Electronic effect of substituents on anilines favors 1,4-addition to: Trans -β-nitrostyrenes: Access to N -substituted 3-arylindoles and 3-arylindoles

Article abstract of DOI:10.1039/c8ob00736e

A simple and an efficient method for the regioselective synthesis of N-alkyl/aryl/H 3-arylindole derivatives from N-substituted anilines and trans-β-nitrostyrenes has been described using 10 mol% of bismuth(iii) triflate as a catalyst in acetonitrile at 80 °C. The present protocol profits from the formation of new C-C and C-N bonds, broad substrate scope and moderate to good yields.

Full text of DOI:10.1039/c8ob00736e

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Electronic Effect of Substituents on Anilines Favors 1,4-Addition to
trans-β-nitrostyrenes: Access to N-Substituted 3-Arylindoles and
3-Arylindoles
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Radhakrishna Gattu,a Suchandra Bhattacharjee,a Karuna Mahatoa and Abu T. Khan*a
www.rsc.org/
A simple and an efficient method for the regioselective synthesis of N-alkyl/aryl/H 3-arylindole derivatives from N-
substituted anilines and trans-β-nitrostyrenes has been described using 10 mol % of bismuth(III) triflate as a catalyst in
acetonitrile at 80 °C. The present protocol profits from the formation of new C-C and C-N bonds, broad substrate scope
and
moderate
to
good
yields.
arylindoles is highly desirable. In literature, few reported methods
are available to construct the 3-arylindoles. Some of the important
procedures includes direct metal catalysed C3-arylation7 of indoles
and intramolecular cyclisation reactions such as aza-Wacker-type
cyclization of 2-alkenylanilines,8a-d Ullmann coupling of 2-
bromoarylaminoalkanes,8e palladium catalysed cylisation of
enaminoesters,8f heteroannulation of α-aminoacetophenones,9a,b
amination of an aromatic C–H-bond.9c The intermolecular
Introduction
Indole scaffolds are widely distributed in nature as alkaloids,1a,b
terpenoids1c,d and they exhibit a broad range of biological activities.
Moreover, indoles and their derivatives found to have widespread
applications in pharmaceuticals,2 agrochemicals,3 functionalized
materials,4 dye5 and as a flavour enhancer. In addition, many non-
natural indole derivatives particularly 3-arylindole derivatives show
interesting biological activity6 and some of them are depicted in
Figure 1.
cyclisation
involves
the
reaction
of
nitrosoarenes,10
arylhydroxylamines11 and nitroarenes12 with alkynes as well as 2-
iodoanilines13 with triethyl(phenylethynyl)silane. Since, there is a
competition for the formation of 2-arylindole and 3-arylindole
regioisomers and hence it is a highly challenging task for chemists
to synthesis exclusively 3-arylindoles. Recently, the synthesis of 3-
arylindoles have been reported through intermolecular C-C and C-N
bond formation from the reactions of N-substituted arylamines14
and cinnamic acids/alkenes which are shown in Scheme 1.
CN
OH
R1
R2
N
H
N
MeO2S
N
N
N
NMe2
N
R1 = F, R2 = H
R1 =H, R2 = F
Previous reports:
H
10 mol% Pd(OAc)2
SO2Ph
Ar
Scheme: 1a (Ref 14a)
20 mol%
1,10-phenanthroline
Benedalin
(Antidepressant)
Estrogen receptor
ligand
Progesterone receptor
antagonist
Inhibitor of brassinin
glucosyltransferase
COOH
N
+
CF3
H
Cu(OAc)2.H2O (1 equiv.)
K2CO3 (3 equiv)
CN
Me
O
Ar
NC
N
Ar
Ar
30-89%
O
N
Ar
H2O, MeOH, 100 °C, 21 h
X
(1 equiv)
(4 equiv)
X
OMe
O
5 mol% Pd(OAc)2
10 mol% 4,7-disubstituted-
1,10-phenanthroline
Scheme: 1c
(Ref 14b)
Ar
N
H
N
H
N
H
X = NH2, NO2
3-Aryl(heteroaryl)indoles)
(Antibacterial activity)
Murrapanine
(anticancer)
3-Indolyl pyridine derivatives
(Analgesic and Anti-inflammatory)
Ar
+
2 equiv. Cu(OAc)2.H2O
N
H
N
Ts
56-85%
(1 equiv.) 1,4-benzoquinone
toluene (0.1 M)
Ts
(1 equiv)
(2 equiv)
120 °C, 24 h, air
Figure 1. Some of the biologically active 3-arylindoles
Present work: 1c
Ar
NO2
Since the biological importance of 3-arylindoles has been well
established, a concise and flexible method for the synthesis of 3-
Bi(OTf)3 (10 mol%)
H
N
+
CH3CN / 80 °C
1.5 - 36.0 h
N
Ar
(1 equiv)
R
R
(1 equiv)
58-90%
R = alkyl, aryl, H
Scheme 1. The synthetic strategies for 3-arylindoles from N-
substituted anilines and alkenes
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Despite of having great advantages, these reported methods have found that most of the these solvents gave either poor or no yield
some shortcomings such as the need of costly catalysts, use of of the expected product (Table 1, entries 12-18). The best solvent
ligands and additives, limited substrate scope, restricted reaction was found to be acetonitrile. Thus it was concluded that 10 mol %
conditions and failure of the reactions with simple anilines/N- of Bi(OTf)3 in acetonitrile at 80 °C provided the best optimized
alkylanilines. Zhang and co-workers have reported the metal free reaction condition to obtain 3-arylindole derivatives from N-
synthesis of 3-arylbenzoindoles from trans-β-nitrostyrenes and methylaniline and (E)-1-methoxy-4-(2-nitrovinyl)benzene.
naphthylamines. However, they also failed to obtain 3-arylindoles
from anilines.15a Consequently, there is a large scope to develop a
Table 1. Optimization of Reaction Conditionsa,b,c,d
new methodology for the regioselective synthesis of N-alkylated 3-
arylindoles15b and 3-arylindoles with high reactivity of N-
alkylanilines and aniline derivatives respectively.
The importance and usefulness of trans-β-nitrostyrenes16a-d is well
reviewed for the construction of five and six membered
heterocycles.16e,f Thus, we envisaged that this prized moiety can be
further explored for the synthesis of 3-arylindoles. Bismuth(III)
triflate is found to be a non-toxic, and easy handling reagent.17 This
is also proven as a versatile and efficient Lewis-acid catalyst for
Entry
1
Catalyst
Bi(OTf)3
No catalyst
Bi(OTf)3
Bi(OTf)3
Yb(OTf)3
Sc(OTf)3
AgOTf
Mol%
05
-
Solvent Time
Yield 3(%)b
52
various organic transformations.18 Thus the remarkable properties
of bismuth(III) triflate led us to believe that it can be used to
facilitate as a catalyst for synthesis of indole derivatives. Herein, we
report Bi(OTf)3 catalysed highly regioselective synthesis of 3-
arylindole from readily available substituted arylamines and trans-
β-nitrostyrenes (Scheme 1c).
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CNc
DMSO
DMF
20 h
24 h
16 h
16 h
18 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
2
NR
3
10
15
10
10
10
10
10
10
10
10
10
10
10
10
10
10
74
4
74
5
68
Results and discussion
6
46
N-methylaniline 1a (1.0 mmol) and (E)-1-methoxy-4-(2-
nitrovinyl)benzene 2a (1.0 mmol) were selected as the model
substrates to find out the optimum reaction conditions from a
series of reactions. Initially, the ideal reaction was examined using 5
mol% of Bi(OTf)3 as a catalyst in CH3CN solvent 80 °C and the results
are summarized in (Table 1, entry 1). After chromatographic
purification, yellow semi-solid product 3a was isolated in 52% yield.
No strong absorption peaks appeared at 1350 cm-1 and 1550 cm-1
corresponding to the NO2 group in the IR spectrum, which clearly
indicating that -NO2 group is eliminated during the reaction. In 1H
NMR spectrum, 3a showed two singlet peaks at δ 3.86 and 3.89
ppm due to the presence of N-Me and -OMe groups. In addition,
compound 3a was also confirmed by HRMS.
7
Trace
Trace
NR
8
Cu(OTf)2
Cu(OAc)2
FeCl3
9
10
11
12
13
14
15
16
17
18
NR
Bi(OTf)3
Bi(OTf)3
Bi(OTf)3
Bi(OTf)3
Bi(OTf)3
Bi(OTf)3
Bi(OTf)3
Bi(OTf)3
NR
NR
NR
DCEd
62
DCMd
Toluene
H2O
25
48
To determine the optimal conditions, same set of reaction was
scrutinized in absence of catalyst, the result was futile (Table 1,
entry 2). It was observed that, the reaction proceeded much faster
and offered better yield, when the Bi(OTf)3 catalyst load was
increased from 5 mol% to 10 mol% (Table 1, entry 3). Furthermore,
on increasing the catalyst load to 15 mol% no significant change
was observed in reaction time and yield (Table 1, entry 4). In order
to ascertain the efficacy of various metal triflates, as a catalyst for
the synthesis of 3-arylindole derivatives, the identical set of
reaction was performed with 10 mol% of Yb(OTf)3, Sc(OTf)3, AgOTf
and Cu(OTf)2. It was found that, while Yb(OTf)3 and Sc(OTf)3
provided lower yields, and other metal triflates were unproductive
(Table 1, entries 5-8). In addition to the metal triflates, the same
reaction was also explored with Cu(OAc)2 and FeCl3, but
unfortunately, these catalysts for this particular reaction were
found to be ineffective (Table 1, entries 9-10). The reaction was
unsuccessful when it was performed at room temperature (Table 1,
entry 11). Next, various polar solvents were also screened for the
similar reaction in the presence of 10 mol % of Bi(OTf)3, it was
56
THFd
28
aAll the reactions were performed using N-methylaniline 1a (1.0 mmol), (E)-
1-methoxy-4-(2-nitrovinyl)benzene 2a (1.0 mmol) at 80 °C. bIsolated yield.
cReaction performed at room temperature. dReaction performed at 50 °C.
NR (No desired product).
With the optimized conditions in hand, the scope of the protocol
was investigated for the reaction of N-methylaniline 1a with a series
of various substituted trans-β-nitrostyrenes 2a-j, as represented in
Table 2. The reaction was feasible for various trans-β-nitrostyrenes
with electron-donating groups like 4-Me, 4-OH, 2,4-OMe, 3,4,5-
OMe and as well as electron-withdrawing group such as 4-F, 4-Cl
giving the products 3a-h in moderate to good yields. The best yield
(85%) was obtained in the case of (E)-2-(2-nitrovinyl)naphthalene
3i. In addition, it was found that, the (E)-2-(2-nitrovinyl)thiophene
worked well under the same protocol, whereas (E)-2-(2-
nitrovinyl)furan fail to obtain the desired product.
2 | J. Name., 2012, 00, 1-3
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Table 2: Reaction of N-methylaniline with various trans-β- aryl ring to involve in micheal addition to form 3-arylindole product
nitrostyrenesa,b
as compared to p-anisidine group which was reflected in the sharp
decrease of yield from 86 % to 58 % in the case of 4a and 4f. To our
delight the reaction underwent smoothly with N-methyl-2-
aminofluorene affording the product 4g in 62% yield. The reason for
the better yield in case of 4b may be due to +M (mesomeric) effect
of the 3-OMe group and +I (Inductive) effect of N-methyl group
which increase the nucleophilicity in a synergistic manner at the C6
position of 3-methoxy-N-methylaniline to enhance 1,4-addition.
The reaction with electron withdrawing groups such as 4-F, 4-Cl,
and 4-Br substituted N-methylanilines (1i-k) failed which might be
due to less electron density on the aromatic ring and hence
reluctance to form C-C bond through 1,4-addition with trans-β-
nitrostyrene.
Next, the present procedure was further extended for the synthesis
of 1-substituted-3-phenyl-1H-indole derivatives using various N-
substituted anilines and trans-β-nitrostyrenes with the optimized
reaction condition to offer the corresponding products 5a-h with
62-78% yields, as depicted in Table 4. The electron withdrawing
groups such N-tosyl and N-benzoyl anilines on reaction with trans-
β-nitrostyrene fail to obtain desired product due to less electron
density at ortho position of aniline to form 1,4 addition with trans-
β-nitrostyrene.
aThe reactions were carried out using N-methylaniline 1a (1 mmol), trans-β-
nitrostyrenes 2a-j (1 mmol), CH3CN (2 mL) and Bi(OTf)3 (10 mol %) 80 °C.
bIsolated yield.
Table 4: Reaction of various N-substituted anilines with trans-β-
nitrostyrenea,b
The strong electron-withdrawing groups such as 4-Br, 4-NO2 groups
on phenyl ring of trans-β-nitrostyrene failed to give corresponding
3-arylindoles. The (E)-(2-nitroprop-1-en-1-yl)benzene failed to give
1,2-dimethyl-3-phenyl-1H-indole which may be due to steric
crowding between methyl groups of N-methylaniline and (E)-(2-
nitroprop-1-en-1-yl)benzene.
Table 3: Substrate scope of various N-methylaniline with (E)-(2-
nitrovinyl)benzenea,b
aThe reactions were carried out using N-substituted anilines 1l-s (1 mmol),
trans-β-nitrostyrenes 2b and 2c (1 mmol), CH3CN (1 mL) and Bi(OTf)3 (10 mol
%) at 80 °C. bIsolated yield.
aThe reactions were carried out using N-arylamines1b-h (1 mmol), (E)-(2-
nitrovinyl)benzene 2b (1 mmol), CH3CN (1 mL) and Bi(OTf)3 (10 mol %) at 80
°C. bIsolated yield.
Under the similar reaction conditions, a variety of anilines were
converted to the corresponding 3-phenyl-1H-indoles 6a-g with 68-
90 % yield. The anilines having electron-donating groups such as 3-
OMe, 2,4-Me, 3,5-OMe and 3,4-(Methylenedioxy) were well
tolerated. 3-Fluoroaniline on reaction with trans-β-nitrostyrene
gave the product 6e. Similarly, the reaction worked well with 1-
naphthylamine and 2-naphthylamines, the successful results are
illustrated in Table 5.
To study the generality of the present protocol, the reactions were
performed with various substituted N-methylaniline 1b-h with (E)-
(2-nitrovinyl)benzene 2b as shown in Table 3. It was found that N-
methylanilines having the electron-donating groups 3-OMe, 3-Me,
3,5-di-Me, 4-OMe and electron-withdrawing groups like 3-F, 3-Cl
worked well giving the products 4a-f in 58-86% yield. The m-
anisidine imparts high electron density on the π-electrons of the
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Table 5: Reaction of various arylamines with trans-β-nitrostyrenea,b
present on the phenyl ring of trans-β-nitrostyrene. Whereas, (E)-(2-
nitroprop-1-en-1-yl)benzene on reaction with m-anisidine gave 6-
methoxy-2-methyl-3-phenyl-1H-indole 7f as shown in Table 6. The
yield obtained in these reactions was quite good. We have not
observed the formation of other isomer product when the reaction
was performed with meta substituted anilines and trans-β-
nitrostyrenes.
Ph
NH2
NO2
10 mol% Bi(OTf)3
R
+
R
N
CH3CN, 80 °C
H
Ph
6a-g
2b
1aa-ag
Ph
OMe
Ph
Ph
Ph
Me
Finally, the scale up procedure was investigated using N-ethylaniline
1l (10 mmol) and (E)-1-methyl-4-(2-nitrovinyl)benzene 2c (10 mmol)
which resulted in the formation of the product 5i in 64% yield as
shown in Scheme 2.
O
O
N
N
H
N
MeO
6a,
N
H
MeO
H
H
Me
1.5h, 85%
6b,
4.5h, 74%
6c, 5h, 80%
6d,
2h, 68%
Ph
Scheme 2. Gram-Scale Synthesis
Ph
Ph
Me
N
H
N
H
F
N
H
NO2
10 mol% Bi(OTf)3
CH3CN, 80 °C
6e,
2h, 74%
6f,
6g,
4h, 82%
4h, 90%
+
N
Me
N
aThe reactions were carried out using various arylamines 1aa-ag (1 mmol),
(E)-(2-nitrovinyl)benzene 2b (1 mmol), CH3CN (2 mL) and Bi(OTf)3 (10 mol %)
at 80 °C. bIsolated yield.
Et
H
Et
, 64% (1.42 g)
1l (10 mmol)
2c (10 mmol)
5i
But, the reaction completely failed to offer the desired product with
4-F/4-Cl/4-Br aniline. Thus, it may be concluded that when the
electron-withdrawing groups were present at the para position of
aniline, the reaction is unsuccessful due to less electron density on
the π-electrons of the aryl ring to participate in 1,4-addition with
trans-β-nitrostyrene to form the corresponding 3-arylindole
derivative. The synthesized compound 6e is an inhibitor of brassinin
glucosyltransferase19 as shown in Figure 1.
All the synthesized compounds 3-7 were characterized by IR, 1H
NMR, 13C NMR spectra and HRMS. In addition, the structure of
compound 3h was confirmed through single X-ray crystallographic
data.
Table 6: Reaction of m-anisidine with various trans-β-nitrostyrenea,b
NO2
R2
R1
R1
NH2
10 mol% Bi(OTf)3
CH3CN, 80 °C
R2
+
N
MeO
MeO
H
2
1aa
7a-f
R1 = EDG, EWG
R
2 = H, Me
Me
OH
OMe
Figure 2. ORTEP Diagram of compound 3h with 40% ellipsoid
probability (CCDC no. 1576147)
In general, the aniline derivatives undergo aza-Michael addition20 to
trans-β-nitrostyrene to form (N-C bond) aza-Michael adduct. It was
observed that the presence of alkyl group on nitrogen atom of
aniline or electron donating group on arene ring of anilines favours
the 1,4 addition (C-C bond) rather than aza-michael addition.
OMe
N
N
N
MeO
MeO
7b, 2h, 76%
Cl
MeO
H
H
H
7a, 2h, 82%
7c, 2.5h, 72%
F
The proposed mechanism for the formation of N-methyl 3-
arylindoles from N-methylaniline 1a and (E)-1-methyl-4-(2-
nitrovinyl)benzene 2c in presence of Bi(OTf)3 catalyst in acetonitrile
at 80 °C as shown in the scheme 3. Initially, N-methylaniline
undergoes 1,4-addition at the C2 position as well as at the C4
position with (E)-1-methyl-4-(2-nitrovinyl)benzene to furnish 1,4-
adduct B and F through pathway A and pathway B respectively. The
1,4-adduct B subsequently undergoes concomitant cyclisation to
form C, followed by aromatization, to afford the desired product 3c.
Whereas, through pathway B intermediate F does not involve in
cyclisation was isolated in 12% yield.
Me
N
H
MeO
N
H
N
H
MeO
MeO
7f, 3h, 74%
7d, 2.5h, 68%
7e, 2h, 70%
aThe reactions were carried out using m-anisidine 1aa (1 mmol), various
trans-β-nitrostyrenes 2 (1 mmol), CH3CN (2 mL), Bi(OTf)3 (10 mol %), 80 °C.
bIsolated yield.
Further, the reaction condition was fruitfully applied for the
reaction of m-anisidine 1aa with various trans-β-nitrostyrenes 2
having electron-donating as well as electron-withdrawing group
4 | J. Name., 2012, 00, 1-3
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Me
Me
Me
+
Bi(OTf)3
Pathway A
1,4- addition at
C2 position
O
O
N
H
C2
N
+ OH
O
H
H
NH
Me
N
Bi(OTf)3
+
O
N
N
O
Me
B
Me
1a
2c
A
1,4-adduct
at C2 position
(Not Isolated)
Me
Me
Me
H
N
H
O
N
OH
OH
N
OH
[O]
N
N
-HNO
-H2O
H
Me
Me
Me
3c
D
C
Bi(OTf)3
O
O N
O
Me
O
O N
+
Pathway B
C4- Michael
addition
N
C3
[1,3 H] Shift
O
Me
C2
2c
+
Me
C4
H
Bi(OTf)3
C-C bond
H
E
N
F
C1
H
N
H
Me
C4-Michael adduct
(Isolated Intermediate)
N
Me
1a
Me
Scheme 3: Proposed mechanism for the synthesis of 3-arylindole derivatives.
Conclusions
Experimental
In summary, the +I (Inductive) and +M (Mesomeric) effect of an
alkyl and alkoxy groups which are present on aromatic ring of
aniline or nitrogen atom of aniline increases the nucleophilicity at
the ortho position of aniline which ultimately prefers 1,4-addition to
l. General Information and Methods.
Melting points were determined on a melting point apparatus and
are uncorrected. 1H and 13C NMR spectra were recorded on 400,
600, 75, 100 and 150 MHz NMR spectrometer. TMS as internal
reference; chemical shifts (δ scale) are reported in parts per million
(ppm). 1H NMR Spectra are reported in the order: multiplicity,
trans-β-nitrostyrenes
instead
of
aza-Michael
addition.
Consequently, 3-arylindoles/N-substituted 3-arylindoles can be
accomplished easily in good yield with a wide substrates scope
using inexpensive Bi(OTf)3 as a catalyst. Our protocol is also coupling constant (J value) in hertz (Hz) and no. of protons; signals
applicable for the synthesis of biologically active compound 6e
which acts as an inhibitor of Brassinin glucosyltransferase. To the
best of our knowledge, this is the first report of Bi(OTf)3 catalyzed
synthesis of 3-arylindole derivatives from arylamines and trans-β-
nitrostyrenes.
were characterized as
s (singlet), d (doublet), t (triplet), m
(multiplet) and bs (broad). IR spectra were recorded on IR
spectrophotometer. HRMS spectra were recorded using mass
analyser type TOF. The X-ray crystal structure was determined using
a single XRD diffractometer.
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1.0 Hz, 1H), 7.20 (m, 1H), 7.18 (s, 1H), 6.96 – 6.92 (m, 2H), 3.86 (s,
3H); 13C NMR (150 MHz, CDCl3): δ 154.0, 137.5, 128.9, 128.6, 126.4,
126.1, 122.1, 120.0, 119.8, 116.6, 115.9, 109.7, 33.0; IR
(KBr)νmax3491, 2923, 2853, 1550, 1468, 1375, 1187, 1017, 924 cm-1;
HRMS (ESI) Calcd For C15H14NO 224.1070 (M + H+); Found 224.1078.
3-(2,4-dimethoxyphenyl)-1-methyl-1H-indole (3e): Yield 71% (189
mg), light yellow semi-solid, 1H NMR (600 MHz, CDCl3): δ 7.73 (d, J =
8.0 Hz, 1H), 7.50 (d, J = 8.2 Hz, 1H), 7.34 (d, J = 8.2 Hz, 1H), 7.29 (s,
1H), 7.26 – 7.22 (m, 1H), 7.15 – 7.11 (m, 1H), 6.61 (t, J = 2.6 Hz, 1H),
6.61 – 6.58 (m, 1H), 3.87 (s, 3H), 3.84 (s, 3H), 3.84 (s, 3H); 13C NMR
(75 MHz, CDCl3): δ 159.4, 157.8, 137.0, 131.0, 128.4, 127.4, 121.7,
120.7, 119.5, 117.3, 111.7, 109.5, 104.5, 99.3, 55.7, 33.0; IR
(KBr)νmax 3049, 2936, 2843, 1669, 1604, 1475, 1183, 1008, 928 cm-1;
II. General Procedure for Synthesis of N-alkyl/aryl 3-arylindoles 3,
4 and 5.
Into a dry 10 mL round bottomed flask a mixture N-alkyl aniline 1a
(1.0 mmol), trans-β-nitrostyrene 2 (1.0 mmol) was taken in 2 mL
acetonitrile followed by the addition of bismuth(III) triflate (0.065 g,
0.10 mmol) and the reaction mixture was stirred at 80 °C in an oil
bath. The progress of the reaction was monitored by TLC. After
completion of the reaction the solvent was removed on a rotatory
evaporator and treated with aqueous layer to dissolve the salts, the
organic compound was extracted with ethyl acetate (2 x 25 mL).
The organic extract was dried over sodium sulfate and concentrated
under reduced pressure. Finally, the crude residue was purified
through silica gel (60-120 mesh) column chromatography with
petroleum ether/ethyl acetate (9.8 : 0.2, v/v) to obtain the pure
product 3, 4 and 5.
HRMS (ESI) Calcd For C17H18NO2 268.1332 (M
268.1332.
+
H+); Found
1-methyl-3-(3,4,5-trimethoxyphenyl)-1H-indole (3f)21c: Yield 64%
(190 mg), colourless semi-solid, 1H NMR (400 MHz, CDCl3): δ 7.92
(d, J = 8.1 Hz, 1H), 7.38 (d, J = 8.5 Hz, 1H), 7.30 (t, J = 7.6 Hz, 1H),
7.22 (s, 1H), 7.20 (s, 1H), 6.86 (s, 2H), 3.94 (s, 6H), 3.91 (s, 3H), 3.86
(s, 3H); 13C NMR (150 MHz, CDCl3): δ 153.7, 137.6, 136.6, 131.6,
126.6, 126.3, 122.3, 120.2, 119.9, 117.1, 109.8, 104.8, 61.2, 56.4,
33.1; IR (KBr)νmax 3050, 2934, 2843, 1672, 1567, 1463, 1125, 1055,
925 cm-1; HRMS (ESI) Calcd For C18H20NO3 298.1438 (M + H+); Found
298.1438.
III. General Procedure for Synthesis of 3-Arylindoles 6 and 7.
To a mixture aryl amine 1aa (1.0 mmol), trans-β-nitrostyrene 2 (1.0
mmol), and Bismuth(III) triflate (0.065 g, 0.10 mmol)
2 mL
acetonitrile was added and allowed to stir at 80 °C. The completion
of the reaction was monitored by TLC. The solvent was removed
under reduced pressure, the residue was treated with aqueous
layer to dissolve the salts and compound was extracted with ethyl
acetate (2 x 25 mL). The organic layer was dried over sodium sulfate
and concentrated under reduced pressure. Finally, the crude
reaction mixture was purified through silica gel (60-120 mesh)
column chromatography with petroleum ether/ethyl acetate (9.5 :
0.5, v/v) to obtain the pure products 6 and 7.
3-(4-fluorophenyl)-1-methyl-1H-indole (3g)21b: Yield 65% (146 mg),
white solid, mp 72-73˚C, 1H NMR (400 MHz, CDCl3): δ 7.78 (d, J =
8.0 Hz, 1H), 7.49 (dd, J = 8.3, 5.5 Hz, 2H), 7.26 (d, J = 8.2 Hz, 1H),
7.19 (t, J = 7.5 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 7.06 (s, 1H), 7.03 (t, J
= 8.6 Hz, 2H), 3.71 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 163.1, 159.8,
137.5, 131.8, 131.8, 128.9, 128.8, 126.5, 126.2, 122.2, 120.1, 119.8,
115.9, 115.6, 109.8, 33.0; IR (KBr)νmax 3048, 2924, 2852, 1568, 1397,
1071, 924 cm-1; HRMS (ESI) Calcd For C15H13FN 226.1027 (M + H+);
Found 226.1028.
The synthesised compounds 3d, 3e, 4a-4e, 4g, 5d, 5g, 5h, 7b and 7c
are new compounds and not reported in the literature.
3-(4-chlorophenyl)-1-methyl-1H-indole (3h)9a: Yield 68% (163 mg),
3-(4-methoxyphenyl)-1-methyl-1H-indole (3a)9a: Yield 74% (176
mg), light yellow solid, mp 95-96˚C, 1H NMR (600 MHz, CDCl3): δ
7.89 (d, J = 8.0 Hz, 1H), 7.59 – 7.55 (m, 2H), 7.36 (d, J = 8.2 Hz, 1H),
7.28 (dd, J = 7.1, 0.9 Hz, 1H), 7.19 – 7.16 (m, 1H), 7.16 (s, 1H), 7.01 –
6.98 (m, 2H), 3.86 (s, 3H), 3.84 (s, 3H). 13C NMR (150 MHz, CDCl3): δ
158.1, 137.6, 128.7, 128.4, 126.5, 126.1, 122.1, 120.0, 119.9, 116.6,
114.5, 109.6, 55.6, 33.0; IR (KBr)νmax3055, 2923, 2852, 1601, 1488,
1372, 1132, 1034, 861 cm-1; HRMS (ESI) Calcd For C16H16NO
238.1226 (M + H+); Found 238.1229.
light brown solid, mp 95-96˚C, 1H NMR (600 MHz, CDCl3): δ 7.81 (d,
J = 8.0 Hz, 1H, H-4), 7.51 (d, J = 8.4 Hz, 2H, H-3’ & H-5’), 7.32 (d, J =
8.4 Hz, 2H, H-2’ & H-6’), 7.30 (d, J = 8.4 Hz, 1H, H-7), 7.22 (t, J = 7.6
Hz, 1H, H-6), 7.16 (s, 1H, H-2), 7.13 (t, J = 7.5 Hz, 1H, H-5); 13C NMR
(150 MHz, CDCl3): δ 137.6 (C9), 134.3 (C4’), 131.4 (C1’), 129.1 (C2’ &
C6’), 128.6 (C3’ & C5’), 126.8 (C2), 126.1 (C8), 122.3 (C6), 120.3 (C5),
119.8 (C4), 115.7 (C3), 109.8 (C7), 33.2 (CH3); IR (KBr)νmax3049,
2922, 2852, 1568, 1398, 1289, 996, 972 cm-1; HRMS (ESI) Calcd For
C15H13ClN 242.0731 (M + H+); Found 242.0741.
1-methyl-3-phenyl-1H-indole (3b)9a: Yield 68% (141 mg), light
yellow solid, mp 64-65˚C, 1H NMR (600 MHz, CDCl3): δ 7.96 (d, J =
8.0 Hz, 1H), 7.67 (d, J = 7.8 Hz, 2H), 7.45 (t, J = 7.7 Hz, 2H), 7.38 (d, J
= 8.2 Hz, 1H), 7.32 – 7.27 (m, 2H), 7.25 (s, 1H), 7.20 (t, J = 7.5 Hz,
1H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 137.8, 135.9, 128.9,
127.5, 126.7, 125.9, 122.2, 120.1, 120.1, 117.0, 109.7, 32.9; IR
(KBr)νmax 3049, 2929, 1718, 1603, 1550, 1483, 1262, 1016, 939 cm-1;
HRMS (ESI) Calcd For C15H14N 208.1121 (M + H+); Found 208.1126.
1-methyl-3-(p-tolyl)-1H-indole (3c)9a: Yield 70% (155 mg), light
yellow solid, mp 63-64˚C, 1H NMR (600 MHz, CDCl3): δ 7.83 (d, J =
8.0 Hz, 1H), 7.46 (d, J = 7.9 Hz, 2H), 7.27 (d, J = 8.2 Hz, 1H), 7.19 (d, J
= 7.1 Hz, 1H), 7.16 (d, J = 6.4 Hz, 2H), 7.11 (s, 1H), 7.08 (dd, J = 7.9,
7.1 Hz, 1H), 3.74 (s, 3H), 2.30 (s, 3H); 13C NMR (150 MHz, CDCl3): δ
137.6, 135.5, 132.9, 129.7, 127.5, 126.5, 126.4, 122.1, 120.2, 119.9,
116.9, 109.7, 33.1, 21.4; IR (KBr)νmax 3051, 2928, 2856, 1614, 1485,
1365, 1038, 857 cm-1; HRMS (ESI) Calcd For C16H16NO 222.1277 (M +
H+); Found 222.1278.
1-methyl-3-(naphthalen-2-yl)-1H-indole (3i)9a: Yield 85% (219 mg),
colourless semi-solid, 1H NMR (600 MHz, CDCl3): δ 8.14 (s, 1H), 8.09
(d, J = 8.0 Hz, 1H), 7.92 (d, J = 8.5 Hz, 1H), 7.89 (dd, J = 16.5, 8.1 Hz,
2H), 7.83 (dd, J = 8.4, 1.7 Hz, 1H), 7.53 – 7.49 (m, 1H), 7.46 (td, J =
7.5, 6.9, 1.2 Hz, 1H), 7.43 (d, J = 8.2 Hz, 1H), 7.39 (s, 1H), 7.36 – 7.32
(m, 1H), 7.27 – 7.25 (m, 1H), 3.91 (s, 3H); 13C NMR (150 MHz, CDCl3):
δ 137.8, 134.2, 133.4, 132.1, 128.4, 127.9, 127.9, 127.2, 126.6,
126.5, 126.3, 125.3, 125.1, 122.3, 120.2, 120.2, 116.8, 109.8, 33.1;
IR (KBr)νmax 3051, 2957, 2853, 1629, 1478, 1240, 1016, 857 cm-1;
HRMS (ESI) Calcd For C19H16N 258.1277 (M + H+); Found 258.1275.
1-methyl-3-(thiophen-2-yl)-1H-indole (3j)21a: Yield 64% (129 mg),
1
light green liquid, H NMR (600 MHz, CDCl3): δ 7.98 (dd, J = 7.9, 1.0
Hz, 1H), 7.36 (dd, J = 8.2, 1.0 Hz, 1H), 7.30 (d, J = 1.9 Hz, 2H), 7.26 –
7.25 (m, 1H), 7.23 (dd, J = 7.8, 1.1 Hz, 1H), 7.22 – 7.20 (m, 1H), 7.13
– 7.10 (m, 1H), 3.83 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 137.8,
137.2, 127.5, 126.5, 125.8, 122.2, 122.1, 122.0, 120.1, 120.0, 110.3,
109.5, 32.8.; IR (KBr)νmax 3054, 2922, 2851, 1566, 1370, 1188, 1016,
4-(1-methyl-1H-indol-3-yl)phenol (3d): Yield 68% (152 mg),
colourless semi-solid, 1H NMR (600 MHz, CDCl3): δ 7.90 (d, J = 8.0
Hz, 1H), 7.56 – 7.52 (m, 2H), 7.38 (d, J = 8.2 Hz, 1H), 7.30 (dd, J = 7.0,
6 | J. Name., 2012, 00, 1-3
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924 cm-1; HRMS (ESI) Calcd For C13H12NS 214.0685 (M + H+); Found cm-1; HRMS (ESI) Calcd For C22H18N 296.1434 (M + H+); Found
214.0691.
296.1426.
6-methoxy-1-methyl-3-phenyl-1H-indole (4a): Yield 86% (203 mg), 11-ethyl-3-phenyl-1H-indole (5a)21e: Yield 68% (150 mg), yellow
yellow semi-solid, 1H NMR (600 MHz, CDCl3): δ 7.83 (d, J = 8.7 Hz, semi-solid, mp 77-78 ˚C, 1H NMR (600 MHz, CDCl3): δ 7.98 (d, J = 8.0
1H), 7.65 (dd, J = 8.2, 1.3 Hz, 2H), 7.46 – 7.42 (m, 2H), 7.29 – 7.26 Hz, 1H), 7.72 – 7.66 (m, 2H), 7.46 (t, J = 7.7 Hz, 2H), 7.41 (d, J = 8.2
(m, 1H), 7.14 (s, 1H), 6.88 (dd, J = 8.7, 2.3 Hz, 1H), 6.82 (d, J = 2.3 Hz, Hz, 1H), 7.32 (s, 1H), 7.28 (dd, J = 11.5, 4.5 Hz, 2H), 7.21 (dd, J =
1H), 3.92 (s, 3H), 3.79 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 156.7, 11.0, 4.0 Hz, 1H), 4.24 (q, J = 7.3 Hz, 2H), 1.53 (t, J = 7.3 Hz, 3H); 13
C
138.4, 135.9, 128.9, 127.3, 125.8, 125.5, 120.9, 120.7, 116.9, 109.9, NMR (75 MHz, CDCl3): δ 136.6, 135.9, 128.9, 127.5, 126.4, 125.8,
93.2, 55.9, 33.1; IR (KBr)νmax 3049, 2928, 2859, 1611, 1558, 1067, 125.0, 122.0, 120.2, 120.0, 116.9, 109.8, 41.22, 15.68; IR (KBr)νmax
1021, 987 cm-1; HRMS (ESI) Calcd For C16H16NO 238.1226 (M + H+); 3051, 2957, 2867, 1619, 1466, 1365, 1068, 957 cm-1; HRMS (ESI)
Found 238.1229.
Calcd For C16H16N 222.1277 (M + H+); Found 222.1267.
1,6-dimethyl-3-phenyl-1H-indole (4b): Yield 72% (159 mg), yellow 1-butyl-3-phenyl-1H-indole (5b)21f: Yield 72% (179 mg), yellow
semi-solid, 1H NMR (400 MHz, CDCl3): δ 7.84 (d, J = 8.1 Hz, 1H), 7.72 semi-solid, 1H NMR (400 MHz, CDCl3): δ 7.96 (d, J = 8.0 Hz, 1H), 7.68
– 7.62 (m, 2H), 7.44 (t, J = 7.8 Hz, 2H), 7.30 – 7.25 (m, 1H), 7.17 (d, J (dt, J = 8.1, 1.3 Hz, 2H), 7.45 (td, J = 7.8, 1.4 Hz, 2H), 7.40 (d, J = 8.1
= 3.4 Hz, 2H), 7.04 (d, J = 8.2 Hz, 1H), 3.81 (s, 3H), 2.54 (s, 3H); 13C Hz, 1H), 7.29 (s, 1H), 7.29 – 7.24 (m, 2H), 7.22 – 7.16 (m, 1H), 4.17
NMR (75 MHz, CDCl3): δ 138.0, 136.0, 132.0, 128.9, 127.3, 126.1, (t, J = 7.1 Hz, 2H), 1.97 – 1.82 (m, 2H), 1.40 (q, J = 7.5 Hz, 2H), 0.97
125.7, 124.1, 121.8, 119.8, 116.6, 109.7, 32.9, 22.1; IR (KBr)νmax (td, J = 7.3, 1.2 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ 136.9, 135.9,
3058, 2921, 2858, 2252, 1602, 1552, 1383, 1028, 967 cm-1; HRMS 128.9, 127.5, 126.4, 125.8, 121.9, 120.2, 119.9, 116.7, 109.9, 46.4,
(ESI) Calcd For C16H16N 222.1277 (M + H+); Found 222.1279.
32.5, 20.4, 13.9; IR (KBr)νmax 3054, 2962, 2857, 1602, 1289, , 996 cm-
6-fluoro-1-methyl-3-phenyl-1H-indole (4c): Yield 68% (153 mg), 1; HRMS (ESI) Calcd For C18H20N 250.1590 (M + H+); Found 250.1589.
1
brown semi-solid, H NMR (600 MHz, CDCl3 δ 7.84 (dd, J = 8.8, 5.3 2-(3-phenyl-1H-indol-1-yl)ethanol (5c): Yield 68% (161 mg),
1
Hz, 1H), 7.64 – 7.60 (m, 2H), 7.46 – 7.41 (m, 2H), 7.31 – 7.26 (m, colourless semi-solid, H NMR (600 MHz, CDCl3): δ 7.96 (dt, J = 8.0,
1H), 7.21 (s, 1H), 7.03 (dd, J = 9.7, 2.3 Hz, 1H), 6.95 (ddd, J = 9.4, 8.7, 1.0 Hz, 1H), 7.69 – 7.64 (m, 2H), 7.46 – 7.43 (m, 2H), 7.43 – 7.41 (m,
2.3 Hz, 1H), 3.79 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 160.9, 159.4, 1H), 7.36 (s, 1H), 7.28 (m, 2H), 7.20 (m, 1H), 4.34 (t, J = 5.3 Hz, 2H),
137.8, 137.7, 135.4, 129.0, 127.5, 126.9, 126.9, 126.2, 122.9, 121.0, 4.02 (t, J = 5.3 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 136.9, 135.5,
120.9, 117.2, 108.8, 108.7, 96.2, 95.9, 33.2; IR (KBr)νmax 3046, 2924, 128.9, 127.4, 126.4, 126.3, 125.9, 122.2, 120.3, 120.2, 117.1, 109.9,
2852, 1608, 1560, 1016, 996 cm-1; HRMS (ESI) Calcd For C15H13FN 61.8, 48.8; IR (KBr)νmax 3021, 2920, 2836, 1708, 1632, 1355, 1111,
226.1027 (M + H+); Found 226.1015.
996 cm-1; HRMS (ESI) Calcd For C16H16NO 238.1226 (M + H+); Found
6-chloro-1-methyl-3-phenyl-1H-indole (4d): Yield 58% (139 mg), 238.1245.
1
colourless semi-solid, H NMR (400 MHz, CDCl3): δ 7.84 (d, J = 8.5 1-cyclohexyl-3-phenyl-1H-indole (5d): Yield 62% (170 mg),
Hz, 1H), 7.65 – 7.59 (m, 2H), 7.45 (t, J = 7.7 Hz, 2H), 7.36 (d, J = 1.9 colourless semisolid, 1H NMR (400 MHz, CDCl3): δ 7.81 (d, J = 7.9
Hz, 1H), 7.29 (t, J = 7.4 Hz, 1H), 7.22 (s, 1H), 7.16 (dd, J = 8.5, 1.9 Hz, Hz, 1H), 7.53 (dd, J = 8.0, 1.4 Hz, 2H), 7.33 – 7.26 (m, 3H), 7.26 (s,
1H), 3.81 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 139.0, 135.2, 129.0, 1H), 7.14 – 7.09 (m, 2H), 7.06 – 7.00 (m, 1H), 4.19 – 4.06 (m, 1H),
128.2, 127.5, 127.3, 126.2, 124.9, 121.1, 120.7, 117.2, 109.8, 33.2; 2.06 (d, J = 12.5 Hz, 2H), 1.90 – 1.76 (m, 2H), 1.62 (dt, J = 12.6, 8.9
IR (KBr)νmax 3054, 2928, 2859, 1645, 1491, 1184, 1069, 956 cm-1; Hz, 2H), 1.41 (d, J = 3.4 Hz, 2H), 1.24 – 1.13 (m, 2H); 13C NMR (75
HRMS (ESI) Calcd For C15H13ClN 242.0731 (M + H+); Found 242.0740. MHz, CDCl3): δ 136.5, 136.1, 128.9, 127.5, 126.3, 125.8, 122.2,
1,4,6-trimethyl-3-phenyl-1H-indole (4e): Yield 72% (169 mg), light 121.8, 120.2, 120.0, 116.9, 109.9, 53.3, 33.79, 26.2, 25.8; IR
1
yellow semi-solid, H NMR (400 MHz, CDCl3): δ 7.56 – 7.49 (m, 2H), (KBr)νmax 3042, 2938, 2842, 1638, 1384, 1298, 1016, 978 cm-1;
7.45 (tdd, J = 7.7, 2.1, 1.2 Hz, 2H), 7.42 – 7.35 (m, 1H), 7.09 (s, 1H), HRMS (ESI) Calcd For C20H22N 276.1747 (M + H+); Found 276.1751.
6.97 (d, J = 1.4 Hz, 1H), 6.83 (s, 1H), 3.82 (d, J = 1.2 Hz, 3H), 2.56 (d, J 1,3-diphenyl-1H-indole (5e)8c: Yield 66% (177 mg), white solid, mp
= 2.2 Hz, 3H), 2.36 (d, J = 2.5 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ 103-104 ˚C, 1H NMR (400 MHz, CDCl3): 8.01 (dd, J = 6.9, 1.9 Hz, 1H),
137.6, 137.3, 131.8, 131.1, 130.7, 127.7, 127.3, 126.3, 123.7, 123.2, 7.77 – 7.71 (m, 2H), 7.65 – 7.61 (m, 1H), 7.57 (d, J = 1.8 Hz, 3H), 7.54
118.2, 107.2, 32.8, 21.8, 20.9; IR (KBr)νmax 3058, 2921, 2858, 2252, (d, J = 11.0 Hz, 2H), 7.49 (t, J = 7.7 Hz, 2H), 7.40 (tt, J = 6.2, 2.2 Hz,
1602, 1552, 1085, 967 cm-1; HRMS (ESI) Calcd For C17H18N 236.1434 1H), 7.36 – 7.31 (m, 1H), 7.31 – 7.25 (m, 2H); 13C NMR (75 MHz,
(M + H+); Found 236.1438.
CDCl3): δ 139.7, 136.8, 135.3, 129.9, 129.0, 127.8, 127.3, 126.9,
5-methoxy-1-methyl-3-phenyl-1H-indole (4f)21d: Yield 58% (138 126.4, 125.7, 124.7, 123.0, 121.1, 120.3, 119.3, 111.0; IR (KBr)νmax
mg),light yellow semi-solid, 1H NMR (600 MHz, CDCl3): δ 7.68 – 7.63 3056, 2921, 2851, 1598, 1018, 999 cm-1; HRMS (ESI) Calcd For
(m, 2H), 7.49 – 7.43 (m, 2H), 7.41 (d, J = 2.5 Hz, 1H), 7.29 (d, J = 8.0 C20H16N 270.1277 (M + H+); Found 270.1278.
Hz, 1H), 7.27 (d, J = 2.3 Hz, 1H), 7.22 (s, 1H), 6.97 (dd, J = 8.9, 2.4 Hz, 1-benzyl-3-phenyl-1H-indole (5f)21e: Yield 78% (221 mg), white
1H), 3.89 (s, 3H), 3.84 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 154.8, solid, mp 105 – 106 ˚C, 1H NMR (400 MHz, CDCl3): δ 8.02 (dd, J =
136.0, 133.1, 129.0, 127.4, 127.4, 126.6, 125.8, 116.5, 112.4, 110.5, 7.1, 1.7 Hz, 1H), 7.74 – 7.68 (m, 2H), 7.47 (t, J = 7.6 Hz, 2H), 7.39 –
101.9, 56.3, 33.3; IR (KBr)νmax 3052, 2924, 2853, 1608, 1466, 1177, 7.29 (m, 6H), 7.29 – 7.26 (m, 1H), 7.24 (dd, J = 7.6, 1.6 Hz, 1H), 7.22
996 cm-1; HRMS (ESI) Calcd For C16H16NO 238.1226 (M + H+); Found – 7.17 (m, 2H), 5.37 (s, 2H); 13C NMR (75 MHz, CDCl3): δ 137.4,
238.1236.
137.3, 135.7, 129.0, 128.9, 127.9, 127.6, 127.1, 126.6, 126.1, 126.0,
3-methyl-1-phenyl-3,10-dihydroindeno[2,1-e]indole (4g): Yield 122.3, 120.3, 120.2, 117.5, 110.2, 50.3; IR (KBr)νmax 3059, 2922,
62% (182 mg), white solid, mp 202–203 ˚C, 1H NMR (400 MHz, 2853, 1601, 1546, 1259, 1181, 1000, 970 cm-1; HRMS (ESI) Calcd For
CDCl3): δ 8.30 (s, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 8.0 Hz, 2H),
C
21H18NS 284.1434 (M + H+); Found 284.1434.
7.54 - 7.48 (m, 4H), 7.39 (t, J = 8.0 Hz, 1H), 7.32 (t, J = 8.0 Hz, 1H), 1-phenethyl-3-phenyl-1H-indole (5g): Yield 64% (190 mg),
1
7.28-7.23 ( m, 2H), 4.04 (s, 2H), 3.87 (s, 3H); 13C NMR (75 MHz, colourless semi-solid, H NMR (600 MHz, CDCl3): δ 7.98 (dt, J = 8.0,
CDCl3): δ 143.1, 142.7, 138.5, 137.9, 135.8, 134.9, 128.8, 127.4, 1.0 Hz, 1H), 7.65 – 7.61 (m, 2H), 7.45 (t, J = 7.7 Hz, 2H), 7.42 (dd, J =
126.6, 125.7, 125.6, 124.8, 125.1, 119.3, 116.9, 110.5, 105.9, 36.7, 8.2, 0.9 Hz, 1H), 7.34 – 7.29 (m, 3H), 7.28 (d, J = 7.8 Hz, 2H), 7.22 (m,
33.10; IR (KBr)νmax 3057, 2956, 2869, 1642, 1548, 1368, 1062, 962 1H), 7.17 – 7.13 (m, 2H), 7.12 (s, 1H), 4.43 – 4.40 (m, 2H), 3.18 (t, J =
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7.5 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 138.6, 136.7, 135.8, 129.0, 1H), 7.38 – 7.32 (m, 1H); 13C NMR (150 MHz, CDCl3): δ 135.7, 131.5,
128.9, 128.9, 127.5, 126.9, 126.5, 125.9, 122.1, 120.3, 120.1, 116.9, 130.7, 129.0, 129.1, 127.9, 126.4, 125.8, 124.4, 121.9, 121.8, 121.5,
109.8, 48.4, 36.9; IR (KBr)νmax 3054, 2982, 2852, 1655, 1545, 1018, 120.5, 120.1, 119.9, 119.6; IR (KBr)νmax 3049, 2919, 2851, 1648,
998 cm-1; HRMS (ESI) Calcd For C22H20NS 298.1590 (M + H+); Found 1553, 1072, 1018, 998 cm-1; HRMS (ESI) Calcd For C18H14N 244.1121
298.1595.
(M + H+); Found 244.1112.
2-(5-methyl-3-(p-tolyl)-1H-indol-1-yl)-1-phenylethanol (5h): Yield 1-phenyl-3H-benzo[e]indole (6g)15a: Yield 90% (219 mg), brown
62% (211 mg), white solid, mp 80-81˚C, 1H NMR (600 MHz, CDCl3): δ colour oily liquid, 1H NMR (600 MHz, CDCl3): δ 8.43 (s, 1H), 8.18 (m,
7.64 (s, 1H), 7.45 (d, J = 8.0 Hz, 2H), 7.36 – 7.30 (m, 4H), 7.29 – 7.27 1H), 7.95 (dd, J = 7.9, 1.6 Hz, 1H), 7.70 – 7.66 (m, 3H), 7.55 – 7.51
(m, 1H), 7.26 (d, J = 8.4 Hz, 1H), 7.18 (d, J = 8.1 Hz, 2H), 7.12 (s, 1H), (m, 3H), 7.49 – 7.46 (m, 1H), 7.43 – 7.39 (m, 1H), 7.39 – 7.34 (m,
7.05 – 7.02 (m, 1H), 5.04 (dd, J = 8.3, 3.7 Hz, 1H), 4.29 – 4.20 (m, 1H), 7.15 (d, J = 2.5 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ 137.3,
2H), 2.41 (s, 3H), 2.33 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 141.2, 132.9, 130.3, 129.9, 128.9, 128.8, 128.5, 126.9, 125.6, 123.9, 123.5,
135.6, 135.5, 132.8, 129.6, 128.9, 128.5, 127.5, 126.9, 126.3, 126.1, 123.4, 121.7, 121.3, 119.6, 113.1; IR (KBr)νmax 3052, 2916, 2848,
123.9, 119.9, 116.9, 109.6, 73.8, 54.6, 21.8, 21.4; IR (KBr)νmax 3054, 1652, 1448, 1180, 992 cm-1; HRMS (ESI) Calcd For C18H14N 244.1121
2982, 2852, 1655, 1114, 1018, 998 cm-1; HRMS (ESI) Calcd For (M + H+); Found 244.1125.
C24H24NO 342.1852 (M + H+); Found 342.1865.
6-methoxy-3-(p-tolyl)-1H-indole (7a)8e: Yield 82% (195 mg), brown
1
6-methoxy-3-phenyl-1H-indole (6a)21g: Yield 85% (187 mg), brown semisolid, H NMR (600 MHz, CDCl3): δ 8.07 (s, 1H), 7.79 (d, J = 8.7
1
colour semi-solid, H NMR (600 MHz, CDCl3): δ 8.17 – 8.07 (m, 1H), Hz, 1H), 7.57 – 7.54 (m, 2H), 7.25 (d, J = 7.6 Hz, 2H), 7.23 (d, J = 2.4
7.84 (d, J = 8.7 Hz, 1H), 7.73 – 7.64 (m, 2H), 7.51 – 7.42 (m, 2H), 7.33 Hz, 1H), 6.91 (d, J = 2.2 Hz, 1H), 6.86 (dd, J = 8.7, 2.3 Hz, 1H), 3.87 (s,
– 7.30 (m, 1H), 7.29 (d, J = 2.3 Hz, 1H), 6.93 (d, J = 2.3 Hz, 1H), 6.90 3H), 2.40 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 156.8, 137.6, 135.7,
(dd, J = 8.7, 2.3 Hz, 1H), 3.90 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 132.8, 129.6, 127.4, 120.7, 120.4, 120.3, 118.4, 110.3, 94.9, 55.9,
156.8, 137.7, 135.8, 128.9, 127.5, 126.1, 120.7, 120.7, 120.3, 118.5, 21.4; IR (KBr)νmax 3056, 2850, 1568, 1532, 1187, 1018, 997 cm-1;
110.5, 94.9, 55.9; IR (KBr)νmax 3056, 2850, 1568, 1532, 1018, 997 HRMS (ESI) Calcd For C16H16NO 238.1226 (M + H+); Found 238.1241.
cm-1; HRMS (ESI) Calcd For C15H14NO 224.1070 (M + H+); Found 4-(6-methoxy-1H-indol-3-yl)phenol (7b): Yield 76% (182 mg),
224.1072.
brown semi-solid, 1H NMR (600 MHz, CDCl3): δ 8.06 (s, 1H), 7.74 (d,
Yield 74% (163 mg), J = 8.7 Hz, 1H), 7.54 – 7.50 (m, 2H), 7.18 (d, J = 2.4 Hz, 1H), 6.91 (dd,
5,7-dimethyl-3-phenyl-1H-indole (6b)21h
:
yellow colour semi-solid, H NMR (600 MHz, CDCl3): δ 8.08 (s, 1H), J = 8.2, 2.0 Hz, 3H), 6.85 (dd, J = 8.7, 2.3 Hz, 1H), 3.87 (s, 3H).; 13C
7.71 – 7.66 (m, 2H), 7.60 (s, 1H), 7.46 (td, J = 7.7, 1.6 Hz, 2H), 7.33 (t, NMR (150 MHz, CDCl3): δ 155.1, 154.6, 136.9, 127.1, 126.3, 119.4,
J = 2.2 Hz, 1H), 7.32 – 7.28 (m, 1H), 6.92 (s, 1H), 2.50 (s, 3H), 2.47 (s, 119.2, 119.1, 115.9, 114.9, 108.7, 94.1, 54.7; IR (KBr)νmax 3262,
3H); 13C NMR (75 MHz, CDCl3): δ 136.1, 134.7, 130.0, 128.9, 127.7, 2928, 2856, 1614, 1187, 1019, 998; cm-1; HRMS (ESI) Calcd For
126.0, 125.6, 124.8, 121.9, 120.4, 118.4, 117.2, 21.7, 16.7; IR C15H14NO2 240.1019 (M + H+); Found 240.1020.
1
(KBr)νmax 3046, 2847, 1609, 1188, 1020, 996 cm-1; HRMS (ESI) Calcd 3-(2,4-dimethoxyphenyl)-6-methoxy-1H-indole (7c): Yield 72% (203
For C16H16N 222.1277 (M + H+); Found 222.1273.
mg), brown semi-solid, 1H NMR (600 MHz, CDCl3): δ 8.09 (s, 1H),
4,6-dimethoxy-3-phenyl-1H-indole (6c)9b: Yield 80% (202 mg), 7.61 (d, J = 8.7 Hz, 1H), 7.51 (d, J = 8.2 Hz, 1H), 7.32 (d, J = 2.4 Hz,
1
colourless solid mp 56-57 ˚C, H NMR (600 MHz, CDCl3): δ 8.09 (s, 1H), 6.91 (d, J = 2.3 Hz, 1H), 6.83 (dd, J = 8.7, 2.3 Hz, 1H), 6.63 (d, J =
1H), 7.66 – 7.59 (m, 2H), 7.37 (t, J = 7.7 Hz, 2H), 7.28 – 7.25 (m, 1H), 2.4 Hz, 1H), 6.62 (dd, J = 8.2, 2.5 Hz, 1H), 3.89 (s, 3H), 3.88 (s, 3H),
7.01 (dd, J = 2.4, 0.8 Hz, 1H), 6.50 (dd, J = 2.0, 0.9 Hz, 1H), 6.27 (d, J 3.85 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 159.5, 157.9, 156.6,
= 2.0 Hz, 1H), 3.85 (s, 3H), 3.80 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 136.9, 130.9, 122.4, 121.4, 121.3, 117.3, 113.6, 109.9, 104.5, 99.3,
157.8, 155.1, 138.5, 136.2, 129.7, 127.8, 125.8, 120.6, 119.2, 110.5, 94.8, 55.9, 55.7, 55.7; IR (KBr)νmax 3054, 2938, 2848, 2827, 1604,
92.4, 86.9, 55.8, 55.3; IR (KBr)νmax 3048, 2959, 2840, 1706, 1625, 1214, 1036, 978 cm-1; HRMS (ESI) Calcd For C17H18NO3 284.1281 (M
1047, 995 cm-1; HRMS (ESI) Calcd For C16H16NO2 254.1176 (M + H+); + H+); Found 284.1298.
Found 254.1188.
3-(4-fluorophenyl)-6-methoxy-1H-indole (7d)21c: Yield 68% (165
7-phenyl-5H-[1,3]dioxolo[4,5-f]indole (6d): Yield 68% (161 mg), mg), brown liquid, 1H NMR (600 MHz, CDCl3): δ 8.11 (s, 1H), 7.73
1
brown colour solid, mp < 320˚C, H NMR (400 MHz, CDCl3): δ 8.11 (dt, J = 8.7, 0.7 Hz, 1H), 7.63 – 7.56 (m, 2H), 7.21 (d, J = 2.4 Hz, 1H),
(s, 1H), 7.65 – 7.58 (m, 2H), 7.45 (t, J = 7.7 Hz, 2H), 7.33 (d, J = 0.7 7.17 – 7.09 (m, 2H), 6.92 (d, J = 2.3 Hz, 1H), 6.87 (dd, J = 8.7, 2.3 Hz,
Hz, 1H), 7.32 – 7.27 (m, 1H), 7.22 (d, J = 2.5 Hz, 1H), 6.87 (d, J = 0.6 1H), 3.87 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 162.4, 160.8, 156.9,
Hz, 1H), 5.97 (s, 2H); 13C NMR (75 MHz, CDCl3): δ 145.3, 143.7, 137.6, 131.8, 131.8, 128.9, 128.9, 120.4, 120.4, 120.3, 117.6, 115.8,
135.7, 131.7, 128.9, 127.4, 126.1, 120.6, 119.8, 118.7, 100.9, 98.6, 115.7, 110.6, 94.9, 55.9; IR (KBr)νmax 3052, 2957, 2868, 1652, 1269,
92.3; IR (KBr)νmax 3052, 2958, 2857, 1628, 1028, 978 cm-1; HRMS 1048, 972 cm-1; HRMS (ESI) Calcd For C15H13NO 242.0976 (M + H+);
(ESI) Calcd For C15H12NO2 238.0863 (M + H+); Found 238.0850.
Found 242.0978.
6-fluoro-3-phenyl-1H-indole (6e)8e: Yield 74% (200 mg), colourless 3-(4-chlorophenyl)-6-methoxy-1H-indole (7e)8e: Yield 70% (181
solid, mp 45-46˚C, 1H NMR (400 MHz, CDCl3): δ 8.24 (s, 1H), 7.85 mg), brown oily liquid, 1H NMR (600 MHz, DMSO-d6): δ 11.23 (s,
(dd, J = 8.8, 5.3 Hz, 1H), 7.69 – 7.62 (m, 2H), 7.47 (t, J = 7.6 Hz, 2H), 1H), 7.71 (d, J = 8.7 Hz, 1H), 7.70 – 7.65 (m, 2H), 7.59 (d, J = 2.5 Hz,
7.36 – 7.34 (m, 1H), 7.31 (d, J = 7.3 Hz, 1H), 7.11 (dd, J = 9.5, 2.3 Hz, 1H), 7.46 – 7.41 (m, 2H), 6.95 (d, J = 2.3 Hz, 1H), 6.75 (dd, J = 8.7, 2.4
1H), 7.01 – 6.93 (m, 1H); 13C NMR (150 MHz, CDCl3): δ 161.1, 159.5, Hz, 1H), 3.78 (s, 3H); 13C NMR (75 MHz, DMSO-d6): δ 155.8, 137.9,
136.8, 136.7, 135.3, 129.0, 127.7, 126.4, 122.6, 122.1, 122.1, 120.9, 134.9, 129.5, 128.8, 127.8, 122.6, 119.7, 119.1, 114.5, 110.1, 94.9,
120.8, 118.7, 109.3, 109.2, 97.9, 97.7; IR (KBr)νmax 3046, 2916, 2848, 55.3; IR (KBr)νmax 3050, 2994, 2935, 2833, 1647, 1091, 968 cm-1;
1642, 1254, 1068, 992 cm-1; HRMS (ESI) Calcd For C14H11FN HRMS (ESI) Calcd For C15H13ClNO 258.0680 (M + H+); Found
212.0870 (M + H+); Found 212.0878.
258.0673.
3-phenyl-1H-benzo[g]indole (6f)15a: Yield 82% (200 mg), colourless 6-methoxy-2-methyl-3-phenyl-1H-indole (7f)21i
: Yield 74% (175
solid, mp 234-235˚C, 1H NMR (400 MHz, CDCl3): δ 8.92 (s, 1H), 8.05 mg), light yellow solid mp 152-153, 1H NMR (600 MHz, CDCl3): δ
– 8.01 (m, 1H), 8.01 – 7.94 (m, 2H), 7.77 – 7.70 (m, 2H), 7.60 (d, J = 7.84 (s, 1H), 7.53 (d, J = 8.6 Hz, 1H), 7.52 – 7.48 (m, 2H), 7.45 (dd, J =
8.7 Hz, 1H), 7.55 (m, 1H), 7.53 – 7.46 (m, 3H), 7.40 (d, J = 2.6 Hz, 8.6, 6.9 Hz, 2H), 7.32 – 7.27 (m, 1H), 6.85 (d, J = 2.3 Hz, 1H), 6.78
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(dd, J = 8.7, 2.3 Hz, 1H), 3.86 (s, 3H), 2.48 (s, 3H); 13C NMR (150
MHz, CDCl3): δ 156.3, 136.1, 135.7, 130.2, 129.5, 128.7, 125.9,
122.4, 119.6, 114.4, 109.5, 94.6, 55.9, 12.7; IR (KBr)νmax 3052, 2990,
2931, 2838, 1642, 1039, 964 cm-1; HRMS (ESI) Calcd For C16H16NO
238.1226 (M + H+); Found 238.1211.
1-ethyl-3-(p-tolyl)-1H-indole (5i): Yield 64% (150 mg),Yellow semi-
solid, 1H NMR (600 MHz, CDCl3): δ 7.94 (dd, J = 8.1, 1.0 Hz, 1H), 7.59
– 7.55 (m, 2H), 7.40 (d, J = 8.2 Hz, 1H), 7.28 (s, 1H), 7.27 – 7.25 (m,
3H), 7.18 (td, J = 7.5, 7.1, 1.1 Hz, 1H), 4.22 (q, J = 7.3 Hz, 2H), 2.41 (s,
3H), 1.52 (t, J = 7.3 Hz, 3H); 13C NMR (150 MHz, CDCl3): δ 136.6,
135.4, 132.9, 129.6, 127.4, 126.5, 124.7, 121.9, 120.3, 119.9, 116.9,
109.7, 41.2, 21.4, 15.7; IR (KBr)νmax 3048, 2923, 2853, 1613, 1099,
967 cm-1; HRMS (ESI) Calcd For C17H18N 236.1434 (M + H+); Found
236.1451.
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7.21 (m, 2H), 7.09 (d, J = 7.8 Hz, 2H), 7.08 – 7.06 (m, 2H), 6.47 – 6.43
(m, 2H), 5.58 (s, 1H), 5.20 (qd, J = 13.2, 8.4 Hz, 2H), 4.60 (t, J = 8.3
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148.9, 138.14, 135.8, 129.1, 128.1, 127.4, 126.9, 111.7, 78.9, 47.6,
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Conflicts of interest
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There are no conflicts to declare.
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RK, SB and KM are thankful to IIT Guwahati for their research
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16. (a) N. Zhang, Z. -J. Quan, Z. Zhang, Y. –X. Da and X. –C.
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