Facile synthesis of bis(indolyl)methanes catalyzed by ferric dodecyl sulfonate [Fe(DS)3] in water at room temperature

Article abstract of DOI:10.1080/00397910701873318

Ferric dodecyl sulfonate [Fe(DS)3] is easily prepared and can be used as a Lewis acid surfactant catalyst in water to conduct the highly efficient electrophilic substitution reaction of indoles with aliphatic or aromatic aldehydes at room temperature. Copyright Taylor & Francis Group, LLC.

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Facile Synthesis of Bis(indolyl)methanes
catalyzed by Ferric Dodecyl Sulfonate
[Fe(DS)3] in Water at Room Temperature
Shun‐Yi Wang a & Shun‐Jun Ji a
a Key Laboratory of Organic Synthesis of Jiangsu Province, College of
Chemistry and Chemical Engineering, Suzhou University, Suzhou, China
Version of record first published: 17 Apr 2008.
To cite this article: Shun‐Yi Wang & Shun‐Jun Ji (2008): Facile Synthesis of Bis(indolyl)methanes catalyzed
by Ferric Dodecyl Sulfonate [Fe(DS)3] in Water at Room Temperature, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 38:8, 1291-1298
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Synthetic Communicationsw, 38: 1291–1298, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701873318
Facile Synthesis of Bis(indolyl)methanes
catalyzed by Ferric Dodecyl Sulfonate
[Fe(DS)3] in Water at Room Temperature
Shun-Yi Wang and Shun-Jun Ji
Key Laboratory of Organic Synthesis of Jiangsu Province, College of
Chemistry and Chemical Engineering, Suzhou University,Suzhou, China
Abstract: Ferric dodecyl sulfonate [Fe(DS)3] is easily prepared and can be used as a
Lewis acid surfactant catalyst in water to conduct the highly efficient electrophilic sub-
stitution reaction of indoles with aliphatic or aromatic aldehydes at room temperature.
Keywords: Bisindolymethanes, Fe(DS)3, indole, water
INTRODUCTION
Water has many potential advantages as a solvent for organic reactions from
the vantage point of its cost, safety, and environmental concern.[1] Recently,
some attempts to achieve organic reactions in aqueous media have been
performed, and consequently some successful examples have appeared in
the literature.[2]
Lewis acid-surfactant-combined catalysts (LASC) have been easily
prepared, developed, and applied to Lewis acid–catalyzed organic reactions
in water. These catalysts have been successfully used for various typical
carbon–carbon bond-forming reactions such as aldol, allylation, Mannich-
type reactions, and Michael addition in water.[3]
Received May 10, 2007
Address correspondence to Shun-Jun Ji, Key Laboratory of Organic Synthesis of
Jiangsu Province, College of Chemistry and Chemical Engineering, Suzhou Univer-
sity, Renai Road, Suzhou Industrial Park, Suzhou 215123, China. E-mail: chemjsj@
suda.edu.cn
1291

1292
S.-Y. Wang and S.-J. Ji
Figure 1.
Scheme 1.
Furthermore, bis(indolyl)methanes are gaining prominence in view of
their occurrence in bioactive metabolites of terrestrial and marine origin.[4]
Bis(indolyl)methanes have been obtained by reactions of indoles with
various aldehydes or ketones in the presence of protic acids,[5] Lewis
acids,[6] solid acids,[7] trichloro-1,3,5-triazine (TCT),[8] NaHSO4 SiO2,[9]or
.
KHSO4.[10] Most of the previously reported methods suffer from several
setbacks such as requirement of a stoichiometric amount of the Lewis acid,
expensive and toxic catalysts, and toxic solvents such as CH3CN. However,
these problems were overcome to some extent by recently reported methods,
such as the use of Re(PFO)3,[11] ionic liquids,[12] and I2.[13] Hence, a more
efficient and practical alternative using an inexpensive and environmentally
friendly reagent and solvent are still desirable. While we were preparing this
article, another important work was reported of a similar reaction carried out
in a protic solvent in the presence sodium dodecyl sulfate to afford bis(indo-
lyl)-methanes.[14] However, there have been no reports on the electrophilic
substitution reaction of indoles with aliphatic or aromatic aldehydes in water
employing Fe(DS)3 as a catalyst. (Figure 1)
Bearing the LASC concept in mind, we describe Fe(DS)3 as an efficient
LASC for electrophilic substitution reaction of indoles with aliphatic or
aromatic aldehydes in water at room temperature (Scheme 1).
RESULTS AND DISCUSSION
To show the strong catalytic effect of Fe(DS)3, the reaction of indole and ben-
zaldehyde in the absence of Fe(DS)3 was also studied in water. It is interesting
to note that the desired bis(indolyl)phenylmethane (Table 1, entry 1) could be
obtained in 60% yield after a prolonged reaction time (24 h). We have also
studied a similar reaction in the presence of FeCl.36H2O in water (Table 1,
entry 7). The reaction proceeded sluggishly and the desired product was
obtained in 45% yield after 24 h. Among the various metal dodecyl sulfonates
[15]
such as Yb(DS)3, Sm(DS)3, and In(DS)3
studied for this transformation,

Synthesis of Bis(indolyl)methanes
1293
Table 1. Reaction of indole 1a with benzaldehyde catalyzed by
different catalysts in watera
Entry
Lewis acids
Time (h)
Yield (%)b
1
2
3
4
5
6
7
—
InCl3
24
24
6
60
70
83
80
79
90
45
In (DS)3
Yb(DS)3
Sm(DS)3
Fe(DS)3
6
6
6
24
.
FeCl3 6H2O
aThese reactions were performed using 1 mol% catalysts at
room temperature.
ferric(III) dodecyl sulfonate was found to be the most effective catalyst in
terms of conversion and reaction rates. These results showed that the combi-
nation of a Lewis acid moiety (cationic part) and a surfactant (anionic part) in
Fe(DS)3 was important for the reactions to proceed in water.
The scope and generality of this process is illustrated with respect to
various indoles and a wide range of aldehydes, and the results are presented
in Tables 2 and 3. In all cases, aldehydes reacted more rapidly. Aliphatic
(Table 2, entry 1), aromatic (Table 2, entries 2–7), and heteroaromatic
(Table 2, entries 7 and 8) similarly gave the corresponding bis(indolyl)-
methanes 3a, b–g, (h–j) smoothly in 80–97% yields within 2–12 h. Even
solid aldehydes such as p-chlorobenzaldehyde (mp 47–508C) reacted
smoothly (Table 2, entry 3) to give the product 3c in 80% yield. The
reaction of 2k (1 mmol) with 1 (4 mmol) proceeded well in the presence of
Fe(DS)3 in water to give 3k and 3k0 in 59% and 33% respectively
(Scheme 2). Unfortunately, the reaction of a ketone 2l (Table 2, entry 12)
could not give the bisindole derivatives in 12 h under identical conditions.
Table 3 shows the scope and generality of the present method with respect
to various indoles. However, 3-substituted indole (Table 3, entry 2) did not
1
participate in the reaction. All products were characterized by H NMR and
mass spectral analysis and comparison with authentic samples. The Lewis
acid part of the catalyst activates the aldehyde and the surfactant part,
affecting the solubility of the substrates in water at the same time. When
these two factors are in play together, a drastic enhancement of the rates
and the yields of the products are observed.

1294
S.-Y. Wang and S.-J. Ji
Table 2. Reaction of indole 1a with various aldehydes and acetophenone catalyzed
by Fe(DS)3 in watera
Entry
RCHO
HCHO
Number
Products
Time (h)
Yield (%)b
1
2
2a
2b
3a
3b
10
6
83
90
3
2c
3c
4
80
4
5
2d
2e
3d
3e
2
5
93
97
6
7
2f
3f
4
8
81
80
2g
3g
8
9
2h
2i
3h
3i
6
80
90
12
10
11
2j
3j
6
6
95
2k
3k/3k0
92 (64:36)
12
2l
—
12
—
a1 mol% catalyst was used.
bIsolated yield.
In conclusion, in this study we have introduced Fe(DS)3 as an efficient
catalyst and water as solvent for synthesis of bis(indolyl)methane derivatives
at room temperature. The use of easily accessible Fe(DS)3 as a LASC and
water as solvent makes this procedure quite simple, convenient, and environ-
mentaly friendly. The application of Fe(DS)3 as a catalyst for other reactions
of indoles in water is in process in our laboratory.

Synthesis of Bis(indolyl)methanes
1295
Table 3. Reaction of 2e with various indoles 1(b–g) catalyzed by Fe(DS)3 in watera
Entry
1
Indoles
Number
Products
Time/(h)
Yield (%)b
87
1b
3l
3
2
3
1c
—
12
6
—
82
1d
3m
4
5
1e
1f
3n
3o
6
88
73
10
6
1g
3q
4
93
a1 mol% catalyst was used.
bIsolated yield.
Scheme 2.
EXPERIMENTAL
General
Melting points were recorded on an Electrothermal digital melting-point
1
apparatus and are uncorrected. H NMR (400-MHz) spectra were recorded
on a Varian Mercury MHz spectrometer in CDCl3. IR spectra were
obtained on a Nicolet FT-IR500 spectrophotometer using KBr pellets. High-
resolution mass spectra (HRMS) were obtained using a GCT-TOF instrument.

1296
S.-Y. Wang and S.-J. Ji
General Procedure for Synthesis of 3
A mixture of benzaldehyde (1 mmol), indole (2 mmol), and Fe(DS)3 (1 mol%)
were stirred together in water at room temperature for a proper time. After
completion of the reaction as monitored by thin-layer chromatagraphy
(TLC), the mixture was filtered to give the crude solid 3a, which was
purified by column chromatography (ethyl acetate–petroleum ether ¼ 1:9)
to afford the pure product (yield: 90%).
Data
1H,10H-3,30-Phenylmethanediyl-bis-indole, 3a: colorless needle; mp 150–
152 8C(lit.[13a] 150–152 8C). IR (KBr): n 744, 1093, 455, 1600, 1618, 3055,
3412 cm21 1H NMR (400 MHz, CDCl3): d5.89 (s, 1H, Ar-CH), 6.67
;
(s, 2H), 7.00 (t, 2H, J ¼ 6.8 Hz), 7.15–7.23 (m, 3H), 7.28–7.30 (m, 2H),
7.34–7.40 (m, 6H), 7.94 (br, s, 2H, NH). Anal. calcd for C23H18N2: C,
85.68; H, 5.63; N, 8.69. Found: C, 85.75; H, 5.56; N, 8.56.
ACKNOWLEDGMENTS
This work was partially supported by the Key Laboratory of Organic
Chemistry of Jiangsu Province (No. JSK008), the National Science Foun-
dation of Jiangsu Province (No. BK2004038), the National Natural Science
Foundation of China (Nos. 20472062 and 20672079), and a research grant
from the Innovation Project for Graduate Students of Jiangsu Province.
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