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P. H. Tran et al. / Tetrahedron Letters 55 (2014) 205–208
aromatic compounds under microwave irradiation. To the best of
our knowledge, this is the first time this catalytic system has been
used for the Friedel–Crafts benzoylation under microwave
irradiation.
out in closed vessels using a CEM Discover monomode oven with
strict control of the temperature. The results are summarized in
Table 1.
The Friedel–Crafts benzoylation of aromatic compounds with
benzoyl chloride to obtain the corresponding benzophenone deriv-
atives using bismuth triflate in the presence of alkylmethylimi-
dazolium trifluoromethanesulfonates was carried out under
microwave activation.48 This catalytic system promoted the reac-
tion in good yields, short reaction times, and employed simple
work-up. Under microwave irradiation (120 °C, 30 min), this reac-
tion provides a 98% conversion of anisole into 4-methoxybenz-
ophenone in [BMIM]OTf; a lower conversion was observed when
[HMIM]OTf (85%) and [OMIM]OTf (82%) were used. Six metal tri-
flates (Li, Cu, Gd, La, Nd, and Pr) were also tested in [BMIM]OTf.
However, Bi(OTf)3/[BMIM]OTf showed the highest activity was
chosen as the catalytic system for this research. No reaction was
observed in the absence of Bi(OTf)3 and only 77% yield of the prod-
uct was obtained when [BMIM]OTf was not used. The reaction
scope with respect to the arene substrate is presented in Table 2.
Benzoylation of electron-rich arenes proceeded efficiently and
the corresponding products were obtained in good yields with
70–95% selectivity for the p-benzoylated products (Table 2, entries
1–4). Dimethoxybenzenes, dimethylresorcinol, and dimethylhy-
droquinone were found to be less reactive than veratrol due to ste-
ric hindrance when these substituents direct the electrophile to the
ortho-position (Table 2, entries 8 and 9). However, substantial ste-
ric hindrance was tolerated in the benzoylation of m-xylene and p-
cymene (entries 5 and 6). Interestingly, mesitylene was benzoylat-
ed in excellent yields (entry 10). Under microwave irradiation,
naphthalene was also benzoylated in good yields (entry 11). Fur-
thermore, the reactivity of the catalytic system was also examined
under conventional heating (oil bath) in the benzoylation of sub-
strates such as veratrole, dimethylresorcinol, dimethylhydroqui-
none, mesitylene, and naphthalene; however, the yields were not
as good as those under the microwave irradiation (Table 2, entries
7–11). A similar yield was obtained in the case of benzoylation of
dimethylresorcinol under conventional heating; however, a higher
temperature was required (Table 2, entry 8).
In our previous work, we found that Friedel–Crafts acylation
proceeded smoothly using the Bi(OTf)3/[BMIM]PF6 catalytic sys-
tem.45 Although the products were obtained in good yields with
the electron-rich substituents such as –OMe and –SMe, the cata-
lytic system was not suitable for alkylbenzenes such as toluene,
ethylbenzene, and xylene. Besides, the recycling of the catalytic
system was not good under microwave irradiation and the yield
was decreased in three consecutive cycles (from 74% to 64%), and
strongly in the fourth cycle (only 35%). In order to solve these prob-
lems, we decided to use alkylmethylimidazolium triflate ([RMI-
M]OTf) as an alternative to [BMIM]PF6. Kobayashi and Iwamoto
demonstrated that the main reactant in the Friedel–Crafts acyla-
tion when using a metal triflate as the catalyst was acyl triflate
(R0COOTf), which reacts with aromatic compounds to afford the
corresponding ketones.11 Mechanistic investigations showed that
the strong acylating agent, acyl triflate R0COOTf, is generated when
Clꢀof acyl chloride exchanged by TfOꢀ of AgOTf46 or Bi(OTf)3.12,47
For this reason, TfOꢀ plays an important role when a metal triflate
is used as the catalyst for Friedel–Crafts acylation. Consequently,
we decided to use bismuth triflate and [RMIM]OTf in our research.
When using [RMIM]OTf as the solvent, the concentration of TfOꢀ
increased in the reaction medium and acyl triflate (R0COOTf) was
generated easily. Indeed, slightly activated substrates such as tolu-
ene, m-xylene, ethylbenzene, p-cymene, mesitylene, and even
naphthalene were benzoylated in good yield when compared with
bismuth triflate in [BMIM]PF6.
In initial studies, we attempted to synthesize three ionic
liquids: 1-butyl-3-methylimidazolium triflate [BMIM]OTf, 1-hexyl-
3-methylimidazolium triflate [HMIM]OTf, and 1-octyl-3-methyl-
imidazolium triflate [OMIM]OTf under microwave irradiation
(Scheme 1). The procedure consisted of two steps: the first
involved the preparation of an alkylated bromide ionic liquid pre-
cursor and the second involved an anion metathesis of alkylmethy-
limidazolium bromide with lithium triflate.48 The procedure for
the preparation of these ILs is environmentally benign. Under
microwave irradiation, the reaction was carried out in a short reac-
tion time, under solvent-free conditions, and without using the
molar excess of reagents. The MW-assisted reaction was carried
Attempts were made to recover and reuse the catalytic system
Bi(OTf)3/[BMIM]OTf. After extraction with diethyl ether, the ionic
liquid layer was dried under vacuum for 90 min. The benzoylation
of veratrol was run for three consecutive cycles at 80 °C for 15 min
under microwave irradiation. The isolated yields were slightly de-
creased after each cycle (88%, 86%, and 83%). Under conventional
heating, the catalytic system was also run for three consecutive cy-
cles at 120 °C for 30 min (82%, 83%, and 79% isolated yields). The
slightly decreased activity after each cycle showed that Bi(OTf)3/
[BMIM]OTf was an efficient catalytic system for the Friedel–Crafts
benzoylation.
Br
MW, solvent-free
+
N
N
R
N
N
RBr
Me
Me
R= -C4H9, -C6H13, C8H17
In conclusion, bismuth triflate in [BMIM]OTf is an efficient cat-
alytic system for the Friedel–Crafts benzoylation reaction under
microwave irradiation. Activated arenes and naphthalene were
benzoylated smoothly to give aryl ketones in good yields and in
MW, solvent-free
Br
OTf
R
LiOTf
+
N
N
R
+ LiBr
N
N
Me
Me
Scheme 1. Synthesis of alkylmethylimidazolium trifluoromethanesulfonates.
Table 1
The preparation of alkylmethylimidazolium trifluoromethanesulfonates under solvent-free conditions
Entry
ILa
Conditions
Yieldb (%)
Step 1
Step 2
Microwave activation
Conventional heating
1
2
3
[BMIM]OTf
[HMIM]OTf
[OMIM]OTf
80 °C, 20 min
80 °C, 20 min
80 °C, 20 min
100 °C, 20 min
100 °C, 20 min
120 °C, 30 min
96
95
87
74
76
64
a
[BMIM]OTf: 1-butyl-3-methylimidazolium trifluoromethanesufonate, [HMIM]OTf: 1-hexyl-3-methylimidazolium trifluoromethanesufonate, [OMIM]OTf: 1-octyl-3-
methylimidazolium trifluoromethanesufonate.
b
Isolated yield.