An efficient procedure for the preparation of mono, and di-bis-indolyl methanes catalyzed by molibdatophosphoric acid

Article abstract of DOI:10.1080/10426500490484904

H₃PMo₁₂O₄₀·xH₂O was found to be an effective catalyst for the preparation of bis-indolyl derivatives from indole and aromatic, aliphatic, heterocyclic aldehydes or ketones in ethanol at room temperature.

Full text of DOI:10.1080/10426500490484904

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Phosphorus, Sulfur, and Silicon
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AN EFFICIENT PRO CEDURE
FOR THE PREPARATION OF
MONO, AND DI-BIS-INDOLYL
METHANES CATALYZED BY
MOLIBDATOPHOSPHORIC ACID
Mohammad Ali Zolfigol a , Peyman Salehi b &
Morteza Shiri a
a Chemistry Department, College of Science, Bu-Ali
Sina University, Hamadan, I. R. Iran
b Department of Phytochemistry, Aromatic and
Medicinal Plants and Drug Research Institute, Shahid
Beheshti University, Tehran, Iran
Version of record first published: 16 Aug 2010.
To cite this article: Mohammad Ali Zolfigol , Peyman Salehi & Morteza Shiri (2004):
AN EFFICIENT PRO CEDURE FOR THE PREPARATION OF MONO, AND DI-BIS-INDOLYL
METHANES CATALYZED BY MOLIBDATOPHOSPHORIC ACID, Phosphorus, Sulfur, and
Silicon and the Related Elements, 179:11, 2273-2277
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Phosphorus, Sulfur, and Silicon, 179:2273–2277, 2004
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490484904
AN EFFICIENT PROCEDURE FOR THE
PREPARATION OF MONO, AND DI-BIS-INDOLYL
METHANES CATALYZED BY
MOLIBDATOPHOSPHORIC ACID
Mohammad Ali Zolfigol,a Peyman Salehi,b and Morteza Shiria
Chemistry Department, College of Science, Bu-Ali Sina
University, Hamadan, I. R. Iran;a and Department of
Phytochemistry, Aromatic and Medicinal Plants and Drug
Research Institute, Shahid Beheshti University, Evin,
Tehran, Iranb
(Received May 4, 2004; accepted May 4, 2004)
H3PMo12O40 · xH2O was found to be an effective catalyst for the prepa-
ration of bis-indolyl derivatives from indole and aromatic, aliphatic,
heterocyclic aldehydes or ketones in ethanol at room temperature.
Keywords: Aldehyde; bis-indolyl methanes; heteropolyacids; indole;
ketone
Acids are widely used as catalysts in industry for producing more than
1 × 108 mt/year of products. The most commonly used are HF, H2SO4,
HClO4, and H3PO4 (in liquid form or supported on Keiselguhr). Solid
acids have many advantages such as simplicity in handling, decreased
reactor and plant corrosion problems, and more environmentally safe
disposal. Also, wastes and by-products can be minimized or avoided
by developing cleaner synthesis routes. On the other hand, reduction
in the amount of liquid acid needed and/or simplification in handling
procedures is required for risk reduction, economic advantage, and en-
vironment protection.1 Uses of heteropolyacids (HPAs) as catalysts for
fine organic synthetic processes have been developed that are very im-
portant for industries related to fine chemicals, such as flavors, phar-
maceuticals, and food industries.2 Heteropolyacids are cheap, reusable,
heterogeneous, and easily available catalysts.3 In recent years,
Address correspondence to Mohammad Ali Zolfigol, Chemistry Department, College
of Science, Bu-Ali Sina University, Hamadan 65174, P.O. Box 4135, I. R. Iran. E-mail:
Zolfi@basu.ac.ir
2273

2274
M. A. Zolfigol et al.
heteropolyacids and their salts have received considerable atten-
tion as powerful reaction mediums for effecting various organic
transformations3 such as selective bromination of aromatic compounds,
silylation of alcohols, oxidation of aromatic amines to nitro compounds,
thioacetalization and transthioacetalization reactions, oxidation of hy-
droxy groups to their corresponding carbonyl functions, gem-acylation,4
and Friedel-Crafts5 reactions. The use of Lewis acids in the synthesis
of bis-indolyl methanes is also well known.6 Lewis acids such as AlCl3
and LiClO73, I82 have been used for this purpose. However, the reaction
can also be assisted by IR irradiation using a bentonitic clay as cata-
lyst under solvent-free conditions.9 The above-mentioned applications
of Lewis acids suffer from two limitations. First, more than stoichio-
metric amounts of the Lewis acid are needed in many cases. Second,
these Lewis acids are moisture sensitive and easily decomposed and
deactivated in the presence of even a small amount of water. Recently,
lanthanide and indium triflates were reported as effective catalysts in
the reaction of indoles with aldehydes or ketones.10 While these salts
are active in aqueous solution, longer reaction times (12–36 h) are re-
quired to obtain the desired product in good yield. Furthermore, lan-
thanide triflates are highly expensive. During the course of our work
towards the application of solid acids in organic reactions11 we found
that H3PMo12O40·xH2O is an efficient catalyst for the condensation of
indole and aldehyde or ketones. Here we wish to report a rapid and
convenient procedure for the preparation of bis-indolyl methanes from
indole and aldehydes or ketones in the presence of H3PMo12O40·xH2O
in ethanol (Scheme 1 and Table I).
The reaction of benzaldehyde and indole in the presence
molybdatophosphoric acid (5% eq) was complete after 20 min in ethanol
as solvent at room temperature (entry 1). Both aromatic and het-
erocyclic aldehydes reacted similarly to give the corresponding bis-
indolyl derivatives in high yields and short reaction times (entries
1–7 and 10). Aliphatic aldehyde and ketones reacted smoothly pro-
viding the corresponding products in good-to-moderate yields (entries
8, 9, 11). The reaction of 3-nitrobenzaldehyde was complete after
2 h but 4-nitrobenzaldehyde produced the corresponding bis-indolyl
methane’s after 6 h. Interestingly, when we used terephetalaldehyde,
p-bis-indolylmethane benzaldehyde was produced in excellent yield
(Scheme 1). Also p-di(bis-indolylmethane)benzene was obtained in
dimethyl sulfoxide (DMSO) as solvent at 120◦C after 1 h in high
yield.
In conclusion, the cheapness and ready availability of the catalyst,
easy and clean workup, and good yields make this method attractive
for organic chemists.

Bis-Indolyl Methanes
2275
SCHEME 1
EXPERIMENTAL
General
Chemicals were purchased from Fluka, Merck, and Aldrich chemical
companies. Yields refer to isolated pure products. Products were char-
acterized by comparison of their spectral (IR, 1H NMR), thin layer chro-
matography (TLC), and physical data with authentic samples.
General Procedure for Mono Bis-Indolylmethanes
H3PMo12O40 · xH2O (0.05 mmol) was added to the stirring solution of
indole (2 mmol), aldehyde, or ketone (1 mmol) in EtOH (5 ml) at room
temperature. The reaction was followed by TLC. On completion H2O
(20 mL) was added to the reaction mixture. The products were precipi-
tated and filtered. Then the residue was purified by column chromatog-
raphy on silica gel (n-hexane/ethyl acetate: 8:2).
Typical Procedure for 1,4-Phenylene-di(bis-
indolylmethane)
The mixture of indole (4 mmol), terephethalaldehyde (1 mmol), and
H3PMo12O40 · xH2O (0.10 mmol) in DMSO (10 ml) was heated to 120◦C.
Reaction was complete after 1 h (monitored by TLC). H2O (30 ml) was

2276
M. A. Zolfigol et al.
TABLE I Preparation of Bis-Indolyl Methanes from Indole and
Aldehydes or Ketones in the Presence of H3PMo12O40 as a
Catalyst in Ethanol at Room Temperature
Entry
1
Substrate
Time (h)
0.33
Isolated yield (%)
93
2
0.18
92
3
4
5
6
1
90
95
90
91
0.5
6
2
7
8
2
92
81
10
9
15
73
10
11
0.5
18
80
90
added to the reaction mixture. The red product precipitated and was
isolated by filtration. Then the residue was washed with diethyl ether.
Pure p-di(bis-indolylmethane) benzene was obtained.
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2277
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