Microwave-assisted facile and rapid friedel-crafts benzoylation of arenes catalyzed by bismuth trifluoromethanesulfonate

Article abstract of DOI:10.1080/00397911.2014.906042

The catalytic activity of metal triflates was investigated in Friedel-Crafts benzoylation under microwave irradiation. Friedel-Crafts benzoylation with benzoyl chloride of a variety of arenes containing electron-rich and electron-poor rings using bismuth triflate under microwave irradiation is described. This method allows the preparation of aryl ketones under solventless conditions in good to excellent yields and short reaction time. Bismuth triflate was easily recovered and reused five times without significant loss of the catalytic activity.

Full text of DOI:10.1080/00397911.2014.906042

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Microwave-Assisted Facile and Rapid Friedel-Crafts
Benzoylation of Arenes Catalysed by Bismuth
Trifluoromethanesulfonate
Phuong Hoang Tran a , Poul Erik Hansen b , Thuy Thanh Pham a , Vy Thanh Huynh a , Vy Hieu
Huynh a , Thao Du Thi Tran a , Thanh Van Huynh a & Thach Ngoc Le a
a Department of Organic Chemistry, Faculty of Chemistry , University of Science, Vietnam
National University , Hochiminh city , Vietnam
b Department of Science, Systems and Models , Roskilde University , Roskilde DK , Denmark
Accepted author version posted online: 10 Jun 2014.
To cite this article: Phuong Hoang Tran , Poul Erik Hansen , Thuy Thanh Pham , Vy Thanh Huynh , Vy Hieu Huynh , Thao
Du Thi Tran , Thanh Van Huynh & Thach Ngoc Le (2014): Microwave-Assisted Facile and Rapid Friedel-Crafts Benzoylation
of Arenes Catalysed by Bismuth Trifluoromethanesulfonate, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, DOI: 10.1080/00397911.2014.906042
To link to this article: http://dx.doi.org/10.1080/00397911.2014.906042
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Microwave-assisted facile and rapid Friedel-Crafts benzoylation of arenes catalysed
by bismuth trifluoromethanesulfonate
Phuong Hoang Tran1, Poul Erik Hansen2, Thuy Thanh Pham1, Vy Thanh Huynh1, Vy
Hieu Huynh1, Thao Du Thi Tran1, Thanh Van Huynh1, Thach Ngoc Le1
1Department of Organic Chemistry, Faculty of Chemistry, University of Science,
Vietnam National University, Hochiminh city, Vietnam, 2Department of Science,
Systems and Models, Roskilde University, Roskilde DK, Denmark
Corresponding author: Email: lenthach@yahoo.com
Abstract
Metal triflates were investigated the catalytic activity for Friedel-Crafts benzoylation
under microwave irradiation. Among these, bismuth triflate was found to be the most
effective. Friedel-Crafts benzoylation of a variety of arenes containing electron-rich and
electron-poor rings with benzoyl chloride using bismuth triflate under microwave
irradiation is described. This method allows the preparation of aryl ketones under
solventless condition in good to excellent yields and short reaction time. Bismuth triflate
was easily recovered and reused five times without significant loss of the catalytic
activity.
KEYWORDS: Friedel-Crafts benzoylation, bismuth triflate, microwave irradiation, aryl
ketone
INTRODUCTION
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The Friedel-Crafts benzoylation of arenes is a fundamental and useful reaction to
synthesize aryl ketones, which are important precursors in the pharmaceutical and
agrochemical industries.[1] Characteristic for Friedel-Crafts reactions is the use of
moisture sensitive strong Lewis acids in greater than stoichiometric amounts and the
decomposition of the catalysts during work-up.[1] Therefore, the development of
moisture-stable and recyclable catalysts is the most interesting challenge in the Friedel-
Crafts acylation.[2]
Metal triflates were found to be efficient and green catalysts for the Friedel-Crafts
acylation.[3–6] These catalysts are water-tolerant Lewis acids, the metal triflates are used
only catalytic amounts and still active in the coexistence of Lewis bases.[7] The metal
triflates are also easily recovered and reused without significant loss of the catalytic
activity. However, under conventional heating, metal triflates-catalyzed Friedel-Crafts
acylations involve long reaction time[8–11] and a large excess of hazardous solvent.[12–15]
From the viewpoint of the green chemistry, safer solvents (or solventless) and energy
efficiency are required for environmental and economic processes.[16] Microwave
irradiation has been achieved great success in organic synthesis.[17] Microwave irradiation
promotes the organic reactions only a few minutes with minimum energy because the
energy is transferred directly to the reaction mixture.[18] The Friedel-Crafts acylation
under microwave irradiation has been studied intensively in the presence of various
catalysts such as EPZG,[19] aluminum metal powder,[20] amberlite XAD-4TM resin,[21]
zeolite,[22–24] ZnO,[25] metal chloride,[26]... However, metal triflates-catalyzed the Friedel-
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Crafts acylation of arenes under microwave irradiation appeared only in a few reports. In
1999, Dubac and co-workers investigated the acylation of aromatic ethers using
Bi(OTf)3, Sn(OTf)2, Sc(OTf)3, Yb(OTf)3 and Ce(OTf)3 under monomode microwave
irradiation.[27] In 2003, Koshima and Kubota reported the synthesis of
alkylbenzophenones with indium triflate in the absence of solvents using multimode
microwave irradiation.[28] In 2005, Gronnow and co-workers reported the Friedel-Crafts
acetylation of methyl salicylate with copper triflate on silica and other solid acid catalysts
under monomode microwave irradiation.[29] Three years later, in 2008, Berardi and co-
workers investigated the acylation of ferrocene using scandium triflate under both
conventional and monomode microwave heating.[30] More recently, Jie Li and co-workers
reported Yb(OTf)3/TfOH co-catalyzed synthesis of xanthones and thioxanthones by
intramolecular Friedel-Crafts reaction under domestic microwave irradiation.[31]
In our previous work,[32] we examined the Friedel-Crafts acylation of electron rich
aromatic compounds in ionic liquids using bismuth triflate as the catalyst. The aim of the
present paper is to examine the catalytic activity of metal triflates under solventless
conditions. Moreover, microwave-assisted Friedel-Crafts benzoylation allowed the
synthesis of aryl ketones in good to excellent yields with short reaction time and widened
the substrate scope of the reaction.
RESULTS AND DISCUSSION
Initially, anisole was used as the model substrate for the Friedel-Crafts benzoylation with
benzoyl chloride as benzoylating agent (Scheme 1). Microwave irradiation was found
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ineffective in the absence of catalyst. Consequently, bismuth triflate known to be a good
catalyst for Friedel-Crafts acylation was suggested. As shown in Table 1, no product was
obtained without bismuth triflate, but the reaction could afford 39% conversion when
only 1 mol% bismuth triflate catalyst relative to anisole was used. Interestingly, a
conversion of over 99% was achieved using 10 mol% bismuth triflate at 100 °C in 10
min without the need for an inert atmosphere. It is found that lower catalyst loading gave
incomplete conversion. In addition, the decrease of reaction temperature or reaction time
led to diminished conversion (Table 1, entries 6-10). In general, the reaction proceeded
smoothly with major selectivity to p-benzoylanisole (>95%) in short reaction time using
bismuth triflate under monomode CEM microwave irradiation.
The Friedel-Crafts benzoylation of anisole was tested to compare the catalytic activity of
each metal triflate. Fourteen commercially available metal triflates were investigated
using microwave irradiation at 100 °C (Table 2). The best conversion was observed
when bismuth triflate was used as Lewis acid catalyst. Similar conversions were obtained
when La(OTf)3, Pr(OTf)3, Nd(OTf)3, Gd(OTf)3, Dy(OTf)3 and Er(OTf)3 were used as
catalysts. Anisole can be benzoylated in 92% conversion with copper triflate.
Surprisingly, some of the rare-earth metal triflates such as Eu(OTf)3, Tm(OTf)3 and
Yb(OTf)3 are not efficient catalysts under these reaction conditions although these rare-
earth metal triflates possess a strong Lewis acidity to give a better conversion in many
cases. Consequently, bismuth triflate was a chosen for study of Friedel-Crafts acylation
reactions. Although bismuth triflate catalyzed Friedel-Crafts acylation has been
investigated extensively under conventional heating, the combination of bismuth triflate
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and microwave irradiation was only carried out in the Friedel-Crafts benzoylation of
anisole.[27] To the best of our knowledge, this is the first time that MW irradiation is
applied to the Friedel-Crafts benzoylation of various substrates containing both electron-
rich and electron-poor substituents using bismuth triflate as catalyst.
The results with respect to arenes (Scheme 2) are presented in Table 3. The benzoylation
of arenes shows that both electron-poor (entries 8-11) and most of the electron-rich
aromatic compounds are reactive. The benzoylation of unsubstituted aromatics was
observed in benzene, naphthalene and anthracene with 85%, 86% and 64% yield. The
benzoylation product of anthracene was found to decompose under the high temperature
using microwave irradiation, so all attempts to improve yield further were unsuccessful.
Naphthalene is benzoylated in both the α-position and β-position (α/β=60/40). The
benzoylation of arenes with one electron-donating substituent can be achieved in
excellent yields (entries 1-7). Interestingly, electron-deficient halobenzenes were
benzoylated in good yields although higher temperature and longer reaction time were
required. The reactivity of halobenzenes was shown to decrease in the sequence
fluorobenzene > chlorobenzene > bromobenzene > iodobenzene (Table 3).
Fluorobenzene was benzoylated in 85% yield, but iodobenzene gave only 65% yield in
comparison. In the latter case it was previously shown that iodobenzene could
disproportionate in the presence of AlCl3.[33] Good yields have been reported but in
nitrobenzene as solvent.[34] Something similar is also found in the present study in which
benzophenone and 1,4-diiodobenzene could be identified. We observe the same
selectivity as described[8,10,35] under conventional heating. In conventional heating, a
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surplus of the starting material (starting material/acylating reagent = 2/1)[36] was added
whereas the ratio of starting material/benzoyl chloride = 1/1 was used in our method. In
addition, the benzoylated products were obtained in high yields with solid starting
materials under solventless condition (Table 3, entries 12, 15, 21–23).
1,3-Dimethoxybenzene, 1,4-dimethoxybenzene, p-cymene and p-bromotoluene were
benzoylated in moderate yields (entries 14, 15, 16, 18). The yield was slightly increased
in the benzoylation of m-xylene, mesitylene (entries 17, 19). Biphenyl was benzoylated in
75% yield. Fluorene was benzoylated in 72% yield with 99% regioselectivity in the 2-
position. This result can be compared to the more complicated synthesis using 2-
benzyloxypyridine in trifluoroacetic acid.[37] Recycling of bismuth triflate was also
carried out in the benzoylation of anisole under microwave irradiation. Interestingly, after
running for five consecutive cycles at 100 °C in 10 min, yields were only slightly
decreased after each cycle (Table 4).
CONCLUSION
In conclusion, a facile and efficient method for the Friedel-Crafts benzoylation reactions
using bismuth triflate under microwave irradiation has been developed. A variety of
electron-rich and electron-poor aromatic compounds can be benzoylated. If the substrate
is less reactive, a longer reaction time and higher temperature are required. Additionally,
bismuth triflate could be easily recovered and reused up to five times without loss of the
catalytic activity. The further investigation to focus on carboxylic acids as acylating agent
under microwave irradiation is now in progress.
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EXPERIMENTAL
General Procedure For Benzoylation
A 10 mL pressurized glass tube with Teflon-coated septum equipped with a magnetic
stirrer was charged substrate (1 mmol), benzoyl chloride (1 mmol) and metal triflate (0.1
equiv). The tube was sealed and placed into CEM microwave at the temperature for the
appropriate time. The reaction mixture was allowed to cool to the room temperature in
MW oven. After cooling, water (15 mL) was added to the mixture and the product was
extracted by ethyl acetate or dichloromethane given similar results (3 x 15 mL). The
organic layer was decanted, washed with water, aqueous NaHCO3, and brine, and dried
with MgSO4. The solvent was then removed on a rotary evaporator and subjected to flash
chromatography on silica gel (mixture of hexane and ethyl acetate solvent to elute the
product). The fractions containing product were concentrated and dried under vacuum to
yield pure product. All products are known compounds, the purity and identity of all
products were confirmed by GC-MS, 1H and 13C NMR spectroscopy.
Supplemental data for this article can be accessed on the publisher's website.
FUNDING
We are grateful to Nafosted (Grant No. 104.01-2010.34) and Vietnam National
University – Hochiminh city (Grant No. 33/ĐHQG/KHCN) for financial support.
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Table 1. Effects of reaction conditions on benzoylation of anisolea
Entry Amount of catalyst
(mol%)
Reaction time
(min)
Temperature
(°C)
100
Conversion
(%)b
1
2
3
4
5
6
7
8
9
10
0
10
10
10
10
10
10
10
1
0
1
100
39
55
78
>99
67
80
45
72
83
5
100
7
100
10
10
10
10
10
10
100
70
90
100
5
100
8
100
aThe mixture of anisole (1 mmol) and benzoyl chloride (1 mmol) with bismuth triflate
was activated under monomode CEM microwave oven.
bConversion based on anisole was determined by GC-FID using naphthalene as internal
standard.
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Table 2. Benzoylation of anisole catalyzed by metal triflates under microwave irradiation
at 100 °Ca
Entry Metal triflate Time (min) Conversion (%)b
1
LiOTf
20
10
10
10
10
10
20
10
10
10
10
20
20
10
80
2
Cu(OTf)2
La(OTf)3
Ce(OTf)3
Pr(OTf)3
Nd(OTf)3
Eu(OTf)3
Gd(OTf)3
Tb(OTf)3
Dy(OTf)3
Er(OTf)3
Tm(OTf)3
Yb(OTf)3
Bi(OTf)3
92
3
95
4
86
5
91
6
94
7
78
8
93
9
84
10
11
12
13
14
92
91
72
68
>99 (94)c
aReaction conditions: anisole (1 mmol), benzoyl chloride (1 mmol), metal triflate (0.1
mmol).
bConversion based on anisole was determined by GC using naphthalene as internal
standard.
cYield in parenthesis is isolated yield.
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Table 3. Benzoylation of various aromatic compounds catalyzed by bismuth triflate
under microwave irradiationa
Entry Areneb
Temperature Time Product
Yieldc Isomer
(min)
(%)
94
ratiod
(°C)
1
100
10
o-/p-=2/98
2
3
100
120
10
40
92
90
o-/p-=0/100
o-/m-/p-
=19/4/77
o-/m-/p-
4
140
40
92
=10/6/84
o-/p-=7/93
5
6
100
100
20
20
86
78
o-/m-/p-
=8/6/86
7
100
10
88
o-/p-=6/94
8
9
140
140
40
40
86
81
>99
o-/m-/p-
=14/2/84
o-/m-/p-
=14/6/80
10
140
40
76
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11
140
40
65
o-/m-/p-
=17/5/78
>99
12
13
100
100
20
10
75
82
>99
100
100
14
15
100
100
10
10
75
70
16
100
20
60
79/21
17
18
100
100
10
40
86
58
>95
62/38
19
20
100
80
10
40
82
85
100
100
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21
100
20
86
α/β=60:40
22
23
100
60
10
5
72
64
>99
>95
aReaction conditions: arene (1 mmol), benzoyl chloride (1 mmol), bismuth triflate (0.1
mmol).
bLow boiling substrates such as: benzene, toluene and fluorobenzene were performed
under high pressure (100 psi) and substrates with electron withdrawing substituents such
as acetophenone and nitrobenzene were not suitable for this method.
cIsolated yield.
dIsomer ratio was determined by GC-FID.
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Table 4. Recycling of bismuth triflate on benzoylation of anisolea
Cycle
Reaction time (min) Yield (%)b
Temperature (°C)
1
2
3
4
5
100
100
100
100
100
10
10
10
10
10
94
93
92
92
90
aAfter the reaction, bismuth triflate was recovered from aqueous layer by removal of
water under vacuum.
bIsolated yield
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Scheme 1. Benzoylation of anisole.
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Scheme 2. Benzoylation of aromatic compounds.
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