Ionic liquid supported nanoporous silica (SBA-IL) as an efficient and heterogeneous catalyst in the domino synthesis of polyhydroquinoline derivatives

Article abstract of DOI:10.1007/s11164-015-2036-z

A simple, efficient, and environmentally benign protocol for the synthesis of polyhydroquinoline derivatives was developed using a bio-compatible, heterogeneous, and recoverable mesoporous ionic liquid supported nanoporous silica as a nano-catalyst. The p

Full text of DOI:10.1007/s11164-015-2036-z

Res Chem Intermed
DOI 10.1007/s11164-015-2036-z
Ionic liquid supported nanoporous silica (SBA-IL)
as an efficient and heterogeneous catalyst in the domino
synthesis of polyhydroquinoline derivatives
Ghodsi Mohammadi Ziarani1 Leila Seyedakbari1
•
•
Shima Asadi1 Alireza Badiei2 Marzieeh Yadavi2
•
•
Received: 19 January 2015 / Accepted: 25 March 2015
ꢀ Springer Science+Business Media Dordrecht 2015
Abstract A simple, efficient, and environmentally benign protocol for the synthesis of
polyhydroquinoline derivatives was developed using a bio-compatible, heterogeneous,
and recoverable mesoporous ionic liquid supported nanoporous silica as a nano-catalyst.
The polyhydroquinoline derivatives were obtained by the four-component reaction of
aldehyde, Meldrum’s acid, dimedone, and ammonium acetate in excellent yields.
Graphical Abstract
Keywords Four component reaction ꢀ SBA-IL ꢀ Polyhydroquinoline derivatives ꢀ
Nanoporous ꢀ Heterogeneous catalyst
&
Ghodsi Mohammadi Ziarani
gmziarani@hotmail.com
1
2
Department of Chemistry, Alzahra University, Vanak Square, Tehran, Iran
School of Chemistry, College of Science, University of Tehran, Tehran, Iran
123

G. Mohammadi Ziarani et al.
Introduction
The application of ionic liquids (ILs) as ‘‘green’’ alternatives has become
increasingly important in recent years. ILs have the potential to exhibit low human
toxicities and eco-toxicities [1, 2]. In addition, ILs are nonvolatile, stable, and can
be reused [3, 4]. ILs as a solvent were found to produce unique selectivities and
reactivities. Because of these singularities, these materials have become promising
alternatives to volatile organic solvents. Immobilization of ILs on the solid supports
by covalent bonds between silanol groups and the anion or the cation of the ILs
transfers the catalytic properties of the liquids to a solid catalyst known as
‘‘immobilised’’ or ‘‘heterogenised’’ liquids [5, 6]. Supported ILs as heterogeneous
catalysts led to more improvements in efficiency than homogenous ILs because of
their easy handling, separation, and reusability in addition to simple work-up
procedure and reducing waste products [5, 7, 8].
1,4-Dihydropyridines (1,4-DHPs) are compounds known for their pharmaco-
logical activity as calcium channel modulators [9]. After this discovery, many
works have been directed towards the synthesis of novel 1,4-DHPs acting as
calcium antagonists [10, 11]. 1,4-DHPs possess a variety of biological activities,
such as vasodilator, bronchodilator, anti-atherosclerotic, antitumor, geroprotec-
tive, hepatoprotective, and antidiabetic properties [12–15]. Investigation of a new
method for the synthesis of DHPs is mandatory because the previous methods
have some drawbacks such as long reaction time, low yields, and using harmful
solvents. In connection with our research interest in the development of novel
methods for the preparation of various biologically important heterocyclic
compounds [16–18], herein we would like to report the application of SBA-ILs
as a new nano-catalyst to prepare the 2,5-dioxo-1,2,3,4,5,6,7,8-octahydroquino-
line derivatives. The previous studies revealed that this method is the first report
using a heterogeneous catalyst system for the synthesis of octahydroquinoline
compounds.
Experimental
Materials
Surface area was measured using the Brunnauer–Emmett–Teller (BET) method;
pore size distributions were calculated from the nitrogen isotherms using the
Barret–Joyner–Halenda (BJH) method. IR spectra were recorded from KBr and
NaCl disk using a FT-IR Bruker Tensor 27 instrument. Melting points were
measured by using the capillary tube method with an Electrothermal 9200
apparatus. The 1H NMR (500 MHz) was run on a Bruker DPX at 400 MHz
using TMS as an internal standard (DMSO-d6 solution). GC-MS analysis was
performed on a GC-Mass model 5973 Network Mass Selective Detector, GC
6890 Agilent. Calcinations were carried out in a box furnace under conditions of
flowing air.
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Ionic liquid supported nanoporous silica (SBA-IL) as an…
Preparation of ionic liquid supported nanoporous silica (SBA-IL)
Synthesis of the mesoporous silica SBA-15
In a typical synthesis, pluronic 123 (90 g) was dissolved in 2700 g of an aqueous
HCl 2 mol l-1 and stirred for 3 h. Then 191.75 g of tetraethylorthosilicate was
added to the homogeneous solution. This gel was continuously stirred at 313 K for
24 h, and then the solid product was filtered, washed with distilled water, and dried
in air at room temperature; silica was washed with boiling ethanol using a Soxhlet
apparatus for 192 h, followed by drying at room temperature to removal ethanol.
The material was calcined in air at 873 K for 6 h to decompose the triblock
copolymer and to obtain a white powder SBA-15. IR (NaCl): mmax/cm-1 = 3434
(O–H stretch), 1086 (Si–O–Si asymmetric stretch), 814 (Si–O–Si symmetric
stretch).
Synthesis of N-methyl-N0-propyltrimethoxysilylimidazolium chloride
A mixture of N-methyl-N0-propyltrimidazole (6.57 g, 80 mmol) and 3-(chloro-
propyl)trimethoxysilane (15.89 g, 80 mmol) were stirred in a dry 100 ml flask
under inert atmosphere (Ar) at 95 ꢁC for 24 h. After cooling at room temperature,
the resulting liquid product was extracted with ether. The final compound was
obtained as a yellow liquid. IR (NaCl): mmax/cm-1 = 1568 (C=C, C=N), 1457 (C–H
asymmetric stretch), 1373 (C–H symmetric stretch), 625 (mono 4-substituted
imidazole).
Synthesis of imidazolium functionalized material
Reaction was carried out under inert atmosphere (Ar) in a flask that was equipped
with a reflux condenser and a magnetic stirrer. 2.0 g of mesoporous SBA-15 silica
was warmed under vacuum for 2 h to remove the adsorbed water. Dried toluene
(100 ml) was added to the calcined and activated SBA-15 and stirred for 30 min.
Then N-methyl-N0-propyltrimethoxysilyl-imidazolium chloride (5.61 g) was added
to the resulting mixture. This mixture was stirred for 48 h under inert atmosphere
(Ar). Then, toluene was removed and the functionalized silica was washed with
boiling dichloromethane using a Soxhlet apparatus for 48 h, followed by drying
under vacuum to remove dichloromethane.
General procedure in the domino synthesis of 2,5-dioxo-1,2,3,4,5,6,7,8-
octahydroquinoline derivatives
The SBA-IL (0.02 g) was activated in vacuum at 100 ꢁC and then after cooling to
room temperature, dimedone 7 (1.5 mmol) and ammonium acetate 8 (2.4 mmol)
were added to it. In solvent-free conditions, the whole reaction mixture was heated
at 90 ꢁC for 30 min. After completion of the first step and without any work-up,
Meldrum’s acid 10 (1.5 mmol) and aldehyde 11a–i (1.5 mmol) were added to the
reaction mixture, as reported in Table 2, at 90 ꢁC.
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G. Mohammadi Ziarani et al.
The completion of two steps of the reaction was indicated by TLC, the resulting
solid product was dissolved in hot ethanol, filtered to remove the unsolvable
catalyst, and the filtrate was cooled to afford the pure product. The spectroscopic
and analytical data for new compounds are presented in the following section.
4-(20-Methoxyphenyl)-7,7-dimethyl-2,5-dioxo-1,2,3,4,5,6,7,8-octahydroquinoline
(12h)
IR(KBr): tmax = 3260 (NH), 2959, 1711(C=O), 1614 (C=O), 1464, 1379, 1282,
1
1149, 1024, 758 cm-1; H NMR (500 MHz, CDCl3) dH: 9.16 (brs, 1H, NH), 7.18
(t.d, J = 7.8 Hz, 1H, Ar–H), 7.00 (d, J = 7.5 Hz, 1H, Ar–H), 6.85 (d.d,
J = 8.2 Hz, 1H, Ar–H), 6.81 (t.d, J = 7.4 Hz, 1H, Ar–H) 4.59 (d, J = 8.8 Hz,
1H, CH), 3.81 (s, 3H, OCH3), 2.86 (dd, J = 16.8, 9.0 Hz, 1H, CH), 2.73 (d,
J = 16.7 Hz, 1H, CH), 2.42 (q, J = 17.3, 16.0 Hz, 2H, CH2), 2.28 (d, J = 3.15 Hz,
2H, CH2), 1.08 (s, 3H, CH3), 1.06 (s, 3H, CH3) ppm; MS (EI): m/z: 299 (100 %),
268, 240, 215, 192.
4-(20,30-Dichloro)-7,7-dimethyl-2,5-dioxo-1,2,3,4,5,6,7,8-octahydroquinoline (12i)
IR(KBr): tmax = 3250 (NH), 2958, 1719(C=O), 1615 (C=O), 1464, 1374, 1280,
1
1147, 1042, 784 cm-1; H NMR (500 MHz, DMSO-d6) dH: 10.26 (brs, 1H, NH),
7.53 (t, J = 7.4 Hz, 1H, ArH), 7. 29 (d, J = 7.8 Hz, 1H, ArH), 6.95 (d, J = 7.6 Hz,
1H, Ar–H), 4.52 (d, J = 8.6 Hz, 1H, CH), 3.07 (dd, J = 16.7, 8.9 Hz, 1H, CH),
2.50 (m, J = 17.5, 10.5, 1.5 Hz, 2H,CH2), 2.32 (d, J = 16.4 Hz, 1H, CH), 2.20 (q,
J = 15.9, 9.6 Hz, 2H, CH2), 1.08 (s, 3H, CH3), 1.06 (s, 3H, CH3) ppm; MS(EI):
m/z: 304 (M?2), 303 (M?1), 302 (100 %), 260, 246, 204.
Result and discussion
Preparation of ionic liquid supported nanoporous silica (SBA-IL)
Ionic liquid supported SBA-15 material was synthesized by following the procedure
reported in the literature [19–22]. The N-methyl-N0-propyltrimethoxysilylimida-
zolium chloride 3 was prepared as follows. A mixture of N-methyl-N0-propy-
ltrimidazole 1 and 3-(chloropropyl)trimethoxysilane 2 was stirred under inert
atmosphere (Ar) at 70 ꢁC. The final compound was obtained as a yellow liquid
(Scheme 1).
Scheme 1 Synthesis of N-methyl-N0-propyl trimethoxysilylimidazolium chloride
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Ionic liquid supported nanoporous silica (SBA-IL) as an…
Scheme 2 Preparation of functionlized SBA-15 (SBA-IL)
Fig. 1 N2 adsorption–
desorption isotherms of a SBA-
15, b SBA-IL (inset) BJH pore
size distribution curves
Table 1 The pore diameters (DBJH), BET surface area (SBET) and the total pore volumes (Vtotal) from
nitrogen adsorption–desorption for the SBA-15, SBA-IL
Molecular sieves
DBJH (nm)
SBET (m2/g)
Vtotal (cm3/g)
SBA-15
SBA-IL
6.2
5.5
587
71
0.780
0.128
Subsequently, N-methyl-N0-propyltrimethoxysilyl-imidazolium chloride 5 was
added to calcined and activated solid mesoporous SBA-15 silica 4 to produce the
functionalized SBA-15 silica 6 (Scheme 2). The surface of the catalyst was
analyzed by different methods such as BET, BJH methods, and FT-IR which were
demonstrated that the organic groups were immobilized into the pores.
Nitrogen adsorption–desorption
The textural properties of SBA-15 and SBA-IL were evaluated by the nitrogen
adsorption–desorption isotherms (Fig. 1). The samples exhibit a typical irreversible
123

G. Mohammadi Ziarani et al.
Fig. 2 FT-IR spectra of a SBA-15 b SBA-IL
Scheme 3 Synthesis of 2,5-dioxo-1,2,3,4,5,6,7,8-octahydroquinoline derivatives 12a–i in two steps
type IV nitrogen adsorption isotherm with an H1 hysteresis loop as defined by
IUPAC [23]. There is a shift of the hysteresis position toward low relative pressures
and a slight decreasing trend in overall nitrogen adsorption volume as the loading of
123

Ionic liquid supported nanoporous silica (SBA-IL) as an…
imidazole. The pore size distribution can be calculated from the BJH method based
on the desorption branch of the N2 adsorption isotherm. In a typical BJH plot from
modified SBA-15 with imidazole, a narrow pore size distribution is observed. The
uniformity of the mesopores in SBA-IL is comparable to the SBA-15, indicating
that the integrity of the original inorganic wall structure of the SBA-15, is retained.
In comparison with SBA-15, decrement in the pore diameter value by about 0.7 nm
is observed for SBA-IL. The textural parameters, specific surface areas (BET
method), pore diameters (BJH method), and total pore volumes are given in
Table 1, which shows a trend of decreasing in surface area, pore volume and pore
diameter caused by functionalization inside the channels of SBA-15.
FT-IR measurements
Figure 2 shows FT-IR spectra of SBA-15and SBA-IL. In the FT-IR spectrum of the
SBA-15 silica the band at 3434 cm-1 can be assigned to the stretching vibration of
OH groups. The bands at 814 and 1086 cm-1 are attributed to Si–O–Si symmetric
and asymmetric stretching vibrations, respectively [24]. After grafting N-methyl-N0-
propyltrimethoxysilylimidazolium chloride on the surface of SBA-15, the intensity
of the band at 3434 cm-1 is decreased. Meanwhile, the SBA-IL showed the new
Fig. 3 SBA-IL as a nanoreactor
Table 2 Synthesis of 12b in
different solvents
Entry
Solvent
Time
Yielda (%)
1
2
3
4
EtOH
MeCN
H2O
–
1.5 h
50
50
–
3.5 h
No reaction
45 min
90
a
Isolated yields
123

G. Mohammadi Ziarani et al.
Table 3 Synthesis of 2,5-dioxo-1,2,3,4,5,6,7,8-octahydroquinolines 12a–i
Entry
1
X
Product
Time (min) Yielda (%)
Mp (ꢁC) Mp (l)
3-NO2
60 85
202–207 193–194 [25]
12a
2
4-Cl
45
90
189–191 188–190 [26]
12b
12c
3
4-Br
65
83
80
85
83
202–205 196–197 [26]
4
5
6
4-OMe
2,4-Cl
4-OH
60
218–220 218–220 [27]
12d
12e
70
200–202 180–182 [27]
140
[300
[300 [28]
12f
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Ionic liquid supported nanoporous silica (SBA-IL) as an…
Table 3 continued
Entry
7
X
H
Product
Time (min)
70
Yielda (%)
80
Mp (ꢁC)
Mp (l)
226–228
217–219 [25]
12g
8
2-OMe
60
87
188–190
New
12h
12i
9
2,3-Cl
40
93
248–250
New
Table 4 Comparison of different conditions in the synthesis of 12g
Entry
Catalyst
Solvent
Condition
Time (h)
Yield (%)
Lit.
1
2
3
4
–
AcOH
Reflux
30
60
[27]
–
–
MW
3 min
4
72.4
89
[26]
–
[bmim][BF4]
–
Heating (80 ꢁC)
Heating (90 ꢁC)
[25]
SBA-IL
1.16
80
This work
adsorption bands at 1568 (C=C, C=N), 1457 (C–H asymmetric stretch), 1373 (C–H
symmetric stretch), 625 (mono 4-subistituted imidazole).
In this paper, SBA-IL as an efficient nanoreactor catalyzed the four-component
reaction of dimedone 7, ammonium acetate 8, Meldrum’s acid 10, and various
aromatic aldehydes 11a–i (Scheme 3; Fig. 3).
For optimizing the conditions of the reaction in the synthesis of 2,5-dioxo-
1,2,3,4,5,6,7,8-octahydroquinolines, dimedone 7, ammonium acetate 8, Meldrum’s
acid 10, and 4-chlorobenzaldehyde 11b were selected as a model of reaction in the
presence of SBA-IL. Initially, different solvents such as EtOH, MeCN, H2O, and
solvent-free condition were applied as shown in Table 2. The results indicated that
the solvent-free condition gave a higher yield and shorter reaction time than other
solvents, and among the different solvents water was found to be the worst solvent
at 100 ꢁC (Table 2, entry 3). To investigate the effect of immobilization on the
silica surface, a further reaction with pure silica used as support was performed, but
the reaction proceeded slowly, and after 5 h the product was obtained in 60 % yield.
123

G. Mohammadi Ziarani et al.
Scheme 4 Plausible mechanism of the reaction
The scope and generality of this method were illustrated with respect to various
aromatic aldehydes. The results were good in terms of yields (80–93 %) and short
reaction time (40–140 min) as shown in Table 3.
The efficiency of various catalysts in synthesis of polyhydroquinoline derivatives
was compared in Table 4. The best yield and short reaction time is attributed to the
high efficiency of the nano-catalyst of SBA-IL.
A possible mechanism for this SBA-IL-catalyzed transformation is depicted in
Scheme 4. In the first step, dimedone 7 and ammonium acetate 2 gave intermediate
9 via a condensation reaction. In this step, the SBA-IL could activate the methylene
group of dimedone. The intermediate 13 is obtained by the condensation of
Meldrum’s acid 10 and aldehyde 11. After that, the reaction of intermediate 13 and
9 led to adduct product 14 through Michael addition. Finally, intramolecular
cyclodehydration of the intermediate 14 released acetone and carbon dioxide and
gave target compound 12.
Conclusion
In this study, we have demonstrated the successful incorporation of heterogeneous
and mesoporous ionic liquid supported nanoporous silica (SBA-IL) in a four-
component process. In this procedure, polyhydroquinoline derivatives were
synthesized in excellent yields, mild and green reaction conditions, short reaction
times, and easy work-up process.
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Ionic liquid supported nanoporous silica (SBA-IL) as an…
Acknowledgments We gratefully acknowledge financial support from the Research Council of Alzahra
University and the University of Tehran.
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