Synthesis of 3,4-dihydropyrimidinones via phase transfer catalysis

Article abstract of DOI:10.1002/jhet.830

3,4-Dihydropyrimidinone and derivatives were synthesized by the one-pot, three-component Biginelli condensation of an aldehyde, β-dicarbonyl compound and urea. Synthesis was carried out in aqueous sodium hydroxide using Aliquat-336 as a phase transfer agent. Compared to the classical Biginelli reaction conditions, this new method cousistently has the advantage of excellent yields and short reaction time.

Full text of DOI:10.1002/jhet.830

Month 2013
Synthesis of 3,4-Dihydropyrimidinones via Phase
Transfer Catalysis
Younes Moussaouia,b and Ridha Ben Salem
b
*
aScience Faculty of Gafsa, Gafsa University, Zarroug city Gafsa 2112, Tunisia
bScience Faculty of Sfax, Sfax University, Physical Organic Chemistry Laboratory,
Sfax 3018, Tunisia
*
E-mail: ridha.bensalem@voila.fr
Received October 21, 2010
DOI 10.1002/jhet.830
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
R
EtO2C
R1
O
C
NH
NH
R1 C CH2 CO2Et
O
RCHO
+
H2N
+
NH2
O
R= CH3; C2H5; C3H7; C4H9; C6H5; 4Cl-C6H4; 4MeO-C6H4;
4Me-C6H4; 4NO2-C6H4;4OH-C6H4; R1= CH3; C2H5
3,4-Dihydropyrimidinone and derivatives were synthesized by the one-pot, three-component Biginelli
condensation of an aldehyde, β-dicarbonyl compound and urea. Synthesis was carried out in aqueous sodium
hydroxide using Aliquat-336 as a phase transfer agent. Compared to the classical Biginelli reaction condi-
tions, this new method cousistently has the advantage of excellent yields and short reaction time.
J. Heterocyclic Chem., 00, 00 (2013).
INTRODUCTION
We report, herein, the synthesis of some dihydropyri-
midinones in aqueous NaOH using Aliquat-336 as a phase
transfer agent and an environmentally friendly, high yield-
ing and short time reaction in comparison to the classical
Biginelli procedure.
Dihydropyrimidinones and their derivatives represent
a heterocyclic system of remarkable pharmacological
and biological efficiency [1,2]. They exhibit wide range
of biological activities such as antiviral, antifilorial,
anti-inflammatory, antibacterial, and antitumor actions
[3–9]. Dihydropyrimidinones exhibit pharmacological
activites as calcium channel blockers, antihypertensive
agents, α-1a-antagonists, and neuropeptideY antagonists
[10–12].
The original procedure for the preparation of these
type of compounds was reported by Biginelli [13]
involving one-pot condensation of benzaldehyde, ethyl
acetoacetate, and urea under strongly acidic conditions.
Because of their medicinal properties, the synthesis of
the dihydropyrimidinones nucleus has received much
attention [14–19]. This classical method often suffers
from low yields of products in the case of substituted
aromatic and aliphatic aldehyde [3,20,21]. This has led
to the recent disclosure of several one-pot methodologies
for the synthesis of dihydropyrimidinones derivatives
involving the use of a number of catalysts such as CuCl2
[22], ZrCl4 [23,24], ZnBr2 [25], LiBr [26], BiCl3 [27],
Cu(OTf)2 [28], Yb(OTf)3 [29], Bi(NO3)3 [30], PPh3
[31], CaF2 [16], YbCl3 [17]. However, many of these
methods also suffer from drawbacks, such as the involve-
ment of expensive reagents, harsh conditions and high
reaction times. In search of inexpensive and environmen-
tally benign catalyst, Aliquat-336 was tested as an alterna-
tive catalyst with various substrates.
RESULTS AND DISCUSSION
Dihydropyrimidinones were prepared by three compo-
nent one-pot Biginelli condensation of an aldehyde, β-
ketoester, and urea. Aldehydes, 1,3-dicarbonyl compounds
and urea, in the presence of chlorhydric acid in ethanol or
Aliquat-336 in aqueous sodium hydroxide, gave the corre-
sponding 3,4-dihydropyrimidinones (Table 1). The reactiv-
ity of aromatic aldehydes in the Biginelli reaction is better
than aliphatic aldehydes. Furthermore, aromatic aldehydes,
carrying either electron donating or electron withdrawing
substituents, reacted well, giving excellent yields in aque-
ous sodium hydroxide in the presence of Aliquat-336.
The higher yields and shorter reaction times validated
mechanistic approach suggested by Kappe [15] and
Ahmed et al. [32], whereby the aldol adduct formed from
aldehyde and urea is approached by the β-ketoester in
enolate form as the attaking species.
The Aliquat-336 plays an important role as a phase
transfer catalyst in the synthesis of the dihydropyrimidi-
nones derivatives. The Aliquat-336 participation in cata-
lyzing the Biginelli reaction can be understood by given
mechanism. The proposed reaction mechanism includes
the reaction of β-ketoester with sodium hydroxide
affords the Na+-enolate, which is further transformed to
© 2013 HeteroCorporation

Y. Moussaoui and R. B. Salem
Vol 000
Table 1
phase and loses the quaternary ammonium ions to produce
the β-ketoester enolate. This enolate reacts with the electro-
philic system which is generated by addition of Q+ to the
acyl imine intermediate to produce the open-chain uride
intermediate. The intermediate product undergoes cycliza-
tion with the removal of one mole of water molecule
leading to the desired 3,4-dihydropyrimidinone as the final
product (Scheme 1).
The use of Aliquat-336 improved the yields profile and
time to complete the reaction in shorter span than the
classical method for the Biginelli reaction (Table 1).
However, the optimized best yields and time profiles were
obtained with a molar ratio of 1:1:1.5:1:0.15 of aldehyde,
β-ketoester, urea, sodium hydroxide, and Aliquat-336 as
phase transfer catalyst, respectively.
Synthesis of dihydropyrimidinones.
Yield (%)
R
R1
Product
a
b
C6H5
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
74
96
89
95
92
90
92
76
84
88
86
90
86
91
86
90
85
75
82
86
85
4Cl-C6H4
4MeO-C6H4
4Me-C6H4
4NO2-C6H4
4OH-C6H4
CH3
C2H5
C3H7
C4H9
C6H5
4Cl-C6H4
4MeO-C6H4
4Me-C6H4
4NO2-C6H4
4OH-C6H4
CH3
C2H5
C3H7
C4H9
56
61
55
54
66
26
30
30
32
44
58
32
55
60
42
25
31
32
32
CONCLUSIONS
In summary, we have disclosed a simple modification
of the Biginelli dihydropyrimidinones synthesis. Through
the use of Aliquat-336 as phase transfer agent in aque-
ous NaOH, the yields in the one-pot Biginelli protocol
can be increased on average by 30–60% as compared
with traditional method. This one-step synthesis of
dihydropyrimidinones in a short time and good yields
from aromatic and aliphatic aldehydes.
CH3
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
aAldehyde (10 mmol), dicarbonyl compound (10 mmol), urea (15 mmol),
HCl in EtOH, reflux (18h).
EXPERIMENTAL
bAldehyde (10 mmol), dicarbonyl compound (10 mmol), urea (15 mmol),
NaOH (10 mmol), Aliquat-336 (1.5 mmol), water (5 mL), 100ꢀC
(45 min).
1
All compounds were characterized by IR, H NMR spectra,
and 13C NMR spectra. The IR spectra were recorded in KBr with
a JASCO FT-IR-420 spectrometer, with a precision of 2cm−1 in
Q+-enolate by an ion exchange between quaternary ammo-
nium ion Q+ from Aliqut-336 and Na+-enolate ion in the
aqueous media. Then, Q+-enolate is transferred to organic
1
the range 400–4000 cm−1. The H NMR spectra (300 MHz) and
13C NMR spectra (75 MHz) were obtained on a Bruker AC300
spectrometer using DMSO-d6 as solvent and TMS as an internal
Scheme 1. Proposed machanism of Biginelli reaction in aqueous sodium hydroxide using Aliquat-336.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Synthesis of 3,4-Dihydropyrimidinones via Phase Transfer Catalysis
standard, chemical shift are given in ppm. Melting points were
taken on a Reichert-Heizbank apparatus.
(DMSO-d6) d ppm 14.45, 18.43, 54.12, 59.78, 98.87, 124.16,
128.18, 147.20, 149.80, 152.19, 152.49, 165.54.
Procedure a. A mixture of aldehyde (10 mmol), β-ketoester
(10 mmol), urea (15 mmol) and conc. HCl (2 mL) in ethanol
(20 mL) was heated under reflux for 18 h. After cooling, the
reaction mixture was poured into crushed ice. The product was
filtered, washed with cold water and a mixture of ethanol/water,
and then dried. The solid crude products were recrystalized
from ethanol or ethylacetate/n-hexane.
5-Ethoxycarbonyl-6-methyl-4-(4-hydroxyphenyl)-3,4-dihy-
dropyrimidin-2(1H)-one (6).
mp = 226–227ꢀC. IR: 3442,
3290, 3124, 2920, 1706, 1650, 1622, 1495, 1422, 1390. 1H
NMR (DMSO-d6) d ppm 1.06 (t, 3H, J = 7.02 Hz), 2.42 (s,
3H), 3.98 (q, 2H, J = 7.02 Hz), 5.37 (s, 1H), 6.94–7.26 (m,
4H), 7.80 (b, 1H), 8.91 (b, 1H), 9.16 (b, 1H). 13C NMR
(DMSO-d6) d ppm 13.87, 15.76, 55.52, 63.21, 110.30,
114.93, 128.31, 136.67, 148.13, 152.92, 158.56, 168.49.
5-Ethoxycarbonyl-4,6-dimethyl-3,4-dihydropyrimidin-2
Procedure b. Aldehyde (10 mmol), β-ketoester (10 mmol)
and urea (15 mmol) were mixed together followed by addition
NaOH (10 mmol in 5-mL water) and catalytic amount of
Aliquat-336 (1.5 mmol) in a 25-mL flask. The reaction mixture
was heated with stirring at 100ꢀC for 45 min. After completion,
the resultant mass was poured into crushed ice and solid
obtained was filtered through Buckner funnel, washed with ice-
cold water, twice with petroleum-ether, and air-dried over
Buckner. The obtained oily material was separated, neutralized
with 5% aq. HCl, water washed, dried over anhydrous sodium
sulphate, and concentrated under vacuo. The solid crude
products were recrystalized from ethanol or ethylacetate/n-hexane.
All the products were confirmed by comparing their melting
(1H)-one (7).
mp = 193–195ꢀC. IR: 3260, 3108, 1702,
1650. 1H NMR (DMSO-d6) d ppm 1.08 (d, 3H, J = 6.60
Hz), 1.10 (t, 3H, J = 6.90 Hz), 2.17 (s, 3H), 4.03–4.27 (m,
3H), 7.20 (b, 1H), 9.01 (b, 1H). 13C NMR (DMSO-d6) d
ppm 14.32, 17.42, 23.61, 46.00, 59.11, 100.60, 147.36,
152.70, 165.43.
5-Ethoxycarbonyl-6-methyl-4-ethyl-3,4-dihydropyrimidin-2
(1H)-one (8).
IR: 3248, 3120, 1709, 1658. 1H NMR
(DMSO-d6) d ppm 0.78 (t, 3H, J = 7.02 Hz), 1.14 (t, 3H,
J = 7.02 Hz), 1.29–1.41 (m, 2H), 2.13 (s, 3H), 3.98–4.56
(m, 3H), 7.26 (b, 1H), 8.90 (b, 1H). 13C NMR (DMSO-d6)
1
points, IR, H NMR and 13C NMR data with literature data [1,
d
ppm 9.21, 14.91, 18.39, 30.30, 51.97, 59.70, 99.37,
16, 30, 33–38].
149.16, 153.50, 166.20.
5-Ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-
2(1H)-one (1). mp = 199–201ꢀC. IR: 3242, 3113, 2975, 2938,
1720, 1704, 1647, 1600 cm−1. 1H NMR (DMSO-d6) d ppm 1.10
(t, 3H, J = 7.02 Hz), 2.25 (s, 3H), 3.98 (q, 2H, J = 7.02 Hz), 5.34
(s, 1H), 7.12–7.32 (m, 5H), 7.78 (b, 1H), 9.20 (b, 1H). 13C NMR
(DMSO-d6) d ppm 14.50, 18.22, 54.24, 59.62, 106.41, 126.69,
127.70, 128.78, 145.28, 148.83, 152.61, 165.60.
5-Ethoxycarbonyl-6-methyl-4-propyl-3,4-dihydropyrimidin-2
(1H)-one (9). mp = 179–181ꢀC. IR: 3250, 3120, 2960, 2934,
1
2875, 1718, 1646. H NMR (DMSO-d6) d ppm 0.86 (t, 3H, J =
6.90 Hz), 1.19 (t, 3H, J = 5.10 Hz), 1.26–1.41 (m, 4H), 2.15 (s,
3H), 4.03–4.11 (m, 3H), 7.33 (b, 1H), 8.94 (b, 1H). 13C NMR
(DMSO-d6) d ppm 9.70, 12.82, 15.91, 18.96, 31.40, 52.00,
60.70, 99.87, 148.80, 153.06, 166.05.
5-Ethoxycarbonyl-6-methyl-4-(4-chlorophenyl)-3,4-dihydro-
pyrimidin-2(1H)-one (2). mp = 210–213ꢀC. IR: 3224, 3102,
2980, 2931, 1724, 1651 cm−1.1H NMR (DMSO-d6) d ppm
1.10 (t, 3H, J = 6.9 Hz), 2.25 (s, 3H), 3.99 (q, 2H, J = 6.9
Hz), 5.10 (s, 1H), 7.19–7.42 (m, 4H), 7.81 (b, 1H), 9.25
(b, 1H). 13C NMR (DMSO-d6) d ppm 14.25,18.72, 50.70,
53.54, 98.57, 128.10, 128.35, 131.74, 143.52, 148.90,
151.92, 165.63.
5-Ethoxycarbonyl-6-methyl-4-butyl-3,4-dihydropyrimidin-2
(1H)-one (10). mp = 164–166ꢀC. IR: 3245, 3116, 1728, 1706,
1
1652. H NMR (DMSO-d6) d ppm 0.85 (t, 3H, J = 7.20 Hz),
1.11–1.36 (m, 9H), 2.14 (s, 3H), 3.93–4.11 (m, 3H), 7.30 (b,
1H), 8.92 (b, 1H). 13C NMR (DMSO-d6) d ppm 12.95, 14.56,
18.01, 24.06, 28.50, 33.40, 51.00, 60.72, 109.80, 140.80,
155.06, 166.01.
5-Ethoxycarbonyl-6-ethyl-4-phenyl-3,4-dihydropyrimidin-2
(1H)-one (11). mp = 129–131ꢀC. IR: 3230, 3107, 3029, 2979,
5-Ethoxycarbonyl-6-methyl-4-(4-methoxyphenyl)-3,4-dihy-
1
2938, 1702, 1641 cm−1. H NMR (DMSO-d6) d ppm 1.08–1.20
dropyrimidin-2(1H)-one (3).
mp = 202–203ꢀC. IR: 3226,
3100, 2929, 2835, 1710, 1652, 1614, 1581, 1510 cm−1
.
1H
(m, 6H), 2.65–2.71 (m, 2H), 4.05 (q, 2H, J = 7.20 Hz), 5.36 (s,
1H), 7.14–7.32 (m, 5H), 7.76 (b, 1H), 8.93 (b, 1H). 13C NMR
(DMSO-d6) d ppm 12.60, 14.21, 25.42, 55.41, 59.90, 100.25,
126.50, 127.83, 128.75, 143.90, 152.15, 154.20, 165.45.
NMR (DMSO-d6) d ppm 1.26 (t, 3H, J = 7.11 Hz), 2.24 (s,
3H), 3.72 (s, 3H), 4.03 (q, 2H, J = 7.11 Hz), 5.09 (s, 1H),
6.85 (d, 2H, J = 8.7 Hz), 7.15 (d, 2H, J = 8.7 Hz), 7.68 (b,
1H), 9.13 (b, 1H). 13C NMR (DMSO-d6) d ppm 14.00, 17.56,
53.32, 54.80, 58.69, 99.95, 113.46, 127.13, 136.90, 147.54,
152.00, 158.00, 165.23.
5-Ethoxycarbonyl-6-ethyl-4-(4-chlorophenyl)-3,4-dihydro-
pyrimidin-2(1H)-one (12). mp = 140–141ꢀC. IR: 3239, 3115,
2980, 2935, 2881, 1697, 1643 cm−1 1H NMR (DMSO-d6) d
.
5-Ethoxycarbonyl-6-methyl-4-(4-methylphenyl)-3,4-dihydro-
ppm 1.10–1.18 (m, 6H), 2.64–2.71 (m, 2H), 4.07 (q, 2H, J =
7.20 Hz), 5.34 (s, 1H), 7.20–7.29 (m, 4H), 7.80 (b, 1H), 8.84
(b, 1H). 13C NMR (DMSO-d6) d ppm 12.50, 14.15, 25.32,
54.94, 60.18, 100.82, 127.93, 128.85, 133.60, 142.34, 152.18,
153.90, 165.31.
pyrimidin-2(1H)-one (4). mp = 215–216ꢀC. IR: 3325, 3154,
1690, 1564, 1230, 1052, 874 cm−1 1H NMR (DMSO-d6) d
.
ppm 1.08 (t, 3H, J = 7.02 Hz), 2.21 (s, 3H), 3.32 (s, 3H), 3.96
(q, 2H, J = 7.02 Hz), 5.09 (s, 1H), 7.02–7.21 (m, 4H), 7.66 (b,
1H), 9.13 (b, 1H). 13C NMR (DMSO-d6) d ppm 14.21, 17.79,
20.86, 53.78, 59.13, 99.65, 126.31, 129.08, 136.43, 142.19,
148.20, 152.43, 165.53.
5-Ethoxycarbonyl-6-ethyl-4-(4-methoxyphenyl)-3,4-dihydro-
pyrimidin-2(1H)-one (13). mp = 145–147ꢀC. IR: 3233, 3106,
1
2980, 2936, 1692, 1612, 1588, 1519 cm−1. H NMR (DMSO-
5-Ethoxycarbonyl-6-methyl-4-(4-nitrophenyl)-3,4-dihydro-
d6) d ppm 1.10–1.21 (m, 6H), 2.63–2.72 (m, 2H), 3.72 (s, 3H),
4.01 (q, 2H, J = 7.20 Hz), 5.22 (s, 1H), 6.87 (d, 2H, J = 8.7
Hz), 7.25 (d, 2H, J = 8.7 Hz), 8.23 (b, 1H), 9.29 (b, 1H). 13C
NMR (DMSO-d6) d ppm 12.85, 14.01, 24.13, 53.52, 59.80,
100.89, 116.70, 127.65, 137.03, 148.90, 152.00, 156.68,
164.23.
pyrimidin-2(1H)-one (5). mp = 206–208ꢀC. IR: 3230, 3118,
2980, 1710, 1652, 1595, 1520 cm−1 1H NMR (DMSO-d6) d
.
ppm 1.07 (t, 3H, J = 6.90 Hz), 2.26 (s, 3H), 3.97 (q, 2H, J =
6.90 Hz), 5.27 (s, 1H), 7.50 (d, 2H, J = 7.35 Hz), 7.84 (b,
1H), 8.23 (d, 2H, J = 7.35 Hz), 9.35 (b, 1H). 13C NMR
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Y. Moussaoui and R. B. Salem
Vol 000
[3] Kappe, C. O. Tetrahedron 1993, 49, 6937.
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[5] Kappe, C. O. Acc Chem Res 2000, 33, 879.
5-Ethoxycarbonyl-6-ethyl-4-(4-methylphenyl)-3,4-dihydro-
pyrimidin-2(1H)-one (14). IR: 3338, 3156, 1695, 1560 cm−1
.
1H NMR (DMSO-d6) d ppm 1.06–1.20 (m, 6H), 2.28 (q, 2H,
J = 7.20 Hz), 2.92 (s, 3H), 4.17 (q, 2H, J = 7.11 Hz), 5.23
(s, 1H), 7.00–7.23 (m, 4H), 7.71 (b, 1H), 9.19 (b, 1H). 13C
NMR (DMSO-d6) d ppm 12.70, 14.30, 21.68, 25.81, 52.79,
60.07, 101.05, 126.65, 129.32, 136.73, 141.69, 146.92,
154.34, 165.93.
[6] Refouvelet, B.; Guyon, C.; Jacquot, Y.; Girard, C.; Fein, H.;
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5-Ethoxycarbonyl-6-ethyl-4-(4-nitrophenyl)-3,4-dihydro-
pyrimidin-2(1H)-one (15).
mp = 222–224ꢀC. IR: 3225,
3106, 2976, 2935, 2875, 1703, 1640, 1595, 1520 cm−1
.
1H
NMR (DMSO-d6) d ppm 1.07–1.26 (m, 6H), 2.58–2.70
(m, 2H), 3.97 (q, 2H, J = 7.20 Hz), 5.27 (s, 1H), 7.47
(d, 2H, J = 7.8), 7.86 (b, 1H), 8.21 (d, 2H, J = 7.8 Hz), 9.35
(b, 1H). 13C NMR (DMSO-d6) d ppm 12.85, 13.95, 24.20,
54.02, 59.70, 98.78, 124.06, 127.80, 132.90, 146.90,
150.80, 154.19, 165.04.
5-Ethoxycarbonyl-6-ethyl-4-(4-hydroxyphenyl)-3,4-dihydro-
pyrimidin-2(1H)-one (16). IR: 3440, 3290, 3121, 2918, 1702,
1647, 1618 cm−1. 1H NMR (DMSO-d6) d ppm 1.07–1.20 (m, 6H),
2.30 (q, 2H, J = 7.20 Hz), 4.00 (q, 2H, J = 7.11 Hz), 5.31 (s, 1H),
6.96–7.17 (m, 4H), 7.76 (b, 1H), 8.76 (b, 1H), 9.02 (b, 1H). 13C
NMR (DMSO-d6) d ppm 11.90, 13.94, 25.40, 52.50, 60.31,
108.90, 114.23, 127.62, 136.70, 147.00, 150.50, 157.52, 167.00.
5-Ethoxycarbonyl-6-ethyl-4-methyl-3,4-dihydropyrimidin-2
(1H)-one (17).
IR: 3250, 3120, 1710, 1654. 1H NMR
(DMSO-d6) d ppm 1.08 (t, 3H, J = 7.06 Hz), 1.27 (t, 3H, J =
7.20 Hz), 1.38 (d, 3H, J = 6.90 Hz), 2.26 (q, 2H, J = 7.20 Hz),
4.13–4.36 (m, 3H), 7.16 (b, 1H), 8.83 (b, 1H). 13C NMR
(DMSO-d6) d ppm 12.32, 14.00, 19.30, 25.60, 48.12, 59.42,
101.02, 146.00, 154.60, 165.00.
5-Ethoxycarbonyl-6-ethyl-4-ethyl-3,4-dihydropyrimidin-2
(1H)-one (18).
IR: 3255, 3117, 1715, 1660. 1H NMR
(DMSO-d6) d ppm 0.90–1.10 (m, 6H), 1.41 (t, 3H, J = 7.20
Hz), 1.69–1.81 (m, 2H), 2.10 (q, 2H, J = 7.20 Hz), 4.01–
4.36 (m, 3H), 7.60 (b, 1H), 8.94 (b, 1H). 13C NMR (DMSO-
d6) d ppm 9.07, 9.22, 14.21, 25.23, 28.39, 50.81, 60.27,
109.50, 148.26, 155.58, 166.12.
[28] Paraskar, A. S.; Dewkar, G. K.; Sudalai, A. Tetrahedron Lett
2003, 44, 3305.
[29] Ma, Y.; Qian, C.; Wang, L.; Yuang, M. J Org Chem 2009, 65,
3864.
[30] Chari, M. A.; Shodha, D.; Kumar, T. K.; Dubey, P. K. Arkivoc
2005, (xv), 74.
[31] Deboche, A.; Amimour, M.; Belfaitah, A.; Rhouati, S.;
Carboui, B. Tetrahedron Lett 2008, 49, 6119.
[32] Ahmed, B.; Khan, R. A.; Habibullah, Keshari, M. Tetrahedron
Lett 2009, 50, 2889.
[33] Yu, Y.; Liu, D.; Liu, C.; Luo, G. Bioorg Med Chem Lett 2007,
17, 3508.
[34] Hu, E. H.; Sidler, D. R.; Dolling, Ulf-H. J Org Chem 1998, 63,
3454.
[35] Joseph, J. K.; Jain, S. L.; Sain, B. J Mol Cat A Chem 2006,
247, 99.
5-Ethoxycarbonyl-6-ethyl-4-propyl-3,4-dihydropyrimidin-2
(1H)-one (19). IR: 3250, 3117, 2962, 2935, 2874, 1720, 1650.
1H NMR (DMSO-d6) d ppm 0.98–1.12 (m, 6H), 1.27–1.61 (m,
7H), 2.15 (q, 2H, J = 7.20 Hz), 4.15–4.32 (m, 3H), 7.44 (b, 1H),
8.96 (b, 1H). 13C NMR (DMSO-d6) d ppm 9.12, 14.02, 14.40,
18.20, 25.84, 36.20, 50.30, 60.90, 113.20, 147.60, 157.20, 166.04.
5-Ethoxycarbonyl-6-ethyl-4-butyl-3,4-dihydropyrimidin-2
(1H)-one (20). IR: 3248, 3110, 1726, 1704, 1651. 1H NMR
(DMSO-d6) d ppm 0.95–1.13 (m, 6H), 1.18–1.39 (m, 7H),
1.51–1.60 (m, 2H), 2.10 (q, 2H, J = 7.20 Hz), 4.10–4.26 (m,
3H), 7.38 (b, 1H), 8.94 (b, 1H). 13C NMR (DMSO-d6) d ppm
9.45, 13.95, 14.46, 24.06, 25.60, 28.05, 33.50, 51.00, 60.80,
109.20, 146.80, 157.00, 166.00.
[36] Gupta, R.; Paul, S.; Gupta, R. J Mol Cat A Chem 2007, 266,
50.
REFERENCES AND NOTES
[37] Gholap, A. R.; Toti, K. S.; Shirazi, F.; Deshpande, M. V.;
Srinivasan, K. V. Tetrahedron 2008, 64, 10214.
[38] Kapadia, M. A.; Patel, M. M.; Joshi, J. D. Inorg Chim Acta
2009, 362, 3292.
[1] Falsone, F. S.; Kappe, C. O. Arkivoc 2001, (ii), 122.
[2] Chikhale, R. V.; Bhole, R. P.; Khedekar, P. B.; Bhusari, K. P.
Eur J Med Chem 2009, 44, 3645.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet