Catalytic Friedel-Crafts Acylation Reactions

Giovanni Sartori, Raimondo Maggi, and Veronica Santacroce 

Universitd degli Studi di Parma, Parma, Italy 

The Friedel-Crafts acylation reaction generates aromatic ketone products from the combination of an aromatic substrate with an acyl component typically in the presence of a catalyst [1]. Interest in this electrophilic process and the optimization of preparative methods is generated by the considerable practical value of the aromatic ketone products. In fact, these compounds constitute fundamental intermediates or target products in the pharmaceutical, fragrance, flavor, dye, and agrochemical industries [2-4], 

Depending on the strength of the Lewis acid and on the structure of the R substituent, the actual acylating agent may be the acid-base complex 1 or the acyl cation 2. The active reagents 1 or 2 or even a mixture of both undergo the electrophilic aromatic substitution affording the final ketone products [1]. 

Friedel-Crafts acylation follows the established activation-orientation rules of electrophilic aromatic substitution. However, the acylation of some highly activated aromatic compounds such as phenols and aromatic amines preferentially occurs at the substituent heteroatom, affording esters or amides instead of the more valuable aromatic ketones. These ort/io-hydroxy- or 

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Hachiya, I., Moriwaki, M., Kobayashi, S. Catalytic Friedel-Crafts acylation reactions using hafnium triflate as a catalyst in lithium perchlorate-nitromethane. Tetrahedron Lett. 1995, 36,409-412. 

As already underlined in the introduction to this book, catalytic homogeneous acylation reactions represent a remarkable improvement in the preparation of aromatic ketones because, in the conventional Lewis-acid-promoted reactions, formation of a stable complex between the ketone product and the catalyst implies that at least a stoichiometric amount of catalyst must be utilized. This drawback prompted a great number of studies aimed at setting up the experimental conditions to make catalytic Friedel-Crafts acylation reactions. Some positive results from fhe homogeneous catalytic Friedel-Crafts acylations are described here, with special attention to crucial economic and environmental advantages such as the recycling of expensive catalysts and the development of solvenf-free and highly selective synthetic processes. 

Harada, T., Ohno, T., Kobayashi, S., and Mukaiyama, T. 1991. The catalytic Friedel-Crafts acylation reaction and the catalytic Beckmann rearrangement promoted by gallium(Itl) or an antimony(V) cationic species. Synthesis 1216-1220. 

Izumi, J. and Mukaiyama, T. 1996. The catalytic Friedel-Crafts acylation reaction of aromatic compounds with carboxylic anhydrides using combined catalysts system of titanium(IV) chloride tris(trifluoromethanesulfonate) and trifluoromethanesulfonic acid. Chem. Lett. 739-740. 

Nevertheless, the even difficult comparative analysis of articles and patents allowed some exciting conclusions concerning, in particular, the feasibility of very efficient catalytic Friedel-Crafts acylation reactions. 

FIf(OTf)4 was found to be effective in the catalytic Friedel-Crafts acylation reactions of various substituted benzenes with acid anhydrides in lithium perchlorate-nitromethane (LiC104-MeN02) (eq 24). This same system was also used for... 

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