A clean synthesis of bis(indolyl)methane and biscoumarin derivatives using P4VPy-CuO nanoparticles as a new, efficient and heterogeneous polymeric catalyst

Article abstract of DOI:10.1039/c6ra04893e

P₄VPy-CuO nanoparticles as a novel solid catalyst were synthesized using an ultrasound irradiation method and characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier Trans

Full text of DOI:10.1039/c6ra04893e

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PAPER
A clean synthesis of bis(indolyl)methane and
biscoumarin derivatives using P4VPy–CuO
nanoparticles as a new, efficient and
heterogeneous polymeric catalyst
Cite this: RSC Adv., 2016, 6, 48469
*
Farhad Shirini, Abdollah Fallah-Shojaei, Laleh Samavi and Masoumeh Abedini
P4VPy–CuO nanoparticles as a novel solid catalyst were synthesized using an ultrasound irradiation method
and characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron
microscopy (TEM) and Fourier Transform Infrared (FT-IR) spectroscopy. The prepared catalyst was
applied to the green, simple and highly efficient synthesis of bis(indolyl)methanes and
3,30-(arylmethylene)bis(4-hydroxycoumarins). This methodology has some advantages such as short
reaction times, environmentally friendly conditions, easy work-up, and excellent yields. This catalyst can
be easily separated and re-used without any appreciable loss in its activity.
Received 24th February 2016
Accepted 3rd May 2016
DOI: 10.1039/c6ra04893e
www.rsc.org/advances
quick-precipitation.17 Some of these methods have limitations
due to the requirement of high temperatures, expensive
1. Introduction
instruments and special catalysis. For cost-effectiveness and
simplicity of operation, sonochemical method is preferred. On
other hand in recent years, ultrasound irradiation has been
established as a signicant technique in synthetic organic
chemistry. Shorter reaction times, simple experimental proce-
dure, high yields, improved selectivity and clean reaction
conditions are the main benets of ultrasound-assisted
reactions.18–21
Nowadays, synthesis of bis-heterocyclic compounds have
received signicant attention because they play a vital role in
plant growth and in many pharmacological and biological
activities.22 Indoles are very important class of heterocyclic
compounds. The indole nucleus as a “privileged structure” is
present in many natural products isolated from marine and
terrestrial organisms.23 Among them, bis(indolyl)alkane deriv-
atives have found a great deal of interest because of their
applications in pharmaceuticals. For example, they show anti-
tumor,24 antileishmanial,25 antihyperlipidemic26 and anticancer
activities.27 Among various methods which are used for the
synthesis of bis(indolyl)methanes, generally, these compounds
can be obtained via the condensation of indole with aromatic
(or aliphatic) aldehydes in the presence of a variety of catalyst.
Some of the applied catalysts are I2,28 [bmim]BF4 ionic liquid,29
sulfated zirconia nanoparticles,30 PEG–SO3H,31 ZrOCl2$8H2O,
camphor sulphonic acid,32 benzyltriphenylphosphonium tri-
bromide33 and ceric ammonium nitrate.34
In recent years, nano-catalysts have been considered as
sustainable and competitive alternatives to conventional cata-
lysts. These reagents have a high surface-to-volume ratio that
enhances their activity and selectivity and on the other hand,
they maintain the intrinsic features of heterogeneous catalysts.1
During the past decade the synthesis of metal oxide nano-
particles such as those of titanium, zinc, iron and magnesium
has attracted the attention of many researchers. Among these
metal oxides, CuO nanoparticles have been investigated quite
considerably. This oxide is used as an antimicrobial2 and pho-
tothermal and photoconductive agent,3 in chemical and bio-
logical sensing,4,5 as a promoter in catalytic reactions,6 in
lithium ion batteries7 and solar cells.8 In the synthesis of metal
oxide nanoparticles, polymers are used to stabilize the aggre-
gation of metal oxides.9 Poly(vinylpyridine) (PVP) is an attractive
polymer for immobilization of nanoparticles because of the
strong affinity of the pyridyl group to metals and its ability to
undergo hydrogen bonding with polar species. In addition, PVP
can interact electrostatically in quaternized or protonated forms
with charged surfaces10,11 and a variety of different PVP-sup-
ported reagents have been designed in this context to catalyze
a range of organic reactions.
Throughout the past decade different routes have been
suggested to fabricate the CuO nanoparticles, including elec-
trochemical method,12 wet chemical reaction,13 hydrothermal
method,14 thermal oxidation,15 microwave irradiation16 and
Coumarins are another important class of heterocyclic
compounds. Coumarins have received increasing attention due
to their wide range of biological properties such as anti-HIV,35
anti-bacterial,36 anti-cancer,37 anti-coagulant,38 anti-hepatitis C
Department of Chemistry, Faculty of Science, University of Guilan, P.O. Box:
41335-1914, Rasht, Iran. E-mail: Shirini@guilan.ac.ir; Fax: +981333367262; Tel:
+981333367262
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virus,39 anti-tumor,40 and spasmolytic41 activities. Biscoumarins,
the bridge substituted dimers of coumarin were also used as
anti-inammatories, antipyretics, antifungals, antiseptics42 and
as urease inhibitors.43 Biscoumarins are usually synthesized
through the Knoevenagel–Michael reactions of aldehydes with
4-hydroxycoumarin. For this purpose, a variety of catalysts
including I2,44 p-dodecylbenzenesulfonic acid/piperidine,45
nano silica chloride,46 sodium dodecyl sulfate (SDS)47 cellulose
sulfonic acid48 and poly(4-vinylpyridine)-supported dual acidic
ionic liquid49 have been reported.
Although the above mentioned procedures provide efficient
access to the coumarin and indole structures, most of them
suffer from disadvantages such as the use of expensive catalysts,
long reaction times, harsh reaction conditions, the use of large
excesses of toxic reagents or organic solvents, tedious work-up,
low selectivity and un-reusable catalyst. Based on these limita-
tions, introduction of a simple, efficient and clean procedure by
use of a re-usable nano-catalyst without any discernible loss in
its activity for the development of the synthesis of compounds
belonging to these structural classes is still in demand.
2.4. General procedure for the synthesis of bis(indolyl)
methane derivatives
A mixture of aldehyde (1 mmol), indole (2 mmol), and P4VPy–
CuO (20 mg) was heated at 80 ꢂC under solvent-free conditions
for the appropriate time. Aer completion of the reaction
(monitored by TLC using a 3 : 7 mixture of EtOAc/n-hexane),
ethanol (10 mL) was added to the mixture and the catalyst was
collected by ltration. Then, water was added and the precipi-
tated product was collected by ltration in high purity.
The spectral data for the new compound are shown below:
Compound 1V. FT-IR (KBr, cmꢃ1): n ¼ 3400 (NH str.), 3100
(aromatic C–H), 2840 (aliphatic C–H str.), 1679 (aromatic C]C
str.), 580 (C–Br); 1H NMR (DMSO-d6, 400 MHz): d ¼ 1.26 (6H, d, J
¼ 6.92 Hz, CH3), 2.8–2.9 (1H, m, CH), 5.7 (1H, s, Ar–CH), 6.48
(2H, s), 7.18 (2H, d, J ¼ 8), 7.22 (2H, d, J ¼ 8 Hz), 7.25 (2H, d, J ¼
8.2), 7.28 (2H, d, J ¼ 8.2 Hz), 7.76 (2H, s), 9.96 (s, NH); 13C NMR
(DMSO-d6, 400 MHz): d ¼ 22.9, 32.6, 38.4, 111.4, 112.5, 116.1,
121.2, 122.1, 123.8, 125.5, 127.3, 128.6, 133.3, 134.3, 141.6.
Compound 1W. FT-IR (KBr, cmꢃ1): n ¼ 3400 (NH str.), 3100
(aromatic C–H), 2840 (aliphatic C–H str.), 1681 (aromatic C]C
str.), 580 (C–Br); 1H NMR (DMSO-d6, 400 MHz): d ¼ 3.78 (3H, s,
OCH3), 5.75 (1H, s, Ar–CH), 6.84 (2H, s), 7.12 (2H, d, J ¼ 8), 7.38
(2H, d, J ¼ 8), 7.64–7.67 (2H, m), 7.83 (2H, s), 9.76 (s, NH); 13C
NMR (DMSO-d6, 400 MHz): d ¼ 40.2, 55.7, 108.7, 111.9, 117.8,
120.3, 123.4, 124.6, 125.9, 128.5, 129.1, 133.2, 134.7, 142.3.
2. Experimental
2.1. General
All chemicals were purchased from Merck or Fluka Chemical
Companies and used without further purication. All yields refer
to the isolated products. Products were characterized by their
physical constants, and through a comparison with authentic
samples. The reactions were monitored by thin layer chromatog-
raphy (TLC) using silica gel SIL G/UV 254 TLC plates (Germany).
2.5. General procedure for the synthesis of 3,30-
(arylmethylene)-bis-(4-hydroxycoumarins) derivatives
A mixture of aldehyde (1 mmol), 4-hydroxycoumarin (2 mmol)
and P4VPy–CuO (20 mg) in H2O (5 mL) was stirred at reux
temperature for the appropriate time. The progress of the
reaction was monitored by TLC (EtOAc : n-hexane; 1 : 4). Upon
completion of the reaction the mixture was cooled to room
temperature and ltered to separate the catalyst. Aer evapo-
ration of the solvent the residue was recrystallized from
a mixture of EtOH and water (95 : 5) to afford the pure product.
2.2. Instrumentation
X-ray diffraction (XRD) measurements were performed at room
temperature on a D8-Bruker Advanced X-ray powder diffractom-
˚
eter, using Ni lter and Cu-Ka radiation (k ¼ 1.542 A). Scanning
electron microscopy (SEM) and energy-dispersive X-ray spec-
troscopy (EDX) studies were carried out with SEM HITCHI S4160.
TEM studies were carried out with PHILIPS CM10. The FT-IR
spectra were recorded on a run on a VERTEX 70 Bruker
3. Results and discussion
3.1. Catalyst characterization
1
company (Germany) spectrometer. H NMR spectra were recor-
ded on a Bruker Avance 400 MHz instrument (Germany) and the
13C NMR data were collected on a Bruker Avance 100 MHz
instrument. All the chemical shis from the NMR spectra have
been reported relative to TMS using deuterated solvent. Melting
In order to understand the chemical and structural nature of the
synthesized P4VPy–CuO-NPs, FT-IR analysis was carried out. In
Fig. 1(a), which shows the FT-IR of P4VPy the absorption bands at
1600, 1556, 1498, and 1414 cmꢃ1 are assigned to the character-
istic vibrations of the pyridine ring. The absorption bands at 1069
and 995 cmꢃ1 are assigned to the in-plane and out-of-plane
bending of the C–H bonds of the ring, respectively.50 Metal
¨
points were recorded on a Buchi B-545 apparatus (Germany) in
open capillary tubes. Elf (with a frequency of 50 Hz and a nominal
power 200 W) ultrasonic bath was used for ultrasonic irradiation.
oxides commonly show absorption bands below 1000 cmꢃ1
.
51 In
2.3. Preparation of P4VPy–CuO nanoparticles (PC-NPs)
this Fig. 1(b) the absorption bands which are observed at 604 and
A
mixture of poly(4-vinylpyrridine) (100 mg) [poly(4- 504 cmꢃ1 are related to bare Cu–O. Fig. 1(c) shows the FT-IR
vinylpyridine) cross-linked with 2% DVB ꢀ60 mesh, MW: spectrum of the prepared catalyst. In this Fig. the bands related
60 000] and bulk copper(II) oxide (35 mg, 0.437 mmol) in to the pyridine ring are appeared at 1603, 1558, 1499 and 1415
ethanol (10 mL) was irradiated by ultrasound for 2 hours. Then, cmꢃ1 while their intensities are decreased. The two characteristic
the black solid powder was separated by centrifugation and bands of CuO were also observed at 608 and 511 cmꢃ1
.
52
washed three times with ethanol (3 ꢁ 2 mL) and dried at 60 ꢂC
The P4VPy and P4VPy–CuO-NPs samples were also analyzed
by powder X-ray diffraction (XRD) (Fig. 2). All of the peaks in the
(125 mg).
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Fig. 1 FT-IR spectra of (a) P4VPy (b) CuO and P4VPy–CuO-NPs (c).
Fig. 2 XRD patterns of (a) P4VPy and (b) P4VPy–CuO-NPs.
diffraction diagram could be assigned to the CuO. The peaks at
2q values of 32.86, 35.89, 39.09, 46.37, 49.04, 54.15, 58.63, 61.88,
66.62, 68.46, 72.58, and 75.34 correspond to the crystal planes of
copper oxide 110, 002, 111, 112, 202, 020, 202, 113, 311, 113,
311, and 004, respectively, which are in good agreement with
the recent observations.52 No other peak is observed belonging
to the impurities, indicating the high purity of as-obtained
samples. These values are consistent with the respective Joint
Committee on Powder Diffraction Standard card no. 45-0937.
Scanning electron microscopy (SEM) is used to determine
the size of the CuO particles (Fig. 3). This method claried that
these particles are in nano size. On the basis of the obtained
results it can be concluded that because of the reduction of the
size of the CuO particles which increases its surface area the
activity of the prepared reagent in the requested reactions
became higher (as described in the next sections).
3.2. Catalyst activity
As we have mentioned previously, CuO is one of the most
prominent catalysts and is extensively used in environmental
catalysis. CuO nanoparticles typically have higher catalytic
activity than their bulk or micro counterparts caused by their
large surface area.53 In addition, CuO on various supporters
have also been extensively investigated and is known to be
highly active.54
In the present study and aer preparation and identication
of P4VP–CuO-NPs and in order to solve the previously
mentioned drawbacks we were interested to investigate the
applicability of this reagent in the promotion of different types
of the synthesis of 3,30-(arylmethylene)bis(4-hydroxycoumarins)
and bis(indolyl)methanes.
At rst, we focused our attention on the synthesis of bis(in-
dolyl)methanes compounds. For optimization of the reaction
conditions, the reaction between 4-chlorobenzaldehyde and
indole to give the corresponding product was selected as
Typical transmission electron microscopy (TEM) displays the
morphologies of the prepared sample. In Fig. 4 nanorod and
nanosphere structures can be observed for the prepared reagent.
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Fig. 3 SEM images of (a) P4VPy and (b and c) P4VPy–CuO-NPs and EDX of P4VPy–CuO-NPs (d).
Fig. 4 TEM images of P4VPy–CuO-NPs.
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Scheme 1 Synthesis of bis(indolyl)methane derivatives in the presence of P4VPy–CuO-NPs.
a model reaction and the various conditions including the high yields (Table 1, entries 1–15). Also, 2-methyl indole, 5-nitro
amount of catalyst, solvent and temperature were examined. indole and 5-bromo indole, were successfully converted to the
The best result was achieved by carrying out the reaction of the corresponding bis(indolyl)methanes under the optimized
aldehyde (1 mol) and indol (2 mol) in the presence of 20 mg of conditions (Table 1, entries 16–24). The results showed that when
P4VPy–CuO at 80 ꢂC under solvent-free conditions, as shown in 2-methyl indole was used in the reaction, the desired bis(indolyl)
Scheme 1. Any further increasing in the amount of the catalyst methanes were obtained in short reaction times rather than
or temperature did not improve the reaction time or yield.
other indoles. For more investigation, acetophenone as a ketones
Using these optimized conditions, the reaction of various was examined under this conditions. It was seen that no product
aldehydes with different indole derivatives, including: indole, was obtained which indicates the chemoselectivity of the catalyst.
2-methyl indole, 5-nitro indole, and 5-bromo indole was This chemoselectivity can be attributed to the higher electro-
explored (Table 1).
philicity of aldehydes in comparison with ketones, aldehydes are
Aromatic aldehydes containing electron-withdrawing (Cl, Br, more reactive than ketones.
and NO2) or electron-donating (CH3, OCH3 and OH) groups, as
Aer the successful application of P4VPy–CuO-NPs as
well as a,b-unsaturated (cinnamaldehyde), and heterocyclic a polymer-supported catalyst in the synthesis of bis(indolyl)
(isatin) aldehydes, all reacted smoothly with indole in the pres- methanes, we decided to use it in the condensation of 4-
ence of the P4VPy–CuO-NPs to give the corresponding products in hydroxycoumarin with aldehydes in aqueous medium to form
Table 1 Preparation of bis(indolyl)methane derivatives catalyzed by P4VPy–CuO-NPsa
Melting point (ꢂC)
Entry
Ar
R1
R2
Product
Time (min)
Yieldb (%)
Found
Reported
Ref.
1
2
3
4
5
6
7
8
C6H5–
2-Cl–C6H4–
4-Cl–C6H4–
4-Br–C6H4–
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CH3
CH3
CH3
CH3
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
1r
10
8
5
6
4
90
87
92
90
92
94
90
86
89
87
85
88
90
79
90
94
95
91
92
90
83
80
89
—
126–128
76–78
78–80
112–114
220–222
221–223
90–92
166–168
184–186
150–152
172–174
122–124
98–100
305–307
252–254
244–246
242–244
102–104
300–302
316–318
242–244
262–264
254–256
—
126–127
75–76
78–80
116–117
219–221
222–224
89–91
28
55
32
56
55
55
55
57
31
58
32
32
32
34
32
55
32
32
59
59
58
—
—
—
3-NO2–C6H4–
4-NO2–C6H4–
4-Me–C6H4–
3-MeO–C6H4–
4-MeO–C6H4–
4-(CH3)2CH–C6H4–
4-(CH3)2N–C6H4
4-OH–C6H4–
C6H5–CH]CH–
Isatin
5
12
15
10
10
22
35
10
45
5
3
3
5
30
35
25
35
15
120
165
9
186–187
153–154
170–172
124–126
100–101
>300
250–253
247–248
241–243
102–103
304–306
317–319
246–248
—
10
11
13
14
15
16
17
18
19
20
21
22
23
24
25
C6H5–
4-Cl–C6H4–
4-NO2–C6H4–
4-MeO–C6H4–
4-NO2–C6H4–
4-MeO–C6H4–
C6H5–
4-(CH3)2CH–C6H4–
4-MeO–C6H4–
Acetophenone
H
H
NO2
NO2
Br
Br
Br
H
1s
1t
1u
1v
1w
1x
—
—
H
a
Reaction conditions: aldehyde (1 mmol), indole (2 mmol), P4VPy–CuO-NPs (20 mg) at 80 ꢂC under solvent free conditions. b Isolated yields.
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Scheme 2 Synthesis of 3,30-(arylmethylene)-bis-(4-hydroxycoumarin) derivatives in the presence of P4VPy–CuO-NPs.
3,30-(arylmethylene)bis(4-hydroxycoumarins). For this purpose
Subsequently, a broad range of aromatic and aliphatic alde-
and to obtain the optimum reaction conditions, the reaction hydes were reacted with 4-hydroxycoumarin under the optimized
between 4-clorobenzaldehyde and 4-hydroxycoumarin was conditions and the corresponding 3,30-(arylmethylene)-bis-(4-
studied as a model reaction in different conditions.
hydroxycoumarins) were obtained in good to high yields, as
Several different solvents were examined in the model reaction, shown in Table 2. Various aromatic aldehydes containing electron-
including ethanol, diethyl ether, dichloromethane and water that withdrawing or electron-donating groups (Cl, Br, NO2, CH3, OCH3,
gave the best results in terms of the yield and reaction time. N(CH3)2, SCH3 and OH) and also a,b-unsaturated aldehydes (cin-
Finally, the optimal reaction conditions for this reaction was ob- namaldehyde and 2-nitrocinnamaldehyde) were efficiently
tained using 1 mmol aldehyde, 2 mmol 4-hydroxycoumarin and 20 condensed with 4-hydroxycoumarin in very good yields and times
mg P4VPy–CuO-NPs as the catalyst in 5 mL H2O at reux (Table 2, entries 1–17). Furthermore, using this method, 3-phe-
temperature, as shown in Scheme 2.
nylpropionaldehyde and 2-phenylpropionaldehyde as aliphatic
Table 2 Preparation of 3,30-(arylmethylene)-bis-(4-hydroxycoumarins) derivatives catalyzed by P4VPy–CuO-NPsa
Melting point (ꢂC)
Found
Entry
Ar
Product
Time (min)
Yieldb (%)
Reported
Ref.
1
2
3
4
5
6
7
8
C6H5–
2-Cl–C6H4–
3-Cl–C6H4–
4-Cl–C6H4–
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
20
55
35
15
20
20
15
10
60
25
25
35
30
25
50
90
88
90
93
89
91
94
95
85
92
92
89
93
91
85
232–234
217–219
225–227
255–257
268–270
198–200
233–235
230–232
219–221
265–267
240–242
248–250
220–222
259–261
228–230
230–232
220–222
228–230
256–258
266–268
200–202
235–237
230–232
221–223
265–266
238
47
48
47
47
46
60
48
48
47
48
43
47
47
59
46
4-Br–C6H4–
2-NO2–C6H4–
3-NO2–C6H4–
4-NO2–C6H4–
2-Me–C6H4–
4-Me–C6H4–
3-MeO–C6H4–
4-MeO–C6H4–
4-(CH3)2N–C6H4–
4-MeS–C6H4–
4-OH–C6H4–
9
10
11
12
13
14
15
246–248
222–224
258–260
222–224
16
17
18
2p
2q
2r
25
55
60
90
88
90
226–228
188–190
196–198
230–232
190–192
190
44
61
43
19
2s
45
80
194–196
198
43
a
Reaction conditions: 4-hydroxycoumarin (2 mmol), aldehyde (1 mmol), P4VPy–CuO-NPs (20 mg) and water (5 mL) at reux temperature. b Isolated
yields.
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Table
3
Comparison of the results obtained from the synthesis of 3,30-(4-chlorophenylmethylene)-bis-(1H-indole) and
3,30-(4-chlorophenylmethylene)-bis-(4-hydroxycoumarin) in the presence of P4VPy–CuO-NPs with those obtained using other catalysts
Product
Catalyst (loading)
Reaction conditions
Time (min)
Yield (%)
Ref.
FeCl3–RiH (150 mg)
80 ꢂC/EtOH
10
96
90
89
90
92
55
56
32
62
Ni nanoparticles (10 mol%)
ZrOCl2$8H2O (5 mol%)
Mg(HSO4)2 (1 mmol)
80 ꢂC/solvent-free
r.t./H2O–EtOH
r.t./EtOH
100
540
450
5
P4VPy–CuO-NPs (20 mg)
80 ꢂC/solvent free
(This work)
Cellulose sulfonic acid (20 mg)
[P4VPy–BuSO3H]HSO4 (0.1 mmol)
CuO–CeO2 nano-composite (50 mg)
SDS (20 mol%)
Reux/H2O
90 ꢂC/toluene
Reux/H2O
60 ꢂC/H2O
120
48
10
180
15
80
94
93
98
93
48
49
63
47
P4VPy–CuO-NPs (20 mg)
Reux/H2O
(This work)
Table 4 Reusability of P4VPy–CuO-NPs in the synthesis of bisindoles and biscoumarins
3,30-(4-Chlorophenylmethylene)-
bis-(1H-indole)
3,30-(4-Chlorophenylmethylene)-
bis-(4-hydroxycoumarin)
Run
Time (min)
Yield (%)
Time (min)
Yield (%)
1
2
3
5
7
10
92
90
86
15
18
23
93
90
83
Scheme 3 The possible mechanism for synthesis of biscoumarines in the presence of P4VP–CuO-NPs.
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Scheme 4 The plausible mechanism for synthesis of bisindoles in the presence of P4VP–CuO-NPs.
Table
3,30-(4-chlorophenylmethylene)-bis-(4-hydroxycoumarin) in the presence of P4VPy, bulk CuO and P4VPy–CuO-NPs
5
Comparison of the results obtained from the synthesis of 3,30-(4-chlorophenylmethylene)-bis-(1H-indole) and
3,30-(4-Chlorophenylmethylene)-
bis-(1H-indole)
3,30-(4-Chlorophenylmethylene)-
bis-(4-hydroxycoumarin)
Conversion
(%)
Entry
Catalyst
Time (min)
Conversion (%)
Time (min)
1
2
3
P4VP
CuO
P4VP–CuO-NPs
25
30
5
100
50
100
35
25
15
70
80
100
aldehydes were converted to their corresponding products in good activated by P4VPy–CuO-NPs. The intermediate undergoes
yields (Table 2, entries 18, 19). a second nucleophilic attack by another 4-hydroxycoumarin to
In order to show the merit of our newly developed proce- provide the nal product.63
dures, we have compared our results for the synthesis of 3,30-(4-
For synthesis of bisindoles, the condensation reaction
and probably proceeds through the activation of a carbonyl group by
chlorophenylmethylene)-bis-(1H-indole)
3,30-(4-chlorophenylmethylene)-bis-(4-hydroxycoumarin) using P4VPy–CuO-NPs. Then, indole attacks to the activated carbonyl
the P4VPy–CuO nanocatalyst with the results of some of the group to form intermediate which is subsequently attacks by
catalysts reported in the literature for the same transformation a second molecule of indole to product bis(indolyl)methanes as
(Table 3). The P4VPy–CuO-NPs as
improved the reaction very effectively and gave the desired
a
supported catalyst, shown in Scheme 4.
The reusability of the catalyst was also investigated for both
products in short reaction times. This catalyst is prepared easily types of the reactions. The model reactions were studied under
and a very low amount of the catalyst is used for the preparation the optimized reaction conditions. Aer completion of the
of the required reactions (Table 4).
reactions, the catalyst was separated by ltration, washed with
The proposed mechanism for the preparation of biscou- acetone, dried and used again in the same reaction. This
marines in the presence of P4VPy–CuO-NPs as the catalyst, process was repeated for at least three runs for each type of the
based on the reported pathway in literature,63 is shown in reactions with good activity.
Scheme 3. At rst, the aldehyde is activated by P4VPy–CuO-NPs.
In the next attempt, the catalytic activity of P4VPy–CuO
Nucleophilic attack of 4-hydroxycoumarin to activated aldehyde nanoparticles was compared with bulk CuO and P4VPy for the
followed by loss of H2O generates intermediate, which is further synthesis of 3,30-(4-chlorophenylmethylene)-bis-(1H-indole)
48476 | RSC Adv., 2016, 6, 48469–48478
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Fig. 5 TEM images of P4VPy–CuO-NPs by precipitation (left) and reflux (right) method.
and 3,30-(4-chlorophenylmethylene)-bis-(4-hydroxycoumarin).
Acknowledgements
The results proved the efficiency of the prepared catalyst as
shown in Table 5.
We are thankful to the University of Guilan Research Council
for the partial support of this work.
During a separate investigation and in order to evaluate the
ability of the method used for the preparation of the catalyst,
the reagent was also synthesized via two other methods, too. In
rst method, P4VPy–CuO nanoparticles were synthesized by
quick precipitation route. For this purpose, Cu(NO3)2$3H2O was
added to the suspension of P4VPy in deionized water and stirred
for 15 min. Then, a solution of NaOH 1 M was added to the
mixture at 60 ꢂC to form black nanoparticles.9 In the second
method, P4VPy–CuO nanoparticles were prepared via the reac-
tion of CuO and P4VPy in ethanol at reux temperature under
ambient conditions according the method reported by Albadi
et al.64
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