Nano TiO2: An efficient catalyst for the synthesis of biscoumarins in aqueous medium

Article abstract of DOI:10.13005/ojc/300223

An easy method for the synthesis of biscoumarins through a one-pot reaction of 4- hydroxycoumarin and aryl aldehydes under very mild reaction conditions using nano TiO2 as catalyst in aqueous medium is described. The products were obtained in short reacti

Full text of DOI:10.13005/ojc/300223

ISSN: 0970-020 X
CODEN: OJCHEG
2014, Vol. 30, No. (2):
Pg. 577-580
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
www.orientjchem.org
Nano TiO2: An Efficient Catalyst for the Synthesis
of Biscoumarins in Aqueous Medium
HAMIDE BABAEI* and NASER MONTAZERI
Department ofchemistry, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
*Corresponding author: E-mail: hb_chem@Yahoo.com
http://dx.doi.org/10.13005/ojc/300223
(Received: February 20, 2014; Accepted: March 25, 2014)
ABSTRACT
An easy method for the synthesis of biscoumarins through a one-pot reaction of 4-
hydroxycoumarin and aryl aldehydes under very mild reaction conditions using nano TiO2 as
catalyst in aqueous medium is described. The products were obtained in short reaction times with
excellent yields under reflux. This method is of great value because of its environmentally benign
character, high yield processing, and easy handling. We believe this applicability of nano-TiO2 with
mentioned advantages makes our method superior over all previous reported methods to the
synthesis of biscoumarins.
Key words: Biscoumarins, Aqueous medium, 4-hydroxycoumarin, nano-TiO2, aryl aldehydes.
INTRODUCTION
generation has been a topic of great interest in
recent times. The general method for synthesis of
biscoumarin derivatives involves the reaction of 4-
hydroxycoumarin with aryl aldehydes in the
presence of different catalysts such as
Zn(proline)220, nano SiO2Cl21, K2CO3 in acetic
anhydride22, ruthenium(III) chloride hydrate23,
Et2AlCl in acetonitrile or dichloromethane at room
temperature24, piperidine9, molecular iodine25,
sodium dodecyl sulfate(SDS)26, phosphotungstic
acid27, heteropolyacids28, tetrabutylammonium
bromide(TBAB)29, 1,8-diazabicyclo[5.4.0] undec-7-
ene(DBU)30, POCl3 in dry DMF31, andmanganous
chloride32.However, some of these procedures have
disadvantages, for example tedious work up and
use of expensive reagents in organic solvents.
Coumarin derivatives and especially
biscoumarins have long been the subject of
numerous studies on account of their
pharmacological and biological properties1-7
Compounds with these ring system have diverse
pharmaceutical activities such as antioxidant,
.
antimicrobial,
anticoagulant,
anti-HIV,
antithrombotic, antieancer, enzyme inhibitory,
urease inhibitory and cytotoxicity8-16. A number of
biscoumarins are useful as malignant melanoma,
metastatic renal cell carcinoma and prostate cancer
drugs17-19. In view of different biological and chemical
applications of biscoumarins, the development of
suitable synthetic methodologies for their

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BABAEI & MONTAZERI, Orient. J. Chem., Vol. 30(2), 577-580 (2014)
These problems prompted us towards further friendly conditions. In this article, we present a one-
investigation in search for a new catalyst, which will pot reaction for the preparation of biscoumarins
carry out the synthesis of biscoumarins under derivatives in the presence of nano TiO2 in aqueous
simpler experimental set up and environmentally medium(Scheme1).
Scheme 1: Nano TiO2 catalyzed synthesis of biscoumarins
EXPERIMENTAL
employed as a model reaction to examine the effect
of various solvents such as EtOH, MeOH, CHCl3
All of the chemical material used in this and H2O and varying amount of nano TiO2 (5, 10, 15
work purchased from Fluka or Merk and without and 20mol%) as catalyst. In an optimized reaction
further purification. Melting points were recorded conditions, 4-hydroxycoumarin (2 mmol) and
on an Electrothermal type 9100 melting point benzaldehyde (1 mmol) in H2O (10 ml) were mixed
apparatus.The IR spectra were obtained on a 4300 in the presence of nano TiO2 (0.05 mmol) for 5 min.
Shimadzu spectrophotometer in KBr disks. The1H The reaction proceeds very cleanly under reflux and
NMR(500 MHz) spectra were recorded on a Bruker- was free of side products. After completion of the
Ac-500 spectrometer.
reaction (monitored by TLC), a simple work up
affords the products in high yields (Table 2). Among
General procedur for the synthesis of the solvents tested, the reaction in chloroform using
biscoumarins (3a-h) 5 mol% of the catalyst gave a low yield of the desired
A solution of 4-hydroxycoumarin 1 product. Ethanol and methanol gave moderate to
(2mmol), an aromatic aldehyde 2a-h (1 mmol) and good yields under this conditions. However, the
nano TiO2(5 mol% based on aromatic aldehyde) in reaction in H2O with 5mol% of catalyst afforded
H2O (10 ml) was heated on the oil bath under reflux product 3a in 96% yields. Using more than 5 mol%
for the time period as indicated in table 2. of catalyst, has less effect of the yield and time of
Theprogress of the reaction was monitored by TLC. the reaction.
After completion of the reaction, the mixture was
cooled to room temperature and the solid product
As shown in table 1, no desirable products
was collected by filtration and washed with cold could be detected in the absence of catalyst for 120
water.The solid residue was diluted with chloroform min, which indicated that the catalyst should be
(5 ml) and the catalyst was separated. The filtrate absolutely necessary for this reaction. Only a trace
was evaporated on rota-evaporator to give a solid product was obtained in the solvent-free conditions
which was dried and recrystallized from ethanol to in the presence of 5 mol% of the catalyst even at
afford pure products 3a-h in high yields. All the 110°C. After optimization of the reaction conditions
products were identified by comparing the analytical to experimental trials illustrating this method for the
data(Melting point, IR, H NMR) with those reported synthesis of derivatives were conducted.The results
or with authentic samples prepared by the are summarized in table 2.
conventional method, in which we used nano TiO2
as the catalyst. The results are summarized in the
table 2.
Benzaldehyde and other aromatic
aldehydes containing electron-withdrawing groups
(such as halide and nitro groups) or electron-
donating groups (such as hydroxyl, methyl and
methoxy groups) were employed which were found
RESULT AND DISCUSSION
To initiation our study the reaction of4- to react well to give the corresponding biscoumarin
hydroxycoumarin with benzaldehyde were derivatives in high yields.

BABAEI & MONTAZERI, Orient. J. Chem., Vol. 30(2), 577-580 (2014)
579
Table 1: Effect of nano TiO2amount and solvent on the model reactiona
Entry
Catalyst (mol%)
T (°C)
Solvent
Time (min)
Yield (%)b
1
2
3
4
5
6
7
8
-
-
5
5
5
5
5
5
10
15
20
10
10
10
110
reflux
r.t.
-
120
120
120
120
60
20
30
5
-
-
H2O
H2O
-
CHCl3
EtOH
MeOH
H2O
H2O
H2O
trace
trace
30
82
78
96
87
82
80
35
78
72
110
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
9
5
10
11
12
13
14
10
10
60
20
25
H2O
CHCl3
EtOH
MeOH
a2mmol 4-hydroxycoumarin and 1 mmolbenzaldehyde under different conditions.
bIsolated yields.
Table 2: Nano TiO2 catalyzedsynthesis of biscoumarins 3a-ha
Entry
Ar
productb
Time (min) Yield (%)c
m.p (°C)
Found
Reported
1
2
3
4
5
6
7
8
C6H5
3a
3b
3c
3d
3e
3f
5
5
8
5
5
5
5
10
96
95
90
84
94
95
95
92
226-228
252-253
265-266
245-247
233-234
230-233
221-223
219-223
228-230[20]
252-254[23]
266-268[21]
246-248[21]
234-236[21]
233-234[21]
224-226[21]
222-225[20]
4-Cl C6H4
4-MeC6H4
4-MeOC6H4
3- NO2C6H4
4- NO2C6H4
2-ClC6H4
4-OH C6H4
3g
3h
a2mmol 4-hydroxycoumarin, 1 mmol aryl aldehyde and 5 mol% nano TiO2 in H2O (10 ml) under reflux.
bThe products were characterized by comparison of their spectroscopic and physical data with authentic samples
synthesized by reported procedures.
cIsolated yield.
CONCLUSIONS
yields, make the procedure an attractive alternative
to the existing methods for the synthesis of
biscoumarin derivatives.
In conclusion, we have described a highly
efficient one-pot synthesis for the preparation of
biscoumarin derivatives in the reaction of 4-
hydroxycoumarin and aryl aldehydes in the
presence of nano TiO2 as catalyst. Easy work up,
short reaction time, environmentally, ready
commercial availability of the catalyst and high
ACKNOWLEDGMENTS
We gratefully acknowledgements the financial
support of this research by Islamic Azad University,
Tonekabon Branch.

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BABAEI & MONTAZERI, Orient. J. Chem., Vol. 30(2), 577-580 (2014)
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