Montmorillonite K10-catalyzed michael addition of indoles to nitroolefins under solvent-free conditions

Article abstract of DOI:10.1080/00397910802632555

Montmorillonite K10 is a very inexpensive and readily available reagent and efficiently catalyzes the Michael addition of indoles to nitroolefins under solvent-free conditions. Reasonable to excellent yields of the desired products were obtained in most c

Full text of DOI:10.1080/00397910802632555

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Montmorillonite K10–Catalyzed
Michael Addition of Indoles to
Nitroolefins Under Solvent-
Free Conditions
Wei-Yi Chen a & Xin-Sheng Li b
a College of Chemistry, Chemical Engineering and
Materials Science , Suzhou University , Suzhou,
China
b Zhejiang Key Laboratory for Reactive Chemistry
on Solid Surfaces, Institute of Physical Chemistry ,
Zhejiang Normal University , Jinhua, China
Published online: 27 Apr 2009.
To cite this article: Wei-Yi Chen & Xin-Sheng Li (2009) Montmorillonite K10–Catalyzed
Michael Addition of Indoles to Nitroolefins Under Solvent-Free Conditions, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:11, 2014-2021, DOI: 10.1080/00397910802632555
To link to this article: http://dx.doi.org/10.1080/00397910802632555
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Synthetic Communications1, 39: 2014–2021, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802632555
Montmorillonite K10–Catalyzed Michael
Addition of Indoles to Nitroolefins Under
Solvent-Free Conditions
Wei-Yi Chen1 and Xin-Sheng Li2
1College of Chemistry, Chemical Engineering and Materials Science,
Suzhou University, Suzhou, China
2Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces,
Institute of Physical Chemistry, Zhejiang Normal University,
Jinhua, China
Abstract: Montmorillonite K10 is a very inexpensive and readily available
reagent and efficiently catalyzes the Michael addition of indoles to nitroolefins
under solvent-free conditions. Reasonable to excellent yields of the desired
products were obtained in most cases.
Keywords: Indole, Michael addition, montmorillonite K10, nitroolefin, solvent-
free
Indole and many of its derivatives are present in many substances
commonly found in nature, as well as in many compounds that show
pharmacological and biological activities.[1–3] Thus, the development of
a new, efficient, selective, and green synthetic method for the preparation
of indole derivatives has attracted much attention in recent years.
Because the 3-position of the indole is the ideal site for electrophilic
attack, 3-substituted indoles are versatile intermediates for the synthesis
of a wide variety of indole derivatives. A variety of methods have been
explored for the Michael addition reaction of indoles with a,b-substituted
Received August 8, 2008.
Address correspondence to Wei-Yi Chen, College of Chemistry, Chemical
Engineering and Materials Science, Suzhou University, Suzhou 215123, China.
E-mail: suzhoucwy@163.com
2014

Michael Addition of Indoles to Nitroolefins
2015
acceptors in the presence of protic or Lewis acids for the preparation of
substituted indoles.[4–15]
Nowadays, the ‘‘greening’’ of global chemical processes has become a
major issue in chemical research.[16] While designing a new methodology
under investigation, chemists always keep in mind the legislation on
environmental friendliness in synthetic pathways and processes to prevent
waste, avoid the use of auxiliary substances (e.g., solvents, separation
agents), and minimize the potential for chemical accidents (e.g., explo-
sion, fire).[17] Among many methods, the use of solid acids such as clay
and zeolites as catalysts in organic reactions (which can minimize waste
emission and the formation of large quantities of environmentally hazar-
dous toxic substances) is one of the most attractive methods to establish
clean chemical processes. Montmorillonite K10, which is very cheap and
commercially available, is an efficient catalyst for CꢀC bond formation
reactions in organic synthesis.[18–21]
Herein, we report the results obtained from our study of Michael
addition reaction of indoles with nitroolefins using montmorillonite
K10 as a very inexpensive, easily available, and efficient catalyst under
solvent-free conditions.
In our initial study, indole was first reacted with b-nitrostyrene in
EtOH at rt for 2 h; the expected product was obtained smoothly in
86% yield in the presence of a catalytic amount of montmorillonite K10
(100 mg=mmol) (Table 1, entry 1). Next, the effect of solvent was investi-
gated; when the reaction was carried out in MeOH, tetrahydrafuran
Table 1. Reaction of indole and b-nitrostyrene at various conditionsa
Entry
Solvent
Temperature
Time (h)
Yield (%)b
1
2
3
4
5
6
EtOH
MeOH
THF
DCM
Toluene
—
rt
rt
rt
rt
rt
rt
2
2.5
3
3
3
0.5
86
84
80
81
79
96
aReaction conditions: indole (0.2 mmol), b-nitrostyrene (0.21 mmol), and mon-
tmorillonite K10 (20 mg).
bIsolated yield.

2016
W.-Y. Chen and X.-S. Li
(THF), dichloromethane (DCM), and toluene, moderate to good yields
could be obtained (Table 1, entries 2–5). However, the reaction could be
completed in a short time and afforded the desired product in excellent
yield when it was carried out under solvent-free conditions (Table 1, entry
6). The acceleration effect was probably attributed to the concentration
effect.[22] To show the strong catalytic effect of montmorillonite K10, the
reaction of indole and b-nitrostyrene in the absence of montmorillonite
K10 was also studied. The desired Michael adduct was not observed even
after a prolonged reaction time (24h). Lesser yield was obtained by
decreasing the amount of added montmorillonite K10. Furthermore, in
all cases, leaving the reaction to proceed longer (>1 h) did not improve
the yield of the reaction. These results showed that montmorillonite
K10 was essential for the success of the Michael addition of indole to
b-nitrostyrene.
Encouraged by the remarkable results obtained with indole and
b-nitrostyrene, a variety of substituted indoles and nitroolefins were
tested using this Michael addition method. The results clearly demon-
strate that montmorillonite K10 is an excellent catalyst for this reaction
under solvent-free conditions (Table 2).
By using substituted indoles (Figure 1), good to excellent yields were
obtained. The substituents did not affect the reactivity of indoles signifi-
cantly (Table 2, entries 2–7). The method is equally effective with nitroolefins
bearing electron-withdrawing or electron-donating substituents on the aro-
matic ring. In all cases, no undesired side products were obtained under these
reaction conditions. The only significant difference in reactivity was
observed for aliphatic nitroolefins, which gave a smaller yield in comparison
with aromatic nitroolefins (Table 2, entries 14, 15). Finally, montmorillonite
K10 could easily be recovered by filtration and recycled for use in subse-
quent reactions with comparable activity; for example, the reaction of indole
and b-nitrostyrene under the present reaction conditions furnished the
desired product in 96, 94, and 95% yields over three cycles.
Figure 1. Structures of indoles.

Michael Addition of Indoles to Nitroolefins
2017
Table 2. Michael addition of indoles to nitroolefins under solvent-free conditionsa
Entry
Indole
R0
Product
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1a
1b
1c
1d
1e
1f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3a
3b
3c
3d
3e
3f
0.5
0.5
1
0.5
0.5
0.5
1
1
0.5
1
96
92
86
94
90
95
85
86
90
83
90
88
92
82
80
1g
1a
1a
1a
1a
1a
1d
1a
1a
3g
3h
3i
4-Me2NC6H4
4-MeOC6H4
2-Naphth
4-ClC6H4
2-Fury
4-MeOC6H4
i-Bu
PhCH2CH2
3j
3k
3l
0.5
0.5
0.5
2
3m
3n
3o
2
aReaction conditions: indole (0.2 mmol), nitroolefin (0.21 mmol), and mon-
tmorillonite K10 (20 mg).
bIsolated yield.
In conclusion, we have demonstrated a very simple, efficient, and
practical method for Michael addition of indoles to nitroolefins catalyzed
by montmorillonite K10. The main features of our new reaction are as
follows: (1) the procedure is operationally simple and can furnish a wide
variety of important 3-substituted indole derivatives in good yields; (2)
the condensation reaction could be performed by exclusively using cheap,
commercially available chemicals; (3) the catalyst could be recycled with
comparable activity; and (4) there was no need for any other additive to
promote the reaction. These results show a novel way to synthesize
important 3-substituted indole derivatives.
EXPERIMENTAL
1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were obtained for
solution in CDCl3 with Me4Si as internal standard on a Varian Mercury

2018
W.-Y. Chen and X.-S. Li
spectrometer. High-resolution mass spectra were obtained using a
GCT-TOF Micromass instrument.
All experiments were operated according to the following general pro-
cedure: Indole 23.4 mg (0.2 mmol), b-nitrostyrene 31.3 mg (0.21 mmol),
and montmorillonite K10 20 mg were mixed and stirred at room tempera-
ture. After the completion of the reaction as monitored by thin-layer
chromatography (TLC), the reaction mixture was filtered and washed
with dichloromethane. The combined organic layers were concentrated
in vacuo and purified by column chromatography on silica gel to furnish
3-(20-nitro-10-phenylethyl)-1H-indole (3a) in 96%.
3-(20-Nitro-10-phenylethyl)-1H-indole (3a)
1H NMR (400 MHz, CDCl3): dH 8.08 (s, 1H), 7.43 (d, J ¼ 7.8 Hz, 1H)
7.31–7.15 (m, 7H), 7.06 (t, J ¼ 7.6 Hz, 1H), 7.00 (d, J ¼ 2.4 Hz, 1H),
5.18 (t, J ¼ 8.1 Hz, 1H), 5.02 (dd, J ¼ 7.6, 12.4 Hz, 1H), 4.90 (dd,
J ¼ 8.6, 12.4 Hz, 1H). 13C NMR (100 MHz, CDCl3): dC 139.2, 136.5,
128.9, 127.8, 127.6, 126.1, 122.7, 121.6, 119.9, 118.9, 114.5, 111.4, 79.6,
41.6. HRMS calcd. for C16H14N2O2: 266.1055; found: 266.1056.
5-Methoxy-3-(20-nitro-10-phenylethyl)-1H-indole (3b)
1H NMR (400 MHz, CDCl3): dH 8.02 (s, 1H), 7.36–7.21 (m, 6H), 6.97 (d,
J ¼ 2.4 Hz, 1H), 6.85 (d, J ¼ 2.4 Hz, 1H), 6.82 (d, J ¼ 1.5 Hz, 1H), 5.14 (t,
J ¼ 8.0 Hz, 1H), 5.03 (dd, J ¼ 12.3, 7.5 Hz, 1H), 4.93 (dd, J ¼ 12.3, 8.1 Hz,
1H), 3.78 (s, 3H). 13C NMR (100 MHz, CDCl3): dC 154.2, 139.3, 131.6,
128.8, 127.6, 127.5, 126.4, 122.3, 114.1, 112.6, 112.1, 100.9, 79.4, 55.9,
41.5. HRMS calcd. for C17H16N2O3: 296.1161; found: 296.1170.
3-(10-(Furano-2-yl)-20-nitroethyl)-1H-indole (3l)
1H NMR (400 MHz, CDCl3): dH 8.09 (s, 1H), 7.54–7.06 (m, 6H), 6.29–
6.14 (m, 2H), 5.26–5.22 (m, 1H), 5.06–4.86 (m, 2H). 13C NMR
(100 MHz, CDCl3): dC 152.5, 142.8, 136.6, 126.1, 123.2, 123.0, 120.4,
119.2, 112.1, 111.9, 110.8, 107.8, 78.3, 36.2. HRMS calcd. for
C14H12N2O3: 256.0848; found: 256.0856.
3-(30-Methyl-10-nitromethyl-butyl)-1H-indole (3n)
1H NMR (400 MHz, CDCl3): dH 8.07 (s, 1H), 7.63 (d, J ¼ 7.9 Hz, 1H),
7.35 (d, J ¼ 8.1 Hz, 1H), 7.24–9.19 (m, 1H), 7.14 (t, J ¼ 7.5 Hz, 1H),

Michael Addition of Indoles to Nitroolefins
2019
7.02 (d, J ¼ 2.3 Hz, 1H), 4.64 (dd, J ¼ 7.5, 11.8 Hz, 1H), 4.58 (dd, J ¼ 7.6,
11.8 Hz, 1H), 3.91–3.84 (m, 1H), 1.95–1.86 (m, 1H), 1.52–1.46 (m, 2H),
0.90 (d, J ¼ 5.4 Hz, 3H), 0.87 (d, J ¼ 5.4 Hz, 3H). 13C NMR (100 MHz,
CDCl3): dC 136.5, 126.1, 122.4, 122.1, 119.8, 118.8, 114.0, 111.6, 81.0,
41.4, 34.5, 25.4, 23.4, 21.6. HRMS calcd. for C14H18N2O2: 246.1368;
found: 246.1362.
3-(10-Nitromethyl-30-phenylpropyl)-1H-indole (3o)
1H NMR (400 MHz, CDCl3): dH 8.04 (s, 1H), 7.60 (d, J ¼ 7.8 Hz, 1H),
7.35 (d, J ¼ 7.8 Hz, 1H), 7.319ꢀ7.12 (m, 5H), 7.06 (d, J ¼ 6.9 Hz, 2H),
6.98 (d, J ¼ 2.2 Hz, 1H), 4.69 ꢀ 4.56 (m, 2H), 3.83ꢀ3.74 (m, 1H), 2.68ꢀ
2.48 (m, 2H), 2.24–2.05 (m, 2H). 13C NMR (100 MHz, CDCl3): dC
141.3, 136.5, 128.5, 128.3, 126.0, 125.9, 122.4, 122.2, 119.7, 118.8,
113.3, 111.6, 80.4, 35.8, 33.9, 33.4. HRMS calcd. for C18H18N2O2:
294.13683; found: 294.13688.
ACKNOWLEDGMENT
We thank Suzhou University for financial support.
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