ZnO nanoparticles solid phase acidic catalyst for one-pot synthesis of octahydroquinazolinone derivatives

Article abstract of DOI:10.3184/174751912X13371679868473

The reaction between dimedone, an aromatic aldehyde and urea catalysed by ZnO nanoparticles (ZnO NPs) in refluxing ethanol as a solvent provided a simple and efficient one-pot route for the synthesis of octahydroquinazolinone derivatives in excellent yields.

Full text of DOI:10.3184/174751912X13371679868473

JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 391
JULY, 391–392
ZnO nanoparticles solid phase acidic catalyst for one-pot synthesis of
octahydroquinazolinone derivatives
Bahareh Sadeghia*, Zahra Nasiriana and Alireza Hassanabadib
aDepartment of Chemistry, Yazd Branch, Islamic Azad University, PO Box 89195-155, Yazd, Iran
bDepartment of Chemistry, , Zahedan Branch, Islamic Azad University PO Box 98135-978, Zahedan, Iran
The reaction between dimedone, an aromatic aldehyde and urea catalysed by ZnO nanoparticles (ZnO NPs) in reflux-
ing ethanol as a solvent provided a simple and efficient one-pot route for the synthesis of octahydroquinazolinone
derivatives in excellent yields.
Keywords: ZnO nanoparticles, dimedone, aromatic aldehyde, urea, solid acid, octahydroquinazolinones
Octahydroquinazolinone derivatives have attracted attention
in recent years owing to their antibacterial activity against
Staphylococcus aureus, Escherichia coli, Pseudomonas aeru-
ginosa1, and also as calcium antagonists2,3. Methods employed
for their synthesis are variants on the classical one-pot multi-
component Biginelli reaction involving dimedone, aromatic
aldehydes and urea4. There are very few reports for the synthe-
sis of octahydroquinazolinone derivatives using catalysts1,4–9
in the extension of the Biginelli reaction, However, many of
these procedures are expensive, harmful and are difficult to
handle especially on large scale, require longer reaction times,
use strongly acidic conditions and give unsatisfactory yields
the formation of side products5. We have now used ZnO
nanoparticles (ZnO NPs) as a solid phase acidic green
catalyst which affords excellent yields and in the synthesis of
octahydroquinazolinones.
The results indicated that different solvents affected the
efficiency of the reaction. Most of these solvents required a
longer time and gave moderate yields, and the best results were
obtained when ethanol was used as solvent (Table 3, entry 4).
To optimise the temperature in the mentioned reaction, we
have carried out a model study with a benzaldehyde, urea and
dimedone using 0.009 g of catalyst at various temperatures
(Table 4). Table 4 clearly demonstrates that reflux is an
effective temperature in terms of reaction time and yield.
Table 1 Evaluation of the activity of different catalysts for the
condensation of benzaldehyde, urea and dimedone in ZnO
NPs
Entry
Catalyst
Time/h
Yield/%a
1
2
3
4
5
6
7
8
Conc.H2SO4
HClO4–SiO2
Conc.HCl
Acid Alumina
VCl3
3
85
54
6
6.5
6
2
0.06
1.5
0.17
35
40
67–92
89
95
95
Results and discussion
VB1b
In continution of our investigations of the application of
solid acids in organic synthesis10–14 we have investigated the
synthesis of octahydroquinazolinone derivatives by the three-
component condensation of an aromatic aldehyde 1, urea 2,
and 5,5-dimethyl-1,3-cyclohexanedione (dimedone) 3 and in
the presence ZnO NPs catalyst (Scheme 1). The best condition
for octahydroquinazolinone formation involved the use of
(0.009 g) ZnO NPs with 1 mmol reactants and 10mL ethanol
at reflux.
TMSCl
ZnO NPs
a Isolated yield.
b Thiamine hydrochloride (VB1).
Table 2 Optimisation of the amount of ZnO NPs on the
reaction of condensation of 1mmol benzaldehyde, urea and
dimedone in ethanol at 10 mL reflux
Entry
Catalyst/g
Time/min
Yield/%a
The stable catalyst is easily prepared15 and used for prepara-
tion of octahydroquinazolinones. In order to demonstrate the
advantageous catalytic activity of ZnO NPs, we compared
the reaction using other catalysts at reflux and for 10 min. The
results are listed in Table 1 (Table 1). ZnO NPs, a solid acid, is
a versatile catalyst that makes the reaction more convenient,
more economical and environmentally benign.
In order to determine the optimum quantity of ZnO NPs, the
reaction of benzaldehyde, urea and dimedone was carried out
at reflux using different quantities of ZnO NPs (Table 2). ZnO
NPs of 0.009 g gave an excellent yield in 10 min (Table 2,
entry 3).
1
2
3
4
0.001
0.007
0.009
0.1
10
10
10
10
65
79
93
95
a Isolated yield.
Table 3 Effect of the solvent on the reaction between benzalde-
hyde, urea and dimedone by (1mmol each) ZnO NPs (0.009 g)
Entry
Solvent
Time/min
Yield/%a
1
2
3
4
5
6
7
CH2Cl2
H2O
45
45
88
87
48
98
32
28
21
The above reaction was also examined in various solvents
(Table 3).
CH3CN
45
EtOH
45
CH3COOH
n-Hexane
Solvent-free
45
45
100
a Isolated yield.
Table 4 Optimisation of temperature using EtOH as solvent
Entry
Temperature/°C
Time/min
Yield/%a
Scheme 1 Synthesis of octahydroquinazolinones by
condensation of an aromatic aldehyde, urea and dimedone
using ZnO NPs (0.009 g) as catalyst.
1
2
3
25
60
Reflux
240
120
10
58
65
95
a Isolated yield.
* Correspondent. E-mail: bsadeghia@gmail.com

392 JOURNAL OF CHEMICAL RESEARCH 2012
Table 5 Reaction between aromatic aldehyde, urea and dimedone by ZnO NPs (0.009 g) in ethanol at reflux
Entry
Ar
Product
Time/min
Yield/%a
M.p/°C
Reported2,5,8,9
Found
1
2
C6H5
4-ClC6H4
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
10
10
10
10
10
10
10
10
10
10
10
10
10
10
95
91
93
96
94
95
81
88
90
89
91
90
84
82
292–293
>300
290–291
>300
3
3-ClC6H4
284–285
135–137
190–193
298–300
293–294
245–247
>300
282–283
135–136
191–192
300–301
295–296
246–247
>300
4
4-FC6H4
5
4-OH-3-OMeC6H3
953-NO2C6H4
4-NO2C6H4
4-MeOC6H4
4-BrC6H4
6
7
8
9
10
11
12
13
14
4-MeC6H4
>300
>300
3-MeOC6H4
2,4-Cl2C6H3
4-NMe2C6H4
4-OHC6H4
245–247
270–271
231–233
299–300
247–248
268–270
231–232
300–302
a Yields refer to the pure isolated products.
finally calcined at 230 °C for 2h to give samples with 10–40 nm
particle size.15
To study the scope of the reaction, the reaction of a series
of aromatic aldehydes, urea and dimedone catalysed by ZnO
NPs were examined. The results are shown in Table 5. In all
cases, aromatic aldehydes substituted with either electron-
donating or electron-withdrawing groups underwent the
reaction smoothly and gave products in excellent yields.
The compounds 4a–n were characterised by their 1H,
General procedure
ZnO NPs (0.009 g) was added to a stirred mixture of the aromatic
aldehyde (1 mmol), urea (1 mmol) and dimedone (1 mmol) in EtOH
(10 mL). The reaction mixture was then stirred for 10 min at reflux.
The progress of the reaction was followed by TLC (n-hexane:ethyl-
acetate). After completion of the reaction, the mixture was filtered
to remove the catalyst. After evaporation of the solvent, the crude
product was recrystallised from hot ethanol to obtain the pure
compound.
13CNMR, IR and mass spectra.2,5,8,9
.
In conclusion, a series of octahydroquinazolinones have
been synthesised efficiently by the condensation of aldehydes
1, urea 2 and dimedone 3 respectively in the presence of ZnO
NPs (0.009 g) in ethanol at reflux conditions. This has shown
that this catalyst has advantages such as shorter reaction times,
simple work-up, and affords excellent yield. The solid phase
acidic catalyst was re-usable for a number of times without
appreciable loss of activity. The present method does not
involve any hazardous organic solvent. Therefore, this proce-
dure may be classified as green chemistry.
Received 9 March 2012; accepted 16 April 2012
Paper 1201202 doi: 10.3184/174751912X13371679868473
Published online: 26 June 2012
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