Silica sulfuric acid-catalyzed Friedel-Crafts alkylation of indoles with nitro olefins

Article abstract of DOI:10.1080/00397910701650815

The 1,4-conjugate addition of indoles to nitro olefins was efficiently carried out using an environmentally benign catalyst, silica sulfuric acid, at ambient temperature. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701650815

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Silica Sulfuric Acid–Catalyzed Friedel–Crafts
Alkylation of Indoles with Nitro Olefins
a
a
a
G. Sri Hari , M. Nagaraju & M. Marthanda Murthy
a
Organic Chemistry Division‐II, Indian Institute of Chemical Technology,
Hyderabad, India
Published online: 25 Jan 2008.
To cite this article: G. Sri Hari , M. Nagaraju & M. Marthanda Murthy (2007): Silica Sulfuric Acid–Catalyzed
Friedel–Crafts Alkylation of Indoles with Nitro Olefins, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 38:1, 100-105
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Synthetic Communications , 38: 100–105, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701650815
Silica Sulfuric Acid–Catalyzed Friedel–
Crafts Alkylation of Indoles with Nitro
Olefins
G. Sri Hari, M. Nagaraju, and M. Marthanda Murthy
Organic Chemistry Division-II, Indian Institute of Chemical Technology,
Hyderabad, India
Abstract: The 1,4-conjugate addition of indoles to nitro olefins was efficiently carried
out using an environmentally benign catalyst, silica sulfuric acid, at ambient
temperature.
Keywords: C-C bond formation, conjugate addition reactions, indole, nitro olefins,
silica sulfuric acid
INTRODUCTION
Indoles and their derivatives occur in nature and have a variety of biological
[
1]
activities. Because of this, indoles and their derivatives have great import-
ance in synthetic organic chemistry. The 3-position of indole is the
preferred site for the electrophillic substitution reaction; 3-alkyl or acyl
indoles are versatile intermediates for the synthesis of a wide range of
[
2]
indole derivatives. In recent years, catalytic Michael-type additions of
nucleophiles to nitro olefins have emerged as a powerful method for the
[3]
formation of new C-C bonds in organic synthesis. Nitro olefins are very
attractive Michael acceptors because the nitro group is the strongest
[4]
electron-withdrawing group known and has been widely used in organic
Received in the USA May 15, 2007
IICT Communication No. 070512
Address correspondence to M. Marthanda Murthy, Organic Chemistry Division-II,
Indian Institute of Chemical Technology, Hyderabad, India. E-mail: marthanda52@
yahoo.com
1
00

Alkylation of Indoles
101
Scheme 1.
[
5]
[6]
synthesis. Among the strongest Michael acceptors, nitro olefins are also
attractive because the nitro group can served as a masked functionality.
Recently, silica sulfuric acid is a powerful and an efficient solid acid for
[
7]
various chemical transformations. Silica sulfuric acid was prepared by
treating silica gel with chloro sulfonic acid in which sulfuric acid immobilized
[8]
on the surface of silica gel via a covalent bond (Scheme 1). The acid-
[9]
catalyzed conjugate addition of indoles has been reported, where many pro-
cedures involve careful control of acidity to prevent side reactions such as
dimerization or polymerization, require long reaction times, elevated tempera-
tures, and expensive reagents, and result in low yields. To over come these
drawbacks, we describe the remarkable catalytic activity of silica sulfuric
acid in the conjugate addition of indoles to nitro olefins.
RESULTS AND DISCUSSION
General treatment of the indole with the trans b-nitro styrene (Scheme 2) in
the presence of a catalytic amount of the silica sulfuric acid in dichloro
ethane gave the corresponding 3-alkylated products in high yields (71–93%)
at ambient temperature under optimal reaction conditions. A variety of nitro
olefins and indoles were investigated, and the results are summarized in
Table 1. Most nitro olefins reacted with indole and its derivatives to
produce alkylated indoles in good yields. The reactions were clean, and the
products were obtained in high yields without the formation of any side
products such as dimers or trimers. This procedure does not require any
promoters, activators, or anhydrous conditions. All the products were
1
isolated and characterized by H NMR, mass, and IR spectroscopy.
Scheme 2.

1
02
G. S. Hari, M. Nagaraju, and M. M. Murthy
Table 1. Silica sulfuric acid–catalyzed addition of indoles with nitro olefins
a
b
Entry Nucleophile
Electrophile
Product
Time (h) Yield (%)
a
2.5
2.2
85
b
c
84
3.0
2.5
80
93
d
e
f
2.5
3.0
78
79
g
3.0
78
h
i
3.5
4.0
75
72
j
3.0
75
(
continued)

Alkylation of Indoles
103
Table 1. Continued
a
b
Entry Nucleophile
Electrophile
Product
Time (h) Yield (%)
k
l
3.0
75
3.5
78
m
n
2.5
2.5
3.0
75
71
72
o
a
1
All products were characterized by IR, H NMR, and mass spectroscopy.
Isolated and unoptimized yields.
b
CONCLUSION
In summary, we have demonstrated that silica sulfuric acid is a superior acid
catalyst for the alkylation of indoles with nitro olefins. This procedure has the
advantages of mild reaction conditions, high yields of products, short reaction
times, and simple experimental/product-isolation techniques, which make it a
useful and attractive process for the synthesis of alkylated indole derivatives.
General Procedure for the Addition of Indoles to Nitro Olefins
A mixture of indole 1 (5 mmol), nitro olefin 2 (5 mmol), and silica sulfuric
acid (catalytic, 30 mg) in dichloro ethane (2 ml) was stirred at room tempera-
ture for an appropriate time (Table 1). After complete conversion as indicated
by thin-layer chromatography (TLC), the compound was purified by column
chromatography on silica gel (hexane–ethyl acetate 9:1) to afford the pure
products 3 (Table 1).

1
04
Selected Data for Compounds
Compound 3b: Solid. Mp: 124–1268C; IR (KBr, cm ): 3402, 2931, 1591,
G. S. Hari, M. Nagaraju, and M. M. Murthy
2
1
1
1
550, 1507, 1459, 1424, 1125, 1003, 745; H NMR (200 MHz, CDCl ):
3
d ¼ 10.45 (1H, s), 7.48 (1H, d), 7.31 (1H, d), 7.15–6.95 (2H, m), 6.80
þ
(
2H, s), 5.30–5.10 (3H, m), 3.78 (9H, s), 2.50 (3H, m); LC-MS m/z: 370 (M ).
2
1
Compound 3e: Solid. Mp: 100–1028C; IR (KBr, cm ): 3408, 2918, 1550,
1
1
458, 1429, 1377, 1301, 744, 700; H NMR (300 MHz, CDCl ): d ¼ 7.75
3
(
1H, s), 7.30–6.90 (9H, m), 5.18–5.03 (3H, m), 2.25 (3H, s); EI-MS m/z:
þ
280 (M ).
2
Compound 3h: Pale brown viscous oil. IR (neat, cm ): 3406, 2919, 1552,
1
1
502, 1460, 1429, 1378, 1302, 1189, 1142, 1032, 742; H NMR (200 MHz,
1
CDCl ): d ¼ 7.85 (1H, s), 7.38–6.95 (4H, m), 6.94–6.92 (1H, d), 6.28–
3
6.22 (1H, m), 6.05–6.01 (1H, d), 5.18–4.85 (3H, m), 2.25 (3H, s); EI-MS
m/z: 270 (M ).
þ
2
Compound 3k: Pale brown viscous oil. IR (neat, cm ): 3399, 2922, 1617,
1
1
1
555, 1458, 1218, 1110, 745; H NMR (300 MHz, CDCl ): d ¼ 7.80 (1H, s),
3
7.38–6.78 (8H, m), 5.12–4.96 (3H, m), 2.30 (3H, s), 2.24 (3H, s); LC-MS
m/z: 294 (M ).
þ
21
Compound 3n: Solid. Mp: 110–1118C; IR (KBr, cm ): 3406, 2924, 1612,
1
550, 1510, 1460, 1377, 1247, 1113, 1029, 745; H NMR (300 MHz,
1
CDCl ): d ¼ 7.78 (1H, s), 7.32–7.14 (4H, m), 7.08–6.94 (2H, m), 6.78–6.75
3
þ
(
2H, d), 5.18–4.95 (3H, m), 3.75 (3H, s), 2.37 (3H, s); LC-MS m/z: 310 (M ).
ACKNOWLEDGMENT
The authors thank Director J. S. Yadav and V. V. Narayana Reddy, head of the
division, for their constant support throughout this work.
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