M. M. Khodaei et al. / Tetrahedron Letters 48 (2007) 4199–4202
4201
Tf2O
A possible reaction mechanism is presented in Scheme 4
in which the mixed anhydride was produced initially
which then reacted with the aromatic compound in the
presence of TfOH (Scheme 4).
PhCO
OMe
PhCO2H
OMe +
CH3NO2, 45 0C
Scheme 2.
The literature results of the FC-acylation reactions of
aromatic compounds with carboxylic acids in the pres-
ence of a catalyst and using trifluoroacetic anhydride
as the acylating agent are listed in Table 2. The reaction
in the presence of Tf2O without using any catalyst is also
included. The FC-acylation reaction reported here is
comparable with the other methods.
rapidly converted into the corresponding ketone in 96%
yield (Scheme 2).
Table 1 includes results for the Tf2O-mediated benzoyl-
ation of aromatics. Interestingly, anisole was converted
to p-acetyl anisole with high regioselectivity while, tolu-
ene was benzoylated to the corresponding aryl ketones
with an ortho:para ratio of 20:80. Deactivated benzenes
such as chlorobenzene and iodobenzene were inactive
towards both acetic and benzoic acids under these reac-
tion conditions.
In conclusion, we have developed an FC-acylation of
aromatic compounds with carboxylic acids as acylating
agents in the presence of Tf2O without using any cata-
lyst under mild conditions.11,12 Short reaction times,
high efficiency and high selectivity of the products are
advantages of this method.
A competitive experiment was carried out to follow the
selectivity of the reaction. Thus, a mixture of anisole and
toluene (1:1) was reacted with acetic acid in the presence
of Tf2O under solvent-free conditions at room tempera-
ture. Methoxyacetophenone was obtained as the sole
product in 95% yield indicating a high selectivity be-
tween alkoxy and methyl groups on the benzene ring
(Scheme 3).
Acknowledgement
The authors thank the Razi University Research Coun-
cil for financial assistance.
References and notes
1. (a) Olah, G. A. In Friedel Crafts and Related Reactions;
Wiley Interscience: New York and London, 1963–1964;
Vols. I–IV; (b) Heaney, H. In Comprehensive Organic
Synthesis; Trost, B. M., Ed.; Pergamon Press: Oxford,
1991; Vol. 2, p 753.
MeCO
Tf2O
OMe
OMe
95%
MeCO2H
+
MeCO
2. Olah, G. A. Friedel–Crafts Chemistry; Wiley-Interscience:
New York, 1973.
CH3
0%
Neat, rt
CH3
3. (a) Schiemenz, G. P.; Schmidt, U. Liebigs Ann. Chem.
1976, 1514; (b) Chiche, B.; Finiels, A.; Gauthier, C.;
Geneste, P. J. Org. Chem. 1986, 51, 2128; (c) Wang, Q. L.;
Ma, Y.; Ji, X.; Yan, H.; Qiu, Q. J. Chem. Soc., Chem.
Commun. 1995, 2307; (d) Pandey, A. K.; Singh, A. P.
Catal. Lett. 1997, 44, 129; (e) Izumi, Y.; Ogawa, M.;
Nohara, W.; Urabe, K. Chem. Lett. 1992, 1987; (f) Kaur,
J.; Kozhevnikov, I. V. Chem. Commun. 2002, 2508; (g)
Kobayashi, S.; Moriwaki, M.; Hachiya, I. Tetrahedron
Lett. 1996, 37, 4183; (h) Kawamura, M.; Cui, D.-M.;
Yayashi, T.; Shimada, S. Tetrahedron Lett. 2003, 44, 7715;
(i) Firouzabadi, H.; Iranpoor, N.; Nowrouzi, F. Tetrahe-
dron 2004, 60, 10843; (j) Kawamura, M.; Cui, D.-M.;
Shimada, S. Tetrahedron 2006, 62, 9201.
Scheme 3.
O
OH
RC
O
SO2CF3
RCOO
+ F3CSO3H
2F3CSO3H
+CF3SO2
SO2CF3
..
F3CSO3H
RCO
+
R
+
RCO
R
O
SO2CF3
4. Suzuki, K.; Kitagawa, H.; Mukaiyama, T. T. Bull. Chem.
Soc. Jpn. 1993, 66, 3729.
Scheme 4.
Table 2. Comparison of the literature results for the FC-acylation of aromatic compounds with carboxylic acids using anhydrides with the result
using this method
Entry Acid
Aromatic compound Conditions
Catalyst
Yield (%) Time
1
2
3
4
5
6
Benzoic acid
Benzoic acid
Benzoic acid
Phenyl acetic acid
p-MeO2S-phenyl acetic acid Toluene
Benzoic acid Anisole
Anisole
Anisole
Anisole
Anisole
TFAA (1.5 equiv), 30 ꢁC
Bi(OTf)3
AlPW12O40
Al2O3
H3PO4
TfOH
98
96
80
80
83
12 h7
TFAA (1.5 equiv), rt
2.5 h6
10 min8
1 min9
1 h10
TFAA (1.5 equiv), rt
TFAA (4 equiv), rt
TFAA (2 equiv), 80 ꢁC, toluene
Tf2O (1.1 equiv), 45 ꢁC, nitromethane No catalyst 96
1 min