Boron trifluoride supported on nano-SiO2: An efficient and reusable heterogeneous catalyst for the synthesis of bis(indolyl)methanes and oxindole derivatives

Article abstract of DOI:10.1007/s11164-013-1021-7

Boron trifluoride supported on nano-SiO₂ was used as an efficient and heterogeneous catalyst for the electrophilic substitution reaction of indole with various aromatic aldehydes and isatins in methanol to afford the corresponding bis(indolyl)m

Full text of DOI:10.1007/s11164-013-1021-7

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Res Chem Intermed
DOI 10.1007/s11164-013-1021-7
Boron trifluoride supported on nano-SiO2: an efficient
and reusable heterogeneous catalyst for the synthesis
of bis(indolyl)methanes and oxindole derivatives
Ali Saffar-Teluri
Received: 21 November 2012 / Accepted: 3 January 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract Boron trifluoride supported on nano-SiO2 was used as an efficient and
heterogeneous catalyst for the electrophilic substitution reaction of indole with
various aromatic aldehydes and isatins in methanol to afford the corresponding
bis(indolyl)methanes and oxindole derivatives in high yields at room temperature
and under reflux conditions, respectively. The catalyst can be reused several times
without loss of its catalytic activity.
Keywords Boron trifluoride Á Heterogeneous catalyst Á Bis(indolyl)methanes Á
Oxindole
Introduction
Boron trifluoride-etherate (BF3.OEt2) as a homogeneous catalyst is widely used in
many organic reactions [1]. Heterogenization of the BF3 catalyst with solid support
has attracted much attention in organic synthesis owing to its easy work-up
procedure, easy filtration, and minimization of cost and waste generation, especially
during BF3 recovery, due to its reuse and recycling [2].
The synthesis of oxindoles and their derivatives has been of considerable interest
because a large number of natural products and drugs contain this heterocyclic unit
[3]. Oxindoles are used as antibacterial, antiflammatory, and laxatives [4, 5].
Furthermore, these heterocyclic compounds have been recently isolated from plants
[6].
Bis(indolyl)methanes are important intermediates in organic synthesis and
exhibit various physiological properties and pharmacological activities [7], such as
A. Saffar-Teluri (&)
Faculty of Material Science & Engineering, Najafabad Branch, Islamic Azad University,
P. O. Box 85141-43131, Najafabad, Iran
e-mail: a.saffar.t@iaun.ac.ir
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A. Saffar-Teluri
useful estrogen metabolism promoter [8], inhibitory of human prostate cancer cells
[9], and radical scavenging activity associated with cancer cells [10]. A number of
natural products containing bis(indolyl)methane moieties have been also isolated
from marine sources [11].
Numerous methods have been reported for the synthesis of these compounds.
Amongst them, the acid-catalyzed electrophilic substitution reaction of indole with
carbonyl compounds is one of the straightforward approaches for the synthesis of
oxindole derivatives and bis(indolyl)methanes. A variety of reagents such as protic
acids [12], Lewis acids [13], heterogeneous acids [14, 15], and ionic liquids [16]
have been employed to achieve these transformations. However, there are still some
drawbacks in these catalytic systems such as the requirement for a stiochiometric
amount of Lewis acid, an expensive and toxic catalyst, long reaction times, harsh
acidic conditions, and in some cases low yields of products and large amounts of
catalyst.
In continuation of our interest in the synthesis of heterocyclic compounds and the
use of heterogeneous catalysts in organic reactions [17–19], we used boron
trifluoride supported on nano-SiO2 (nano-SiO2–BF3-CH3OH2?) as an efficient and
reusable heterogeneous catalyst for the synthesis of oxindole derivatives (Scheme 1)
and bis(indolyl)methanes (Scheme 2) at room temperature and under reflux
conditions.
Experimental
All materials were of commercial reagent grade. Aldehydes, boron trifluoride-
etherate, isatin, and indole were obtained from Merck. All the products are known
compounds and were identified by comparison of their physical and spectroscopic
data with those of authentic samples.
Catalyst preparation
The catalyst was synthesized by the reported procedure [2]. In a typical procedure, a
mixture of BF3.OEt2 (3.42 g, 24 mmol) and preheated silica gel (3.0 g) in MeOH
1
R
N
2
R
O
2
R
_
O
+
Nano SiO2-BF3 CH3OH2
+
O
CH3OH / reflux
N
N
N
H
N
1
H
R
H
3a-f
1
2
Scheme 1 Nano-SiO2–BF3-CH3OH2?-catalyzed synthesis of oxindole derivatives
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Boron trifluoride supported on nano-SiO2
3
R
4
R
3
_
R
+
Nano SiO2-BF3 CH3OH2
CHO
+
CH3OH / r.t.
N
N
H
N
4
R
H
H
1
4
5a-j
Scheme 2 Nano-SiO2–BF3-CH3OH2?-catalyzed synthesis of bis(indolyl)methanes
b
4000 3600 3200 2800 2400 2000 1600 1200
800
400
Wavenumber (cm-1)
a
?
Fig. 1 FT-IR spectra of a SiO2, b nano-SiO2–BF3-CH3OH2
(20 ml) was prepared and stirred for 3 h at room temperature. The slurry was dried
slowly at 40 °C. The obtained solid was dried in an ambient temperature for 2 h.
For identification of the structure of catalyst, we studied FT-IR spectra of SiO2
?
and nano-SiO2–BF3-CH3OH2 (Fig 1). In both of them, the absorption bands for
Si–OH and Si–O–Si appeared at 800 cm-1 and 1,100 cm-1, respectively. In the
nano-SiO2–BF3-CH3OH2? spectrum, the absorption of the B–F and B–O bands was
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A. Saffar-Teluri
observed in 700, 900, and 1,520 cm-1, respectively. These observations clearly
indicated that the catalyst had been synthesized.
General procedure for the synthesis of oxindole derivatives
In order to synthezise oxindole derivatives, a round-bottomed flask (25 ml) was
equipped with a condenser and a magnetic stirrer, and a mixture of indole 1
(1 mmol), isatin 2 (0.5 mmol), catalyst (0.3 g), and methanol (10 ml) was stirred
under reflux conditions for the appropriate time (Table 1). The progress of the
reaction was monitored by TLC (eluent: ethyl acetate/n-hexane, 1/1). After the
reaction was completed, the mixture was filtrated, and the methanol was removed
under reduced pressure. The resulting solid was recrystallized from ethanol to afford
the pure product.
General procedure for the synthesis of bis(indolyl)methanes
For preparation of bis(indolyl)methanes, a mixture of indole 1 (1 mmol), aldehyde 4
(0.5 mmol), catalyst (0.3 g), and methanol (10 ml) was stirred at room temperature
for the appropriate time (Table 2). The progress of the reaction was monitored by
TLC (eluent: ethyl acetate/n-hexane, 1/3). After the reaction was completed, the
mixture was filtrated, and the methanol was removed under reduced pressure. The
resulting solid was recrystallized from ethanol to afford the pure product.
Results and discussion
For optimizing the reaction conditions, we conducted the reaction of isatin 2a with
indole 1 in various solvents such as CH3OH, CH3CH2OH, H2O, CH3CN, CH2Cl2,
CHCl3, and CCl4. The results showed that the higher product yield was obtained in
methanol and then all reactions were carried out in methanol. Then, the effect of the
?
Table 1 nano-SiO2–BF3-CH3OH2 catalyzed the reaction of indole with isatins
Entry
3
R1
R2
Time (h)a
Yield (%)b
m.p. (°C)
Lit. m.p. (°C)
1
2
3
4
5
6
a
a
b
c
d
e
f
H
H
0.33
0.25
0.17
0.45
0.45
0.50
95, 95, 93, 92, 92c
313–5
310–2
297–9
321–3
293–5
288–9
312–4 [20]
310–1 [21]
298–9 [21]
321–2 [21]
292–3 [20]
288–9 [21]
H
Br
NO2
Me
H
94
93
95
96
97
H
H
Me
PhCH2
H
Reaction times under reflux
Isolated yield under reflux
The reusability and recycling of nano-SiO2–BF3-CH3OH2 in the synthesis of compound 3a
b
c
?
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