Friedel-Crafts acylation with ketenes

Route (b), based on an aliphatic Friedel-Crafts reaction, gives a good yield of (31) which is duly acylated with ketene dimer. 

Solid Catalysts. Nafion-H is an active catalyst for acylation with aroyl halides and anhydrides.60,61 The reaction is carried out at the boiling point of the aromatic hydrocarbons. Yields with benzoyl chloride using 10-30% Nafion-H for benzene, toluene, and p-xylene are 14%, 85% and 82%, respectively. Attempted acylation with acetyl chloride, however, led to HC1 evolution and ketene formation. Nation resin-silica nanocomposite materials containing a dispersed form of the resin within silica exhibits significantly enhanced activity in Friedel-Crafts acylations.62,63... 

The most important method for the preparation of aryl ketones is known as Friedel-Crafts acylation. The reaction is of wide scope. Reagents other than acyl halides can be used," including carboxylic acids," anhydrides, and ketenes. Oxalyl chloride has been used to give diaryl 1,2-diketones." Carboxylic esters usually give alkylation as the predominant product (see 11-11)." A-Carbamoyl p-lactams reacted with naphthalene in the presence of trifluoromethanesulfonic acid to give the keto-amide." ... 

Isomerization of silyl ketene acetm by migration of the silyl group from ox alkanoic esters, is very facile (5 min. r Friedel-Crafts acylation. The recovered and reused without decrease Cleavage of small heterocyeles. opened with amines when catalyzed b with the pressure reaction."... 

The ability of iron(iii) chloride to genuinely catalyze Friedel-Crafts acylation reactions has also been recognized by HOlderich and coworkers [76]. By immobilizing the ionic liquid [BMIM]Cl-FeQ3 on a solid support HOlderich was able to acetylate mesitylene, anisole and m-xylene with acetyl chloride in excellent yield. The performance of the iron-based ionic liquid was then compared with the corresponding chlorostannate(ii) and chloroaluminate(iii) ionic liquids. The results are given in Scheme 5.2-30 and Table 5.2-3. As can be seen, the iron catalyst gave superior results to the aluminum or tin-based catalysts. The reactions were also carried out in the gas phase at between 200 and 300 °C. The acetylation reaction was complicated by two side reactions. For example, in the reaction of acetyl chloride with m-xylene, the decomposition of acetyl chloride to ketene and the formation of l-(l-chlorovmyl)-2,4-dimethylbenzene were also found to occur [76]. 

At oxidation level 3, acid chlorides occupy a key position, since they may serve as a nearly universal substrate for an isohypsic transformation into any kind of carboxylic acid derivative. Acid halides are electrophiles that are synthetically equivalent to acyl cations (RCO ). In this capacity they are used for the synthesis of such important compounds as esters, amides (and hence, nitriles), thioesters, etc. (see Scheme 2.57), and for the formation of C-C bonds in the Friedel-Crafts reaction (see above). Acid chlorides may readily lose HCl upon treatment with triethylamine. This isohypsic conversion leads to ketenes, important reagents widely employed in [2 + 2] cycloadditions, as we will see later. 

Acylketenes generated by Wolff rearrangement undergo uncatalyzed Friedel-Crafts type reactions with different nitrogen heterocycles, including N-methylpyrrole, as in the example shown (Eqn (4.126)). The acylation was also successful with dihydrofuran and dihydropyran. At higher temperatures ketene dimerization also occurred. 

Acylation of both aromatic and aliphatic compounds can be carried out with relative ease using acyl halides, acid anhydrides, ketenes, nitriles, amides, acids and esters in the presence of Friedel-Craft catalysts to give ketones. Similar substitution reactions with formic acid derivatives are therefore expected to yield the appropriate aldehydes. However, since the anhydride and acyl halides of formic acid, with the exception of formyl fluoride, are either not known or are not sufficiently stable to be used in Friedel-Crafts type acylation reactions, this objective cannot be fully realized. Table 1.1 compares the main ketone syntheses (based on acylating reagents) with the corresponding aldehyde syntheses (based on formylating reagents). 

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