Friedel-Crafts acylation report

Many organic chemical transformations have been carried out in ionic liquids hydrogenation [4, 5], oxidation [6], epoxidation [7], and hydroformylation [8] reactions, for example. In addition to these processes, numerous synthetic routes involve a carbon-carbon (C-C) bond-forming step. As a result, many C-C bondforming procedures have been studied in ambient-temperature ionic liquids. Among those reported are the Friedel-Crafts acylation [9] and allcylation [10] reactions, allylation reactions [11, 12], the Diels-Alder reaction [13], the Heck reaction [14], and the Suzuld [15] and Trost-Tsuji coupling [16] reactions. 

Unlike alkylation, Friedel-Crafts acylation has been generally considered to be irreversible, but a number of instances of electrofugal acyl groups have been reported, especially where there are two ortho substituents, for example the hydro-de-benzoylation of 42. ... 

In 1978, Sugasawa et al., at Shionogi Pharmaceutical Co. reported ortho-selective Friedel-Craft acylation with free anilines with nitrile derivatives [4]. Sugasawa reported that the reaction requires two different Lewis acids (BC13 and A1C13) and does not proceed when N,N-dialkyl anilines are used. He proposed that boron bridging between nitriles and anilines led to exclusive ortho-acylation but a conclusive mechanism was not elucidated. The report did not offer any reason why two different Lewis acids were required and why the reaction did not progress with N,N-dialkyl anilines. Therefore, we initiated mechanistic studies. 

Catalytic amounts of I fCl4-AgC104 and Hf(OTf)4 are used for activation of acid halides and acid anhydrides for Friedel -Crafts acylation (Scheme 42) 178 the reactions of both reactive and unreactive aromatic substrates proceed smoothly in the presence of Hf(OTf)4. Furthermore, the Fries rearrangement179,180 and direct C-acylation of phenolic compounds181,182 take place using Hf(OTf)4. Formation of esters and Mannich-type reactions and allylation of imines have been also reported.152... 

Friedel-Crafts acylation is widely used for the production of aromatic ketones applied as intermediates in both fine chemicals and pharmaceutical industries. The reaction is carried out by using conventional homogenous catalysts, which represents significant technical and environmental problems. The present work reports the results obtained in the Friedel-Crafts acylation of aromatic substrates (anisole and 2-methoxynaphthalene) catalyzed by Beta zeolite obtained by crystallization of silanized seeds. This material exhibits hierarchical porosity and enhanced textural properties. For the anisole acylation, the catalytic activity over the conventional Beta zeolite is slightly higher than with the modified Beta material, probably due to the relatively small size of this substrate and the weaker acidity of the last sample. However, the opposite occurred in the acylation of a bulky substrate (2-methoxynaphthalene), with the modified Beta showing a higher conversion. This result is interpreted due to the presence of a hierarchical porosity in this material, which favors the accessibility to the active sites. 

The present work reports the results obtained in the Friedel-Crafts acylation of different aromatic substrates catalyzed by zeolite Beta obtained according to a novel method based on the crystallization of silanized seeds, as a way to perturb the subsequent crystal growth step and to modify the zeolite textural properties [5], The catalytic behavior of this material is compared with that of the conventional Beta zeolite. 

Use of graphite-supported methodology has been reported for three types of reaction - the Friedel-Crafts acylation [15, 16, 27, 66], the acylative cleavage of ethers [15, 16], and the ketodecarboxylation of carboxylic diacids [67, 68], either with conventional heating (GS/A) or MW irradiation (GS/MW coupling) these are discussed below. First, however, we describe the analysis of two commercial graphites of different purity which are used for these experiments. 

Otera has reported that fluorous distannoxanes such as 23, which dissociate to give Lewis acidic species, catalyze transesterifications in or-ganic/fluorous solvent mixtures [8,9]. Although 23 was insoluble in toluene at room temperature, it dissolved at reflux and efficiently promoted the transformation in reaction D of Scheme 4, as well as others. The catalyst precipitated upon cooling, but a fluorous solvent extraction was utilized for recovery (100%). Another thermomorphic fluorous Lewis acid catalyst was developed by Mikami [11]. He found that the ytterbium tris(sulfonamide) 24 could be used for Friedel-Crafts acylations imder homogeneous conditions in CICH2CH2CI at 80 °C, and precipitated upon cooHng to -20 °C (reaction E, Scheme 4). 

Recently, the same authors reported a different route for the total synthesis of olivacine (238a) and ellipticine (228) starting from 2,4,6-tiimethoxypyiidine (1244) with N-benzylindole-2,3-dicarboxylic anhydride (852) (717,718). Interestingly, this method also uses the same common precursor, N-benzylindole-2,3-dicarboxylic anhydride (852) as shown in Schemes 5.204 and 5.205. Contrary to the earlier route, this sequence involves a Friedel-Crafts acylation of 2,4,6-trimethoxypyridine (1244) with N-benzylindole-2,3-dicarboxylic anhydride (852) (717,718). 

On the basis of these initial results, various rare earth metal triflates, including Sc(OTf)3, Hf(OTf)4 and Yb(OTf)3 were applied as catalysts [27-29]. Recently Beller and coworkers developed efficient Friedel-Crafts alkylations with catalytic amounts of Rh, W, Pd, Pt and Ir complexes [30] or FeCl3 [31-34] as Lewis acid catalysts. However, in the latter cases high catalyst loadings had to be applied. To overcome these major drawbacks, we decided to develop a Bi(III)-catalyzed Friedel-Crafts alkylation of arenes with benzyl alcohols. Although bismuth-catalyzed Friedel-Crafts acylations were well known at this time, Friedel-Crafts alkylations using benzyl alcohols had not been reported. 

Essentially the same route is followed for the synthesis of the triphenylethylene nitromifene (8-5). The sequence starts with Friedel-Crafts acylation of the alkylation product (8-1) from phenol and 1,2-dibromoethane with the acid chloride from anisic acid (8-2). The displacement of bromine in the product (8-3) with pyrrolidine leads to the formation of the basic ether and thus (8-4). Condensation of that product with benzylmagnesium bromide gives the tertiary alcohol (8-5). This product is then treated with a mixture of nitric and acetic acids. The dehydration products from the first step almost certainly consist of a mixture of the E and Z isomers for the same reasons advanced above. The olefin undergoes nitration under reaction conditions to lead to nitromifene (8-6) as a mixture of isomers [8] the separated compounds are reported to show surprisingly equivalent agonist/antagonist activities. 

By in situ MAS NMR spectroscopy, the Koch reaction was also observed upon co-adsorption of butyl alcohols (tert-butyl, isobutyl, and -butyl) and carbon monoxide or of olefins (Ao-butylene and 1-octene), carbon monoxide, and water on HZSM-5 (Ksi/ Ai — 49) under mild conditions (87,88). Under the same conditions, but in the absence of water (89), it was shown that ethylene, isobutylene, and 1-octene undergo the Friedel-Crafts acylation (90) to form unsaturated ketones and stable cyclic five-membered ring carboxonium ions instead of carboxylic acids. Carbonylation of benzene by the direct reaction of benzene and carbon monoxide on solid catalysts was reported by Clingenpeel et al. (91,92). By C MAS NMR spectroscopy, the formation of benzoic acid (178 ppm) and benzaldehyde (206 ppm) was observed on zeolite HY (91), AlC -doped HY (91), and sulfated zirconia (SZA) (92). 

In the case of the tricarbonylarene metals, enhancement of nucleophilic substitution relative to the free arene is reported 106), In contrast to earlier reports 106) Friedel-Crafts acylation of tricarbonylbenzene chromium occurs under mild conditions 18), Molecular-orbital calculations of the 7r-electron activation energies for these reactions 63) confirm enhanced nucleophilic reactivity and suggest electrophilic activity similar to that of the free arene. The nucleophilic displacement of halide by methoxide ion... 

New Soluble Catalysts. Trifluoromethansulfonic acid (triflic acid, TfOH)42 and acyl triflates, that is mixed anhydrides of carboxylic acids and triflic acid,43 44 were first reported to be effective for Friedel-Crafts acylation in 1972. Significantly lower yields (<30%) were obtained with other Brpnsted acids. High activities were also observed for perfluorobutanesulfonic acid.37... 

However, although it is reported that nitration occurs in the 6-position,425 Friedel-Crafts acylation is said to occur in the 5-position.426,427 These reactions deserve reexamination. 

Friedel-Crafts acylation of alkenes.9 C2H5A1C12 is an effective catalyst for acylation of alkenes with acyl chlorides or anhydrides in CH2C12. The reaction proceeds in higher yield than that previously reported with other Lewis acid catalysts (such as ZnCl2). The reaction provides a useful route to /J,y-enones. 

In 2000, Dubac s group reported the microwave-assisted Friedel-Crafts acylation of slightly activated and deactivated arenes under solvent-free conditions with FeCl3 as catalyst. Here, for the acylation of toluene a 90% product yield is obtained after 5 min of irradiation and an overall reaction time of 30 min in the presence of only 5 mol% of FeCl3. A sequential MW irradiation at 300 W afforded the acylation of fluorobenzene with 2 -chlorobenzoyl chloride, with a surprisingly high yield of 92% of 2-chloro-4 -fluorobenzophenone (Scheme 6.11). 

Although Friedel-Crafts acylation is well known with carboxylic acids, anhydrides, and acid halides, there are virtually no reports of Friedel-Crafts acylations being done with amides.63 These results demonstrate the application of distonic superelectrophiles to accomplish such a difficult... 

Synthesis of standards. Friedel-Crafts acylation of 2,3-dimethylthiophene with hexadecanoic acid and a subsequent reduction of the ketone with LiAlD4 yielded the 2,3-dimethyl-5-(l ,l -d2-hexadecyl)thiophene (II, Table II). Experimental details of these reactions have been reported elsewhere (10). Ionic hydrogenation of the 2,3-dimethyl-5-(l ,l -d2-hexadecyl)thiophene in trifluoroacetic acid using triethylsilane and BF3.etherate as catalyst yielded 2,3-dimethyl-5-(l ,l -d2-hexadecyl)thiolane (IV, Table II). For... 

For catalytic Friedel-Crafts acylation, several excellent catalysts other than RE have recently been reported [11], Although some are more active than RE, most are water-sensitive and cannot be recovered and reused after the reactions. 

In Figure 4.2, log f1/2 is plotted against Hammett substituent constant straight line correlation, and a large negative value of p (—3). Such a result is consistent with that already observed for acylation of aromatic compounds on CeY zeolite[28] and for the conventional acid catalysed Friedel-Crafts acylation. These electronic effects are analogous to those reported in the case of classical electrophilic aromatic substitutions. 

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