MoO2Cl2 as a novel catalyst for Friedel-Crafts acylation and sulfonylation

The use of MoO₂Cl₂ as a novel catalyst for Friedel-Crafts acylation and sulfonylation is described. A series of aromatic ketones and sulfones were prepared in moderate to good yields using acyl chloride or sulfonyl chloride in the presence of MoO₂Cl₂ (20 mol %), under solvent-free conditions.     

Lewis acid-catalyzed Friedel-Crafts acylation reaction using carboxylic acids as acylating agents

Rare-earth metal Lewis acids, in particular Eu(NTf₂)₃, were found to be efficient catalysts for Friedel-Crafts acylation reaction using aliphatic as well as aromatic carboxylic acids as acylating agents at high temperature.     

Hf[N(SO2C8F17)2]4-catalyzed Friedel-Crafts acylation in a fluorous biphase system

In a fluorous biphase system, Hf[N(SO₂C₈F₁₇)₂]₄ complex (1 mol %) catalyzes Friedel-Crafts acylation of aromatic compounds such as anisole, toluene and chlorobenzene, and the corresponding aromatic ketones are obtained in satisfactory to high yields. The catalyst is selectively soluble in lower fluorous phase and can be easily recovered by simple phase separation. Furthermore, the catalyst can be reused without decrease of activity in most cases.     

The efficient one-pot synthesis of tetraalkyl substituted furans from symmetrical acetylenes,EtAlCl2, and carboxylic esters catalyzed by Cp2TiCl2

A new one-pot method for the synthesis of tetraalkyl substituted furans in 74–80% yields has been implemented via the reaction between symmetrical acetylenes, ethylaluminum dichloride, and carboxylic esters in the presence of metallic Mg as an acceptor of halide ions, catalyzed by bis(cyclopentadienyl)titanium dichloride. A mechanism for the reaction is proposed and discussed.     

SiO2负载磷钨杂多酸催化的甲苯与乙酸酐酰化反应

以SiO2负载12-磷钨酸（PW）为催化剂,对甲苯与乙酸酐(AA)的酰化反应进行了研究。采用XRD、BET、TGA和NH3-TPD等对PW/SiO2催化剂进行了表征。结果表明,PW负载量及焙烧温度对PW/SiO2的酸性、PW在SiO2上的分散状态以及酰化催化活性有明显的影响。PW的负载量40%（按质量计）、焙烧温度300℃制备的PW(40%)/SiO2催化剂,其PW在载体表面的分散度好,酸量及酸强度适宜,对甲苯与乙酸酐的酰化反应具有较高的催化活性。在130℃,催化剂/乙酸酐（质量比）2.2时,催化反应效果最佳。     

An efficient one-pot synthesis of 3-glyoxylic acids of electron-deficient substituted azaindoles by ionic liquid imidazolium chloroaluminate-promoted Friedel-Crafts acylation

An efficient, one-pot Friedel-Crafts acylation/hydrolysis reaction promoted by the acidic ionic liquid 1-ethyl-3-methylimidazolium chloroaluminate (generated from 1-ethyl-3-methylimidazolium chloride (EmimCl) and aluminum chloride (X(AlCl₃), mole fraction X = 0.75) for the formation of 3-glyoxylic acid derivatives of electron-deficient, substituted 4- and 6-azaindoles is described.     

Friedel-Crafts acylation of ferrocene with alkynoic acids

Ferrocene reacts with alkynoic acids (conjugated or nonconjugated terminal), trifluoroacetic anhydride and triflic acid (or boron trifluoride etherate) to afford the corresponding ferrocenyl ynones in good yields. Only in the case of propynoic- and 3-butynoic acid complex, untreatable reaction mixtures were obtained. However, propynoilferrocene was obtained by desilylation of (trimethylsilyl)propynoilferrocene with KF/18-crown-6. Reaction with nonconjugated terminal alkynoic acids, carried out in the presence of a large excess of triflic acid (4 equiv.) results in formation of complex mixtures of products (in the reaction with 4-pentynoic acid enol triflate of ferrocenyl 1,4-diketone and 2-ferrocenyl-5-methylfuran were isolated). Ferrocenyl ynones obtained in this work can be used for synthesis of more complex ferrocenyl systems by “click” chemistry.     

Efficient synthesis of N-acylarenesulfenamides by acylation of arenesulfenamides

Acylation of arenesulfenamides proceeds efficiently by using either perfluorocarboxylic anhydrides or acid chlorides in the presence of pyridine as a base at low temperatures to give N-acylarenesulfenamides. Some N-alkylcarbonyl derivatives exist with imidic acid tautomers in an aprotic solvent.     

A new synthesis of oxcarbazepine using a Friedel-Crafts cyclization strategy

A novel, simple, and straightforward process for the large-scale synthesis of oxcarbazepine, the active ingredient of Trileptal^®, a medicine for the treatment of epilepsy, has been developed. Starting from readily available 1,3-dihydro-1-phenyl-2H-indol-2-one, a Friedel-Crafts cyclization strategy provides a direct route to the tricyclic framework of the target molecule. Crucial to the success of the strategy was the choice of the proper nitrogen-protecting group.     

Friedel-Crafts alkylation of indoles with trichloroacetimidates

Substituted indole scaffolds are often utilized in medicinal chemistry as they regularly possess significant pharmacological activity. Therefore the development of simple, inexpensive and efficient methods for alkylating the indole heterocycle continues to be an active research area. Reported are reactions of trichloroacetimidate electrophiles and indoles to address the challenges of accessing alkyl decorated indole structures. These alkylations perform best when either the indole or the imidate is functionalized with electron withdrawing groups to avoid polyalkylation.     

Comparisons of O-acylation and Friedel-Crafts acylation of phenols and acyl chlorides and Fries rearrangement of phenyl esters in trifluoromethanesulfonic acid: effective synthesis of optically active homotyrosines

Reactions involving phenol derivatives and acyl chlorides have to be controlled for competitive O-acylations and C-acylations (Friedel-Crafts acylations and Fries rearrangements) in acidic condition. The extent for these reactions in trifluoromethanesulfonic acid (TfOH), which is used as catalyst and solvent, is examined. Although diluted TfOH was needed for effective O-acylation, concentrated TfOH was required for effective C-acylations in mild condition. These results have been applied to the novel synthesis of homotyrosine derivatives. Both Fries rearrangement of N-TFA-Asp(OBn)-OMe and Friedel-Crafts acylation of phenol with N-TFA-Asp(Cl)-OMe in TfOH afforded the homotyrosine skeleton, followed by reduction and deprotection afforded homotyrosines maintaining stereochemistry of Asp as an optically pure form.     

Selective,C-3 Friedel-Crafts acylation to generate functionally diverse,acetylated Imidazo[1,2-a]pyridine derivatives

Carbon-carbon bonds are integral for pharmaceutical discovery and development. Frequently, CC bond reactions utilize expensive catalyst/ligand combinations and/or are low yielding, which can increase time and expenditures in pharmaceutical development. To enhance CC bond formation protocols, we developed a highly efficient, selective, and combinatorially applicable Friedel-Crafts acylation to acetylate the C-3 position of imidazo[1,2-a]pyridines. The reaction, catalyzed by aluminum chloride, is both cost effective and more combinatorial friendly compared to acetylation reactions requiring multiple, stoichiometric equivalents of AlCl₃. The protocol has broad application in the construction of acetylated imidazo[1,2-a]pyridines with an extensive substrate scope. All starting materials are common and the reaction requires inexpensive, conventional heating methods for adaptation in any laboratory. Further, the synthesized compounds are predicted to possess GABA activity through a validated, GABA binding model. The developed method serves as a superior route to generate C-3 acetylated imidazo[1,2-a]pyridine building-blocks for combinatorial synthetic efforts.     

Tf2O as a rapid and efficient promoter for the dehydrative Friedel-Crafts acylation of aromatic compounds with carboxylic acids

The Friedel-Crafts acylation of aromatic compounds with carboxylic acids was investigated in the presence of Tf₂O. The reaction was carried out efficiently and very rapidly under mild reaction conditions without the need of any catalyst.     

The Synthesis of 4-Arylcarbonyl-3-methoxycarbonyl-2-phenylfurans by Friedel-Crafts Acylation Reactions

Keto esters 8, 4-arylcarbonyl-3-methoxycarbonyl-2-phenylfurans, potential precursors of the synthesis of furofuran lignans, were obtained from dimethyl 2-phenylfuran-3,4-dicarboxylate 2.Diester 2 was selectively hydrolyzed to monoacid 6 followed by converting to its acid chloride 7.Friedel-Crafts acylation reactions of 7 with aromatic compounds afforded keto esters 8.The geometric structures of 8 and its precursors were elucidated and verified by NMR spectra.     

Niobium pentachloride-silver perchlorate as an efficient catalyst in the Friedel-Crafts acylation and Sakurai-Hosomi reaction of acetals

Friedel-Crafts acylation catalyzed by niobium pentachloride with silver salt is described. Aromatic compounds with Ac₂O or Bz₂O were smoothly converted into the corresponding ketones in good to excellent yields. This system was also applied to the Sakurai-Hosomi reaction using acetals. The reaction proceeded quite rapidly to give the desired products in excellent yields.     

Friedel-Crafts acylation of aromatic compounds with carboxylic acids in the presence of P2O5/SiO2 under heterogeneous conditions

A convenient and efficient procedure for the Friedel-Crafts acylation of aromatic compounds with carboxylic acids in the presence of P₂O₅/SiO₂ is described. Both aromatic and aliphatic carboxylic acids reacted easily to afford the corresponding aromatic ketones. The use of non-toxic and inexpensive materials, simple and clean work-up, short reaction times and good yields of the products are the advantages of this method.     

Advances in liquid-phase Friedel-Crafts acylation of aromatics catalyzed by heterogeneous solids

In the last few decades, significant improvements toward the development of environmentally benign processes have been achieved in the liquid-phase Friedel-Crafts acylation reactions. Many efforts have been devoted to the research on solid catalysts adequate to substitute homogeneous protonic acids or Lewis acids as traditionally employed catalysts in the acid-catalyzed Friedel-Crafts acylation processes. This short article describes the recent developments on catalysis by gallium (Ga), indium (In) and thallium (Tl) based novel heterogeneous solids for the liquid-phase Friedel-Crafts acylation of aromatics by acyl halide. The above heterogeneous catalysts are efficient for Friedel-Crafts acylation reaction and exhibited superior activity than the traditionally employed strongly acidic solid catalysts. Unlike conventional acidic catalyst, the acylation activity of Ga, In and Tl based solids, additionally having redox functions, does not depend solely on their acidic properties, even present. These solids in their non-acidic or basic form also show high acylation activity. Based on the catalytic results over these novel solids a plausible reaction mechanism for the acylation is proposed.Dedicated to Professor Seitaro Namba on the occasion of his 64th birthday.     

Highly selective catalytic Friedel-Crafts acylation and sulfonylation of activated aromatic compounds using indium metal

The Friedel-Crafts acylation of activated benzenes with various aromatic and aliphatic acid chlorides was studied in the presence of indium metal. The reaction was accomplished in high isolated yields under solvent or solvent-less conditions. The method is also applicable for preparing diaryl sulfones from aromatic compounds and aryl sulfonyl chlorides.     

Friedel-Crafts acylation of W(CO)5-complexes of azaferrocenes

Blocking of the lone pair of electrons on the nitrogen in azaferrocene by co-ordination to the W(CO)₅ moiety enables Friedel-Crafts acylation of this heteroferrocene. W(CO)₅-complexes of azaferrocene and 2,5-dimethylazaferrocene react with acetyl- and propionyl chloride or acetic anhydride in the presence of aluminium chloride in dichloromethane at r.t. to give W(CO)₅-complexes of 1′-acylazaferrocenes in 10-50% isolated yields. The low yields presumably result from instability of the products in the reaction medium. The X-ray structure of the complex of 1′-acetylazaferrocene has been determined.