Experimental and theoretical study on a one-pot, three-component route to 3,4-dihydropyrimidin-2(1H)-ones/thiones TiCl3OTf-[bmim]Cl

Article abstract of DOI:10.1007/s11164-015-2092-4

In this study a synthetic method using TiCl₃OTf-ionic liquid was reported for synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones (3,4-DHPMs). Condensation reactions were carried out for aldehydes, ethyl acetoacetate, and ammonium acetate. In

Full text of DOI:10.1007/s11164-015-2092-4

Res Chem Intermed
DOI 10.1007/s11164-015-2092-4
Experimental and theoretical study on a one-pot, three-
component route to 3,4-dihydropyrimidin-2(1H)-ones/
thiones TiCl OTf-[bmim]Cl
3
1
2
2
•
Asadollah Farhadi
Maryam Albakhtiyari
•
Jalil Noei
1
•
Rasoul Haji Aliyari
1
Mohammad Ali Takassi
•
Received: 6 February 2015 / Accepted: 30 April 2015
Ó Springer Science+Business Media Dordrecht 2015
Abstract In this study a synthetic method using TiCl OTf-ionic liquid was reported
3
for synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones (3,4-DHPMs). Conden-
sation reactions were carried out for aldehydes, ethyl acetoacetate, and ammonium
acetate. In the reaction 1-butyl-3-methylimidazolium chloride ([bmim]Cl) was used
as an ionic liquid in the presence of TiCl OTf catalyst under solvent-free conditions at
3
1
40 °C. The advantages of this method are high yield of product, short reaction time,
and reusable catalyst. A mechanism was proposed for this condensation reaction, and
all steps of the suggested mechanism were confirmed by density functional theory
calculations using the B3LYP/6-311G level of theory.
Keywords Ionic liquid Á 3,4-Dihydropyrimidin-2(1H)-ones Á TiCl OTf Á
3
[
bmim]Cl Á DFT Á Mechanism
Introduction
In many bioactive natural products and therapeutic compounds, heterocyclic moiety
is a very important structure. The preparation method of potential biologically active
substances includes multicomponent reactions. For example, the Biginelli type
product is very important due to possessing some biological and pharmacological
activities. 3,4-DHPMs have appeared as essential pillars of some calcium channel
blockers and prevent the binding of HIVgp-120-CD4 cells [1, 2]. A simple one-pot
condensation synthesis of an aldehyde, b-ketoester, and urea was reported by
Biginelli [3]. The Biginelli type products can be synthesized using different catalysts
&
Asadollah Farhadi
farhadichem@put.ac.ir
1
2
Petroleum University of Technology, Faculty of Science, 61981-44471 Ahwaz, Iran
Department of Chemistry, Mahshahr Branch, Islamic Azad University, 63519 Mahshahr, Iran
123

A. Farhadi et al.
and conditions. [4–8]. One-pot synthesis that includes environmentally friendly
chemical processes, and is economically sustainable has received attention as a next
policy for ‘green’ organic syntheses [9].
The growth of very active, stable, friendly to environment, and economically
practicable catalysts has been an important objective for chemists in organic
synthesis. Lately, ionic liquids have been demonstrated to be an effective method to
improve the catalytic activity and its recycling process in organic synthesis. It has
been reported that a combinational system of TiCl OTf-ionic liquid serves as an
3
active catalyst for the synthesis of thioamides and arylnitriles from aldoximes [10,
11]. Here, following further research on this catalytic system, we would like to
report a one-pot procedure for the synthesis of some 3,4-dihydropyrimidin-2(1H)-
ones/thiones using TiCl OTf-[bmim]Cl (Scheme 2). The advantage of this method
3
is synthesis of Biginelli type product in the green chemistry condition with high
yields and short reaction times. Furthermore, the theoretical and experimental data
were used to propose the mechanism for this condensation reaction.
Experimental section
General procedure
In a model reaction (Scheme 1), an equivalent amount of benzaldehyde (1 mmol),
ethyl acetoacetate (1 mmol), and urea (1.2 mmol) was studied with different ionic
liquids (ILs) in the presence of small amount of the TiCl OTf catalyst. The effects of
3
solvents, temperature, time of reaction, and amount of catalyst were studied for the rate
of reaction. The results are summarized in Table 1. Ethanol, acetonitrile, and
dichloromethane were also used as solvents in this reaction. These solvents made the
reactionslow withloweryields. However, thecombinationofTiCl OTfwith[bmim]Cl
3
at a reaction temperature of 140 °C displayed the best result (Table 1, entry 6).
Results and discussion
Based on the optimized theoretical results, we studied the substrate scope in a
Biginelli reaction. In these reactions various aromatic aldehydes with different
substituents were used at the optimized reaction conditions. In order to study the
O
O
H
O
O
O
TiCl OTf
EtO
N
3
+
+
C H CHO
6
5
OEt
NH2
NH
2
different conditions
CH3
H C
N
3
H
1
Scheme 1 Synthesis of ethyl 6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one-5-carboxylate using
TiCl OTf-[bmim]Cl under different conditions
3
1
23

Experimental and theoretical study on one-pot, three-component…
Table 1 Synthesis of ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidin-5-carboxylate 1 in
different conditions
b
Entry
Catalyst
15 % mol)
Solvent (5 mL)/IL
(2 mmol)
Temperature
(°C)
Time
(min)
Yield %
a
(
1
2
3
4
5
6
7
8
a
TiCl
TiCl
TiCl
TiCl
TiCl
TiCl
TiCl
TiCl
3
3
3
3
3
3
3
3
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
CH
3
CN
Reflux
Reflux
Reflux
140
120
150
135
20
25
70
20
45
73
90
84
70
C
2
H
5
OH
CH
2
Cl
2
[bmim]OTf
[bmim]Br
[bmim]Cl
[bmim]Cl
[bmim]Cl
140
20
140
20
120
45
90
70
The times are given after maximum progression of the reaction
Isolated yield
b
Ar
O
X
O
H
N
O
TiCl OTf / [bmim]Cl
EtO
3
+
+
ArCHO
a-l
NH2
NH
2
o
CH3
OEt
solvent-free /140 C
H C
N
H
a-l
X
1
3
2
X = O, S
Ar = a: C H -, b: 2-ClC H -, c: 3-ClC H -, d: 4-ClC H -, e: 2-BrC H -, f: 3-BrC H -,
6
5
6
4
6
4
6
4
6
4
6
4
g: 4-BrC H -, h: 3-NO C H -, i: 4-NO C H -, j: 4-CH C H -, k: 3-CH OC H -, l :4-CH OC H -
6
4
2
6
4
2
6
4
3
6
4
3
6
4
3
6
4
3
Scheme 2 The synthesis of Biginelli-type products in the presence of TiCl OTf as catalyst and
[bmim]Cl as ionic liquid
generality of this procedure, using a similar process, a series of 3,4-dihydropyrim-
idin-2(1H)-ones were synthesized (Scheme 2).The results are shown in Table 2.
The reactions, which were carried out at a temperature of 140 °C, were
completed in 15–50 min under the abovementioned conditions. The steric effect of
ortho-substituents has relatively little influence on the reaction time and yield. As it
is presented in Table 2, 2-chlorobenzaldehyde and 2-bromobenzaldehyde reacted
slower than 4-chlorobenzaldehyde and 4-bromobenzaldehyde. A minor electronic
effect was also observed. For example, aldehydes with an electron-withdrawing
group such as 4-nitrobenzaldehyde enhanced the rate of reaction, while the presence
of electron-rich groups such as 4-methyl or 4-methoxy diminished the rate of
reaction. Moreover, thiourea was used at similar conditions to prepare the
corresponding 3,4-dihydropyrimidin-2(1H)-thiones. According to these experimen-
tal data and theoretical data (Table 3), the following mechanism was proposed
(
scheme 3).
Ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (2a) mp.
2
2
01–203 °C (204–206 °C [7]); UV/Vis (CH CN), k
(log emax): 274.4 nm (4.01),
1
3
max
-
1
28.6 (3.91); IR, m~ /cm : 1720 (CO C H ), 1700 (2-CO), 1640 (C=C); H NMR
2
2 5
123

A. Farhadi et al.
Yield %
Table 2 One-pot synthesis of
,4-dihydropyrimidin-2(1H)-
ones/thiones using TiCl OTf-
bmim]Cl under solvent-free
conditions at a reaction
temperature of 140 °C
Comp.
X
Time (min)
3
3
2
a
O
O
O
O
O
O
O
O
O
O
O
O
S
20
50
25
20
40
35
35
15
20
20
30
30
30
35
40
90
70
90
95
80
85
90
90
95
80
85
80
65
75
70
[
2b
2c
2
2
2
2
2
2
2
2
2
2
2
2
d
e
f
g
h
i
j
k
l
a
d
l
S
S
Table 3 Calculation of the
Mullikan’s charges on the
different atoms Z and E isomers
with a B3LYP/6-31G level
Comp. Z isomer
Atoms
E isomer
Atoms
C1
C3
C4
C1
C3
C4
Ia
Ib
Ic
Id
Ie
If
-2.108 -1.480 0.278
0.041 -0.697 0.227
-0.161
-0.147
-0.168
0.440 0.323 -0.140
0.384 0.346 -0.168
0.432 0.343 -0.170
0.485 0.286
0.470 0.346
0.467 0.347
-2.294 -2.001 0.370 -0.116 -0.642 0.200
-2.432 -1.818 0.232 -0.043 -0.789 0.265
-2.225 -1.805 0.193 -0.057 -0.847 0.285
Ig
Ih
Ii
-2.182 -2.143 0.234 -0.013 -0.71
0.197
-2.308 -1.868 0.084
-0.170
0.208 -0.723 0.245
Ij
0.428 0.341 -0.173
0.465 0.345
Ik
Il
-1.564 -1.796 0.261 -0.164 -0.588 0.161
-2.313 -1.575 0.177 0.206 -0.687 0.259
(
J = 7.07 Hz, OCH CH ), 5.14 (d, J = 3 Hz, 1H, CCHNH), 7.22–7.34 (m, 5H, Ar),
DMSO-d ), d: 1.08 (t, 3H, J = 7.07 Hz, OCH CH ), 2.24 (s, 3H, CCH ), 3.97 (q, 2H,
6
2
3
3
2
3
7
.72 (s, 1H, NH), 9.17 (s, 1H, NH).
Ethyl 6-methyl-4-(4-methylphenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxy-
late (2b) mp. 211–214 °C (212–215 °C [12]); UV/Vis (CH CN), k (log
3
max
-
1
emax): 276 nm (3.45), 232 (3.70); IR, m~ /cm : 1710 (CO C H ), 1700 (2-CO), 1650
2
2 5
1
23

Experimental and theoretical study on one-pot, three-component…
Scheme 3 E and Z isomers of
different benzylidenes of ethyl
acetoacetate
O
3
O
3
O
4
O
4
2
2
CH3
OEt
CH3
OEt
and
Ar
E (I a-l)
1
H
H
1
Ar
Z (I a-l)
1
(
C=C); H NMR (DMSO-d ), d: 1.12 (t, 3H, J = 7.5 Hz, OCH CH ), 2.28, 2.30 (s,
6
2
3
3
H), 4.00 (q, 2H, J = 7.5 Hz, OCH CH ), 5.11 (d, 1H, J = 3.0 Hz, CCHNH), 7.25
2 3
(
m, 4H), 7.70 (br s, 1H, NH), 9.19 (br s, 1H, NH).
Ethyl 6-methyl-4-(3-methylphenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxy-
late (2c) mp. 211–214 °C (210–212 °C [13]); UV/Vis (CH CN), k (log
3
max
-
1
emax): 274 nm (3.47), 230 (3.75); IR, m~ /cm : 1725 (CO C H ), 1700 (2-CO), 1650
2
2 5
(
C=C).
Ethyl 6-methyl-4-(2-methylphenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxy-
late (2d) mp. 207–210 °C (208–209 °C [12]); UV/Vis (CH CN), k (log
3
max
-
1
emax): 276.5 nm (3.52), 227 (3.36); IR, m~ /cm : 1700 (CO C H ), 1645 (2-CO),
2
2 5
1
595 (C=C).
Ethyl
boxylate (2e) mp. 201–202 °C (201–205 °C [7]); UV/Vis (CH CN), k
4-(4-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-car-
(log
emax): 274 nm (3.47), 230 (3.75); IR, m~ /cm : 1725(CO C H ), 1700 (2-CO), 1650
3
max
-
1
2
2 5
1
(C=C); H NMR (DMSO-d ), d: 1.10 (t, 3H, J = 7.08 Hz, OCH CH ), 2.23 (s, 3H,
CCH ), 3.71 (s, 3H, OCH3), 3.97 (q, 2H, J = 7.07 Hz, OCH CH ), 5.09 (d, 1H,
6
2
3
3
2
3
J = 2.9 Hz, CCHNH), 6.87 (d, 2H, J = 8.5 Hz, Ar), 7.14 (d, 2H, J = 8.5 Hz, Ar),
.66 (s, 1H, NH), 9.15 (s, 1H, NH).
7
Ethyl
boxylate (2f) mp. 207–209 °C (207–208 °C [7]); UV/Vis (CH CN), k
4-(3-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-car-
(log
emax): 276.5 nm (3.52), 227 (3.36); IR, m~ /cm : 1700 (CO C H ), 1645 (2-CO),
3
max
-
1
2
2 5
1
1
595 (C=C); H NMR (DMSO-d ), d: 1.10 (t, 3H, J = 7 Hz, OCH CH ), 2.24 (s,
6
2
3
3
H, CCH ), 3.72 (s, 3H, OCH ), 3.99 (q, 2H, J = 7 Hz, OCH CH ), 5.11 (d, 1H,
3
3
2
3
J = 2.2 Hz, CCHNH), 6.77–6.83 (m, 3H, Ar), 7.24 (t, 1H, J = 7.8 Hz, Ar), 7.73 (s,
H, NH), 9.19 (s, 1H, NH).
1
Ethyl
boxylate (2g) mp. 259–260 °C (262–263 °C [7]); UV/Vis (CH CN), k
4-(2-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-car-
(log
emax): 276.5 nm (3.52), 227 (3.36); IR, m~ /cm : 1700 (CO C H ), 1645 (2-CO),
3
max
-
1
2
2 5
1
1
595 (C=C); H NMR (DMSO-d ), d: 1.06 (t, 3H, J = 7.04 Hz, OCH CH ), 2.07 (s,
6
2
3
3
H, CCH ), 3.87 (s, 3H, OCH ), 4.04 (q, 2H, J = 7.04 Hz, OCH CH ), 5.58 (s, 1H,
3
3
2
3
CCHNH), 6.57–6.93 (m, 1H, Ar), 7.01–7.07 (m, 2H, Ar), 7.24–7.33 (m, 1H, Ar),
.56 (s, 1H, NH), 9.12 (s, 1H, NH).
7
123

A. Farhadi et al.
Ethyl 4-(4-chlorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxy-
late (2h) mp. 209–211 °C (210–212 °C [14]); UV/Vis (CH CN), k
(log
max
3
-
1
emax): 280 nm (3.46), 233 (3.27); IR, m~ /cm : 1720 (CO C H ), 1690 (2-CO), 1615
(C=C); H NMR (DMSO-d ), d: 1.15 (t, 3H, J = 7.2 Hz, OCH CH ), 2.33 (s, 3H,
CCH ), 4.10 (q, 2H, J = 7.8 Hz, OCH CH ), 5.30 (s, 1H, CCHNH), 7.26–7.33 (m,
2
2 5
1
6
2
3
3
2
3
4
H, Ar), 7.69 (s, 1H, NH), 9.17 (s, 1H, NH).
Ethyl 4-(3-chlorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxy-
late (2i) mp. 193–195 °C (197–198 °C [7]); UV/Vis (CH CN), k (log emax):
3
max
-
1
2
78.5 nm (3.52), 229 (3.36); IR, m~ /cm : 1710 (CO C H ), 1690 (2-CO), 1650
2
2 5
1
(C=C); H NMR (DMSO-d ), d: 1.08 (t, 3H, J = 7.0 Hz, OCH CH ), 2.24 (s, 3H,
CCH ), 3.98 (q, 2H, J = 7.0 Hz, OCH CH ), 5.14 (s, 1H, CCHNH), 7.36–7.17 (m,
6
2
3
3
2
3
4
H, Ar), 7.7 (s, 1H, NH), 9.24 (s, 1H, NH).
Ethyl 4-(2-chlorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxy-
late (2j) mp. 216–218 °C (218–219 °C [7]); UV/Vis (CH CN), k (log emax):
3
max
-
1
2
78.5 nm (3.52), 229 (3.36); IR, m~ /cm : 1705 (CO C H ), 1690 (2-CO), 1635
2
2 5
1
(C=C); H NMR (DMSO-d6), d 0.98 (t, 3H, J = 6.9 Hz, OCH CH ), 2.28 (s, 3H,
CCH ), 3.87 (q, 2H, J = 6.9 Hz, OCH CH ), 5.61 (d, 1H, J = 2.98 Hz, CCHNH),
2
3
3
2
3
7
.28–7.33 (m, 3H, Ar), 7.36–7.39 (m, 1H), 7.70 (s, 1H, NH), 9.25 (s, 1H, NH).
Ethyl 4-(4-bromophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxy-
late (2k) mp. 210–212 °C (213–215 °C [15]); UV/Vis (CH CN), k (log
3
max
-
1
emax): 285 nm (3.35), 230 (3.30); IR, m~ /cm : 1710 (CO C H ), 1685 (2-CO), 1610
(C=C); H NMR (DMSO-d6), d: 1.13 (t, 3H, J = 7.0 Hz, OCH CH ); 2.29 (s, 3H,
CCH ), 4.02 (q, 2H, OCH CH , J = 7.0 Hz,), 5.17 (d, 1H, J = 2.2 Hz, CCHNH),
2
2 5
1
2
3
3
2
3
7
.23 (d, 2H, J = 8.2 Hz,), 7.56 (d, 2H, J = 8.2 Hz,), 7.80 (s, 1H), 9.28 (s, 1H).
Ethyl 4-(3-bromophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxy-
late (2l) mp. 190–193 °C (196–197 °C [16]); UV/Vis (CH CN), k (log emax):
3
max
-
1
2
75 nm (3.45), 235 (3.25); IR, m~ /cm : 1700 (CO C H ), 1680 (2-CO), 1615 (C=C).
2
2 5
Ethyl 4-(2-bromophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxy-
late (2m) mp. 198–200 °C (205–207 °C [16]); UV/Vis (CH CN), k (log
3
max
-
1
emax): 280 nm (3.40), 228 (3.32); IR, m~ /cm : 1720 (CO C H ), 1680 (2-CO), 1600
2
2 5
(
C=C).
Ethyl 6-methyl-4-(4-nitrophenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
2n) mp. 207–209 °C (207–208 °C [7]); UV/Vis (CH CN), k
(
(log emax):
3
max
-
1
2
1
64 nm (3.31), 225 (3.17); IR, m~ /cm : 1725 (CO C H ), 1700 (2-CO), 1640 (C=C);
H NMR (DMSO-d6), d: 1.09 (t, 3H, J = 6.9 Hz, OCH CH ), 2.26 (s, 3H, CCH3),
2
2 5
2
3
3
.98 (q, 2H, J = 7.2 Hz, OCH CH ), 5.27 (d, 1H, J = 3.3 Hz, CCHNH), 7.49–7.52
2 3
(
m, 2H, Ar), 7.89 (s, 1H, NH), 8.20–8.23 (m, 2H, Ar), 9.36 (s, 1H, NH).
Ethyl 6-methyl-4-(3-nitrophenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
(log emax):
(
2o) mp. 223–225 °C (226–227 °C [17]); UV/Vis (CH CN), k
3
max
-
1
2
1
64 nm (3.31), 225 (3.17); IR, m~ /cm : 1720 (CO C H ), 1690 (2-CO), 1640 (C=C);
2
2 5
H NMR (DMSO-d6), d: 1.09 (t, 3H, J = 7.0 Hz, OCH CH ), 2.26 (s, 3H, CCH ),
2
3
3
1
23

Experimental and theoretical study on one-pot, three-component…
3
.98 (q, 2H, J = 7.0 Hz, OCH CH ), 5.30 (d, 1H, J = 2.5 Hz, CCHNH), 7.62–7.71
2 3
(
m, 2H, Ar), 7.90 (s, 1H, NH), 8.08–8.15 (m, e)
Theoretical section
Structural and electronic characteristics of the abovementioned compounds were
calculated using B3LYP/6-311G. The optimized geometries were analyzed in the
following sections. All computations were carried out using the Gaussian 98
package [18].
Electronic parameters
Currently, numerous attempts have been made to study molecules from theoretical
point of views. Among different quantum mechanical methods, density functional
theory (DFT) provides a reasonable theoretical framework for the study of both
reactivity and selectivity of molecular systems [19]. In this study the Mullikan’s
charges were calculated on the different atoms of some benzylidene derivatives and
aldehydes (Scheme 3), (Tables 3, 4).
Analysis of data reported in the Table 3, shows that nucleophilic attachment on
the C4 atom is times as fast as C1 atom in two isomers. (Scheme 4 entry 3)
Furthermore, Mullikan’s charges on the N atom on the urea and thiourea are -0.594
and -0.484, respectively. These data are in agreement with time reactions for
synthesis of Biginelli type products.
Comparison of the Mullikan’s charges on carbon atoms of aldehydes demon-
strated that the charge densities on the carbon atom of carbonyl groups are more
positive. However, nucleophilic attachment can be carried out on the carbonyl group
of aldehydes is times as fast as C1 atom of benzylidene compounds.
Table 4 Calculation of the
Comp.
CHO
Mullikan’s charges on the
carbonyl group of some different
aldehydes with a B3LYP/6-31G
level
1
a
0.160
0.160
0.163
0.174
0.159
0.155
1b
1
1
1
1
1
1
1
1
1
l
c
d
e
f
g
h
i
0.348
0.174
0.259
0.239
0.244
j
k
123

A. Farhadi et al.
Mechanism
Ti4+
.
.
O
.
O .
TiCl OTf
1
.
3
H
Ar
H
Ar
Ti4+
.
.
O
3
.
O .
O
4
O
O
2
2.
+
CH3
OEt
H
O
CH3
OEt
Ar
Ar
1
H
I
NH2
O
X
X
N
O
CH3
OEt
3
.
+
NH2
NH
2
CH3
Ar
H
OEt
X= O, S
Ar
H
II
O
O
Ar
X
O
or
CH3
OEt
EtO
NH
+
NH2
NH
2
Ar
H
CH3
OH
O
III
Ar
NH
2
O
H
O
condensation reaction
N
EtO
CH3
4.
I or III
N
H
3
Scheme 4 Proposed mechanism for synthesis of DHPMs by using TiCl OTf-[bmim]Cl
Conclusion
We have introduced a new procedure for preparation of 3,4-dihydropyrimidin-
(1H)-ones/thiones using TiCl OTf-[bmim]Cl as catalyst. High yield, short time of
2
3
reaction, easy work-up, and no use of toxic solvents are the advantages of this
method. Furthermore, comparative results of the experimental and theoretical
investigation were reported for some 3,4-dihydropyrimidin-2(1H)-one. Finally a
mechanism was proposed for this synthetic reaction.
Acknowledgments The authors are grateful to the Islamic Azad University, Mahshahr branch, and the
Petroleum University of Technology for partial support of this work.
1
23

Experimental and theoretical study on one-pot, three-component…
References
1
2
3
4
5
6
. C.O. Kappe, Eur. Med. Chem. 35, 1043–1052 (2000)
. C.O. Kappe, O.V. Shishkin, G. Uray, P. Verdino, Tetrahedron 56, 1859–1862 (2000)
. P. Biginelli, Gazz. Chim. Ital. 23, 360–416 (1893)
. M. Nasr-Esfahani, S.J. Hoseini, F. Mohammadi, Chin. J. Catal. 32, 1484–1489 (2011)
. J.T. Starcevich, T.J. Laughlin, R.S. Mohan, Tetrahedron Lett. 54, 983–985 (2013)
. R. Tayebee, M.M. Amini, M. Ghadamgahi, M. Armaghan, J. Mol. Catal. A Chem. 366, 266–274
(2013)
7. A. Farhadi, M.A. Takassi, L. Hejazi, Z. Naturforsch. 68b, 51–56 (2013)
8. H. Kiyani, M. Ghiasi, Res. Chem. Intermed. In press, doi:10.1007/s11164-014-1621-x (2014)
9. A.R. Katritzky, O. Meth-Cohn, C.W. Rees, Comprehensive Organic Functional Group Transfor-
mations (Pergamon, Oxford, 1995)
1
1
1
1
1
1
1
0. J. Noei, A.R. Khosropour, Tetrahedron Lett. 49, 6969–6971 (2008)
1. J. Noei, A.R. Khosropour, A. Mirjafari, Bull. Korean Chem. Soc. 33, 2102–2104 (2012)
2. R. Tayebee, M. Ghadamgahi, Arab. J. Chem. In press, doi:10.1016/j.arabjc.2012.12.001 (2013)
3. A. Debache, L. Chouguiat, R. Boulcina, B. Carbonib, Open Org. Chem. J. 6, 12–20 (2012)
4. G.H. Mahdavinia, H. Sepehrian, Chin. Chem. Lett. 19, 1435–1439 (2008)
5. X.L. Shi, H. Yang, M. Tao, W. Zhang, R. Soc. Chem. Adv. 3, 3939–3945 (2013)
6. K.K. Pasunooti, H. Chai, C.N. Jensen, B.K. Gorityala, S. Wang, X.-W. Liu, Tetrahedron Lett. 52,
8
0–84 (2011)
7. K.A. Dilmaghani, B. Zeynizadeh, H. Parsajam, Phosphorus Sulfur Silicon Relat. Elem. 187, 544–553
2012)
1
1
(
8. M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, V.G. Zakr-
zewski, J.A. Montgomery Jr, R.E. Stratmann, J.C. Burant, S. Dapprich, J.M. Millam, A.D. Daniels,
K.N. Kudin, M.C. Strain, O. Farkas, J. Tomasi, V. Barone, M. Cossi, R. Cammi, B. Mennucci, C.
Pomelli, C. Adamo, S. Clifford, J. Ochterski, G.A. Petersson, P.Y. Ayala, Q. Cui, K. Morokuma,
D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J. Ciolowski, J.V. Ortiz, B.B. Stefanov,
G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R.L. Martin, D.J. Fox, T. Keith, M.A.
Al-Laham, C.Y. Peng, A. Nanayakkara, C. Gonzalez, M. Challacombe, P.M.W. Gill, B. Johnson, W.
Chen, M.W. Wong, J.L. Andres, M. Head-Gordon, E.S. Replogle, J.A. Pople, Gaussian 98 (Gaussian
Inc., Pittsburg PA, 1998)
19. A. Farhadi, M.A. Takassi, P. Madmoli, J. Am. Sci. 8, 2024–2038 (2012)
123