Substrate-Controlled Regioselective Arylations of 2-Indolylmethanols with Indoles: Synthesis of Bis(indolyl)methane and 3,3′-Bisindole Derivatives

Article abstract of DOI:10.1021/acs.joc.6b02850

A substrate-controlled regioselective arylation of 2-indolylmethanols with indoles has been established, which efficiently afforded bis(indolyl)methane and 3,3′-bisindole derivatives in high yields and with a broad substrate scope (up to 98% yield, 36 examples). This approach will not only provide an important strategy for the diversified synthesis of bis(indolyl)methane and 3,3′-bisindole derivatives but also serve as a good example for substrate-controlled regioselective reactions.

Full text of DOI:10.1021/acs.joc.6b02850

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Article
Substrate-Controlled Regioselective Arylations of 2-Indolylmethanols with
Indoles: Synthesis of Bis(indolyl)methane and 3,3'-Bisindole Derivatives
Ying-Ying He, Xiao-Xue Sun, Guo-Hao Li, Guang-Jian Mei, and Feng Shi
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02850 • Publication Date (Web): 03 Feb 2017
Downloaded from http://pubs.acs.org on February 3, 2017
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Substrate-Controlled Regioselective Arylations of
2-Indolylmethanols with Indoles: Synthesis of Bis(indolyl)methane
and 3,3'-Bisindole Derivatives
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Ying-Ying He‡, Xiao-Xue Sun‡, Guo-Hao Li‡, Guang-Jian Mei* and Feng Shi*
School of Chemistry & Chemical Engineering, and Jiangsu Key Laboratory of Green Synthetic
Chemistry for Functional Materials, Jiangsu Normal University, Xuzhou, 221116, China
E-mail: fshi@jsnu.edu.cn; guangjianM@126.com
‡These authors contributed equally to the work.
Abstract: A substrate-controlled regioselective arylation of 2-indolylmethanols with indoles has
been established, which efficiently afforded bis(indolyl)methane and 3,3'-bisindole derivatives in
high yields and with broad substrate scope (up to 98% yield, 36 examples). This approach will not
only provide an important strategy for the diversified synthesis of bis-(indolyl)methane and
3,3'-bisindole derivatives, but also serve as a good example for substrate-controlled regioselective
reactions.
Introduction
Indole derivatives are pharmaceutically significant compounds.1 Especially, indole
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derivatives containing bis(indolyl)methane or 3,3'-bisindole motifs are widely found in various
bioactive natural products, synthetic compounds, and pharmaceuticals (Figure 1).2 For example,
the bis(indolyl)methane compound I is cytotoxic against MCF-7 cells,2b and compound II shows
acetylcholinesterase inhibitory activity.2a In addition, the core structures of bioactive compounds
III-IV and natural alkaloid V are 3,3'-bisindole skeletons,3,4 which belong to a class of privileged
heterocyclic frameworks. So, in recent years, continuous attentions from the chemical community
have been paid to the synthesis of bis-(indolyl)methanes and 3,3'-bisindoles.3-5
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Figure 1. Selected bioactive indole derivatives containing bis(indolyl)methane or
3,3'-bisindole motifs.
Regioselectivity is one important issue in organic synthesis, and many strategies have been
developed to control the regioselectivity of the reaction.6 Among them, substrate-controlled
regioselective reaction has become a powerful method to obtain high regioselectivity or
diversified regioselectivity. In this regard, it is highly desired to develop substrate-controlled
regioselective reactions for the synthesis of bis-(indolyl)methane and 3,3'-bisindole derivatives in
a diversified mode.
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Indolylmethanols have proven to be one kind of robust synthons.7-15 Due to their
characteristics of being easily converted into highly reactive resonance intermediates, numerous
3-indolylmethanol-invovled reactions such as substitutions,7-8 [3+2],9 [3+3]10 and [4+3]11
cyclizations have been developed to synthesize indole derivatives or construct indole-fused cyclic
frameworks. In this context, with promising applications in the synthesis of natural products,12
2-indolylmethanols show great potential in the synthesis of indole derivatives. However, there are
only very limited investigations on the chemistry of 2-indolylmethanols.13-14 In addition, Han and
co-workers have discovered the regioselective issue in 2-indolylmethanol-involved reactions
(Scheme 1a), and only the mixture of two regioisomers could be obtained.13b When the
C3-position of 2-indolylmethanol was blocked, only one regioisomer could be generated (Scheme
1b).13d However, by using the C3-substituted 2-indolylmethanols, 3,3'-bisindole framework could
hardly be constructed. Thus, it has become an urgent task to develop 2-indolylmethanol-involved
regioselective transformations for the synthesis of biologically important indole derivatives.
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H
N
HN
OH
acid
a)
N
+
+
N
N
N
H
O
O
O
mixture of two regioisomers
H
R2
N
R2
chiral
phosphoramide
OH
Ar
R1
b)
+
R1
R
R
N
R3
N
N
R3
Ar
H
Scheme 1. Regioselective issue in 2-indolylmethanol-involved reactions
In order to develop substrate-controlled regioselective reactions for the synthesis of
bis-(indolyl)methane and 3,3'-bisindole derivatives, as well as to discover new transformations of
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2-indolylmethanols, we designed a substrate-controlled regioselective reaction based on our
previous experiences in synthesizing indole derivatives.15 As illustrated in Scheme 2, in the
presence of a Brønsted acid (B-H), 2-indolylmethanols can be converted into their reactive
resonant hybrids of carbocations A-B, vinyliminium and delocalized cation intermediates . If the
carbocation A was attacked by nucleophiles such as indole, a normal regioselective substitution
would take place (eq. 1). If the carbocation B was attacked by nucleophiles as exemplified by
indole, an abnormal regioselective substitution would occur (eq. 2). In this transformation, the
reactivity of C3-position of indole was switched from nucleophilic to electrophilic. Traditionally,
the C3-position of the indole is nucleophilic, which is the basis of indole-involved transformations.
So, the abnormal regioselective transformation of carbocation B is a scarcely reported strategy in
indole chemistry.16 As a result, the regioselectivity of 2-indolylmethanol-involved substitutions
may strongly be affected by the steric hindrance of carbocations A and B, wherein the structures
of 2-indolylmethanols play an important role. When R group of 2-indolylmethanol is an aromatic
one (Ar), the two bulky Ar groups will block the attack of nucleophiles to the benzylic position,
which makes the nucleophilic attack occur at the C3-position of the indole ring, thus leading to an
abnormal regioselectivity (eq. 2). On the contrary, when R group of 2-indolylmethanol is a
hydrogen atom (H), the carbocation A will be more easily to be attacked by nucleophiles at this
benzylic position, thus resulting in a normal regioselective substitution (eq. 1). Based on this
design, this substrate-controlled regioselective substitution of 2-indolylmethanols with indoles will
be an important strategy for the diversified synthesis of bis-(indolyl)methane and 3,3'-bisindole
derivatives.
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Scheme 2. Design of the substrate-controlled regioselective substitutions of 2-indolylmethanols
Herein, we report a substrate-controlled regioselective arylation of 2-indolylmethanols
with indoles under Brønsted acid catalysis. By tuning the structure of 2-indolylmethanols,
two series of bis(indolyl)methane and 3,3'-bisindole derivatives were selectively
synthesized in high yields (up to 98% yield) and with broad substrate scopes.
Results and Discussion
Initially, 2-indolylphenylmethanol 1a was employed as a receptor to react with indole 2a
(Table 1). As expected, a normal regioselective substitution occurred and the bis(indolyl)methane
product 4aa was obtained as the sole product in the presence of an Brønsted acid 3a (entry 1). The
observed regioselectivity may be related to the less steric hindrance of the benzylic position and
the fast trapping of the corresponding carbocation A by indole 2a. Then, this reaction was
employed as a model reaction to further optimize the conditions. After screening a series of
Brønsted acids (entries 1-6), we found that p-methylbenzenesulfonic acid 3a exhibited the highest
catalytic activity (entry 1 vs 2–6). So, this Brønsted acid was selected as the optimal catalyst for
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further evaluation on the solvents (entries 7–11), which disclosed that chloroform was the most
suitable solvent (entry 11). Subsequent optimization of conditions revealed that lowering the
temperature or increasing the amount of substrate 2a and the catalyst loading of 3a could increase
the yield to a high level (entries 12–15). Finally, the optimal condition was set in line with what
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o
entry 15 illustrated (Brønsted acid 3a as a catalyst, at 0 C and using chloroform as a solvent),
which could deliver the product 4aa in a highest yield of 74%. Under the optimal conditions, we
also tried to lower down the molar ratio of 1a:2a from 1:8 to 1:3, but the yield decreased to some
extent (entry 16). Furthermore, we also tried using some Lewis acids as catalysts under the
optimal conditions (entries 17-20). However, the yields in these cases were lower than that under
the catalysis of Brønsted acid 3a.
Table 1. Condition optimization for normal regioselective substitutionsa
x
yield (%)b
entry
cat. (3)
TsOH (3a)
solvent
toluene
10
10
10
10
10
10
30
29
1
2
3
4
5
6
7
CF3CO2H (3b)
CH3CO2H (3c)
CF3SO3H (3d)
HBr (3e)
toluene
trace
28
toluene
toluene
15
toluene
HCl (3f)
17
toluene
TsOH (3a)
10
1,4-dioxane
27
TsOH (3a)
TsOH (3a)
TsOH (3a)
TsOH (3a)
TsOH (3a)
10
10
10
10
10
EtOAc
acetone
CH3CN
CHCl3
CHCl3
22
trace
28
8
9
10
11
12c
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13c,d
14c,e
15c,e
16c,d
17c,e
18c,e
19c,e
20c,e
TsOH (3a)
TsOH (3a)
TsOH (3a)
TsOH (3a)
InCl3
10
10
20
20
20
20
20
20
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
42
61
74
48
34
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11
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InBr3
Y(OTf)3
Cu(OTf)2
aUnless otherwise indicated, the reaction was carried out at the 0.1 mmol scale in a solvent (1
b
c
mL) at 50°C for 15 h, and the molar ratio of 1a:2a was 1:1.5. Isolated yield. The reaction was
carried out at 0°C. d1a:2a=1:3. e1a:2a=1:8.
With the optimized condition in hand, we then investigated the substrate generality of the
normal regioselective substitution. As shown in Table 2, this reaction was applicable to a wide
range of indoles 2 as nucleophiles bearing different R2 groups at diferent positions, giving the
bis(indolyl)methane products 4 in moderate to good yields (54%-89%, entries 1-6). In detail,
electron-rich indoles gave higher yields in comparision with the electron-deficient
fluoro-substituted indole (entries 2–4 vs 5). This phenomenon may be related to the
nucleophilicities of indoles. While the reactivity of C6 chloro-substituted indole was similar to
that of the unsubstituted indole in terms of the yield (entry 6 vs 1). In addition, the substrate scope
of 2-indolylmethanols 1 was examined (entries 7-13). The property of the R1 groups had some
effects on the yields. For example, electron-rich aromatic groups (entries 7-8) were superior to
electron-deficient one (entry 9) with regard to the yield. Besides, excellent yields were observed
when both electron-rich 2-indolylmethanols and indoles participated in the reaction (entries 10-12).
Notably, an alkyl R1 group could also be amenable to the reaction to give the corresponding
substituted product (entry 13). When R1 group was replaced by bulkier groups such as 1-naphthyl
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and i-Pr (entries 14-15), the reaction could still take place with normal regioselectivity to afford
the corresponding products 4ka and 4la, but the yields of the products were just in a moderate
level.
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Table 2. Substrate scope of normal regioselective substitutionsa
R1 (1)
Ph (1a)
yield (%)b
74
entry
1
4
4aa
R2(2)
H (2a)
4ab
4ac
4ad
4ae
4af
4ba
4ca
4da
4bg
4ec
4fc
Ph (1a)
69
2
5-Me (2b)
5-MeO (2c)
7-Me (2d)
5-F (2e)
Ph (1a)
89
3
Ph (1a)
84
4
Ph (1a)
54
5
Ph (1a)
74
6
6-Cl (2f)
H (2a)
m-MeC6H4 (1b)
p-MeC6H4 (1c)
p-FC6H4 (1d)
m-MeC6H4 (1b)
m-MeOC6H4 (1e)
p-MeOC6H4 (1f)
n-pentyl (1j)
83
7
71
8
H (2a)
46
9
H (2a)
95
10
11
12
13
6-Me (2g)
5-MeO (2c)
5-MeO (2c)
5-MeO (2c)
85
97
4jc
44
4ka
4la
1-naphthyl (1k)
i-Pr (1l)
56
31
14
H (2a)
H (2a)
15c
aUnless otherwise indicated, the reaction was carried out at the 0.1 mmol scale in CHCl3 (1 mL) in the presence of
20 mol% TsOH at 0 °C for 15 h, and the molar ratio of 1:2 was 1:8. bIsolated yield. cThe reaction time was 20 h.
Interestingly, when 2-indolyl(diphenyl)methanol 5a was applied to the similar
conditions, the normal regioselective product 6aa’ was not observed. Instead, the abnormal
regioselective product 6aa was obtained in an excellent yield (Scheme 3). The
corresponding carbocation
B was involved in the abnormal regioselective substitution.
During the whole reaction, the reactivity of C3-position of indolylmethanol 5a was
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switched from nucleophilic to electrophilic. This reaction provides a new strategy for
indole chemistry. And the product 6aa possesses a 3,3'-bisindole skeleton, which is the
elementary unit of some bioactive compounds and natural alkaloids.3-4
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Scheme 3. 2-Indolylmethanol-involved abnormal regioselective substitution.
With this result, we carried out an investation on the substrate scope of the abnormal
regioselective substitutions (Table 3). Firstly, indoles
2 with various substituents at
different positions were found to be suitable substrates for this reaction (entries 2–12). In
particular, indoles bearing electronic-deficient groups were less nucleophilic in normal
regioselective substitutions (Table 2, entries 5-6). However, in the abnormal regioselective
substitutions (entries 4, 7-9 and 11-12), these substrates could successfully take part in the
reaction to give the desired 3,3'-bisindole products in excellent yields (78%-90%).
Secondly, a series of 2-indolylmethanols
5
bearing different Ar/R1 substituents were also
accommodated in the reaction (entries 13-21). It seems that the position of the substituents
linked to the indole ring (R1) had some effect on the reactivity (entries 14-16). In addition,
the position of the substituents on the phenyl ring (Ar group) seems to have some influence
on the yield, because meta-substituted Ar groups afforded the products in higher yields
than their para-substituted counterparts (entries 17-18 vs 20-21).
Table 3. Substrate scope of abnormal regioselective substitutionsa
Ar /R1(5)
Ph/H (5a)
Ph/H (5a)
yield (%)c
entry
6
6aa
R2 (2)
H (2a)
98
86
1
2
6ab
5-Me (2b)
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6ac
6ae
6ag
6ah
6ai
Ph/H (5a)
86
87
95
76
90
89
82
97
78
85
78
88
91
75
89
97
76
69
85
3
5-MeO (2c)
Ph/H (5a)
4
5-F (2e)
Ph/H (5a)
6-Me (2g)
Ph/H (5a)
5
6
4-Me (2h)
Ph/H (5a)
5-Br (2i)
Ph/H (5a)
7
10
11
12
13
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6aj
6al
8
6-F (2j)
Ph/H (5a)
6-Cl (2l)
Ph/H (5a)
9
6am
6an
6ao
6ba
6ca
6da
6ea
6fa
10
11
12
13
14
15
16
17
18
19
20
21
7-Me (2m)
Ph/H (5a)
7-F (2n)
Ph/H (5a)
7-Cl (2o)
Ph/4-Me (5b)
H (2a)
Ph/5-Br (5c)
H (2a)
Ph/6-Br (5d)
H (2a)
Ph/7-Br (5e)
H (2a)
m-MeC6H4/H (5f)
H (2a)
6ga
6ha
6ia
m-FC6H4/H (5g)
H (2a)
p-MeOC6H4/H (5h)
H (2a)
p-MeC6H4/H (5i)
H (2a)
p-FC6H4/H (5j)
6ja
H (2a)
aUnless otherwise indicated, the reaction was carried out at the 0.1 mmol scale in CHCl3 (1
b
mL) in the presence of 10 mol% TsOH at 0 °C, and the molar ratio of 5:2 was 1:1.5. Isolated
yield.
Interestingly, when substrates 5k-5m bearing alkyl groups were employed to the reactions
with indole 2a under the sandard conditions, the regioselectivity was switched to generate the
normal regioselective products 6ka‘-6ma‘ (eq. 3-5). These results indicated that the existence of
two phenyl groups in 2-indolylmethanols is necessary for performing the abnormal regioselective
substitutions.
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NH
10 mol% TsOH
+
CHCl3, 0 o
C
N
(3)
N
H
H
OH
Et
5k:2a = 1:1.5
N
H
2a
5k
6ka' 59% yield
NH
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10 mol% TsOH
+
(4)
Et
CHCl3, 0 o
C
N
H
Et
N
H
OH
5l:2a = 1:1.5
N
Et
H
2a
5l
6la'
79% yield
NH
Me
Ph
OH
10 mol% TsOH
+
(5)
CHCl3, 0 o
5m:2a = 1:1.5
C
N
H
Me
N
H
N
Ph
H
2a
5m
6ma' 90% yield
The structures of all products 4, 6
and 6’ were unambiguously assigned by H and 13C
1
NMR, IR and HR MS. Furthermore, the structure of product 6ai was confirmed by X-ray
single crystal analysis (see the Supporting Information for details).17
In order to gain some insights into the two regioselective substitutions, we performed
two series of control experiments under the standard conditions (Scheme 4). In the case of
normal regioselective substitution (Scheme 4a), either N-methyl protected
2-indolylmethanol 1m or N-methyl protected indole 2k was utilized to the reaction, which
resulted in the finding that the yields of normal regioselective products 4ak or 4ma were
decreased. Moreover, the double N-protected product 4mk was obtained only in a low
yield of 55%. These results implied that both of the N-H groups of 2-indolylmethanols
1
and indoles had an important role in controlling the reactivity of the normal
2
regioselective substitution. However, in the case of abnormal regioselective substitution
(Scheme 4b), N-protected indole 2k still displayed a high reactivity to react with
2-indolylmethanol 5a and gave the product 6ak in an excellent yield of 97%. In contrast,
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the reactivity of N-protected 2-indolylmethanol 5n was decreased to some extent in the
abnormal regioselective substitution because the yields of product 6na and 6nk were
inferior to that of 6aa and 6ak. These results indicated that only the N-H group of
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2-indolylmethanols
5 played an important role in controlling the reactivity of the abnormal
regioselective substitution.
Scheme 4. Control experiments to investigate the role of N-H groups.
In addition, the two regioselective substitutions of 2-indolylmethanols and indoles
could be performed at 1 mmol scale under the standard conditions to generate the
corresponding bis(indolyl)methane 4fc and 3,3'-bisindole 6ai at good yields (Scheme 5).
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Scheme 5. Preparative scale synthesis.
Conclusions
In summary, we have established substrate-controlled regioselective arylations of
2-indolylmethanols with indoles, which efficiently afforded bis(indolyl)methane and
3,3'-bisindole derivatives in high yields and with broad substrate scope (up to 98% yield, 36
examples). This approach will not only provide an important strategy for the diversified
synthesis of bis-(indolyl)methane and 3,3'-bisindole derivatives, but also serve as a good
example for substrate-controlled regioselective reactions. Moreover, this finding will greatly
enrich the chemistry of 2-indolylmethanols which is an underdeveloped research area.
Experimental Section
1H and C NMR spectra were measured at 400 and 100 MHz, respectively. The solvent used
13
for NMR spectroscopy was CDCl3 and acetone-d6, using tetramethylsilane as the internal
reference. HRMS (ESI) was determined by a HRMS/MS instrument. Analytical grade solvents for
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the column chromatography were used after distillation and commercially available reagents were
used as received.
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General procedure for the synthesis of bis(indolyl)methane derivatives 4
To the mixture of 2-indolylphenylmethanols 1 (0.1 mmol), indoles 2 (0.8 mmol) and TsOH 3a
o
(0.02 mmol) was added chloroform (1 mL), which was stirred at 0 C for 15 h. After the
completion of the reaction which was indicated by TLC, the reaction mixture was directly purified
through preparative thin layer chromatography on silica gel to afford pure products 4.
General procedure for the synthesis of 3,3'-bisindole derivatives 6
To the mixture of 2-indolyldiphenylmethanols 5 (0.1 mmol), indoles 2 (0.15 mmol) and TsOH 3a
o
(0.01 mmol) was added chloroform (1 mL), which was stirred at 0 C for 15 h. After the
completion of the reaction which was indicated by TLC, the reaction mixture was directly purified
through preparative thin layer chromatography on silica gel to afford pure products 6.
3-((1H-indol-2-yl)(phenyl)methyl)-1H-indole (4aa): Preparative thin layer chromatography:
petroleum ether/ethyl acetate=4/1; yield: 74% (23.9 mg); yellowish solid, m.p. 52-53 oC; 1H NMR
(400 MHz, CDCl3) δ 7.97 (s, 1H), 7.92 (s, 1H), 7.54 (d, J = 7.5 Hz, 1H), 7.38 (d, J = 7.0 Hz, 2H),
7.35 – 7.28 (m, 5H), 7.21 (t, J = 7.2 Hz, 2H), 7.16 – 7.09 (m, 2H), 7.08 – 7.02 (m, 1H), 6.75 (s,
1H), 6.25 (s, 1H), 5.84 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 142.3, 141.0, 136.6, 136.0, 128.7,
128.6, 126.9, 126.8, 123.6, 122.4, 121.3, 120.2, 119.8, 119.7, 119.6, 117.8, 111.2, 110.7, 101.7,
42.8; IR (KBr): 3404, 3052, 2922, 2852, 1489, 1452, 1413, 1339, 1288, 1091, 1016, 744 cm-1; ESI
FTMS exact mass calcd for (C23H18N2-H)- requires m/z 321.1392, found m/z 321.1380.
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3-((1H-indol-2-yl)(phenyl)methyl)-5-methyl-1H-indole (4ab): Preparative thin layer
chromatography: petroleum ether/dichloromethane= 2/1; yield: 69% (23.3 mg); yellowish solid,
m.p. 48-49 oC; 1H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.84 (s, 1H), 7.56 (d, J = 7.5 Hz, 1H),
7.35-7.32 (m, 4H), 7.32 – 7.28 (m, 1H), 7.26 (d, J = 3.2 Hz, 1H), 7.23 (d, J = 8.9 Hz, 2H), 7.18 –
7.10 (m, 2H), 7.07 (t, J = 7.6 Hz, 1H), 6.69 (s, 1H), 6.25 (s, 1H), 5.82 (s, 1H), 2.39 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 142.5, 141.2, 136.0, 134.9, 129.1, 128.7, 128.5, 127.0, 126.8, 124.1,
123.8, 121.3, 120.2, 119.6, 119.1, 117.3, 110.9, 110.7, 101.7, 42.6, 21.5; IR (KBr): 3404, 3025,
2919, 2853, 1488, 1453, 1415, 1288, 1094, 1020, 793, 745 cm-1; ESI FTMS exact mass calcd for
(C24H20N2-H)- requires m/z 335.1548, found m/z 335.1539.
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3-((1H-indol-2-yl)(phenyl)methyl)-5-methoxy-1H-indole (4ac): Preparative thin layer
chromatography: petroleum ether/ethyl acetate=4/1; yield: 89% (31.5 mg); yellow solid, m.p.
55-56oC; 1H NMR (400 MHz, Acetone-d6) δ 10.04 (s, 1H), 10.01 (s, 1H), 7.45 (d, J = 7.7 Hz, 1H),
7.41 (d, J = 7.4 Hz, 2H), 7.31 (t, J = 7.8 Hz, 4H), 7.23 (t, J = 7.2 Hz, 1H), 7.02 (t, J = 7.5 Hz, 1H),
6.95 (t, J = 7.4 Hz, 1H), 6.91 (d, J = 2.3 Hz, 1H), 6.79 (d, J = 2.2 Hz, 1H), 6.77 – 6.72 (m, 1H),
6.12 (d, J = 1.0 Hz, 1H), 5.84 (s, 1H), 3.59 (s, 3H); 13C NMR (100 MHz, Acetone-d6) δ 153.7,
143.4, 142.2, 136.8, 132.2, 128.7, 128.6, 128.2, 127.5, 126.4, 124.6, 120.6, 119.7, 118.9, 116.9,
112.0, 111.4, 110.8, 101.2, 100.7, 54.9, 42.7; IR (KBr): 3430, 1696, 1581, 1485, 1448, 1338, 1289,
1203, 1164, 1017, 780, 743 cm-1; ESI FTMS exact mass calcd for (C24H20N2O-H)- requires m/z
351.1498, found m/z 351.1496.
3-((1H-indol-2-yl)(phenyl)methyl)-7-methyl-1H-indole (4ad): Preparative thin layer
chromatography: petroleum ether/dichloromethane= 2/1; yield: 84% (28.4 mg); claret-colored
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solid, m.p. 39-40 C; H NMR (400 MHz, CDCl3) δ 7.89 (s, 1H), δ 7.88 (s, 1H), 7.55 (d, J = 7.4
Hz, 1H), 7.37 – 7.29 (m, 5H), 7.26 – 7.19 (m, 2H), 7.17 – 7.08 (m, 2H), 7.04 (d, J = 7.0 Hz, 1H),
6.99 (t, J = 7.5 Hz, 1H), 6.75 (s, 1H), 6.26 (d, J = 0.7 Hz, 1H), 5.84 (s, 1H), 2.50 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 142.4, 141.1, 136.2, 136.0, 128.7, 128.6, 126.8, 126.4, 123.4, 122.9, 121.3,
120.4, 120.2, 120.0, 119.7, 118.3, 117.4, 110.7, 101.7, 42.8, 16.6; IR (KBr): 3407, 3051, 2921,
2852, 1610, 1492, 1451, 1340, 1288, 1070, 784, 740 cm-1; ESI FTMS exact mass calcd for
(C24H20N2-H)- requires m/z 335.1548, found m/z 335.1545.
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3-((1H-indol-2-yl)(phenyl)methyl)-5-fluoro-1H-indole
(4ae):
Preparative
thin
layer
chromatography: petroleum ether/dichloromethane= 2/1; yield: 54% (18.4 mg); claret-colored
solid, m.p. 60-61 oC; 1H NMR (400 MHz, CDCl3) δ 8.04 (s, 1H), 7.90 (s, 1H), 7.52 (d, J = 7.6 Hz,
1H), 7.36 – 7.29 (m, 5H), 7.28 (d, J = 4.3 Hz, 1H), 7.24 (s, 1H), 7.13 (t, J = 7.4 Hz, 1H), 7.07 (t, J
= 7.3 Hz, 1H), 7.02 – 6.97 (m, 1H), 6.97 – 6.91 (m, 1H), 6.84 (d, J = 2.0 Hz, 1H), 6.23 (s, 1H),
5.76 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 157.7 (J = 231), 141.9, 140.5, 136.1, 133.1, 128.6,
128.5, 127.0, 125.3, 121.4, 120.3, 119.7, 118.0, 111.8 (J = 10), 111.0, 110.7, 110.6, 104.7, 104.5,
101.9, 42.6; IR (KBr): 3407, 2921, 1581, 1484, 1452, 1416, 1288, 1166, 935, 794, 747, 711 cm-1;
ESI FTMS exact mass calcd for (C23H17FN2-H)- requires m/z 339.1298, found m/z 339.1288.
3-((1H-indol-2-yl)(phenyl)methyl)-6-chloro-1H-indole
(4af):
Preparative
thin
layer
chromatography: petroleum ether/dichloromethane= 2/1; yield: 74% (26.4 mg); yellowish solid,
m.p. 70-71 oC; 1H NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 7.90 (s, 1H), 7.52 (d, J = 7.6 Hz, 1H),
7.37 (d, J = 1.6 Hz, 1H), 7.35 – 7.27 (m, 5H), 7.26 – 7.22 (m, 2H), 7.12 (t, J = 7.3 Hz, 1H), 7.07 (t,
J = 7.4 Hz, 1H), 7.01 – 6.95 (m, 1H), 6.79 (d, J = 2.3 Hz, 1H), 6.22 (s, 1H), 5.79 (s, 1H); 13C
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NMR (100 MHz, CDCl3) δ 141.9, 140.5, 136.9, 136.1, 128.6, 128.4, 128.3, 127.0, 125.4, 124.2,
121.4, 120.6, 120.3, 119.7, 118.1, 111.1, 110.6, 109.9, 42.6; IR (KBr): 3407, 2921, 1486, 1452,
1406, 1335, 1290, 1090, 905, 802, 743, 675 cm-1; ESI FTMS exact mass calcd for
(C23H17ClN2-H)- requires m/z 355.1002, found m/z 355.1000.
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3-((1H-indol-2-yl)(m-tolyl)methyl)-1H-indole (4ba): Preparative thin layer chromatography:
o
1
petroleum ether/ethyl acetate= 2/1; yield: 83% (28.0 mg); claret-colored solid, m.p. 40-41 C; H
NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.91 (s, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.38 (t, J = 7.5 Hz,
2H), 7.25 – 7.19 (m, 3H), 7.17 (s, 1H), 7.13 (d, J = 6.9 Hz, 2H), 7.09 (d, J = 8.1 Hz, 2H), 7.07 –
7.01 (m, 1H), 6.77 (d, J = 2.2 Hz, 1H), 6.25 (d, J = 0.7 Hz, 1H), 5.80 (s, 1H), 2.32 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 142.2, 141.2, 138.2, 136.6, 136.0, 129.4, 128.7, 128.4, 127.6, 126.8,
125.7, 123.6, 122.3, 121.3, 120.2, 119.8, 119.7, 119.6, 117.9, 111.2, 110.7, 101.6, 42.6, 21.5; IR
(KBr): 3626, 3400, 3048, 2920, 1536, 1485, 1452, 1412, 1339, 1287, 1090, 741 cm-1; ESI FTMS
exact mass calcd for (C24H20N2-H)- requires m/z 335.1548, found m/z 335.1547.
3-((1H-indol-2-yl)(p-tolyl)methyl)-1H-indole (4ca): Preparative thin layer chromatography:
o
1
petroleum ether/ethyl acetate= 2/1; yield: 71% (23.7 mg); claret-colored solid, m.p. 56-57 C; H
NMR (400 MHz, CDCl3) δ 8.00 (s, 1H), 7.91 (s, 1H), 7.52 (d, J = 7.6 Hz, 1H), 7.37 (d, J = 8.4 Hz,
2H), 7.25 – 7.17 (m, 4H), 7.15 – 7.05 (m, 4H), 7.02 (d, J = 7.8 Hz, 1H), 6.79 (d, J = 2.0 Hz, 1H),
6.24 (s, 1H), 5.80 (s, 1H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 141.2, 139.3, 137.0, 136.6,
136.4, 136.0, 129.2, 128.6, 128.5, 127.3, 126.8, 123.6, 122.3, 121.2, 120.2, 119.7, 119.6, 118.0,
111.2, 110.6, 101.6, 42.3, 21.1; IR (KBr): 3402, 2921, 1649, 1511, 1452, 1412, 1339, 1287, 1157,
1088, 1031, 740 cm-1; ESI FTMS exact mass calcd for (C24H20N2-H)- requires m/z 335.1548,
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found m/z 335.1544.
3-((4-fluorophenyl)(1H-indol-2-yl)methyl)-1H-indole
(4da):
Preparative
thin
layer
8
9
chromatography: petroleum ether/ethyl acetate= 2/1; yield: 46% (15.7 mg); claret-colored solid,
m.p. 55-56 oC; 1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 7.91 (s, 1H), 7.53 (d, J = 7.6 Hz, 1H),
7.39 (d, J = 8.1 Hz, 1H), 7.34 (d, J = 8.0 Hz, 1H), 7.31 – 7.27 (m, 2H), 7.23 (t, J = 7.8 Hz, 2H),
7.13 (t, J = 7.1 Hz, 1H), 7.10 – 7.03 (m, 2H), 7.03 – 6.98 (m, 2H), 6.79 (d, J = 2.2 Hz, 1H), 6.21 (s,
1H), 5.82 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 161.8 (J = 244), 140.8, 138.0, 136.6, 136.0,
130.1 (J = 8), 128.5, 126.6, 123.5, 122.5, 121.4, 120.3, 119.9, 119.7, 119.5, 117.7, 115.3 (J = 21),
111.3, 110.7, 101.8, 41.9; IR (KBr): 3401, 2920, 1503, 1453, 1414, 1339, 1288, 1220, 1093, 1011,
807, 742 cm-1; ESI FTMS exact mass calcd for (C23H17FN2-H)- requires m/z 339.1298, found m/z
339.1299.
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3-((1H-indol-2-yl)(m-tolyl)methyl)-6-methyl-1H-indole (4bg): Preparative thin layer
chromatography: petroleum ether/dichloromethane= 2/1; yield: 95% (33.4 mg); claret-colored
solid, m.p. 92-93 oC; 1H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.83 (s, 1H), 7.54 (d, J = 7.5 Hz,
1H), 7.28 – 7.25 (m, 1H), 7.22 (d, J = 3.2 Hz, 1H), 7.21 (d, J = 2.9 Hz, 1H), 7.16 (d, J = 5.7 Hz,
2H), 7.14 (d, J = 3.4 Hz, 1H), 7.13 – 7.07 (m, 3H), 6.88 (d, J = 8.1 Hz, 1H), 6.68 (s, 1H), 6.26 (s,
1H), 5.77 (s, 1H), 2.47 (s, 3H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 142.4, 141.3, 138.1,
137.1, 136.0, 132.2, 129.4, 128.7, 128.4, 127.6, 125.7, 124.7, 123.0, 121.5, 121.2, 120.2, 119.6,
119.3, 117.7, 111.2, 110.7, 101.6, 42.7, 21.7, 21.6; IR (KBr): 3401, 2917, 1612, 1452, 1409, 1336,
1287, 1088, 1042, 798, 737, 682 cm-1; ESI FTMS exact mass calcd for (C25H22N2-H)- requires m/z
349.1705, found m/z 349.1701.
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3-((1H-indol-2-yl)(3-methoxyphenyl)methyl)-5-methoxy-1H-indole (4ec): Preparative thin
layer chromatography: petroleum ether/dichloromethane=1/1; yield: 85% (32.6 mg); yellowish
solid, m.p. 82-83 oC; 1H NMR (400 MHz, CDCl3) δ 7.97 (s, 1H), 7.92 (s, 1H), 7.53 (d, J = 7.6 Hz,
1H), 7.25 – 7.20 (m, 3H), 7.12 (t, J = 7.1 Hz, 1H), 7.09 – 7.04 (m, 1H), 6.95 – 6.90 (m, 2H), 6.87
– 6.83 (m, 1H), 6.83 – 6.80 (m, 1H), 6.78 – 6.75 (m, 2H), 6.26 (d, J = 0.8 Hz, 1H), 5.76 (s, 1H),
3.75 (s, 3H), 3.67 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.8, 154.0, 144.0, 140.8, 136.1, 131.7,
129.5, 128.6, 127.2, 124.4, 121.3, 121.2, 120.2, 119.6, 117.2, 114.7, 112.5, 111.9, 110.7, 101.7,
101.4, 55.8, 55.2, 42.7; IR (KBr): 3733, 3403, 2926, 1591, 1483, 1449, 1261, 1209, 1159, 1033,
747, 689 cm-1; ESI FTMS exact mass calcd for (C25H22N2O2-H)- requires m/z 381.1603, found
m/z 381.1604.
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3-((1H-indol-2-yl)(4-methoxyphenyl)methyl)-5-methoxy-1H-indole (4fc): Preparative thin
layer chromatography: petroleum ether/dichloromethane= 1/1; yield: 97% (37.1 mg); yellow solid,
m.p. 80-81 oC; 1H NMR (400 MHz, CDCl3) δ 7.94 (s, 1H), 7.90 (s, 1H), 7.53 (d, J = 7.6 Hz, 1H),
7.25 (s, 1H), 7.24 (s, 1H), 7.23 – 7.20 (m, 2H), 7.12 (t, J = 7.2 Hz, 1H), 7.08 (t, J = 7.8 Hz, 1H),
6.86 (d, J = 8.5 Hz, 3H), 6.77 (d, J = 2.2 Hz, 1H), 6.73 (d, J = 2.2 Hz, 1H), 6.24 (s, 1H), 5.74 (s,
1H), 3.80 (s, 3H), 3.67 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.4, 154.0, 141.4, 136.0, 134.4,
131.7, 129.6, 128.6, 127.2, 124.3, 121.3, 120.2, 119.6, 117.8, 113.9, 112.4, 111.9, 110.7, 101.6,
101.4, 55.8, 55.3, 41.8; IR (KBr): 3403, 2926, 1582, 1509, 1452, 1292, 1247, 1212, 1173, 1026,
800, 746 cm-1; ESI FTMS exact mass calcd for (C25H22N2O2-H)- requires m/z 381.1603, found
m/z 381.1607.
3-(1-(1H-indol-2-yl)hexyl)-5-methoxy-1H-indole (4jc): Preparative thin layer chromatography:
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petroleum ether/dichloromethane= 2/1; yield: 44% (15.3 mg); pink solid, m.p. 175-176 C; H
NMR (400 MHz, Acetone-d6) δ 9.90 (s, 1H), 9.84 (s, 1H), 7.47 (d, J = 7.4 Hz, 1H), 7.25 (t, J = 9.3
Hz, 2H), 7.21 (s, 1H), 7.00 (d, J = 1.8 Hz, 1H), 6.98 – 6.90 (m, 2H), 6.76 – 6.70 (m, 1H), 6.41 (s,
1H), 4.40 (t, J = 7.6 Hz, 1H), 3.67 (s, 3H), 2.28 – 2.20 (m, 2H), 1.49 – 1.31 (m, 6H), 0.86 (t, J =
7.1 Hz, 3H); 13C NMR (100 MHz, Acetone-d6) δ 153.6, 143.5, 136.5, 132.1, 128.9, 127.4, 122.9,
120.2, 119.4, 118.7, 117.2, 111.8, 111.2, 110.6, 101.1, 98.5, 54.9, 36.4, 34.7, 31.7, 27.6, 22.4, 13.5;
IR (KBr): 3410, 3296, 2924, 2857, 1486, 1451, 1290, 1210, 1174, 922, 796, 743 cm-1; ESI FTMS
exact mass calcd for (C23H26N2O-H)- requires m/z 345.1967, found m/z 345.1960.
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3-((1H-indol-2-yl)(naphthalen-1-yl)methyl)-1H-indole
(4ka):
Preparative
thin
layer
chromatography: petroleum ether/ dichlormethane =2/1; Reaction time = 15 h; yield: 56% (21.0
mg); yellowish solid, m.p 54-56 oC; 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 8.5 Hz, 1H), 7.95
– 7.85 (m, 3H), 7.81 (d, J = 8.2 Hz, 1H), 7.55 – 7.45 (m, 2H), 7.44 – 7.33 (m, 4H), 7.25 – 7.18 (m,
3H), 7.16 – 7.07 (m, 2H), 7.07 – 7.01 (m, 1H), 6.60 (s, 2H), 6.28 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 140.6, 138.1, 136.6, 136.0, 134.0, 131.7, 128.8, 128.7, 127.7, 126.8, 126.3, 126.3, 125.7,
125.6, 124.3, 124.0, 122.4, 121.3, 120.3, 119.8, 119.7, 119.6, 117.6, 111.2, 110.7, 102.1, 38.7; IR
(KBr): 3404, 1717, 1596, 1541, 1508, 1456, 1339, 1289, 1250, 789, 745 cm-1; ESI FTMS exact
mass calcd for (C27H20N2-H)- requires m/z 371.1548, found m/z 371.1537.
3-(1-(1H-indol-2-yl)-2-methylpropyl)-1H-indole (4la): Preparative thin layer chromatography:
petroleum ether/ dichlormethane =2/1; Reaction time = 20 h; yield: 31% (9.0 mg); yellowish oil;
1H NMR (400 MHz, CDCl3) δ 8.07 (s, 1H), 7.82 (s, 1H), 7.61 – 7.54 (m, 1H), 7.53 (d, J = 8.0 Hz,
1H), 7.37 (d, J = 8.1 Hz, 1H), 7.18 (t, J = 7.1 Hz, 2H), 7.12 (s, 1H), 7.10 – 7.00 (m, 3H), 6.48 (s,
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1H), 4.19 (d, J = 7.3 Hz, 1H), 2.71 – 2.51 (m, 1H), 1.04 (t, J = 6.5 Hz, 6H); 13C NMR (100 MHz,
CDCl3) δ 141.5, 136.2, 135.6, 128.7, 127.5, 122.3, 122.2, 120.8, 119.9, 119.6, 119.4, 116.4, 111.1,
110.4, 100.1, 43.8, 31.8, 21.6, 21.2; IR (KBr): 3405, 2956, 1718, 1541, 1456, 1417, 1383, 1288,
1095, 1043, 1012, 743 cm-1; ESI FTMS exact mass calcd for (C20H20N2-H)- requires m/z 287.1548,
found m/z 287.1550.
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2-benzhydryl-1H,1'H-3,3'-biindole (6aa): Preparative thin layer chromatography: petroleum
o
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ether / ethyl acetate = 4/1; yield: 98% (38.9 mg); yellowish solid, m.p. 56-57 C; H NMR (400
MHz, CDCl3) δ 8.00 (s, 1H), 7.86 (s, 1H), 7.66 (d, J = 7.9 Hz, 1H), 7.61 (d, J = 7.9 Hz, 1H), 7.42
(d, J = 8.1 Hz, 1H), 7.35 – 7.31 (m, 5H), 7.30 – 7.25 (m, 3H), 7.24 (d, J = 7.1 Hz, 1H), 7.20 – 7.12
(m, 6H), 6.79 (d, J = 2.1 Hz, 1H), 5.85 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 143.1, 136.3, 136.2,
135.7, 129.9, 129.1, 129.0, 128.7, 128.0, 127.8, 126.8, 123.1, 122.1, 121.8, 121.0, 120.5, 119.7,
119.6, 111.2, 110.8, 110.0, 108.3, 48.4; IR (KBr): 3443, 3025, 1593, 1488, 1449, 1409, 1334, 1088,
1017, 921, 810, 740 cm-1; ESI FTMS exact mass calcd for (C29H22N2-H)- requires m/z 397.1705,
found m/z 397.1709.
2-benzhydryl-5'-methyl-1H,1'H-3,3'-biindole (6ab): Preparative thin layer chromatography:
o
petroleum ether/dichloromethane= 2/1; yield: 86% (35.5 mg); yellowish solid, m.p. 144-145 C;
1H NMR (400 MHz, CDCl3) δ 7.99 (s, 1H), 7.84 (s, 1H), 7.60 (d, J = 7.9 Hz, 1H), 7.34 (d, J = 3.5
Hz, 2H), 7.31 (d, J = 7.6 Hz, 5H), 7.28 (d, J = 6.9 Hz, 2H), 7.21 (t, J = 7.6 Hz, 1H), 7.16 (d, J =
7.2 Hz, 4H), 7.13 (d, J = 7.7 Hz, 1H), 7.09 (d, J = 8.6 Hz, 1H), 6.80 (d, J = 2.3 Hz, 1H), 5.82 (s,
1H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 143.1, 136.4, 135.7, 134.5, 129.1, 129.0, 128.8,
128.7, 128.3, 126.7, 123.7, 123.3, 121.7, 120.5, 119.6, 110.8, 110.7, 109.4, 108.4, 48.3, 21.5; IR
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(KBr): 3446, 2919, 1594, 1486, 1451, 1335, 1087, 1021, 922, 797, 743, 702 cm-1; ESI FTMS
exact mass calcd for (C30H24N2-H)- requires m/z 411.1861, found m/z 411.1857.
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NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 7.89 (s, 1H), 7.60 (d, J = 7.9 Hz, 1H), 7.36 – 7.31 (m,
4H), 7.30 – 7.27 (m, 3H), 7.26 – 7.20 (m, 2H), 7.19 – 7.13 (m, 4H), 7.11 (t, J = 7.4 Hz, 1H), 6.98
(d, J = 1.9 Hz, 1H), 6.93 – 6.89 (m, 1H), 6.88 (d, J = 2.3 Hz, 1H), 5.84 (s, 1H), 3.58 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 154.1, 143.1, 136.3, 135.8, 131.2, 129.0, 128.7, 128.4, 126.8, 124.0,
121.8, 120.4, 119.7, 112.8, 111.9, 110.9, 109.7, 108.3, 101.9, 55.6, 48.4; IR (KBr): 3408, 1588,
1484, 1446, 1283, 1207, 1083, 1021, 909, 801, 743, 699 cm-1; ESI FTMS exact mass calcd for
(C30H24N2O-H)- requires m/z 427.1811, found m/z 427.1808.
2-benzhydryl-5'-fluoro-1H,1'H-3,3'-biindole (6ae): Preparative thin layer chromatography:
petroleum ether/dichloromethane=2/1; yield: 87% (36.0 mg); yellowish solid, m.p. 173-174 oC; 1H
NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 7.87 (s, 1H), 7.56 (d, J = 7.9 Hz, 1H), 7.34 (d, J = 7.9 Hz,
4H), 7.32 – 7.26 (m, 4H), 7.26 – 7.21 (m, 2H), 7.21 – 7.09 (m, 5H), 7.06 - 6.92 (m, 1H), 6.82 (d, J
= 2.2 Hz, 1H), 5.81 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 157.9 (J = 233), 136.5, 135.7, 132.7,
129.0, 128.9, 128.8, 128.5, 126.9, 124.9, 121.9, 120.3, 119.9, 111.8, 111.7, 110.9, 110.7, 110.4,
110.2, 107.7, 105.8, 105.6, 48.4; IR (KBr): 3447, 2919, 1587, 1484, 1281, 1174, 1083, 1022, 914,
801, 742, 703 cm-1; ESI FTMS exact mass calcd for (C29H21FN2-H)- requires m/z 415.1611, found
m/z 415.1608.
2-benzhydryl-6'-methyl-1H,1'H-3,3'-biindole (6ag): Preparative thin layer chromatography:
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petroleum ether/ethyl acetate = 8/1; yield: 95% (39.0 mg); yellowish solid, m.p. 180-181oC; H
NMR (400 MHz, CDCl3) δ 7.95 (s, 1H), 7.81 (s, 1H), 7.59 (d, J = 7.8 Hz, 1H), 7.50 (d, J = 8.1 Hz,
1H), 7.35 – 7.28 (m, 5H), 7.27 (d, J = 7.2 Hz, 2H), 7.25 – 7.19 (m, 2H), 7.18 – 7.11 (m, 4H), 7.10
(t, J = 7.4 Hz, 1H), 6.97 (d, J = 8.1 Hz, 1H), 6.73 (d, J = 2.2 Hz, 1H), 5.83 (s, 1H), 2.52 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 143.1, 136.6, 136.2, 135.7, 131.9, 129.0, 128.7, 126.7, 125.9,
122.4, 121.7, 121.3, 120.6, 120.5, 119.6, 111.1, 110.8, 109.8, 108.4, 48.3, 21.7; IR (KBr): 3411,
2918, 1628, 1450, 1335, 1160,1102, 1024, 926, 801, 750, 699 cm-1; ESI FTMS exact mass calcd
for (C30H24N2-H)- requires m/z 411.1861, found m/z 411.1862.
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2-benzhydryl-4'-methyl-1H,1'H-3,3'-biindole (6ah): Preparative thin layer chromatography:
petroleum ether/ethyl acetate = 8/1; yield: 76% (31.3 mg); yellowish solid, m.p. 104-105 C; 1H
o
NMR (400 MHz, CDCl3) δ 8.04 (s, 1H), 7.85 (s, 1H), 7.39 (d, J = 7.8 Hz, 1H), 7.38 – 7.32 (m,
3H), 7.30 (d, J = 7.4 Hz, 3H), 7.28 (s, 2H), 7.23 – 7.15 (m, 4H), 7.14 (d, J = 7.4 Hz, 2H), 7.09 (t, J
= 7.5 Hz, 1H), 6.90 (d, J = 7.0 Hz, 1H), 6.75 (d, J = 1.7 Hz, 1H), 5.77 (s, 1H), 2.21 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 143.5, 142.5, 137.4, 136.4, 135.4, 131.8, 131.3, 129.0, 128.9, 128.7,
128.5, 127.4, 126.8, 126.6, 124.6, 122.1, 121.7, 121.0, 120.3, 119.9, 110.7, 110.0, 109.0, 108.9,
48.3, 19.1; IR (KBr): 3410, 3052, 2920, 1600, 1492, 1449, 1335, 1099, 1023, 920, 746, 702 cm-1;
ESI FTMS exact mass calcd for (C30H24N2-H)- requires m/z 411.1861, found m/z 411.1860.
2-benzhydryl-5'-bromo-1H,1'H-3,3'-biindole (6ai): Preparative thin layer chromatography:
o
petroleum ether/dichloromethane= 2/1; yield: 90% (42.9 mg); yellowish solid, m.p. 165-166 C;
1H NMR (400 MHz, CDCl3) δ 8.07 (s, 1H), 7.87 (s, 1H), 7.70 (d, J = 0.8 Hz, 1H), 7.53 (d, J = 7.9
Hz, 1H), 7.38 – 7.33 (m, 4H), 7.32 – 7.28 (m, 2H), 7.29 (s, 1H), 7.27 (d, J = 2.5 Hz, 1H), 7.24 (d,
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J = 4.0 Hz, 1H), 7.21 (d, J = 7.9 Hz, 1H), 7.14 (t, J = 8.2 Hz, 5H), 6.80 (d, J = 2.3 Hz, 1H), 5.77 (s,
1H); 13C NMR (100 MHz, CDCl3) δ 142.8, 136.7, 135.6, 134.7, 129.8, 129.0, 128.9, 128.8, 126.9,
125.0, 124.3, 123.3, 121.9, 120.1, 120.0, 113.0, 112.6, 110.9, 109.7, 107.4, 48.4; IR (KBr): 3446,
1488, 1453, 1406, 1333, 1283, 1089, 921, 877, 793, 741, 699 cm-1; ESI FTMS exact mass calcd
for (C29H21BrN2-H)- requires m/z 475.0810, found m/z 475.0813.
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2-benzhydryl-6'-fluoro-1H,1'H-3,3'-biindole (6aj): Preparative thin layer chromatography:
petroleum ether/ethyl acetate = 8/1; yield: 89% (36.9 mg); yellowish solid, m.p. 166-167oC; 1H
NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 7.85 (s, 1H), 7.55 (d, J = 7.9 Hz, 1H), 7.52 – 7.45 (m,
1H), 7.40 – 7.30 (m, 5H), 7.28 (d, J = 6.8 Hz, 2H), 7.21 (t, J = 7.5 Hz, 1H), 7.15 (d, J = 7.4 Hz,
4H), 7.13 – 7.06 (m, 2H), 6.93 – 6.84 (m, 1H), 6.75 (d, J = 2.1 Hz, 1H), 5.81 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 160.0 (J = 236), 142.9, 136.5, 136.1, 136.0, 135.7, 129.0, 128.9, 128.8, 126.8,
124.6, 123.2, 121.8, 121.7, 121.6, 120.3, 119.8, 110.9, 110.1, 108.4, 108.2, 107.8, 97.5, 97.2, 48.4;
IR (KBr): 3414, 2921, 1492, 1450, 1333, 1236, 1136, 1084, 956, 806, 746, 701 cm-1; ESI FTMS
exact mass calcd for (C29H21FN2-H)- requires m/z 415.1611, found m/z 415.1610.
2-benzhydryl-6'-chloro-1H,1'H-3,3'-biindole (6al): Preparative thin layer chromatography,
petroleum ether/dichloromethane= 2/1; yield: 82% (35.5 mg); yellowish solid, m.p. 201-202oC; 1H
NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 7.83 (s, 1H), 7.50 (d, J = 7.9 Hz, 1H), 7.45 (d, J = 8.5 Hz,
1H), 7.38 (s, 1H), 7.36 – 7.31 (m, 1H), 7.30 – 7.25 (m, 5H), 7.23 (d, J = 5.2 Hz, 1H), 7.18 (t, J =
7.6 Hz, 1H), 7.17 – 7.11 (m, 4H), 7.10 – 7.02 (m, 2H), 6.75 (d, J = 1.9 Hz, 1H), 5.76 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 142.8, 136.5, 135.6, 128.9, 128.8, 128.1, 126.8, 126.6, 123.6, 121.9,
121.7, 120.3, 120.2, 119.8, 111.0, 110.9, 110.2, 107.6, 48.4; IR (KBr): 3440, 3403, 1485, 1450,
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1393, 1333, 1106, 1020, 917, 797, 749, 701 cm-1; ESI FTMS exact mass calcd for
(C29H21ClN2-H)- requires m/z 431.1315, found m/z 431.1318.
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2-benzhydryl-7'-methyl-1H,1'H-3,3'-biindole (6am): Preparative thin layer chromatography,
petroleum ether/dichloromethane=2/1; yield: 97% (39.8 mg); yellowish solid, m.p. 172-173 oC; 1H
NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.84 (s, 1H), 7.60 (d, J = 7.9 Hz, 1H), 7.57 – 7.49 (m,
1H), 7.36 – 7.30 (m, 6H), 7.28 (d, J = 6.0 Hz, 1H), 7.22 (t, J = 7.5 Hz, 1H), 7.20 – 7.14 (m, 4H),
7.13 – 7.05 (m, 3H), 6.76 (d, J = 2.2 Hz, 1H), 5.84 (s, 1H), 2.54 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 143.1, 136.3, 135.7, 129.0, 128.7, 127.6, 126.7, 122.8, 122.6, 121.7, 120.5, 120.3, 119.8,
119.6, 118.7, 110.8, 110.4, 108.4, 48.4, 16.7; IR (KBr): 3430, 2919, 1596, 1488, 1446, 1335, 1256,
1087, 1025, 784, 740, 702 cm-1; ESI FTMS exact mass calcd for (C30H24N2-H)- requires m/z
411.1861, found m/z 411.1865.
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2-benzhydryl-7'-fluoro-1H,1'H-3,3'-biindole (6an): Preparative thin layer chromatography,
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petroleum ether/dichloromethane= 2/1; yield: 78% (32.4 mg); yellowish solid, m.p. 175-176 C;
1H NMR (400 MHz, CDCl3) δ 8.24 (s, 1H), 7.87 (s, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.39 (d, J = 7.7
Hz, 1H), 7.38 – 7.32 (m, 5H), 7.30 (s, 1H), 7.29 – 7.24 (m, 1H), 7.23 (d, J = 7.1 Hz, 1H), 7.22 –
7.15 (m, 4H), 7.13 (s, 1H), 7.07 – 6.95 (m, 2H), 6.81 (d, J = 2.3 Hz, 1H), 5.82 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 149.7 (J = 242), 142.9, 136.6, 135.7, 131.7, 129.0, 128.9, 128.8, 126.9, 124.6,
124.5, 123.7, 121.9, 120.3, 119.8, 119.7, 116.7, 110.9, 110.8, 107.7, 107.0, 106.8, 48.4; IR (KBr):
3442, 1578, 1491, 1448, 1405, 1237, 1158, 1086, 1033, 912, 740, 702 cm-1; ESI FTMS exact mass
calcd for (C29H21FN2-H)- requires m/z 415.1611, found m/z 415.1609.
2-benzhydryl-7'-chloro-1H,1'H-3,3'-biindole (6ao): Preparative thin layer chromatography,
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petroleum ether/dichloromethane= 2/1; yield: 85% (36.6 mg); yellowish solid, m.p. 110-111 C;
1H NMR (400 MHz, CDCl3) δ 8.30 (s, 1H), 7.87 (s, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.51 (d, J = 8.0
Hz, 1H), 7.38 – 7.33 (m, 5H), 7.32 – 7.26 (m, 3H), 7.21 (t, J = 7.5 Hz, 1H), 7.20 – 7.12 (m, 4H),
7.11 (d, J = 7.3 Hz, 1H), 7.05 (t, J = 7.8 Hz, 1H), 6.84 (d, J = 2.2 Hz, 1H), 5.81 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 142.9, 136.6, 135.6, 133.4, 129.5, 129.0, 128.9, 128.8, 126.8, 123.7, 121.8,
121.5, 120.3, 120.2, 119.8, 119.6, 116.6, 111.1, 110.9, 107.6, 48.4; IR (KBr): 3733, 3440, 1637,
1492, 1442, 1156, 1081, 1026, 889, 780, 741, 697 cm-1; ESI FTMS exact mass calcd for
(C29H21ClN2-H)- requires m/z 431.1315, found m/z 431.1313.
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2-benzhydryl-4-methyl-1H,1'H-3,3'-biindole (6ba): Preparative thin layer chromatography:
o
petroleum ether/dichloromethane= 2/1; yield: 78% (32.0 mg); yellowish solid, m.p. 175-176 C;
1H NMR (400 MHz, CDCl3) δ 7.99 (s, 1H), 7.88 (s, 1H), 7.36 (d, J = 8.2 Hz, 1H), 7.26 (s, 10 H),
7.17 – 7.12 (m, 1H), 7.05 – 6.98 (m, 2H), 6.89 (d, J = 6.5 Hz, 1H), 6.87 – 6.81 (m, 2H), 6.80 (d, J
= 2.4 Hz, 1H), 6.38 (d, J = 1.9 Hz, 1H), 2.49 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 145.7, 142.9,
136.9, 135.5, 130.1, 129.9, 127.9, 127.7, 127.3, 126.6, 125.4, 122.2, 121.8, 121.6, 119.9, 119.8,
111.1, 108.3, 102.5, 55.3, 18.9; IR (KBr): 3407, 1486, 1448, 1407, 1336, 1238, 1101, 1021, 905,
802, 743, 697 cm-1; ESI FTMS exact mass calcd for (C30H24N2-H)- requires m/z 411.1861, found
m/z 411.1866.
2-benzhydryl-5-bromo-1H,1'H-3,3'-biindole (6ca): Preparative thin layer chromatography:
o
1
petroleum ether/dichloromethane= 2/1; yield: 88% (41.9 mg); yellowish solid, m.p. 65-66 C; H
NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.87 (s, 1H), 7.68 (s, 1H), 7.57 (d, J = 7.9 Hz, 1H), 7.43
(d, J = 8.1 Hz, 1H), 7.36 – 7.30 (m, 4H), 7.30 – 7.26 (m, 4H), 7.18 (d, J = 8.9 Hz, 2H), 7.17 – 7.10
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(m, 4H), 6.78 (d, J = 2.1 Hz, 1H), 5.79 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 142.7, 137.8, 136.1,
134.3, 130.9, 128.9, 128.8, 127.8, 126.9, 124.6, 123.3, 122.8, 122.3, 120.6, 119.9, 113.0, 112.3,
111.2, 109.1, 108.0, 48.4; IR (KBr): 3432, 3051, 2921, 1596, 1455, 1409, 1294, 1088, 931, 796,
742, 699 cm-1; ESI FTMS exact mass calcd for (C29H21BrN2-H)- requires m/z 475.0810, found
m/z 475.0817.
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2-benzhydryl-6-bromo-1H,1'H-3,3'-biindole (6da): Preparative thin layer chromatography:
o
petroleum ether/dichloromethane= 2/1; yield: 91% (43.2 mg); yellowish solid, m.p. 115-116 C;
1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 7.82 (s, 1H), 7.57 (d, J = 7.9 Hz, 1H), 7.47 – 7.39 (m,
3H), 7.35 – 7.30 (m, 4H), 7.29 – 7.22 (m, 3H), 7.20 (d, J = 8.4 Hz, 1H), 7.18 – 7.12 (m, 5H), 6.76
(d, J = 1.7 Hz, 1H), 5.79 (s, 1H); 13C NMR (101 MHz, CDCl3) δ 142.7, 137.0, 136.4, 136.2, 128.9,
128.8, 127.9, 126.9, 123.2, 122.9, 122.3, 121.7, 120.7, 119.7, 115.2, 113.8, 111.2, 109.3, 108.4,
48.3; IR (KBr): 3421, 2918, 2850, 1492, 1451, 1404, 1331, 1087, 920, 810, 743, 699 cm-1; ESI
FTMS exact mass calcd for (C29H21BrN2-H)- requires m/z 475.0810, found m/z 475.0809.
2-benzhydryl-7-bromo-1H,1'H-3,3'-biindole (6ea): Preparative thin layer chromatography:
o
petroleum ether/dichloromethane= 2/1; yield: 75% (35.6 mg); yellowish solid, m.p. 106-107 C;
1H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.87 (s, 1H), 7.69 (s, 1H), 7.57 (d, J = 7.9 Hz, 1H),
7.43 (d, J = 8.1 Hz, 1H), 7.35 – 7.30 (m, 4H), 7.30 – 7.26 (m, 4H), 7.18 (d, J = 8.7 Hz, 2H), 7.17 –
7.12 (m, 4H), 6.78 (d, J = 2.2 Hz, 1H), 5.79 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 142.7, 137.8,
136.1, 134.3, 130.9, 128.9, 128.8, 127.8, 126.9, 124.6, 123.3, 122.8, 122.3, 120.6, 119.9, 113.0,
112.3, 111.2, 109.1, 108.0, 48.4; IR (KBr): 3419, 3025, 2918, 1454, 1408, 1293, 1088, 969, 928,
795, 741, 698 cm-1; ESI FTMS exact mass calcd for (C29H21BrN2-H)- requires m/z 475.0810,
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found m/z 475.0813.
2-(di-m-tolylmethyl)-1H,1'H-3,3'-biindole (6fa): Preparative thin layer chromatography:
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9
o
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petroleum ether/dichloromethane= 2/1; yield: 89% (38.0 mg); yellowish solid, m.p. 43-44 C; H
NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 7.87 (s, 1H), 7.66 (d, J = 7.9 Hz, 1H), 7.61 (d, J = 7.8 Hz,
1H), 7.44 (s, 1H), 7.37 (s, 1H), 7.29 (d, J = 7.4 Hz, 1H), 7.27 – 7.19 (m, 3H), 7.17 – 7.07 (m, 4H),
7.02 – 6.92 (m, 4H), 6.79 (d, J = 2.2 Hz, 1H), 5.76 (s, 1H), 2.31 (s, 6H); 13C NMR (100 MHz,
CDCl3) δ 143.2, 138.4, 136.6, 136.2, 135.7, 129.7, 129.1, 128.6, 128.0, 127.5, 126.1, 123.1, 122.1,
121.6, 121.0, 120.5, 119.6, 119.5, 111.1, 110.9, 110.1, 108.1, 48.3, 21.5; IR (KBr): 3420, 3049,
2918, 1599, 1484, 1454, 1418, 1091, 1008, 804, 743, 697 cm-1; ESI FTMS exact mass calcd for
(C31H26N2-H)- requires m/z 425.2018, found m/z 425.2016.
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2-(bis(3-fluorophenyl)methyl)-1H,1'H-3,3'-biindole
(6ga):
Preparative
thin
layer
chromatography: petroleum ether/dichloromethane= 2/1; yield: 97% (42.2 mg); yellowish solid,
m.p. 43-44 oC; 1H NMR (400 MHz, CDCl3) δ 8.10 (s, 1H), 7.81 (s, 1H), 7.62 – 7.53 (m, 2H), 7.43
(d, J = 8.1 Hz, 1H), 7.35 (d, J = 8.1 Hz, 1H), 7.30 – 7.26 (m, 2H), 7.25 – 7.19 (m, 2H), 7.15 – 7.08
(m, 2H), 7.01 – 6.94 (m, 2H), 6.92 (d, J = 7.7 Hz, 2H), 6.89 – 6.80 (m, 3H), 5.79 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 164.4, 161.9, 144.9, 144.9, 136.2, 135.8, 134.9, 130.4, 130.3, 128.9,
127.9, 124.6, 123.1, 122.3, 122.2, 120.8, 120.6, 120.0, 119.7, 116.0, 115.8, 114.2, 114.0, 111.2,
111.9, 109.6, 108.9, 47.8; IR (KBr): 3408, 3053, 1585, 1484, 1446, 1255, 1087, 965, 926, 880,
746, 690 cm-1; ESI FTMS exact mass calcd for (C29H20F2N2-H)- requires m/z 433.1517, found m/z
433.1519.
2-(bis(4-methoxyphenyl)methyl)-1H,1'H-3,3'-biindole
(6ha):
Preparative
thin
layer
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chromatography: petroleum ether/dichloromethane= 2/1; yield: 76% (34.7 mg); yellowish solid,
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m.p. 186-187 C; H NMR (400 MHz, CDCl3) δ 7.94 (s, 1H), 7.87 (s, 1H), 7.53 (d, J = 7.4 Hz,
1H), 7.33 (d, J = 8.1 Hz, 1H), 7.20 – 7.13 (m, 6H), 7.12 – 7.04 (m, 2H), 6.88 – 6.82 (m, 2H), 6.80
– 6.74 (m, 5H), 6.34 (d, J = 1.9 Hz, 1H), 3.78 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 158.0, 144.4,
138.0, 136.9, 135.8, 130.8, 128.1, 127.3, 125.2, 122.4, 122.3, 122.1, 121.4, 120.4, 119.8, 119.6,
113.0, 111.1, 110.7, 103.8, 55.2, 53.9; IR (KBr): 3408, 2924, 1607, 1505, 1454, 1293, 1248, 1177,
1027, 811, 743 cm-1; ESI FTMS exact mass calcd for (C31H26N2O2-H)- requires m/z 457.1916,
found m/z 457.1914.
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2-(di-p-tolylmethyl)-1H,1'H-3,3'-biindole (6ia): Preparative thin layer chromatography:
petroleum ether/dichloromethane= 2/1; yield: 69% (29.5 mg); yellowish solid, m.p. 60-61oC; H
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NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 7.83 (s, 1H), 7.65 (d, J = 7.9 Hz, 1H), 7.59 (d, J = 7.8 Hz,
1H), 7.43 (d, J = 8.1 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.27 (d, J = 9.4 Hz, 1H), 7.20 (t, J = 7.5 Hz,
1H), 7.15 – 7.08 (m, 6H), 7.04 (d, J = 8.0 Hz, 4H), 6.80 (d, J = 2.2 Hz, 1H), 5.75 (s, 1H), 2.36 (s,
6H); 13C NMR (100 MHz, CDCl3) δ 140.3, 136.8, 136.2, 136.2, 135.7, 129.4, 129.1, 128.8, 128.0,
123.1, 122.1, 121.6, 121.0, 120.5, 119.6, 119.5, 111.1, 110.8, 110.1, 108.0, 47.6, 21.1; IR (KBr):
3410 ,2919, 1509, 1450, 1409, 1333, 1234, 1087, 1012, 905, 816, 738 cm-1; ESI FTMS exact mass
calcd for (C31H26N2-H)- requires m/z 425.2018, found m/z 425.2011.
2-(bis(4-fluorophenyl)methyl)-1H,1'H-3,3'-biindole
(6ja):
Preparative
thin
layer
chromatography: petroleum ether/dichloromethane= 2/1; yield: 85% (37.0 mg); yellowish solid,
o
1
m.p. 174-175 C; H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 7.76 (s, 1H), 7.57 (d, J = 7.6 Hz,
2H), 7.44 (d, J = 8.1 Hz, 1H), 7.35 (d, J = 8.1 Hz, 1H), 7.30 – 7.26 (m, 1H), 7.22 (t, J = 7.5 Hz,
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