Cerous p-Toluenesulfonate as an Efficient and Recyclable Catalyst for the Synthesis of N1-Substituted-4-aryl-3,4-dihydropyrimidin-2(1H)-ones

Full text of DOI:10.1080/00304948.2018.1525672

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
ISSN: 0030-4948 (Print) 1945-5453 (Online) Journal homepage: http://www.tandfonline.com/loi/uopp20
Cerous p-Toluenesulfonate as an Efficient and
Recyclable Catalyst for the Synthesis of N1-
Substituted-4-aryl-3,4-dihydropyrimidin-2(1H)-ones
Min Wang, Hongxu Jiang, Shun Zhang & He Pan
To cite this article: Min Wang, Hongxu Jiang, Shun Zhang & He Pan (2018) Cerous p-
Toluenesulfonate as an Efficient and Recyclable Catalyst for the Synthesis of N1-Substituted-4-
aryl-3,4-dihydropyrimidin-2(1H)-ones, Organic Preparations and Procedures International, 50:5,
482-492, DOI: 10.1080/00304948.2018.1525672
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Organic Preparations and Procedures International, 50:482–492, 2018
# 2018 Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2018.1525672
Cerous p-Toluenesulfonate as an Efficient and
Recyclable Catalyst for the Synthesis of N1-
Substituted-4-aryl-3,4-dihydropyrimidin-2(1H)-ones
Min Wang, Hongxu Jiang, Shun Zhang, and He Pan
College of Chemistry and Chemical Engineering, Bohai University, Jinzhou
121013, China
Dihydropyrimidinones (DHPMs) have a wide range of synthetic importance due to the
six functionable points on the heterocycles. DHPMs also possess diverse biological and
pharmaceutical activities as calcium channel blockers, antihypertensive agents and a1a-
antagonists.1–5
Since the first straightforward synthetic method for DHPMs was reported by
Biginelli in 1893,6 many improved protocols were developed.7–13 Not only new cata-
lysts and reaction conditions were explored but also some novel reactive species were
formed. The scope of the Biginelli reaction extended to various building blocks, so a
large number of multifunctional pyrimidine derivatives with important biological prop-
erties were achieved. Among them, N1-substituted DHPMs possess important biological
activity and regioselectivity too.14,15 However, there are only a few references concern-
ing the N1-alkylation of DHPMs and they have limitations in terms of yields, toxic
reagents, and reaction conditions.16–21 The substituent on urea was mostly limited to
Me and Et. This encouraged us to develop a novel and efficient method for synthesizing
more N1-substituted DHPMs.
As water-tolerant Lewis acids catalysts, metal sulfonates are believed to have
extensive prospects of application in synthetic chemistry. They are efficient, non-toxic
and can be reused. As a continuation of our work on metal sulfonates-catalyzed
Biginelli reaction,22,23 we report here the first synthesis of N1-functionalized DHPM
analogs by a three-component condensation of aromatic aldehydes, b-ketoesters, and N-
substituted (thio)urea using cerous p-toluenesulfonate (Ce(p-CH3C6H4SO3)3ꢀ4H2O,
abbreviated as CePTS) as a catalyst (Scheme 1). The diversity is a distinct advantage of
the process. Besides N-alkylsubstituted urea, p-tolylurea was also employed. Many new
N1-substituted DHPMs heterocycles are reported.
In order to select the most effective catalyst, seven metal p-toluenesulfonates were
screened in a model reaction of benzaldehyde (10 mmol), ethyl acetoacetate (10 mmol)
and methylurea (13 mmol) at 80 ꢁC (Table 1). Among them, CePTS (0.5 mmol)
Received April 13, 2017; in final form April 8, 2018.
Address correspondence to Min Wang, College of Chemistry and Chemical Engineering, Bohai
University, Jinzhou 121013, China. E-mail: minwangszg@hotmail.com
Color versions of one or more figures in this article can be found online at www.tandfonline.
com/uopp.
482

N1-Substituted-4-aryl-3,4-dihydropyrimidin-2(1H)-ones
483
Scheme 1.
Table 1
Compare of Catalytic Activity among Different Metal p-toluenesulfonates
Entry
Catalyst (5 mol%)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
Ce(p-CH3C6H4SO3)3ꢀ4H2O
Sm(p-CH3C6H4SO3)3ꢀ2H2O
La(p-CH3C6H4SO3)3ꢀ2H2O
Zn(p-CH3C6H4SO3)2ꢀ5H2O
Nd(p-CH3C6H4SO3)2ꢀ2H2O
Cu(p-CH3C6H4SO3)2ꢀ6H2O
Al(p-CH3C6H4SO3)3ꢀ5H2O
None
10
23
35
27
40
21
25
3 h
94, 90, 85
95
86
85
85
84
78
40
emerged as the best candidate, thus affording the desired N1-substituted DHPMs in
yields as high as 94% within 10 min (Table 1, Entry 1). Reactions catalyzed by other
metal toluenesulfonates obtained lower yields and longer reaction times. Only 40%
yield of the product was obtained in the absence of a catalyst (Entry 8). Furthermore,
we optimized the reaction conditions by varying the amount of catalyst and reaction
temperature. The experimental results emerged that 5 mol% catalyst and 80 ꢁC
were optimal.
Next, the reuse of CePTS was investigated. When the reaction was completed, the
reaction mixture was washed with water. The catalyst remaining in aqueous phase could
be recovered by evaporating the filtrate. Then, CePTS can be reused for the next two
consecutive reactions. This demonstrated that CePTS was water-tolerant and recyclable
(Entry 1, yields of 90% and 85%).
To probe the substrate scope, a series of aromatic or aliphatic aldehydes, b-dicar-
bonyl compounds, and N-substituted (thio)ureas were subjected to the optimized reac-
tion conditions (Table 2). Aromatic aldehydes carrying either electron-withdrawing or
electron-donating groups afforded high yields. What’s more, the position of substituents
on the aromatic ring had no effect on the reactions. Both ethyl acetoacetate and methyl
acetoacetate reacted smoothly. We were delighted to discover that the same reaction
conditions could be extended to N-arylsubstituted urea besides N-alkylsubstituted urea,
which yielded the corresponding N1-substituted DHPMs (Entries b'-d'). In addition,

484
Wang et al.
Table 2
Synthesis of N1-Substituted 3,4-dihydropyrimidin-2(1H)-ones Catalyzed by CePTS
Mp (ꢁC)
Yield (%)
Entry
R1
R2
R3
X
(Time (min))
Found
Reported
a
b
c
d
e
H
2-Cl
4-Cl
4-CH3
2-CH3O
4-CH3O
3-NO2
3-OH
4-OH
Et
Et
Et
Et
Et
Et
Et
Et
Et
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
Et
Et
Et
O
O
O
O
O
O
O
O
O
O
S
O
O
O
O
O
O
O
O
O
S
O
O
O
O
O
O
O
O
O
94(10)
91(13)
93(27)
84(60)
89(45)
80(60)
88(50)
94(7)
90(35)
94(13)
51(6 h)
88(5)
84(14)
91(30)
94(16)
91(60)
93(21)
94(7)
95(10)
81(10)
80(6 h)
71(60)
92(60)
94(60)
86(60)
87(60)
87(60)
86(58)
86(15)
89(40)
178–180 176–17724
134–136
–
132–134 133–13525
112–114 119–12025
147–149 145–14619
138–140 138–14026
137–139 136–13724
f
g
h
i
j
k
l
m
n
o
p
q
r
209–211
–
184–186 178–18026
4-OH-3-CH3O Et
181–183
–
H
H
2-Cl
Et
145–146 146–14718
Me
Me
Me
Me
Me
Me
Me
Me
193–195 190–19226
171–173
135–137
162–163
147–149
–
–
–
–
4-Cl
2,4-Cl2
4-CH3
2-CH3O
3-OH
4-OH
171–173 170–17219
220–222
245–247
204–206
–
–
–
s
t
4-OH-3-CH3O Me
u
v
w
x
y
z
a'
b'
c'
d'
H
H
Me
Et
Et
Et
Et
Et
Me
Et
160–161 160–16216
113–115
114–116
118–120
182–184
122–124
133–135
179–181
208–210
155–157
11814
2-Cl
3-NO2
3-OH
4-CH3
H
H
4-Cl
H
–
–
–
–
–
–
–
–
Et
Et
p-CH3C6H4
p-CH3C6H4
Et
Me p-CH3C6H4
N-substituted thiourea resulted in moderate yields (Entries k and u). Unfortunately, sub-
strates with aliphatic aldehydes or acetylacetone gave no desired product.
The crystal structure and the cell stacking diagram of the compound i are shown in
Figures 1 and 2. The crystal structure of the compound i is stabilized by the H-bond
interactions. They are connected by N-Hꢀ ꢀO hydrogen bonding interactions to generate
a dimer (Figure 3). Furthermore, there are N(3)-H(3A)ꢀꢀꢀO(2) and O(2)-H(2A)ꢀꢀO(1)
hydrogen bond interactions, which made i present the 3D supramolecular framework
(Figure 4).
A mechanism similar to that of Kappe for the Biginelli reaction was proposed.27
The first and key step is the formation of acylimine intermediate, which formed by the

N1-Substituted-4-aryl-3,4-dihydropyrimidin-2(1H)-ones
485
Figure 1. The molecular structure of compound i.
Figure 2. The molecule packing diagram of compound i.

486
Wang et al.
Figure 3. The compound i formed dimers by hydrogen bonds.
Figure 4. The compound i formed 3D supramolecular framework by two hydrogen bonds.
reaction of an aldehyde with a urea. A subsequent addition of the b-carbonyl compound
to the acylimine produces an open-chain ureide, which undergoes cyclization and dehy-
dration to afford the corresponding DHPMs.
In summary, we have developed an efficient and green cyclic condensation from
aromatic aldehydes, b-ketoesters and N-substituted urea or thiourea by catalytic amount

N1-Substituted-4-aryl-3,4-dihydropyrimidin-2(1H)-ones
487
(5 mol%) of CePTS to afford N1-substituted-4-aryl-3,4-dihydropyrimidin-2(1H)-ones.
The reaction is convenient, nontoxic and atom-economic. Besides N-methylurea and N-
ethylurea, phenylurea, p-tolylurea and N-methylthiourea were employed. The catalyst
can be reused several times. All the advantages make it a useful and attractive strategy
for the preparation of DHPMs. The extension of this procedure to include N,N’-disub-
stituted ureas and thioureas will be the subject of future work.
Experimental Section
All chemicals were obtained commercially and used without further purification.
CePTS was synthesized according to a reported literature.28 Thin layer chromatography
was performed on Merck Silica gel 60 F254 plates. Melting points were determined in
an open glass capillary on an RY-1 micromelting point apparatus. A Varian Scimitar
2000 series Fourier transform instrument was used for recording the IR spectra using
1
potassium bromide pellets in the range of 400–4000 cmꢂ1. The H and 13C NMR spec-
tra were recorded on an Agilent 400-MR spectrometer in DMSO-d6 using TMS as an
internal standard. Mass spectra were measured at an Agilent 1100 series LC/MSD VL
ESI facility. Elemental analyses (C, H, N) were conducted using the Elemental
Analyser EA 2400II (Perkin Elmer), their results were found to be in good agreement
( 0.3%) with the calculated values. Crystallographic data for the title complexes were
collected on a Bruker Smart Apex II diffractometer with Mo Ka radiation (k ¼ 0.71069
Å) at 296 K using 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. Semiempirical absorption corrections were applied using SADABS
program. The 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. X-ray crystalligraphy data for
compound i were submitted to the Editors for review and are available from the authors
upon request.
General Procedure for the Synthesis of N1-substituted-4-aryl-3,4-dihydropyrimidin-
2(1H)-(thio)ones (a-d')
An aldehyde (10 mmol), b-dicarbonyl compound (10 mmol), N-substituted urea or thio-
urea (13 mmol) and CePTS (0.363 g, 0.5 mmol) were added successively to a 25 mL
dried round-bottom flask. The mixture was stirred at 80 ꢁC for an appropriate time. The
completion of the reaction was determined on TLC plates using ethyl acetate/petroleum
ether (V/V ¼ 3:7) mixture as a mobile phase. After completion, the mixture was cooled
to room temperature, then crushed ice was added to precipitate the product. The solid
precipitate was separated by filtration through a Buckner funnel, and washed with cold
water to remove excess N-substituted urea. Then, it was air dried. It was further purified
by recrystallization from hot ethanol to afford pure DHPM derivatives. The products
1
were characterized by IR, H NMR, 13C NMR, MS, and elemental analysis. Spectral
data for the novel compounds are given below.
5-Ethoxycarbonyl-1,6-dimethyl-4-(2-chlorophenyl)-3,4-dihydropyrimidin-2(1H)-
one (b). Pale yellow solid. IR (KBr, cmꢂ1): 3341, 3214, 3109, 2984, 1686, 1635, 769.
1H NMR (400MHz, DMSO-d6): d ¼ 7.96 (s, 1H, NH), 7.31ꢃ 7.42 (m, 4H,ArH), 5.65 (s,
1H, CH), 3.94 (q, 2H, J ¼ 8.0 Hz, CH2), 3.17 (s, 3H, NCH3), 2.57 (s, 3H, C ¼ CCH3),

488
Wang et al.
1.01 (t, 3H, J ¼ 8.0 Hz, OCH2CH3). 13C NMR (100 MHz, DMSO-d6): d ¼ 165.64,
152.64, 151.98, 141.33, 132.18, 129.85, 129.65, 128.93, 128.20, 101.40, 59.85., 50.50,
30.04, 16.43, 14.30. MS (ESI): m/z (%) 309 (MþþH, 100).
Anal. Calcd. for C15H17N2O3Cl: C, 58.35; H, 5.55; N, 9.07. Found: C, 58.21; H,
5.64; N, 9.01.
5-Ethoxycarbonyl-1,6-dimethyl-4-(3-hydroxyphenyl)-3,4-dihydropyrimidin-
2(1H)-one (h). Pale yellow solid. IR (KBr, cmꢂ1): 3341, 3236, 3108, 2989, 1694,
1
1669, 785. H NMR (400 MHz, DMSO-d6): d ¼ 9.40 (s, 1H, OH), 7.95 (s, 1H, NH),
6.67 ꢃ 7.11 (m, 4H, ArH), 5.13 (s, 1H, CH), 4.08 (q, 2H, J ¼ 4.0 Hz, CH2), 3.12 (s,
3H, NCH3), 2.49 (s, 3H, C ¼ CCH3), 1.17 (t, 3H, J ¼ 4.0 Hz, OCH2CH3). 13C NMR
(100 MHz, DMSO-d6): d ¼ 166.07, 157.81, 153.66, 150.57, 145.94, 129.79, 117.00,
114.64, 113.34, 103.17, 59.99, 52.70, 30.14, 16.45, 14.48. MS (ESI): m/z (%) 291
(MþþH, 100).
Anal. Calcd. for C15H18N2O4: C, 62.06; H, 6.25; N, 9.65. Found: C, 62.21; H,
6.22; N, 9.61.
5-Ethoxycarbonyl-1,6-dimethyl-4-(4-hydroxy-3-methoxyphenyl)-3,4-dihydro-
pyrimidin-2(1H)-one (j). Orange solid. IR (KBr, cmꢂ1): 3336, 3278, 2968, 2361,
1
1683, 1644, 767. H NMR (400 MHz, DMSO-d6): d ¼ 8.94 (s, 1H, OH), 7.87 (s, 1H,
NH), 6.60 ꢃ 6.79 (m, 3H, ArH), 5.08 (s, 1H, CH), 4.06 (q, 2H, J ¼ 4.0 Hz, CH2),
3.74 (s, 3H, OCH3), 3.11 (s, 3H, NCH3), 2.49 (s, 3H, C ¼ CCH3), 1.15 (t, 3H,
J ¼ 4.0, OCH2CH3). 13C NMR (100 MHz, DMSO-d6): d ¼ 166.12, 153.65, 150.47,
147.74, 146.24, 135.50, 118.50, 115.70, 110.95, 103.32, 59.91, 55.93, 52.46, 30.07,
16.43, 14.56. MS (ESI): m/z (%) 321 (MþþH, 100).
Anal. Calcd. for C16H20N2O5: C, 59.99; H, 6.29; N, 8.74. Found: C, 59.87; H,
6.32; N, 8.81.
5-Methoxycarbonyl-1,6-dimethyl-4-(2-chlorophenyl)-3,4-dihydropyrimidin-
2(1H)-one (m). Pale yellow solid. IR (KBr, cmꢂ1): 3213, 3096, 2946, 2361, 2342,
1
1695, 1631, 765. H NMR (400 MHz, DMSO-d6): d ¼ 7.95 (s, 1H, NH), 7.40-7.29
(m, 4H, ArH), 5.61 (s, 1H, CH), 3.47 (s, 3H, OCH3), 3.14 (s, 3H, NCH3), 2.55 (s,
3H, C ¼ CCH3). 13C NMR (100 MHz, DMSO-d6): d ¼ 166.16, 152.76, 152.27,
141.12, 132.22, 129.99, 129.71, 128.83, 128.22, 101.18, 51.48, 50.39, 30.11, 16.50.
MS (ESI): m/z (%) 295 (MþþH, 100).
Anal. Calcd. for C14H15N2O3Cl: C, 57.05; H, 5.13; N, 9.50. Found: C, 56.93; H,
5.20; N, 9.53.
5-Methoxycarbonyl-1,6-dimethyl-4-(4-chlorophenyl)-3,4-dihydropyrimidin-
2(1H)-one (n). Pale yellow solid. IR (KBr, cmꢂ1): 3215, 3102, 2950, 2361, 1691,
1
1622, 793. H NMR (400 MHz, DMSO-d6): d ¼ 8.07 (s, 1H, NH), 7.40 ꢃ 7.26 (m,
4H, ArH), 5.19 (s, 1H, CH), 3.58 (s, 3H, OCH3), 3.11 (s, 3H, NCH3), 2.51 (s, 3H,
C ¼ CCH3). 13C NMR (100 MHz, DMSO-d6): d ¼ 166.37, 153.37, 151.72, 143.25,
132.37, 128.89, 128.39, 102.13, 52.14, 51.53, 30.19, 16.51. MS (ESI): m/z (%) 295
(MþþH, 100).
Anal. Calcd. for C14H15N2O3Cl: C, 57.05; H, 5.13; N, 9.50. Found: C, 57.18; H,
5.11; N, 9.45.
5-Methoxycarbonyl-1,6-dimethyl-4-(2,4-dichlorophenyl)-3,4-dihydropyrimidin-
2(1H)-one (o). Pale yellow solid. IR (KBr, cmꢂ1): 3343, 3016, 2953, 2361, 2342, 1683,
1
1632, 748. H NMR (400 MHz, DMSO-d6): d ¼ 8.01 (s, 1H, NH), 7.56 ꢃ 7.36 (m, 3H,
ArH), 5.62 (s, 1H, CH), 3.50 (s, 3H, OCH3), 3.17 (s, 3H, NCH3), 2.57 (s, 3H,
C ¼ CCH3). 13C NMR (100 MHz, DMSO-d6): d ¼ 166.00, 152.55, 152.47, 140.35,

N1-Substituted-4-aryl-3,4-dihydropyrimidin-2(1H)-ones
489
133.26, 133.22, 130.34, 129.33, 128.32, 100.76, 51.44, 50.17, 30.11, 16.50. MS (ESI):
m/z (%) 330 (MþþH, 100).
Anal. Calcd. for C14H14N2O3Cl2: C, 51.08; H, 4.29; N, 8.51. Found: C, 51.16; H,
4.32; N, 8.45.
5-Methoxycarbonyl-1,6-dimethyl-4-(4-methylphenyl)-3,4-dihydropyrimidin-
2(1H)-one (p). Pale yellow solid. IR (KBr, cmꢂ1): 3229, 3169, 3095, 2952, 2362,
1
1699, 784. H NMR (400 MHz, DMSO-d6): d ¼ 7.99 (s, 1H, NH), 7.13 (s, 4H, ArH),
5.17 (s, 1H, CH), 3.58 (s, 3H, OCH3), 3.11 (s, 3H, NCH3), 2.51 (s, 3H, C ¼ CCH3),
2.27 (s, 3H, ArCH3). 13C NMR (100 MHz, DMSO-d6): d ¼ 166.53, 153.59, 151.16,
141.37, 136.91, 129.43, 126.34, 102.72, 52.36, 51.46, 30.13, 21.03, 16.46. MS
(ESI): m/z (%) 275 (MþþH, 100).
Anal. Calcd. for C15H18N2O3: C, 65.68; H, 6.61; N, 10.21. Found: C, 65.77; H,
6.55; N, 10.26.
5-Methoxycarbonyl-1,6-dimethyl-4-(3-hydroxyphenyl)-3,4-dihydropyrimidin-
2(1H)-one (r). Pale yellow solid. IR (KBr, cmꢂ1): 3377, 3309, 2951, 2360, 2342,
1
1682, 787. H NMR (400 MHz, DMSO-d6): d ¼ 9.39 (s, 1H, OH), 7.95 (s, 1H, NH),
7.08-6.63 (m, 4H, ArH), 5.08 (s, 1H, CH), 3.58 (s, 3H, OCH3), 3.08 (s, 3H, NCH3),
2.47 (s, 3H, C ¼ C-CH3). 13C NMR (100 MHz, DMSO-d6): d ¼ 166.57, 157.84,
153.67, 151.04, 145.74, 129.88, 116.93, 114.66, 113.25, 102.78, 52.47, 51.55, 30.20,
16.51. MS (ESI): m/z (%) 277 (MþþH, 100).
Anal. Calcd. for C14H16N2O4: C, 60.86; H, 5.84; N, 10.14. Found: C, 60.98; H,
5.92; N, 10.11.
5-Methoxycarbonyl-1,6-dimethyl-4-(4-hydroxyphenyl)-3,4-dihydropyrimidin-
2(1H)-one (s). Pale yellow solid. IR (KBr, cmꢂ1): 3283, 3082, 2951, 2360, 2342,
1
1664, 754. H NMR (400 MHz, DMSO-d6): d ¼ 9.35 (s, 1H, OH), 7.87 (s, 1H, NH),
7.00 ꢃ 6.99(d, J ¼ 4.0 Hz, 2H, ArH), 6.68 ꢃ 6.67 (d, J ¼ 4.0 Hz, 2H, ArH), 5.04 (s,
1H, CH), 3.54 (s, 3H, OCH3), 3.07 (s, 3H, C ¼ CCH3), 2.46 (s, 3H, NCH3). 13C NMR
(100 MHz, DMSO-d6): d ¼ 166.60, 157.05, 153.56, 150.78, 134.79, 127.64, 115.53,
103.02, 52.18, 51.49, 30.14, 16.49. MS (ESI): m/z (%) 277 (MþþH, 100).
Anal. Calcd. for C14H16N2O4: C, 60.86; H, 5.84; N, 10.14. Found: C, 60.68; H,
5.82; N, 10.11.
5-Methoxycarbonyl-1,6-dimethyl-4-(4-hydroxy-3-methoxyphenyl)-3,4-dihydro-
pyrimidin-2(1H)-one (t). Orange solid. IR (KBr, cmꢂ1): 3340, 2949, 2360, 2342,
1
1684, 1647, 767. H NMR (400 MHz, DMSO-d6): d ¼ 8.93 (s, 1H, OH), 7.88 (s, 1H,
NH), 6.77 ꢃ 6.55 (m, 3H, ArH), 5.05 (s, 1H, CH), 3.71 (s, 3H, ArOCH3), 3.56 (s, 3H,
OCH3), 3.07 (s, 3H, C ¼ CCH3), 2.47 (s, 3H, NCH3). 13C NMR (100 MHz, DMSO-d6):
d ¼ 166.61, 153.66, 150.91, 147.81, 146.27, 135.23, 118.38, 115.67, 110.90, 102.88,
55.91, 52.30, 51.50, 30.11, 16.47. MS (ESI): m/z (%) 307 (MþþH, 100).
Anal. Calcd. for C15H18N2O5: C, 58.82; H, 5.92; N, 9.14. Found: C, 58.70; H,
5.97; N, 9.10.
5-Ethoxycarbonyl-1-ethyl-6-methyl-4-(2-chlorophenyl)-3,4-dihydropyrimi-
din-2(1H)-one (w). Pale yellow solid. IR (KBr, cmꢂ1): 3233, 3101, 2984, 2961, 2342,
1
1695, 1628, 762. H NMR (400 MHz, DMSO-d6): d ¼ 7.89 (s, 1H, NH), 7.42 ꢃ 7.31 (m,
4H, ArH), 5.66 (s, 1H, CH), 3.94 (q, 2H, J ¼ 8.0 Hz, OCH2), 3.70 (q, 2H, J ¼ 8.0 Hz,
NCH2), 2.59 (s, 3H, C ¼ CCH3), 1.15 (t, 3H, J ¼ 8.0 Hz, OCH2CH3), 1.02 (t, 3H,
J ¼ 8.0 Hz, NCH2CH3). 13C NMR (100 MHz, DMSO-d6): d ¼ 165.69, 152.06, 150.83,
141.43, 132.22, 129.89, 129.61, 128.88, 128.08, 101.67, 59.85, 50.71, 37.44, 15.81,
15.23, 14.25. MS (ESI): m/z (%) 323 (MþþH, 100).

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Anal. Calcd. for C16H19N2O3Cl: C, 59.54; H, 5.93; N, 8.68. Found: C, 59.71; H,
5.88; N, 8.61.
5-Ethoxycarbonyl-1-ethyl-6-methyl-4-(3-nitrophenyl)-3,4-dihydropyrimi-
din-2(1H)-one (x). Pale yellow solid. IR (KBr, cmꢂ1): 3255, 3109, 2988, 2360,
2342, 1708, 1681, 764. 1H NMR (400 MHz, DMSO-d6): d ¼ 8.12 (s, 1H, NH),
8.08-7.66 (m, 4H, ArH), 5.28 (s, 1H, CH), 4.02 (q, 2H, J ¼ 4.0 Hz, OCH2), 3.61
(q, 2H, J ¼ 4.0 Hz, NCH2), 2.51 (s, 3H, C ¼ CCH3), 1.09 (t, 3H, J ¼ 4.0 Hz,
OCH2CH3), 1.07 (t, 3H, J ¼ 4.0 Hz, NCH2CH3). 13C NMR (100 MHz, DMSO-d6):
d ¼ 165.70, 152.62, 151.00, 148.21, 146.80, 133.27, 130.65, 122.84, 121.31,
102.37, 60.18, 52.56, 37.39, 15.92, 15.15, 14.39. MS (ESI): m/z (%) 334
(MþþH, 100).
Anal. Calcd. for C16H19N3O5: C, 57.65; H, 5.74; N, 12.61. Found: C, 57.56; H,
5.71; N, 12.53.
5-Ethoxycarbonyl-1-ethyl-6-methyl-4-(3-hydroxyphenyl)-3,4-dihydropyri-
midin-2(1H)-one (y). Pale yellow solid. IR (KBr, cmꢂ1): 3352, 3282, 2989, 2361,
1
2342, 1694, 1668, 766. H NMR (400 MHz, DMSO-d6): d ¼ 9.37 (s, 1H, OH), 7.84
(s, 1H, NH), 7.08-6.62 (m, 4H, ArH), 5.05 (s, 1H, CH), 4.01 (q, 2H, J ¼ 8.0 Hz,
OCH2), 3.60 (q, 2H, J ¼ 8.0 Hz, NCH2), 2.46 (s, 3H, C ¼ CCH3), 1.12 (t, 3H,
J ¼ 8.0 Hz, OCH2CH3), 1.06 (t, 3H, J ¼ 8.0 Hz, NCH2CH3). 13C NMR (100 MHz,
DMSO-d6): d ¼ 166.11, 157.80, 153.01, 149.47, 146.10, 129.79, 117.02, 114.62,
113.41, 103.43, 60.00, 52.89, 37.37, 15.91, 15.26, 14.50. MS (ESI): m/z (%) 305
(MþþH, 100).
Anal. Calcd. for C16H20N2O4: C, 63.15; H, 6.62; N, 9.20. Found: C, 63.32; H,
6.55; N, 9.13.
5-Ethoxycarbonyl-1-ethyl-6-methyl-4-(4-methylphenyl)-3,4-dihydropyrimi-
din-2(1H)-one (z). Pale yellow solid. IR (KBr, cmꢂ1): 3219, 3100, 2976, 2933,
1
2361, 2342, 1672, 1625, 775. H NMR (400 MHz, DMSO-d6): d ¼ 7.87 (s, 1H, NH),
7.10 (s, 4H, ArH), 5.12 (s, 1H, CH), 4.00 ꢃ 3.60 (m, 4H, O-CH2&N-CH2), 2.48 (s,
3H, C ¼ CCH3), 2.24 (s, 3H, ArCH3), 1.10 ꢃ 1.06(m, 6H, OCH2CH3&NCH2CH3).
13C NMR (100 MHz, DMSO-d6): d ¼ 166.06, 152.98, 149.64, 141.74, 136.88,
129.35, 126.43, 103.43, 59.94, 52.72, 37.32, 21.04, 15.86, 15.23, 14.47. MS (ESI):
m/z (%) 303 (MþþH, 100).
Anal. Calcd. for C17H22N2O3: C, 67.58; H, 7.34; N, 9.27. Found: C, 67.76; H,
7.27; N, 9.21.
5-Methoxycarbonyl-1-ethyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one
(a'). Pale yellow solid. IR (KBr, cmꢂ1): 3215, 3100, 2985, 2945, 2361, 2342, 1690,
1
716. H NMR (400 MHz, DMSO-d6): d ¼ 7.95 (s, 1H, NH), 7.31-7.25 (m, 5H, ArH),
5.17 (s, 1H, CH), 3.81 (q, 2H, J ¼ 6.8 Hz, NCH2), 3.55 (s, 3H, OCH3), 2.51 (s, 3H,
C ¼ CCH3), 1.07 (t, 3H, J ¼ 7.0 Hz, NCH2CH3). 13C NMR (100 MHz, DMSO-d6):
d ¼ 166.56, 153.01, 150.19, 144.50, 128.90, 127.77, 126.48, 103.02, 52.90, 51.48,
37.40, 15.94, 15.21. MS (ESI): m/z (%) 275 (MþþH, 100).
Anal. Calcd. for C15H18N2O3: C, 65.72; H, 6.62; N, 10.22. Found: C, 65.81; H,
6.57; N, 10.15.
5-Ethoxycarbonyl-1-(4-methylphenyl)-6-methyl-4-phenyl-3,4-dihydropyri-
midin-2(1H)-one (b'). Pale yellow solid. IR (KBr, cmꢂ1): 3234, 3110, 2978, 2360,
2342, 1693, 1624, 758. 1H NMR (400 MHz, DMSO-d6): d ¼ 8.18 (s, 1H, NH),
7.12 ꢃ 7.43 (m, 9H, ArH), 5.34 (s, 1H, CH), 4.07 (q, 2H, J ¼ 4.0 Hz, OCH2), 2.36
(s, 3H, C ¼ CCH3), 2.07 (s, 3H, ArCH3), 1.14 (t, 3H, J ¼ 4.0 Hz, CH2CH3). 13C

N1-Substituted-4-aryl-3,4-dihydropyrimidin-2(1H)-ones
491
NMR (100 MHz, DMSO-d6): d ¼ 165.89, 152.61, 149.55, 144.54, 137.86, 135.55,
129.83, 129.05, 127.92, 126.71, 118.64, 103.98, 60.14, 53.55, 21.10, 18.49, 14.46.
MS (ESI): m/z (%) 351 (MþþH, 100).
Anal. Calcd. for C21H22N2O3: C, 71.98; H, 6.33; N, 7.99. Found: C, 72.07; H,
6.25; N, 8.02.
5-Ethoxycarbonyl-1-(4-methylphenyl)-6-methyl-4-(4-chlorophenyl)-3,4-dihy-
dropyrimidin-2(1H)-one (c'). Pale yellow solid. IR (KBr, cmꢂ1): 3215, 3101, 2982,
1
2936, 2361, 2342, 1698, 1628, 721. H NMR (400 MHz, DMSO-d6): d ¼ 8.18 (s, 1H,
NH), 7.48 ꢃ 7.11 (m, 8H, ArH), 5.29 (s, 1H, CH), 4.05 (q, 2H, J ¼ 6.0 Hz, OCH2),
2.35 (s, 3H, C ¼ CCH3), 2.05 (s, 3H, ArCH3), 1.13 (t, 3H, J ¼ 6.0 Hz, OCH2CH3).
13C NMR (100 MHz, DMSO-d6): d ¼ 165.75, 152.40, 149.98, 143.40, 137.93,
135.39, 132.46, 130.00,129.83, 129.07, 128.65, 103.36, 60.21, 52.92, 21.10, 18.49,
14.47. MS (ESI): m/z (%) 385 (MþþH, 100).
Anal. Calcd. for C21H21N2O3Cl: C, 65.54; H, 5.50; N, 7.28. Found: C, 65.36; H,
5.53; N, 7.31.
5-Methoxycarbonyl-1-(4-methylphenyl)-6-methyl-4-phenyl-3,4-dihydropyrimi-
din-2(1H)-one (d'). Pale yellow solid. IR (KBr, cmꢂ1): 3430, 3313, 3219, 2360, 2342,
1
1693, 1655, 763. H NMR (400 MHz, DMSO-d6): d ¼ 8.21 (s, 1H, NH), 7.43 ꢃ 7.04
(m, 9H, ArH), 5.34 (s, 1H, CH), 3.61 (s, 3H, OCH3), 2.35 (s, 3H, C ¼ CCH3), 2.08 (s,
3H, ArCH3). 13C NMR (100 MHz, DMSO-d6): d ¼ 166.41, 152.67, 149.89, 144.34,
137.90, 135.50, 129.85, 129.12, 127.96, 126.64, 118.29, 103.73, 53.36, 51.63, 21.09,
18.55. MS (ESI): m/z (%) 337 (MþþH, 100).
Anal. Calcd. for C20H20N2O3: C, 71.41; H, 5.99; N, 8.33. Found: C, 71.55; H,
5.92; N, 8.35.
Acknowledgments
This research work was financially supported by the Program for Liaoning Excellent
Talents in University (No. LJQ2015002), the Natural Science Foundation of Liaoning
Province (No. 2015020201), and the National Natural Science Foundation of China
(No. 21406016).
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