Montmorillonite K10: Catalyst for friedel-crafts alkylation of indoles and pyrrole with nitroalkenes under solventless conditions

Article abstract of DOI:10.1080/00397910903219344

Montmorillonite K10 was found to catalyze the Michael addition of indoles or pyrrole with nitroalkenes efficiently under solventless condition. The short reaction time, simple workup, and excellent yields were noteworthy. The green catalyst could be reused for three runs without considerable variation in yield. Copyright

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Montmorillonite K10: Catalyst for
Friedel–Crafts Alkylation of Indoles
and Pyrrole with Nitroalkenes Under
Solventless Conditions
Li-Tao An a b , Li-Li Zhang b , Jian-Ping Zou b & Guang-Liang Zhang b
a Jiangsu Key Laboratory for Chemistry of Low-Dimensional Material,
Department of Chemistry, Huaiyin Teachers College, Huaian,
Jiangsu, China
b Key Laboratory of Organic Synthesis of Jiangsu Province, College
of Chemistry and Chemical Engineering, Suzhou University, Suzhou,
Jiangsu, China
Version of record first published: 08 Jun 2010.
To cite this article: Li-Tao An , Li-Li Zhang , Jian-Ping Zou & Guang-Liang Zhang (2010):
Montmorillonite K10: Catalyst for Friedel–Crafts Alkylation of Indoles and Pyrrole with Nitroalkenes
Under Solventless Conditions, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 40:13, 1978-1984
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Synthetic Communications1, 40: 1978–1984, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903219344
MONTMORILLONITE K10: CATALYST FOR
FRIEDEL–CRAFTS ALKYLATION OF INDOLES
AND PYRROLE WITH NITROALKENES UNDER
SOLVENTLESS CONDITIONS
Li-Tao An,1,2 Li-Li Zhang,2 Jian-Ping Zou,2 and
Guang-Liang Zhang2
1Jiangsu Key Laboratory for Chemistry of Low-Dimensional Material,
Department of Chemistry, Huaiyin Teachers College, Huaian, Jiangsu, China
2Key Laboratory of Organic Synthesis of Jiangsu Province, College of
Chemistry and Chemical Engineering, Suzhou University, Suzhou, Jiangsu,
China
Montmorillonite K10 was found to catalyze the Michael addition of indoles or pyrrole with
nitroalkenes efficiently under solventless condition. The short reaction time, simple workup,
and excellent yields were noteworthy. The green catalyst could be reused for three runs
without considerable variation in yield.
Keywords: Alkylation; heterogenous catalysis; indole; montmorillonite K10; nitroalkene
INTRODUCTION
The Michael reaction has attracted much attention as one of the most
important carbon–carbon (C–C) bond-formation reactions in organic synthesis.
Particularly, it is a completely atom-efficient procedure.[1] Among the Michael
acceptors, nitroalkenes are very attractive, because the nitro group is one of the most
electron-withdrawing groups known.[2] The use of the nitroalkenes as Michael
acceptors opens the way to synthetically useful C–C bond-forming reactions.[3]
The nitro group can be transformed subsequently into a range of different function-
alities.[2] The adducts of indole with nitroalkenes are versatile intermediates for the
synthesis of many biologically active indole derivatives.[4–6] Usually, Michael
addition of arenes to nitroalkenes was catalyzed by Lewis acid or organocatalysts.
Several catalysts, such as Bi(NO3)3,[7] I2,[8] SmI3,[9] CeCl3 ꢀ 7H2O-NaI-SiO2,[10] and
[11]
H3PW12O40
have emerged for the Michael addition. However, to the best of
our knowledge, there are few reports about the reaction catalyzed by solid catalysts
in solvent-free conditions.[10,12,13] Because of the importance of indole derivatives
Received July 6, 2008.
Address correspondence to Jian-Ping Zou, Key Laboratory of Organic Synthesis of Jiangsu
Province, College of Chemistry and Chemical Engineering, Suzhou University, No. 199 Renai Street,
Suzhou 215123, Jiangsu, China. E-mail: jpzou@suda.edu.cn
1978

FRIEDEL–CRAFTS ALKYLATION OF INDOLES AND PYRROLE
1979
and increasing environmental concerns, it is desirable to develop new, metal-free,
efficient, and cost-effective catalysts for the Michael addition. Thus, we attempted
to carry out the reaction on solid mineral supports without any solvent.
On the other hand, montmorillonite clays are known for their acidic properties
and have generated widespread interest in synthetic organic chemistry.[14–17] In parti-
cular, they make the reaction convenient, more economical, and environmentally
benign. Their importance is likely to increase with demanding environmental legis-
lation, public pressure, and the drive toward clean technology. To our knowledge,
there is no report on the Michael addition of nitroalkene to indole catalyzed by
montmorillonite K10. In a continuation of our interest in the development of K10
as catalyst in organic synthesis,[18] we report herein our results on the neat reaction
of nitroalkenes with indoles or pyrrole in the presence of K10.
RESULTS AND DISCUSSION
The Michael reaction of indole (1.0 mmol) and b-nitrostyrene (1.1 mmol) was
performed first at room temperature in the presence of K10; it was very slow, but
3-(20-nitro-10-phenylethyl)-1H-indole 4a was obtained in 87% yield after 10 h
(Table 1, entry 1). When conventional heating was employed, the reaction remark-
ably accelerated (Scheme 1; Table 1, entry 5). It was completed within 15 min in
91% yield. Then, the addition of indole to b-nitrostyrene was chosen as the test reac-
tion to explore the effect of catalyst loading (Scheme 1). As shown in Table 1,
although more catalyst could reduce the reaction time, the yield was not improved
accordingly (Table 1, entry 6). The product was obtained in comparable yield even
if 0.2 g of K10 was used, albeit the reaction time was a bit longer (Table 1, entry 3).
Much less catalyst could not bring favorable results in terms of reaction time and
yield (Table 1, entry 2). Thus, 0.2 g of K10 was sufficient to promote the reaction
of indole and b-nitrostyrene.
To gain more insight into the scope and limitations of the catalyst, different
indoles were reacted with b-nitrostyrenes, and 3-substituted indole derivatives were
obtained exclusively in good to excellent yields (Scheme 2; Table 2, entries 1–3 and
5–13). An exception was that the electrophilic substitution occurred at the 2-position
of 3-methyl indole (Table 2, entry 4). The interesting regioselectivity demonstrates
Table 1. Effect of catalyst loading of K10 on the synthesis of 3-(20-nitro-10-phenylethyl)-
1H-indole (4a)a
Entry
Catalyst loading (g)
Time
Yield (%)b
1
2
3
4
5
6
0.5
0.1
0.2
0.4
0.5
1
10 h
87c
82
94
93
91
87
35 min
20 min
15 min
15 min
10 min
aReaction conditions: indole 1.0 mmol, b-nitrostyrene 1.1 mmol, oil bath heating at 60 ꢁC.
bIsolated yield.
cPerformed at room temperature.

1980
L.-T. AN ET AL.
Scheme 1. The Michael reaction of indole and b-nitrostyrene.
that the 3-position of the indole is the preferred site for electrophilic attack, as
expected[19–21] Moreover, the electronic and steric effects were also examined. The
electronic density of the heterocycle plays an important role in the reaction. For
example, an indole with an electron-withdrawing group, such as 5-bromoindole,
required fairly longer times than those of indoles carrying electron-donating groups,
and the yield was less (Table 2, entry 2). It may be that the bromo atom reduces the
overall nucleophilicity.[10,13] On the other hand, neither electron-donating nor
electron-withdrawing groups in the nitroalkene moiety had significant effect on
the yield and reaction time (Table 2, entries 1, 11 and entries 6, 7).
Furthermore, we found that the hindered substituent near the reaction center
of indole had a negative effect on the reaction. For example, the reaction of 4-
methylindole with b-nitrostyrene needed less time and resulted in greater yield than
that of 4-benzyloxyindole (Table 2, entries 5 and 6). It is noteworthy that the substi-
tution of 3-methylindole occurred at the 2-position, which was probably formed by
initial attack of b-nitrostyrene at C-3, followed by a 1,2-shift in the intermediate cat-
ion.[19] This may explain why the reaction of 3-methylindole required longer time
(Table 2, entry 4). In addition, the reaction of 3-methylindole with b-nitrostyrene
completed smoothly at room temperature in 12 h (Table 2, entry 4), which was much
less than the other catalyst in this case (2 days).[8]
It is known that the a-position of pyrrole is the electron-rich site for Michael
addition.[20,21] As shown in Table 3, pyrrole also readily reacted with several
nitroalkenes under the same reaction conditions in good to excellent yields
(Scheme 2; Table 3, entries 1–5), affording the corresponding 2-((10-aryl-20-nitro)-
ethyl)pyrrole. As shown in Tables 2 and 3, 1,4-bis-(trans-2-nitrovinyl)-benzene
derived from benzenedicarboxaldehyde could also afford the corresponding Michael
adducts (Table 2, entry 9; Table 3, entry 4).
Scheme 2. The Friedel–Crafts alkylation of indoles and pyrrole with nitroalkenes.

FRIEDEL–CRAFTS ALKYLATION OF INDOLES AND PYRROLE
1981
Table 2. Michael addition of indoles to nitroalkenes catalyzed by K10 under solvent-free conditionsa
Entry
1
Indole
Nitroalkene
Product
Product label Time (min) Yield (%)b
4a
4b
20
60
94
83
2
3
4
5
6
4c
4d
4e
4f
20
60 (12 h)c
20
94
86 (88)c
92
60
84
7
8
4g
4h
75
30
81
92
9
4i
30
84
10
11
4j
45
15
85
96
4k
(Continued )

1982
Entry
12
L.-T. AN ET AL.
Table 2. Continued
Indole
Nitroalkene
Product
Product label Time (min) Yield (%)b
4l
60
45
87
91
13
4m
aReaction conditions: indole 1.0 mmol, b-nitrostyrene 1.1 mmol, oil bath heating at 60 ꢁC.
bIsolated yield.
cThe reaction was carried out at room temperature.
Finally, the reusability of the catalyst was investigated. When the reaction
of indole with b-nitrostyrene was completed, the catalyst montmorillonite K10
was filtered off, washed with acetone, dried in an oven at 110 ꢁC for 3 h, and sub-
jected to a second run with the same substrate. After three runs, the recovered
catalyst was satisfactory and did not give considerable variation in yield
(Table 4, entries 2–4).
Table 3. Michael addition of pyrrole to nitroalkenes catalyzed by K10 under solvent-free conditionsa
Entry Pyrrole
Nitroolefin
Product
Product label Time (min) Yield (%)b
1
5a
5b
20
35
93
89
2
3
5c
30
84
4
5
5d
5e
30
35
93
90
aReaction conditions: pyrrole 1.5 mmol, b-nitrostyrene 1.0 mmol, oil bath heating at 60 ꢁC.
bIsolated yield.
cThe reaction was carried out at room temperature.

FRIEDEL–CRAFTS ALKYLATION OF INDOLES AND PYRROLE
1983
Table 4. Reusability of recovered catalyst on the reaction of indole with b-nitrostyrenea
Entry
Run
Reaction time (min)
Yield (%)b
1
2
3
4
1
2
3
4
20
20
20
20
94
92
92
89
aReaction conditions: indole 1.0 mmol, b-nitrostyrene 1.1 mmol, oil bath heating at 60 ꢁC.
bIsolated yield.
CONCLUSION
In summary, we have demonstrated a novel, highly efficient, and environmen-
tally benign protocol for Friedel–Crafts alkylation of indole or pyrrole with several
nitroalkenes under solventless conditions. This procedure offers the advantages such
as high yields, simple workup, green and reusable catalyst, dry reaction and short
reaction time, which makes it an attractive addition to the present methodology
for the synthesis of these important heterocycles.
EXPERIMENTAL
Montmorillonite K10 was purchased from Alfa-Aesar company. It was used as
obtained.
General Procedure for the Synthesis of Compound 4a
Indole (0.12 g, 1 mmol), b-nitrostyrene (0.17 g, 1.1 mmol), and montmorillonite
K10 (0.2 g) were added to a vial. Then the vial was submerged into a hot oil bath
(about 60 ꢁC) for an appropriate time. On completion of the reaction (monitored
by thin-layer chromatography, TLC), the catalyst was filtered off, and the reaction
mixture was washed with acetone. The filtrate was evaporated to dryness prior to
column chromatography (acetone–petroleum ether 1:8 as eluent) to give 0.25 g of
1
pure 4a (yield 94%). The structures of all products were confirmed by H NMR
and 13C NMR.
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China (No. 20772088)
and the Natural Science Foundation of the Jiangsu Higher Education Institutions of
China (No. 08KJD150011) for the financial support.
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