Improvement of the Friedel-Crafts benzoylation by using bismuth trifluoromethanesulfonate in 1-butyl-3-methylimidazolium trifluoromethanesulfonate ionic liquid under microwave irradiation

Article abstract of DOI:10.1016/j.tetlet.2013.10.155

Bismuth trifluoromethanesulfonate (bismuth triflate) catalyzed the Friedel-Crafts benzoylation of activated aromatic compounds when dissolved in 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([BMIM]OTf) ionic liquid. Immobilization of bismuth triflate (5 mol %) in [BMIM]OTf allowed the synthesis of aryl ketones in good to excellent yields with short reaction times under microwave irradiation. This catalytic system was easily recovered and reused several times without any significant loss of the activity.

Full text of DOI:10.1016/j.tetlet.2013.10.155

Tetrahedron Letters 55 (2014) 205–208
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Tetrahedron Letters
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Improvement of the Friedel–Crafts benzoylation by using bismuth
trifluoromethanesulfonate in 1-butyl-3-methylimidazolium
trifluoromethanesulfonate ionic liquid under microwave
irradiation
⇑
Phuong HoangTran, Ngoc BichLe Do, Thach NgocLe
Department of Organic Chemistry, Faculty of Chemistry, University of Science, Vietnam National University, Hochiminh City 70000, Viet Nam
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 July 2013
Revised 13 October 2013
Accepted 31 October 2013
Available online 8 November 2013
Bismuth trifluoromethanesulfonate (bismuth triflate) catalyzed the Friedel–Crafts benzoylation of acti-
vated aromatic compounds when dissolved in 1-butyl-3-methylimidazolium trifluoromethanesulfonate
([BMIM]OTf) ionic liquid. Immobilization of bismuth triflate (5 mol %) in [BMIM]OTf allowed the synthe-
sis of aryl ketones in good to excellent yields with short reaction times under microwave irradiation. This
catalytic system was easily recovered and reused several times without any significant loss of the
activity.
Keywords:
Friedel–Crafts benzoylation
Bismuth triflate
Ó 2013 Elsevier Ltd. All rights reserved.
Microwave activation
Aryl ketone
1-Butyl-3-methylimidazolium triflate
The Friedel–Crafts benzoylation of aromatic compounds is an
important carbon–carbon bond forming reaction in organic syn-
thesis.1–5 Traditionally, this reaction is catalyzed by so-called con-
ventional Lewis acids such as AlCl3, FeCl3, ZnCl2, and TiCl4 in
appropriate organic solvents.6 However, more than a stoichiome-
tric amount of catalyst is required and these catalysts could not
be recovered and reused after the usual aqueous work-up.6 There-
fore, it is necessary to replace these traditional Lewis acids by
greener catalysts which are efficient under mild conditions.1 In
addition, the catalysts should be reused to reduce the amount of
waste in industrial processes.1,7
Metal triflates are efficient catalysts for Friedel–Crafts acylation
of aromatic compounds.8 These triflates possess strong Lewis acid-
ity, exhibit high tolerance toward water, and are easily recycled
after the reaction.9–12 Therefore, various organic reactions can be
catalyzed by metal triflates under green conditions in good
yields,13 and the use of metal triflates in the green media has been
developed.1,8
green chemistry, ILs are benign reaction media for organic synthe-
ses.25–30 Friedel–Crafts acylation reactions using metal triflates in
ILs have been studied extensively. In 2002, Ross and Xiao used
Cu(OTf)2 in [BMIM]BF4 for the benzoylation and acetylation of acti-
vated arenes.31 Vaultier et al. have reported the acylation of arenes
using bismuth derivatives in [EMIM]NTf2 and in [BMIM]NTf2.32
Furthermore, Li et al. showed that the Friedel–Crafts acylation of
ferrocene using Yb(OTf)3 in [BPy]BF4 proceeded smoothly under
mild conditions,33 whilst Thompson reported a kinetic study of
the metal triflate catalyzed benzoylation of anisole in ionic liq-
uids.34 More recently, Galloni et al. reported an improvement of
ferrocene acylation using Sc(OTf)3 in alkylmethylimidazolium-
based ionic liquids,35 and Leitner has reported continuous catalytic
Friedel–Crafts acylation in the biphasic medium of an ionic liquid
and supercritical carbon dioxide (scCO2).36
Microwave (MW) activation provides a valuable tool for organic
synthesis.37 MW-assisted reactions have emerged as green meth-
ods which promote much faster, cleaner reactions than conven-
tional heating.38–41 Microwave-assisted organic syntheses in
green media or in the absence of solvent have received significant
interest due to simple and environmentally benign proce-
dures.35,42–44
Many papers have been focused on the use of ionic liquids (ILs)
as a green alternative to volatile organic solvents.14–21 They are
non-volatile or have very low vapor pressure, exhibit high thermal
stability, dissolve a range of organic and inorganic compounds and
can be recovered easily.22–24 Consequently, from the viewpoint of
As part of our interest in the application of metal triflates in io-
nic liquids as catalysts for the Friedel–Crafts benzoylation, we re-
port herein the use of bismuth triflate in [BMIM]OTf as a green
catalytic system that promoted Friedel–Crafts benzoylation of
⇑
Corresponding author.
E-mail address: lenthach@yahoo.com (T.N. Le).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.10.155

206
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.

P. H. Tran et al. / Tetrahedron Letters 55 (2014) 205–208
207
Table 2
Benzoylation of various aromatic compounds catalyzed by bismuth triflate in [BMIM]OTf under microwave irradiationa
Entry
Areneb
Temp.(°C)
Time (min)
Product
MeO
Me
Conversionc (%)
Yieldd (%)
94
o/m/pe
O
1
120
30
98
5/0/95
MeO
Ph
O
2
3
4
140
140
120
30
30
30
89
92
80
70
84
75
26/3/71
23/7//70
10/0/90
Me
Et
Ph
O
Ph
Et
O
MeS
Ph
MeS
Me
Me
Ph
O
5
6
140
140
30
30
98
82
82
75
100
Me
Me
O
i-Pr
i-Pr
Me
Ph
79/21f
Me
MeO
MeO
MeO
Ph
7
8
80 (120)
80 (120)
15 (30)
15 (15)
97 (87)
82 (84)
90 (83)
76 (75)
100
100
MeO
O
OMe
OMe
Ph
O
MeO
MeO
MeO
MeO
Ph
O
OMe
9
120 (120)
30 (30)
98 (77)
80 (76)
100
OMe
Me
Me
Ph
Me
Me
10
11
140 (140)
140 (140)
30 (30)
30 (30)
99 (82)
84 (46)
95 (78)
76 (30)
100
O
Me
Me
O
83/17g
Ph
a
Reaction conditions: arene (1 mmol), benzoyl chloride (2 mmol), bismuth triflate (0.05 mmol), [BMIM]OTf (0.1 g), MW (CEM Discover, closed-vessel). Values in paren-
theses are those conditions employed and the results obtained under conventional heating.
b
Low boiling point substrates such as benzene were not convenient for use, no product was obtained with deactivated substrates such as halobenzenes and nitrobenzene.
Conversion based on the arene was determined by GC using hexadecane as an internal standard.
Isolated yield.
Determined by GC.
2-Isopropyl-5-methylbenzophenone/5-isopropyl-2-methylbenzophenone = 79/21.
1-Benzoylnaphthalene/2-benzoylnaphthalene = 83/17 (the same selectivity was observed under both microwave activation and conventional heating).
c
d
e
f
g
2. Bernardo, P. H.; Chai, C. L. L. J. Org. Chem. 2003, 68, 8906–8909.
3. Mizuno, M.; Inagaki, A.; Yamashita, M.; Soma, N.; Maeda, Y.; Nakatani, H.
short reaction times. The catalytic system Bi(OTf)3/[BMIM]OTf is
stable to moisture and could be easily recovered and reused with-
out any significant loss of the catalytic activity.
Tetrahedron 2006, 62, 4065–4070.
4. Wu, Y. S.; Coumar, M. S.; Chang, J. Y.; Sun, H. Y.; Kuo, F. M.; Kuo, C. C.; Chen, Y.
J.; Chang, C. Y.; Hsiao, C. L.; Liou, J. P.; Chen, C. P.; Yao, H. T.; Chiang, Y. K.; Tan, U.
K.; Chen, C. T.; Chu, C. Y.; Wu, S. Y.; Yeh, T. K.; Lin, C. Y.; Hsieh, H. P. J. Med. Chem.
2009, 52, 4941–4945.
Acknowledgment
5. Yadav, G. D.; George, G. Microporous Mesoporous Mater. 2006, 96, 36–43.
6. Olah, G. A. Friedel-Crafts Chemistry; John Wiley and Sons: New York, 1973.
7. Afonso, C. A. M.; Crespo, J. P. Green Separation Processes; Wiley-VCH: Weinheim,
2005.
8. Luo, S.; Zhu, L.; Talukdar, A.; Zhang, G.; Mi, X.; Cheng, J.-P.; Wang, P. G. Mini-
Rev. Org. Chem. 2005, 2, 177–202.
We are grateful to Nafosted (National Foundation for Science
and Technology Development—Vietnam) for financial support
through contract No. 104.01-2010.34.
9. Hachiya, L.; Moriwaki, M.; Kobayashi, S. Tetrahedron Lett. 1995, 36, 409–412.
10. Desmurs, J. R.; Labrouillère, M.; Roux, C. L.; Gaspard, H.; Laporterie, A.; Dubac, J.
Tetrahedron Lett. 1997, 38, 8871–8874.
References and notes
1. Sartori, G.; Maggi, R. Advances in Friedel-Crafts Acylation Reactions: Catalytic and
Green Processes; Taylor & Francis: Boca Raton, 2010.
11. Kobayashi, S.; Lwamoto, S. Tetrahedron Lett. 1998, 39, 4697–4700.

208
P. H. Tran et al. / Tetrahedron Letters 55 (2014) 205–208
12. Répichet, S.; Roux, C. L.; Dubac, J.; Desmurs, J.-R. Eur. J. Org. Chem. 1998, 2743–
2746.
13. Kobayashi, S.; Sugiura, M.; Kitagawa, H.; Lam, W. W.-L. Chem. Rev. 2002, 102,
2227–2302.
37. Loupy, A. Microwaves in Organic Synthesis; Wiley-VCH: Weinheim, 2012.
38. Koshima, H.; Kubota, M. Synth. Commun. 2003, 33, 3983–3988.
39. Varma, R. S. Green Chem. Lett. Rev. 2007, 1, 37–45.
40. Su, W.; Li, J.; Jin, C. Heterocycles 2011, 83, 855.
14. Hallett, J. P.; Welton, T. Chem. Rev. 2011, 111, 3508–3576.
15. Martins, M. A.; Frizzo, C. P.; Moreira, D. N.; Zanatta, N.; Bonacorso, H. G. Chem.
Rev. 2008, 108, 2015–2050.
41. Majumder, A.; Gupta, R.; Jain, A. Green Chem. Lett. Rev. 2013, 6, 151–182.
42. Sunitha, P.; Kumar, K. S.; Rao, B. R.; Venkateshwarlu, G. Green. Chem. Lett. Rev.
2008, 1, 179–183.
16. Skouta, R. Green Chem. Lett. Rev. 2009, 2, 121–156.
17. Sawant, A. D.; Raut, D. G.; Darvatkar, N. B.; Salunkhe, M. M. Green Chem. Lett.
Rev. 2011, 4, 41–54.
18. Gorlov, M.; Kloo, L. Dalton Trans. 2008, 2655–2666.
19. Fang, D.; Cheng, J.; Gong, K.; Shi, Q.-R.; Zhou, X.-L.; Liu, Z.-L. J. Fluorine Chem.
2008, 129, 108–111.
20. Aupoix, A.; Pégot, B.; Vo-Thanh, G. Tetrahedron 2010, 66, 1352–1356.
21. Namboodiri, V. V.; Varma, R. S. Tetrahedron Lett. 2002, 43, 5381–5383.
22. Sandhu, J. S. Green Chem. Lett. Rev. 2011, 4, 289–310.
23. Sandhu, J. S. Green Chem. Lett. Rev. 2011, 4, 311–320.
24. Wasserscheid, P.; Welton, T. Ionic Liquids in Synthesis; Wiley-VCH: Weinheim,
2008.
25. Parvulescu, V. I.; Hardacre, C. Chem. Rev. 2007, 107, 2615–2665.
26. Al-Zaydi, K. M.; Nhari, L. M.; Borik, R. M.; Elnagdi, M. H. Green Chem Lett. Rev.
2010, 3, 93–99.
27. Attri, P.; Pal, M. Green Chem. Lett. Rev. 2010, 3, 249–256.
28. Das, S.; Majee, A.; Hajra, A. Green Chem. Lett. Rev. 2011, 4, 349–353.
29. Fauzi, A. H. M.; Amin, N. A. S. Renewable Sustainable Energy Rev. 2012, 16, 5770–
5786.
30. Jain, N.; Kumar, A.; Chauhan, S.; Chauhan, S. M. S. Tetrahedron 2005, 61, 1015–
1060.
31. Ross, J.; Xiao, J. Green Chem. 2002, 4, 129–133.
32. Gmouh, S.; Yang, H.; Vaultier, M. Org. Lett. 2003, 5, 2219–2222.
33. Li, J.; Su, W.; Lin, J.; Chen, M.; Li, J. Synth. Commun. 2005, 35, 1929–1937.
34. Goodrich, P.; Hardacre, C.; Mehdi, H.; Nancarrow, P.; Rooney, D. W.; Thompson,
J. M. Ind. Eng. Chem. Res. 2006, 45, 6640–6647.
43. Dicks, A. P. Green Chem. Lett. Rev. 2009, 2, 87–100.
44. Dicks, A. P. Green Chem. Lett. Rev. 2009, 2, 9–21.
45. Tran, P. H.; Duus, F.; Le, T. N. Tetrahedron Lett. 2012, 53, 222–224.
46. Effenberger, F.; Epple, G. Angew. Chem., Int. Ed. Engl. 1972, 11, 299–300.
47. Roux, C. L.; Dubac, J. Synlett 2002, 181–200.
48. Typical procedure for preparation of the ILs: a mixture of 1-methylimidazole
(0.4105 g, 5 mmol), 1-bromobutane (0.6850 g, 5 mmol) was heated under
microwave irradiation (or conventional heating) in a 10 mL pressurized glass
tube fitted with a Teflon-coated septum at 80 °C for 20 min. Then, LiOTf (0.78 g,
5 mmol) was added and the mixture was irradiated at 100 °C for 20 min. After
cooling, the mixture was diluted with MeCN (5 mL), and after removal of the
precipitated salt LiBr, the filtrate was then filtered through Celite. The crude
product was washed with Et2O and concentrated to give a colorless to pale
yellow liquid (1.382 g, 96% yield). The [BMIM]OTf was dried under reduced
pressure. The purity and authenticity of the ionic liquids were confirmed by 1
and 13C NMR spectroscopy.
H
Typical procedure for the benzoylation reaction in ionic liquids: a glass tube was
filled with Bi(OTf)3 (0.0328 g, 0.05 mmol), [BMIM]OTf (0.1 g), anisole (0.108 g,
1 mmol), and benzoyl chloride (0.281 g, 2 mmol) and reacted at 120 °C for
30 min under microwave activation. After cooling, the mixture was extracted
with Et2O (3 ꢁ 20 mL). The organic layer was decanted, washed with water
(10 mL), aqueous NaHCO3 (2 ꢁ 20 mL), brine (10 mL), and dried over MgSO4.
The solvent was removed using
a rotary evaporator. Conversion was
determined by GC analysis using n-hexadecane as the internal standard. The
isolated yield was determined after purification by flash chromatography (n-
hexane, then 10% EtOAc in n-hexane) to give 4-methoxybenzophenone
(0.1993 g, 94% yield). The purity and authenticity of the product were
confirmed by GC–MS and 1H NMR spectroscopy.
35. Berardi, S.; Conte, V.; Fiorani, G.; Floris, B.; Galloni, P. J. Organomet. Chem. 2008,
693, 3015–3020.
36. Zayed, F.; Greiner, L.; Schulz, P. S.; Lapkin, A.; Leitner, W. Chem. Commun. 2008,
79–81.
The same procedure was carried out under conventional heating method.