Phosphoric acid-on-silica gel: A green catalyst for the synthesis of symmetrical bis(indolyl)alkanes

Article abstract of DOI:10.3987/COM-06-10783

Orthophosphoric acid, adsorbed on TLC-grade silica gel, has been demonstrated to be an efficient green catalyst for an expeditious and solvent-free one-step synthesis of symmetrical bis(indolyl)alkanes from the reaction of indoles with aryl aldehydes at 6

Full text of DOI:10.3987/COM-06-10783

HETEROCYCLES, Vol. 68, No. 8, 2006
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HETEROCYCLES, Vol. 68, No. 8, 2006, pp. 1659 - 1668. © The Japan Institute of Heterocyclic Chemistry
Received, 8th May, 2006, Accepted, 26th June, 2006, Published online, 27th June, 2006. COM-06-10783
PHOSPHORIC ACID-ON-SILICA GEL: A GREEN CATALYST FOR THE
SYNTHESIS OF SYMMETRICAL BIS(INDOLYL)ALKANES
Manas Chakrabarty,a* Ratna Mukherjee,a Ajanta Mukherji,a Shiho Arima,b
and Yoshihiro Harigayab
aDepartment of Chemistry, Bose Institute, 93/1, A. P. C. Road, Kolkata 700009,
India
Email:chakmanas@yahoo.co.in
bSchool of Pharmaceutical Sciences, Kitasato University, Minato-ku, Tokyo 108,
Japan
Abstract – Orthophosphoric acid, adsorbed on TLC-grade silica gel, has been
demonstrated to be an efficient green catalyst for an expeditious and solvent-free
one-step synthesis of symmetrical bis(indolyl)alkanes from the reaction of indoles
with aryl aldehydes at 60-70 °C.
INTRODUCTION
Bis(indolyl)alkanes (BIAs), primarily of synthetic origin, constitute an important group of bioactive
metabolites isolated from terrestrial and marine sources.1 The BIAs have emerged in recent years as a class
of compounds with potent pharmaceutical activity. The symmetrical BIAs in particular are fast proving to
be useful molecules. Thus, the symmetrical bis(indolyl)methane derivatives affect the central nervous
system2 and are used as tranquilizers.3 Bis(indol-3-yl)methane itself4 and bis(5-methoxyindol-3-yl)methane5
have potent anti-carcinogenic properties. Recently, oxidised bis(indol-3-yl)phenylmethane has been used
as a selective colorimetric sensor,6 which makes the symmetrical BIAs even more important.
The symmetrical BIAs are mainly prepared by the reaction of indoles or indolyl Grignard reagents with
carbonyl compounds or their masked forms using acids as catalysts.7 Most of these methods have various
disadvantages like the use of stoichiometric or larger amounts of acids, creation of toxic wastes, use of
expensive Lewis acids and preformed reagents, very long reaction periods and very low or widely varying
yields. The principles of Green Chemistry necessitate the use and generation of non-toxic and non-hazardous
chemicals and methodologies.8 Consequently, the symmetrical BIAs have been recently synthesised in ionic
liquids,9 using solid acids like Lewis acid-supported silica gel,10 clay,11 zeolite,12 ion-exchange resin13 and
heteropoly acids,14 sometimes using ultrasound, infrared or microwave irradiation, and even in water.15 But

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even these methods suffer from drawbacks, viz. the use of hazardous chemicals in preparing the
reagents,10c,15a long reaction times (e.g. 24 h9a / 48 h13c) and low yields of the final products (e.g. 12%9a /
35%13b).
Except for reactions in aqueous medium, which have attracted considerable attention in recent years,16 it is
advisable to avoid the use of any volatile organic compound (voc) as solvent from the point of view of green
chemistry.8 Indeed, the use of solvent-free conditions in combination with heterogeneous catalysts
represents one of the powerful green technology procedures.17 Indoles and their derivatives have been our
major synthetic targets in recent years.18 In continuation of our interest, we wanted to develop asolvent-free
and environmentally benign acidic catalyst for an expeditious synthesis of the symmetrical BIAs. We have
achieved success and report herein that 10 mol% of orthophosphoric acid (H3PO4), adsorbed on TLC-grade
silica gel (SiO2), can efficiently catalyse the reaction of indoles with mainly aryl aldehydes to form
expeditiously symmetrical BIAs in excellent yields.
RESULTS AND DISCUSSION
Since a solvent-free method was planned, we chose SiO2 as the solid matrix, on which H3PO4 was to be
adsorbed, because it possesses alarge surface area but proved not to be acidic enough to catalyse the reaction
of indole (1a) with benzaldehyde (2a) to form the expected symmetrical BIA, bis(indol-3-yl)phenylmethane
(3aa) even at 60-70 °C (Entry 1; Table 1). In order to ascertain a suitable concentration of H3PO4, 1a was
treated with 2a (0.75 equiv.) on SiO2 containing 5, 10 and 20 mol% of H3PO4 at 60-70 °C (oven) in three
separate experiments. The reactions were complete in 30, 10 and 10 min, respectively to furnish 3aa as the
sole product in comparable yields (Entries 2-4; Table 1) in each case. Just for comparison, 1a was also
treated with 2a (0.75 equiv.) in ethyl acetate containing 10 mol% H3PO4 at rt and at 60-70 °C (oil bath)
separately, which furnished 3aa in 85% and 87% yields, respectively in 4.5 h and 1.5 h (Entry 5; Table 1).
H3PO4 (10 mol%)-SiO2 thus emerged to be the reagent of choice.
Table 1. Effect of catalysts and their concentrations on the formation of 3aa at 60-70 °C
Entry
Catalyst
Reaction time
2 h
Yield of 3aa
Nil
a
1
2
3
4
5
SiO2
a
H3PO4 (5 mol%)-SiO2
30 min
10 min / 1 hb
91%
a
a
H3PO4 (10 mol%)-SiO2
H3PO4 (20 mol%)-SiO2
93% / 92%
93%
10 min
1.5 h / 4.5 hb
H3PO4 (10 mol%) / EtOAc
87% / 85%
aRefers to TLC-grade silica gel; bCarried out at room temperature

HETEROCYCLES, Vol. 68, No. 8, 2006
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In order to test the generality of the reaction, five different indoles (1a-e) were separately treated with
0.75-1.0 equiv.19 of several benzaldehydes (2a-j) and three heteroaryl aldehydes (2k-m) on H3PO4 (10
mol%)-SiO2 at 60-70 °C. For the reactions of indole with 2-formylpyrrole (2m) and of 5-nitroindole (1d)
with benzaldehyde (2a) and vanillin (2d) (Entries 13, 18 and 19, respectively; Table 2), no reaction took
place. In other cases, the indoles were fully consumed in 5-30 min (except for the reaction of 1a with
4-dimethylaminobenzaldehyde (2f); Entry 6; Table 2), and the corresponding symmetrical BIAs (3aa-al,
bd, bg, cd, cg, ed) were isolated as the sole products in 80-95% yields (Scheme 1, Table 2).
Ar
Y
Y
Y
O
10 mol% H3PO4-SiO2
+
60-70 °C, oven
5 min-1 h, 80-95%
Ar
H
X
N
X
N
N
X
H
H
H
2a-m
1a-e
X = H, Me
Y = OMe, Br, NO2
3aa-al, bd, bg, cd, cg, ed
Scheme 1
The results reflect the influence of the electronic nature of the substituents in both indoles and aryl aldehydes
on the reaction periods and the yields of the BIAs. Thus, the reactions of indole (1a)and indoles (1b, 1c, 1e)
bearing electron-donating groups with the benzaldehydes (2a-e) were quite fast (5-15 min) to furnish the
BIAs (3aa-ae, bd, cd, ed) in excellent yields (92-95%). However, we are unable to explain why the reaction
of 1a with 2f (Entry 6; Table 2) took a much longer period (1 h) for completion, which furnished the BIA
(3af) in 85% yield. The reactions of 4-trifluoromethoxybenzaldehyde (2g) with the indoles (1a-c) were
somewhat slower to furnish the BIAs (3ag-cg) in 89-93% yields. In contrast, the presence of a stronger
electron-withdrawing group (NO2) in aryl aldehydes or indole resulted in noticeably different results. Thus,
whereas the reactions of 4/3/2-nitrobenzaldehydes (2h-j) with indole (1a) required slightly longer time
(30-45 min) for completion to furnish the expected BIAs (3ah-aj) in somewhat lower yields (80-87%;
Entries 8, 9, 10), 5-nitroindole (1d) did not react at all with benzaldehyde and vanillin (2d) (Entries 18, 19).
The results of the reactions of the three heteroaryl aldehydes (2k-m) with indole (1a) using H3PO4-SiO2
parallel the results obtained using silicotungstic acid (STA)14b as the catalyst but differed from those resulting
from the use of the catalyst, montmorillonite K10 clay.18c Both these acidic solids had earlier been
demonstrated by us to be effective catalysts for a similar synthesis of the symmetrical BIAs. Thus, in the
present case, the 2-thienyl and 2-furyl aldehydes (2k, 2l) required 20 min for completion to furnish the
respective BIAs (3ak, 3al) in 92% and 86% respective yields, whereas the 2-pyrrolyl aldehyde (2m)
completely failed to react. A comparison of the results with 2k-m using the three aforesaid catalysts is

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presented in Table 3, which shows that H3PO4-SiO2 is marginally better (than clay and STA) for
2-formylthiophene (2k), much better for furfural (2l) but ineffective for 2-formylpyrrole (2m).
Table 2. Formation of BIAs (3) using 10 mol% H3PO4-SiO2 as the catalyst
Entry
Indole
(1)
ArCHO (2)
Equiv
of (2)
Time
BIA
(3)
Yield
(%)a
Ar =
1
a: X=Y=H
a: Ph
0.75
10 min aa
10 min ab
10 min ac
15 min ad
15 min ae
93
2
a
a
a
a
a
a
a
a
a
a
a
a
b: 4-MeOC6H4
c: 4-HOC6H4
0.75
0.75
95
95
94
95
85
89
87
80
85
92
86
-
3
4
d: 3-MeO-4-HOC6H3 0.75
5
e: 3,4-(MeO)2C6H3
f: 4-Me2NC6H4
g: 4-CF3OC6H4
h: 4-NO2C6H4
i: 3-NO2C6H4
j: 2-NO2C6H4
k: 2-Thienyl
0.75
1.0
6
1 h
af
7
1.0
20 min ag
30 min ah
30 min ai
45 min aj
20 min ak
20 min al
8
1.0
9
0.75
0.75
1.0
10
11
12
13
14
15
16
17
18
19
20
l: 2-Furyl
1.0
6 hb
-
m: 2-Pyrrolyl
1.0
b: X=H; Y=OMe d
0.75
1.0
5 min bd
15 min bg
10 min cd
20 min cg
95
93
95
92
-
b
g
d
g
a
d
d
c: X=H; Y=Br
0.75
1.0
c
6 hb
-
d: X=H; Y=NO2
d
1.0
6 hb
-
1.0
-
e: X=Me; Y=H
1.0
15 min ed
92
aRefer to isolated pure products; bNo product was formed (TLC) even after 6 h.

HETEROCYCLES, Vol. 68, No. 8, 2006
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Table 3. Reactions of 2k-m with indole (1a) using different catalysts: A comparative evaluation
Araldehyde
Product, Reaction Time and Yield using
c
Claya
3ak
STAb
H3PO4-SiO2
3ak
Conclusion
3ak
H3PO4-SiO2:
2k (X=S)
2l (X=O)
10 min, 80%
3al
7 min, 90%
3al
20 min, 92%
3al
marginally better
H3PO4-SiO2:
1 h, 81%
30 min, 73%
No reaction
6 h
20 min, 86%
No reaction
6 h
considerably better
TIM formed via
expected product
(3am)
1,1,1-Tris(indol-3-yl)-
methane (TIM)18c
4 h, 88%
2m (X=NH)
(in situ generated)
b
aMontmorillonite K10 clay (2 g) / 1 mmol indole / room temperature; 2 mol% silicotungstic acid / EtOAc / room
temperature; c10 mol% H3PO4-SiO2 / 60-70 °C (oven)
In order to test the applicability of H3PO4-SiO2 to alkanals and ketones, indole was separately treated with
each of formaldehyde, acetaldehyde (2n), propionaldehyde, glyceraldehyde, crotonaldehyde, ethyl methyl
ketone, acetophenone, isatin (2o) (as an example of a ketone contained within a heteroarene) and finally
3-formylindole (2p). Interestingly, the reagent proved to be of success only in the cases of 2n, 2o and 2p to
furnish the respective symmetrical BIAs, vibrindole A1e,1i (3an), trisindoline1i,20 (3ao) and
tris(indol-3-yl)methane1i (3ap). All the three symmetrical molecules are natural products isolated from
different strains of the bacteria Vibrio parahaemolyticus (Scheme 2).
Indole (1a)
H3PO4-SiO2
60-70 °C
2o
45 min
2n
40 min
H
2p
10 min
N
CH3
O
N
N
CH
H
N
H
N
H
)
H
3
3an (60%)
3ao (80%)
N
H
3ap (75%)
Scheme 2

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In conclusion, we have demonstrated that orthophosphoric acid (10 mol%)-on-silica gel (TLC-grade) is a
highly efficient and eco-friendly catalyst for the solvent-free and fast one-step synthesis of symmetrical
BIAs in excellent yields from the reaction of indoles with aryl aldehydes. Easy availability of the cheap
reagent, mild reaction conditions and clean work-up of the present methodology make it a highly attractive
protocol for the synthesis of diverse and new bioactive symmetrical BIAs.
EXPERIMENTAL
Mps were determined on a Toshniwal apparatus and are uncorrected. IR spectra (Nujol) were recorded on a
Nicolet Impact 410 spectrophotometer, LR EI-MS on JEOL JMS-AX505HA and HR EI-MS on JEOL
JMS-700 MStation mass spectrometers, 1H (both 300 and 400 MHz) and 13C (both 75 and 100 MHz) NMR
spectra, both 1D and 2D, including DEPT 135, HMQC and HMBC spectra, on Varian MERCURY plus 300
and Varian UNITY-400 NMR spectrometers. Individual 1H and 13C NMR spectral assignments of 3bd, 3bg,
3cd, 3cg and 3ed were additionally based on HMQC and HMBC NMR spectra. TLCs were carried out on
silica gel G(Merck, India) plates. PE refers to petroleum ether, bp 60-80 °C. Orthophosphoric acid Pure was
used as procured from Merck, India.
Reaction in EtOAc solution at rt. A solution of indole (1a; 1mmol) and benzaldehyde (2a; 0.75 equiv.) in
EtOAc (5 mL) was treated with ca. 0.7 mL of H3PO4 from astock solution (see below) and stirred at rt until
(4.5 h) indole was fully consumed (TLC). The reaction mixture was then washed successively with 2% aq.
NaHCO3, water, dried (Na2SO4), filtered, solvent removed and the resulting residue directly purified by
column chromatography (CC) over silica gel (grade SQ, Qualigens, India). 5% EtOAC/PE eluates furnished
3aa in 85% yield. It was identified as stated below.
Reaction in EtOAc solution at 60-70 °C. The above reaction was repeated at 60-70 °C in an oil bath, when
indole was consumed in 1.5 h. A similar work-up of reaction mixture and purification by CC over silica gel
furnished 3aa in 87% yield.
Preparation of H3PO4-SiO2. Each time areaction was carried out using 1.0mmol of the indole, the catalyst
was prepared by taking 0.7 mL of H3PO4 from a stock solution (0.15 mL H3PO4, made up to 15 mL with
EtOAc) and adsorbing it on silica gel G (2 g). The solution was then allowed to evaporate off at rt inside a
hood. Within few minutes it led to a free-flowing solid, which was H3PO4 (10 mol%)-SiO2.
General experimental procedure. A solution of indole (1.0 mmol) and aldehyde (0.75-1.0 equiv.) in ≤0.5
mL of CH2Cl2 (or EtOAc for substrates insoluble in CH2Cl2) was adsorbed on freshly prepared H3PO4-SiO2
(2g). The solvent was then allowed to evaporate off at rt and then the contents heated in an oven at 60-70 °C.
After the completion of the reaction (TLC), the reaction mixture was leached with CH2Cl2 (or EtOAc; 3×10
mL) and filtered. The filtrate was freed from acid by washing with 2% aq. NaHCO3, washed with water until
free from alkali, dried (Na2SO4) and the solvent removed. The resulting residue was purified by preparative

HETEROCYCLES, Vol. 68, No. 8, 2006
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TLC using PE-EtOAc (except for 3ai which was purified by direct crystallisation) to afford the pure BIAs.
Unless otherwise stated, the BIAs were crystallised from PE-EtOAc.
The following BIAs were identified by direct comparison (for available samples)or by comparing their mps
1
with the reported mps along with H NMR spectroscopic data. 3aa: mp 148-150 °C (PE-CH2Cl2) (lit.,14b
148 °C); 3ab: mp 194-195 °C (PE-CH2Cl2) (lit.,14b 194-195 °C); 3ac: mp 132-134 °C (lit.,14b 134-136 °C);
3ad: mp 106-108 °C (lit.,21 110-112 °C); 3ae: mp 194-196 °C (lit.,22 198-200 °C); 3af: mp 142-144 °C (lit.,23
not available); 3ag: mp 270-272 °C (lit.,14b 272-274 °C); 3ah: mp 236 °C (lit.,14b 240 °C); 3ai: mp
216-218 °C (lit.,14b 218-220 °C); 3aj: mp 142-144 °C (lit.,14b 141-143 °C); 3ak: mp 162 °C (lit.,14b 160 °C);
3al: mp >300 °C (lit.,24 325 °C); 3an: mp 154-156 °C (lit.,24 156 °C); 3ao: mp 312 °C (lit.,25 312-314 °C);
3ap: mp 238-240 °C (lit.,26 242-244 °C).
Bis(5-methoxyindol-3-yl)(4′-hydroxy-3′-methoxyphenyl)methane (3bd): mp 124 °C (PE-CH2Cl2); IR:
3409, 1613, 1580, 1507, 1268, 1208, 1169, 1122, 1029, 923, 804, 771, 731 cm-1; 1H NMR (CDCl3): δ 3.70
(6H, s, 2×5-OCH3), 3.72 (3H, s, 3′- OCH3), 5.70 (1H, s, Ar3CH), 6.62 (2H, dd, J1=2 Hz, J2=1 Hz, 2×H-2),
6.82 (1H, d, J=9 Hz, H-5′), 6.83 (2H, d, J=2.5 Hz, 2×H-4), 6.80-6.86 (4H, m), 6.87 (1H, d, J=1.5 Hz, H-2′),
13
7.21 (2H, d, J=9 Hz, 2×H-7), 7.89 (2H, d, J=2 Hz, 2×NH); C NMR: δ 39.9 (Ar3CH), 55.81 (3′- OCH3),
55.86 (2×5-OCH3), 102.0 (2×CH-6), 111.4 (CH-2′), 111.6 (2×CH-7), 111.7 (2×CH-4), 113.9 (CH-5′), 119.3
(2×C-3), 121.2 (CH-6′), 124.3 (2×CH-2), 127.4 (2×C-3a), 131.8 (2×C-7a), 136.0 (C-1′), 143.7 (C-4′), 146.3
(C-3′), 153.5 (2×C-5); EI-MS: m/z (%) 428 (M+, 100), 427 (23), 413 (4), 397 (6), 305 (26), 304 (5), 281 (8),
280 (7), 266 (3), 251 (2); HRMS (EI): calcd for C26H24N2O4, 428.1737; found 428.1732; Anal. Calcd for
C26H24N2O4: C, 72.89; H, 5.60; N, 6.54. Found: C, 72.97; H, 5.61; N, 6.52.
Bis(5-methoxyindol-3-yl)(4′-trifluoromethoxyphenyl)methane (3bg): mp 136-138 °C; IR: 3404, 1622,
1581, 1513, 1493, 1260, 1208, 1167, 1101, 1056, 1016, 924, 804, 711 cm-1; 1H NMR (CDCl3): δ 3.70 (6H,
s, 2×5-OCH3), 5.80 (1H, s, Ar3CH), 6.63 (2H, d, J=1.5 Hz, 2×H-2), 6.78 (2H, d, J=2 Hz, 2×H-4), 6.85 (2H,
dd, J1=8.5 Hz, J2=2 Hz, 2×H-6), 7.12 (2H, d, J=8 Hz, H-3′, 5′), 7.24 (2H, d, J=9 Hz, 2×H-7), 7.35 (2H, d,
J=9 Hz, H-2′, 6′), 7.90 (2H, s, 2×NH); 13C NMR: δ 39.6 (Ar3CH), 55.8 (2×5-OCH3), 101.7 (2×CH-4),
111.8 (2×CH-7), 111.9 (2×CH-6), 118.6 (2×C-3), 120.5 (q, J=255 Hz, 4′-OCF3), 120.6 (CH-3′, 5′), 124.4
(2×CH-2), 127.2 (2×C-3a), 129.9 (CH-2′, 6′), 131.8 (2×C-7a), 142.6 (C-1′), 147.5 (q, J=1.7 Hz, C-4′),
153.7 (2×C-5); EI-MS: m/z (%) 466 (M+, 100), 465 (23), 435 (8), 319 (9), 305 (35); HRMS (EI): calcd for
C26H21N2O3F3, 466.1504; found 466.1515; Anal. Calcd for C26H21N2O3F3: C, 66.95; H, 4.50; N, 6.00.
Found: C, 66.87; H, 4.49; N, 6.02.
Bis(5-bromoindol-3-yl)(4′-hydroxy-3′-methoxyphenyl)methane (3cd): mp 216 °C; IR: 3494, 3461, 3422,
1613, 1508, 1275, 1208, 1155, 1096, 1036, 883, 870, 797cm-1; 1H NMR (DMSO-d6): δ 3.65 (3H, s, 3′-
OCH3), 5.71 (1H, s, Ar3CH), 6.66-6.68 (2H, s, H-5′, 6′), 6.86 (2H, d, J=2 Hz, 2×H-2), 6.93 (1H, s, H-2′), 7.13

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HETEROCYCLES, Vol. 68, No. 8, 2006
(2H, dd, J1=9 Hz, J2=2 Hz, 2×H-6), 7.31 (2H, d, J=8 Hz, 2×H-7), 7.41 (2H, d, J=2 Hz, 2×H-4), 8.76 (1H, br
13
s, 4′-OH), 11.03 (2H, d, J=2 Hz, 2×NH); C NMR: δ 38.5 (Ar3CH), 55.6 (3′- OCH3), 110.7 (2×C-5), 112.7
(CH-2′), 113.5 (2×CH-7), 115.1 (CH-5′), 118.1 (2×C-3), 120.3 (CH-6′), 121.2 (2×CH-4), 123.3 (2×CH-6),
125.1 (2×CH-2), 128.4 (2×C-3a), 135.1 (C-1′), 135.2 (2×C-7a), 144.7 (C-4′), 147.2 (C-3′); EI-MS: m/z (%)
528 (M+4, 48), 526 (M+2, 100), 524 (M+, 50), 511 (3), 509 (4), 507 (2), 405 (10), 403 (21), 401 (15); HRMS
79
(EI): calcd for C24H18N2O2 Br2, 523.9735; found 523.9726; Anal. Calcd for C24H18N2O279+81Br2: C, 54.75;
H, 3.42; N, 5.32. Found: C, 54.84; H, 3.43; N, 5.33.
Bis(5-bromoindol-3-yl)(4′-trifluoromethoxyphenyl)methane (3cg): mp 126 °C; IR: 3418, 1719, 1606,
1566, 1503, 1420, 1255, 1218, 1162, 1102, 1029, 923, 883, 794 cm-1; 1H NMR (DMSO-d6): δ 5.93 (1H, s,
Ar3CH), 6.91 (2H, d, J=2 Hz, 2×H-2), 7.14 (2H, dd, J1=8.5 Hz, J2=2 Hz, 2×H-6), 7.27 (2H, d, J=8.5 Hz, H-3′,
5′), 7.33 (2H, d, J=8.5 Hz, 2×H-7), 7.43 (2H, d, J=8.5 Hz, H-2′, 6′), 7.44 (2H, d, J=2 Hz, 2×H-4), 11.11 (2H,
13
d, J=2 Hz, 2×NH); C NMR: δ 47.5 (Ar3CH), 120.5 (2×C-5), 123.1 (2×CH-7), 126.7 (2×C-3), 129.6 (q,
J=256.5 Hz, 4′-OCF3), 130.2 (CH-3′, 5′), 130.5 (2×CH-4), 133.0 (2×CH-6), 134.7 (2×CH-2), 137.7
(2×C-3a), 139.3 (CH-2′, 6′), 144.7 (2×C-7a), 153.3 (C-1′), 156.0 (q, J=1.5 Hz, C-4′); EI-MS: m/z (%) 566
(M+4, 53), 564 (M+2, 100), 562 (M+, 52), 485 (9), 483 (13), 405 (14), 403 (30), 401 (17), 369 (11), 367
(10), 323 (5), 288 (15); HRMS (EI): calcd for C24H15N2O79Br2F3, 561.9503; found 561.9500; Anal. Calcd
for C24H15N2O79+81Br2F3: C, 51.06; H, 2.66; N, 4.96. Found: C, 51.20; H, 2.67; N, 4.98.
Bis(2-methylindol-3-yl)(4′-hydroxy-3′-methoxyphenyl)methane (3ed): mp 184 °C; IR: 3546, 3379, 1613,
1508, 1241, 1122, 1023, 857, 824, 751 cm-1; 1H NMR (DMSO-d6): δ 2.04 (6H, s, 2×2-CH3), 3.55 (3H, s, 3′-
OCH3), 5.80 (1H, s, Ar3CH), 6.51 (1H, dd, J1=8 Hz, J2=1.5 Hz, H-6′), 6.63 (1H, d, J=8 Hz, H-5′), 6.66 (2H,
dt, J1=8 Hz, J2=1.5 Hz, 2×H-6), 6.80 (1H, d, J=1.5 Hz, H-2′), 6.84 (2H, dd, J1=8 Hz, J2=1.5 Hz, 2×H-7), 6.86
(2H, dt, J1=8 Hz, J2=1.5 Hz, 2×H-5), 7.18 (2H, d, J=8 Hz, 2×H-4), 8.70 (1H, s, 4′-OH), 10.66 (2H, s, 2×NH);
13C NMR: δ11.9 (2×2-CH3), 38.1 (Ar3CH), 55.6 (3′- OCH3), 110.2 (2×CH-4), 112.7 (2×C-3), 113.4 (CH-2′),
114.9 (CH-5′), 117.8 (2×CH-6), 118.5 (2×CH-7), 119.4 (2×CH-5), 120.8 (CH-6′), 128.3 (2×C-7a), 131.8
(2×C-2), 135.0 (C-1′, 2×C-3a), 144.5 (C-4′), 147.3 (C-3′); EI-MS: m/z (%)396 (M+, 100), 395 (25), 381 (84),
365 (5), 273 (29), 265 (26), 264 (27), 257 (16), 130 (10); HRMS (EI): calcd for C26H24N2O2, 396.1837;
found 396.1846; Anal. Calcd for C26H24N2O2: C, 78.78; H, 6.06; N, 7.07. Found: C, 78.89; H, 6.07; N, 7.08.
ACKNOWLEDGEMENTS
The authors express their sincere thanks to the Director, Bose Institute for providing laboratory facilities,
the C.S.I.R., Govt. of India for providing fellowships (R. M. and A. M.), Mr. B. Majumder, NMR Facilities
and Mr. P. Dey, Microanalytical Laboratory, both of Bose Institute, for recording the spectra.

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