Antimony(III) chloride impregnated on alumina - An efficient and economical Lewis acid catalyst for one-pot synthesis of dihydropyrimidinones under solvent-free conditions

Article abstract of DOI:10.1139/V06-019

The antimony(III) chloride impregnated on alumina efficiently catalyses a one-pot, three-component condensation reaction among an aldehyde, a β-ketoester, and urea or thiourea to afford the corresponding dihydropyrimidinones in good to excellent yields. T

Full text of DOI:10.1139/V06-019

4
33
Antimony(III) chloride impregnated on alumina —
An efficient and economical Lewis acid catalyst
for one-pot synthesis of dihydropyrimidinones
under solvent-free conditions
Kamal. K. Kapoor, Bilal A. Ganai, Satish Kumar, and Charanjeet S. Andotra
Abstract: The antimony(III) chloride impregnated on alumina efficiently catalyses a one-pot, three-component conden-
sation reaction among an aldehyde, a β-ketoester, and urea or thiourea to afford the corresponding dihydropyrimidinones
in good to excellent yields. The reactions are probed in microwave (MW), ultrasonic, and thermal conditions and the
best results are found using MW under solvent-free conditions.
Key words: Biginelli dihydropyrimidinones synthesis, SbCl –Al O , MW, sonication, solid supported.
3
2
3
Résumé : Le chlorure d’antimoine(III) imprégné sur de l’alumine catalyse efficacement la réaction de condensation
monotope de trois composants, un aldéhyde, un β-cétoester et une urée ou une thiourée, pour conduire à la formation
des dihydropyrimidinones correspondants avec des rendements allant de bons à excellents. Les réactions ont été réali-
sées sous l’influence de micro-ondes (MO), d’ultrasons ou de la chaleur et on a trouvé que les conditions de micro-
ondes, sans solvant, donnent les meilleurs résultats.
Mots clés : synthèse de Biginelli de dihydropyrimidinones, SbCl –Al O , micro-ondes, soniquation, supporté sur un solide.
3
2
3
[
Traduit par la Rédaction] Kapoor et al. 437
Introduction
BF ·OEt , InCl , BiCl , LiCl , ZrCl , La(OTf) , NiCl ,
3 2 3 3 4 4 3 2
FeCl , KSF, Yb(OTf) , PPE, Bi(OTf) , CAN, CuCl , CeCl ,
3
3
3
2
3
The dihydropyrimidinones (DHPMs) and their derivatives
have attracted considerable interest in organic and medicinal
chemistry because of their fascinating array of pharmacolog-
ical and therapeutic properties such as antiviral, antitumor,
antibacterial, and antiinflammatory calcium channel
blockers, antihypertensives, α -adrenergic antagonists, and
Cu(OTf) , Me SiI, LiBr , MgBr , InBr , NH Cl, SrCl , sil-
2
3
2
2
3
4
2
ica-sulphuric acid, boric acid, and ionic liquids. However, in
spite of their potential utility, many of these methods in-
volve expensive reagents, a stoichiometric amount of cata-
lysts, strongly acidic conditions, longer reaction times, high
temperature, unsatisfactory yields, and tedious work-up.
1
a
neuropeptide Y (NPY) antagonists (1, 2). Moreover, the po-
The use of reagents impregnated on inorganic supports (7)
offer advantages such as (a) simple work-up and product pu-
rification, (b) enhanced or reduced reactivity of the func-
tional groups, (c) selectivity that may be different from that
in solution, and (d) manipulative simplicity. Among the
large number of Lewis acids used in organic synthesis, anti-
mony(III) chloride has not been explored much for its cata-
lytic activity. Recently, synthesis of some novel heterocycles
catalyzed by antimony(III) chloride under solvent-free con-
ditions has been reported from our laboratory (8). We
wished to explore the use of antimony(III) chloride impreg-
nated on alumina for the synthesis of DHPMs.
The condensation reaction between benzaldehyde (10 mmol),
ethyl acetoacetate (10 mmol), and urea (10 mmol) was car-
ried out in a microwave (MW) under solvent-free conditions
for 1 min with 0.5 mmol (5 mol%, 0.05 equiv.) of anti-
mony(III) chloride, (i) alone and (ii) impregnated on differ-
ent amounts of alumina (1–8 g), which gave yields of 42%,
tent HIVgp–120–CD inhibitor batzelladine alkaloids (3) ba-
4
sically contain a dihydropyrimidine core unit. A simple
synthesis of this biologically important pharmacophore was
reported (4) by Biginelli in 1893 by one-pot reflux of a β-
ketoester, an aromatic aldehyde, and urea in ethanol contain-
ing a catalytic amount of HCl. The major drawbacks of this
protocol are low yields of products (20%–50%) and less
functional group tolerance on the reactants. Consequently,
this has led to the discovery of multistep strategies produc-
ing somewhat higher yields, but lacking the simplicity of
original Biginelli reaction (5). Therefore, this reaction con-
tinues to be the focus of the researchers striving to find
milder and more efficient procedures for the synthesis of
DHPMs. This has led to the development of several syn-
thetic methodologies using various catalysts (6) such as
Received 7 December 2005. Published on the NRC Research
Press Web site at http://canjchem.nrc.ca on 31 March 2006.
7
0%, 96%, 93%, 90%, 74%, 60%, and 45%, respectively, as
1
K.K. Kapoor, B.A. Ganai, S. Kumar, and C.S. Andotra.
shown in Fig. 1. In the absence of alumina, the reaction gave
a low yield of the product (4a). However, increasing the
amounts of antimony(III) chloride to 0.1, 0.2, 0.5, and
1.0 equiv. resulted in the formation of an unidentifiable tarry
Department of Chemistry, University of Jammu, Jammu
Tawi-180 006, India.
1Corresponding author (e-mail: k2kapoor@yahoo.com).
Can. J. Chem. 84: 433–437 (2006)
doi:10.1139/V06-019
© 2006 NRC Canada

4
34
Can. J. Chem. Vol. 84, 2006
Fig. 1. The influence of the amount of alumina on the yields of
Table 1. Various solvents used for the synthesis of 4a in an
reaction.
ultrasonicator.
1
20
Entry
1
Solvent
Time (h)
3
Yield (%)
15
1
00
H O
2
2
3
4
THF
THF–H O (3:2)
CHCl3
4
3
5
40
20
45
80
60
40
20
0
2
5
6
CH CN
1
5
94
50
3
Toluene
SbCl as a Lewis acid supported on alumina for the synthesis
0
1
2
3
4
5
6
7
8
9
3
of DHPMs.The present catalyst is cheap, easily available,
easy to handle, and works efficiently in MW, thermal, and
ultrasonic conditions.
Grams of alumina for 0.114g ( 0.5 mmol) of antimony(III)chloride
material. It is evident that the amount of alumina used for
impregnation is decisive in the completion of the three-
component reaction. The results reveal that the most appro-
priate ratio of antimony(III) chloride and alumina is approxi-
mately 1:26 (w/w), which gives 96% isolated yield of 4a.
The decrease or increase of the amount of alumina led to the
decrease in the yield of the desired product. It is presumed
that the alumina acts as a carrier increasing the surface area
of the heterogeneous reaction, and it is very probable that
the antimony salt interacts with the oxide groups at the sur-
face of the support forming new active sites on the alumina
local structure.
Experimental
General
Melting points were measured in open capillaries on a
Perfit melting point apparatus and are uncorrected. IR on
1
KBr were recorded on a Bruker-4800 IR spectrometer. H
13
and C NMR spectra were recorded on a Bruker AC-200
spectrometer. The mass spectra were obtained on a JEOL D-
3
00 mass spectrometer. TLC was performed on 0.5 mm
thick plates using BDH silica gel G as adsorbent and eluted
in a 1:1 mixture of EtOAc and petroleum ether. The plates
were developed with iodine vapors, 2,4-dinitrophenyl-
hydrazone in acidic methanol solution, and anisaldehyde so-
lution in acidic alcohol. All solvents were distilled before
use. Microwave irradiation was carried out in an IFB micro-
wave oven at the 5 power level and the sonication was car-
ried out in a Bransonic-2510 ultrasonic cleaner.
In another set of experiments, when the reaction mixture
comprised of benzaldehyde (10 mmol), ethyl acetoacetate
(
10 mmol), urea (10 mmol), and 5 mol% of antimony(III)
chloride (0.5 mmol) impregnated on 3 g of alumina was
i) heated at 100 °C on an oil bath without any solvent, a
clean conversion to 4a (95% yield) was noticed in less than
h and (ii) sonicated in an ultrasonicator in a variety of sol-
(
1
vents such as water, tetrahydrofuran, acetonitrile, chloro-
General procedures
form, toluene, and THF–H O, produced the results
2
summarized in Table 1. From Table 1, acetonitrile appears to
be the best solvent (yield 94% in 1 h) of all the solvents
tested under similar reaction conditions. The present find-
ings in the ultrasonicator are superior in terms of yield and
time to the earlier reported method (6q).
Encouraged by these results and to establish the versatility
of antimony(III) chloride impregnated on alumina, various
substrates were subjected to the optimized condensation re-
action and the results are depicted in Table 2.
Preparation of the catalyst SbCl –Al O
3
3
2
To an antimony(III) chloride (2.28 g, 10 mmol) solution
in 100 mL of distilled ethanol was added 60 g of neutral alu-
mina. The mixture was stirred at room temperature for 1 h,
followed by removal of solvent under reduced pressure on a
rotovap. The resultant free-flowing powder was then acti-
vated at 110 °C in an oven for 2 h and was used throughout
the experimentation.
The efficiency of SbCl –Al O as a Lewis acid catalyst is
3
2
3
Typical procedures for the three-component condensation
reaction
comparable to those reported in the literature (6), such as
BF ·OEt, FeCl , Bi(OTf) , Yb(OTf) , InCl , Sc(OTf) ,
3
3
3
3
3
3
(
i) Under microwave irradiation
YbCl , MgBr , and SrCl , as is evident from Table 3. The
3
3
2
A mixture of ethyl acetoacetate (10 mmol), aryl aldehyde
10 mmol), urea (10 mmol), and the 3.1 g of the catalyst was
present catalyst, SbCl –Al O , enjoys benefits in terms of
3
2
3
(
easy handling, economy, and simple workup (Scheme 1).
The reaction is believed to proceed through the acylimine
intermediate formed in situ by reaction of the aldehyde with
urea. The subsequent addition of the β-diketon enolate to the
acylimine, followed by cyclization and dehydration, afforded
the corresponding DHPMs (Scheme 2).
placed in a 100 mL beaker. It was then irradiated in an IFB
microwave oven at the 5 power level until the completion of
reaction as monitored by TLC. The reaction mixture was
cooled to room temperature and ethyl acetate (100 mL) was
added, stirred well, and filtered through Celite under suction.
The organic layer was washed twice with water (30 mL) and
brine (30 mL). After drying over anhydr. Na SO , the sol-
2
4
Conclusion
vent was evaporated under reduced pressure and the residue
was recrystallized from ethanol to afford the pure product.
In conclusion, we have unraveled a newer application of
©
2006 NRC Canada

Kapoor et al.
435
Table 2. SbCl –Al O catalyzed synthesis of DHPMs.
3
2
3
Time (min), (yield in %)b
Melting point (°C)
c
Subsititution
R1
Producta
R2
X
Thermal
MW
Sonication
Obs.
Lit. (ref. 6)
4
4
4
4
4
a
b
c
d
e
OEt
OEt
OEt
OEt
OEt
H
OMe
Cl
F
NO2
O
O
O
O
O
55 (95)
70 (92)
50 (89)
75 (91)
60 (88)
1.0 (96)
1.5 (94)
1.0 (90)
1.5 (92)
2.0 (90)
60 (94)
75 (92)
80 (90)
90 (87)
60 (86)
203 to 204
201 to 204
211–214
177 to 178
210–212
202–204
201–203
213–215
175–177
208–211
4
4
4
4
4
4
f
OEt
Me
OMe
OMe
OMe
OMe
OH
H
H
OMe
Cl
NO2
O
O
O
O
O
O
65 (90)
45 (90)
50 (83)
75 (84)
60 (91)
65 (80)
2.5 (92)
1.0 (96)
2.0 (96)
2.0 (95)
1.5 (94)
1.5 (82)
90 (90)
75 (87)
90 (84)
90 (91)
70 (89)
60 (93)
233–235
240–242
209–212
193–195
203–205
234 to 235
232 to 233
242–244
208–210
192–194
204–207
235–237
g
h
i
j
k
4
4
4
4
l
OMe
OEt
OMe
OEt
F
H
H
OMe
O
S
S
S
70 (92)
80 (89)
80 (90)
65 (81)
2.0 (94)
2.0 (95)
1.5 (94)
2.0 (91)
65 (87)
65 (89)
85 (90)
90 (84)
190 to 191
205–207
235–237
192–194
207 to 208
236–238
m
n
o
a
152 to 153
152 to 153
1
All products were characterized by H NMR, IR, and mass spectra.
Isolated yields.
Melting points are uncorrected.
b
c
Table 3. Comparison of various catalysts with SbCl –Al O for the synthesis of 4a.
3
2
3
Entry
Catalyst used
SbCl –Al O
Reaction conditions
Amount of catalyst (mol%)
Yield (%)
Reference
1
2
3
4
5
6
7
8
9
CH CN, sonication, 1 h
5
130
60
2
94
94
93
90
83
95
95
96
66
—
6o
6n
6b
6r
6v
—
6r
6r
3
2
3
3
BF ·OEt–CuCl
THF, reflux, 18 h
EtOH, reflux, 4 h
3
FeCl –HCl
3
Bi(OTf)3
Yb(OTf)3
InCl3
CH CN, rt, 1 h
3
CH CN, reflux, 6 h
5
3
THF, ∆, 7 h
10
5
SbCl –Al O
No solvent, 100 °C
No solvent, 100 °C
No solvent, 100 °C
3
2
3
Sc(OTf)3
5
YbCl3
5
1
1
0
1
MgBr
La(OTf)3
No solvent, 100 °C
No solvent, 100 °C
10
5
92
89
6u
6r
1
1
2
3
SbCl3
No solvent, MW
No solvent, MW
5
5
30
96
—
—
SbCl –Al O
3
3
2
Scheme 1.
2
R
O
O
O
O
X
1
H
R
NH
SbCl –Al O
3
3
2
+
+
1
R
H
2
N
NH
2
2
R
N
H
X
MW, ))), and
1
2
3
4
(
ii) Under thermal conditions
temperature and worked up in the same manner as men-
tioned in (i).
A mixture of ethyl acetoacetate (10 mmol), aryl aldehyde
10 mmol), urea (10 mmol), and 3.1 g of the catalyst was
placed in a 100 mL round bottom flask was heated on an oil
bath at 100 °C until the completion of the reaction as moni-
tored by TLC. The reaction mixture was cooled to room
(
(
iii) Under sonication
A mixture of ethyl acetoacetate (10 mmol), aryl aldehyde
(10 mmol), urea (10 mmol), and the 3.1 g of catalyst was
©
2006 NRC Canada

4
36
Can. J. Chem. Vol. 84, 2006
Scheme 2.
OH
X
X
O
X
N
H
NH2
N
NH
2
H
+
H
2
N
NH
2
-
H O
2
R2
R2
R2
SbCl3
2
3
2
2
2
2+
R
R
R
Sb
O
O
1
H C
3
R
O
O
O
C
-
H2O
1
1
1
R
NH
R
NH
R
NH
X
H C
3
O
H C
3
N
H
X
H
N
OHH
X
2
H N
3
4
placed in a 100 mL round bottom flask containing 15 mL of
acetonitrile. After the completion of the reaction (TLC), the
solvent was removed and ethyl acetate was added to the resi-
due and worked up in the same manner as mentioned in (i).
5-Ethoxycarbonyl-6-methyl-4-(4-nitrophenyl)-3,4-
dihydropyrimidin-2(1H)-one (4e)
–
1
Melting point 208–211 °C. IR (KBr, cm ): 3232, 3108,
1
2977, 1701, 1641, 1591, 1522. H NMR (DMSO-d ) δ: 9.37
6
(
s, 1H), 8.20–7.50 (m, 4H), 7.91 (d, J = 2.46 Hz, 1H), 5.27
5
-Ethoxycarbonyl-6-methyl-4-phenyl-3,4-
(d, J = 1.6 Hz, 1H), 3.98 (q, J = 7.1 Hz, 2H), 2.27 (s, 3H),
1
3
dihydropyrimidin-2(1H)-one (4a)
1.09 (t, J = 7.1 Hz, 3H). C NMR (DMSO-d6) δ: 164.9,
–
1
Melting point 203 to 204 °C. IR (KBr, cm ): 3233, 3110,
151.9, 151.7, 149.3, 146.6, 127.5, 123.7, 59.3, 53.6, 17.8,
1
+
2
975, 2938, 1725, 1708, 1650, 1595. H NMR (DMSO-d )
13.9. MS m/z: 306 (M + 1).
6
δ: 1.12 (t, J = 7.2 Hz, 3H), 2.29 (s, 3H), 4.02 (q, J = 7.2 Hz,
2
2
1
1
H), 5.19 (d, J = 2.7 Hz), 7.27–7.42 (m, 5H), 7.75 (d, J =
5
-Ethoxycarbonyl-6-methyl-4-(4-hydroxyphenyl)-3,4-
.7 Hz, 1H), 9.21 (s, 1H). 13C NMR (DMSO-d , 75 MHz) δ:
6
dihydropyrimidin-2(1H)-one (4f)
4.1, 17.9, 54.2, 59.3, 99.5, 126.4, 127.4, 128.5, 145.0,
–1
Melting point 233–235 °C. IR (KBr, cm ): 3510, 3276,
+
48.5, 152.3, 165.5. MS m/z: 261 (M + 1).
1
3
3
125, 2970, 1682, 1642. H NMR (DMSO-d ) δ: 1.06 (t,
6
H, J = 6.90 Hz), 2.21 (s, 3H), 3.94 (q, 2H, J = 6.90 Hz),
5
-Ethoxycarbonyl-4-(4-methoxyphenyl)-6-methyl-3,4-
5.02 (d, 1H, J = 2.76 Hz), 6.67–7.0 (m, 4H), 7.64 (s, 1H),
dihydropyrimidin-2(1H)-one (4b)
9.11 (s, 1H), 9.30 (s, 1H).
–
1
Melting point 202 to 203 °C. IR (KBr, cm ): 3222, 3095,
1
2
932, 2831, 1713, 1650, 1615, 1584, 1516. H NMR
5
-Acetyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-
(
DMSO-d ) δ: 1.09 (t, J = 7 Hz, 3H), 2.23 (s, 3H), 3.70 (s,
6
one (4g)
3
H), 3.97 (q, J = 7 Hz, 2H), 5.09 (d, J = 3.1 Hz), 6.87–7.15
–
1
1
3
Melting point 240–242 °C. IR (KBr, cm ): 3270, 3008,
(
1
1
m, 4H), 7.66 (s, 1H), 9.12 (s, 1H). C NMR (DMSO-d ) δ:
6
1
2
975, 2835, 1702, 1645, 1588. H NMR (DMSO-d ) δ: 2.12
6
5.0, 18.6, 54.3, 55.9, 60.1, 100.5, 114.6, 128.3, 138.0,
+
(s, 3H), 2.30 (s, 3H), 5.28 (s, 1H), 7.24–7.32 (m, 5H), 7.82
48.9, 153.1, 159.4, 166.3. MS m/z: 291 (M + 1).
(
s, 1H), 9.20 (s, 1H).
4
-(4-Chlorophenyl)-5-ethoxycarbonyl-6-methyl-3,4-
5
-Methoxycarbonyl-6-methyl-4-phenyl-3,4-
dihydropyrimidin-2(1H)-one (4h)
Melting point 209–212 °C. IR (KBr, cm ): 3368, 3240,
dihydropyrimidin-2(1H)-one (4c)
–
1
Melting point 213 to 214 °C. IR (KBr, cm ): 3230, 3091,
–
1
1
2
6
974, 2935, 1700, 1642. H NMR (DMSO-d ) δ: 1.10 (t, J =
6
1
3
092, 3032, 2948, 1750, 1708, 1655. H NMR (DMSO-d )
.7 Hz, 3H), 2.24 (s, 3H), 3.97 (q, J = 6.7 Hz, 2H), 5.14 (d,
6
δ: 8.06 (s, 1H), 7.32 (m, 5H), 5.74 (s, 1H), 5.40 (d, J =
J = 3.1 Hz), 7.23–7.38 (m, 4H), 7.76 (s, 1H), 9.23 (s, 1H).
1
3
1
3
2.7 Hz, 1H), 3.64 (s, 3H), 2.34 (s, 3H). C NMR (DMSO-
d ) δ: 165.5, 152.2, 148.8 144.5, 128.3, 127.2, 126.0, 98.9,
C NMR (DMSO-d ) δ: 14.9, 18.7, 54.3, 60.1, 99.7, 129.0,
6
+
1
1
29.2, 132.7, 144.6, 149.6, 152.8, 166.2. MS m/z: 295 (M +
6
+
5
3.9, 50.7, 17.8. MS m/z: 247 (M + 1).
).
4
-(4-Fluorophenyl)-5-ethoxycarbonyl-6-methyl-3,4-
5-Methoxycarbonyl-4-(4-methoxyphenyl)-6-methyl-3,4-
dihydropyrimidin-2(1H)-one (4d)
dihydropyrimidin-2(1H)-one (4i)
Melting point 192–194 °C. IR (KBr, cm ): 3238, 3102,
3000, 2952, 2838, 1692, 1640, 1609, 1516. H NMR
–
1
–1
Melting point 177 to 178 °C. IR (KBr, cm ): 3235, 3090,
1
1
2
6
975, 2930, 1705, 1645. H NMR (DMSO-d ) δ: 2.0 (t, J =
6
.9 Hz, 3H), 2.26 (s, 3H), 3.99 (q, J = 6.9 Hz, 2H), 5.15 (d,
(DMSO-d ) δ: 8.58 (s, 1H), 7.25–6.80 (m, 4H), 5.95 (s, 1H),
6
J = 3.1 Hz), 7.21–7.40 (m, 4H), 7.76 (s, 1H), 9.23 (s, 1H).
5.30 (d, J = 2.0 Hz, 1H), 3.76 (s, 3H), 3.65 (s, 3H), 2.30 (s,
1
3
13
C NMR (DMSO-d ) δ: 14.5, 17.5, 53.3, 60.1, 99.1, 116.0,
3H). C NMR (CDCl ) δ: 163.5, 151.2, 143.6, 133.5, 125.4,
6
3
+
1
29.2, 142.7, 148.6, 153.6, 165.2.
111.2, 52.7, 52.5, 48.5, 16.2. MS m/z: 277 (M + 1).
©
2006 NRC Canada

Kapoor et al.
437
4
-(4-Chlorophenyl)-5-methoxycarbonyl-6-methyl-3,4-
dihydropyrimidin-2(1H)-one (4j)
Melting point 204–207 °C. IR (KBr, cm ): 3240, 3114,
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–
1
1
2
1
1
1
5
950, 2875, 1702, 1645. H NMR (DMSO-d ) δ: 9.28 (s,
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6
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(
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+
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Freyer, C. De Brosse, S. Mai, A. Truneh, D.J. Faulkner, B.
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5
-Methoxycarbonyl-6-methyl-4-(4-nitrophenyl)-3,4-
dihydropyrimidin-2(1H)-one (4k)
–
1
Melting point 235–237 °C. IR (KBr, cm ): 3265, 3234,
1
3
111, 2952, 1700, 1648, 1599, 1522. H NMR (DMSO-d )
6
δ: 9.36 (s, 1H), 8.22–7.52 (m, 4H), 7.95 (s, 1H), 5.26 (s,
1
1
1
H), 3.54 (s, 3H), 2.28 (s, 3H). 13C NMR (DMSO-d ) δ:
6
4
5
65.5, 151.7, 149.5, 146.6, 127.5, 123.7, 97.9, 53.4, 50.8,
. (a) B.C. O’Reilly and K.S. Atwa. Heterocycles, 26, 1185
+
7.8. MS m/z: 292 (M + 1).
(
1987); (b) K.S. Atwal, B.C. O’Reilly, J.Z. Gougoutas, and
M.F. Malley. Heterocycles, 26, 1189 (1987); (c) A.D. Shutalev,
E.A. Kishko, N. Sivova, and A.Y. Kuznetsov. Molecules, 3,
100 (1998).
4
-(4-Fluorophenyl)-5-methoxycarbonyl-6-methyl-3,4-
dihydropyrimidin-2(1H)-one (4l)
–
1
Melting point 190 to 191 °C. IR (KBr, cm ): 3260, 3135,
6. (a) M. Gohain, D. Prajapati, and J.S. Sandhu. Synlett, 2, 235
(2004); (b) R. Varala, M.M. Alam, and S.R. Adapa. Synlett, 1,
1
2
1
1
1
1
992, 2898, 1725, 1658. H NMR (DMSO-d ) δ: 9.30 (s,
6
6
7 (2003); (c) D. Subhas Bose, L. Fatima, and H.B. Mereyala.
H), 7.7 (s, 1H), 7.45–7.27 (m, 4H), 5.15 (d, J = 3.3 Hz,
H), 3.55 (s, 3H), 2.26 (s, 3H). 13C NMR (DMSO-d ) δ:
J. Org. Chem. 68, 587(2003); (d) A.S. Paraskar, G.K. DewKar,
and A. Sudalai. Tetrahedron Lett. 44, 3305 (2003); (e) G.
Sabitha, G.S.K.K. Reddy, C.S. Redy, and J.S. Yadav. Synlett,
6
64.6, 150.8, 147.9, 143.6, 130.9, 128.3, 128.2, 99, 53, 50.6,
7.6.
1
, 58 (2003); ( f ) P. Salehi, M. Dabiri, M.A. Zolfigol, and
M.A. Bodagh Ford. Tetrahedron Lett. 44, 2889 (2003); (g) P.P.
Baruah, S. Gadhwal, D. Prajapati, and J.S. Sandhu. Chem.
Lett. 1038 (2002); (h) G. Maiti, P. Kundu, and C. Guin. Tetra-
hedron Lett. 44, 2757 (2003); (i) S. Tu, F. Fang, C. Miao, H.
Jiang, Y. Feng, D. Shi, and X. Wang. Tetrahedron Lett. 44,
6153 (2003); ( j) C.V. Reddy, M. Mahesh, K.V.P. Raju, T.
Romeshbabu, and N.V.V. Reddy. Tetrahedron Lett. 43, 2657
(2002); (k) N. Fu, Y. Yuan, Z. Cao, S. Wang, J. Wang, and C.
Peppe. Tetrahedron, 58, 4801 (2002); (l) J. Lu and Y. Bai. Syn-
thesis, 4, 466 (2002); (m) A. Shaabani, A. Bazgir, and F.
Teimouri. Tetrahedron Lett. 44, 857 (2003); (n) L. Jun and M.
Huairang. Synlett, 1, 63 (2000); (o) H.E. Hu, D.R. Sidler, and
U.H. Dolling. J. Org. Chem. 63, 3454 (1998); (p) F. Bigi, S.
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K.S. Raj, and A.R. Prasad. J. Chem. Soc. Perkin Trans. 1,
Ethyl 6-methyl-4-phenyl-2-thiooxo-1,2,3,4-
tetrahydropyrimidine-5-carboxylate (4m) –
1
Melting point 206–208 °C. IR (KBr, cm ): 3330, 3172,
1
3
(
105, 2980, 1670, 1575, 1467. H NMR (DMSO-d ) δ: 1.08
6
t, 3H, J = 7.02 Hz), 2.26 (s, 3H), 3.98 (q, 2H, J = 7.02 Hz),
5
1
.15 (d, 1H, J = 3.57 Hz), 7.20–7.35 (m, 5H), 9.65 (s, 1H),
0.35 (s, 1H).
6
-Methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydro-
pyrimidine-5-carboxylic acid methyl ester (4n)
–
1
Melting point 235–237 °C. IR (KBr, cm ): 3296, 3203,
1
2
3
5
994, 1610, 1577, 1462. H NMR (DMSO-d ) δ: 2.14 (s,
6
H), 2.32 (s, 3H), 5.26 (d, 1H, J = 3.57 Hz), 7.20–7.38 (m,
+
H), 9.75 (s, 1H), 10.28 (s, 1H). MS m/z: 247 (M + 1).
1
939 (2001); (r) Y. Ma, C. Qian, L. Wang, and M. Yang. J.
Ethyl 6-methyl-4-methoxyphenyl-2-thiooxo-1,2,3,4-
tetrahydropyrimidine-5-carboxylate (4o)
Org. Chem. 65, 3864 (2000); (s) C.O. Kappe and S.F.
Falsome. Synlett, 718 (1998); (t) A.K. Kumar, M. Kasthuraiah,
C.S. Reddy, and C.D. Reddy. Tetrahedron Lett. 42, 7873
(2001); (u) H. Salehi and Q. Guo Xiang. Synth. Commun. 34,
171 (2004); (v) B.C. Ranu, A. Hajra, and U. Janu. J. Org.
Chem. 65, 6270 (2000).
. (a) V.S. Ley, I.R. Baxendale, and A.L. Lee. J. Chem. Soc.
Perkin Trans. 1, 1850 (2002); (b) R.S. Varma. Green. Chem. 1,
4
–
1
Melting point 152 to 153 °C. IR (KBr, cm ): 3446, 3315,
178, 2965, 1669, 1619, 1578, 1512. H NMR (DMSO-d )
1
3
6
δ: 1.09 (t, 3H, J = 6.93 Hz), 2.26 (s, 3H), 3.74 (s, 3H), 3.98
q, 2H, J = 6.93 Hz), 5.12 (d, 1H, J = 3.6 Hz), 6.88–7.10 (m,
H), 9.62 (s, 1H), 10.30 (s, 1H).
(
4
7
8
3 (1999); (c) J.O. Metzger. Angew. Chem. Int. Ed. 37, 2975
(
1998); (d) P. Laszlo. In Solid supports and catalysts in organic
Acknowledgement
synthesis. Edited by K. Smith. Harwood, Chichester, UK.
1992. pp. 288–310.
. B.A. Ganai, S. Koul, T.K. Razdan, and C.S. Andotra. Synth.
Commun. 34, 1823 (2004).
One of the authors (S. Kumar) is thankful to the Council
of Scientific and Industrial Research, New Delhi, India for a
Junior Research Fellowship.
©
2006 NRC Canada