Vanadatesulfuric acid: A novel, recyclable, and heterogeneous catalyst for the one-pot synthesis of dihydropyrimidinones and dihydropyrimidinthiones under solvent-free conditions

Article abstract of DOI:10.1080/10426507.2012.694001

Vanadatesulfuric acid (VSA), as a novel and heterogeneous catalyst, was used for an efficient synthesis of 3,4-dihydropyrimidin-2(1H)-ones (thiones) using an aldehyde, urea, or thiourea and an acyclic β-dicarbonyl compound under solvent-free conditions. V

Full text of DOI:10.1080/10426507.2012.694001

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Phosphorus, Sulfur, and Silicon and the
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Vanadatesulfuric Acid: A Novel,
Recyclable, and Heterogeneous
Catalyst for the One-Pot Synthesis
of Dihydropyrimidinones and
Dihydropyrimidinthiones Under Solvent-
Free Conditions
Masoud Nasr-Esfahani a & Tooba Abdizadeh a
a Department of Chemistry , Yasouj University , Yasouj , Iran
Accepted author version posted online: 24 May 2012.Published
online: 31 May 2013.
To cite this article: Masoud Nasr-Esfahani & Tooba Abdizadeh (2013): Vanadatesulfuric Acid: A Novel,
Recyclable, and Heterogeneous Catalyst for the One-Pot Synthesis of Dihydropyrimidinones and
Dihydropyrimidinthiones Under Solvent-Free Conditions, Phosphorus, Sulfur, and Silicon and the
Related Elements, 188:5, 596-608
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Phosphorus, Sulfur, and Silicon, 188:596–608, 2013
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2012.694001
VANADATESULFURIC ACID: A NOVEL, RECYCLABLE,
AND HETEROGENEOUS CATALYST FOR THE ONE-POT
SYNTHESIS OF DIHYDROPYRIMIDINONES AND
DIHYDROPYRIMIDINTHIONES UNDER SOLVENT-FREE
CONDITIONS
Masoud Nasr-Esfahani and Tooba Abdizadeh
Department of Chemistry, Yasouj University, Yasouj, Iran
GRAPHICAL ABSTRACT
Abstract Vanadatesulfuric acid (VSA), as a novel and heterogeneous catalyst, was used for
an efficient synthesis of 3,4-dihydropyrimidin-2(1H)-ones (thiones) using an aldehyde, urea, or
thiourea and an acyclic β-dicarbonyl compound under solvent-free conditions. VSA is prepared
via the reaction of sodium metavanadate and chlorosulfonic acid in high purity. The catalyst
was characterized by FTIR, X-ray diffraction (XRD), and transmission electron microscopy
(TEM) analysis. Compared to the classical Biginelli reactions, this method consistently has
the advantage of high yields, simple workup, short reaction times, and reusability of the catalyst.
Received 28 January 2012; accepted 9 May 2012.
We are thankful to Yasouj University for partial support of this work.
Address correspondence to Masoud Nasr-Esfahani, Department of Chemistry, Yasouj University, Yasouj
75918-74831, Iran. E-mail: manas@mail.yu.ac.ir
596

VSA: A NOVEL AND HETEROGENEOUS CATALYST
597
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords Vanadatesulfuric acid; 3,4-dihydropyrimidin-2(1H)-ones (thiones); reusable cata-
lyst; solvent-free; heterogeneous catalyst
INTRODUCTION
Multicomponent condensation reactions (MCRs) are powerful synthetic tools in or-
ganic and medicinal chemistry because of the fact that different products can be synthesized
by varying the substrate in a one-pot procedure.1 In the drug discovery process, multi-
component reaction strategies offer significant advantages over conventional linear-type
syntheses.2 From a synthetic point of view, three or more reactants come together in a
single reaction vessel to form new products that contain portions of all the components.
Therefore, the discovery of new MCRs, or the full exploitation of the already known mul-
ticomponent reactions is of considerable current interest. One such MCR that belongs to
the latter category is the synthesis of dihydropyrimidinone (DHPM) derivatives.
The Biginelli reaction is a well-known, simple, and straightforward acid-catalyzed
procedure for the three-component condensation of β-ketoesters, an aliphatic or aromatic
aldehyde, and an urea leading to the formation of 3,4-dihydropyrimidinones (DHPMs), first
reported by Pietro Biginelli in 1893.3 DHPMs and their derivatives possess a wide range of
pharmacological and therapeutic properties such as calcium channel modulation,4 mitotic
kinesin Eg 5 inhibition,5 antiviral,6 antibacterial and antifungal,7 and anticancer activities.8
Recently, DHPMs have been used as starting material for the synthesis of so-called ‘‘su-
perstation” rosuvastatin selective and competitive inhibitor of 3-hydroxy-3-methylglutaryl-
coenzyme A (HMG-CoA) reductase, the enzyme responsible for the biosynthesis of choles-
terol.9 Several alkaloids, such as batzelladine alkaloids containing the DHPMs core unit,
have been found to be potent human immunodeficiency virus (HIV) (gp-CD4) inhibitors.10a
Moreover, the DHPM motif is present in many products isolated from natural material such
as several species of sponges.10b
In the last few years, many synthetic methods have been developed for preparing
these compounds by using Lewis acids or Brønsted acids promoters as well as microwave11
and ultrasound irradiation12 to improve and modify this reaction.
To replace the strong protic acid used in the classic Biginelli reaction, triflates,13
aluminum hydrogen sulfate (Al(HSO4)3),14 silicasulfuric acid,15 p-toluenesulfonic acid (p-
TSA),16 L-prolines,17 Nafion-50,18 propanephosphoric acid,19 p-dodecylbenzenesulfonic
acid (DBSA),20 polystyrenepoly(ethylene glycol) sulfuric acid (PS–PEG–SO3H),21
imidazol-1-yl-acetic acid,22 N,Nꢁ-dichlorobis(2,4,6-trichlorophenyl)urea,23 p-sulfonic acid
calixarenes,24 and ytterbium perfluorooctanoate (Yb(PFO)3)25 have been used.
However, many of the existing methods suffer from the use of expensive catalysts,
longer reaction time, tedious workup, and low yields.26 Therefore, the search for improved
catalysts that are recyclable and capable of performing the reaction under mild conditions
have gained particular attention.
Solid acids have emerged as potential alternate catalysts to the common liquid acids
due to their safe nature, enhanced selectivity, requirements in catalytic amounts, and easier
work-up.27 The ease of separation without resulting into problem of waste disposal and
option of reuse of the solid acid catalysts render the processes employing solid acid catalysts
as green processes.

598
M. NASR-ESFAHANI AND T. ABDIZADEH
In continuation of the above and of our studies on the application of solid acids,28
we found that anhydrous sodium metavanadate reacts with chlorosulfonic acid (1:1 mole
ratio) to give vanadatesulfuric acid (VSA). The reaction is performed easily and cleanly
and the product, VSA, was isolated by dilution of the mixture with water and then simple
filtration (Scheme 1).
O
O
O
O
V OSO3H
V ONa
+
ClSO3H
+
NaCl
Scheme 1
RESULTS AND DISCUSSION
In connection with our recent interest in the synthesis of 3,4-dihydropyrimidin-
2(1H)-ones (thiones),29,30 herein, we wish to report a simple and efficient method for such
a reaction by using VSA as a new, green, recyclable, and heterogeneous catalyst under
solvent-free conditions (Scheme 2).
R1
O
O
O
X
H
R2
Me
N
O2VOSO3H
R1CHO
R2
Me
+
+
H2N
NH2
solvent-free
80 oC
X
N
H
X= O, S
Scheme 2
Characterization of VSA
In the infrared (IR) spectrum of NaVO3, several absorptions appear, which are ap-
parently the result of V–O stretching modes for each of several, different oxygen atoms
according to the particular location or arrangement within the lattice.31 At lower frequency,
a broad and general absorption occurs, which is apparently caused by lower frequency
V–O bonding. Here, the V–O stretching mode is observed as a medium band located at
950 cm−1. These two spectra tend to locate the ‘‘normal” position for this stretching vi-
bration between oxygen and vanadium. Other broad bands are present in the spectrum of
sodium metavanadate, centering at 845 and 690 cm−1. The VO3− structure consists of V–O
bonding of variable bond lengths, some of which vibrate at lower frequencies than others.
The 950 cm−1 band has been assigned to a V–O bond, which is considerably shorter than
other bonds in the structure; the 845 cm−1 band very probably arises from the stretching
modes of the longer V–O bonds (Figure 1).
For VSA, the IR vibration bands are consigned as follows: the bands found at 3450 and
1640 cm−1 are attributed to the stretching and bending vibration of –OH group, respectively.
The bands at 1050 and 1180 cm−1 are assigned for the sulfonic acid bonds, S–OH, S = O

VSA: A NOVEL AND HETEROGENEOUS CATALYST
599
Figure 1 FTIR spectra of (a) sodium metavanadate; (b) vanadatesulfuric acid.
stretching, and S = O asymmetric stretching, respectively. The bands appearance in 960,
840, and 603 cm−1 related to V = O and V–O stretching (Figure 1).
The crystalline structure of the VSA was determined by powder X-ray diffraction
(XRD) (Figure 2). A number of prominent Bragg reflections reveal that the resultant
particles of VSA have a monoclinic structure (space group: P2/m; a = 12.170 Å, b =
3.602 Å, c = 7.780 Å, JCPDS card no. 16–0601). The size of the VSA particles was also
determined from X-ray line broadening using the Debye–Scherrer formula (D = kλ/βcosθ,
where k is Scherrer constant, λ the X-ray wavelength, β the peak width of half-maximum,
and θ is the Bragg diffraction angle). For the (0 0 1) reflection the average size of the VSA
particles was estimated to be around 16 nm.
The morphology and size of VSA were investigated by transmission electron mi-
croscopy (TEM) (Figure 3). They had needle-like morphology with a narrow size distribu-
tion from 15 to 20 nm and a mean size of 17 nm. The presence of some larger particles
should be attributed to aggregating or overlapping of smaller particles. In addition, elemen-
tal analysis of catalyst was performed by means of X-ray fluorescence analysis (XRF) such
that the obtained result confirmed the elemental composition of VSA.
Effect of Solvent and Catalyst Concentration on the Synthesis
of 3,4-Dihydropyrimidin-2(1H)-ones
Initially, in order to evaluate the catalytic activity of VSA, the three-component
reaction of benzaldehyde, urea, and ethyl acetoacetate under solvent-free condition as a
model reaction was investigated. The corresponding product was obtained in 92% yield

600
M. NASR-ESFAHANI AND T. ABDIZADEH
Figure 2 Powder X-ray diffraction pattern of the VSA particles.
during 30 min. This compound has been synthesized under various conditions by other
researchers, some of which are presented in Table 1 that have comparable or lower yield/time
ratios in comparison to current conditions.
Then, the solvent effect in the condensation of benzaldehyde (1 mmol), urea
(1.5 mmol), and ethyl acetoacetate (1mmol) in the presence of VSA (0.15 mmol) as a
Table 1 Comparison of efficiency of various catalysts in synthesis of 5-(ethoxycarbonyl)-6-methyl-4-phenyl-
3,4-dihydropyrimidin-2(1H)-ones
Entry
Catalyst
Sr(OTf)2
[Al(H2O)6](BF4)3
Zr(H2PO4)2
LiBr
SbCl3
Cu(OTf)2
SiO2-KAl(SO4)2
CaF2
Chloroacetic acid
NH4Cl
Amount of catalysta
Conditions
Yield/timeb
Ref.
1
2
3
4
5
6
7
8
5
10
7
10
100
1
25
10
10
40
10
0.99
10
15
Solvent-free/70 ◦C
CH3CN (reflux)
Solvent-free/90 ◦C
CH3CN (reflux)
CH3CN (reflux)
CH3CN/25 ◦C
Solvent-free/80 ◦C
C2H5OH/(reflux)
Solvent-free/90 ◦C
Solvent-free/100 ◦C
Solvent-free/100 ◦C
Dioxane/2-propanol (reflux)
Solvent-free/100 ◦C
Solvent free/80 ◦C
97/4
81/20
88/1
92/3
90/18
95/6
92/4
98/2
92/3
90/3
32
33
34
35
36
13
14
37
38
39
40
21
41
–
9
10
11
12
13
14
Triphenylphosphine
PS–PEG–SO3Hc
TiCl4–MgCl2
VSA
70/10
80/10
90/3
94/0.5
aAmount of catalysts are in mol%.
bValues refer to yield (%)/time (h).
c0.3 g (0.99 mmol –SO3H) of the catalyst vs. 1 mmol aldehyde.

VSA: A NOVEL AND HETEROGENEOUS CATALYST
601
Figure 3 The TEM image showing needle-like VSA particles of 15–20 nm in size.
Table 2 Solvent effect on the reaction of benzaldehyde, urea, and ethyl acetoacetate catalyzed by VSA
Entry
Solvent (reflux)
Time (h)
Yielda (%)
1
2
3
4
5
6
CH3CH2OH
CH3OH
CH3CN
H2O
CH3Cl
Solvent-freeb
20
20
20
20
20
0.5
73
70
62
65
55
94
aIsolated yields.
bAt 80 ◦C.

602
M. NASR-ESFAHANI AND T. ABDIZADEH
Table 3 The influence of the amount of catalyst and heat on the synthesis of 5-(ethoxycarbonyl)-6-methyl-4-
phenyl-3,4-dihydropyrimidin-2(1H)-ones
Entry
VSA (mol%)
Temperature (◦C)
Time (min)
Yielda (%)
1
2
3
4
5
6
7
8
None
5
80
80
80
80
80
80
80
25
40
60
80
100
24 h
60
50
42
30
35
37
60
55
45
30
20
Trace
85
87
90
94
94
92
75
80
7.5
10
15
20
25
15
15
15
15
15
9
10
11
12
85
94
93
aIsolated yields.
model reaction has been studied. As shown in Table 2, among the tested solvents, such
as ethanol (EtOH), methanol (MeOH), acetonitrile, water, chloroform, and a solvent-free
system, the best result was obtained after 30 min under solvent-free conditions in excellent
yield (94%).
The reaction condition was then optimized by conducting the reaction in different
temperature and employing different catalyst loading. The best result was obtained by
◦
carrying out the reaction with 15 mol% of catalyst under solvent-free condition at 80 C
(Table 3, entry 5).
In the absence of VSA, according to thin layer chromatography (TLC) monitoring,
◦
the model reaction gives only trace of the product after 24 h at 80 C under solvent-free
condition (Table 3, entry 1). The conversion and yield of the corresponding DHPM increased
with incremental increase in the catalyst concentration from 5 to 25 mol%. Further addition
of catalyst had no noticeable effect on the yield. This was due to the fact that beyond a
certain concentration, there exist excess of catalyst sites over what are actually required by
the reactant molecules, and hence, the additional catalyst does not increase the rate of the
reaction. Therefore, in all further reactions 15 mol% of the catalyst were used because of
satisfactory yield of the product (94%) in reasonably short time.
In other to improve the yields, the reaction is performed using different quantites
of reagents. The best results were obtained with a 1:1:1.5 ratio of benzaldehyde, ethyl
acetoacetate, and urea, respectively.
To generalize this procedure, a series of Biginelli compounds were synthesized with
benzaldehyde derivatives and the results are shown in Table 4. The reaction worked well
with electron withdrawing (NO2, Br, Cl, etc.) as well as electron donating (Me, OMe, etc.)
substituents giving various DHPMs in 80–95% yields. Moreover, acid sensitive aldehydes
such as furyl (entry 10), thienyl carbaldehyde (entry 11), and cinammaldehyde (entry 14)
furnished products in yield of 83%, 80%, and 81%, respectively.
The activity of the recycled VSA was also examined according to the typical ex-
perimental condition. After completion of the reaction of benzaldehyde, urea, and ethyl
acetoacetate, the catalyst was recovered from the reaction mixture. The recovered catalyst

VSA: A NOVEL AND HETEROGENEOUS CATALYST
603
Table 4 Preparation of substituted DHPMs catalyzed by VSA under solvent-free conditions
mp (◦C)
Entry
R1
X
R2
Time (min)
Yieldb (%)
Founda
Reported
1
2
3
4
5
6
7
8
C6H5
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
S
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OMe
OMe
OMe
OMe
OMe
Me
30
35
30
30
35
45
35
40
45
50
55
75
45
70
15
45
30
35
55
40
45
35
45
45
50
30
35
40
45
35
40
40
50
40
45
50
94
93
91
88
95
85
90
94
91
83
80
75
92
81
92
89
90
90
85
87
90
87
93
85
90
93
85
88
90
95
93
91
87
90
90
86
203–205
207–209
213–215
201–202
212–214
252–254
249–251
227–229
213–215
207–209
214–216
177–179
216–218
228–230
230–232
229–231
236–238
191–193
285–287
193–195
232–234
254–256
232–234
250–253
171–169
205–207
197–199
147–149
187–189
207–209
205–206
223–225
151–153
223–225
186–188
219–221
202–20326
207–21042
215–21643
210–20226
215–21644
255–25750
248–25044
229–23143
210–21245
208–21044
215–21744
180–18244
215–21651
227–23044
231–23320
–
4-O2N-C6H4
4-CH3-C6H4
4-CH3O-C6H4
4-Cl-C6H4
2-CH3O-C6H4
2,4-Cl-C6H3
3-O2N-C6H2
2-O2N-C6H2
2-Furyl
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
2-Thienyl
CH3CH2CH2
2-Cl-C6H4
C6H5CH = CH
4-BrC6H4
2-HO-5-O2NC6H3
2,4-(CH3)2C6H3
C6H5
2-CH3OC6H4
4-CH3OC6H4
4-O2NC6H4
2,4-(CH3)2C6H3
C6H5
4-CH3C6H4
4-CH3OC6H4
C6H5
4-HOC6H4
4-CH3OC6H4
4-CH3C6H4
4-ClC6H4
–
191–19342
283–28546
194–19644
236–23854
–
234–23540
256–25752
168–17040
208–21043
202–20353
150–15243
192–19444
208–21032
206–20732
221–22244
149–15055
–
Me
Me
OEt
OEt
OEt
OEt
OEt
OEt
OMe
OMe
OMe
OMe
OMe
S
S
S
S
S
S
S
S
3-O2NC6H4
C6H5
4-CH3OC6H4
2-O2NC6H4
2-BrC6H4
S
S
–
–
3-CH3O-4-ClC6H3
aAll products were characterized by 1H NMR and IR spectroscopy and comparison with these reported in the
literature.
bIsolated yields.
was then added to fresh substrates under the same experimental conditions for four runs
without a noticeable decrease in the product yield and its catalytic activity.
As shown in Scheme 3, three possible mechanisms are proposed for Biginelli reaction
according to the literature, but generally accepted reaction mechanism includes the acid-
catalyzed formation of C–N bond from the benzaldehyde and urea (pathway B).49 According
to reported results, the pathway B is characteristic for the Brønsted type of catalysts, whereas
Lewis acid type of catalysts follow the pathway C (ureido-crotonate mechanism).36 To
clarify the role of VSA, three separated reactions were conducted (pathways A–C) under

604
M. NASR-ESFAHANI AND T. ABDIZADEH
the optimized reaction condition (15 mol% of VSA at 80 ◦C in solvent-free condition and
reflux temperature in acetonitrile during 30 min and 20 h, respectively). The prolonged
heating of benzaldehyde and ethyl acetoacetate (pathway A) or ethyl acetoacetate and urea
(pathway C) did not undergo the expected reactions to yield products, whereas the reaction
of benzaldehyde and urea furnished the arylidene–urea (pathway B). These observations
clearly indicate that Biginelli reaction catalyzed by VSA proceeds predominately through
arylidene–urea intermediate (pathway B), which supports the prediction that Biginelli
reaction is catalyzed by Brønsted type catalysis.
CHO
OHC
+
A
B
EtO2C
+
O
N
O
O
CO2Et
H2N
NH2
H2N
H3C
O
O
H3C
O
CO2Et
H3C
H2N
NH2
O
Ph
H
EtO
Me
N
O
N
H
CHO
O
H2N
EtO
H3C
O
N
H
C
O
O
CO2Et
+
H2N
NH2
H3C
Scheme 3
CONCLUSIONS
We have found an efficient, nonhygroscopic, and inexpensive catalyst, and a straight-
forward procedure for one-pot synthesis of DHPMs (thiones) using VSA as a catalyst.
Also, it was found that the performance of the catalytic system is greatly improved when

VSA: A NOVEL AND HETEROGENEOUS CATALYST
605
used without solvents, which is important from the viewpoint of green chemistry. The at-
tractive features of this simple protocol are short reaction time, high yields, simple workup,
reusability of the catalyst, and simple purification of the products.
EXPERIMENTAL
Chemicals were purchased from Merck, Fluka, and Aldrich chemical companies.
TEM was studied using a Philips, CM-10 TEM instrument operated at 100 kV. Melting
points (mp) were determined using a Barnstead Electrothermal (BI 9300) apparatus and
are uncorrected. The IR spectra were obtained using a FTIR JASCO-680 spectrometer
instrument. The NMR spectra were taken with a Bruker 400 MHz Ultrashield spectrometer
at 400 MHz (1H) and 125 MHz (13C) using deuterated dimethyl sulfoxide (DMSO-d6) as
1
the solvent with tetramethylsilane (TMS) as the internal standard. Sample H and 13C
NMR spectra for 5-methoxycarbonyl-4-(2-nitrophenyl)-6-methyl-3,4-dihydropyrimidin-
2(1H)-thione are given in Figures S1 and S2 (available online in Supplemental Materials).
Preparation of VSA
Anhydrous sodium metavanadate was prepared by drying of sodium metavanadate
monohydrate (NaVO3·H2O, MW = 139.94) in the oven at 200 ◦C for 4 h. To chlorosulfonic
acid (0.1 mol, 11.6 g, 7.7 mL) in 250 mL round bottom flask in an ice-bath, anhydrous
sodium metavanadate (0.1 mol, 12.2 g) was added gradually with stirring. After the com-
pletion of addition of anhydrous sodium metavanadate, the reaction mixture was shaken
for 1 h. Then cold water (50 mL) was added to the reaction mixture and stirred fo◦r 10 min.
The mixture was filtered and a dark red solid of VSA, 16.3 g (91%), mp 256 C (dec.)
was obtained. Characteristic IR bands (KBr, cm−1): 3540–3300 (OH, bs), 1640 (OH, m),
1250–1140 (S = O, bs), 1050 (S–O, m), 960 (V = O, m), 840 (V = O, m), 630 (V–O, m).
General Procedure for Preparation of DHPMs
A mixture of aldehyde (1 mmol), β-dicarbonyl (1 mmol), urea or thiourea (1.5 mmol),
◦
and VSA (0.15 mmol) was heated at 80 C under stirring for an appropriate time. The
progress of the reaction was monitored by TLC using ethyl acetate:n-hexane (1:3) as
eluent. After completion of the reaction, the crude product from the reaction mixture was
dissolved in hot EtOH and the catalyst was separated by filtration and was poured into cold
water and the solid was collected and washed with water and recrystallized from EtOH to
give pure product in 75–95% yields (Table 4). The physical and spectroscopic data of the
novel compounds is given below:
5-Ethoxycarbonyl-4-(2-hydroxy-5-nitrophenyl)-6-methyl-3,4-dihydropy-
rimidin-2(1H)-one (Table 4, entry 16). Mp: 229–231 ◦C; Rf = 0.49 (n-hexane:ethyl
acetate = 3:1); IR (KBr): 3402, 3237, 3115, 2988, 1727, 1694, 1642, 1523, 1489,1434,
1
1336, 1226, 1160, 837, 787, 638 cm−1; H NMR (400 MHz, DMSO-d6) δ (ppm): 1.02
(t, J = 6.8 Hz, 3H), 2.26 (s, 3H), 3.91 (q, J = 6.8 Hz, 2H), 5.45 (s, 1H),6.95 (d, J =
8.8 Hz, 1H), 7.44 (s, 1H), 7.86 (d, J = 2.4 Hz, 1H), 8.03 (dd, J = 6.4, J = 2.4 Hz, 1H),
9.25(s, 1H), 11.37 (s, 1H); 13C NMR (125 MHz, DMSO-d6) δ (ppm): 14.3, 18.2, 50.4,
59.6, 97.1, 116.4, 124.4, 125.4, 131.5, 139.6, 149.7, 152.3, 162.1, 165.6; Anal. calcd. for
C14H15N3O6: C, 52.34; H, 4.71; N, 13.08; O, 29.88; found: C 52.40, H 4.78, N 13.02.

606
M. NASR-ESFAHANI AND T. ABDIZADEH
5-Ethoxycarbonyl-4-(2,4-dimethylphenyl)-6-methyl-3,4-dihydropyrimidin-
2(1H)-one (Table 4, entry 17). Mp: 236–238 ◦C; Rf = 0.48 (n-hexane:ethyl acetate =
3:1); IR (KBr): 3367, 3218, 3104, 2966, 1697, 1644, 1498, 1455, 1320, 1222, 1092, 812,
657, 544 cm−1; 1H NMR (400 MHz, DMSO-d6) δ (ppm): 1.10 (t, J = 6.4 Hz, 3H), 2.30
(s, 3H), 2.45 (s, 6H), 4.02 (q, J = 6.4 Hz, 2H), 5.66 (s, 1H), 6.97–7.00 (m, 2H), 7.15 (d, J
= 6.8 Hz, 1H), 7.68 (s, 1H), 9.09 (s, 1H); 13C NMR (125 MHz, DMSO-d6) δ (ppm): 13.9,
17.6, 18.5, 20.5, 50.1, 59.0, 99.3, 126.5, 127.0, 130.6, 134.4, 136.1, 140.3, 148.2, 151.6,
165.2; Anal. calcd. for C16H20N2O3: C, 66.65; H, 6.99; N, 9.72; O, 16.65; found: C 66.70,
H 7.05, N 9.76.
5-Methoxycarbonyl-4-(2,4-dimethylphenyl)-6-methyl-3,4-dihydropyrimi
din-2(1H)-one (Table 4, entry 22). Mp: 254–256 ◦C; Rf = 0.46 (n-hexane:ethyl
acetate = 3:1); IR (KBr): 3370, 3216, 3100, 2947, 1698, 1644, 1498, 1455, 1321, 1223,
1095, 812, 662 cm−1; 1H NMR (400 MHz, DMSO-d6) δ (ppm): 2.20 (s, 3H), 2.72 (s, 3H),
2.35 (s, 3H), 3.34 (s, 3H), 5.34 (s, 1H), 6.91–6.94 (m, 2H), 7.04 (d, J = 8.0 Hz, 1H), 7.59
(s, 1H), 9.16 (s, 1H); 13C NMR (125 MHz, DMSO-d6) δ (ppm): 18.2, 19.0, 21.0, 50.6,
51.2, 99.7, 126.9, 127.5, 131.3, 134.9, 136.7, 140.8, 148.8, 152.2, 166.2; Anal. calcd. for
C15H18N2O3: C, 65.68; H, 6.61; N, 10.21; O, 17.50; found: C 65.71, H 6.67, N 10.26.
5-Methoxycarbonyl-4-(2-nitrophenyl)-6-methyl-3,4-dihydropyrimidin-
2(1H)-thione (Table 4, entry 34). Mp: 223–225 ◦C; Rf = 0.46 (n-hexane:ethyl acetate
= 3:1) ; IR (KBr): 3329, 3216, 3103, 2965, 1707, 1629, 1525, 1455, 1223, 1087, 704 cm−1
;
1H NMR (400 MHz, DMSO-d6) δ (ppm) : 2.28 (s, 3H), 3.33 (s, 3H), 5.89 (s, 1H),
7.50–7.89 (m, 4H), 9.70 (s, 1H), 10.50 (s, 1H); 13C NMR (125 MHz, DMSO-d6) δ (ppm)
: 17.6, 49.6, 51.5, 100.3, 124.6, 129.6, 129.8, 134.6, 138.5, 146.3, 147.8, 165.5, 174.8;
Anal. calcd. for C13H13N3O4S: C, 50.81; H, 4.26; N, 13.67; O, 20.82; S, 10.43; found: C
50.88, H 4.32, N 13.70.
5-Methoxycarbonyl-4(2-boromophenyl)-6-methyl-3,4-dihydropyrimidin-
2(1H)-thione (Table 4, entry 35). Mp: 186–187 ◦C; Rf = 0.56 (n-hexane:ethyl acetate
= 3:1); IR (KBr): 3345, 3227, 3112, 2977, 1695, 1640, 1566, 1456, 1371, 1227, 1096,
1
746 cm−1; H NMR (400 MHz, DMSO-d6) δ (ppm) : 2.31 (s, 3H), 3.33 (s, 3H), 5.59 (s,
1H), 7.20–7.57 (m, 4H), 9.63 (s, 1H), 10.41 (s, 1H); 13C NMR (125 MHz, DMSO-d6) δ
(ppm) : 22.3, 56.2, 59.2, 105.2, 127.4, 133.8, 134.5, 135.0, 138.0, 147.6, 150.9, 170.5,
179.1; Anal. calcd. for C13H13BrN2O2S: C, 45.76; H, 3.84; Br, 23.42; N, 8.21; O, 9.38; S,
9.40; found: C 45.82, H 3.90, N 8.18.
5-Methoxycarbonyl-4-(3-methoxy-4-chlorophenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-thione (Table 4, entry 36). Mp: 219–221 ◦C; Rf
=
0.50 (n-hexane:ethyl acetate = 3:1); IR (KBr): 3349, 3235, 3122, 2983, 1698, 1636, 1520,
1454, 1230, 1089, 890, 743 cm−1; 1H NMR (400 MHz, DMSO-d6) δ (ppm): 1.48 (s, 3H),
3.67 (s, 3H), 3.71 (s, 3H), 4.54 (s, 1H),6.70–7.10 (m, 3H), 9.08–9.21 (s, 2H); 13C NMR
(125 MHz, DMSO-d6) δ (ppm): 23.8, 42.5, 48.5, 52.5, 55.8, 81.7, 112.4, 120.5, 121.3,
124.7, 140.1, 148.3, 168.8, 176.9; Anal. calcd. for C14H15ClN2O3S: C, 51.45; H, 4.63; Cl,
10.85; N, 8.57; O, 14.69; S, 9.81; found: C 51.40, H 4.70, N 8.52.
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