Br?nsted acidic ionic liquid–catalyzed tandem trimerization of indoles: An efficient approach towards the synthesis of indole 3,3′-trimers under solvent-free conditions

Article abstract of DOI:10.1002/jhet.3914

We have observed the role of 1-butane sulfonic acid-3-methylimidazolium tosylate, [BSMIM]OTs, as an organocatalyst for the tandem type trimerization of indoles to synthesize indole 3,3′-trimers under neat conditions. Using this developed protocol synthesis of indole trimers with various substituted indoles, which are biologically important, has been reported. From the control experiments and literature, a possible mechanism has been proposed via the generation of indolinium cation in the presence of the ionic liquid catalyst. The catalyst has been recycled for several times. The significant advantages of our methodology are clean reaction with very short time, no chromatography for purification, commercially available substrates, neat reaction conditions, and in the absence of metal. Using the protocol, the MDM2-p53 inhibitor has been synthesized in gram scale with high yield.

Full text of DOI:10.1002/jhet.3914

Received: 5 December 2019
DOI: 10.1002/jhet.3914
Revised: 12 January 2020
Accepted: 20 January 2020
A R T I C L E
Brønsted acidic ionic liquid–catalyzed tandem
trimerization of indoles: An efficient approach towards
the synthesis of indole 3,30-trimers under solvent-free
conditions
Rana Chatterjee1 | Sougata Santra2 | Grigory V. Zyryanov2,3 | Adinath Majee1
1Department of Chemistry, Visva-Bharati
Abstract
(A Central University), Santiniketan,
India
We have observed the role of 1-butane sulfonic acid-3-methylimidazolium
tosylate, [BSMIM]OTs, as an organocatalyst for the tandem type trimerization
of indoles to synthesize indole 3,30-trimers under neat conditions. Using
this developed protocol synthesis of indole trimers with various substituted
indoles, which are biologically important, has been reported. From the
control experiments and literature, a possible mechanism has been pro-
posed via the generation of indolinium cation in the presence of the ionic
liquid catalyst. The catalyst has been recycled for several times. The signifi-
cant advantages of our methodology are clean reaction with very short
time, no chromatography for purification, commercially available sub-
strates, neat reaction conditions, and in the absence of metal. Using the
protocol, the MDM2-p53 inhibitor has been synthesized in gram scale with
high yield.
2Department of Organic & Biomolecular
Chemistry, Chemical Engineering
Institute, Ural Federal University,
Yekaterinburg, Russian Federation
3I. Ya. Postovsky Institute of Organic
Synthesis, Ural Division of the Russian
Academy of Sciences, Yekaterinburg,
Russian Federation
Correspondence
Adinath Majee, Department of Chemistry,
Visva-Bharati (A Central University),
Santiniketan 731235, India.
Email: adinath.majee@visva-bharati.ac.in
1 | INTRODUCTION
of methodologies due to its acidic nature. We are actively
engaged to develop various important methodologies in
The application of ionic liquids (ILs) is increasing day by
day to carry out many chemical transformations. Ionic
liquids has been considered as organocatalyst as well as
solvent in both organic and inorganic chemistry for its
unique properties.[1] Based on its different structure,
ionic liquids can behave as catalyst, and many other pur-
poses in organic reactions.[2] Though ILs have some limi-
tation as solvents,[3] varying the cations and anions a
variety of ILs has been developed, which are very useful
for different applications.[4] Forbes and Davis synthesized
ILs based on phosphonium and imidazolium ion with a
suspended acidic sulfonic acid moiety and another Brøn-
sted acidic ionic liquids (BAILs), which are very impor-
tant in the area of organocatalysis.[5] With normal
properties of ionic liquids, BAILs show a strong acidic
nature. Accordingly, BAILs have been used for a number
using imidazole-based zwitterions and BAILs as catalysts
in organic transformations.[6]
Indole is the core structure of a variety of biologically
and pharmaceutically active compounds and well known
as Lord of the Rings of heterocyclic moiety.[7] Particularly,
indole derivatives containing bis(indolyl)alkane or 3,30-
bisindole moiety have wide applications as bioactive nat-
ural products and pharmaceuticals drugs.[8] For instance,
the bis(indolyl)methane compounds are considered as
cytotoxic in opposition to MCF-7 cells and able to exhibit
acetylcholinesterase (AChE) inhibitory activity.[9] Some
valuable alkaloids like arundine,[10] vidrindole,[11] antibi-
otic turbomycins[12] or arsindoline B,[13] and
streptindole[14] contain bis(indolyl)methane motif
(Figure 1). Various biological activities of bis(indolyl)meth-
anes like antimicrobial,[15] anti-fungal,[16] antibacterial and
J Heterocyclic Chem. 2020;1–12.
wileyonlinelibrary.com/journal/jhet
© 2020 Wiley Periodicals, Inc.
1

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CHATTERJEE ET AL.
anti-inflammatory,[17] and anti-hyperlipidemic[18] have been
observed. In addition, bis(indolyl)methanes act as potential
hypolipidemic and antiobesity agents,[19] and its oxidized
form can be used as colorimetric sensors.[20]
2 | RESULTS AND DISCUSSION
Initially, for the reaction, we have taken simple indole
(1a) in the presence of the catalyst 1-butane sulfonic
acid-3-methylimidazolium tosylate (10 mol%), [BSMIM]
OTs (BAIL-1) at 80ꢀC for 1 hour, under neat conditions
(Table 1, entry 1). We are delighted to note that the
desired 3,30-trimer product, namely, 2-(2,2-di[1H-indol-
3-yl]ethyl)aniline (2a) was obtained in 85%. Immediately,
we extended the reaction time under the same reaction
condition from 1 to 3 hours, but the yield was not
improved. Secondly, the role of various ionic liquids such
as BAIL-2, BAIL-3, and BAIL-4 have been checked
(Table 1, entries 2-4), but BAIL-1 was found to be the best
for the formation of indole trimer product. No desired
products have been found using other ionic liquids like
IL-2 and [BMIM]BF4 (Table 1, entries 5 & 6). The role of
various solvents has been examined to realize the solvent
effects. Some protic solvents like water, different alco-
hols, and polyethylene glycol (PEG) (Table 1, entries
7-11) produced very less product and some aprotic sol-
vents like 1,2-DCE, CH3CN afforded poor yields (Table 1,
entries 12 & 13). We observed 84% yield of the desired
product under neat conditions at temperature 80ꢀC in
1 hour (Table 1, entry 1). So, it may be concluded that
the solvent has no significant role for this reaction. High
temperature was not beneficial for this reaction (Table 1,
entry 14), but we observed fewer yields on decreasing
temperature (Table 1, entry 15). Finally, we have
observed that 10 mol% of BAIL-1 afforded better yield
(85%) compared with 5 mol% (67% yield) (Table 1, entry
16). Increasing the catalyst loading to 20 mol%, there is
no development of the reaction conversion (Table 1,
entry 17). It is worthy to mention that without catalyst,
there is no conversion (Table 1, entry 18). So, the
Accordingly, a number of methods have been reported
to synthesize bis(indolyl)alkanes with the combination of
indoles and aldehydes using Lewis or protic acid or other
catalytic reagents.[21] Other than using aldehydes, several
methods have been reported to achieve bis(indolyl)meth-
ane derivatives using different reagents and reaction condi-
tions.[22] On the other hand, it is well established that
indole itself gets polymerized to dimer or trimer by self-
addition catalyzed by Brønsted or Lewis acids. It is worthy
to mention that very few methods are available for the syn-
thesis of indole 3,30-trimers. After the first report by
Keller,[23] few methods have been developed by using dif-
ferent acid catalysts such as HCl/ZnCl2-AcOH, TFA, p-
toluenesulfonic acid, HCO2H, and Lewis acid catalysts
such as InCl3, Sc(OTf)3, AlCl3, and SnCl2.[24] The main dis-
advantages of these protocols are low yields, formation of
undesired products, and long reaction time. In these
reported methods, the indole 3,30-trimers were formed
along with the other polymers of indole, 2,30-trimers, and
dimer in different yields. BAILs are very useful in many
organic syntheses, and we are also actively working with
this.[6] Here, as an outcome, we report a very selective syn-
thesis of indole 3,30-trimers in good to excellent yields
without any side products in the presence of 1-butane sul-
fonic acid-3-methylimidazolium tosylate, [BSMIM]OTs
(BAIL-1) (10 mo%) at 80ꢀC (Scheme 1). This present reac-
tion proceeded under neat conditions, the desired 3,30-
trimers with various N-protected indoles obtained in major
yield suppressing the formation of other polymers. No col-
umn chromatography has been performed to purify the
crude compounds.
FIGURE 1 Few bioactive
bisindolyl derivatives
SCHEME 1 BAIL-catalyzed
synthesis of bis(indolyl)alkane

CHATTERJEE ET AL.
3
TABLE 1 Optimization of the reaction conditions
Entry
1
Catalysts (10 mol%)
BAIL-1
BAIL-2
BAIL-3
BAIL-4
IL-2
Solvents
neat
Temp., ꢀC
Yieldsa, %
85, 82b
74
80
80
80
80
80
80
80
80
80
80
80
80
80
100
60
80
80
80
2
neat
3
neat
70
4
neat
75
5
neat
trace
nr
6
[BMIM]BF4
BAIL-1
BAIL-1
BAIL-1
BAIL-1
BAIL-1
BAIL-1
BAIL-1
BAIL-1
BAIL-1
BAIL-1
BAIL-1
--
neat
7
H2O
61
8
EtOH
n-PrOH
n-BuOH
PEG
40
9
28
10
11
12
13
14
15
16
17
18
22
19
1,2-DCE
CH3CN
neat
30
33
83
neat
71
neat
67c
85d
NDe
neat
neat
Note: Reaction conditions: indole (1.0 mmol), BAIL-1 (10 mol%), stirred for 1 hour.
aIsolated yields.
bReaction time 3 hours.
c5 mol% BAIL-1 was used.
d20 mol% BAIL-1 was used.
eNot detected in TLC.

4
CHATTERJEE ET AL.
optimized reaction conditions have been considered by
employing 10 mol% BAIL-1 at 80ꢀC under solvent-free
conditions for 1 h (Table 1, entry 16).
n-Propyl and iso-propylprotected indoles also gave the
corresponding 3,30-trimer products (2j, 2k) in good yields.
In addition, iso-butyl protected indole derivative provided
the respective product (2l) with 70% yield. Similarly, long
chain alkyl group like n-butyl and n-pentyl protected
indoles nicely underwent the reaction under the opti-
mized conditions and afforded the corresponding prod-
ucts (2m, 2n) in satisfactory yields. Next, N-allyl and
propargyl substituted indoles were also introduced to
react where the corresponding trimers (2o, 2p) were
formed in good yields keeping the unsaturated group
unaffected. N-benzylindole afforded the corresponding
product (2q) in 74% yield. Other substituted indoles like
5-methyl, 5-methoxy, and 5-chloro substituted N-methyl
indoles reacted smoothly, and the products 2r, 2s, and 2t
were furnished with good yields. In addition, 5-methoxy
and 5-chloro substituted N-ethyl indoles also gave the
corresponding products (2u and 2v) in satisfactory yields.
We have subjected pyrrole under the same reaction con-
ditions but could not isolate any considerable product.
The reactions need no inert medium and were per-
formed under an open atmosphere. No column
Various indoles (1) were examined for trimerization
reaction using these reaction conditions, which are sum-
marized in Table 2. During optimization, we have seen
that simple indole (1a) gave the trimer product in 85%
yield, which is an MDM2-p53 inhibitor. The reaction
underwent smoothly with indole derivatives substituted
with electron-donating substituents (5-Me, 5-OMe) to
give the corresponding 3,30-trimer products (2b, 2c) in
excellent yields. Similarly, indoles with different electron-
withdrawing groups such as –fluoro, –chloro, and –
bromo groups at C-5 position reacted to provide the
respective 3,30-trimer products (2d-2f) in good yields;
6-chloro-substituted indole also underwent the reaction
to provide desired product 2g in moderate yield.
Then, the substrate scope with the N-protected
indoles under the similar reaction conditions has been
explored as summarized in Table 3. N-methylindole and
N-ethylindole reacted very smoothly to give the product
2h in 81% yield and 2i in 79% yield, respectively.
TABLE 2 Synthesis of 3,30-trimer derivatives of various indoles in presence of BAIL-1
Note: Reaction conditions: 1 mmol of 1, BAIL-1 (10 mol%) at 80ꢀC. All are isolated yields.

CHATTERJEE ET AL.
5
TABLE 3 Synthesis of 3,30-trimer derivatives of various N-protected indoles
Note: All reactions were carried out on 1 mmol scale using BAIL-1 (10 mol%) at 80ꢀC. All are isolated yields.
chromatography has been performed for purification.
Small amount of water was added to the reaction mixture
after completion and was then filtered to get the crude
product. To get the pure compound, the crude product
was washed with ethanol. In our method, no other poly-
mers of indole, 2,30-trimers, and dimers were observed.
All the synthesized compounds, which are reported ear-
lier, have been compared with their spectral data. The

6
CHATTERJEE ET AL.
new compounds were characterized by spectral as well as
their analytical data. The structure of the compound
2-(2,2-Bis[5-chloro-1-ethyl-1H-indol-3-yl]ethyl)-4-chloro-
N-ethylaniline (2v) have been confirmed by X-ray crystal-
lographic analysis as shown in Figure 2.[25]
B. The intermediate B gets broken and converted to C,
which then involves the addition of third indole to produce
the indole trimer 2a through the formation of D.
Our methodology is also valid for gram scale synthesis
as shown in Scheme 2. Compound 2a has been isolated
1.4 g, which acts as an MDM2-p53 inhibitor in 82% yield.
After the successful preparation of bis(indolyl)methane
compounds (3,30-trimer), we checked the recovery and reus-
ability of the catalyst. For this purpose, we have taken 1H-
indole (1a) in presence of BAIL-1 (10 mol%) and the reac-
tion was carried out under the optimized reaction condi-
tions. After completion of the reaction, water was added to
the reaction mixture and allowed to cool at room tempera-
ture and filtered. Evaporation of water from the solution
ionic liquid has been recovered. The catalyst has been tested
for five times in this way and found a comparable activity
as shown in Table 4 and Figure 3.
A plausible mechanistic pathway for the trimersation of
indole has been suggested as shown in Scheme 3. Indole
3,30-trimers transformation occurs possibly through the gen-
eration of indolinium cation A by taking a proton from
BAIL-1. After that, another indole moiety attacks the
indolinium cation from C-3 position to form intermediate
3 | CONCLUSION
In conclusion, an efficient methodology has been reported
to synthesize indole 3,30-trimer derivatives by the self-
coupling of indoles using Brønsted acidic ionic liquid
(BAIL-1) as catalyst. No other polymers of indole, 2,30-tri-
mers, and dimers were observed during the reaction. Pos-
sibly, the reaction goes through the formation of
indolinium cation in tandem fashion in the presence of
BAIL-1. A library of indole 3,30-trimer derivatives has been
synthesized using the present reaction conditions. We
have found that there is no considerable role of external
solvent for this reaction. The reusability of the catalyst
BAIL-1 has been tested, and it is effective for five times
without comparable catalytic activities. The reported
methodology shows a very clean reaction, reaction time is
very short, the product can be easily isolated, chromatog-
raphy is not needed, and all the reactants are easily avail-
able. Above all, the reaction is under neat condition and
TABLE 4 Synthesis of 2aa and recycling of BAIL
No. of cycle
Yields, %b
Catalyst Recovery, %
1
2
3
4
5
85
84
80
80
77
95
92
88
85
82
a1a (1 mmol), 10 mol% of catalyst (BAIL-1) under neat condition at 80ꢀC for
1 hour.
bIsolated yields.
120
Yields (%)
Catalyst Recovery (%)
100
80
60
40
20
0
95
92
88
85
FIGURE 2 X-ray crystallographic structure of compound 2v
85
84
82
80
80
77
1
2
3
4
5
No. of Cycle
SCHEME 2 Gram-scale reaction
FIGURE 3 Representation of catalyst recycling and recovery

CHATTERJEE ET AL.
7
SCHEME 3 Proposed
mechanistic pathway for synthesis of
indole 3,30-trimer
in the absence of any solvent. The MDM2-p53 inhibitor
can be synthesized in gram scale under the present condi-
tion in high yield. Our present methodology thus may be a
meaningful effort to synthesize biologically active indole
3,30-trimer with different substituents.
4.2.1 | 2-(2,2-Di[1H-indol-3-yl]ethyl)
aniline (2a)
1
Yield: 85%, 99 mg; H NMR (CDCl3, 400 MHz): δ 7.83 (s,
2H), 7.49 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8 Hz, 2H),
7.16-7.12 (m, 2H), 7.01-6.96 (m, 4H), 6.92 (d, J = 2.4 Hz,
2H), 6.66-6.62 (m, 1H), 6.56-6.54 (m, 1H), 4.86 (t,
J = 14.8 Hz, 1H), 3.41 (d, J = 7.2 Hz, 2H), 3.25 (s, 1H);
13C NMR (CDCl3, 100 MHz): δ 144.8, 136.6, 130.4, 127.0
(2C), 126.1, 122.0, 121.9, 119.7, 119.6, 119.2, 118.8, 115.8,
111.2, 37.2, 34.5.[24e]
4 | EXPERIMENTAL SECTION
4.1 | General information
A glass disk with an electric hot plate has been used for
determination of melting points and is uncorrected.
DMSO-d6 and CDCl3 solutions have been used to
4.2.2 | 2-(2,2-Bis[5-methyl-1H-indol-3-yl]
ethyl)-4-methylaniline (2b)
1
record H NMR (400 MHz) and 13C NMR (100 MHz)
spectra. Before the reaction, all the purchased sub-
strates have been distilled. Different reagents and sol-
vents were bought from Aldrich, Merck, Fluka, SRL,
Process Chemicals, and Spectrochem. Oven-dried glass
wares were used for all the reactions. We have pre-
pared the Brønsted acidic ionic liquids following the
literature.[26]
1
Yield: 82%, 107 mg; H NMR (CDCl3, 400 MHz): δ 7.75
(s, 2H), 7.28 (s, 2H), 7.19 (d, J = 8 Hz, 2H), 7.02-6.99 (m,
2H), 6.93-6.83 (m, 4H), 6.48 (d, J = 8 Hz, 2H), 4.83 (t,
J = 14.4 Hz, 1H), 3.38 (d, J = 7.2 Hz, 2H), 3.09 (s, 2H),
2.40 (s, 6H), 2.20 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ
142.3, 134.9, 130.9, 128.2, 128.0, 127.3, 127.2, 126.5, 123.4,
122.2, 119.4, 119.3, 116.0, 110.7, 37.3, 34.6, 21.5, 20.6.[24e]
4.2 | General procedure for the synthesis
of 2-(2,2-di[1H-indol-3-yl]ethyl)aniline (2a)
4.2.3 | 2-(2,2-Bis[5-methoxy-1H-indol-
3-yl]ethyl)-4-methoxyaniline (2c)
In the reaction vessel, BAIL-1 (10 mol%) was added with
indole (1a, 1 mmol), and then the mixture was stirred
continuously for 1 hour at 80ꢀC. Water was added to the
reaction mixture after its completion (TLC). By filtration,
the crude product was separated, and by evaporation of
the water, the ionic liquid was recovered. Again, after
reactivation of the recovered ionic liquid, it was reused
for another new reaction. Ethanol has been used to wash
the crude product to afford the desired pure product (2a)
as brown solid.
1
Yield: 80%, 117 mg; H NMR (CDCl3, 400 MHz): δ 7.85
(s, 2H), 7.21 (s, 1H), 7.18 (s, 1H), 6.99 (d, J = 2.4 Hz,
2H), 6.85 (d, J = 2.4 Hz, 2H), 6.79 (d, J = 2.4 Hz, 1H),
6.77 (d, J = 2.4 Hz, 1H), 6.58-6.54 (m, 2H), 6.47 (d,
J = 8.4 Hz, 1H), 4.71 (t, J = 14.8 Hz, 1H), 3.69 (s, 6H),
3.55 (s, 3H), 3.38 (d, J = 7.2 Hz, 2H); 13C NMR (CDCl3,
100 MHz): δ 153.7, 152.9, 138.7, 131.9, 128.0, 127.5,
122.7, 119.5, 117.1, 116.3, 112.7, 112.1, 111.8, 101.8, 55.9,
55.7, 37.7, 35.0.[24e]

8
CHATTERJEE ET AL.
4.2.4 | 2-(2,2-Bis[5-fluoro-1H-indol-3-yl]
ethyl)-4-fluoroaniline (2d)
4.2.8 | 2-(2,2-Bis[1-methyl-1H-indol-3-yl]
ethyl)-N-methylaniline (2h)
1
1
Yield: 77%, 103 mg; H NMR (CDCl3, 400 MHz): δ 7.99
Yield: 81%, 106 mg; H NMR (CDCl3, 400 MHz): δ 7.49
(s, 2H), 7.25-7.22 (m, 2H), 7.09 (d, J = 2.4 Hz, 2H),
7.00-6.97 (m, 2H), 6.89-6.84 (m, 2H), 6.69-6.66 (m, 1H),
6.60-6.57 (m, 1H), 6.52-6.48 (m, 1H), 4.66 (t, J = 16 Hz,
1H), 3.34 (d, J = 7.6 Hz, 2H), 3.20 (s, 2H); 13C NMR
(CDCl3, 100 MHz): δ 157.6 (d, JC-F = 233 Hz), 140.8,
133.2, 127.2 (d, JC-F = 15 Hz), 123.5, 119.0 (d, JC-
(d, J = 8 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 7.21-7.17 (m,
2H), 7.13-7.08 (m, 1H), 7.02-6.98 (m, 3H), 6.86 (s, 2H),
6.63-6.59 (m, 1H), 6.48 (d, J = 7.6 Hz, 1H), 4.82 (t,
J = 14.8 Hz, 1H), 3.71 (s, 6H), 3.36 (d, J = 7.2 Hz, 2H),
2.42 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 147.8, 137.4,
129.9, 127.4, 127.2, 126.6, 125.8, 121.5, 119.8, 118.7, 118.4,
117.1, 109.7, 109.2, 37.7, 34.5, 32.8, 30.7.[24e]
= 7 Hz), 116.9, 116.7 (d, JC-F = 7 Hz), 113.7, 113.4,
F
111.9, 111.8, 110.7, 110.5, 104.5 (d, JC-F = 23 Hz), 36.9,
34.5.[24e]
4.2.9 | 2-(2,2-Bis[1-ethyl-1H-indol-3-yl]
ethyl)-N-ethylaniline (2i)
4.2.5 | 2-(2,2-Bis[5-chloro-1H-indol-3-yl]
ethyl)-4-chloroaniline (2e)
Yield: 79%, 114 mg; brown solid; mp 148-150ꢀC; 1H NMR
(CDCl3, 400 MHz): δ 7.49 (d, J = 7.6 Hz, 2H), 7.31 (d,
J = 8.4 Hz, 2H), 7.19-7.15 (m, 2H), 7.10-7.05 (m, 2H),
7.00-6.96 (m, 2H), 6.93 (s, 2H), 6.65-6.61 (m, 1H), 6.48 (d,
J = 7.6 Hz, 1H), 4.77 (t, J = 14.4 Hz, 1H), 4.13-4.07 (m,
4H), 3.40 (d, J = 7.2 Hz, 2H), 2.72-2.67 (m, 2H), 1.40 (t,
J = 14.8 Hz, 6H), 0.77 (t, J = 14.8 Hz, 3H); 13C NMR
(CDCl3, 100 MHz): δ 147.0, 136.4, 130.3, 127.5, 127.1,
126.2, 125.1, 121.3, 120.1, 118.6, 118.3, 117.0, 110.4, 109.3,
40.9, 38.4, 37.5, 35.6, 15.7, 14.2.
1
Yield: 79%, 119 mg; H NMR (CDCl3, 400 MHz): δ 8.02
(s, 2H), 7.30 (d, J = 2 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H),
7.08-7.06 (m, 2H), 7.00 (d, J = 2.4 Hz, 2H), 6.95-6.92 (m,
1H), 6.81 (d, J = 2.4 Hz, 1H), 6.48 (d, J = 8.4 Hz, 1H),
4.66 (t, J = 14.8 Hz, 1H), 3.28 (d, J = 7.6 Hz, 2H); 13C
NMR (CDCl3, 100 MHz): δ 143.4, 135.0, 133.7, 130.1,
127.8, 127.1, 125.1, 123.4, 123.2, 122.5, 119.0, 118.6, 117.0,
112.4, 36.9, 34.3.[24e]
4.2.6 | 2-(2,2-Bis[5-bromo-1H-indol-3-yl]
ethyl)-4-bromoaniline (2f)
4.2.10 | 2-(2,2-Bis[1-propyl-1H-indol-3-yl]
ethyl)-N-propylaniline (2j)
1
1
Yield: 78%, 151 mg; H NMR (CDCl3, 400 MHz): δ 8.05
Yield: 77%, 122 mg; white solid; mp 128-130ꢀC; H NMR
(s, 2H), 7.43 (d, J = 8 Hz, 2H), 7.22-7.16 (m, 4H),
7.09-7.06 (m, 1H), 6.98 (d, J = 2.4 Hz, 2H), 6.94 (d,
J = 2.4 Hz, 1H), 6.43 (d, J = 8.4 Hz, 1H), 4.65 (t,
J = 14.8 Hz, 1H), 3.27 (d, J = 7.6 Hz, 2H); 13C NMR
(CDCl3, 100 MHz): δ 143.9, 135.3, 133.0, 130.1, 128.5,
127.5, 125.1, 123.0, 122.1, 118.5, 117.5, 112.8, 112.7, 110.6,
37.0, 34.3.[24e]
(CDCl3, 400 MHz): δ 7.57 (d, J = 8 Hz, 2H), 7.35 (d,
J = 8.4 Hz, 2H), 7.23-7.19 (m, 2H), 7.15-7.08 (m, 2H),
7.05-7.01 (m, 2H), 6.97 (s, 2H), 6.65 (t, J = 14.8 Hz, 1H),
6.55 (d, J = 8 Hz, 1H), 4.85 (t, J = 14 Hz, 1H), 4.05 (t,
J = 14.4 Hz, 4H), 3.45 (d, J = 6.8 Hz, 2H), 3.29 (s, 1H),
2.74 (t, J = 14.4 Hz, 2H), 1.90-1.81 (m, 4H), 1.23-1.16 (m,
2H), 0.94 (t, J = 14.8 Hz, 6H), 0.88 (t, J = 14.8 Hz, 3H);
13C NMR (CDCl3, 100 MHz): δ 146.9, 136.7, 130.2, 127.4,
126.9, 126.4, 125.8, 121.2, 120.0, 118.4, 117.9, 116.7, 110.2,
109.3, 47.9, 45.8, 37.2, 35.3, 23.5, 22.3, 11.7, 11.5.
4.2.7 | 2-(2,2-Bis[6-chloro-1H-indol-3-yl]
ethyl)-3-chloroaniline (2g)
1
Yield: 65%, 98 mg; H NMR (CDCl3, 400 MHz): δ 8.04 (s,
4.2.11 | 2-(2,2-Bis[1-isopropyl-1H-indol-
3-yl]ethyl)-N-isopropylaniline (2k)
2H), 7.29 (d, J = 1.6 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H),
6.97 (d, J = 1.6 Hz, 2H), 6.92-6.89 (m, 2H), 6.75-6.72 (m,
1H), 6.56-6.53 (m, 2H), 4.68 (t, J = 16 Hz, 1H), 3.35 (s,
2H), 3.30 (d, J = 7.6 Hz, 2H); 13C NMR (CDCl3,
100 MHz): δ 145.8, 136.9, 132.3, 131.5, 128.0, 125.3, 123.7,
122.3, 120.3, 120.0, 119.1, 118.5, 115.3, 111.1, 36.5,
34.3.[24e]
Yield: 76%, 120 mg; brown solid; mp 112-114ꢀC; 1H NMR
(CDCl3, 400 MHz): δ 7.42 (d, J = 8 Hz, 2H), 7.21 (d,
J = 8 Hz, 2H), 7.05-7.01 (m, 2H), 6.95-6.91 (m, 4H),
6.88-6.84 (m, 2H), 6.49-6.46 (m, 1H), 6.36 (d, J = 8 Hz,
1H), 4.62 (t, J = 14 Hz, 1H), 4.52-4.45 (m, 2H), 3.30 (d,

CHATTERJEE ET AL.
9
J = 6.8 Hz, 2H), 3.30-3.22 (m, 1H), 2.98 (s, 1H), 1.36 (d,
J = 6.4 Hz, 6H), 1.31 (d, J = 6.8 Hz, 6H), 0.63 (d,
J = 6 Hz, 6H); 13C NMR (CDCl3, 100 MHz): δ 145.8,
136.4, 130.7, 127.5, 126.9, 126.4, 121.7, 121.1, 120.1, 118.6,
118.2, 116.5, 110.9, 109.5, 46.9, 43.4, 37.4, 36.4, 22.9, 22.8.
121.1, 119.9, 118.4, 117.8, 116.7, 110.1, 109.2, 53.4, 46.1,
37.1, 35.4, 29.9, 29.4, 29.0, 29.7, 22.4, 22.3, 14.0, 13.9.
4.2.15 | N-Allyl-2-(2,2-bis[1-allyl-1H-
indol-3-yl]ethyl)aniline (2o)
1
4.2.12 | 2-(2,2-Bis[1-isobutyl-1H-indol-
3-yl]ethyl)-N-isobutylaniline (2l)
Yield: 73%, 114 mg; brown solid; mp 84-86ꢀC; H NMR
(CDCl3, 400 MHz): δ 7.45 (d, J = 8 Hz, 2H), 7.25 (d,
J = 8.4 Hz, 2H), 7.15-7.11 (m, 2H), 7.06-6.91 (m, 6H),
6.61-6.57 (m, 1H), 6.46 (d, J = 8 Hz, 1H), 5.98-5.89 (m,
2H), 5.60-5.52 (m, 1H), 5.16-5.13 (m, 2H), 5.06-4.98 (m,
4H), 4.80 (t, J = 14.4 Hz, 1H), 4.65-4.63 (m, 4H), 3.40 (d,
J = 7.2 Hz, 2H), 3.36-3.34 (m, 2H); 13C NMR (CDCl3,
100 MHz): δ 146.4, 136.9, 135.5, 133.8, 130.3, 127.6, 127.1,
126.0, 125.8, 121.5, 120.0, 118.8, 118.7, 117.3, 117.0, 115.9,
110.7, 109.6, 48.8, 46.6, 37.5, 35.1.
1
Yield: 70%, 121 mg; white solid; mp 106-108ꢀC; H NMR
(CDCl3, 400 MHz): δ 7.50 (d, J = 8 Hz, 2H), 7.27-7.25 (m,
2H), 7.14-7.10 (m, 2H), 7.05-7.01 (m, 1H), 6.97-6.92 (m,
3H), 6.89 (s, 2H), 6.54-6.48 (m, 2H), 4.78 (t, J = 14.8 Hz,
1H), 3.83-3.80 (m, 4H), 3.40 (d, J = 7.2 Hz, 2H), 3.38 (s,
1H), 2.59 (d, J = 6.8 Hz, 2H), 2.18-2.09 (m, 2H), 0.88 (d,
J = 6.4 Hz, 12H), 0.81 (d, J = 6.4 Hz, H); 13C NMR
(CDCl3, 100 MHz): δ 146.8, 137.0, 130.3, 127.4, 127.0,
126.4, 125.6, 121.2, 120.0, 118.5, 117.8, 116.6, 110.2, 109.6,
54.0, 52.0, 37.2, 35.1, 31.7, 29.6, 20.7, 20.4.
4.2.16 | 2-(2,2-Bis(1-[prop-2-yn-1-yl]-1H-
indol-3-yl)ethyl)-N-(prop-2-yn-1-yl)
aniline (2p)
4.2.13 | 2-(2,2-Bis[1-butyl-1H-indol-3-yl]
ethyl)-N-butylaniline (2m)
Yield: 71%, 110 mg; brown solid; mp 108-110ꢀC; 1H NMR
(CDCl3, 400 MHz): δ 7.32 (d, J = 8 Hz, 2H), 7.27 (d,
J = 8.4 Hz, 2H), 7.12-7.09 (m, 2H), 7.03-6.96 (m, 2H),
6.92-6.88 (m, 4H), 6.62-6.58 (m, 1H), 6.45 (d, J = 8 Hz,
1H), 4.70-4.67 (m, 5H), 3.37 (s, 1H), 3.31-3.27 (m, 4H),
2.27 (t, J = 4.8 Hz, 2H), 2.03 (t, J = 4.4 Hz, 1H); 13C NMR
(CDCl3, 100 MHz): δ 145.7, 136.5, 130.4, 127.9, 127.2,
126.6, 125.1, 122.0, 120.1, 119.4, 119.3, 118.5, 111.1, 109.4,
81.4, 78.2, 73.5, 71.0, 37.8, 35.9, 35.0, 31.7.
Yield 72%, 124 mg; brown gummy mass; column chroma-
tography done (eluent: ethyl acetate/petroleum
1
ether = 10/90); H NMR (CDCl3, 400 MHz): δ 7.48 (d,
J = 8 Hz, 2H), 7.27 (d, J = 8 Hz, 2H), 7.15-7.11 (m, 2H),
7.07-7.00 (m, 2H), 6.97-93 (m, 2H), 6.89 (s, 2H), 6.60-6.56
(m, 1H), 6.46 (d, J = 8 Hz, 1H), 4.74 (t, J = 14 Hz, 1H),
4.05-4.00 (m, 4H), 3.38 (d, J = 7.2 Hz, 2H), 3.16 (s, 1H),
2.67 (t, J = 14.4 Hz, 2H), 1.78-1.70 (m, 4H), 1.30-1.21 (m,
6H), 1.08-1.02 (m, 2H), 0.91 (t, J = 14.8 Hz, 3H), 0.84 (t,
J = 14.4 Hz, 3H); 13C NMR (CDCl3, 100 MHz): δ 147.2,
136.8, 131.1, 130.4, 129.0, 127.5, 127.1, 125.9, 121.3, 120.1,
118.5, 117.9, 110.4, 109.4, 46.0, 37.3, 35.6, 32.5, 31.2, 20.5,
20.3, 19.3, 14.0, 13.9.
4.2.17 | N-Benzyl-2-(2,2-bis[1-benzyl-1H-
indol-3-yl]ethyl)aniline (2q)
1
Yield: 74%, 153 mg; white solid; mp 135-137ꢀC; H NMR
(CDCl3, 400 MHz): δ 7.53 (d, J = 8 Hz, 2H), 7.33-7.24 (m,
11H), 7.19-7.05 (m, 12H), 6.66 (t, J = 14.8 Hz, 1H), 6.54
(d, J = 8 Hz, 1H), 5.27 (s, 4H), 4.94 (t, J = 14.8 Hz, 1H),
3.97 (s, 2H), 3.86 (s, 1H), 3.52 (d, J = 8 Hz, 2H); 13C NMR
(CDCl3, 100 MHz): δ 146.5, 139.7, 138.0, 137.0, 130.4,
128.8, 128.6, 127.6, 127.5, 127.4, 127.1, 127.0, 126.6, 126.2,
125.7, 121.7, 120.0, 119.0, 118.7, 117.3, 110.8, 109.8, 49.9,
48.2, 37.3, 35.0.
4.2.14 | 2-(2,2-Bis[1-pentyl-1H-indol-3-yl]
ethyl)-N-pentylaniline (2n)
Yield: 67%, 125 mg; brown gummy mass; column chro-
matography done (eluent: ethyl acetate/petroleum
1
ether = 10/90); H NMR (CDCl3, 400 MHz): δ 7.41 (d,
J = 8 Hz, 2H), 7.19 (d, J = 8 Hz, 2H), 7.07-7.03 (m, 2H),
6.97-6.92 (m, 2H), 6.88-6.85 (m, 2H), 6.81 (s, 2H),
6.52-6.48 (m, 1H), 6.39 (d, J = 7.6 Hz, 1H), 4.66 (t,
J = 8 Hz, 1H), 3.96-3.92 (m, 4H), 3.31 (t, J = 7.2 Hz, 2H),
3.09 (s, 1H), 2.58 (t, J = 15.2 Hz, 2H), 1.75-1.61 (m, 6H),
1.24-1.15 (m, 12H), 0.81-0.78 (m, 9H); 13C NMR (CDCl3,
100 MHz): δ 146.8, 136.6, 130.2, 127.3, 126.9, 125.9, 125.7,
4.2.18 | 2-(2,2-Bis[1,5-dimethyl-1H-indol-
3-yl]ethyl)-N,4-dimethylaniline (2r)
1
Yield: 76%, 122 mg; white solid; mp 154-156ꢀC; H NMR
(CDCl3, 400 MHz):
δ 7.29-7.28 (m, 2H), 7.21 (d,

10
CHATTERJEE ET AL.
J = 8.4 Hz, 2H), 7.05 (d, J = 8.4 Hz, 2H), 6.98-6.94 (m,
2H), 6.84 (s, 2H), 6.42 (d, J = 8 Hz, 1H) 4.79 (t,
J = 13.2 Hz, 1H), 3.71 (s, 6H), 3.33 (d, J = 5.6 Hz, 2H),
2.42 (s, 6H), 2.39 (s, 3H), 2.22 (s, 3H); 13C NMR (CDCl3,
100 MHz): δ 145.8, 135.9, 130.8, 127.7, 127.6, 126.8, 126.3,
126.1, 123.1, 119.7, 118.2, 110.0, 108.8, 38.0, 34.7, 32.8,
31.0, 21.6, 20.6.
4.2.22 | 2-(2,2-Bis[5-chloro-1-ethyl-1H-
indol-3-yl]ethyl)-4-chloro-N-
ethylaniline (2v)
1
Yield: 74%, 132 mg; brown solid; mp 145-47ꢀC; H NMR
(CDCl3, 400 MHz): 7.28-7.27 (m, 2H), 7.20 (d,
δ
J = 8.8 Hz, 2H), 7.01-7.07 (m, 2H), 7.03-7.01 (m, 1H), 6.93
(s, 2H), 6.85 (d, J = 2.4 Hz, 1H), 6.37 (d, J = 8.8 Hz, 1H),
4.57 (t, J = 14.4 Hz, 1H), 4.13-4.06 (m, 4H), 3.26 (d,
J = 7.6 Hz, 2H), 2.98 (s, 1H), 2.70-2.65 (m, 2H), 1.40 (t,
J = 14.4 Hz, 6H), 0.80 (t, J = 14 Hz, 3H); 13C NMR
(CDCl3, 100 MHz): δ 145.6, 134.9, 130.1, 128.3, 127.2,
127.1, 126.2, 124.6, 121.9, 121.6, 119.3, 117.0, 111.5, 110.5,
41.2, 38.6, 36.9, 35.4, 15.7, 14.3.
4.2.19 | 2-(2,2-Bis[5-methoxy-1-methyl-
1H-indol-3-yl]ethyl)-4-methoxy-N-
methylaniline (2s)
1
Yield: 76%, 122 mg; brown solid; mp 79-81ꢀC; H NMR
(CDCl3, 400 MHz): δ 7.16-7.13 (m, 2H), 6.83-6.81 (m, 6H),
6.68-6.66 (m, 2H), 6.40-6.37 (m, 1H), 4.66 (t, J = 14.4 Hz,
1H), 3.71 (s, 6H), 3.68 (s, 6H), 3.59 (s, 3H), 3.31 (d,
J = 7.2 Hz, 2H), 2.32 (s, 3H); 13C NMR (CDCl3,
100 MHz): δ 153.5, 151.9, 142.5, 132.9, 127.9, 127.7, 127.2,
118.0, 116.9, 112.2, 111.7, 111.0, 109.9, 101.9, 56.0, 38.2,
34.8, 33.0, 31.5.
ACKNOWLEDGMENTS
A. Majee acknowledges the financial support from the
DST-RSF Major Research Project (Ref. No. INT/RUS/
RSF/P-08). S. Santra is thankful to the Russian Science
Foundation - Russia (Ref. # 18-73-00301) for funding. We
are thankful to the DST-FIST and UGC-SAP program.
ORCID
4.2.20 | 2-(2,2-Bis[5-chloro-1-methyl-1H-
indol-3-yl]ethyl)-4-chloro-N-
methylaniline (2t)
Adinath Majee https://orcid.org/0000-0002-5439-6851
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indol-3-yl]ethyl)-N-ethyl-
4-methoxyaniline (2u)
Yield: 75%, 131 mg; white solid; mp 70-72ꢀC; 1H
NMR (CDCl3, 400 MHz): δ 7.19-7.17 (m, 2H), 6.92 (s,
2H), 6.82-6.80 (m, 4H), 6.72 (d, J = 2.8 Hz, 1H),
6.67-6.64 (m, 1H), 6.38 (d, J = 8.8 Hz, 1H), 4.63 (t,
J = 14.8 Hz, 1H), 4.09-4.04 (m, 4H), 3.69 (s, 6H), 3.64
(s, 3H), 3.37 (d, J = 7.2 Hz, 2H), 2.58-2.52 (m, 2H),
1.38 (t, J = 14.4 Hz, 6H), 0.73 (t, J = 14.4 Hz, 3H);
13C NMR (CDCl3, 100 MHz): δ 153.3, 151.8, 141.8,
131.8, 128.4, 127.8, 125.5, 117.7, 116.8, 112.1, 111.7
(2C), 109.9, 101.9, 55.9, 55.8, 41.1, 39.1, 37.8, 36.0,
15.7, 14.3.

CHATTERJEE ET AL.
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How to cite this article: Chatterjee R, Santra S,
Zyryanov GV, Majee A. Brønsted acidic ionic
liquid–catalyzed tandem trimerization of indoles:
An efficient approach towards the synthesis of
indole 3,30-trimers under solvent-free conditions.
J Heterocyclic Chem. 2020;1–12. https://doi.org/10.
1002/jhet.3914
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