TiO2 nanoparticles: An efficient heterogeneous catalyst for synthesis of bis(indolyl)methanes under solvent-free conditions

Article abstract of DOI:10.1007/s00706-009-0205-8

Some bis(indolyl)methanes have been synthesized, in excellent yields, under solvent free conditions, by reaction of indoles with aromatic and aliphatic aldehydes in the presence of nano titanium(IV) oxide as an efficient, heterogeneous, reusable, and non-toxic catalyst.

Full text of DOI:10.1007/s00706-009-0205-8

Monatsh Chem (2009) 140:1465–1469
DOI 10.1007/s00706-009-0205-8
ORIGINAL PAPER
TiO2 nanoparticles: an efficient heterogeneous catalyst
for synthesis of bis(indolyl)methanes under solvent-free conditions
•
Mohammad Rahimizadeh Zahra Bakhtiarpoor
•
•
Hossein Eshghi Mehdi Pordel Ghadir Rajabzadeh
•
Received: 31 May 2009 / Accepted: 11 October 2009 / Published online: 18 November 2009
Ó Springer-Verlag 2009
Abstract Some bis(indolyl)methanes have been synthe-
sized, in excellent yields, under solvent free conditions, by
reaction of indoles with aromatic and aliphatic aldehydes in
the presence of nano titanium(IV) oxide as an efficient,
heterogeneous, reusable, and non-toxic catalyst.
process chemistry. However, many of these methods still
suffer from drawbacks, for example long reaction time,
expensive reagents, low yields of products in some cases,
high catalyst loading, corrosive reagents, and large
amounts of solid supports which eventually result in the
generation of large amounts of toxic waste. Recently,
nanomaterials have been a topic of interest as heteroge-
neous catalysts, because they have extraordinary properties
relative to bulk materials. Currently, nanometal oxides
have attracted researchers’ attention, because of their
unusual physical and chemical catalytic properties [13–17].
Among the nanometal oxides employed, nano-TiO2 has
been proved to be a good catalyst because of its high activity,
non-toxicity, easy availability, reusability, strong oxidizing
power, and long-term stability [18–20]. Moreover, titanium
dioxide is a prominent material for various kinds of industrial
applications related to catalysis, e.g. in the selective reduc-
tion of nitrite or nitrate ions in stationary sources,
photocatalysis for pollutant elimination or organic synthesis,
and photovoltaic devices, sensors, and paints [21].
Keywords Aldehydes Á Bis(indolyl)methanes Á
Heterogeneous catalyst Á Indoles Á Nano-TiO2
Introduction
Indole and its derivatives have been identified as an
important class of heterocyclic compounds in medicinal
chemistry. The reaction of indoles with aromatic or ali-
phatic aldehydes and ketones produces azafulvenium salts.
The azafulvenium salts can undergo further addition with a
second molecule of indole to afford bis(indolyl)methanes
[1]. Bis(indolyl)methanes are found widely distributed in
the bioactive metabolites of terrestrial and marine organ-
isms [2, 3]. Some compounds have potent pharmaceutical
activity, for example as tranquilizers [4] or anticarcinogens
[5, 6]. Because of their intriguing physiological activity,
many synthetic procedures have been reported [7–9] in
which development of environmentally benign aspects, by
employing Lewis acid in ionic liquids [10, 11] or task-
specific acidic ionic liquids [12], is of current interest in
In this paper, nanoparticles of TiO2 are introduced as a
new and efficient low loading-catalyst for electrophilic
condensation of indoles with aldehydes.
Results and discussion
Synthesis of different sizes of nano-TiO2
M. Rahimizadeh (&) Á Z. Bakhtiarpoor Á H. Eshghi Á M. Pordel
Department of Chemistry, School of Sciences,
Ferdowsi University of Mashhad, 91775-1436 Mashhad, Iran
e-mail: rahimizh@yahoo.com
Nanoparticles of TiO2 were prepared by the sol–gel method
by gradually adding titanium tetra-n-butoxide to a solution
of deionized water in ethanol. The gel was prepared by
aging the sol at room temperature for 24 h. The obtained
gel was dried and calcined at 350, 450, or 550 °C to give
nano-TiO2 of different particle size.
G. Rajabzadeh
Department of Chemistry, Khorasan Science and Technology
Park (KSTP), Mashhad, Iran
123

1466
M. Rahimizadeh et al.
XRD diagrams of TiO2 nanoparticles represent the (101)
crystal face of anatase corresponding to a diffraction angle
(2h) of 25.25°, and the nanocrystalline anatase structure
was confirmed by 2h = 37.82 (004)°, 47.98 (200)°, 53.59
(106)°. The average crystalline size of TiO2 was estimated
by use of Scherrer’s equation.
The intensity of the anatase peak increased and the
width of (101) plane at 2h = 25.25° became narrower with
increasing calcination temperature (from 350 to 550 °C),
indicating the particles grew larger in size.
Figures 1, 2, 3 show transmission electron microscopy
(TEM) photographs of different particles of nano-TiO2.
These particle sizes were in agreement with the calculated
value of the crystallite size determined by XRD and using
the Scherrer equation [22]. The particle size distribution
was estimated to be 15, 30, and 50 nm.
Fig. 2 TEM image of the TiO2 nanoparticles prepared by calcination
of the gel at 450 °C
Optimization of the reaction conditions
In order to determine the best reaction conditions, we
studied the reaction of indole with benzaldehyde in the
presence of different amounts of nano-TiO2 at 80 °C under
different conditions. As shown in Table 1, the best result
was obtained with 10 mol% of nano-TiO2 under solvent-
free conditions (entry 2).
Based on the optimized reaction conditions, the proce-
dure was applied to a variety of different aldehydes and
indoles (Scheme 1). The results are summarized in
Table 2.
This method is effective for aldehydes bearing both
electron-withdrawing and electron-donating substituents on
the aromatic ring. Aliphatic aldehydes also react satisfac-
torily under these conditions.
Fig. 3 TEM image of the TiO2 nanoparticles prepared by calcination
of the gel at 550 °C
Table 1 Determining the best reaction conditions for treatment of
indole with benzaldehyde and different amounts of nano-TiO2
Entry
Catalyst
Solvent
Time (min)
Yield (%)
1
2
3
4
5
6
7
5% nano-TiO2
10% nano-TiO2
20% nano-TiO2
30% nano-TiO2
10% nano-TiO2
10% nano-TiO2
10% nano-TiO2
None
10
3
95
95
95
95
50
65
60
None
None
3
None
3
CH2Cl2
CH3CN
MeOH
250
220
220
Fig. 1 TEM image of the TiO2 nanoparticles prepared by calcination
of the gel at 350 °C
123

TiO2 nanoparticles
1467
Scheme 1
R
H
R2
R2
R2
O
Nano-TiO2
Solvent free, 80 oC
R
H
N
H
R1
N
H
R1
R1
N
H
1
2
2a
: R , R =H
2b : R1= Me, R2= H
2c : R1= H, R2= CN
1
3a-3t
1
2
2d
: R = Me, R = NO2
Table 2 Synthesis of BIMs by
reaction of indoles and
aldehydes in the presence of
nano-TiO2 under solvent free
conditions
Entry
Aldehyde/R
Indole
Product
Time (min)
Yield (%)
M.p. (°C)
1
C6H5
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2c
2c
2c
2d
2d
2d
2d
2d
3a
3b
3c
3d
3e
3f
3
3
95
90
80
85
90
91
93
91
93
70
85
95
94
87
90
85
80
85
77
80
124–127 (Ref. [23] 124–126)
192–194 (Ref. [23] 194)
2
4-OMeC6H4
4-ClC6H4
4-MeC6H4
4-NO2C6H4
4-OHC6H4
2-OMeC6H4
3-NO2C6H4
C6H5
3
5
79–81 (Ref. [24] 76–78)
4
5
95–97 (Ref. [23] 96–98)
5
3
241–243 (Ref. [23] 245–246)
120–123 (Ref. [23] 119–121)
129–132 (Ref. [23] 131–133)
267–269 (Ref. [23] 261–263)
247–248 (Ref. [24] 244–246)
Oily Liquid (Ref. [25])
6
3
7
3g
3h
3i
5
8
5
9
5
10
11
12
13
14
15
16
17
18
19
20
CH3(CH2)6
4-MeC6H4
4-NO2C6H4
C6H5
3j
35
5
3k
3l
175–177 (Ref. [24] 175–177)
239–241 (Ref. [24] 241–243)
241–243 (Ref. [23] 240–242)
245–248 (Ref. [23] 245)
5
3m
3n
3o
3p
3q
3r
3s
5
4-OMeC6H4
4-NO2C6H4
4-NO2C6H4
1-C10H7
5
5
157–159 (Ref. [23] 158–159)
171–173 (Ref. [25] 170–172)
156–159 (Ref. [25] 156–159)
139–140 (Ref. [25] 138–140)
148 (Ref. [25] 145–147)
The products were characterized
by comparison of their
spectroscopic and physical data
with those from authentic
samples synthesized by the
procedures given in the
references
15
20
20
20
25
3-OHC6H4
4-ClC6H4
2-OHC6H4
3t
135–137 (Ref. [25] 135–137)
To demonstrate the reusability of the catalyst, it was
recovered from the reaction of indole with benzaldehyde
by centrifugation and washed with 2 9 3 cm3 ethyl ace-
tate. It was then used without further purification for the
next reaction. There were no significant decreases in effi-
ciency of the recovered catalyst compared to the fresh
material. The catalyst was reusable at least up to four
times.
condition proves that using the nanoparticles substantially
reduces the reaction time.
In conclusion, we have developed a new method for the
synthesis of bis(indolyl)methanes from aldehydes and
indoles using nano-TiO2 as a very efficient, practical,
heterogeneous, and reusable catalyst.
Experimental
Comparing nano-TiO2 with some reported methods
Melting points were recorded on an Electrothermal type
9100 melting-point apparatus. The IR spectra were
obtained on a 4300 Shimadzu spectrometer and only
noteworthy absorptions are listed. The 1H NMR
(100 MHz) spectra were recorded on a Bruker AC 100
spectrometer. Chemical shifts are reported in ppm down-
field from TMS as internal standard; coupling constants J
are given in Hertz. The mass spectra were scanned on a
In order to assess the capability of this method compared
with reported methods for the preparation of bis(indo-
lyl)methanes from indoles and carbonyl compounds, the
synthesis of compound 3a was compared with reported
methods. As can be seen from Table 3, the nano-TiO2
method is more efficient than some others. Comparing the
nano-TiO2 catalyst with bulk TiO2 catalyst under the same
123

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M. Rahimizadeh et al.
General procedure for preparation of BIMs 3a–3t
Table 3 Comparison of our results for condensation of indole with
benzaldehyde with results obtained by other groups
In a typical reaction, a mixture of 1.5 g 4-nitrobenzalde-
hyde (10 mmol), 3.6 g 2-methyl-5-nitroindole (20 mmol),
and 0.08 g nano-TiO2 (1 mmol) were added to a test tube
and heated in an oil bath at 80 °C for an appropriate time
(Table 2). After completion of the reaction, as indicated by
TLC, the catalyst was filtered, followed by washing with
3 9 50 cm3 ethyl acetate. The volume was concentrated
under reduced pressure. After drying in air, practically pure
product was obtained.
Entry Reagent and conditions
Time Yielda Ref.
(min) (%)
b
1
Nano-TiO2, Solvent-free, 80 °C
3
180
30
95
98
94
91
61
95
84
71
95
90
92
–
2
TiO2, Solvent-free, 80 °C
P2O5/SiO2, Solvent-free, rt
Zn(HSO4)2
[26]
[24]
[28]
[29]
[30]
[31]
[32]
[33]
[34]
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3
4
180
30
5
PPh3ÁHClO4/CH3CN
Ln(OTf)3/EtOH.H2O
ZrOCl2.8H2O, Solvent-free, 50 °C
In(OTf)3/CH3CN
6
720
40
7
8
25
9
Zeokarb-255/CH3CN
La(PFO)3/EtOH
450
30
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10
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AlPW12O40,CH3CN, rt
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