Synthesis of 3-arylindole derivatives from nitroalkane precursors

Article abstract of DOI:10.1039/c6ra21144e

3-Arylindole derivatives were synthesized by Cu(i) catalysed intramolecular Ullmann coupling of 2-bromoarylaminoalkanes. 2-Bromoarylaminoalkanes were synthesized from 2-bromoarylnitroalkanes, which in turn prepared through AlCl₃-mediated Friede

Full text of DOI:10.1039/c6ra21144e

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Synthesis of 3-arylindole derivatives from
nitroalkane precursors†
Cite this: RSC Adv., 2016, 6, 96049
Chia-Yu Huang,‡ Chun-Wei Kuo,‡ Ashok Konala, Tang-Hao Yang, Lyu Lin,
*
Yu-Wen Chen, Veerababurao Kavala and Ching-Fa Yao
Received 23rd August 2016
Accepted 2nd October 2016
3-Arylindole derivatives were synthesized by Cu(I) catalysed intramolecular Ullmann coupling of
2-bromoarylaminoalkanes. 2-Bromoarylaminoalkanes were synthesized from 2-bromoarylnitroalkanes,
which in turn prepared through AlCl3-mediated Friedel–Crafts alkylation of bromo-substituted
b-nitrostyrenes and arenes.
DOI: 10.1039/c6ra21144e
www.rsc.org/advances
Sclerotinia sclerotiorum.2 Another example is murrapanine, it
was isolated from the root bark of Murraya paniculata var.
Introduction
omphalocarpa and used for the treatments for lymphocytic
leukaemia, lung adenocarcinoma and colon adenocarcinoma.3
Fluvastatin, a multi-purpose medicine for high cholesterol
and cardiovascular disease prevention, also found to have
antiviral activity against hepatitis C.4 Also, 3-arylindoles acts as
a potent and efficacious progesterone receptor (PR) antagonists
and can be used for the treatment of uterine broids.5
The indole skeleton is a key structural component in various
natural products, pharmaceutical compounds, dyes, agricul-
tural compounds, cosmetics, nutraceuticals, and avourings.1
3-Aryl indole, a derivative of indole also exhibit various inter-
esting activities as shown in Fig. 1. For example, 4-uoro-3-
phenylindole can inhibit brassinin glucosyltransferase, a kind
of phytoalexin detoxication enzyme which comes from fungus
In the light of the importance of these bioactive molecules,
several synthetic protocols have been reported.6 Various
methods known for the exclusive synthesis of 3-arylindoles are
conventional Fischer indole synthesis,7 transition-metal-
catalyzed coupling of indoles with coupling partners such as
aryl halides,8 diaryl-iodine(III) reagent,9 carboxylic acids,10 aryl-
hydrazine/amine,11 other miscellaneous methods.12 In 2010,
Siva Murru et al. reported Au and Cu versions of annulation of
nitrosoarenes and alkynes for the synthesis of 3-arylindoles.13
Recently, Kumar et al. reported the t-BuOK-mediated transition
metal free synthesis of 3-(2/4-nitroaryl)-indoles through inter-
molecular oxidative coupling of indole with nitroarenes.14 Most
of the developed methodologies requires N-protection or C-2
substitution of indoles or requires costly additives/ligands and
harsh reaction conditions to obtain exclusively 3-arylindoles.
Hence there is a need to develop an alternative and direct
method to access the valuable 3-arylindoles.
Results and discussion
In 1991, Russell and Yao et al. reported the synthesis of 3-aryl-
derivatives from a-phenyl-b-nitrostyrenes in the presence of
triethylphosphite15 (Scheme 1). Since the starting material
a-phenyl-b-nitrostyrenes are very tedious to prepare, the same
protocol is applied on easily available starting material
b-nitrostyrenes. But didn't nd any desired 3-arylindole product
and end up with a mixture of products.16 As a part of our interest
in developing fascinating methodologies for the synthesis of
Fig. 1 Pharmaceutically active 3-arylindole derivatives.
Department of Chemistry, National Taiwan Normal University, 88, section 4, Tingchow
road, Taipei, Taiwan 116, Republic of China. E-mail: cheyaocf@ntnu.edu.tw
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c6ra21144e
‡ Equal contribution.
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Table 1 Synthesis of 2-bromoarylnitroalkane derivativesa,b
Scheme 1 Earlier synthetic approaches from nitrostyrenes.
Entry
R1
R2
3
Time
Yield%
1
2
3
4
5
6
7
8
9
H
OMe
OMe
OMe
OMe
OMe
OMe
H
3a
3b
3c
3d
3e
3f
3g
3h
3i
3 h
3 h
3 h
5 h
5 h
1 h
5 h
4 h
2 h
98%
70%
71%
64%
64%
76%
89%
72%
67%
biologically active heterocycles17 using easily available starting
materials, we envisioned that 3-arylindoles can be synthesized
from Cu catalyzed intramolecular Ullmann coupling of 2-bro-
moarylamino alkanes. The required aminoalkanes prepared
from racemic 2-bromoarylnitroalkanes, which in turn prepared
from our reported method18 using AlCl3-mediated Friedel–
Cras alkylation of bromo-substituted b-nitrostyrenes and are-
nes as shown in Scheme 2. 2-Bromoarylnitroalkanes may
undergo reduction to form 2-bromoarylaminoalkanes followed
by Cu catalyzed intramolecular coupling may afford the desired
3-arylindole product.
5-OMe
4,5-DiOMe
4,5-OCH2O–
5-OPr
3,4-(CH4)
H
H
H
Me
iPr
a
Reaction conditions: 1 (5 mmol), 2 arene (10 mmol), AlCl3 (10 mmol),
DCM (20 mL), ꢀ78 ꢁC, under N2. b Isolated yields.
In order to check the validity of our hypothesis we initially
synthesized various 2-bromo-b-nitrostyrene derivatives (1) from
nitromethane and corresponding 2-bromobenzaldehydes
through Knoevenagel condensation followed by Friedel–Cras
alkylation with AlCl3 to obtain the corresponding nitroalkane
derivatives (3a–3i) (Table 1). Most of the substrates produced
nitroalkanes in moderate to good yields. Starting from simple 2-
bromo-b-nitrostyrene various substituents such as OMe,
OCH2O, OPr, naphthyl afford the corresponding nitroalkane
derivatives 3a–3f in good yield with its coupling partner anisole.
Its noteworthy that the current protocol not only works well with
strong donating groups like OMe on aryl ring but also works
well with Me, i-Pr, H substituents (3g, 3h and 3i) with simple 2-
bromo-b-nitrostyrene. In all these entries, the insertion of
bromo group on b-nitrostyrene was needed which conned the
versatility of our method. For this reason, we attempted to
develop another synthetic route, using 3-bromoanisole as
substrate in the Friedel–Cras alkylation. We synthesized
another series of nitroalkanes (3j–3r) Table 2 as precursors from
the same Friedel–Cras alkylation procedure. The reactions
took longer times compared to its former entries due to both
steric hindrance and electron-withdrawing effect of bromo
group. Most of the substrates produced nitroalkanes in
moderate to good yields, while few substrates like 2-methyl, 1-
naphthyl and 3-chloro substituted b-nitrostyrene produced poor
yields of corresponding nitroalkanes (3k, 3o, 3p) as shown in
Table 2.
Aer the preparation of various nitroalkane derivatives, 1-
bromo-2-(1-(4-methoxyphenyl)-2-nitroethyl)benzene (3a) was
taken as the model substrate and reduced with reagents Fe/
AcOH and NaBH4/BF3$THF. A mixture of 2-(2-bromophenyl)-2-
(4-methoxyphenyl)ethan-1-amine (4a) and debromonated
amine was observed. If we use LAH as reducing reagent, the
reaction produced the desired 2-(2-bromophenyl)-2-(4-
methoxyphenyl)ethan-1-amine as sole product in quantitative
Table
2
Synthesis
of
4-methoxy-2-bromoarylnitroalkane
derivativesa,b
Entry
R1
R2
3
Yield%
1
2
3
4
5
6
7
8
9
H
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
3j
3k
3l
3m
3n
3o
3p
3q
3r
97%
27%
80%
90%
61%
36%
34%
70%
94%
2-Me
4-Me
4-t-Bu
3-OMe
2,3-(CH)4
3-Cl
4-Cl
2-NO2
a
Reaction conditions: 1 (5 mmol), 2 arene (10 mmol), AlCl3 (10 mmol),
DCM (20 mL), ꢀ78 ꢁC, under N2. b Isolated yields.
Scheme 2 Synthetic strategy for 3-aryl indoles.
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yield, as a result, we utilized the 2-bromoarylamine 4a for the yield increase of desired indole. Finally, aer a series of tunings,
coupling reactions without further purication. Initially we we found the coupling of bromoamine 4a had best performance
conducted the reaction of 2-bromoarylamine 4a with 10 mol% when treated with 10 mol% of CuI, 20 mol% of L-phenylalanine
ꢁ
of CuI, 20 mol% of L-proline and 2 eq. of K2CO3 in DMSO at 80 and 2 eq. of K2CO3 in DMSO at 100 C under O2 atmosphere.
ꢁC as the model reaction (Entry 1, Table 3). The reaction The other bromoamine derivatives were also directly subjected
produced 49% of indoline (5a) and 16% of desired indole
product (6a). We then focused on variation of other reaction
parameters in order to increase the yield of indole product as
Table
4 Synthesis of 3-arylindole derivatives from 2-bromoni-
troalkane precursorsa,b
presented in Table 3. In the ligand tuning, except L-phenylala-
nine other ligands resulted in lower yields (Entries 2–6). Using L-
phenylalanine as ligand, showed better result as the tempera-
ꢁ
ꢁ
ture raised from 80 C to 100 C (Entries 4, 5). In the solvent
tuning, DMSO prevailed other solvents. In 1986, Speier et al.
reported a kinetics and mechanism research about Cu-catalyzed
oxidation of indolines to indoles, the experiments showed that
there is a positive correlation between the oxidant's concen-
tration and the oxidation rate in the presence of Cu(I) catalysts.19
Based on this, we ran a reaction under O2 atmosphere, and the
yield of indole (6a) improved to 72%, and the reaction time was
shortened from 1 h to 30 min (Entry 9), showing that O2 indeed
assisted the oxidation process of indoline in the reaction. As
a result, the following optimizations were conducted under O2
atmosphere. We further tested different copper catalysts
including Cu(I), Cu(II) and Cu(I)/Cu(II) as co-catalyst, but did not
receive good result (Entries 10–14). Interestingly, if the reaction
was conducted under microwave irradiation, bromoamine was
consumed within 5 min and produced 60% of indoline 5a and
13% of indole 6a (Entry 15). Whereas, as we prolonged the
reaction time, indoline experienced decomposition without any
Entry
R1
R2
6
Yield%
1
2
3
4
5
6
7
8
9
H
OMe
OMe
OMe
OMe
OMe
OMe
H
6a
6b
6c
6d
6e
6f
6g
6h
6i
70%
72%
57%
23%
28%
24%
84%
63%
67%
5-OMe
4,5-DiOMe
4,5-OCH2O–
5-OPr
3,4-(CH4)
H
H
H
Me
iPr
a
Reaction conditions: (i) 3 (1 mmol), LAH (4 mmol), ether (10 mL), 0 ꢁC,
N2, 1 h. (ii) CuI (0.1 mmol), L-phenylalanine (0.2 mmol), K2CO3 (2
mmol), DMSO (1 mL), 100 ꢁC, under O2, 30 min. b Isoated yields.
Table 3 Optimization of indolization of amine
Yield (%)
Entrya
Ligand
Base
Catalyst
Solvent
Temp. (ꢁC)
Time (h)
5ae
6ae
1
2
3
4
5
6
7
8
L-Proline
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cul
Cul
Cul
Cul
Cul
Cul
Cul
Cul
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
1,4-Dioxane
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
80
80
80
80
3
3
3
3
1
1
1
1
49
30
8
16
17
30
54
60
64
54
49
72
50
58
49
34
39
13
4-Hydroxyproline
1,10-Phenanthroline
L-Phenylalanine
L-Phenylalanine
L-Phenylalanine
L-Phenylalanine
L-Phenylalanine
L-Phenylalanine
L-Phenylalanine
L-Phenylalanine
L-Phenylalanine
L-Phenylalanine
L-Phenylalanine
L-Phenylalanine
—
—
—
—
—
—
—
—
—
—
—
60
100
100
100
100
100
100
100
100
100
100
100
9b
10b
11b
12b
13bc
14b
15d
Cul
0.5
2
3
CuCl
CuBr
Cu(OAc)2
CuSO4
Cul/Cu(OAc)2
Cul
1
2.5
2.5
0.083
a
Reaction conditions: 4a (1 mmol), catalyst (10 mol%), ligand (20 mol%), K2CO3 (2 eq.), solvent (1 mL). b Under O2. c CuI : Cu(OAc)2 ¼ 5 mol% : 5
mol%. d Microwave 100 W. e NMR yields.
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to the coupling reactions without further purication under
optimized reaction conditions as shown in Table 4. In the case
of 5-methoxy-substituted bromoamine (Table 4, Entry 2), the
reaction yielded desired indole derivative in 72% yield. The
current protocol works with other strong electron donating
groups in obtaining the desired product in low to moderate
yields (Table 4, Entries 3, 4 and 5). In case of naphthyl derivative
also the desired indole product was obtained in low yield (Table
3, Entry 6). There is a signicant enhancement in the yield of
the desired indole product in case of substituents like Me, i-Pr
and unsubstituted derivatives (Table 4, Entries 7, 8 and 9).
Latter the scope of the current protocol was examined on
other nitroalkane derivatives derived from 3-bromoanisole and
subjected to optimized reaction conditions. But we found that
under optimized reaction conditions along with the formation
Scheme 3 Synthesis of 3-arylindole 6r.
minutes and got excellent yield of 3-arylindole (6r) as sole
product (Scheme 3).
Experimental section
General information
of desired 3-arylindole derivatives, 10–20% of indolines were Reagents and solvents were purchased from various commer-
observed which was difficult to separate by column chroma- cial sources and were used directly without any further puri-
tography. Subsequently we treated the crude mixtures with cation, unless otherwise stated. Column chromatography was
MnO2 as oxidant and it oxidized the indolines to the corre- performed with 63–200 mesh silica gel. 1H and 13C NMR spectra
sponding indole products without decomposition. Therefore, were recorded at 400 and 100 MHz, or 500 and 125 MHz,
for the synthesis of these 3-arylindoles (6j–6q), we conducted respectively. Chemical shis are reported in parts per million
additional oxidation process of crude products aer Ullmann (d) using TMS and chloroform as internal standards and
reaction, and achieved 3-arylindole derivatives with moderate to coupling constants are expressed in Hertz. Melting points were
good yields as shown in Table 5. The present method works well recorded using an electro thermal capillary melting point
with various substituents such as Me, OMe, Cl and naphthyl in apparatus and are uncorrected. HRMS spectra were recorded
delivering the desired indole derivatives in good yield. But in using ESI-TOF or EI+ mode. The starting material b-nitrostyrene
the presence of t-butyl substituent desired indole product (6m) derivatives 1 were synthesized from functionalized benzalde-
obtained in low yield. Interestingly, as we trying to reduce hydes and nitromethane followed by the reported literatures.
nitroalkane (3r) with LAH, the reaction did not produce the
General procedure for nitroalkanes 3. b-Nitrostyrene deriv-
expected bromoamine, but the mixture of indoline and indole ative 1 (5 mmol) and granular AlCl3 (1.334 g, 10 mmol) were
(6r) was observed in poor yield. Latter nitroalkane 3r treated placed in an oven-dried round bottom ask and thoroughly
with SiO2-supported with Fe in reuxing AcOH/EtOH for 10 lled it with N2. Dry DCM (20 mL) was then added to the ask,
and the mixture was stirred at ꢀ78 ꢁC for 10 min. The arene (6
mmol) was then added dropwise to the ask via a syringe, and
the reaction was monitored by TLC. Aer the reaction was
Table 5 Synthesis of 3-arylindole derivatives from 4-methoxy-2-
bromonitroalkane precursorsa,b,c
nished, the reaction was quenched with ice-cold brine. The
reaction mixture was extracted with DCM and water, and the
DCM layer was separated, dried over anhydrous MgSO4 and
concentrated under vacuum to give the crude product. The
crude product was furthered puried by column chromatog-
raphy using EA/hexane as eluent to yield the desired product 3.
General procedure for indole 6a–6i. An oven-dried 50 mL
round bottom ask with dropping funnel was added LAH
(0.1518 g, 4 mmol) and lled with N2. The ask was cooled to
Entry
R1
R2
6
Yield%
0
ꢁC and added dry ether/THF (4 mL), and the nitroalkane
1
2
3
4
5
6
7
8
9
H
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
6j
6k
6l
6m
6n
6o
6p
6q
6r
62%
65%
74%
21%
62%
80%
56%
60%
00%
derivative 3 (1 mmol) in ether/THF (6 mL) was slowly added to
the ask, and stirred for 1 h. Aer that, the reaction was care-
fully quenched with H2O (1.5 mL) and the precipitate was
ltered. The ltrate was dried over anhydrous MgSO4, concen-
trated at low temperature and dried under vacuum to give the
amine 4.
2-Me
4-Me
4-t-Bu
3-OMe
2,3-(CH)4
3-Cl
4-Cl
2-NO2
The amine 4 was then dissolved in DMSO (1 mL) and added
CuI (0.019 g, 0.1 mmol) and L-phenylalanine (0.033 g, 0.2
a
Reaction conditions: (i) 3 (1 mmol), LAH (4 mmol), ether (10 mL), 0 ꢁC, mmol), which was then heated to 100 ꢁC for 2–5 min before
N2, 1 h. (ii) CuI (0.1 mmol), L-phenylalanine (0.2 mmol), K2CO3 (2
K2CO3 (0.2764 g, 2 mmol) was added. Aer that, the reaction
was stirred with an O2 balloon for 30 min, and then quenched
b
mmol), DMSO (1 mL), 100 ꢁC, under O2, 30 min. Isoated yields.
c
MnO2 (10 eq.), DCM (5 mL), silica gel (0.25 g), reux, 12 h.
with water. The reaction mixture was extracted with EA and
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water, the EA layer was washed with water, dried over anhydrous 128.9, 115.1, 114.6, 113.5, 108.2, 102.2, 78.1, 55.4, 46.9; HRMS
MgSO4 and concentrated under vacuum to give the crude (EI) m/z calcd for C16H14NO5Br (M+) 379.0048, found 379.0055.
product. The crude product was furthered puried by column
1-Bromo-2-(1-(4-methoxyphenyl)-2-nitroethyl)-4-propoxyben-
1
chromatography using EA/hexane as eluent to yield the desired zene (3e). Yield: 315 mg, 64%. Yellow oil. H-NMR (400 MHz,
product 6a–6j. For indole 6b, the crude product was dissolved in CDCl3) d 7.45 (d, J ¼ 8.7 Hz, 1H), 7.20 (d, J ¼ 8.7 Hz, 2H), 6.86 (d,
DCM and treated with DDQ (0.227 g, 1 mmol) for 1 h before J ¼ 8.7 Hz, 2H), 6.75 (d, J ¼ 2.9 Hz, 1H), 6.67 (dd, J ¼ 8.7, 2.9 Hz,
purication.
1H), 5.31 (t, J ¼ 8.2 Hz, 1H), 4.98–4.82 (m, 2H), 3.84 (t, J ¼ 6.6 Hz,
General procedure for indole 6k–6r. The general procedure 2H) 3.77 (s, 3H), 1.83–1.73 (m, 2H), 1.02 (t, J ¼ 7.4 Hz, 3H); 13C-
was as same as the procedure for 6a–6i. The crude product 6k– NMR (100 MHz, CDCl3) d 159.2, 158.9, 139.5, 134.3, 129.7, 129.3,
6r was dissolved in DCM (5 mL) and added MnO2 (0.87 g, 10 115.7, 114.9, 114.5, 78.2, 70.0, 55.4, 47.2, 22.6, 10.6; HRMS (EI)
mmol), SiO2 (0.25 g), and heated to reux for 12 h. Aer the m/z calcd for C19H22NO4Br (M+) 393.0576, found 393.0585.
indoline was consumed, the solvent was dried and the cruRe-
public of Chinade was puried by column chromatography (3f). Yield: 294 mg, 76%. Red oil. 1H-NMR (400 MHz, CDCl3)
using EA/hexane as eluent to yield the desired product 6k–6r.
1-Bromo-2-(1-(4-methoxyphenyl)-2-nitroethyl)naphthalene
d 8.39 (d, J ¼ 8.5 Hz, 1H), 7.81 (d, J ¼ 6.6 Hz, 2H), 7.64 (t, J ¼ 7.2
General procedure for indole 6r. A mixture of nitroalkane 3r Hz, 1H), 7.55 (t, J ¼ 7.4 Hz, 1H), 7.35–7.28 (m, 3H), 6.94 (d, J ¼
(0.381 g, 1 mmol), iron powder (0.28 g, 5 mmol) and SiO2 (0.25 8.6 Hz, 2H), 5.85 (t, J ¼ 8.1 Hz, 1H), 5.07 (d, J ¼ 8.1 Hz, 2H) 3.80
g) iꢁn EtOH (1.25 mL) was added AcOH (1.25 mL) and heated to (s, 3H); 13C-NMR (100 MHz, CDCl3) d 159.1, 136.5, 133.8, 132.8,
80 C for 10 min. The reaction was ltered through celite and 130.1, 129.1, 128.6, 128.3, 128.1, 128.0, 127.1, 125.1, 124.9,
washed with EA, the ltrate was then concentrated under 114.6, 78.1, 55.4, 47.9; HRMS (EI) m/z calcd for C19H16NO3Br
vacuum to give the crude product. The crude product was (M+) 385.0314, found 385.0314.
furthered puried by column chromatography using EA/hexane
as eluent to yield the desired product 3r.
1-Bromo-2-(2-nitro-1-phenylethyl)benzene (3g). Yield: 272
mg, 89%. Yellow oil. 1H-NMR (400 MHz, CDCl3) d 7.63 (d, J ¼ 7.9
Hz, 1H), 7.40–7.34 (m, 2H), 7.34–7.28 (m, 4H), 7.28–7.23 (m,
1H), 7.20–7.14 (m, 1H), 5.49 (t, J ¼ 8.1 Hz, 1H), 5.06–4.93 (m,
2H); 13C-NMR (100 MHz, CDCl3) d 138.3, 137.9, 134.0, 129.3,
Spectral data of compounds
1-Bromo-2-(1-(4-methoxyphenyl)-2-nitroethyl)benzene (3a). 129.2, 128.5, 128.2, 128.1, 127.9, 125.1, 78.1, 47.8; HRMS (EI) m/
Yield: 329 mg, 98%. Colorless solid. Mp: 78–80 ꢁC. 1H-NMR (400 z calcd for C14H12NO2Br (M+) 305.0051, found 305.0053.
MHz, CDCl3) d 7.59 (d, J ¼ 7.9 Hz, 1H), 7.30 (td, J ¼ 8.0, 1.0 Hz,
1-Bromo-2-(2-nitro-1-(p-tolyl)ethyl)benzene (3h). Yield: 231
1H), 7.23–7.16 (m, 3H), 7.16–7.10 (td, J ¼ 7.1, 1.6 Hz, 1H), 6.86 mg, 72%. Yellow oil. 1H-NMR (400 MHz, CDCl3) d 7.60 (d, J ¼ 8.0
(d, J ¼ 4.4 Hz, 2H), 5.38 (t, J ¼ 8.1 Hz, 1H), 4.97 (dd, J ¼ 13.2, 7.5 Hz, 1H), 7.32.7.25 (m, 1H), 7.24–7.20 (m, 1H), 7.19–7.11 (m, 5H),
Hz, 1H), 4.89 (dd, J ¼ 13.2, 8.8 Hz, 1H), 3.78 (s, 3H); 13C-NMR 5.42 (t, J ¼ 8.1 Hz, 1H), 5.01–4.88 (m, 2H); 13C-NMR (100 MHz,
(100 MHz, CDCl3) d 159.3, 138.7, 134.0, 129.8, 129.3, 129.3, CDCl3) d 138.6, 137.7, 134.8, 134.0, 129.9, 129.2, 128.5, 128.1,
128.4, 128.1, 125.1, 114.6, 78.3, 55.5, 47.2; HRMS (EI) m/z calcd 125.1, 78.2, 47.5, 21.2; HRMS (EI) m/z calcd for C15H14NO2Br
for C15H14NO3Br (M+) 335.0157, found 335.0158.
(M+) 319.0208, found 319.0208.
1-Bromo-4-methoxy-2-(1-(4-methoxyphenyl)-2-nitroethyl)
1-Bromo-2-(1-(4-isopropylphenyl)-2-nitroethyl)benzene (3i).
benzene (3b). Yield: 256 mg, 70%. Yellow oil. 1H-NMR (400 Yield: 233 mg, 67%. Yellow oil. 1H-NMR (400 MHz, CDCl3) d 7.59
MHz, CDCl3) d 7.47 (d, J ¼ 7.8 Hz, 1H), 7.20 (d, J ¼ 8.4 Hz, 2H), (d, J ¼ 8.0 Hz, 1H), 7.33–7.25 (m, 1H), 7.25–7.20 (m, 1H), 7.18 (s,
6.86 (d, J ¼ 8.4 Hz, 2H), 6.75 (d, J ¼ 2.5 Hz, 1H), 6.68 (dd, J ¼ 8.8, 4H), 7.16–7.10 (m, 1H), 5.42 (t, J ¼ 8.1 Hz, 1H), 5.01–4.88 (m,
2.6 Hz, 1H), 5.32 (t, J ¼ 8.0 Hz, 1H), 5.00–4.83 (m, 2H), 3.77 (s, 2H), 1.23 (s, 3H), 1.21 (s, 3H); 13C-NMR (100 MHz, CDCl3)
3H), 3.74 (s, 3H); 13C-NMR (100 MHz, CDCl3) d 159.3, 159.2, d 148.6, 138.6, 135.1, 134.0, 129.2, 128.6, 128.1, 127.3, 125.1,
139.6, 134.4, 129.6, 129.3, 115.3, 115.2, 114.6, 113.9, 78.2, 55.6, 78.2, 47.5, 33.9, 24.1; HRMS (EI) m/z calcd for C17H18NO2Br (M+)
55.4, 47.2. HRMS (EI) m/z calcd for C16H16NO4Br (M+) 365.0263, 347.0521, found 347.0519.
found 365.0255.
2-Bromo-4-methox-1-(2-nitro-1-phenylethyl)benzene
(3j).
1-Bromo-4,5-dimethoxy-2-(1-(4-methoxyphenyl)-2-nitroethyl) Yield: 326 mg, 97%. Yellow oil. 1H-NMR (400 MHz, CDCl3)
ꢁ
benzene (3c). Yield: 281 mg, 71%. Yellow solid. Mp: 71–72 C. d 7.39–7.31 (m, 2H), 7.31–7.24 (m, 3H), 7.16 (d, J ¼ 2.5 Hz, 1H),
1H-NMR (400 MHz, CDCl3) d 7.17 (d, J ¼ 8.6 Hz, 2H), 7.03 (s, 1H), 7.12 (d, J ¼ 8.7 Hz, 1H), 6.85 (dd, J ¼ 8.6, 2.5 Hz, 1H), 5.39 (t, J ¼
6.85 (d, J ¼ 8.6 Hz, 2H), 6.66 (s, 1H), 5.29 (t, J ¼ 8.3 Hz, 1H), 4.97– 8.2 Hz, 1H), 4.96 (dd, J ¼ 13.4, 7.7 Hz, 1H), 4.92 (dd, J ¼ 13.2, 8.6
4.84 (m, 2H), 3.81 (s, 3H), 3.77 (s, 3H), 3.75 (s, 3H); 13C-NMR Hz, 1H), 3.77 (s, 3H); 13C-NMR (100 MHz, CDCl3) d 159.4, 138.3,
(100 MHz, CDCl3) d 159.1, 149.0, 148.8, 130.3, 130.0, 128.9, 130.2, 129.1, 128.9, 128.0, 127.8, 125.2, 119.1, 114.1, 78.2, 55.7,
116.3, 114.8, 114.5, 111.3, 78.2, 56.2, 55.3, 46.8; HRMS (ESI) m/z 47.1; HRMS (EI) m/z calcd for C15H14NO3Br (M+) 335.0157,
calcd for C17H18NO5BrNa (M+ + Na) 418.0260, found 418.0252. found 335.0151.
5-Bromo-6-(1-(4-methoxyphenyl)-2-nitroethyl)benzo[d][1,3]
2-Bromo-4-methoxy-1-(2-nitro-1-(o-tolyl)ethyl)benzene (3k).
dioxole (3d). Yield: 243 mg, 64%. Yellow solid. Mp: 106–107 ꢁC. Yield: 95 mg, 27%. Yellow oil. 1H-NMR (400 MHz, CDCl3) d 7.29–
1H-NMR (400 MHz, CDCl3) d 7.18 (d, J ¼ 8.7 Hz, 2H), 7.03 (s, 1H), 7.20 (m, 4H), 7.21 (d, J ¼ 2.4 Hz, 1H), 6.98 (d, J ¼ 8.7 Hz, 1H),
6.87 (d, J ¼ 8.7 Hz, 2H), 6.67 (s, 1H), 5.93 (dd, J ¼ 6.6, 1.1 Hz, 6.80 (dd, J ¼ 8.7, 2.6 Hz, 1H), 5.51 (dd, J ¼ 9.1, 7.1 Hz, 1H), 4.95–
2H), 5.32 (t, J ¼ 8.2 Hz, 1H), 4.84 (d, J ¼ 8.2 Hz, 2H), 3.77 (s, 3H); 4.82 (m, 2H), 3.79 (s, 3H), 2.31 (s, 3H); 13C-NMR (100 MHz,
13C-NMR (100 MHz, CDCl3) d 159.1, 148.0, 147.8, 131.7, 129.9, CDCl3) d 159.5, 137.1, 136.3, 131.5, 129.8, 129.4, 127.8, 126.4,
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125.9, 125.2, 118.8, 114.0, 76.6, 55.7, 44.0, 19.6; HRMS (EI) m/z 1H), 7.47–7.42 (m, 1H), 7.26–7.24 (m, 1H), 7.16 (d, J ¼ 8.6 Hz,
calcd for C16H16NO3Br (M+) 349.0314, found 349.0308.
1H), 7.12 (d, J ¼ 2.6 Hz, 1H), 6.85 (dd, J ¼ 8.6, 2.6 Hz, 1H), 5.86
2-Bromo-4-methoxy-1-(2-nitro-1-(p-tolyl)ethyl)benzene (3l). (dd, J ¼ 8.6, 7.3 Hz, 1H), 5.09–4.97 (m, 2H), 3.76 (s, 3H); 13C-
Yield: 280 mg, 80%. Yellow oil. 1H-NMR (400 MHz, CDCl3) NMR (100 MHz, CDCl3) d 159.9, 150.0, 133.5, 132.8, 130.0,
d 7.16–7.13 (m, 5H), 7.11 (d, J ¼ 8.7 Hz, 1H), 6.84 (dd, J ¼ 8.7, 2.6 128.9, 128.6, 128.3, 125.9, 125.5, 119.7, 113.8, 76.2, 55.8, 43.1;
Hz, 1H), 5.34 (t, J ¼ 8.2 Hz, 1H), 4.96–4.86 (m, 2H), 3.77 (s, 3H), HRMS (ESI) m/z calcd for C15H13N2O5Br (M + Na+) 402.9900,
2.32 (s, 3H); 13C-NMR (100 MHz, CDCl3) d 159.2, 137.2, 135.2, found 402.9915.
130.3, 129.6, 128.7, 127.7, 125.0, 118.8, 113.8, 78.1, 55.4, 46.6,
20.9; HRMS (EI) m/z calcd for C16H16NO3Br (M+) 349.0315, Yield: 306 mg, 99%. Colorless oil. H-NMR (400 MHz, CDCl3)
found 349.0308.
2-(2-Bromophenyl)-2-(4-methoxyphenyl)ethanamine
(4a).
1
d 7.51 (d, J ¼ 7.8 Hz, 1H), 7.35–7.25 (m, 2H), 7.21 (d, J ¼ 8.6 Hz,
2-Bromo-1-(1-(4-isobutylphenyl)-2-nitroethyl)-4-methoxy- 2H), 7.08 (ddd, J ¼ 7.8, 6.6, 2.2 Hz, 1H), 6.88 (d, J ¼ 8.6 Hz, 2H),
benzene (3m). Yield: 353 mg, 90%. Yellow oil. 1H-NMR (400 4.48 (t, J ¼ 7.5 Hz, 1H), 3.80 (s, 3H), 3.30 (dd, J ¼ 12.9, 7.2 Hz,
MHz, CDCl3) d 7.17–7.09 (m, 6H), 6.84 (dd, J ¼ 8.6, 2.6 Hz, 1H), 1H), 3.27 (dd, J ¼ 13.2, 7.9 Hz, 1H), 1.28 (s, 2H); 13C-NMR (100
5.35 (t, J ¼ 8.2 Hz, 1H), 4.97–4.87 (m, 2H), 3.77 (s, 3H), 2.44 (d, J MHz, CDCl3) d 158.5, 142.4, 133.6, 133.5, 129.6, 128.7, 128.1,
¼ 7.2 Hz, 2H), 1.88–1.78 (m, 1H), 0.89 (d, J ¼ 6.6 Hz, 6H); 13C- 127.9, 125.9, 114.2, 55.4, 53.0, 47.0; HRMS (EI) m/z calcd for
NMR (100 MHz, CDCl3) d 159.4, 141.3, 135.6, 130.5, 129.9,
C
15H16NOBr (M+) 305.0415, found 305.0421.
129.0, 127.7, 125.3, 119.0, 114.1, 78.4, 55.7, 46.8, 45.2, 30.3, 22.6;
3-(4-Methoxyphenyl)indoline (5a). Colorless solid. Mp: 67–69
1
HRMS (ESI) m/z calcd for C19H22NO3Br (M+ + Na) 414.0675, ꢁC. H-NMR (400 MHz, CDCl3) d 7.20 (d, J ¼ 8.5 Hz, 2H), 7.11–
found 414.0683.
7.04 (m, 1H), 6.91 (d, J ¼ 7.0 Hz, 1H), 6.86 (d, J ¼ 8.7 Hz, 2H),
2-Bromo-4-methoxy-1-(1-(3-methoxyphenyl)-2-nitroethyl) 6.68–6.75 (m, 2H), 4.45 (t, J ¼ 9.2 Hz, 1H), 3.91 (t, J ¼ 9.0 Hz, 1H),
benzene (3n). Yield: 223 mg, 61%. Yellow oil. 1H-NMR (400 3.80 (s, 3H), 3.46 (t, J ¼ 9.0 Hz, 1H); 13C-NMR (100 MHz, CDCl3)
MHz, CDCl3) d 7.27–7.23 (m, 1H), 7.15 (d, J ¼ 2.7 Hz, 1H), 7.12 d 158.7, 151.7, 135.9, 132.9, 139.3, 127.9, 125.2, 119.3, 114.2,
(d, J ¼ 8.7 Hz, 1H), 6.86–6.80 (m, 4H), 5.36 (t, J ¼ 8.2 Hz, 1H), 110.0, 57.0, 55.5, 48.2. HRMS (EI) m/z calcd for C15H15NO (M+)
4.96–4.87 (m, 2H), 3.77 (s, 3H), 3.76 (s, 3H); 13C-NMR (100 MHz, 225.1154, found 225.1156.
CDCl3) d 160.1, 159.4, 139.9, 130.1, 128.9, 125.2, 120.1, 119.0,
114.3, 114.0, 112.7, 78.1, 55.6, 55.3, 47.0, 29.8; HRMS (EI) m/z Colorless solid. Mp: 133–134 ꢁC. 1H-NMR (400 MHz, CDCl3)
calcd for C16H16NO4Br (M+) 365.0263, found 365.0268.
3-(4-Methoxyphenyl)-1H-indole (6a). Yield: 156 mg, 70%.
d 8.17 (s, 1H), 7.96 (d, J ¼ 7.9 Hz, 1H), 7.64 (d, J ¼ 8.7 Hz, 2H),
1-(1-(2-Bromo-4-methoxyphenyl)-2-nitroethyl)naphthalene 7.44 (d, J ¼ 8.0 Hz, 1H), 7.34–7.21 (m, 3H), 7.06 (d, J ¼ 8.7 Hz,
(3o). Yield: 139 mg, 36%. Yellow oil. 1H-NMR (400 MHz, CDCl3) 2H), 3.91 (s, 3H); 13C-NMR (100 MHz, CDCl3) d 158.3, 136.8,
d 8.08 (d, J ¼ 8.3 Hz, 1H), 7.89 (d, J ¼ 7.8 Hz, 1H), 7.84 (d, J ¼ 7.9 128.8, 128.3, 126.1, 122.5, 121.4, 120.3, 119.9, 118.2, 114.5,
Hz, 1H), 7.58–7.43 (m, 4H), 7.26 (d, J ¼ 2.8, 1H), 7.00 (d, J ¼ 8.7 111.6, 55.6. HRMS (EI) m/z calcd for C15H13NO (M+) 223.0997,
Hz, 1H), 6.71 (dd, J ¼ 8.7, 2.6 Hz, 1H), 6.20 (dd, J ¼ 8.8, 7.2 Hz, found 223.1002.
1H), 5.09 (dd, J ¼ 13.7, 9.2 Hz, 1H), 4.97 (dd, J ¼ 13.7, 9.2 Hz,
5-Methoxy-3-(4-methoxyphenyl)-1H-indole (6b). Yield: 182
1
1H), 3.71 (s, 3H); 13C-NMR (100 MHz, CDCl3) d 159.5, 134.3, mg, 72%. Colorless solid. Mp: 193–194 C. H-NMR (400 MHz,
134.0, 131.4, 129.7, 129.7, 129.1, 128.7, 127.0, 126.1, 125.2, CDCl3) d 7.50 (d, J ¼ 8.7 Hz, 2H), 7.39 (d, J ¼ 8.9 Hz, 1H), 7.30 (d,
124.9, 124.0, 123.2, 119.0, 114.0, 76.6, 55.5, 43.5; HRMS (ESI) m/ J ¼ 2.3 Hz, 1H), 7.24 (s, 1H), 6.98 (d, J ¼ 8.7 Hz, 2H), 6.94 (dd, J ¼
ꢁ
z calcd for C19H16NO3Br (M + Na+) 408.0205, found 408.0206.
8.9, 2.3 Hz, 1H), 6.31 (s, 1H), 3.85 (s, 3H), 3.84 (s, 3H); 13C-NMR
2-Bromo-1-(1-(3-chlorophenyl)-2-nitroethyl)-4-methoxy- (100 MHz, CDCl3) d 158.5, 155.3, 132.0, 128.9, 127.9, 127.7,
benzene (3p). Yield: 126 mg, 34%. Yellow oil. 1H-NMR (400 124.8, 118.6, 114.6, 113.1, 110.4, 102.6, 56.2, 55.6. HRMS (EI) m/
MHz, CDCl3) d 7.30–7.26 (m, 3H), 7.21–7.19 (m, 2H), 7.12 (d, J ¼ z calcd for C16H15NO2 (M+) 253.1103, found 253.1106.
8.6 Hz, 1H), 6.89 (dd, J ¼ 8.6, 2.6 Hz, 1H), 5.4 (t, J ¼ 8.1 Hz, 1H),
5,6-Dimethoxy-3-(4-methoxyphenyl)-1H-indole (6c). Yield:
4.97–4.91 (m, 2H), 3.81 (s, 3H); 13C-NMR (100 MHz, CDCl3) 161 mg, 57%. Colorless solid. Mp: 207–208 ꢁC. 1H-NMR (400
d 159.6, 140.4, 135.0, 130.4, 129.4, 128.8, 128.3, 128.1, 126.2, MHz, CDCl3) d 8.04 (s, 1H), 7.56 (d, J ¼ 8.7 Hz, 2H), 7.30 (s, 1H),
125.2, 119.2, 114.2, 77.9, 55.7, 46.8; HRMS (EI) m/z calcd for 7.16 (d, J ¼ 2.3 Hz, 1H), 7.01 (d, J ¼ 8.7 Hz, 2H), 6.92 (s, 1H), 3.93
C
15H13NO3ClBr (M+) 368.9767, found 368.9775.
(s, 6H), 3.87 (s, 3H); 13C-NMR (100 MHz, CDCl3) d 158.3, 147.6,
2-Bromo-1-(1-(4-chlorophenyl)-2-nitroethyl)-4-methoxy- 145.7, 131.2, 128.7, 128.6, 119.9, 119.0, 118.2, 114.5, 101.8, 94.9,
benzene (3q). Yield: 259 mg, 70%. Yellow oil. 1H-NMR (400 56.7, 56.4, 55.6. HRMS (EI) m/z calcd for C17H17NO3 (M+)
MHz, CDCl3) d 7.30 (d, J ¼ 8.4 Hz, 2H), 7.19 (d, J ¼ 8.4 Hz, 2H), 283.1208, found 283.1213.
7.15 (d, J ¼ 2.6 Hz, 1H), 7.07 (d, J ¼ 8.7 Hz, 1H), 6.85 (dd, J ¼ 8.7,
7-(4-Methoxyphenyl)-5H-[1,3]dioxolo[4,5-f]indole (6d). Yield:
2.6 Hz, 1H), 5.34 (t, J ¼ 16.3 Hz, 1H), 4.96–4.85 (m, 2H), 3.78 (s, 61 mg, 23%. Colorless solid. Mp: 169–170 ꢁC. 1H-NMR (400
3H); 13C-NMR (100 MHz, CDCl3) d 159.6, 136.9, 133.8, 129.7, MHz, CDCl3) d 8.04 (s, 1H), 7.54–7.50 (m, 2H), 7.25 (s, 1H), 7.16
129.5, 129.3, 128.8, 125.2, 119.2, 114.2, 78.1, 55.8, 46.6; HRMS (d, J ¼ 2.5 Hz, 1H), 7.01–6.97 (m, 2H), 6.87 (s, 1H), 5.95 (s, 2H),
(EI) m/z calcd for
C
15H13NO3ClBr (M+) 368.9767, found 3.86 (s, 3H); 13C-NMR (100 MHz, CDCl3) d 158.3, 145.3, 143.7,
368.9775.
131.7, 128.7, 128.3, 120.1, 120.0, 118.6, 114.5, 100.9, 98.6, 92.3,
2-Bromo-4-methoxy-1-(2-nitro-1-(2-nitrophenyl)ethyl)benzene 55.6. HRMS (EI) m/z calcd for C16H13NO3 (M+) 267.0895, found
(3r). Yield: 358 mg, 94%. Yellow solid. Mp: 115–116 ꢁC 1H-NMR 267.0898.
(400 MHz, CDCl3) d 7.94 (dd, J ¼ 8.1, 1.2 Hz, 1H), 7.57–7.53 (m,
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3-(4-Methoxyphenyl)-5-propoxy-1H-indole (6e). Yield: 79 mg,
RSC Advances
6-Methoxy-3-(p-tolyl)-1H-indole (6l). Yield: 176 mg, 74%.
28%. Colorless oil. H-NMR (400 MHz, CDCl3) d 8.08 (s, 1H), Colorless solid. Mp: 110–111 ꢁC. 1H-NMR (400 MHz, CDCl3)
7.56 (d, J ¼ 7.9 Hz, 2H), 7.34–7.26 (m, 3H), 7.01 (d, J ¼ 7.9 Hz, d 8.05 (s, 1H), 7.79 (d, J ¼ 8.8 Hz, 1H), 7.55 (d, J ¼ 8.0 Hz, 2H),
2H), 6.91 (d, J ¼ 8.8 Hz, 1H), 3.97 (t, J ¼ 6.6 Hz, 2H), 3.87 (s, 3H), 7.24–7.23 (m, 2H), 6.91 (d, J ¼ 2.2 Hz, 1H), 6.86 (dd, J ¼ 8.8, 2.2
1.88–1.81 (m, 2H), 1.06 (t, J ¼ 4.8 Hz, 3H); 13C-NMR (100 MHz, Hz, 1H), 3.87 (s, 3H), 2.40 (s, 3H); 13C-NMR (100 MHz, CDCl3)
CDCl3) d 158.3, 154.3, 132.0, 128.7, 128.5, 126.6, 122.1, 118.1, d 156.9, 137.7, 135.7, 132.9, 129.6, 127.4, 120.7, 120.5, 120.4,
114.5, 113.3, 112.1, 103.1, 70.8, 55.6, 23.0, 10.8. HRMS (EI) m/z 118.5, 110.3, 95.0, 55.9, 21.3. HRMS (EI) m/z calcd for C16H15NO
1
calcd for C18H19NO2 (M+) 281.1416, found 281.1412.
(M+) 237.1154, found 237.1151.
3-(4-Methoxyphenyl)-1H-benzo[g]indole (6f). Yield: 66 mg,
3-(4-Isobutylphenyl)-6-methoxy-1H-indole (6m). Yield: 59
24%. Gray solid. Mp: 251–252 ꢁC. H-NMR (400 MHz, CDCl3) mg, 21%. Colorless solid. Mp: 77–78 ꢁC. 1H-NMR (400 MHz,
d 8.91 (s, 1H), 8.03 (d, J ¼ 8.6 Hz, 1H), 7.95 (d, J ¼ 8.9 Hz, 2H), CDCl3) d 8.06 (s, 1H), 7.81 (d, J ¼ 8.7 Hz, 1H), 7.56 (d, J ¼ 8.1 Hz,
7.64 (d, J ¼ 8.6 Hz, 2H), 7.59–7.53 (m, 2H), 7.47–7.44 (m, 1H), 2H), 7.24 (d, J ¼ 2.3 Hz, 1H), 7.21 (d, J ¼ 8.1 Hz, 2H), 6.90 (d, J ¼
7.36 (d, J ¼ 2.4 Hz, 1H), 7.03 (d, J ¼ 8.6 Hz, 2H), 3.88 (s, 3H); 13C- 2.2 Hz, 1H), 6.85 (dd, J ¼ 8.8, 2.3 Hz, 1H), 3.87 (s, 3H), 2.51 (d, J
NMR (100 MHz, CDCl3) d 158.5, 131.4, 130.8, 129.1, 128.3, 125.8, ¼ 7.1 Hz, 2H), 1.96–1.86 (m, 1H), 0.95 (d, J ¼ 6.6 Hz, 6H); 13C-
124.3, 122.0, 122.0, 121.2, 120.2, 119.9, 119.5, 119.5, 114.5, 55.6. NMR (100 MHz, CDCl3) d 156.9, 139.6, 137.7, 133.1, 129.7,
HRMS (EI) m/z calcd for C19H15NO (M+) 273.1154, found 127.2, 120.8, 120.6, 120.4, 118.6, 110.3, 95.0, 55.9, 45.4, 30.5,
1
273.1149.
22.6. HRMS (EI) m/z calcd for C19H21NO (M+) 279.1623, found
3-Phenyl-1H-indole (6g). Yield: 162 mg, 84%. Colorless solid. 279.1629.
Mp: 85–87 ꢁC. 1H-NMR (400 MHz, CDCl3) d 8.23 (s, 1H), 7.96 (d, J
6-Methoxy-3-(3-methoxyphenyl)-1H-indole (6n). Yield: 157
¼ 7.9 Hz, 1H), 7.69 (d, J ¼ 7.8 Hz, 2H), 7.49–7.42 (m, 3H), 7.38 (d, mg, 62%. Colorless oil. 1H-NMR (400 MHz, CDCl3) d 8.09 (s, 1H),
J ¼ 2.6 Hz, 1H), 7.33–7.18 (m, 3H); 13C-NMR (100 MHz, CDCl3) 7.81 (d, J ¼ 8.8 Hz, 1H), 7.37–7.33 (m, 1H), 7.27 (d, J ¼ 2.1 Hz,
d 136.9, 135.8, 129.0, 127.7, 126.2, 126.0, 122.6, 121.9, 120.5, 1H), 7.23–7.20 (m, 1H), 6.91–6.83 (m, 3H), 3.87 (s, 3H); 13C-NMR
120.0, 118.6, 111.6. HRMS (EI) m/z calcd for C14H11N (M+) (100 MHz, CDCl3) d 160.2, 157.0, 137.7, 137.2, 129.9, 120.8,
193.0891, found 193.0891.
120.8, 120.4, 120.1, 118.5, 113.2, 111.6, 110.5, 95.0, 55.9, 55.5.
3-(p-Tolyl)-1H-indole (6h). Yield: 130 mg, 63%. Colorless HRMS (EI) m/z calcd for C16H15NO2 (M+) 253.1103, found
1
ꢁ
solid. Mp: 88–90 C. H-NMR (400 MHz, CDCl3) d 8.21 (s, 1H), 253.1105.
7.98 (d, J ¼ 7.8 Hz, 1H), 7.62 (d, J ¼ 8.0 Hz, 2H), 7.45 (d, J ¼ 8.0
6-Methoxy-3-(naphthalen-1-yl)-1H-indole (6o). Yield: 219 mg,
Hz, 1H), 7.36 (d, J ¼ 1.2 Hz, 1H), 7.33–7.20 (m, 4H), 2.45 (s, 3H); 80%. Red oil. 1H-NMR (400 MHz, CDCl3) d 8.21 (s, 1H), 8.10 (d, J
13C-NMR (100 MHz, CDCl3) d 136.8, 135.8, 132.8, 129.7, 127.6, ¼ 8.5 Hz, 1H), 7.92 (d, J ¼ 8.1 Hz, 1H), 7.86 (d, J ¼ 8.1 Hz, 1H),
126.0, 122.5, 121.7, 120.4, 120.1, 118.5, 111.5, 21.4. HRMS (EI) 7.60–7.48 (m, 3H), 7.43–7.36 (m, 2H), 7.27–7.26 (m, 1H), 6.97 (d,
m/z calcd for C15H13N (M+) 207.1048, found 207.1049.
J ¼ 2.1 Hz, 1H), 6.80 (dd, J ¼ 8.8, 2.1 Hz, 1H), 3.89 (s, 3H); 13C-
3-(4-Isopropylphenyl)-1H-indole (6i). Yield: 157 mg, 63%. NMR (100 MHz, CDCl3) d 157.0, 137.0, 134.2, 133.3, 132.8, 128.5,
Colorless solid. Mp: 163–165 ꢁC. 1H-NMR (400 MHz, CDCl3) 127.8, 127.3, 126.8, 125.9, 125.9, 125.8, 122.5, 122.4, 121.2,
d 8.20 (s, 1H), 7.95 (d, J ¼ 7.88 Hz, 1H), 7.61 (d, J ¼ 8.2 Hz, 2H), 116.8, 110.3, 94.9, 56.0. HRMS (EI) m/z calcd for C19H15NO (M+)
7.43 (d, J ¼ 8.0 Hz, 1H), 7.35 (d, J ¼ 2.5 Hz, 1H), 7.32 (d, J ¼ 8.2 273.1154, found 273.1151.
Hz, 2H), 7.28–7.16 (m, 2H), 3.00–2.94 (m, 1H), 1.33 (s, 3H), 1.31
3-(3-Chlorophenyl)-6-methoxy-1H-indole (6p). Yield: 144 mg,
(s, 3H); 13C-NMR (100 MHz, CDCl3) d 146.8, 136.9, 133.2, 127.7, 56%. Colorless solid. Mp: 195–196 ꢁC. 1H-NMR (400 MHz,
127.0, 126.1, 122.5, 121.7, 120.4, 120.1, 118.6, 111.5, 34.1, 24.3. CDCl3) d 7.79 (d, J ¼ 8.7 Hz, 1H), 7.60–7.59 (m, 1H), 7.51–7.48
HRMS (EI) m/z calcd for C17H17N (M+) 235.1361, found (m, 1H), 7.38–7.34 (m, 1H), 7.28–7.25 (m, 2H), 6.98 (d, J ¼ 2.1
235.1361.
Hz, 2H), 6.92 (dd, J ¼ 8.8, 2.2 Hz, 1H), 6.31 (s, 1H), 3.86 (s, 3H);
6-Methoxy-3-phenyl-1H-indole (6j). Yield: 138 mg, 62%. 13C-NMR (100 MHz, CDCl3) d 157.5, 137.7, 136.9, 134.8, 130.2,
Colorless solid. Mp: 147–148 ꢁC. 1H-NMR (500 MHz, CDCl3) 127.5, 126.5, 125.7, 123.6, 121.2, 121.1, 118.2, 110.8, 93.8, 55.9.
d 8.10 (s, 1H), 7.81 (d, J ¼ 8.8 Hz, 1H), 7.65 (d, J ¼ 7.3 Hz, 2H), HRMS (EI) m/z calcd for C15H12NOCl (M+) 257.0607, found
7.43 (t, J ¼ 7.6 Hz, 2H), 7.30–7.24 (m, 2H), 6.90 (d, J ¼ 2.1 Hz, 257.0601.
1H), 6.87 (dd, J ¼ 8.8, 2.1 Hz, 1H), 3.87 (s, 3H); 13C-NMR (125
3-(4-Chlorophenyl)-6-methoxy-1H-indene (6q). Yield: 155
MHz, CDCl3) d 156.9, 137.7, 135.8, 128.9, 127.5, 126.1, 120.7, mg, 60%. Yellow solid. Mp: 154–155 ꢁC. 1H-NMR (400 MHz,
120.7, 120.4, 118.6, 110.5, 95.0, 55.9. HRMS (EI) m/z calcd for CDCl3) d 8.10 (s, 1H), 7.75 (d, J ¼ 8.7 Hz, 1H), 7.59–7.55 (m, 2H),
C
15H13NO (M+) 223.0997, found 223.1001.
7.41–7.38 (m, 2H), 7.24 (d, J ¼ 2.5 Hz, 1H), 6.91 (d, J ¼ 2.2 Hz,
6-Methoxy-3-(o-tolyl)-1H-indole (6k). Yield: 154 mg, 65%. 1H), 6.87 (dd, J ¼ 8.7, 2.2 Hz, 1H), 3.87 (s, 3H); 13C-NMR (100
1
Colorless oil. H-NMR (400 MHz, CDCl3) d 8.09 (s, 1H), 7.43– MHz, CDCl3) d 157.0, 137.7, 134.3, 131.7, 129.1, 128.6, 120.8,
7.38 (m, 2H), 7.33–7.31 (m, 1H), 7.27–7.24 (m, 2H), 7.08 (s, 1H), 120.5, 120.1, 117.3, 110.7, 95.1, 55.9. HRMS (EI) m/z calcd for
6.92 (s, 1H), 6.82 (d, J ¼ 8.7 Hz, 1H), 3.87 (s, 3H), 2.33 (s, 3H);
C
15H12NOCl (M+) 257.0607, found 257.0602.
3-(2-Bromo-4-methoxyphenyl)-1H-indole (6r). Yield: 275 mg,
13C-NMR (100 MHz, CDCl3) d 156.8, 137.0, 136.9, 134.8, 131.0,
130.5, 126.9, 125.8, 121.9, 121.7, 121.0, 117.7, 110.1, 94.9, 55.9, 91%. Yellow solid. Mp: 122–123 ꢁC. 1H-NMR (400 MHz, CDCl3)
20.9. HRMS (EI) m/z calcd for C16H15NO (M+) 237.1154, found d 8.26 (s, 1H), 7.58 (d, J ¼ 7.9 Hz, 1H), 7.43 (d, J ¼ 4.2 Hz, 2H),
237.1148.
7.36 (d, J ¼ 2.5 Hz, 1H), 7.29 (d, J ¼ 2.5 Hz, 1H), 7.26–7.22 (m,
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1H), 7.18–7.14 (m, 1H), 6.95 (dd, J ¼ 8.5, 2.6 Hz, 1H), 3.86 (s,
3H); 13C-NMR (100 MHz, CDCl3) d 159.0, 135.9, 132.7, 128.3,
127.1, 124.5, 123.9, 122.5, 120.3, 120.2, 118.6, 116.6, 113.7,
111.4, 55.8. HRMS (EI) m/z calcd for C15H12NOBr (M+) 301.0102,
found 301.0109.
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Conclusions
In summary, we successfully synthesized unprotected NH 3-
arylindole derivatives via Cu catalysed intramolecular Ullmann
reaction of bromoamines starting from easily available nitro-
styrene starting materials. The substructures on both indole
and 3-aryl groups can be exible based on the choices of b-
nitrostyrenes and arenes.
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Acknowledgements
Financial support by the Ministry of Science and Technology of
the Republic of China (MOST 103-2113-M-003-008-MY3),
National Taiwan Normal University (103-07-C) and Instrumen-
tation Centre at National Taiwan Normal University is gratefully
acknowledged. The authors are grateful to Ms Hsiu-Ni Huan,
Ms Chiu-Hui He and Ting-Shen Kuo for providing HRMS, NMR
spectral and crystallographic data respectively.
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