Friedel-Crafts acylation reversal

When the reverse order of steps is attempted it is observed that the Friedel-Crafts acylation of nitrobenzene fails... 

Friedel-Crafts acylation sometimes shows a modest kinetic isotope effect. This observation suggests that the proton removal is not much faster than the formation of the (j-complex and that the formation of the n-complex may be reversible under some conditions. 

Friedel-Crafts reactions in the ionic liquid system l-methyl-3-ethylimidazolium chlo-ride-aluminium(ni) chloride can be performed with excellent yields and selectivities, and in the case of anthracene, have been found to be reversible. This ionic liquid has been shown to demonstrate catalytic activity in reactions such as Friedel-Crafts acylations (Surette et al., 1996 Boon et al., 1986) alkylation reactions (Koch et al., 1976),... 

The acetyl group is attached to the ring by Friedel-Crafts acylation. It is a meta director, and its nitration gives the proper orientation of substituents. The order of the first two steps cannot be reversed, because Friedel-Crafts acylation of nitrobenzene is not possible (Section 12.16). Once prepared, m-nitroacetophenone can be reduced to m-nitroaniline by any of a number of reagents. Indeed, all three reducing combinations described in the text have been employed for this transformation. 

Reversing the order of introduction of the nitro and acyl groups is incorrect. It is possible to nitrate ethyl phenyl ketone but not possible to carry out a Friedel-Crafts acylation on nitrobenzene, owing to the strong deactivating influence of the nitro group. 

Friedel-Crafts acylations are unknown for the azoles, clearly because of interaction between the basic nitrogen and the Lewis-acid catalyst. It is, however, possible to 2-aroylate 1-alkyl-imidazoles " or indeed imidazole itself by reaction with the acid chloride in the presence of triethylamine, the substitution proceeding via an iV-acyl-imidazolium ylide. Trifluoroacetylation of iV-substituted imidazoles, and some oxazoles and thiazoles, also produces 2-substituted products in good yields. In the reverse sense, 2-acyl-substituents can be cleaved by methanolysis, the mechanism again involving an imidazolium ylide. ... 

Bexarotene is an RXR-selective retinoid marketed by Ligand Pharmaceuticals Inc., for treatment of refractory advanced-stage cutaneous T-cell lynq>homa. Bexarotene is orally administered, safe and side effects are reversible.(Jtl) The synthesis of Bexarotene starts with tetrahydronaphthalene 11, prepared in 91% yield by Friedel-Crafts alkylation of toluene with 2,5-dichloro-2,S-dime1hylhexane 10 (Scheme 5).(31-33) Friedel-Crafts acylation of 11 with chloromethylterphthalate 12 afforded ester 13 in 72% yield. 

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