2D-2D Nanocomposite of MoS2-Graphitic Carbon Nitride as Multifunctional Catalyst for Sustainable Synthesis of C3-Functionalized Indoles

Article abstract of DOI:10.1002/cctc.201800369

A nanocomposite of two-dimensional MoS₂ supported on graphitic C₃N₄ nanosheets has been prepared by a facile ultrasonication method followed by demonstrating its ability to catalyze the synthesis of several indole derivatives. The as-prepared nanocomposite catalyst was characterized in detail by using different microscopic and spectroscopic techniques to understand its structure and physicochemical properties. Subsequently, this nanocomposite catalyst was used as a heterogeneous multifunctional catalyst to synthesize several C3-functionalized indoles in the aqueous medium. The employed strategy also provided very good catalyst recyclability and versatility for the synthesis of various precursors of medicinally significant indoles, such as serotonin, melatonin, and various β-carboline alkaloids. In addition, a natural product derivate has been prepared on the gram-scale by using this methodology. Furthermore, high atom economy (100 %) and lower E-factor (0.042) makes this strategy a sustainable approach for the synthesis of C3-functionalized indoles.

Full text of DOI:10.1002/cctc.201800369

Accepted Article
Title: 2D-2D Nanocomposite of MoS2-Graphitic Carbon Nitride
as Multifunctional Catalyst for Sustainable Synthesis of 3C-
functionalized Indoles
Authors: Ashish Bahuguna, Ashwani Kumar, Suneel Kumar, Tripti
Chhabra, and Venkata Krishnan
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
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the VoR from the journal website shown below when it is published
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To be cited as: ChemCatChem 10.1002/cctc.201800369
Link to VoR: http://dx.doi.org/10.1002/cctc.201800369
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10.1002/cctc.201800369
ChemCatChem
2D-2D Nanocomposite of MoS2-Graphitic Carbon Nitride as
Multifunctional Catalyst for Sustainable Synthesis of
3C-functionalized Indoles
Ashish Bahuguna, Ashwani Kumar, Suneel Kumar, Tripti Chhabra and Venkata Krishnan*
School of Basic Sciences and Advanced Materials Research Center, Indian Institute of
Technology Mandi, Kamand, Himachal Pradesh 175005, India.
Email: vkn@iitmandi.ac.in
Abstract
A nanocomposite of two dimensional MoS2 supported on gC3N4 nanosheets has been prepared
by a facile ultrasonication method followed by demonstrating its ability to catalyze the
synthesis of several indole derivatives. The as-prepared nanocomposite catalyst was
characterized in detail using different microscopic and spectroscopic techniques to understand
its structure and physico-chemical properties. Subsequently, this nanocomposite catalyst was
used as a heterogeneous multifunctional catalyst to synthesize several 3C-functionalized
indoles in the aqueous medium. The employed strategy also provided very good catalyst
recyclability and versatility for the synthesis of various precursors of medicinally significant
indoles, such as serotonin, melatonin and various beta-carboline alkaloids. In addition, a natural
product derivate has been prepared in gram-scale using this methodology. Furthermore, high
atom economy (100%) and lower E-factor (0.042) makes this strategy a sustainable approach
for the synthesis of 3C-functionalized indoles.
Keywords: Two dimensional material; nanocomposite; multifunctional catalyst; sustainable
synthesis; functionalized indoles
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Introduction
Catalysis and catalytic processes, such as homogeneous and heterogeneous processes,
are involved in all the major chemical production of the world.1 Traditional heterogeneous
catalysts have been found to be comparatively low active due to limited or less accessibility of
the reagents to the active sites of the catalysts. A catalyst support material can overcome this
problem by supporting the active sites on different other porous inorganic solids, such as
zeolite,2, 3 silica4-6 and various other mesoporous or even organic polymeric materials.4, 7-9
Therefore, selection of an appropriate catalytic support is of utmost importance.
Carbon and carbonaceous materials play a very significant role in catalysis, either as a
catalyst or a catalyst support for various chemical, biological and enzymatic transformation
reactions. There are several advantages of these materials due to their large surface area,
excellent electron conductivity, high porosity and relatively chemical inertness in mild reaction
conditions. Metal catalysts on carbon supports have various advantages over other catalytic
materials for various types of reactions.10-13 The future success of catalysis demands to design
new kinds of multifunctional catalytic materials possibly emerging from carbonaceous
materials, such as charcoal,14, 15carbon nanotubes,16, 17 carbon fibers,18, 19 carbon aerogels,20
graphene,21, 22 graphitic carbon nitride(GCN),23, 24 etc. Activated carbon25, 26 and carbon black27,
28
have been preferred choices of the materials among the carbon-supported catalysts due to
their high surface area, low cost and easy availability in large quantities. In the recent decade,
carbon materials, such as graphitic materials and activated carbons have been extensively used
in heterogeneous catalysis as catalyst supports.29-31 The physiochemical properties of these
materials, such as their mechanical strength, tunable porosity, chemical/ thermal stability and
surface chemistry make them suitable for many catalytic application processes.
In recent years, organic transformations using the environmentally benign(Green)
approaches of synthesis and sustainable methods are in demand from industries and society.32
Among several Green methods of synthesis, nanocomposite catalyzed organic transformations
has drawn significant attention from a wide range of researchers working in different fields of
chemistry.33, 34 Organic transformations using nanocomposites has several advantages, such as
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simple filtration due to heterogeneous nature, easy to handle, efficient recovery and reusability
of catalyst, etc. Minimization of waste leads to higher atom economy and lower E-factor play
significant role in Green and sustainable chemistry. Moreover, nanocomposite catalyzed
reaction with two dimensional (2D) metal dichalcogenides35, 36 such as, MoS2 has attracted
much attention recently. In addition to its wide application in material chemistry, MoS2 is now
becoming one of the preferred choices for synthetic chemists as well, due to its large surface
area and 2D nature. There are several examples available in the literature based on composites
of different materials with MoS2 such as MoS2-ZnO, MoS2-graphene, MoS2-reduced graphene
oxide (RGO) and MoS2-GCNwith varying surface area due to the difference in their interfacial
contact with each other. MoS2-RGO and MoS2-GCN, due to 2D-2D nature have larger surface
areas among several other composites. Graphitic carbon nitride (GCN) is a recently evolving
material having unique structure and properties such as, 2D structure, good chemical stability,
tunable electronic property and slight basic character due to nitrogen richness, which makes it
suitable catalyst or catalyst support for various organic transformation reactions such as,
oxidation,37 hydrogenation,38 activation of benzene,39 acetylene hydrochlorination,40
Knoevenagel condensation reactions,41 cyclisation of nitriles and alkynes,42 copper catalyzed
azide–alkyne cycloaddition43 and so on. In all these organic transformation reactions GCN either
acts as a base or as a catalyst support.
MoS2 based nanocomposites have shown their potential for some of the organic
transformation reactions recently. Zhang et al. reported Mo over GO-Fe3O4 as an efficient
catalyst for synthesis of spiro-oxindole scaffolds.44 Wang et al. reported MoS2-TiO2
nanocomposite for thiocynation of indoles.45 In addition, our group has also developed
nanocomposite of MoS2-RGO as Green catalyst for one-pot synthesis of indole alkaloids.46
Although several metal oxide and sulfides have been integrated with GCN for photocatalytic
48
applications,47,
there are only limited reports on metal oxide and sulfide-based
nanocomposites for of the synthesis of indoles and their derivatives.3C-substituted indole
derivatives have drawn a lot of attention of synthetic chemists due to their vast applications as
building blocks for several biologically active molecules. Various medicinally significant 3-
substituted indoles such as, serotonin, melatonin, tryptamine, tryptophan, etc. are some of the
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important key examples, whose chemical structures are shown in Figure 1. In addition, these
3C-functionalized indoles are the precursor to various natural products such as indoles
alkaloids, beta-carboline alkaloids and various potent drugs as well49-51. Yonemitsu et al. were
the first to report one-pot synthesis of 3-substituted indoles using aldehydes, indoles and
Maldrum’s acid.52 Recently, Gu et al. reported Yonemitsu reaction for synthesis of 3-substituted
indoles using aldehydes, indole, and dimedone in the presence of L-proline as a homogeneous
catalyst.53 Recently, Rawat et al. reported a heterogeneous ZnO-RGO nanocomposite for the
synthesis of 3-substituted indole using aldehydes, indoles and a secondary amine.54 Inspired by
our continuous effort towards Green and sustainable synthesis, herein we report MoS2-GCN
nanocomposite catalyzed synthesis of 3C-functionalized indole derivatives of nitro alkenes and
isatins. The proposed method is a mild, Green and very efficient method for the synthesis of
various 3C-substituted indole derivatives. All the reactions have been carried out using the
universal Green solvent, water. Due to the absence of by-products in the developed protocol
and carrying out reactions in aqueous medium provide high value of atom economy (99%) and
low E-factor (0.04), which are essential parameters for a sustainable synthetic method.
Figure 1. Representative examples of bioactive 3C-substituted indoles.
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Results and discussion
Synthesis and characterization of nanocomposites
The nanocomposites of MoS2-GCN were prepared by a facile ultrasonication route using
appropriate precursors. In this work, MoS2amount in GCN nanosheets was varied to form MoS2-
GCN(1:1), MoS2-GCN(1:2) and MoS2-GCN(1:4) nanocomposites. The determine the structure of
as prepared nanocomposites and bare catalysts x-ray diffraction (XRD) measurements were
performed and the results are presented in Figure 2 (a).It can be seen that GCN exhibits two
distinct diffraction peaks at the 2θ values of 13.0° and 27.5°, which are assigned to (100) and
(002) reflection planes, respectively. The strong diffraction peak at 27.5°corresponds to
interlayer d-spacing of 0.336 nm of GCN and represents the stacking of the conjugated double
bonds, while weak diffraction peak at 13.0° corresponds to an inter planar separation of 0.672
nm.55 These two diffraction peaks are in good agreement with reported literature (JCPDS 87-
1526)for GCN.55 The XRD pattern of MoS2 has three discernible diffraction peaks at the 2θ
values of 14.2°, 32.5°, and 57.0° which could be indexed to the(002), (100) and (110) reflection
planes of crystalline MoS2as previously reported (JCPDS no. 37-1492).56The main diffraction at
around 14.2°, indicate the lamellar structure of layered MoS2nanosheets and corresponds to d-
spacing of 0.62 nm. It is noteworthy to mention here that the MoS2-GCN (1:1) nanocomposite
shows all diffraction peaks corresponding to both MoS2 and GCN confirming the successful
synthesis of the nanocomposite.
FTIR spectra provide useful structural insights into bare catalysts and nanocomposites.
From the results presented in Figure 2(b), it can be seen that bare GCN exhibit a series of peaks
related to its polymeric structure. The broad absorption band in 3500-3000 cm-1originates from
stretching vibration of N-H bonds, associated with uncondensed amino groups, whereas, a
series of peaks in 1600-1200 cm-1could be assigned to the stretching vibrations of C-N
heterocycles.55 The above distinct mode of vibrations confirms the formation of C-N-C bond in a
graphitic material. Furthermore, the sharp peak at 806 cm−1 could be assigned to the distinct
breathing vibrations of the 1,3,5-triazine ring. As can be seen from the FTIR spectrum of bare
MoS2, the band at 467 cm−1 could be assigned to stretching vibration of the Mo–S bond.57 The
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FTIR spectrum of MoS2-GCN(1:1) nanocomposite shows the presence of similar peaks as of bare
GCN, verifying that the structure of GCN remains unchanged even after the nanocomposites
formation with MoS2.
Figure 2.(a) XRD patterns of GCN, MoS2and MoS2-GCN(1:1) nanocomposite and (b) FTIR spectra
of GCN, MoS2and MoS2-GCN(1:1) nanocomposite.
The morphology of as-prepared catalysts MoS2, GCN and MoS2-GCN (1:1)
nanocomposite were analyzed by field emission scanning electron microscopy (FESEM)
technique and are presented in Figure 3. It is clear from Figure 3(a) that, bare GCN exhibit
wrinkled, sheet-like morphology with smooth surface. The SEM micrograph of MoS2 also shows
aggregated sheet-like morphology to form groove-like structure (Figure 3b). In the SEM images
of MoS2-GCN (1:1) nanocomposite, sheet-like layered structure of MoS2 adhered on the surface
of GCN nanosheets could be evidenced (Figure 2c). Hence, it is clear that MoS2 is well dispersed
onto GCN nanosheets to form the desired nanocomposite. Furthermore, the presence of all
constituent elements (Mo, S, C, and N) in MoS2-GCN (1:1) nanocomposite has been affirmed by
energy dispersive x-ray (EDAX) technique as presented in Figure S1 (a).
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Figure 3. SEM images of (a) GCN, (b) MoS2 and (c) MoS2- GCN (1:1) nanocomposite.
Furthermore, transmission electron microscopy (TEM) analysis was used to further
investigate the surface morphology of MoS2, GCN and MoS2-GCN (1:1) nanocomposite at
nanometer scale and the obtained TEM images have been presented in Figure3. Bare GCN
shows thin sheet-like morphology of π-conjugated polymeric structure of C and N atoms (Figure
4a). It can be clearly seen in Figure 4(b) that MoS2 shows lamellar structure. The TEM image of
MoS2-GCN (1:1) nanocomposite in Figure 4(c) reveals the presence of both components
MoS2and GCN confirming the successful formation of the nanocomposite showing intimate
contact between MoS2 and GCN. All the constituent elements in representative MoS2-GCN (1:1)
nanocomposite were further confirmed by EDAX analysis presented in Figure S1 (b).
Figure 4.TEM images of (a) GCN, (b) MoS2 and (c) MoS2-GCN (1:1) nanocomposite.
The adsorption capacity of the catalysts is an important factor for understanding the
catalytic reaction. In this regard, Brunauer–Emmett–Teller (BET) surface area measurements of
bare GCN, MoS2, and MoS2-GCN (1:1) nanocomposite were performed by using nitrogen
adsorption-desorption isotherms and are presented in Figure 5. The Figure 5(a, b, c) presents
the isotherm curves of GCN, MoS2 and MoS2-GCN (1:1) nanocomposite together with
corresponding multipoint BET plots (Figure 5 d, e, f), respectively. The adsorption–desorption
isotherms of all three catalysts exhibit characteristic type IV curve with a hysteresis loop. The
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MoS2-GCN (1:1) nanocomposite was found to exhibit the largest surface area, 35.154 m2g−1,
while the surface area of the bare GCN was 20.099 m2 g−1 and that of MoS2 was 21.982 m2 g−1.
The increased specific surface area of MoS2-GCN (1:1) nanocomposite resulted from the
combination of 2D structures of GCN and MoS2 nanosheets to form a hybrid material.
Figure 5. N2 adsorption-desorption isotherms of (a) GCN, (b) MoS2, (c) MoS2-GCN (1:1)
nanocomposite and multipoint BET plots of (d) GCN, (e) MoS2, and (f) MoS2-GCN (1:1)
nanocomposite.
Thermogravimetric analysis (TGA) was performed to analyze the thermal stability of
GCN, MoS2 and MoS2-GCN (1:1) nanocomposite (Figure 6) under the N2 atmosphere from 25°C
to 800°C. As it is evident from Figure 6, the decomposition of GCN starts after 500°C and about
98% degradation completes around 740°C, attributable to the burning of GCN into carbon and
nitrogen. While, the slight decrease in weight of MoS2 starts at 100°C, which indicates the loss
of intercalated water molecules and again another weight loss of about 11% at 300°C attributed
to the oxidation of MoS2 to MoO3. Similarly, for MoS2-GCN nanocomposite loss of weight was
observed after 500°C which resembles to weight loss due to GCN decomposition. Furthermore,
this weight loss of about 52% in MoS2-GCN nanocomposite also confirms the amount of MoS2:
GCN (1:1) in nanocomposite.
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Figure 6. TGA profile of GCN, MoS2and MoS2-GCN (1:1) nanocomposite.
Hydrophilicity study has been carried out by contact angle measurement, in which water
contact angle of GCN, MoS2 and MoS2-GCN nanocomposite were measured (Figure S2, refer
supporting information). GCN showed a water contact angle of 51°, which shows very good
hydrophilicity of the material. MoS2 showed 86°, which reveals its tendency towards less
hydrophilicity in comparison to GCN. Finally water contact angle of MoS2-GCN (1:1)
nanocomposite was measured, and it was found to be 69°, which is in intermediate range
between more hydrophilic GCN and less hydrophilic MoS2. We observed from our study that
this intermediate range of hydrophilicity of the catalyst favors the reaction to undergo
efficiently in aqueous medium.
Catalytic activity studies
The inherent catalytic potential of MoS2-GCN nanocomposite has been investigated for
the synthesis of 3C-functionalized indole derivatives by reaction of indoles with nitroalkenes
and isatin. The catalytic activity of MoS2-GCN nanocomposite was initially investigated on a
model reaction of indole and beta-nitrostyrene to obtain a 3-(2-nitro-1-phenylethyl)indole
using 10 wt % of the catalyst in water at 55°C (Scheme 1).Optimization studies have been
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shown in Table 1, which shows that the nanocomposites with different ratios of MoS2-GCN
were prepared and evaluated for their catalytic potential. Reactions were performed with
nanocomposite comprising 1:1, 1:2 and 1:4 ratios of MoS2 and GCN, respectively. Initially
reactions were performed at room temperature with the varying amount of catalyst but the
yields were found to be very poor. When reactions were tried at higher temperatures,
significant improvement in yields was observed. As it is evident from the optimization results
(Table 1), that10 wt % of MoS2-GCN (1:1) nanocomposite was found to be the best catalyst,
which resulted in 96% yield. When 20 wt% of MoS2-GCN (1:1) nanocomposite was used in the
reaction, not much difference in reactivity was observed. But when the reaction was tried with
bare MoS2, the formation of some unknown side products was observed which resulted in the
decrease in yield of the reaction. Finally, reaction was performed with bare GCN, but no
reactivity was observed after 12h also.
In order to extend the substrate scope and generality of MoS2-GCN nanocatalytic
system, various substituted indoles and nitroalkenes were tried (Table 2). Reactions were
performed with indoles having fluoro, chloro, bromo, methoxy, nitro and hydroxyl
functionalities, which demonstrated the good substrate scope with both electron withdrawing
and electron donating groups present on indole rings. Since reaction was not successful at
55°Cin case of 5-nitroindole, hence reaction was performed at 90°C to get the desired
product.7-azaindole being exceptional was found to be reluctant towards nitroalkenes, unlike
other indoles. Similarly reactions were performed with varying electron withdrawing and
electron donating groups at nitroalkene moiety, but it has no effect on reactivity of the catalyst.
Moreover, the reaction was also performed with other Green solvents, such as ethyl acetate
(EtOAc), ethanol (EtOH) and isopropyl alcohol (IPA) to see the change in reactivity with different
other solvents. It was evidenced that the reactions in EtOH proceeded better than the reactions
in EtOAc and IPA (Table 2, entry 17-20) under the similar reaction conditions.
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Scheme 1. MoS2- GCN catalyzed Green synthesis of 3C- functionalized indoles
Table 1. Optimization of MoS2-GCN catalyzed Michael type synthesis of 3-(2-nitro-1-
phenylethyl)-1H-indole
Sl.No.
Catalyst
Catalyst
Temp. (oC)
and solvent
RT, H2O
RT, H2O
RT, H2O
RT, H2O
40, H2O
55, H2O
55, H2O
55, H2O
55, H2O
55, H2O
Time (h)
% Yield
wt%
5
1
MoS2-GCN (1:1)
MoS2-GCN (1:1)
MoS2-GCN (1:1)
MoS2-GCN (1:1)
MoS2-GCN (1:1)
MoS2-GCN (1:1)
MoS2-GCN (1:1)
MoS2-GCN(1:1)
MoS2-GCN (1:1)
MoS2-GCN (1:2)
12
24
24
24
12
12
12
24
12
12
Trace
15
2
5
3
8
22
4
10
10
10
6
32
5
45
6
96
7
95
8
6
81
9
20
10
91
10
53
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11
12
13
14
15
16
17
18
19
20
MoS2-GCN (1:2)
MoS2-GCN(1:4)
MoS2
20
10
10
10
10
00
10
10
10
20
55, H2O
55, H2O
55, H2O
55, H2O
55, H2O
55, H2O
55, EtOAc
55, IPA
12
12
12
24
12
12
12
12
12
12
67
20
69
51
00
00
54
63
72
78
MoS2
GCN
No catalyst
MoS2- GCN (1:1)
MoS2- GCN (1:1)
MoS2- GCN (1:1)
MoS2- GCN (1:1)
55, EtOH
55, EtOH
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Table 2. Substrate scope for the synthesis of 3C-functionalized indole derivatives of
nitroalkenes
a
b
Reaction was performed at 90 oC temperature and reaction was performed in ethanol instead of water.
Furthermore, to investigate the wide applicability of MoS2-GCN, we performed reactions
of indoles with isatin.A model reaction of indole and isatin was performed similar to the above
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reaction. But in case of the reaction of indole with isatin, interesting results were obtained.
When the reaction was performed at ambient temperature, the product formed was different
from the product obtained by performing reaction at 55 °C (Scheme 2).When reaction of indole
and isatin was carried out at room temperature, 3-hydroxy-3-(1H-indol-3-yl)indolin-2-one
(Table 4, 6a) was observed as major product, but [3,3':3',3''-terindolin]-2'-one was found to be
the major product when the same reaction was carried out at 55°C (Table 4, 5a). Optimization
of reaction conditions have been presented in Table 3, and similar to the reaction with beta-
nitrostyrene, the best catalytic system for reaction of indole with isatin was found to be 10 wt%
of MoS2-GCN (1:1). Wide substrate scope was observed by varying the substituent at indole and
isatin (Table 4). Reactivity of isatin was found to be equally good with indoles having electron
withdrawing or electron donating groups except for 5-nitroindole. Again, reaction with 5-
nitroindole was performed at 90°C, while rest of all the reactions were carried out at 55°C
(Table 4, 5a-5d & 5f-5i).
Scheme 2. Synthesis of 3C- functionalized indole derivatives of isatin
Table 3. Optimization of MoS2-GCN catalyzed synthesis 3C- functionalized indole derivatives of
isatin
Sl.No.
Catalyst
Catalyst
Temp.
Time (h)
% Yield
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wt%
5
(oC)
5a
6a
1
MoS2-GCN (1:1)
MoS2-GCN (1:1)
MoS2- GCN(1:1)
MoS2-GCN (1:1)
MoS2-GCN (1:1)
MoS2- GCN (1:1)
MoS2-GCN (1:2)
MoS2-GCN (1:2)
MoS2-GCN (1:2)
MoS2-GCN (1:4)
MoS2-GCN (1:4)
MoS2
RT
RT
55
55
40
55
55
55
55
55
55
55
55
RT
RT
RT
RT
12
24
12
12
12
12
12
18
24
12
24
12
12
12
24
12
12
Trace
10
38
91
59
90
20
39
63
07
12
63
00
05
12
27
20
63
72
54
08
37
09
45
50
36
29
36
18
00
63
81
62
54
2
8
3
5
4
10
10
20
10
10
10
5
5
6
7
8
9
10
11
12
13
14
15
16
17
10
10
10
10
10
20
10
GCN
MoS2- GCN (1:1)
MoS2- GCN (1:1)
MoS2- GCN (1:1)
MoS2
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Table 4. Substrate scope for the synthesis of 3C-functionalized indole derivatives of isatin
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Scheme 3. Gram-Scale Synthesis of 3-(2-nitro-1-phenylethyl)-1H-indol-5-ol (3e)
Pharmaceutical or other industrial benefits of the developed catalytic system could be
demonstrated by performing a gram-scale reaction (Scheme 3) for the synthesis of3e, a
precursor of substituted tryptamine (phenyl derivate of serotonin precursor). Starting from 1g
of 5-hydroxyindole, and 1 g of beta-nitrostyrene, 1.87 g (94%) of product 3e was obtained. This
result reveals the potential of our catalyst for pharmaceutical industrial application, wherein
reaction could be carried out at large-scale for the synthesis of substituted tryptamine
precursor in mild reaction conditions using water as a solvent. For a standard sustainable and
Green reaction, atom economy (AE)/ reaction mass efficiency (RME) should be high, and
environmental factor(E-factor)along with process mass intensity(PMI) should be low46. We have
calculated Green chemistry matrices for our developed and optimized reaction, and found very
high atom economy (A.E. = 100%), good reaction mass efficiency (R.M.E. = 95.9%) and small
environmental factor (E-factor = 0.042) and low process mass intensity (P.M.E. = 1.042) (refer
supporting information).
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Scheme 4. Further transformation of 3m to synthesize some bioactive scaffolds
Furthermore, we also synthesized two bioactive molecules, tryptamine (3mm) and a
beta-carboline analogue (3mn) to show the biological/ medicinal significance of the developed
molecules. The structure of 3mn has been reconfirmed by single crystal x-ray diffraction
experiment (CCDC 1821503, Figure S3). Our developed protocol gives access to easy one or
two-step synthesis of various substituted tryptamine (i.e. neurotransmitter such as, serotonin)
and beta-carboline alkaloids, unlike several other multi-step synthesis methods.
Table 5. Comparison of catalytic activity of MoS2- GCN with other metal/support based
catalysts for synthesis of 3-substituted indoles
Entry Product Catalyst
Solvent Time
Yield
(%)
Ref
58
59
1
2
3a
3a
Organopalladium(II)
complexes
DCM
DCM
10 days 99
NHC complexes of Ni(II)
and Hg(II)
24h
85-86
60
61
62
3
4
5
3a
3a
3a
HY zeolite
Neat
ACN
1h
93
98
99
Urea based MOF
Squaramide-based MOF
18h
24h
CHCl3
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63
64
65
66
67
6
3a
3a
3a
3a
3a
Gold(I)-mediated thiourea DCM
organocatalyst
18h
0.5h
8h
93
84
96
85
81
7
Silica-supported sodium
hydrogen sulfate
ACN
8
CeCl3.7H2O-NaI supported ACN
on SiO2
9
Nano n-propylsulfonated Neat
c-Fe2O3
1h
10
Cationic NCN Pincer
Platinum(II) Aquo
Complex
Toluene 36h
68
11
12
3a
3a
Nanocrystalline
titanium(IV) Oxide
MoS2-GCN
DCM
4h
79
96
Water
12h
This
work
69
13
14
5a
5a
Bismuth(III) triflate
Silica sulfuric acid
ACN
3h
92
92
DCM
2 h
70
15
5a
MoS2-GCN
Water
12 h
91
This
work
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Scheme 5.Mechanism of catalytic activity of MoS2-GCN nanocomposite
In general, MoS2 is a Lewis acid catalyst and GCN is a base catalyst. Although bare MoS2
shows some catalytic activity, the nanocomposite comprising of MoS2 and GCN shows excellent
activity, which could be attributed to the synergistic effects due to the formation of Lewis acid-
base non-bonding adducts. The mechanism of the proposed catalytic cycle is shown in Scheme
5. As depicted in the scheme, MoS2 makes the nitrostyrene more electron-deficient and prone
to attack by a nucleophile. Furthermore, GCN being a base facilitates the proton transfer during
the reaction. The catalytic cycle shows that, at the surface of catalyst the electron deficient
alkene (beta nitrostyrene) due to its electrophilic nature gets attacked by 3-position of indole.
Then the reaction proceeds in a fashion similar to Michael addition and forms an intermediate
2, which after exchanging the proton forms the product 3. Similarly, isatin also becomes more
electrophilic at the catalyst surface and easily gets nucleophilic attack by indole molecule to
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10.1002/cctc.201800369
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form a hydroxyl intermediate 2’. The hydroxyl intermediate 2’ then again gets attacked by
another indole molecule to form the final product 3’ after removal of a water molecule. The
hydroxyl intermediate can be isolated if the experiment is performed in controlled conditions
(i.e. either by performing reaction at RT or by using equal moles of indole and isatin).Finally, the
recyclability studies were performed for the MoS2-GCN (1:1) nanocomposite catalyst for the
synthesis of 3-substituted indole 3a under the optimized reaction conditions as per Table 1.
There was no significant loss in activity of the catalyst even after 6 cycles (refer Figure 7). The
small decrease in activity between the different cycles could be attributed to the loss of small
amount of catalyst during recovery process.
Figure 7. Recyclability study of MoS2-GCN (1:1) nanocomposite catalyst for the synthesis of 3C-
functionalized indole 3a.
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Conclusion
In summary, it has been demonstrated that MoS2-GCNnanocompositesact as highly
efficient and recyclable heterogeneous multifunctional catalyst for the synthesis of various 3-C
functionalized indoles. The MoS2-GCN catalytic system has several advantages such as high
catalytic performance, good yields in moderate reaction times, applicability to a wide range of
indole-based organic reactions and use of water as a Green solvent. The MoS2-GCN catalyst can
be easily recovered from reaction mixtures and recycled multiple times without significant loss
in activity. In addition, the high atom economy (99%) and lower E-factor (0.042) makes this
strategy a sustainable approach for the synthesis of several bioactive indole derivatives.
Experimental Section
Instrumentation
X-ray diffraction (XRD) measurements were performed on Rigaku Smart Lab 9 kW
rotating anode X-ray diffractometer with Ni-filtered Cu Kα irradiation (λ = 0.1542 nm) at 45 kV
and 100 mA in 2θ ranging from 5° to 80° with a scan rate of 2° per minute with stepping size of
0.02°. Morphology of the materials was examined by using a field emission scanning electron
microscope (FESEM), FEI Nova Nano SEM-450, and a transmission electron microscope (TEM),
FEI Tecnai G2 20 S-twin microscope operating at 200 kV. Energy dispersive X-ray spectra (EDAX)
were acquired using the same SEM and TEM instruments. X-ray photoelectron spectroscopic
(XPS) measurements were performed on a PREVEC photoemission spectrometer having an Al-
Kα (1486.6 eV) duel anode as a source operating a 12 kV anode and 23mA filament current. The
XPS data were collected with a pass energy of 50 eV at 6.1x 10-10 m bar vacuum using a Scienta
R3000 electron energy analyzer. The data obtained from the instrument were processed and
deconvoluted using CASA software. Thermogravimetric analysis (TGA) was carried out by using
a PerkinElmer Pyris 1 instrument, wherein the samples were heated from room temperature to
800 °C at a heating rate of 10 °C min−1 under the air with a flow rate of 20 mL min−1. Contact
angle measurements were performed using the Phoenix 300 contact angle instrument. Melting
points were determined using an open capillary method. NMR spectra were recorded on a
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JEOL-USA (JNMECX500) spectrometer in CDCl3 and DMSO-d6 taking TMS (tetramethylsilane) as
1
an internal standard. The H-NMR and 13C-NMR chemical shifts were reported in ppm relative
1
to 7.26, 2.50 ppm, and 77.0 and 39.5 ppm, for CDCl3 and DMSO-d6. H-NMR spectra were
recorded in 500 MHz frequency, and 13C-NMR spectra were recorded at 125 MHz frequency.
FT-IR spectra were acquired on a PerkinElmer Spectrum 2 spectrometer. Mass spectra were
recorded on an advance Bruker Daltonics (impact HD) UHR-QqTOF (ultra-high resolution
Qqtime-of-flight) mass spectrometer. Synthesis of catalyst and all the reactions were carried
out in deionized water (18.2 MΩ cm), which was obtained from a double stage water purifier
(ELGA PURELAB Option-R7).
Chemicals
All of the necessary chemicals were procured from Sigma Aldrich, Fluka, Alfa Aesar, Merck, and
TCI suppliers based in India. For MoS2 nanosheets synthesis, sodium molybdate dihydrate
(Na2MoO4· 2H2O) was purchased from by Merck, India and L-Cysteine (98%) was supplied by
Alfa Aesar, India. Hexane and ethyl acetate for column chromatography was supplied by Fischer
Scientific and AVRA chemicals, respectively.
Synthesis of MoS2 nanosheets
MoS2 nanosheets were prepared by referring a reported procedure.71 In short, 250 mg of
sodium molybdate dihydrate, 400 mg of L-cysteine and 40 mL of de-ionised water were mixed
in a 100 mL beaker and kept on stirring for 1h. Followed by stirring, the reaction mixture was
then transferred into a Teflon-lined autoclave and temperature was maintained at 180oC for
24h. The obtained material was recovered by centrifugation at 7000 rpm followed by repeated
washing with water for 3-4 times. Finally, the material was dried at 70-80 oC for 12h to obtain
pure MoS2 nanosheets.
Synthesis of GCN nanosheets
Graphitic carbon nitride (GCN) nanosheets were prepared by a reported literature method. In
brief, 5 g of dicyandiamide was taken in a crucible and heated at 550oC (at a rate of 5oC per
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10.1002/cctc.201800369
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minute) in a muffle furnace for 3h. After this step, the material was crushed to powder in a
mortar-pestle and re-calcinated again at 550oC for 3h to obtain the final product.
Synthesis of MoS2-GCN nanocomposite
MoS2-GCN nanocomposite was synthesized by ultrasonic dispersion method72 described here.
Firstly, 200 mg of the synthesized GCN powder was dissolved in 20 mL of ethanol and varying
amounts (50,100,200 mg) of MoS2 was added to make nanocomposites in different ratios (1:4,
1:2 and 1:1). The mixture was stirred for 3h followed by ultrasonic dispersion for another 3h.
Finally, obtained composites were centrifuged and washed with water and ethanol (3 times)
and dried at 70oC for 12h. Three different nanocomposites of MoS2-GCN (1:1, 1:2, and 1:4)
were fabricated varying MoS2 content.
General procedure for synthesis of 3C-functionalized indole derivatives of nitroalkenes (3a -
3l)
In a 10 mL round bottomed flask, a mixture of indole (1 mmol), nitroalkene (1mmol), MoS2-
GCNcatalyst (10 wt %), and water (2 mL) were placed and stirred at 55oC temperature. Progress
of the reaction was time-to-time monitored by TLC. After completion of the reaction, water was
decanted from reaction and ethanol was added to the reaction mixture accompanied by
centrifugation of reaction mixture to separate the nanocomposite catalyst. The organic layer
was dried over sodium sulfate, and the solvent was removed using rotary evaporator under
reduced pressure. The obtained crude product was purified by column chromatography. All the
compounds were characterized by melting point, 1H &13C NMR spectral data.
General procedure for synthesis of 3C-functionalized indoles derivatives of isatin (5a- 5i)
In a 10 mL round-bottomed flask, a mixture of indole (1 mmol), isatin (0.5 mmol), MoS2-GCN
catalyst (10 wt %), and water (2 mL) were placed and stirred at 55oC temperature (with
exception to the reaction of nitroindole and isatin, which was proceeded at 90oC). Progress of
the reaction was monitored by TLC. After completion of the reaction, water was decanted from
reaction and ethanol was added to the reaction mixture accompanied by centrifugation of
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reaction mixture to separate the nanocomposite catalyst. The organic layer was dried over
sodium sulfate,and the solvent was removed at rotary evaporator under reduced pressure. The
obtained crude product was purified by column chromatography. All the compounds were
characterized by melting point, 1H &13C NMR spectral data.
Procedure for synthesis of 2-(1H-indol-3-yl)ethanamine (3mm) from 3-(2-nitroethyl)-1H-
indole (3m)73
To a stirring solution of compound 3m (0.5 mmol) in methanol (2 mL) were added Pd/C 10%
and HCOONH4 (2.5 mmol). The reaction mixture was stirred at ambient temperature for 12 h.
After completion of the reaction, mixture was filtered on a celite pad, and the pad was washed
three times with methanol and the solvent was evaporated under reduced pressure. The solid
residue was dissolved in EtOAc, washed with saturated Na2CO3, brine, and the aqueous phase
was extracted twice with EtOAc. The organic phase was dried over Na2SO4 and evaporated to
afford compound 3mm as a white-orange solid in 81% yield.
Procedure for the synthesis of 1-phenyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (3mn)
from 3-(2-nitroethyl)-1H-indole (3m)73
It is a two-step synthetic procedure in which the first step of the synthesis is the same as
described above (i.e. 3m to 3mm). In the second step, to a stirred solution of crude 3mm (0.5
mmol) in dry acetonitrile (9 mL), were sequentially added CF3COOH (1.0mmol) and
benzaldehyde (0.55 mmol). The resulting solution was kept on stirring at 80 °C for 24h. After
completion of the reaction, the mixture was cooled to ambient temperature and was poured
into sat. NaHCO3 and then extracted thrice with dichloromethane. The organic phase was dried
over Na2CO3 and concentrated. The product was then isolated by chromatography on silica gel
(EtOAc/Hexane (70:30) mixture) in 72% yield as a yellowish orange solid 3mn.
Compound characterization
3-(2-nitro-1-phenylethyl)-1H-indole74-76:92%,(Rf= 0.45, 15:85 EtOAc/Hex),1H NMR (CDCl3, 500
MHz) δ 8.05 (brs, 1H), 7.43 (d, 1H, J = 8.2 Hz), 7.33-7.28 (m, 5H), 7.26-7.22 (m,1H), 7.18 (t, 1H, J
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ChemCatChem
= 6.9 Hz), 7.06 (t, 1H, J = 6.9 Hz), 6.99 (d, 1H, J = 2.7Hz), 5.17 (t, 1H, J = 7.5Hz), 5.06-5.02 (m, 1H),
4.94-4.90 (m, 1H); 13C NMR (CDCl3, 125 MHz) δ 139.1, 136.4, 128.9, 127.7, 127.5, 126.0, 122.6,
121.6, 119.9, 118.8, 114.3, 111.3, 79.5, 41.5.
5-chloro-3-(2-nitro-1-phenylethyl)-1H-indole76:91%,(Rf = 0.5, 15:85 EtOAc/Hex), 1H NMR
(CDCl3, 500 MHz) δ 8.15 (brs,1H), 7.37 (s, 1H), 7.33-7.22 (m, 6H), 7.12(dd, 1H, J = 1.4 & 8.25 Hz),
7.05 (s, 1H), 5.11 (t, 1H, J = 7.6 Hz), 5.02-4.98 (m, 1H), 4.92-4.88 (m, 1H); 13C NMR (CDCl3, 125
MHz) δ 138.7, 134.7, 129.0, 127.7, 127.6, 127.1, 125.6, 123.0, 122.8, 118.3, 114.0, 112.4, 79.3,
41.3.
5-bromo-3-(2-nitro-1-phenylethyl)-1H-indole75:88%,(Rf = 0.5, 12:88 EtOAc/Hex), 1H NMR
(CDCl3, 500 MHz) δ 8.17 (brs, 1H ), 7.53 (d, 1H, J = 1.3 Hz ), 7.32-7.22 (m, 6H ), 7.16 (d, 1H, J =
8.2 Hz ), 7.00 (d, 1H, J = 2.7 Hz), 5.09 (t, 1H, J = 7.5 Hz), 5.00-4.96 (m, 1H ), 4.91-4.86 (m, 1H); 13C
NMR (CDCl3, 125 MHz) δ 138.6, 135.0, 129.0, 127.8, 127.7, 127.6, 125.5, 122.7, 121.3, 113.8,
113.1, 112.8, 41.2.
1
5-methoxy-3-(2-nitro-1-phenylethyl)-1H-indole76: 86%,(Rf = 0.40, 20:80 EtOAc/Hex), H NMR
(CDCl3, 500MHz) δ 8.01 (brs,1H), 7.33-7.29 (m, 4H), 7.25-7.19 (m, 2H), 6.95 (s, 1H), 6.85-6.83
(m, 2H), 5.12 (t, 1H, J = 7.5 Hz), 5.04-5.00 (m, 1H), 4.93-4.89 (m, 1H), 3.76 (s, 3H); 13C NMR
(CDCl3, 125 MHz) δ 154.1, 139.1, 131.5, 128.9, 127.7, 127.5, 126.5, 122.2, 113.9, 112.6, 112.1,
100.7, 79.4, 55.8, 41.4.
3-(2-nitro-1-phenylethyl)-1H-indol-5-ol77:97%,(Rf = 0.50, 40:60 EtOAc/Hex), 1H NMR (CDCl3, 500
MHz) δ 8.10 (brs, 1H), 7.22-7.14 (m, 5H), 7.04 (d, 1H, J = 8.2 Hz), 6.83 (d, 1H, J = 2.05 Hz), 6.79
(d, 1H, J = 2.05 Hz), 6.70 (dd, 1H, J = 2.75 Hz & 6.1 Hz), 5.87 (s, 1H), 4.96 (t, 1H, J = 8.2 Hz), 4.88-
4.84 (m, 1H), 4.79-4.75 (m, 1H); 13C NMR (CDCl3, 125 MHz) δ 149.4, 139.0, 131.5, 128.7, 127.6,
127.4, 126.6, 122.6, 113.3, 112.4, 112.1, 103.3, 79.2, 41.4.
6-fluoro-3-(2-nitro-1-phenylethyl)-1H-indole60:92%,(Rf = 0.40, 20:80 EtOAc/Hex), 1H NMR
(CDCl3, 500 MHz) δ 8.15 (brs,1H), 7.29-7.19 (m, 6H), 6.94-6.92 (m, 2H), 6.79-6.75 (m, 1H), 5.10
(t, 1H, J = 8.2 Hz), 4.99-4.95 (m, 1H), 4.88-4.84 (m,1H); 13C NMR (CDCl3, 125 MHz)δ 160.9, 159.0,
138.9, 136.4, 136.3, 128.9, 128.7, 127.6, 127.6, 127.4, 122.6, 121.7, 119.6, 119.5, 114.1, 108.6,
108.4, 97.7, 97.5, 79.4, 41.3.
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1
3-(1-(4-methoxyphenyl)-2-nitroethyl)-1H-indole75: 81%,(Rf = 0.40, 25:75 EtOAc/Hex), H NMR
(CDCl3, 500 MHz) δ 8.12 (brs,1H), 7.43 (d, 1H, J = 7.5 Hz), 7.35 (d, 1H, J = 8.2 Hz), 7.25-7.17 (m,
3H), 7.08-7.01 (m, 2H), 6.84 (d, 2H, J = 8.9 Hz), 5.13 (t, 1H, J = 7.5 Hz), 5.06-5.02 (m, 1H), 4.91-
4.87 (m, 1H); 13C NMR (CDCl3, 125 MHz) δ 158.8, 136.5, 131.1, 128.8, 126.0, 122.6, 121.4, 119.9,
118.9, 114.7, 114.2, 111.3, 79.7, 55.2, 40.8.
1
3-(1-(4-chlorophenyl)-2-nitroethyl)-1H-indole75: 86%,(Rf = 0.5, 20:80 EtOAc/Hex), H NMR
(CDCl3, 500 MHz) δ 8.12 (brs, 1H), 7.38 (d, 1H, J = 8.2 Hz), 7.33 (d, 1H, J = 8.2 Hz), 7.27-7.18 (m,
5H), 7.07 (t, 1H, J = 7.5 Hz), 6.96 (s, 1H), 5.14 (t, 1H, J = 7.5 Hz), 5.04-5.00 (m, 1H), 4.89-4.85 (m,
1H) ); 13C NMR (CDCl3, 125 MHz) δ 137.6, 136.4, 133.3, 129.1, 129.0, 125.8, 122.8, 121.5, 120.0,
118.7, 113.8, 111.4, 79.2, 40.0.
3-(1-(4-chlorophenyl)-2-nitroethyl)-5-methoxy-1H-indole67: 89%,(Rf = 0.40, 25:75 EtOAc/Hex),
1H NMR (CDCl3, 500 MHz) δ 8.13 (brs, 1H), 7.27-7.19 (m, 6H), 6.93 (d, 1H, J = 2.0 Hz), 6.84 (dd,
1H, J = 2.7 Hz & 6.2 Hz), 6.78 (d, 1H, J = 2.0 Hz), 5.08 (t, 1H, J = 8.2 Hz), 5.01-4.97 (m, 1H), 4.87-
4.83 (m, 1H), 3.76 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 154.1, 137.6, 133.3, 131.5, 129.1, 129.0,
126.3, 122.2, 113.3, 112.7, 112.2, 100.6, 79.1, 55.8, 40.8.
5-methoxy-3-(1-(4-methoxyphenyl)-2-nitroethyl)-1H-indole78: 81%,(Rf
=
0.40, 40:60
EtOAc/Hex),s1H NMR (CDCl3, 500 MHz) δ 7.99 (brs, 1H), 7.25-7.23 (m, 4H), 6.99 (d, 1H, J = 2.7
Hz), 6.85-6.82 (m, 4H), 5.08 (t, 1H, J = 15.8 Hz), 5.04-5.00 (m, 1H), 4.90-4.86 (m, 1H), 3.77 (s,
6H); 13C NMR (CDCl3, 125 MHz) δ 158.8, 154.1, 131.5, 131.1, 128.8, 126.5, 122.1, 114.4, 114.2,
112.7, 112.0, 100.8, 79.7, 55.8, 55.2, 40.8..
1H,1''H-[3,3':3',3''-terindol]-2'(1'H)-one79:91%,(Rf = 0.40, 40:60 EtOAc/Hex), 1H NMR (DMSO-d6,
500 MHz) δ 10.96 (s, 2H), 10.61 (s, 1H), 7.35(d , 2H, J = 8.2 Hz), 7.24-7.21 (m, 4H), 7.03-6.98 (m,
3H), 6.92 (t, 1H, J = 7.5 Hz), 6.86 (d, 2H, J = 2.7 Hz), 6.80 (t, 2H, J = 7.5 Hz); 13C NMR (DMSO-d6,
125 MHz) δ 178.7, 141.3, 136.9, 134.6, 127.8, 125.7, 124.9, 124.3, 121.4, 120.9, 120.8, 118.2,
114.3, 111.6, 109.6, 52.6.
5,5''-dichloro-1H,1''H-[3,3':3',3''-terbenzo[b]pyrrol]-2'(1'H)-one80:93%,(Rf
=
0.40, 30:70
EtOAc/Hex), 1H NMR (DMSO-d6, 500 MHz) δ 11.22 (s, 2H), 10.74 (s, 1H), 7.39 (d, 2H, J = 8.9 Hz),
7.26 (dt, 1H, J = 1.3 Hz & 6.2 Hz), 7.19-7.17 (m, 3H), 7.05-6.9 (m, 4H), 6.93 (d, 2H, J = 2.7 Hz); 13C
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NMR (DMSO-d6, 125 MHz) δ 178.4, 141.2, 135.4, 128.3, 126.6, 126.1, 124.9, 122.9, 121.8,
121.1, 119.6, 113.9, 113.4, 109.8, 52.1.
5,5''-dibromo-1H,1''H-[3,3':3',3''-terbenzo[b]pyrrol]-2'(1'H)-one81:90%,(Rf
=
0.50, 30:70
EtOAc/Hex), 1H NMR (DMSO-d6, 500 MHz) δ 11.22 (s, 2H), 10.74 (s, 1H), 7.36-7.34 (m, 4H), 7.27
(t, 1H, J = 7.5 Hz), 7.17-7.14 (m, 3H), 7.02-6.97 (m, 2H), 6.90 (d, 2H, J = 2.7 Hz); 13C NMR (DMSO-
d6, 125 MHz) δ 178.4, 141.2, 135.7, 133.6, 128.3, 127.2, 126.0, 124.9, 123.6, 122.6, 121.8,
113.8, 113.8, 111.0, 109.8, 52.1, 40.0.
5,5''-dihydroxy-1H,1''H-[3,3':3',3''-terbenzo[b]pyrrol]-2'(1'H)-one:95%,(Rf
=
0.50, 75:25
1
EtOAc/Hex), H NMR (DMSO-d6, 500 MHz) δ 10.62 (s, 2H), 10.50 (s, 1H), 8.47 (s, 2H), 7.22-7.17
(m, 2H), 7.12 (d, 2H, J = 8.9 Hz), 6.96-6.90 (m, 2H), 6.69 (d, 2H, J = 2.7 Hz), 6.63 (d, 2H, J = 2.0
Hz), 6.53 (dd, 2H, J = 11 Hz & 6.8 Hz); 13C NMR (DMSO-d6, 125 MHz) δ 178.8, 149.7, 141.3,
134.7, 131.5, 127.6, 126.5, 124.7, 121.2, 113.2, 111.7, 111.3, 109.5, 105.1, 52.5.
5,5''-dinitro-1H,1''H-[3,3':3',3''-terbenzo[b]pyrrol]-2'(1'H)-one79: 89%,(Rf
=
0.40, 50:50
1
EtOAc/Hex), H NMR (DMSO-d6, 500 MHz) δ11.82 (s, 2H), 10.98 (s, 1H), 8.23 (d, 2H, J = 2.0 Hz),
7.95 (dd, 2H, J = 2.7 Hz & 6.8 Hz), 7.57 (d, 2H, J = 8.9 Hz), 7.31 (t, 1H, J = 7.5 Hz), 7.24-7.21 (m,
3H), 7.07 (d, 1H, J = 7.5 Hz), 7.01 (t, 1H, J = 7.5 Hz); 13C NMR (DMSO-d6, 125 MHz) δ 178.0,
141.2, 140.2, 132.9, 128.7, 128.3, 124.9, 124.6, 122.2, 117.5, 116.7, 112.5, 110.2, 52.1.
6,6''-difluoro-1H,1''H-[3,3':3',3''-terbenzo[b]pyrrol]-2'(1'H)-one:90%,(Rf
=
0.40,
40:60
1
EtOAc/Hex), H NMR (DMSO-d6, 500 MHz) δ11.05 (s, 2H), 10.65 (s,1H), 7.21-6.69 (m, 12H); 13C
NMR (DMSO-d6, 125 MHz)δ 174.5, 159.6, 157.7, 141.3, 136.8, 136.8, 134.1, 128.0, 124.8, 122.5,
121.7, 121.6, 114.4, 109.7, 107.0, 106.8, 97.6, 97.4, 52.3.
5'-bromo-1H,1''H-[3,3':3',3''-terbenzo[b]pyrrol]-2'(1'H)-one82: 87%,(Rf
=
0.40, 40:60
EtOAc/Hex), 1H NMR (DMSO-d6, 500 MHz) δ 11.04 (s, 2H), 10.64 (s, 1H), 7.25-7.16 (m, 4H), 7.12
(d, 2H, J = 2.0 Hz), 6.96 (dd, 2H, J = 7.5 Hz & 9.6 Hz ), 6.84 (d, 2H, J = 2.0 Hz), 6.70-6.66 (m, 2H);
13C NMR (DMSO-d6, 125 MHz) δ 178.5, 159.5, 157.7, 141.2, 136.8, 136.7, 134.1, 128.0, 124.8,
122.4, 121.7, 121.6, 114.4, 109.7, 107.0, 106.8, 97.5, 97.3, 52.3.
1
3-hydroxy-3-(1H-indol-3-yl)indolin-2-one83: 80%,(Rf = 0.40, 50:50 EtOAc/Hex), H NMR (DMSO-
d6, 500 MHz) δ 10.98 (s, 1H), 10.34 (s, 1H), 7.33 (t, 2H, J = 8.2 Hz), 7.26-7.22 (m, 2H), 7.06 (d, 1H,
J = 2.7 Hz), 7.02 (dt, 1H, J = 1.4 Hz & 6.8 Hz), 6.94 (t, 1H, J = 6.9 Hz), 6.90-6.84 (m, 2H), 6.35 (s,
Page 28 of 35
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10.1002/cctc.201800369
ChemCatChem
1H); 13C NMR (DMSO-d6, 125 MHz) δ 179.0, 142.2, 137.3, 133.9, 129.6, 125.4, 125.3, 124.0,
122.2, 121.5, 120.8, 119.0, 115.9, 112.0, 110.1, 75.4.
3-(5-methoxy-1H-indol-3-yl)indolin-3-ol83, 84: 82%,(Rf = 0.40, 30:70 EtOAc/Hex), 1H NMR
(DMSO-d6, 500 MHz) δ 10.91 (s, 1H), 10.52 (s, 1H), 7.34-7.30 (m, 2H), 7.23 (d, 1H, J = 8.9 Hz),
7.11 (d, 1H, J = 2.0 Hz), 7.03 (t, 1H, J = 6.9 Hz), 6.92 (d, 1H, J = 7.6 Hz), 6.82 (d, 1H, J = 2.7 Hz),
6.72 (dd, 1H, J = 2.0 Hz & 6.2 Hz), 3.67 (s, 3H); 13C NMR (DMSO-d6, 125 MHz) δ 176.1, 152.8,
142.2, 132.0, 129.7, 129.0, 125.6, 125.2, 124.8, 121.9, 112.5, 112.1, 111.5, 110.0, 103.1, 80.7.
55.1.
5-bromo-3-hydroxy-3-(1H-indol-3-yl)indolin-2-one83:78%,(Rf = 0.50, 50:50 EtOAc/Hex), 1H NMR
(DMSO-d6, 500 MHz) δ 11.05 (s, 1H), 10.5 (s, 1H), 7.44-7.42 (m, 1H), 7.34 (d, 2H, J = 8.9 Hz), 7.30
(d, 1H, J = 2.1 Hz), 7.10 (d, 1H, J = 2.0 Hz), 7.04 (t, 1H, J = 8.2 Hz), 6.90-6.86 (m, 2H), 6.53 (s, 1H);
13C NMR (DMSO-d6, 125 MHz)δ 177.9, 136.8, 135.9, 131.7, 127.3, 124.7, 123.6, 121.2, 120.0,
118.7, 114.6, 113.3, 111.8, 111.6, 74.9.
3-(2-nitroethyl)-1H-indole85:81%,(Rf = 0.50, 20:80 EtOAc/Hex),1H NMR (CDCl3, 500 MHz) δ 8.04
(brs, 1H), 7.56 (d, 1H, J = 7.6 Hz), 7.35 (d, 1H, J = 8.2 Hz), 7.21 (t, 1H, J = 7.6 Hz), 7.15 (t, 1H, J =
8.2 Hz), 7.01 (d, 1H, J = 2.7 Hz), 4.64 (t, 2H, J = 6.8 Hz), 3.47 (t, 2H, J = 6.8 Hz; 13C NMR (CDCl3,
125 MHz)δ 136.1, 126.5, 122.5, 122.4, 119.8, 118.0, 111.4, 109.8, 75.6, 23.5.
2-(1H-indol-3-yl)ethanamine86:81%,(Rf = 0.50, 10:90DCM/MeOH),1H NMR (CDCl3, 500 MHz) δ
8.31 (brs, 1H), 7.61 (d, 1H, J = 8.2 Hz), 7.35 (d, 1H, J = 8.2 Hz), 7.19 (t, 1H, J = 8.2 Hz), 7.11 (t, 1H,
J = 8.2 Hz), 7.01 (d, 1H, J = 2.0 Hz), 3.04 (t, 2H, J = 6.8 Hz), 2.91 (t, 2H, J = 6.8 Hz), 1.25(brs, 2H);
13C NMR (CDCl3, 125 MHz)δ 136.4, 127.4, 122.5, 121.9, 119.2, 118.8, 113.6, 111.1, 42.3, 29.5.
1-phenyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole87, 88:72%,(Rf = 0.50, 70:30EtOAc/Hex),1H
NMR (DMSO-d6, 500 MHz) δ 10.42 (s, 1H), 7.40 (d, 1H, J = 7.5 Hz), 7.34-7.27 (m, 5H), 7.21 (d,
1H, J = 8.2 Hz), 7.01-6.92 (m, 2H), 5.07 (s, 1H), 3.07-3.02 (m, 1H), 2.95- 2.90 (m, 1H), 2.83( brs,
1H), 2.75- 2.70 (m, 1H),2.68- 2.63 (m, 1H); 13C NMR (DMSO-d6, 125 MHz)δ 143.2, 135.9, 135.4,
128.5, 128.1, 127.2, 126.8, 120.5, 118.2, 117.5, 111.0, 108.2, 56.6, 41.2, 22.2.
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