Tetrabutylammonium tribromide as efficient catalyst in the synthesis of bis(indolyl)methanes

Article abstract of DOI:10.1134/S1070428010010136

An efficient procedure has been developed for the synthesis of bis(indolyl)methane derivatives by condensation of aldehydes with indole in the presence of tetrabutylammonium tribromide as catalyst.

Full text of DOI:10.1134/S1070428010010136

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 1, pp. 126–128. © Pleiades Publishing, Ltd., 2010.
Published in Russian in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 1, pp. 125–127.
Tetrabutylammonium Tribromide as Efficient Catalyst
in the Synthesis of Bis(indolyl)methanes*
S. K. Kundu, S. Islam, A. Hajra, and A. Majee
Department of Chemistry, Visva-Bharati University, Santiniketan, West Bengal, 731235 India
e-mail: adinathm@ yahoo.com
Received July 2, 2009
Abstract—An efficient procedure has been developed for the synthesis of bis(indolyl)methane derivatives by
condensation of aldehydes with indole in the presence of tetrabutylammonium tribromide as catalyst.
DOI: 10.1134/S1070428010010136
Indoles and their derivatives are important as phar-
macologically and biologically active compounds [1].
Bis(indolyl)methanes and their derivatives are widely
recognized as bioactive metabolites of terrestrial and
marine origin [2–6]. Significant efforts have been
made to synthesize such compounds. They are usually
prepared by condensation of indole with carbonyl
compounds in the presence of a protic [7] or Lewis
acid [8]. However, the problem in using Lewis acids is
their sensitivity to moisture, and in many cases more
than stoichiometric amount is required due to trapping
by nitrogen-containing substrate. This problem may be
avoided to some extent by using lithium perchlorate
Taking the above stated into account, development
of a mild and efficient alternative procedure for the
synthesis of bis(indolyl)methanes seems to be im-
portant. Our continuous studies in this line [15–21]
showed that tetrabutylammonium tribromide (TBATB)
effectively catalyzes formation of bis(indolyl)methanes
in the condensation of various aldehydes with indoles
in ethanol at room temperature (Scheme 1). The ex-
perimental procedure is very simple. It involves
mixing equimolar amounts of aldehyde and indole and
8 mol % of TBATB in ethanol at room temperature and
allowing the reaction to go to completion (the progress
of the reaction being monitored by thin-layer chroma-
tography). The results are summarized in table. It is
seen that the reaction is general: various aliphatic,
aromatic, heterocyclic, and α,β-unsaturated carbonyl
compounds reacted with indole in the presence of
TBATB to produce the corresponding bis(indolyl)-
methane derivatives in good yields. The conditions
were so mild that no other transformations, e.g.,
isomerization of double bond, occurred. The yields of
the condensation products from aromatic aldehydes
with electron-withdrawing substituents were compared
with those obtained from other aliphatic and aromatic
aldehydes containing electron-donating groups, the
reaction time being 2–4 h.
[9], but the latter is expensive, and the reaction time is
longer. Some other reagents like NaHSO –SiO , I ,
4
2
2
NBS, and K-10 montmorillonite were also used to
catalyze the above reaction [10]. Some syntheses in the
presence of rare earths, such as LnCl , Ln(OTf) , and
3
3
Re(PFO) , were recently reported as alternative of
3
conventional Lewis acid catalysis [11, 12]. However,
many of these procedures require long reaction time
and large amounts of the catalyst. Ionic liquid [13]
and surfactant [14] were used very recently to catalyze
synthesis of bis(indolyl)methanes, but ionic liquids are
expensive and the use of surfactant makes the experi-
mental procedure very tedious.
Scheme 1.
R
O
Bu NBr , EtOH
4
3
2
+
N
R
H
H
HN
NH
*
The text was submitted by the authors in English.
1
26

TETRABUTYLAMMONIUM TRIBROMIDE AS EFFICIENT CATALYST
127
Scheme 2.
Bu NBr
+
EtOH
HBr
+
BrOEt
OH
+
Bu NBr
4
4
3
R
R
H
H
OH
H
+
–
H O
2
N
R
H
N
H
N
H
H
R
R
N
H
H
–H+
H
HN
HN
NH
N
H
A probable reaction mechanism is shown in
Scheme 2. Tetrabutylammonium tribromide is an ex-
cellent source of anhydrous hydrogen bromide, and the
acidity of the medium can be tuned by choosing an ap-
propriate solvent. In our case, anhydrous HBr liber-
ated in the reaction of TBATB with ethanol catalyzes
addition of indole to carbonyl compounds.
Yields of bis(1H-indol-3-yl)methanes in reactions of indole
with aldehydes
a
R
Time, h
Yield, %
Ph
02.5
03.5
72
70
1
2
4
-Naphthyl
-O NC
-HOC
2
6
H
4
02.0
03.0
03.0
06.0
03.0
04.0
03.0
80
65
60
60
65
65
75
To conclude, the proposed procedure ensures highly
efficient synthesis of bis(indolyl)methane derivatives
at room temperature. It is advantageous due to opera-
tional simplicity, mild conditions, ecological safety,
compatibility with various functional groups, high
yields, and the use of easily accessible and inexpensive
reagent as catalyst.
6
H
4
6 4
4-ClC H
4
4
3
2
2
2
-MeC
-MeOC
,4,5-(MeO)
6 4
H
6 4
H
3
C
6
H
2
,4-(MeO)
-Furyl
2
C
6
H
3
EXPERIMENTAL
15.0
01.0
04.0
70
75
60
-Thienyl
3
,3′-Benzylidenedi(1H-indole) (typical proce-
dure). A mixture of 106 mg (1 mmol) of benzaldehyde,
34 mg (2 mmol) of indole, and 40 mg (8 mol %) of
Pr
2
7 15
C H
0
0
5.0
4.0
60
60
65
tetrabutylammonium tribromide in 3 ml of ethanol was
stirred for 2.5 h at room temperature. When the reac-
tion was complete (TLC), the mixture was evaporated,
and the residue was extracted with diethyl ether. The
extract was dried over Na SO and concentrated, and
PhCH=CH
C
9
H
19
06.0
a
Preparative yield after purification; the products were charac-
terized by IR and H NMR spectra.
2
4
1
the crude product was purified by column chromatog-
raphy on silica gel using hexane–ethyl acetate (9:1) as
eluent. Yield 231 mg (72%). The product was iden-
tified by spectral data and comparison with an authen-
tic sample. The other compounds were synthesized in
a similar way.
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