Page 829 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

812 Table 9.10. Reactant and Position Selectivity in Friedel-Crafts
Acylation Reactions
CHAPTER 9
Electrophilic reagents k tol /k benz Toluene o:p ratio
Aromatic Substitution
1 CH 3 COCl-AlCl 3 a 134 0 012
2 CH 3 CH 2 COCl-AlCl 3 b 106 0 033
3 CH 3 C≡O SbF 6 −c 125 0 014
+
4 HCOF-BF 3 d 35 0 82
5 2,4-Dinitrobenzoyl chloride-AlCl 3 d 29 0 78
6 Pentafluorobenzoyl chloride-AlCl 3 d 16 0 61
7 PhCOCl-AlCl 3 d 153 0 09
8 p-Toluoyl chloride-AlCl 3 d 164 0 08
9 p-Methoxybenzoyl chloride-AlCl 3 d 233 0 2
a. G. A. Olah, M. E. Moffatt, S. J. Kuhn, and B. A. Hardie, J. Am. Chem. Soc., 86,
2198 (1964).
b. G. A. Olah, J. Lukas, and E. Lukas, J. Am. Chem. Soc., 91, 5139 (1969).
c. G. A. Olah, S. J. Kuhn, S. H. Flood, and B. A. Hardi, J. Am. Chem. Soc., 86, 2203
(1964).
d. G. A. Olah and S. Kobayashi, J. Am. Chem. Soc., 93, 6964 (1972).

One other feature of the data in Table 9.10 is worthy of further comment. Note
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 is that the aroyl compounds are reacting via free acylium ions, whereas the alkyl
systems may involve more bulky acid-chloride catalyst complexes.
Friedel-Crafts acylation sometimes shows a modest kinetic isotope effect. 106 This
observation suggests that the proton removal is not much faster than the formation
of the cyclohexadienylium ion and that its formation may be reversible under some
conditions. It has been shown that the o:p ratio can depend on the rates of deprotonation
of the complex. With toluene, for example, aroyl triflates give higher ratios of
ortho product when a base, (2,4,6-tri-t-butylpyridine) is present. 107 This is because
in the absence of base, reversal of acylation leads to reaction through the more
easily deprotonated para intermediate. Steric effects on deprotonation have also been
surmised to be a factor in the 1- versus 2-acylation of naphthalene by acetyl chloride-
AlCl . 108 The two competing reactions show different concentration dependence, with
3
1-acylation being second order in acylating agent, whereas 2-acylation is first order:

Rate (1-acylation) = k naphth CH COCl-AlCl 2
1 3 3
Rate (2-acylation) = k naphth CH COCl-AlCl
2 3 3
The 2-acylation also showed a much larger H/D isotope effect (∼5.4 versus 1.1). The
postulated mechanism suggests that breakdown of the more hindered complex for
1-acylation is bimolecular, whereas a unimolecular deprotonation process occurs for
2-acylation.

106
G. A. Olah, S. J. Kuhn, S. H. Flood, and B. A. Hardie, J. Am. Chem. Soc., 86, 2203 (1964); D. B. Denney
and P. P. Klemchuk, J. Am. Chem. Soc., 80, 3285, 6014 (1958).
107 F. Effenberger and A. H. Maier, J. Am. Chem. Soc., 123, 3429 (2001).
108
D. Dowdy, P. H. Gore, and D. N. Walters, J. Chem. Soc., Perkin Trans. 1, 1149 (1991).