Substrate and position selectivity in Friedel-Crafts acylation reactions

Acetyl chloride-AlCl3 Propionyl chloride-AlCls CHsteO SbFe  

Formyl fluoride-BFs 2,4-Dinitrobenzoyl chloride-AICI3 Pentafluorobenzoyl chloride-AlQ3 Benzoyl chloride-AlCl3 p-Methylbenzoyl chloride-AICI3 p-Methoxybenzoyl chloride-AICI3 

One other feature of the data in Table 9.11 is worthy of further comment. Notice that alkyl (acetyl, propionyl)-substituted acylium ions exhibit a smaller o p ratio than the various aroyl systems. If steric factors were dominating the position selectivity, one would expect the opposite result. A possible explanation for this feature of the data could be that the aryl compounds are reacting via free acylium ions, whereas the alkyl systems may involve the more bulky acid chloride-catalyst complex. 

Steric factors, of course, do enter into determining the o p ratio. The hindered 2,4,6-trimethylbenzoyl group is introduced with a 50 1 preference for the para position. Similarly, in the benzoylation of alkylbenzenes by benzoyl chloride-aluminum chloride, the amount of ortho product decreases (10.3%, 6.0%, 3.1%, 0.6%, respectively) as the branching of the alkyl group is increased along the series methyl, ethyl, 2-propyl, f-butyl. 

Friedel-Crafts acylation sometimes shows a modest kinetic isotope effect. This effect suggests that the proton removal is not much faster than the formation of the 7-complex, and that the formation of the o--complex may be reversible under some conditions. 

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Table 10.10. Substrate and Position Selectivity in Friedel-Crafts Acylation Reactions...

Substrate and position selectivity in Friedel-Crafts acylation reactions... 

Kinetic studies of acylation reactions are somewhat limited by the insolubility of the acyl halide-Lewis acid complexes in many of the solvent systems that are used. However, useful results have been obtained and, as far as we are concerned, relative rates of reactions are of greater importance than absolute values. In any case it is not possible to distinguish between the two mechanistic extremes on the basis of the observed kinetics." Friedel-Crafts acylations are generally characterized by high substrate selectivity and frequently by high positional selectivity. Relative rate data show, as expected, that toluene is more reactive than benzene and that /n-xylene is the most reactive of the dimethylbenzenes. Values, relative to benzene, for benzoylation catalyzed by aluminum chloride were r-butylbenzene (72), toluene (1.1 X 10 ), p-xylene (1.4 x 10 ), o-xylene (1.12 x 10 ), and m-xylene (3.94 x 10- ). Competition data for the trifluoroacetylation of a number of heterocycles using trifluoroacetic anhydride at 75 "C gave the relative rates thiophene (1.0), furan (1.4 x lO ), 2-methylfuran (1.2 x 10 ) and pyrrole (5.3 x 10 ). ... 

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