Highly efficient synthesis of unsymmetrical 3,3'-bis(1h-indol-3-yl)methanes in water

Article abstract of DOI:10.1002/cjoc.201200496

A simple and practical approach for the preparation of unsymmetric bis(indolyl)methanes (BIMs) was realized by Lewis acid InBr₃- catalyzed Friedel-Crafts reaction of indoles with 3-indolyl-substituted phthalides in water. A simple and practical approach for the preparation of unsymmetric bis(indolyl)-methanes (BIMs) was realized by Lewis acid InBr ₃-catalyzed Friedel-Crafts reaction of indoles with 3-indolyl-substituted phthalides in water. Copyright

Full text of DOI:10.1002/cjoc.201200496

FULL PAPER
DOI: 10.1002/cjoc.201200496
Highly Efficient Synthesis of Unsymmetrical
3,3'-Bis(1H-indol-3-yl)methanes in Water
Lin, Huaa(林华)
Zang, Yanga(臧扬)
Sun, Xingwen*,a(孙兴文)
Lin, Guoqiang*,b(林国强)
a Department of Chemistry, Fudan University, Shanghai 200433, China
b Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, China
A simple and practical approach for the preparation of unsymmetric bis(indolyl)methanes (BIMs) was realized
by Lewis acid InBr3-catalyzed Friedel-Crafts reaction of indoles with 3-indolyl-substituted phthalides in water.
Keywords unsymmetric bis(indolyl)methanes, InBr3, Friedel-Crafts reaction, indole, 3-indolyl-substituted
phthalide
Introduction
gramine using an expensive catalyst.[6d] Bhuyan and
co-workers reported the synthesis of 3-alkylated indoles
from a three-components reaction of indole, aldehyde,
and N,N-dimethylbarbituric acid, undergoing an elimi-
nation-addition reaction with another indole molecule
and giving unsymmetrical BIMs in the absence of a
catalyst.[6e]
Developing new and environmentally benign syn-
thetic methods is important in organic synthesis. In re-
cent years, organic reactions that can proceed in aque-
ous media have attracted great interest because of its
significant environmental and economical advantages
over those occurring in organic solvents.[7] Thus, it is of
interest to develop a practical and general method for
the synthesis of unsymmetrical BIMs in water in view
of economical and environmental concerns. Following
our interest in green chemistry and medicinal chemistry,
we herein present a new route to synthesize unsymmet-
rical BIMs in pure water.
The indole ring is widely present in a variety of bio-
logically active compounds and has become an impor-
tant structural component in many pharmaceutical
agents.[1] Among various indole derivates, bis(indolyl)-
methanes (BIMs) which were isolated from various ter-
restrial and marine natural sources exhibit a wide range
of biological activities,[2] such as, promoting beneficial
estrogen metabolism and inducing apoptosis in human
cancer cell.[3] Especially, its various potent anticancer
activities made it beginning clinical trials as a therapeu-
tic for numerous forms of cancer. Therefore, the demand
for efficient synthesis of BIMs become an increasing
interest in organic synthesis.[4] Although the synthesis of
symmetrical BIMs has been studied extensively over the
past decades, the synthesis of unsymmetrical BIMs is
still highly sought-after in synthetic community.[5] To
the best of our knowledge, there were only a few reports
published for the synthesis of unsymmetrical BIMs to
date.[6] Vallee and co-workers reported the first synthe-
sis of such BIMs from hydroxyamines and indoles, but
the procedure was a little bit complicated.[6a] Chakra-
barty and co-workers reported the preparation of BIMs
through the Michael reaction of 3-(2-nitrovinyl)indole
with indoles.[6b] However, the method was limited to
2,2-bis(indol-3-yl)-1-nitroethane derivatives. Ji and
co-workers reported the synthesis of unsymmetrical
BIMs from the reaction of indoles bearing electron-
donating group with (1H-indol-3-yl)-(alkyl)methanols
catalyzed by ammonium cerium(IV) nitrate under ul-
trasonic irradiation in good yields.[6c] Csaky and
co-workers have synthesized unsymmetrical BIMs from
Results and Discussion
Recently, we reported the synthesis of 3-indolyl-
substituted phthalides in water in the absence of a cata-
lyst.[8] During the investigation, we observed that the
product of the Friedel-Crafts reaction between indole
and 2-formylbenzoic acid depended on the loading ratio
of the two reactants when the reaction was performed in
the presence of Lewis acid catalyst (InBr3, in CH2Cl2,
Scheme 1). When the loading ratio of reactants 1a and
2a was 1∶1.5, 3-indoly-substituted phthalide 3a was
obtained in 95% yield. However, when the ratio was
changed to 5∶1, BIM 4a was obtained in 94% yield. It
*
E-mail: sunxingwen@fudan.edu.cn; Tel.: 0086-021-55664460
Received May 22, 2012; accepted June 4, 2012; published online XXXX, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201200496 or from the author.
Chin. J. Chem. 2012, XX, 1—6
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1

Lin et al.
FULL PAPER
is reasonable to propose that 3-indolylsubstituted
phthalide 3a was formed first, and then it reacted with
another molecule of indole 1a to afford BIM 3a. In vi-
sion of this, we could introduce another different sub-
stituted indole molecule to 3-indolyl-substituted
phthalides in order to obtain unsymmetrical BIMs.
Unfortunately, there was no desired product obtained
at room temperature after 24 h (Table 1, Entry 2). Then
we examined the effects of the reaction temperature
(Table 1, Entries 3—5). Finally, we found that the de-
sired BIM product can be obtained in 91% yield at 80
℃ (Table 1, Entry 5).
With the optimal reaction conditions in hand (Table
1, Entry 5), the scope of this reaction was investigated.
To our delight, the 5- or 6-position-substituent of the
phenyl ring of indole with either an electron-donating
(Me, OMe, OBn) or -withdrawing group (Br, Cl, F)
could be successfully employed to afford the corre-
sponding BIMs in excellent yields (Table 2, Entries
1—7, yield＞90%). Also the indole with strong
electron-withdrawing group (NO2) at 6-position could
give the desired BIM product in 87% yield in the stan-
dard condition. But unfortunately, the indole bearing
NO2 group at 7-position was not a suitable substrate.
However, the reaction of indole with the 3-indole sub-
stituted phthalide which bears NO2 group on the
7-position of phenyl ring of indole underwent smoothly,
giving the corresponding BIM in 80% yield respectively
(Table 2, Entry 9). Furthermore, this method was appli-
cable to various 3-indolyl-substituted phthalides. With
not only electron-donating group but also electron-
withdrawing group at the phthalide ring, 3-indolyl-sub-
stituted phthalides were suitable substrates. The corre-
sponding BIMs were obtained in good to excellent
yields (Table 2, Entries 10—12).
Scheme 1 InBr3 catalysted Friedel-Crafts reaction between
indole and 2-formylbenzoic acid
O
O
InBr3
O
(5 mol%)
+
CH2Cl2
r.t., 4 h
OH
N
H
N
O
2a
H
1a
3a
95%
1 equiv.
1.5 equiv.
O
COOH
InBr3
(5 mol%)
+
OH
CH2Cl2
r.t., 4 h
N
H
N
N
H
H
O
4a
2a
1a
94%
1 equiv.
5 equiv.
With this idea in mind, preliminary experiment was
performed by using 5-methylindole 1b and 3-indolyl-
substituted phthalide 3a as model substrates, CH2Cl2 as
solvent and InBr3 as catalyst. Pleasingly the reaction
processed smoothly at room temperature, to afford the
desired BIM 4b in 97% yield (Table 1, Entry 1). In the
view of green chemistry, we next carried out the reac-
tion in water.
Conclusions
In summary, we have developed a simple, novel and
efficient synthetic protocol for the synthesis of unsym-
metric BIMs by InBr3-catalyzed Friedel-Crafts reaction
of indoles with 3-indolyl-substituted phthalides in water
in good to excellent yields. We are currently investigat-
ing the bioactivity of the BIM compounds. To our de-
light, preliminary experiments indicated that this BIM
compounds present excellent anti-Alzheimer’s Disease
activity, and the results will be reported in due course.
Table 1 Optimization of the reaction conditionsa
O
InBr3
(5 mol%)
O
Me
+
solvent
N
H
N
H
1b
3a
COOH
Experimental
Me
General procedure for synthesis of unsymmetric
bis(1H-indol-3-yl)alkanes in water
N
H
N
H
4b
InBr3 (5 mol%) was added to a suspension of
3-indolyl substituted phthalide (0.2 mmol) and indole
(0.3 mmol) in water. Then the mixture was heated to 80
℃ until completion indicated by TLC. The reaction
mixture was extracted with CH2Cl2 (10 mL×3). The
organic phase was washed with brine, dried over anhy-
drous Na2SO4, filtered and concentrated. The residue
was purified on silica gel to afford the desired product.
2-((1H-Indol-2-yl)(5-methyl-1H-indol-2-yl)meth-
yl)benzoic acid (4b) White solid; 1H NMR (400 MHz,
Acetone-d6) δ: 9.90 (s, 1H), 9.79 (s, 1H), 7.91 (d, J＝8.4
Hz, 1H), 7.32—7.40 (m, 4H), 7.22—7.28 (m, 2H), 7.19
Solvent (0.2
mol/L)
Entry
Temp./℃
Time/h
Yieldb/%
1
2
3
4
5
CH2Cl2
H2O
25
25
50
50
80
5
24
5
97
n.r.
<10
47
H2O
H2O
24
H2O
5
91
a The reaction was performed using 5-methylindole 1b (0.3 mmol,
1.5 equiv.), 3-indole substituted phthalide 3a (0.2 mmol, 0.2
mol/L), InBr3 (5 mol%). b isolated yield.
2
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, XX, 1—6

Highly Efficient Synthesis of Unsymmetrical 3,3'-Bis(1H-indol-3-yl)methanes in Water
Table 2 Substrate scopesa
R2
O
COOH
InBr3
(5 mol%)
O
R3
R1
R1
R3
+
R2
N
H2O (0.2 mol/L)
N
H
N
H
H
N
H
3
1
4
Entry
1
R1, R2, R3
Product
Temp./℃
Time/h
5
Yieldb/%
COOH
Me
5-Me, H, H
80
91
N
N
H
H
4b
COOH
MeO
5-OMe, H, H
5-OBn, H, H
5-Br, H, H
2
3
4
80
80
80
5
5
5
98
92
96
N
N
H
H
4c
COOH
BnO
N
H
N
H
4d
COOH
Br
N
N
H
H
4e
COOH
Cl
5-Cl, H, H
5-F, H, H
6-F, H, H
5
6
7
80
80
80
5
5
5
94
90
91
N
H
N
H
4f
COOH
F
N
N
H
H
4g
COOH
F
N
H
N
H
4h
Chin. J. Chem. 2012, XX, 1—6
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www.cjc.wiley-vch.de
3

Lin et al.
FULL PAPER
Continued
Yieldb/%
Entry
R1, R2, R3
Product
Temp./℃
Time/h
24
COOH
6-NO2, H, H
8
90
87
80
96
72
70
O2N
N
H
N
H
4i
COOH
9c
10
11
12
90
80
80
80
48
H, H, 7-NO2
N
N
H
H
NO2
4j
OMe
OMe
COOH
5-OMe, 3,4-(OMe)2, H
5-Me, 3,4-(OCH2O), H
5-OMe, 5-Br, H
5
MeO
N
N
H
H
4k
O
O
COOH
5
Me
N
N
H
H
4l
Br
COOH
MeO
7
N
N
H
H
4m
a
The reaction was performed by using indole 2 (0.3 mmol, 1.5 equiv.), 3-indole substituted phthalide 1 (0.2 mmol, 0.2 mol/L), InBr3 (5
mol%). See Supporting Information for details. b Isolated yield. c The reaction was performed by using 1H-indole (0.3 mmol, 1.5 equiv.),
3-(7-nitro-1H-indole) substituted phthalide (0.2 mmol, 0.2 mol/L), InBr3 (5 mol%).
(s, 1H), 7.16 (s, 1H), 7.05 (dd, J＝7.2, 7.2 Hz, 1H), 6.89
(dd, J＝7.2, 7.2 Hz, 2H), 6.67 (s, 1H), 6.62 (s, 1H), 2.25
(s, 3H); 13C NMR (125 MHz, acetone-d6) δ: 169.8,
146.7, 140.0, 136.5, 136.3, 131.9, 131.6, 131.0, 130.9,
128.5, 128.2, 128.0, 126.6, 125.0, 124.8, 124.7, 123.8,
122.1, 120.4, 120.0, 119.4, 112.1, 111.8, 35.9, 21.7;
(EI-HRMS m/z calcd for C25H20N2O2 380.1525 [M]＋,
found 380.1521).
7.06 (dd, J＝8.4, 7.2 Hz, 1H), 6.85—6.91 (m, 2H),
6.69—6.74 (m, 3H), 3.60 (s, 3H); 13C NMR (100 MHz,
acetone-d6) δ: 169.2, 153.6, 145.8, 137.3, 132.4, 131.1,
130.8, 130.1, 129.9, 127.8, 127.4, 125.8, 124.7, 124.0,
121.3, 119.7, 118.9, 118.8, 118.7, 118.5, 111.9, 111.3,
101.6, 54.3, 35.1; (ESI-HRMS m/z calcd for
C25H20N2NaO3 419.1372 [M＋Na]＋, found 419.1354).
2-((5-(Benzyloxy)-1H-indol-2-yl)(1H-indol-2-yl)-
1
2-((1H-Indol-2-yl)(5-methoxy-1H-indol-2-yl)me-
methyl)benzoic acid (4d) White solid; H NMR (400
1
thyl)benzoic acid (4c) White solid; H NMR (400
MHz, acetone-d6) δ: 11.22 (s, 1H), 9.93 (s, 1H), 9.81 (s,
1H), 7.90 (d, J＝7.2 Hz, 1H), 7.36—7.43 (m, 6H),
7.24—7.31 (m, 6H), 7.11 (s, 1H), 7.01—7.05 (m, 2H),
6.89 (dd, J＝8.0, 7.2 Hz, 1H), 6.80 (d, J＝8.8 Hz, 1H),
MHz, acetone-d6) δ: 11.23 (s, 1H), 9.93 (s, 1H), 9.79 (s,
1H), 7.87—7.91 (m, 1H), 7.42—7.53 (m, 1H),
7.35—7.38 (m, 2H), 7.19—7.29 (m, 3H), 7.11 (s, 1H),
4
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Highly Efficient Synthesis of Unsymmetrical 3,3'-Bis(1H-indol-3-yl)methanes in Water
6.72 (s, 1H), 4.91 (s, 2H); 13C NMR (100 MHz, ace-
tone-d6) δ: 169.5, 152.7, 145.8, 138.2, 137.3, 132.5,
131.1, 130.7, 130.1, 128.3, 127.7, 127.5, 127.4, 127.3,
125.8, 124.7, 124.0, 121.3, 119.6, 119.5, 118.9, 118.8,
118.5, 112.0, 111.9, 111.3, 103.2, 70.2, 35.2;
(ESI-HRMS m/z calcd for C31H24N2NaO3 495.1685
[M＋Na]＋, found 495.1693).
8.39 (d, J＝2.4 Hz, 1H), 7.96 (d, J＝8.0 Hz, 1H), 7.84
(dd, J＝2.4, 8.8 Hz, 1H), 7.53 (d, J＝8.8 Hz, 1H),
7.30—7.40 (m, 5H), 7.24 (s, 1H), 7.13 (d, J＝6.8 Hz,
1H), 7.08 (dd, J＝6.8, 7.2 Hz, 1H), 6.91 (dd, J＝6.8 Hz,
6.8 Hz, 1H), 6.73 (s, 1H); 13C NMR (100 MHz, ace-
tone-d6) δ: 169.0, 145.1, 142.9, 137.3, 135.5, 131.9,
131.5, 130.6, 130.5, 130.0, 127.1, 126.2, 124.1, 121.5,
120.5, 119.5, 119.3, 118.7, 118.4, 113.8, 111.5, 108.3,
35.0; (ESI-HRMS m/z calcd for C24H17N3NaO4
434.1117 [M＋Na]＋, found 434.1139).
2-((5-Bromo-1H-indol-2-yl)(1H-indol-2-yl)me-
1
thyl)benzoic acid (4e) White solid; H NMR (400
MHz, acetone-d6) δ: 10.18 (d, J＝13.6 Hz, 1H), 9.96 (s,
1H), 8.00 (dd, J＝6.8, 6.8 Hz, 1H), 7.62 (d, J＝8.4 Hz,
1H), 7.18—7.44 (m, 8H), 7.10 (dd, J＝7.2, 8.0 Hz, 1H),
6.94 (dd, J＝7.2, 7.2 Hz, 1H), 6.80 (s, 1H), 6.75 (s, 1H);
13C NMR (100 MHz, acetone-d6) δ: 169.9, 145.5, 137.4,
136.0, 131.8, 130.6, 130.2, 129.3, 127.5, 126.3, 125.9,
124.3, 121.9, 121.8, 119.7, 119.3, 119.1, 119.0, 113.6,
112.1, 111.7, 35.2; (ESI-HRMS m/z calcd for C24H17Br-
N2NaO2 467.0371 [M＋Na]＋, found 467.0381).
2-((5-Chloro-1H-indol-2-yl)(1H-indol-2-yl)meth-
yl)benzoic acid (4f) White solid; 1H NMR (400 MHz,
acetone-d6) δ: 11.27 (s, 1H), 10.19 (d, J＝13.6 Hz, 1H),
9.98 (s, 1H), 7.95 (dd, J＝6.8, 7.2 Hz, 1H), 7.34—7.42
(m, 6H), 7.28—7.32 (m, 1H), 7.12—7.17 (m, 1H),
7.01—7.06 (m, 2H), 6.90 (dd, J＝6.8, 7.2 Hz, 1H),
6.78—6.80 (m, 1H), 6.71 (s, 1H); 13C NMR (100 MHz,
acetone-d6) δ: 169.1, 145.4, 145.0, 137.3, 135.7, 131.3,
130.3, 130.0, 128.5, 127.3, 126.2, 126.0, 125.8, 124.0,
121.5, 121.4, 119.4, 119.2, 118.7, 118.6, 112.9, 112.8,
111.4, 34.9; (ESI-HRMS m/z calcd for C24H18ClN2O2
401.1057 [M]＋, found 401.1707).
2-((5-Fluoro-1H-indol-2-yl)(1H-indol-2-yl)meth-
yl)benzoic acid (4g) White solid; 1H NMR (400 MHz,
Acetone-d6) δ: 10.05 (s, 1H), 9.96 (s, 1H), 7.91 (d, J＝
6.4Hz, 1H), 7.24—7.41 (m, 6H), 7.11 (s, 1H),
7.01—7.05 (m, 2H), 6.79—6.88 (m, 3H), 6.71 (s, 1H);
13C NMR (125 MHz, acetone-d6) δ: 169.4, 158.2 (d, J＝
184.5 Hz), 146.3, 138.0, 134.5, 132.1, 131.0 (d, J＝18.3
Hz), 128.2, 126.7 (d, J＝4.4 Hz) 124.7, 122.2, 120.3,
119.6, 119.4, 113.0, 112.1, 110.3, 110.1, 105.0, 104.8,
36.0; (EI-HRMS m/z calcd for C24H17N2O2F 384.1274
[M]＋, found 384.1270).
2-((1H-indol-2-yl)(7-nitro-1H-indol-2-yl)methyl)-
1
benzoic acid (4j) Yellow solid; H NMR (400 MHz,
acetone-d6) δ: 10.97 (s, 1H), 10.03 (s, 1H), 8.08 (d, J＝
8.4 Hz, 1H), 7.97 (d, J＝7.2 Hz, 1H), 7.85 (d, J＝8.4 Hz,
1H), 7.36—7.41 (m, 4H), 7.27—7.32 (m, 2H),
7.04—7.11 (m, 2H), 6.94 (s, 1H), 6.91 (dd, J＝7.2, 7.2
Hz, 1H), 6.74 (s, 1H); 13C NMR (125 MHz, acetone-d6)
δ: 169.6, 145.8, 138.0, 133.8, 132.4, 131.3, 130.8, 128.6,
127.9, 127.8, 127.6, 127.1, 125.0, 124.8, 122.4, 122.1,
120.1, 119.6, 119.5, 112.3, 110.9, 35.7; (EI-HRMS m/z
calcd for C24H17N3O4 411.1219 [M]＋, found 411.1220).
2-((1H-Indol-2-yl)(5-methoxy-1H-indol-2-yl)me-
thyl)-4,5-dimethoxybenzoic acid (4k) White solid;
1H NMR (400 MHz, acetone-d6) δ: 9.91 (s, 1H), 9.75 (s,
1H), 7.34—7.39 (m, 2H), 7.24 (d, J＝8.4 Hz, 1H),
6.98—7.05 (m, 3H), 6.89 (s, 1H), 6.87 (s, 1H), 6.75 (s,
1H), 6.68—6.71 (m, 2H), 6.00 (s, 1H), 3.84 (s, 3H),
3.77 (s, 3H), 3.63 (s, 3H); 13C NMR (125 MHz, ace-
tone-d6) δ: 169.3, 154.5, 151.6, 146.2, 138.0, 134.8,
133.0, 131.0, 128.4, 128.1, 125.7, 125.3, 124.7, 122.1,
119.4, 119.3, 114.0, 112.6, 112.2, 112.1, 102.3, 61.4,
56.2, 55.8, 37.1; (EI-HRMS m/z calcd for C27H26N2O5
458.1842 [M]＋, found 458.1856).
5-((1H-Indol-2-yl)(5-methyl-1H-indol-2-yl)meth-
yl)benzo[d][1,3]dioxole-4-carboxylic acid (4l) White
1
solid; H NMR (400 MHz, DMSO-d6) δ: 12.86 (s, 1H),
10.73 (s, 1H), 10.61 (s, 1H), 7.31 (d, J＝7.6 Hz, 1H),
7.24 (d, J＝7.6 Hz, 1H), 7.20 (d, J＝8.4 Hz, 1H), 7.04
(s, 1H), 7.01 (dd, J＝7.2, 6.8 Hz, 1H), 6.79—6.85 (m,
3H), 6.58—6.61 (m, 2H), 6.53—6.57 (m, 1H), 6.38 (s,
1H), 6.02 (s, 2H), 2.23 (s, 3H); 13C NMR (100 MHz,
DMSO-d6) δ: 167.3, 146.2, 146.1, 137.1, 136.9, 135.5,
127.4, 127.2, 127.0, 124.5, 124.4, 123.0, 122.2, 121.4,
119.5, 118.9, 118.7, 118.7, 118.0, 116.4, 111.9, 111.7,
109.6, 102.0, 35.0, 21.8; (ESI-HRMS m/z calcd for
C26H20N2NaO4 447.1321 [M＋Na]＋, found 447.1315).
2-((1H-Indol-2-yl)(5-methoxy-1H-indol-2-yl)me-
thyl)-4-bromobenzoic acid (4m) White solid; 1H
NMR (400 MHz, acetone-d6) δ: 10.02 (s, 1H), 9.88 (s,
1H), 7.85 (d, J＝8.4 Hz, 1H), 7.58 (d, J＝2.4 Hz, 1H),
7.50 (dd, J＝2.4, 8.4 Hz, 1H), 7.39 (dd, J＝8.4, 8.4 Hz,
2H), 7.28 (d, J＝8.8 Hz, 1H), 7.12 (s, 1H), 7.08 (dd, J＝
8.4, 8.4 Hz, 1H), 6.92 (dd, J＝8.4, 8.4 Hz, 2H),
6.71—6.78 (m, 3H), 3.62 (s, 3H); 13C NMR (100 MHz,
Acetone-d6) δ: 168.2, 153.8, 148.5, 137.3, 132.8, 132.3,
132.2, 130.0, 129.1, 127.5, 127.2, 125.5, 124.8, 124.1,
121.5, 119.4, 118.7, 118.2, 118.0, 112.1, 111.5, 101.3,
54.9, 35.2; (ESI-HRMS m/z calcd for C25H19BrN2NaO3
2-((6-Fluoro-1H-indol-2-yl)(1H-indol-2-yl)meth-
yl)benzoic acid (4h) White solid; 1H NMR (400 MHz,
acetone-d6) δ: 10.02 (d, J＝9.2 Hz, 1H), 9.93 (s, 1H),
7.97 (d, J ＝ 7.2 Hz, 1H), 7.34—7.45 (m, 5H),
7.25—7.30 (m, 1H), 7.23 (s, 1H), 7.15 (d, J＝6.8 Hz,
1H), 7.19 (dd, J＝6.8, 8.4 Hz, 1H), 6.94 (dd, J＝6.8, 7.6
Hz, 1H), 6.72—6.77 (m, 3H); 13C NMR (100 MHz,
acetone-d6) δ: 169.3, 159.8 (d, J＝233.6 Hz), 145.6,
137.3 (d, J＝7.6 Hz), 137.1, 131.4, 130.6, 130.3, 130.1,
127.4, 126.0, 124.7 (d, J＝2.9 Hz), 124.2 (d, J＝15.2
Hz), 121.5, 120.5 (d, J＝9.5 Hz), 119.6 (d, J＝15.3 Hz),
119.2, 119.0, 118.7, 111.5, 107.2 (d, J＝23.8 Hz), 97.5
(d, J ＝ 25.7 Hz), 35.1; (ESI-HRMS m/z calcd for
C24H17FN2NaO2 407.1172 [M＋Na]＋, found 407.1189).
2-((1H-Indol-2-yl)(6-nitro-1H-indol-2-yl)methyl)-
1
benzoic acid (4i) Yellow solid; H NMR (400 MHz,
acetone-d6) δ: 11.30 (s, 1H), 10.72 (s, 1H), 10.03 (s, 1H),
Chin. J. Chem. 2012, XX, 1—6
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
5

Lin et al.
FULL PAPER
497.0477 [M＋Na]＋, found 497.0489).
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Acknowledgement
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Financial support from the National Natural Science
Foundation of China (Nos. 21072031 and 20802009),
and the Shanghai Municipal Committee of Science and
Technology (No. 10ZR1404100) is greatly acknowl-
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6
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