1,3-Disulfonic acid benzimidazolium chloride as an efficient and recyclable ionic liquid catalyst for the synthesis of 3,4-dihydropyrimidine-2-(1H)-ones/thiones

Article abstract of DOI:10.1007/s11164-015-2211-2

1,3-Disulfonic acid benzimidazolium chloride ionic liquid ([Dsbim]Cl) was prepared, characterized and applied as an efficient, homogeneous and recyclable catalyst for the synthesis of 3,4-dihydropyrimidine-2-(1H)-ones/thiones through the one-pot three-com

Full text of DOI:10.1007/s11164-015-2211-2

Res Chem Intermed
DOI 10.1007/s11164-015-2211-2
1
,3-Disulfonic acid benzimidazolium chloride
as an efficient and recyclable ionic liquid catalyst
for the synthesis of 3,4-dihydropyrimidine-2-(1H)-ones/
thiones
1
Mohsen Abbasi
Received: 12 May 2015 / Accepted: 3 August 2015
Ó Springer Science+Business Media Dordrecht 2015
Abstract 1,3-Disulfonic acid benzimidazolium chloride ionic liquid ([Dsbim]Cl)
was prepared, characterized and applied as an efficient, homogeneous and recy-
clable catalyst for the synthesis of 3,4-dihydropyrimidine-2-(1H)-ones/thiones
through the one-pot three-component condensation of aromatic aldehydes, urea/
thiourea and ethyl acetoacetate under solvent-free conditions. The key advantages
of this novel protocol are its short reaction time, high yields, mild and clean con-
ditions, practical simplicity and its capacity for reuse several times without a
noticeable decrease in catalytic activity.
Keywords 1,3-Disulfonic acid benzimidazolium chloride Á Ionic liquid Á
Solvent-free Á 3,4-Dihydropyrimidine-2-(1H)-ones
Introduction
The development of cleaner technologies is a major focus in green chemistry. One
of the key principles of green chemistry is the elimination of solvents in chemical
processes or the replacement of hazardous solvents with those that are environ-
mentally friendly [1, 2]. In this regard, ionic liquids have attracted significant
research interest in the context of green synthesis due to their adjustable physical
and chemical properties [3]. They have been introduced as an alternative green
reaction medium given their exceptional features including high thermal and
chemical stability, low vapor pressure, nonflammability, non-volatile nature, large
electrochemical window, potential recyclability, and the ability to dissolve many
organic and inorganic materials [4–6]. These compounds have been used
extensively in electrochemistry, spectroscopy, and extraction and separation
&
Mohsen Abbasi
mohsen.abbasi90@gmail.com
1
Department of Chemistry, Lamerd Branch, Islamic Azad University, Lamerd, Fars, Iran
123

M. Abbasi
processes [7]. Multicomponent reactions (MCRs) are powerful tools in which three
or more different starting materials react to form novel and complex molecules in a
one-pot strategy with high efficiency, time savings and reduced waste [8–10]. One
such prominent MCR that produces an interesting class of nitrogen-containing
heterocycles is the venerable Biginelli [11] reaction established by Italian chemist
Pietro Biginelli (University of Florence) in 1893 for the synthesis of 3,4-
dihydropyrimidinones (DHPMs) under strong acidic conditions. However, this
reaction suffered from harsh conditions, long reaction times and low yield. DHPMs
have received special attention given their wide range of biological and
pharmaceutical activities, including antibacterial, antiviral, anticancer, antitumor,
antifungal, antioxidant, anti-inflammatory, and antihypertensive properties, their use
as calcium channel modulators, a -antagonists, neuropeptide Y(NPY) antagonists,
1
A
and other related properties [12–16]. Over the past decade, several methods have
been reported for the synthesis of DHPMs using LaCl –graphite [15], CuCl Á2H O
3
2
2
[
16], Yb(OTf) [17], phytic acid [18], triphenylphosphine (PPh ) [19], silica-bonded
3 3
N-propyl sulfamic acid [20], Fe(OTs) Á6H O [21], bioglycerol-based sulfonic acid
3
2
functionalized carbon [22], sulfonated carbon materials (SCM) [23], InCl [24],
3
phosphotungstic acid (H PW O ) [25], Mn(OAc) Á2H O [26], b-cyclodextrin
3
12 40
3
2
[
(
27], cerium(III) trislaurylsulfonate (Ce(LS) ) [28], phthalimide-N-sulfonic acid
3
PISA) [29], nano ZnO [30], MCM-41-R-SO H [31], Fe O NPs [32], sulfated
3
3 4
tungstate [33] and silica-bonded S-sulfonic acid (SBSSA) [34]. While existing
synthetic methods are effective for the preparation of target compounds, some suffer
shortcomings such as long reaction time (2.5–43 h), elevated temperature (refluxing
EtOH or MeCN and solvent-free 140 °C), low yields, the use of hazardous organic
solvents (e.g., EtOH, MeCN, AcOH, THF, isopropanol) or unrecyclable catalysts
(
e.g., CuCl Á2H O, InCl , Yb(OTf) , Fe(OTs) Á6H O), and poor compliance with
2
2
3
3
3
2
the green chemistry protocols. Consequently, a simple, efficient and recyclable
catalyst is needed for the synthesis of these high-value compounds. As part of our
continuing interest in developing green protocols for the synthesis of biologically
active compounds [35–37], we focused our attention on a simple and efficient
preparation of 1,3-disulfonic acid benzimidazolium chloride ([Dsbim]Cl) ionic
liquid as a powerful and recyclable catalyst for the synthesis of 3,4-dihydropyrim-
idin-2(1H)-ones/thiones via one-pot three-component condensation of aromatic
aldehydes, urea/thiourea and ethyl acetoacetate under solvent-free conditions, with
high yields and very short reaction times (Scheme 1). To the best of our knowledge,
there is no report on the synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones using
([Dsbim]Cl) ionic liquid as catalyst. The homogeneous catalyst can be easily
recovered and reused many times without significant loss of its catalytic activity.
Experimental
General
All reagents were purchased from Merck KGaA (Darmstadt, Germany) and Sigma-
Aldrich Co. LLC (St. Louis, MO, USA), and used without further purification. The
1
23

1,3-Disulfonic acid benzimidazolium chloride as an…
Ar
O
O
X
O
O
[
Dsbim]Cl 10 mol%
HN
OEt
+
+
Ar
H
OEt
H
N
2
NH
2
0
Solvent free, 80 C
X
N
H
X= O, S
Scheme 1 General formulation for the preparation of 1,3-disulfonic acid benzimidazolium chloride
Dsbim]Cl) and its use for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones/thiones
[
products were identified by comparison of their melting points (MP) and spectral
data with those in the literature. The progress of reactions was monitored by thin-
layer chromatography (TLC) using silica gel SIL G/UV 254 plates. MP were
recorded on an Electrothermal IA9000 apparatus (Bibby Scientific Ltd, Stafford-
shire, UK), without correction. FT-IR spectra were recorded using KBr pellets on an
Avatar 370 FT-IR Thermo Nicolet spectrometer (Thermo Scientific, Waltham, MA,
USA). NMR spectra were collected on a Bruker Avance (Bruker Corporation,
Billerica, MA, USA) 400 MHz spectrometer (d in ppm). Mass spectra were
obtained on a Varian Mat CH-7 at 70 eV (Varian Medical Systems, Palo Alto, CA,
USA). Elemental analysis was performed on a Thermo Finnigan FlashEA (Thermo
Scientific) microanalyser.
General procedure for the preparation of the [Dsbim]Cl ionic liquid
To a round-bottom flask (100 mL) containing benzimidazole (0.708 g, 6.0 mmol) in
dry CH Cl (50 mL), chlorosulfonic acid (1.40 g, 12 mmol) was added drop-wise
2
2
over a period of 20 min at room temperature. After the addition was completed, the
reaction mixture was stirred for 12 h under a nitrogen atmosphere (to remove the
produced HCl), was let stand for 5 min, and the CH Cl was decanted. The residue
2
2
was washed with dry CH Cl (3 9 50 mL) and dried under a vacuum to give
2
2
[
Dsbim]Cl as a viscous pale yellow oil in (1.97 g, 98 % yield) [6].
Spectral data: IR (Nujol): t 574, 679, 750, 886, 1063, 1189, 1331, 1530, 1631,
-
1 1
2
8
536–3432 cm ; H NMR (400 MHz, DMSO-d ): d 8.09 (t, J = 7.45 Hz, 2H),
6
13
.43 (t, J = 7.81 Hz, 1H), 8.90 (d, J = 5.76 Hz, 2H), 13.64 (s, 2H); C NMR
(
100 MHz, DMSO-d ): d 112.80, 125.61, 136.79, 143.24; MS: m/z = 315
? ? ? ? ?
6
(
M ? 1), 314 (M ), 279 (M -Cl), 232 (M -SO H), 198 (M -SO H and Cl),
3 3
?
?
1
62 (2SO H), 154 (M -2SO H), 118 (M -2SO H and Cl) and 81 (SO H).
3 3 3 3
123

M. Abbasi
General procedure for the preparation of 3,4-dihydropyrimidin-2-(1H)-
ones/thiones (4a–r)
In a 10-mL round-bottom flask equipped with a condenser, a mixture of the aromatic
aldehyde (1 mmol), ethyl acetoacetate (1 mmol), urea or thiourea (1.5 mmol) and
[
Dsbim]Cl (0.0376 g, 10 mol%) was stirred at 80 °C, and the resulting mixture was
kept under continuous stirring for lengths of time as specified in Table 3, with the
progress of the reaction was followed by TLC. After completion of the reaction, the
mixture was cooled to room temperature, and 3 mL of water was added. The ionic
liquid was dissolved in water and filtered for separation of the crude product. The
separated product was washed twice with water (2 9 3 mL). For recycling the
catalysts, after the solid products were thoroughly washed with water, the water
containing the ionic liquid (IL is soluble in water) was evaporated under reduced
pressure, and the ionic liquid was recovered and reused. The solid product was
purified by a recrystallization procedure in ethanol. All of the desired product(s) were
characterized by comparison of their physical data with those of known compounds.
Spectral data of the selected products
3
,4-Dihydro-5-ethoxycarbonyl-4-(4-phenyl)-6-methyl-pyrimidine-2(1H)-one (4a)
-
1
Melting point: 203–205 °C (Ref. [23]: 204–206 °C): IR (KBr, cm ): 3239, 3118,
1
2
CH ), 2.25 (s, 3H, CH ), 3.94 (q, 2H, J = 6.8 Hz, CH ), 5.31 (s, 1H, CH), 6.13 (s,
985, 1720, 1645; H NMR (400 MHz, DMSO-d ): d 1.08 (t, 3H, J = 7.2 Hz,
6
3
3
2
1
1
H, NH), 7.53–7.22 (m, 5H), 9.26 (s, 1H, NH); C NMR (100 MHz, DMSO-d ): d
6
1
4.18, 18.34, 55.53, 60.32, 101.27, 126.45, 127.93, 129.42, 144.61, 146.12, 152.73,
66.345; Elemental analysis for: C H N O : C, 64.60; H, 6.20; N, 10.76. Found:
1
C, 64.38; H, 6.09; N, 10.63 %.
1
4 16 2 3
3
,4-Dihydro-5-ethoxycarbonyl-4-(4-nitrophenyl)-6-methylpyrimidine-2(1H)-one (4f)
-
1
Melting point: 210–211 °C (Ref. [23]: 209–211 °C): IR (KBr, cm ): 3215, 3110,
1
2
CH ), 2.27 (s, 3H, CH ), 4.05 (q, 2H, J = 7.2 Hz, CH ), 5.24 (d, 1H, J = 2.8 Hz,
973, 1712, 1653; H NMR (400 MHz, DMSO-d ): d 1.07 (t, 3H, J = 7.6 Hz,
6
3
3
2
CH), 7.43 (d, 2H, J = 7.6 Hz, ArH), 7.89 (s, 1H, NH), 8.26 (d, 2H, J = 6.8 Hz,
1
3
ArH), 9.33 (s, 1H, NH); C NMR (100 MHz, DMSO-d ): d 15.32, 18.95, 55.42,
6
6
analysis for: C H N O : C, 55.08; H, 4.95; N, 13.76. Found: C, 55.26; H, 4.43; N,
0.86, 100.37, 122.52, 125.27, 128.12, 142.6, 151.24, 155.75, 166.34; Elemental
1
4 15 3 5
1
3.89 %.
3,4-Dihydro-5-ethoxycarbonyl-4-(4-chlorophenyl)-6-methylpyrimidine-2(1H)-one (4i)
-
1
Melting point: 208–210 °C (Ref. [25]: 209–211 °C): IR (KBr, cm ): 3246, 3112,
1
2
CH ), 2.21 (s, 3H, CH ), 3.97 (q, 2H, J = 8.0 Hz, CH ), 5.19 (d, 1H, J = 2.8 Hz,
969, 1704, 1645; H NMR (400 MHz, DMSO-d ): d 1.14 (t, J = 6.8 Hz, 3H,
6
3
3
2
CH), 6.27 (s, 1H, NH), 6.94 (d, 2H, J = 8.0 Hz, ArH), 7.16 (d, 2H, J = 8.0 Hz,
1
23

1,3-Disulfonic acid benzimidazolium chloride as an…
1
3
ArH), 9.71 (s, 1H, NH); C NMR (100 MHz, DMSO-d ): d 14.67, 18.26, 54.71,
6
60.67, 101.32, 121.39, 124.25, 127.21, 143.28, 149.24, 154.52, 167.84; Elemental
analysis for: C H ClN O : C, 57.05; H, 5.13; N, 9.50. Found: C, 56.94; H, 5.21;
N, 9.42 %.
1
4
15
2 3
Results and discussion
Characterization of the catalyst
The structure of ionic liquid 1,3-disulfonic acid benzimidazolium chloride
1
Dsbim]Cl was identified by FT-IR, H NMR, C NMR, and mass spectra. The
13
[
FT-IR spectrum of [Dsbim]Cl showed broad and strong bands at 2536–3432 cm
-
1
related to the OH of the SO H groups. In addition, two peaks observed at 1063 and
3
-
1
1
189 cm were assigned to the vibrational modes of the N–SO and O–SO bonds.
2 2
This indicates that the sulfonic acid groups were successively incorporated onto the
catalyst surface (Fig. 1).
1
The H NMR and C NMR spectra of the ionic liquid obtained in DMSO-d are
13
6
1
displayed in Figs. 2 and 3. As Fig. 2 indicates, the important peaks of H NMR
spectrum of ionic liquid were related to the acidic hydrogens (SO H), which was
3
observed at 13.64 ppm. In order to prove that the ionic liquid was synthesized, we
1
ran the H NMR spectra of chlorosulfonic acid in DMSO-d as presented in
6
literature [38]. The peaks of the acidic hydrogens of ClSO H are at 13.45 ppm. The
3
difference between the peaks of the acidic hydrogens of ([Dsbim]Cl) and its starting
Fig. 1 FT-IR spectra of benzimidazole (a) and 1,3-disulfonic acid benzimidazolium chloride
([Dsbim]Cl) (b)
123

M. Abbasi
1
Fig. 2 H NMR spectrum of 1,3-disulfonic acid benzimidazolium chloride ([Dsbim]Cl)
materials confirmed that this catalyst was exactly synthesized. Moreover, while
benzimidazole and ClSO H are readily soluble in CH Cl , ([Dsbim]Cl) ionic liquid
is insoluble in CH Cl .
3
2
2
2
2
The mass spectrum of the 1,3-disulfonic acid benzimidazolium chloride
[Dsbim]Cl) ionic liquid is shown in Fig. 4. The important peaks of MS spectrum
(
of the ionic liquid were related to the 315 (M ? 1), 314 (M ), 279 (M -Cl), 232
?
?
?
?
?
?
?
(
M -SO H), 198 (M -SO H and Cl), 162 (2SO H), 154 (M -2SO H), 118 (M -
3 3 3 3
2
SO H and Cl) and 81 (SO H).
3 3
Application of [Dsbim]Cl for the synthesis of 3,4-dihydropyrimidin-2-(1H)-
ones/thiones
After characterization and identification of [Dsbim]Cl, we examined its catalytic
activity for the preparation of 3,4-dihydropyrimidin-2-(1H)-ones/thiones. For this
purpose, as a model reaction, the condensation of 4-chlorobenzaldehyde (1 mmol),
ethyl acetoacetate (1 mmol) and urea (1.5 mmol) was examined using different
amounts of 1,3-disulfonic acid benzimidazolium chloride ([Dsbim]Cl) at a
temperature range of 70–100 °C under solvent-free conditions. The results are
summarized in Table 1. The best results were obtained when 10 mol% of the
catalyst was used at 80 °C (Table 1, entry 4). A control experiment was also
conducted at 80 °C in the absence of our catalyst, which did not lead to noticeable
1
23

1,3-Disulfonic acid benzimidazolium chloride as an…
1
Fig. 3 The C NMR spectrum of 1,3-disulfonic acid benzimidazolium chloride ([Dsbim]Cl)
3
Fig. 4 Mass spectra of 1,3-disulfonic acid benzimidazolium chloride ([Dsbim]Cl)
123

M. Abbasi
a
Table 1 Effect of the amount of the catalyst and temperature on the model reaction
b
Entry
Catalyst (mol%)
Temperature (°C)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
a
–
5
80
80
200
10
10
7
–
65
89
95
95
90
96
74
82
7.5
10
15
10
10
10
15
80
80
80
7
90
7
100
80
7
7
70
10
Reaction conditions: 4-chlorobenzaldehyde (1 mmol), ethyl acetoacetate (1 mmol) and urea
1.2 mmol)
(
b
Isolated yield
product, even after a long reaction time (Table 1, entry 1). Increasing the reaction
temperature and catalyst loading did not improve the rate of the reaction (Table 1,
entries 5–9).
In the next step, the model reaction was examined using 10 mol% of ([Dsbim]Cl)
with various solvents under reflux conditions compared to solvent-free conditions.
The results are depicted in Table 2, which shows that solvent-free conditions
yielded a better reaction.
To investigate the effect of varying the solvent, the same reaction was carried out
in different solvents, including EtOH, CH CN, CH Cl and H O. As shown in
3
2
2
2
Table 2, the reaction in ethanol led to the highest yield among solvents. The non-
occurrence of the reaction in other solvents may be due to the poor solubility of the
ionic liquid. In the case of H O solvent, 1,3-disulfonic acid benzimidazolium
2
chloride [Dsbim]Cl was soluble in water, but the starting materials were not.
Moreover, the catalyst hydrolyzes in the aqueous media.
In the next section, the generality and efficiency of ([Dsbim]Cl) in the synthesis
of 3,4-dihydropyrimidin-2(1H)-ones/thiones was explored under optimized reaction
a
Table 2 Effect of various solvents on the model reaction
b
Entry
Solvent
Temperature (°C)
Time (min)
Yield (%)
1
2
3
4
5
a
EtOH
Reflux
Reflux
Reflux
Reflux
80
45
50
81
64
31
-
CH
CH
3
CN
Cl
2
2
100
100
7
2
H O
Solvent-free
95
Reaction conditions: 4-chlorobenzaldehyde (1 mmol), ethyl acetoacetate (1 mmol) and urea
1.2 mmol), [Dsbim]Cl (10 mol%)
(
b
Isolated yield of products
1
23

1,3-Disulfonic acid benzimidazolium chloride as an…
Table 3 One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones using ionic liquid as catalyst
under solvent-free conditions
a
Entry
Ar
X
Product
Time
min)
Yield
(%)
Mp
(°C)
Lit. Mp
(°C) [ref]
(
1
2
3
4
5
6
7
8
9
C
6
H
4
O
O
O
O
O
O
O
O
O
O
O
O
S
4a
4b
4c
4d
4e
4f
6
91
92
93
92
92
97
94
95
95
92
94
91
90
91
89
88
93
203–205
258–260
199–200
214–216
227–228
210–211
229–231
207–208
208–210
194–196
215–216
205–207
208–210
197–199
191–193
141–142
207–209
204–206 [23]
255–257 [19]
198–201 [25]
214–215 [26]
225–226 [19]
209–211 [23]
227–228 [23]
207–208 [26]
209–211 [25]
190–192 [32]
212–214 [23]
208–209 [19]
205–206 [23]
193–195 [32]
190–192 [32]
138–140 [25]
206–207 [25]
2-MeO-C
6
6
4
H
H
4
4
10
8
4-MeO-C
2-Cl-C
6
H
7
4-OH-C
6
H
4
9
4-NO
2
2
-C
6
H
H
4
5
3-NO
-C
6
4
4
4g
4h
4i
6
2-NO2-
C
6
H
6
4-Cl-C
6
H
4
4
7
1
1
1
1
1
1
1
1
a
0
1
2
3
4
5
6
7
3-Cl-C
6
H
4j
8
4-Me-C
6
H
4
4
4k
4l
7
3-Me-C
6
H
9
C
6
H
4
4m
4n
4o
4p
4q
8
4-Cl-C
4-Me-C
4-MeO-C
3-NO -C
6
H
4
S
9
6
H
4
S
9
6
H
4
S
10
8
2
6
H
4
S
Reaction conditions: aromatic aldehydes (1 mmol), ethyl acetoacetate (1 mmol), urea or thiourea
1.5 mmol), [Dsbim]Cl (10 mol%), solvent-free, 80 °C
(
b
Yield of isolated product
conditions by the reaction of ethyl acetoacetate, various arylaldehydes with a broad
range of electron-releasing substituents, electron-withdrawing substituents and
halogens on their aromatic rings, and urea or thiourea, and in solvent-free
conditions. As shown in Table 3, all benzaldehyde derivatives, urea or thiourea, and
ethyl acetoacetate afforded the desired 3,4-dihydropyrimidin-2(1H)-ones/thiones in
good to excellent product yields and short reaction times.
A plausible mechanism for the three-component condensation of urea/thiourea,
ethyl acetoacetate, and an arylaldehyde for the synthesis of DHPMs in the presence
of [Dsbim]Cl is shown in Scheme 2 [23, 39]. The proposed mechanism for the
Biginelli reaction involves the nucleophilic attack of the enol tautomer 2 of
acetoacetic ester 1 to aryl aldehyde 3, activated by the [Dsbim]Cl catalyst to form 4,
which convents to 5 upon dehydration (see Scheme 2). In the next step, 6 is attacked
by 7 to form intermediate 8, and 8 subsequently tautomerizes to 9, which cyclizes in
the presence of the [Dsbim]Cl catalyst to 11. Finally, dehydration of 11 results in the
final product 12.
To show the merit of the present work, we compared the results of our catalyst
with various reported catalysts for the synthesis of similar 3,4-dihydropyrimidin-
2(1H)-ones/thiones. The results of these catalysts in the performance of the one-pot
multicomponent condensation of 4-chlorobenzaldehyde, ethyl acetoacetate and urea
123

M. Abbasi
Cl-
3
SO H
N
O
N +
S
O
O
H O
Ar
(
3)
H
O
O
O
O
H
O
O
O
O
(
Dsbim)Cl
H
OEt
Ar
OEt
OEt
2
-H O
OEt
(
1)
(2)
HO
Ar
4)
(
5)
(
Ar
O
O
X
Ar
O
OH
Ar
O
HN
OEt
H
2
N
NH
2
(
Dsbim)Cl
HN
OEt
OH
X
OEt
Ar
(7)
NH
2
X
NH
2
(9)
(
6)
(
8)
Ar
O
O
Ar
O
H
HN
OEt
(
Dsbim)Cl
HN
OEt
OH
HN
OEt
X
2
-H O
X
N
H
X
N
H
NH
2
OH
(
10)
(12)
(
11)
Scheme 2 The proposed mechanism for the Biginelli reaction using [Dsbim]Cl
are tabulated in Table 4. It is clear that the process is markedly improved with our
catalyst in various terms {reaction time, yield and turnover frequency (TOF)}. The
present catalyst exhibited higher product yields in shorter reaction times, did not
Table 4 Comparison the results of the synthesis of ethyl 4-(4-chlorophenyl)-6-methyl-2-oxo-1,2,3,4-
tetrahydropyrimidine-5-carboxylate using different catalysts
a
b
Entry
Catalyst/conditions [ref.]
Catalyst
loading (mol%)
Time
(h)
Yield
(%)
TOF
-
1
(h )
1
2
3
4
5
6
7
8
9
Phytic acid/neat, 100 °C [18]
10
5
4 h
81
90
92
92
68
88
59
94
93
90
95
2.02
0.92
25.91
1.41
1.94
2.93
0.98
1.66
18.6
9
Fe(OTs)
SCM/neat, 140 °C [23]
InCl /THF, reflux [24]
Mn(OAc) O/CH CN, reflux [26]
3
Á6H
2
O/isopropanol, 70 °C [21]
19.5 h
30 min
6.5 h
3.5 h
3 h
7.1
10
10
10
5
3
3
Á2H
2
3
PISA/neat, 120 °C [29]
Nano ZnO/neat, 60 °C [30]
MCM-41-R-SO H/MeCN, reflux [31]
12 h
3
11.3
20
10
10
5 h
Fe
3
O
4
NPs/neat, 80 °C [32]
15 min
60 min
7 min
1
1
a
0
Sulfated tungstate/neat, 80 °C [33]
[Dsbim]Cl/neat, 80 °C [This work]
1
81.42
Isolated yield
b
Turnover frequency
1
23

1,3-Disulfonic acid benzimidazolium chloride as an…
100
9
0
0
0
0
0
0
0
0
0
8
7
6
5
4
3
2
1
0
1
2
3
4
Yeild (%)
95
95
93
90
Fig. 5 Condensation of 4-chlorobenzaldehyde, ethyl acetoacetate and urea in the presence of reused
Dsbim]Cl (10 mol%) under solvent-free conditions at 80 °C
[
require the use of organic solvents, and resulted in higher TOFs compared to the
other reported systems.
One of the important properties of this catalyst is its reusability. The recyclability
of [Dsbim]Cl was investigated for the reaction upon condensation of 4-chloroben-
zaldehyde, ethyl acetoacetate and urea. For the recycling experiment, the reaction
was carried out under the same conditions. At the end of the reaction, the mixture
was cooled to room temperature, and 3 mL of water was added. The ionic liquid
was dissolved in water and filtered for separation of the crude product. The
separated product was washed twice with water (2 9 3 mL). For the recycling of
the catalysts, after thorough washing of the solid products with water, the water
containing the ionic liquid (IL is soluble in water) was evaporated under reduced
pressure, and the ionic liquid was recovered and reused. The solid product was
purified using a recrystallization procedure in ethanol. The recovered catalysts were
reused five times with no loss of activity (Fig. 5).
Conclusions
In summary, we have introduced an efficient, recyclable and homogeneous Brønsted
acidic ionic liquid, [Dsbim]Cl as a catalyst and have used it in the one-pot synthesis
of 3,4-dihydropyrimidine-2-(1H)-ones/thiones from the three-component conden-
sation of aromatic aldehydes, urea/thiourea and ethyl acetoacetate under solvent-
free conditions. The present methodology offers several advantages, including short
reaction times, low cost, high yields, easy workup, mild reaction conditions, and an
eco-friendly reaction media, avoiding the need for hazardous organic solvents and
toxic catalysts.
Acknowledgments I gratefully acknowledge the Islamic Azad University of Lamerd Research Councils
for support of this work.
123

M. Abbasi
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