Water-promoted synthesis of 3,3′-di(indolyl)oxindoles

Article abstract of DOI:10.1080/00397910802654690

The reaction of isatin and indoles in refluxing water/ethanol (7:3) affords 3,3'-di(indolyl)oxindoles in excellent yields.

Full text of DOI:10.1080/00397910802654690

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Water-Promoted Synthesis of
3,3′-Di(indolyl)oxindoles
Mohit L. Deb a & Pulak J. Bhuyan a
a Medicinal Chemistry Division, North East Institute
of Science and Technology, Jorhat, Assam, India
Published online: 12 May 2009.
To cite this article: Mohit L. Deb & Pulak J. Bhuyan (2009): Water-Promoted Synthesis
of 3,3′-Di(indolyl)oxindoles, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 39:12, 2240-2243
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Synthetic Communications1, 39: 2240–2243, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802654690
Water-Promoted Synthesis of
3,30-Di(indolyl)oxindoles
Mohit L. Deb and Pulak J. Bhuyan
Medicinal Chemistry Division, North East Institute of Science and
Technology, Jorhat, Assam, India
Abstract: The reaction of isatin and indoles in refluxing water=ethanol (7:3)
affords 3,30-di(indolyl)oxindoles in excellent yields.
Keywords: 3,30-Di(indolyl)oxindoles, indole, isatin, water-promoted reaction
The importance of indole and its derivatives is well recognized by
synthetic as well as biological chemists.[1] Therefore, considerable efforts
have been made to synthesize analogs of 3,30-di(indolyl)oxindoles, which
were prepared from the reaction of isatin and indoles using a broad range
of acidic catalysts such as protic acid,[2] ceric ammonium nitrate
(CAN)=ultrasound,[3] KAl(SO4)2,[4] silica sulfuric acid,[5] and Bi(OTf)3.[6]
Continuing our interest in indoles and the development of green
procedures for the synthesis of diverse heterocyclic compounds of biolo-
gical significance,[7] we report a simple and efficient method for 3,30-
di(indolyl)oxindoles by the reaction of isatin and indoles in H2O–EtOH
(Scheme 1).
One equivalent of isatin 1a and 2 equiv. of indole 2a in a water–
ethanol mixture (7:3) were heated under reflux for 7 min to afford 3,30-
di(indolyl)oxindole 3a in 85% yield. The structure of the compound
was supported by the spectroscopic data, elemental analysis, and compari-
son with the sample prepared by the literature procedure.[3,5]
Received August 7, 2008.
Address correspondence to Pulak J. Bhuyan, Medicinal Chemistry Division,
North East Institute of Science and Technology, Jorhat 785006, Assam, India.
E-mail: pulak_jyoti@yahoo.com
2240

Synthesis of 3,30-Di(indolyl)oxindoles
2241
Scheme 1. Synthesis of 3,30-di(indolyl)oxindoles.
We have synthesized a series of compounds 3b–n by utilizing isatin
derivatives (1a–d) and indole derivative (2a–e) under similar conditions
(Table 1). It is interesting to note that 5-methyl indole had the greatest
reactivity, but 3-methyl indole did not react.
We also studied the reaction in various solvents such as dichloro-
methane, acetonitrile, toluene, and tetrahydrofuran (THF) under reflux-
ing conditions in the absence of a catalyst. However, we could not get
satisfactory results. When methanol=ethanol was used as the reaction
medium, it gave a good yield of the product, but when we used aqueous
methanol or ethanol, it greatly increased the yield and reduced the reac-
tion time. However, because of the toxicity of methanol, reactions were
carried out using only EtOH=H2O.
In conclusion, we report a very simple and efficient method for the
synthesis of 3,30-di(indolyl)oxindoles from the reaction of isatins and
Table 1. Reaction of isatin 1 with various indoles 2
Product
R
R1
R2
R3
Time (min)
Yield (%)a
3a
3b
3c
3d
3e
3f
H
H
H
H
H
CH3
CH3
CH3
CH3
Ts
Ts
Ts
Allyl
Allyl
H
H
H
CH3
H
H
H
H
CH3
H
H
H
CH3
H
H
H
H
CH3
H
H
H
H
H
CH3
H
Br
H
H
CH3
H
H
H
CH3
H
7
10
5
10
38
8
12
5
8
10
12
8
10
12
85
75
86
80
55
82
70
83
74
78
77
80
75
75
3g
3h
3i
3j
3k
3l
CH3
H
H
CH3
H
H
H
3m
3n
H
aIsolated yields.

2242
M. L. Deb and P. J. Bhuyan
indoles, in the absence of any added catalyst. As far as possible, the
reactions were carried out in an environmentally friendly by using water
as a major part of the solvent system, thereby reducing the use of organic
solvents. The products were obtained in excellent yields in a short reac-
tion time. A suitable mechanism is put forward for the reaction where
the solvent itself promotes the reaction. Undoubtedly it will be a valuable
addition to the chemistry of indoles.
ACKNOWLEDGMENTS
We thank the Department of Science and Technology, New Delhi, for
financial support. M. L. D. thanks the Council of Scientific and Indus-
trial Research (India) for the award of a senior research fellowship.
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Synthesis of 3,30-Di(indolyl)oxindoles
2243
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