Polyvinylsulfonic acid: An efficient, water-soluble and reusable bronsted acid catalyst for the three-component synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones in water and ethanol

Article abstract of DOI:10.1007/s10562-012-0873-6

A facile and environmentally benign protocol has been developed for the one-pot three-component synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones from the cyclocondensation reaction of aldehyde, ethyl acetoacetate (β-dicarbonyl compound) and urea or th

Full text of DOI:10.1007/s10562-012-0873-6

Catal Lett (2012) 142:1505–1511
DOI 10.1007/s10562-012-0873-6
Polyvinylsulfonic Acid: An Efficient, Water-Soluble and Reusable
Brønsted Acid Catalyst for the Three-Component Synthesis
of 3,4-Dihydropyrimidin-2(1H)-ones/thiones in Water and Ethanol
Ali Rahmatpour
Received: 13 May 2012 / Accepted: 4 July 2012 / Published online: 18 September 2012
Ó Springer Science+Business Media, LLC 2012
Abstract A facile and environmentally benign protocol
has been developed for the one-pot three-component syn-
thesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones from
the cyclocondensation reaction of aldehyde, ethyl aceto-
acetate (b-dicarbonyl compound) and urea or thiourea
using polyvinylsulfonic acid as a reusable homogeneous
Brønsted acid- and metal-free organocatalyst in water and
ethanol. This new protocol has the advantages of easy
availability, stability, reusability and eco-friendly of the
catalyst, high to excellent yields, simple experimental and
work-up procedure.
A variety of procedures using homogeneous Lewis acid as
well as protic acid or heterogeneous catalysts such as
BF3ÁEt2O/CuCl [10], CeCl3Á7H2O [12, 13], InBr3 [14],
BiCl3 [15], Cu(OTf)2 [16], FeCl3Á6H2O/HCl [17, 18], I2
[19], Sr(NO3)2 [20], LaCl3Á7H2O/HCl [21], ZrCl4 [22],
Mn(OAc)3 [23], LiClO4 [24], VCl3 [25], Zn(NH2SO3)2
[26], Cu(NH2SO3)2 [27], H3BO3 [28], p-TSA [29], KHSO4
[30], iodoxy benzoic acid [31], silica sulfuric acid [32],
Dowex-50 W [33], zeolite [34], metallophthalocyanine
[35], montmorillonite KSF [36], Ag3PW12O40 [37], cellu-
lose sulfuric acid [38], PS/AlCl3 [39], H3PMo12O40 [40],
Yb(III)-resin [41], Amberlyst-70 [42], and Lewis base such
as PPh3 [43] have been reported to accomplish this trans-
formation. Additionally, the above cyclocondensation
process could proceed in ionic liquid [44, 45] or ultrasonic
and microwave irradiation [46]. However, in spite of their
potential utility, many of these reported protocols suffer
from different drawbacks such as the use of expensive
catalysts, toxic solvents and metal-based catalysts, non-
recyclability, harsh reaction conditions, long reaction
times, the need of an additive, tedious work-up and envi-
ronmental pollution. Another disadvantage of most of the
existing methods is that the catalysts are destroyed during
the work-up procedure and their recovery and reuse is often
impossible, which limit their use under the aspect of
environmentally benign processes. Consequently, the
design of efficient, metal-free and green approaches for the
Biginelli reaction is still in demand.
Keywords Polyvinylsulfonic acid Á Brønsted acid Á
Biginelli reaction Á 3,4-Dihydropyrimidin-2(1H)-one
1 Introduction
In the past few decades, 3,4-dihydropyrimidin-2(1H)-one
(DHPM) scaffold has been under intensive investigation
[1–3] as it has a very broad pharmacological profile such as
calcium channel modulators [4], antihypertensive agents
[5], antiviral [6], anti-inflammatory [7], antifungal [8], and
antitumor agents [9]. In general, the classic approach to
DHPMs is based on the ternary condensation of ethyl
acetoacetate, aromatic aldehyde and urea under strong
acidic conditions, first reported by Biginelli [10]. The
reaction is carried out in a one-pot manner by heating a
mixture of the three components dissolved in ethanol with
a catalytic amount of hydrogen chloride under reflux.
From many years, functional polymers have been
employed as reagents and catalysts in organic synthesis.
The important advantages to use functionalized polymer as a
catalyst is the simple product work-up, easy separation, and
isolation procedure. Polyvinylsulfonic acid (PVSA) is the
solid-state organic analogue of sulfuric acid and has a high
acid density (ion exchange capacity; IEC = 9.2 meq/g)
A. Rahmatpour (&)
Polymer Science and Technology Division, Research Institute
of Petroleum Industry (RIPI), 14665-1137 Tehran, Iran
e-mail: rahmatpoura@ripi.ir
123

1506
A. Rahmatpour
OH
SO2
CH
Ar
O
CH
X
O
O
2
n
NH
C H O
2
5
PVSA
H O or Ethanol
2 H O
2
ArCHO
+
+
OC H
+
H N
H C
2
5
3
NH
2
2
2
H C
3
X
N
H
X= O, S
1a-1w
2
3
4a-4w
Scheme 1 PVSA catalyzed synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones
[47, 48]. PVSA exhibited very high acid properties in both
aqueous and water-free states (acid dissociation constant of
VSA: pKHI?A- = 0.049 in water, -4.9 in acetonitrile).
PVSA is a strong aliphatic polymeric sulfonic acid and has
high solubility in water and lower alcohols [49]. Conven-
tional strong mineral Brønsted acid catalysts, such as sul-
furic acid, are miscible with reaction medium, and need to
be neutralized after the reaction to separate the product
from the toxic acid, generating considerable waste [50–52].
Metal-containing Lewis acid catalysts, like aluminium tri-
chloride, also require careful removal after the reaction,
which also produces a large amount of waste [53, 54]. The
use of a polymeric Brønsted acid catalyst system is thus
preferable from an environmental and economical point of
view. Distinct advantages of PVSA over conventional
Brønsted acid catalyst can include low toxicity and low
corrosiveness, cost-effectiveness, ease of handling, recov-
ery and reuse in liquid phase reactions, and tunable
Brønsted acidity. We have recently reported the utility of
PVSA as an aliphatic polymeric Brønsted acid catalyst for
aqueous synthesis of benzoxanthenes [55].
polyvinylsulfonic acid (Na-PVSA) was prepared from the
polymerization of sodium vinylsulfonate monomer using
potassium persulfate and sodium bisulfite as an initiator
system (number average molecular weight & 53000) in
the first step and then the free acid (PVSA) was prepared
by ion exchange technique (The solution of Na-PVSA was
passed through a cation exchange column). FT-IR spec-
trum of Na-PVSA showed two absorption peaks at 724 and
1189 cm-1, which are assigned to the methylene groups
(-CH2-) in polymer backbone and sulfonate groups,
respectively. Polymeric sulfonic acid is a strong polybasic
acid comparable to sulfuric acid and protons are considered
to be localized along the polymer chain, as a result, the
reaction takes place only in the neighborhood of polymer
molecule. Hence, the proton density in solutions may be
locally concentrated, unlike as in homogeneous mineral
Brønsted acid. In such a case, the rate of reaction by a
polymeric sulfonic acid more than that of reaction with
homogeneous acidic catalysts [61]. This water-soluble
catalyst (PVSA) is eco-friendly and easily accessible.
To optimize the reaction conditions, initial studies were
concentrated on treatment of benzaldehyde, ethyl aceto-
acetate and urea as a model reaction. As shown in Table 1,
the reaction parameters, such as type of solvents, amount of
catalyst, temperature and reactant ratio were examined.
The model reaction was performed in solvents such as
CHCl3, CH3CN, CH3OH, C2H5OH and H2O and also under
solvent-free conditions (entries 1–5, 8). The reaction in
H2O and C2H5OH gave the best results, respectively
(entries 4, 5). The highest yields obtained by using H2O
and C2H5OH as the solvent can be ascribed to the high
solubility of the polymer network of the catalyst in these
media, allowing the adequate access of substrates to the
active sites (the sulfonic acid groups along the polymer
chain) of the catalyst to effect the catalysis. No reaction
occurred when non polar solvent such as toluene was used,
because of the aggregation of the catalyst caused by its
hydrophilic nature, leading to inadequate access of sub-
strates to the active sites of the catalyst. To determine the
appropriate molar ratio of reactants, the same reaction was
investigated with different molar ratio of reactants
In view of environmental mandates, there is a global
effort to replace conventional catalysts by eco-friendly
catalysts. As part of our continuous efforts to develop eco-
friendly catalytic processes [56–59], herein we report for
the first time the use of PVSA as a reusable aliphatic
polymeric Brønsted acid catalyst for a simple, facile and
green three-component synthesis of 3,4-dihydropyrimidin-
2(1H)-ones/thiones by the reaction of aldehyde, ethyl
acetoacetate (b-dicarbonyl compound) and urea or thiourea
in water and ethanol (Scheme 1). To the best of our
knowledge in the open literature, the Biginelli reaction
involving a water-soluble and reusable polymeric Brønsted
acid catalyst is unprecedented.
2 Results and Discussion
For this study, PVSA was prepared in two steps by a
method described in earlier published article [55] and the
slight modified Breslow’s method [60]. The sodium salt of
123

Polyvinylsulfonic Acid as Component Synthesizer
1507
model reaction was also carried out in the presence of other
different Brønsted-acidic catalysts and various ion
exchange resins such as Nafion NR-50, Amberlyst-15, and
Amberlite IRP-64 under similar experimental conditions
(molar ratio, temperature and 10 mol% of the catalyst) to
compare the efficiency of PVSA; the corresponding prod-
uct 4a was obtained lower to moderate yields in water
(Table 1, entries 15–21). As shown in Table 1, PVSA
catalyzes the reaction better than other catalysts, and sat-
isfactory results were obtained only with PVSA (entry 5).
The reason is that a high density of the sulfonic acid groups
is present along the polymer chain of PVSA. Further,
PVSA as a homogeneous polymeric Brønsted acid catalyst,
in comparison with sulfuric acid, offers the advantages of
easy separation, non-corrosiveness and low pollution
effects.
Table 1 Optimization of the reaction conditions for synthesis of 4a
Entry Catalyst
Solvent
Catalyst T (°C) Time Yielda
loading
(mol%)
(h)
(%)
1
PVSA
PVSA
PVSA
PVSA
PVSA
PVSA
PVSA
PVSA
PVSA
PVSA
–
CHCl3
10
Reflux
Reflux
Reflux
Reflux
90
4
4
4
1
1
1
1
1
1
1
8
8
4
4
1
48
2
CH3CN 10
CH3OH 10
C2H5OH 10
56
3
78
4
88
5
H2O
H2O
H2O
H2O
H2O
–
10
10
10
5
94
6b
7c
8
90
63
90
77
90
80
9
15
10
90
93
10
11
12
13
14
15
90
61
C2H5OH 10
Reflux
90
Trace
Trace
80
–
H2O
H2O
H2O
H2O
10
10
10
10
Encouraged by our initial studies and the remarkable
results obtained, we then investigated the generality and
versatility of our method. A wide range of aromatic alde-
hydes were investigated for their reaction with ethyl ace-
toacetate and urea or thiourea in the presence of PVSA
under the optimized reaction conditions and the results are
summarized in Table 2. Several aromatic aldehydes car-
rying either electron-releasing (Table 2, entries 2, 3, 7, 10,
11) or electron-withdrawing substituents (Table 2, entries
4–6, 8, 9) in the ortho, meta and para positions and also
multicyclic aromatic systems (Table 2, entries 13, 14)
afforded high yields of the products. Another important
feature of this method is the tolerance of various functional
groups such as methoxy, nitro, hydroxyl, etc. to the reac-
tion conditions, as well as the compatibility without for-
mation of side products of acid sensitive aldehyde such as
cinnamaldehyde (Table 2, entry 12), due to the mild
reaction conditions. Thiourea was used with similar suc-
cess to provide the corresponding dihydropyrimidin-2(1H)-
thiones (Table 2, entries 15–23). The present protocol is
equally effective for urea or thiourea and the yields were
significantly better in comparison with the classical Bigi-
nelli procedure. The experimental and work-up procedure
for these transformations is remarkably simple which
includes filtration of resultant mixture for product separa-
tion, and no requires any toxic organic solvents. Compared
with traditional homogeneous Brønsted acid catalyst, it is
easy for PVSA to be reused, which is prior to the con-
ventional homogeneous acid catalysts. Hence, we then
turned our attention towards the reusability of Brønsted-
acidic PVSA for the synthesis of 4a. After the separation of
product, the filtrate containing catalyst was evaporated to
remove water, and the resulting catalyst was reused directly
for the next run. As shown in Table 3, the polymeric
Brønsted-acidic PVSA can be recycled at least five times
without any treatment and without a significant decrease in
catalytic activity. Thus PVSA/H2O is a green catalyst for
PVSA
PVSA
H2SO4
65
25
47
90
80
(98 % w/w)
16
17
18
19
p-TSA
H2O
H2O
H2O
H2O
10
10
10
10
90
90
90
90
1
1
1
1
79
76
62
72
CH3SO3H
NH2SO3H
Nafion
NR-50
20
21
Amberlyst-15 H2O
10
10
90
90
1
1
62
53
Amberlite
IRP-64
H2O
All reactions were carried out with molar ratio 1:1:1.5 of benzalde-
hyde (1a), 2 and 3 in 5 mL of solvent
a
Isolated yields based on 1
b
The molar ratio of 1a/2/urea is 1:1:1
c
The molar ratio of 1a/2/urea is 1:1:1.2
(Table 1, entries 5–7) and the highest yield of the desired
product 4a was obtained with 1:1:1.5 of benzaldehyde,
ethyl acetoacetate and urea (entry 5). To find the optimized
amount of PVSA, the same condensation reaction was
carried out by using different amounts of the catalyst.
Maximum yield was obtained with 10 mol% of the catalyst
(Table 1, entry 5, 94 %). Further increase in amount of
PVSA did not affect the product yield (Table 1, entry 9,
93 %), but a lower amount of the catalyst led to lower yield
(Table 1, entry 8, 80 %). To illustrate the need of PVSA
for this condensation, we examined the model reaction in
the absence of catalyst in H2O and C2H5OH solvents. In
these cases the reactions did not proceed even after 8 h
(entries 11, 12). Furthermore, the effect of reaction tem-
perature was examined (Table 1, entries 13, 14) and we
found that 90 °C is the optimal temperature (Table 1, entry
5, 94 %) and the reaction was incomplete at lower tem-
peratures even after 4 h (65 °C, 80 %; 25 °C, 47 %). The
123

1508
A. Rahmatpour
Table 2 PVSA catalyzed synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones
Entry
Ar
X
Time/min
Product
Yielda (%)
m.p. (oC) found
Lit. m.p. (oC) Reference
Ethanol
Water
1
C6H5
O
O
O
O
O
O
O
O
O
O
O
O
O
O
S
60
60
65
60
80
85
70
90
90
95
60
70
95
100
120
70
95
100
70
90
85
100
80
4a
4b
4c
4d
4e
4f
88
87
90
91
88
87
90
87
86
87
86
88
84
83
82
90
85
84
86
90
82
81
83
94
91
94
94
91
91
92
91
90
90
92
90
88
86
85
92
89
89
89
90
89
87
87
204–205
213–214
201–202
210–212
222–223
213–215
226–227
208–209
228–229
252–253
176–178
233–234
289–291
282–283
267–268
206–208
192–193
151–152
208–209
205–206
192–194
168–169
184–185
205–206 [11]
214–215 [11]
201–203 [11]
212–213 [12, 13]
223–224 [12, 13]
215 [40]
2
4-CH3C6H4
4-CH3OC6H4
4-ClC6H4
3
4
5
2-ClC6H4
6
4-BrC6H4
7
4-OHC6H4
4g
4h
4i
227–228 [17, 18]
210 [11]
8
4-NO2C6H4
3-NO2C6H4
4-N(CH3)2C6H4
3,4-(CH3O)2C6H3
C6H5CH = CH
Naphthalen-2-yl
6-CH3O-naphthalen-2-yl
Naphthalen-2-yl
C6H5
9
230–232 [41]
253–254 [32]
178 [38]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
4j
4k
4l
232–235 [12, 13]
4m
4n
4o
4p
4q
4r
4s
S
208–209 [41]
192–194 [21]
152–154 [41]
209–210 [21]
206–207 [21]
195–196 [12, 13]
168–169 [12, 13]
184–186 [32]
4-CH3C6H4
4-CH3OC6H4
4-N(CH3)2C6H4
3-NO2C6H4
3-ClC6H4
S
S
S
S
4t
S
4u
4v
4w
2-ClC6H4
S
3-OHC6H4
S
Reaction conditions: Aldehyde (1, 1 mmol), ethyl acetoacetate (2, 1 mmol), urea or thiourea (3, 1.5 mmol), PVSA (10 mol%), 90 °C
a
Isolated yield based on aldehyde 1
intermediate 6 formed by the reaction of aldehyde with
urea, is rate-determining step. Further addition of the
iminium ion by the enol tautomer of activated ethyl ace-
oactate gives an ureido 7 which subsequently cyclized to
dihydropyrimidinone 4 with expulsion of water. The cat-
alytic effect of polyvinylsulfonic acid, which is Brønsted
polymeric acid catalyst, probably arises acidity of it, par-
ticipating in acid catalyzed formation of 6, as well as the
activation of ethyl acetoacetate and stabilizing the resulting
‘‘enolate ion’’ through hydrogen bonding, thus facilitating
the addition of ethyl acetoacetate to the more electrophilic
iminium carbon center. The suggested mechanism is
illustrated in Scheme 2.
Table 3 Reuse of PVSA for synthesis of 4a
Run
1
2
3
4
5
Yielda (%)
94
92
90
86
84
Reaction conditions: 1a (1 mmol), 2 (1 mmol), 3 (1.5 mmol), and
PVSA (10 mol%) in water (5 mL) at 90 °C for 60 min
a
Isolated yield
the Biginelli condensation as the aqueous medium is non-
hazardous and non-toxic to the environment, and PVSA in
ethanol is also suitable medium for this transformation
because of its ease of availability and non-hazardous nat-
ure. It is also noteworthy to mention that these reactions are
working well in aqueous medium without using any phase
transfer catalyst.
The efficiency and applicability of the presented method
for the synthesis of 4a has been compared with some of the
previously reported methods in Table 4. The results have
been compared with respect to the reaction times, mol% of
the catalyst used, and yields. As demonstrated in Table 4,
PVSA is an equally or more efficient catalyst for this three-
component reaction in terms of yield and reaction rate.
Exact mechanism of this reaction is unclear, but
according to the experimental results and by referring to
the literature [1–3] for the Biginelli reaction, the acid cat-
alyzed formation of N-acyliminium ion as active
123

Polyvinylsulfonic Acid as Component Synthesizer
1509
Scheme 2
OH
X
Ar
Ar
H
X
H-Y
-H O
2
NH
HN
NH
2
NH
2
ArCHO
+
HN
Y
H N
NH
2
2
X
6
H
O
O
Ar
O
Ar
O
OEt
C H O
NH
H C
EtOOC
2
5
3
H-Y
-H O
2
H C
3
X
H C
X
3
O
N
H
4
NH
2
7
OH
SO2
CH
H
Y
=
CH
2
n
PVSA
Table 4 Comparison of the results obtained for the preparation of 4a using different catalysts
Entry
Catalyst (mol%)
Conditions
Reaction
time (h)
Yield (%)
Reference
1
Montmorillonite KSF
Silica sulfuric acid (30)
H3PMo12O40 (2 mol%)
Dowex-50 W (100 mg)
VCl3 (10 mol%)
Solvent-free/130 °C
Ethanol/Reflux
48
6
82
91
80
92
44
70
79
71
90
77.8
90
80
94
92
80
82
96
89
96
85
70
50
94
[36]
[32]
[40]
[33]
[25]
[43]
[14]
[11]
[22]
[20]
[37]
[41]
[41]
[43]
[34]
[9]
2
3
HOAc/Reflux
5
4
Solvent-free/130 °C
CH3CN/Reflux
3
5
5
6
PPh3 (10 mol%)
Solvent-free/100 °C
Ethanol/Reflux
10
10
18
4
7
InBr3 (10 mol%)
8
BF3.OEt2/CuCl (20 mmol)
ZrCl4 (10 mol%)
Sr(NO3)2 (5 mol%)
Ag3PW12O40
HOAc/Reflux
9
Ethanol/Reflux
10
11
12
13
14
15
16
17
18
19
20
21
22
23
HOAc/Reflux
6
Ethanol/Reflux
2.5
48
6.5
3.5
12
18
2
Yb(III)-resin
Solvent-free/120 °C
Ethanol/Reflux
In(OTf)3 (2 mol%)
Ceric ammonium nitrate
Zeolite (0.5 g)
Sonication/CH3OH/60 °C
Toluene, reflux
H2SO4
Cellulose sulfuric acid (0.1 g)
PS-AlCl3 (10)
Ethanol, reflux
Ethanol/Reflux
CH3CN/Reflux
CH3CN/Reflux
CH3CN/Reflux
Water/90 °C/microwave
Water/90 °C
[38]
[39]
[62]
[62]
[62]
[63]
[Table 2]
3
Nafion NR-50 (0.25 g)
Amberlyst-15 (0.25 g)
Amberlite IRP-64 (0.25 g)
Nafion-H
3
5.5
6
0.5
1
PVSA (10)
3 Conclusion
nonvolatile, easily-handled, and reusable homogeneous
Brønsted acid- and metal-free organocatalyst. The use of
A mild, easy, efficient, and green catalytic method for the
synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones has
been proposed through Biginelli reaction in the presence of
polyvinylsulfonic acid as an inexpensive, noncorrosive,
polyvinylsulfonic acid as a green and recoverable
organocatalyst in this transformation makes the method
economically and environmentally viable, simple and a
user-friendly process for the synthesis of target products.
123

1510
A. Rahmatpour
Furthermore, simple wok-up, short reaction times and high
yields of the products and performing the reactions both in
aqueous media and ethanol are other noteworthy advanta-
ges of this catalytic system.
n-hexane), the reaction mixture was cooled to room tem-
perature and to it, ethyl acetate (10 mL) and water (5 mL)
was added. The product was extracted in organic phase
(ethyl acetate), washed with water (10 mL) and dried over
anhydrous Na2SO4. Evaporation of the solvent under
reduced pressure gave crude product. The resulting crude
product was recrystallized from ethanol to obtain pure 3,
4-dihydropyrimidin-2(1H)-ones/thiones. The aqueous layer
and the aqueous washings of the reaction mixture were
collected and evaporated under vacuum in rotary evapo-
rator. After removal of the water, PVSA was recovered.
4 Experimental
Polyvinylsulfonic acid (PVSA) was prepared according to
the previously reported method [55]. The monomer, ion
exchange resins, and chemicals used in this work were
purchased from Fluka and Merck chemical companies and
used without further purification. Melting points were
determined using Electrothermal 535 apparatus and were
uncorrected. FT-IR spectra were run on a Shimadzu FTIR-
4.1.3 Catalyst Recovery and Reuse
After completion of the reaction, water (20 mL) was added
to the reaction mixture and stirred for 10 min. The undis-
solved solid (product) was filtered. The filtrate was then
evaporated under vacuum in rotary evaporator to dryness
and PVSA was recovered. The performance of the recov-
ered catalyst was found to be as good as the same amount
of fresh catalyst. Recovery of PVSA catalyst after five runs
is as follows: filtrate and washings of the reaction mixture
were combined and were passed through an activated cat-
ion exchange resin (such as, Indion 225) column. Distilled
water washings were given till pH was acidic. Collected
fraction was evaporated to dryness in rotary evaporator.
The content of flask was dissolved in appropriate quantity
of water and ethanol and was used in recycle experiments.
8300 spectrophotometer in the range of 400–4000 cm-1
.
1H NMR and 13C NMR spectra were recorded on a Bruker
Avance DRX instrument (300 MHz) using TMS as internal
standard. Viscosity measurements were carried out using
Ubbelohde viscometer. The progress of the reactions was
monitored by TLC on silica gel Polygram SIL/UV 254
plates.
4.1 General Experimental Procedure for Synthesis
of 3,4-Dihydropyrimidin-2(1H)-ones/thiones
4.1.1 Water Process
PVSA (50 % w/w) (0.1 mmol, 21.6 mg) was added to a
mixture of ethyl acetoacetate (3, 1 mmol), aldehyde (2,
1 mmol) and urea or thiourea (4, 1.5 mmol) in water
(5 mL). The reaction mixture was heated at 90 °C in oil
bath with stirring for the lengths of time shown in Table 2.
The progress of the reaction was monitored by TLC (elu-
ent: n-hexane/ethyl acetate; 4/1). After completion of the
reaction, the reaction mixture was cooled to room tem-
perature and the solid residue was filtered and finally
washed with (2 9 10 mL) of cold water to remove any
adhered unreacted reagent. The resulting crude product was
recrystallized from ethanol. The PVSA is soluble in water
and simply is separated from product. All the products,
except 4 m–o, are known compounds and were character-
ized by IR and NMR spectroscopy data and their melting
points, which agreed with reported values.
4.1.4 The Spectral Data for new Compounds
4.1.4.1 4-Ethyl-(naphthalen-2-yl)-6-methyl-2-oxo-1,2,3,
4-tetrahydropyrimidine-5-carboxylate (4 m, entry 13) IR
(KBr): m = 3356 (N–H), 1695 (C = O), 1092 (C–O) cm-1
;
1
MS (EI) m/z 308.05 (M?); H NMR (250 MHz, DMSO-
d6): d = 9.20 (s, 1H, NH), 7.57 (s, 1H, NH), 7.78 (dd, 1H,
J = 8.40 Hz), 7.39 (d, 1H, J = 1.80 Hz), 7.34 (d, 1H,
J = 6.50 Hz), 7.26 (d, 1H, J = 2.20 Hz), 7.20 (d, 1H,
J = 6.50 Hz), 7.10 (d, 1H), 5.25 (d, 1H, J = 2.60 Hz),
2.50 (q, 2H), 2.31 (s, 3H), 1.10 (t, 3H) ppm; 13C NMR
(62.50 MHz, DMSO-d6): d = 164.22, 157.08, 151.56,
148.32, 139.69, 133.56, 129.29, 128.0, 127.21, 125.31,
124.46, 118.70, 105.66, 99.11, 55.06, 54.09, 17.66,
14.12 ppm.
4.1.2 Ethanol Reflux Process
4.1.4.2 4-Ethyl-(6-methoxynaphthalen-2-yl)-6-methyl-
2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (4n, entry
14) IR (KBr): m = 3358 (N–H), 1695 (C = O), 1093
(C–O) cm-1; MS (EI) m/z 338.04 (M?); 1H NMR (250 MHz,
DMSO-d6): d = 9.20 (s, 1H, NH), 7.57 (s, 1H, NH), 7.78
(dd, 1H, J = 8.40 Hz), 7.39 (d, 1H, J = 1.80 Hz), 7.34
(d, 1H, J = 6.50 Hz), 7.26 (d, 1H, J = 2.20 Hz), 7.20
(d, 1H, J = 6.50 Hz), 7.10 (d, 1H), 5.25 (d, 1H,
To a solution of ethyl acetoacetate (3, 1 mmol), aldehyde
(2, 1 mmol) and urea or thiourea (4, 1.5 mmol) in ethanol
(5 mL) was added PVSA (50 % w/w) (0.1 mmol,
21.6 mg). The mixture was heated at reflux in oil bath for
the specified period of time (Table 2). After completion of
the reaction as indicated by TLC (eluent: 1/4 ethyl acetate-
123

Polyvinylsulfonic Acid as Component Synthesizer
1511
23. Kumar KA, Kasthuraiah M, Reddy CS, Reddy CD (2001) Tet-
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24. Yadav JS, Reddy BVS, Srinivas R, Venugopal C, Ramalingam T
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J = 2.60 Hz), 2.50 (q, 2H), 2.31 (s, 3H), 1.10 (t, 3H) ppm;
13C NMR (62.50 MHz, DMSO-d6): d = 164.22, 157.08,
151.56, 148.32, 139.69, 133.56, 129.29, 128.0, 127.21,
125.31, 124.46, 118.70, 105.66, 99.11, 59.10, 55.09, 54.14,
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4.1.4.3 4-Ethyl-(naphthalen-2-yl)-6-methyl-2-thioxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (4o, entry
15) IR (KBr): m = 3297 (N–H), 2985 (C–H), 1735 (C =
O), 1664 (C = C), 1550 (C = S), 1016 (C–O) cm-1; MS
1
(EI) m/z 327.12 (M?); H NMR (250 MHz, DMSO-d6):
d = 10.15 (s, 1H, NH), 9.80 (s, 1H, NH), 7.75 (d, 1H,
J = 8.60 Hz), 7.35 (d, 1H, J = 6.85 Hz), 7.34 (d,
1H, J = 1.80 Hz), 7.26 (d, 1H, J = 2.50 Hz), 7.19 (d, 1H,
J = 2.50 Hz), 7.11 (d, 1H, J = 2.50 Hz), 5.27 (s, 1H),
2.32 (s, 3H), 1.10 (t, 3H) ppm; 13C NMR (62.50 MHz,
DMSO-d6): d = 164.22, 157.08, 151.56, 148.32, 139.69,
133.56, 129.29, 128.0, 127.21, 125.31, 124.46, 118.70,
105.66, 99.11, 55.09, 54.14, 17.82, 14.12 ppm.
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