Tris(hydroxymethyl)methane ammonium hydrogensulphate as a nano ionic liquid and its catalytic activity in the synthesis of bis(indolyl)methanes

Article abstract of DOI:10.1016/j.molliq.2016.10.136

In this study, tris(hydroxymethyl)methane ammonium hydrogensulphate [(THA)(HSO₄)] was synthesized as the first nanoaliphatic ammonium-based ionic liquid via a simple chemical route in water. The [(THA)(HSO₄)] ionic liquid was charact

Full text of DOI:10.1016/j.molliq.2016.10.136

Tris(hydroxymethyl)methane ammonium hydrogensulphate as a nano ionic
liquid and its catalytic activity in the synthesis of bis(indolyl)methanes
Moones Honarmand, Elaheh Esmaeili
PII:
DOI:
Reference:
S0167-7322(16)32325-X
doi: 10.1016/j.molliq.2016.10.136
MOLLIQ 6540
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Accepted date:
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11 September 2016
31 October 2016
Please cite this article as:
Moones Honarmand,
Elaheh Esmaeili,
Tris(hydroxymethyl)methane ammonium hydrogensulphate as a nano ionic liquid
and its catalytic activity in the synthesis of bis(indolyl)methanes, Journal of Molecular
Liquids (2016), doi: 10.1016/j.molliq.2016.10.136
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ACCEPTED MANUSCRIPT
Tris(hydroxymethyl)methane ammonium hydrogensulphate as a
nano ionic liquid and its catalytic activity in the synthesis of
bis(indolyl)methanes
Moones Honarmand,* Elaheh Esmaeili
Department of Chemical Engineering, Faculty of Mining, Civil and Chemical Engineering, Birjand University of
Technology, Birjand 97175/569, Iran
E-mail: honarmand@birjandut.ac.ir; honarmand.moones@yahoo.com; Tel: +98 56 32391306; Fax: +98 53
3
2391238
Abstract: In this study, tris(hydroxymethyl)methane ammonium hydrogensulphate [(THA)(HSO )] was synthesized
4
as the first nano aliphatic ammonium-based ionic liquid via a simple chemical route in water. The [(THA)(HSO )]
4
1
13
ionic liquid was characterized by various techniques such as XRD, SEM, TEM, AFM, H NMR, C NMR, FT-IR,
MS, TG, DTG and elemental analysis and successfully applied as an eco-friendly and recyclable catalyst for the
synthesis of bis(indolyl)methane derivatives at room temperature under solvent-free conditions. Taking the
environment and economy into consideration, the work presented here has the merits of environmental friendliness,
high yields, simple work-up, easy operation and the avoidance of the organic solvents and inexpensive catalysts. In
this work, some bis(indolyl)methane derivatives were synthesized and reported for the first time.
Keywords: Nanocatalyst; Ammonium-based ionic liquid; Bis(indolyl)methanes; Recyclability
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1
.
Introduction
In recent years, ionic liquids as catalyst have attracted significant attention due to their peculiar properties including
low vapour pressure, excellent thermal and chemical stability, tunable polarity, high ionic conductivity and
immiscibility with certain organic solvents [1-6]. The widespread range of possible cation and anion combinations
represents the various applications and tunable interactions [7]. Most studies on ionic liquids have focused on the
imidazolium-based ionic liquids [8]. Recently, Zolfigol and his co-workers have been reported the first nano ionic
liquid namely 1-methylimidazolium trinitromethanide and employed it for Hanztsch four-component condensation
[
9]. The air and moisture stability and the ease of preparation of ammonium-based ionic liquids from cheap starting
materials [10] make them attractive for catalytic application.
The synthesis of bis(indolyl)methanes has become the center of interest among world scientists as key moieties
having extensive applications in medicinal and biological chemistry [11-14]. Bis(indolyl)methanes are employed in
laser technologies and fluorescent materials for visualization of biomolecules [15]. A number of methods were
reported for the synthesis of bis(indolyl)methanes by the electrophilic substitution of indole with the various
aldehydes in the presence of the different catalysts [16-18] and sources of energy like microwave [19] and ultrasound
[
20]. Moreover, ionic liquids including [bmim][PF ], [bmim][BF ] [21], [bmim][MeSO ] [22] (bmim = 1-butyl-3-
6 4 4
methylimidazolium) and guanidinium ILs [23] were found as promoter for the synthesis of bis(indolyl)methanes. In
view of the importance of bis(indolyl)methane a development of newer methodology is desirable.
In our ongoing works on the introduce of efficient and environmentally benign procedures using ionic liquids [24-
2
7], herein, we have synthesized tris(hydroxymethyl)methane ammonium hydrogensulphate [(THA)(HSO )] as a
4
novel nano ammonium-based ionic liquid via a simple chemical route in water. To explore the catalytic activity of
(THA)(HSO )] ionic liquid in organic reactions, we have used it as a novel, green and reusable nano catalyst for the
[
4
efficient synthesis of bis(indolyl)methanes.
2
2
.
Experimental section
General Information
.1.
Chemicals were purchased from Merck Chemical Company and used as received. Melting points were determined
by Buchi 510 apparatus and are uncorrected. NMR spectra were recorded on a Bruker Avance DPX-400 using
deutrated DMSO-d as solvent and TMS as internal standard. The purity of the products and the progress of the
6
reactions were accomplished by TLC on silicagel polygram SILG/UV254 plates. TEM analysis was performed
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using TEM microscope (Philips CM30). FT-IR spectra were recorded on a Shimadzu Fourier Transform Infrared
Spectrophotometer (FT-IR-8300). A Shimadzu thermo gravimetric analyzer (TG-50) was applied to characterize the
gravimetric (TG) and differential thermal gravimetric (DTG) behavior of the [(THA)(HSO4)] ionic liquid.
Elemental analysis was carried out by a ECS4010 CHNSO analyzer. The morphology of the products was
determined by using Hitachi Japan, model s4160 Scanning Electron Microscopy (SEM) at accelerating voltage of 15
kV. Power X-ray diffraction (XRD) patterns were obtained through a Bruker D8-advance X-ray diffractometer with
Cu Ka (k = 0.154 nm) radiation. Mass spectra were recorded by a Shimadzu GCMS-QP5050A. An atomic force
microscopy (DME Model Igloo) was also utilized for AFM images.
2
.2.
Typical procedure for the synthesis of [(THA)(HSO )]
4
A solution of Tris(hydroxymethyl)aminomethane (50 mmol, 6.057 g) in water (15 mL) was dropwisely added to an
aqueous solution of sulfuric acid (50 mmol, 5.004 g) at room temperature. However, the stirring of the resultant
solution was preserved for another 20 h at the same conditions. Then water was removed by distillation under
reduced pressure at room temperature and the residue was dried at room temperature to reach up to [(THA)(HSO )]
4
as a white solid.
o
Tris(hydroxymethyl)methane ammonium hydrogensulphate [(THA)(HSO )]. M.P: 97-98 C; Yield: 98% (10.733 g);
4
-
1 1
IR (KBr): υ 2500-3500, 1211, 1186, 610 cm ; H NMR (400 MHz, DMSO-d ): δ 7.64 (s, 3 H), 5.57 (br, 3 H), 3.49
6
13
+
(
s, 6 H); C NMR (100 MHz, DMSO-d ): δ 59.7, 61.4; MS: m/z = 219 [M] .
6
2
.3.
General procedure for the synthesis of bis(indolyl)methanes in the presence of [(THA)(HSO )]
4
A mixture of aldehyde (1 mmol), indole (2 mmol) and [(THA)(HSO )] (2 mol%, 0.004 g) was stirred at room
4
temperature, for the appropriate time, as observed in Table 2. The progress of the reaction was monitored by TLC.
After completion of the reaction, water (20 mL) was added to the reaction mixture and the resulted solid was filtered
and washed with H O (2 × 10 mL), followed by the recrystallization in EtOH. Nano ammonium-based ionic liquid
2
was recovered by evaporation of the filtrate and drying in vacuum at room temperature.
Spectral data of unknown bis(indolyl)methanes
1
3
,3'-((2-chlorophenyl)methylene)bis(2-methyl-1H-indole) (2). M.P. 233-234 ºC; H NMR (400 MHz, DMSO-d ): δ
6
1
0.80 (s, 2 H, NH), 7.45 (d, J = 7.2 Hz, 1 H, Ar), 7.30-7.26 (m, 1 H, Ar), 7.25-7.22 (m, 4 H, Ar), 6.91 (td, J = 7.4
Hz, J = 1.2 Hz, 2 H, Ar), 6.76 (d, J = 8.0 Hz, 2 H, Ar), 6.69 (t, J = 7.6 Hz, 2 H, Ar), 6.09 (s, 1 H, CH), 2.02 (s, 6 H,
13
CH3); C NMR (100 MHz, DMSO-d ): δ 12.1, 34.4, 110.3, 111.0, 118.2, 118.8, 120.3, 125.0, 128.1, 128.6, 131.0,
6
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1
1
7
3
1
1
6
1
32.8, 133.1, 135.5, 138.3, 150.6; FT-IR (KBr) (υmax/cm ): 3442, 3389, 1459, 473; Anal. Calcd for C H ClN : C,
25 21 2
8.01; H, 5.50; N, 7.28. Found: C, 78.04; H, 5.55; N, 7.29.
1
,3'-((2-nitrophenyl)methylene)bis(2-methyl-1H-indole) (3). M.P. 248-249 ºC; H NMR (400 MHz, DMSO-d ): δ
6
0.87 (s, 2 H, NH), 7.85 (d, J = 7.8 Hz, 1 H, Ar), 7.58 (td, J = 7.6, J = 1.6, 1 H, Ar), 7.51 (td, J = 7.6 Hz, J= 1.2 Hz,
H, Ar), 7.28 (d, J = 7.2, 1 H, Ar), 7.24 (d, J = 8 Hz, 2 H, Ar), 6.92 (t, J = 7.6 Hz, 2 H, Ar), 6.76-6.69 (m, 4 H, Ar),
1
3
.60 (s, 6 H, CH), 2.08 (s, 6 H), , C NMR (100 MHz, DMSO-d ): δ 142.1, 135.5, 134.0, 132.7, 131.2, 129.8,
6
-
1
28.8, 128.4, 127.1, 120.1, 118.6, 118.3, 111.0, 110.9, 37.3, 12.2; FT-IR (KBr) (υmax/cm ): 3482, 3390, 1526, 773;
Anal. Calcd for C H N O : C, 75.93; H, 5.35; N, 10.63. Found: C, 75.95; H, 5.38; N, 10.69.
2
5
21
3
2
1
3
,3'-(naphthalen-1-ylmethylene)bis(2-methyl-1H-indole) (16). M.P. 290-291 ºC; H NMR (400 MHz, DMSO-d ): δ
6
1
0.77 (s, 2 H, NH), 7.98 (d, J = 8.4 Hz, 1 H, Ar), 7.94 (d, J = 7.6 Hz, 1 H, Ar), 7.84 (d, J = 8.0 Hz, 1 H, Ar), 7.45 (t,
J = 6.8 Hz, 1 H, Ar), 7.38 (t, J = 8.0 Hz, 1 H, Ar), 7.36 (t, J = 8.0 Hz, 1 H, Ar), 7.22 (t, J = 6.4 Hz, 3 H, Ar), 6.89 (t,
J = 7.6 Hz, 2 H, Ar), 6.81 (d, J = 7.2 Hz, 2 H, Ar), 6.66 (t, J = 7.6 Hz, 2 H, Ar), 6.53 (s, 1 H, CH), 1.98 (s, 6 H,
13
CH3); C NMR (100 MHz, DMSO-d ): δ 140.4, 135.6, 133.9, 132.7, 132.3, 129.1, 129.0, 127.4, 126.5, 126.3,
6
-
1
1
25.8, 125.7, 124.4, 120.1, 118.7, 118.6, 112.5, 110.9, 36.6, 12.3; FT-IR (KBr) (υmax/cm ): 3422, 3402, 1460, 745;
Anal. Calcd for C H N : C, 86.97; H, 6.04; N, 6.99. Found: C, 86.99; H, 6.05; N, 7.01.
2
9
24
2
2
.4.
Procedure for the reusability test of [(THA)(HSO )] nanocatalyst
4
A mixture of aldehyde (5 mmol), indole (10 mmol) and [(THA)(HSO )] (2 mol%, 0.02 g) was stirred at room
4
temperature for 5 min. After completion of the reaction, water (40 mL) was added to the reaction mixture and the
resulted solid was filtered and washed with H O (2 × 10 mL). Nano ammonium-based ionic liquid was recovered by
2
evaporation of the filtrate and drying in vacuum at room temperature. [(THA)(HSO )] was then reused at the same
4
conditions as above for at least five reaction runs and delivered the corresponding product (1) in high yield.
3
3
.
Results and discussion
.1.
Characterization of tris(hydroxymethyl)methane ammonium hydrogensulphate [(THA)(HSO )] as a
4
nano ionic liquid
Tris(hydroxymethyl)methane ammonium hydrogensulphate [(THA)(HSO )] as a novel ammonium-based ionic
4
1
13
liquid was synthesized and fully characterized by XRD, SEM, TEM, AFM, H NMR, C NMR, FT-IR, MS, TG,
DTG and elemental analysis.
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13
The H NMR and C NMR spectra of [(THA)(HSO )], in DMSO-d were shown in Figure 1. In The presence of a
4
6
peak in δ = 3.49 ppm was allocated to hydrogens of methylene group. The peaks related to OH and NH groups on
13
cationic moiety were appeared at δ = 5.57 and 7.64 ppm, respectively. Also, in C NMR spectrum of
[
(THA)(HSO )], carbons of cationic moiety were observed in δ = 61.4 and 59.6 ppm.
4
Figure 1.
FT-IR spectra of [(THA)(HSO )], tris(hydroxymethyl) aminomethane and sulfuric acid were implied in Figure 2. In
4
the FT-IR spectra of [(THA)(HSO )], tris(hydroxymethyl) aminomethane and sulfuric acid, a broad peak centered at
4
-
1
2
500-3500 cm was attributed to stretching vibrations of N-H, O-H and C-H bands. The peaks were appeared at
-
1
about 1211 and 1186 cm in the spectra of [(THA)(HSO )] and sulfuric acid, could be related to the stretching
4
-
1
vibrations of S=O bond. Also, an absorption peak at 601 cm was well assigned to the stretching vibrations of S-O
bond.
Figure 2.
In the mass spectrum of [(THA)(HSO )], the parent peak was displayed at 219 m/z (Figure 3) which was in good
4
agreement with the elemental analysis data (N = 6.42 %, C = 21.96 %, H = 5.99 % and S = 14.68 %).
Figure 3.
The thermogravimetric (TG) and differential thermal gravimetric (DTG) analyses were used to determine the
thermal stability of [(THA)(HSO )] (Figure 4). According to the results of TG and DTG exhibited in Figure 4, the
4
weight loss of [(THA)(HSO )] ionic liquid occurred in a single step after 244 ºC was indicative of its good thermal
4
stability up to 244 ºC.
Figure 4.
Size, shape and morphology of [(THA)(HSO )] were studied through scanning electron microscopy (SEM),
4
transmission electron microscopy (TEM), x-ray diffraction (XRD) pattern, and atomic force microscopy (AFM)
analysis imaging demonstrations.
SEM images of [(THA)(HSO )] were clearly presented the morphology of nano ammonium-based ionic liquid
4
(
Figure 5). Taking into consideration of the TEM photography, [(THA)(HSO )] had a unique spherical morphology
4
with good monodispersity (Figure 6). The particle size distribution of [(THA)(HSO )] evaluated by the use of TEM
4
results found to be at the range of 8-24 nm.
Figure 5.
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Figure 6.
XRD patterns of [(THA)(HSO )] in a domain of 10-60 degree was illustrated in Figure 7. As shown in Figure 7,
4
XRD patterns presented the diffraction lines including high crystalline nature at 2θ ≈ 16.06º, 17.72º, 18.59º, 20.09º,
2
1.56º, 30.34º, 31.31º, 35.88º, 43.83º and 45.24º. The mean crystallite size was calculated via the Scherrer equation
[
D = Kλ/(βcosθ)] (Where D is the crystallite size, K is the shape factor, λ is the x-ray wavelength, β is the full width
at half maximum of the diffraction peak, and θ is the Bragg diffraction angle in degree). It was found that mean
crystallite size to be in the nanometer range (15.1-24.6 nm) which corresponded with what referred from TEM, as
well.
Figure 7.
The AFM images of [(THA)(HSO )] gave good information about surface morphology of nano structure
4
ammonium-based ionic liquid. AFM images were derived from 2.1 μm * 2.1 μm scan part of the samples (Figure 8).
2
No key division area in size was recognized in the illustrations. From three-dimensional 2.1 μm * 2.1 μm
framework, it came out that the achieved nano structure ammonium-based ionic liquid showed an interrupted
structure with a superior beyond planarity. Using AFM results, in the surface conformation of the coat,
[
(THA)(HSO )] was obviously detected with the size distribution less than 15 nm.
4
Figure 8.
3
.2.
Catalytic activity of [(THA)(HSO )] ionic liquid in the synthesis of bis(indolyl)methanes
4
The catalytic activity of the prepared ammonium-based ionic liquid was examined through the synthesis of
bis(indolyl)methanes. For this purpose, initially, the reaction of benzaldehyde and 2-methyl-1H-indole at room
temperature was chosen as a model reaction for the optimizing of the reaction parameters such as the amount of the
catalyst and the solvent. The model reaction in the presence of different catalytic amounts of [(THA)(HSO )] was
4
investigated under solvent-free conditions (Figure 9) and the desired product obtained in high yield just after 5 min
in the presence of 2 mol% of the catalyst. However, no significant improvement of the yield was observed when the
amount of catalyst increased. In order to show the role of the catalyst, the model reaction in the absence of the
catalyst was examined under solvent-free conditions. The obtained result was shown that the reaction did not
proceed and the starting materials remained intact after 5 min (Figure 9).
Figure 9.
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The model reaction was also examined in several solvents including H O, EtOH, EtOAc, acetone and n-hexane in
2
the presence of 2 mol % of catalyst (Figure 10). The volatile and toxic nature of many organic solvents has caused a
serious threat to the environment because of significantly contribution in the production of the chemical wastes.
Therefore, there are numerous demands for development of the solvent-free methods which work at the ambient
temperature to prevent the utilization of the volatile organic compounds. As shown in Figure 10, the best result was
obtained under solvent-free conditions.
Figure 10.
The generality and versatility of this method for the synthesis of bis(indolyl)methane derivatives were investigated
by the reaction of various aldehydes and indoles under optimized reaction conditions (2 mol% of nano ammonium-
based ionic liquid at room temperature under solvent-free). The results of these studies were summarized in Table 1.
As indicated in Table 1, the reaction of substituted benzaldehydes bearing electron-releasing and electron
withdrawing groups with 2-methyl-1H-indole were proceeded well and produced the corresponding products in
good to high yields after 5 to 20 min (Table 1, entries 1-6). Indole was also applied in the target condensation
reaction with some substituted benzaldehydes bearing electron with-drawing and electron donating substituents
(
Table 1, entries 7-15). The comparison of the obtained results obviously confirmed that the 2-methyl-1H-indole
was more reactive towards the condensation reaction than indole. It seems that the electronically nature impact of
the methyl substituent on 2-methyl-indole positively affected the electrophilic attack of indole group to the aldehyde
molecule which facilitates the generation of indolyl carbinol intermediate. Interestingly, [(THA)(HSO )] efficiently
4
improved the synthesis of bis(indolyl)methanes without polymerization or decomposition by the use of acid-
sensitive aldehydes such as 1-naphtaldehyde as a polynuclear aldehyde and furfural and indole-3-carbaldehyde as
the heteroaromatic aldehydes (Table 1, entries 16-19). The nano ammonium-based ionic liquid was also successfully
applied for the synthesis of bis(indolyl)methanes from the reaction of indoles with aliphatic aldehyde (Table 1,
entries 20 and 21). It was noteworthy that both carbonyl groups in terephthalaldehyde react with indole leading to
the production of desired compounds (22) in high yield (Table 1, entry 22).
Table 1.
To show the special catalytic behavior of [(THA)(HSO )] ionic liquid in the synthesis of bis(indolyl)methanes, the
4
reaction of benzaldehyde and indole was performed in the presence of the various ammonium salts such as
NH OAc, (NH ) CO , NH Cl, (NH ) C O .H O, (NH ) SO , NH NO , NH SCN and (NH ) Cr O at room
4
4 2
3
4
4 2
2
4
2
4 2
4
4
3
4
4 2
2
7
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temperature under solvent-free conditions (Table 2, entries 1-9). As is evident from Table 2, [(THA)(HSO )] ionic
4
liquid was the most effective catalyst for this purpose leading to the formation of bis(indolyl)methane 7 in high yield
in a short reaction time. To elucidate the role of the cationic moiety of ionic liquid, the similar reactions was carried
out in the presence of NaHSO , NH HSO and Et NHHSO and the desired product (7) formed after 2, 1 and 6 h in
4
4
4
3
4
5
7, 88 and 49 yields, respectively (Table 2, entries 10-12). Also, the effect of hydroxyl functional groups of
[
(THA)(HSO )] on the catalytic process was investigated. The catalytic activity of tert-butylammonium
4
hydrogensulfate was checked under the same reaction conditions and bis(indolyl)methane 7 obtained after 1 h in 86
yield (Table 1, entry 13). The obtained result was indicated the catalytic activity of [(THA)(HSO )] was
%
4
originated somewhat from the hydroxyl functional groups in the structure of [(THA)(HSO )].
4
Table 2.
Since, the catalyst reusability is of considerable importance, the recovery of [(THA)(HSO )] ionic liquid in the
4
model reaction of benzaldehyde and 2-methyl-indole under the optimized reaction conditions was investigated. The
reaction was very clean with no side-product formation and the desired product was obtained in excellent yield.
Following the completion of the reaction, water was subsequently added to the reaction mixture. Since,
[
(THA)(HSO )] was completely soluble in water, the desired product was filtered off and purified by
4
recrystallization in EtOH. The nano ammonium-based ionic liquid was recovered after the evaporation of the filtrate.
Therefore, nano ammonium-based ionic liquid could be completely isolated easily by simple filtration and reused at
least five times without any significant loss of the initial catalytic activity (Figure 11).
Figure 11.
The comparison of TEM images of the used (Figure 12) and fresh catalyst (Figure 6) showed that the morphology of
[
(THA)(HSO )] remained intact after five recovery times. Furthermore, the elemental analysis data (CHNS)
4
confirmed the accuracy of the recovered catalyst.
Figure 12.
The title methodology is cost-effective, environmentally friendly and industrially important because of using
reusable, eco-friendly and inexpensive catalyst. These advantages for this high yielding condensation method
offered ready scalability. For example, in the present investigation, the condensation of benzaldehyde and 2-methyl
indole in a 20 mmol scale in the presence of the [(THA)(HSO )] ionic liquid was investigated. As expected, the
4
8

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reaction proceeded similarly to the smaller scale, and the desired product was obtained at the same isolated yield and
reaction time.
4
.
Conclusions
In summary, in this work, tris(hydroxymethyl)methane ammonium hydrogensulphate [(THA)(HSO )] was
4
synthesized as a green and environmentally friendly ammonium-based ionic liquid in water from readily available
1
13
starting materials. The [(THA)(HSO )] was fully characterized by XRD, SEM, TEM, AFM, H NMR, C NMR,
4
FT-IR, MS, TG, DTG and elemental analysis techniques. Catalytic application of [(THA)(HSO )] nano ionic liquid
4
was studied in the synthesis of bis(indolyl)methanes at room temperature under solvent-free conditions. The most
important advantages of this study are high yields, cleaner reaction profile, short reaction time, the avoidance of the
organic solvents and easy work-up. In addition to the above-mentioned advantageous, excellent recyclability of the
catalyst was environmentally benign and cost-effective. Hence, our methodology was found to possess high
generality which could make it proper for the industrial goals.
Acknowledgments
We are thankful to Birjand University of Technology Research Council for their support on this work.
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References
[
1]
Sarkar A, Roy SR, Parikh N, Chakraborti AK (2011) Nonsolvent application of ionic liquids: organo-
catalysis by 1-alkyl-3-methylimidazolium cation based room-temperature ionic liquids for chemoselective
N-tert-butyloxycarbonylation of amines and the influence of the C-2 hydrogen on catalytic efficiency. J
Org Chem 76:7132-7140.
[
[
[
2]
3]
4]
Roy SR, Jadhavar PS, Seth K, Sharma KK, Chakraborti AK (2011) Organocatalytic application of ionic
liquids: [bmim][MeSO ] as a recyclable organocatalyst in the multicomponentr for the preparation of
4
dihydropyrimidinones and -thiones. Synthesis 2261-2267.
Sarkar A, Roy SR, Chakraborti AK (2011) Ionic liquid catalysed reaction of thiols with α,β-unsaturated
carbonyl compounds-remarkable influence of the C-2 hydrogen and the anion. Chem Commun 47:4538-
4
540.
Roy SR, Chakraborti AK (2010) Supramolecular assemblies in ionic liquid catalysis for Aza-Michael
reaction, Org. Lett 12:3866-3869.
[
[
5]
6]
Chakraborti AK, Roy SR (2009) On Catalysis by ionic liquids. J Am Chem Soc 131:6902-6903.
Zare A, Abi F, Moosavi-Zare AR, Beyzavi MH, Zolfigol MA (2013) Synthesis, characterization and
application of ionic liquid 1,3-disulfonic acid imidazolium hydrogen sulfate as an efficient catalyst for the
preparation of hexahydroquinolines. J Mol Liq 178:113-121.
[
[
7]
8]
Patel DD, Lee JM (2012) Applications of ionic liquids. Chem Rec 12:329-355.
Gogoi P, Dutta AK, Sarma P, Borah R (2015) Development of Brönsted-Lewis acidic solid catalytic
system of 3-methyl-1-sulfonic acid imidazolium transition metal chlorides for the preparation of
bis(indolyl)methanes. Appl Catal A: Gen 492:133-139.
[
9]
Zolfigol MA, Baghery S, Moosavi-Zare AR, Vahdat SM, Alinezhad H, Norouzi M (2014) Synthesis of
the first nano ionic liquid 1-methylimidazolium trinitromethanide {[HMIM]C(NO ) } and its catalytic use
2
3
for Hanztsch four-component condensation. RSC Adv 4:57662-57670.
[
[
10] Wang C, Guo L, Li H, Wang Y, Weng J, Wu L (2006) Preparation of simple ammonium ionic liquids and
their application in the cracking of dialkoxypropanes. Green Chem 8:603-607.
11] Shiri M, Zolfigol MA, Kruger HG, Tanbakouchian Z (2010) Bis- and Trisindolylmethanes (BIMs and
TIMs). Chem Rev 110:2250-2293.
1
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[
[
[
[
12] Sivaprasada Q, Perumala PT, Prabavathyb VR, Mathivanan N (2006) Synthesis and anti-microbial activity
of pyrazolylbisindoles-Promising anti-fungal compounds. Bioorg Med Chem Lett 16:6302-6305.
13] Sujatha K, Perumal PT, Muralidharan D, Rajendran M (2009) Synthesis, analgesic and anti-inflammatory
activities of bis(indolyl)methanes. Indian J Chem 48:267-269.
14] Benabadji SH, Wen R, Zheng J, Dong X, Yuan S (2004) Anticarcinogenic and antioxidant activity of
diindolyl- methane derivatives. Acta Pharmacol Sin 25:666-671.
15] Kumar GSS, Prabu AM, Jenniefer SJ, Bhuvanesh N, Muthiah BP, Kumaresan S (2013) Syntheses of
phenoxyalkyl esters of 3,3′-bis(indolyl)methanes and studies on their molecular properties from single
crystal XRD and DFT techniques. J Mol Str 1047:109-120.
[
[
16] Liang D, Huang W, Yuan L, Ma Y, Ma J, Deman N (2014) An underrated cheap Lewis acid: Molecular
bromine as a robust catalyst for bis(indolyl)methanes synthesis. Catal Commun 55:11-14.
17] Mobaraki A, Movassagh B, Karimi B (2014) Hydrophobicity-enhanced magnetic solid sulfonic acid: A
simple approach to improve the mass transfer of reaction partners on the surface of the heterogeneous
catalyst in water-generating reactions. Appl Catal A: Gen 472:123-133.
[
18] Rames C, Banerjee J, Pal R, Das B (2003) Silica supported sodium hydrogen sulfate and amberlyst-15:
two efficient heterogeneous catalysts for facile synthesis of bis-and tris(1H-indol-3-yl)methanes from
indoles and carbonyl compounds. Adv Synth Catal 345:557-559.
[
[
[
[
19] Zahran M, Abdin Y, Salama H (2008) Eco-friendly and efficient synthesis of bis(indolyl)methanes under
microwave irradiation. ARKIVOC xi:256-265.
20] Li JT, Sun MX, He GY, Xu XY (2011) Efficient and green synthesis of bis(indolyl)methanes catalyzed by
ABS in aqueous media under ultrasound irradiation. Ultrason Sonochem 18:412-414.
21] Yadav JS, Reddy BVS, Sunitha S (2003) Efficient and eco-friendly process for the synthesis of bis(1H-
indol-3-yl)methanes using ionic liquids. Adv Synth Catal 345:349-352.
22] Chakraborti AK, Roy SR, Kumar D, Chopra P (2008) Catalytic application of room temperature ionic
liquids: [bmim][MeSO ] as a recyclable catalyst for synthesis of bis(indolyl)methanes. Ion-fishing by
4
MALDI-TOF-TOF MS and MS/MS studies to probe the proposed mechanistic model of catalysis. Green
Chem 10:1111-1118.
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ACCEPTED MANUSCRIPT
[
[
[
23] Rad-Moghadam K, Sharifi-Kiasaraie M (2009) Indole 3-alkylation/vinylation under catalysis of the
guanidinium ionic liquids. Tetrahedron 65:8816-8820.
24] Sobhani S, Honarmand M (2013) A simple and efficient method for one-pot three-component synthesis of
terminal vinylphosphonates using a task-specific ionic liquid. Synlett 24:236-240.
25] Sobhani S, Honarmand M (2013) 2-Hydroxyethylammonium acetate: A reusable task-specific ionic liquid
promoted one-pot, three-component synthesis of 2-amino-3,5-dicarbonitrile-6-thio-pyridines. CR Chimie
1
6:279-286.
[
[
26] Sobhani S, Nasseri R, Honarmand M (2012) 2-Hydroxyethylammonium acetate as a reusable and cost-
effective ionic liquid for the efficient synthesis of bis(pyrazolyl)methanes and 2-pyrazolyl-1-nitroalkanes.
Can J Chem 90:798-804.
27] Sobhani S, Honarmand M (2012) 5-Hydroxypentylammonium acetate as a reusable ionic liquid catalyzes
Tandem Knoevenagel-phospha-Michael reaction of aldehydes, malononitrile and phosphites. J Iran Chem
Soc 9:661-669.
[
[
28] Sobhani S, Safaei E, Hasaninejad AR, Rezazadeh S (2009) An eco-friendly procedure for the efficient
synthesis of bis(indolyl)methanes in aqueous media. J Organometal Chem 694:3027-3031.
29] He F, Li P, Gu Y, Li G (2009) Glycerol as a promoting medium for electrophilic activation of aldehydes:
catalyst-free synthesis of di(indolyl)methanes, xanthene-1,8(2H)-diones and 1-oxo-hexahydroxanthenes.
Green Chem 11:1767-1773.
[
[
30] Teimouri MB, Mivehchi H (2005) Efficient hexamethylenetetramine‐bromine (HMTAB)‐catalyzed
synthesis of bis(indolyl)methanes in water. Synth Commun 35:1835-1843.
31] Kubczyk TM, Williams SM, Kean JR, Davies TE, Taylor SH, Graham AE (2011) Nanoporous
aluminosilicate catalyzed Friedel-Crafts alkylation reactions of indoles with aldehydes and acetals. Green
Chem 13:2320-2325.
[
[
32] Yang Q, Yin ZL, Ouyang BL, Peng Y (2011) Pyridinium tribromide catalyzed condensation of indoles
and aldehydes to form bisindolylalkanes. Chin Chem Lett 22:515-518.
33] Ghorbani-Vaghei R, Veisi H, Dehghani AAA (2010) Practical and efficient synthesis of
bis(indolyl)methanes in water, and synthesis of di-, tri-, and tetra(bis-indolyl)methanes under thermal
conditions catalyzed by oxalic acid dihydrate. Mol Div 14: 87-96.
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[
[
34] Mazaahir K (2011) Niobium (V) pentachloride-catalyzed efficient and highly rapid synthesis of
bis(indolyl)-methanes under mild conditions. Indian J Chem B 50:229-232.
35] Pradip K (2008) A mild and versatile synthesis of bis(indolyl)-methanes and tris(indolyl)alkanes catalyzed
by antimony trichloride. Indian J Chem B 47:1402-1406.
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Figure captions
Figure 1. (a) The 1H NMR spectrum of [(THA)(HSO4)]; (b) The 13C NMR spectrum of
(THA)(HSO4)].
[
Figure 2. The FT-IR spectra of [(THA)(HSO4)], tris(hydroxymethyl)aminomethane and sulfuric acid.
Figure 3. The mass spectrum of [(THA)(HSO4)].
Figure 4. (a) The thermal gravimetric (TG) and (b) derivative thermal gravimetric (DTG) analysis of
[
(THA)(HSO4)].
Figure 5. Scanning electron microscopy (SEM) of [(THA)(HSO4)].
Figure 6. Transmission electron microscopy (TEM) of [(THA)(HSO4)].
Figure 7. The XRD pattern of [(THA)(HSO4)].
Figure 8. Two-dimensional (a) and three-dimensional (b) AFM topography images of [(THA)(HSO4)].
Figure 9. The screening of catalyst amounts on the reaction of benzaldehyde (1 mmol) and 2-
methylindole (2 mmol) at room temperature under solvent-free.
Figure 10. The screening of solvent nature (2 mL) on the reaction of benzaldehyde (1 mmol) and 2-
methylindole (2 mmol) in the presence of [(THA)(HSO4)] (2 mol% ) at room temperature after 5 min.
Figure 11. Recycling experiment of [(THA)(HSO4)].
Figure 12. TEM image of [(THA)(HSO4)] after five recovery times.
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a
Table 1. Synthesis of Bis(indolyl)methanes in the Presence of [(THA)(HSO )].
4
Entry
Aldehyde
Indole
Product
Time
min)
Yield
Mp (ºC)
found/
b
(
(%)
ref
(
reported)
2
46-247/
1
2
3
5
98
99
99
2
45–247 [28]
2
33-234
7
2
48-249
8
1
77-178/
4
10
95
1
74-176 [20]
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2
41-242/
5
20
94
2
40-242 [29]
1
00-101/
6
10
95
9
9-101 [30]
1
41-142/
c
7
8
10
10
90
95
1
42-144 [20]
7
2-73/
c
7
4-76 [28]
7
8-79/
c
9
30
91
7
8-80 [28]
1
40-141/
c
1
0
30
92
1
39-140 [28]
2
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1
10-111/
c
1
1
35
90
1
08-111 [31]
9
7-98/
c
1
2
20
89
9
5-97 [31]
3
41-342/
c
340-342 [32]
1
1
3
4
35
30
93
88
1
35-136/
c
1
34-136 [33]
1
86-187/
c
1
5
15
94
1
90-192 [31]
2
90-291
1
6
5
96
2
9