Catalytic activity of TiO2 nanoparticles in the synthesis of some 2,3-disubstituted dihydroquinazolin-4(1H)-ones

Article abstract of DOI:10.1016/j.cclet.2013.11.040

Green chemistry is playing an important role for synthesizing organic compounds, due to its eco-friendly nature and low cost. In green chemistry, metal nanoparticles exhibited some useful physical and chemical properties (catalytic activity). Due to its diverse properties, nanoparticles can be utilized as a catalyst in various organic reactions. Recent research has been directed towards the utilization of eco-friendly and bio-friendly plant materials in nanoparticles synthesis. In our present work, TiO₂ nanoparticles (TiO₂ NPs) were synthesized using Annona squamosa peel extract and their catalytic applications were studied on the 2,3-disubstituted dihydroquinazolin-4(1H)-one synthesis. Synthesized compounds were confirmed using FT-IR, ¹H NMR, ¹³C NMR and GC-MS analyses.

Full text of DOI:10.1016/j.cclet.2013.11.040

Chinese Chemical Letters 25 (2014) 324–326
Contents lists available at ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
Original article
Catalytic activity of TiO2 nanoparticles in the synthesis of some
2,3-disubstituted dihydroquinazolin-4(1H)-ones
b
a
A. Bharathi a, Selvaraj Mohana Roopan a, , Amir Kajbafvala , R.D. Padmaja ,
*
M.S. Darsana a,c, G. Nandhini Kumari a,c
a Chemistry Research Laboratory, Organic Chemistry Division, School of Advanced Sciences, VIT University, Vellore 632 014, India
b Department of Materials Science and Engineering, North Carolina State University, Raleigh NC 27695-7907, USA
c Department of Chemistry, PSGR Krishnammal College for Women, Coimbatore 641 004, India
A R T I C L E I N F O
A B S T R A C T
Article history:
Green chemistry is playing an important role for synthesizing organic compounds, due to its eco-friendly
nature and low cost. In green chemistry, metal nanoparticles exhibited some useful physical and
chemical properties (catalytic activity). Due to its diverse properties, nanoparticles can be utilized as a
catalyst in various organic reactions. Recent research has been directed towards the utilization of eco-
friendly and bio-friendly plant materials in nanoparticles synthesis. In our present work, TiO2
nanoparticles (TiO2 NPs) were synthesized using Annona squamosa peel extract and their catalytic
applications were studied on the 2,3-disubstituted dihydroquinazolin-4(1H)-one synthesis. Synthesized
compounds were confirmed using FT-IR, 1H NMR, 13C NMR and GC–MS analyses.
Received 22 May 2013
Received in revised form 11 November 2013
Accepted 13 November 2013
Available online 28 November 2013
Keywords:
TiO2 nanoparticles
Quinazolin-4(1H)-one
Green chemistry
ß 2013 Selvaraj Mohana Roopan. Published by Elsevier B.V. on behalf of Chinese Chemical Society.
All rights reserved.
1. Introduction
reaction, combining the advantages of both homogeneous and
heterogeneous catalysts. Although many synthetic technologies
Nowadays nanoparticles have drawn the attention of scientists,
because of their extensive application in the development of new
technologies in the areas of electronics, material sciences, catalyst
and medicine at the nanoscale [1–3]. The development of green
processes using agricultural waste for the synthesis of nanopar-
ticles is evolving into an important branch of nanotechnology [4–
6]. The use of environmentally benign materials like plant leaf
extract [7], bacteria [8], fungi [9] and enzymes [10] for the
synthesis of metal nanoparticles offers numerous benefits such as
eco-friendliness and compatibility for pharmaceutical and other
biomedical applications as they do not use toxic chemicals in the
synthetic protocols. Eco-friendly reagents, catalysts, and reaction
medium such as water, supercritical fluids, ionic liquids or solvent-
free reactions for green chemical approaches have been studied. In
this context, metal oxide nanoparticles are attractive candidates as
solid supports for the highly active and recyclable catalytic
systems. Due to their large surface area, which can carry a high
payload of catalytically active species, nanoparticles exhibit very
high catalytic activity and chemical selectivity under mild
conditions [11]. In addition, they can be recovered through a
centrifugation or filtration process and reused for the next
are present, worldwide the researchers are continuously searching
suitable bio-methods for the synthesis of desired nanoparticles
[12].
Currently, TiO2 nanoparticles have emerged as an attractive
multi-functional material. TiO2 nanoparticles have unique prop-
erties such as high stability, long lasting, safe and broad-spectrum
anti-biosis [13]. TiO2 nanoparticles in particular have been the
centre of attention because of their photo-catalytic activities. TiO2
nanoparticles have been used as a green catalyst in many organic
reactions [14]. One-pot multicomponent reactions become in-
creasingly important in organic and medicinal chemistry. The
strategies of MCRs offer significant advantages over conventional
linear-type syntheses in terms of high degree of atom economy,
convergence, and ease of execution [15]. Multicomponent reac-
tions leading to the formation of nitrogen-containing heterocyclic
systems such as pyridine and pyrimidine have recently been
studied [16,17]. The achievement of making multiple bonds in a
one-pot multicomponent coupling reaction provides a sustainable
synthetic approach in new molecule discovery [18].
Quinazolin-4(1H)-ones are important N-heterocyclic com-
pounds having various biological activities [19–24]. However,
methods for the selective synthesis of 2,3-dihydroquinazolin-
4(1H)-ones have not been explored before. Thus, developing
versatile approaches to synthesize 2,3-dihydroquinazolin-4(1H)-
ones still remains a highly desired goal in organic synthesis. In our
present work of solvent free synthesis of quinazolinone, we
*
Corresponding author.
E-mail addresses: mohanaroopan.s@vit.ac.in, mohanaroopan.s@gmail.com
(S.M. Roopan).
1001-8417/$ – see front matter ß 2013 Selvaraj Mohana Roopan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2013.11.040

A. Bharathi et al. / Chinese Chemical Letters 25 (2014) 324–326
325
Table 3
utilized bio-inspired TiO2 NPs as catalyst in the 4(1H)-quinazo-
Synthesis of 2,3-disubstituted 2,3-dihydroquinazolin-4(1H)-ones, 4a–g.
linone synthesis.
O
O
O
N
O
TiO NPs
2
+
H N CH
2
2. Experimental
+
3
H
R
.
o
70 C, 3 h
N
H
R
N
H
O
2.1. Bio-fabricated TiO2 nanoparticles
3a-g
2
4a-g
1
Compounds
R
Yielda (%)
Mp (8C)
Biosynthesis of rutile TiO2 nanoparticles (TiO2 NPs) was
achieved by a novel, biodegradable and convenient procedure
using fruit peel Annona squamosa aqueous extract. Rutile TiO2 NPs
were characterized using UV, XRD, SEM and TEM studies [25].
4a
98
156–158
2.2. General procedure for synthesis of 2,3-disubstituted 2,3-
4b
4c
91
164–166
200–202
dihydroquinazolin-4(1H)-ones, 4a–g
N
A mixture of isatoic anhydride, 1 (0.234 g, 2 mmol), methyl
amines, 2 (68.7
mL, 2 mmol), benzaldehydes 3a–g (2 mmol) and
95
TiO2 NPs (5 mol%) was heated at 70 8C for 30 min. The reaction was
monitored by TLC analysis using petroleum ether-ethyl acetate
(1:4, v/v). After the completion of the reaction, the reaction
mixture was cooled to room temperature. The solid residue was
dissolved in hot ethanol and centrifuged to remove the catalyst.
Then the filtrate was subjected to column chromatography eluting
with petroleum ether-ethyl acetate (1:4, v/v) to isolate the desired
compounds. The isolated compounds were confirmed by FTIR,
1H NMR, 13C NMR and GC–MS analyses.
OCH3
OCH3
4d
4e
97
94
178–180
138–140
OCH3
H3CO
O2N
3. Results and discussion
4f
4g
a
93
96
164–165
153–155
NH2
We isolated the 2,3-dihydro-3-methyl-2-phenylquinazolin-
4(1H)-one analogues, 4a–g by column chromatography in >90%
yield. These products were characterized using FT-IR, 1H NMR, 13
C
NMR and mass analyses. Analysis results are given in Supporting
information. In FT-IR, compound 4a showed peaks at
3452.58 cmÀ1, corresponding to –NH stretching, 3265.49 cmÀ1
for –NCH3, and 1622.13 cmÀ1 for the –C55O group. In proton NMR,
NO2
Isolated yield.
the singlet at
peak at 4.48 is corresponding to –NH proton, peak at
corresponding to –CH proton and peaks at 6.52–7.97 belong to
aromatic protons. In 13C NMR, the methyl group appears at
32, –
CH group appears at 74, aromatic carbons appears at a 114–145
and –C55O appears at 163. We optimizeded the reaction with
various amount (mol%) of TiO2 NPs. Catalyst concentration plays a
major role in the product yields. It was observed that increasing the
loading of the catalyst from 2 to 5 mol% gave an improved yield of
91% of the product (Table 1). Further increase of catalyst loading
leads to lower reaction yields because the products tend to be
absorbed on the catalyst.
d
2.88 corresponds to methyl protons (–CH3), the
d
d
5.71 is
In order to elucidate the role of the solvents, various solvents
were used in order to evaluate the scope and limitation of the
reaction. After screening different solvents, it was found that TiO2
NPs catalyzed syntheses of quinazolinone were not only faster, but
also resulted in better yields under solvent free conditions
(Table 2).
In general, the polar protic solvents (EtOH and water) result in
good yields. The aprotic solvents (CHCl3 and DCM) give the lowest
yield. The dielectric constant measures the solvent’s ability to
reduce the field strength of the electric field surrounding a charged
particle immersed in it. The protic solvents have higher dielectric
constant values compared with aprotic (non-polar) solvents. The
protic (polar) solvents that can donate proton easily can form
hydrogen bonds with the reactants. These could be the reasons that
we are getting better yields in protic solvents than in aprotic
solvents. In Table 3, the results of isatoic anhydride, 1 methyl-
amine, 2 with various substituted aromatic aldehydes, 3a–g under
solvent free conditions using TiO2 NPs are shown. All products
were isolated by column chromatography in good yields (>90%).
d
d
d
d
d
Table 1
Optimization of the amount of TiO2 NPs in the synthesis of 2,3-dihydro-3-methyl-2-
(4-(dimethylamino)phenyl)quinazolin-4(1H)one, 4b.
Catalyst (mol%)
2
3
4
5
6
Yield GC–MS (%) 4b
49.68
54.53
76.42
91.86
89.47
Table 2
Effect of solvent for the synthesis of 2,3-dihydro-3-methyl-2-(4-(dimethylamino)-
phenyl)quinazolin-4(1H)one, 4b.
4. Conclusion
Solvent
Time (min)
Yield GC–MS (%) 4b
We have successfully synthesized the TiO2 nanoparticles using
aqueous A. squamosa peel extract. These synthesized TiO2
nanoparticles were characterized using UV, XRD and TEM.
Synthesized TiO2 nanopowders were used as a catalyst for
2,3-dihydro-3-methyl-2-phenylquinazolin-4(1H)-one analogues,
DCM
90
60
45
30
30
36.76
40.54
73.64
76.05
91.86
CHCl3
EtOH
H2O
Solvent free

326
A. Bharathi et al. / Chinese Chemical Letters 25 (2014) 324–326
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Acknowledgments
We thank the management of VIT University for providing all
the facilities to carry out this work. We acknowledge the support
extended by VIT-SIF for NMR and GC–MS analysis. Also Dr. S.
Mohana Roopan thanks DBT for providing DBT-RGYI project (No.
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Appendix A. Supplementary data
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Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.cclet.2013.11.040.
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