Microwave-assisted Friedel-Crafts acylation of indole with acetic anhydride over tungstophosphoric acid modified Hβ zeolite

Article abstract of DOI:10.1016/j.catcom.2012.09.028

Friedel-Crafts acylation of indole with acetic anhydride has been carried out over zeolites under microwave and conventional heating, respectively. A tungstophosphoric acid modified Hβ (PW-Hβ) zeolite showed better catalytic performance than parent Hβ zeolite due to its higher amount of strongly acidic sites and lower amount of Lewis acid sites, confirmed from NH₃ temperature-programmed desorption (NH₃-TPD) and Fourier Transform Infrared Spectrometer after adsorption of pyridine (Py-IR). Particularly, microwave radiation was found to make this transformation not only more efficient but also selective to 3-acetylindole compared with conventional heating. Furthermore, PW-Hβ has shown good stability in this reaction.

Full text of DOI:10.1016/j.catcom.2012.09.028

Catalysis Communications 29 (2012) 114–117
Contents lists available at SciVerse ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Microwave-assisted Friedel–Crafts acylation of indole with acetic anhydride over
tungstophosphoric acid modified Hβ zeolite
Guoyi Bai ⁎, Tianyu Li, Yonghui Yang, Huanhuan Zhang, Xingwang Lan, Fei Li, Jie Han, Zheng Ma,
Qingzhi Chen, Guofeng Chen
Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, Hebei, 071002, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 May 2012
Received in revised form 31 July 2012
Accepted 25 September 2012
Available online 2 October 2012
Friedel–Crafts acylation of indole with acetic anhydride has been carried out over zeolites under microwave
and conventional heating, respectively. A tungstophosphoric acid modified Hβ (PW-Hβ) zeolite showed
better catalytic performance than parent Hβ zeolite due to its higher amount of strongly acidic sites and
3 3
lower amount of Lewis acid sites, confirmed from NH temperature-programmed desorption (NH -TPD)
and Fourier Transform Infrared Spectrometer after adsorption of pyridine (Py-IR). Particularly, microwave ra-
diation was found to make this transformation not only more efficient but also selective to 3-acetylindole
compared with conventional heating. Furthermore, PW-Hβ has shown good stability in this reaction.
© 2012 Elsevier B.V. All rights reserved.
Keywords:
Microwave
Friedel–Crafts acylation
Zeolite
Acid modified
3-Acetylindole
1
. Introduction
The synthesis of indoles, especially 3-substituted indoles, has attracted
knowledge, few results are available on the Friedel–Crafts acylation
under microwave and over zeolites.
Herein, we report our recent studies on the synthesis of 3-acetylindole
via the Friedel–Crafts acylation of indole with acetic anhydride over
zeolites under microwave and conventional heating, respectively. A
tungstophosphoric acid modified Hβ (PW-Hβ) zeolite was found to
have the best catalytic performance under microwave in this reaction.
The activities of the modified and parent Hβ zeolites were investigated
and were found to correlate well with their structures using a range of
characterizations.
much interest, not only because they are important intermediates and
chiral auxiliaries in organic reactions, but also because they have been
found wide applications in many biological areas including antibacterial,
anticancer, and antibiotic activities [1]. Though a wide variety of 3-
substituted indoles has been prepared by several well-known synthetic
methods such as Friedel–Crafts acylation, Vilsmeier–Haack reaction, and
Grignard reaction [2], these methods are restricted by the use of expen-
sive or toxic reactants and catalysts. There has been great demand to
develop a green method due to environmental and economical concerns.
Solid acid catalysts, such as zeolites, clays, and ionic resins, are impor-
tant in green processes [3,4]. Friedel–Crafts acylations of aromatic com-
pounds such as anisole, 2-methoxynaphthalene, and isobutylbenzene
have been reported over different kinds of zeolites [5,6]. For example,
Derouane et al. have reported an efficient protocol for the synthesis of
p-methoxyacetophenone from the acetylation of anisole by acetic anhy-
dride over Hβ zeolite [6]. Furthermore, acid modifications have been
proven to be important for improving the activity of zeolites [7,8]. On
the other hand, microwave-assisted processes have become popular in
recent years due to the dramatic reduction in reaction time and higher
product yields for a wide range of synthetic transformations, compared
with the traditional heating method [9]. However, to the best of our
2. Experimental
2.1. Catalyst preparation
Tungstophosphoric acid modified Hβ zeolite was prepared by impreg-
nating 4.0 g of the parent Hβ zeolite (Tianjin Chemist Catalyst Co., Ltd.)
into 40 mL of an aqueous solution of 1.0 mol/L tungstophosphoric acid
at 80 °C for 1 h. After that, the samples were filtered, washed with deion-
ized water, dried at 120 °C and then calcined at 500 °C for 4 h. The pre-
pared catalyst was labeled as PW-Hβ. Moreover, oxalic acid, tartaric
acid, and hydrochloric acid modified Hβ zeolites were prepared with
the same method and labeled as OA-Hβ, TA-Hβ, HCl-Hβ, respectively.
2.2. Catalyst characterization
⁎
Corresponding author at: No.180 Wusi East Road, Baoding City, 071002, Hebei, PR
X-ray diffraction (XRD) analysis was carried out on a Bruker D8
China. Tel.: +86 312 5079359; fax: +86 312 5937102.
E-mail address: baiguoyi@hotmail.com (G. Bai).
advance diffractometer using Cu Kα radiation. Bulk compositions were
1566-7367/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.catcom.2012.09.028

G. Bai et al. / Catalysis Communications 29 (2012) 114–117
115
determined by inductively coupled plasma (ICP) on a Thermo VISTA-
MPX spectrometer. BET surface areas and total pore volume of the
catalysts were identified using a Micromeritics Tristar II 3020 surface
reactions [11], we speculated that microwave radiation favors genera-
tion of 3-acetylindole by reducing side reactions as a consequence of
shortening the reaction time. In comparison, the conversion of indole
to and the selectivity for 3-acetylindole are only 76.2% and 73.4% over
pure tungstophosphoric acid under microwave radiation. So there
must be some synergistic effect between tungstophosphoric acid and
Hβ zeolite to cause the PW-Hβ zeolite to have the highest activity in
this reaction. Thus, PW-Hβ zeolite was chosen as the appropriate catalyst
for further investigation and microwave radiation was selected as the
best heating method for this reaction.
3
area and pore analyzer. NH temperature-programmed desorption
(
NH -TPD) experiments were performed on a TP-5000 instrument with
3
a thermal conductivity detector. Fourier Transform Infrared Spectrometer
after adsorption of pyridine (Py-IR) was recorded using a Bruker EQUI-
NOX55 spectrometer coupled to a conventional high vacuum system.
2
.3. Catalyst activity test
Moreover, a service life test was performed under the optimum reac-
tion conditions. It was found that the regenerated catalyst showed stable
catalytic activity in five subsequent cycles. The conversion of indole
remained above 95.0% and the selectivity to 3-acetylindole was up to
78.0% during the whole test. Thus, PW-Hβ zeolite was proven to have
good stability in this reaction.
Friedel–Crafts acylations of indole were carried out by two methods.
In a typical run of conventional heating, 2.5 mmol indole, 5 mmol acetic
anhydride, and 0.05 g zeolite were charged to a 25 mL round flask and
reacted at 120 °C for 3 h with stirring. The microwave-assisted reactions
were performed on a CEM Discover S-class. In a typical run, 2.5 mmol
indole, 5 mmol acetic anhydride, and 0.05 g zeolite were charged to a
A possible mechanism for indole acylation is proposed based on the
GC-MS results and previous literature [12] (Scheme 1). 3-Acetylindole is
the initial product as a result of preferential acetylation of the indole nu-
cleus. Further N-acetylation of 3-acetylindole will yield 1,3-diacetylindole
as the major by-product. On the other hand, if N-acylation occurs first, the
resultant N-acetylindole produced is resistant to further C-acylation
giving N-acetylindole as another possible by-product. Furthermore,
considering the polydentate strong nucleophilic nature of indole, compet-
ing side reactions such as Mannich-type indole oligomerizations, acyla-
tion of oligomerized products, and the less common formation of di-
indolylmethanes or the oxidation products are also possible competing
pathways that could reduce the yield of the desired 3-acetylindole.
Although it is documented that the 3-position of the indole nucleus is
most susceptible to electrophilic attack, the selectivity for 3-acetylindole
was still low under the conventional heating method. In contrast, micro-
wave radiation is shown to favor 3-acetylation of the indole nucleus,
reducing formation of 1,3-diacetylindole both over parent and acid mod-
ified zeolites. Exactly why this should be so is not absolutely clear to us
but we suggest that the increased rate of reaction under microwave
heating conditions simply reduces the amount of side reactions occurring,
as also reported by Kappe et al. [13].
1
0 mL microwave vessel equipped with a standard cap. After the vessel
was sealed, the sample was irradiated at 120 °C for 8 min, which was
plotted in Synergy software applying the power of 150 W or 200 W.
Reaction mixtures were analyzed by a gas chromatography using a
30 m SE-54 capillary column. The product structures were confirmed
1
using GC-MS (Agilent 5975C) and H NMR (Bruker Avance III 600 MHz).
3
. Results and discussion
3
.1. Catalyst selection
Friedel–Crafts acylation of indole leads to 1,3-diacylated material as
the major product, due to the rapid N-acylation of the 3-acylated inter-
mediate, so the selection of a suitable catalyst is crucial to the highly
efficient monoacylation of indole [10]. Therefore, we first chose several
different kinds of parent zeolites to investigate their catalytic activities
in this reaction and the results are listed in Table 1. Among the zeolites
studied, Hβ zeolite was found to show the best catalytic performance.
Noticeably, the reaction rate increased significantly when the reaction
was carried out in the presence of microwave radiation, compared
with conventional heating. With the combination of microwave radia-
tion and Hβ zeolite, the conversion of indole can achieve 77.8% and the
selectivity to 3-acetylindole is 70.7%, but still below our expectation.
Considering the benefits of acid modification, a series of acid modi-
fied Hβ zeolites were prepared and investigated under the same reaction
conditions (Table 2). As can be seen, some acid modified zeolites, espe-
cially a PW-Hβ zeolite, exhibited higher activities than parent Hβ zeolite.
Particularly, the conversion of indole and the selectivity to 3-acetylindole
are 100% and 82.9% over the PW-Hβ zeolite under microwave radiation
at 200 W. Combined with the mechanism of microwave-assisted organic
3.2. Catalyst characterization
XRD patterns of Hβ and PW-Hβ zeolites are shown in Fig. 1. The char-
acteristic diffraction peaks of PW-Hβ zeolite were at about 7.5° and 22.5°,
just like parent Hβ zeolite, indicating that no obvious structural changes
occurred under this acid treatment. Moreover, a characteristic diffraction
3
peak of WO was also detected at about 25° in the curve of PW-Hβ
Table 2
Effect of different acid modified zeolites and heating methods on Friedel–Crafts acylation
Table 1
of indole.
Effect of different zeolites and heating methods on Friedel–Crafts acylation of indole.
Catalyst Heating Conversion Selectivity (%)
method (%)
Catalyst
Heating Conversion Selectivity (%)
method (%)
1
-acetylindole 3-acetylindole 1,3-diacetylindole
1
-
3-
1,3-
HCl-Hβ
OA-Hβ
TA-Hβ
PW-Hβ
A
B
A
B
A
B
A
B
C
A
B
99.8
99.1
97.7
93.6
47.0
98.6
100
100
100
9.6
6.8
7.7
9.0
9.9
12.6
7.8
35.4
9.9
67.9
59.4
76.7
65.7
70.0
68.2
71.7
28.7
82.9
73.4
25.6
15.7
23.9
10.0
17.0
1.4
acetylindole acetylindole diacetylindole
MCM-41
ZSM-5(38)
ZSM-5(50)
HY
A
B
A
B
A
B
A
B
A
B
30.7
35.5
7.7
12.3
17.8
17.1
36.9
43.8
77.8
76.5
15.1
26.4
13.9
27.8
13.1
43.2
14.7
22.9
9.3
64.0
42.4
44.2
30.3
55.9
32.7
66.6
46.7
70.7
54.5
13.4
15.1
16.4
5.0
17.9
11.0
12.2
17.9
14.0
13.7
8.4
17.4
27.0
0.9
13.9
16.5
PW
76.2
93.8
7.6
33.8
Hβ
6.1
Reaction conditions: indole (2.5 mmol), acetic anhydride (5 mmol), catalyst (0.05 g),
120 °C.
Microwave heating 8 min at 150 W.
Conventional heating 3 h.
Microwave heating 8 min at 200 W.
Reaction conditions: indole (2.5 mmol), acetic anhydride (5 mmol), catalyst (0.05 g),
20 °C.
A
1
A
B
Microwave heating 8 min at 150 W.
Conventional heating 3 h.
B
C

116
G. Bai et al. / Catalysis Communications 29 (2012) 114–117
Scheme 1. Proposed side reactions competing with 3-acylation of indole.
zeolite, implying that tungstophosphoric acid has decomposed to WO
3
is assigned to the weakly acidic sites and the peak in the range of
400–600 °C to the strongly acidic sites, in accordance with previous
reports in the literatures [8,15]. It was obvious that the amount of weakly
acidic sites decreased notably, while the amount of strongly acidic sites
increased markedly after tungstophosphoric acid modification. Further-
3
during the calcination process [14] and WO should play an important
role in this reaction.
The bulk Si/Al molar ratios of Hβ and PW-Hβ zeolites were
calculated from ICP results and are listed in Table 3. As can be seen,
the Si/Al molar ratio increased from 12.06 to 26.50 after the
tungstophosphoric acid modification and thus dealumination of the
zeolite occurred during this process, and in turn, offered more active
centers in the modified catalyst. Furthermore, it was also found that
3
more, the total amounts of desorbed NH decreased after this acid mod-
ification. Thus, it is suggested that the lower number of weakly acidic
sites and higher number of strongly acidic sites are responsible for the
effect observed.
Py-IR was carried out to study the effect of tungstophosphoric acid
modification on the Lewis and Brønsted acid properties of the Hβ zeolite.
The spectra of Hβ and PW-Hβ zeolites are shown in Fig. 3. It is clear that
the amount of Lewis acid sites decreased markedly; whereas the amount
of Brønsted acid sites increased slightly after the tungstophosphoric acid
modification, indicating that the tungstophosphoric acid modification
causes different variation on the acid sites. Thus, combined with the
2
2
BET surface area of the zeolite increased from 381 m /g to 440 m /g,
3
3
and the pore volume increased from 0.25 cm /g to 0.28 cm /g after
exposure to tungstophosphoric acid (Table 3), which can be attributed
to dealumination during the modification process. Thus, the better
catalytic performance of PW-Hβ zeolite should be ascribed to the
dealumination of Hβ zeolite caused by tungstophosphoric acid
modification.
NH
There is only one large peak in the range of 150–400 °C in the NH
desorption profile of the parent Hβ zeolite, which could be assigned to
weakly acidic sites. In contrast, there are two peaks in the NH desorp-
3
-TPD profiles of Hβ and PW-Hβ zeolites are presented in Fig. 2.
3
reaction data (Table 2) and NH -TPD results, we suggested that a catalyst
3
having lower amount of Lewis acid sites and higher amount of Brønsted
acid sites is effective for this transformation, as also reported by Selvin et
al. [16].
3
tion profile of the PW-Hβ zeolite. The peak in the range of 150–400 °C
4
. Conclusions
In conclusion, a simple, efficient and eco-friendly protocol for the
synthesis of 3-acetylindole has been reported in this paper. A
PW-Hβ zeolite was found to have the best activity and selectivity
due to the synergistic effect between tungstophosphoric acid and Hβ
zeolite. Particularly, the reaction rate of this microwave-assisted
method is 50 to 75 times faster than that of the conventional heating
a
wo3
b
2
4.0
24.5
25.0
25.5
26.0
3
method using AlCl as a catalyst [17]. Thus, due to its good activity
and stability, this green process involving a PW-Hβ zeolite is poten-
tially applicable to large-scale reactions for the selective synthesis of
a
3
-acetylindole.
Table 3
Morphological properties of zeolites.
b
Catalyst
Bulk
Si/Al
BET surface area
(m /g)
Pore volume
(cm /g)
Pore size
(nm)
a
2
3
0
10
20
30
40
50
60
Hβ
PW-Hβ
12.06
26.50
381
440
0.25
0.28
26.3
25.9
2
Theta (degree)
a
Fig. 1. XRD patterns of Hβ (a) and PW-Hβ (b) zeolites.
Calculated from the ICP results.

G. Bai et al. / Catalysis Communications 29 (2012) 114–117
117
Foundation of China (20806018) and the Natural Science Foundation of
Hebei Province (B2011201017) are gratefully acknowledged.
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Acknowledgments
The authors thank Professor L. M. Harwood and Professor G. Ma for
their kind assistance. Financial support by the National Natural Science