Novel catalytic application of Ni@ZnO nanoparticles and ZnO nanoflakes in aqueous solution of NaPTS hydrotrope at room temperature via a green synthesis of 3,4-dihydropyrimidin-2(1H)-ones

Article abstract of DOI:10.1007/s11164-018-3295-2

We investigated a novel catalytic application of nickel-doped zinc oxide (Ni-ZnO) nanoparticles and zinc oxide (ZnO) nanoflakes at room temperature in an aqueous hydrotropic solution for the synthesis of biologically active dihydropyrimidones (DHPMs). Ni-

Full text of DOI:10.1007/s11164-018-3295-2

Res Chem Intermed
https://doi.org/10.1007/s11164-018-3295-2
Novel catalytic application of Ni@ZnO nanoparticles
and ZnO nanoꢀakes in aqueous solution of NaPTS
hydrotrope at room temperature via a green synthesis
of 3,4‑dihydropyrimidin‑2(1H)‑ones
1
1
1
3
1
Bipin Shinde · Santosh Kamble · Pramod Gaikwad · Vishvanath Ghanwat ·
1
1
1,2
Sagar Tanpure · Pavan Pagare · Bhausaheb Karale · Arvind Burungale
Received: 19 October 2017 / Accepted: 17 January 2018
©
Springer Science+Business Media B.V., part of Springer Nature 2018
Abstract We investigated a novel catalytic application of nickel-doped zinc oxide
(
Ni-ZnO) nanoparticles and zinc oxide (ZnO) nanoꢀakes at room temperature in an
aqueous hydrotropic solution for the synthesis of biologically active dihydropyrimi-
dones (DHPMs). Ni-ZnO is a stable, recyclable, green, eꢁcient heterogeneous cata-
lyst which shows maximum yield in a shorter reaction time than ZnO nanoꢀakes in
very mild conditions of hydrotropic aqueous medium for DHPMs syntheses.
Keywords Ni-ZnO · ZnO · DHPMs · Band gap · NaPTS
Introduction
Catalysis is a promising ꢂeld of chemistry. There are two types of catalysis: homo-
geneous and heterogeneous [1]. The main advantage of homogeneous catalysis is
that it gives high activities, high regio, and chemoselectivity. The main disadvantage
is the recovery of the catalyst. To overcome this diꢁculty, heterogeneous catalysis
Electronic supplementary material The online version of this article (https://doi.org/10.1007/
s11164-018-3295-2) contains supplementary material, which is available to authorized users.
*
*
Bipin Shinde
bipinshinde448@gmail.com
Arvind Burungale
asburungale@gmail.com
1
Department of Chemistry, Yashavantrao Chavan Institute of Science, Satara,
Maharashtra 415001, India
2
3
Department of Chemistry, S.M. Joshi College, Hadpsar, Pune, Maharashtra 411028, India
Department of Chemistry, Radhabai Kale Mahila Mahavidyalaya, Ahmednager,
Maharashtra 414001, India
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B. Shinde et al.
is a more suitable methodology for organic transformation. It shows excellent acces-
sibility and stability [2], but it has some shortcomings, such as inferior catalytic
performance due to reduced contact between the substrate and the catalyst. It also
shows longer reaction times [3]. Therefore, new catalytic systems like nanocatalysts
have been introduced to overcome the drawbacks of homogeneous catalysis. Nano-
materials act as a heterogeneous catalyst which is recovered easily and is as active as
a homogeneous catalyst [4].
The reaction between urea, ethyl acetoacetate and benzaldehyde was discovered
in 1893. This condensation reaction is called a Biginelli cyclocondensation reaction.
The result of this Biginelli reaction is a heterocyclic system of dihydropyrimidi-
nones (DHPMs), a multicomponent reaction in a single ꢀask [5]. At the beginning
of DHPM synthesis by Biginelli condensation, the product yield was only 25–45%
[
6]. The dihydropyrimidinone nucleus has received much more attention due to its
active medicinal properties, for example, as antihypertensive agents, calcium chan-
nel blockers, neuropeptide Y antagonists and alpha 1a-antagonists [7–9]. Batzel-
ladine alkaloids are the most important examples of a potent HIV group-120-CD4
inhibitor [10, 11]. DHPMs have recently received charismatic assessment due to
their wide range of pharmacological and therapeutic properties, such as antibacte-
rial, antiviral, anti-inꢀammatory and antitumor [12].
Recently, several methods like microwave-assisted, mechanical grinding, ultra-
sound reactions, etc. have been reported for the synthesis of DHPMs. These reac-
tions are catalyzed using protic acids, Lewis acids, Bronsted acid, heteropoly
acids, polyphosphate ester, clay zeolite, ferric chloride/tetraethyl orthosilicate,
iodine–alumina, trimethylchlorosilane, silica gel supported-sodium hydrogen sul-
fate, Ziegler–Natta catalyst, sulfated tungstate, methanesulfonic acid, Naꢂon-H,
montmorillonite K10, amberlyst-15, conc. HCl, Baker’s yeast, AlCl , [Al(H O) ]
3
2
6
(
BF ) , ZnCl , CuCl ·2H O, FeCl ·6H O, LaCl ·7H O, LiClO [13–32], etc. These
4 3 2 2 2 3 2 3 2 4
methods have limitations like a requirement for expensive reagents, highly acidic
conditions, special apparatus, stoichiometric amounts of the catalyst, unsatisfactory
yield, comparatively high temperature and incompatibility with other functional
groups [33–35]. Most of the DHPM reactions have been carried out in solvents such
as methyl cyanide, ethanol, acetonitrile, chloroform, etc., but very few reactions
have been performed in water medium at room temperature. These reactions are also
carried out at elevated temperatures due to a solubility problem of the multicompo-
nent reactants in water. DHPM synthesis can also be catalyzed by using ionic liquid-
like [bmim]BF and [bmim]PF under solvent-free conditions [36]. Especially, imi-
4
6
dazolium-based ionic liquids contain PF and BF anions which are toxic in nature
6
4
and liberate lethal HF; hence, the use of ionic liquids is a not much greener approach
during organic transformation. Syntheses of DHPMs have also been catalyzed using
PEG at an elevated temperature, 100 °C [37]. Microwave-assisted solvent-free syn-
thesis has also been reported, but it produces internal heating by direct coupling of
microwave irradiation energy with the reactants. This indicates that the proposed
condensation reaction is not successful at room temperature. To overcome these lim-
itations, we have chosen to use the sodium p-toluene sulfonate (NaPTS) hydrotrope
which dissolves reactants in water at room temperature and can be catalyzed using
Ni-ZnO nanoparticles and ZnO nanoꢀakes.
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Novel catalytic application of Ni@ZnO nanoparticles and ZnO…
In recent years, hydrotropes, which are salts of low molecular weight organic
compounds, have attracted extensive research interest as they have favorable proper-
ties such as high thermal stability, negligible vapor pressure and non-inꢀammabil-
ity [38]. Hydrotropes are also known as ‘green agents’ due to their unique property
of dissolving various organic reactants in water [39]. Hydrotropes are emerging as
green agents in organic transformations. We have chosen the NaPTS hydrotrope for
a proposed reaction along with distilled water because NaPTS reduces the surface
tension of water. Organic solutes and water show excellent interaction in the pres-
ence of NaPTS and also show greater solubility of an organic solute in water [40].
Over the past few decades, nanocatalyzed reactions have also gained wide recog-
nition because they can increase yield by decreasing the number of steps involved
in conducting reactions and also reduce the use of chemicals and solvents [41].
Recently, the use of nanomaterials has attracted much research attention in the syn-
thesis of heterocycles because they can positively increase the rate of reaction [42].
The Biginelli reaction is carried out in acidic conditions, and is a homogeneous
acid-catalyzed reaction. Howvever, it is very tedious to remove homogeneous cata-
lysts from the reaction mixture. The synthesis of 3,4-dihydropyrimidin-2(1H)-ones
was carried in the presence of solvents like 1,4-dioxane, THF, DMF, toluene, etc.
Here, we report a catalytic application of zinc oxide nanoꢀakes and nickel-doped
zinc oxide nanoparticles in water for the synthesis of DHPMs at room temperature.
This is a novel, powerful, economical, highly eꢁcient and extremely rapid method-
ology in water for the synthesis of DHPMs at room temperature. To the best of our
knowledge, this is the ꢂrst report of the catalytic application of ZnO nanoꢀakes and
Ni-ZnO nanoparticles for the synthesis of DHPMs in water at room temperature in
the presence of hydrotropes.
Experimental
Preparation of ZnO nanoꢀakes and Ni‑ZnO nanoparticles
All chemicals required for the synthesis of ZnO nanoꢀakes and Ni-ZnO nanoparti-
cles were analytical reagent grade such as ZnCl , NaOH, NiCl and 2-propanol and
2
2
distilled water.
A high degree of saturation was required to obtain a nucleation rate greater than
the growth rate. ZnCl (5.5 g) was dissolved in a beaker containing 200 mL distilled
2
water at 100 °C. The whole assembly was kept in an oil bath to achieve a 100 °C
temperature, and was gently stirred for 15 min. Next, 20 mL of 5 M NaOH aque-
ous solution was added dropwise to the ZnCl solution. A sedimentation technique
2
was used to separate out the precipitate. The supernatant solution was discarded and
distilled water was used to wash the precipitate, and about 800 mL of distilled water
was used to completely remove the NaCl, and an AgNO solution was used to check
3
its removal. The puriꢂed particles were then peptized with 2-propanol in the ultra-
sonic bath for 15 min at room temperature. Centrifugation was used to collect the
particles at 4500 rpm for 20 min. Thermal treatment was given to the collected par-
ticles at 300 °C for 4 h which led to the formation of ZnO nanoꢀakes.
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B. Shinde et al.
NiCl (0.4 g) and ZnCl (4.5 g) were dissolved in a beaker containing 200 mL
2
2
distilled water at 100 °C and the solution was held in an oil bath in order to attain
a 100 °C temperature. The solution of ZnCl and NiCl was gradually stirred for
2
2
1
5 min, and then 20 mL of 5 M NaOH aqueous solution was added dropwise. The
supernatant solution was discarded by using a sedimentation technique so that a pre-
cipitate settled at the bottom of the beaker. Distilled water (about 100 mL) was again
added to the precipitate, and the solution was ꢂltered through Whatmann paper
No. 41. Then, about 800 mL of distilled water was used to completely remove the
NaCl from the precipitate and the removal was tested by using AgNO solution. The
3
precipitate was further peptized in a 500 mL beaker containing 100 mL of 2-pro-
panol. The 2-propanol was removed from the precipitate by using centrifugation at
4
500 rpm for 20 min. The puriꢂed particles were dried initially and then kept in
a crucible for thermal treatment at 300 °C for 4 h which led to the formation of
Ni doped ZnO nanoparticles.
Procedure for the synthesis of DHPMs
A one-pot condensation of ethyl acetoacetate (1 mmol), aldehyde (1 mmol), and
urea (1 mmol) was carried out by using a hydrotropic solution of NaPTS in a
1
00 mL round-bottom ꢀask containing 10 mL distilled water under normal temper-
ature and pressure conditions. Ni-ZnO nanoparticles or ZnO nanoꢀakes (1 mol%)
were, respectively, used as a catalyst. The reaction mixture was stirred by using a
magnetic stirrer under normal temperature and pressure conditions. The reaction
was monitored by using the TLC technique (ethyl acetate:hexane 2:8, v/v). Ethyl
acetate (15 mL) was added to the reaction mixture after completion of the reaction.
Finally, the reaction mixture was centrifuged at 4000 rpm for 10 min. The catalyst
settled at the bottom of the reaction mixture and the product was taken out of the
pot. The catalyst was washed with deionized water and ethyl acetate and then dried
in an oven at 120 °C before recycling. The procedure for the synthesis of DHPMs is
shown in Fig. 1.
Characterizations
The crystal structures of the ZnO and Ni-ZnO materials were characterized by using
the X-ray diꢃraction (XRD) technique with the model Bruker D8 Advance with Cu
Kα radiation (λ = 1.54 Å) in the range 2θ 20°–80°. The surface morphology and
chemical composition were studied by using scanning electron microscopy (SEM)
with energy dispersive X-ray spectroscopy (EDAX) using the model JEOL JSM-
6
360 with an operating bias voltage of 20 kV. A UV–Visible spectrophotometer,
SYSTRONICS 119, was used for optical absorption study. The products were con-
1
13
ꢂrmed by IR, H-NMR and C-NMR with model lambda (Bruker) with an operat-
ing frequency of 400 Hz.
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3

Novel catalytic application of Ni@ZnO nanoparticles and ZnO…
Fig. 1 Graphical representation
of proposed reaction
Results and discussion
In the present study, our aim is to demonstrate the catalytic application of nanomate-
rials in water at room temperature for organic transformation. We decided to prepare
Ni-ZnO, ZnO heterogeneous catalysts via a co-precipitation method and studied
their catalytic application for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones in
aqueous hydrotropic solution at room temperature. Characterization of Ni-ZnO and
ZnO catalysts are described below
Catalyst characterization
Optical measurement
UV–visible spectroscopy was used to study the optical properties of ZnO and Ni-
ZnO materials. Optical absorption spectra of ZnO and Ni-ZnO were studied in the
wavelength range 375–800 nm shown in Fig. 2a. The band gap of ZnO and Ni-ZnO
materials were calculated by using Eq. (1) [43].
n
(ꢀhꢁ) = (Eg − hꢁ)
(1)
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B. Shinde et al.
2
Fig. 2 a Optical absorption spectrum and b (αhν) versus hν plot of Ni-ZnO and ZnO
where ‘hν’ is the incident photon energy, ‘α’ is an absorption coeꢁcient, ‘A’ is a
constant and ‘n’ determines electronic transition. The band gap of ZnO and Ni-ZnO
2
were determined by plotting the graph of (αhν) versus hν in Fig. 2b. The linear por-
tion of the plot is extrapolated to the X-axis to measure the exact band gap. The band
gap is 3.09 eV for ZnO nanoꢀakes and 3.18 eV for Ni-ZnO nanoparticles. The band
gap for Ni-ZnO nanoparticles (3.18 eV) is increased than ZnO nanoꢀakes (3.09 eV)
showing lower particle size. This increase in band gap for Ni-ZnO nanoparticles
++
++
conꢂrms the incorporation of Ni on the Zn site of the ZnO lattice, which proves
the doping of Ni in ZnO. We have obtained diꢃerent band gaps for ZnO nanoꢀakes
and Ni-ZnO nanoparticles compared with earlier reported results [44].
Structural study of ZnO and Ni‑ZnO
The structural properties of ZnO and Ni-ZnO were studied by using the XRD
technique. The XRD patterns of the ZnO and Ni-ZnO nanoparticles are shown in
Fig. 3. The XRD patterns of the ZnO nanoꢀakes show a polycrystalline nature. The
XRD patterns of the ZnO and Ni materials are in agreement with JCPDS card nos.
0
5-0664 and 75-0197, respectively. The XRD patterns of the ZnO material show a
maximum intensive hkl plane (101) at 2θ 36.34°. The asterisk (*) indicates the peak
of nickel with a hkl plane (200) at 2θ 43.30°, which proves the doping of Ni in ZnO.
The lattice spacing d was calculated by using Bragg’s diꢃraction law in Eq. (2)
2
d sin ꢀ = nꢁ
(2)
where ‘λ’ is the wavelength of the X-rays, ‘n’ is the order of diꢃraction and ‘θ’ is a
diꢃraction angle. Table 1 shows the 2θ, respective hkl planes, observed d values and
standard d values of Ni-ZnO nanoparticles.
The crystallite sizes (D) of ZnO and Ni-ZnO were calculated by the Debye–Scher-
rer formula, shown in Eq. (3) [45].
kꢀ
D =
(3)
ꢁ
cos ꢂ
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3

Novel catalytic application of Ni@ZnO nanoparticles and ZnO…
Fig. 3 XRD patterns for ZnO
nanoꢀakes and Ni-ZnO nano-
particles
ZnO
(200)*
Ni-ZnO
20
30
40
50
60
70
80
2
θ (Degree)
Table 1 The 2θ, hkl planes,
observed and standard ‘d’ values
of Ni-ZnO nanoparticles
Sr. no.
2θ (°)
hkl planes
Observed
Standard ‘d’ values
‘
d’ values
1
2
3
4
5
6
7
8
9
31.72
34.50
36.34
43.30
47.75
56.60
62.95
66.45
69.10
72.70
77.05
100
002
101
200 (Ni)*
102
110
103
200
201
2.8180
2.6045
2.4700
2.0872
1.9100
1.6240
1.4766
1.4070
1.3585
1.3010
1.2376
2.8160
2.6020
2.4760
2.0850
1.9110
1.6260
1.4770
1.4070
1.3590
1.3010
1.2380
1
0
004
202
1
1
*
Doping of Nickel
where ‘λ’ is a wavelength of the X-rays, ‘θ’ is the Bragg’s angle, ‘K’ is a constant
and ‘β’ is the full width at half maximum. The crystallite size of the more inten-
sive peak (101) of ZnO material is 24.28 nm; however, for Ni-ZnO it is found to be
1
2.15 nm. The results show a decrease in crystallite size when nickel is doped in
ZnO material.
Surface morphology of ZnO nanoꢀakes and Ni‑ZnO nanoparticles
The surface morphology of the materials was analyzed by using the SEM technique.
Higher and lower magniꢂcation images of ZnO nanoꢀakes are shown in Fig. 4a
and b, respectively, and of Ni-ZnO nanoparticles in Fig. 4c and d, respectively. The
surface morphology of the ZnO material shows nanoꢀakes; however, the Ni-ZnO
material displays a granular nanoparticulate like morphology. The ZnO nanoꢀakes
show 40 nm width and about 60 nm length, while the Ni-ZnO nanoparticles show
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B. Shinde et al.
Fig. 4 SEM images (a and b) for ZnO nanoꢀakes and (c and d) for Ni-ZnO nanoparticles at lower and
higher magniꢂcations, respectively
an average grain size of 80 nm. It is observed that, when Ni is doped in ZnO, the
surface morphology of ZnO is changed from nanoꢀakes to nanoparticles due to the
doping of nickel, which proves that nickel was doped successfully in the Ni-ZnO
nanoparticles. This result is in accordance with the UV and XRD analyses.
Composition study of ZnO nanoꢀakes and Ni‑ZnO nanoparticles
The chemical compositions of ZnO and Ni-ZnO nanoparticles were analyzed by the
EDAX technique, as shown in Fig. 5. The presence of peaks at 0.270 and 1.260 keV
for ZnO in Fig. 5a conꢂrms the presence of O and Zn, respectively. The presence of
peaks at 0.525, 0.851 and 1.012 keV for Ni-ZnO in Fig. 5b conꢂrms the presence
of O, Ni and Zn, respectively. The peak at 0.851 keV conꢂrms the doping of Ni in
ZnO. This result is in accordance with the UV, XRD, and SEM analyses of the ZnO
nanoꢀakes and Ni-ZnO nanoparticles.
Eꢁect of amount of catalyst on synthesis of DHPMs
The reaction of aldehyde (1 mmol), ethyl acetoacetate (1 mmol) and urea (1 mmol)
in the presence of catalytic amounts of Ni-ZnO nanoparticles and ZnO nanoꢀakes in
the hydrotropic aqueous solution of NaPTS at room temperature with stirring condi-
tion resulted into 3,4-dihydropyrimidin-2(1H)-ones (Scheme 1).
1
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Novel catalytic application of Ni@ZnO nanoparticles and ZnO…
Fig. 5 EDAX patterns for (a) ZnO and (b) Ni-ZnO nanoparticles
O
C
R
O
1
O
C
O
C
O
Nano ZnO / Ni -ZnO
CH2
O
C
C
NH
C
R
H +
H C
O
CH2
CH3
+ H N
2
NH2
3
4gm NaPTS +10 ml Distilled Water
Stirring (Room Temp.)
CH2
H C
3
H C
2
3
N
H
O
3
4
( a - i)
Scheme 1 The Biginelli reaction between aromatic aldehyde, ethyl acetoacetate and urea. Reaction con‑
a
b
dition: Aldehyde (1 mmol), ethyl acetoacetate (1 mmol), Urea (1 mmol), nanocatalyst (mol%), NaPTS,
c
yield (%) and distilled water (10 mL)
Lower yields were obtained with lower amounts of the catalysts used, e.g.,
8
mol% (Fig. 6). The yield was not increased to much extent when there was a fur-
ther rise in the amount of catalyst, e.g., more than 8 mol%. Ni-ZnO nanoparticles
8 mol%) and ZnO nanoꢀakes (8 mol%) show an excellent yield of product. We
(
achieved 96% yield of DHPMs at 8 mol% of nanocatalysts. Ni-ZnO nanoparticles
showed better results than ZnO nanoꢀakes (Fig. 6). It was observed that, due to a
decrease in particle size for Ni-ZnO nanoparticles, the catalytic activity of Ni-ZnO
is much increased compared with ZnO nanoꢀakes in water. The proposed reaction
was completed in the absence of a nanocatalyst with 80% yield in the longer reaction
time of 7 h. The time of the reaction was decreased up to 1.8 h in the presence of
the Ni-ZnO nanocatalyst (Fig. 7). The yield of the product was increased to 96% for
8
mol% of the Ni-ZnO nanocatalyst (Fig. 6).
Fig. 6 Eꢃect of the amount
of Ni-ZnO nanocatalyst on the
yield for DHPMs
ZnO
Ni-ZnO
90
81
9
6
96
85
96
85
100
8
7
8
8
4
8
3
80
7
7
5
7
3
8
6
4
2
0
0
0
0
0
Nil
2
4
6
8
10
15
Amount of Ni-ZnO (mol%)
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B. Shinde et al.
Fig. 7 Eꢃect of the amount of
Ni-ZnO nanoctalyst on the time
of the reaction
Fig. 8 Eꢃect of NaPTS on the
yield of DHPMs
Eꢁect of NaPTS on synthesis of DHPMs
A one-pot synthesis of DHPMs is not possible without a solvent with the stirring
condition at room temperature. We used distilled water as a solvent for DHPMs
syntheses and also used NaPTS for completely dissolving the reactants in water.
DHPMs were without a yield only in the presence of water as the solvent at room
temperature due to the dissolving problem of organic reactants in water; hence,
NaPTS was used to make the organic reactants soluble in water (Fig. 8). DHPMs
were synthesized with 35 and 96% yields for 1 and 4 g of NaPTS, respectively. The
yield of the product was increased with increasing amounts of NaPTS. We obtained
a 96% yield of DHPM for 4 g of NaPTS. Various aromatic aldehydes, ethyl acetoac-
etate and urea showed excellent solubility in water for 4 g of NaPTS (Fig. 8).
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Novel catalytic application of Ni@ZnO nanoparticles and ZnO…
Fig. 9 Eꢃect of solvent on the
yield of DHPMs
Eꢁect of solvent on the synthesis of DHPMs
We successfully synthesized DHPMs with outstanding yields in water as a solvent
because NaPTS shows good activity in the presence of water. Here, in the case of the
proposed reaction, NaPTS completely dissolves the reactants only in water and not
in the tested organic solvents like methanol, chloroform, acetone, or acetonitrile. We
successfully synthesized DHPMs in the presence of ZnO nanoꢀakes and Ni-ZnO
nanoparticles. In our study, It was observed that water is the best solvent in terms of
yield compared with methanol, chloroform, acetone, and acetonitrile (Fig. 9). To the
best of our knowledge, the Ni-ZnO nanocatalyst shows excellent catalytic activity in
water and is very stable, as shown in (Fig. 9). This is a much greener approach than
any other existing methodologies for the synthesis of DHPMs.
Recyclability of Ni‑ZnO nanoparticles and ZnO nanoꢀakes
Successive condensations of benzaldehyde, ethyl acetoacetate and urea were car-
ried out to check the reusability of the Ni-ZnO nanoparticles and ZnO nanocatalyst.
Yields were between 94 and 96% with the reusability of nanocatalysts (Fig. 10). The
nanocatalyst was centrifuged at 4000 rpm from the ꢂnal product during work-up and
settled at the bottom. It was then dried at 120 °C in a hot-air oven and reused ꢂve
times in reactions. It was observed that the nanocatalyst showed the same activity
during its recycling process for the proposed reaction.
The rate of reaction is aꢃected by the size of nanoparticles. Nanocatalysts with
smaller particle sizes give a more eꢃective yield than nanocatalysts with larger parti-
cle sizes. Ni-ZnO nanoparticles have an average particle size of 80 nm whereas ZnO
nanoꢀakes are 40 nm in width and about 60 nm in length. The results show that Ni-
ZnO nanoparticles are smaller in particle size and higher in surface area (due to the
smaller particle size) than ZnO nanoꢀakes. Therefore, the yield of DHPMs is much
better in the presence of Ni-ZnO nanoparticles than ZnO nanoꢀakes (Table 2).
The yield of DHPMs is excellent and increased from 15–40% to 92–96% in
water as a solvent. Aromatic rings containing electron-withdrawing groups such
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B. Shinde et al.
Fig. 10 Recyclability for Ni-
ZnO nanoparticles
Table 2 Eꢃect of Ni-ZnO nanoparticles and ZnO nanoꢀakes on the time of reaction and the yield in
b
NaPTS
DHPMs
Substrate (R)
C H
aNanocatalyst
Time (h)
cYield (%)
4
4
4
4
4
4
4
4
4
4
a
b
c
d
e
f
Ni-ZnO
ZnO
Ni-ZnO
ZnO
Ni-ZnO
ZnO
Ni-ZnO
ZnO
Ni-ZnO
ZnO
Ni-ZnO
ZnO
Ni-ZnO
ZnO
Ni-ZnO
ZnO
1.8
3.0
2.0
3.5
1.5
2.5
1.5
2.5
1.4
2.5
1.9
3.0
1.5
2.5
1.4
2.4
1.7
2.6
1.6
2.5
92
85
90
86
94
86
94
84
96
87
94
90
92
90
94
84
94
92
96
90
6
5
2-(OH)-4-(OMe)-C H
6
3
4-Br-C H
6
4
4-(NO )-C H
2
6
4
4-Cl-C H
6
4
3,4-(OMe)-C H
6
3
g
h
i
4-(OMe)-C H
6
4
3-(Br)-C H
6
4
4-(CH )-C H
4
Ni-ZnO
ZnO
Ni-ZnO
3
6
j
3,4,5-(OMe)-C H
6
3
ZnO
Reaction condition: Aldehyde (1 mmol), ethyl acetoacetate (1 mmol), Urea (1 mmol), ananocatalyst
b
c
(
8 mol%), NaPTS (4 g), yield (%) and distilled water (10 mL)
as bromine, chlorine, and the nitro group were easily converted into the respective
,4-dihydropyrimidinones and gave excellent yields (Table 2, entries 4c, 4e, 4d, 4h).
The rate of reaction and yield is increased because the carbonyl carbon of aromatic
3
1
3

Novel catalytic application of Ni@ZnO nanoparticles and ZnO…
aldehyde becomes electron-deꢂcient due to the electron-withdrawing group which
leads to an eꢃective nucleophilic attack. Aromatic rings containing electron-donat-
ing groups like (OCH ), OH, CH groups also give yields of more than 90%, even
3
3
though there is an electron-donating eꢃect (Table 2, entries 4f, 4g, 4i, 4j). This is
seen because NaPTS completely the dissolves reactants in water.
The structures and melting points of the DHPMs are as shown in Table 3.
Spectroscopic data of some synthesized dihydropyrimidones
4
c: Ethyl4‑(4‑bromophenyl)‑6‑methyl‑2‑oxo‑1,2,3,4‑tetrahydropyrim
idine‑5‑carboxylate
(
Table 3, Entry 4c) IR ν
(KBr) 3385(NH), 1724(–O–CO–), 1649(–CO–N),
max
−1
1
1
460(C=C), 610(C–Br) cm
H‑NMR (CDCl , 400 MHz) δ:1.21(t,3H),
3
1
3
2
.27(s,3H), 4.01 (q,2H), 5.27 (s,1H), 6.58 (s,2H), 7.15(d,2H), 7.36(d,2H,) C‑NMR
(
CDCl ,100 MHz) δ: 14.43 (CH –CH ), 15.03(CH ), 49.15 (C-4), 61.08 (CH –
3
2
3
3
2
CH ), 106.03 (C-5), 121.18 (C-4′), 129.35 (C-2′, C-6′), 131.33 (C-3′, C-5′), 142.25
3
(
C-1′), 148.21 (C-6), 150.10 (–C=O), 165.40 (Et-O-C=O). The spectroscopic values
are shown in supplementary data (SD1).
4e: Ethyl4‑(4‑chlorophenyl)‑6‑methyl‑2‑oxo‑1,2,3,4‑tetrahydropyrimidine‑5‑carbox‑
ylate
(
Table 3, Entry 4e) IR ν
(KBr) 3416(NH), 1728(–O–CO–), 1664(–CO–N),
max
−
1 1
1
3
462(C=C), 700(C–Cl) cm
H‑NMR (CDCl , 400 MHz) 1.10 (t, 3H), 2.17 (s,
3
H), 3.93 (q,2H), 5.20 (d,1H, H-4), 6.07(s,2H), 7.04 (d, 2H, H-2′, H-6′), 7.18 (d,2H,
1
3
H-3′, H-5′), C‑NMR (CDCl ,100 MHz) δ:14.51 (CH –CH ), 15.31(CH ), 50.12
3
2
3
3
(
C-4), 61.30 (CH –CH ), 106.53(C-5), 128.50 (C-2′, C-6′), 130.81 (C-3′, C-5′),
2
3
1
33.11 (C-1′), 143.51 (C-4′), 147(C-2), 153.21(C-6), 170.01(Et-OC=O) The spec-
troscopic values are shown in supplementary data (SD2).
4
g: Ethyl4‑(4‑methoxyphenyl)‑6‑methyl‑2‑oxo‑1,2,3,4‑tetrahydropyrimidine‑5‑car‑
boxylate
(
Table 3, Entry‑4g) IR ν
(KBr) 3442(NH), 1734(–O–CO–), 1647(–CO–N),
max
−1
1
1
445(C=C), 1219(C–O–C) cm
H‑NMR (CDCl 400 MHz) δ: 1.20(t, 3H),
3
2
.34(s,3H), 3.91(s,3H), 4.09(q, 2H), 5.35 (s,1H), 5.96 (s,2H), 6.84(d,2H H-3′ &
1
3
H-5′), 7.28(d, 2H, H-2′ & H-6′) C‑NMR (CDCl , 100 MHz) δ: 14.27 (CH –CH ),
3
2
3
1
6.79(CH ), 49.69 (C-4), 55.79 (–O–CH ), 61.07 (CH –CH ), 106.76 (C-5), 114.64
3 3 2 3
(
C-2′, C-6′), 127.20 (C-3′, C-5′), 135.42 (C-1′), 145.62 (C-6), 150.25 (–C=O),
58.21 (C-4′), 167.09 (Et-O-C=O). The spectroscopic values are shown in supple-
mentary data (SD3).
1
1
3

B. Shinde et al.
Table 3 Biginelli reactions of various aromatic aldehydes, ethyl acetoacetate and urea
0
Aromatic
Ethyl Aceto
M.P ( C)
DHPMs
Urea
Product
Aldehydes
Acetate
Found
O
O
O
O
O
4
a
H
203
H
3
C
O
CH
3
H N
NH2
NH
2
H C
H C
3
N
H
O
3
OCH3
O
O
O
O
O
OH
O
4
b
H
234
H
3
C
O
CH
3
H N
NH2
2
NH
H CO
OH
3
H C
H C
3
N
H
3
Br
O
O
O
O
O
4
c
H
214
H
3
C
O
CH
3
H N
NH2
2
NH
Br
H C
H C
3
N
H
O
3
NO2
O
O
O
O
O
O
O
O
O
O
O
4
d
H
207
214
176
H
3
C
C
C
O
O
O
CH
3
H N
NH2
2
NH
O N
2
H C
H C
3
N
H
O
3
Cl
O
O
4
e
H
H
3
CH
3
H N
2
NH2
NH
Cl
H C
H C
3
N
H
O
3
OCH
3
O
OCH3
H
O
4
f
H
3
CH
3
H N
2
NH2
H CO
NH
3
OCH3
H
3
C
H
3
C
N
H
O
1
3

Novel catalytic application of Ni@ZnO nanoparticles and ZnO…
Table 3 (continued)
0
Aromatic
Ethyl Aceto
Acetate
M.P ( C)
DHPMs
Urea
Product
Aldehydes
Found
OCH3
O
O
O
O
O
4
g
H
202
H
3
C
O
CH
3
H N
NH2
2
NH
H CO
3
H C
3
H C
3
N
H
O
Br
O
O
O
O
O
H
4
h
185
H
3
C
O
CH
3
H N
NH2
NH
2
Br
H C
3
H C
3
N
H
O
CH3
O
O
O
O
H
O
4
i
212
160
H
3
C
O
CH
3
H N
2
NH2
H C
3
NH
H C
H C
N
H
O
3
3
OCH
3
O
H
3
CO
OCH3
H CO
3
O
H
O
O
O
4
j
H
3
C
O
CH
3
H N
2
NH2
H CO
NH
3
OCH3
H
3
C
H
3
C
N
H
O
4
h: Ethyl 4‑(3‑bromophenyl)‑6‑methyl‑2‑oxo‑1,2,3,4‑tetrahydropyrimidine‑5‑car‑
boxylate
(
Table 3, Entry 4h) IR ν
(KBr) 3350(NH), 1730(–O–CO–), 1633(–CO–N),
max
−1
1
1
1
450(C=C), 685(C–Br) cm
H‑NMR (CDCl 400 MHz) δ: 1.21(t, 3H),
3
.89(s,3H), 4.07 (q, 2H), 5.36 (s,1H), 6.07 (s,2H), 7.28(m,4H H-2′, H-4′ H-5′, H-6′),
C‑NMR (CDCl , 100 MHz) δ: 14.15 (CH –CH ), 15.00(CH ), 55.30 (C-5), 60.20
1
3
3
2
3
3
(
CH –CH ), 106.82(C-1) 122.64 (C-3′), 125.37 (C-6′), 130.37 (C-4′), 131.08 (C-5′),
2
3
1
32.31(C-2′), 145.85(C-1′), 146.71(C-2), 150.19(C-4),165.34 (Et-O-C=O). The
spectroscopic values are shown in supplementary data (SD4).
1
3

B. Shinde et al.
4
j: Ethyl 6‑methyl‑2‑oxo‑4‑(3,4,5‑trimethoxyphenyl)‑1,2,3,4‑tetrahydro‑
pyrimidine‑5‑carboxylate
(
Table 3, Entry 4j) IR νmax (KBr) 3433(NH), 1749 (–O–CO–), 1684(–CO–N),
−1 1
1
592(C=C), 1232(C–O–C) cm
H‑NMR (CDCl , 400 MHz) δ: 1.33(t, 3H),
3
1
.77(s,3H), 3.83(s,3H), 3.84(s,3H), 3.95(s,3H), 4.02 (q, 2H), 5.65 (s,1H), 6.07
1
3
(
s,2H), 6.15(s,2H H-2′ & H-6′), C‑NMR (CDCl , 100 MHz) δ: 15.67 (CH –CH ),
3
2
3
1
1
1
7.79(CH ), 50.29 (C-5), 56.29 (–O–CH ), 61.01 (CH –CH ), 104.38 (C-2′, C-6′),
3 3 2 3
06.47(C-1) 137.72 (C-1′, C-4′), 147.62 (C-2), 150.25 (–C=O), 150.66 (C-3′, C-5′),
65.74 (Et-O-C=O). The spectroscopic values are shown in supplementary data
(
SD5).
The above described products have been conꢂrmed by IR, H-NMR and 13C-NMR.
1
Conclusion
We successfully synthesized Ni-ZnO nanoparticles and ZnO nanoꢀakes by the co-
precipitation method and characterized them by various analytical techniques. An
increase in band gap is found when Ni is doped insitu ZnO. The crystallite size is
found to be 24.28 and 12.15 nm for ZnO nanoꢀakes and Ni-ZnO nanoparticles,
respectively. The decrease in crystallite size and the change in surface morphology
from nanoꢀakes to nanoparticles is observed due to doping of Ni in ZnO. We car-
ried out the synthesis of DHPMs in organic solvent-free condition, i.e. in distilled
water, successfully for the ꢂrst time under room temperature condition using ZnO
nanoꢀakes and Ni-ZnO nanoparticles. Ni-ZnO shows excellent yields of DHPMs
because the particle size of Ni-ZnO is smaller and, hence, this results in a larger
surface area for the proposed reaction compared with the ZnO nanoꢀakes. There-
fore, the Ni-ZnO nanocatalyst is a much better aqueous hydrotropic nanocatalyst
for the synthesis of biologically active DHPMs at room temperature than the ZnO
nanoꢀakes.
Acknowledgement Authors are grateful to the Department of Chemistry, Yashavantrao Chavan Insti-
tute of Science, Satara, for providing the laboratory facility to complete this work.
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