Zirconia Sulfuric Acid: An Efficient Heterogeneous Catalyst for the One-Pot Synthesis of 3,4-Dihydropyrimidinones Under Solvent-Free Conditions

Article abstract of DOI:10.1007/s10562-016-1723-8

Abstract: In this article, zirconia sulfuric acid (ZrSA) has been synthesized from the reaction of ZrO₂ with chlorosulfonic acid. It was characterized by (FT-IR, XRD, TGA, SEM, EDS, BET, BJH, ICP and pH analysis). This catalyst was employed for

Full text of DOI:10.1007/s10562-016-1723-8

Catal Lett
DOI 10.1007/s10562-016-1723-8
Zirconia Sulfuric Acid: An Efficient Heterogeneous Catalyst
for the One-Pot Synthesis of 3,4-Dihydropyrimidinones Under
Solvent-Free Conditions
1
1
1
1
•
Maliheh M. Hosseini
Mohammad Ali Zolfigol
•
Eskandar Kolvari
2
•
Nadiya Koukabi
•
Maryam Ziyaei
Received: 19 February 2016 / Accepted: 28 February 2016
Ó Springer Science+Business Media New York 2016
Abstract In this article, zirconia sulfuric acid (ZrSA) has
been synthesized from the reaction of ZrO with chloro-
Keywords Zirconia sulfuric acid Á Solid acid catalyst Á
Biginelli Á 3,4-Dihydropyrimidinones Á Recyclability
2
sulfonic acid. It was characterized by (FT-IR, XRD, TGA,
SEM, EDS, BET, BJH, ICP and pH analysis). This catalyst
was employed for the synthesis of 3,4-dihydropyrimidi-
nones via cyclocondensation of b-ketoester, aromatic
aldehydes and urea/thiourea under solvent-free conditions.
Main advantages of the catalyst were non toxic nature, high
stability and reusability.
1 Introduction
Acid-catalyzed reactions are overwhelming favorite topics
in terms of widespread applications in the chemical
industry. Conventional liquid inorganic acids including
H SO , HCl and H PO are part of the homogeneous acid
2
4
3
4
Graphical Abstract
catalysts. Despite their usage in the large-scale production
of industrial chemicals, they suffer from several disad-
vantages such as high toxicity, corrosive nature, hazards in
handling and difficult separation from the products. These
disadvantages are far from the concept of ‘‘Green Chem-
istry’’. In this respect, in order to solve or minimize
drawbacks of these catalysts, replacement of them by
novel, nontoxic, eco-friendly, recyclable heterogeneous
catalysts with improved efficiency have been the subject of
intensive investigation during the past decade. Heteroge-
neous catalysts play crucial role in aspects of environ-
mental and economic in many industrial activities. They
offer some advantages including high reactivity, opera-
tional simplicity, low toxicity, non-corrosive nature and the
potential of the catalyst to be recyclable. Additionally,
most of the heterogeneous catalysts show higher ‘‘target’’
product selectivity, so that waste production can be avoided
.
[
1–4]. Immobilizing of homogenous precursors on a solid
support is one of the important routes for developing novel
heterogeneous catalysts [5, 6].
&
Eskandar Kolvari
kolvari@semnan.ac.ir
Currently, the commonly used support for heteroge-
neous catalysts are polymers [7], mesoporous materials [8],
zeolites [9], active carbon [10], ion-exchange resins [11]
Mohammad Ali Zolfigol
zolfi@basu.ac.ir
1
2
Department of Chemistry, Semnan University, Semnan, Iran
Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran
and metal oxides [12]. Metal oxides such as ZrO with high
2
surface area, mechanical strength and thermal stability
123

M. M. Hosseini et al.
have attracted attention as promising support materials.
melting points. NMR spectra were recorded on a Bruker
Avance 300 MHz instruments (1H NMR 300 MHz) in pure
deuteriated chloroform and dimethyl sulfoxide with
tetramethylsilane (TMS) as the internal standard. Melting
points were recorded on a THERMO SCIENTIFIC 9100
apparatus. All reactions were monitored by TLC and all
yields refer to isolated products.
Zirconia (ZrO ) is one of the most important ceramic
2
materials that are widely used in chemical industry due to
their unique electrical, mechanical, optical and thermal
properties [13–16]. Hence, there has been an intensified
focus towards new heterogeneous catalysts for multicom-
ponent reactions that would reinforce environmental
benefits.
Synthesis of 3,4-dihydropyrimidin-2(1H)-one (DHPMs)
are important for therapeutic and pharmacological prop-
erties [17–20]. The Biginelli reaction which was reported
for the first time by the Italian chemist Pietro Biginelli in
2.2 Preparation of ZrO –SO H (ZrSA)
2
3
A suction flask equipped with a constant-pressure dropping
funnel and a gas inlet tube for conducting HCl gas over an
adsorbing solution (i.e., water) was used. It was charged
with ZrO (1 g, 12.5 mmol) and dry CH Cl (20 ml). Then
1
891 [21], is an easy and useful multicomponent reaction
(
MCR) for the synthesis of 3,4-dihydropyrimidin-2(1H)-
2
2
2
ones (DHPMs). The reaction is accomplished from one-pot
condensation of b-dicarbonyl compound, aldehyde and
urea or (thiourea) in the presence of various catalyst such
as Bronsted acids [22], Lewis acids [23], heteropolyacids
chlorosulfonic acid (0.25 ml, 3.76 mmol) was added
dropwisely over a period of 30 min in an ice bath (0 °C).
HCl gas immediately evolved from the reaction vessel. The
mixing was continued over one hour to evaluation of HCl
was seized. Then, the CH Cl was removed under reduced
[
24] and nanocatalysts [25]. The improvement of the
2
2
reaction catalyst has received much attention in recent
years.
pressure and the solid powder was washed with water
(10 ml) and dried at 100 °C. The prepared ZrSA stored in
vacuum desiccator over anhydrous silica gel, then, was
dried in 100 °C for 6 h.
Growing concern about environmental damage leads to
an urgent requirement for the development of ecofriendly
technology and economic processes. In this regard, here in,
we report preparation of ZrO –SO H as newly acid catalyst
2.3 General Procedure for the Synthesis of 3,4-
Dihydropyrimidin-2(1H)-ones
2
3
for the facile synthesis of 3,4-Dihydropyrimidin-2(1H)-
ones (DHPM) under solvent-free conditions.
A mixture of aromatic aldehyde (1 mmol), b-dicarbonyl
compounds (1 mmol), and urea (or thiourea) (1.5 mmol)
was stirred at 90 °C utilizing ZrSA (0.05 g, 15 wt%) for
the appropriate time in solvent free condition until the
reaction was complete. The reaction was monitored by thin
layer chromatography (TLC) [7:3 hexane:ethyl acetate].
After the completion of the reaction the resulting mixture
was cooled, eluted with hot ethanol (5 ml), centrifuged and
filtrated to collect the formed precipitate. The crude pro-
duct was recrystallized from ethanol to yield pure 3,4-di-
hydopyrimidin-2(1H)-ones derivatives.
2
Experimental Section
2
.1 General Remarks
All reagents were purchased from Merck and Aldrich and
used without further purification. Zirconium oxide (ZrO2)
was purchased from Aldrich. Fourier transform infrared
spectroscopy (FT-IR) was recorded on a Shimadzu 8400 s
spectrometer using KBr pressed powder discs. The TGA
curve of catalyst was recorded by using a thermogravi-
metric analyzer on a Du Pont 2000 thermal analysis
-
1
apparatus at heating rate of 5 °C min under air atmo-
sphere over the temperature range of 25–800 °C. X-ray
diffraction (XRD) patterns of samples were taken on a
Siemens D5000 (Siemens AG, Munich, Germany) X-ray
3 Results and Discussion
Herein, we report the synthesis of zirconia sulfuric acid
(ZrSA) and discuss its performance as a novel solid acid
catalyst as a part of our ongoing investigation in develop-
ing new and efficient heterogeneous solid acid catalysts
[26–28]. This catalyst was prepared by the reaction of ZrO2
with chlorosulfonic acid at room temperature (Scheme 1).
The loading process proceeded cleanly and HCl evolved
from the reaction vessel immediately as the only by-
product. The synthesized catalyst was characterized by IR,
XRD, TGA, SEM, EDS, BET, BJH, ICP and acid–base
titration.
diffractometer using Cu-Ka radiation of wave-length
˚
.54 A. Scanning electron Microscopy, SEM-EDX, anal-
1
ysis was performed using Tescanvega II XMU Digital
Scanning Microscope. BET surface areas were acquired on
a Beckman Coulter SA3100 surface area analyzer. The
loading value of sulfur in the catalyst was estimated by
inductively coupled plasma ICP analysis with an ICP MS
ELAN DRC-e. Products were characterized by spec-
troscopy data (FTIR, 1H NMR and 13C NMR spectra) and
1
23

Zirconia Sulfuric Acid: An Efficient Heterogeneous Catalyst for the One-pot Synthesis…
-
072, 1006, 891 and 852 cm , which are attributed to the
1
1
O=S=O asymmetric and symmetric stretching vibration
and S–O stretching vibration of the sulfonic groups (–
SO H), respectively [27]. The spectrum also shows a rel-
3
-
1
atively broad band around 2700–3600 cm due to OH
stretching absorption of the SO H group. All these obser-
3
vations confirm that the sulfonic groups have functional-
ized the surface of the ZrO2.
Scheme 1 Schematic representation of the synthesis of zirconia
sulfuric acid (ZrSA)
3
.1 Catalyst Characterization
3.1.3 X-ray Diffraction (XRD) Analysis
3
.1.1 PH Analysis of Catalyst
The powder XRD patterns of ZrO and ZrSA are shown in
2
Fig. 2. It seems that the peak intensities of ZrO and ArSA
2
The amounts of sulfonic acid groups on ZrSA were
determined by acid–base potentiometric titration of the
aqueous suspension of the washed catalyst with standard
NaOH solution. For this purpose 100 mg ZrSA was dis-
are almost same and the peaks remained intact under the
conditions used for modification. These results indicate that
mesoporosity of the support remains intact after
modification.
persed in 20 ml H O by ultrasonic bath for 60 min. The
2
amount of the acid was neutralized by addition of standard
NaOH solution (0.1 N) to the equivalence point of titration.
The required volume of NaOH to this point was 2.89 ml.
3
.1.4 Thermo Gravimetric Analysis (TGA)
?
Thermo gravimetric analysis (TGA) of ZrSA in compar-
ison with ZrO is shown in Fig. 3. The TGA curve of ZrO
The optimum concentration of H sites was 2.89 mmol/g
2
2
of catalyst (values calculated by the weight of ZeSA) at
?
(Fig. 3a) reveals an initial weight loss, occurring below
2
5 °C. The value of H per gram of acid corresponds to
200 °C, quite likely due to the removal of adsorbed water.
ratio of mmol of chlorosulfonic acid to total mass of ZrSA.
.1.2 FT-IR Spectra
The second weight loss occurring in the range 180–800 °C,
is attributed to the dehydroxylation of ZrO2.
3
As shown in Fig. 3b the TGA of ZrSA shows two-stage
decomposition. The weight loss below 200 °C is related to
the loss of adsorbed solvent or trapped water from the
catalyst and a mass loss of weight occurred between 590
Figure 1 shows the FT-IR results of ZrO particles with
2
and without SO H loading, respectively. For the bare ZrO
3
2
-
Fig. 1a), the vibration band at 746 and 588 cm are the
1
(
and 700 °C that is related to the sudden mass loss of SO H
3
typical IR absorbance induced by structure Zr–O vibration.
-
The vibration band at around 1616 cm is due to Zr–OH
1
groups [30–32]. From the evaluation of the weight loss in
the mentioned temperature range, it can be understood that
ZrSA has a great thermal stability (up 160 °C) confirming
that it could be safely used in organic reactions at tem-
peratures in the range of 80–150 °C.
-
1
vibration and the absorbance band at around 3431 cm
was certified to the adsorbed water which is consistent with
the reported IR spectra for ZrO [29]. In the case of ZrSA
2
(
Fig. 1b), some new bands appeared at 1338, 1286, 1172,
Fig. 1 FT-IR spectra of a ZrO
2
, b ZrSA
2
Fig. 2 Powder XRD patterns of (a) ZrO (b) ZrSA
123

M. M. Hosseini et al.
3
.2 Catalytic Performances in Multicomponent
One-Pot Synthesis of Dihydropyrimidinone
Derivatives
After characterization, catalytic activity of the catalyst was
examined in multicomponent reactions for the synthesis of
dihydropyrimidinone derivatives. The structures of the
final products were well characterized by using spectral
(IR, 1H NMR) data.
Dihydropyrimidinone was prepared by the reaction of
aromatic aldehyde, b-dicarbonyl compound and urea or
(
thiourea) with 15 wt% of ZrSA at 90 °C under solvent-
free conditions (Scheme 2).
2
Fig. 3 TGA weight loss curves of (a) ZrO (b) ZrSA
In order to optimize the reaction conditions with respect
to catalytic efficiency of ZrSA and to examine the effect of
solvent and temperature on the reaction yield, initially a
model study was carried out on the synthesis of dihy-
dropyrimidinone by the condensation of benzaldehyde
(1 mmol), methyl acetoacetate (1 mmol) and urea
(1.5 mmol) in different sets of reaction conditions. In
preliminary experiment, to minimize the formation of
byproducts and to achieve good yield of the desired pro-
duct, the reaction is optimized by varying the amount of
catalyst (5, 10, 15 and 20 mol%). The percentage of the
product formation using ZrSA as the catalyst was found 69,
77, 97 and 89 %, respectively (Table 3, entries 2–5).
Therefore, it was found that the use of 15 mol% of the
catalyst was sufficient to promote the reaction. Larger
amounts of the catalyst were found to have an inhibitory
effect on the formation of the product. The results show
clearly that catalyst is effective for this transformation and
in the absence of it, the reaction did not take place even
after higher reaction time (Table 3, entry 1).
3
.1.5 FESEM-EDS Analysis
The surface features and elementary composition of ZrO2
and ZrSA were examined with FESEM and EDS, as shown
in Fig. 4. EDS spectrum of ZrSA (Fig. 4b) reveals the
appearance of sulfur and excess oxygen elements that
reconfirm the formation of SO H groups after modification
3
of ZrO (Fig. 4d) by sulfunation agent.
2
FESEM spectrum shows that the pure ZrO (Fig. 4a) has
2
been composed of the micron-size sphere particles.
According to the FESEM image of the modified material
(
Fig. 4c), it was found that there is no clear change in the
morphology of the obtained modified material. The mate-
rial is still sphere structure and the particles sizes were
smaller than that for pure material.
3
.1.6 BET and BJH Texture Analysis
The effect of temperature was studied by carrying out
the model reaction at different temperatures (50, 70, 90 and
110 °C) in the presence of 15 mol% of ZrSA under sol-
vent-free condition and the best results were obtained at
90 °C (Table 3, entries 4, 6–8). This reaction was also
carried out in various solvents, with ZrSA (15 wt %) as a
catalyst. The reaction could be carried out in refluxing
The BET surface area and pore volume and Pore width
were calculated using the Brunauer–Emmett–Teller (BET)
and BJH equations. BET surface areas were acquired on a
Beckman Coulter SA3100 Surface Area Analyzer. Prior to
N -physical adsorption measurements, the samples were
2
degassed at 150 °C for 120 min in the nitrogen atmo-
sphere. The specific surface area (SBET) of the obtained
materials was determined with adsorption–desorption iso-
EtOH, H O and MeOH as solvents and gave product in
2
moderate yield (Table 3, entries 9–11). It was very sur-
prising that the reaction proceeded in excellent yields
(97 %) under solvent-free condition (Table 3, entry 4).
Therefore, the solvent-free condition was used for the
synthesis of dihydropyrimidinones derivatives.
therms of N at 77 K. The surface area, pore volumes, pore
2
width and pore diameter size of the material are summa-
rized in Table 1.
The decrease in the surface of the ZrSA proved the
presence of –SO H as acidic groups on the surface of the
3
To establish the generality and applicability of this
method, a series of aromatic aldehydes with the electron-
donating and electronwithdrawing substituent were reacted
with methyl or (ethyl) acetoacetate and urea or (tiourea)
under the optimized conditions. The results are presented in
Table 4. Aromatic aldehydes containing both electron
solid catalyst (Table 1). It can be concluded that the sul-
fonation of ZrO has taken place, because the physical
2
adsorption of nitrogen gas after functionalization using
chlorosulfonic acid was decreased. Also, Table 2 shows the
textural properties of ZrO and ZrSA.
2
1
23

Zirconia Sulfuric Acid: An Efficient Heterogeneous Catalyst for the One-pot Synthesis…
2
Fig. 4 FESEM-EDS analysis of a and b ZrO c and d ZrSA
Table 1 BET data showing the
Sample
2
BET surface area (m g
-1
3
Pore volume (cm g
-1
)
)
Pore width (nm)
textural properties of the
obtained materials
ZrO
2
6.7
1.9
0.0051
0.0016
1.7
4.2
ZrSA
Table 2 BJH data showing the
textural properties of the
obtained materials
Property
ZrO
2
ZrSA
2
-1
-1
2
5.419 m g
3
0.0094 cm g
-1
Desorption surface area
11.8 m g
3
-1
Cumulative desorption pore volume
Desorption pore diameter
0.014 cm g
3.6 nm
3.5 nm
donating and electron withdrawing groups afforded high
yields of the desired products.
condensation of aldehydes 1 and b-ketoester 2, and I after
dehydration gives the olefin II. Nucleophilic attack of the
amino group in urea or thiourea 3 at the b-carbon of the
a,b-unsaturated carbonyl group followed by cyclization
yields the product 4.
A plausible mechanism for the Biginelli reaction in the
presence of ZrSA is shown in Scheme 3. ZrSA facilitates
the formation of the intermediate I by Knoevenagel
123

M. M. Hosseini et al.
Scheme 2 Synthesis of
dihydropyrimidinone using of
zirconia sulfuric acid (ZrSA)
Table 3 Optimization of
synthesis of
dihydropyrimidinones
a
Entry
Solvent
Condition
Amount of catalyst (mol%)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Ethanol
90 °C
90 °C
90 °C
90 °C
90 °C
50 °C
70 °C
110 °C
Reflux
Reflux
Reflux
–
5
50
95
70
50
55
55
50
45
60
50
65
Trace
69
10
15
20
15
15
15
15
15
15
77
97
89
56
48
77
89
1
1
0
1
Methanol
85
Water
20
Reaction condition: benzaldehyde (1 mmol), methyl acetoacetate (1 mmol), urea (1.5 mmol)
a
Isolated yields
The efficiency of ZrSA was compared with some other
published works in literature for the Biginelli reaction
3.4 Physical and Spectroscopic Data for Selected
Compounds
(
Table 5). Each of these methods has their own advantages,
but they often suffer from some troubles including reaction
conditions, time and product yields. As can be seen in this
table, the present catalyst was found to be the most efficient
catalyst for the synthesis of dihydropyrimidinones.
3.4.1 5-(Ethoxycarbonyl)-6-methyl-4-phenyl-3,4-
dihydropyrimidin-2(1H)-one (4n)
1
Mp: 205–207 °C; H NMR (CDCl
, 300 MHz):d (ppm):
3
8
.62 (s, 1H, NH), 7.24e7.31 (m, 5H, ArH), 6.1 (s, 1H, NH),
5
.38 (s, 1H, CH), 4.03 (q, 2H, OCH CH ), 2.32 (s, 3H,
2
3
1
3
3
.3 Reusability of the Catalyst
CH ), 1.13 (t, 3H, OCH CH ).
3
C NMR (CDCl3,
2
3
75 MHz): d (ppm): 14.12, 18.55, 55.59, 59.97, 101.23,
The recovery and reuse of catalysts are highly preferable
for a green process. In this regard, reusability of the
catalyst was evaluated in the model reaction. After
completing the reaction, ZrSA was recovered from the
reaction mixture via centrifuge, washed with ethanol and
dried in oven at 100 °C and was reused for another batch
of the reaction. This process has been repeated for 4
consecutive runs without observable decrease in catalytic
activity of the catalyst. ICP analysis of fresh and recycled
catalyst showed 3.8 and 2.7 % of S content respectively.
Moreover, the XRD pattern of recycled catalyst showed
that the ZrSA was the similar to the initial one after four
runs (Fig. 5).
126.56, 127.88, 128.66, 143.73, 146.48, 153.73, 165.65. IR
-
(KBr) cm : 3247.90, 3116.75, 2977.89, 1720.39, 1643.24.
1
3.4.2 5-(Ethoxycarbonyl)-6-methyl-4-(p-tolyl)-3,4-
dihydropyrimidin-2(1H)-one (4q)
1
Mp: 215–217 °C. H NMR (CDCl , 300 MHz): d (ppm):
3
8.75 (s, 1H, NH), 7.09e7.21 (m, 4H, ArH), 6.22 (s,1H,
NH), 5.34 (s, 1H, CH), 4.04 (q, 2H, OCH CH ), 2.3 (s, 3H,
2
3
1
3
CH ),1.15(t, 3H, OCH CH ). C NMR (CDCl , 75 MHz):
3
2
3
3
d (ppm): 14.16, 18.50, 21.09, 55.18, 59.93, 101.35, 126.45,
129.30, 137.52, 140.91, 146.41, 153.99, 165.74. IR (KBr)
-
cm : 3245.97, 3114.82, 2979.82, 1724.24, 1649.02.
1
1
23

Zirconia Sulfuric Acid: An Efficient Heterogeneous Catalyst for the One-pot Synthesis…
Table 4 ZrSA-catalyzed one-
pot synthesis of
a
Entry Ar
R
X
Product Time (min) Yield (%)
MP
MP(Ref)
dihydropyrimidinones
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
C
6
H
5
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
S
4a
4b
4c
4d
4e
4f
25
50
50
60
45
45
50
60
50
60
55
60
60
30
25
50
60
70
70
50
45
45
50
40
99
91
83
92
98
88
94
86
82
92
84
81
72
92
96
91
85
90
92
93
81
95
90
91
216–218 209–216 [33]
239–241 241–242 [34]
215–217 213–215 [35]
252–253 252–253 [36]
204–206 204–207 [37]
280–283 283–285 [38]
193–194 192–194 [39]
214–216 214–215 [40]
234–236 235–237 [33]
279–281 279–280 [36]
224–226 224–225 [41]
252–254 253–254 [35]
176–179 178 [42]
4-HO–C
6 4
H
3 2 6 4
4-(CH ) NC H
2-Cl–C
4-Cl–C
6
H
H
4
4
6
6
6
2-MeO–C
4-MeO–C
H
4
H
4
4g
4h
4i
4-Me–C
H
6 4
4-O
3-O
2-O
2
2
2
N–C
N–C
N–C
6
6
6
H
4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
H
4
4
4j
H
4k
4l
3-EtO-4-HO–C
3,4-(OMe)2–C
6 3
H
H
6 3
4m
4n
4o
4p
4q
4r
C
H
6 5
Et
205–207 205–206 [43]
230–231 228 [44]
4-HO–C
4-O N–C
4-Me–C
H
6 4
Et
2
H
6 4
Et
213–215 208–211 [39]
215–217 215–216 [45]
214–216 213–215 [46]
216–218 216–218 [47]
232–234 232–233 [48]
206–208 208–209 [49]
204–206 202–203 [50]
193–195 193–194 [51]
227–229 221–222 [38]
H
6 4
Et
4-Cl–C
2-Cl–C
6
H
H
4
4
Et
6
Et
4s
4t
3-EtO–4-HO–C
H
6 3
Et
C
H
6 5
Et
4u
4v
4w
4x
4-HO–C
H
6 4
Et
S
4-O N–C
2
H
6 4
Et
S
C
H
6 5
Me
S
Reaction condition aromatic aldehyde (1 mmol), b-dicarbonyl compound (1 mmol), urea or (thiourea)
(
a
1.5 mmol), ZrSA (15 mol%), solvent-free, 90 °C
Isolated yields
-
1
3
.4.3 5-(Ethoxycarbonyl)-4-(4-chlorophenyl)-6-methyl-
148.48, 152.29, 165.43. IR (KBr) cm : 3247.90, 3116.75,
1712.67, 1650.95.
3
,4-dihydropyrimidin-2(1H)-one (4r)
1
Mp: 214–216 °C; H NMR (CDCl , 300 MHz): d (ppm):
3.4.5 5-(Ethoxycarbonyl)-4-(2-chlorophenyl)-6-methyl-
3
8
.44 (s, 1H, NH), 7.22e7.29 (m, 4H, ArH), 6.1 (s, 1H, NH),
3,4-dihydropyrimidin-2(1H)-one (4s)
5
.36 (s, 1H, CH), 4.04 (q, 2H, OCH CH ), 2.32 (s, 3H,
2
3
1
3
1
CH ), 1.15 (t, 3H, OCH CH ).
2
C NMR (CDCl3,
Mp: 216–218 °C; H NMR (CDCl , 300 MHz): d (ppm):
3
3
3
7
1
5 MHz): d (ppm): 14.15, 18.63, 55.02, 60.14, 101.02,
27.99, 128.84, 133.69, 142.19, 146.54, 153.48, 165.45. IR
9.08 (s, 1H, NH), 7.19e7.37 (m, 4H, ArH), 5.98 (s, 1H,
NH), 5.86 (s, 1H, CH), 3.97 (q, 2H, OCH CH ), 2.41 (s,
2
3
-
KBr) cm : 3240.19, 3116.75, 2977.89, 1704.96, 1650.95.
1
(
3H, CH ), 1.02 (t, 3H, OCH CH ).13C NMR (CDCl ,
3 2 3 3
75 MHz): d (ppm): 13.97, 18.23, 52.06, 59.93, 98.8,
3
.4.4 5-(Ethoxycarbonyl)-6-methyl-4-(3,4-
127.51, 128.03, 129.23, 129.75, 132.55, 139.58, 148.56,
-
1
dimethoxyphenyl)-3,4-dihydropyrimidin-2(1H)-one
153.42, 165.33. IR (KBr) cm : 3234.40, 3110.97,
1701.10, 1645.17.
(
4m)
1
Mp: 176–179 °C; H NMR (CDCl , 300 MHz): d (ppm):
3.4.6 5-(Ethoxycarbonyl)-4-(3-ethoxy-4-hydroxyphenyl)-
3
9
.15 (s, 1H, NH), 7.68 (s, 1H, NH), 5.09 (s, 1H, CH), 3.95
6-methyl-3,4-dihydropyrimidin-2(1H)-one (4t)
(
q, 2H, OCH CH ), 3.37 (s, 3H, CH ), 3.95 (q, 2H,
2
3
3
1
3
1
OCH CH ), 2.24 (s, 3H, CH ).
2
C NMR (CDCl3,
Mp: 232–234 °C; H NMR (CDCl , 300 MHz): d (ppm):
3
3
3
7
9
5 MHz): d (ppm): 14.15, 17.76, 53.49, 55.4, 55.52, 59.19,
9.39, 110.45, 111.72, 117.9, 137.35, 148.06, 148.15,
7.27 (s, 1H, NH), 6.79 (s, 1H, NH), 5.31(s, 1H, CH), 4.75(s,
1H, OH) 4.03 (q, 2H, OCH CH ), 2.33 (s, 3H, CH ), 1.39
2
3
3
123

M. M. Hosseini et al.
Scheme 3 Proposed mechanism for the synthesis of dihydropyrimidinones ZrSA
Table 5 Comparing the
Entry
Catalyst
Condition
Time (h)
Yeild (%)
References
efficiency of ZrSA with some
different reported catalysts in
Biginelli reaction
a
1
2
3
4
5
6
7
8
9
a
SBSSA
Solvent-free/110 °C
Solvent-free/100 °C
Solvent-free/80 °C
EtOH/reflux
1
81
89
94
91
93
92
80
98
92
[52]
b
CD-SO
c
3
H
2
[53]
DBSA
d
SSA
3
[54]
6
[6]
e
Ce(LS)3
EtOH/80 °C
8
[55]
Sulfated tungstate
f
CSA
Solvent-free/80 °C
1
[56]
2
H O/100 °C
5
[57]
12-Tungstophosphoric acid
ZrSA
AcOH/reflux
6
[58]
Solvent-free/90 °C
0.5
Peresent work
Silica-bonded s-sulfonic acid
Sulfonated b-cyclodextrine
p-dodecylbenzenesulfonic acid
Silica sulfuric acid
b
c
d
e
f
Cerium(III) trislaurylsulfonate
Cellulose sulfuric acid
1
23

Zirconia Sulfuric Acid: An Efficient Heterogeneous Catalyst for the One-pot Synthesis…
References
1
2
3
4
5
6
. Zhang F, Wu X, Liang C, Li X, Wang Z, Li H (2014) Green
Chem 16:3768–3777
. Pua F-l, Fang Z, Zakaria S, Guo F, Chia C-h (2011) Biotechnol
Biofuels 4:56
. Aworanti O, Agarry S, Ajani A (2013) Br Biotechnol J
3
:116–132
. Niknam K, Zolfigol MA, Hossieninejad Z, Daneshvar N (2007)
Chin J Catal 28:591–595
. Amoozadeh A, Rahmani S (2015) J Mol Catal A: Chem
3
96:96–107
. Salehi P, Dabiri M, Zolfigol MA, Fard MAB (2003) Tetrahedron
Lett 44:2889–2891
. Dong Z, Ye Z (2015) Appl Catal A 489:61–71
7
8
. Artz J, Mallmann S, Palkovits
:672–679
. a´ del Pino C (1991) J Chem Soc Chem Commun 1253–1255
R (2015) ChemSusChem
8
9
1
0. Planeix J, Coustel N, Coq B, Brotons V, Kumbhar P, Dutartre R,
Geneste P, Bernier P, Ajayan P (1994) J Chem Soc, Chem
Commun 116:7935–7936
1
1
1. Kuzminska M, Backov R, Gaigneaux EM (2015) Catal Commun
5
2. Gawande MB, Branco PS, Parghi K, Shrikhande JJ, Pandey RK,
Ghumman C, Bundaleski N, Teodoro O, Jayaram RV (2011)
Catal Sci Technol 1:1653–1664
9:222–225
1
1
1
1
1
3. Tichit D, Coq B, Armendariz H, Figueras F (1996) Catal Lett
3
8:109–113
4. Kuzminska M, Kovalchuk TV, Backov R, Gaigneaux EM (2014)
J Catal 320:1–8
Fig. 5 Reusability of ZrSA in the Biginelli reaction
5. Huckel M, Wirth HJ, Hearn MT (1996) J Biochem Biophys
Methods 31:165–179
6. Mallik S, Dash SS, Parida KM, Mohapatra B (2006) J Colloid
Interface Sci 300:237–243
7. Ashok M, Holla BS, Kumari NS (2007) Eur J Med Chem
(
t, 3H, OCH CH ), 1.15 (t, 3H, OCH CH ). 13C NMR
2 3 2 3
(
CDCl , 75 MHz): d (ppm): 14.13, 14.77, 17.74, 53.55,
3
5
1
3
9.15, 63.93, 99.64, 112.3, 115.38, 118.45, 135.9, 146.13,
-
4
2:380–385
1
46.32, 147.84, 152.31, 165.47. IR (KBr) cm : 3417,
263, 2985.60, 1704.96, 1650.95.
18. Fewell SW, Smith CM, Lyon MA, Dumitrescu TP, Wipf P, Day
BW, Brodsky JL (2004) J Biol Chem 279:51131–51140
1
9. Atwal KS, Rovnyak GC, Kimball SD, Floyd DM, Moreland S,
Swanson BN, Gougoutas JZ, Schwartz J, Smillie KM, Malley MF
(
1990) J Med Chem 33:2629–2635
4
Conclusion
20. Rovnyak GC, Kimball SD, Beyer B, Cucinotta G, DiMarco JD,
Gougoutas J, Hedberg A, Malley M, McCarthy JP (1995) J Med
Chem 38:119–129
In the present work, we have introduced zirconia sulfuric
acid (ZrSA) as a highly powerful heterogeneous solid
acid catalyst for the one-pot synthesis of 3,4-dihy-
dropyrimidin-2(1H)-ones under solvent-free conditions.
All the reactions work easily for a variety of aldehydes
with both electron-donating and electron-withdrawing
groups to give corresponding products in excellent
yields. Furthermore, the application of ZrSA as a highly
efficient, inexpensive, easy handling and reusable catalyst
makes all process more economical and industrially
important. The notable advantages of this method are
high catalytic activity, short reaction time, mild reaction
conditions, excellent yields, reusable catalyst and simple
work-up.
2
1. Sepehri S, Sanchez HP, Fassihi A (2015) J Pharm Pharm Sci
8:1–52
22. Shekouhy M (2012) Catal Sci Technol 2:1010–1020
3. Nakajima K, Noma R, Kitano M, Hara M (2014) J Mol Catal A:
Chem 388:100–105
1
2
2
4. Blasco T, Corma A, Martinez A, Martinez-Escolano P (1998) J
Catal 177:306–313
25. Hattori M, Einaga H, Daio T, Tsuji M (2015) J Mater Chem A
(8):4453
3
2
2
2
2
3
6. Koukabi N, Kolvari E, Zolfigol MA, Khazaei A, Shaghasemi BS,
Fasahati B (2012) Adv Synth Catal 354:2001–2008
7. Kolvari E, Koukabi N, Hosseini MM (2015) J Mol Catal A:
Chem 397:68–75
8. Kolvari E, Koukabi N, Hosseini MM, Khandani Z (2015) RSC
Adv 5:36828–36836
9. Chakravarty R, Shukla R, Ram R, Tyagi A, Dash A, Venkatesh
M (2010) Chroma 72:875–884
0. Fu B, Gao L, Niu L, Wei R, Xiao G (2009) Energy Fuels
23:569–572
31. Li B, Gonzalez RD (1997) Appl Catal A 165:291–300
Acknowledgments The authors are thankful to the Semnan
University research council for the partial support of this work.
123

M. M. Hosseini et al.
3
3
2. Navarra MA, Croce F, Scrosati B (2007) J Mater Chem
7:3210–3215
3. Bahekar SS, Kotharkar SA, Shinde DB (2004) Mendeleev
Commun 14:210–212
46. Heravi MM, Asadi S, Lashkariani BM (2013) Mol Divers
17:389–407
47. Fu NY, Yuan YF, Cao Z, Wang SW, Wang JT, Peppe C (2002)
Tetrahedron 58:4801–4807
1
3
3
4. Liu CJ, Wang JD (2009) Molecules 14:763–770
5. Su W, Li J, Zheng Z, Shen Y (2005) Tetrahedron Lett
48. Salehi P, Dabiri M, Zolfigol MA, Fard MAB (2003) Tetrahedron
Lett 44:2889–2891
4
6:6037–6040
6. Shaabani A, Bazgir A, Teimouri F (2003) Tetrahedron Lett
4:857–859
7. Shaabani A, Bazgir A, Teimouri F (2003) Tetrahedron Lett
4:857–859
8. Nasr-Esfahani M, Hoseini SJ, Mohammadi F (2011) Chin J Catal
2:1484–1489
9. Nasr-Esfahani M, Khosropour AR (2005) Bull Korean Chem Soc
6:1331
49. Ghosh R, Maiti S, Chakraborty A (2004) J Mol Catal A: Chem
217:47–50
50. Kumar A, Maurya RA (2007) Tetrahedron Lett 48:4569–4571
51. Mobinikhaledi A, Zendehdel M, Nasab MH, Fard MAB (2009)
Heterocycl Commun 15:451–458
52. Tajbakhsh M, Ranjbar Y, Masuodi A, Khaksar S (2012) Chin J
Chem 33:1542–1545
53. Asghari S, Tajbakhsh M, Kenari BJ, Khaksar S (2011) Chin
Chem Lett 22:127–130
3
3
3
3
4
4
4
3
2
0. Hekmatshoar R, Heidari M, Heravi M, Baghernejad B (2009) J
Korean Chem Soc 53:90–94
54. Bigdeli MA, Gholami G, Sheikhhosseini E (2011) Chin Chem
Lett 22:903–906
4
4
1. Maradur SP, Gokavi GS (2007) Catal Commun 8:279–284
2. Salehi P, Dabiri M, Zolfigol MA, Fard MAB (2004) J Braz Chem
Soc 15:773–776
55. Qiu Y, Sun H, Ma Z, Xia W (2014) J Mol Catal A: Chem
392:76–82
56. Salim SD, Akamanchi KG (2011) Catal Commun 12:1153–1156
57. Rajack A, Yuvaraju K, Praveen C, Murthy Y (2013) J Mol Catal
A: Chem 370:197–204
4
4
4
3. Hu EH, Sidler DR, Dolling UH (1998)
3:3454–3457
J Org Chem
6
4. Reddy KR, Reddy CV, Mahesh M, Raju P, Reddy VN (2003)
Tetrahedron Lett 44:8173–8175
5. Moghaddas M, Davoodnia A, Heravi MM, Tavakoli-Hoseini N
58. Heravi MM, Derikvand F, Bamoharram FF (2005) J Mol Catal A:
Chem 242:173–175
(2012) Chin J Catal 33:706–710
1
23