Green Synthesis and Structural Characterization of C6-Phenyl Substituted 3,4-Dihydropyrimidinones

Full text of DOI:10.1080/00304948.2020.1794222

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/uopp20
Green Synthesis and Structural Characterization of
C6-Phenyl Substituted 3,4-Dihydropyrimidinones
Min Wang , Xiaoyu Jiang , Chunyan Cao , Shuang Zhao & Xin Wan
To cite this article: Min Wang , Xiaoyu Jiang , Chunyan Cao , Shuang Zhao & Xin
Wan (2020): Green Synthesis and Structural Characterization of C6-Phenyl Substituted
3,4-Dihydropyrimidinones, Organic Preparations and Procedures International, DOI:
10.1080/00304948.2020.1794222
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Published online: 05 Sep 2020.
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ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
https://doi.org/10.1080/00304948.2020.1794222
EXPERIMENTAL PAPER
Green Synthesis and Structural Characterization of
C6-Phenyl Substituted 3,4-Dihydropyrimidinones
Min Wang, Xiaoyu Jiang, Chunyan Cao, Shuang Zhao, and Xin Wan
College of Chemistry and Chemical Engineering, Bohai University, Jinzhou, P. R. China
ARTICLE HISTORY Received 26 February 2020; Accepted 5 May 2020
Dihydropyrimidinones and their derivatives (DHPMs) possess extensive and important
biological and pharmacological activities such as antiviral, antibacterial, anticancer and
antitumor properties.1–3 Multifunctionalized DHPMs can be used as calcium channel
blockers and a1a-antagonists,4 antioxidants5 and antituberculosis drugs.6 The classical
synthesis method is the Biginelli reaction, which involves the one-pot three-component
condensation of an aromatic aldehyde, ethyl acetoacetate and urea catalyzed by HCl.7
With the continuing study on DHPMs, researchers focused their attention on the selec-
tion of catalysts, the optimization of reaction conditions, and the scope of starting mate-
rials. Therefore, synthetic routes and the diversity of product structures have been
improved. In the meantime, many novel multifunctional DHPMs have been
obtained.8–13
In recent years, we carried out research on the Biginelli reaction to prepare novel
products and develop green synthetic methods. Various derivatives such as C6-methyl
substituted 3,4-dihydropyrimidinones14 and N1-alkyl/aryl substituted 3,4-dihydropyrimi-
dinones14,15 were synthesized using metal organic sulfonates as catalysts. We found that
metal organic sulfonates possess high catalytic activity, good water-resistance, and recyc-
lability. They showed good catalytic effect on esterifications,16 tetrahydropyran forma-
tion,17 Mannich reactions,18 cyclocondensations19 and diacetylations.20
A b-dicarbonyl compound is one of the three components of the Biginelli reaction.
Acetoacetates are commonly used, giving a methyl group at the C6 position of 3,4-dihy-
dropyrimidinones. Recently, a few papers reported that acetoacetates can be replaced
with benzoylacetates in this reaction.21–28 However, only a few products were synthe-
sized. As a further study, we carried out the one-pot three-component reaction of an
aromatic aldehyde, ethyl benzoylacetate, and a urea derivative (e.g. urea, thiourea, N-
methylurea, or N-methyl thiourea) in the presence of cerium(III) p-toluenesulfonate
tetrahydrate (Ce(p-CH3C6H4SO3)3ꢀ4H2O, abbreviated as CePTS) under solvent-free con-
ditions (Scheme 1).
In order to screen the optimal conditions, we investigated catalysts, reaction tempera-
ture, and the molar ratio of starting materials. At first, nine metal p-toluenesulfonates
(0.3 mmol) were evaluated using the model reaction of benzaldehyde (10 mmol), ethyl
benzoylacetate (10 mmol) and methylurea (10 mmol) at 80 ꢁC. As shown in Table 1,
CONTACT Min Wang
minwangszg@hotmail.com
College of Chemistry and Chemical Engineering, Bohai University,
Jinzhou, P. R. China.
ß 2020 Taylor & Francis Group, LLC

2
M. WANG ET AL.
R
X
O
O
O
CHO
CePTS
80 oC
solvent-free
R
HN NH2
R1
+
+
Ph
OEt
EtO
Ph
NH
X
N
R1
1
4 (a-t)
2
3
X = O, S
R1 = H, CH3
Scheme 1. Three-component synthesis of C6-phenyl substituted 3,4-dihydropyrimidinones.
Table 1. Comparison of catalytic effects for different metal p-toluenesulfonates.
Entry
Catalyst
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
Ce(p-CH3C6H4SO3)3ꢀ4H2O
Nd(p-CH3C6H4SO3)3ꢀ2H2O
Al(p-CH3C6H4SO3)3ꢀ5H2O
Cu(p-CH3C6H4SO3)2ꢀ6H2O
La(p-CH3C6H4SO3)3ꢀ2H2O
Zn(p-CH3C6H4SO3)2ꢀ5H2O
Ca(p-CH3C6H4SO3)2
Co(p-CH3C6H4SO3)2ꢀ4H2O
Mg(p-CH3C6H4SO3)2ꢀ6H2O
None
0.7
0.8
1.2
1.5
1.5
2.0
2.0
2.0
2.5
6.0
91
87
84
66
61
60
55
50
44
12
9
10
CePTS possesses the best catalytic activity. It afforded the desired product in 91% yield
within 0.7 h (Entry 1, Table 1). In the absence of catalyst, a poor yield of product was
obtained, even after a prolonged reaction time (Entry 10, Table 1).
The effect of the molar ratio of the starting materials on the reaction results was also
examined in Table 2. We found that product yields improved slightly as the amount of
methylurea increased. However, we determined that the optimal molar ratio of aromatic
aldehyde, ethyl benzoylacetate and methyl urea was 1.0:1.0:1.0 (Entry 1, Table 2) in
order to minimize both the cost of reagents and the amount of waste generated.
Finally, the effect of the catalyst loading and the reaction temperature were investi-
gated (Table 3). The results showed the preferable conditions were 3 mol% catalyst and
80 ˚C (Entry 3, Table 3). The recyclability of CePTS was also studied (Entry 3, Table 3).
When the reaction was complete, the crude product was washed with cold water. The
catalyst remained in the aqueous phase and could be recovered by evaporating the fil-
trate. We found that after the catalyst was used three times, the yield of the product
decreased slightly.
A series of C6-phenyl substituted 3,4-dihydropyrimidinones were synthesized using
the optimized conditions described above (Table 4). In order to further explore the
scope of this reaction, the uses of urea, thiourea, N-methylurea, and N-methylthiourea
were investigated, and all proved to be effective in this transformation. All of the corre-
sponding target products were obtained within short reaction times, which demon-
strated that CePTS has good catalytic effect and a wide scope across different substrates.
In order to confirm the identity of the products and examine the orientation of
groups in space, a crystal structure of compound 4i was obtained (Figure 1).

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
3
Table 2. The effect of starting material ratios on product yields.a
Entry
n
n
: n
methyl urea
Time (h)
Yield (%)
aromatic aldehyde :
ethyl benzoylacetate
1
2
3
4
1.0 : 1.0 : 1.0
1.0 : 1.0 : 1.1
1.0 : 1.0 : 1.2
1.0 : 1.0 : 1.3
0.7
0.7
0.8
0.9
91
92
92
93
aReaction conditions: benzaldehyde (10 mmol), ethyl benzoylacetate (10 mmol), CePTS (0.3 mmol), solvent-free, 80 ꢁC.
Table 3. The effect of catalyst loading and reaction temperature on product yields.a
Entry
Catalyst (mmol)
Temperature (oC)
Time (h)
Yield (%)
1
2
3
4
5
6
7
0.1
0.2
0.3
0.4
0.3
0.3
0.3
80
80
80
80
60
70
90
3.0
1.0
0.7
0.6
1.1
1.0
0.7
87
90
91, 87, 82b
89
84
86
88
aReaction conditions: benzaldehyde (10 mmol), ethyl benzoylacetate (10 mmol), methylurea (10 mmol).
bCePTS was reused three times, successively.
Table 4. The synthesis of C6-phenyl substituted 3,4-dihydropyrimidinones.a
Mp (˚C)
Yield (%)
Product
R
R1
X
(Time (h))
Found
Reported
17129
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
H
2-Cl
4-Cl
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
O
O
O
O
O
O
O
O
O
O
S
S
S
S
S
S
S
S
O
O
91 (0.7)
74 (0.8)
93 (0.3)
79 (0.7)
92 (0.3)
91 (1.2)
94 (1.0)
93 (1.0)
87 (0.9)
95 (1.7)
87 (1.5)
94 (0.6)
84 (0.5)
90 (0.6)
91 (2.3)
92 (2.6)
92 (1.0)
90 (1.0)
61 (2.7)
64 (3.0)
175-177
144-146
200-202
145-147
222-224
179-181
169-171
182-184
194-196
139-141
118-120
162-164
191-193
179-181
192-193
184-186
167-169
177-179
158-160
230-232
–
203-20523
2,4-Cl2
4-CH3
2-CH3O
4-CH3O
3-NO2
4-NO2
3-OH
H
–
223-22523
–
–
–
190-19223
–
–
–
–
4-Cl
4-NO2
3-OH
H
–
19230
185-18825
171-17425
177-18025
157-15927
233-23528
4-Cl
H
H
H
H
4-CH3O
4-CH3
H
4s
4t
3-NO2
H
aReaction conditions: aromatic aldehyde (10 mmol), ethyl benzoylacetate (10 mmol), urea (10 mmol), CePTS
(0.3 mmol), 80 ꢁC.
A possible mechanism for the reaction is shown in Scheme 2.31 First, the aldehyde
reacts with a (thio)urea to form an acylimine intermediate. Addition of the b-ketoester
to the acylimine forms an open-chain urea derivative, which then undergoes cyclization
and dehydration to form the target product.
In summary, numerous C6-phenyl substituted 3,4-dihydropyrimidinones were synthe-
sized by a three-component condensation of equimolar amounts of an aromatic alde-
hyde, ethyl benzoylacetate, and a urea using CePTS as a catalyst at 80 ꢁC. Advantages of
the method include: operational simplicity, mild reaction conditions, formation of
diverse product structures, and green chemistry. Finally, the CePTS exhibits high

4
M. WANG ET AL.
Figure 1. X-ray molecular structure of compound 4i, showing thermal displacement ellipsoids at the
50% probability level. Hydrogen atoms have been omitted for clarity.
R
Ce3+
X
CHO
-H2O
O
O
H
+
+
R
HN NH2
R1
H
Ph
OEt
N
N
R1
Ce3+
X
X = O, S
R
R
O
-H2O
O
EtO
Ph
NH
EtO
Ph
NH
N
X
O
X
HN
R1
R1
4
Scheme 2. Proposed mechanism for the 3-component coupling reaction.
catalytic activity, reusability, and wide substrate scope, furnishing several novel 3,4-
dihydropyrimidinones.
Experimental section
Melting points were determined using an RD-II micromelting point apparatus (Tianjin
Tianguang Optical Instrument Limited Company, China). Infrared spectra were
recorded on a Varian Scimitar 2000 infrared spectrometer (Agilent Technologies Inc.,
1
USA) using potassium bromide pellets. H and 13C NMR spectra were recorded on an
Agilent 400-NMR spectrometer (Agilent Technologies Inc., USA) in DMSO-d6 using
TMS as an internal standard (d 0.00 ppm). Elemental analyses (C, H, N) were carried
out using a Perkin Elmer Elemental Analyser EA 2400II. Crystallographic data for

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
5
compound 4i were collected using a Bruker Smart Apex II diffractometer (Bruker
Corporation, Germany) with Mo Ka radiation (k ¼ 0.71069 Å) at 296 K using the
x-scan technique. The diffraction data were integrated by using the SAINT program,
which was also used for the intensity corrections for the Lorentz and polarization
effects. Semi-empirical absorption corrections were applied using the SADABS program.
Structures were solved by direct methods, and all of the non-hydrogen atoms were
refined anisotropically on F2 by the full-matrix least-squares technique using the
SHELXTL crystallographic software package. Thin layer chromatography was performed
on Merck Silica gel 60 F254 plates using a mixture of ethyl acetate/petroleum ether (v/v
¼ 3:7) as the mobile phase. Metal p-toluenesulfonates were synthesized according to a
reported literature procedure.32 All other reagents were commercially available
(Shanghai Chemical Reagent Company, China) and were used without further
purification.
Preparation of C6-phenyl substituted 3,4-dihydropyrimidinones (4)
A mixture of aromatic aldehyde (10 mmol), ethyl benzoylacetate (10 mmol), urea
(10 mmol) and CePTS (0.3 mmol) was stirred at 80 ꢁC on an oil bath until the reaction
was determined to be complete by TLC. The reaction mixture was cooled to room tem-
perature, and ice water was added. The crude products were obtained by filtration and
drying and were purified by recrystallization from hot ethanol. All of the products were
1
characterized by IR, H/13C NMR and elemental analysis. The spectral data of the new
products are as follows:
5-Ethoxycarbonyl-1-methyl-6-phenyl-4-(2-chlorophenyl)-3,4-dihydropyrimidin-
2(1H)-one (4b)
White solid, mp 144-146 ꢁC; IR (KBr, cmꢂ1): v 3335, 3230, 3089, 2988, 1688, 1636, 762;
1H NMR (400 MHz, DMSO-d6): d 8.12 (s, 1H, NH), 7.61 (d, J ¼ 7.6 Hz, 1H, ArH), 7.48
(d, J ¼ 6.4 Hz, 4H, ArH), 7.43 (t, J ¼ 7.2 Hz, 2H, ArH), 7.35 (t, J ¼ 7.6 Hz, 2H, ArH),
5.75 (d, J ¼ 3.2 Hz, 1H, CH), 3.63 (q, J ¼ 6.8 Hz, 2H, OCH2CH3), 2.72 (s, 3H, NCH3),
0.67 (t, J ¼ 6.8 Hz, 3H, OCH2CH3); 13C NMR (100 MHz, DMSO-d6): d 164.03, 151.93,
151.24, 140.16, 134.51, 131.71, 129.36, 129.07, 128.47, 128.42, 128.27, 128.03, 127.88,
127.65, 127.12, 101.98, 58.84, 50.52, 31.54, 12.92.
Anal. Calcd. for C20H19N2O3Cl: C, 64.78; H, 5.16; N, 7.55. Found: C, 64.66; H, 5.14;
N, 7.56.
5-Ethoxycarbonyl-1-methyl-6-phenyl-4-(2,4-dichlorophenyl)-3,4-dihydropyrimidin-
2(1H)-one (4d)
White solid, mp 145-147 ꢁC; IR (KBr, cmꢂ1): v 3350, 3227, 3086, 2976, 1685, 1626, 787;
1H NMR (400 MHz, DMSO-d6): d 8.15 (s, 1H, NH), 7.62 (t, J ¼ 8.4 Hz, 2H, ArH), 7.48
(t, J ¼ 4.0 Hz, 4H, ArH), 7.41 (s, 1H, ArH), 7.31 (s, 1H, ArH), 5.69 (d, J ¼ 3.6 Hz, 1H,
CH), 3.61 (q, J ¼ 6.4 Hz, 2H, OCH2CH3), 2.69 (s, 3H, NCH3), 0.65 (t, J ¼ 6.4 Hz, 3H,
OCH2CH3); 13C NMR (100 MHz, DMSO-d6): d 160.08, 147.87, 147.56, 135.57, 130.56,

6
M. WANG ET AL.
128.81, 128.74, 126.21, 124.84, 124.46, 124.17, 123.97, 123.25, 97.70, 55.03, 46.38,
27.72, 9.07.
Anal. Calcd. for C20H18N2O3Cl2: C, 59.27; H, 4.48; N, 6.91. Found: C, 59.35; H, 4.47;
N, 6.90.
5-Ethoxycarbonyl-1-methyl-6-phenyl-4-(2-methoxyphenyl)-3,4-dihydropyrimidin-
2(1H)-one (4f)
Pale yellow solid, mp 179-181 ꢁC; IR (KBr, cmꢂ1): v 3361, 3231, 3098, 2984, 1687, 1631,
1
756; H NMR (400 MHz, DMSO-d6): d 7.65 (s, 1H, NH), 7.43 ꢃ 7.24 (m, 7H, ArH),
7.01 (d, J ¼ 8.0 Hz, 1H, ArH), 6.92 (t, J ¼ 7.2 Hz, 1H, ArH), 5.47 (d, J ¼ 3.6 Hz, 1H, CH),
3.80 (s, 3H, OCH3), 3.58 (q, J ¼ 7.2 Hz, 2H, OCH2CH3), 2.62 (s, 3H, NCH3), 0.61 (t,
J ¼ 7.2 Hz, 3H, OCH2CH3); 13C NMR (100 MHz, DMSO-d6): d 165.15, 157.40, 153.47,
151.63, 135.55, 130.75, 129.39, 128.91, 128.65, 127.79, 120.67, 111.67, 102.32, 59.45,
55.85, 49.43, 32.30, 13.70.
Anal. Calcd. for C21H22N2O4: C, 68.84; H, 6.05; N, 7.65. Found: C, 68.92; H, 6.04;
N, 7.62.
5-Ethoxycarbonyl-1-methyl-6-phenyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-
2(1H)-one (4g)
Pale yellow solid, mp 169-171 ꢁC; IR (KBr, cmꢂ1): v 3334, 3224, 3088, 2979, 1696, 1635,
1
752; H NMR (400 MHz, DMSO-d6): d 8.10 (d, J ¼ 4.0 Hz, 1H, NH), 7.45 (t, J ¼ 2.4 Hz,
3H, ArH), 7.32-7.26 (m, 4H, ArH), 6.95 (d, J ¼ 8.4 Hz, 2H, ArH), 5.17 (d, J ¼ 3.6 Hz,
1H, CH), 3.76 (s, 3H, OCH3), 3.66 (q, J ¼ 7.2 Hz, 2H, OCH2CH3), 2.64 (s, 3H, NCH3),
0.67 (t, J ¼ 7.2 Hz, 3H, OCH2CH3); 13C NMR (100 MHz, DMSO-d6): d 165.30, 159.01,
153.54, 151.08, 136.25, 135.29, 129.33, 128.98, 128.73, 128.59, 127.81, 114.34, 104.48,
59.59, 55.48, 52.54, 32.36, 13.72.
Anal. Calcd. for C21H22N2O4: C, 68.84; H, 6.05; N, 7.65. Found: C, 68.75; H, 6.07;
N, 7.67.
5-Ethoxycarbonyl-1-methyl-6-phenyl-4-(3-nitrophenyl)-3,4-dihydropyrimidin-2(1H)-
one (4h)
Pale yellow solid, mp 182-184 ꢁC; IR (KBr, cmꢂ1): v 3348, 3228, 3089, 2981, 1678, 1624,
1
787; H NMR (400 MHz, DMSO-d6): d 8.35 (d, J ¼ 3.6 Hz, 1H, NH), 8.26 (s, 1H, ArH),
8.20 (d, J ¼ 8.4 Hz, 1H, ArH), 7.89 (d, J ¼ 7.6 Hz, 1H, ArH), 7.74 (t, J ¼ 7.6 Hz, 1H,
ArH), 7.47 (s, 3H, ArH), 7.30 (d, J ¼ 13.2 Hz, 2H, ArH), 5.39 (d, J ¼ 3.6 Hz, 1H, CH),
3.69 (q, J ¼ 7.2 Hz, 2H, OCH2CH3), 2.66 (s, 3H, NCH3), 0.67 (t, J ¼ 7.2 Hz, 3H,
OCH2CH3); 13C NMR (100 MHz, DMSO-d6): d 160.61, 148.66, 147.70, 143.68, 141.64,
130.32, 128.69, 126.33, 124.61, 124.55, 124.18, 124.11, 123.32, 118.42, 116.97, 98.64,
55.24, 48.01, 27.93, 9.06.
Anal. Calcd. for C20H19N3O5: C, 62.99; H, 5.02; N, 11.02. Found: C, 63.10; H, 5.03;
N, 10.99.

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
7
5-Ethoxycarbonyl-1-methyl-6-phenyl-4-(3-hydroxyphenyl)-3,4-dihydropyrimidin-
2(1H)-one (4j)
Pale yellow solid, mp 139-141 ꢁC; IR (KBr, cmꢂ1): v 3350, 3222, 3093, 2985, 1687, 1621,
1
784; H NMR (400 MHz, DMSO-d6): d 9.43 (s, 1H, ArOH), 8.07 (d, J ¼ 3.6 Hz, 1H,
NH), 7.42 (t, J ¼ 2.4 Hz, 3H, ArH), 7.23 (q, J ¼ 3.6 Hz, 2H, ArH), 7.13 (t, J ¼ 8.0 Hz, 1H,
ArH), 6.78 (d, J ¼ 8.0 Hz, 2H, ArH), 6.63 (m, 1H, ArH), 5.10 (d, J ¼ 3.6 Hz, 1H, CH),
3.63 (q, J ¼ 7.2 Hz, 2H, OCH2CH3), 2.59 (s, 3H, NCH3), 0.63 (t, J ¼ 7.2 Hz, 3H,
OCH2CH3); 13C NMR (100 MHz, DMSO-d6): d 165.29, 157.90, 153.58, 151.25, 145.51,
135.28, 130.02, 129.01, 117.25, 114.81, 113.34, 104.23, 59.63, 52.94, 32.38, 13.71.
Anal. Calcd. for C20H20N2O4: C, 68.17; H, 5.72; N, 7.95. Found: C, 68.27; H, 5.70;
N, 7.93.
5-Ethoxycarbonyl-1-methyl-4,6-phenyl-3,4-dihydropyrimidin-2(1H)-thione (4k)
1
White solid, mp 118-120 ꢁC; IR (KBr, cmꢂ1): v 3193, 3064, 2981, 1732, 754; H NMR
(400 MHz, DMSO-d6): d 8.71 (s, 1H, NH), 7.47-7.30 (m, 9H, ArH), 7.18 (s, 1H, ArH),
4.94 (d, J ¼ 12.0 Hz, 1H, CH), 3.48-3.37 (m, 2H, OCH2CH3), 2.90 (s, 3H, NCH3), 0.54
(t, J ¼ 7.2 Hz, 3H, OCH2CH3); 13C NMR (100 MHz, DMSO-d6): d 178.98, 166.74,
140.97, 138.10, 128.48, 127.94, 127.86, 127.58, 125.81, 85.50, 59.18, 58.60, 53.30,
36.91, 12.98.
Anal. Calcd. for C20H20N2O2S: C, 68.16; H, 5.72; N, 7.95. Found: C, 68.08; H, 5.73;
N, 7.93.
5-Ethoxycarbonyl-1-methyl-6-phenyl-4-(4-chlorophenyl)-3,4-dihydropyrimidin-
2(1H)-thione (4l)
Pale yellow solid, mp 162-164 ꢁC; IR (KBr, cmꢂ1): v 3174, 3028, 2993, 1728, 1685, 702;
1H NMR (400 MHz, DMSO-d6): d 10.09 (d, J ¼ 4.4 Hz, 1H, NH), 7.49 (d, J ¼ 8.4 Hz, 5H,
ArH), 7.41 (d, J ¼ 8.4 Hz, 2H, ArH), 7.32 (s, 1H, ArH), 7.26 (s, 1H, ArH), 5.26 (d,
J ¼ 4.8 Hz, 1H, CH), 3.73 (q, J ¼ 7.2 Hz, 2H, OCH2CH3), 3.01 (s, 3H, NCH3), 0.69 (t,
J ¼ 7.2 Hz, 3H, OCH2CH3); 13C NMR (100 MHz, DMSO-d6): d 173.86, 160.40, 144.49,
136.73, 129.79, 128.28, 125.30, 124.91, 124.63, 124.30, 124.17, 123.95, 123.33, 101.86,
55.66, 47.74, 9.07.
Anal. Calcd. for C20H19N2O2SCl: C, 62.09; H, 4.95; N, 7.24. Found: C, 61.98; H, 4.96;
N, 7.22.
5-Ethoxycarbonyl-1-methyl-6-phenyl-4-(4-nitrophenyl)-3,4-dihydropyrimidin-2(1H)-
thione (4m)
Pale yellow solid, mp 191-193 ꢁC; IR (KBr, cmꢂ1): v 3192, 3003, 2949, 1720, 1605, 752;
1H NMR (400 MHz, DMSO-d6): d 8.94 (s, 1H, NH), 8.20 (d, J ¼ 8.4 Hz, 2H, ArH), 7.72
(d, J ¼ 8.8 Hz, 2H, ArH), 7.48-7.27 (m, 5H, ArH), 5.07 (d, J ¼ 11.6 Hz, 1H, CH), 3.50 (q,
J ¼ 7.2 Hz, 2H, OCH2CH3), 2.89 (s, 3H, NCH3), 0.55 (t, J ¼ 7.2 Hz, 3H, OCH2CH3); 13C
NMR (100 MHz, DMSO-d6): d 175.07, 162.75, 143.06, 141.98, 136.91, 125.83, 123.99,
123.80, 122.08, 119.06, 81.66, 55.58, 53.95, 48.94, 33.07, 9.10.

8
M. WANG ET AL.
Anal. Calcd. for C20H19N3O4S: C, 60.44; H, 4.82; N, 10.57. Found: C, 60.36; H, 4.84;
N, 10.61.
5-Ethoxycarbonyl-1-methyl-6-phenyl-4-(3-hydroxyphenyl)-3,4-dihydropyrimidin-
2(1H)-thione (4n)
1
White solid, mp 179-181 ꢁC; IR (KBr, cmꢂ1): v 3295, 3212, 2997, 1728, 1606, 701; H
NMR (400 MHz, DMSO-d6): d 9.44 (s, 1H, ArOH), 8.65 (s, 1H, NH), 7.42-7.34 (m, 4H,
ArH), 7.13 (t, J ¼ 7.2 Hz, 2H, ArH), 6.79 (d, J ¼ 7.2 Hz, 2H, ArH), 6.68 (d, J ¼ 8.4 Hz,
1H, ArH), 4.85 (d, J ¼ 12.0 Hz, 1H, CH), 3.51 (q, J ¼ 7.2 Hz, 2H, OCH2CH3), 2.89 (s,
3H, NCH3), 0.57 (t, J ¼ 7.2 Hz, 3H, OCH2CH3); 13C NMR (100 MHz, DMSO-d6): d
178.93, 166.71, 156.76, 140.96, 139.47, 128.88, 127.91, 127.59, 125.74, 118.37, 114.81,
114.62, 85.43, 59.21, 53.76, 53.19, 36.91, 13.01.
Anal. Calcd. for C20H20N2O3S: C, 65.20; H, 5.47; N, 7.60. Found: C, 65.36; H, 5.46;
N, 7.58.
Acknowledgments
This work was supported by the Natural Science Foundation of Liaoning Province under Grant
number 2019-MS-005; the Foundation of Liaoning Province Education Administration under
Grant numbers LJ2019007 and LQ2017010; and the Doctoral Start-up Foundation of Liaoning
Province under Grant numbers 2019-BS-005 and 20180540007.
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