Synthesis of Some Novel 3-Substituted Indole Derivatives Using Polyamine Functionalized Heterogeneous Catalyst

Article abstract of DOI:10.1002/jhet.2265

In present work, we have described the use of polyamine solid supported GN3 as catalyst in organic transformations using 1H-indole-3-carbaldehyde. To the best of our knowledge, reports for the synthesis of chromen substituted at 3C position of indole are extremely rare in the literature. The polyamine functionalized immobilized silica (GN3) was found to be an excellent catalyst for synthesis of novel 2-amino-4-(1H-indol-3-yl)-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile derivatives and Knoevenagel condensation. Catalyst GN3 was able to furnish excellent yield for a wide range of products. Moreover, the catalyst was reusable and reused for several times without loss of its catalytic activity.

Full text of DOI:10.1002/jhet.2265

Month 2014
Synthesis of Some Novel 3-Substituted Indole Derivatives Using
Polyamine Functionalized Heterogeneous Catalyst
a
a
a
a
a
Rupali L. Magar, Prashant B. Thorat, Jagdish L. Waware, Rameshwar R. More, Usha A. Solanke,
b
a
Bhagwan R. Patil, and Rajendra P. Pawar *
a
Deogiri College, Aurangabad, 431005, MS, India
b
Sharda Mahavidyalaya, Parbhani, 431401, MS, India
*
E-mail: rppawar@yahoo.com; roopma08@gmail.com
Additional Supporting Information may be found in the online version of this article.
Received February 12, 2014
DOI 10.1002/jhet.2265
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
NH2
OH
O
X
CHO
R1+
Catalyst GN3
Water
O
O
X
+
N
CN
RN
O
R
O
R1
94-87%
O
Catalyst GN3 OHC
Catalyst GN3
Water
Water
R1
X
NR
N
RN
O
O
OH
NC
X
CN
R
R1
R1
9
6-93%
96-87%
O
O
In present work, we have described the use of polyamine solid supported GN3 as catalyst in organic
transformations using 1H-indole-3-carbaldehyde. To the best of our knowledge, reports for the synthesis
of chromen substituted at 3C position of indole are extremely rare in the literature. The polyamine function-
alized immobilized silica (GN3) was found to be an excellent catalyst for synthesis of novel 2-amino-4-
(
1H-indol-3-yl)-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile derivatives and Knoevenagel
condensation. Catalyst GN3 was able to furnish excellent yield for a wide range of products. Moreover,
the catalyst was reusable and reused for several times without loss of its catalytic activity.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
catalyst recovery that avoids tedious processes of catalyst
separation, and most importantly can be reused in reaction
cycle. The application of solid acidic and basic catalysts in
clean technologies and sustainable chemistry is a “green”
alternative for chemical processes.
Indole nucleus is the basic skeleton, frequently found in
natural products, pharmaceuticals, functional materials, and
agrochemicals [9]. Owing to the diverse biological proper-
ties of indole derivatives, the synthesis of these molecules
has accomplished great consideration [10]. Particularly,
For the last few years, ordered mesoporous silicas have
been studied to a great extent as catalysts, catalyst sup-
ports, adsorbents, and containers for cluster/nanowire
growth [1]. Owing to their well-ordered structure, silica
materials have attracted great attention of synthetic chem-
ists to form heterogeneous catalyst by tethering active
organic or inorganic homogeneous material [2]. Recently,
some of the fundamental organic transformations such as
Knoevenagel condensations [3] and the aldol condensa-
tions [4–6] were reported to be catalyzed by mono
aminopropyl functionalized mesoporous silica materials
as base material. Moreover, reports of the catalysts also
exist in which organic material is grafted on ordered silica
surface and metal is trapped in these organic compounds
by chelation, which makes an effective catalyst system
for organic transformation [7]. Recently, we have reported
silica supported organo-amine catalysts, which was
designated as GN3, and applied it in the synthesis of
oxygen heterocycles (Fig. 1) [8].
3
-substituted indole derivatives, which are important build-
ing blocks used for the synthesis of biologically important
compounds. Some of the 3-substituted indole derivatives
have displayed significant cytotoxicity against various
human cancer cell lines [11].
Chromene derivatives constitute a class of heterocycles
known for their applications as bioactive compounds
[12]. The subclass of chromeno indoles, which are formed
by merging indole and chromen, has been also identified as
biologically active compounds [13]. Some of the chromeno
indole derivatives exhibit the antiproliferative activity [14].
Owing to the useful biological properties of both 3-
substituted indoles and chromene derivatives and in
The use of such heterogeneous catalysts offers several
advantages in prospect of green chemistry as these cata-
lysts effectively work in aqueous medium, has simple
©
2014 HeteroCorporation

R. L. Magar, P. B. Thorat, J. L. Waware, R. R. More, U. A. Solanke, B. R. Patil, and R. P. Pawar Vol 000
Conversion
90
Selectivity
9
6
97
1
9
00
96
97
100
90
80
70
60
50
40
30
8
6
0
0
0
0
0
0
0
82
8
7
93
8
7
6
5
4
3
86
71
41
35
Figure 1. Structure of solid supported basic catalyst GN3.
25
45
55
65
75
85
Temperature °C
Figure 2. Influence of temperature on synthesis of 4a. Reaction condi-
tions: 1H-indole-3-carbaldehyde : 4-hydroxy coumarine : malanonitrile
continuation of our work on the synthesis of heterocyclic com-
pound using heterogeneous catalysts [15] in the present study,
we have coupled chromen molecule at 3C position of indole
to enhance biological properties of the combined resultant
structure. Herein, we report the use of heterogeneous poly-
amine-based solid catalyst in the preparation of rarely synthe-
sized 2-amino-4-(1H-indol-3-yl)-5-oxo-4,5-dihydropyrano
(1:1:1); catalyst GN3 0.03 g; 3 h.
catalyst GN3, and the obtained results are plotted in
Figure 3. The reaction products were collected from time
to time and analyzed by gas chromatography (GC). As it
can be seen from Figure 3, the percentage of conversion
of aldehyde and the selectivity of product 4a showed
appreciable variation with reaction time. Almost all
aldehyde was converted to the product after 30 min of
reaction time. But the desired product selectivity plot was
gradually increasing. When reaction time was reached to
1 h, product 4a formation was high with excellent 98%
selectivity. When reaction was carried out for longer
time, decrease in the selectivity was observed, signifying
that an extended reaction time leads to more byproducts.
[3,2-c]chromene-3-carbonitrile derivatives.
In our initial experiments toward the development of
novel methodologies under green chemical approaches,
we selected synthesis of 2-amino-4-(1H-indol-3-yl)-5-
oxo-4, 5-dihydropyrano[3,2-c]chromene-3-carbonitrile 4a
(Scheme 1). The condensation reaction of 1H-indole-3-
carbaldehyde, 4-hydroxy coumarine, and malanonitrile
using catalyst GN3 in water was studied to obtain 4a as a
model compound. The application of base material GN3
as catalyst to this condensation reaction in a pure water
was studied under various parameters.
Effect of 1H-indole-3-carbaldehyde to 4-hydroxy coumarine
and malanonitrile.
The molar ratio of indole aldehyde
Effect of temperature on the reaction.
Temperature
effect of reaction was studied to establish the optimum
temperature for this reaction. Condensation was performed
in temperature range of room temperature to 80°C using
solid GN3 catalyst in water solvent for 3 h. Figure 2 shows
that the temperature did not show strong effect on
conversion of aldehyde; however, selectivity for compound
proved to be a vital parameter in the reaction. In order to
Conversion
95 95
98
Selectivity
98 98
1
00
100
90
80
70
60
50
40
30
9
0
9
8
7
0
0
0
8
5
4
a radically varies with the temperature. At near to room
88
84
7
3
temperature conditions, although conversion of indole
aldehyde was high, the selectivity for product 4a was very
low owing to the formation of Knoevenagel adducts. The
highest selectivity 97% for the 4a was observed at 60°C
where 96% of aldehyde was converted principally to the
product yield (93%). Further elevation in temperature
considerably decreased selectivity of product 4a, which
indicates that more side reaction occurs at high temperatures.
60
50
40
30
5
7
3
4
1
5
30 45 60 75 90
Reaction time (min)
Figure 3. Influence of reaction time on synthesis of 4a; reaction condi-
tions: 1H-indole-3-carbaldehyde : 4-hydroxy coumarine : malanonitrile
Effect of reaction time.
Variation in product and
(1:1:1); catalyst GN3, 60°C; catalytic loading 0.03 g.
conversion of aldehyde with time were studied using
Scheme 1. Synthesis of 2-amino-4-(1H-indol-3-yl)-5-oxo-4, 5-dihydropyrano[3,2-c]chromene-3-carbonitrile (4a).
NH
2
CHO
OH
CN
CN
CN
O
O
Catalyst GN3
+
+
N
H
O
O
NH
O
1a
2
3a
4a
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis of Some Novel 3-Substituted Indole Derivatives Using Polyamine
Functionalized Heterogeneous Catalyst
obtain high selectivity for product 4a, it was very necessary
to pick suitable molar ratio of aldehyde (Fig. 4). A
decreasing trend was observed in plot of effect of indole
aldehyde concentration. At lower concentration, high
conversion of indole aldehyde was seen with high
selectivity. The reaction also yielded unreacted 4-hydroxy
coumarine and malanonitrile as byproducts. At equimolar
concentration of indole aldehyde, conversion and
selectivity were highest at 98%. When concentration was
increased further, selectivity dropped drastically and
reached 26% at highest molar ratio.
The results obtained from aforementioned studies dem-
onstrated that catalyst GN3 was the most efficient basic
catalyst for the Knoevenagel condensation and the synthe-
sis of chromeno indoles under different temperature condi-
tions in aqueous medium. The best optimum conditions for
both reactions were obtained at 0.03 g catalyst loading in
water solvent. The Knoevenagel condensation worked well
at room temperature to provide excellent yields of corre-
sponding products, whereas for the synthesis of chromeno
indoles, the temperature was raised to 60°C for 60 min,
which offered superior 93% yield of desired product 4a
with greatest selectivity 98% with respect to indole
aldehyde.
(Scheme 2). The catalyst was able to draw excellent yields
for all desired products with maximum selectivity.
The catalytic scope of the catalyst GN3 was also
extended to the Knoevenagel condensation between 1H-
indole-3-carbaldehyde and 4-hydroxy coumarine or active
methylene compound at room temperature (Table 2). The
base promoted reaction of 1H-indole-3-carbaldehyde with
malonic esters offered 3-substituted indoles as products in
excellent yields (Scheme 3).
Based on obtained results and literature support [8,16],
the mechanism of reaction is drawn in Scheme 4. The
mechanism for one pot reaction is supposed to start with
the Knoevenagel condensation in situ. Step I shows the
Knoevenagel condensation, and the reaction starts with
the removal of hydrogen atom from C–H active com-
pounds with the help of catalysts GN3 to generate nucleo-
phile X or Y. Owing to the bendable [17] aminopropyl
chain in the catalyst GN3, removed proton was assembled
between nitrogen atoms, which reinforce the basicity of the
catalyst GN3. Subsequently, these nucleophiles on reaction
with 1H-indole carboxaldehyde form Knoevenagel product
5 or 6. In the second step, reaction takes place by two
pathways, A and B. In the reaction pathway A, compound
5 reacts with anion Y to give intermediate III. Similarly, in
pathway B, compound 6 after reaction with anion X
transforms into cyclic structure. Desired product 4a was
obtained after the rearrangement and tautomeric proton shift
of cyclic structure.
In order to evaluate the generality of the process, several
indole aldehydes were employed. The results are summa-
rized in Table 1. The reactions of several substituted indole
aldehydes proceeded smoothly with 4-hydroxyl coumarine
and C–H acid in the presence of solid acid catalyst GN3
offering the corresponding products in excellent yields
Reusability of catalyst. Reusability is another important
parameter of efficient catalysts. After the completion of
reaction, chloroform was added to the reaction mixture,
and the catalyst was separated by a simple filtration from
the resulting heterogeneous mixture, washed with water,
and dried at 150°C for 2 h. The catalyst was reused for a
consecutive run under similar reaction conditions. The
average isolated yields of 4a for five consecutive runs were
Conversion
98
Selectivity
1
9
00
100
90
80
70
60
50
40
30
20
9
8
4
9
4
6
0
0
0
0
0
0
0
0
98
8
8
7
6
5
4
3
2
79
51
7
7
2
6
9
1%, which clearly demonstrates the practical reusability
of GN3 catalyst.
In summary, we have reported the use of solid base
material GN3 as catalyst synthesis of 2-amino-4-(1H-
indol-3-yl)-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-
carbonitrile and Knoevenagel condensation under mild
reaction conditions. To the best of our knowledge, reports
for the synthesis of chromen substituted at 3C position of
indole are extremely rare in the literature. The catalysts
showed excellent stability and activity for both reactions.
The scope of catalyst GN3 was further explored using
other indole aldehydes. The reactions proceeded well for
various indole aldehydes, giving excellent yield of the
respective products. Finally, silica supported polyamine
catalyst GN3 can be recovered by simple filtration process
and can be used again without any loss in its activity.
All the solvents were used as commercial anhydrous grade
without further purification. The column chromatography
2
0.5
1
1.2
1.5
2
benzaldehyde (molar ratio)
Figure 4. The effect of 1H-indole-3-carbaldehyde concentration on
the synthesis of 4a. Reaction conditions: 1H-indole-3-carbaldehyde :
4
-hydroxy coumarine : malanonitrile (x:1:1); catalyst GN3, 60°C;
catalytic loading 0.03 g; 60 min.
Scheme 2. Synthesis of 3-substituted chromeno indole derivatives 4(a–h).
NH
2
OH
CHO
X
X
O
O
Catalyst
CN Water, 600
+
1
R +
C
N
O
O
N
R
(a-d)
O
1
2
3(a,b)
R
1
R
4
(a-h)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. L. Magar, P. B. Thorat, J. L. Waware, R. R. More, U. A. Solanke, B. R. Patil, and R. P. Pawar Vol 000
Table 1
a
Synthesis of 3-substituted chromeno indole derivative.
b
Sr. no.
1
Substrate 1
Substrate 2
Substrate 3
Product
Time (min)
60
Yield (%)
93
2
60
91
3
4
60
60
94
90
5
60
90
6
60
92
7
60
87
(Continues)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis of Some Novel 3-Substituted Indole Derivatives Using Polyamine
Functionalized Heterogeneous Catalyst
Table I.
(
Continued)
b
Sr. no.
8
Substrate 1
Substrate 2
Substrate 3
Product
Time (min)
60
Yield (%)
89
a
Reaction conditions: catalyst GN3 (0.025 g), indole aldehyde (1 mmol), 4-hydroxycoumarin (1 mmol), and malononitrile/ethylcyanoacetate (1 mmol) in
water solvent at 60°C. Progress of reaction was monitored by gas chromatography.
b
Isolated yields.
Scheme 3. Synthesis of 3-substituted indole derivatives.
7.32–7.43 (m, 2H), 7.11–7.22 (m, 3H), 6.93 (br s, 2H, NH),
13
4
.21 (s, 1H); C NMR (75 MHz, CDCl ): δ 167.1, 164.2,
R1
R
3
O
OH
O
N
163.1, 153.7, 136.8, 133.3, 127.6, 127.2, 123.1, 122.7,
20.0, 115.8, 115.4, 113.1, 112.8, 111.6, 103.1, 103.8, 56.2,
Catalyst GN3
Water, rt
1
O
O
+
+
+
42.3; GC–MS m/z 355 (M ). Elemental analysis: Calcd.
CHO
R1
O
5(a-d)
2
C H N O : C, 70.98; H, 3.69; N, 11.83. Found: C,
21 1H3 3 3
R1
R
71.01; H, 3.72; N, 11.85.
N
N
X
2-Amino-4-(2-methyl-1H-indol-3-yl)-5-oxo-4,5-dihydropyrano
R
(a-d)
NC
3
X
1
Catalyst GN3
Water, rt
1
a/3b
[3,2-c]chromene-3-carbonitrile (4b). White solid; H NMR
CN
(
300MHz, CDCl ): δ 13.11 (br s, 1H, NH), 8.17–8.25
3
6(a-h)
(m, 1H), 7.71–7.81–7.88 (m, 1H), 7.49–7.70 (m, 2H),
.19–7.32 (m, 3H), 6.99 (br s, 2H, NH), 4.29 (s, 1H), 2.52
7
13
(
s, 3H); C NMR (75 MHz, CDCl ): δ 167.2, 166.3,
3
1
13
was carried out over silica gel (80–120 mesh). H and
C
1
65.6, 154.7, 139.4, 132.8, 131.0, 129.3, 127.9, 126.8,
NMR spectra were recorded on Bruker 300MHz spectrome-
ter (Brucker Avance 300 MHz, Hydrabad, India) in CDCl3
solvent. Mass spectra were taken on Polaris-Q
Thermoscientific GC–MS (Pune, India).
126.1, 125.3, 117.7, 116.5, 110.1, 107.7, 103.3, 61.2, 43.4,
+
16.8; GC–MS m/z 369 (M ). Elemental analysis: Calcd.
C H N O : C, 71.54; H, 4.09; N, 11.38. Found: C,
22 15
3 3
7
1.57; H, 4.11; N, 11.41.
2
-Amino-4-(1-methyl-1H-indol-3-yl)-5-oxo-4,5-dihydropyrano
General procedure for the synthesis of catalysts GN3. The
synthesis and characterization of the catalyst are reported in
our earlier communication [8] and also in literature [18].
1
[
3,2-c]chromene-3-carbonitrile (4c). White solid; H NMR
(
(
(
(
300MHz, CDCl ): δ 8.00–8.08 (m, 1H), 7.79–7.88
m, 1H), 7.47 –7.69 (m, 4H), 7.10–7.19 (m, 3H), 6.99
3
General procedure for the synthesis of 2-amino-4H-chromene
derivative. The mixture of 3-indole aldehydes (1 mmol),
-hydroxy coumarine (1 mmol), and active methylene
compound was taken in water solvent. To this mixture,
.03 g of silica gel polyamine catalyst GN3 was added. The
reaction mixture was stirred at 60°C for appropriate time (as
shown in Table 1), and the progress of reaction was
monitored by GC. After completion of reaction, reaction
mixture was cooled at room temperature, and to the cooled
reaction mixture solvent, chloroform was added. The solid
heterogeneous catalyst GN3 was removed by a simple
filtration process. The organic layer was collected, and
solvent was removed under vacuum to obtain crude product.
The obtained product was purified by column
chromatography using Pet ether : ethyl acetate (7:3) as
elluent to obtain the desired compound 4(a–h).
br s, 2H, NH), 6.69–6.77 (m, 1H), 4.22 (s, 1H), 3.52
13
s, 3H); C NMR (75 MHz, CDCl ): δ 166.1, 164.2,
3
4
1
1
3
7
63.8, 158.4, 141.4, 127.7, 126.2, 125.0, 124.4, 120.0,
14.6, 113.8, 111.5, 107.0, 61.9, 31.6, 24.6; GC–MS m/z
0
+
69 (M ). Elemental analysis: Calcd. C H N O : C,
2
2 15 3 3
1.54; H, 4.09; N, 11.38. Found: C, 71.56; H, 4.06; N, 11.37.
2
-Amino-5-oxo-4-(1-phenyl-1H-indol-3-yl)-4,5-dihydropyrano
1
[3,2-c]chromene-3-carbonitrile (4d). White solid; H NMR
(300MHz, CDCl ): δ 7.91–8.06 (m, 2H), 7.07–7.81
3
(m, 10H), 6.94 (br s, 2H, NH), 6.71–6.80 (m, 2H), 4.21
13
(
s, 1H); C NMR (75 MHz, CDCl ): δ 162.9, 161.4,
3
1
1
1
61.0, 154.1, 148.0, 141.3, 131.8, 131.2, 131.0, 126.1,
25.3, 124.9, 122.6, 122.0, 119.8, 118.2, 113.0, 112.1,
07.8, 106.5, 106.0, 59.8, 42.0; GC–MS m/z 431 (M ).
+
Elemental analysis: Calcd. C H N O : C, 75.16; H, 3.97;
27 17 3 3
N, 9.74. Found: C, 75.19; H, 3.94; N, 9.76.
Characterization data for representative compound. 2-
Ethyl
2-amino-4-(1H-indol-3-yl)-5-oxo-4,5-dihydropyrano
1
Amino-4-(1H-indol-3-yl)-5-oxo-4,5-dihydropyrano[3,2-c]chromene-
[3,2-c]chromene-3-carboxylate (4e). White solid; H NMR
1
3
-carbonitrile (4a). White solid; H NMR (300 MHz, CDCl ):
(300MHz, CDCl ): δ 13.09 (br s, 1H, NH), 7.90–8.01
3
3
δ 13.09 (br s, 1H, NH), 7.86–7.92 (m, 1H), 7.54–7.72 (m, 3H),
(m, 2H), 7.63–7.80 (m, 2H), 7.29–7.32 (m, 2H), 7.22
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. L. Magar, P. B. Thorat, J. L. Waware, R. R. More, U. A. Solanke, B. R. Patil, and R. P. Pawar Vol 000
Table 2
a
Synthesis of 3-substituted indole derivative.
b
Sr. no.
1
Substrate 1
Substrate 2
Product
Time (min)
30
Yield (%)
96
2
30
92
3
4
5
30
30
20
91
93
94
6
7
20
20
96
93
8
20
89
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis of Some Novel 3-Substituted Indole Derivatives Using Polyamine
Functionalized Heterogeneous Catalyst
Table 2
(
Continued)
b
Sr. no.
9
Substrate 1
Substrate 2
Product
Time (min)
20
Yield (%)
90
1
1
0
1
20
20
91
89
12
20
87
a
Reaction conditions: catalyst GN3 (0.025 g), indole aldehyde (1 mmol), 4-hydroxycoumarin/malononitrile/ethylcyanoacetate (1 mmol) in water solvent
at room temperature. Progress of reaction was monitored by gas chromatography.
b
Isolated yields.
(
(
m, 1H), 7.08–7.21 (m, 2H), 6.97 (br s, 2H, NH), 4.49–4.69
(m, 2H), 7.72–7.87 (m, 1H), 7.54–7.72 (m, 2H), 7.32–7.51
(m, 2H), 7.23 (s, 1H), 6.99 (br s, 2H, NH), 4.70–4.90
(q, J = 6.8 Hz, 2H), 4.30 (s, 1H), 3.68 (s, 3H), 1.20
13
q, J = 7.4 Hz, 2H), 4.21 (s, 1H), 1.29 (t, J = 8.1 Hz, 3H);
C
NMR (75 MHz, CDCl ): δ 169.0, 163.7, 158.2, 157.7,
3
1
3
1
1
4
50.2, 135.9, 130.8, 129.9, 126.2, 124.1, 123.6, 121.2,
(t, J = 8.0 Hz, 3H); C NMR (75 MHz, CDCl ): δ
3
17.0, 114.4, 114.0, 113.1, 109.0, 101.9, 100.3, 71.8, 63.0,
166.9, 159.1, 157.2, 156.9, 152.0, 140.0, 125.9, 125.3,
123.0, 129.8, 122.5, 120.7, 114.9, 114.0, 112.9, 109.2,
108.0, 101.8, 100.7, 78.9, 61.9, 40.6, 34.5, 19.0; GC–MS
+
0.5, 29.5, 18.1; GC–MS m/z 402 (M ). Elemental
analysis: Calcd. C H N O : C, 68.65; H, 4.51; N, 6.96.
Found: C, 68.67; H, 4.53; N, 6.99.
23 18 2 5
+
m/z 416 (M ). Elemental analysis: Calcd. C H N O : C,
2
4 20 2 5
Ethyl 2-amino-4-(2-methyl-1H-indol-3-yl)-5-oxo-4,5-dihydropyrano
6
9.22; H, 4.84; N, 6.73. Found: C, 69.24; H, 4.87; N, 6.76.
1
[
3,2-c]chromene-3-carboxylate (4f). White solid; H NMR
Ethyl 2-amino-5-oxo-4-(1-phenyl-1H-indol-3-yl)-4,5-dihydropyrano
1
(
300 MHz, CDCl ): δ 13.04 (br s, 1H, NH), 7.77–7.89
[3,2-c]chromene-3-carboxylate (4h). White solid; H NMR
3
(m, 1H), 7.61–7.72 (m, 1H), 7.41–7.53 (m, 2H), 7.20–7.40
(300MHz, CDCl ): δ 7.90–8.08 (m, 2H), 7.60–7.89
3
(
2
m, 4H), 6.91 (br s, 2H, NH), 4.52–4.72 (q, J = 7.1 Hz,
H), 4.25 (s, 1H), 2.69 (s, 3H), 1.27 (t, J = 7.9 Hz, 3H); C
(m, 4H), 7.34–7.56 (m, 5H), 7.29 (s, 1H), 7.01 (br s, 2H,
NH), 6.61–7.80 (m, 1H), 4.40–4.66 (q, J = 7.9 Hz, 2H),
13
13
NMR (75 MHz, CDCl ): δ 164.6, 160.8, 159.4, 157.7,
4.21 (s, 1H), 1.22 (t, J = 7.7 Hz, 3H); C NMR (75 MHz,
CDCl ): δ 165.9, 160.2, 159.9, 159.3, 155.7, 151.0, 141.7,
3
1
1
6
52.0, 138.1, 131.2, 128.9, 128.3, 122.5, 121.8, 121.2,
3
19.9, 119.3, 119.1, 116.7, 115.7, 11.2, 110.8, 113.0, 78.1,
130.1, 129.1, 127.8, 127.2, 126.1, 124.9, 124.5, 121.1,
+
2.8, 38.9, 19.8, 16.1; GC–MS m/z 416 (M ). Elemental
117.2, 116.0, 114.2, 113.7, 108.8, 106.5, 102.6, 76.5, 64.1,
+
analysis: Calcd. C H N O : C, 69.22; H, 4.84; N, 6.73.
43.7, 17.2; GC–MS m/z 478 (M ). Elemental analysis:
24 20 2 5
Found: C, 69.19; H, 4.86; N, 6.71.
Calcd. C29H N O : C, 72.79; H, 4.63; N, 5.85. Found: C,
22 2 5
72.81; H, 4.66; N, 5.88.
Ethyl 2-amino-4-(1-methyl-1H-indol-3-yl)-5-oxo-4,5-dihydropyrano
1
[
3,2-c]chromene-3-carboxylate (4g). White solid; H NMR
General procedure for Knoevenagel condensation. The
(
300MHz, CDCl ): δ 8.22–8.34 (m, 1H), 7.98–8.18
preceding procedure was carried out using 3-indole aldehydes
3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. L. Magar, P. B. Thorat, J. L. Waware, R. R. More, U. A. Solanke, B. R. Patil, and R. P. Pawar Vol 000
Scheme 4. Possible mechanism of chromene derivatives using GN3 catalyst.
Step-I:
OH
Si
1/3
NH3
1/3
OH
Si
O
O
O
O
NH2
NH2
O
O
OH
O
OCH3
OCH3
OH
OH
O
+
-H
O
Si
N
H
Si
O
H
O
OCH3
3
OCH3
OH
O
OH
O
O
1/3
O
X
O
Si
N
O
Si
NH2
O
H3
O
OH
OH
O
O
O
O
H C
NH
NH
HN
O
O
O
5
X
Step-II:
O
H C
X
Catalyst GN3
-H
X
X
CN
NC
Y
CN
HN
6
Path B
X
NH
NH
NH
O
NH
O
O
O
X
Path A
X
X
HN
O
X
O
O
C
NC
N
O
O
O
OH
Y
H2N
O
+
(
1 mmol) and 4-hydroxy coumarine/active methylene
compound (1mmol) at room temperature conditions.
-[(1H-Indol-3-yl)methylene]chroman-2,4-dione (5a). White
MS m/z 303 (M ). Elemental analysis: Calcd. C H NO :
19 13 3
C, 75.24; H, 4.32; N, 4.62. Found: C, 75.26; H, 4.30; N, 4.66.
3-[(1-Phenyl-1H-indol-3-yl)methylene]chroman-2,4-dione
(5d). White solid; H NMR (300 MHz, CDCl
3
1
1
solid; H NMR (300 MHz, CDCl ): δ 13.48 (br s, 1H, NH),
8
): δ 8.39
3
3
.89 (s, 1H), 7.82–7.89 (m, 1H), 7.58–7.70 (m, 2H), 7.31–
(s, 1H), 8.04–8.13 (m, 1H), 7.88–7.92 (m, 1H), 7.51–7.73
(
m, 2H), 7.21–7.48 (m, 2H), 6.89–7.18 (m, 6H), 6.68–6.80
7
.42 (m, 2H), 7.05–7.17 (m, 2H), 6.81–6.92 (m, 1H) 6.51
13
13
(s, 1H); C NMR (300 MHz, CDCl ): δ 178.0, 157.6,151.9,
(m, 2H); C NMR (75 MHz, CDCl
153.5, 153.3, 147.1, 138.8, 134.1, 133.2, 130.0, 129.1,
28.3, 128.1, 127.3, 126.9, 126.0, 125.3, 124.8, 121.1,
): δ 177.1, 160.0,
3
3
154.1, 138.0, 132.3, 131.9, 130.3, 129.9, 129.1, 123.3,
1
1
24.4, 120.2, 118.8, 117.7, 113.1, 107.7, 107.3, GC–MS
+
+
m/z 289 (M ). Elemental analysis: Calcd. C H NO : C,
120.5, 119.9, 116.1, 115.8, 109.6; GC–MS m/z 365 (M ).
Elemental analysis: Calcd. C24 : C, 78.89; H, 4.14;
N, 3.83. Found: C, 78.92; H, 4.17; N, 3.85.
1
8
11
3
7
4.73; H, 3.83; N, 4.84. Found: C, 74.76; H, 3.85; N, 4.82.
H15NO
3
3
-[(2-Methyl-1H-indol-3-yl)methylene]chroman-2,4-dione
1
(
5b). White solid; H NMR (300 MHz, CDCl ): δ 13.12
2-[(1H-Indol-3-yl)methylene]malononitrile (6a). Blackish
3
1
(
(
(
br s, 2H, NH), 8.60 (s, 1H), 8.23–8.33 (m, 1H), 7.82–7.98
m, 2H) 7.40–7.49 (m, 1H), 7.08–7.17 (m, 1H), 6.71–6.97
m, 3H), 2.65 (s, 1H); C NMR (300 MHz, CDCl ): δ
solid; H NMR (300 MHz, CDCl ): δ 13.01 (bs, 1H, NH),
3
8.52–8.78 (m, 2H), 7.39–7.61 (m, 2H), 7.06–7.18 (m, 1H);
13
13
C NMR (75 MHz, CDCl ): δ 157.8, 143.8, 130.1, 128.1,
3
3
1
1
1
78.7, 158.8, 152.9, 152.3, 132.9, 132.5, 129.1, 128.9,
123.9, 122.5, 121.3, 115.6, 112.1, 110.4, 85.6; GC–MS m/z
+
29.6, 126.8, 126.4, 124.1, 121.1, 119.9, 116.2, 111.9,
193 (M ). Elemental analysis: Calcd. C H N : C, 74.60; H,
12 7 3
+
10.2, 102.3, 14.5; GC–MS m/z 303 (M ). Elemental
3.65; N, 21.75. Found: C, 74.57; H, 3.68; N, 21.73.
analysis: Calcd. C H NO : C, 75.24; H, 4.32; N, 4.62.
Found: C, 75.26; H, 4.35; N, 4.64.
2-((2-Methyl-1H-indol-3-yl)methylene)malononitrile (5b). Gray
1
9
13
3
1
solid; H NMR (300 MHz, CDCl ): δ 13.30 (bs, 1H, NH),
3
3
-[(1-Methyl-1H-indol-3-yl)methylene]chroman-2,4-dione
8.46 (s, 1H), 7.49–7.65 (m, 1H), 6.94–7.28 (m, 3H), 2.54
1
13
(
5c). White solid; H NMR (300 MHz, CDCl ): δ 8.78
3
(s, 3H); C NMR (75 MHz, CDCl ): δ 157.1, 139.9,
3
(s, 1H), 8.46–8.55 (m, 1H), 8.20–8.30 (m, 2H) 7.81–7.93
133.1, 122.2, 120.0, 114.5, 112.6, 104.8, 91.3, 14.2; GC–
+
(m, 2H), 7.56–7.69 (m, 2H), 7.19–7.40 (m, 2H), 4.10 (s,
MS m/z 207 (M ). Elemental analysis: Calcd. C H N : C,
1
3 9 3
13
1
1
1
H); C NMR (75MHz, CDCl ): δ 175.1, 161.2, 155.1,
54.3, 139.0, 138.1, 137.5, 136.8, 129.5, 129.128.5, 128.1,
27.2, 121.1, 199.9, 118., 111.2, 109.0, 108.0, 35.8; GC–
3
75.35; H, 4.38; N, 20.28. Found: C, 75.37; H, 4.41; N, 20.31.
2-[(1-Methyl-1H-indol-3-yl)methylene]malononitrile (6c). Gray
1
solid; H NMR (300MHz, CDCl ): δ 8.46 (s, 1H), 8.09–
3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis of Some Novel 3-Substituted Indole Derivatives Using Polyamine
Functionalized Heterogeneous Catalyst
8
1
1
1
.18 (m, 1H), 7.59 (s. 1H), 7.20–7.40 (m, 2H), 6.99–7.08 (m,
C H N O : C, 75.93; H, 5.10; N, 8.86. Found: C, 75.95;
20 16 2 2
H, 5.13; N, 8.89.
1
3
H), 3.80 (s, 3H); C NMR (75 MHz, CDCl ): δ 169.1,
3
36.0, 132.7, 127.8, 122.9, 121.0, 119.9, 115.4, 114.0,
+
13.1, 91.8, 39.9; GC–MS m/z 207 (M ). Elemental
analysis: Calcd. C H N : C, 75.35; H, 4.38; N, 20.28.
Found: C, 75.32; H, 4.35; N, 20.26.
-[(1-Phenyl-1H-indol-3-yl)methylene]malononitrile (6c). Black
Acknowledgment. The authors are thankful to the Principal, Dr.
S. Thore, Deogiri College, Aurangabad, for the encouragement
during the process of carrying out this work.
13 9 3
2
1
solid; H NMR (300 MHz, CDCl ): δ 8.49 (s, 1H), 8.33
3
(
(
s, 1H), 7.98–8.09 (m, 1H), 7.19–7.71 (m, 6H), 6.89–6.98
13
REFERENCES AND NOTES
m, 2H); C NMR (75 MHz, CDCl ): δ 159.4, 145.6,
3
1
1
37.7, 127.5, 124.9, 124.3, 123.9, 122.8, 121.0, 115.5,
14.8, 114.1, 107.8, 90.9; GC–MS m/z 269 (M ).
[
1] (a) Sivakumar, K.; Kathirvel, A.; Lalitha, A. Tetrahedron Lett 2010,
51, 3018; (b) Nagawade, R. R.; Shinde, D. B. Acta Chim Slov 2007, 54, 642.
2] (a) Chow, W. S.; Chan, T. H. Tetrahedron Lett 2009, 50, 1286; (b)
+
[
Elemental analysis: Calcd. C H N : C, 80.28; H, 4.12; N,
1
1
8 11 3
Balalaie, S.; Arabanian, A. Green Chem 2002, 2, 274; (c) Samanta, S. K.;
Kylanlahti, I.; Yli-Kauhaluoma, J. Bioorg Med Chem Lett 2005, 15, 3717.
5.60. Found: C, 80.31; H, 4.15; N, 15.57.
Ethyl 2-cyano-3-(1H-indol-3-yl)acrylate (6e).
Colorless
[
3] Kidwai, M.; Mothsra, P.; Bansal, V.; Somvanshi, R. K.;
Ethayathulla, A. S.; Dey, S.; Singh, T. P. J Mol Catal A: Chem 2007,
65, 177.
4] Kantevari, S.; Vuppalapati, S. V. N.; Biradar, D. O.; Nagarapu, L.
1
solid; H NMR (300 MHz, CDCl ): δ 13.29 (br s, 1H,
NH), 8.44 (s, 1H), 7.96 (s, 1H), 7.49–7.54 (m, 1H),
7
3
2
[
.25–7.39 (m, 2H), 6.92–7.21 (m, 2H); 3.61–3,75
J Mol Catal A: Chem 2007, 266, 109.
13
(
(
q, J = 6.4 Hz, 2H), 1.20 (t, J = 7.8 Hz, 3H); C NMR
75 MHz, CDCl ): δ 159.4, 145.6, 137.7, 127.5, 124.9,
[5] (a) Heravi, M. M.; Derikvand, F.; Bamoharram, F. F. J Mol
Catal A: Chem 2007, 263, 112; (b) Nagarapu, L.; Apuri, S.;
Kantevari, S. J Mol Catal A: Chem 2007, 266, 104.
3
1
9
24.3, 123.9, 122.8, 121.0, 115.5, 114.8, 114.1, 107.8,
[6] Karimi, A. R.; Alimohammadi, Z.; Azizian, J.; Mohammadi, A. A.;
+
0.9; GC–MS m/z 240 (M ). Elemental analysis: Calcd.
Mohammadizadeh, M. R. Catal Commun 2006, 7, 728.
C H N O : C, 69.99; H, 5.03; N, 11.66. Found: C,
[7] Samai, S.; Nandi, G. C.; Singh, P.; Singh, M. S. Tetrahedron
009, 65, 10155.
14 12 2 2
2
7
0.02; H, 5.05; N, 11.64.
[8] Magar, R. L.; Thorat, P. B.; Jadhav, V. B.; Tekale, S. U.;
Ethyl 2-cyano-3-(2-methyl-1H-indol-3-yl)acrylate (6f). Colorless
Dake, S. A.; Patil, B. R.; Pawar, R. P. J Mol Catal A: Chem 2013,
374–375, 118.
1
solid; H NMR (300 MHz, CDCl ): δ 13.20 (br s, 1H, NH),
3
[
9] (a) Faulkner, D. J Nat Prod Rep 2001, 18, 1; (b) Ninomiya, I.
J Nat Prod 1992, 55, 564.
10] (a) Eicher, T.; Hauptmann, S. The Chemistry of Heterocycles,
8
4
3
1
1
.79 (s, 1H), 7.56–7.71 (m, 2H), 6.95–7.21 (m, 2H), 4.28–
.49 (q, J = 6.9 Hz, 2H), 2.60 (s, 3H), 1.27 (t, J = 7.8 Hz,
[
13
H); C NMR (75 MHz, CDCl ): δ 162.1, 153.6, 138.7,
3
2nd edn; Wiley-VCH: Weinheim, 2003; pp 99–110; (b) Steffan, N.;
Grundmann, A.; Yin, W. B.; Kremer, A.; Li, S. M. Curr Med Chem
2009, 16, 218; (c) Manera, C.; Tuccinardi, T.; Martinelli, A. Med Chem
008, 8, 370; (d) Gupta, L.; Talwar, A.; Chauhan, P. M. S. Curr Med
Chem 2007, 14, 1789.
29.0, 128.9, 121.3, 122.8, 116.7, 116.3, 112.1, 107.4,
+
6.9, 61.8, 14.7, 15.3; GC–MS m/z 254 (M ). Elemental
2
analysis: Calcd. C H N O : C, 70.85; H, 5.55; N, 11.02.
1
5
14
2
2
Found: C, 70.82; H, 5.58; N, 11.04.
[11] Sharma, V.; Kalia, R.; Raj, T.; Gupta, V. K.; Suri, N.;
Saxena, A. K.; Sharma, D.; Bhella, S. S.; Singh, G.; Ishar, M. P. S.
Acta Pharm Sin B 2012, 2, 32.
Ethyl 2-cyano-3-(1-methyl-1H-indol-3-yl)acrylate (6g). White
1
solid; H NMR (300 MHz, CDCl ): δ 8.41–8.50 (m, 1H),
3
[12] Kogan, N. M.; Rabinowitz, R.; Levi, P.; Gibson, D.; Sandor, P.;
7.80 (s, 1H), 7.52–7.60 (m, 1H), 7.19–7.39 (m, 2H),
Schlesinger, M.; Mechoulam, R. J Med Chem 2004, 47, 3800.
[13] (a) Abramovitch, R. A.; Hey, D. H. J Chem Soc 1954, 1697;
(b) Ryder, S. PCT Int. Appl. WO 2010151799 A2(20101229); (c)
Goldfarb, D. S. US 20090163545.
[14] Peng, W.; Switalska, M.; Wang, L.; Mei, Z. W.; Edazawa, Y.;
Pang, C. Q.; El-Sayed, I.; Wietrzyk, J.; Inokuchi, T. Eur J Med Chem
2012, 58, 441.
6.91–7.00 (m, 1H), 4.06–4.17 (q, J = 6.7 Hz, 2H), 3.69
13
(s, 3H), 1.29 (t, J= 8.1 Hz, 3H); C NMR (75MHz,
CDCl ): δ 162.2, 156.8,134.1, 130.7, 129.6, 123.0, 121.4,
3
1
19.8, 117.2, 108.3, 108.1, 107.9, 57.5, 46.3, 18.1; GC–MS
+
m/z 254 (M ). Elemental analysis: Calcd. C H N O : C,
1
5 14 2 2
[15] (a) Magar, R. L.; Thorat, P. B.; Thorat, P. B.; Thorat, V. V.;
7
0.85; H, 5.55; N, 11.02. Found: C, 70.87; H, 5.53; N, 10.99.
Patil, B. R.; Pawar, R. P. Chin Chem Lett 2013, 24, 1070; (b) Joshi, V. M.;
Magar, R. L.; Thorat, P. B.; Tekale, S. U.; Patil, B. R.; Kale, M. P.;
Pawar, R. P. Chin Chem Lett 2014, 25, 455.
Ethyl 2-cyano-3-(1-phenyl-1H-indol-3-yl)acrylate (6h). White
1
solid; H NMR (300 MHz, CDCl ): δ 8.19–8.30 (m, 2H),
3
[16] (a) Hasaninejad, A.; Shekouhy, M.; Golzar, N.; Zare, A.;
8
.02 (s, 1H), 7.79 (s, 1H), 7.29–7.60 (m, 6H), 6.89–7.05
Doroodmand M. M. Appl Catal A 2011, 402, 11; (b) Xu, J. C.; Li, W. M.;
Zheng, H.; Lai, Y. F.; Zhang, P. F. Tetrahedron 2011, 67, 9582.
[17] (a) Yokoi, T.; Kubota, Y.; Tatsumi, T. Appl Catal A 2012,
(
(
m, 2H), 4.04–4.18 (q, J = 7.1 Hz, 2H), 3.69 (s, 3H), 1.10
t, J = 7.9 Hz, 3H); C NMR (75 MHz, CDCl ): δ 163.3,
1
3
3
421–422, 14; (b) Lin, X.; Chuah, G. K.; Jaenicke, S. J Mol Catal A: Chem
1
54.8, 143.2, 137.4, 128.7, 128.3, 127.7, 124.6, 124.3,
1999, 150, 287.
1
21.1, 119.9, 118.7, 118.3, 114.7, 107.8, 107.2, 60.1, 16.2;
[18] Manu, V.; Mody, H. M.; Bajaj, H. C.; Jasra, R. V. Ind Eng
+
GC–MS m/z 316 (M ). Elemental analysis: Calcd.
Chem Res 2009, 48, 8954.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet