An efficient and practical process for the synthesis of bis(indolyl)methanes catalyzed by zirconium tetrachloride

Article abstract of DOI:10.1055/s-2005-869959

Zirconium tetrachloride is used as a catalyst for the electrophilic substitution reaction of indole with aldehydes or ketones at ambient temperature to afford the corresponding bis(indolyl)methanes in good to excellent yields. Georg Thieme Verlag Stuttgar

Full text of DOI:10.1055/s-2005-869959

PAPER
1949
An Efficient and Practical Process for the Synthesis of Bis(indolyl)methanes
Catalyzed by Zirconium Tetrachloride
An
Efficient and
h
Practical
P
a
rocess for
t
n
-
of
B
is(in
H
dolyl)methanes ui Zhang, Liang Yin, Yong-Mei Wang*
Department of Chemistry and the State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, P. R. China
Fax +86(22)23502654; E-mail: zhanhui@mail.nankai.edu.cn
Received 24 December 2004; revised 10 March 2005
eration of a large amount of toxic waste. For this reason,
Abstract: Zirconium tetrachloride is used as a catalyst for the elec-
superior catalysts, which are cheap, less toxic, easily
available, air-stable, and water-tolerant, are desirable.
trophilic substitution reaction of indole with aldehydes or ketones at
ambient temperature to afford the corresponding bis(indolyl)meth-
anes in good to excellent yields.
In recent years, zirconium tetrachloride has been explored
Key words: indole, aldehydes, ketones, bis(indolyl)methanes, extensively in organic reactions.20 Industrially its applica-
tions are steadily increasing.21 Furthermore, the high
electrophilic substitution, zirconium tetrachloride
abundance of zirconium(IV) compounds in the earth’s
crust make them less costly and easily available as well as
this they also display low toxicity.22 In particular, zirconi-
Indole and its derivatives are important intermediates in
um tetrachloride has been found to be a more effective
catalyst than conventional Lewis acids in promoting vari-
ous transformations including the synthesis of nitriles,23
Biginelli reaction,24 the synthesis of chloromethyl es-
ters,25 selective deprotection of tert-butyldimethylsilyl
ethers,26 cleavage of prenyl ethers and para-methoxyben-
zyl ethers,27 one-pot conversion of tert-butyldimethylsilyl
ethers and tetrahydropyranyl ethers to the corresponding
acetates,28 nucleophilic-opening of epoxides,29 conver-
sion of aldehydes to geminal-diacetates and dipivalates,30
the deprenylation of ethers and esters,31 the iodination of
alcohols,32 selective tosylation of alcohols,33 Boc-protec-
tion of amines,34 cyclization of ortho-allylphenols,35 con-
version of epoxides into b-chlorohydrins,36 and the
preparation of MOM ether.37 In continuation of our inter-
est in the use of Lewis acids as efficient catalysts in vari-
ous transformations,38 we herein report the synthesis of
bis(indolyl)methanes from indole and carbonyl com-
pounds in the presence of a catalytic amount of zirconium
tetrachloride (5 mol%) at room temperature (Scheme 1).
organic synthesis and exhibit various physiological prop-
erties and pharmacological activities.1 Over the past
decade, a number of natural products containing bis(in-
dolyl)methanes or bis(indolyl)ethanes have been isolated
from marine sources.2 Bis(indolyl)methanes are found in
cruciferous plants and are known to promote beneficial
estrogen metabolism3 and induce apoptosis in human can-
cer cell. Therefore the preparation of these intermediates
has received increased attention from synthetic organic
chemists and biologists. The reaction of indole with alde-
hydes or ketones produces azafulvenium salts, which then
undergo further addition with the second indole molecule
to afford bis(indolyl)ethanes.4 Generally, this reaction is
promoted using protic acids,5 Lewis acids (such as zinc
chloride, indium chloride, indium triflate, dysprosium tri-
flate, lanthanide triflate, lithium perchlorate, ferric chlo-
ride,6 or heteropolyacid7), and heterogeneous catalysts
(zeolites, clay, and supported reagents8). Other catalysts
such as iodine,9 NBS,10 potassium hydrogen sulfate,11
triphenyl phosphonium perchlorate,12 CAN,13 and hexam-
ethylenetetraamine-bromine14 have also been used to cat-
alyze this reaction. This reaction also proceeds in ionic
liquids such as 1-butyl-3-methylimidazolium tetrafluo-
roborate or 1-butyl-3-methylimidazolium hexafluoro-
phosphate15 or in the solid-state by employing a high-
pressure mercury lamp.16 Recently, rare-earth perfluoroo-
canoates [RE(PFO)3],17 trichloro-1,3,5-triazine,18 and ion-
ic liquids in conjunction with In(OTf)3 or FeCl3·6H2O19
were employed for this transformation. Although these
methods are suitable for certain syntheses, there some-
times exist some drawbacks such as long reaction time
(e.g. 10 days5a), expensive reagents (e.g. dysprosium
triflate6d), low yields of products in some cases, high cat-
alyst loading, corrosive reagents, and large amounts of
solid supports, which would eventually result in the gen-
R1
R2
ZrCl4
O
+
CH3CN, r.t.
R1
R2
N
H
N
H
N
H
1
2
3
Scheme 1
Initially, we carried out the reaction of indole with benzal-
dehyde in the presence of 5 mol% of zirconium tetrachlo-
ride in different anhydrous solvents at room temperature.
The results are shown in Table 1. Among the solvents ex-
amined, acetonitrile proved to be the most effective. Sim-
ilar results were observed in dichloromenthane, but with
longer reaction times, however, utilizing other solvents
proved to be quite unsatisfactory.
SYNTHESIS 2005, No. 12, pp 1949–1954
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x.
x
x
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Advanced online publication: 24.06.2005
DOI: 10.1055/s-2005-869959; Art ID: F18804SS
© Georg Thieme Verlag Stuttgart · New York

1950
Z.-H. Zhang et al.
PAPER
Table 1 Effect of Solvent on the Conversion of Indole and Benzal- having electron-withdrawing groups on the aromatic ring
dehyde to Phenyl-3,3¢-diindoylmenthanea
(i.e. NO2, F) react faster than benzaldehyde and an elec-
tron-donating substituent (i.e. CH3, OCH3, OH) deactivat-
Entry
Solvent
CH3CN
CH3COOC2H5
CH2Cl2
CH3OH
C2H5OH
THF
Time (h)
Yield (%)b
ed aryl aldehydes remarkably. Furthermore, unsaturated
aldehydes, such as cinnamaldehyde, gave the correspond-
ing bis(indolyl)methanes without polymerization under
the above reaction conditions. The heterocyclic aldehydes
such as furfural and 2-thiophenecarboxaldehyde also
worked well without the formation of any side products.
4-(Diethylamino)benzaldehyde (2ab), however, remained
unaffected even when the reaction mixture was stirred at
room temperature for one day; the starting material could
be quantitatively recovered. This result may be due to the
coordination of zirconium ion with the diethylamino
group, which deactivates the catalyst. Ketones required
longer reaction times, which is most probably due to the
electron-donating and steric effects of the methyl group.
1
2
3
4
5
6
7
0.5
1
96
86
92
80
76
84
42
1
4
4
20
25
DMF
a All reactions were carried out using a catalytic amount of ZrCl4 (5.0
mol% based on the amount of indole) at r.t.
b Isolated yields.
The reaction conditions are mild enough not to induce any
isomerization of conjugated aldehydes (2z) and damage to
moieties such as methoxy (2n, 2o, and 2t), methylene-
dioxy (2p), and allyloxy (2w), which often undergo cleav-
age under strong acidic reaction conditions. In the absence
of zirconium tetrachloride, the reaction did not yield any
product at room temperature even after a long reaction
time. The efficacy of various Lewis acids was tested for
this conversion, and the results are shown in Table 3.
Among these catalysts, zirconium tetrachloride was found
to be superior in terms of yield and reaction rate; a result
of the mild Lewis acidity of the zirconium ion, which ac-
tivates the carbonyl group to promote the reaction.
Next, we carried out the zirconium tetrachloride catalyzed
electrophilic substitution reaction of indole with a variety
of aldehydes or ketones to better understand both the
scope and the generality of this method (Table 2).
As shown in Table 2, a series of aromatic, aliphatic and
heterocyclic aldehydes underwent electrophilic substitu-
tion reaction with indole smoothly to afford a wide range
of substituted bis(indolyl)methanes in good to excellent
yields. Many of the pharmacologically relevant substitu-
tion patterns on the aromatic ring could be introduced
with high efficiency by using this procedure. The electron
deficiency and the nature of the substituents on the aro-
matic ring affect the conversion rate; aromatic aldehydes
Table 2 Zirconium Tetrachloride Catalyzed Synthesis of Bis(indolyl)methanes
2
3
Mp (°C)
Entry
1
R1
R2
Time (min)
Yield (%)a
Recrystallization solvent Found
Reported
125–1278j
140–14216a
265–2668j
222–22813
72–749a
Ph
H (2a)
H (2b)
H (2c)
H (2d)
H (2e)
H (2f)
H (2g)
H (2h)
H (2i)
H (2j)
H (2k)
H (2l)
H (2m)
30
20
10
15
25
28
25
20
20
25
35
45
40
96
95
93
94
93
94
96
95
94
93
92
94
95
EtOAc–hexane
EtOH–CCl4
125–126
141–143
260–262
220–222
73–75
2
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2-ClC6H4
3-ClC6H4
4-ClC6H4
2,4-Cl2C6H3
3,4-Cl2C6H3
4-FC6H4
3
Et2O–EtOH
4
hexane
5
EtOAc–hexane
EtOAc–hexane
MeOH–H2O
6
89–91
7
103–106
103–105
155–157
72–74
104–1058b
154–1566f
78–809a
8
EtOAc–hexane
EtOAc–hexane
EtOAc–hexane
EtOAc–hexane
EtOAc–hexane
EtOAc–hexane
9
10
11
12
13
2-OH-5-ClC6H3
2-MeC6H4
4-MeC6H4
80–82
100–102
96–98
95–976f
Synthesis 2005, No. 12, 1949–1954 © Thieme Stuttgart · New York

PAPER
An Efficient and Practical Process for the Synthesis of Bis(indolyl)methanes
1951
Table 2 Zirconium Tetrachloride Catalyzed Synthesis of Bis(indolyl)methanes (continued)
2
3
Mp (°C)
Entry
14
R1
R2
Time (min)
Yield (%)a
Recrystallization solvent Found
Reported
2-OMeC6H4
4-OMeC6H4
3,4-(OCH2O)C6H3
2-OHC6H4
H (2n)
H (2o)
H (2p)
H (2q)
H (2r)
H (2s)
H (2t)
H (2u)
H (2v)
50
45
94
94
90
91
97
86
95
90
92
95
EtOAc–hexane
MeOH–H2O
134–136
190–193
102–104
342–344
101–103
120–122
102–103
67–69
15
191–1938j
97–996f
3495a
16
60
EtOAc–hexane
benzene–hexane
EtOAc–hexane
EtOAc–hexane
EtOAc–hexane
EtOAc–hexane
EtOAc–hexane
EtOAc–hexane
17
120
60
18
3-OHC6H4
985a
19
4-OHC6H4
80
122–12413
99–1016c
68–706f
66–686h
20
3-MeO-4-OHC 6H3
CH3(CH2)4
45
21
80
22
CH3(CH2)5
90
68–70
23
50
153–155
CHO
OCH2CH=CH2
(2w)
24
25
26
30
60
90
89
81
benzene–hexane
hexane
320–322
186–188
96–98
32214
CHO
O
(2x)
188–1908c
995a
CHO
S
(2y)
120
EtOAc–hexane
CHO
(2z)
27
45
94
EtOAc–hexane
236–239
2406f
CHO
(2aa)
4-Et2NC6H4
b
28
29
30
H (2ab)
24 h
6 h
–
CH3
CH3(2ac)
89
92
EtOAc–hexane
EtOAc–hexane
165–167
116–118
167–16813
118–1206f
6 h
O
(2ad)
Ph
31
32
CH3 (2ae)
CH3 (2af)
6 h
6 h
85
87
EtOH
188–190
232–235
190–19213
234–2366a
4-NO2C6H4
EtOAc–hexane
a Isolated yield after purification.
b No reaction.
This reaction was further explored for the synthesis of tet- In conclusion, zirconium tetrachloride has been employed
raindolyl compounds 6 and 7 by the condensation of for the first time as a novel and efficient catalyst for the
terephthalaldehyde 4 and 2,2¢-di(formylphenoxy) pro- synthesis of bis(indolyl)methanes by the electrophilic
pane 5 with four equivalents of indole under similar con- substitution reaction of indole with aldehydes or ketones.
ditions in excellent yields (Scheme 2).
This method is applicable to a wide range of aldehydes,
including aromatic, aliphatic, a,b-unsaturated and hetero-
Synthesis 2005, No. 12, 1949–1954 © Thieme Stuttgart · New York

1952
Z.-H. Zhang et al.
PAPER
Table 3 Effect of Different Lewis Acids on the Reaction of Indole
with Benzaldehydea
Entry
Catalyst
None
Time (h)
Yield (%)b
1
2
3
4
5
6
10
5
0
87
86
93
91
92
BiCl3
Bi(NO3)5·5H2O
CuCl2
4
2
InCl3
6
InBr3
2
7
8
In(OTf)3
0.42
0.8
716c
78
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
CoCl2·6H2O
ZnCl2
24
24
24
24
5
37
11
20
73
90
trace
46
90
92
8
ZnBr2
FeCl3
Scheme 2
Cu(OTf)2
NiCl2·6H2O
Mg(ClO4)2
Ga(ClO4)3
Pr(ClO4)3
LaCl3
24
24
8
Melting points were recorded on X-4 apparatus and are uncorrected.
IR spectra were recorded on a Bio-Rad FTS 135 spectrophotometer
using KBr optics. NMR spectra were recorded with a Bruker spec-
trometer at 300 (1H NMR) and 75 (13C NMR) MHz using TMS as
internal standard. Mass spectra were recorded on a VG-7070E mass
spectrometer. Elemental analyses were performed on a Yanaca
CDRDER MT-3 analyzer.
8
15
24
24
15
4
LiBr
18
16
0
Synthesis of Bis(indolyl)methanes 3; General Procedure
A mixture of indole (2.0 mmol), aldehyde or ketone (1.0 mmol), and
ZrCl4 (0.023 g, 0.1 mmol) in MeCN (5 mL) was stirred at r.t. for the
appropriate time (Table 2). After completion of the reaction, as in-
dicated by TLC, the mixture was quenched with H2O (5 mL) and
extracted with EtOAc (2 × 10 mL). The combined organic layer
was separated and dried (Na2SO4), concentrated in vacuo, and the
product was purified by column chromatography on silica gel
(EtOAc–cyclohexane, 1:9) to give pure bis(indolyl)methanes.
LiCl
SrCl2·6H2O
Ti(SO4)2
AlCl3
92
89
73
84
62
88
96
15
20
8
ZrO(NO3)2·2H2O
ZrSO4·4H2O
ZrOCl2·8H2O
Zr(NO3)5·5H2O
ZrCl4
3,3¢-Bisindolyl-3-chlorophenylmethane (3f)
IR: 742, 1010, 1093, 1294, 1337, 1417, 1455, 1592, 2923, 3054,
3409 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.02 (s, 1 H), 6.57 (s, 2 H), 7.00
(t, J = 7.8 Hz, 2 H), 7.06–7.22 (m, 6 H), 7.36 (d, J = 7.8 Hz, 4 H),
7.90 (br s, 2 H, NH).
20
5
0.5
13C NMR (75 MHz, CDCl3): d = 40.1, 111.3, 119.1, 119.6, 120.0,
a The reaction was carried out according to the typical experimental
122.3, 123.8, 126.6, 127.0, 129.0, 129.7, 134.2, 136.8, 146.3.
procedure.
b Isolated yields.
EIMS: m/z (%) = 358 [33, (M + 2)+], 356 (100, M+), 245 (24), 239
(6).
Anal. Calcd for C23H17ClN2: C, 77.41; H, 4.80; N, 7.85. Found: C,
77.48; H, 4.85; N, 7.82.
cyclic substrates, and ketones. The attractive features of
this procedure are the mild reaction conditions, high con-
versions, cleaner reaction profiles, inexpensive and envi-
ronmentally friendly catalyst, all of which make it an
attractive strategy for the preparation of bis(indolyl)meth-
anes.
3,3¢-Bisindolyl-2,4-dichlorophenylmethane (3h)
IR: 739, 794, 864, 1096, 1456, 1586, 2848, 3055, 3405 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.27 (s, 1 H), 6.84 (s, 2 H), 7.03
(t, J = 7.8 Hz, 4 H), 7.37 (d, J = 7.8 Hz, 6 H), 7.45 (d, J = 2.1 Hz, 1
H), 7.95 (br s, 2 H, NH).
Synthesis 2005, No. 12, 1949–1954 © Thieme Stuttgart · New York

PAPER
An Efficient and Practical Process for the Synthesis of Bis(indolyl)methanes
1953
13C NMR (75 MHz, CDCl3): d = 36.5, 110.0, 111.4, 117.9, 119.6,
119.9, 122.4, 124.0, 127.2, 129.5, 131.4, 132.6, 134.8, 136.9, 140.2.
3,3¢-Bisindolyl(methyl)phenylmethane (3ae)
IR: 741, 1010, 1336, 1455, 2848, 2923, 3053, 3410 cm–1.
EIMS: m/z (%) = 390 (100, M+), 392 [61, (M + 2)+], 274 (41), 245
(50), 176 (24), 117 (56).
1H NMR (300 MHz, CDCl3): d = 2.29 (s, 3 H), 6.54 (s, 2 H), 6.86
(t, J = 7.8 Hz, 2 H), 7.06 (t, J = 7.8, 2 H), 7.14–7.18 (m, 4 H), 7.23–
7.34 (m, 5 H), 7.78 (br s, 2 H, NH).
13C NMR (75 MHz, CDCl3): d = 28.8, 43.7, 111.2, 118.9, 121.5,
122.1, 123.4, 124.7, 125.8, 126.5, 127.8, 128.1, 137.1, 148.1.
Anal. Calcd for C23H16Cl2N2: C, 70.60; H, 4.12; N, 7.16. Found: C,
70.62; H, 4.20; N, 7.18.
3,3¢-Bisindolyl-4-fluorophenylmethane (3j)
EIMS: m/z (%) = 336 (85, M+), 243 (100), 245 (48), 220 (58), 77
(38).
IR: 737, 862, 1039, 1502, 1600, 1502, 1456, 3059, 3440 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.87 (s, 1 H), 6.65 (s, 2 H), 6.96
(t, J = 8.4 Hz, 2 H), 7.02 (d, J = 7.8 Hz, 2 H), 7.20 (t, J = 7.8 Hz, 2
H), 7.27–7.32 (m, 2 H), 7.36 (d, J = 8.7 Hz, 4 H), 7.94 (br s, 2 H,
NH).
13C NMR (75 MHz, CDCl3): d = 39.6, 111.3, 115.0, 115.3, 119.5,
120.1, 122.2, 123.8, 127.1, 130.3, 136.9, 139.9, 160.0.
Anal. Calcd for C24H20N2: C, 85.68; H, 5.99; N, 8.33. Found: C,
85.66; H, 5.98; N, 8.40.
3,3¢,3¢¢,3¢¢¢-Tetraindolyl(terephthalyl)dimethane (6)
Colorless solid (contains 2 EtOAc molecules; EtOAc–hexane, 1:2);
mp 138–139 °C (Lit.16b 138–140 °C).
EIMS: m/z (%) = 340 (2, M+), 121 (100), 117 (38), 95 (12), 89 (42),
IR: 742, 776, 1295, 1455, 1720, 2849, 2920, 3052, 3411 cm–1.
77 (9).
1H NMR (300 MHz, acetone-d6): d = 1.29 (t, J = 7.2 Hz, 6 H, CH3),
2.05 (s, 6 H, CH3), 4.04–4.09 (m, 4 H, CH2), 5.89 (s, 2 H, ArCH),
6.81 (t, J = 7.8 Hz, 4 H), 6.91 (t, J = 7.8 Hz, 4 H), 7.05 (t, J = 7.8
Hz, 4 H), 7.34–7.38 (m, 12 H), 9.97 (br s, 4 H, NH).
Anal. Calcd for C23H17FN2: C, 81.16; H, 5.03; N, 8.23. Found: C,
81.22; H, 5.10; N, 8.16.
3,3¢-Bisindolyl-2-methylphenylmethane (3l)
13C NMR (75 MHz, acetone-d6): d = 14.4, 20.8, 40.8, 60.5, 112.0,
119.2, 120.0, 120.3, 121.9, 124.3, 124.5, 128.1, 129.2, 138.0, 143.4,
170.8.
EIMS: m/z (%) = 566 (3, M+), 452 (10), 336 (68), 245 (10), 117 (8),
116 (100), 89 (50).
IR: 740, 1092, 1337, 1455, 1484, 1600, 2923, 3040, 3414 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.05 (s, 3 H), 5.87 (s, 1 H), 6.68
(s, 2 H), 7.02 (t, J = 8.1 Hz, 2 H), 7.16–7.21 (m, 6 H), 7.37 (d,
J = 8.1 Hz, 4 H), 7.94 (br s, 2 H, NH).
13C NMR (75 MHz, CDCl3): d = 19.5, 36.2, 110.9, 119.2, 119.8,
121.9, 123.8, 125.8, 126.0, 127.2, 128.3, 130.1, 134.4, 136.0, 136.7,
142.0.
Anal. Calcd for C48H46N4O4: C, 77.60; H, 6.24; N, 7.54. Found: C,
77.62; H, 6.40; N, 7.48.
EIMS: m/z (%) = 336 (3, M+), 121 (100), 117 (57), 108 (34), 91
(17), 89(78), 77 (21).
2,2¢-Bis[(3,3¢-diindolyl)methylphenoxy]propane (7)
Colorless solid (EtOAc–hexane); mp 145–147 °C.
Anal. Calcd for C24H20N2: C, 85.68; H, 5.99; N, 8.33. Found: C,
85.63; H, 6.03; N, 8.46.
IR: 742, 1240, 1467, 1596, 2849, 2924, 3055, 3415 cm–1.
1H NMR (300 MHz, acetone-d6): d = 2.81–2.84 (m, 2 H), 3.86 (t,
J = 8.7 Hz, 4 H), 6.34 (s, 2 H), 6.58 (d, J = 7.8 Hz, 2 H), 6.75–6.89
(m, 10 H), 7.02–7.12 (m, 8 H), 7.36 (t, J = 7.8 Hz, 8 H), 9.87 (br s,
4 H, NH).
13C NMR (75 MHz, acetone-d6): d = 29.0, 33.1, 65.0, 112.1, 112.2,
119.2, 119.6, 120.1, 120.6, 121.9, 124.6, 127.8, 128.2, 129.8, 134.0,
138.0, 157.0.
3,3¢-Bisindolyl-2-methoxyphenylmethane (3n)
IR: 745, 1102, 1337, 1456, 1486, 1595, 2932, 3056, 3407 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.82 (s, 3 H), 6.35 (s, 1 H), 6.64
(s, 2 H), 6.81 (t, J = 7.2 Hz, 1 H), 6.95 (t, J = 8.1 Hz, 1 H), 7.01 (d,
J = 7.8 Hz, 2 H), 7.12–7.22 (m, 4 H), 7.33 (d, J = 8.1 Hz, 2 H), 7.40
(d, J = 7.8 Hz, 2 H), 7.84 (br s, 2 H, NH).
13C NMR (75 MHz, CDCl3): d = 32.3, 56.0, 110.0, 110.8, 111.1,
119.2, 119.8, 120.2, 120.6, 121.9, 123.7, 127.3, 129.9, 132.5, 136.9,
157.1.
EIMS: m/z (%) = 716 (3, M+), 482 (5), 480 (41), 117 (9), 116 (100),
89 (26).
Anal. Calcd for C49H40N4O2: C, 82.10; H, 5.62; N, 7.82. Found: C,
82.12; H, 5.58; N, 7.80.
EIMS: m/z (%) = 352 (35, M+), 351 [100, (M – 1)+], 335 (41), 245
(10), 236 (35), 220 (52).
Acknowledgment
Anal. Calcd for C24H20N2O: C, 81.79; H, 5.72; N, 7.95. Found: C,
81.86; H, 5.78; N, 7.98.
The authors thank the National Natural Science Foundation of Chi-
na (20472032) and the State Key Laboratory of Elemento-Organic
Chemistry for financial support.
3,3¢-Bisindolyl-4-allyloxyphenylmethane (3w)
IR: 745, 791, 1455, 1506, 1608, 2849, 3052, 3418 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.45 (dt, J = 5.2, 1.5 Hz, 2 H), 5.41
(dd, J = 14.2, 1.5 Hz, 2 H), 5.83 (s, 1 H), 6.01–6.12 (m, 1 H), 6.55
(s, 2 H), 6.83 (d, J = 8.4 Hz, 2 H), 7.02 (t, J = 7.2 Hz, 2 H), 7.18 (t,
J = 6.0 Hz, 2 H), 7.37 (t, J = 8.4 Hz, 2 H), 7.37 (d, J = 8.4 Hz, 4 H),
7.91 (br s, 2 H, NH).
13C NMR (75 MHz, CDCl3): d = 39.5, 69.0, 111.2, 114.6, 117.8,
119.4, 120.2, 122.1, 123.7, 127.2, 129.8, 133.7, 136.6, 136.9, 157.1.
References
(1) Sundberg, R. J. The Chemistry of Indoles; Academic Press:
New York, 1970.
(2) Ge, X.; Yannai, S.; Rennert, G.; Gruener, N.; Fares, F. A.
Biochem. Biophys. Res. Commun. 1996, 228, 153.
(3) Zeligs, M. A. J. Med. Food 1998, 1, 67.
EIMS: m/z (%) = 378 (100, M+), 337 (29), 261 (42), 219 (63), 116
(83).
(4) Remers, W. Chem. Heterocycl. Compd. 1972, 25, 1.
(5) (a) Kamal, A.; Qureshi, A. A. Tetrahedron 1963, 19, 513.
(b) Noland, W. E.; Venkiteswaran, M. R.; Richards, G. G. J.
Org. Chem. 1961, 26, 4241. (c) Noland, W. E.;
Venkiteswaran, M. R. J. Org. Chem. 1961, 26, 4263.
Anal. Calcd for C26H22N2O: C, 82.51; H, 5.86; N, 7.40. Found: C,
82.56; H, 5.88; N, 7.36.
Synthesis 2005, No. 12, 1949–1954 © Thieme Stuttgart · New York

1954
Z.-H. Zhang et al.
PAPER
(16) (a) Meng, J.-B.; Du, D.-M.; Xiong, G.-X.; Wang, W.-G.;
(6) (a) ZnCl2: Du, D.-M.; Meng, S.-M.; Wang, Y.-M.; Meng, J.-
B.; Zhou, X.-Z. Chin. J. Chem. 1995, 13, 520. (b) InCl3:
Babu, G.; Sridhar, N.; Perumal, P. T. Synth. Commun. 2000,
30, 1609. (c) In(OTf)3: Nagarajan, R.; Perumal, P. T.
Tetrahedron 2002, 58, 1229. (d) Dy(OTf)3: Mi, X.-L.; Luo,
S.-Z.; He, J.-Q.; Cheng, J.-P. Tetrahedron Lett. 2004, 45,
4567. (e) Ln(OTf)3: Chen, D.; Yu, L.; Wang, P. G.
Tetrahedron Lett. 1996, 37, 4467. (f) LiClO4: Yadav, J. S.;
Reddy, B. V. S.; Murthy, C. V. S. R.; Kumar, G. M.; Madan,
C. Synthesis 2001, 783. (g) FeCl3: Xia, M.; Wang, S.-B.;
Yuan, W.-B. Synth. Commun. 2004, 34, 3175. (h) InF3:
Bandgar, B. P.; Shaikh, K. A. J. Chem. Res., Synop. 2004,
34.
Wang, Y.-M.; Koshima, H.; Matsuura, T. J. Heterocycl.
Chem. 1994, 31, 121. (b) Meng, J.-B.; Wang, W.-G.; Xiong,
G .-X.; Wang, Y.-M.; Fu, D.-C.; Du, D.-M.; Wang, R.-J.;
Wang, H.-G.; Koshima, H.; Matsuura, T. J. Photochem.
Photobiol. A: Chem. 1993, 74, 43.
(17) Wang, L.-M.; Han, J.-W.; Tian, H.; Sheng, J.; Fan, Z.-Y.;
Tang, X.-P. Synlett 2005, 337.
(18) Sharma, G. V. M.; Reddy, J. J.; Lakshmi, P. S.; Krishna, P.
R. Tetrahedron Lett. 2004, 45, 7729.
(19) (a) Ji, S.-J.; Zhou, M.-F.; Gu, D.-G.; Wang, S.-Y.; Loh, T.-
P. Synlett 2003, 2077. (b) Ji, S.-J.; Zhou, M.-F.; Gu, D.-G.;
Jiang, Z.-Q.; Loh, T.-P. Eur. J. Org. Chem. 2004, 1584.
(20) Bora, U. Synlett 2003, 1073.
(7) H3PMo12O40·xH2O: Zolfigol, M. A.; Salehi, P.; Shirl, M.
Phosphorus, Sulfur Silicon Relat. Elem. 2004, 179, 2273.
(8) (a) Zeolite: Karthik, M.; Tripathi, A. K.; Gupta, N. M.;
Palanichamy, M.; Murugesan, V. Catal. Commun. 2004, 5,
371. (b) See also: Reddy, A. V.; Ravinder, K.; Reddy, V. L.
N.; Goud, T. V.; Ravikanth, V.; Venkateseswarlu, Y. Synth.
Commun. 2003, 33, 3687. (c) Montmorillonite K-10:
Chakrabary, M.; Sarkar, S. Tetrahedron Lett. 2002, 43,
1351. (d) See also: Chakrabarty, M.; Gosh, N.; Basak, R.;
Harigaya, Y. Tetrahedron Lett. 2002, 43, 4075. (e) See
also: Maiti, K. A.; Bhattacharyya, B. J. Chem. Res., Synop.
1997, 424. (f) Zeokarb-225: Magesh, C. J.; Nagarajan, R.;
Karthik, M.; Perumal, P. T. Appl. Catal., A. 2004, 266, 1.
(g) Amberlyst-15: Farhanullah, S. A.; Maulik, P. R.; Ram,
V. J. Tetrahedron Lett. 2004, 45, 5099. (h) Amberlyst-15
and NaHSO4·SiO2: Ramesh, C.; Baneree, J.; Pal, R.; Das, B.
Adv. Synth. Catal. 2003, 345, 557. (i) [SO3H]–MSU: Li, J.;
Zhou, M.; Li, B.-G.; Zhang, G.-L. Synth. Commun. 2004, 34,
275. (j) Bentonitic clay: Penieres-Carrillo, G.; García-
Estrada, J. G.; Gutiérrez-Ramírez, J. L.; Alvarez-Toledano,
C. Green Chem. 2003, 5, 337. (k) CeCl·7H2O/NaI/SiO2:
Bartoli, G.; Bosco, M.; Foglia, G.; Giuliani, A.; Marcantoni,
E.; Sambri, L. Synthesis 2004, 895.
(21) Chakraborti, A. K.; Gulhane, R. Synlett 2004, 627.
(22) Emsley, J. The Elements, 3rd ed.; Clarendon: Oxford, 1998.
(23) Tsuji, C.; Miyazawa, E.; Sakamoto, T.; Kikugawa, Y. Synth.
Commun. 2002, 32, 3871.
(24) Reddy, C. h. V.; Mahesh, M. M.; Raju, P. V. K.; Babu, T. R.;
Reddy, V. V. N. Tetrahedron Lett. 2002, 43, 2657.
(25) Mudryk, B.; Rajaraman, S.; Soundararajan, N. Tetrahedron
Lett. 2002, 43, 6317.
(26) Sharma, G. V. M.; Srinivas, B.; Krishna, R. R. Tetrahedron
Lett. 2003, 44, 4689.
(27) (a) Babu, K. S.; Raju, B. C.; Srinivas, P. V.; Rao, J. M.
Tetrahedron Lett. 2003, 44, 2525. (b) Sharma, G. V. M.;
Reddy, C. G.; Krishna, P. R. J. Org. Chem. 2003, 68, 4574.
(28) Reddy, Ch. S.; Smitha, G.; Chandrasekhar, S. Tetrahedron
Lett. 2003, 44, 4693.
(29) Chakraborti, A. K.; Kondaskar, A. Tetrahedron Lett. 2003,
44, 8315.
(30) Smitha, G.; Reddy, Ch. S. Tetrahedron 2003, 59, 9571.
(31) Sharma, G. V. M.; Reddy, Ch. G.; Krishna, P. R. Synlett
2003, 1728.
(32) Firouzabadi, H.; Iranpoor, N.; Jafarpour, M. Tetrahedron
Lett. 2004, 45, 7451.
(33) Das, B.; Reddy, M. R.; Reddy, V. S.; Ramu, R. Chem. Lett.
2004, 33, 1526.
(34) Sharma, G. V. M.; Reddy, J. J.; Lakshmi, P. S.; Krishna, P.
R. Tetrahedron Lett. 2004, 45, 6963.
(9) (a) Ji, S.-J.; Wang, S.-Y.; Zhang, Y.; Loh, T.-P. Tetrahedron
2004, 60, 2051. (b) Bandgar, B. P.; Shaikh, K. A.
Tetrahedron Lett. 2003, 44, 1959.
(10) Koshima, H.; Matsuaka, W. J. Heterocycl. Chem. 2002, 39,
1089.
(35) Meshram, H. M.; Premalatha, K. P.; Rameshbabu, K.;
Eeshwaraiah, B.; Yadav, J. S. Synth. Commun. 2004, 34,
3091.
(36) Smiyha, G.; Reddy, Ch. S. J. Chem. Res., Synop. 2004, 300.
(37) Sharma, G. V. M.; Reddy, K. L.; Lakshmi, P. S.; Krishna, P.
R. Tetrahedron Lett. 2004, 45, 9229.
(11) Nagarajan, R.; Perumal, P. T. Chem. Lett. 2004, 33, 288.
(12) Nagarajan, R.; Perumal, P. T. Synth. Commun. 2002, 32,
105.
(13) Ramesh, C.; Ravindranath, N.; Das, B. J. Chem. Res., Synop.
2003, 72.
(14) Bandgar, B. P.; Bettigeri, S. V.; Joshi, N. S. Monatsh. Chem.
2004, 135, 1265.
(15) Yadav, J. S.; Reddy, B. V. S.; Sunitha, S. Adv. Synth. Catal.
(38) (a) Yin, L.; Zhang, Z.-H.; Wang, Y.-M.; Pang, M.-L. Synlett
2004, 1727. (b) Zhang, Z.-H.; Yin, L.; Wang, Y.-M.; Liu, J.-
Y.; Li, Y. Green Chem. 2004, 6, 563. (c) Zhang, Z.-H.; Yin,
L.; Li, Y.; Wang, Y.-M. Tetrahedron Lett. 2005, 46, 889.
2003, 345, 349.
Synthesis 2005, No. 12, 1949–1954 © Thieme Stuttgart · New York