An efficient synthesis of 3,4-dihydropyrimidin-2(1H)-one and 5,6-diphenylpyrimidine derivatives under solvent-free and base conditions

Article abstract of DOI:10.1007/s11164-016-2842-y

An efficient and convenient Biginelli-like reaction one-pot synthesis of a series of 4-aryl-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one and 4-aryl-5,6-diphenylpyrimidine derivatives under solvent-free conditions from the reaction of aromatic aldehydes, 1,2-diphenylethanone, urea, guanidine carbonate or acetamidine hydrochloride has been reported. This methodology has the advantages of short reaction time, mild reaction conditions, easy work-up and environmental friendliness. Moreover, 4-aryl-5,6-diphenylpyrimidine derivatives were first reported in this process. The structures of the title compounds were further determined by X-ray diffraction. More importantly, different from general Biginelli reaction, this reported method was carried out under base conditions.

Full text of DOI:10.1007/s11164-016-2842-y

Res Chem Intermed
DOI 10.1007/s11164-016-2842-y
An efficient synthesis of 3,4-dihydropyrimidin-2(1H)-
one and 5,6-diphenylpyrimidine derivatives
under solvent-free and base conditions
Jing Xu1 Ganlu Hao1 Xu Gao1 Hui Xu1
Liangce Rong1
•
•
•
•
Received: 4 October 2016 / Accepted: 16 December 2016
Ó Springer Science+Business Media Dordrecht 2017
Abstract An efficient and convenient Biginelli-like reaction one-pot synthesis of a
series of 4-aryl-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one and 4-aryl-5,6-
diphenylpyrimidine derivatives under solvent-free conditions from the reaction of
aromatic aldehydes, 1,2-diphenylethanone, urea, guanidine carbonate or acet-
amidine hydrochloride has been reported. This methodology has the advantages of
short reaction time, mild reaction conditions, easy work-up and environmental
friendliness. Moreover, 4-aryl-5,6-diphenylpyrimidine derivatives were first repor-
ted in this process. The structures of the title compounds were further determined by
X-ray diffraction. More importantly, different from general Biginelli reaction, this
reported method was carried out under base conditions.
Keywords 3,4-Dihydropyrimidin-2(1H)-one Á 5,6-Diphenylpyrimidine Á 1,2-
Diphenylethanone Á Solvent-free Á Synthesis
Introduction
As we all know, N-heterocyclic compounds, such as pyrimidines and dihydropy-
rimidinones, are very important synthetic intermediates in organic synthesis.
Pyrimidines show diverse biological activities, such as antiviral [1, 2], antitumor
[3], antioxidant [4], and other activities [5–8]. In addition, dihydropyrimidinones
Electronic supplementary material The online version of this article (doi:10.1007/s11164-016-2842-y)
contains supplementary material, which is available to authorized users.
&
Liangce Rong
lcrong2005@yahoo.com
1
Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, College of
Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou 221116, Jiangsu,
People0s Republic of China
123

J. Xu et al.
and their derivatives have also attracted considerable attention due to their wide
range of biological activities [9–16]. Thus, it is of great significance to synthesize
these types of compounds. The Biginelli reaction is one of the most important
procedures for the synthesis of dihydropyrimidinones [17]. The improved Biginelli-
like reaction was reported by Wang et al. [18] using FeCl3Á6H2O and TMSCl as
catalysts. Many other improved Biginelli-like reactions have been reported by
several groups [19–25]. However, many of the established methods still suffer from
high reaction temperatures, expensive metal precursors, acid catalysts, or prolonged
reaction time.
Organic reactions under solvent-free conditions are ideal protocols for the
development of environmentally friendly and economically advantageous chemical
processes [26–28]. Such methods not only meet the requirements of sustainable
development, but also reflects the concept of low-carbon economy. Herein, we
describe a novel mild base-promoted (NaOH) one-pot synthesis of 3,4-dihydropy-
rimidin-2(1H)-one (or 2-amine-5,6-diphenylpyrimidine) via a three-component
condensation of aromatic aldehyde, 1,2-diphenylethanone and urea (guanidine
carbonate or acetamidine hydrochloride) with excellent yields under solvent-free
conditions.
Results and discussion
Initially, we investigated the reaction of aromatic aldehyde, 1,2-diphenylethanone
and urea in reported literatures. It was found that only several approaches were
reported by some research groups. Kefayati reported this reacton could be operated
in DMF using Me3SiCl and Co(OAc)2 4H2O as catalysts [29] or carried out this
reaction catalyzed by Me3SiCl in ionic liquid [30]. In 2014, Lokwani completed this
reaction in EtOH using K2CO3 as catalyst under reflux condition [31]. In 2010, Ji
and his co-workers reported this Biginelli-type reaction in the presence of t-BuOK as
catalyst in refluxing EtOH [32]. However, this process must be carried out under
anhydrous conditions, and the reaction time is very long (7–24 h). Therefore, other
simpler methods for the synthesis of these kinds of compounds are still needed.
In order to find a simple operation and to easily obtain the catalyst, we initiated
our studies by investigating the effect of different solvents, temperatures, and
catalysts using 4-chlorobenzaldehyde, 1,2-diphenylethanone and urea as standard
materials. The results are summarized in Table 1. It is shown that the Lewis acids
such as ZnCl2, FeCl3, HgCl2, and I2 had no effect on the reaction (Table 1, entries
1–4). Using proton acid (HCl, 37%) as catalyst, the yield is still poor (Table 1, entry
5). Our attention then turned to investigate the effect of common alkalic catalysts
like Ba(OH)2, K2CO3, NaOH. Initially, we found that the yields were poor when
Na2CO3 or Ba(OH)2 was used in model reaction (Table 1, entries 6–7). When
NaOH was used as catalyst in different solvents (EtOH, DMF, THF, MeOH, or
toluene), the yields are still lower than expected (Table 1, entries 8–12).
Surprisingly, excellent yield is obtained when the reaction is carried out under
solvent-free conditions using NaOH as a catalyst (Table 1, entry 13). Further study
found that the similar yields can be obtained when the loading amount of NaOH is
123

An efficient synthesis of 3,4-dihydropyrimidin-2(1H)-one…
Table 1 Optimization of
Entry Conditions
Yield (%)
reaction conditions using
different catalysts and
temperatures
1
ZnCl2 (1 equiv), EtOH, 70 °C, 30 min
0
2
HgCl2 (1 equiv), EtOH, 70 °C, 30 min
FeCl3 (1 equiv), EtOH, 70 °C, 30 min
I2 (1 equiv), EtOH, 70 °C, 30 min
0
3
0
4
0
5
HCl (37%, 1 equiv), EtOH, 70 °C, 30 min
Na2CO3 (1 equiv), EtOH, 70 °C, 30 min
Ba(OH)2 (1 equiv), EtOH, 70 °C, 30 min
NaOH (1 equiv), EtOH, 70 °C, 30 min
NaOH (1 equiv), DMF, 100 °C, 30 min
NaOH (1 equiv), toluene, 100 °C, 30 min
NaOH (1 equiv), MeOH, 70 °C, 30 min
NaOH (1 equiv), THF, 70 °C, 30 min
NaOH (1 equiv), solvent-free, 70 °C, 30 min
Trace
20
15
40
32
20
44
18
88
6
7
8
9
10
11
12
13
14
15
16
The reaction conditions:
4-chlorobenzaldehyde
(1 mmol), 1,2-diphenylethanone
(1 mmol), urea (1.5 mmol),
solvents (5 mL)
NaOH (0.5 equiv), solvent-free, 70 °C, 30 min 90
NaOH (0.3 equiv), solvent-free, 70 °C, 30 min 89
NaOH (1 equiv), solvent-free, 50 °C, 60 min
30
reduced to 0.5 or 0.3 equiv (90 and 89% yields, Table 1, entries 14–15) under the
same reaction conditions. The study also found that low temperature is not
conducive to the completion of the model reaction (Table 1, entry 16; Scheme 1).
Therefore, taking overall factors of reaction time, temperature, solvent, and
amount of catalyst into consideration, we will perform the reaction at 70 °C using a
catalytic amount of NaOH (30 mol%) under solvent-free conditions. In order to
examine the substrate scope of this Biginelli-like reaction, we applied the approach
to various aromatic aldehydes carrying electron-withdrawing or electron-donating
substituents under the above-optimized reaction conditions (Scheme 2). From the
results, it can be seen that aromatic aldehydes with different substituted groups can
be successfully applied to this synthesis method. The results are listed in Table 2.
In order to expand the scope of this study, and to obtain other nitrogen-containing
heterocyclic compounds, guanidine carbonate was also invovled in this process; the
novel 4-aryl-5,6-diphenylpyrimidine derivatives were obtained with high yields
Cl
CHO
Ph
Ph
O
O
Solvent-free
Ph
Ph
+
NH
+
H2N
NH2
N
H
O
Cl
1d
2
3
4d
Scheme 1 The model reaction of compound 4d
123

J. Xu et al.
R1
CHO
Ph
Ph
O
O
Solvent-free
Ph
Ph
+
R1
NH
+
H2N
NH2
N
H
O
1
2
3
4
Scheme 2 Synthesis of 3,4-dihydropyrimidin-2(1H)-one derivatives
Table 2 The results of
synthesis of 3,4-
Entry
R1
Product
Time (min)
Yields (%)
dihydropyrimidin-2(1H)-one
derivatives
1
4-FC6H4
4a
4b
4c
4d
4e
4f
30
30
30
30
30
30
30
35
45
35
35
30
40
30
30
85
94
92
89
86
88
92
83
89
91
88
96
94
88
89
2
2-ClC6H4
3
3-ClC6H4
4
4-ClC6H4
5
2,4-Cl2C6H3
3,4-Cl2C6H3
3-BrC6H4
6
7
4g
4h
4i
8
C6H5
9
3,4-(CH3)2C6H3
2-CH3OC6H4
4-CH3OC6H4
2,5-(CH3O)2C6H3
3,4-(CH3O)2C6H3
3,4-OCH2O-C6H3
2-pyridyl
10
11
12
13
14
15
4j
4k
4l
4m
4n
4o
R1
CHO
Ph
O
NH
Ph
Solvent-free
N
HX
n
R2
NH2
+
R1
+
Ph
N
R2
Ph
HX = H2CO3, R2 = NH2, n=2
HX = HCl,
R2 = CH3, n=1
1
2
5
6
Scheme 3 Synthesis of 2-amine-5,6-diphenylpyrimidine derivatives
(Scheme 3). At the same time, we found that acetamidine hydrochloride was not
suitable for this research method; only two corresponding products were obtained.
The results are listed in Table 3.
The structures of all the products were confirmed by spectroscopic data,
1
1
particularly IR, H NMR, 13C NMR and HRMS. For example, in H-NMR of 4i, it
shows two singlets signals at delta 2.19 and 2.20 due to the two CH3 protons and
123

An efficient synthesis of 3,4-dihydropyrimidin-2(1H)-one…
Table 3 The results of synthesis of 2-amine-5,6-diphenylpyrimidine derivatives
Entry
R1
R2
Product
Time (min)
Yields (%)
1
C6H5
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
CH3
CH3
6a
6b
6c
6d
6e
6f
45
35
40
40
38
42
50
40
45
40
35
90
88
90
91
85
95
87
89
83
90
86
2
4-FC6H4
3
3,4-Cl2C6H3
4-BrC6H4
4
5
4-CH3C6H4
6
3,4-(CH3)2C6H3
2,5-(CH3O)2C6H3
3,4-(CH3O)2C6H3
3,4-OCH2OC6H3
4-CH3OC6H4
3,4-(CH3)2C6H3
7
6g
6h
6i
8
9
10
11
6j
6k
two singlets at delta 7.45 and 8.65 due to the –NH– protons. A doublet signal at
5.04 ppm is a proton of C4-H. The 13 aromatic hydrogen protons distribute from
6.79 to 7.26 ppm. In 13C-NMR, the chemical shifts of 24 carbon atoms show at
19.1, 19.6, 59.0, 109.5, 124.4, 125.8, 127.7, 128.0, 128.1, 128.2, 129.2, 129.4,
129.7, 134.6, 135.1, 135.3, 136.2, 138.2, 141.3 and 153.1 respectively. In the HRMS
spectrum, the calculated m/z for C24H22N2O [M ? Na]? is 377.1624, and we found
m/z to be 377.1640.
In IR of 6f, the wave numbers of –NH2 could be found at 3495, 3282 and
3155 cm-1. In its 1H-NMR, the two singlets appear at delta 2.10 and 2.15 due to the
two CH3 protons. The 13 aromatic hydrogen protons could be found from 6.82 to
7.25 ppm. The 13C chemical shifts are 19.1, 19.3, 120.3, 126.4, 126.7, 127.3, 127.8,
127.9, 128.3, 129.1, 130.5, 131.4, 135.2, 136.3, 136.4, 137.4, 139.2, 162.2, 165.6
and 165.9 respectively. In the HRMS spectrum, the calculated m/z for C24H21N3
[M ? H]? is 352.1808, and it is found at 352.1807.
The structures of 4o and 6h are additionally confirmed by X-ray diffraction
analysis. The crystal structures are shown in Figs. 1 and 2.
Conclusions
In summary, we have described a successful, simple and efficient green approach
for the preparation of 3,4-dihydropyrimidin-2(1H)-one and 2-amine-5,6-diphenyl
pyrimidine derivatives involing aromatic aldehydes 1, 1,2-diphenylethanone 2, urea
3 or guanidine carbonate and acetamidine hydrochloride 5 under solvent-free
conditions. Advantages of this method include mild reaction conditions, low cost,
operational simplicity and reduced environmental impact. Moreover, the products
were obtained in excellent yields within short reaction times and the starting
materials are also inexpensive and commercially available. More importantly,
different from general Biginelli reaction, this reported method was carried out under
base conditions.
123

J. Xu et al.
Fig. 1 X-ray structure of 4o
Fig. 2 X-ray structure of 6h
123

An efficient synthesis of 3,4-dihydropyrimidin-2(1H)-one…
Experimental
Melting points were determined on an XT-5 microscopic melting point apparatus
1
and were uncorrected. IR spectra were recorded on a FT IR-8101 spectrometer. H
NMR and 13C NMR spectra were obtained from solution in DMSO-d6 with Me4Si
as internal standard using a Bruker-400 spectrometer. HRMS spectra were obtained
with a Bruker micrOTOF-Q 134 instrument. X-ray diffractions were recorded on a
Siemens P4 or Simart-1000 diffractometer. All reagents were purchased from
chemical reagent companies and used without further purification.
General Procedure for the synthesis of 3,4-dihydropyrimidin-2(1H)-one
and 2-amine-5,6-diphenylpyrimidine derivatives
A mixture of aromatic aldehydes 1 (1 mmol), 1,2-diphenylethanone 2 (1 mmol),
urea 3 (1.5 mmol) or guanidine carbonate and acetamidine hydrochloride 5
(1 mmol), and NaOH (0.3 mmol) was heated in a round-bottom flask at 70 °C over
the course of 30 min. After the reaction was completed (monitored by thin-layer
chromatography, TLC), the reaction mixture was poured into water, and then
washed with water thoroughly. The product was filtered, dried, and recrystallized
from 95% ethanol.
4-(4-Fluorophenyl)-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one (4a)
m.p. 253–255°C; IR (KBr, m, cm-1): 3207, 3082, 1688, 1602, 1508, 1475, 1329,
1276, 1223, 1186, 1155, 1073, 840, 766, 698, 665, 588, 513 cm-1 1H NMR
;
(400 MHz, DMSO-d6) (d, ppm): 5.18 (1H, d, J = 2.8 Hz, C4-H), 6.80 (2H, t,
J = 7.6 Hz, ArH), 6.98–7.04 (3H, m, ArH), 7.17 (2H, t, J = 8.8 Hz, ArH),
7.21–7.25 (5H, m, ArH), 7.40 (2H, dd, J = 6.0 Hz, J = 8.8 Hz, ArH), 7.54 (1H, s,
NH), 8.69 (1H, s, NH); 13C NMR (100 MHz, DMSO-d6) (d, ppm): 58.6, 109.5,
114.5, 114.7, 115.1, 115.2, 115.4, 125.9, 127.0, 127.6, 127.8, 127.9, 128.0, 128.9,
129.1, 129.3, 131.5, 134.7, 134.8, 135.1, 137.9, 140.0, 140.1, 153.2, 160.3, 161.1,
162.7, 163.6; HRMS m/z calculated for C22H17FN2O [M ? Na]?: 367.1223, found:
367.1246.
4-(2-Chlorophenyl)-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one (4b)
m.p. 235–236°C (lit. [32] 237–239 °C); IR (KBr, m, cm-1): 3226, 3100, 1696, 1645,
1
1495, 1463, 1455, 1267, 1189, 762, 744, 697, 589 cm-1; H NMR (400 MHz,
DMSO-d6) (d, ppm): 5.70 (1H, d, J = 2.4 Hz, C4-H), 6.77 (2H, dd, J = 2.4 Hz,
J = 7.6 Hz, ArH), 6.97–7.01 (3H, m, ArH), 7.19–7.25 (5H, m, ArH), 7.28 (1H, d,
J = 8.4 Hz, ArH), 7.35–7.40 (2H, m, ArH), 7.48 (1H, s, NH), 7.64 (1H, d,
J = 7.6 Hz, ArH), 8.72 (1H, s, NH); 13C NMR (100 MHz, DMSO-d6) (d, ppm):
56.6, 108.5, 126.1, 126.6, 127.0, 127.6, 127.7, 127.9, 128.0, 128.2, 128.9, 129.2,
129.3, 129.4, 129.6, 129.7, 131.8, 134.8, 135.0, 137.4, 140.7, 152.8, 162.3; HRMS
m/z calculated for C22H17ClN2O [M ? Na]?: 383.0922, found: 383.0943.
123

J. Xu et al.
4-(3-Chlorophenyl)-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one (4c)
m.p. 214–216°C (lit. [29] 199–201 °C); IR (KBr, m, cm-1): 3230, 3085, 1698, 1596,
1573, 1431, 1321, 1267, 1178, 1078, 1000, 851, 765, 699, 590, 512 cm-1; 1H NMR
(400 MHz, DMSO-d6) (d, ppm): 5.21 (1H, d, J = 2.8 Hz, C4-H), 6.80 (2H, d,
J = 8.0 Hz, ArH), 6.99–7.05 (3H, m, ArH), 7.19–7.26 (5H, m, ArH), 7.32–7.39
(4H, m, ArH), 7.59 (1H, s, NH), 8.73 (1H, s, NH); 13C NMR (100 MHz, DMSO-d6)
(d, ppm): 58.7, 108.9, 125.6, 126.0, 126.9, 127.5, 127.8, 128.1, 128.3, 129.3, 130.6,
133.1, 134.8, 135.1, 137.7, 146.2, 152.9; HRMS m/z calculated for C22H17ClN2O
[M ? H]?: 361.1107, found: 361.1143.
4-(4-Chlorophenyl)-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one (4d)
m.p. 253–254°C (lit. [32] 263–265 °C); IR (KBr, m, cm-1): 3213, 3085, 1689, 1491,
1
1474, 1409, 1329, 1270, 1189, 1091, 1017, 833, 769, 697, 588 cm-1; H NMR
(400 MHz, DMSO-d6) (d, ppm): 5.19 (1H, d, J = 2.8 Hz, C4-H), 6.79 (2H, d,
J = 7.6 Hz, ArH), 6.98–7.03 (3H, m, ArH), 7.19–7.25 (5H, m, ArH), 7.36 (2H, d,
J = 8.4 Hz, ArH), 7.41 (2H, d, J = 8.4 Hz, ArH), 7.55 (1H, s, NH), 8.69 (1H, s,
NH); 13C NMR (100 MHz, DMSO-d6) (d, ppm): 56.5, 108.5, 126.1, 127.7, 127.8,
127.9, 128.1, 129.3, 129.4, 129.5, 129.7, 131.8, 134.8, 135.0, 137.4, 140.6, 152.8,
162.3; HRMS m/z calculated for C22H17ClN2O [M ? Na]?: 383.0922, found:
383.0945.
4-(2,4-Dichlorophenyl)-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one (4e)
m.p. 197–199°C; IR (KBr, m, cm-1): 3223, 3100, 1698, 1644, 1560, 1495, 1464,
1381, 1267, 1184, 1094, 823, 772, 697, 592 cm-1; 1H NMR (400 MHz, DMSO-d6)
(d, ppm): 5.72 (1H, d, J = 2.4 Hz, C4-H), 6.78 (2H, t, J = 8.0 Hz, ArH), 6.97–7.02
(3H, m, ArH), 7.18–7.23 (5H, m, ArH), 7.46 (1H, dd, J = 1.2 Hz, J = 8.4 Hz,
ArH), 7.51 (1H, d, J = 2.0 Hz, ArH), 7.53 (1H, s, NH), 7.62 (1H, t, J = 8.4 Hz,
ArH), 8.76 (1H, s, NH); 13C NMR (100 MHz, DMSO-d6) (d, ppm): 56.4, 108.2,
126.2, 127.8, 127.9, 128.0, 128.2, 128.9, 129.3, 129.4, 131.2, 132.8, 132.9, 134.6,
135.2, 137.2, 139.7, 152.9, 162.3; HRMS m/z calculated for C22H16Cl2N2O
[M ? H]?: 395.0712, found: 395.0711.
4-(3,4-Dichlorophenyl)-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one (4f)
m.p. 235–237°C; IR (KBr, m, cm-1): 3224, 3101, 1692, 1655, 1598, 1541, 1472,
1446, 1400, 1324, 1266, 1188, 1131, 1073, 1032, 877, 818, 771, 736, 698,
590 cm-1; 1H NMR (400 MHz, DMSO-d6) (d, ppm): 5.27 (1H, d, J = 2.8 Hz, C4-
H), 6.81 (2H, dd, J = 2.0 Hz, J = 8.0 Hz, ArH), 6.97–7.02 (3H, m, ArH),
7.17–7.23 (5H, m, ArH), 7.31 (1H, dd, J = 2.8 Hz, J = 7.2 Hz, ArH), 7.45 (1H, d,
J = 8.0 Hz, ArH), 7.56 (1H, s, NH), 7.83 (1H, t, J = 7.6 Hz, ArH), 8.68 (1H, s,
NH); 13C NMR (100 MHz, DMSO-d6) (d, ppm): 58.7, 108.9, 125.6, 126.0, 126.9,
127.5, 127.8, 128.1, 128.3, 129.3, 130.6, 133.1, 134.8, 135.1, 137.7, 146.2, 152.9;
HRMS m/z calculated for C22H16Cl2N2O [M ? Na]?: 417.0532, found: 417.0543.
123

An efficient synthesis of 3,4-dihydropyrimidin-2(1H)-one…
4-(3-Bromophenyl)-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one (4g)
m.p. 193–194°C; IR (KBr, m, cm-1): 3231, 3098, 1697, 1651, 1599, 1568, 1472,
1
1319, 1266, 1176, 1071, 764, 699, 590 cm-1; H NMR (400 MHz, DMSO-d6) (d,
ppm): 5.20 (1H, d, J = 2.8 Hz, C4-H), 6.81 (2H, d, J = 7.6 Hz, ArH), 7.00–7.05
(3H, m, ArH), 7.21–7.26 (5H, m, ArH), 7.32 (1H, d, J = 7.6 Hz, ArH), 7.37 (1H, d,
J = 7.6 Hz, ArH), 7.47 (1H, d, J = 7.6 Hz, ArH), 7.51 (1H, s, ArH), 7.58 (1H, s,
NH), 8.72 (1H, s, NH); 13C NMR (100 MHz, DMSO-d6) (d, ppm): 58.7, 108.9,
120.9, 121.8, 126.0, 127.1, 127.7, 127.8, 128.0, 128.1, 128.3, 129.1, 129.2, 129.3,
129.7, 129.9, 130.4, 130.9, 131.5, 131.8, 134.8, 134.9, 135.1, 137.7, 146.4, 153.0,
162.3; HRMS m/z calculated for C22H17BrN2O [M ? Na]?: 427.0421, found:
427.0442.
4,5,6-Triphenyl-3,4-dihydropyrimidin-2(1H)-one (4h)
m.p. 253–254°C (lit. [32] 241–243 °C); IR (KBr, m, cm-1): 3208, 3082, 1688, 1602,
1508, 1475, 1329, 1276, 1223, 1186, 1155, 1092, 840, 766, 698, 664, 588,
1
513 cm-1; H NMR (400 MHz, DMSO-d6) (d, ppm): 5.18 (1H, d, J = 2.8 Hz,
ArCH), 6.79 (2H, d, J = 7.6 Hz, C4-H), 6.97–7.03 (3H, m, ArH), 7.12–7.25 (8H, m,
ArH), 7.40 (2H, dd, J = 5.6 Hz, J = 8.4 Hz, ArH), 7.54 (1H, s, NH), 8.69 (1H, s,
NH); 13C NMR (100 MHz, DMSO-d6) (d, ppm): 60.5, 76.7, 77.0, 77.3, 77.4, 111.1,
115.2, 115.7, 115.9, 126.7, 128.1, 128.5, 128.7, 128.8, 129.7, 129.8, 133.1, 134.8,
137.1, 138.7, 161.2, 163.7; HRMS m/z calculated for C22H18N2O [M ? Na]?:
349.1317, found: 363.1494.
4-(3,4-Dimethylphenyl)-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one (4i)
m.p. 208–209°C; IR (KBr, m, cm-1): 3228, 3089, 1698, 1649, 1480, 1321, 1268,
1
1180, 1124, 1094, 1023, 773, 699, 591 cm-1; H NMR (400 MHz, DMSO-d6) (d,
ppm): 2.19 (3H, s, CH3), 2.20 (3H, s, CH3), 5.04 (1H, d, J = 2.8 Hz, C4-H), 6.79
(2H, d, J = 7.6 Hz, ArH), 6.97–7.02 (3H, m, ArH), 7.10 (2H, s, ArH), 7.13 (1H, s,
ArH), 7.21–7.26 (5H, m, ArH), 7.45 (1H, s, NH), 8.65 (1H, s, NH); 13C NMR
(100 MHz, DMSO-d6) (d, ppm): 19.1, 19.6, 59.0, 109.5, 124.4, 125.8, 127.7, 128.0,
128.1, 128.2, 129.2, 129.4, 129.7, 134.6, 135.1, 135.3, 136.2, 138.2, 141.3, 153.1;
HRMS m/z calculated for C24H22N2O [M ? Na]?: 377.1624, found: 377.1640.
4-(2-Methoxyphenyl)-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one (4j)
m.p. 251–252°C; IR (KBr, m, cm-1): 3418, 3271, 1694, 1645, 1598, 1556, 1504,
1
1486, 1462, 1445, 1268, 1245, 1186, 1030, 758, 697 cm-1; H NMR (400 MHz,
DMSO-d6) (d, ppm): 3.73 (3H, s, OCH3), 5.48 (1H, d, J = 2.8 Hz, C4-H), 6.77 (2H,
dd, J = 1.6 Hz, J = 7.6 Hz, ArH), 6.96–7.02 (5H, m, ArH), 7.08 (1H, s, NH),
7.22–7.29 (6H, m, ArH), 7.46 (1H, dd, J = 1.2 Hz, J = 7.6 Hz, ArH), 8.61 (1H, s,
NH); 13C NMR (100 MHz, DMSO-d6) (d, ppm): 58.7, 108.9, 120.9, 121.9, 126.0,
127.1, 127.6, 127.7, 127.8, 128.0, 128.1, 128.3, 129.1, 129.3, 129.7, 129.9, 130.4,
123

J. Xu et al.
130.9, 131.5, 131.8, 134.8, 134.9, 135.1, 137.7, 146.4, 153.0, 153.1, 162.3; HRMS
m/z calculated for C23H20N2O2 [M ? Na]?: 379.1417, found: 379.1433.
4-(4-Methoxyphenyl)-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one (4k)
m.p. 211–213°C (lit. [32] 224–226 °C); IR (KBr, m, cm-1): 3217, 3085, 1685, 1611,
1512, 1472, 1306, 1254, 1237, 1173, 1035, 832, 771, 697, 588, 517 cm-1; 1H NMR
(400 MHz, DMSO-d6) (d, ppm): 3.73 (3H, s, OCH3), 5.07 (1H, d, J = 2.4 Hz, C4-
H), 6.79 (2H, d, J = 7.6 Hz, ArH), 6.91 (2H, d, J = 8.4 Hz, ArH), 6.97–7.03 (3H,
m, ArH), 7.21–7.26 (5H, m, ArH), 7.29 (2H, d, J = 8.4 Hz, ArH), 7.43 (1H, s, NH),
8.61 (1H, s, NH); 13C NMR (100 MHz, DMSO-d6) (d, ppm): 55.0, 58.6, 109.7,
113.9, 125.9, 127.7, 128.1, 128.2, 129.2, 129.3, 134.5, 135.0, 135.9, 138.1, 153.1,
158.6; HRMS m/z calculated for C23H20N2O2 [M ? Na]?: 379.1417, found:
379.1434.
4-(2,5-Dimethoxyphenyl)-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one (4l)
m.p. 237–239°C; IR (KBr, m, cm-1): 3206, 3096, 1683, 1664, 1495, 1460, 1447,
1277, 1241, 1210, 1045, 772, 701 cm-1; 1H NMR (400 MHz, DMSO-d6) (d, ppm):
3.67 (3H, s, OCH3), 3.68 (3H, s, OCH3), 5.44 (1H, d, J = 2.8 Hz, C4-H), 6.78 (2H,
d, J = 7.6 Hz, ArH), 6.84 (1H, dd, J = 3.2 Hz, J = 9.2 Hz, ArH), 6.94 (1H, d,
J = 8.8 Hz, ArH), 6.98–7.03 (4H, m, ArH), 7.10 (1H, s, NH), 7.20–7.27 (5H, m,
ArH), 8.65 (1H, s, NH); 13C NMR (100 MHz, DMSO-d6) (d, ppm): 53.0, 55.2, 56.0,
108.5, 112.5, 112.7, 114.0, 125.8, 127.7, 128.1, 128.2, 129.0, 129.3, 132.1, 135.0,
135.3, 138.0, 150.5, 153.2, 153.4; HRMS m/z calculated for C24H22N2O3
[M ? Na]?: 409.1523, found: 409.1541.
4-(3,4-Dimethoxyphenyl)-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one (4m)
m.p. 206–207°C; IR (KBr, m, cm-1): 3236, 3082, 1688, 1657, 1599, 1514, 1449,
1260, 1239, 1181, 1155, 1134, 1084, 1027, 866, 770, 700 cm-1 1H NMR
;
(400 MHz, DMSO-d6) (d, ppm): 3.70 (3H, s, OCH3), 3.73 (3H, s, OCH3), 5.06 (1H,
d, J = 2.8 Hz, C4-H), 6.81 (2H, d, J = 6.8 Hz, ArH), 6.93 (2H, s, ArH), 6.95 (1H,
s, ArH), 6.98–7.03 (3H, m, ArH), 7.22–7.27 (5H, m, ArH), 7.46 (1H, s, NH), 8.66
(1H, s, NH); 13C NMR (100 MHz, DMSO-d6) (d, ppm): 55.3, 55.5, 58.9, 109.5,
110.9, 111.8, 118.9, 125.8, 127.8, 128.1, 128.2, 129.2, 129.3, 129.4, 129.5, 134.7,
135.0, 136.1, 138.2, 148.2, 148.8, 153.4, 153.5, 162.3; HRMS m/z calculated for
C24H22N2O3 [M ? Na]?: 409.1523, found: 409.1511.
4-(Benzo[d][1,3]dioxol-5-yl)-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one (4n)
m.p. 242–244°C (lit. [32] 249–251 °C); IR (KBr, m, cm-1): 3215, 3081, 1687, 1599,
1
1488, 1372, 1304, 1237, 1190, 1103, 1039, 929, 771, 700, 679, 589, 515 cm-1; H
NMR (400 MHz, DMSO-d6) (d, ppm): 5.05 (1H, d, J = 2.8 Hz, C4-H), 6.00 (2H, d,
J = 4.0 Hz, OCH2O), 6.81 (2H, d, J = 8.0 Hz, ArH), 6.85 (1H, s, ArH), 6.88 (1H,
d, J = 7.6 Hz, ArH), 6.92 (1H, s, ArH), 6.98–7.03 (3H, m, ArH), 7.21–7.25 (5H, m,
123

An efficient synthesis of 3,4-dihydropyrimidin-2(1H)-one…
ArH), 7.48 (1H, s, NH), 8.69 (1H, s, NH); 13C NMR (100 MHz, CDCl3) (d, ppm):
55.4, 95.9, 96.2, 102.3, 102.6, 103.1, 104.7, 105.8, 115.4, 119.5, 121.3, 122.0,
122.7, 123.1, 123.2, 123.4, 123.7, 124.1, 124.4, 124.5, 126.4, 128.0, 129.7, 131.8,
132.2, 142.0, 142.2, 143.0, 143.7, 148.8; HRMS m/z calculated for C23H18N2O3
[M ? Na]?: 393.1209, found: 393.1220.
5,6-Diphenyl-4-(pyridin-2-yl)-3,4-dihydropyrimidin-2(1H)-one (4o)
m.p. 216–218°C (lit. [32] 207–209 °C); IR (KBr, m, cm-1): 3219, 3082, 1689, 1590,
1575, 1494, 1473, 1447, 1433, 1331, 1281, 1266, 1189, 765, 747, 698, 591 cm-1
;
1H NMR (400 MHz, DMSO-d6) (d, ppm): 5.27 (1H, d, J = 2.8 Hz, C4-H), 6.81
(2H, dd, J = 2.0 Hz, J = 8.0 Hz, ArH), 6.97–7.03 (3H, m, ArH), 7.17–7.23 (5H, m,
ArH), 7.30–7.33 (1H, m, ArH), 7.45 (1H, d, J = 8.0 Hz, ArH), 7.56 (1H, s, NH),
7.83 (1H, t, J = 7.6 Hz, ArH), 8.53 (1H, d, J = 4.8 Hz, ArH), 8.69 (1H, s, NH); 13
C
NMR (100 MHz, DMSO-d6) (d, ppm): 45.7, 61.5, 73.7, 109.0, 121.4, 122.7, 125.8,
125.9, 126.0, 126.7, 127.7, 127.8, 128.0, 128.1, 129.3, 129.5, 134.9, 137.1, 137.9,
139.1, 145.7, 149.1, 153.1, 162.2; HRMS m/z calculated for C21H17N3O [M ? H]?:
328.1450, found: 328.1470.
4,5,6-Triphenylpyrimidin-2-amine (6a)
m.p. 221–223°C; IR (KBr, m, cm-1): 3486, 3317, 3203, 3055, 1632, 1601, 1583,
1544, 1530, 1493, 1460, 14,386, 1392, 1370, 1275, 1210, 1183, 1077, 1028, 823,
1
774, 698, 669, 625 cm-1; H NMR (400 MHz, DMSO-d6) (d, ppm): 6.89 (1H, d,
J = 3.6 Hz, ArH), 6.91 (1H, J = 2.0 Hz, ArH), 7.08–7.10 (3H, m, ArH), 7.18–7.26
(10H, m, ArH); 13C NMR (100 MHz, DMSO-d6) (d, ppm): 110.4, 120.4, 125.7,
126.4, 127.1, 127.4, 127.6, 127.8, 127.9, 128.0, 128.9, 129.0, 129.1, 129.5, 131.5,
137.1, 139.1, 141.8, 145.9, 162.2, 162.3, 165.9; HRMS m/z calculated for C22H17N3
[M ? H]?: 324.1501, found:. 324.1494.
4-(4-Fluorophenyl)-5,6-diphenylpyrimidin-2-amine(6b)
m.p. 217–219°C; IR (KBr, m, cm-1): 3499, 3294, 3162, 3048, 1630, 1602, 1545,
1530, 1507, 1459, 1438, 1388, 1367, 1227, 1210, 1182, 1159, 1012, 851, 817, 774,
702 cm-1; 1H NMR (400 MHz, DMSO-d6) (d, ppm): 6.87 (2H, s, NH2), 6.89 (1H,
d, J = 3.6 Hz, ArH), 6.91 (1H, d, J = 2.0 Hz, ArH), 7.04 (2H, t, J = 8.8 Hz, ArH),
7.11 (3H, t, J = 2.8 Hz, ArH), 7.19–7.20 (4H, m, ArH), 7.21–7.25 (3H, m, ArH);
13C NMR (100 MHz, DMSO-d6) (d, ppm): 120.4, 126.4, 127.4, 127.8, 128.0, 129.1,
129.2, 131.5, 136.2, 137.3, 137.5, 139.2, 162.2, 165.6, 165.9; HRMS m/z calculated
for C22H16FN3 [M ? H]?: 342.1406, found: 342.1431.
4-(3,4-Dichlorophenyl)-5,6-diphenylpyrimidin-2-amine (6c)
m.p. 181–184°C; IR (KBr, m, cm-1): 3462, 3290, 3160, 3058, 1669, 1635, 1623,
1576, 1541, 1507, 1496, 1472, 1455, 1397, 1367, 1270, 1210, 1181, 1136, 1030,
1
895, 812, 771, 700 cm-1; H NMR (400 MHz, DMSO-d6) (d, ppm): 6.93 (2H, s,
123

J. Xu et al.
NH2), 6.95 (2H, s, ArH), 7.10–7.15 (4H, m, ArH), 7.19–7.25 (5H, m, ArH), 7.45
(2H, s, ArH); 13C NMR (100 MHz, CDCl3) (d, ppm): 122.2, 127.1, 127.8, 128.1,
128.4, 128.7, 128.8, 129.0, 129.3, 129.6, 129.9, 131.4, 131.5, 132.2, 132.8, 136.2,
138.4, 138.8, 161.8, 164.0, 167.4; HRMS m/z calculated for C22H15Cl2N3
[M ? H]?: 392.0716, found: 392.0721.
4-(4-Bromophenyl)-5,6-diphenylpyrimidin-2-amine (6d)
m.p. 247–248°C; IR (KBr, m, cm-1): 3483, 3359, 3198, 3054, 1638, 1612, 1583,
1569, 1527, 1485, 1451, 1438, 1399, 1370, 1210, 1180, 1071, 1010, 845, 814, 771,
700 cm-1; 1H NMR (400 MHz, DMSO-d6) (d, ppm): 6.89 (2H, s, NH2), 6.90–6.92
(2H, m, ArH), 7.10–7.13 (2H, m, ArH), 7.14 (2H, d, J = 8.4 Hz, ArH), 7.19–7.24
(6H, m, ArH), 7.41 (2H, d, J = 8.0 Hz, ArH); 13C NMR (100 MHz, DMSO-d6) (d,
ppm): 111.7, 121.3, 123.4, 126.7, 128.0, 128.2, 128.6, 129.3, 129.4, 130.4, 131.1,
131.8, 133.0, 134.0, 136.8, 141.5, 152.2, 162.3, 170.5, 176.3; HRMS m/z calculated
for C22H16BrN3 [M ? H]?: 402.0606, found: 402.0628.
4,5-Diphenyl-6-p-tolylpyrimidin-2-amine (6e)
m.p. 204–206°C; IR (KBr, m, cm-1): 3486, 3356, 3194, 3055, 1640, 1610, 1583,
1573, 1544, 1529, 1511, 1497, 1451, 1438, 1392, 1371, 1272, 1208, 1184, 1020,
812, 768, 699, 644, 627, 508 cm-1; 1H NMR (400 MHz, DMSO-d6) (d, ppm): 2.23
(3H, s, CH3), 6.80 (2H, s, NH2), 6.88–6.90 (2H, m, ArH), 6.99 (2H, d, J = 7.6 Hz,
ArH), 7.09–7.11 (5H, m, ArH), 7.17–7.24 (5H, m, ArH); 13C NMR (100 MHz,
DMSO-d6) (d, ppm): 20.7, 120.4, 126.4, 127.4, 127.8, 128.0, 129.0, 129.1, 129.2,
129.4, 131.4, 136.2, 137.3, 137.5, 139.1, 162.2, 165.6, 165.9; HRMS m/z calculated
for C23H19N3 [M ? H]?: 338.1652, found: 338.1635.
4-(3,4-Dimethylphenyl)-5,6-diphenylpyrimidin-2-amine (6f)
m.p. 213–215°C; IR (KBr, m, cm-1): 3495, 3282, 3155, 3058, 1620, 1579, 1544,
1531, 1507, 1495, 1462, 1403, 1369, 1271, 1211, 1194, 1134, 1073,1027, 1010,
1
817, 769, 700, 642 cm-1; H NMR (400 MHz, DMSO-d6) (d, ppm): 2.10 (3H, s,
CH3), 2.15 (3H, s, CH3), 6.82 (1H, dd, J = 0.8 Hz, J = 7.6 Hz, ArH), 6.89–6.92
(3H, m, ArH), 7.10–7.12 (4H, m, ArH), 7.19–7.25 (5H, m, ArH); 13C NMR
(100 MHz, DMSO-d6) (d, ppm): 19.1, 19.3, 120.3, 126.4, 126.7, 127.3, 127.8,
127.9, 128.3, 129.1, 130.5, 131.4, 135.2, 136.3, 136.4, 137.4, 139.2, 162.2, 165.6,
165.9; HRMS m/z calculated for C24H21N3 [M ? H]?: 352.1808, found: 352.1807.
4-(2,5-Dimethoxyphenyl)-5,6-diphenylpyrimidin-2-amine (6g)
m.p. 222–223°C; IR (KBr, m, cm-1): 3497, 3268, 3136, 3058, 1660,1651, 1621,
1583, 1550, 1496, 1462, 1421, 1391, 1372, 1300, 1268, 1222, 1184, 1164, 1117,
1
1049, 809, 774, 751, 701 cm-1; H NMR (400 MHz, DMSO-d6) (d, ppm): 3.32
(3H, s, OCH3), 3.64 (3H, s, OCH3), 6.68 (1H, dd, J = 2.0 Hz, J = 7.6 Hz, ArH),
6.74–6.77 (2H, m, ArH), 6.82–6.86 (4H, m, ArH, NH2), 6.99–7.02 (3H, m, ArH),
123

An efficient synthesis of 3,4-dihydropyrimidin-2(1H)-one…
7.17–7.24 (5H, m, ArH); 13C NMR (100 MHz, DMSO-d6) (d, ppm): 55.2, 55.3,
56.1, 111.7, 114.2, 115.3, 121.9, 126.1, 127.1, 127.4, 128.2, 129.1, 129.2, 130.7,
137.0, 138.9, 149.7, 152.3, 162.1, 164.5, 165.5; HRMS m/z calculated for
C24H21N3O2 [M ? Na]?: 406.1526, found: 406.1535.
4-(3,4-Dimethoxyphenyl)-5,6-diphenylpyrimidin-2-amine (6h)
m.p. 200–202°C; IR (KBr, m, cm-1): 3438, 3309, 3203, 1660, 1633, 1603, 1542,
1529, 1511, 1495, 1473, 1462, 1418, 1374, 1329, 1264, 1235, 1207, 1186, 1141,
1
1028, 806, 760, 700 cm-1; H NMR (400 MHz, CDCl3) (d, ppm): 3.37 (3H, s,
OCH3), 3.71 (3H, s, OCH3), 6.66 (1H, d, J = 2.0 Hz, ArH), 6.83 (1H, d = 8.4 Hz,
ArH), 6.93–6.97 (5H, m, ArH, NH2), 7.12–7.14 (3H, m, ArH), 7.18–7.22 (5H, m,
ArH); 13C NMR (100 MHz, DMSO-d6) (d, ppm): 55.5, 55.8, 76.9, 77.2, 77.5, 110.4,
113.1, 121.7, 122.6, 126.6, 127.7, 128.1, 128.3, 129.3, 131.1, 131.6, 137.4, 138.9,
147.8, 149.3, 161.9, 165.9, 166.9; HRMS m/z calculated for C24H21N3O2
[M ? H]?: 384.1707, found: 384.1721.
4-(Benzo[d][1,3]dioxol-5-yl)-5,6-diphenylpyrimidin-2-amine (6i)
m.p. 198–200°C; IR (KBr, m, cm-1): 3463, 3298, 3159, 3058, 1619, 1544, 1533,
1503, 1490, 1459, 1445, 1389, 1372, 1338, 1242, 1207, 1180, 1109, 1037, 932, 894,
1
812, 771, 700, 566 cm-1; H NMR (400 MHz, DMSO-d6) (d, ppm): 5.97 (2H, s,
OCH2O), 6.72–6.76 (3H, m, ArH), 6.84–6.94 (3H, m, ArH, NH2), 7.12–7.13 (3H,
m, ArH), 7.18–7.19 (4H, m, ArH), 7.20–7.24 (2H, m, ArH); 13C NMR (100 MHz,
DMSO-d6) (d, ppm): 56.7, 101.1, 107.3, 108.4, 111.7, 120.5, 126.3, 127.4, 127.9,
128.1, 128.3, 129.2, 129.4, 131.4, 136.6, 137.5, 147.0, 147.7, 152.2, 175.8; HRMS
m/z calculated for C23H17N3O2 [M ? H]?: 368.1394, found: 368.1398.
4-(4-Methoxyphenyl)-2-methyl-5,6-diphenylpyrimidine (6j)
m.p. 181–183°C; IR (KBr, m, cm-1): 3444, 1608, 1532, 1511, 1436, 1421, 1403,
1
1299, 1253, 1178, 1029, 844, 818, 766 cm-1; H NMR (400 MHz, DMSO-d6) (d,
ppm): 2.74 (3H, s,CH3), 3.72 (3H, s, OCH3), 6.79 (2H, d, J = 8.8 Hz, ArH),
7.00–7.02 (2H, m, ArH), 7.19–7.28 (10H, m, ArH); 13C NMR (100 MHz, DMSO-
d6) (d, ppm): 25.7, 55.1, 113.1, 127.3, 127.6, 127.7, 128.2, 128.3, 129.3, 130.3,
130.8, 131.1, 136.4, 138.5, 159.5, 164.0, 164.8, 165.5; HRMS m/z calculated for
C24H20N2O [M ? H]?: 353.1654, found: 353.1666.
4-(3,4-Dimethylphenyl)-2-methyl-5,6-diphenylpyrimidine (6k)
m.p. 117–119°C; IR (KBr, m, cm-1): 3449, 1611, 1579, 1530, 1491, 1442, 1411,
1
1369, 1074, 1006, 815, 770, 702, 669, 649 cm-1; H NMR (400 MHz, DMSO-d6)
(d, ppm): 2.11 (3H, s,CH3), 2.16 (3H, s, CH3), 2.74 (3H, s, CH3), 6.87 (1H, d,
J = 8.8 Hz, ArH), 6.94 (1H, d, J = 8.0 Hz, ArH), 6.98–7.01 (2H, m, ArH), 7.17
(2H, d, J = 4.0 Hz, ArH), 7.19 (2H, d, J = 1.6 Hz, ArH), 7.23–7.28 (5H, m, ArH);
13C NMR (100 MHz, DMSO-d6) (d, ppm): 19.1, 19.3, 25.7, 127.0, 127.2, 127.6,
123

J. Xu et al.
128.0, 128.1, 128.4, 128.6, 129.3, 130.6, 130.8, 135.5, 135.6, 136.3, 136.9, 138.4,
164.5, 164.8, 165.6; HRMS m/z calculated for C25H22N2 [M ? H]?: 351.1861,
found: 351.1844.
Acknowledgements We are grateful to the National Natural Science Foundation of China (NSFC;
21571087), the Open Foundation of Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional
Materials (no. K201312), the Natural Science Foundation of Jiangsu Normal University (13XLR005), the
Priority Academic Program Development of Jiangsu Higher Education Institutions and the Brand Major
of Universities in Jiangsu Province (TAPP) for financial support.
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