Friedel-Crafts-type acylation processes

Friedel-Crafts-type acylation processes (Expts 6.121 to 6.125). 

Acylations with Nitriles. With particularly reactive aromatic nuclei such as phenols, a Friedel-Crafts type reaction may be effected with nitriles in the presence of an acid catalyst such as hydrogen chloride, aluminum chloride, or zinc chloride. The reaction is usually called the IIouben-Hoesch synthesis.700 When hydrogen cyanide is employed, the process leads to aromatic aldehydes even with a number of aromatic... 

There is a specific interest in Ga-containing MTS, which stems from the high selectivity to aromatics shown by Ga-containing zeolites in the catalytic conversion of hydrocarbons [140-143]. For example, the commercial Cyclar process, where C3-C5 alkanes are dehydrocycHzed to yield aromatic hydrocarbons, proceeds over [Ga]-ZSM-5, whereas conventional ZSM-5 aluminosilicates mainly yield paraffins. It has also been shown that Ga-containing MCM-41 is very active for Friedel-Crafts type benzylation and acylation reactions [143,144]. 

C. Punta, F. Minisci, Minisci reaction a Friedel-Crafts type process with opposite reactivity and selectivity. Selective homolytic alkylation, acylation, carboxylation and carbamoylation of heterocyclic aromatic bases. Trends Het. Chem. 13 (2008) 1 8. 

In comparison with molecular catalysts, solid catalysts can be isolated from the reaction mixtures by filtration or used in continuous processes this is both environmentally friendly and useful in laboratory-scale experiments. The most important reactions catalyzed by solid superbases are isomerization reactions and the alkylation of substituted arenes in the side chain (Scheme 2). They proceed at room temperature or below with high yield (typically >99%). The surperbase-cata-lyzed alkylation of aromatic compounds complements the acid-type Friedel-Crafts alkylation and acylation, because the latter results in ring alkylation, whereas the former results in side-chain alkylation. 

Owing to its powerful Lewis acidity, BF3 is an effective reagent in organic synthesis, for example, promoting the conversion of alcohols and acids to esters, the polymerization of olefins and olefin oxides, and acylations and alkylations (in a manner similar to Friedel-Crafts processes). Mechanistic studies of some reactions of the latter type, such as the ethylation of benzene by QH5F, have shown that the BF3 functions as a scavenger for HF via the formation of HBF4 and thus participates stoichiometrically rather than catalytically. 

A process patent and subsequent publication by Fujita and cowoikers, disclosed an improved, large-scale synthesis of fingohmod. In particular, the problem of competing styrene formation that plagued the original synthesis was addressed. In this approach, a Friedel-Crafts acylation of phenylethyl bromide (8) with octanoyl chloride yielded ketone 9 (Scheme 2). Treatment of ketone 9 with sodium ethoxide affords the expected styrene product (10) however, in this case, styrene 10 can function as a Michael-type acceptor to generate the desired amino malonate product 11 in 55% yield (2 steps). Next, hydrogenolysis of the ketone with palladium on carbon in ethanol provided... 

Carbocations are formed by several reactions. One example has been discussed already in the context of the SnI reaction (Scheme 2.2.8a). Other important options include the addition of protons to double bonds, for example, the addition of a Br0nsted acid to an alkene or ketone (Scheme 2.2.8b and c, respectively). The addition of a Lewis acid to a carbonyl group can also lead to a type of carbocation, an effect that is exploited in all kinds of technical Friedel-Crafts acylation reactions (Scheme 2.2.8d). Finally, in high-temperature refinery processes, the formation of carbocations from alkanes is of highest relevance. Here acidic catalysts are usually applied that abstract a hydride from the alkane to form hydrogen and a carbocation at the alkane substrate (Scheme 2.2.8e). 

We also have to beware of the limitations of each type of substitution process. We recall that Friedel— Crafts acylation does not occur when the ring contains a meta-directing group. For example, we can make w-nitroacetophenone by nitration of acetophenone, but not from Friedel—Crafts acylation of nitrobenzene. 

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