The synthesis of polysubstituted pyridines using nano Fe3O4 supported hydrogensulfate ionic liquid

Article abstract of DOI:10.1007/s11164-015-1951-3

Reaction of 1-methylimidazole with 3-(trimethoxysilyl)propyl chloride resulted in formation of 1-methyl-3-(trimethoxysilyl)propyl imidazolium chloride ([pmim]Cl). Anchoring of the ionic liquid on to silica-coated magnetic Fe₃O₄ particles afforded the corresponding supported ionic liquid MNP-[pmim]Cl. Exchanging the Cl^- anion by treatment with H₂SO₄ gave the Bronsted ionic liquid MNP-[pmim]HSO₄. FT-IR, XRD, SEM, TEM, TG/DTG, VSM, and CHN analysis were used to characterize the supported ionic liquid. The results indicated the catalyst was a nanostructure. The catalytic activity of the supported ionic liquid was examined in the synthesis of the polysubstituted pyridines by reaction of aromatic aldehydes, and acetophenones or indan-1-one with ammonium acetate under solvent-free conditions. The catalyst could be easily recovered, by applying an external magnetic field, and reused at least six runs without deterioration of its catalytic activity.

Full text of DOI:10.1007/s11164-015-1951-3

Res Chem Intermed
DOI 10.1007/s11164-015-1951-3
The synthesis of polysubstituted pyridines using nano
Fe3O4 supported hydrogensulfate ionic liquid
Heshmatollah Alinezhad1 Mahmood Tajbakhsh1
•
•
Neda Ghobadi1
Received: 5 November 2014 / Accepted: 3 February 2015
Ó Springer Science+Business Media Dordrecht 2015
Abstract Reaction of 1-methylimidazole with 3-(trimethoxysilyl)propyl chloride
resulted in formation of 1-methyl-3-(trimethoxysilyl)propyl imidazolium chloride
([pmim]Cl). Anchoring of the ionic liquid on to silica-coated magnetic Fe3O4 parti-
cles afforded the corresponding supported ionic liquid MNP-[pmim]Cl. Exchanging
the Cl- anion by treatment with H2SO4 gave the Brønsted ionic liquid MNP-[p-
mim]HSO4. FT-IR, XRD, SEM, TEM, TG/DTG, VSM, and CHN analysis were used
to characterize the supported ionic liquid. The results indicated the catalyst was a
nanostructure. The catalytic activity of the supported ionic liquid was examined in the
synthesis of the polysubstituted pyridines by reaction of aromatic aldehydes, and
acetophenones or indan-1-one with ammonium acetate under solvent-free conditions.
The catalyst could be easily recovered, by applying an external magnetic field, and
reused at least six runs without deterioration of its catalytic activity.
Keywords Magnetic nanoparticles Á Supported ILs Á Polysubstituted pyridines Á
Nano Fe3O4 Á Solvent-free conditions
Introduction
Room-temperature ionic liquids (RTILs) as homogeneous catalysts [1] have
attracted increasing interest in green chemistry because of their specific properties,
for example undetectable vapor pressure and ability to dissolve many organic and
inorganic substances [2]. The acidic nature of these ionic liquids has resulted in their
use as catalysts or as dual catalysts–solvents [3]. Although these compounds have
promising advantages, their widespread practical application is still hampered by
disadvantages which lead to economical and environmental problems. High
&
Heshmatollah Alinezhad
alinezhad_n@yahoo.com; heshmat@umz.ac.ir
1
Faculty of Chemistry, University of Mazandaran, P. O. Box 47415, Babolsar, Iran
123

H. Alinezhad et al.
viscosity limits their mass transfer during catalytic reactions and makes their
handling difficult. Moreover, use of relatively large amounts of ionic liquids, and
their homogeneity, cause environmental problems [4–6]. These problems and the
priority of the chemical industry to use heterogeneous catalysts has resulted in
immobilization of ILs on to solid supports [7–9]. Among methods reported for
preparation of supported ionic liquids, in recent years magnetic nanoparticles
(MNPs) have recently appeared as a new type of catalyst support, because of their
high stability and facile separation [10, 11]. In this regard, nano-Fe3O4 has attracted
much attention, because of its unique physical properties, for example high surface
area, excellent thermal and chemical stability, low toxicity, and potential
applications. Magnetic catalysts can be recycled by use of an external magnetic
field and reused in subsequent reactions. Owing to these properties and other
attractive features, Fe3O4 has been used as a promising support for ILs [12–15].
Multicomponent reactions (MCRs) have attracted much interest because of their
atom-economy and straightforward reaction design, because this results in
substantial reduction of waste, labor, time, and cost [16–18]. Use of solvent-free
conditions in reactions, a central tenet of Green Chemistry, has gained importance
because of several advantages, including experimental simplicity, less energy
requirement, and almost quantitative reactivity of the substrates [19, 20].
Pyridine ring systems, particularly 2,4,6-triarylpyridines have potential pharma-
ceutical activity and are already used as antimalarial, vasodilator, anesthetic,
anticonvulsant, anti-epileptic, and antitumor compounds, and as agrochemicals, e.g.,
fungicides, pesticides, and herbicides [21–23]. Because of their p-stacking ability,
they are prominent synthons in supramolecular chemistry [24–26]. Their excellent
thermal stability has resulted in investigation of their use as monomeric building
¨
blocks in thin films and organometallic polymers [27, 28]. Pyridines (Krohnke
pyridines) have been synthesized by use of a variety of methods. Traditionally, these
compounds have been synthesized by reaction of N-phenacylpyridinium salts with
a,b-unsaturated ketones in the presence of NH4OAc [29, 30]. Recently, several new,
improved methods have been developed for synthesis of 2,4,6-triarylpyridines.
Among all these methods, one-pot synthesis of poly-substituted pyridines from
acetophenones, arylaldehydes, and NH4OAc is well-established. These procedures
include use of: NaOH in PEG [31–33], catalytic amounts of HOAc [34], HClO4–SiO2
[35], the Preyssler type heteropolyacid H14 [NaP5W30O110] [36], wet 2,4,6-trichloro-
1,3,5-triazine (TCT) [37], and Brønsted acidic ionic liquids [38], among others.
O
O
O
N
N
O
Si
Cl
N
O
Si
N
N
OH
SiO2
Fe3O4
O
Cl
OH
OH
O
SiO2
Fe3O4
H2SO4
O
O
O
SiO2
Fe3O4
Si
N
O
O
Si
N
N
Cl
HSO4
Scheme 1 Immobilization of the ionic liquid on the nanoparticle surface
123

The synthesis of polysubstituted pyridines…
Ar1
N
MNP-[pmim]HSO4
Solvent-free
Ar1CHO
2 Ar2COCH3
+
NH4OAc
+
Ar2
Ar2
Scheme 2 Synthesis of triarylpyridines catalyzed by MNP-[pmim]HSO4
In this study, we synthesized the IL 1-methyl-3-(trimethoxysilyl)propyl imidazolium
hydrogensulfate supported on nano-Fe3O4 (MNP-[pmim]HSO4) (Scheme 1) and used
it as a recyclable catalyst for synthesis of poly-substituted pyridines (Scheme 2).
Experimental
General information
Chemical materials were purchased from Merck and Aldrich and used without
further purification. All solvents were distilled, dried, and purified by standard
procedures. The samples were analyzed as KBr pellets by use of a Vector 22 FT–IR
spectrometer (Bruker). NMR spectra were recorded on a Bruker DRX-400 Avance
1
instrument (400.1 MHz for H, 100.6 MHz for 13C) with DMSO-d6 as solvent.
Chemical shifts (d) are given in parts per million (ppm) relative to TMS, and
coupling constants (J) are reported in hertz (Hz). Mass spectra were recorded on a
Finnigan-Mat 8430 mass spectrometer operating at an electron energy of 70 eV.
Elemental analysis was performed with a Heraeus CHNS/O-Rapid analyzer.
Thermogravimetric analysis (TGA) was performed with a Stanton Redcraft STA-
780 (London, UK). XRD was performed with a Philips Xpert Pro diffractometer
˚
using with Cu Ka source (k = 1.5418 A). Field-emission scanning electron
microscopy was performed (FESEM) was performed with an Hitachi S-1460
instrument at an AC voltage of 15 kV. Transmission electron microscopy (TEM)
was performed on compounds Fig. 5a and b on a Zeiss-EM10C with an accelerating
voltage of 80 kV and on compound Fig. 5c with a Philips EM 208 electron
microscope. Magnetic measurements were performed using vibration sample
magnetometry (VSM, MDK, Model 7400) analysis. Melting points were measured
on an Electrothermal 9100 apparatus.
General procedure for synthesis of the catalyst
Silica-coated magnetite nanoparticles (Fe3O4@SiO2) were prepared as described
elsewhere [39, 40]. The ionic liquid 1-methyl-3-(trimethoxysilyl)propyl imidazoli-
um chloride ([pmim]Cl) was synthesized as described elsewhere [41]. For anchoring
of ([pmim]Cl on the-silica coated magnetite nanoparticles, [pmim]Cl (0.5 g,
1.3 mmol) was dissolved in 25 ml dry toluene and treated with 1 g previously
prepared Fe3O4@SiO2. After heating of the slurry at 90 °C for 16 h the resulting
solid was then separated by use of an external magnet and washed with 100 ml
123

H. Alinezhad et al.
dichloromethane. Unreacted ionic liquid was then removed by extraction for 24 h
with boiling dichloromethane (Soxhlet extraction) and the MNP-[pmim]Cl was
dried under high vacuum. For exchange of the Cl- anion, MNP[pmim]Cl (1 g) was
suspended in 20 ml dry CH2Cl2. During vigorous stirring, concentrated H2SO4
(1.3 mmol 98 %) was introduced dropwise at 0 °C. The mixture was warmed to
room temperature then heated under reflux for 48 h. The mixture was cooled,
filtered, and dried to give the supported hydrogensulfate ionic liquid MNP-
[pmim]HSO4.
General procedure for synthesis of triarylpyridines and diindenopyridines
MNP-([pmim]HSO4) (0.012 g, 1.2 mol% H?) was added to a mixture of aldehyde
(1.0 mmol), ketone (2.0 mmol), and ammonium acetate (1.3 mmol) and the
resulting mixture was stirred at 100 °C. Progress of the reaction was monitored
by TLC. After completion of the reaction, EtOAc (10 ml) was added to the cooled
reaction mixture. The catalyst was separated by use of an external magnet, washed
with EtOAC, dried, and reused for a consecutive run under the same reaction
conditions. Evaporation of the organic solvent under reduced pressure gave the
crude products. Pure products were obtained by recrystallization from aqueous
1
EtOH. The products were characterized by IR, H NMR and 13C NMR spectra.
Spectral data for selected products
1
4-(4-Fluorophenyl)-2,6-diphenylpyridine (Table 2, entry 2): H NMR (400 MHz,
DMSO-d6, d/ppm): 7.49–7.51 (m, 2H), 7.55–7.57 (m, 4H), 7.86 (b, 3H), 7.88 (b,
2H), 8.21–8.23 (m, 5H).13C NMR (100 MHz, DMSO-d6, d/ppm): 112.7, 116.8,
118.5, 127.6, 127.9, 128.8, 129.2, 129.4, 132.9, 139.0, 143.6, 143.2, 157.9. IR (KBr
disc): (cm-1): 1,600, 1,542, 1,514, 1,246, 1,179, 1,026, 826, 753. m/z (ESI) 325.1
(M?Á).
1
11-(Phenyl)diindeno[1,2-b:20,10-e]pyridine (Table 3, entry 1): H NMR (400 MHz,
DMSO-d6, d/ppm): 3.93 (s, 4H, 2CH2), 7.44 (t, J = 7.6 Hz, 2H), 7.53 (t,
J = 8.4 Hz, 3H), 7.58–7.63 (m, 4H), 7.78 (d, J = 6.8 Hz, 2H), 8.12 (d,
J = 7.2 Hz, 2H).13C NMR (100 MHz, DMSO-d6, d/ppm): 34.5, 101.9, 112.6,
120.8, 123.8, 125.9, 127.6, 128.8, 129.0, 129.3, 133.8, 137.0, 141.1, 144.7. IR (KBr
disc): (cm-1): 3,049, 1,562, 1,502, 1,401, 1,366, 1,285, 1,202, 1,021, 853, 739, 709.
m/z (ESI) 331.2 (M?Á).
11-(4-Nitrophenyl)diindeno[1,2-b:20,10-e]pyridine (Table 3, entry 5): 1H NMR
(400 MHz, DMSO-d6, d/ppm): 3.86 (s, 2H, CH2), 3.94 (s, 2H, CH2), 7.14 (b,
2H), 7.43–7.49 (b, 4H), 7.61 (b, 2H), 7.75 (b, 2H), 8.10 (b, 2H).13C NMR
(100 MHz, DMSO-d6, d/ppm): 34.3,114.6, 120.7, 125.8, 127.5, 128.7, 130.5, 133.8,
138.4, 141.2, 144.7, 159.7. IR (KBr disc): (cm-1): 3,050, 1,562, 1,461, 1,434, 1,366,
1,314, 1,285, 1,179, 1,024, 860, m/z (ESI) 376.4 (M?Á).
11-(4-Cyanophenyl)diindeno[1,2-b:20,10-e]pyridine (Table 3, entry 6): 1H NMR
(400 MHz, DMSO-d6, d/ppm): 3. 92 (s, 2H), 4.14 (s, 2H), 7.45 (b, 1H), 7.47–7.53
(m, 3H), 7.58 (b, 1H), 7.61 (d, J = 7.2 Hz, 1H), 7.68 (d, J = 7.6 Hz, 1H),7.74 (t,
J = 7.6, 1H), 7.81 (d, J = 7.6,1H), 8.01 (d, J = 8 Hz, 1H), 8.06 (d, J = 8 Hz, 1H),
123

The synthesis of polysubstituted pyridines…
8.12 (d, J = 7.2 Hz, 1H). 13C NMR (100 MHz, DMSO-d6, d/ppm): 32.3, 119.0,
124.3, 125.9, 127.2, 128.3, 129.0, 130.2, 131.2, 131.6, 133.2, 135.8, 137.3, 138.7,
139.9, 150.6. IR (KBr disc): (cm-1): 3,052, 2,922, 2,224, 1,702, 1,629, 1,568, 1,465,
1,442, 1,403, 1,325, 1,288, 1,204, 1,094, 858, 746. m/z (ESI) 357.2 (M?Á).
1
11-(4-Hydroxyphenyl)diindeno[1,2-b:20,10-e]pyridine (Table 3, entry 9): H NMR
(400 MHz, DMSO-d6, d/ppm): 3.88 (s, 4H), 6.97 (d, J = 8.4 Hz, 2H), 7.41 (t,
J = 7.2 Hz, 2H), 7.48 (t, J = 7.2 Hz, 2H), 7.57 (d, J = 7.2 Hz, 2H), 7.62 (d,
J = 8.8 Hz, 2H) 0.8.08(d, J = 7.2 Hz, 2 H), 9.9 (b. 1H). 13C NMR (100 MHz,
DMSO-d6, d/ppm): 34.2, 115.9, 120.7, 125.82, 127.3, 127.4, 128.6, 130.4, 133.7,
141.2, 143.5, 144.6, 158.2.IR (KBr disc): (cm-1): 3,427, 3,051, 2,923, 1,608, 1,563,
1,512, 1,464, 1,395, 1,287, 1,287, 1,229, 857, 752. m/z (ESI) 347.1 (M?Á).
11-(N,N-dimethylphenyl)diindeno[1,2-b:20,10-e]pyridine (Table 3, entry 10):
1H NMR (400 MHz, DMSO-d6, d/ppm): 3.00 (s, 6H), 3.95 (s, 4H), 6.88 (d,
J = 8.4 Hz, 2H), 7.42 (t, J = 7.2 Hz, 2H), 7.49 (t, J = 7.2 Hz, 2H), 7.62 (t,
J = 8.8 Hz, 4H), 8.09 (d, J = 7.2 Hz, 2H).13C NMR (100 MHz, DMSO-d6, d/
ppm): 34.5, 55.9, 112.5, 120.7, 123.9, 125.8, 127.4, 128.6, 130.0, 133.6, 141.2,
143.7, 144.7, 150.6, 159.6. IR (KBr disc): (cm-1): 2,898, 1,611, 1,525, 1,365, 1,285,
1,198, 947, 818, 747. m/z (ESI) 374.3 (M?Á).
Results and discussion
Characterization of the catalyst
The external surface of magnetite nanoparticles was coated with silica (Fe3O4@SiO2)
to protect the magnetic nanoparticles from possible decomposition induced by the
surrounding environment and to prevent further aggregation. Treatment of the silanol
groups of Fe3O4@SiO2 with 1-methyl-3-(trimethoxysilyl)propyl imidazolium chlo-
ride and [pmim]Cl resulted in anchored [pmim]Cl. Ion exchange of Cl- anions with
H2SO4 afforded MNP-[pmim]HSO4. The FT-IR spectra of MNPs (a), MNP@SiO2
(b), [pmim]Cl (c), MNP-[pmim]Cl (d), and MNP-[pmim]HSO4 (e) are shown in
Fig. 1. Peaks from pure magnetic nanoparticles appeared at approximately 590 cm-1
ascribed to Fe–O stretching, 3,420 cm-1, ascribed to stretching vibration of
physisorbed water, and, potentially, surface hydroxyl groups, and 1,630 cm-1
,
,
ascribed to deformation vibration of bonded O–H [39] (Fig. 1a). The other FT-IR
spectra shown in Fig. 1b, d, and e confirmed the presence of the magnetic core in the
prepared nanomaterials. In Fig. 1b, in addition to characteristic peaks of MNP, the
absorption peak at 1,061 cm-1 most probably arises as a result of stretching vibration
of the framework and of Si–O–Si groups [42]. In the FT-IR spectrum of 1-methyl-3-
(trimethoxysilyl)propyl imidazolium chloride, [pmim]Cl (Fig. 1c), characteristic
peaks of C=N and C–N stretching vibrations appeared at 1,642 and 1,588 cm-1
,
respectively. For MNP-[pmim]Cl (d) the band at 1,093 cm-1 was assigned to
asymmetric vibration of Si–O–Si; the C–H stretching band was observed at
2,955 cm-1 and the band at 3,402 cm-1 was ascribed to symmetric and asymmetric
stretching vibrations of OH groups, which is in good agreement with reported FT-IR
data [43]. In the spectrum of MNP-[pmim]HSO4 (e), peaks arising from O=S=O
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H. Alinezhad et al.
Fig. 1 FTIR spectra of MNPs
(a), MNP@SiO2 (b), [pmim]Cl
(c), MNP-[pmim]Cl (d), MNP-
[pmim]HSO4 (e)
asymmetric and symmetric stretching modes, at 1,133 and 1,076 cm-1, respectively,
and the broad OH stretching absorption at 2,800–3,380 cm-1 confirmed exchange of
Cl- ions with HSO-4 ions.
The crystalline structure of MNP-[pmim]HSO4 was characterized by X-ray
diffraction (XRD). The diffraction pattern of MNPs (Fig. 2a) contained character-
istic peaks at 2h values 30.2°, 35.6°, 43.3°, 53.7°, 57.2°, and 62.8° assigned to the
(220), (311), (400), (422), (511), and (440) crystal planes in the Fe3O4 cubic lattice,
which agrees with the Fe3O4 standard (JCPDS 19-0629). In the XRD pattern of
MNP@SiO2 (Fig. 2b), in comparison with pure MNP peaks (Fig. 2a), the peaks
from amorphous silica at 2h = 20–30 demonstrate successful coating of Fe3O4
nanoparticles with SiO2 [39]. The XRD pattern of MNP-[pmim]HSO4 (Fig. 2c) is
very similar to that of MNP@SiO2 which confirms that the structure of the Fe3O4
nanoparticles is not changed by coating with SiO2 and [pmim]HSO4.
Results from TGA analysis of MNP@SiO2 and MNP-[pmim]HSO4 are shown in
Fig. 3. For MNP@SiO2 (Fig. 3a) the weight loss at approximately 200 °C is
attributed exclusively to physically adsorbed water molecules and surface hydroxyl
groups on the magnetite surface. For MNP-[pmim]HSO4 (Fig. 3b), weight loss from
0–160 °C (2.75 %) is because of loss of physically adsorbed moisture whereas the
123

The synthesis of polysubstituted pyridines…
Fig. 2 XRD patterns of MNP (a), MNP@SiO2 (b) and MNP-[pmim]HSO4 (c)
Fig. 3 TGA thermograms of
MNP@SiO2 (a) MNP-
[pmim]HSO4 (b)
major weight losses at 160–340 °C (10.03 %) and 360–650 °C (11.83 %) are
related to decomposition of 1-methyl-3-propylimidazolium groups grafted on the
MNP@SiO2 surface.
The morphology of the catalyst surface was studied by scanning electron
microscopy (SEM) (Fig. 4). The SEM images (Fig. 4) showed floccules without a
123

H. Alinezhad et al.
Fig. 4 SEM images of MNP@SiO2 (left) and MNP-[pmim]HSO4 (right)
Fig. 5 TEM images of MNP (a), MNP@SiO2 (b), and MNP-[pmim]HSO4 (c)
regular structure. The shape of the particles is mostly spherical and the surface is
non-smooth, which results in an increase in the surface areas of the particles. TEM
images (Fig. 5) reveal that the diameter of MNPs (a) and MNP@SiO2 (b) nanopar-
ticles are approximately 10 and 15 nm, respectively, and that for MNP-
[pmim]HSO4 (c) is approximately 20 nm because of agglomeration of Fe3O4 and
surface growth of an homogenous layer on the shell (Fig. 5a–c). The TEM image of
MNP@SiO2 nanoparticles (Fig. 5b) clearly shows a dark nano-Fe3O4 core
surrounded by a grey silica shell.
The amount of IL ([pmim]HSO4) bonded to the MNP was quantified on the basis
of C, H, and N content, determined by elemental analysis (C: 8.36 %, H: 1.32 %, N:
2.67 % and S: 3.19 %). The ratio of C-to-N content (3.13) is very near the
theoretical value (3.00). The sulfur content also confirmed the amount loaded on the
MNP. The amount of IL (0.99 mmol/g) on the MNP was determined on the basis of
the chloride content of MNP-[pmim]Cl, determined by titration [44]; the result was
in good agreement with that obtained by TGA and conventional elemental analysis.
123

The synthesis of polysubstituted pyridines…
Fig. 6 VSM curve of MNP@SiO2 (a) MNP-[pmim]HSO4 (b)
Magnetic hysteresis measurements were obtained for both MNP@SiO2 and
MNP-[pmim]HSO4 by VSM at 300 K, with field sweeping from -8,000 to ?8,000
Oe. As shown in Fig. 6 the magnetic saturation values for MNP@SiO2 and MNP-
[pmim]HSO4 reached 57.2 and 43.6 emu/g respectively. The hysteresis loop for the
particles was completely reversible, showing that the nanoparticles have super-
paramagnetic characteristics and zero coercivity. The reversibility of the graph
confirms that the nanoparticles do not aggregate in the magnetic fields. The lower
magnetic saturation of the MNP@SiO2 nanoparticles suggests successful coating
with the [pmim]HSO4 ionic liquid. After characterization of the catalyst (MNP-
[pmim]HSO4) its catalytic activity was investigated in the one-pot synthesis of
2,4,6-triarylpyridines.
Synthesis of triarylpyridines and diindeno pyridines catalyzed by MNP-
[pmim]HSO4
The three-component reaction of benzaldehyde (1 mmol), acetophenone (2 mmol),
and NH4OAc (1.3 mmol) was chosen as model reaction for optimization of the
molar ratio of the catalyst, the temperature, and the solvent (Table 1). To
demonstrate the effect of the catalyst, the model reaction was performed in the
absence of catalyst (entry 1) and in the presence of MNP@SiO2 (entry 2) and MNP-
[pmim]Cl (entry 3) under the same reaction conditions; only trace amounts of the
product were obtained. However, when the reaction conducted in the presence of
imidazolium hydrogensulfate ([Hmim]HSO4) and methyl imidazolium hydrogen
chloride ([Hmim]Cl) as two non-supported ILs the desired product was obtained in
40 and 30 % yields, respectively (Table 1, entries 4, 5).
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H. Alinezhad et al.
Table 1 Optimization of the reaction conditions for synthesis of triarylpyridines
Entry
Catalyst (mol%)
Solvent
Temperature
Time (h:min)
Yield (%)a
1
–
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
H2O
100 °C
100 °C
100 °C
100 °C
100 °C
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
100 °C
100 °C
100 °C
100 °C
4
–
2
MNP@SiO2
4
Trace
Trace
40
3
MNP-[pmim]Cl (1.2)
[Hmim]HSO4 (1.2)
4
4
1:10
5
[Hmim]Cl (1.2)
1:30
30
6
MNP-[pmim]HSO4 (1.2)
MNP-[pmim]HSO4 (1.2)
MNP-[pmim]HSO4 (1.2)
MNP-[pmim]HSO4 (1.2)
MNP-[pmim]HSO4 (1.2)
MNP-[pmim]HSO4 (1.2)
MNP-[pmim]HSO4 (1.2)
MNP-[pmim]HSO4 (1.4)
MNP-[pmim]HSO4 (1.2)
MNP-[pmim]HSO4 (1)
MNP-[pmim]HSO4 (0.8)
4
50
7
EtOH
4
40
9
MeOH
4
25
9
CH3CN
4
45
10
11
12
13
14
15
16
EtOAC
4
40
CH2Cl2
4
55
Toluene
4
60
Solvent free
Solvent free
Solvent free
Solvent free
00:50
00:50
2
90
90
85
3
80
Conditions: benzaldehyde:acetophenone:NH4OAc 1:2:1.3
a
Isolated yields
When the model reaction was performed in the presence of 1.2 mol% MNP-
[pmim]HSO4 in the polar solvents H2O, MeOH, EtOH a low yield of the product
was obtained (Table 1, entries 6-8). This could be because of insolubility of the
reactants in H2O and the low boiling points of MeOH and EtOH. However, reaction
in the nonpolar solvents CH2Cl2, ethyl acetate, and toluene did not give a reasonable
yield of the expected product (Table 1, entries 10–12). The model reaction under
solvent-free conditions resulted in suitable yields of the product (Table 1, entries
13–16). Because the best solvent from the perspective of green chemistry is no
solvent, because of minimization of environmental effects, and because combina-
tion of solvent-free conditions with multi-component reactions has been shown to
be a powerful strategy for synthesis of complex molecular structures. It was found
that the best yield of the product was obtained at 100 °C under solvent-free
conditions in the presence of 1.2 mol% of MNP-[pmim]HSO4 (Table 1, entry 14).
Increasing the amount of catalyst did not improve the yield of the product any
further but reducing the amount of catalyst led to a decrease in product yield
(Table 1, entries 13, 16).
To establish the scope of this method, synthesis of a variety of triarylpyridines
from different aldehydes and acetophenones was studied under the optimized
reaction conditions (Table 2).
As it is clear from the Table 2, aromatic and heteroaromatic aldehydes tolerated
well in this reaction and varieties of aldehydes with electron-donating or electron-
123

The synthesis of polysubstituted pyridines…
Table 2 Synthesis of 2,4,6-triphenylpyridines
Entry
Ar1
Ar2
Time (min)
Yielda
M.p. (°C) Ref
1
C6H5–
C6H5–
50
55
45
40
40
60
70
75
80
65
85
80
45
35
50
45
90
87
95
90
85
90
87
87
90
83
78
75
85
90
89
88
133–134 [45]
204–206
2
4-FC6H4–
C6H5–
3
4-ClC6H4–
4-BrC6H4–
4-NO2C6H4–
4-MeC6H4–
4-MeOC6H4–
4-OHC6H4–
4-N(Me)2C6H4–
Pyridine-4yl
Thiophen-2-yl
Furan-2-yl
C6H5–
C6H5–
124–125 [45]
102–104 [45]
196–198 [45]
122–124 [45]
99–100 [45]
195–197 [45]
138–140 [34]
187–190 [34]
161–163 [45]
179–181 [45]
126–128 [46]
269–270 [47]
118–119 [46]
190–191 [46]
4
C6H5–
5
C6H5–
6
C6H5–
7
C6H5–
8
C6H5–
9
C6H5–
10
11
12
13
14
15
16
C6H5–
C6H5–
C6H5–
4-ClC6H4–
4-ClC6H4–
4-ClC6H4–
4-ClC6H4–
4-ClC6H4–
4-MeC6H4–
4-MeOC6H4
Conditions: aldehyde:acetophenone:NH4OAc:MNP-[pmim]HSO4: 1:2:1.3:0.012, 100 °C, solvent-free
a
Yields refer to pure isolated products
withdrawing groups on the aromatic ring had little effect on the reaction rate and
desired products were formed in good yields (Table 2, entries 1–8 and entries
13–16). Heteroaromatic aldehydes also tolerate the condensation reaction to afford
the corresponding pyridines in good yields (Table 2, entries 10–12).
Furthermore, this versatile method was also examined for the indan-1-one. The
products 11-aryldiindeno [1,2-b:20,10-e]pyridines (Scheme 3) were obtained in high
yields under the same optimal reaction conditions (Table 3).
A plausible mechanism for formation of 2,4,6-triarylpyridines catalyzed by
MNP-[pmim]HSO4 is shown in Scheme 4. The first step of the process involves
Knoevenagel condensation of the aldehyde with acetophenone to form the
corresponding chalcone (A). The reaction proceeds via Michael addition of a
second molecule of acetophenone to A followed by nucleophilic attack of
ammonium acetate on the carbonyl group of adduct B, then intramolecular
cyclization with loss of a water molecule to produce the dihydropyridine C.
Aromatization and oxidation of C by air under these reaction conditions give
pyridines as the final products.
Recovery and reuse of the catalyst is highly desirable for a catalytic process. In
this regard the recyclability of MNP-([pmim]HSO4 was investigated in the model
reaction of benzaldehyde with acetophenone and ammonium acetate under the
optimized reaction conditions. After completion of the reaction, EtOAc was added
and all the MNP-[pmim]HSO4 was separated from the product simply by use of an
external magnet. The recovered catalyst was washed with ethyl acetate, dried at
123

H. Alinezhad et al.
Ar1
N
O
MNP-[pHim]HSO4
Solvent-free
Ar1CHO
2
+
+ NH4OAc
Scheme 3 Synthesis of 11-aryldiindeno [1,2-b:20,10-e]pyridines catalyzed by MNP-[pmim]HSO4
Table 3 Synthesis of
11-aryldiindeno [1,2-b:20,10-
e]pyridines
Entry Ar1
Time (min) Yielda M. p (°C) Ref
1
2
C6H5–
50
55
45
50
50
45
60
65
75
90
88
85
87
85
90
90
80
87
85
267–268
4-FC6H4–
[300 [48]
[300 [48]
[300 [48]
234–235
3
4-ClC6H4–
4-BrC6H4–
4-NO2C6H4
4-CNC6H4–
4-MeC6H4–
4-MeOC6H4–
4-OHC6H4–
4
5
6
287–289
Conditions: aldehyde:indan-1-
one:NH4OAc:MNP-
7
[300 [48]
257–258 [48]
255–257
[pmim]HSO4 1:2:1.3:0.012,
100 °C, solvent-free
8
9
a
Yields refer to pure isolated
products
10
4-N(Me)2C6H4– 80
276–278
O
Ar2C
MNP-[pmim]HSO4
Ar2CCH3
Ar2CCH3
OH
Knovenagel condensation
Ar2C
OH
CH2
Ar1
-H2O
Ar1CH
OH
O
(A)
Micheal reaction
O
Ar1
O
MNP-[pmim]HSO4
Ar2C
OH
CH2
Ar1
Ar1
Ar2
Ar2
Ar1
H
(B)
-H2O
Ar2
Ar2
NH4OAc
Ar2
N
H
Ar2
Ar2
NH2
O
Ar2
NH2
O
(C)
Ar1
Air oxidation
Ar2
N
Ar2
Scheme 4 Plausible mechanism for synthesis of 2,4,6-triphenylpyridines catalyzed by MNP-
([pmim]HSO4
room temperature, and reused for six consecutive trials, without significant loss of
its catalytic activity in comparison with the fresh catalyst (Fig. 7).
The recyclability test was stopped after six runs. Comparison of the SEM image
and FT-IR spectrum of the used catalyst (Fig. 8) with those of the fresh catalyst
(Figs. 4, 1d) showed that the size and structure of MNP-[pmim]HSO4 remained
intact after six recoveries.
123

The synthesis of polysubstituted pyridines…
Fig. 7 Recycling of MNP-[pmim]HSO4
Fig. 8 SEM image (left) and FT-IR spectrum (right) of recovered MNP-[pmim]HSO4
Conclusions
In summary, we successfully synthesized a supported IL, 1-methyl-3-(trimethoxysi-
lyl)propyl imidazolium hydrogensulfate (MNP-[pmim]HSO4), from readily avail-
able starting materials. It was applied as a magnetically recyclable heterogeneous
catalyst for one-pot, three-component synthesis of triarylpyridines and diindenopy-
ridines. This catalyst efficiently promoted condensation of aromatic aldehydes and
ketones with ammonium acetate, leading to the corresponding pyridines in good
123

H. Alinezhad et al.
yields under solvent-free conditions. Product separation and catalyst recycling are
readily achieved by use of an external magnet. The catalyst can be recovered and
reused six times without significant degradation of its activity.
Acknowledgments This research was supported by the Research Council of the University of
Mazandaran, Iran.
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