Monolayer-protected silver nanoparticles: An efficient and versatile reagent for the synthesis of 3,4-dihydropyrimidine-2-(1H)-ones (thiones)

Article abstract of DOI:10.3184/174751912X13352025454801

Silver nanoparticles has been prepared and shown to efficiently catalyse the one-pot, three-component reaction of an aromatic aldehyde, urea or thiourea and a 1,3-diketone at reflux, to afford the corresponding 3,4-dihydropyrimidine- 2-(1H)-ones in high y

Full text of DOI:10.3184/174751912X13352025454801

JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 343
JUNE, 343–346
Monolayer-protected silver nanoparticles: an efficient and versatile
reagent for the synthesis of 3,4-dihydropyrimidine-2-(1H)-ones (thiones)
Bahareh Sadeghia*, Salehe Zavara and Alireza Hassanabadib
aDepartment of Chemistry, Islamic Azad University, Yazd Branch, PO Box 89195-155, Yazd, Iran
bDepartment of Chemistry, Islamic Azad University, Zahedan Branch, PO Box 98135-978, Zahedan, Iran
Silver nanoparticles has been prepared and shown to efficiently catalyse the one-pot, three-component reaction of
an aromatic aldehyde, urea or thiourea and a 1,3-diketone at reflux, to afford the corresponding 3,4-dihydropyrimi-
dine-2-(1H)-ones in high yield.
Keywords: silver nanoparticles, 1,3-diketones, aromatic aldehyde, Biginelli reaction, 3,4-dihydropyrimidine-2-(1H)-ones
3,4-Dihydropyrimidine-2-(1H)-ones (DHPMs) have received
considerable attention due to their interesting pharmacological
properties.1–5 These compounds can be easily prepared the
Biginelli reaction, a one-pot condensation using β-dicarbonyl
compounds with aldehydes (aromatic and aliphatic aldehydes)
and urea or thiourea. Since Biginelli6 first reported this
method using strongly acidic conditions, improvements in the
syntheses have been made in order to keep the simplicity of
the original one-pot Biginelli protocol and at the same time
overcome its drawbacks such as low yields, especially in the
case of substituted aromatic and aliphatic aldehydes7. Recently,
modifications and improvements have included the use of
Lewis acids as well as Br¢nsted acids/bases, primary amines,
chlorotrimethylsilane and hexaaquaaluminium tetrafluorobo-
rate as a propagator.8–21 Many other synthetic methods have
been reported including the use of the classical conditions with
microwave22,23 and ultrasound irradiation.24–26
Over the past decade, nanomaterials have attracted interest
due to their potential applications in microelectronics, cataly-
sis and optics. metallic nanoparticles show unique properties
which differ from those of the bulk species because of their
singular electronic structure and extremely large surface
area.27–29 Silver nanoparticles have been of interest due to their
size-dependent optical and surface plasmon properties, includ-
ing surface-enhanced Raman effects.30 Silver nanoparticles
are mostly synthesised by various colloidal processes giving
surfactant-stabilized silver nanoparticles in liquid phases and
involving the chemical reduction of silver salts in aqueous
solutions. With some exceptions, most of these synthetic
approaches are based on the reduction of water-soluble silver
salt precursors, such as AgNO3 and its derivatives, using boron
hydrides, sodium citrate, ascorbate and LiAlH4.31,32 The size
distributions of these nanoparticles are often broad and the
stability of these colloids has been problematic, as they aggre-
gate and precipitate out over time from aqueous solution.
In continution of our investigations of the application of
solid acids in organic synthesis,33–35 we have investigated the
synthesis of silver nanoparticles as a catalyst and applied
them to the synthesis of 3,4-dihydropyrimidine-2-(1H)-ones
(thiones).
Results and discussion
We attempted to synthesise organic-soluble silver nanoparti-
cles using silver nitrate as a precursor by adsorption method
for use in an organic phase as a versatile reagent for the
synthesis of 3,4-dihydropyrimidine-2-(1H)-ones (thione). This
synthesis involved the three-component condensation of an
aromatic aldehyde 1, 1,3-diketones 2, and urea or thiourea 3
(Scheme 1).
The stable catalyst was easily prepared and used for
preparation of 3,4-Dihydropyrimidine-2-(1H)-ones (thiones)
(Figs 1–5).
Initially, the fully organic phase system contained silver
nitrate as a silver precursor, n-butylamine (CH3(CH2)3NH2) as
a solvent for dissolving the silver salt, dodecanoic acid
(CH3(CH2)10CO2H) [DDA] as a capping molecule, toluene as a
reaction medium, and NaBH4 as the reducing reagent. The
silver NPs which were synthesized were used without further
purification. The dodecanoic acid was held as a silver salt and
the mechanistic role of the silver ions was used to stabilise the
enolates of the 1,3-dicarbonyl compound that are required
for the reaction. A scheme for the direct synthesis of silver
nanoparticles from silver nitrate in the organic phase is
illustrated in Fig. 1. The formation of silver nanoparticles was
observed with UV spectroscopy, which showed surface plas-
mon peaks in the range between 380 and 450 nm in Fig. 2.
The product was characterised by SEM in Fig. 3. The SEM
image showed that the particle size was between 70 and 100nm.
The nanoparticles were typically dispersed in toluene for
further characterization using field emission transmission
TEM. TEM samples were prepared by placing a drop of the
colloidal dispersion in toluene on an amorphous carbon-coated
grid in Fig. 4. The TEM image showed nanopores with a size
of 5 nm. The molecular structure of the capping molecule on
1
the synthesised nanoparticles was investigated through H
NMR in Fig. 5. It shows that there were no protons in polar
groups such as amino or carboxylic acid, but only in hydrocar-
bon (C–H).
To optimise the reaction conditions, the reaction of 4-
nitrobenzaldehyde, ethyl acetoacetate and urea was used as a
Scheme 1 Synthesis of 3,4-dihydropyrimidine-2-(1H)-ones (thiones) in the presence of silver NPs as catalyst.
* Correspondent. E-mail: bsadeghia@gmail.com

344 JOURNAL OF CHEMICAL RESEARCH 2012
Fig. 1 Experimental schemes for direct synthesis of silver nanoparticles in fully organic phase through in situ ligand exchange.
Fig. 2 UV–Vis spectrum for silver nanoparticles dissolved into
toluene.
Fig. 4 The TEM images of silver nanoparticles.
Fig. 3 The SEM images of silver nanoparticles.
Fig. 5 The 1H NMR spectrum of silver nanoparticles dissolved
into deuteriatedchloroform.

JOURNAL OF CHEMICAL RESEARCH 2012 345
Table 1 Evaluation of the activity of different catalysts for the
synthesis of 5-ethoxycarbonyl-6-methyl-4-(4-nitrophenyl)-3-4-
dihydropyrimidin-2(1H)-one
Table 2 Optimisation amount of NPs silver for the synthesis
of 5-ethoxycarbonyl-6-methyl-4-(4-nitrophenyl)-3-4-dihydropy-
rimidin-2(1H)-one
Entry
Catalyst
Time
/min
Yielda /%
Entry
Catalyst
Time/min
Yielda/%
1
2
3
4
5
0.008
0.004
0.003
0.002
0.001
10
10
10
10
10
93
92
90
90
40
1
2
–
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
8
Ni(NTf2)2
CeCl3
28
15
71
54
32
10
24
11
48
30
35
52
45
92
76
3
4
Al(H2O)6(BF4)3
Yb(OTf)3
Cu(OTf)2
BiONO3
5
a Isolated yield.
6
7
8
BiCl3
9
NiCl2.6H2O
BF3.Et2O
CuCl/HOAc
FeCl3.6H2O
Zn(OTf)2
SbCl3
Table 3 Effect of the solvent on the synthesis of 5-ethoxycar-
bonyl-6-methyl-4-(4-nitrophenyl)-3-4-dihydropyrimidin-2(1H)-
one by silver NPs
10
11
12
13
14
15
16
Entry
Solvent
Time /min
Yielda/%
1
2
3
4
5
CH2Cl2
H2O
CH3CN
EtOH
15
10
10
10
25
80
80
87
90
60
Silver NPs
[DDPA][HSO4]
a Isolated yield.
CH3COOH
a Isolated yield.
model reaction. In order to establish the high catalytic activity
of silver NPs, we have compared the reaction using other cata-
lysts at reflux and for 10 min. The results are listed in Table 1.
The problems of the reported protocols such as prolonged
reaction time and poor yields prompted us to explore this solid
phase catalyst for the synthesis of 3,4-dihydropyrimidine-2-
(1H)-ones.
In order to determine the optimum quantity of NPs silver,
the reaction of 4-nitrobenzaldehyde, ethyl acetoacetate and
urea (1 mmol each) was carried out at reflux in EtOH (10 mL)
using different quantities of silver NPs (Table 2). A concentra-
tion of silver NPs of 0.002 g gave an excellent yield in 10 min
(Table 2, entry 4).
Table 4 Optimisation of temperature using silver NPs as
catalyst
Entry
Temperature /°C
Time /min
Yielda /%
1
2
3
25
60
Reflux
240
120
10
50
65
90
a Isolated yield.
To optimise the temperature in the mentioned reaction, we
have carried out a model study with a 4-nitrobenzaldehyde,
ethyl acetoacetate and urea using 0.002 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.
The above reaction was also examined in various solvents
(Table 3). The results indicated that different solvents affected
the efficiency of the reaction. Most of these solvents required a
longer time and gave moderate yields. The best results were
obtained when ethanol was used as solvent (Table 3, entry 4).
Table 5 Condensation of an aromatic aldehyde, 1,3-diketones, and urea or thiourea in the presence of silver NPs catalyst in ethanol
at refluxa
Entry
Ar
R
X
Product
Time/min
Yield/%b
M.p./°C
Found
Reported[Ref.]
1
2
C6H5
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
CH3
CH3
CH3
OEt
O
O
O
O
O
O
O
S
S
S
S
S
4a
4b
4c
4d
4e
4f
4g
4h
4i
10
10
10
10
10
10
10
10
10
10
10
10
96
93
90
86
80
85
83
90
91
88
83
85
206–207
202–203
212–214
213–214
255–257
220–222
213–214
207–208
192–194
210–211
160–161
192–194
206–20736
203–20436
212–21336
213–21436
256–25837
220–22136
215–21636
209–21038
192–19436
208–20936
161–16336
191–19336
4-MeOC6H4
4-NO2C6H4
4-ClC6H4
3
4
5
4-Me2NC6H4
3-MeOC6H4
4-MeC6H4
4-Me2NC6H4
C6H5
4-ClC6H4
4-MeOC6H4
4-MeC6H4
6
7
8
9
10
11
12
4j
4k
4l
a The compounds 4a–l were known and their structures were deduced by comparison of melting points and spectral data with
authentic samples.
b Yields refer to the pure isolated products.

346 JOURNAL OF CHEMICAL RESEARCH 2012
To study the scope of the reaction, a series of aromatic alde-
hydes, methyl or ethylacetoacetate and urea (thiourea) cata-
lysed by silver NPs as catalyst were examined. The results are
shown in Table 5. In all cases, aromatic aldehyde substituted
with either electron-donating or electron-withdrawing groups
underwent the reaction smoothly and gave the expected
products in good yields.
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Received 4 February 2012; accepted 15 March 2012
Paper 1201147 doi: 10.3184/174751912X13352025454801
Published online: 4 June 2012

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