Tetrachlorosilane catalyzed multicomponent one-step fusion of biopertinent pyrimidine heterocycles

Article abstract of DOI:10.1016/j.tet.2008.03.078

Multicomponent one-step fusion of a variety of pharmacologically pertinent pyrimidine heterocycles has efficiently been achieved from their respective aldehydes, β-dicarbonyl compounds, and urea/thiourea in the presence of a catalytic amount of tetrachlor

Full text of DOI:10.1016/j.tet.2008.03.078

Tetrahedron 64 (2008) 5023–5031
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Tetrachlorosilane catalyzed multicomponent one-step fusion
of biopertinent pyrimidine heterocycles
*
Chennan Ramalingan, Young-Woo Kwak
Department of Chemistry, Kyungpook National University, Taegu 702-701, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Multicomponent one-step fusion of a variety of pharmacologically pertinent pyrimidine heterocycles has
efficiently been achieved from their respective aldehydes, b-dicarbonyl compounds, and urea/thiourea in
the presence of a catalytic amount of tetrachlorosilane in DMF/AN mixture at normal ambient temperature.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 27 February 2008
Received in revised form 21 March 2008
Accepted 21 March 2008
Available online 28 March 2008
1. Introduction
FeCl3, and CuCl catalyzed reactions require concd HCl, tetraethyl-
orthosilicate, and AcOH/BF3$OEt2, respectively, in addition to high
Multicomponent one-pot synthesis to furnish new chemical
entities possessing partial structures of each reactant undoubtedly
receives much attention in organic and medicinal chemistries.1
Biginelli’s dihydropyrimidone (DHPM) synthesis,2 a venerable
acid catalyzed multicomponent one-pot assembly of aldehyde, b-
ketoester, and urea, discovered in 1893, which was largely ignored
for many years apart from a series of publications by Folkers3 in the
early 1930s, has recently attracted a great deal of attention since
DHPMs are important heterocyclic motif in the realm of natural and
synthetic organic chemistries due mainly to their wide spectra of
biological activities.4–6 Synthetic DHPM analogous apart, several
marine natural products with interesting biological activities con-
taining the DHPM scaffold have recently been isolated7 and many of
them were synthesized employing a ‘tethered Biginelli condensa-
tion’ as one of the key steps.8
Although Biginelli’s one-pot methodology is appealing due to its
simplicity, the demerits, however, associated with this synthetic
protocol are represented by the modest yield (20–50%) and/or
the cumbersome method of product isolation.3,9 To preserve its
simplicity with better yield, extensive efforts including catalytic
methods with robust reaction conditions have been devoted in the
recent past.10–16 Despite the other significant developments, cata-
lytic versions of the Biginelli reaction are particularly arousing
interest for practical applications because they normally simplify
processing conditions while minimizing reactant use as well as
waste production. The catalytic protocols reported to-date, how-
ever, require high/low reaction temperature and/some additives:
reaction temperature to effect the DHPMs. Further, the catalysts
used in most of the methods are either expensive or need to be
synthesized. Considering the above demerits, disclosed herein is
an efficient, simple, and high yielding protocol for the synthesis of
DHPMs/DHPM thiones involving the three-component, one-pot
assembly of aldehydes, b-dicarbonyl compounds, and urea/thio-
urea into DHPMs/DHPM thiones using readily available tetra-
chlorosilane (SiCl4) as a catalyst at normal ambient temperature.
2. Results and discussion
First, the optimization of the reaction was groped, for which the
reaction of benzaldehyde, ethylacetoacetate, and urea was selected
as a model. It was hypothesized that a critical choice of metal halide
might efficiently catalyze the one-step fusion of DHPMs/DHPM
thiones by forming a better activated intermediate (see the Scheme
2). A preliminary examination showed that SiCl4 in N,N-dime-
thylformamide (DMF)/acetonitrile (AN) in the ratio of 1:2, re-
spectively, among several solvents effectively catalyzed the model
reaction at ambient temperature. Of the reactions using different
quantities of reactants, the best results were obtained using 1.0:1.0:1.3
ratios of benzaldehyde, ethylacetoacetate, and urea, respectively.
When a mixture of benzaldehyde, ethylacetoacetate, and urea
in DMF/AN (1:2) was stirred in the presence of SiCl4 (10 mol %) at
ambient temperature for 4 h under nitrogen atmosphere, the fused
heterocyclic product, 5-ethoxycarbonyl-4-phenyl-6-methyl-3,4-
dihydropyrimidin-2(1H)-one, was produced in excellent yield (95%,
Scheme 1). At the same time, decreasing the amount of catalyst
from 10 mol % to 5 mol % lowered the DHPM yield (59%) while in-
creasing the amount of catalyst from 10 mol % to 25 mol % did not
show any significant impact on the DHPM yield indicating that the
above reaction condition was appropriate for the one-pot assembly.
e.g., L-pro–OMe$HCl, Yb(NTf2)2, Cu(OTf)2, and In(OTf)3 catalyzed
reactions require high/low reaction temperature while LaCl3$7H2O,
* Corresponding author. Tel.: þ82 53 950 5339; fax: þ82 53 950 6330.
E-mail address: ywkwak@knu.ac.kr (Y.-W. Kwak).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.03.078

5024
C. Ramalingan, Y.-W. Kwak / Tetrahedron 64 (2008) 5023–5031
O
and 4 h, respectively. This remarkable activation in reaction rate
O
NH2
O
prompted us to explore the potential of this protocol for the syn-
thesis of a variety of DHPMs/DHPM thiones and the results are
summarized in Table 2. All the aforementioned reactions proceeded
expeditiously and delivered better to excellent product yields ac-
commodating a wide range of aromatic aldehydes bearing both
electron-donating and electron-withdrawing substituents. The
overall yields ranged from 98% of 5-ethoxycarbonyl-4-(4-chloro-
phenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (entry 6) to
75% of 5-methoxycarbonyl-4-(2-methoxyphenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-thione (entry 28).
NH
O
H2N
Me
O
HN
SiCl4 (10 mol%)
O
+
Me
O
Solvent
Ambient temp., 4 h
H
Me
Me
O
Scheme 1. Synthesis of 5-ethoxycarbonyl-4-phenyl-6-methyl-3,4-dihydropyrimidin-
2(1H)-one.
X
N
X
N
Of the one-pot assembly of various substituted aldehydes, ethyl-
acetoacetate, and urea, the use of aldehydes possessing electron-
withdrawing substituents produced the corresponding DHPMs with
higher yields compared to the use of aldehydes possessing electron
releasing substituents (compare the entries 2 and 3 or entries 4/5
and 6). Thiourea was also used with similar success along with
substituted aldehydes and ethylacetoacetate (entries 7–11) al-
though the yields of DHPM thiones were slightly lower than those of
their corresponding DHPMs.
Replacing the b-ketoester, ethylacetoacetate, by a diketone,
2,4-pentadione, in the model one-pot assembly also produced an
excellent yield of its corresponding DHPM (entry 12). Consequently,
one-pot assembly of various substituted aldehydes, 2,4-penta-
dione, and urea delivered their corresponding DHPMs in better
to excellent yields (entries 12–16). Of those, the use of ortho
methoxybenzaldehyde produced its corresponding DHPM in the
lowest yield (entry 14) while para chlorobenzaldehyde produced
its corresponding DHPM in the highest yield (entry 16). One-pot
assembly of various substituted aldehydes, 2,4-pentadione, and
thiourea as well afforded their corresponding DHPM thiones in
better to excellent yields (entries 17–20). As DHPM analogues,
the DHPM thione analogue containing ortho methoxy substituent
on the aryl moiety was also formed in the lowest yield (entry 18)
while its para chloro analogue was afforded in the highest yield
(entry 20).
H
NH2
OH
NH2
O
+
H
H
SiCl4
X
O
NH2
Si
H
H
H2N
R
(B)
(A)
(C)
(D)
R
R
Si4+
Si4+
H
N
X
X
X
NH2
H
NH2
H
H
Si4+
+H N
O
R2
R1
N
HN
(or)
R1
R1
H
O
O
Si4+
(G)
O
R
R
R
Si4+
R2
O
H
R2
O
H
(E)
(F)
(H)
(G)
H
N
X
X
H
O
R2
NH
R2
R1
HN
HN
H
R1
O
O
R
R
(I)
(J)
Scheme 2. Mechanism for the tetrachlorosilane catalyzed one-step fusion of pyrimi-
dine heterocycles.
Switching over to the use of methylacetoacetate in place of
ethylacetoacetate in the model one-pot assembly delivered its
corresponding DHPM with similar success (entry 21). The use of
various substituted aldehydes, methylacetoacetate, and urea
afforded their corresponding DHPMs in better to excellent yields
(entries 21–26). Akin to the DHPMs, DHPM thiones were also
formed in better to excellent yields when urea was replaced by
thiourea (entries 27–30).
The one-pot assembly of ortho substituted aldehydes, ethyl-
acetoacetate/2,4-pentadione/methylacetoacetate, and urea pro-
duced their DHPMs in lower yields compared to the one-pot
assembly of their corresponding para substituted/unsubstituted
aldehydes, ethylacetoacetate/2,4-pentadione/methylacetoacetate,
and urea. A similar trend has been noticed in the case of DHPM
thiones as well. Probably, the bulky ortho substituent partially hin-
ders either the initial nucleophilic addition reaction of aldehyde and
urea/thiourea or the formation of the open chain intermediate H
(see the Scheme 2) due to steric effect.
The attention was then focused toward the effect of solvents on
the yields of the one-pot assembly of the model and the results are
depicted in Table 1. Replacing DMF/AN (1:2) by dimethyl sulfoxide
(DMSO)/AN (1:2) produced the model in an appreciable yield (entry
2) albeit lower than that of the one produced by the former (entry 1).
Other solvents such as AN, DMF, DMSO, tetrahydrofuran (THF),
benzene, and 1,4-dioxane accomplished the model in moderate
yields (60–69%; entries 3–5 and 7–9) while diethyl ether, dimethoxy
ethane (DME), toluene, n-hexane, acetone, and dichloromethane
(DCM) produced still lower yields (30–50%; entries 6 and 10–14).
Optimized conditionwas established in DMF/AN mixture (1:2) as
a solvent system using a reaction temperature and time of ambient
Table 1
Effect of solvents on the yield of the one-step fusion of 5-ethoxycarbonyl-4-phenyl-
6-methyl-3,4-dihydropyrimidin-2(1H)-one
Entry
Solvent
Yield (%)
1
2
3
4
5
6
7
8
DMF/AN (1:2)
DMSO/AN (1:2)
AN
DMF
DMSO
Diethyl ether
THF
Benzene
1,4-Dioxane
DME
Toluene
n-Hexane
Acetone
DCM
95
79
60
65
61
48
69
66
62
33
31
50
37
30
Considering the mechanism for the formation of DHPMs via
acylimine intermediate, described by Folkers et al.,3 the following
mechanism has been proposed (Scheme 2). The mechanism con-
sists of an initial step of a reaction between the respective alde-
hydes (A) and urea/thiourea (B) to form their corresponding
hemiaminals, N-(1-hydroxybenzyl/substituted benzyl)ureas/thio-
ureas (C) via standard nucleophilic addition reaction. Although the
above nucleophilic addition reaction is likely to be an equilibrium
reaction, the hemiaminals C are expected to undergo rapid con-
densation with SiCl4 to provide the intermediate D, which may
be formulated as a highly reactive intermediate either E or F.17
Simultaneously, the respective b-ketoesters/b-diketone possibly
9
10
11
12
13
14

C. Ramalingan, Y.-W. Kwak / Tetrahedron 64 (2008) 5023–5031
5025
Table 2
Tetrachlorosilane catalyzed one-step fusion of pyrimidine heterocycles
Entry
Aldehyde
Dicarbonyl compound
Urea/thiourea
Pyrimidone/pyrimidinethione (%)
Yield (%)
O
Me
O
O
H
NH
NH2
HN
Me
1
95
H2N
O
O
O
Me
O
O
Me
O
Me
O
O
H
NH
NH2
O
HN
Me
2
Cl
90
Cl
H2N
O
O
Me
O
O
Me
O
Me
O
O
H
NH
NH2
O
HN
Me
Me
3
O
H
79
O
Me
H2N
O
O
Me
O
O
Me
Me
O
O
Me
O
NH
HN
Me
NH2
O
4
85
H2N
O
O
O
Me
O
O
Me
H
Me
O
O
O
Me
O
NH
HN
NH2
O
Me
5
86
H2N
O
O
Me
O
O
Me
Me
Me
O
O
O
H
H
Me
O
NH
HN
NH2
O
Me
6
98
H2N
O
O
Me
O
O
Cl
Me
Cl
S
Me
O
NH
HN
NH2
S
Me
7
91
H2N
O
O
Me
O
O
Me
S
Me
O
O
H
NH
NH2
S
HN
Me
Me
8
O
77
O
Me
H2N
O
O
Me
O
O
Me
S
O
H
Me
O
NH
HN
Me
NH2
S
9
82
H2N
O
O
O
Me
O
Me
O
Me
Me
O
(continued on next page)

5026
C. Ramalingan, Y.-W. Kwak / Tetrahedron 64 (2008) 5023–5031
Table 2 (continued)
Entry
Aldehyde
Dicarbonyl compound
Urea/thiourea
Pyrimidone/pyrimidinethione (%)
Yield (%)
S
O
H
Me
NH
HN
O
NH2
Me
10
85
H2N
S
O
O
O
Me
Me
O
O
Me
Me
Me
S
O
H
H
Me
NH
HN
O
NH2
S
Me
11
12
92
H2N
O
O
O
Me
Cl
Cl
O
O
Me
NH
NH2
O
HN
Me
Me
94
O
H2N
Me
O
O
O
O
H
Me
O
NH
NH2
O
HN
Me
Me
13
14
Cl
93
78
Cl
H2N
H2N
Me
Me
O
O
O
O
O
H
Me
O
NH
NH2
O
HN
Me
Me
Me
O
O
Me
O
O
O
O
O
H
NH
Me
O
HN
Me
NH2
O
15
16
82
H2N
Me
Me
Me
O
O
O
Me
Me
O
H
NH
Me
O
HN
Me
Me
NH2
O
95
H2N
O
Cl
Cl
S
H
Me
O
NH
NH2
S
HN
17
18
90
76
Me
H2N
H2N
Me
Me
O
O
Me
O
S
O
H
Me
O
NH
NH2
S
HN
Me
O
O
Me
Me
Me
O
S
O
H
Me
O
NH
HN
NH2
S
19
Me
83
H2N
Me
O
Me
O
Me
Me

C. Ramalingan, Y.-W. Kwak / Tetrahedron 64 (2008) 5023–5031
5027
Table 2 (continued)
Entry
Aldehyde
Dicarbonyl compound
Urea/thiourea
Pyrimidone/pyrimidinethione (%)
Yield (%)
S
O
H
NH
Me
O
HN
Me
NH2
20
94
H2N
S
Me
O
Me
O
Cl
Cl
O
Me
NH
O
H
O
HN
Me
NH2
O
21
95
O
H2N
Me
O
O
O
O
O
Me
O
Me
Me
NH
O
H
O
HN
Cl
NH2
O
Me
22
Cl
92
O
H2N
Me
Me
O
O
Me
O
NH
O
H
O
HN
NH2
O
Me
Me
O
23
O
H
80
O
Me
H2N
O
O
Me
O
O
NH
Me
O
HN
NH2
O
Me
24
85
O
H2N
O
Me
O
O
O
Me
Me
H
Me
O
O
O
NH
Me
Me
O
HN
NH2
O
Me
25
86
O
H2N
O
Me
Me
O
O
O
Me
Me
Me
O
O
O
H
H
NH
O
HN
NH2
O
Me
26
96
O
H2N
O
O
Cl
Me
Cl
S
NH
Me
Me
O
HN
NH2
S
Me
27
28
89
O
H2N
Me
Me
O
O
O
O
Me
S
NH
O
H
O
HN
NH2
S
Me
Me
O
O
75
O
Me
H2N
O
O
Me
(continued on next page)

5028
C. Ramalingan, Y.-W. Kwak / Tetrahedron 64 (2008) 5023–5031
Table 2 (continued)
Entry
Aldehyde
Dicarbonyl compound
Urea/thiourea
Pyrimidone/pyrimidinethione (%)
Yield (%)
S
O
H
NH
Me
Me
O
HN
Me
NH2
29
81
O
H2N
S
O
O
Me
Me
O
O
O
Me
Me
Me
O
S
O
H
NH
O
HN
NH2
S
Me
30
84
O
H2N
O
O
Me
Me
Me
their enol form activated by Si4þ (G) attacks the iminium carbon of
the active intermediate either E or F to afford the open chain
intermediates H. The cyclized intermediate possessing hydroxyl
group I is produced from H by further nucleophilic addition, which
in turn eventually undergoes dehydration to furnish the DHPMs/
DHPM thiones (J).
Furthermore, in order to clarify whether a silicon species or only
an in situ generation of HCl, as it is possible in the Biginelli reaction,
is involved in the acceleration of the reaction, a couple of
experiments were carried out using only HCl (40 mol %) as a cata-
lyst. Replacing SiCl4 by HCl in the multicomponent reaction of
p-chlorobenzaldehyde, ethylacetoacetate, and urea under similar
experimental conditions provided the corresponding DHPM in 54%
yield while similar replacement in the reaction of o-methoxy-
benzaldehyde, 2,4-pentadione, and thiourea afforded its corre-
sponding DHPM thione in 28% yield unlike better to excellent yields
in their original reactions (Table 2, entries 6 and 18). These results
suggest that silicon species might have played a major role in the
activation/promotion of the reaction by possibly forming the
intermediates either E or F and G as shown in the mechanism.
4.1.1. Tetrachlorosilane catalyzed multicomponent one-step fusion
of pyrimidine heterocycles: synthesis of 5-ethoxycarbonyl-4-phenyl-
6-methyl-3,4-dihydropyrimidin-2(1H)-one (Table 2, entry 1)
To a stirring mixture of benzaldehyde (0.20 mL, 2 mmol), ethyl-
acetoacetate (0.25 mL, 2 mmol), and urea (0.16 g, 2.6 mmol) in DMF/
AN (2.5 mL/5.0 mL) under a nitrogen atmosphere was added tetra-
chlorosilane (0.024 mL, 0.2 mmol). After being stirred at ambient
temperature for 4 h, water (10 mL) was added to the reaction mix-
ture and was stirred for a couple of minutes. The obtained precipitate
was filtered and washed with water followed by ethanol/water
mixture (1:1) and dried. Crystallization from aqueous ethanol
afforded pure 5-ethoxycarbonyl-4-phenyl-6-methyl-3,4-dihy-
dropyrimidin-2(1H)-one as a white solid (0.49 g, 95%), mp 208–
209 ꢀC.16d 1H NMR dH (400 MHz, DMSO-d6, Me4Si, 25 ꢀC) 9.22 (1H, br
s), 7.76 (1H, br s), 7.34–7.30 (2H, m), 7.25–7.23 (3H, m), 5.15 (1H, d,
J¼3.52 Hz), 3.98(2H, q, J¼7.03 Hz), 2.25(3H, s),1.09(3H,t, J¼7.02 Hz).
Similar procedure was adopted for the synthesis of the following
compounds.
4.1.2. 5-Ethoxycarbonyl-4-(2-chlorophenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-one (Table 2, entry 2)
2-Chlorobenzaldehyde (0.23 mL, 2 mmol), ethylacetoacetate
(0.25 mL, 2 mmol), urea (0.16 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) afforded
5-ethoxycarbonyl-4-(2-chlorophenyl)-6-methyl-3,4-dihydropyr-
3. Conclusion
In conclusion, a catalytic amount of tetrachlorosilane efficiently
catalyses the multicomponent one-step fusion of DHPMs/DHPM
thiones in a DMF/AN solvent system at normal ambient tempera-
ture. This procedure does not require any additives or activators or
high/low reaction temperatures. This protocol not only preserves
the simplicity of the Biginelli reaction, but also produces excellent
yields of the DHPMs/DHPM thiones. b-Diketones and thiourea have
also been used with similar success to produce their corresponding
DHPM analogues, which are also of much interest with respect to
their biological activities.
imidin-2(1H)-one (0.53 g, 90%). Mp 214–215 ꢀC.10d 1H NMR d
H
(400 MHz, DMSO-d6, Me4Si, 25 ꢀC) 9.29 (1H, br s), 7.73 (1H, br s),
7.41 (1H, d, J¼7.52 Hz), 7.32–7.25 (3H, m), 5.63 (1H, d, J¼3.00 Hz),
3.89 (2H, q, J¼7.03 Hz), 2.30 (3H, s), 0.99 (3H, t, J¼7.02 Hz).
4.1.3. 5-Ethoxycarbonyl-4-(2-methoxyphenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-one (Table 2, entry 3)
2-Methoxybenzaldehyde (0.24 mL, 2 mmol), ethylacetoacetate
(0.25 mL, 2 mmol), urea (0.16 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) produced 5-
ethoxycarbonyl-4-(2-methoxyphenyl)-6-methyl-3,4-dihydropyr-
4. Experimental
4.1. General
imidin-2(1H)-one (0.46 g, 79%). Mp 256–257 ꢀC.14b 1H NMR d
H
(400 MHz, DMSO-d6, Me4Si, 25 ꢀC) 9.14 (1H, br s), 7.30 (1H, br s),
7.25–7.21 (1H, m), 7.05 (1H, dd, J¼7.54, 1.50 Hz), 6.98 (1H, d,
J¼8.00 Hz), 6.87 (1H, t, J¼7.28 Hz), 5.49 (1H, d, J¼3.00 Hz), 3.91 (q,
J¼3.00 Hz), 3.79 (3H, s), 2.28 (3H, s), 1.02 (3H, t, J¼7.04 Hz).
All melting points were measured in open capillaries and are un-
corrected. Reagent grade reagents were purchased and were used
without further purification. All solvents used herein were distilled
prior to use. 1H NMR spectra were acquired at 400 MHz by using
DMSO-d6 as a solvent and TMS as an internal standard. The NMR
multiplicities br s, s, d, dd, q, t, and m stand for broad singlet, singlet,
doublet, doublet of doublet, quartet, triplet, and multiplet, respectively.
4.1.4. 5-Ethoxycarbonyl-4-(4-methoxyphenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-one (Table 2, entry 4)
4-Methoxybenzaldehyde (0.24 mL, 2 mmol), ethylacetoacetate
(0.25 mL, 2 mmol), urea (0.16 g, 2.6 mmol), and tetrachlorosilane

C. Ramalingan, Y.-W. Kwak / Tetrahedron 64 (2008) 5023–5031
5029
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) afforded 5-
ethoxycarbonyl-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyri-
(0.024 mL, 0.2 mmol)in DMF/AN (2.5 mL/5.0 mL) afforded5-ethoxy-
carbonyl-4-(4-methylphenyl)-6-methyl-3,4-dihydropyrimidin-
2(1H)-thione (0.49 g, 85%). Mp 190–192 ꢀC.15a 1H NMR dH (400 MHz,
DMSO-d6, Me4Si, 25 ꢀC) 10.32 (1H, br s), 9.63 (1H, br s), 7.15 (2H, d,
J¼8.00 Hz), 7.10 (2H, d, J¼8.52 Hz), 5.13 (1H, d, J¼3.52 Hz), 4.00 (2H,
q, J¼7.01 Hz), 2.29 (3H, s), 2.26 (3H, s), 1.11 (3H, t, J¼7.02 Hz).
midin-2(1H)-one (0.49 g, 85%). Mp 202–203 ꢀC.16d 1H NMR d
H
(400 MHz, DMSO-d6, Me4Si, 25 ꢀC) 9.17 (1H, br s), 7.69 (1H, br s), 7.15
(2H, d, J¼8.52 Hz), 6.88 (2H, d, J¼8.56 Hz), 5.09 (1H, d, J¼3.52 Hz),
3.98 (2H, q, J¼7.19 Hz), 3.72 (3H, s), 2.24 (3H, s),1.10 (3H, t, J¼7.02 Hz).
4.1.5. 5-Ethoxycarbonyl-4-(4-methylphenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-one (Table 2, entry 5)
4.1.11. 5-Ethoxycarbonyl-4-(4-chlorophenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-thione (Table 2, entry 11)
4-Methylbenzaldehyde (0.24 mL, 2 mmol), ethylacetoacetate
(0.25 mL, 2 mmol), urea (0.16 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) gave 5-ethoxy-
carbonyl-4-(4-methylphenyl)-6-methyl-3,4-dihydropyrimidin-
2(1H)-one (0.47 g, 86%). Mp 210–211 ꢀC.10d 1H NMR dH (400 MHz,
DMSO-d6, Me4Si, 25 ꢀC) 9.18 (1H, br s), 7.71 (1H, br s), 7.12 (4H, s),
5.11 (1H, d, J¼3.52 Hz), 3.98 (2H, q, J¼7.01 Hz), 2.26 (3H, s), 2.24
(3H, s), 1.10 (3H, t, J¼7.04 Hz).
4-Chlorobenzaldehyde (0.28 g, 2 mmol), ethylacetoacetate
(0.25 mL,2 mmol), thiourea(0.20 g, 2.6 mmol), andtetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) gave 5-ethoxy-
carbonyl-4-(4-chlorophenyl)-6-methyl-3,4-dihydropyrimidin-
2(1H)-thione (0.57 g, 92%). Mp 193–194 ꢀC.18 1H NMR dH (400 MHz,
DMSO-d6, Me4Si, 25 ꢀC) 10.40 (1H, br s), 9.68 (1H, br s), 7.43 (2H, d,
J¼7.04 Hz), 7.22 (2H, d, J¼7.04 Hz), 5.16 (1H, br s), 4.00 (2H, q,
J¼7.01 Hz), 2.29 (3H, s), 2.26 (3H, s), 1.10 (3H, t, J¼7.04 Hz).
4.1.6. 5-Ethoxycarbonyl-4-(4-chlorophenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-one (Table 2, entry 6)
4.1.12. 5-Acetyl-4-phenyl-6-methyl-3,4-dihydropyrimidin-2(1H)-
one (Table 2, entry 12)
4-Chlorobenzaldehyde (0.28 g, 2 mmol), ethylacetoacetate
(0.25 mL, 2 mmol), urea (0.16 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) afforded 5-
ethoxycarbonyl-4-(4-chlorophenyl)-6-methyl-3,4-dihydropyrimi-
din-2(1H)-one (0.58 g, 98%). Mp 212–213 ꢀC.16d 1H NMR dH
(400 MHz, DMSO-d6, Me4Si, 25 ꢀC) 9.27 (1H, br s), 7.80 (1H, br s), 7.40
(2H, d, J¼8.52 Hz), 7.26 (2H, d, J¼8.52 Hz), 5.15 (1H, d, J¼3.04 Hz),
3.98 (2H, q, J¼7.19 Hz), 2.26 (3H, s), 1.10 (3H, t, J¼7.04 Hz).
Benzaldehyde (0.20 mL, 2 mmol), acetylacetone (0.21 mL,
2 mmol), urea (0.16 g, 2.6 mmol), and tetrachlorosilane (0.024 mL,
0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) provided 5-acetyl-4-phenyl-
6-methyl-3,4-dihydropyrimidin-2(1H)-one (0.43 g, 94%). Mp 233–
235 ꢀC.16d 1H NMR d (400 MHz, DMSO-d6, Me4Si, 25 ꢀC) 9.19 (1H,
H
br s), 7.84 (1H, br s), 7.34–7.31 (2H, m), 7.26–7.23 (3H, m), 5.26 (1H,
d, J¼3.52 Hz), 2.29 (3H, s), 2.10 (3H, s).
4.1.13. 5-Acetyl-4-(2-chlorophenyl)-6-methyl-3,4-dihydropyri-
midin-2(1H)-one (Table 2, entry 13)
4.1.7. 5-Ethoxycarbonyl-4-phenyl-6-methyl-3,4-dihydropyrimidin-
2(1H)-thione (Table 2, entry 7)
2-Chlorobenzaldehyde (0.23 mL, 2 mmol), acetylacetone
(0.21 mL, 2 mmol), urea (0.16 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) yielded pure
5-acetyl-4-(2-chlorophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-
one (0.49 g, 93%). Mp 228–229 ꢀC.19 1H NMR dH(400 MHz, DMSO-
d6, Me4Si, 25 ꢀC) 9.28 (1H, br s), 7.74 (1H, br s), 7.44 (1H, dd, J¼7.28,
1.76 Hz), 7.34–7.25 (3H, m), 5.67 (1H, d, J¼3.52 Hz), 2.34 (3H, s),
2.06 (3H, s).
Benzaldehyde (0.20 mL, 2 mmol), ethylacetoacetate (0.25 mL,
2 mmol), thiourea (0.20 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) produced 5-
ethoxycarbonyl-4-phenyl-6-methyl-3,4-dihydropyrimidin-2(1H)-
thione (0.50 g, 91%). Mp 203–205 ꢀC.14b 1H NMR d (400 MHz,
H
DMSO-d6, Me4Si, 25 ꢀC) 10.36 (1H, br s), 9.68 (1H, br s), 7.37–7.33
(2H, m), 7.30–7.22 (3H, m), 5.18 (1H, d, J¼3.52 Hz), 4.01 (2H, q,
J¼7.03 Hz), 2.30 (3H, s), 1.10 (3H, t, J¼7.02 Hz).
4.1.14. 5-Acetyl-4-(2-methoxyphenyl)-6-methyl-3,4-dihydropyri-
midin-2(1H)-one (Table 2, entry 14)
4.1.8. 5-Ethoxycarbonyl-4-(2-methoxyphenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-thione (Table 2, entry 8)
2-Methoxybenzaldehyde (0.24 mL, 2 mmol), acetylacetone
(0.21 mL, 2 mmol), urea (0.16 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) afforded 5-acetyl-
4-(2-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one
2-Methoxybenzaldehyde (0.24 mL, 2 mmol), ethylacetoacetate
(0.25 mL,2 mmol), thiourea(0.20 g, 2.6 mmol), andtetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) gave 5-ethoxy-
carbonyl-4-(2-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-
2(1H)-thione (0.47 g, 77%). Mp 200–202 ꢀC.4 1H NMR dH (400 MHz,
DMSO-d6, Me4Si, 25 ꢀC) 10.24 (1H, br s), 9.26 (1H, br s), 7.28–7.24
(1H, m), 7.05 (1H, dd, J¼7.54, 1.50 Hz), 7.00 (1H, d, J¼8.52 Hz), 6.90
(1H, t, J¼7.26 Hz), 5.50 (1H, d, J¼3.52 Hz), 3.97–3.91 (2H, m), 3.79
(3H, s), 2.29 (3H, s), 1.04 (3H, t, J¼7.02 Hz).
(0.41 g, 78%). Mp 249–250 ꢀC.20 1H NMR d (400 MHz, DMSO-d6,
H
Me4Si, 25 ꢀC) 9.14 (1H, br s), 7.36 (1H, br s), 7.28–7.23 (1H, m), 7.05–
7.00 (2H, m), 6.89 (1H, t, J¼7.54 Hz), 5.57 (1H, d, J¼3.04 Hz), 3.82
(3H, s), 2.29 (3H, s), 2.02 (3H, s).
4.1.15. 5-Acetyl-4-(4-methylphenyl)-6-methyl-3,4-dihydro-
pyrimidin-2(1H)-one (Table 2, entry 15)
4.1.9. 5-Ethoxycarbonyl-4-(4-methoxyphenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-thione (Table 2, entry 9)
4-Methylbenzaldehyde (0.24 mL, 2 mmol), acetylacetone
(0.21 mL, 2 mmol), urea (0.16 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) gave 5-acetyl-
4-(4-methylphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one
4-Methoxybenzaldehyde (0.24 mL, 2 mmol), ethylacetoacetate
(0.25 mL, 2 mmol), thiourea (0.20 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) yielded 5-ethoxy-
carbonyl-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-
2(1H)-thione (0.50 g, 82%). Mp 152–153 ꢀC.18 1H NMR dH (400 MHz,
DMSO-d6, Me4Si, 25 ꢀC) 10.31 (1H, br s), 9.62 (1H, br s), 7.13 (2H, d,
J¼8.52 Hz), 6.90 (2H, d, J¼8.52 Hz), 5.12 (1H, d, J¼3.52 Hz), 4.00
(2H, q, J¼7.01 Hz), 3.72 (3H, s), 2.29 (3H, s), 1.11 (3H, t, J¼7.02 Hz).
(0.40 g, 82%). Mp 203–205 ꢀC.15a 1H NMR d (400 MHz, DMSO-d6,
H
Me4Si, 25 ꢀC) 9.15 (1H, br s), 7.78 (1H, br s), 7.13 (4H, br s), 5.21 (1H,
d, J¼3.52 Hz), 2.28 (3H, s), 2.26 (3H, s), 2.08 (3H, s).
4.1.16. 5-Acetyl-4-(4-chlorophenyl)-6-methyl-3,4-dihydro-
pyrimidin-2(1H)-one (Table 2, entry 16)
4.1.10. 5-Ethoxycarbonyl-4-(4-methylphenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-thione (Table 2, entry 10)
4-Methylbenzaldehyde (0.24 mL, 2 mmol), ethylacetoacetate
(0.25 mL,2 mmol), thiourea(0.20 g, 2.6 mmol), andtetrachlorosilane
4-Chlorobenzaldehyde (0.28 g, 2 mmol), acetylacetone (0.21 mL,
2 mmol), urea (0.16 g, 2.6 mmol), and tetrachlorosilane (0.024 mL,
0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) provided 5-acetyl-4-(4-
chlorophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (0.50 g,

5030
C. Ramalingan, Y.-W. Kwak / Tetrahedron 64 (2008) 5023–5031
95%). Mp 204–206 ꢀC.16d 1H NMR d (400 MHz, DMSO-d6, Me4Si,
4.1.23. 5-Methoxycarbonyl-4-(2-methoxyphenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-one (Table 2, entry 23)
H
25 ꢀC) 9.24 (1H, br s), 7.87 (1H, br s), 7.39 (2H, d, J¼8.04 Hz), 7.26 (2H,
d, J¼8.56 Hz), 5.26 (1H, d, J¼3.52 Hz), 2.29 (3H, s), 2.13 (3H, s).
2-Methoxybenzaldehyde (0.24 mL, 2 mmol), methylacetoacetate
(0.22 mL, 2 mmol), urea (0.16 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) gave 5-methoxy-
carbonyl-4-(2-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-
4.1.17. 5-Acetyl-4-phenyl-6-methyl-3,4-dihydropyrimidin-2(1H)-
thione (Table 2, entry 17)
Benzaldehyde (0.20 mL, 2 mmol), acetylacetone (0.21 mL,
2 mmol), thiourea(0.20 g,2.6 mmol), andtetrachlorosilane(0.024 mL,
0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) afforded 5-acetyl-4-phenyl-6-
methyl-3,4-dihydropyrimidin-2(1H)-thione (0.44 g, 90%). Mp 222–
224 ꢀC.18 1H NMR dH (400 MHz, DMSO-d6, Me4Si, 25 ꢀC) 10.29 (1H, br
s), 9.77 (1H, br s), 7.37–7.33 (2H, m), 7.29–7.23 (3H, m), 5.30 (1H, d,
J¼3.48 Hz), 2.34 (3H, s), 2.16 (3H, s).
2(1H)-one (0.44 g, 80%). Mp 282–283 ꢀC.16a 1H NMR d (400 MHz,
H
DMSO-d6, Me4Si, 25 ꢀC) 9.09 (1H, br s), 7.23 (1H, br s), 7.19 (1H, br s),
7.01–6.98 (2H, m), 6.87 (1H, br s), 5.48 (1H, br s), 3.80 (3H, s), 3.47
(3H, s), 2.28 (3H, s).
4.1.24. 5-Methoxycarbonyl-4-(4-methoxyphenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-one (Table 2, entry 24)
4-Methoxybenzaldehyde (0.24 mL, 2 mmol), methylacetoacetate
(0.22 mL, 2 mmol), urea (0.16 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) provided 5-
methoxycarbonyl-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyr-
imidin-2(1H)-one (0.47 g, 85%). Mp 195–196 ꢀC.10b 1H NMR dH
(400 MHz, DMSO-d6, Me4Si, 25 ꢀC) 9.14 (1H, br s), 7.65 (1H, br s), 7.16
(2H, d, J¼8.56 Hz), 6.88 (2H, d, J¼8.52 Hz), 5.11 (1H, d, J¼3.04 Hz),
3.73 (3H, s), 3.54 (3H, s), 2.26 (3H, s).
4.1.18. 5-Acetyl-4-(2-methoxyphenyl)-6-methyl-3,4-dihydropyri-
midin-2(1H)-thione (Table 2, entry 18)
2-Methoxybenzaldehyde (0.24 mL, 2 mmol), acetylacetone
(0.21 mL, 2 mmol), thiourea (0.20 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) yielded 5-acetyl-
4-(2-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-thi-
one (0.42 g, 76%). Mp 179–180 ꢀC. 1H NMR dH (400 MHz, DMSO-d6,
Me4Si, 25 ꢀC) 10.21 (1H, br s), 9.33 (1H, br s), 7.30–7.26 (1H, m), 7.05–
7.02 (2H, m), 6.91 (1H, t, J¼7.52 Hz), 5.60 (1H, d, J¼3.52 Hz), 3.81 (3H,
s), 2.29 (3H, s), 2.09 (3H, s).
4.1.25. 5-Methoxycarbonyl-4-(4-methylphenyl)-6-methyl-3,4-di-
hydropyrimidin-2(1H)-one (Table 2, entry 25)
4-Methylbenzaldehyde (0.24 mL, 2 mmol), methylacetoacetate
(0.22 mL, 2 mmol), urea (0.16 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) afforded 5-
methoxycarbonyl-4-(4-methylphenyl)-6-methyl-3,4-dihydropyr-
imidin-2(1H)-one (0.45 g, 86%). Mp 208–210 ꢀC.13a 1H NMR dH
(400 MHz, DMSO-d6, Me4Si, 25 ꢀC) 9.14 (1H, br s), 7.66 (1H, br s),
7.13 (4H, br s), 5.13 (1H, d, J¼3.52 Hz), 3.54 (3H, s), 2.27 (3H, s), 2.26
(3H, s).
4.1.19. 5-Acetyl-4-(4-methylphenyl)-6-methyl-3,4-dihydro-
pyrimidin-2(1H)-thione (Table 2, entry 19)
4-Methylbenzaldehyde (0.24 mL, 2 mmol), acetylacetone
(0.21 mL,2 mmol), thiourea(0.20 g, 2.6 mmol), andtetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) provided 5-acetyl-
4-(4-methylphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-thi-
one (0.43 g, 83%). Mp 215–217 ꢀC. 1H NMR dH (400 MHz, DMSO-d6,
Me4Si, 25 ꢀC) 10.25 (1H, br s), 9.72 (1H, br s), 7.16–7.10 (4H, m), 5.26
(1H, d, J¼3.52 Hz), 2.33 (3H, s), 2.27 (3H, s), 2.13 (3H, s).
4.1.26. 5-Methoxycarbonyl-4-(4-chlorophenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-one (Table 2, entry 26)
4.1.20. 5-Acetyl-4-(4-chlorophenyl)-6-methyl-3,4-dihydro-
pyrimidin-2(1H)-thione (Table 2, entry 20)
4-Chlorobenzaldehyde (0.28 g, 2 mmol), methylacetoacetate
(0.22 mL, 2 mmol), urea (0.16 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) gave 5-methoxy-
carbonyl-4-(4-chlorophenyl)-6-methyl-3,4-dihydropyrimidin-
4-Chlorobenzaldehyde (0.28 g, 2 mmol), acetylacetone (0.21 mL,
2 mmol), thiourea(0.20 g,2.6 mmol), andtetrachlorosilane(0.024 mL,
0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) gave 5-acetyl-4-(4-chloro-
phenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-thione (0.53 g, 94%).
Mp 207–208 ꢀC.19 1H NMR dH (400 MHz,DMSO-d6, Me4Si, 25 ꢀC) 10.34
(1H, br s), 9.78 (1H, br s), 7.42 (2H, d, J¼8.52 Hz), 7.24 (2H, d,
J¼8.04 Hz), 5.30 (1H, d, J¼3.52 Hz), 2.34 (3H, s), 2.18 (3H, s).
2(1H)-one (0.54 g, 96%). Mp 204–206 ꢀC.10b 1H NMR d (400 MHz,
H
DMSO-d6, Me4Si, 25 ꢀC) 9.23 (1H, br s), 7.75 (1H, br s), 7.38 (2H, d,
J¼7.04 Hz), 7.24 (2H, d, J¼7.00 Hz), 5.15 (1H, br s), 3.53 (3H, s), 2.25
(3H, s).
4.1.27. 5-Methoxycarbonyl-4-phenyl-6-methyl-3,4-dihydropyri-
midin-2(1H)-thione (Table 2, entry 27)
4.1.21. 5-Methoxycarbonyl-4-phenyl-6-methyl-3,4-dihydropyri-
midin-2(1H)-one (Table 2, entry 21)
Benzaldehyde (0.20 mL, 2 mmol), methylacetoacetate (0.22 mL,
2 mmol), thiourea (0.20 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) afforded 5-
methoxycarbonyl-4-phenyl-6-methyl-3,4-dihydropyrimidin-2(1H)-
Benzaldehyde (0.20 mL, 2 mmol), methylacetoacetate (0.22 mL,
2 mmol), urea (0.16 g, 2.6 mmol), and tetrachlorosilane (0.024 mL,
0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) afforded 5-methoxycarbonyl-
4-phenyl-6-methyl-3,4-dihydropyrimidin-2(1H)-one (0.47 g, 95%).
thione (0.46 g, 89%). Mp 237–239 ꢀC.10b 1H NMR d (400 MHz,
H
DMSO-d6, Me4Si, 25 ꢀC) 10.30 (1H, br s), 9.62 (1H, br s), 7.36–7.33
(2H, m), 7.28–7.21 (3H, m), 5.19 (1H, d, J¼3.52 Hz), 3.56 (3H, s), 2.30
(3H, s).
Mp 208–210 ꢀC.10b 1H NMR d (400 MHz, DMSO-d6, Me4Si, 25 ꢀC)
H
9.17 (1H, br s), 7.71 (1H, br s), 7.34–7.30 (2H, m), 7.25–7.22 (3H, m),
5.16 (1H, d, J¼3.52 Hz), 3.53 (3H, s), 2.26 (3H, s).
4.1.22. 5-Methoxycarbonyl-4-(2-chlorophenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-one (Table 2, entry 22)
4.1.28. 5-Methoxycarbonyl-4-(2-methoxyphenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-thione (Table 2, entry 28)
2-Chlorobenzaldehyde (0.23 mL, 2 mmol), methylacetoacetate
(0.22 mL, 2 mmol), urea (0.16 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) yielded
5-methoxycarbonyl-4-(2-chlorophenyl)-6-methyl-3,4-dihydropyr-
imidin-2(1H)-one (0.52 g, 92%). Mp 223–225 ꢀC.21 1H NMR dH
(400 MHz, DMSO-d6, Me4Si, 25 ꢀC) 9.25 (1H, br s), 7.65 (1H, br s),
7.40 (1H, d, J¼7.52 Hz), 7.31–7.24 (3H, m), 5.62 (1H, d, J¼3.00 Hz),
3.45 (3H, s), 2.30 (3H, s).
2-Methoxybenzaldehyde (0.24 mL, 2 mmol), methylacetoacetate
(0.22 mL, 2 mmol), thiourea (0.20 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) yielded 5-methoxy-
carbonyl-4-(2-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-
2(1H)-thione (0.44 g, 75%). Mp 253–255 ꢀC. 1H NMR d (400 MHz,
H
DMSO-d6, Me4Si, 25 ꢀC) 10.22 (1H, br s), 9.18 (1H, br s), 7.25 (1H, br
s), 6.95 (3H, br d), 5.48 (1H, br s), 3.81 (3H, s), 3.51 (3H, s), 2.31
(3H, s).

C. Ramalingan, Y.-W. Kwak / Tetrahedron 64 (2008) 5023–5031
5031
7. (a) Patil, A. D.; Freyer, A. J.; Taylor, P. B.; Carte, B.; Zuber, G.; Johnson, R. K.;
Faulkner, D. J. J. Org. Chem. 1997, 62, 1814–1819; (b) Heys, L.; Moore, C. G.;
Murphy, P. J. Chem. Soc. Rev. 2000, 29, 57–67.
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Cohen, F.; Collins, S. K.; Overman, L. E. Org. Lett. 2003, 5, 4485–4488; (c) Cohen,
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9. (a) Brown, D. J. The Pyrimidines; Wiley: New York, NY, 1962; (b) Kappe, C. O.
Tetrahedron 1993, 49, 6937–6963; (c) Atwal, K. S.; Rovnyak, G. C.; O’Reilly, B. C.;
Schwartz, J. J. Org. Chem. 1989, 54, 5898–5907; (d) Barluenga, J.; Tomas, M.;
Rubio, V.; Gotor, V. J. Chem. Soc., Chem. Commun. 1979, 675–676.
10. (a) Gupta, R.; Paul, S.; Gupta, R. J. Mol. Catal. A 2007, 266, 50–54; (b) Kapoor,
K. K.; Ganai, B. A.; Kumar, S.; Andotra, C. S. Can. J. Chem. 2006, 84, 433–437;
(c) Rafiee, E.; Shahbazi, F. J. Mol. Catal. A 2006, 250, 57–61; (d) Fazaeli, R.;
4.1.29. 5-Methoxycarbonyl-4-(4-methoxyphenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-thione (Table 2, entry 29)
4-Methoxybenzaldehyde (0.24 mL, 2 mmol), methylacetoacetate
(0.22 mL, 2 mmol), thiourea (0.20 g, 2.6 mmol), and tetrachlorosilane
(0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) afforded 5-
methoxycarbonyl-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyri-
midin-2(1H)-thione (0.47 g, 81%). Mp 182–183 ꢀC.22 1H NMR d
H
(400 MHz, DMSO-d6, Me4Si, 25 ꢀC)10.28(1H, brs), 9.59(1H, brs), 7.13
(2H, br s), 6.90 (2H, br s), 5.13 (1H, br s), 3.73 (3H, s), 3.56 (3H, s), 2.30
(3H, s).
Tangestaninejad, S.; Aliyan, H.; Moghadam, M. Appl. Catal.,
44–51.
A 2006, 309,
4.1.30. 5-Methoxycarbonyl-4-(4-methylphenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-thione (Table 2, entry 30)
11. (a) Groß, G. A.; Mayer, G.; Albert, J.; Riester, D.; Osterodt, J.; Wurziger, H.;
Schober, A. Angew. Chem., Int. Ed. 2006, 45, 3102–3106; (b) Pisani, L.;
Prokopcova, H.; Kremsner, J. M.; Kappe, C. O. J. Comb. Chem. 2007, 9, 415–421;
(c) Gross, G. A.; Wurziger, H.; Schober, A. J. Comb. Chem. 2006, 8, 153–155.
12. (a) Hassani, Z.; Islami, M. R.; Kalantari, M. Bioorg. Med. Chem. Lett. 2006, 16,
4479–4482; (b) Chen, X. H.; Xu, X. Y.; Liu, H.; Cun, L. F.; Gong, L. Z. J. Am. Chem.
Soc. 2006, 128, 14802–14803; (c) Dondoni, A.; Massi, A.; Sabbatini, S.; Bertolasi,
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14. (a) Legeay, J. C.; Eyndeb, J. J. V.; Bazureaua, J. P. Tetrahedron 2005, 61,
12386–12397; (b) Zumpe, F. L.; Flu’ß, M.; Schmitz, K.; Lender, A. Tetrahedron
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49–51.
4-Methylbenzaldehyde (0.24 mL, 2 mmol), methylacetoacetate
(0.22 mL, 2 mmol), thiourea (0.20 g, 2.6 mmol), and tetra-
chlorosilane (0.024 mL, 0.2 mmol) in DMF/AN (2.5 mL/5.0 mL) gave
5-methoxycarbonyl-4-(4-methylphenyl)-6-methyl-3,4-dihydropyr-
imidin-2(1H)-thione (0.46 g, 84%). Mp 155–156 ꢀC. 1H NMR dH
(400 MHz, DMSO-d6, Me4Si, 25 ꢀC) 10.29 (1H, br s), 9.60 (1H, br s),
7.11 (4H, br d), 5.14 (1H, br s), 3.56 (3H, s), 2.30 (3H, s), 2.27 (3H, s).
Acknowledgements
Financial support from Korea Research Foundation (KRF-2006-
005-J02401) is gratefully acknowledged.
15. (a) Fu, N. Y.; Yuan, Y. F.; Cao, Z.; Wang, S. W.; Wang, J. T.; Peppe, C. Tetrahedron
2002, 58, 4801–4807; (b) Fu, N. Y.; Yuan, Y. F.; Pang, M. L.; Wang, J. T.; Peppe, C.
J. Organomet. Chem. 2003, 672, 52–57; (c) Mabry, J.; Ganem, B. Tetrahedron Lett.
2006, 47, 55–56; (d) Bose, D. S.; Fatima, L.; Mereyala, H. B. J. Org. Chem. 2003, 68,
587–590.
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