The synthesis of 2,3-dihydroquinazolin-4(1H)-ones using zinc oxide nanotubes modified by SiO2 as a catalyst with recyclable effect

Article abstract of DOI:10.13005/ojc/340109

Zinc oxid nano tubes have attracted much attention in recent years. Hardly, direct uses of zinc oxid nano tubes which modified by SiO₂ as a catalyst with recyclability has been applied for several organic reactions. The average particle size of

Full text of DOI:10.13005/ojc/340109

ISSN: 0970-020 X
CODEN: OJCHEG
2018, Vol. 34, No.(1):
Pg. 86-92
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
www.orientjchem.org
The Synthesis of 2,3-dihydroquinazolin-4(1H)-ones Using
Zinc Oxide Nanotubes Modified by SiO2 as a Catalyst with
Recyclable effect
RAKHSHAN HAKIMELAHI1,2* and MOHAMMAD H. MOUSAZADEH3
1Chemistry Department, Jahrom Branch, Islamic Azad University, Jahrom, Iran.
2Chemistry Department, Shiraz Branch, Islamic Azad University, Shiraz, Iran.
3 Department of chemistry, Amirkabir University of Technology, Tehran, Iran.
*Corresponding author E-mail: hakimelahi@jia.ac.ir
http://dx.doi.org/10.13005/ojc/340109
(Received: September 22, 2017; Accepted: December 25, 2017)
ABSTRACT
Zinc oxid nano tubes have attracted much attention in recent years. Hardly, direct uses of
zinc oxid nano tubes which modified by SiO2 as a catalyst with recyclability has been applied for
several organic reactions. The average particle size of ZnO catalysts is 57 nm, it has been
characterized by XRD. Nano tubes surfaces have high density defects. The condensation of
isatoic anhydride and an aromatic aldehyde exposed to ammonium acetate in the presence of few
amounts of zinc oxide nano tubes modified by SiO2 as a catalyst can be a simple, suitable and
efficient method for the quinazolin derivatives synthesis, the positive aspect is recyclable ability of
the catalyst. It is clear that some characterization of catalyst such as combination of the small
particle size and high-density surface defects of zinc oxid nano tubes which modified by SiO2 is
the basic reason for unique catalytic activity of the catalyst. The practical and simple method led
to unbeatable yields of the 2,3-Di hydro quinazolin-4(1H)-one derivatives at short times under mild
conditions.
Keywords: Reusable catalyst, 2,3-Dihydroquinazolin-4(1H)-one derivatives, zinc oxide
nanotubes, SiO2.
INTRODUCTION
homogeneous catalysts (high activity and
selectivity, etc.) and engineering promotes of
heterogeneous catalysts (easy catalyst separation,
easily regeneration, long catalytic life, thermal
stability and recyclable ability)1. Since solid acids
have many promotes such as decreased reactor
Heterogenization of homogeneous
catalysts has been a fantastic area of research from
the industrial point of view. This approach, relieves
the ability to use simultaneously the benefits of
This is an
Open Access article licensed under a Creative Commons Attribution-NonCommercial-ShareAlike
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HAKIMELAHI et al., Orient. J. Chem., Vol. 34(1), 86-92 (2017)
and depletion of plant corrosion problems, simplicity have been already published in some papers and
in handling and more environmentally safe the reactions such as formylation and acetylation of
disposal2–7, the application of solid acids have hydroxyl groups have been reported3.
important role in organic transformation. 2,3-di hydro
quinazolinones are a class of hetero cycles which
possess a wide range of high activities,
MATERIALS AND METHODS
pharmaceutically including anti fertility, Instrumentation
antibacterial, antitumor, anti-fungi and Monoamine-
The commercial necessary materials were
oxidase inhibitor (MAOI)8–11, so they have attracted purchased from Fluka (Buchs, Switzerland), Merck
much attention recently. Several synthetic methods (Darmstadt, Germany), and Aldrich(Germany). TLC
for the preparation of 2,3- dihydro quinazolinones (silica-gel 60 F254, n-hexane: ethyl acetate) was
have been reported, the most direct procedure used for monitoring of the reaction. A FTIR
includes accumulation of alkyl, aryl and heteroaryl Shimadzu- 470 Spectrometer was used for IR
aldehydes with anthranilamide in the presence of spectra. the 1HNMR Spectra were achieved with a
p-toluene sulfonic acid as a catalyst12–14. Also, the Brucker-Instrument DPX- 400 MHz Avance 2 model.
synthesis of 2,3-dihydroquinazolinones was The similarity of their spectra and physical data were
accomplished by reductive cyclisation of o-nitro applied for identification of products and their
benzaldehyde or oazido benzamide15,16. Some of characterizatons. The Powder X-ray diffraction
the stylish reported methods include materials as (XRD) patterns were obtained on a Bruker Advance
isatoic anhydride, and aldehydes exposed to D8 Diffractometer with Cu Kα radiation (λ=0.154
ammonium acetate or primary amine in the nm). A Philips CM 200 FEG/HRTEM instrument (high
resolution transmission electron microscope)
operated at 200 Kv was usedd for TEM
measurements.
presence of different types of reagents or catalysts,
namely p-toluenesulfonic acid17, amberlyst-15
microwave-assisted18, montmorillonite K-1019, silica
sulfuric acid20, ionic liquid21, Zn(PFO)2 22, and
ceric ammonium nitrate23, silica-bonded N-
propylsulfamic acid (SBNPSA)24. Recently, zinc oxid
nanotubes are faced with increasing attentions
because of fascinating chemical and physical
characteristics and having potential technological
applications25, these are distinct both from those of
the bulk phase and those from isolated atoms or
molecules. The preparation26 and applications27,28
of nano-sized zinc oxid nanotubes modified by SiO2
Recyclability
One of the excellences of zinc oxide
nanotubes modified by SiO2 is separating them from
the reaction mixture, on the other hand, they have
recycling power. They participated as the same
reaction again as a catalyst and their catalytic activity
such as their efficacy was checked in subsequent
reactions. Fig. 1 shows the relation between the
number of cycles of the reaction and the catalytic
activity according to the yield.
Fig 1. Recyclability of zinc oxid nanotubes modified by SiO2 for the formation of 2,3-di
hydro quinazolinones derivatives

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HAKIMELAHI et al., Orient. J. Chem., Vol. 34(1), 86-92 (2017)
General procedure for the synthesis of
2,3- dihydro quinazolinones
RESULT AND DISCUSSION
The characterization of the catalyst was
done by XRD; it shows high-density defects on nano
tubes surfaces (Fig. 2). Zinc oxide nano tubes
modified by SiO2 as catalyst were used to establish
the reaction of synthesis of derivatives of
2,3-Dihydro quinazolinones. The condensation
reaction of isatoic anhydride and an aromatic
aldehyde exposed to ammonium acetate
ammonium acetate (1b) redounds to the product.
To estimate the optimization conditions of the
reaction, various amounts of zinc oxide nano tubes
modified by SiO2 were taken in the range of 0.5-2.0
mmol% at 120 oC (Table). The reaction surveys at
different concentrations of the catalyst showed that
the condensation reaction could be efficiently
proceeded using 1 mmol% of the catalyst under
solvent free conditions and thermal conditions.
A mixture of isatoic anhydride (1 mmol),
ammonium acetate (3 mmol) besides substituted
aromatic aldehydes (1 mmol), zinc oxide nanotubes
modified by SiO2 (1.0 mmol%) under solvent free
conditions were applied at 120 oC for the
appropriate time. In order to find when the reaction
is completed, it should be monitored by TLC (thin
layer chromatography). Finally, after completion,
the reaction mixture should be cooled to the room
temperature, filtered and washed with water
(2 × 5 mL). Purification of the solid products were
done by recrystallization of the catalyst from ethyl
acetate, hence the catalyst was taken apart the pure
product. Afterwards melting point of the product(s)
were measured and the yeild of the reaction was
determined.
Fig. 2. XRD pattern zinc oxide nanotubes modified by SiO2 catalyst
Before, some studies have been showed
new routes by using solid acid catalysts to synthesize
heterocycles with favorable substitutes29-32. In this
research has been reported a valid and an
efficient procedure in order to synthesize
2,3-dihydroquinazolinones. This reaction is a kind
of one-pot condensation which the reactants are
isatoic anhydride, aldehydes and NH4OAc or
primary amine. It has been performed in the
presence of few amounts of zinc oxide nanotubes
modified by SiO2 as an inexpensive catalyst
(Fig. 3). The effect of catalyst on the condensation
of mentioned reactants was studied which was the
corresponding of 2,3-dihydroquinazolinones
production. The condensation reaction of isatoic
anhydride, NH4OAc and 4-chloro-benzaldehyde
was chosen as a model reaction in solvent free
conditions (Table.1). The results show clearly that
zinc oxide nano tubes modified by SiO2 is an
effective catalyst for this transformation whereas in
the absence of zinc oxide nano tubes modified by
SiO2 the reaction could not take place, even after
120 minutes. (Table.1, entry 1). The best result has
been obtained with an amount of (1.0 mmol%) zinc
oxide nano tubes modified by SiO2 in terms of
reaction time and isolated yield. To demonstrate
the generality of this process, many of aldehydes
with divers substitution and different structurally
were employed to synthesize the corresponding
products which engendered very good yields
(Table. 2). Also, a wide range of aniline derivatives
and 2-phenylethyl amine were used and finally
2,3-dihydroquinazolinones were obtained in
efficiency yield. The possibility of the catalyst

89
The studies were extended with various
HAKIMELAHI et al., Orient. J. Chem., Vol. 34(1), 86-92 (2017)
recycling was examined, therefore the reaction of
isatoic anhydride and 4-chloro benzaldehyde with aromatic aldehydes in order to prepare a series of
NH4OAc in the presence of zinc oxide nano tubes 2,3-Di hydro quinazolinones derivatives, the
modified by SiO2 was studied in solvent free generality of the reaction was demonstrated in
conditions.
optimized conditions (Scheme 1).
Table. 1:The reaction of isatoic anhydride, ammonium acetate and
4-chlorobenzaldehyde exposed to different amounts of zinc oxide nano tubes
modified by SiO2 catalyst in solvent freea conditions
Entry
The amounts of catalyst (mmol)
Time (min.)
Yield (%)b
1
2
3
4
-
120
30
20
-
0. 5
1.0
2.0
84
92
92
20
a
o
The molar ratios of isatoic anhydride, NH4OAc and 4-chlorobenzaldehyde at 120 C
have been found before.
b
Isolated Yield.
O
O
R2
N
O
ZnO nano tubes
Solvent free ,120
+ R1 CHO + R2 NH2
R1
N
H
O
N
H
Scheme 1. synthesis of 2,3-dihydroquinazolinones catalyzed with zinc oxide nano
tubes modified by SiO2 in solvent free conditions.
Table. 2: Synthesis of 2,3-dihydroquinazolinone derivatives catalyzed with zinc oxide nano tubes
modified by SiO2 in solvent free conditions
Entry
R1
R2
Product
Time (min.)
Yield (%)b
1
2
3
4
5
6
7
8
4-CH3C6H4
4-CH3OC6H4
4-ClC6H4
H
H
H
H
H
C6H5
C6H5
C6H5
C6H5
3a
3b
3c
3d
3e
3f
3g
3h
3i
120
2.5
86
88
80,120c
3.0
84, 81c
87
4-BrC6H4
2-Thionyl
4-CH3C6H4
4-ClC6H4
3.0
3.0
2.5
3.0
3.0
3.0
3.0
81
84
86
83
83
83
82
4-FC6H4
9
10
11
2-Thionyl
4-CH3C6H4
4-CH3C6H4
C6H5CH2CH2
4-HO-C6H4
3j
3k
a
The molar ratios of isatoic anhydride: aldehyde: ammonium acetate has been found before.
(1 mmol%) zinc oxide nano tubes modified by SiO2, at solvent free condition.
Isolated Yield.
b
c
The reaction was accomplished exposed to reused catalyst.

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HAKIMELAHI et al., Orient. J. Chem., Vol. 34(1), 86-92 (2017)
ZnO nano tube
O
H
H
-CO2
N
R2
NH
4
H
O
R2-NH2
O
O
5
H
3
N
R2
NH2
O
O
R1-CHO
ZnO nano tube
ZnO nano tube
6
O
N
H
ZnO nano tube
O
NH
O
H
1
O
- H
H
N
2
O
R2
R1
N
H
O
H
R2
R1
ZnO nano tube
7
N
N
H
8
Scheme 2.Proposed mechanism for the synthesis of 2,3-dihydroquinazolinones exposed to
zinc oxide nano tubes modified by SiO2
As it was pointed, the reaction mixture was
group, then the N-nucleophilic amine (3) attack
occurs on the carbonyl group of the intermediate
(2) to produce another species as intermediate (4),
which after decarboxylation reaction followed by
proton transfer, in turn affords the intermediate
named (5). Subsequently, the aldehyde activated
by zinc oxid nanotubes modified by SiO2, participate
in a condensation reaction with (5) to proceeds the
imine intermediate (7), which the general cyclic
process forms finally yields proposed product (8).
In conclusion, heterogeneous conditions get easy
and clean work-up approach, with high yields which
this method could be practical for multi-component
reactions because of the catalyst recovery. So the
present methodology could be a significant manner
which added to other methods.
solvent free. The product was recrystallized and
separated from catalyst using hot ethanol. The
catalyst after recycling could be employed four times
without any treatment. Catalyst turnover is perfect
and there is no decreased efficiency (Table. 2). For
the mentioned one-pot reaction, some possible
mechanisms had been reported before by
Baghbanzadeh, co-workers17 and Wang et al.,22.
According to the experimental results, a credible
mechanism has been proposed in Scheme 2. In
the presence of zinc oxide nano tubes which is
modified by SiO2 as catalyst, first the isatoic
anhydride (1) is rearranged and formed an
intermediate (2) with positive charge on carbonyl

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HAKIMELAHI et al., Orient. J. Chem., Vol. 34(1), 86-92 (2017)
Compound 3i: mp 198–200 8C. IR (neat): (d, 2H, J = 8.07 Hz), 7.12-7.15 (m, 3H), 7.39 (d, 1H,
3285.62, 3024.37, 1631.68, 1609.55, 1503.79, J = 2.28 Hz), 7.61 (dd, 1H, J1 = 7.64 Hz, J2 = 1.5
1483.88, 1387.95, 1366.74, 1317.89, 1258.12, Hz), 9.35 (s, 1H). 13C NMR (100 MHz, DMSO-d6): d
1191.04, 1158.03, 1069.94, 836.88, 793.58, 754.82, 20.73, 73.15, 114.62, 115.12, 115.42, 117.32,
1
713.91, 694.77 cm-1. H NMR (400 MHz, DMSO- 126.56, 127.91, 127.95, 128.89, 132.24, 133.53,
d6): d 6.53 (d, 1H, J = 2.5 Hz), 6.77 (dt, 1H, J1 = 7.55 137.60, 138.02, 146.64, 155.55, 162.34. Anal. Calcd
Hz, J2 = 1.01 Hz), 6.82 (d, 1H, J = 7.81 Hz), 6.86 for C21H18N2O2: C, 76.44; H, 5.51; N, 8.49; Found:
(dd, 1H, J1 = 5.03 Hz, J2 = 3.51 Hz), 6.97 (d, 1H, J = C, 76.25; H, 5.33; N, 8.29.
3.52 Hz), 7.21-7.26 (m, 1H), 7.32-7.41 (m, 6H), 7.72
(d, 1H, J = 2.75 Hz), 7.73 (dd, 1H, J1 = 7.81 Hz, J2 =
1.5 Hz). 13C NMR (100 MHz, DMSO-d6): d 69.56,
115.28, 115.66, 118.15, 125.93, 126.34, 126.36,
CONCLUSION
In summary, we have established a new
126.40, 126.52, 127.97, 128.71, 133.84, 140.49, application of zinc oxide nanotubes modified by SiO2
144.63, 146.38, 161.59. Anal. Calcd for as an effective, suitable and reusable catalyst. A
practical and simple method which redounds to
excellent yields of the 2,3-Di hydro quinazolin-
4(1H)-one derivatives under mild conditions and
within short times. The reason proposed for higher
catalytic activity of zinc oxide nano tubes modified
by SiO2 is a combination effect of the small particle
size and high-density surface defects. In these
reactions, ammonium acetate and different types of
aromatic aldehydes as initial materials have
potential green chemistry advantages. This method
is reasonable from economic point of view and
environmentally, due to little waste production.
Some advantages like as simple preparation,
C18H14N2OS: C, 70.62; H, 4.63; N, 9.16; S, 10.51;
Found: C, 70.41; H, 4.52; N, 9.07; S, 10.36.
Compound 3j: mp 152-154 8C. IR (neat): 3282.12,
3027.52, 1628.2, 1609.22, 1583.63, 1506.14,
1485.19, 1408.12, 1311.41, 1173.38, 822.38,
750.44, 693.89 cm-1. H NMR (400 MHz, DMSO-
1
d6): d 6.31 (d, 1H, J = 2.5 Hz), 6.73(dt, 1H, J1 = 7.55
Hz, J2 = 1.01 Hz), 6.77 (d, 1H, J = 7.79 Hz), 7.11-
7.23 (m, 3H), 7.28-7.33 (m, 3H), 7.32-7.37 (m, 2H),
7.41-7.46 (m, 2H), 7.65 (d, 1H, J = 2.5 Hz), 7.76 (dd,
1H, J1 = 7.83 Hz, J2 = 1.5 Hz). 13C NMR (100 MHz,
DMSO-d6): d 72.09, 114.88, 115.18, 115.29,
115.34, 117.66, 126.14, 126.48, 127.99, 128.67, stability of catalyst, easy handling, short reaction
128.79, 128.89, 133.85, 136.88, 140.64, 146.59, times, having a procedure with simple work-up and
160.69, 162.28, 163.11. Anal. Calcd for C23H22N2O: the high yields of products, put this reaction at the
C, 80.69; H, 6.51; N, 8.22; Found: C, 80.53; H, 6.37; best existing methodologies. No necessary of using
N, 8.03. Compound 3k: mp 249-253 8C. IR (neat): toxic organic solvents as media, is another positive
3311.08, 3119.81, 3015.72, 2891.34, 2359.39, sight.
1633.77, 1612.59, 1595.97, 1580.45, 1514.48,
1444.67, 1421.48, 1266.71, 1225.65, 1150.56,
1117.88, 1018.55, 870.02, 839.52, 806.59, 770.74,
752.55, 695.39cm-1. 1H NMR (400 MHz, DMSO-d6):
ACKNOWLEDGEMENT
The authors gratefully appreciate partial
d 2.11 (s, 3H), 5.94 (d, 1H, J = 2.5 Hz), 6.54-6.62 (m, support of this research by the Islamic Azad
4H), 6.92 (dt, 2H, J1 = 8.83 Hz, J2 = 2.02 Hz), 6.99 University, Jahrom and Shiraz Branch, Iran.
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