Efficient Catalytic Synthesis of 3,4-Dihydropyrimidin-2-ones/thiones via Little Acidic Ionic Liquid Combined with Rapid Heating Ways

Article abstract of DOI:10.1002/jhet.3292

Catalytic synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones was efficiently promoted by as little as 2.5?mol% of Br?nsted acidic ionic liquid [(CH₂)₃SO₃HMIM]HSO₄ catalyst loading via rapid heating ways. Inter

Full text of DOI:10.1002/jhet.3292

Month 2018
Efficient Catalytic Synthesis of 3,4-Dihydropyrimidin-2-ones/thiones via
Little Acidic Ionic Liquid Combined with Rapid Heating Ways
Guo-Ping Zhang,a,b
Da-Yu Tian,a and Wang-Ming Shia
*
aDepartment of Chemistry and Materials Science, Huaibei Normal University, Huaibei 235000, China
bDepartment of Chemistry, School of Information, Huaibei Normal University, Huaibei 235000, China
*E-mail: hbzgp-1@163.com
Received April 14, 2018
DOI 10.1002/jhet.3292
Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com).
Catalytic synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones was efficiently promoted by as little as
2.5 mol% of Brønsted acidic ionic liquid [(CH2)3SO3HMIM]HSO4 catalyst loading via rapid heating ways.
Interestingly, rapid heating effectively improved yields to avoid side products. Furthermore, the mechanism
has been speculated that the reaction proceeds may be via rapidly one-step condensation rather than slowly
step-by-step condensation. In addition, the catalyst can be recovered for repeated use (up to seven times), and
a whole green reaction process adds to its practical applicability.
J. Heterocyclic Chem., 00, 00 (2018).
INTRODUCTION
reagents [9], and nan catalysts [10]. However, many of
these reported protocols suffer from various drawbacks
such as the use of expensive and highly corrosive
catalysts, tedious separation procedures, and prolonged
reaction times. When the environmental effects are taken
into account, many ionic liquids have been developed to
carry out this Biginelli reaction, such as TrBuHTA [11],
BMI·NTf2 [12], BIL-1 [13], MNPs-IL-HSO4 [14],
GlyNO3 [15], and [(HOCH2CH2)3N]CH3COOꢀ [16].
However, these catalytic protocols also suffer from
certain drawbacks such as the harsh reaction conditions,
high dosage of catalyst, narrow scope of substituents in
all three components, and inevitable byproducts.
Recently, Brønsted acidic ionic liquids have been
developed as a kind of environment-friendly catalysts that
is widely used in many organic syntheses [17] because it
possesses HSOꢀ4 with effective catalyst. Taking the
environment and economy into account, the development
of efficient, whole green catalytic systems for the
synthesis of Biginelli compounds is an active ongoing
research area that attracted much attention in the recent
years [18].
Dihydropyrimidinones (DHPMs) and their derivatives
exhibited diverse biological and pharmacological
properties such as antiviral, antitumor, anti-human
immunodeficiency virus, antibacterial, anti-inflammatory,
antihypertensive, calcium channel blockers, α-1-
antagonists, and neuropeptide Y antagonists [1]. Besides,
some drugs based on DHPM motif were developed in
medicinal chemistry [2]. Therefore, the synthesis of
DHPMs compounds has received extensive attention. At
present, the universal strategy to synthesize DHPMs is
the Biginelli reaction, which is
a multicomponent
condensation reaction of aldehydes with urea (or
thiourea) and β-dicarbonyl compounds [3]. Usually, this
kind of reaction occurred in organic solvents at a high
temperature in the presence of an acid catalyst with low
yields (20–50%) [4]. The main reason is that any two
materials generate some side products via acid-catalyzed
condition [5] such as bisureides, unsaturated carbonyl
compounds, and ureide. Therefore, the synthesis of
DHPMs with excellent yield to avoid the earlier side
products is still a challenge.
Herein, we report a high efficient and reusable protocol
for synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones
via Brønsted acidic ionic liquid [(CH2)3SO3HMIM]HSO4
in rapid heating ways (Fig. 1). Notably, rapid heating was
found to effectively avoid side products in this reaction.
In recent years, a number of methods have been
developed to effectively accomplish the synthesis of these
compounds, such as using various Brønsted acids [6],
Lewis acids [7], basic catalysts [8], polymer-supported
© 2018 Wiley Periodicals, Inc.

G.-P. Zhang, D.-Y. Tian, and W.-M. Shi
Vol 000
Figure 1. Rapid heating green synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones via little acidic ionic liquids (BIL-HSO4). [Color figure can be
viewed at wileyonlinelibrary.com]
Table 1
Furthermore, the mechanism has been speculated that the
Optimizations of reaction conditions for the synthesis of 4a catalyzed by
reaction proceeds may be via rapidly one-step
condensation rather than slowly step-by-step condensation.
Our findings of three molecule one-step condensation
pathway provide additional insights in Biginelli reactions.
ionic liquid (BIL).
Catalyst
(mol%)
Temperature
(°C)
Time
(h)
Yield
(%)d
Entrya
1b
2b
3b
4b
5c
—
80
80
80
80
80
80
80
80
80
80
80
24
6
6
6
3
3
3
3
3
6
6
0
41
69
55
99
92
95
99
98
81
56
BIL-Cl (10)
BIL-HSO4 (10)
KHSO4 (10)
BIL-HSO4 (10)
BIL-Cl (10)
KHSO4 (10)
BIL-HSO4 (5)
BIL-HSO4 (2.5)
BIL-HSO4 (1.0)
BIL-HSO4
RESULTS AND DISCUSSION
6c
Synthesis. The Biginelli reaction of benzaldehyde (1a)
with ethyl acetoacetate (2a) and urea (3a) was chosen as a
model reaction to optimize reaction conditions, and the
results are summarized in Table 1. It was observed that
the reaction failed to give any product without the catalyst
(Table 1, entry 1). In initial studies, different catalysts were
screened in ethanol as the solvent (1 mL) at 80°C (Table 1,
entries 2–7). It was found that the rapid heating ways could
effectively improve the yield (Table 1, entries 5–7) than
slow heating ways with the same catalyst (Table 1,
entries 2–4). Among them, the catalyst (BIL-HSO4)
afforded promising results in short reaction time (Table 1,
entry 5). Almost no change in reactivity was observed
when the loading of BIL-HSO4 was reduced from 10 to
2.5 mol% at directly 80°C (Table 1, entries 5, 8, and 9);
however, the product decreased from 98 to 81% when a
catalyst load was reduced from 2.5 to 1 mol% (Table 1,
entries 9 and 10). Furthermore, obvious decrease of the
yield was observed when the amount of BIL-HSO4 was
reduced from 1 to 0.1 mol% (Table 1, entries 10 and 11).
As a consequence, the optimal results for the Biginelli
condensation reaction were observed at a molar ratio of
benzaldehyde, urea, and ethyl acetoacetate of 1:1.1:1 at
directly 80°C for 3 h in the presence of 2.5 mol% ionic
liquid ([(CH2)3SO3HMIM]HSO4).
7c
8c
9c
10c
11c
(0.1)
aReaction Conditions: Benzaldehyde (2.0 mmol), ethyl acetoacetate (2.0
mmol), and urea (2.0 mmol), ethanol (1 mL).
bReaction Temperature: at directly 80°C that is using rapidly heating
ways.
cHeating from room temperature to 80°C that is using slowly heating
ways.
dIsolated yields.
(Table 2, entry 1). Although the reactivity of other ionic
liquids is also high, their reaction systems need high
catalyst loading, tedious separation procedures, and
inevitable side products. Therefore, these disadvantages
increased the difficulty for its practical applicability.
Compared with the earlier results, the ionic liquid (BIL-
HSO4) was an effective catalyst for the Biginelli reaction.
The reusability of the catalyst (BIL-HSO4) was
investigated, and the results are described in Figure 2.
The reaction mixture was concentrated under reduced
pressure to remove the ethanol. Twenty milliliters of
water was added to the mixture. Then the catalyst was
recovered by using simple filtration technique. The
filtrate containing ionic liquid was dried over vacuum to
remove excess water. This catalyst was directly subjected
to Biginelli reaction using the model reaction with our
optimized reaction conditions. It is important to note that
the recycled catalysts produced excellent yields of DHPM
To further understand the catalytic system, the catalytic
activity of ionic liquid ([(CH2)3SO3HMIM]HSO4) was
compared with those of ionic liquids reported previously
[11–16], and the results are listed in Table 2. Ionic liquid
(BIL-HSO4) is an effective catalyst for the synthesis of
DHPMs with excellent yields in a relatively short time
Journal of Heterocyclic Chemistry
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Efficient Catalytic Synthesis of 3,4-Dihydropyrimidin-2-ones/thiones
Table 2
Various ionic liquids catalyzed synthesis of 4a in the appropriate reaction condition.
Entry
ILa
Condition
Time (h)
Yield (%)b
Reference
1
2
3
4
5
6
7
BIL-HSO4
TrBuHTA
BIL-1
MNPs-IL-HSO4
BMI·NTf2
GlyNO3
Stirring
Stirring
Stirring
Stirring
Stirring
MW
3
98
95
80
95
95
92
90
This work
[11]
[13]
[15]
[12]
0.3
1.0
0.5
4.0
0.17
0.07
[16]
[14]
IL
MW
aThe specific information on catalyst was shown in the corresponding papers.
bIsolated yields.
Because of the excellent reactivity in the presence of
2.5% BIL-HSO4 ionic liquid under rapid heating reaction
condition, it is worth exploring its catalytic mechanism
for the synthesis of DHPMs. Based on the former
literature studies [19], the strongly debated mechanism
for the Biginelli condensation reaction mainly includes
three types: the Knoevenagel mechanism, enamine
mechanism, and iminium mechanism (Fig. 3). In 1973,
Sweet and coworkers [5a] proposed the Knoevenagel
mechanism based on their findings. However, the
condensation of benzaldehyde (1a) and ethyl acetoacetate
in our experiment generated unsaturated carbonyl
compounds (5). Subsequently, the pure compound (5)
was not reacted with urea at the same condition
(Fig. 3b). The results indicated that the Knoevenagel
mechanism was not the reaction pathway. In 1933,
Folkers et al. [5b] presented the enamine mechanism.
However, ethyl acetoacetate in our experiment reacted
with urea to afford the ureide. The ureide was isolated
and also not reacted with benzaldehyde at the same
condition (Fig. 3c). The results also indicated that the
enamine mechanism was not the reaction pathway. In
1997, the iminium mechanism of the Biginelli
condensation reaction (Fig. 3a) was reported by Kappe
[5c] based on NMR experiment. Lately, De Souza and
coworkers [20] also investigated the iminium mechanism
of the Biginelli reaction via NMR, electrospray
ionization–tandem mass spectrometry, and density
functional theory calculations.
Figure 2. Reusability of ionic liquid (BIL-HSO4) for the synthesis of
compound 4a.
(4a) in 95–98%, respectively (Fig. 2). It was observed that
the yields were consistent without significant loss in its
catalytic activity.
With these optimized conditions in hand, we extended
the dihydropyrimidin-2(1H)-ones/thiones; the results are
summarized in Table 3. To our delight, all substituted
aromatic scopes of this methodology in using various
aldehydes via ionic liquid ([(CH2)3SO3HMIM]HSO4) and
rapid heating way could be converted to corresponding
DHPMs and their derivatives in excellent yields of 94–
98% with 1,3-dicarbonyl compounds and urea. Hetero-
aromatic substituent also had been proved to be good
substrates (products 4l, 4m, and 4w) in excellent yields
of 94–96%. Moreover, aliphatic aldehyde had been
proved to be bad substrates (products 4p and 4q) in low
yields of 32–36%. Interestingly, conjugate aliphatic
aldehydes also were proved to be good substrates
(products 4n and 4o) in high yields of 76–93%. In
addition, thiourea was also successfully used to produce
the corresponding 3,4-dihydropyrimidin-2(1H)-thiones
(Table 3, entries 23–30). Under the same conditions, the
yields of the products with thiourea (products 4A–4H)
were slightly lower than those with urea.
According to the favored iminium mechanism of the
Biginelli condensation reaction, the condensation of a
benzaldehyde (1a) and urea in our experiment should not
generate the imine but mainly obtain the bisureides in the
presence of 2.5% BIL (Fig. 4). Subsequently, the pure
bisureides were isolated and reacted with ethyl
acetoacetate at the same condition. And the corresponding
3,4-dihydropyrimidin-2(1H)-ones (4a) was not obtained
(Fig. 4). Interestingly, the one-pot condensation of
benzaldehyde (1a), urea, and ethyl acetoacetate can obtain
the product (4a) in 67% yield at slow heating 80°C
Journal of Heterocyclic Chemistry
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G.-P. Zhang, D.-Y. Tian, and W.-M. Shi
Vol 000
Table 3
Synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones in rapid heating ways.
Entry
Compound
R1
R2
X
Yield (%)
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
C6H5
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
CH3
CH3
CH3
CH3
CH3
OEt
OEt
OEt
OEt
CH3
CH3
CH3
CH3
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
S
98
97
98
99
97
98
96
97
96
96
97
96
94
93
76
32
36
98
98
97
96
95
91
89
93
92
90
91
94
91
4-CH3C6H4
4-CH3OC6H4
4-ClC6H4
4-BrC6H4
4-OHC6H4
4-NO2C6H4
2-FC6H4
2-CH3C6H4
3-NO2C6H4
3-BrC6H4
2-Thienyl
2-Furan
Cinnamyl
CH3CH2CH¼C (CH3)
(CH3)2CH
CH3CH2CH2
C6H4
4-CH3OC6H4
4-ClC6H4
4-NO2C6H4
2-Thienyl
C6H4
4-CH3OC6H4
4-BrC6H4
4-ClC6H4
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
4s
4t
4u
4v
4A
4B
4C
4D
4E
4F
4G
4H
S
S
S
S
S
S
S
C6H4
4-CH3OC6H4
4-BrC6H4
4-ClC6H4
aRapid heating ways.
bIsolated yields.
(Fig. 5b). The results indicated that one-step reaction can
effectively increase the yield than step-by-step reaction.
Meanwhile, the product (4a) was obtained in excellent
yield (98%) in the rapid heating one-pot way (Fig. 5a).
The results indicated that rapid heating can effectively
accelerate the process of increasing the yield. Based on
the earlier experiment results, a plausible reaction
mechanism for the synthesis of DHPMs catalyzed by
Brønsted acidic ionic liquid [(CH2)3SO3HMIM]HSO4 is
proposed in Figure 5. 3,4-Dihydropyrimidin-2(1H)-
ones/thiones and their derivatives might be formed via
one-step condensation of an aldehyde, urea, and 1,3-
dicarbonyl compounds in the presence of BIL-HSO4.
The rapid heating one-pot condensation of benzaldehyde
(1a), urea, and ethyl acetoacetate can efficiently
improve the yield to avoid the side products. Therefore,
the reaction proceeds via rapidly three molecular one-
step condensation rather than slowly step-by-step
condensation.
2.5 mol% Brønsted acidic ionic liquid [(CH2)3SO3HMIM]
HSO4 catalyst by rapid heating way. This method not
only provided excellent yields of DHPMs but also
simplified post-processing for separation of the product
and the catalyst with water. The catalyst can be recovered
for repeated use (up to seven times). Meanwhile, the
reaction can effectively improve yields to avoid by-
products by rapid heating way. Mechanistic studies
suggest that the reaction proceeds via rapidly three
molecular one-step condensation rather than slowly step-
by-step condensation. In addition, a whole green reaction
process increases the possibility of its application and
applicability, which is more environmental-friendly than
those with metal-based catalysts. The results indicated
that one-step reaction can effectively increase the yield
than step-by-step reaction. Meanwhile, the product (4a)
was obtained in excellent yield (98%) in the rapid
heating one-pot way (Fig. 5a). The results indicated that
rapid heating can effectively accelerate the process of
increasing the yield. Based on the earlier experiment
results, a plausible reaction mechanism for the synthesis
of DHPMs catalyzed by Brønsted acidic ionic liquid
In summary, we have successfully developed an efficient
green procedure for the synthesis of 3,4-dihydropyrimidin-
2(1H)-ones/thiones and their derivatives in the presence of
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Efficient Catalytic Synthesis of 3,4-Dihydropyrimidin-2-ones/thiones
Figure 3. The mainly three types of mechanism for the Biginelli reaction. [Color figure can be viewed at wileyonlinelibrary.com]
Figure 4. The favored iminium mechanism for the Biginelli reaction. [Color figure can be viewed at wileyonlinelibrary.com]
[(CH2)3SO3HMIM]HSO4 is proposed in Figure 5. 3,4-
Dihydropyrimidin-2(1H)-ones/thiones and their derivatives
might be formed via one-step condensation of an
aldehyde, urea, and 1,3-dicarbonyl compounds in the
presence of BIL-HSO4. The rapid heating one-pot
condensation of benzaldehyde (1a), urea, and ethyl
acetoacetate can effectively improve the yield to avoid the
side products. Therefore, the reaction proceeds via rapidly
three molecular one-step condensation rather than slowly
step-by-step condensation.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

G.-P. Zhang, D.-Y. Tian, and W.-M. Shi
Vol 000
Figure 5. The proposed condensation mechanism for the Biginelli reaction. [Color figure can be viewed at wileyonlinelibrary.com]
EXPERIMENTAL
reactions were distilled from appropriate drying agents
prior to use.
Materials and methods. In the reported literature, the
information on the characterization of the products was
almost retrieved. In this work, the identification of the
products using 1H-NMR and 13C-NMR was conducted
and was compared with the reported literature. Proton
and carbon NMR spectra were recorded on a JEOL-ECX
500 (Tokyo, Japan). Proton chemical shifts are reported
in parts per million (δ) relative to tetramethylsilane
(0.0 ppm) with the solvent resonance employed as the
internal standard ((CD3)2SO, 2.49 ppm). Data are
reported as follows: chemical shift multiplicity
(s = singlet, d = doublet, q = quartet, and m = multiplet),
coupling constant (Hz), and integration. 13C chemical
shifts are reported in parts per million from
tetramethylsilane with the solvent resonance as the
internal standard ((CD3)2SO, 40.0 ppm). All reagents
were purchased from commercial suppliers and used
without further purification. All solvents used in the
General synthetic procedure. Preparation of acidic ionic
liquid [18].
N-methylimidazole (100 mmol) and 1,3-
propanesultone (100 mmol) were added to solvent-free
100-mL flask. The mixture was heated at 40°C for 24 h.
The white zwitterions were washed three times with
toluene to remove unreacted material and dried in a
vacuum. Then, a stoichiometric amount of concentrated
sulfuric acid was added dropwise to the zwitterions,
and the mixture was stirred at 40°C for 2–3 days until
liquefied, resulting in the formation of the ionic liquids.
The ionic liquids were washed repeatedly with toluene
and ether to remove unreacted material and dried under
vacuum. The purity of the ionic liquids was more than
95% as characterized by NMR spectroscopy.
Data for acidic ionic liquid (BIL-HSO4).
1H-NMR
(500 MHz, CD3OD) δ 8.92 (s, 1H), 7.65 (s, 1H), 7.65
(d, J = 1.6 Hz, 1H), 7.56 (d, J = 1.5 Hz, 1H), 4.41
(t, J = 7.1 Hz, 2H), 3.93 (s, 3H), 2.82 (t, J = 7.1 Hz,
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Efficient Catalytic Synthesis of 3,4-Dihydropyrimidin-2-ones/thiones
2H), 2.36–2.24 (m, 2H); 13C-NMR (126 MHz, CD3OD)
δ 136.90 (s), 123.77 (s), 122.39 (s), 47.87 (s), 47.19 (s),
35.32 (s), 25.77 (s).
Procedure for synthesis of 3,4-dihydropyrimidin-2-ones/thiones
(4a–4H). Rapid heating synthesis of 3,4-dihydropyrimidin-2-ones/
thiones in one pot via little acidic ionic liquids (BIL-HSO4).
Aldehyde (1.0 mmol), β-ketoester (1.0 mmol), urea or
thiourea (1.0 mmol), and 2.5 mol% Brønsted acidic ionic
liquid were added to 1.0 mL of ethanol. The mixture was
stirred directly at 80°C for 3 h. The resulting mixture was
concentrated under reduced pressure to give crude
product. Twenty milliliters of water was added to the
crude product. The solid product was filtered and washed
with n-hexane (5 mL × 2), which afforded pure 3,4-
2H), 7.24 (d, J = 8.5 Hz, 2H), 5.13 (d, J = 3.3 Hz, 1H), 3.97
(q, J = 6.9 Hz, 2H), 2.24 (s, 3H), 1.08 (t, J = 7.1 Hz, 3H);
13C-NMR (126 MHz, DMSO-d6) δ 165.29 (s), 152.02 (s),
148.82 (s), 143.88 (s), 131.87 (s), 128.49 (s), 128.27 (s),
98.90 (s), 59.35 (s), 53.50 (s), 17.89 (s), 14.16 (s).
5-Ethoxycarbonyl-6-methyl-4-(4-bromophenyl)-3,4-
dihydropyrimidin-2(1H)-one (4e) [6e]. 1H-NMR (500 MHz,
DMSO-d6) δ 9.23 (s, 1H), 7.75 (d, J = 2.1 Hz, 1H), 7.52 (d,
J = 8.4 Hz, 2H), 7.17 (d, J = 8.5 Hz, 2H), 5.11 (d,
J = 3.3 Hz, 1H), 3.97 (q, J = 7.1 Hz, 2H), 2.23 (s, 3H),
1.08 (t, J = 7.1 Hz, 3H); 13C-NMR (126 MHz, DMSO-d6)
δ 165.28 (s), 152.00 (s), 148.83 (s), 144.28 (s), 131.41 (s),
128.63 (s), 120.39 (s), 98.83 (s), 59.35 (s), 53.56 (s),
17.89 (s), 14.16 (s).
5-Ethoxycarbonyl-6-methyl-4-(4-hydroxyphenyl)-3,4-
dihydropyrimidin-2(1H)-ones/thiones (4a–4H) in pure form.
Slow heating synthesis of 3,4-dihydropyrimidin-2-ones/
thiones in one pot via little acidic ionic liquids (BIL-HSO4).
dihydropyrimidin-2(1H)-one (4f) [21]. 1H-NMR (500 MHz,
DMSO-d6) δ 9.31 (s, 1H), 9.09 (s, 1H), 7.60 (s, 1H), 7.01
(d, J = 7.7 Hz, 2H), 6.67 (d, J = 7.5 Hz, 2H), 5.02 (d,
J = 3.0 Hz, 1H), 3.96 (q, J = 7.1 Hz, 2H), 2.22 (s, 3H),
1.08 (t, J = 7.1 Hz, 3H); 13C-NMR (126 MHz, DMSO-d6)
δ 165.51 (s), 156.62 (s), 152.26 (s), 147.86 (s), 135.53 (s),
127.49 (s), 115.07 (s), 99.81 (s), 59.19 (s), 53.51 (s),
39.60 (s), 17.83 (s), 14.20 (s).
Aldehyde (1.0 mmol), β-ketoester (1.0 mmol), urea or
thiourea (1.0 mmol), and 2.5 mol% Brønsted acidic ionic
liquid were added to 1.0 mL of ethanol. The mixture was
heated to 80°C for 6 h. The resulting mixture was
concentrated under reduced pressure to give crude
product. Twenty milliliters of water was added to the
crude product. The solid product was filtered and washed
with n-hexane (5 mL × 2), which afforded crude 3,4-
dihydropyrimidin-2(1H)-ones/thiones containing main
5-Ethoxycarbonyl-6-methyl-4-(4-nitrophenyl)-3,4-
dihydropyrimidin-2(1H)-one
(4g)
[21].
1H-NMR
(500 MHz, DMSO-d6) δ 9.34 (s, 1H), 8.21 (d, J = 8.2 Hz,
2H), 7.88 (s, 1H), 7.50 (d, J = 8.4 Hz, 2H), 5.27 (d,
J = 3.3 Hz, 1H), 3.98 (q, J = 7.0 Hz, 2H), 2.26 (s, 3H),
1.08 (t, J = 7.1 Hz, 3H); 13C-NMR (126 MHz, DMSO-d6)
δ 165.14 (s), 152.08 (s), 151.84 (s), 149.48 (s), 146.80 (s),
127.75 (s), 123.92 (s), 98.27 (s), 59.48 (s), 53.77 (s),
17.97 (s), 14.14 (s).
side product of bisureides.
5-Ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydro-pyrimidin-
2(1H)-one (4a) [21]. 1H-NMR (500 MHz, DMSO-d6) δ
9.16 (s, 1H), 7.70 (s, 1H), 7.35–7.28 (m, 2H), 7.26–7.19
(m, 3H), 5.14 (d, J = 3.3 Hz, 1H), 3.97 (q, J = 7.1 Hz,
2H), 2.24 (s, 3H), 1.08 (t, J = 7.1 Hz, 3H); 13C-NMR
(126 MHz, DMSO-d6) δ 165.40 (s), 152.19 (s), 148.39
(s), 144.93 (s), 128.44 (s), 127.31 (s), 126.30 (s), 99.35
5-Ethoxycarbonyl-6-methyl-4-(4-fluorophenyl)-3,4-
dihydropyrimidin-2(1H)-one
(4h)
[22].
1H-NMR
(500 MHz, DMSO-d6) δ 9.21 (s, 1H), 7.66 (s, 1H), 7.32–
7.22 (m, 2H), 7.18–7.08 (m, 2H), 5.44 (d, J = 2.9 Hz,
1H), 3.91 (q, J = 7.1 Hz, 2H), 2.26 (s, 3H), 1.02 (t,
J = 7.1 Hz, 3H); 13C-NMR (126 MHz, DMSO-d6) δ
165.53 (s), 158.91 (s), 152.07 (s), 149.47 (s), 132.21 (d,
J = 13.8 Hz), 129.88 (d, J = 8.3 Hz), 129.39 (s), 125.02
(s), 115.95 (d, J = 147.42 Hz), 98.01 (s), 59.61 (s), 49.18
(s), 59.23 (s), 54.04 (s), 17.83 (s), 14.13 (s).
5-Ethoxycarbonyl-6-methyl-4-(4-methylphenyl)-3,4-
dihydropyrimidin-2(1H)-one (4b) [6e]. 1H-NMR (500 MHz,
DMSO-d6) δ 9.13 (s, 1H), 7.67 (s, 1H), 7.10 (s, 4H), 5.09
(d, J = 3.3 Hz, 1H), 3.96 (q, J = 7.0 Hz, 2H), 2.25 (s, 3H),
2.22 (s, 3H), 1.09 (t, J = 7.1 Hz, 3H); 13C-NMR
(126 MHz, DMSO-d6) δ 165.89 (s), 152.70 (s), 148.69
(s), 142.49 (s), 136.90 (s), 129.42 (s), 126.68 (s), 99.93
(s), 59.69 (s), 54.15 (s), 21.18 (s), 18.29 (s), 14.63 (s).
5-Ethoxycarbonyl-6-methyl-4-(4-methoxyphenyl)-3,4-
(s), 18.25 (s), 14.41 (s).
5-Ethoxycarbonyl-6-methyl-4-(2-methylphenyl)-3,4-
dihydropyrimidin-2(1H)-one (4i) [23]. 1H-NMR (500 MHz,
dihydropyrimidin-2(1H)-one
(4c)
[21].
1H-NMR
DMSO-d6) δ 9.12 (s, 1H), 7.59 (s, 1H), 7.17–7.03 (m, 4H),
5.37 (d, J = 2.7 Hz, 1H), 3.93–3.78 (m, 2H), 2.38 (s, 3H),
2.26 (s, 3H), 0.96 (t, J = 7.1 Hz, 3H); 13C-NMR (126 MHz,
DMSO-d6) δ 165.78 (s), 152.08 (s), 148.96 (s), 143.79 (s),
135.19 (s), 130.62 (s), 127.69 (s), 127.05 (s), 99.70 (s),
59.60 (s), 50.96 (s), 19.18 (s), 18.22 (s), 14.46 (s).
(500 MHz, DMSO-d6) δ 9.11 (s, 1H), 7.63 (s, 1H), 7.13
(d, J = 8.7 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 5.08 (d,
J = 3.3 Hz, 1H), 3.97 (q, J = 7.1 Hz, 2H), 3.71 (s, 3H),
2.23 (s, 3H), 1.09 (t, J = 7.1 Hz, 3H); 13C-NMR
(126 MHz, DMSO-d6) δ 165.43 (s), 158.50 (s), 152.19
(s), 148.04 (s), 137.12 (s), 127.44 (s), 113.76 (s), 99.64
5-Ethoxycarbonyl-6-methyl-4-(3-nitrophenyl)-3,4-dihydro-
pyrimidin-2(1H)-one (4j) [24].
1H-NMR (500 MHz,
(s), 59.19 (s), 55.12 (s), 53.39 (s), 17.80 (s), 14.16 (s).
5-Ethoxycarbonyl-6-methyl-4-(4-chlorophenyl)-3,4-
DMSO-d6) δ 9.36 (s, 1H), 8.11 (d, J = 7.9 Hz, 1H), 8.05
(s, 1H), 7.89 (s, 1H), 7.65 (dt, J = 15.6, 4.5 Hz, 2H),
5.27 (d, J = 3.3 Hz, 1H), 4.02–3.88 (m, 2H), 2.24 (s,
dihydropyrimidin-2(1H)-one (4d) [6e]. 1H-NMR (500 MHz,
DMSO-d6) δ 9.23 (s, 1H), 7.76 (s, 1H), 7.38 (d, J = 8.5 Hz,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

G.-P. Zhang, D.-Y. Tian, and W.-M. Shi
Vol 000
3H), 1.06 (t, J = 7.1 Hz, 3H); 13C-NMR (126 MHz,
DMSO-d6) δ 165.59 (s), 152.32 (s), 149.99 (s), 148.26
(s), 147.52 (s), 133.54 (s), 130.79 (s), 122.92 (s), 121.54
3H), 0.80 (d, J = 6.9 Hz, 3H), 0.73 (d, J = 6.8 Hz, 3H);
13C-NMR (126 MHz, DMSO-d6) δ 165.90 (s), 153.24
(s), 148.61 (s), 98.23 (s), 59.16 (s), 55.61 (s), 34.70 (s),
(s), 98.83 (s), 59.94 (s), 54.06 (s), 18.40 (s), 14.55 (s).
18.62 (s), 17.84 (s), 16.07 (s), 14.32 (s).
5-Ethoxycarbonyl-6-methyl-4-(3-bromophenyl)-3,4-
5-Acetyl-6-methyl-4-propyl-3,4-dihydropyrimidin-2(1H)-one
dihydropyrimidin-2(1H)-one
(4k)
[25].
1H-NMR
(4q) [6e]. 1H-NMR (500 MHz, DMSO-d6) δ 8.90 (s, 1H),
(500 MHz, DMSO-d6) δ 9.26 (s, 1H), 7.78 (s, 1H), 7.44
(d, J = 7.0 Hz, 1H), 7.38 (s, 1H), 7.29 (t, J = 7.8 Hz,
1H), 7.23 (d, J = 7.7 Hz, 1H), 5.13 (s, 1H), 4.10–3.80
(m, 2H), 2.25 (s, 3H), 1.09 (t, J = 6.2 Hz, 3H); 13C-NMR
(126 MHz, DMSO-d6) δ 165.69 (s), 152.44 (s), 149.48
(s), 148.02 (s), 131.34 (s), 130.67 (s), 129.71 (s), 125.80
(s), 122.06 (s), 99.15 (s), 59.84 (s), 54.14 (s), 18.36 (s),
14.58 (s).
7.29 (s, 1H), 4.10–3.95 (m, 3H), 2.12 (s, 3H), 1.45–1.18
(m, 4H), 1.15 (t, J = 7.1 Hz, 3H), 0.81 (t, J = 7.0 Hz,
3H); 13C-NMR (126 MHz, DMSO-d6) δ 165.98 (s),
153.33 (s), 148.82 (s), 99.94 (s), 59.58 (s), 50.32 (s),
18.23 (s), 17.54 (s), 14.76 (s), 14.29 (s).
5-Acetyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one
(4r) [29]. 1H-NMR (500 MHz, DMSO-d6) δ 9.17 (s, 1H),
7.81 (s, 1H), 7.34–7.28 (m, 2H), 7.24 (d, J = 6.4 Hz, 3H),
5.25 (d, J = 3.5 Hz, 1H), 2.28 (s, 3H), 2.09 (s, 3H); 13C-
NMR (126 MHz, DMSO-d6) δ 194.37 (s), 152.23 (s),
148.23 (s), 144.34 (s), 128.62 (s), 127.44 (s), 126.52 (s),
5-Ethoxycarbonyl-6-methyl-4-(2-thienyl)-3,4-dihydro-
pyrimidin-2(1H)-one (4l) [26].
1H-NMR (500 MHz,
DMSO-d6) δ 9.28 (s, 1H), 7.87 (s, 1H), 7.32 (dd, J = 5.0,
1.3 Hz, 1H), 6.91 (dd, J = 5.0, 3.5 Hz, 1H), 6.86 (d,
J = 3.4 Hz, 1H), 5.38 (d, J = 3.6 Hz, 1H), 4.03 (q,
J = 7.1 Hz, 2H), 2.19 (s, 3H), 1.13 (t, J = 7.1 Hz, 3H);
13C-NMR (126 MHz, DMSO-d6) δ 165.10 (s), 152.32
(s), 148.87 (s), 148.74 (s), 126.75 (s), 124.71 (s), 123.59
(s), 99.86 (s), 59.44 (s), 49.43 (s), 17.77 (s), 14.24 (s).
5-Ethoxycarbonyl-6-methyl-4-(2-furyl)-3,4-dihydro-
109.68 (s), 53.91 (s), 39.60 (s), 30.42 (s), 19.01 (s).
5-Acetyl-6-methyl-4-(4-methoxylphenyl)-3,4-dihydro-
pyrimidin-2(1H)-one (4s) [29].
1H-NMR (500 MHz,
DMSO-d6) δ 9.14 (s, 1H), 7.75 (s, 1H), 7.15 (d,
J = 8.7 Hz, 2H), 6.87 (d, J = 8.7 Hz, 2H), 5.19 (d,
J = 3.4 Hz, 1H), 3.71 (s, 3H), 2.27 (s, 3H), 2.06 (s, 3H);
13C-NMR (126 MHz, DMSO-d6) δ 194.46 (s), 158.60
(s), 152.19 (s), 147.88 (s), 136.47 (s), 127.74 (s), 113.95
pyrimidin-2(1H)-one (4m) [24].
1H-NMR (500 MHz,
(s), 109.70 (s), 55.16 (s), 53.42 (s), 30.26 (s), 18.94 (s).
5-Acetyl-6-methyl-4-(4-chlorophenyl)-3,4-dihydro-pyrimidin-
2(1H)-one (4t) [29]. 1H-NMR (500 MHz, DMSO-d6) δ
9.23 (s, 1H), 7.86 (s, 1H), 7.38 (d, J = 8.5 Hz, 2H), 7.24
(d, J = 8.5 Hz, 2H), 5.24 (d, J = 3.5 Hz, 1H), 2.27 (s,
3H), 2.11 (s, 3H); 13C-NMR (126 MHz, DMSO-d6) δ
194.18 (s), 152.10 (s), 148.52 (s), 143.27 (s), 131.89 (s),
128.45 (d, J = 19.9 Hz), 109.58 (s), 53.14 (s), 30.48 (s),
DMSO-d6) δ 9.24 (s, 1H), 7.75 (s, 1H), 7.54 (dd, J = 1.8,
0.9 Hz, 1H), 6.34 (dd, J = 3.2, 1.8 Hz, 1H), 6.08 (d,
J = 3.2 Hz, 1H), 5.19 (d, J = 3.5 Hz, 1H), 4.05–3.97 (m,
2H), 2.22 (s, 3H), 1.12 (t, J = 7.1 Hz, 3H); 13C-NMR
(126 MHz, DMSO-d6) δ 165.08 (s), 156.01 (s), 152.47
(s), 149.40 (s), 142.20 (s), 110.40 (s), 105.33 (s), 96.83
(s), 59.29 (s), 47.80 (s), 39.60 (s), 17.79 (s), 14.22 (s).
5-Ethoxycarbonyl-6-methyl-4-(2-cinnamenyl)-3,4-dihydro-
pyrimidin-2(1H)-one (4n) [27].
1H-NMR (500 MHz,
19.04 (s).
5-Acetyl-6-methyl-4-(4-nitrophenyl)-3,4-dihydro-pyrimidin-
DMSO-d6) δ 9.13 (s, 1H), 7.53 (s, 1H), 7.37 (d,
J = 7.6 Hz, 2H), 7.28 (t, J = 7.6 Hz, 2H), 7.20 (t,
J = 7.3 Hz, 1H), 6.32 (d, J = 15.8 Hz, 1H), 6.16 (dd,
J = 15.8, 6.1 Hz, 1H), 4.69 (d, J = 9.2 Hz, 1H), 4.15–3.95
(m, 2H), 2.16 (s, 3H), 1.16 (t, J = 7.1 Hz, 3H); 13C-NMR
(126 MHz, DMSO-d6) δ 165.72 (s), 153.12 (s), 149.11 (s),
136.74 (s), 130.47 (s), 129.22 (s), 128.63 (s), 128.13 (s),
126.88 (s), 98.26 (s), 59.76 (s), 52.42 (s), 18.31 (s), 14.80 (s).
5-Acetyl-6-methyl-4-(2-pent-2-en-2-yl)-3,4-dihydro-
2(1H)-one (4u) [29]. 1H-NMR (500 MHz, DMSO-d6) δ
9.22 (s, 1H), 7.85 (d, J = 2.0 Hz, 1H), 7.38 (d,
J = 8.5 Hz, 2H), 7.24 (d, J = 8.5 Hz, 2H), 5.25 (d,
J = 3.5 Hz, 1H), 2.28 (s, 3H), 2.11 (s, 3H); 13C-NMR
(126 MHz, DMSO-d6) δ 194.18 (s), 152.13 (s), 148.54
(s), 143.28 (s), 131.91 (s), 128.55 (s), 128.39 (s), 109.59
(s), 53.15 (s), 30.51 (s), 19.06 (s).
5-Acetyl-6-methyl-4-(2-thienyl)-3,4-dihydropyrimidin-2(1H)-
one (4v) [30]. 1H-NMR (500 MHz, DMSO-d6) δ 9.31 (s,
pyrimidin-2(1H)-one (4o).
1H-NMR (500 MHz,
1H), 7.96 (s, 1H), 7.34 (dd, J = 5.0, 1.4 Hz, 1H), 6.93
(dd, J = 5.0, 3.5 Hz, 1H), 6.90 (d, J = 3.4 Hz, 1H), 5.50
(d, J = 3.6 Hz, 1H), 2.25 (s, 3H), 2.17 (s, 3H); 13C-NMR
(126 MHz, DMSO-d6) δ 193.92 (s), 152.35 (s), 148.74
(s), 148.33 (s), 126.83 (s), 124.99 (s), 124.04 (s), 110.59
DMSO-d6) δ 8.92 (s, 1H), 7.28 (s, 1H), 5.17 (t,
J = 7.0 Hz, 1H), 4.48 (d, J = 3.1 Hz, 1H), 4.10–3.87 (m,
2H), 2.14 (s, 3H), 1.98–1.83 (m, 2H), 1.46 (s, 3H), 1.12
(t, J = 6.9 Hz, 3H), 0.85 (t, J = 7.5 Hz, 3H); 13C-NMR
(126 MHz, DMSO-d6) δ 165.58 (s), 152.56 (s), 148.18
(s), 135.38 (s), 127.22 (s), 97.50 (s), 59.03 (s), 57.68 (s),
20.49 (s), 17.69 (s), 14.18 (d, J = 15.8 Hz), 11.31 (s).
5-Acetyl-6-methyl-4-isopropyl-3,4-dihydropyrimidin-2(1H)-
one (4p) [28]. 1H-NMR (500 MHz, DMSO-d6) δ 8.86 (s,
(s), 49.38 (s), 30.28 (s), 18.97 (s).
5-Ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydro-pyrimidin-
2(1H)-thione (4A) [29]. 1H-NMR (500 MHz, DMSO-d6) δ
10.33 (s, 1H), 9.64 (s, 1H), 7.34 (t, J = 7.6 Hz, 2H), 7.27
(d, J = 7.3 Hz, 1H), 7.21 (d, J = 7.3 Hz, 2H), 5.16 (d,
J = 3.7 Hz, 1H), 4.00 (q, J = 7.0 Hz, 2H), 2.28 (s, 3H),
1.09 (t, J = 7.1 Hz, 3H); 13C-NMR (126 MHz,
1H), 7.26 (s, 1H), 4.11–3.97 (m, 2H), 3.93 (t, J = 3.7 Hz,
1H), 2.16 (s, 3H), 1.70–1.61 (m, 1H), 1.17 (t, J = 7.1 Hz,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Efficient Catalytic Synthesis of 3,4-Dihydropyrimidin-2-ones/thiones
DMSO-d6) δ 174.76 (s), 165.66 (s), 145.57 (s), 144.03 (s),
129.10 (s), 128.22 (s), 126.92 (s), 101.24 (s), 60.13 (s),
5-Acetyl-6-methyl-4-(4-chlorophenyl)-3,4-dihydro-pyrimidin-
2(1H)-thione (4H) [29]. 1H-NMR (500 MHz, DMSO-d6)
δ 10.33 (s, 1H), 9.78 (s, 1H), 7.41 (d, J = 8.5 Hz, 2H), 7.22
(d, J = 8.5 Hz, 2H), 5.28 (d, J = 3.9 Hz, 1H), 2.32 (s, 3H),
2.17 (s, 3H); 13C-NMR (126 MHz, DMSO-d6) δ 194.77
(s), 174.30 (s), 145.06 (s), 141.91 (s), 132.36 (s), 128.73
(s), 128.52 (s), 110.43 (s), 53.12 (s), 30.65 (s), 18.43 (s).
54.57 (s), 17.70 (s), 14.55 (s).
5-Ethoxycarbonyl-6-methyl-4-(4-methoxylphenyl)-3,4-
dihydropyrimidin-2(1H)-thione (4B) [29].
1H-NMR
(500 MHz, DMSO-d6) δ 10.27 (s, 1H), 9.57 (s, 1H), 7.11
(d, J = 8.6 Hz, 2H), 6.89 (d, J = 8.7 Hz, 2H), 5.10 (d,
J = 3.6 Hz, 1H), 3.99 (q, J = 7.0 Hz, 2H), 3.71 (s, 3H),
2.27 (s, 3H), 1.10 (t, J = 7.1 Hz, 3H); 13C-NMR
(126 MHz, DMSO-d6) δ 174.09 (s), 165.22 (s), 158.80
(s), 144.80 (s), 135.77 (s), 127.67 (s), 113.95 (s), 101.03
(s), 59.61 (s), 55.17 (s), 53.51 (s), 17.20 (s), 14.11 (s).
5-Ethoxycarbonyl-6-methyl-4-(4-bromophenyl)-3,4-
Acknowledgments. We gratefully acknowledge the financial
supports of this work by the National Key Research and
Development Program of China (no. 2017YFD0200506), the Na-
tional Natural Science Foundation of China (No.21807037), the
Provincial Major Project of Education Department in Anhui (no.
KJ2018A0386), the Provincial Major Project of Excellent Youth
Talent Support Program in Anhui (no. gxyqZD2018092), and
the Provincial Undergraduate Training Programs for Innovation
(no. 201710373055).
dihydropyrimidin-2(1H)-thione (4C) [29].
1H-NMR
(500 MHz, DMSO-d6) δ 10.36 (s, 1H), 9.64 (s, 1H), 7.53
(d, J = 8.3 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H), 5.12 (d,
J = 3.7 Hz, 1H), 3.97 (q, J = 7.0 Hz, 2H), 2.26 (s, 3H),
1.07 (t, J = 7.1 Hz, 3H); 13C-NMR (126 MHz,
DMSO-d6) δ 174.75 (s), 165.51 (s), 145.94 (s), 143.31
(s), 132.07 (s), 129.20 (s), 121.36 (s), 100.73 (s), 60.21
(s), 54.04 (s), 17.72 (s), 14.55 (s).
REFERENCES AND NOTES
[1] (a) Atwal, K. S.; Swanson, B. N.; Unger, S. E.; Floyd, D. M.;
Moreland, S.; Hedberg, A.; Reilly, B. C. O. J Med Chem 1991, 34, 806;
(b) Kappe, C. O. Eur J Med Chem 2000, 35, 1043; (c) Murata, H.;
Ishitani, H.; Iwamoto, M. Org Biomol Chem 2010, 8, 1202; (d) Kappe,
C. O. Tetrahedron 1993, 49, 6937; (e) Kappe, C. O.; Fabian, W. M. F.
Tetrahedron 1997, 53, 2803.
[2] For reviews on biological activity of dihydropyrimidinones,
see(a)Naikoo, R. A.; Mir, M. A.; Bhat, S.; Tomar, R.; Bhat, R. A.; Malla,
M. A. Curr Bio Comp 2016, 12, 236; (b) Beena, K.; Suresh, P. R.;
Rajasekaranb, A.; Mannaa, P. K. J Pharm Sci & Res 2016, 8, 741.
[3] Biginelli, P. Gazz Chim Ital 1893, 23, 360.
5-Ethoxycarbonyl-6-methyl-4-(4-chlorophenyl)-3,4-
dihydropyrimidin-2(1H)-thione (4D) [29].
1H-NMR
(500 MHz, DMSO-d6) δ 10.36 (s, 1H), 9.64 (s, 1H), 7.39
(d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.5 Hz, 2H), 5.13 (d,
J = 3.0 Hz, 1H), 4.00–3.95 (m, 2H), 2.26 (s, 3H), 1.07 (t,
J = 7.1 Hz, 3H); 13C-NMR (126 MHz, DMSO-d6) δ
174.77 (s), 165.52 (s), 145.92 (s), 142.91 (s), 132.79 (s),
129.14 (s), 128.85 (s), 100.82 (s), 60.20 (s), 53.98 (s),
[4] Atwal, K. S.; Rovnyak, G. C.; O’Reilly, B. C.; Schwartz, J. J
Org Chem 1989, 54, 5898.
17.72 (s), 14.55 (s).
[5] (a) Sweet, F.; Fissekis, J. D. J Am Chem Soc 1973, 95, 8741;
(b) Folkers, K.; Johnson, T. B. J Am Chem Soc 1933, 55, 3784; (c)
Kappe, C. O. J Org Chem 1997, 62, 7201.
[6] (a) Narahari, S. R.; Reguri, B. R.; Guda Parthi, O.; Mukkanti,
K. Tetrahedron Lett 2012, 53, 1543; (b) Rajack, A.; Yuvaraju, K.;
Praveen, C.; Murthy, Y. L. N. J Mol Catal A 2013, 370, 197; (c) Ahmed,
N.; Siddiqui, Z. N. J Mol Catal A 2014, 387, 45; (d) Kolvari, E.; Koukabi,
N.; Armandpour, Q. Tetrahedron 2014, 70, 1383; (e) Ma, J. L.; Zhong, L.
X.; Peng, X. W.; Sun, R. C. Green Chem 2016, 18, 1738.
5-Acetyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-
thione (4E) [29]. 1H-NMR (500 MHz, DMSO-d6) δ 10.26
(s, 1H), 9.74 (s, 1H), 7.33 (t, J = 7.4 Hz, 2H), 7.26 (t,
J = 7.3 Hz, 1H), 7.22 (dd, J = 8.1, 1.2 Hz, 2H), 5.29 (d,
J = 3.9 Hz, 1H), 2.32 (s, 3H), 2.15 (s, 3H); 13C-NMR
(126 MHz, DMSO-d6) δ 194.84 (s), 174.16 (s), 144.61
(s), 142.98 (s), 128.70 (s), 127.76 (s), 126.62 (s), 110.55
(s), 53.86 (s), 30.49 (s), 18.32 (s).
[7] (a) Ranu, B. C.; Hajra, A.; Jana, U. J Org Chem 2000, 65,
6270; (b) Zhang, H.; Zhou, Z.; Yao, Z.; Xu, F.; Shen, Q. Tetrahedron Lett
2009, 50, 1622; (c) Lannou, M. I.; Helion, F.; Namy, J. L. Synlett 2008,
5-Acetyl-6-methyl-4-(4-methoxylphenyl)-3,4-dihydro-
pyrimidin-2(1H)-thione (4F) [29].
1H-NMR (500 MHz,
1,
105; (d) Azizian, J.; Mohammadi, A. A.; Karimi, A. R.;
DMSO-d6) δ 10.22 (s, 1H), 9.68 (s, 1H), 7.13 (d,
J = 8.6 Hz, 2H), 6.89 (d, J = 8.6 Hz, 2H), 5.22 (d,
J = 3.8 Hz, 1H), 3.71 (s, 3H), 2.31 (s, 3H), 2.11 (s, 3H);
13C-NMR (126 MHz, DMSO-d6) δ 194.95 (s), 173.90
(s), 158.85 (s), 144.29 (s), 135.15 (s), 127.92 (s), 114.06
(s), 110.53 (s), 55.18 (s), 53.40 (s), 39.60 (s), 30.32 (s),
Mohammadizadeh, M. R. Applied Catal A 2006, 300, 85; (e) Singh, M.
O.; Devi, N. S. J Org Chem 2009, 74, 3141. (f) Safari, J.; Gandomi-
Ravandi, S. New J Chem 2014, 38, 3514.
[8] (a) Siddiqui, I.; Srivastava, R. A.; Shamim, S.; Waseem, M. A.;
Rahila, S.; Abumhdi, A. A. H.; Rai, P. J Mol Catal A 2014, 382, 126; (b)
Safari, J.; Gandomi-Ravandi, S.; Ashiri, S. New J Chem 2016, 40, 512.
[9] (a) Yarapathi, R. V.; Kurvaand, S.; Tammishetti, S. Catal.
Commun. 2004, 5, 511; (b) Wang, J. H.; Tang, G. M.; Yan, S. C.; Wang,
Y. T.; Zhan, S. J.; Zhang, E.; Sun, Y.; Jiang, Y.; Cui, Y. Z. Appl
Organometal Chem 2016, 30, 1009.
[10] (a) Zamani, F.; Izadi, E. Catal Commun 2013, 42, 104; (b) Sa-
fari, J.; Zarnegar, Z. New J. Chem 2014, 38, 358; (c) Elhamifar, D.;
Shabani, A. Chem Eur J 2014, 20, 3212.
[11] Nagarajan, S.; Shaikh, T. M.; Kandasamy, E. J Chem Sci
2015, 127, 1539.
18.24 (s).
5-Acetyl-6-methyl-4-(4-bromophenyl)-3,4-dihydro-pyrimidin-
2(1H)-thione (4G) [29]. 1H-NMR (500 MHz, DMSO-d6) δ
10.33 (s, 1H), 9.77 (s, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.16
(d, J = 8.5 Hz, 2H), 5.26 (d, J = 3.9 Hz, 1H), 2.32 (s, 3H),
2.17 (s, 3H); 13C-NMR (126 MHz, DMSO-d6) δ 194.72
(s), 174.30 (s), 144.99 (s), 142.29 (s), 131.61 (s), 128.83
(s), 120.90 (s), 110.37 (s), 53.19 (s), 39.60 (s), 30.59 (s),
18.39 (s).
[12] Alvim, H. G. O.; de Lima, T. B.; de Oliveira, H. C. B.; Gozzo,
F. C.; de Macedo, J. L.; Abdelnur, P. V.; Silva, W. A.; Neto, B. A. D.
ACS Catal 2013, 3, 1420.
[13] Srivastava, R. Catal Lett 2010, 139, 17.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

G.-P. Zhang, D.-Y. Tian, and W.-M. Shi
Vol 000
[14] Safari, J.; Zarnegar, Z. New J Chem 2014, 38, 358.
[15] Sharma, N.; Sharma, U. K.; Kumar, R.; Arun, R.; Sinha, K.
RSC Adv 2012, 2, 10648.
[16] Chavan, S. S.; Sharma, Y. O.; Degani, M. S. Green Chem Lett
Rev 2009, 2, 175.
[17] (a) Fan, P.; Xing, S.; Wang, J.; Fu, J.; Yang, L.; Yang, G.;
Miao, C.; Lv, P. Fuel 2017, 88, 483; (b) Suresh, L.; Onkara, P.; Kumar,
P. S. V.; Pydisetty, Y.; Chandramouli, G. V. P. Bioorg Med Chem Lett
2016, 26, 4007; (c) Wu, Z.; Chen, C.; Guo, Q.; Li, B.; Que, Y.; Wang,
L.; Wan, H.; Guan, G. Fuel 2016, 184, 128; (d) Senapak, W.; Saeeng,
R.; Jaratjaroonphong, J.; Kasemsuk, T.; Sirion, U. Org Biomol Chem
2016, 14, 1302; (e) Prado, R.; Brandt, A.; Erdocia, X.; Hallet, J.; Welton,
T.; Labidi, J. Green Chem 2016, 18, 834.
[18] Pasunooti, K. K.; Chai, H.; Jensen, C. N.; Gorityala, B. K.;
Wang, S.; Liu, X. W. Tetrahedron Lett 2011, 52, 80.
[19] Wu, Q.; Chen, H.; Han, M.; Wang, D.; Wang, J. Ind Eng
Chem Res 2007, 46, 7955.
[20] a Ma, Y.; Qian, C.; Wang, L.; Yang, M. J Org Chem 2000, 65,
3864; b Hu, E. H.; Sidler, D. R.; Dolling, U. H. J Org Chem 1998, 63,
3454; c Kappe, C. O. Acc Chem Res 2000, 33, 879; d Alvim, H. G.;
da Silva Júnior, E. N.; Neto, B. A. RSC Adv 2014, 4, 54282; e Ramos,
L. M.; Guido, B. C.; Nobrega, C. C.; Correa, J. R.; Silva, R. G.; de
Oliveira, H. C. B.; Gomes, A. F.; Gozzo, F. C.; Neto, B. A. D. Chem A
Eur J 2013, 19, 4156.
[21] De Souza, R.; da Penha, E. T.; Milagre, H. M. S.; Garden, S.
J.; Esteves, P. M.; Eberlin, M. N.; Antunes, O. A. C. Chem A Eur J
2009, 15, 9799.
[22] Li, J. T.; Han, J. F.; Yang, J. H.; Li, T. S. Ultrason Sonochem
2003, 10, 119.
[23] Gholap, A. R.; Venkatesan, K.; Thomas, D.; Lahoti, R. J.;
Srinivasan, K. V. Green Chem 2004, 6, 147.
[24] Folkers, K.; Harwood, H. J.; Johnson, T. B. J Am Chem Soc
1932, 54, 3751.
[25] Shaabani, A.; Rahmati, A. Catal Lett 2005, 100, 177.
[26] Adibi, H.; Samimi, H. A.; Beygzadeh, M. Catal Commun
2007, 8, 2119.
[27] Yadav, J. S.; Reddy, B. V. S.; Sridhar, P.; Reddy, J. S. S.;
Nagaiah, K.; Lingaiah, N.; Saiprasad, P. S. Eur J Org Chem 2004, 2004,
552.
[28] Sujatha, K.; Shanmugam, P.; Perumal, P. T.; Muralidharan, D.;
Rajendran, M. Bioorg Med Chem Lett 2006, 16, 4893.
[29] Liu, Q.; Pan, N.; Xu, J.; Zhang, W.; Kong, F. Synth Commun
2013, 43, 139.
[30] Putilova, E. S.; Kryshtal, G. V.; Zhdankina, G. M.; Troitskii,
N. A.; Zlotin, S. G. Russ J Org Chem 2005, 41, 512.
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of the
article.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet