catalyzing the Michael-type Friedel-Crafts reactions of indoles and chalcones to afford corresponding 3-substituted indole derivatives in good to excellent yields. The method is metal-free, has mild reaction conditions, and generates good yields of products with greater selectivity, which make it a useful and attractive process for the synthesis of different indole derivatives. [ABSTRACT FROM AUTHOR]

A convenient synthesis of the novel squaric acid derivatives is reported. Unsymmetrically substituted 3,4-diamino-3-cyclobutene-1,2-diones and 3-amino-4-hydroxy-3-cyclobutene-1,2-diones were prepared by interaction of diethyl squarate with different nucleophilic reagents such as alkali, primary and secondary amines and amino acids. Substituted 3-amino-4-aryl-3-cyclobutene-1,2-diones were synthesized by interaction of squaryl dichloride with different arenes followed by arylsquarylation of amines. Efficient procedures were developed for consequent substitution of ethoxy groups in diethyl squarate and chlorine atoms in squaryl dichloride. The synthesized compounds have a great potential of bioactivity and are useful objects for biomedicinal screening. [ABSTRACT FROM AUTHOR]

Intramolecular cyclodehydration of 3-arylpropionic acids catalyzed by heteropoly acids was investigated for the first time. Several 3-arylpropionic acids were refluxed and dehydrated in chlorobenzene in the presence of 0.2 equivalent of heteropoly acids, and 1-indanones were obtained in good yield. At the same time, intermolecular Friedel-Crafts acylation were observed in this experiment. [ABSTRACT FROM AUTHOR]

Hydroxynaphthyl ketones were obtained with high yields under very mild conditions in the presence of AlCl3 via Friedel-Crafts acylation and demethylation from naphthyl ethers. Several Lewis acids were tested, and AlCl3 was the most efficient catalyst. [ABSTRACT FROM AUTHOR]

Graphical Abstract Section [ABSTRACT FROM AUTHOR]

Enantioselective syntheses of (R)-and (S)-2-N-carbomethoxy-5-aminoindanes from (R)- and (S)-phenylalanines, respectively, are described. A Friedel-Crafts reaction employing N-carbomethoxy phenylalanine leads to chiral 2-N-carbomethoxy-1-indanone, which is diastereoselectively reduced to 1-hydroxy-2-N-carbomethoxyindane. After protection of the hydroxyl group, a regioselective nitration gives a 6-nitroindane intermediate, which upon hydrogenation affords (R)-or (S)-2-N-carbomethoxy-5-aminoindane. [ABSTRACT FROM AUTHOR]

The synthesis of 1,1‐dimethyl‐4‐indanols ( 3a,b ) has been achieved by intramolecular Friedel–Crafts cyclization of 2‐(3‐methyl‐2‐butenyl)phenols ( 5a , b ) or 1‐methoxy‐2‐(3‐methyl‐2‐butenyl)benzenes ( 6a,b ) followed by demethylation, respectively.It was found that the solvent was critical for the formation of different products in the intramolecular Friedel–Crafts reactions of 6 . The unexpected product 4‐methoxy‐1,1,6,6‐tetramethyl‐ as ‐hydrindacene ( 11 ) was obtained from the Friedel–Crafts reactions of 6a , and its structure was confirmed by X‐ray diffraction analysis. The key intermediates 5a,b were prepared by ortho ‐alkenylation of phenols with 1‐bromo‐3‐methyl‐2‐butene, and the reaction temperature exerted an obvious impact on the yield of 2‐(3‐methyl‐2‐butenyl)phenol ( 5a ). [ABSTRACT FROM AUTHOR]

A short, high yielding synthesis of a novel substituted pyrrolo[2,3-b]xanthone has been developed. The synthesis begins with a copper catalyzed Ullmann coupling reaction followed by and intramolecular Friedel-Crafts acylation reaction to establish the xanthone core structure. After a regioselective nitration, a Leimgruber-Batcho synthesis establishes the final pyrrole ring. [ABSTRACT FROM AUTHOR]

1,1-Bis(4-alkylthiophenyl)-1-alkenes were conveniently and efficiently prepared from alkyl phenyl sulfides and acyl chlorides via a tandem Friedel--Crafts acylation and alkylation in the presence of anhydrous aluminum chloride. The scope, limitation, and mechanism of the tandem reaction were also discussed. [ABSTRACT FROM AUTHOR]