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Department of Chemistry,
Shri Muktanand College, Gangapur, Dist-Aurangabad-431109, M. S., INDIA.
b
Department of Chemistry,
Deogiri College, Aurangabad-431005, M.S., INDIA.
(Received on: June 22, 2012)
ABSTRACT
An efficient, solvent free, one pot, synthesis of bis (indolyl)
methane using indole and substituted aromatic aldehyde is
achieved, through grinding technique at room temperature, in a
short period of time giving the product in quantitative yield.
Keywords: Trichloroacetic acid, bisindolylmethanes, grinding
technique, solvent free.
INTRODUCTION
Today with the growing epidome of
environmental
pollution
worldwide,
researchers are more concerned to use
environmental
benign
reactions and
techniques
to
perform
organic
transformation that can generate minimum
amount of toxic waste material1. In a routine
generality an organic synthesis is always
performed in solvent system, which can
bring the reactants in the reaction to interact
fastly, solvate the reactant and through
various interactive forces yields the product
easily. But in an idea to generate
environment friendly reactions, basically
Journal of Chemistry and Chemical Sciences, Vol.2, Issue (2&3), 1 July, 2012 (92-137)
129
Vivekanand B. Jadhav, et al., J. Chem. & Cheml. Sci. Vol.2 (2&3), 128-137 (2012)
MeO
S
Cl
Cl
OH
N
HO
NH2
Tenidap
Indomethacin
Fig:01
HOOC
O
NH
H
N
O
HOOC
N
N
H
COOH
COOH
H
N
O
HOOC
COOH
HOOC
Vivekanand B. Jadhav, et al., J. Chem. & Cheml. Sci. Vol.2 (2&3), 128-137 (2012)
Further
a
number
of
bis(indolyl)methanes or bis (indolyl)ethanes
have been also isolated from marine
sources9. Bis(indolyl)methanes was found in
cruciferous plants are shown to promote
beneficial estrogen metabolism in humans10,
act as an anticancer agent by inducing
apoptosis in human11a-c cancer cells (breast
cancer) and can act as highly selective
fluorescent molecular sensors for Cu+2
ions11d. Indole derivatives like di (1-Hindolyl-3-yl) methanes (DIM) and 1, 4-bis
[di (1H-indol-3-yl) methyl] benzenes are
found to be useful in the treatment of
fibromyalgia, chronic fatigue and irritable
Further
these
bowel
syndrome12.
bis(indolyl)alkanes and their derivatives are
shown to normalize abnormal cell growth
associated with cervical dysplasia13. Thus
these indole and 3-substituted indoles
derivatives are shown to exhibit diverse
pharmaceutical and therapeutic applications
in drug discovery including, antiviral14,
antibiotics15, cytotoxic16, antioxidative17,
radical scavengers18, antimicrobial19 and
insecticidal activities17. Further it was
observed that, indole derivatives such as
R1
N R2
R2
NR1
HN
NH
N
H
MeO
O
N
130
OMe
N
H
N
H
lines such as
lungs (HOP-92), renal
(A498) and breast (MDAMB-231/1TCC).
Further it is observed that 1, 1, 3-tri (3-
Journal of Chemistry and Chemical Sciences, Vol.2, Issue (2&3), 1 July, 2012 (92-137)
131
Vivekanand B. Jadhav, et al., J. Chem. & Cheml. Sci. Vol.2 (2&3), 128-137 (2012)
R
R
N
X=H, Me
N
H
R= Aryl
X X
N
H
R= Aryl; X=H, Me
Journal of Chemistry and Chemical Sciences, Vol.2, Issue (2&3), 1 July, 2012 (92-137)
Vivekanand B. Jadhav, et al., J. Chem. & Cheml. Sci. Vol.2 (2&3), 128-137 (2012)
Table 1 Y ield and reaction time of Trichloroacetic acid catalyzed various bis( ind olyl)methanes
Entry
Aromatic
Aldehyde
Time
(min)
Product
Yield %
M. P. (oC)
89
96-98 27
CHO
1.
H
N
H
1a
N
H
Cl
CHO
2.
Cl
N
H
91
76-7827
92
222-22427
N
1b H
NO2
CHO
3.
H
N
H
O2N
1c
N
H
OH
CHO
4.
H
HO
N
H
1d
87
121-12327
88
108-110 28
88
178-18129
90
110-11227
N
H
Br
CHO
5.
H
Br
N
H
1e
N
H
CHO
6.
N
N
H
1f
N
H
OH
OCH3
CHO
7.
HO
OCH3
N
H
1g
N
H
Journal of Chemistry and Chemical Sciences, Vol.2, Issue (2&3), 1 July, 2012 (92-137)
132
133
Vivekanand B. Jadhav, et al., J. Chem. & Cheml. Sci. Vol.2 (2&3), 128-137 (2012)
Entry
Aromatic
Aldehyde
Product
Time
(min)
Yield %
M. P. (oC)
O
O
CHO
O
8.
H
O
N
H
87
87-89 27
91
188-19027
N
H
1h
OCH3
CHO
9.
H
N
H
H 3CO
N
H
1i
O
10.
11.
Me
CHO
N
H
1j
85
320-32227
87
246-248 30
89
208-210 31
N
H
CHO
N
H
2a
N
H
OMe
CHO
12.
Me
N
H
MeO
2b
N
H
NO2
CHO
13.
Me
O 2N
5
N
H
2c
92
N
H
Journal of Chemistry and Chemical Sciences, Vol.2, Issue (2&3), 1 July, 2012 (92-137)
240-24230
Vivekanand B. Jadhav, et al., J. Chem. & Cheml. Sci. Vol.2 (2&3), 128-137 (2012)
Experimental Part
All the chemicals (AR grade) were
purchased from SD fine chemicals and used
without further purification. Melting points
of the products were recorded using
capillaries open at one end and were
uncorrected. 1H and 13C NMR were recorded
on 400 MHz Varian spectrophotometer in
CDCl3 solvent with TMS as an internal
standard. IR was recorded on Bruker Vector
22 FTIR spectrophotometer using KBr discs.
Exact mass of the samples were recorded on
Shimadzu mass analyzer. The progress of
the reaction was monitored by Thin Layer
Chromatography in 20 % ethyl acetate:
hexane.
134
Journal of Chemistry and Chemical Sciences, Vol.2, Issue (2&3), 1 July, 2012 (92-137)
135
Vivekanand B. Jadhav, et al., J. Chem. & Cheml. Sci. Vol.2 (2&3), 128-137 (2012)
CONCLUSION
In summary, we have developed
trichloroacetic acid catalyzed novel, solvent
free, efficient environment benign method
for the synthesis of pharmaceutically
important bis(indolyl) methanes utilizing
grinding technique at room temperature in
excellent yield, which nicely places itself in
the list of solvent free synthesis under
grinding technique. This new protocol has
striking features like cleaner reaction
profiles, simple experimental and work-up
procedures, high conversions, shorter
reaction times to afford the products in
excellent yield, hence believed to be
superior over many existing synthetic
methods of catalysts.
ACKNOWLEDGMENTS
We are sincerely thankful to Dr.
Shivaji B. Munde, Principal, Shri
Muktanand College, Gangapur, DistAurangabad (MS), India for his constant
encouragement and providing us laboratory
facilities during the work.
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Journal of Chemistry and Chemical Sciences, Vol.2, Issue (2&3), 1 July, 2012 (92-137)
Vivekanand B. Jadhav, et al., J. Chem. & Cheml. Sci. Vol.2 (2&3), 128-137 (2012)
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Journal of Chemistry and Chemical Sciences, Vol.2, Issue (2&3), 1 July, 2012 (92-137)
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