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Chemistry Letters Vol.37, No.8 (2008)
An Efficient Method for Aromatic Friedel–Crafts Acylation Reactions
Mohammad Mehdi Khodaei,ꢀ1;2 Kiumars Bahrami,ꢀ1;2 and Fomeida Shahbazi1
1Department of Chemistry, Razi University, Kermanshah 67149, Iran
2Nanoscience and Nanotechnology Research Center (NNRC), Razi University, Kermanshah 67149, Iran
(Received March 4, 2008; CL-080236; E-mail: mmkhoda@razi.ac.ir)
Friedel–Crafts acylation of aromatic compounds was carried
Table 1. Effect of increasing amount of FeCl3 on benzoylation
reaction of methoxybenzene, using [BTBA]Cl–FeCl3 ionic
liquida
out using FeCl3-based ionic liquid. This liquid serves as an
efficient media as well as a Lewis acid catalyst. The significant
advantages of this methodology are excellent yields, short
reaction times, mild reaction conditions, environmentally
friendly method, simple work-up procedure, low cost, and easy
preparation and handling of the catalyst.
[BTBA]Cl–FeCl3
Molar fraction of FeCl3/N
Yield/%b
1:0.4
1:0.5
1:0.7
1:0.9
1:1
0.28
0.33
0.41
0.47
0.5
20
40
50
80
95
One of the main tasks of contemporary industrial chemistry
is the search for catalysts for the production of fine and inter-
mediate chemicals.1 Friedel–Crafts acylation and benzoylation
reactions lead to aromatic ketones, which are important
intermediates in a very wide field of chemistry, including
pharmacologicals, dyes, fragrances, and agrochemicals, such
as fungicides, herbicides, and insecticides. Many of the industri-
al processes still use HF or AlCl3 as catalysts for this kind of
reaction, producing a high amount of contaminated waste.
Considering the ecological and economical problems associated
with waste management in most civilized countries,2 an alterna-
tive, salt-free synthesis would be of high interest.3
Recently, much attention has been focused on the use of
ionic liquids as environmentally benign reaction media.4 This
fact is attributed to some intriguing properties of ionic liquids,
such as high thermal stability, negligible vapor pressure, high
loading capacity, and tunable polarity. In view of these distinct
advantages, ionic liquids have become an exciting area of
research.
aReaction conditions: The reactions were performed with benzoyl
chloride (1 mmol), methoxybenzene (1 mmol), and ionic liquid
b
(1 mmol) for 3 min, at 50 ꢁC. Isolated yield.
Table 2. Benzoylation of methoxybenzene with benzoyl chlo-
ride in the presence of several Lewis acids in [BTBA]Cl–Lewis
acids, N ¼ 0:5
Entry
[BTBA]Cl–Lewis acid
Time/min
Yield/%a
1
2
3
4
[BTBA]Cl–ZrCl4
[BTBA]Cl–ZnCl2
[BTBA]Cl–AlCl3
[BTBA]Cl–FeCl3
b
3
3
3
3
1
10
30
90b
95
aIsolated yields. Ortho/para ratio 40:60 (by H NMR).
[BTBA]Cl–Lewis acids, N ¼ 0:5. The results show that only
FeCl3 is effective for this purpose (Table 2).
To generalize our reagent system, the applicability of the
[BTBA]Cl–FeCl3 system was then examined for the reactions
of a series of aromatic compounds with acyl chloride or benzoyl
chloride under the optimized reaction conditions12 (Table 3).
It was observed that electron-donating groups such as alkyl
and methoxy on the aromatic compound gave rise to excellent
yields of the product (Entries 1–3). Also, deactivated arenes such
as flourobenzene, chlorobenzene, bromobenzene, and nitroben-
zene underwent acylation with good to excellent yields (Entries
8–11). As shown in Table 3, a tremendous enhancement of
para selectivity was observed in each case.
Methyl phenyl sulfide (Entry 5) was benzoylated with
benzoyl chloride, and only 8% of ortho isomer was obtained.
In order to show the efficiency of this method, the results of
the acylation and benzoylation reactions of methoxybenzene by
this method are compared with those reported by other methods.
The results show that this method is superior to some previously
reported methods in terms of yields and reaction times (Table 4).
In conclusion, the use of [BTBA]Cl–FeCl319 in the Friedel–
Crafts acylation and benzoylation of aromatic compounds can be
considered as an interesting alternative to the existing homoge-
neous catalysts. The significant advantages of this methodology
are excellent yields, short reaction times, mild reaction condi-
tions, high selectivity of the products, low cost, and easy prepa-
ration and handling of the catalyst.
Many organic chemical transformations have been carried
out in ionic liquids, for example, hydrogenation,5,6 oxidation,7
epoxidation,8 and hydroformylation9 reactions.
In continuation of our recent work on the acylation reac-
tions,10 with a view towards developing reactions for clean syn-
thesis in ionic liquids,11 we now wish to introduce the FeCl3-
based ionic liquid as effective and highly chemoselective cata-
lysts for Friedel–Crafts acylation and benzoylation of aromatic
compounds under mild reaction conditions (Scheme 1).
To study the effect of increasing amounts of the Lewis acid
in the ionic liquid, acylation of methoxybenzene, as a model sub-
strate, with benzoyl chloride was carried out in benzyltributyl-
ammonium chloride ([BTBA]Cl) at 50 ꢁC. As shown, the best
result was obtained with [BTBA]Cl–FeCl3, N ¼ 0:5 (Table 1).
We also investigated benzoylation of methoxybenzene
with benzoyl chloride in the presence of several Lewis acids in
_
+
N(
)3FeCl4
Ph
Ar COR
Ar
H
RCOCl
+
50 °C
Scheme 1.
R = Ph, Et, Me
Copyright Ó 2008 The Chemical Society of Japan