Synthesis, characterization and application of ionic liquid 1,3-disulfonic acid imidazolium hydrogen sulfate as an efficient catalyst for the preparation of hexahydroquinolines

Article abstract of DOI:10.1016/j.molliq.2012.10.045

In this work, novel Br?nsted acidic ionic liquid 1,3-disulfonic acid imidazolium hydrogen sulfate {[Dsim]HSO₄} is synthesized, and characterized by studying its FT-IR, ¹H NMR, ¹³C NMR, mass, TG, DTG and XRD spectra. This ionic liquid, with three acidic functional groups, is utilized as a highly efficient, homogeneous and reusable catalyst for the preparation of hexahydroquinolines via one-pot multi-component condensation of arylaldehydes, dimedone (5,5-dimethylcyclohexane-1,3-dione), β-ketoesters and ammonium acetate under solvent-free conditions. The catalyst can form dual hydrogen-bond using its SO₃H groups which this subject can direct to its assembly and efficiency.

Full text of DOI:10.1016/j.molliq.2012.10.045

Journal of Molecular Liquids 178 (2013) 113–121
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Liquids
journal homepage: www.elsevier.com/locate/molliq
Synthesis, characterization and application of ionic liquid 1,3-disulfonic acid
imidazolium hydrogen sulfate as an efficient catalyst for the preparation
of hexahydroquinolines
a,
a
b
Abdolkarim Zare ⁎, Fereshteh Abi , Ahmad Reza Moosavi-Zare ,
c
d,
Mohammad Hassan Beyzavi , Mohammad Ali Zolfigol ⁎
Department of Chemistry, Payame Noor University, PO Box 19395-4697 Tehran, Iran
Department of Chemistry, University of Sayyed Jamaleddin Asadabadi, Asadabad, 6541835583, Iran
Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
a
b
c
d
Faculty of Chemistry, Bu-Ali Sina University, Hamedan, 6517838683, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 March 2012
Received in revised form 15 October 2012
Accepted 25 October 2012
Available online 10 December 2012
In this work, novel Brønsted acidic ionic liquid 1,3-disulfonic acid imidazolium hydrogen sulfate {[Dsim]
} is synthesized, and characterized by studying its FT-IR, 1H NMR, C NMR, mass, TG, DTG and XRD
13
HSO
4
spectra. This ionic liquid, with three acidic functional groups, is utilized as a highly efficient, homogeneous
and reusable catalyst for the preparation of hexahydroquinolines via one-pot multi-component condensation
of arylaldehydes, dimedone (5,5-dimethylcyclohexane-1,3-dione), β-ketoesters and ammonium acetate
3
under solvent-free conditions. The catalyst can form dual hydrogen-bond using its SO H groups which this
subject can direct to its assembly and efficiency.
Keywords:
Brønsted acidic ionic liquid
1,3-Disulfonic acid imidazolium hydrogen
© 2012 Elsevier B.V. All rights reserved.
sulfate {[Dsim]HSO
4
}
Hexahydroquinoline
Self-assembly
1
. Introduction
of reactions, complex molecules can be assembled under mild condi-
tions, often regio- and stereoselectively [22]. MCRs have also proven
to be a valuable asset in medicinal chemistry, drug design, and drug
discovery because of their simplicity, efficiency, and high selectivity.
Such protocols can reduce the number of steps and present advan-
tages, such as low energy consumption and little to no waste produc-
tion, leading to desired environmentally friendly processes [23].
The one-pot multi-component symmetrical 1,4-dihydropyridines
(1,4-DHPs) yielding Hantzsch reaction was first established by
Hantzsch in 1881, and has attracted considerable attention over the
years because of its efficiency to yield bioactive dihydropyridines
[24]; therefore, current literature reveals that the synthesis of 1,4-
dihydropyridines is an important goal in organic synthesis for the
reason that 1,4-DHPs exhibit a variety of biological properties such
as a vasodilator, a bronchodilator, an antiatherosclerotic, an anti-
tumor, a geroprotective, and a hepatoprotective, as well as their
antidiabetic activities [25–28]. 1,4-DHPs are used as the most popular
drug as calcium channel blockers and also possess the disordered
heart ratio as a chain cutting agent of factor IV channel [29–31].
Photochemical decomposition of drugs may lead to a decrease in
their therapeutic effectiveness or even to the appearance of toxic prod-
ucts. Sometimes, intake of photochemically changed drugs may induce
hypersensitivity to light resulting possibly in phototoxic and photo-
allergic effects [32,33]. The long list of photosensitive drugs includes,
Ionic liquids (ILs) have attracted a rising interest in the last
decades from chemists because of their unique properties including
non-flammability, non-volatility, wide liquid-state temperature range,
high thermal and chemical stability, large electrochemical window and
favorable salvation behavior [1,2]. These compounds have been exten-
sively applied in electrochemistry [3], spectroscopy, extraction and sep-
aration processes [1], and as a solvent, a catalyst and a reagent in organic
synthesis [1,2,4–10]. Among the different kinds of ILs, Brønsted acidic
ones have offered a possibility for the development of environmental
friendly acid catalysts for organic transformations, because of combining
the advantages of liquid and solid acids, their operational simplicity,
efficacy and selectivity coupled with their green natures [11–18].
A one-pot process is a promising plan of the novel organic synthe-
sis in which a sequence of reactions without isolating intermediates
is performed. In this kind, proceeding with studies on the synthesis
of compounds by one-pot multi-component reactions (MCRs) have
been of ongoing interest, since MCRs preferably are facile, fast, and
efficient with a minimal workup [19–21]. Moreover, in these types
⁎
Corresponding authors. Fax: +98 771 5559489.
E-mail addresses: abdolkarimzare@yahoo.com (A. Zare), mzolfigol@yahoo.com
(M.A. Zolfigol).
0167-7322/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molliq.2012.10.045

114
A. Zare et al. / Journal of Molecular Liquids 178 (2013) 113–121
2
ClSO H (neat)
3
H SO
2
4
CH Cl2
24 h
60 °C
2
+
+
N
N
N
N
N
NH
Cl
HSO4
12 h, r.t.
HO S
3
SO H
3
HO3S
SO3H
[
Dsim]Cl
[Dsim]HSO4
HCl (g)
HCl (g)
4
Scheme 1. The synthesis of 1,3-disulfonic acid imidazolium hydrogen sulfate {[Dsim]HSO }.
DHP derivatives that have been synthesized [34,35]. According to liter-
ature data, one of the methods to decrease the photosensitivity of these
compounds was their modification leading to new groups, e.g.,
hexahydroquinoline derivatives (HHQs) which were synthesized
according to the modified Hantzsch synthesis via the one-pot multi-
component condensation reaction between arylaldehydes, dimedone
their melting points and NMR data with those reported in the literature.
1
13
The H NMR (300 or 400 MHz) and C NMR (75 or 100 MHz) were run
on Bruker Avance DPX FT-NMR spectrometers. Mass spectra were
obtained with a Shimadzu GC–MS-QP 1100 EX model. Melting points
were recorded on a Büchi B-545 apparatus in open capillary tubes.
(
5,5-dimethylcyclohexane-1,3-dione), β-ketoesters and ammonium
2.2. Procedure for the preparation of ionic liquid 1,3-disulfonic acid
acetate, by Safak and coworkers [36,37]. The HHQ derivatives are
structurally similar to the DHP derivatives used for many years in
medical therapy, e.g., their common element is the presence of the
dihydropyridine ring that on illumination is easily oxidized to the
aromatic pyridine ring [38,39]. Moreover, some other methods and
catalysts have been developed for the preparation of HHQs [40–48].
In this work, we report the synthesis of Brønsted acidic ionic liquid
4
imidazolium hydrogen sulfate [Dsim]HSO (Scheme 1)
To a round-bottomed flask (100 mL) containing imidazole (0.340 g,
5 mmol) in dry CH Cl (50 mL), was added chlorosulfonic acid
2
2
(1.1885 g, 10.2 mmol) dropwise over a period of 20 min at room tem-
perature. After the addition was completed, the reaction mixture was
stirred for 12 h under pressure of nitrogen gas, let it stand for 5 min,
1
,3-disulfonic acid imidazolium hydrogen sulfate {[Dsim]HSO
4
}, from
2 2
and the CH Cl was decanted. The residue was washed with dry
available and inexpensive starting materials, for the first time
CH Cl (3×50 mL) and dried under vacuum to give 1,3-disulfonic acid
2
2
1
(
Scheme 1), and its full characterization by using FT-IR, H NMR,
C NMR, TG (thermal gravimetric), DTG (derivative thermal gravi-
imidazolium chloride {[Dsim]Cl} as a viscous pale yellow oil in 95%
yield [16]. Then, sulfuric acid (99.99%) (0.49 g, 5 mmol) was added
dropwise to [Dsim]Cl (1.63 g, 5 mmol) over a period of 5 min at room
temperature under pressure of nitrogen gas (to remove the produced
HCl during the reaction). The resulting mixture was stirred for 24 h at
1
3
metric) and XRD spectra. Afterward, we use this ionic liquid as a high-
ly efficient, homogeneous and recyclable catalyst for the preparation
of hexahydroquinolines via the one-pot multi-component condensa-
tion of dimedone (5,5-dimethylcyclohexane-1,3-dione), arylaldehydes,
β-ketoesters and ammonium acetate under solvent-free conditions
60 °C under continuous flow of nitrogen gas to give [Dsim]HSO
4
as a
viscous yellow oil in 99% yield. IR (Nujol): 624, 1031, 1053, 1085,
−
1
1
(Scheme 2).
1285, 1324, 3100–3400 cm
;
6
H NMR (300 MHz, DMSO-d ): δ
13
Molecular self-assembly including intramolecular and inter-
(ppm) 7.22 (s, 2H), 8.44 (s, 1H), 11.95 (s, 1H), 13.55 (s, 2H); C NMR
(75 MHz, DMSO-d ): δ (ppm) 119.5, 134.0; MS: m/z 326 (M ).
6
+
molecular, is the process by which molecules adopt a defined arrange-
ment without guidance or management from an outside source. Most
often the term molecular self-assembly refers to intermolecular self-
assembly, and assembly of molecules is directed through noncovalent
interactions (such as hydrogen bonding, metal coordination, hydropho-
bic forces, van der Waals forces, π–π interactions and electrostatic) as
well as electromagnetic interactions [49–52]. The specific structure of
2.3. General procedure for the synthesis of hexahydroquinolines (Scheme 2)
To a mixture of dimedone (0.28 g, 2 mmol), arylaldehyde (2 mmol),
β-ketoester (2 mmol) and ammonium acetate (0.185 g, 2.4 mmol) in a
test tube, was added [Dsim]HSO (0.02 g, 0.06 mmol), and the resulting
4
[
Dsim]HSO
4
as a three functional Brønsted acidic ionic liquid with
mixture was firstly stirred magnetically, and after solidification of the
reaction mixture with a small rod, at 50 °C. After completion of the re-
action, as monitored by TLC, the reaction mixture was cooled to room
temperature, ethyl acetate (20 mL) was added, stirred and refluxed
for 3 min, and decanted (the product is soluble in hot ethyl acetate;
dual hydrogen-bond donors for any of these functional groups, can
give it the ability to produce a molecular self-assembly through hydro-
gen bonds (Figs. 1 and 2). On the basis of the structure of [Dsim]HSO , it
4
can act as an efficient catalyst in reactions which need the use of acidic
catalysts to accelerate the rate of reaction.
4
however, [Dsim]HSO is not soluble in this solvent). The viscous oil res-
idue was washed with hot ethyl acetate (10 mL) to give the pure
recycled catalyst. The decanted solutions were then combined, washed
with water (20 mL) and dried. The solvent was evaporated and the
crude product was purified by recrystallization from ethanol (95%) or
column chromatography eluted with n-hexane/ethyl acetate (4/1). In
2
. Experimental
2
.1. General
All chemicals were purchased from Merck, Aldrich or Fluka Chemical
4
this work, [Dsim]HSO was recycled and reused for three times without
Companies. All known compounds were identified by a comparison of
significant loss of its catalytic activity.
O
O
Ar
O
O
O
[
Dsim]HSO (3 mol%)
OR
4
+
Ar-CHO
+
+
NH OAc
4
o
OR
Solvent-free, 50 C
O
N
H
R = Me, Et
1-14
4
Scheme 2. The one-pot multi-component preparation of hexahydroquinolines catalyzed by [Dsim]HSO .

A. Zare et al. / Journal of Molecular Liquids 178 (2013) 113–121
115
2
H), 7.05 (d, J=8.3 Hz, 2H), 8.99 (s, 1H); 13C NMR (75 MHz,
DMSO-d ): δ (ppm) 14.6, 18.7, 26.9, 29.6, 32.6, 35.4, 50.6, 55.3, 59.4,
O
S
O
S
O
S
6
O
N
N
104.4, 110.7, 113.5, 128.8, 140.5, 145.1, 149.7, 157.7, 167.4, 194.7.
O
H
O
H
O
H
O
Ethyl 2,7,7-trimethyl-5-oxo-4-p-tolyl-1,4,5,6,7,8-hexahydro-
O
O
1
quinoline-3-carboxylate (5): H NMR (500 MHz, CDCl
3
): δ (ppm) 0.96
(
s, 3H), 1.08 (s, 3H), 1.24 (t, J=7.1 Hz, 3H), 2.15–2.31 (m, 7H), 2.35
H
O
H
O
H
O
O
S
O
S
O
S
(s, 3H), 4.09 (q, J=7.1 Hz, 2H), 5.04 (s, 1H), 6.76 (s, 1H), 7.02 (d, J=
13
7.8 Hz, 2H), 7.21 (d, J=7.8 Hz, 2H); C NMR (125 MHz, CDCl
ppm) 14.7, 19.7, 21.5, 27.6, 29.8, 33.1, 36.6, 41.3, 51.2, 60.2, 106.6,
12.4, 128.3, 129.0, 135.8, 143.9, 144.7, 149.3, 167.9, 196.1.
Ethyl 4-(4-hydroxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-
3
): δ
O
N
N
(
1
O
O
O
1
hydroquinoline-3-carboxylate (6): H NMR (300 MHz, DMSO-d
6
): δ
4
Fig. 1. Molecular self-assembly of [Dsim]HSO by hydrogen bonds.
(
ppm) 0.86 (s, 3H), 1.00 (s, 3H), 1.14 (t, J=7.0 Hz, 3H), 1.96 (d, J=
1
2
6.0 Hz, 1H), 2.15 (d, J=16.1 Hz, 1H), 2.26 (s, 3H), 2.36–2.49 (m,
H), 3.96 (q, J=7.0 Hz, 2H), 4.74 (s, 1H), 6.56 (d, J=8.1 Hz, 2H), 6.93
2
.4. Selected spectral data of the products
13
(
d, J=8.1 Hz, 2H), 8.94 (s, 1H), 9.01 (s, 1H); C NMR (75 MHz,
DMSO-d
10.8, 114.9, 128.8, 138.9, 144.8, 149.6, 155.7, 167.5, 194.7.
Ethyl 4-(4-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-
6
): δ (ppm) 14.6, 18.7, 26.9, 29.6, 32.6, 35.3, 50.8, 59.4, 104.6,
Ethyl 2,7,7-trimethyl-5-oxo-4-phenyl-1,4,5,6,7,8-hexahydro-
1
1
quinoline-3-carboxylate (1): H NMR (300 MHz, DMSO-d
6
): δ (ppm)
0
2
7
(
2
1
.85 (s, 3H), 1.00 (s, 3H), 1.13 (t, J=7.0 Hz, 3H), 2.01–2.20 (m, 2H),
1
hydroquinoline-3-carboxylate (7): H NMR (300 MHz, DMSO-d
6
): δ
.29 (s, 3H), 2.38–2.50 (m, 2H), 3.97 (q, J=7.0 Hz, 2H), 4.82 (s, 1H),
.05 (m, 1H), 7.18 (t, J=6.7 Hz, 2H), 7.21 (t, J=6.5 Hz, 2H), 9.12
(
ppm) 0.83 (s, 3H), 0.99 (s, 3H), 1.10 (t, J=6.9 Hz, 3H), 1.96 (d, J=
1
2
7
6.0 Hz, 1H), 2.16 (d, J=16.1 Hz, 1H), 2.29 (s, 3H), 2.38–2.49 (m,
1
3
s, 1H); C NMR (75 MHz, DMSO-d
6
): δ (ppm) 14.5, 18.8, 26.8,
H), 3.97 (q, J=7.0 Hz, 2H), 4.84 (s, 1H), 7.11 (d, J=7.2 Hz, 2H),
9.5, 32.6, 36.5, 50.6, 59.6, 103.4, 109.9, 113.5, 126.9, 128.8, 130.5,
46.0, 150.3, 167.0, 194.7.
13
6
.37 (d, J=7.2 Hz, 2H), 9.09 (s, 1H); C NMR (75 MHz, DMSO-d ):
δ (ppm) 14.6, 18.8, 26.9, 29.5, 32.6, 36.2, 50.6, 59.5, 103.5, 110.1,
Ethyl 2,7,7-trimethyl-4-(4-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexa-
1
19.1, 130.2, 131.0, 145.8, 147.4, 150.0, 167.1, 194.7.
1
hydroquinoline-3-carboxylate (2): H NMR (500 MHz, CDCl
3
): δ
Methyl4-(4-methoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-
(
1
(
8
1
1
ppm) 0.92 (s, 3H), 1.10 (s, 3H), 1.19 (t, J=7.1 Hz, 3H), 2.16 (d, J=
6.4 Hz, 2H), 2.24–2.29 (Distorted AB system, 2H), 2.41 (s, 3H), 4.07
1
hydroquinoline-3-carboxylate (12): H NMR (300 MHz, DMSO-d
6
): δ
(ppm) 0.84 (s, 3H), 0.99 (s, 3H), 1.97 (d, J=16.0 Hz, 1H), 2.15 (d, J=
q, J=7.1 Hz, 2H), 5.18 (s, 1H), 6.68 (s, 1H), 7.51 (d, J=8.5 Hz, 2H),
16.1 Hz, 1H), 2.28 (s, 3H), 2.37–2.49 (m, 2H), 3.52 (s, 3H), 3.66 (s, 3H),
.09 (d, J=8.5 Hz, 2H); 13C NMR (125 MHz, CDCl
3
): δ (ppm) 14.6,
4
.81 (s, 1H), 6.73 (d, J=7.4 Hz, 2H), 7.05 (d, J=7.4 Hz, 2H), 9.02
9.8, 27.5, 29.8, 33.1, 37.7, 41.3, 51.0, 60.5, 105.3, 111.4, 123.7,
29.4, 145.0, 146.6, 149.6, 154.9, 167.3, 195.9.
13
(s, 1H); C NMR (75 MHz, DMSO-d
6
): δ (ppm) 18.7, 26.9, 29.6,
3
1
2.6, 35.2, 50.7, 51.1, 55.3, 104.0, 110.7, 113.6, 128.7, 140.3, 145.4, 149.7,
57.7, 167.9, 194.7.
Ethyl 4-(4-methoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (4): 1H NMR (300 MHz, DMSO-d
):
δ (ppm) 0.85 (s, 3H), 1.00 (s, 3H), 1.14 (t, J=7.0 Hz, 3H), 1.96 (d, J=
6
Methyl 4-(3-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-
1
hydroquinoline-3-carboxylate (14): H NMR (300 MHz, DMSO-d
6
): δ
1
3
6.0 Hz, 1H), 2.15 (d, J=16.1 Hz, 1H), 2.27 (s, 3H), 2.37–2.49 (m, 2H),
.66 (s, 3H), 3.97 (q, J=7.0 Hz, 2H), 4.79 (s, 1H), 6.73 (d, J=8.3 Hz,
(
ppm) 0.83 (s, 3H), 1.00 (s, 3H), 1.99 (d, J=16.0 Hz, 1H), 2.18 (d, J=
1
1
6.1 Hz, 1H), 2.30 (s, 3H), 2.39–2.49 (m, 2H), 3.53 (s, 3H), 4.85 (s,
H), 7.14–7.16 (m, 2H), 7.25–7.27 (m, 2H), 9.15 (s, 1H); 13C NMR
(
6
75 MHz, DMSO-d ): δ (ppm) 18.8, 26.8, 29.5, 32.6, 36.3, 103.1, 109.9,
1
21.6, 126.8, 129.1, 130.5, 130.6, 146.3, 150.3, 150.5, 167.5, 194.7; MS:
+
m/z 404 (M ).
Substrate recognition site
O
3
. Results and discussion
O
Bronsted basic site
Bronsted acidic site
S
The structure of Brønsted acidic ionic liquid 1,3-disulfonic acid
O
imidazolium hydrogen sulfate was identified by studying its FT-IR,
O
H
1
13
H NMR, C NMR, mass, TG, DTG and XRD spectra. The full details
of FT-IR, 1H NMR, C NMR and mass spectra were reported in the
13
H
Bronsted acidic site
Experimental section.
O
O
In this section, we study FT-IR, 1H NMR, mass, TG, DTG and XRD
spectra of the ionic liquid:
S
N
O
Bronsted basic site
Lewis acidic site
4
The IR spectrum of [Dsim]HSO showed a broad peak at 3100–
H
−1
3
400 cm
related to the OH of the SO
3
H groups. Moreover, two
N
S
−1
−1
peaks observed in 1085 cm
vibrational modes of N\SO
The 1H NMR spectrum of [Dsim]HSO
and 1285 cm
correspond to the
O
Bronsted basic site
Bronsted acidic site
O
2
bond.
O
showed two peaks related
H
4
to the two types of the acidic hydrogens (SO
3
H) in 13.55 and
1
SO
1.95 ppm. To prove that this peak corresponds to the hydrogen of
H in the compound, we also ran the 1H NMR spectra of the
3
Substrate recognition site
starting materials for the preparation of the ionic liquid (i.e., [Dsim]
Cl and H SO ) in DMSO-d wherein the peaks of the acidic hydrogens
of [Dsim]Cl and H SO were observed in 13.34, and 12.54 ppm,
Dual function by the three-functional IL
2
4
6
2
4
respectively. The difference between the peaks of the acidic hydro-
Fig. 2. The structure of [Dsim]HSO
4
.
gens in the compounds confirmed that the peaks observed in 13.55

116
A. Zare et al. / Journal of Molecular Liquids 178 (2013) 113–121
Fig. 3. TG and DTG diagrams of the ionic liquid.
4
Fig. 4. The XRD patterns of imidazole, [Dsim]Cl and [Dsim]HSO .
and 11.95 ppm of the 1H NMR spectra of [Dsim]HSO
related to the hydrogen of the SO H groups of this compound.
The mass spectrum of the compound gave the correct molecular
ion peak in 326 m/z.
is correctly
water. The absence of AgCl precipitate indicated a complete conver-
sion of the [Dsim]Cl to [Dsim]HSO [13,18].
4
After the full characterization of [Dsim]HSO , we examined its cata-
lytic activity to promote the synthesis of hexahydroquinolines. For this
purpose, as a model reaction, a mixture of dimedone (2 mmol), 4-
methylbenzaldehyde (2 mmol), ethyl acetoacetate (2 mmol) and am-
monium acetate (2.4 mmol) was stirred in the presence of different
4
3
4
Thermal gravimetric (TG) and derivative thermal gravimetric
(
DTG) analyses of 1,3-disulfonic acid imidazolium hydrogen sulfate
were studied in a range of temperature between 25 and 600 °C
Fig. 3). The TG and DTG of the catalyst showed two weight losses;
(
4
amounts of [Dsim]HSO at a range of 40 to 55 °C in the absence of a sol-
the first strong loss weight was observed after 350 °C, and the second
strong weight loss appears after 540 °C. Therefore, the molecular de-
composition of the ionic liquid occurred after 350 °C.
vent; the respective results are summarized in Table 1. As it can be seen
In another study, the XRD patterns of imidazole, [Dsim]Cl and
[
Dsim]HSO
dicates, the XRD pattern of imidazole was revealed in 2θ≈13°, 20°,
4°, 26°, 28°, 31°, 38° and 81°. The XRD pattern of [Dsim]Cl showed
a broad maximum that was assigned to an amorphous peak in
4
in a domain of 0–90° were compared (Fig. 4). As Fig. 4 in-
Table 1
Effect of the catalyst amount and temperature on the reaction between dimedone,
2
4-methylbenzaldehyde, ethyl acetoacetate and ammonium acetate.
Entry
Catalyst
Catalyst amount
mol%)
Temp.
(°C)
Time
(min)
Yielda
(%)
2
2
[
θ≈16–38°. Finally, the XRD pattern of [Dsim]HSO
θ≈14°, 17° and 25°. These results showed that the arrangement in
is more than that of in [Dsim]Cl due to an increase of
4
appeared in
(
Dsim]HSO
4
1
2
3
4
5
6
7
[Dsim]HSO
[Dsim]HSO
[Dsim]HSO
[Dsim]HSO
[Dsim]HSO
4
4
4
4
4
2
3
5
3
3
3
3
50
50
50
40
55
50
50
35
25
25
60
25
25
25
93
96
87
79
96
63
72
the acidic functional groups with dual hydrogen-bond donors for
any of these functional groups, and its molecular self-assembly
(
Figs. 1 and 2).
To confirm that 1,3-disulfonic acid imidazolium chloride {[Dsim]
2
H SO
4
[Dsim]Cl
Cl} was completely converted to [Dsim]HSO
distilled water was added to a solution of the ionic liquid in distilled
4 3
, a solution of AgNO in
a
Isolated yield.

A. Zare et al. / Journal of Molecular Liquids 178 (2013) 113–121
117
Table 2
The solvent-free synthesis of HHQs from dimedone, arylaldehydes, β-ketoesters and ammonium acetate catalyzed by [Dsim]HSO
4
at 50 °C.
Aldehyde
Product
Time (min)
35
Yielda (%)
94
M.p. °C (Lit.)
206–208 (203–205) [40]
CHO
O
O
OEt
N
H
(
1)
35
93
247–249 (242–244) [44]
NO2
O N
2
CHO
O
O
OEt
N
H
(
2)
38
89
178–180 (177–178) [42]
O N
2
NO2
O
CHO
O
OEt
N
H
(
3)
36
89
255–257 (257–259) [43]
OMe
MeO
CHO
O
O
O
O
O
O
OEt
OEt
OEt
N
H
(
4)
2
5
96
256–258 (260–261) [43]
Me
Me
CHO
N
H
(
5)
28
94
234–236 (232–234) [43]
OH
HO
CHO
N
H
(
6)
(continued on next page)

118
A. Zare et al. / Journal of Molecular Liquids 178 (2013) 113–121
Table 2 (continued)
Aldehyde
Product
Time (min)
Yielda (%)
91
M.p. °C (Lit.)
30
255–256 (255–257) [40]
Br
Br
CHO
O
O
OEt
N
H
(
7)
32
88
230–232 (235–237) [40]
Br
Br
CHO
O
O
OEt
N
H
(
Cl
8)
25
89
244–246 (245–246) [42]
Cl
CHO
O
O
O
O
OEt
N
H
(
9)
40
91
260–262 (258–260) [47]
CHO
OMe
N
H
(10)
30
88
229–231 (222–223) [53]
O N
2
NO2
O
CHO
O
OMe
N
H
(
11)
OMe
32
91
257–259 (256–257) [53]
MeO
CHO
O
O
OMe
N
H
(12)
in Table 1, 3 mol% of the ionic liquid was sufficient to catalyze the reac-
tion efficiently at 50 °C; in these conditions, the corresponding HHQ
was obtained in 96% within 25 min (Table 1, entry 2). Moreover, to
prove that the reaction of [Dsim]Cl with H
progressed to give [Dsim]HSO ; the model reaction was also examined
in the presence of 3 mol% of [Dsim]Cl or H SO (Table 1, entries 6 and
2 4
SO was completely
4
2
4

A. Zare et al. / Journal of Molecular Liquids 178 (2013) 113–121
119
Table 2 (continued)
Aldehyde
Product
Time (min)
Yielda (%)
92
M.p. °C (Lit.)
281–283 (285–288) [47]
35
Me
Me
CHO
O
O
OMe
N
H
(13)
25
89
221–223
Br
Br
O
CHO
O
OMe
N
H
(14)
a
Isolated yield.
7
). As it is shown in Table 1, these catalysts afforded the products in
lower yields compared with [Dsim]HSO . These results also showed
that [Dsim]Cl and H SO were completely converted to [Dsim]HSO
and this ionic liquid was the real catalyst of the reaction.
was restored within the limits of the experimental errors for three suc-
cessive recycle runs (see Table 3).
In a proposed mechanism (Scheme 3), we suggest that at first
4
dimedone is converted to its enol form by using [Dsim]HSO . On the
4
2
4
4
,
To assess the efficacy and the generality of the new catalyst,
dimedone was reacted with different arylaldehydes (benzaldehyde
as well as arylaldehyde possessing electron-withdrawing groups,
electron-donating groups and halogens), β-ketoesters (ethyl and
methyl acetoacetate) and ammonium acetate under the optimized re-
action conditions; the results are displayed in Table 2. As it is clear
from Table 2, all reactions proceeded efficiently to afford the corre-
sponding hexahydroquinolines in high yields and in short reaction
other hand, the activated β-ketoester (by the catalyst) and ammonia
(resulted from ammonium acetate) gives enamine I. Afterward, the
enol and enamine I react with the activated aldehyde (by [Dsim]HSO
to afford intermediate II and one molecule H O. II is converted to III by
tautomerization, and intermediate III affords IV by intramolecular nucle-
ophilic attack of the NH group to the activated carbonyl group and then
removes one molecule H O. Finally, hexahydroquinonine forms by
4
)
2
2
2
tautomerization of IV. In fact, the catalyst not only activates carbonyls
4
times. Thus, our new ionic liquid, [Dsim]HSO , was a highly efficient
to accept nucleophilic attack, and amine as well as enamine groups for
and general catalyst for the synthesis of a reaction that needs an acid-
ic catalyst to promote, i.e., the synthesis of HHQs.
An important property of ionic liquids or supported ionic liquids on
solids is their recyclability or regenerability [5,15,16,54,55]. Thus,
3
nucleophilic attack by its three SO H groups, it also can collect and
arrange the starting materials by dual hydrogen-bonding. For these rea-
sons, a small amount of the catalyst (3 mol%) was sufficient to promote
the reaction efficiently. It should be mentioned that in the steps in which
recyclability of the ionic liquid [Dsim]HSO
4
was investigated. For this
4
[Dsim]HSO gives a proton to activate carbonyl groups, the proton is
purpose, the reaction of dimedone (2 mmol), 3-nitrobenzaldehyde
transferred to the catalyst in another step. The mechanism is confirmed
(
(
2 mmol), methyl acetoacetate (2 mmol) and ammonium acetate
2.4 mmol) was performed in the presence of [Dsim]HSO (3 mol%)
by the literature [40,42,44].
4
at 50 °C. After completion of the reaction, the reaction mixture was
cooled to room temperature, ethyl acetate (20 mL) was added, stirred
and refluxed for 3 min, and decanted (the product is soluble in hot
ethyl acetate; however, the catalyst is not soluble in this solvent). The
viscous oil residue was washed with hot ethyl acetate (10 mL) and
dried to give the pure recycled catalyst. The recycled catalyst was
4
. Conclusions
In summary, we have introduced Brønsted acidic ionic liquid
[
4
Dsim]HSO as a novel, highly efficient, general and homogeneous
catalyst for the one-pot multi-component reaction between
dimedone, aromatic aldehydes, β-ketoesters and ammonium ace-
tate leading to hexahydroquinolones. The promising points for the
presented protocols are efficiency, generality, high yields of the
products, short reaction times, cleaner reaction profile, simplicity,
low cost, ease of preparation and recycling of the catalyst.
used for the next run of the reaction. Catalytic activity of [Dsim]HSO
4
Table 3
The condensation of dimedone with 3-nitrobenzaldehyde, methyl acetoacetate and
ammonium acetate using recycled [Dsim]HSO
Acknowledgments
4
.
Run
Time (min)
Yielda (%)
The authors gratefully acknowledge the financial support of this
work from the Research Affairs Office of Payame Noor University and
Bu-Ali Sina University (grant number 32-1716 entitled development
of chemical methods, reagents and molecules), and the Center of Excel-
lence in Development of Chemical Method (CEDCM), Hamedan, I.R.
Iran.
1
2
3
4
30
33
35
40
88
87
85
83
a
Isolated yield.

120
A. Zare et al. / Journal of Molecular Liquids 178 (2013) 113–121
O
S
O
O
S
O
O
S
N
N
O
O
O
O
H
H
H
H
O
O
H
O
C
O
O
Ar
H
H
H
N
H
HO
OR
OR
[
Dsim]HSO4
O
H2N
[
Dsim]HSO4
O
-H2O
I
O
HOAc
-
H2O
OR
O
O
O
Ar
O
NH4OAc
OR
HN
HO
II
[
Dsim]HSO4
O
Ar
O
OR
H2N
III
O
H
-
H2O
O
Ar
O
H
OR
N
H
IV
O
Ar
O
OR
N
H
Hexahydroquinoline
4
Scheme 3. The proposed mechanism for the synthesis of hexahydroquinolines promoted by [Dsim]HSO .
[
18] M.A. Zolfigol, A. Khazaei, A.R. Moosavi-Zare, A. Zare, H.G. Kruger, Z. Asgari, V.
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