Green and efficient synthesis of aryl/alkylbis(indolyl)methanes using Expanded Perlite-PPA as a heterogeneous solid acid catalyst in aqueous media

Article abstract of DOI:10.1007/s12039-017-1246-x

Expanded Perlite-Polyphosphoric acid (EP-PPA) as a novel, efficient, recyclable and eco-benign heterogeneous catalyst has been applied for the green and rapid synthesis of aryl/alkylbis(indolyl)methanes, in water, in good to excellent yields. The catalyst

Full text of DOI:10.1007/s12039-017-1246-x

c
J. Chem. Sci. ꢀ Indian Academy of Sciences.
DOI 10.1007/s12039-017-1246-x
REGULAR ARTICLE
Green and efficient synthesis of aryl/alkylbis(indolyl)methanes using
Expanded Perlite-PPA as a heterogeneous solid acid catalyst in aqueous
media
MARZIEH ESMAIELPOUR, BATOOL AKHLAGHINIA∗ and ROYA JAHANSHAHI
Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad 9177948974, Iran
Email: akhlaghinia@um.ac.ir
MS received 10 October 2016; revised 19 December 2016; accepted 3 February 2017
Abstract. Expanded Perlite-Polyphosphoric acid (EP-PPA) as a novel, efficient, recyclable and eco-benign
heterogeneous catalyst has been applied for the green and rapid synthesis of aryl/alkylbis(indolyl)methanes, in
water, in good to excellent yields. The catalyst was characterized by XRF, FT-IR, TGA/DTG, ICP-OES, SEM-
EDX and pH analysis. Importantly, the newly synthesized heterogeneous solid acid catalyst can be recovered
and reused six times without any significant loss in its catalytic potential. The remarkable features of the
present methodology are high conversions, shorter reaction times, cleaner reaction profiles and simple work-up
procedures.
Keywords. Expanded Perlite-PPA; aryl/alkylbis(indolyl)methanes; carbonyl compounds; heterogeneous
catalyst.
1. Introduction
with carbonyl compounds, catalyzed by either protic
or Lewis acids14,15 such as montmorillonite clay,16,17
oxone,18 NH4Cl,19 cellulose sulfuric acid,20 ionic
liquid,21 oxalic acid,22 La(OTf)3,23 In(OTf)3,24 zirco-
nium tetrakis(dodecyl sulfate),25 H6P2W18O62,26 phos-
phated zirconia,27 12-tungstophosphoric acid supported
on zirconia,28 GaCl3,29 ZnO,30 FeCl3.6H2O,31 Al2O3,32
zirconyldodecylsulfate,33 I2,34 silica gel,35 pyridinium
tribromide,36 SiO2/AlCl3,37 Iron(III) dodecyl sulfate,38
PPA-SiO2,39,40 ammonium niobium oxalate and tetra-
butylammonium hydrogen sulfate.41 The reported met-
hods indicate that the catalysts commonly used for
such a transformation, are generally associated with one
or more of the following disadvantages such as high to-
xicity, high cost, difficulty of handling, low thermal
stability and un-recyclability. In addition to these draw-
backs, tedious methods required for the separation of the
products, along with using the environmentally harmful
organic solvents in some of these approaches, are defi-
nitely far from the concept of “Green Chemistry”. Also,
because of either the strong adsorption or polymeriza-
tion of indole by Lewis acid sites, these methods consume
more reactants than the required amounts, according
to the stoichiometries of the reactions.42 Likewise,
many Lewis acids are deactivated or sometimes decom-
posed by nitrogen-containing reactants, which would
Indole and its natural and synthetic derivatives are impor-
tant heterocyclic compounds due to their wide-ranging
biological and pharmaceutical activities.1 3 Among the
different indole derivatives, aryl/alkylbis(indolyl)met-
hanes are well-known as an old but privileged class of
bioactive metabolites,4 6 due to their representation in
natural products7 and extensive applications in pharma-
ceuticals.8 Over the past few years, a variety of bis
(indolyl)methanes have been isolated from earthly and
marine natural sources such as parasitic bacteria, tuni-
cates, and sponges,3,9and these have exhibited antibac-
terial activity against Staphylococcus aureus, S. albus
and Bacillus subtilis,10 in addition to anti-inflammatory
and antibacterial activity.11
Bis(indolyl)methanes are the most active cruciferous
substances for promoting beneficial estrogen metabo-
lism.12 These can be effective in the prevention of can-
cer and moreover may normalize the abnormal cell
growth associated with cervical dysplasia.13 Therefore,
the synthesis of this class of compounds is of conside-
rable interest for synthetic organic chemists (towards the
development of new protocols) and biologists. To seek
efficient and convenient synthetic routes of bis(indo-
lyl)methanes, great efforts have been made.
Traditionally, bis(indolyl)methanes have been syn- lead to use of more than stoichiometric amounts of
thesized by electrophilic substitution reaction of indoles Lewis acids, besides the generation of harmful wastes,
which would pose environmental problems.42 Further-
∗For correspondence
more, although solid acid catalysts promote the synthesis

Marzieh Esmaielpour et al.
recorded on Brucker Avance 300 and 500 MHz instruments in
of bis(indolyl)methane, some of them require very high
temperature for reactivation.43
CDCl3 and DMSO-d6. Mass spectra were recorded with a Shi-
madzu GC-MS-QP5050 and CH7A Varianmat Bremem instru-
ment at 70 eV, in m/z (rel %). Thermogravimetric analyses (TGA
and DTG) were carried out using a Shimadzu Thermogravimet-
ric Analyzer (TG-50) in the temperature range of 25–900◦C
at a heating rate of 10◦C min−1, under air atmosphere. Induc-
tively coupled plasma optical emission spectroscopy (ICP-
OES) was carried out on a 76004555 SPECTRO ARCOS
ICP-OES analyzer. SEM images were recorded using a
Leo1450 VP scanning electron microscope equipped with an
SC7620 energy-dispersive X-ray spectrometer (EDX), pre-
senting a 133 eV resolution at 20 kV. The chemical compo-
sitions of the expanded perlite were specified with X-ray
fluorescence spectroscopy (XRF), using BRUKER axs-S4
EXPLORER spectrometer. All of the obtained products are
known compounds and their physical (color, melting points)
and spectral (mass spectrometry) data were found to be iden-
tical with those of authentic compounds. The selected com-
Keeping in view the increasing importance of
bis(indolyl)methane derivatives in pharmaceutical and
industrial chemistry, there is still much demand to
develop a better catalytic process, that would abate the
environmental impact of the pollution resulting from
the above mentioned methods reported for the synthesis
of such significant scaffolds.
Polyphosphoric acid (PPA) has been employed as
an efficient protic acid catalyst for numerous organic
reactions.44 Nevertheless, the difficulty of PPA han-
dling, due to its viscous nature, has limited its appli-
cation. To surmount this problem and in continuation
of our ongoing research in synthetic organic chemistry,
for the development of efficient and environmentally
benign heterogeneous catalysts,45 herein, we report
Expanded Perlite-PPA (EP-PPA), as a novel, green and
efficient heterogeneous catalyst (Scheme 1). The cat-
alytic activity of EP-PPA was verified by the synthesis
of aryl/alkylbis(indolyl)methanes through the one-pot
reaction of indole and carbonyl compounds, in water.
Importantly, this distinguished catalyst is easy to pre-
pare and handle and could be separated simply by filtra-
tion and also recycled for six times without significant
loss of its catalytic activity.
1
pounds were further identified by FT-IR, H NMR and 13C
NMR spectroscopy which compared with literature data.
2.3 Preparation of EP-PPA
A mixture of polyphosphoric acid (2.1 g) in CHCl3 (100 mL)
was stirred at 50◦C for 1 h. Expanded Perlite (4.9 g) was
added to the resulting solution and the mixture was stirred
vigorously. After 1 h, CHCl3 was removed under reduced
pressure and the resulting solid was dried in vacuo at room
temperature for 3 h.
2. Experimental
2.1 Materials
2.4 Typical procedure for the synthesis of 3,3ꢁ-
(phenylmethylene)bis(1H-indole) in the presence of
EP-PPA
All chemical reagents and solvents were purchased from
Merck and Sigma-Aldrich and were used as received with-
out further purification. Expanded Perlite was obtained from
Iran: Birjand resources.
To a mixture of indole (2 mmol, 0.234 g) and benzaldehyde
(1 mmol, 0.106 g) in H2O (3 mL), EP-PPA (0.04 g) was
added. The mixture was allowed to stir at 60◦C. Upon com-
pletion of the reaction (monitored by TLC analysis), the cat-
alyst was separated by filtration. After the filtration, H2O
2.2 Instrumentation analysis
The purity determination of the products and the progress of (10 mL) was added and the product was extracted into ethyl
the reactions were monitored by TLC on silica gel polygram acetate (3 × 15 mL). The combined organic layer was dried
STL G/UV 254 plates. The melting points of products were over anhydrous Na2SO4 and then evaporated under vac-
determined with an Electrothermal Type 9100 melting point uum to afford the crude product, which was further purified
apparatus. The FT-IR spectra were recorded on an Avatar 370 by thin layer chromatography (preparative TLC was carried
FT-IR Therma Nicolet spectrometer. The NMR spectra were out using a Merck GF 254 silica gel on a glass support)
Scheme 1. Preparation of Expanded Perlite-PPA.

Synthesis of aryl/alkylbis(indolyl)methanes using Expanded Perlite-PPA
using n-hexane:ethyl acetate (3:1) as eluent. The pure 3,3ꢁ- thermogravimetric/differential thermogravimetric anal-
(phenylmethylene)bis(1H-indole) was obtained in 98% yield
(0.315 g).
ysis (TG/DTG), scanning electron microscopy (SEM),
energy-dispersive X-ray spectroscopy (EDX), Induc-
tively coupled plasma optical emission spectroscopy
(ICP-OES) and pH analysis. The obtained results from
these techniques confirmed the successful preparation
of the new catalyst.
3. Results and Discussion
Expanded Perlite is a green and inexpensive mix-
ture of mineral oxides, which mainly consists of sil-
ica and alumina46 (Table 1). The exclusive features
of Expanded Perlite include high porosity besides
3.1 Characterization of the catalyst
strong adsorbability, thermal and chemical stability, 3.1a FT-IR spectroscopy of the catalyst: FT-IR spec-
low toxicity, low cost, non-corrosiveness and ease tra of Expanded Perlite and EP-PPA are shown in
of handling.47 These distinctive properties make the Figure 1. As it is obvious in Figure 1a, there are five
Expanded Perlite an excellent support for the prepara- significant absorption bands in the infrared spectrum of
tion of heterogeneous catalysts.48 EP-PPA was prepared Expanded Perlite.49 The indicative bands correspond-
by the concise route outlined in Scheme 1. The cur- ing to the stretching and bending modes of hydroxyl
rent method has many advantages such as simplifica- groups on the surface of Expanded Perlite (mainly
tion of the catalyst system and its synthesis, as well as Si–OH groups) and the adsorbed water molecules are
using an inexpensive and available precursor. The as- depicted at 3439 cm−1 and 1625 cm−1, respectively.48b
synthesized white heterogeneous, non-hygroscopic cat- The peaks at 1044 cm−1 and 791 cm−1 are assigned to
alyst is very stable under the reaction conditions. This Si–O stretching vibrations of Si–O–Si and Si–O–Al,
new catalyst was characterized by different techniques respectively.50 Moreover, O–Si–O bending vibrations
such as fourier transform infrared spectroscopy (FT-IR), are evident at about 463 cm−1.49 In the spectrum of
Table 1. The chemical composition of Expanded Perlite based on XRF analysis.
Constituent
SiO2
Al2O3
K2O
Fe2O3
Na2O
CaO
MgO
Percentage
Constituent
Percentage
75.22
BaO
0.08
12.77
SO3
0.06
5.18
ZrO2
0.01
0.74
TiO2
0.11
2.52
Rb2O
0.01
0.60
SrO
0.01
0.22
MnO
0.06
Figure 1. FT-IR spectrum of, (a) Expanded Perlite; (b) EP-PPA and (c) 6th recovered EP-PPA.

Marzieh Esmaielpour et al.
EP-PPA, absorption band at about 1043–977 cm−1 is
ascribed to P–O stretching vibration of PPA.51 Another
band at around 1220–1135 cm−1 is related to stretch-
ing vibration of P=O bond.51 In addition, the P–O–H
stretching modes are observed as broad peaks at about
2441–2327 cm−1.51 It is worth to note that the intensity
of O–H stretching vibration from 3300 to 3450 cm−1 in
the case of EP-PPA is more than that of Expanded Per-
lite, which clearly indicates the incorporation of PPA on
the Expanded Perlite surface.
3.1c pH analysis of the catalyst: The amount of aci-
dic sites in EP-PPA was determined by back-titration
analysis of the catalyst, wherein 100 mg of the catalyst
was stirred with sodium hydroxide solution (0.1 N, 15 ml)
at room temperature, for 12 h. Afterwards, the suspen-
sion was filtered and the filtrate was neutralized using a
standard solution of HCl (0.1 M). The required volume
of HCl to reach the equivalence point of titration was
7.3 ml. Accordingly, the number of acidic sites for EP-
PPA was found to be 4.7 mmol g−1. Furthermore, on the
basis of ICP-OES analysis, the total amount of grafted
P was calculated to be 2.48 mmol g−1, which matched
well with the results evaluated by TGA and pH analysis.
3.1b TGA of the catalyst: Thermogravimetric (TG)
and differential thermogravimetric (DTG) analysis we-
re used to investigate the thermal stability of the
acidic catalyst. TGA thermograms of EP-PPA and bare
Expanded Perlite are shown in Figure 2. The results
demonstrate that the Expanded Perlite (Figure 2a)
showed an initial weight loss, occurring below 120◦C
(about 0.5%) which is attributed to the loss of the physi-
cally adsorbed water molecules. After that, Expanded
Perlite had a steady weight loss at temperature lower
than 600◦C (about 3%), which presumably corresponds
to the dehydroxylation of Expanded Perlite.52
3.1d SEM analysis of the catalyst: Selected SEM
images for the Expanded Perlite and EP-PPA, were used
to study the structure and morphology of the catalyst
(Figure 3). It is clear that the morphology of Expanded
Perlite is a layered porous structure, which remains
constant after the immobilization of PPA on its surface.
3.1e EDX analysis of the catalyst: Figure 4 depicts
TGA thermogram of EP-PPA (Figure 2b) shows ini- the elemental components of Expanded Perlite and
tial weight loss below 200◦C, which is due to the EP-PPA by the energy-dispersive X-ray spectroscopy
absorbed water molecules on the Expanded Perlite sur- (EDX). As can be seen in Figure 4, the presence of C, O,
face. The second step involves the decomposition of Na, Al, Si, and K elements are evident in the EDX anal-
PPA, which started after 200◦C and continued up to ysis of both Expanded Perlite and Expanded Perlite-
600◦C. According to the TGA, the amount of polyphos- PPA. The existence of P element in the EDX analysis
phoric acid supported on the Expanded Perlite is esti- of EP-PPA, confirms the successful immobilization of
mated to be 14%.
PPA on the Expanded Perlite.
Scheme 2. TG/DTG thermograms of (a) Expanded Perlite and (b) EP-PPA.

Synthesis of aryl/alkylbis(indolyl)methanes using Expanded Perlite-PPA
Scheme 3. SEM images of Expanded Perlite (a, b) and EP-PPA (c, d).
3.2 Catalytic synthesis of aryl/alkylbis(indolyl)methane which is certainly related to the sticky state of PPA in
derivatives
the solvent free condition at 80◦C, that has disrupted
the magnetic stirring during the reaction. However,
In the present study, a series of bis(indolyl)methanes in the presence of Expanded Perlite and EP-PPA,
were prepared by the condensation of indole (1), with the corresponding bis(indolyl)methane was obtained in
different carbonyl compounds (2) in the presence of 40% and 70% yields, respectively. As can be seen, EP-
EP-PPA, as heterogeneous green catalyst (Scheme 2). PPA afforded an excellent yield of product in a short
The reactions proceeded efficiently to afford the desired reaction time, in H2O (Table 2, entry 5). To improve
bis(indolyl)methanes (3a–x) in good to excellent yields. the bis(indolyl)methane formation, at the same reac-
At the outset, the reaction between benzaldehyde tion conditions, the effect of temperature and catalyst
(1 mmol) and indole (2 mmol) was studied as a model amount was studied and we found that the best result
reaction from the viewpoint of temperature, solvent, was acquired at 60◦C by applying 0.04 g of EP-PPA
and the amounts of catalyst (Table 2). It is well-known (Table 2, entries 6–9). In an effort to develop still
that indole is not active enough in the Friedel-Crafts better reaction conditions, the reaction was examined
alkylations, without using any catalyst (Table 2, entry in H2O/C2H5OH (1:1, v:v) and C2H5OH as solvent
1). So, choosing a suitable catalyst is crucial for the (Table 2, entries 10–11). In the presence of these sol-
highly efficient alkylation of indole with benzaldehyde. vents, the reaction was sluggish. As shown in Table 2,
Therefore, PPA, Expanded Perlite, and EP-PPA were H2O was found to be the solvent of choice for the prepa-
examined on the model reaction at 80◦C, under solvent- ration of 3,3ꢁ-(phenylmethylene)bis(1H-indole), in the
free condition (Table 2, entries 2–4). It is clear that presence of EP-PPA. Performing the organic reactions
PPA by itself was not effective for this transformation, in aqueous media has attracted much attention owing to

Marzieh Esmaielpour et al.
Scheme 4. EDX analysis of (a) Expanded Perlite and (b) EP-PPA.
the wonderful properties of water. Considering the sig-
With these impressive results in hand, to investigate
nificantly safe, cheap, non-toxic and environmentally the scope of this new methodology, the reaction was
friendly nature of water compared to organic solvents, extended through the condensation of indole with var-
it would be one of the best and greenest reaction media ious carbonyl compounds and the results are summa-
in organic synthesis.53
rized in Table 3. It can be seen that a wide range of
In order to emphasize the efficiency of EP-PPA in aromatic aldehydes can effectively react with indole to
comparison with PPA and Expanded Perlite in aqueous give the corresponding products. However, the nature
media, the reaction was performed in the absence of the of substitution on the aromatic ring showed some effect
catalyst and in the presence of PPA and Expanded Per- on the reaction progress. Aromatic aldehydes bearing
lite (in H2O at 60◦C) (Table 2, entries 12–14). In all electron-withdrawing groups, provided the desired pro-
cases, the product yield was not convincing.
ducts in excellent yields witin shorter reaction times,
′
′
Scheme 2. Synthesis of aryl/alkylbis(indolyl)methane derivatives in the presence of EP-PPA.

Synthesis of aryl/alkylbis(indolyl)methanes using Expanded Perlite-PPA
Table 2. Synthesis of 3,3ꢁ-(phenylmethylene)bis(1H-indole) under different reac-
tion conditions.
Entry Catalyst/g
Solvent
Temperature/◦C Time/min Isolated yield/%
1
0
–
–
–
–
80
80
80
80
80
80
70
60
60
60
60
60
60
60
10/24 h
30
0/0
0
2a
3b
4
0.05
0.05
0.05
0.05
0.04
0.04
0.04
0.03
0.04
0.04
0
60
40
70
98
98
98
98
60
75
50
0
15
5
H2O
10
6
H2O
10
7
H2O
10
8
H2O
10
9
H2O
20
10
11
12
13c
14d
H2O/C2H5OH
C2H5OH
H2O
15
15
15
0.05
0.05
H2O
H2O
15
40
35
15
aThe reaction was performed in the presence of PPA under the solvent-free condition.
bThe reaction was performed in the presence of Expanded Perlite under the solvent-
free condition.
cThe reaction was performed in the presence of PPA in H2O.
dThe reaction was performed in the presence of Expanded Perlite in H2O.
wheras the condensation reaction with aldehydes hav- entries 1–10 vs. 11–16). Heteroaromatic aldehydes such
ing electron-donating groups took a longer time, albeit as thiophene-2-carbaldehyde and pyridine-3-carboxal-
good yield of the products were obtained (Table 3, dehyde were also suitable substrates in this protocol,
Scheme 3. Proposed mechanism for the preparation of aryl/alkylbis(indolyl)methanes in the presence of EP-PPA.

Marzieh Esmaielpour et al.
Table 3. Synthesis of structurally different aryl/alkylbis(indolyl)methanes in the presence of EP-PPA.
Entry
Carbonyl compound
Product
Time/min
Isolated yield/%
3a
1
10
98
3b
3c
3d
3e
2
3
4
5
7
5
7
3
94
96
95
95

Synthesis of aryl/alkylbis(indolyl)methanes using Expanded Perlite-PPA
Table 3. (Continued)
3f
6
5
97
3g
7
8
96
3h
8
15
87
3i
9
10
30
30
90
90
82
3j
10
3k
11

Marzieh Esmaielpour et al.
Table 3. (Continued)
3l
12
30
87
3m
13
35
86
3n
14
30
88
3o
15
20
89
3p
16
17
25
25
91
78
3q

Synthesis of aryl/alkylbis(indolyl)methanes using Expanded Perlite-PPA
Table 3. (Continued)
3r
3s
18
19
15 min/2 h
50/80
48/72
20 min/3 h
3t
20
25
75
3u
3v
21
22
15
25
70
70
3w
23
55
60
3x
24
40
65

Marzieh Esmaielpour et al.
although the corresponding reaction rates were dimin- A plausible mechanism for the EP-PPA catalyzed
ished to some extent (Table 3, entries 17 and 18). synthesis of aryl/alkylbis(indolyl)methanes is shown in
Likewise, structurally hindered aldehydes (such as 1- Scheme 3. In the initial step, EP-PPA activates the
naphthaldehyde), cinnamaldehyde and aliphatic alde- carbonyl group of the carbonyl compound, making it
hydes (such as octanal and hexanal) reacted smoothly susceptible to attack by indole. Nucleophilic attack of
with indole to give the corresponding products in mod- indole to activated carbonyl compound leads to the for-
erate yields (Table 3, entries 19–22). Further, we also mation of intermediate I, which generates II by losing
examined the reaction of some ketones with indole, but water. Further addition of the second molecule of indole
the results were far from satisfactory. In the case of affords intermediate III, which then suffers a hydride
cyclohexanone and isatin, the reactions were not com- shift to furnish aryl/alkylbis(indolyl)methanes forma-
pleted even after a prolonged reaction time and the tion. In the entire mechanism, EP-PPA was regenerated
best obtained yields of the products were low: 60 and and reused for the consecutive runs.
65%, respectively (Table 3, entries 23, 24). Moreover,
Recyclability of the EP-PPA catalyst was checked for
the electrophilic substitution reactions of ethyl methyl the model reaction of indole and benzaldehyde. After
ketone, 2-heptanone, methyl vinyl ketone, isobutyl me- completion of the reaction, the catalyst was separated
thyl ketone, and cyclopentanone with indole were also by filtration and then washed with deionized water and
examined under the optimized condition, but the best ethanol 3 times. The separated catalyst was dried at
obtained range of the products yields were only 10– 50◦C and utilized for subsequent preparation of 3,3ꢁ-
20%, even after a long period of time (data are not given (phenylmethylene)bis(1H-indole). The procedure was
in Table 3). However, no product was obtained when repeated six times without any significant loss of effi-
aryl ketones such as acetophenone and propiophenone ciency, as the catalyst remained active even after the
were used in this reaction under the same conditions sixth run and led to 84% yield of the product (Figure 5).
(data are not given in Table 3). It can be concluded that
Furthermore, the FT-IR spectrum for the reused cat-
the progress of this transformation was not convincing alyst after 6 runs indicates that all of the characteristic
with ketones, which is most probably due to their lower peaks have been well preserved in terms of shape, posi-
reactivity as compared to the aldehydes.
tion, and relative intensity. These results reveal that no
Melting points of the obtained aryl/alkylbis(indolyl) significant changes have occurred in the chemical struc-
methanes were closely matching with those reported in ture of functional groups and the hydrogen bonding net-
the literature. The FT-IR spectra of aryl/alkylbis(indo- work of the catalyst, during the reaction progress and
lyl)methanes reveal the characteristic absorption bands multiple recovery operations.
at 3408–3367 (N–H), 2925–2922 (aliphatic C–H),
The superior catalytic activity of EP-PPA compared
1617–1602 and 1455–1454 cm−1 (aromatic C=C). with some other acidic catalysts for the synthesis
Moreover, 1H NMR spectra confirmed the condensation of 3,3ꢁ-(phenylmethylene)bis(1H-indole) was investi-
reactions by the appearance of the characteristic signals gated and results are shown in Table 4. Among these
at δ 7.9–7.73 (br s, NH), 5.9–5.74 (s, aliphatic C–H) and catalysts, EP-PPA presents the best performance in this
7.03–6.54 (s, pyrrole C–H).
transformation, with respect to shorter reaction time,
100
100
98
97
95
90
98
98
96
95
93
100
90
80
70
60
50
40
30
20
10
0
84
First
Second
Third
Fourth
Fifth
Sixth
Isolated yield
Conversion
Figure 5. Synthesis of 3,3ꢁ-(phenylmethylene)bis(1H-indole) in the presence of reused EP-PPA.

Synthesis of aryl/alkylbis(indolyl)methanes using Expanded Perlite-PPA
Table 4. Comparison between the efficiency of EP-PPA and some other catalysts
for the synthesis of 3,3ꢁ-(phenylmethylene)bis(1H-indole).
Entry
Catalyst
Solvent
Time/min Yield/%
Ref.
22
26
54
55
56
57
58
59
1
2
3
4
5
6
7
8
9
Oxalic acid
H2O
–
H2O
45
40
3/h
2.5/h
10
30
40
96
96
90
86
95
96
88
93
98
H6P2W18O62
Squaric acid
HMTABa
Cu1.5PMo12O40
Cu(BF4)2.SiO2
Cu/MWCNT-GAA@Fe3O4b
Br2
H2O
Ionic liquid
CH2Cl2
H2O
H2O
H2O
6/h
10
EP-PPA
Present study
aHexamethylenetetramine-bromine.
bCopper nanocatalyst based on magnetic guanidine acetic acid (GAA) functionalized
multi-wall carbon nanotube (MWCNT).
lower temperature, and higher yield. In addition, several Acknowledgements
of the previously reported procedures involved using
The authors gratefully acknowledge the partial support of
this study by Ferdowsi University of Mashhad Research
Council (Grant no. p/3/40471).
toxic, non-recyclable, expensive chemicals or difficult
and time-consuming synthesis-based catalysts, whereas
the current catalyst shows unique advantages includ-
ing simplification of the catalytic system and its syn-
thesis, besides the application of inexpensive, natural, References
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