Sulfonated organic heteropolyacid salts: Recyclable green solid catalysts for the highly efficient and green synthesis of bis(indolyl)methanes in water

Article abstract of DOI:10.2174/157017812800221690

In the present study, we introduce two nonconventional ionic liquids [MIMPS]3PW12O40 (a) and [TEAPS]3PW12O40 (b) as green solid acid catalysts for the efficient synthesis of bis(indolyl)methanes. The reaction of indole with aldehydes or ketones in water a

Full text of DOI:10.2174/157017812800221690

138
Letters in Organic Chemistry, 2012, 9, 138-144
Sulfonated Organic Heteropolyacid Salts: Recyclable Green Solid Cata-
lysts for the Highly Efficient and Green Synthesis of Bis(indolyl)methanes
in Water
Seyed M. Vahdat*,a, Samad Khaksara and Saeed Bagheryb
aDepartment of chemistry, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran
bDepartment of chemistry, Young Research Club, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran
Received August 29, 2011: Revised October 14, 2011: Accepted October 21, 2011
Abstract: In the present study, we introduce two nonconventional ionic liquids [MIMPS]3PW12O40 (a) and
[TEAPS]3PW12O40 (b) as green solid acid catalysts for the efficient synthesis of bis(indolyl)methanes. The reaction of
indole with aldehydes or ketones in water afforded the corresponding bis(indolyl)methanes in excellent yields. This
reaction has been carried out in the presence of 1 mol% of catalysts at room temperature. The reusability of the catalysts
was demonstrated by a six-run test. Additionally, the catalysts pose several advantages including mild reaction conditions,
cleaner reactions and shorter reaction times.
Keywords: Bis(indolyl)methane, heteropolyacid salt, ionic liquid, green solid acid catalyst, water solvent.
INTRODUCTION
Performing organic reactions in aqueous media has
attracted much attention because of wonderful water
properties. It would be significantly safe, cheap, non-toxic
and environmentally friendly compared to organic solvents
[32]. Additionally, the catalyst system can be recycled using
the water soluble catalyst and the insoluble products can be
separated by simple filtration. So, development of a mild and
efficient catalyst system for the synthesis of
bis(indolyl)methanes is highly desirable. It should not only
be stable in water but also should be completely soluble in it.
Bis(indolyl)methanes are a biologically valuable group of
organic compounds. A large number of these compounds
have been isolated from earthly and marine natural sources
such as sponges [1]. They are also identified to promote
useful estrogen metabolism and are found in cruciferous
plants [2]. Bis(indolyl)methanes have many applications in
material sciences, agrochemicals, and pharmaceuticals [3].
So, in the recent years, there is a great interest in the
synthesis of these compounds [4, 5].
In recent years, ionic liquids have attracted much
attention as a new class of green solvent and catalyst [33].
These aqueous media is utilized for organic synthesis due to
their astonishingly properties, such as wide liquid range,
favorable solvating capability, low temperature requirement,
tunable polarity, high thermal stability, and ease of
recyclability [34-36]. Ionic liquids also have negligible vapor
pressure, which facilitates product separation by distillation.
Moreover, they are the cheapest and most environmentally
friendly solvents, because water exhibits unique reactivity
and selectivity, which differs from those in conventional
organic solvents. The appropriate property of the ionic
liquids lead to the development and application of so-called
‘‘task-specific’’ ionic liquids to synthesize the desirable
products. Recently, Wang et al. [37], prepared new
heteropolyanion-based ionic liquids containing the acidic
functional group as ‘‘task-specific’’ catalysts (a,b), (Fig. 1).
Many methods are reported to synthesize of bis(indol-3-
yl)methanes. The reaction of 1H-indole with aldehydes or
ketones produces azafulvenium salts which react further with
a
second 1H-indole molecule to form bis(indol-3-
yl)methanes [6]. Nowdays, synthesis of this category of
molecules under mild conditions has been reported in the
presence of promoters, such as, trichloro-1,3,5-triazine [7],
bentonite [8], ZrCl4 [9], Montmorillonite clay K-10 [10], I2
[11], AlPW12O40 [12], zeolites [13], Dy(OTf)3/ionic liquid
[14], In (OTf)3/ionic liquid [15], Sc(OTf)3 [11, 16], HClO4–
SiO2 [17], InCl3 [18], MW/Lewis acids (BiCl3, FeCl3, InCl3,
CoCl2, ZnCl2) [19], silica sulfuric acid (SSA) [20], acidic
ionic liquid [21], NBS [22], TiO2 [23], LiClO4 [24], NaBF4
[25], Ph3CCl [26], metal hydrogen sulfates [27], H3PW12O40
[28], ceric ammonium nitrate (CAN) [29], La(NO3)3 . 6H2O
[30], and Fe(DS)3 [31]. However, some of these reported
methods have one or more disadvantages such as moisture
sensitive, or highly toxic in environment and unpleasant
experimental procedure and reagents which are expensive. A
mild and efficient catalyst for the synthesis of bis(indolyl)
methanes is very desirable.
In the present research, we report two green solid
catalysts for the reaction of indoles with aldehydes or
ketones. They pose much higher activity in comparison with
the other reported catalysts as well as the additional
advantage of reusability. Remarkably, the conventional ionic
liquids (ILs) maintain their liquid state at room temperature
o
*Address correspondence to this author at the Department of chemistry,
Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran; Tel: 0098-
121-2517090; Fax: 0098-121-2517087;
or to some extent higher (20-30 C). However, the catalysts
used here (a,b) exhibit some different and noteworthy
properties compared to the other room temperature ionic
E-mails: m.vahdat@iauamol.ac.ir; vahdat_mohammad@yahoo.com
1875-6255/12 $58.00+.00
© 2012 Bentham Science Publishers

Sulfonated Organic Heteropolyacid Salts
Letters in Organic Chemistry, 2012, Vol. 9, No. 2
139
C2H5
C2H5
3-
N+
C2H5
SO3H
3-
N+
SO3H
PW12O40
PW12O40
3
N
H3C
3
a= [MIMPS]3PW12O40
b= [TEAPS]3PW12O40
Fig. (1).
liquids (RTILs) because of the high value of melting point
In order to show the merit of ILs in comparison with the
other catalysts used for the similar reaction, some of the
results are tabulated in Table 2. According to Table 2, the
required ratio for the most catalysts used for this purpose is
>1 mol% and also the required reaction times are much
longer (1–12 h).
o
(above 100 C). They revealed to be highly efficient green
and homogeneous catalysts because of their good solubility
in water. Also, the catalyst offers several advantages
including mild reaction conditions, shorter reaction times,
cleaner reactions, high yield of the products, simply
recovered and fairly steadily reused, lower catalytic loading
as well as simple experimental and isolation procedures
which make it useful for the synthesis of
bis(indolyl)methanes.
After finding the optimized reaction conditions, the
investigation was preceded by performing the reaction
between a series of aldehydes and ketones with indole. To
show the general applicability of this method, various
aldehydes and ketones were efficiently reacted with two
equivalents of indole in the same conditions. These results
encouraged us to investigate the scope and the generality of
this new protocol for various aldehydes and ketones under
optimized conditions. As shown in Table 3, a series of
aromatic, aliphatic and heterocyclic aldehydes and ketones
underwent electrophilic substitution reaction with indole to
afford a wide range of substituted bis(indolyl)methanes in
good to excellent yields. The nature and electronic properties
of the substituents on the aromatic ring effect the conversion
rate, and aromatic aldehydes having electron-withdrawing
groups on the aromatic ring (Table 3, entries 5, 6, 12) react
faster than electron-donating groups (Table 3, entries 7, 8,
11). Ketones (Table 3, entries 32-37) required longer
reaction times, which is most probably due to the
RESULTS AND DISCUSSION
First, we studied the reaction of benzaldehyde with
indole (1:2 molar ratios) to optimize the reaction conditions
with respect to temperature, time, solvent, molar ratio of
catalyst to the substrate and reusability of catalyst. It was
found that 1 mol% of catalyst was sufficient to obtain the
desired bis(indolyl)methane in 93% yield within 10 min at
room temperature in water using benzaldehyde, (Fig. 2).
The effect of solvent on the yield of bis(indolyl)methane
is given in Table 1. The reaction of indole with
benzaldehyde was chosen as
a model reaction for
investigating the effect of solvent. Among the solvents
examined, water was found to be the most effective solvent.
R2
R2
R2
O
R
R'
i or ii
+
R1
R
R'
N
H
2
1a-c
N
H
N
H
R1
R1
3
i= [MIMPS]3PW12O40 (1 mol%), H2O (2mL), r.t.
ii= [TEAPS]3PW12O40 (1 mol%), H2O (2mL), r.t.
1a: R1,R2= H, 1b: R1= Me, R2= H, 1c: R1= H, R2= NO2
Fig. (2).
Table 1. Solvent Effect on the Reaction Between Indole and Benzaldehydea
[MIMPS]3PW12O40
[TEAPS]3PW12O40
Entry
Solvent
Time (min)
Yield (%)b
Time (min)
Yield (%)b
1
2
3
4
5
H2O
CH3CN
CHCl3
10
10
19
13
16
93
91
87
91
90
29
31
41
33
37
89
87
81
87
84
C2H5OH
CH3CO2Et
aReaction condition indole (2 mmol), PhCHO (1mmol), catalyst (1 mol%), solvent (2 mL).
bIsolated yield.

140 Letters in Organic Chemistry, 2012, Vol. 9, No. 2
Vahdat et al.
Table 2. Reaction of Indole with Benzaldehyde in the Presence of Differnt Catalysts
Entry
Catalyst/Temprature
Catalyst (mol %)
Solvent
Time (min)
Yield (%)
Ref.
1
2
[MIMPS]3PW12O40/r.t.
[TEAPS]3PW12O40/r.t.
Ln(OTf)3/r.t.
1
H2O
H2O
10
29
93
89
95
71
90
98
92
80
50
84
This work
This work
[38a]
[38b]
[38c]
[14]
1
10
5
3
EtOH.H2O
CH3CN
EtOH
720
25
4
In(OTf)3/r.t.
5
La(PFO)3/r.t.
5
30
6
Dy(OTf)3/r.t.
2
Ionic Liquid
EtOH
60
7
Al(HSO4)3/r.t.
1
150
120
120
120
[27]
8
HY-Zeolite/r.t.
Yb(CF3CO2)3/r.t.
H3PW12O40/r.t.
0.5gr
5
CH2Cl2
EtOH.H2O
H2O
[13]
9
[38c]
[28]
10
1
Table 3. Reaction of Indole with Carbonyl Compound Under Condition i or ii
Under Condition i
Under Condition ii
Entry
Carbonyl Compound
Indole
Mp (oC) Ref
Time (min)
Yield (%)
Time (min)
Yield (%)
CHO
1
1a
10
93
29
89
146-148 [39a]
X
X= H
X= 2-Cl
X= 4-Cl
X= 2,4-Cl2
X= 2-NO2
X= 4-NO2
X= 4-Me
X=2,4-Me2
X= 2-OH
X= 4-OH
X= 4-OMe
X= 4-CN
X= 4-F
2
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1c
1c
9
8
94
95
94
96
98
95
95
89
91
93
97
95
94
98
93
95
95
93
98
95
91
27
25
25
23
18
25
24
31
29
28
19
25
25
21
28
28
23
28
16
23
29
91
93
92
93
95
93
93
86
88
89
94
93
93
95
87
90
94
88
95
93
88
70-72 [39a]
77-78 [39a]
3
4
8
141-142 [39b]
141-143 [39c]
219-221 [39a]
92-93 [39a]
5
6
6
4
7
8
8
7
182-184
9
11
9
341-343 [9]
210-211 [12]
185-187 [39a]
208-209 [39d]
73-75 [38c]
10
11
12
13
14
15
16
17
18
19
20
21
22
8
5
8
X= 4-Br
X= 4-Ph
X= 3-OPh
X= H
8
110-112 [39e]
247-248
4
9
84-85 [39f]
9
245-247 [39g]
175-177 [39g]
238-240 [12]
241-243 [39g]
146-148 [39h]
134-136 [39h]
X= 4-Me
X= 4-OH
X= 4-NO2
X= 4-Cl
X= 2-OH
X
7
9
3
7
11
23
1a
5
98
21
95
252-254 [39i]
X= 1-CHO

Sulfonated Organic Heteropolyacid Salts
Letters in Organic Chemistry, 2012, Vol. 9, No. 2
141
(Table 3). Contd…..
Mp (oC) Ref
Under Condition i
Time (min) Yield (%)
Under Condition ii
Time (min) Yield (%)
24 93
Entry
Carbonyl Compound
Indole
1a
X= 2-CHO
CHO
24
7
96
235-236 [39j]
242-244 [39j]
25
26
1a
1a
7
95
25
31
93
85
11
93
322-324 [39k]
CHO
X= O
X= S
CHO
X
27
28
1a
1a
13
16
91
85
34
41
84
81
151-152 [39k]
88-89 [39d]
CHO
CHO
CHO
29
30
31
1a
1a
1a
17
17
19
85
83
81
41
44
44
81
80
78
107-109 [39d]
67-68 [39l]
65-67 [39l]
2
4
5
O
32
33
1a
1a
29
24
81
87
51
45
75
78
163-165 [9]
Me
Me
O
118-120 [39a]
O
Me
34
1a
27
85
47
77
188-190 [39a]
X
X= H
X= 4-Cl
35
36
37
1a
1a
1a
23
21
18
87
87
89
43
41
38
81
86
84
108-109 [39c]
257-259 [39c]
235-237 [39m]
X= 3-NO2
X= 4-NO2
electrondonating and steric effects of the methyl group.
Notably, the obtained results depict that the catalyst (a) has
more activity than catalyst (b) which is in accordance with
that of the PS bearing catalyst.
this media, as shown in (Fig. 4), the recovered catalyst can
be reused at least six additional times in subsequent reactions
without appreciable loss in the catalytic activity.
When terephthaldialdehyde (4) was used, p-
bisindolylmethane benzaldehyde [40], (I) was produced in
excellent yield. When we used 4 molar equivalents of indole,
p-di(bis-indolylmethane)benzene [40], (II) was obtained in
excellent yield. The reactions were carried out under two
conditions and the experimental results demonstrate the
higher activity of catalyst a compared to catalyst b, (Fig. 3).
CONCLUSIONS
In summary, two nonconventional ionic liquids (a,b)
were used as an efficient catalyst for the synthesis of
bis(indolyl)methanes which resulted to better yields. Ionic
liquids effectively catalysis the reaction of indole with
aldehydes
or
ketones
in
water
to
produce
bis(indolyl)methanes in excellent yields. The catalyst offers
several advantages including mild reaction conditions,
cleaner reactions, shorter reaction times, high yield of the
products, lower catalytic loading, high melting point, green
solid acid catalyst as well as simple experimental and
The reusability of the catalysts was checked using 4-
nitrobenzadehyde as a model substrate. At the end of the
reaction, CH2Cl2 was added to the mixture. The aqueous
layer was separated and used without further purification. In

142 Letters in Organic Chemistry, 2012, Vol. 9, No. 2
Vahdat et al.
CHO
2
N
H
i or ii
N
H
N
H
CHO
Under Condition i
Under Condition ii
I
Mp (oC) Ref
Entry
Time
(min)
Yield
(%)
Yield
Time
(min)
(%)
H
H
N
N
123-125 40
191-193 40
I
11
13
33
37
91
94
81
87
CHO
II
4
4
N
H
i or ii
N
H
N
H
II
Fig. (3).
100
90
80
70
60
50
40
30
20
10
0
1
2
3
4
5
6
under condition i
under condition ii
98
98
98
97
96
96
95
94
94
93
92
92
Number of experiments
Fig. (4). Reusability studies of catalysts for synthesis of bis-(4-nitrophenyl-1H-indolyl)-methane (Table 3- entry 6).
isolation procedures. Also, the catalysts were able to be
reused easily for six-time experiments with a small decrease
in the catalytic activity of the recovered catalyst.
hexan/ethyl acetate 4:1). After completion of the reaction,
the resulting solid (crude product) was filtered and then
recrystallized from ethanol–water to obtain pure product.
The physical data (mp, NMR, IR) of these known
compounds were found to be identical with those reported in
the literature.
EXPERIMENTAL
Table 3, entry 3
General Procedure for the Synthesis of bis(indolyl)
methanes
o
o
Pale solid, mp 77–78 C (lit, 76-77 C); IR (KBr): 3420,
3385, 3055, 2920, 1605, 1456, 1325, 1130, 1100, 1015, 786,
1
744 cm-1; H NMR (400 MHz, CDCl3): ꢀ 5.74 (s, 1H), 6.35
A mixture of indole (2.0 mmol), aldehyde or ketone (1.0
mmol) and ionic liquids (1 mol%) in water (2 mL) was
stirred at room temperature for an appropriate time. The
progress of the reaction was monitored by TLC (n-
(s, 2H), 6.85–6.96 (m, 2H), 7.03–7.14 (m, 8H), 7.5 (d, 2H,
J= 7.9), 7.7 (br s, 2H); 13C NMR (400 MHz, CDCl3): ꢀ 44.5,

Sulfonated Organic Heteropolyacid Salts
Letters in Organic Chemistry, 2012, Vol. 9, No. 2
143
110.9, 112.3, 119.3, 121.2, 121.5, 122.7, 128.9, 131.1, 132.1,
135.6, 136.7.
CONFLICT OF INTEREST
Declared none.
Table 3, entry 6
Yellow solid, mp 219-221 oC (lit. 217-220 oC); IR (KBr):
REFERENCES
1
3455, 3424, 3385, 1590, 1517, 1456, 1341, 745 cm-1; H
[1]
Riccio, R.; Bifulco, G.; Bruno, I. Further brominated bis- and tris-
indole alkaloidsfrom the deep-water new caledonian marine sponge
Orina sp. J. Nat. Prod., 1995, 58, 1254-1260; (b) Bell, R.;
Carmelli, S.; Sar, N. Vibrindole A, a metabolite of the marine
bacterium Vibrio parahaemolyticus, isolated from toxic mucus of
the boxfish Ostracion cubicus. J. Nat., Prod. 1994, 57, 1587-1590;
(c) Fahy, E.; Potts, B.C.M.; Faulkner, D.J.; Smith, K. 6-
Bromotryptamine derivatives from the Gulf of California tunicate
Didemnum candidum. J. Nat. Prod., 1991, 54, 564-569.
Glasby, J.S. Encyclopedia of the Alkaloids; Plenum Press: New
York, 1975.
NMR (400 MHz, CDCl3): ꢀ 5.92 (s, 1H), 6.63 (d, J= 2.3 Hz,
2H), 6.94 (t, J= 7.9 Hz, 2H), 7.10-7.31 (m, 6H), 7.43 (d, J=
8.6 Hz, 2H), 7.96 (brs, 2H, NH), 8.16 (d, J= 8.8 Hz, 2H); 13C
NMR (400 MHz, CDCl3): ꢀ 40.3, 111.3, 118.1, 119.4, 119.6,
122.5, 123.6, 126.5, 129.7, 136.7, 151.8.
Table 3, entry 11
o
o
[2]
[3]
Brown needles, mp 185–187 C (lit. 185-187 C); IR
(KBr): 3421, 3385, 3052, 2925, 1615, 1457, 1340, 1137,
Ramirez, A.; Garcia-Rubio, S. Current progress in the chemistry
and pharmacology of akuammiline alkaloids. Curr. Med. Chem.,
2003, 10, 1891-1915.
1090, 1015, 786, 740 cm-1; H NMR (400 MHz, CDCl3): ꢀ
1
3.95 (s, 3H), 6.2 (s, 1H), 6.5 (s, 2H), 6.7–7.7 (m, 12H), 7.93
(br s, 2H); 13C NMR (400 MHz, CDCl3): ꢀ 39.7, 55.7, 102.5,
111.2, 119.6, 122.1, 123.7, 128.5, 129.7, 135.9, 136.7, 157.9.
[4]
Chakrabarty, M.; Ghosh, N.; Basak, R.; Harigaya, Y. Dry reaction
of indoles with carbonyl compounds on montmorillonite K-10 clay:
a mild, expedient synthesis of diindolylalkanes and vibrindole A.
Tetrahedron Lett., 2002, 43, 4075-4078.
Table 3, entry 19
[5]
[6]
Reddy, A.V.; Ravinder, K.; Reddy, V.L.N.; Venkateshwer-Goud,
T.; Ravikanth, V.; Venkateswarlu, Y. Zeolite catalyzed synthesis of
bis(indolyl) methanes. Synth. Commun., 2003, 33, 3687-3694.
Remers, W.A. Indoles, part1: properties and reactions of indoles,
isoindoles, and their hydrogenated derivatives. In Houlihan WJ
Heterocyclic compounds; Interscience Publishers: New York,
1972; pp. 1-226.
o
o
Pinkish powder, mp 238–240 C (lit. 237-239 C); IR
(KBr): 3425, 3058, 2971, 1456, 1335, 1225, 1097, 745 cm-1;
1H NMR (400 MHz, CDCl3): ꢀ 9.63 (s, 2H, NH), 8.61 (s, H,
OH), 7.15 (d, 2H, J = 7.7 Hz), 7.01 (d, 2H, J = 7.6 Hz), 6.73
(m, 4H), 6.51 (m, 4H), 5.64 (s, 1H), 1.83 (s, 6H); 13C NMR
(400 MHz, CDCl3) ꢀ 155.2, 135.1, 134.5, 131.8, 129.7,
128.5, 119.7, 118.8, 118.1, 114.8, 113.1, 110.2, 38.1, 12.3.
[7]
Sharma, G.V.M.; Reddy, J.J.; Lakshmi, P.S.; Krishna, P.R.A.
versatile and practical synthesis of bis(indolyl)methanes/ bis
(indolyl)glycoconjugates catalyzed by trichloro-1,3,5-triazine.
Tetrahedron Lett., 2004, 45, 7729-7732.
Table 3, entry 23
[8]
Penieres-Carrillo, G.; García-Estrada, J.G.; Gutiérrez-Ramírez,
J.L.; Alvarez- Toledano, C. Infrared-assisted eco-friendly selective
synthesis of diindolylmethanes. Green Chem., 2003, 5, 337-339.
Zhang, Z.H.; Yin, L.; Wang, Y.M. An efficient and practical
process for the synthesis of bis(indolyl)methanes catalyzed by
zirconium tetrachloride. Synthesis, 2005, 1949-1954.
o
o
Pale pink solid, mp 252-254 C (lit. 252-253 C); IR
(KBr): 3425, 3055, 2925, 2846, 1593, 1456, 1345, 1090, 743
1
cm-1; H NMR (400 MHz, CDCl3): ꢀ 6.56 (s, 1H), 6.67 (S,
[9]
1H), 6.97 (t, J= 7.3 Hz, 2H), 7.20 (t, J= 7.8 Hz, 2H), 7.23-
7.46 (m, 9H), 7.55 (s, 1H), 7.71 (d, J= 7.6 Hz, 1H), 7.94 (brs,
2H, NH), 8.17 (d, J= 8.4 Hz, 1H); 13C NMR (400 MHz,
CDCl3): ꢀ 36.3, 111.4, 119.5, 119.6, 120.1, 122.3, 124.6,
125.6, 125.8, 126.4, 127.3, 127.6, 128.7, 134.1, 137.2.
[10]
[11]
[12]
Chakrabarty, M.; Ghosh, N.; Basak, R.; Harigaya, Y.A. facile and
efficient synthesis of 2,2-bis(3'/2'-indolyl)ethylamines and three
bisindolic natural products. Synth. Commun., 2004, 34, 421-434.
Bandgar, B.P.; Shaikh, K.A. Molecular iodine–catalyzed efficient
and highly rapid synthesis of bis-indolyl-methane under mild
conditions. Tetrahedron Lett., 2003, 44, 1959-1961.
Table 3, entry 32
Firouzabadi,
H.;
Iranpoor,
N.;
Jafari,
A.A.
o
o
Aluminumdodecatungstophosphate (AlPW12O40), a versatile and a
highly water tolerant green Lewis acid catalyzes efficient
preparation of indole derivatives. J. Mol. Catal. A: Chem., 2006,
244, 168-172.
Karthik, M.; Tripathi, A.K.; Gupta, N.M.; Palanichamy, M.;
Murugesan, V. Zeolite catalyzed electrophilic substitution reaction
of indoles with aldehydes: synthesis of bis(indolyl)methanes.
Catal. Commun., 2004, 5, 371-375.
Pale red solid, mp 163-165 C (lit. 165-167 C); IR
(KBr): 3425, 2961, 1623, 1456, 1335, 1099, 745 cm-1; H
1
NMR (400 MHz, CDCl3): ꢀ 1.87 (S, 6H), 6.85 (t, J= 7.3 Hz,
2H), 6.96 (d, J= 2.3 Hz, 2H), 7.17 (d, d, J= 7.1, 7.9 Hz, 2H),
7.25 (d, J= 8.3 Hz, 2H), 7.42 (d, J= 8.03Hz, 2H), 7.79 (brs,
2H, NH); 13C NMR (400 MHz, CDCl3): ꢀ 30.3, 34.8, 111.4,
118.7, 120.6, 121.2, 121.3, 125.5, 126.3, 137.3.
[13]
[14]
[15]
[16]
Mi, X.; Luo, S.; He, J.; Cheng, J.P. Dy(OTf)3 in ionic liquid: an
efficient catalytic system for reactions of indole with aldehydes/
ketones or imines. Tetrahedron Lett., 2004, 45, 4567-4570.
Ji, S.J.; Zhou, M.F.; Gu, D.G.; Wang, S.Y.; Loh, T.P. Efficient
synthesis of bis(indolyl)methanes catalyzed by Lewis acids in ionic
liquids. Synlett, 2003, 2077-2079.
Ma, S.; Yu, S.; Peng, Z. Sc(OTf)3-catalyzed efficient synthesis of
b,b-bis(indolyl) ketones by the double indolylation of acetic acid 2-
methylene-3-oxobutyl ester. Org. Biomol. Chem., 2005, 3, 1933-
1936.
Kamble, V.T.; Kadam, K.R.; Joshi, N.S.; Muley, D.B. SiO2 as a
novel and recyclable catalyst for the synthesis of bis-
indolylmethanes and bis-indolylglycoconjugates. Catal. Commun.,
2007, 8, 498-502.
Table 3, entry 34
Auburn solid, mp 188-190 oC (lit. 189-190 oC); IR (KBr):
1
3421, 3057, 2974, 1456, 1335, 1217, 1099, 745 cm-1; H
NMR (400 MHz, CDCl3): ꢀ 2.44 (S, 3H), 6.62 (d, J= 2.4 Hz,
2H), 6.94(t, J= 7.5 Hz, 2H), 7.08-7.55 (m, 11H), 8.15 (brs,
2H, NH); 13C NMR (400 MHz, CDCl3): ꢀ 28.7, 65.5, 111.4,
119.1, 121.4, 122.3, 123.3, 124.5, 125.7, 126.4, 127.8, 128.3,
138.4.
[17]
[18]
[19]
Pradhan, P.K.; Dey, S.; Giri, V.S.; Jaisankar, P. InCl3-HMTA as a
methylene donor: one-pot synthesis of diindolylmethane (DIM) and
its derivatives. Synthesis, 2005, 1779-1782.
Xia, M.; Wang, S.H.; Yuan, W.B. Lewis acid catalyzed
electrophilic substitution of indole with aldehydes and schiff’s
ACKNOWLEDGEMENT
The authors are thankful for the facilities provided to
carry out research in chemistry research laboratory at
Ayatollah Amoli Branch, Islamic Azad University.

144 Letters in Organic Chemistry, 2012, Vol. 9, No. 2
Vahdat et al.
bases under microwave solvent-free irradiation. Synth. Commun.,
2004, 34, 3175-3182.
Zolfigol, M.A.; Salehi, P.; Shiri, M.; Sayadi, A.; Abdoli, A.;
Keypour, H.; Rezaeivala, M.; Niknam, K.; Kolvari, E. A simple
and efficient route for the synthesis of di and tri(bis(indolyl)
methanes) as new triarylmethanes. Mol. Divers., 2008, 12, 203-
207.
Hagiwara, H.; Sekifuji, M.; Hoshi, T.; Qiao, K.; Yokoyama, C.
Synthesis of bis(indolyl)methanes catalyzed by acidic ionic liquid
immobilized on silica (ILIS). Synlett, 2007, 1320-1322.
Koshima, H.; Matsuaka, W. N-Bromosuccinimide catalyzed
condensation of indole with carbonyl compounds under solventfree
conditions. J. Heterocycl. Chem., 2002, 39, 1089-1091.
Hosseini-Sarvari, M. Titania (TiO2)-catalyzed expedient,
solventless andmild synthesis of bis(indolyl)methanes. Acta Chim.
Slovenica., 2007, 54, 354-359.
Separation Catalysts for Esterification. Ang. Chem. Int. Ed., 2009,
48, 168-171.
[20]
[38]
[39]
(a) Chen, D.; Yu, L.; Wang, P.G. Lewis acid-catalyzed reactions in
protic media. Lanthanide-catalyzed reactions of indoles with
aldehydes or ketones. Tetrahedron Lett., 1996, 37, 4467-4470; (b)
Nagarajan, R.; Perumal, P.T. InCl3 and In(OTf)3 catalyzed
reactions: synthesis of 3-acetyl indoles, bis-indolylmethane and
indolylquinoline derivatives. Tetrahedron., 2002, 58, 1229-1232;
(c) Wang, L.; Han, J.H.; Sheng, T.; Fan, J.Z.; Tang, X. Rare Earth
Perfluorooctanoate [Re(PFO)3]-Catalyzed Condensations of Indole
with Carbonyl Compounds. Synlett, 2005, 337-339.
[21]
[22]
[23]
[24]
[25]
[26]
Ma, Z.C.; Zhang, Z.H. CuBr2-catalyzed synthesisof bis(indolyl)
methanes. Synth. Commun., 2005, 35, 1997-2004; (b) Li, J.T.;
Zhang, X.H.; Song, Y.L. Efficient synthesis of bis(indol-3-
yl)methanes catalyzed by silicotungstic acid under ultrasound
dirradiation. Int. J. Chem. Tech. Res., 2010, 2, 341-345; (c) Li, J.T.;
Dai, H.G.; Xu, W.Z.; Li, T.S. An efficient andpractical synthesis of
bis(indolyl)methanes catalyzedby aminosulfonic acid under
ultrasound. Ultrason. Sonochem., 2006, 13, 24-27; (d) Bandgar,
B.P.; Bettigeri, S.V.; Joshi, N.S. Hexamethylenetetraaminebromine
catalyzed rapid and efficient synthesis of bis(indolyl)methanes.
Monatsh. Chem., 2004, 135, 1265-1273; (e) Vaghei, R.G.; Veisi,
H.; Keypour, H.; Dehghani-Firouzabadi, A.A. A practical and
efficient synthesis of bis(indolyl)methanesin water, and synthesis
of di-, tri-, and tetra(bis-indolyl)methane sunder thermal conditions
catalyzed by oxalic acid dehydrate. Mol. Divers., 2010, 14, 87-96;
(f) Yadav, J. S.; Gupta, M.K.; Jain, R.; Yadav, N.N.; Reddy, B.V.S.
A practical synthesis of bis(indolyl)methanes employing boric acid.
Monatsh. Chem., 2010, 141, 1001-1004; (g) Hasaninejad, A.; Zare,
A.; Sharghi, H.; Niknam, K.; Shekouhy, M. P2O5/SiO2 as an
efficient, mild, and heterogeneous catalytic system for the
condensation of indoles with carbonyl compounds under solvent-
free conditions. Arkivoc., 2007, 14, 39-50; (h) Rahimizadeh, M.;
Eshghi, H.; Bakhtiarpoor, Z.; Pordel, M. Ferric hydrogensulfate as
Mehrazma, S.; Azizi, N.; Saidi, M.R. Clean and facile condensation
reaction of indoles and carbonyl compounds under solvent- free
conditions. Lett. Org. Chem., 2006, 3, 161-164.
Kamble, V.T.; Bandgar, B.P.; Bavikar, S.N. Highly efficient
synthesis of bis(indolyl)methanes catalyzed by sodium
tetrafluoroborate. Chin. J. Chem., 2007, 25, 13-15.
Khalafi-Nezhad, A.; Parhami, A.; Zare, A.; Moosavi Zare, A.R.;
Hasaninejad, A.; Panahi, F. Trityl chloride as a novel and efficient
organic catalyst for room temperature preparation of
bis(indolyl)methanes under solvent-free conditions in neutral
media. Synthesis, 2008, 617-621.
[27]
[28]
[29]
[30]
[31]
Niknam, K.; Zolfigol, M.A.; Sadabadi, T.; Nejati, A. Preparation of
indolylmethanes catalyzed by metal hydrogen sulfates. J. Iran.
Chem. Soc., 2006, 3, 318-322.
Azizi, N.; Torkian, L.; Saidi, M.R. Highly efficient synthesis of
bis(indolyl)methanes in water. J. Mol. Catal. A: Chem., 2007, 275,
109-112.
Deb, M.L.; Bhuyan, P.J. An efficient and clean synthesis of
bis(indolyl)methanes in a protic solvent at room temperature.
Tetrahedron Lett., 2006, 47, 1441-1443.
a
recyclable catalyst for the synthesis of some new
bis(indolyl)methane derivatives. J. Chem. Res., 2009, 5, 269-270;
(i) Banerjee, B.; Mandal, S.K.; Roy, C.S. Efficient synthesis of
bis(indolyl)methanes in aqueous medium catalyzed by molybdenyl
acetylacetonate. Indian J. Chem., Sect B., 2007, 46, 669-673; (j)
Magesh, C.J.; Nagarajan, R.; Karthik, M.; Perumal, P.T. Synthesis
and characterization of bis(indolyl)methanes, tris(indolyl)methanes
and new diindolylcarbazolylmethanes mediated by Zeokarb-225, a
novel, recyclable, eco-benign heterogenous catalyst. Appl. Catal.
A: General., 2004, 266, 1-10; (k) Ji, S.J.; Wang, S.Y.; Zhang, Y.;
Loh, T.P. Facile synthesis of bis(indolyl)methanes using catalytic
amount of iodine at room temperature under solvent-free conditions
original research article. Tetrahedron., 2004, 60, 2051-2055; (l)
Aliyan, H.; Fazaeli, R.; Naghash, H.J.; Massah, A.R.; Momeni,
A.R.; Iravani, Z. Bulk and supported tungstophosphoric acidas
friendly, efficient, recyclable catalysts for the synthesis of bis-
indolylmethanes under solvent-free conditions. Heteroatom
Chemistry., 2009, 20, 325-331; (m) Du, D.M.; Meng, S.M.; Wang,
Y.M.; Meng, J.B.; Zhou, X.Z. Solid state reaction of aromatic
ketones withheteroaromatics. Chin. J. Chem., 1995, 13, 520-524.
Zolfigol, M. A.; Salehi, P.; Shiri, M.; Tanbakouchian, Z. A new
catalytic method for the preparation of bis-indolyl and tris-indolyl
methanes in aqueous media. Catal. Commun., 2007, 8, 173-178.
Selvam, J.; Venkateswarlu, Y. Lanthanum(III) nitrate hexahydrate:
A versatile reagent for the synthesis of bis(indolyl) methanes under
solvent-free conditions. Synth. Commun., 2008, 38, 1760-1767.
Wang, S.Y.; Ji, S.J. Facile synthesis of bis-indolyl-methanes
catalyzed by ferric dodecyl sulfonate [Fe(DS)3] in water at room
temperature. Synth. Commun., 2008, 38, 1291-1298.
[32]
[33]
Li, C.J.; Chan, T.H. Organic reaction in aqueousemedia; Wiley:
New York, 1997; pp. 1-189.
Khalafi-Nezhad, A.; Mokhtari, B. Tetrabutylammonium bromide:
an efficient media for dimethoxytritylation of the 5ꢀ-hydroxyl
function of nucleosides. Tetrahedron Lett., 2004, 45, 6737-6739.
Welton, T. Room-Temperature Ionic Liquids. Solvents for
Synthesis and Catalysis. Chem. Rev., 1999, 99, 2071-2084.
Wasserscheid, P.; Keim, W. Ionic liquids – New ' solutions' for
transition metal catalysis. Ang. Chem. Int. Ed., 2000, 39, 3772-
3789.
[34]
[35]
[36]
[37]
Welton, T. Ionic liquids in catalysis. Coord. Chem. Rev., 2004,
248, 2459-2477.
Leng, Y.; Wang, J.; Zhu, D.; Ren, X.; Ge, H.; Shen, L.
Heteropolyanion-Based Ionic Liquids: Reaction-Induced Self-
[40]