New three-component cyclocondensation reaction: microwave-assisted one-pot synthesis of 5-unsubstituted-3,4-dihydropyrimidin-2(1H)-ones under solvent-free conditions

Article abstract of DOI:10.1016/j.tet.2006.12.062

Sixteen 5-unsubstituted-3,4-dihydropyrimidin-2(1H)-ones have been synthesized by microwave-assisted Biginelli reactions in a short and concise manner employing ZnI₂ as a catalyst under solvent-free conditions. All products were identified by IR

Full text of DOI:10.1016/j.tet.2006.12.062

Tetrahedron 63 (2007) 1981–1986
New three-component cyclocondensation reaction: microwave-
assisted one-pot synthesis of 5-unsubstituted-3,4-
dihydropyrimidin-2(1H)-ones under
solvent-free conditions
a
Bing Liang,a Xitian Wang,a Jin-Xian Wanga,b, and Zhengyin Du
*
aInstitute of Chemistry, Department of Chemistry, Northwest Normal University, 967 Anning Road (E.),
Lanzhou, Gansu 730070, PR China
bState Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, PR China
Received 8 October 2006; revised 19 December 2006; accepted 20 December 2006
Available online 22 December 2006
Abstract—Sixteen 5-unsubstituted-3,4-dihydropyrimidin-2(1H)-ones have been synthesized by microwave-assisted Biginelli reactions in
a short and concise manner employing ZnI2 as a catalyst under solvent-free conditions. All products were identified by IR, NMR, elemental
analysis and HRMS. The advantages of this novel protocol include the excellent yield, operational simplicity, short time and the avoidance of
the use of organic solvents and expensive catalysts.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
(or acetylacetone) and urea or thiourea. The first Biginelli-
like reaction, reported by Wang et al.,15 was conducted in
CH3CN by using aldehydes, ketones and urea as substrates
and FeCl3$6H2O and TMSCl as catalysts, which remarkably
broadened the Biginelli reaction. However, it suffered from
its drawbacks, especially the use of highly toxic organic sol-
vent (CH3CN), long reaction time (12 h) and stoichiometric
TMSCl.
It is well known that 3,4-dihydropyrimidin-2-(1H)-ones
(DHPMs) and their derivatives exhibit a wide range of bio-
logical activities, pharmaceutical and therapeutic properties,
such as antiviral, antitumour, antibacterial and anti-inflam-
matory activities.1–5 Therefore, the preparation of this het-
erocyclic nucleus has gained great importance in organic
synthesis. The simple and direct method for the synthesis
of DHPMs known as Biginelli reaction involves the one-
pot condensation of an aldehyde, a b-ketoester and urea
under strong acidic conditions, which was first reported by
Biginelli in 1893.6 However, the yields of products were very
low (just 20–50%). From then on, many new techniques,
such as microwave-assisted synthesis technique,7 ionic liq-
uids,8 ultrasound irradiation,9 solvent-free techniques10 and
many new catalysts, such as InBr3,11 ZrCl4,12 CdCl2,13
BiCl3,14 etc., were used to improve this transformation. In
spite of their potential utility, many of these methods involve
expensive reagents, strongly acidic conditions, long reaction
times, high temperatures and stoichiometric amounts of cat-
alysts and unsatisfactory yields. Furthermore, the scope of
substrates was limited to aromatic aldehydes, acetoacetate
With our continuous investigation on the methodology of
green synthesis,16 we report herein, for the first time,
Biginelli-like reaction, i.e., three-component cycloconden-
sation of an aldehyde, acetophenone and urea, can be
successfully accomplished by using inexpensive ZnI2
as catalyst under solvent-free condition and microwave
(MW) irradiation, which is an efficient and environmen-
tally friendly preparation of 5-unsubstituted-3,4-dihydro-
pyrimidin-2(1H)-ones.
2. Results and discussion
We first began to study the reaction involving benzaldehyde
(5.0 mmol), acetophenone (5.0 mmol) and urea (6.0 mmol)
by examining the type of catalysts (Scheme 1). Many cata-
lysts or promoters, such as CH3COOH, Fe2(SO4)3,
(CH3)3SiCl, MgSO4, Mg(ClO4)2, HCl, H2SO4, etc., were
used to explore the reaction under solvent-free,
Keywords: Biginelli reactions; Solvent-free; Microwave-assisted; One-pot;
5-Unsubstituted-3,4-dihydropyrimidin-2(1H)-ones; Zinc iodide.
* Corresponding author. Tel.: +86 931 7970567; fax: +86 931 7768159;
e-mail: wangjx@nwnu.edu.cn
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.12.062

1982
B. Liang et al. / Tetrahedron 63 (2007) 1981–1986
O
O
O
O
HN
NH
acidic catalyst
H
CH3
+
H2N
NH2
+
MW, solvent-free
1a
Scheme 1. Microwave-assisted Biginelli-like reactions by various catalysts under solvent-free conditions.
microwave-assisted conditions (Table 1, entries 1–12). From
these results, we found that most of the Lewis acids and
Brønsted acids could promote the reaction, but the yields
were not so high. In comparison with other catalysts, the
use of 1.5 mmol of ZnI2 could make the yield reach 48% un-
der the microwave power (P) of 525 W and the irradiation
time of 5 min. From the results, we concluded that the reason
for ZnI2 being the best catalyst may be its strongly acidic
character. The amount of ZnI2 was further examined and
the results are summarized in Table 1, entries 14–18. It could
be seen that 20% molar amount of ZnI2 gave the best result
of this reaction, although other factors could not yet be
optimized.
could be found that with the increase of the microwave
power from 75 W to 750 W, the yield of 1b showed a linear
increase from 10% to 78% when the irradiation time was
5 min. However, with the microwave power of 750 W,
when we increased the microwave irradiation time, the
yield of 1b increased first, then showed a slight decrease
when the time was more than 9 min. So the optimized
microwave power and the irradiation time were 750 W and
8 min, respectively.
In order to examine the substrate scope of this Biginelli-like
reaction, various aromatic aldehydes with different substitu-
ents were used under the above-optimized reaction condi-
tions (Scheme 3); the results are shown in Table 3. From
the results, we could see that all reactions proceeded
smoothly to afford the corresponding DHPMs in moderate
to high yields. We also found that all aromatic aldehydes
carrying either electron-donating or electron-withdrawing
substituents reacted efficiently to give improved yields
compared to the classical Biginelli reaction. When some
aliphatic aldehydes and all solid materials were used in this
protocol under the above-optimized conditions, unfortu-
nately, the expected products could not be obtained. Further
investigations are underway.
Based on the above optimized results, i.e., 20% molar
amount of ZnI2 as a catalyst, we further examined the
effects of the microwave power and the irradiation time
on the Biginelli-like reaction, involving 3-methoxyphen-
aldehyde, acetophenone and urea to afford DHPM 1b, as
shown in Scheme 2. The results are listed in Table 2. It
Table 1. Effects of the type and the amount of catalysts on the formation
of 1aa
Entry
Catalyst (mmol)
t (min)
Yieldb (%)
1
2
3
4
5
6
7
8
—
CH3COOH (1.5)
HCl (1.5)
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
—
32
24
40
12
30
33
1.6
—
24
48
19
27
11
34
49
48
47
Table 2. Effects of the microwave power and the irradiation time on the for-
mation of 1ba
H2SO4 (1.5)
Fe2(SO4)3 (1.5)
FeCl3 (1.5)
AlCl3 (1.5)
(CH3)3SiCl (1.5)
MgSO4 (1.5)
Mg(ClO4)2 (1.5)
ZnI2 (1.5)
Entry
t (min)
P (W)
Yieldb (%)
1
2
3
4
5
6
7
8
5
5
5
5
5
5
2
4
6
75
150
300
450
600
750
750
750
750
750
750
750
10
16
30
45
56
78
17
54
81
89
89
88
9
10
11
12
13
14
15
16
17
18
I2 (1.5)
Al2O3 (1.5)
ZnI2 (0.1)
ZnI2 (0.5)
ZnI2 (1.0)
ZnI2 (1.2)
ZnI2 (2.0)
9
10
11
12
8
9
10
a
a
Reaction conditions: benzaldehyde 5.0 mmol; acetophenone 5.0 mmol;
urea 6.0 mmol; P¼525 W.
Reaction conditions: 3-methoxyphenaldehyde 5.0 mmol; acetophenone
5.0 mmol; urea 6.0 mmol; ZnI2 1.0 mmol.
Isolated yield.
b
b
Isolated yield.
O
O
O
O
HN
NH
ZnI2
MW, solvent-free
O
H
CH3
+
O
H2N
NH2
+
1b
Scheme 2. Microwave-assisted Biginelli-like reactions catalyzed by ZnI2 under solvent-free conditions.

B. Liang et al. / Tetrahedron 63 (2007) 1981–1986
1983
O
O
O
O
HN
NH
ZnI2, 8 min
MW (P=750 W), solvent-free
H
CH3
+
H2N
NH2
+
R
R
1a-p
Scheme 3. Microwave-assisted Biginelli-like reactions of various aromatic aldehydes.
It was noteworthy that highly symmetric Biginelli prod-
uct 1p was obtained with excellent yield when acetophe-
none was replaced by ethyl acetoacetate to react with
p-phthalaldehyde and urea (Table 3, entry 16). The other
Biginelli-like reactions including p-phthalaldehyde are
under investigation and will be reported in our future work.
Table 3. Cyclocondensation of aromatic aldehydes, acetophenone and urea
under microwave irradiation and solvent-free conditionsa
Table 3. (continued)
Yieldb (%)
Entry R
Product
Yieldb (%)
Entry R
Product
O
O
HN
HN
NH
NH
HN
NH
1
2
H
94
10
4-(CH3)3C
74
1a
1j
O
HN
HN
NH
O
O
3-CH3O
89
93
81
Br
1b
1c
11
3,5-Dibromo-4-OH
71
O
OH
NH
Br
1k
3
4
4-Cl
O
Cl
HN
NH
O
12
13
4-CH3
92
87
76
HN
NH Cl
2,6-Dichloro
1l
Cl
1d
O
O
O
O
HN
HN
NH
HN
NH Cl
4-CH3O
5
6
7
2,4-Dichloro
83
88
77
O
1m
Cl
Br
1e
1f
NH
O
HN
HN
NH
NH
O
O
3-Br
14
15
3,4-Dimethoxyl
1n
O
HN
NH Cl
4-OH
2-Cl
73
96
OH
1g
1h
1o
O
HN
NH
O
O
O
O
8
9
3-CH3O-4-OH
80
NH
O
16c
4-CHO
HN
NH
O
OH
HN
O
O
1p
HN
NH O
a
2-CH3O
75
Reaction conditions: aromatic aldehydes 5.0 mmol; acetophenone
5.0 mmol; urea 6.0 mmol; ZnI2 1.0 mmol; P¼750 W.
Isolated yield.
b
c
1i
(continued)
Acetophenone was replaced by ethyl acetoacetate.

1984
B. Liang et al. / Tetrahedron 63 (2007) 1981–1986
3. Conclusion
NH), 7.58–6.83 (m, 9H, Ar–H), 5.18 (d, 1H, J¼4.4 Hz,
C]CH), 5.10 (d, 1H, J¼4.4 Hz, CH), 3.43 (br, 1H, NH);
13C NMR (100 MHz, DMSO-d6): d 146.7, 159.4, 135.5,
134.0, 129.6, 128.5, 128.4, 118.3, 113.7, 112.4, 112.0,
143.1, 98.6, 55.0, 54.8. Anal. Calcd for C17H16N2O2:
C 72.84, H 5.75, N 9.99, found C 72.04, H 5.63, N 10.00;
HRMS (ESI) for [M+H] found (expected): 281.1289
(281.1285).
In conclusion, an efficient and high-yield protocol for the
synthesis of 5-unsubstituted-3,4-dihydropyrimidin-2(1H)-
ones involving three-component, one-pot condensation of
an aromatic aldehyde, acetophenone and urea using ZnI2
as catalyst under microwave irradiation and solvent-free
conditions was developed. High efficiency, short reaction
time, solvent-free condition and the use of inexpensive cat-
alyst were the advantages of this protocol. The described
procedure expanded the scope of the substrate and improved
the yield of three-component Biginelli-like cyclocondensa-
tion reactions as compared to classical Biginelli reaction.
It is believed that this versatile method applicable to parallel
synthesis will be of great value for the rapid generation of
structurally related compound libraries.
4.2.3. 3,4-(4-Chlorophenyl)-3,4-dihydro-6-phenylpyrimi-
din-2(1H)-one15 1c. White solid; mp 267–269 ꢀC; IR (KBr)
nmax: 3228, 2930, 1680, 1576, 1465 cmꢁ1 1H NMR
;
(400 MHz, DMSO-d6): d 8.69 (s, 1H, NH), 8.11 (s, 1H,
NH), 7.50–7.28 (m, 9H, Ar–H), 5.49 (d, J¼2.8 Hz, 1H,
]CH), 5.15 (d, 1H, J¼2.8 Hz, CH); 13C NMR (100 MHz,
DMSO-d6): d 153.7, 141.7, 136.3, 133.8, 130.3, 129.5,
128.9, 128.6, 128.4, 128.0, 127.8, 125.3, 96.1, 52.4. Anal.
Calcd for C16H13ClN2O: C 67.49, H 4.60, N 9.84, Cl
12.45, found C 66.99, H 4.58, N 10.00, Cl 12.52.
4. Experimental
4.1. General remarks
4.2.4. 4-(2,6-Dichlorophenyl)-3,4-dihydro-6-phenyl-pyri-
midin-2(1H)-one 1d (firstly reported). White solid; mp
274–276 ꢀC; IR (KBr) nmax: 3235, 2920, 1650, 1570,
All reactions were performed under a nitrogen atmosphere
with oven-dried glassware in the refitted stove.17 All reac-
tants were obtained from commercial sources and freshly
distilled prior to use. Reactions were monitored by TLC
on silica gel 60H with detection by charring with iodine.
Melting points were determined with an X-4 apparatus and
were not corrected. 1H (400 MHz) and 13C (100 MHz) NMR
spectra were recorded for DMSO-d6 solutions with TMS
as an internal standard at room temperature unless otherwise
specified. HRMS spectra were acquired with the use of
APEX II 47e spectrometer; IR spectra were obtained by
using an Alpha Centauri FT-IR spectrophotometer.
1402 cmꢁ1 1H NMR (400 MHz, DMSO-d6): d 8.57 (s,
;
1H, NH), 8.20 (s, 1H, NH), 8.16–7.28 (m, 8H, Ar–H), 5.89
(d, J¼4 Hz, 1H, ]CH), 5.56 (d, J¼4 Hz, 1H, CH); 13C
NMR (100 MHz, DMSO-d6): d 153.3, 142.2, 137.6, 132.3,
131.7, 128.7, 127.7, 126.3, 126.4, 125.6, 96.4, 32.1. Anal.
Calcd for C16H12Cl2N2O: C 60.20, H 3.79, N 8.78, Cl
22.21, found C 59.82, H 4.00, N 8.67, Cl 21.94.
4.2.5. 4-(2,4-Dichlorophenyl)-3,4-dihydro-6-phenylpyri-
midin-2(1H)-one 1e (firstly reported). White solid; mp
271–274 ꢀC; IR (KBr) nmax: 3279, 2952, 1655, 1587,
1415 cmꢁ1; 1H NMR (400 MHz, DMSO-d6): d 8.91 (s, 1H,
NH), 7.62–6.76 (m, 8H, Ar–H), 6.26 (d, J¼6.4 Hz, 1H,
]CH), 5.62 (s, 1H, NH), 5.31 (d, J¼6.4 Hz, 1H, CH); 13C
NMR (100 MHz, DMSO-d6): d 154.2, 142.7, 135.3, 134.4,
133.2, 129.3, 128.4, 127.4, 127.1, 126.3, 125.4, 95.3, 43.1.
Anal. Calcd for C16H12Cl2N2O: C 60.20, H 3.79, N 8.78,
Cl 22.21, found C 60.37, H 3.68, N 9.00, Cl 21.87.
4.2. Typical experimental procedure for the
synthesis of 1a
To a 50 mL flame dried round-bottom flask were added
0.53 g (5.0 mmol) of benzaldehyde, 0.60 g (5.0 mmol) of
acetophenone, 0.36 g (6.0 mmol) of urea and 0.319 g
(1.0 mmol) of ZnI2. The resulting mixture was placed into
the microwave reactor. After the reaction was completed,
distilled water was added into the flask and stirred for several
minutes and then filtrated through a sintered funnel to afford
the crude product, which was further purified by recrystalli-
zation (EtOH).
4.2.6. 4-(3-Bromophenyl)-3,4-dihydro-6-phenylpyrimi-
din-2(1H)-one 1f (firstly reported). White solid; mp 256–
258 ꢀC; IR (KBr) nmax
:
3122, 2923, 1693, 1572,
1401 cmꢁ1
;
1H NMR (400 MHz, DMSO-d6): d 9.16 (s,
1H, NH), 8.32–7.30 (m, 9H, Ar–H), 7.12 (s, 1H, NH), 5.52
(d, J¼5.6 Hz, 1H, ]CH), 5.14 (d, J¼5.6 Hz, 1H, CH);
13C NMR (100 MHz, DMSO-d6): d 152.9, 147.4, 135.8,
133.7, 130.3, 129.7, 128.7, 128.5, 128.0, 125.1, 124.9,
121.4, 121.3, 97.6, 54.2. Anal. Calcd for C16H13BrN2O: C
58.38, H 3.98, N 8.51, Br 24.27, found C 57.84, H 4.12, N
8.49, Br 24.12.
4.2.1. 3,4-Dihydro-4,6-diphenylpyrimidin-2(1H)-one15
1a. White solid; mp 245–246 ꢀC; IR (KBr) nmax: 3225,
2922, 1687, 1602, 1451 cmꢁ1
;
1H NMR (400 MHz,
DMSO-d6): d 8.57 (s, 1H, NH), 7.54–7.28 (m, 10H, Ar–H),
5.18 (d, 1H, J¼3.6 Hz, C]CH), 5.13 (d, 1H, J¼3.6 Hz,
CH), 3.43 (br, 1H, NH); 13C NMR (100 MHz, DMSO-d6):
d 153.5, 145.2, 134.1, 128.5, 128.3, 128.4, 127.2, 126.2,
125.3, 135.4, 98.7, 54.9. Anal. Calcd for C16H14N2O: C
76.78, H 5.64, N 11.19, found C 76.23, H 5.54, N 11.20;
HRMS (ESI) for [M+H] found (expected): 251.1183
(251.1179).
4.2.7. 3,4-Dihydro-4-(4-hydroxyphenyl)-6-phenylpyrimi-
din-2(1H)-one 1g (firstly reported). Yellow solid; mp 255–
257 ꢀC; IR (KBr) nmax: 3389, 2922, 1631, 1515, 1450 cmꢁ1
;
1H NMR (400 MHz, DMSO-d6): d 9.26 (s, 1H, NH), 8.17–
7.53 (m, 9H, Ar–H), 7.38–7.36 (s, 1H, NH), 7.23 (d,
J¼8.8 Hz, 1H, ]CH), 5.50 (s, 1H, OH), 5.13 (d,
J¼8.8 Hz, 1H, CH); 13C NMR (100 MHz, DMSO-d6):
d 156.8, 141.6, 131.4, 129.4, 128.9, 127.6, 127.5, 127.3,
124.1, 123.8, 124.9, 96.6, 55.4. Anal. Calcd for
4.2.2. 3,4-Dihydro-4-(3-methoxyphenyl)-6-phenylpyri-
midin-2(1H)-one 2b (firstly reported). White solid; mp
257–258 ꢀC; IR (KBr) nmax: 3209, 2933, 1689, 1598,
1402 cmꢁ1; 1H NMR (400 MHz, DMSO-d6): d 8.55 (s, 1H,

B. Liang et al. / Tetrahedron 63 (2007) 1981–1986
1985
C16H14N2O2: C 72.17, H 5.30, N 10.52, found C 72.00, H
5.31, N 10.34.
259–261 ꢀC; IR (KBr) nmax: 3381, 2932, 1613, 1515,
1
1402 cmꢁ1; H NMR (400 MHz, DMSO-d6): d 11.91 (s,
1H, NH), 9.33 (s, 1H, NH), 8.33–7.24 (m, 9H, Ar–H), 6.96
(d, J¼8.8 Hz, 1H, ]CH), 5.44 (d, J¼8.8 Hz, 1H, CH), 3.77
(s, 3H, OCH3); 13C NMR (100 MHz, DMSO-d6): d 162.1,
159.4, 152.8, 133.2, 131.4, 129.4, 128.7, 127.4, 114.2,
113.8, 79.2, 62.4, 55.5. Anal. Calcd for C17H16N2O2: C
72.84, H 5.75, N 10.00, found C 72.57, H 5.76, N 10.11.
4.2.8. 3,4-Dihydro-4-(4-hydroxy-3-methoxyphenyl)-6-
phenylpyrimidin-2(1H)-one 1h (firstly reported). White
solid; mp 267–268 ꢀC; IR (KBr) nmax: 3226, 2941, 1681,
1
1589, 1412 cmꢁ1; H NMR (400 MHz, DMSO-d6): d 8.83
(s, 1H, NH), 8.71–7.48 (m, 8H, Ar–H), 8.15 (s, 1H, NH),
7.11 (d, J¼4.8 Hz, 1H, ]CH), 5.32 (s, 1H, OH), 4.82 (d,
J¼4.8 Hz, 1H, CH); 13C NMR (100 MHz, DMSO-d6):
d 164.6, 163.1, 152.8, 136.6, 131.4, 129.4, 129.0, 128.0,
123.0, 121.5, 112.0, 111.4, 101.6, 55.9, 55.8. Anal. Calcd
for C17H16N2O3: C 68.91, H 5.44, N 9.45, found C 69.12,
H 5.33, N 9.63.
4.2.14. 3,4-Dihydro-4-(3,4-dimethoxyphenyl)-6-phenyl-
pyrimidin-2(1H)-one 1n (firstly reported). Yellow solid;
mp 243–245 ꢀC; IR (KBr) nmax: 3275, 2933, 1614, 1512,
1
1459 cmꢁ1; H NMR (400 MHz, DMSO-d6): d 11.95 (s,
1H, NH), 8.58 (s, 1H, NH), 8.58–7.44 (m, 8H, Ar–H), 7.82
(d, J¼8.4 Hz, 1H, ]CH), 7.06 (d, J¼8.4 Hz, 1H, CH),
3.91 (s, 3H, OCH3), 3.89 (s, 3H, OCH3); 13C NMR
(100 MHz, DMSO-d6): d 159.3, 151.8, 148.7, 131.3,
128.7, 127.5, 121.2, 111.4, 110.4, 79.1, 55.7, 55.6. Anal.
Calcd for C18H18N2O3: C 69.66, H 5.85, N 15.50, found C
69.65, H 5.84, N 9.01.
4.2.9. 3,4-Dihydro-4-(2-methoxyphenyl)-6-phenylpyri-
midin-2(1H)-one 1i (firstly reported). White solid; mp
266–267 ꢀC; IR (KBr) nmax: 3208, 2953, 1688, 1593,
1465 cmꢁ1 1H NMR (400 MHz, DMSO-d6): d 9.34 (s,
;
1H, NH), 8.51 (s, 1H, NH), 8.51–6.09 (m, 9H, Ar–H), 5.71
(d, J¼6.4 Hz, 1H, ]CH), 5.34 (d, J¼6.4 Hz, 1H, CH),
3.78 (s, 3H, OCH3); 13C NMR (100 MHz, DMSO-d6):
d 156.4, 153.0, 135.6, 134.5, 134.2, 132.5, 129.8, 128.6,
126.3, 126.0, 120.5, 111.2, 110.9, 97.5, 58.3, 55.4. Anal.
Calcd for C17H16N2O2: C 72.84, H 5.75, N 9.99, found C
71.89, H 5.88, N 10.00.
4.2.15. 4-(2-Chlorophenyl)-3,4-dihydro-6-phenylpyrimi-
din-2(1H)-one15 1o. White solid; mp 260–263 ꢀC; IR
1
(KBr) nmax: 3289, 2942, 1654, 1589, 1418 cmꢁ1; H NMR
(400 MHz, DMSO-d6): d 8.60 (s, 1H, NH), 8.15 (s, 1H,
NH), 7.42–7.15 (m, 9H, Ar–H), 5.45 (d, J¼4.4 Hz, 1H,
]CH), 5.12 (d, 1H, J¼2.8 Hz, CH); 13C NMR (100 MHz,
DMSO-d6): d 154.7, 145.7, 138.3, 135.8, 131.6, 129.5,
128.8, 128.6, 128.4, 128.1, 127.5, 125.5, 94.1, 54.3. Anal.
Calcd for C16H12Cl2N2O: C 60.21, H 3.79, N 8.78, Cl
22.21, found C 60.31, H 3.71, N 9.00, Cl 21.96.
4.2.10. 4-(4-tert-Butylphenyl)-3,4-dihydro-6-phenylpyri-
midin-2(1H)-one 1j (firstly reported). White solid; mp
238–240 ꢀC; IR (KBr) nmax: 3221, 2960, 1695, 1577,
1411 cmꢁ1 1H NMR (400 MHz, DMSO-d6): d 8.32 (s,
;
1H, NH), 7.45–7.12 (m, 9H, Ar–H), 5.27 (d, 1H,
J¼4.8 Hz, C]CH), 5.14 (d, 1H, J¼3.6 Hz, CH), 5.54 (s,
1H, NH), 1.45 (s, 6H, CH3); 13C NMR (100 MHz, DMSO-
d6): d 154.6, 143.1, 134.3, 128.6, 128.5, 128.2, 127.2,
126.4, 125.3, 136.5, 99.5, 53.5, 42.2, 30.8. Anal. Calcd for
C20H22N2O: C 78.40, H 7.24, N 9.14, found C 78.41, H
7.32, N 9.04.
4.2.16. Ethyl-4-(4-(5-(ethoxycarbonyl)-1,2,3,4-tetrahy-
dro-6-methyl-2-oxopyrimidin-4-yl)phenyl)-1,2,3,4-tetra-
hydro-6-methyl-2-oxopyrimidine-5-carboxylate 1p
(firstly reported). Slightly yellow solid; mp >350 ꢀC; IR
1
(KBr) nmax: 3355, 2976, 1701, 1646, 1456, 1375 cmꢁ1; H
NMR (400 MHz, pyridine-d6): d 9.16 (s, 4H, NH), 7.67–
7.14 (m, 4H, Ar–H), 5.11–5.14 (m, 2H, CH), 3.99–3.94
(m, 4H, CH2–R), 2.25–2.19 (m, 6H, H3C–C]C), 1.13–
1.03 (m, 6H, CH3–C); 13C NMR (100 MHz, pyridine-d6):
d 165.3, 152.1, 148.3, 143.9, 126.3, 99.2, 59.2, 53.7, 17.7,
14.1; HRMS (ESI) for C22H26N4O6 [M+Na] found (ex-
pected): 465.1756 (465.1759).
4.2.11. 4-(3,5-Dibromo-4-hydroxyphenyl)-3,4-dihydro-6-
phenylpyrimidin-2(1H)-one 1k (firstly reported). Slightly
red solid; mp 256–260 ꢀC; IR (KBr) nmax: 3276, 3089, 1656,
1553, 1408 cmꢁ1; 1H NMR (400 MHz, pyridine-d6): d 9.214
(s, 1H, NH), 8.21–7.56 (m, 9H, Ar–H), 6.45 (s, 1H, NH),
5.47 (d, J¼3.2 Hz, 1H, ]CH), 5.23 (d, J¼3.2 Hz, 1H,
CH), 2.84 (s, 1H, OH); 13C NMR (100 MHz, pyridine-d6):
d 156.7, 146.2, 136.5, 133.6, 130.5, 128.6, 124.8, 121.4,
113.8, 99.1, 55.4. Anal. Calcd for C16H12Br2N2O2: C
45.31, H 2.85, N 6.61, found C 45.25, H 2.78, N 6.55.
Acknowledgements
The work was supported by the Natural Science Foundation
of China (Grants 20272047, 20572086), the Gansu Natural
Science Foundation of China (3ZS051-A25-001) and Key
Laboratory of Eco-Environment-Related Polymer Material
(Northwest Normal University), Ministry of Education of
China.
4.2.12. 3,4-Dihydro-6-phenyl-4-p-tolylpyrimidin-2(1H)-
one15 1l. White solid; mp 248–250 ꢀC; IR (KBr) nmax
:
3235, 2920, 1650, 1570, 1402 cmꢁ1; H NMR (400 MHz,
DMSO-d6): d 9.24 (s, 1H, NH), 8.48 (s, 1H, NH), 7.84–
6.00 (m, 9H, Ar–H), 5.56 (d, J¼6.8 Hz, 1H, ]CH), 5.31
(d, J¼6.8 Hz, 1H, CH), 2.42 (s, 3H, CH3); 13C NMR
(100 MHz, DMSO-d6): d 157.5, 136.4, 133.4, 133.1,
132.5, 129.3, 128.4, 126.2, 125.6, 120.3, 111.1, 110.1,
99.3, 23.1. Anal. Calcd for C17H16N2O: C 77.25, H 6.10,
N 10.60, found C 77.32, H 5.99, N 10.61.
1
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