Mesoporous nanocrystalline MgAl2O4: A new heterogeneous catalyst for the synthesis of 2,4,6-triarylpyridines under solvent-free conditions

Article abstract of DOI:10.2478/s11696-013-0361-5

In this paper, one-pot synthesis of 2,4,6-triarylpyridine by condensation of subsisted acetophenone (II), aromatic aldehydes (I), and ammonium acetate (III) in the presence of nanocrystalline MgAl₂O₄ as a new heterogeneous catalyst under solvent-free conditions is reported. Advantages of this method are the use of spatially-hindered aldehydes such as 2-methoxy-, 2-fluoro-, and 2-chlorobenzaldehydes, a new nanocatalyst with high surface area, shorter reaction time, easier workup, higher yield, and its environmental friendliness. The performance of this reaction under solvent free conditions using heterogeneous catalysts like MgAl₂O₄ could enhance its efficiency from an economic as well as green chemistry point of view.

Full text of DOI:10.2478/s11696-013-0361-5

Chemical Papers 67 (7) 688–695 (2013)
DOI: 10.2478/s11696-013-0361-5
ORIGINAL PAPER
Mesoporous nanocrystalline MgAl2O4:
A new heterogeneous catalyst for the synthesis
of 2,4,6-triarylpyridines under solvent-free conditions
Javad Safari*, Zohre Zarnegar, Mahmoud Borjian Borujeni
Laboratory of Organic Chemistry Research, Department of Organic Chemistry, College of Chemistry, University of Kashan,
P.O Box 87317–51167 Kashan, Iran
Received 20 October 2012; Revised 14 December 2012; Accepted 23 December 2012
In this paper, one-pot synthesis of 2,4,6-triarylpyridine by condensation of subsisted acetophe-
none (II ), aromatic aldehydes (I ), and ammonium acetate (III ) in the presence of nanocrystalline
MgAl2O4 as a new heterogeneous catalyst under solvent-free conditions is reported. Advantages
of this method are the use of spatially-hindered aldehydes such as 2-methoxy-, 2-fluoro-, and 2-
chlorobenzaldehydes, a new nanocatalyst with high surface area, shorter reaction time, easier work-
up, higher yield, and its environmental friendliness. The performance of this reaction under solvent
free conditions using heterogeneous catalysts like MgAl2O4 could enhance its efficiency from an
economic as well as green chemistry point of view.
c
ꢀ 2013 Institute of Chemistry, Slovak Academy of Sciences
Keywords: one-pot synthesis, multicomponent reactions, heterogeneous catalyst, nanocrystalline
magnesium aluminate, solvent-free
Introduction
pyridine are used solid-phase synthesis (Chiu et al.,
1998), one-pot synthesis under microwave irradia-
tion (Khosropour et al., 2011), solvent-free synthesis
(Adib et al., 2006), and synthesis using heteropoly
acids (Heravi et al., 2007), HClO4–SiO2 (Nagarapu
et al., 2007), and ionic liquids (Davoodnia et al.,
2010) as the catalyst. However, many of these pro-
tocols suffer from drawbacks such as expensive cat-
alyst, undesired side products of the reaction with
harsh reagents, long reaction time, cumbersome prod-
uct isolation procedures, and environmental pollution
(Montazeri & Mahjoob, 2012). Therefore, further de-
velopment of versatile reaction conditions of the 2,4,6-
triarylpyridine synthesis using an efficient, inexpen-
sive, reusable, green, and eco-friendly catalyst with
high selectivity is still necessary.
Multi-component reactions (MCR) are an attrac-
tive strategy in organic synthesis. In this strategy,
complex molecules are formed without the isolation
of intermediates after a cascade of bond-forming in-
dividual steps using three or more reactants. Attrac-
tive properties of MCRs are the reduction of the iso-
lation and purification steps, simple operation, and
low costs, energy, time, solvents, and waste production
(Barluenga et al., 2008). MCRs are widely used for
the synthesis of heterocyclic compounds such as pyri-
dine derivatives. Pyridine derivatives have a unique
position in the synthetic chemistry because they are
present in natural products, pharmaceuticals such
as vasodilators, anticonvulsants, antiepileptics, anaes-
thetics, and in agrochemicals such as pesticides and
herbicides (Kim et al., 2004; Enyedy et al., 2003; Pil-
lai et al., 2003; Klimešová et al., 1999; Constable et
al., 2000).
On the other hand, environmental concerns requir-
ing the reduction of the amount of pollutants pro-
duced, including harmful organic solvents whose re-
covery is subject to ever more strict laws, have to
be considered (Safari et al., 2010). Hence, the chal-
Several methods for the synthesis of 2,4,6-triaryl
*Corresponding author, e-mail: Safari@kashanu.ac.ir

J. Safari et al./Chemical Papers 67 (7) 688–695 (2013)
689
Fig. 1. Synthesis of 2,4,6-triarylpyridines in the presence of nanocrystalline MgAl2O4 under solvent-free condition: i) nanocrys-
talline MgAl2O4, 120◦C, 3 h, solvent-free.
lenges for asustainable environment calls for the use
of clean procedures, where the use of organic solvents
can be avoided. The increasing interest in this class of
compounds led to the development of other synthetic
strategies with alternative catalysts.
performed with a Carlo Erba model EA 1108 ana-
lyzer (Italy). The N2 adsorption/desorption analysis
(BET) was performed at 196◦C using an automated
gas adsorption analyser (Tristar 3000, Micromeritics,
USA). Transmission electron microscopy (TEM) was
performed with a Jeol JEM-2100UHR (China), oper-
ated at 200 kV.
In recent years, nanomaterials have been proven
as powerful catalysts in various organic transfor-
mations such as cobalt nanoparticles in the syn-
thesis of 1,4-dihydropyridines (Safari et al., 2011),
nanocrystalline magnesium oxide in the synthesis of
2,4,5-trisubstituted imidazole derivatives (Safari et
al., 2010), and silica nanoparticles in the preparation
of highly substituted pyridines (Banerjee & Sereda,
2009). Magnesium aluminate (MgAl2O4) spinel has
many applications as a catalyst. Because of its unique
properties such as chemical inertness, high surface
area, small crystallite size, and higher number of ac-
tive sites (Guo et al., 2004; Navaei Alvar et al., 2010).
Nanoscale supports form catalysts with high sur-
face area and mesoporous structure, which can lead
to higher performance of the catalyst. Herein, a con-
venient and simple multi-component, one-pot synthe-
sis of 2,4,6-triaryl pyridine whit high yields achieved
by using nanocrystalline magnesium aluminate spinel
with high specific surface area and the crystallite size
of approximately 4–12 nm as a novel and efficient cat-
alyst (Fig. 1) is reported.
Preparation of nanocrystalline MgAl2O4
Nanocrystalline MgAl2O4 spinel was prepared by
means of a procedure reported elsewhere (Navaei Al-
var et al., 2010). In short, stoichiometric amounts of
magnesium nitrate and aluminum nitrate and of the
desired amount of hexadecyl-trimethyl-ammonium
bromide (cetyl trimethylammonium bromide; CTAB)
were added to well stirred deionised water. Then, am-
monia solution was added dropwise to the well stirred
slurry to adjust the pH value to around 9. After pre-
cipitation, the slurry was stirred for another 30 min
and then refluxed at 80◦C for 24 h under continuous
stirring. The mixture was then cooled to room tem-
perature and filtered. The final product was dried at
100◦C for 24 h under flowing air and calcined at dif-
ferent temperatures.
Preparation of 2,4,6-triaryl pyridine by use of
nanocrystalline magnesium aluminate spinel
Experimental
Aromatic aldehydes (1 mmol), NH4OAc (4 mmol),
acethophenones (2 mmol), and nanocrystalline
MgAl2O4 (7 mole %) were mixed and then heated
in a sealed tube at 120◦C for 3 h. Upon comple-
tion, monitored by TLC, hot ethanol was added to
the mixture and the insoluble catalyst was filtered off.
Pure products were obtained by recrystallisation from
95 % ethanol. Structure of these compounds was in-
vestigated using different methods of spectroscopy and
spectrometry (1H NMR, 13C NMR, IR, MS, and el-
emental analysis). Physico–chemicaly data as well as
spectroscopic characterisations of the newly prepared
compounds are given in Tables 1 and 2.
Chemicals were purchased from Merck (Germany)
and Fluka (Germany) in high purity. All materials
were of commercial reagent grade. IR spectra were
recorded as KBr pellets on a Perkin–Elmer 781 spec-
trophotometer (USA) and on an Impact 400 Nicolet
FTIR spectrophotometer (USA). 1H NMR (400 MHz)
and 13C NMR (100 MHz) spectra were recorded on
a Bruker DPX-400 Avance spectrometer (Germany).
Tetramethyl silane (TMS) was used as the internal
reference. Chemical shifts are given in δ related to
TMS. Melting points were determined by a Yanagi-
moto micro melting point apparatus (China). Purity
determination of the substrates and reaction moni-
toring were accomplished by thin layer chromatogra-
phy (TLC) on silica gel POLYGRAMꢀ SILG/UV 254
plates (Taiwan). Elemental analysis (C, H, N) was
Results and discussion
A mixture of acetophenone (II; 2 mmol), benzalde-

690
J. Safari et al./Chemical Papers 67 (7) 688–695 (2013)
Table 1. Characterisation data of newly prepared compounds
wi(calc.)/%
wi(found)/%
Yield
M.p./◦C
Compound
Formula
Mr
Appearence
C
H
N
%
Found Reported
IVa
IVb
IVc
IVd
IVe
IVf
IVg
IVh
IVi
IVj
IVk
IVl
C23H17
N
307.40
341.84
337.15
325.13
311.13
297.31
321.38
337.39
350.41
89.87
89.82
80.81
80.75
85.43
85.39
84.90
85.85
84.86
84.83
84.82
84.78
89.68
89.63
85.43
85.41
85.68
85.65
73.42
73.36
70.95
70.91
70.95
71.03
70.95
70.99
70.07
69.78
68.87
68.86
71.60
71.55
67.26
67.22
89.51
89.33
89.36
89.27
85.45
85.36
74.72
74.58
5.57
5.55
4.72
4.70
5.68
5.59
4.96
4.85
5.50
5.45
5.08
5.02
5.96
5.93
5.68
5.64
6.33
6.28
4.02
4.01
4.22
4.18
4.22
4.18
4.22
4.12
3.58
3.46
3.58
3.54
4.81
4.78
3.44
3.39
6.31
6.19
6.63
6.51
6.34
6.25
5.02
4.93
4.56
4.51
4.10
4.08
4.15
4.12
5.84
5.78
4.50
4.45
4.71
4.68
4.36
4.30
4.15
4.11
7.99
7.95
3.72
3.67
3.45
3.41
3.45
3.51
3.45
3.51
3.55
3.41
3.82
3.75
6.68
6.63
3.41
3.40
4.18
4.09
4.01
3.88
3.83
3.74
3.49
3.38
85
87
85
88
85
88
80
80
86
90
86
83
80
86
87
79
80
80
75
70
80
White solid
White solid
White solid
Hite solid
135–137 134–135a
127–128 124–126b
C23H16ClN
C24H19NO
C24H19NO
C24H19NO
C21H15NO
124–127
119–120
–
–
–
Light brown solid 162–164
Light brown solid 160–162 164–165a
119–120 123–124b
98–100
99–101b
C24H19
N
White solid
White solid
Yellow solid
White solid
White solid
White solid
White solid
White solid
White solid
Yellow solid
White solid
White solid
White solid
White solid
White solid
C24H19NO
C26H22N2
137–139 136–138a
175–178 188–190c
C23H15Cl2N 376.23
C24H17Cl2NO 406.28
C24H17Cl2NO 405.07
C24H17Cl2NO 405.07
C23H14Cl2FN 394.26
C21H13Cl2NO 365.04
C25H20Cl2N2 418.10
C23H14Cl3N 409.02
190–191
164–166
159–160
144–148
144–146
139–140
168–170
–
–
–
–
–
–
–
IVm
IVn
IVo
IVp
IVq
IVr
IVs
IVt
IVu
C25H21
C26H23
N
N
335.43
349.47
365.47
154–156 153–155a
174–176 176–177a
156–158 155–157a
114–116 115–116b
C26H23NO
C25H20ClNO2 401.89
a) Maleki et al. (2010);b) Adib et al. (2006); c) Chiu et al. (1998).
hyde (I; 1 mmol), ammonium acetate (III; 4 mmol),
and nanocrystalline MgAl2O4 (7 mole %) as the cat-
alyst was heated at 120◦C for 3 h under solvent free
conditions. Progress of the reaction was monitored by
TLC (petroleum ether/ethyl acetate, ϕr = 7 : 3). Af-
ter adding hot ethanol to the mixture, the insoluble
catalyst was filtered off. It is important to note that in
the absence of a catalyst, the reaction yield decreased
to 5–15 % even at 140◦C after 10 h.
mole % of the catalyst provided the maximum yield
(85 %). A higher amount of the catalyst did not in-
crease the yield of the process. Pore volume and pore
size were also calculated from the N2 adsorption re-
sults; the pore size was approximately 23.59 nm and
the pore volume was approximately 0.58 cm3 g−1
.
TEM analysis showed that the crystallite sizes of the
sample calcined at 700◦C was between 3–10 nm and
increased to 4–12 nm after the calcinations at 800◦C
(Navaei Alvar et al., 2010).
On the other hand, nanocrystalline MgAl2O4
spinel has high surface area and plate like shape, which
Therefore, nanocrystalline MgAl2O4 spinel with a
high specific surface area was used as the catalyst with
higher activity and better selectivity. The use of 7

J. Safari et al./Chemical Papers 67 (7) 688–695 (2013)
Table 2. Spectral data of newly prepared compounds
691
Compound
Spectral data
IVa
IR ν˜/cm−1 (KBr): 3069, 1597, 1552, 1494, 1440, 1398, 1178, 1074, 1027, 867, 759, 692
1H NMR (400 MHz, DMSO-d6), δ: 8.37 (d, 2H, J = 7.2 Hz, ArH), 8.33 (d, 2H, J = 7.5 Hz, ArH), 8.20 (s, 2H, ArH),
8.06 (d, 2H, J = 7.4 Hz, ArH), 7.60–7. 50 (m, 9H, ArH)
13C NMR (100 MHz, DMSO-d6), δ: 157.0, 150.1, 139.3, 139.2, 129.7, 129.7, 128.7, 128.4, 127.8, 127.4, 117.0
MS, m/z (Ir/%): 307.40 (100) (M+
)
IVb
IVc
IR ν˜/cm−1 (KBr): 3061, 1599, 1543, 1489, 1449, 1414, 1384, 1237, 1090, 1013, 825, 773, 692
1H NMR (400 MHz, DMSO-d6), δ: 8.39 (d, 2H, J = 7.1 Hz, ArH), 8.34 (d, 2H, J = 7.8 Hz, ArH), 8.14 (s, 2H, ArH),
7.81 (d, 2H, J = 7.9 Hz), 7.62 (d, 2H, J = 7.9 Hz, ArH), 7.56–7.53 (m, 6H, ArH)
13C NMR (100 MHz, DMSO-d6), δ: 157.1, 148.6, 139.2, 136.9, 134.7, 129.6, 129.5, 129.4, 129.2, 116.9
MS, m/z (Ir/%): 341.84 (100) (M+
)
IR ν˜/cm−1 (KBr): 3034, 2936, 1596, 1547, 1486, 1444, 1398, 1285, 1255, 1204, 1171, 1037, 872, 775, 692
1H NMR (400 MHz, DMSO-d6), δ: 8.36 (d, 2H, J = 7.5 Hz, ArH), 8.30 (d, 2H, J = 7.6 Hz, ArH), 8.14 (s, 2H, ArH),
7.59–7.50 (m, 8H, ArH), 7.46 (d, 1H, J = 7.4 Hz, ArH), 6.89 (t, 1H, J = 7.4 Hz, ArH), 3.70 (s, 3H, OCH3)
13C NMR (100 MHz, DMSO-d6), δ: 160.4, 157.0, 150.0, 139.8, 139.3, 130.6, 129.7, 129.2, 127.5, 120.1, 117.2, 115.4,
113.2, 55.8
MS, m/z (Ir/%): 337.15 (100) (M+
)
IVd
IR ν˜/cm−1 (KBr): 3031, 1591, 1544, 1490, 1451, 1395, 1288, 1209, 1204, 1114, 1074, 1025, 878, 759, 694
1H NMR (400 MHz, DMSO-d6), δ: 8.36 (d, 2H, J = 7.5 Hz, ArH), 8.31 (d, 2H, J = 7.3 Hz, ArH), 8.10 (s, 2H, ArH),
7.85 (d, 1H, J = 6.9 Hz, ArH), 7.49–7.45 (m, 8H, ArH), 7.07 (d, 1H, J = 7.9 Hz, ArH)
13C NMR (100 MHz, DMSO-d6), δ: 160.4, 157.0, 150.0, 139.8, 139.3, 130.6, 129.7, 129.2, 127.5, 120.1, 117.2, 115.4,
113.2, 55.8
MS, m/z (Ir/%): 325.13 (100) (M+
)
IVe
IVf
IVg
IR ν˜/cm−1 (KBr): 3058, 2927, 1591, 1548, 1495, 1447, 1394, 1237, 1122, 1204, 1114, 1075, 1027, 878, 758, 691
1H NMR (400 MHz, DMSO-d6), δ: 8.35 (d, 2H, J = 7.7 Hz,), 8.27 (d, 2H, J = 7.5 Hz,), 8.18 (s, 2H, ArH), 7.57–7.47
(m, 7H, ArH), 6.34 (s, 1H, J = 7.9 Hz, ArH), 2.50 (s, 3H, CH3)
13C NMR (100 MHz, DMSO-d6), δ: 155.3, 151.4, 146.1, 136.2, 129.3, 127.6, 127.4, 118.6, 107.8, 101.8, 14.1
MS, m/z (Ir/%): 311.13 (100) (M+
)
IR ν˜/cm−1 (KBr): 3058, 1606, 1541, 1487, 1454, 1414, 1244, 1158, 1073, 1010, 868, 772, 690
1H NMR (400 MHz, DMSO-d6), δ: 8.30 (d, 2H, J = 7.6 Hz, ArH), 8.20 (d, 2H, J = 7.5 Hz, ArH), 8.14 (s, 2H, ArH),
7.96 (s, 1H, ArH), 7.57–7.47 (m, 7H, ArH), 6.75–6.74 (d, 1H, J = 8.1 Hz, ArH)
13C NMR (100 MHz, DMSO-d6), δ: 110.9, 113.0, 113.1, 127.2, 129.2, 129.8, 130.0, 139.6, 145.2, 151.4, 157.0
MS, m/z (Ir/%): 297.31 (100) (M+
)
IR ν˜/cm−1 (KBr): 3034, 2936, 1598, 1548, 1442, 1398, 1286, 1254, 1203, 1170, 1036, 871, 775, 691
1H NMR (400 MHz, DMSO-d6), δ: 8.35 (d, 2H, J = 7.3 Hz, ArH), 8.29 (d, 2H, J = 7.5 Hz, ArH), 8.14 (s, 2H, ArH),
7.93 (d, 2H, J = 7.8 Hz, ArH), 7.58 (t, 2H, J = 7.6 Hz, ArH), 7.50 (t, 2H, J = 7.6 Hz, ArH), 7.47 (t, 2H, J = 7.7 Hz,
ArH), 7.35 (d, 2H, J = 7.8 Hz, ArH), 2.48 (s, 3H, CH3)
13C NMR (100 MHz, DMSO-d6), δ: 157.0, 149.0, 139.4, 135.2, 130.1, 129.6, 129.2, 127.5, 127.4, 116.7, 21.3
MS, m/z (Ir/%): 321.38 (100) (M+
)
IVh
IR ν˜/cm−1 (KBr): 3035, 2936, 1596, 1547, 1486, 1444, 1398, 1285, 1255, 1204, 1171, 1037, 750, 691
1H NMR (400 MHz, DMSO-d6), δ: 8.38 (d, 2H, J = 7.6 Hz, ArH), 8.30 (d, 2H, J = 7.3 Hz, ArH), 8.14 (s, 2H,
ArH), 8.03 (d, 2H, J = 7.1 Hz, ArH), 7.61 (t, 4H, J = 6.8 Hz, ArH), 7.50 (t, 4H, J = 6.8 Hz, ArH), 7.48 (d, 2H, J
= 7.3 Hz, ArH), 7.1 (d, 2H, J = 7.1 Hz, ArH), 3.82 (s, 3H, CH3)
13C NMR (100 MHz, DMSO-d6), δ: 160.8, 156.9, 149.5, 139.4, 130.4, 130.3, 129.6, 129.1, 127.4, 116.4, 115.0, 55.8
MS, m/z (Ir/%): 337.39 (100) (M+
)
IVi
IVj
IVk
IR ν˜/cm−1 (KBr): 3037, 2936, 1598, 1525, 1489, 1442, 1398, 1352, 1233, 1199, 1168, 1066, 1023, 818, 773, 695
1H NMR (400 MHz, DMSO-d6), δ: 8.35 (d, 2H, J = 7.4 Hz, ArH), 8.20 (d, 2H, J = 7.6 Hz, ArH), 8.10 (s, 2H, ArH),
7.92 (d, 2H, J = 6.8 Hz, ArH), 7.55–7.44 (m, 6H, ArH), 6.83 (d, 2H, J = 7.4 Hz, ArH), 3.19 (s, 3H, CH3)
13C NMR (100 MHz, DMSO-d6), δ: 155.2, 152.0, 150.1, 136.2, 129.3, 128.3, 127.6, 127.4, 118.0, 114.8, 40.2
MS, m/z (Ir/%): 350.41 (100) (M+
)
IR ν˜/cm−1 (KBr): 3052, 1598, 1544, 1490, 1449, 1413, 1384, 1239, 1174, 1091, 1012, 829, 761, 694
1H NMR (400 MHz, DMSO-d6), δ: 8.42 (d, 2H, J = 7.6 Hz, ArH), 8.33 (d, 2H, J = 7.5 Hz, ArH), 8.23 (s, 2H, ArH),
8.04 (d, 2H, J = 7.7 Hz, ArH), 7.61–7.50 (m, 7H, ArH)
13C NMR (100 MHz, DMSO-d6), δ: 155.8, 150.3, 137.9, 134.7, 129.9, 129.6, 127.9, 117.3
MS, m/z (Ir/%): 376.23 (100) (M+
)
IR ν˜/cm−1 (KBr): 3052, 2928, 1602, 1543, 1512, 1489, 1426, 1381, 1291, 1247, 1177, 1088, 1011, 824
1H NMR (400 MHz, DMSO-d6), δ: 8.40 (d, 2H, J = 7.6 Hz, ArH), 8.29 (d, 2H, J = 7.6 Hz, ArH), 8.17 (s, 2H, J =
7.5 Hz, ArH), 8.60 (d, 2H, J = 6.8 Hz, ArH), 8.50 (d, 2H, J = 6.8 Hz, ArH), 7.48 (d, 2H, J = 7.3 Hz, ArH), 7.12
(d, 2H, J = 7.3 Hz, ArH), 3.84 (s, 3H, CH3)
13C NMR (100 MHz, DMSO-d6), δ: 161.1, 155.8, 134.3, 132.9, 130.2, 129.3, 129.0, 128.4, 118.0, 114.8, 5.8
MS, m/z (Ir/%):406.28 (100) (M+
)

692
J. Safari et al./Chemical Papers 67 (7) 688–695 (2013)
Table 2. (continued)
Compound
Spectral data
IVl
IR ν˜/cm−1 (KBr): 3049, 2948, 1601, 1542, 1512, 1491, 1411, 1383, 1263, 1245, 1175, 1126, 1090, 1014, 827, 749
1H NMR (400 MHz, DMSO-d6), δ: 8.32 (d, 2H, J = 7.6 Hz, ArH), 8.20 (d, 2H, J = 7.4 Hz, ArH), 8.04 (s, 2H, ArH),
7.63 (d, 1H, J = 7.9 Hz, ArH), 7.55–7.53 (m, 4H, ArH), 7.45 (t, 1H, J = 7.2 Hz, ArH), 7.22 (d, 1H, J = 7.2 Hz,
ArH), 7.09 (t, 1H, J = 7.9 Hz, ArH), 3.84 (s, 3H, CH3)
13C NMR (100 MHz, DMSO-d6), δ: 161.1, 155.8, 134.3, 132.9, 130.2, 129.3, 129.0, 128.4, 118.0, 114.8, 55.8
MS, m/z (Ir/%): 405.07 (100) (M+
)
IVm
IR ν˜/cm−1 (KBr): 3062, 2932, 1595, 1546, 1490, 1460, 1411, 1383, 1265, 1211, 1176, 1089, 1012, 833, 787
1H NMR (400 MHz, DMSO-d6), δ: 8.40 (d, 2H, J = 7.5 Hz, ArH), 8.31(d, 2H, J = 7.4 Hz, ArH), 8.20 (s, 2H, ArH),
7.62 (d, 2H, J = 7.6 Hz, ArH), 7.55–7.52 (m, 4H, Ar-H), 7.42 (d, 1H, J = 7.3 Hz, ArH), 7.05 (d, 1H, J = 7.4 Hz,
ArH), 3.88 (s, 3H, CH3)
13C NMR (100 MHz, DMSO-d6), δ: 161.2, 155.2, 152.0, 138.9, 134.3, 132.9, 130.3, 129.3, 129.0, 119.7, 118.0, 114.8,
111.1, 55.8
MS, m/z (Ir/%): 405.07 (100) (M+
)
IVn
IVo
IVp
IR ν˜/cm−1 (KBr): 3061, 1599, 1543, 1490, 1460, 1411, 1383, 1265, 1211, 1176, 1089, 1012, 833, 787
1H NMR (400 MHz, DMSO-d6), δ: 8.38 (d, 2H, J = 7.2 Hz, ArH), 8.30 (d, 2H, J = 7.5 Hz, ArH), 8.18 (s, 2H, ArH),
7.59–7.55 (m, 6H, ArH), 7.50–7.42 (d, 1H, J = 6.9 Hz, ArH), 7.12–7.05 (d, 1H, J = 6.9 Hz, ArH)
13C NMR (100 MHz, DMSO-d6), δ: 166.1, 159.4, 157.6, 151.2, 138.0, 136.6, 133.4, 130.9, 129.8, 117.1, 116.4, 115.7
MS, m/z (Ir/%): 394.26 (100) (M+
)
IR ν˜/cm−1 (KBr): 3061, 1609, 1544, 1488, 1422, 1374, 1265, 1216, 1176, 1090, 1012, 826, 736
1H NMR (400 MHz, DMSO-d6), δ: 8.38 (d, 2H, J = 7.6 Hz, ArH), 8.30 (d, 2H, J = 7.5 Hz, ArH), 8.21 (s, 2H, ArH),
7.98–7.92 (s, 1H, ArH), 7.68–7.52 (d, 5H, ArH), 6.80–6.72 (d, 1H, J = 8.1 Hz, ArH)
13C NMR (100 MHz, DMSO-d6), δ: 155.3, 154.0, 146.1, 142.9, 134.3, 132.9, 129.3, 129.0, 118.0, 107.0, 105.0
MS, m/z (Ir/%): 365.04 (100) (M+
)
IR ν˜/cm−1 (KBr): 3061, 2932, 1597, 1527, 1488, 1432, 1359, 1265, 1189, 1201, 1090, 945, 814
1H NMR (400 MHz, DMSO-d6), δ: 8.38 (d, 2H, J = 7.5 Hz, ArH), 8.31 (d, 2H, J = 7.3 Hz, ArH), 8.12 (s, 2H, ArH),
7.95 (d, 2H, J = 6.8 Hz, ArH), 7.56 (d, 2H, J = 7.5 Hz, ArH), 7.52 (d, 2H, J = 7.5 Hz, ArH), 6.84 (d, 2H, J =
6.8 Hz, ArH), 2.98 (s, 6H, CH3)
13C NMR (100 MHz, DMSO-d6), δ: 155.2, 152.0, 150.1, 134.3, 132.9, 129.0, 128.3, 127.4, 118.0, 114.8, 40.2
MS, m/z (Ir/%): 418.10 (100) (M+
)
IVq
IVr
IVs
IVt
IVu
IR ν˜/cm−1 (KBr): 3034, 1603, 1544, 1490, 1413, 1383, 1263, 1174, 1090, 1012, 824, 751
1H NMR (400 MHz, DMSO-d6), δ: 8.40 (d, 2H, J = 7.5 Hz, ArH), 8.31 (d, 2H, J = 7.3 Hz, ArH), 8.14 (s, 2H, ArH),
7.87 (d, 2H, J = 6.9 Hz, ArH), 7.56–7.52 (m, 4H, ArH), 6.82 (d, 2H, J = 6.9 Hz, ArH)
13C NMR (100 MHz, DMSO-d6), δ: 155.2, 152.0, 138.9, 134.3, 132.9, 132.1, 130.7, 129.3, 129.0, 128.8, 127.4, 118.0
MS, m/z (Ir/%): 409.02 (100) (M+
)
IR ν˜/cm−1 (KBr): 3063, 1587, 1554, 1490, 1438, 1395, 1181, 1079, 1024, 867, 759, 692
1H NMR (400 MHz, DMSO-d6), δ: 8.36 (d, 4H, J = 7.5 Hz, ArH), 8.18 (d, 2H, J = 7.8 Hz, ArH), 7.58 (t, 3H, J =
7.5 Hz, ArH), 7.21 (s, 2H, ArH), 7.10 (d, 4H, J = 7.7 Hz, ArH), 2.35 (s, 6H, 2CH3)
13C NMR (100 MHz, DMSO-d6), δ: 157.6, 150.3, 139.1, 136.9, 136.6, 131.0, 128.9, 127.6, 127.1, 117.3, 20.9
MS, m/z (Ir/%): 335.43 (100) (M+
)
IR ν˜/cm−1 (KBr): 3068, 1576, 1558, 1493, 1442, 1386, 1173, 1065, 1027, 864, 750, 688
1H NMR (400 MHz, DMSO-d6), δ: 8.39–8.33 (m, 6H, ArH), 7.72 (s, 2H, ArH), 7.14–7.12 (m, 6H, ArH), 2.32 (s, 6H,
2CH3), 2.28 (s, 3H, CH3)
13C NMR (100 MHz, DMSO-d6), δ: 157.8, 150.4, 141.1, 136.9, 136.6, 131.0, 129.3, 127.7, 117.5, 21.1, 20.9
MS, m/z (Ir/%): 349.46 (100) (M+
)
IR ν˜/cm−1 (KBr): 3040, 2943, 1588, 1543, 1475, 1440, 1398, 1285, 1252, 1210, 1175, 1031, 753, 695
1H NMR (400 MHz, DMSO-d6), δ: 8.35 (d, 4H, J = 7.6 Hz, ArH), 8.42 (s, 2H, ArH), 8.14 (d, 2H, J = 7.1 Hz, ArH),
7,32 (d, 4H, J = 7.3 Hz, ArH), 6.95 (d, 2H, J = 7.1 Hz, ArH), 3.82 (s, 3H, OCH3), 2.28 (s, 6H, 2CH3)
13C NMR (100 MHz, DMSO-d6), δ: 159.1, 157.7, 150.5, 142.6, 136.9, 130.9, 129.6, 127.7, 117.1, 114.4, 55.3, 20.8
MS, m/z (Ir/%): 365.47 (100) (M+
)
IR ν˜/cm−1 (KBr): 3052, 2938, 1605, 1542, 1512, 1488, 1423, 1376, 1258, 1245, 1175, 1130, 1087, 1014, 825, 744
1H NMR (400 MHz, DMSO-d6), δ: 8.37 (d, 2H, J = 7.1 Hz, ArH), 8.35 (d, 2H, J = 7.8 Hz, ArH), 7.89 (d, 2H, J =
7.9 Hz,), 7.39 (d, 2H, J = 7.9 Hz, ArH), 7.12 (s, 2H, ArH), 6.95 (d, 2H, J = 7.5 Hz, ArH), 6.78 (d, 2H, J = 7.4 Hz,
ArH), 3.80 (s, 6H, 2OCH3)
13C NMR (100 MHz, DMSO-d6), δ: 158.9, 157.9, 150.2, 141.1, 134.7, 133.5, 130.6, 129.5, 129.1, 116.9, 114.0, 55.3
MS, m/z (Ir/%): 401.89 (100) (M+
)
can lead to higher performance of the catalyst com-
pared with the magnesium oxide nanopowder. More-
over, the high efficiency of the nanoparticle oxides is
caused not only by their high surface area but also by
the high concentration of low coordinated sites and
structural defects on their surface. As the particle size
is a few nanometers, the constituting atoms exhibit
highly defective coordination behaviours. Most of the

J. Safari et al./Chemical Papers 67 (7) 688–695 (2013)
693
Table 3. Effect of different ammonia sources on the yield of
the product
Table 5. Effect of solvents on the reaction
Temperature/◦C Time/h Yield/%
Entry Solvent
Ammonia source
Time/h
Yield/%
1
2
3
4
EtOH
AcOH
DMF
Solvent free
78
115
120
120
5
3
3
3
traces
60
55
85
NH4OAc
NH4F
(NH4)2CO3
3
3
5
85
60
30
DMF – N,N-dimethylformamide.
atoms have unsatisfied valencies and reside at the sur-
face of the particles. On the other hand, in this reac-
tion, nanocrystalline MgAl2O4 acts as a mild Lewis
The reaction temperature was optimised by carry-
ing out a model reaction at temperatures ranging from
90–140◦C. It was shown that at 120◦C, the best yield
is obtained (Table 6).
acid with Mg2+ and Al3+
.
To optimise the ammonia source, NH4OAc, NH4F,
and (NH4)2CO3 were studided (Table 3). It was found
that NH4OAc produced acetic acid under the consid-
ered reaction conditions whit a good effect. NH4F pro-
duced strongly acidic HF that damages the Pyrexꢀ
glass.
Subsequent efforts were focused on optimising the
conditions for the formation of 2,4,6-triarylpyridines
by using different amounts of nanocrystalline MgAl2O4
and different temperatures in the presence of different
solvents and in the absence of solvent to determine
their effect on the reaction (Tables 4 and 5). As indi-
cated, the best results were obtained at 120◦C with the
7 mole % nanocrystalline MgAl2O4 under solvent-free
conditions. The reaction yield did not substantially in-
crease with the increasing amount of nanocrystalline
MgAl2O4 and temperature.
The reusability is one of the important properties
of this catalyst. After the reaction completion, hot
ethanol was added to the mixture and the insoluble
catalyst was filtered off. The catalyst was then washed
with acetone, air-dried, and used directly with fresh
substrates under identical conditions without further
purification. It was shown that the catalyst can be
reused for the next cycle without any appreciable loss
of its activity. Similarly, its reusability for sequential
reactions was also determined and the catalyst was
found to be reusable for five cycles (Fig. 2).
The Suggested mechanism is shown in Fig. 3: al-
dol condensation of an aldehyde (I ) and acetophenone
(II ) occurred, and a molecule of acetophenone was
condensed with ammonia and enamine was formed.
The Michael addition of enamine to the aldol prod-
uct and the following cyclisation provided dihydropy-
Table 4. Optimisation of reaction conditions for the synthesis of 2,4,6-triarylpyridines
Entry
Catalyst/mole %
Temperature/◦C
Time/h
Yield/%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
–
3
5
7
9
–
3
5
7
9
–
3
5
7
9
90
90
90
90
90
120
120
120
120
120
140
140
140
140
140
10
8
8
6
6
10
7
4
3
3
10
5
4
3
3
5
30
35
38
38
10
60
75
85
85
15
60
80
85
83

694
J. Safari et al./Chemical Papers 67 (7) 688–695 (2013)
Table 6. Nanocrystalline MgAl2O4-catalysed synthesis of 2,4,
6-triarylpyridines at 120◦C under solvent-free condi-
tions
Entry
Ar
Ar1
Products
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4-ClC6H4
3-MeOC6H4
2-FC6H4
IVaa
IVbb
IVc
IVd
IVe
IVfa
IVgb
IVhb
IVia
IVjc
IVk
5-methylfuran
C4H3O(furan)
4-MeC6H4
4-MeOC6H4
4-N(Me)2C6H4
C6H5
4-MeOC6H4
2-MeOC6H4
3-MeOC6H4
2-FC6H4
C6H5
Fig. 2. Recyclability of MgAl2O4 (7 mole %) in the reaction
of benzaldhyde (1 mmol), NH4OAc (4 mmol), and
acethophenones (2 mmol) under solvent free at 120◦C
for 3 h.
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3OC6H4
IVl
IVm
IVn
IVo
IVp
IVq
IVra
IVsa
IVta
IVub
C4H3O(furan)
4-N(Me)2C6H4
2-ClC6H4
ridine. Finally, air oxidation afforded the final product.
The reaction involves four major stages: aldol con-
densation, Michael addition, cyclisation, and oxida-
tion. Nanocrystalline MgAl2O4 facilitates aldol con-
densation, Michael addition, and precipitated oxida-
tion of dihydropyridine to the final product. Although
the reaction with electron-withdrawing groups of aro-
C6H5
4-CH3C6H4
4-MeOC6H4
4-ClC6H4
a) Maleki et al. (2010); b) Adib et al. (2006); c) Chiu et al.
(1998).
Fig. 3. Proposed mechanism of the reaction.

J. Safari et al./Chemical Papers 67 (7) 688–695 (2013)
695
matic aldehyde is faster than the electron-donating
one, the reaction with a substituted group of aromatic
aldehyde, such as electron-donating and electron-
withdrawing group, occurred.
Most of the products, IVa–IVu, are known and
were identified by comparison of their physical and
spectral data with those of authentic samples (Ta-
ble 4). For example the IR spectrum of IVa showed ab-
sorptions at 3096 cm−1 (CH), 1450 cm−1, 1597 cm−1
Chemical Monthly, 141, 867–870. DOI: 10.1007/s00706-010-
0329-x.
Enyedy, I. J., Sakamuri, S., Zaman, W. A., Johnson, K. M., &
Wang, S. M. (2003). Pharmacophore-based discovery of sub-
stituted pyridines as novel dopamine transporter inhibitors.
Bioorganic & Medicinal Chemistry Letters, 13, 513–517.
DOI: 10.1016/s0960-894x(02)00943-5.
Guo, J. J., Lou, H., Zhao, H., Wang, X. G., & Zheng, X. M.
(2004). Novel synthesis of high surface area MgAl2O4 spinel
as catalyst support. Materials Letters, 58, 1920–1923. DOI:
10.1016/j.matlet.2003.12.013.
−1
—
—
Heravi, M. M., Bakhtiari, K., Daroogheha, Z.,
& Bamo-
(C C aromatic), 1398 cm (C N aromatic), and at
—
—
692 cm−1, 759 cm−1 (aromatic). The H NMR spec-
trum of IVa showed a multiplet for H—Ar (δ 7.50–
7.60), doublet for H—Ar (δ 8.06), singlet for H—Ar
pyridine ring (δ 8.20), and a doublet for H—Ar (δ 8.37
and δ 8.33). The 13C NMR spectrum of IVa showed
11 distinct resonances at δ: 157.0, 150.1, 139.3, 139.2,
129.7 (5 × C arom.); 129.7, 128.7, 128.4, 127.8, 127.4,
117.0 (6 × CH arom.) which are in agreement with
the structure and formula of IVa.
1
harram, F. F. (2007). An efficient synthesis of 2,4,6-
triarylpyridines catalyzed by heteropolyacid under solvent-
free conditions. Catalysis Communications, 8, 1991–1994.
DOI: 10.1016/j.catcom.2007.03.028.
Khosropour, A. R., Mohammadpoor-Baltork, I., & Kiani, F.
(2011). Green, new and efficient tandem oxidation and con-
version of aryl alcohols to 2,4,6-triarylpyridines promoted by
[HMIm]NO3-[BMIm]BF4 as a binary ionic liquid. Comptes
Rendus Chimie, 14, 441–445. DOI: 10.1016/j.crci.2010.10.
002.
Kim, B. Y., Ahn, J. B., Lee, H. W., Kang, S. K., Lee, J.
H., Shin, J. S., Ahn, S. K., Hong, C. I., & Yoon, S. S.
(2004). Synthesis and biological activity of novel substituted
pyridines and purines containing 2,4-thiazolidinedione. Eu-
ropean Journal of Medicinal Chemistry, 39, 433–447. DOI:
10.1016/j.ejmech.2004.03.001.
Klimešová, V., Svoboda, M., Waisser, K., Pour, M., & Kaustová,
J. (1999). New pyridine derivatives as potential antimicro-
bial agents. Il Farmaco, 54, 666–672. DOI: 10.1016/s0014-
827x(99)00078-6.
Maleki, B., Azarifar, D., Veisi, H., Hojati, S. F., Salehabadi,
H., & Nejat Yami, R. (2010). Wet 2,4,6-trichloro-1,3,5-
triazine (TCT) as an efficient catalyst for the synthesis of
2,4,6-triarylpyridines under solvent-free conditions. Chinese
Chemical Letters, 21, 1346–1349. DOI: 10.1016/j.cclet.2010.
06.028.
Montazeri, N., & Mahjoob, S. (2012). Highly efficient and easy
synthesis of 2,4,6-triarylpyridines catalyzed by pentafluo-
rophenylammonium triflate (PFPAT) as a new recyclable
solid acid catalyst in solvent-free conditions. Chinese Chem-
ical Letters, 23, 419–422. DOI: 10.1016/j.cclet.2012.01.035.
Nagarapu, L., Aneesa, Peddiraju, R., & Apuri, S. (2007).
HClO4–SiO2 as a novel and recyclable catalyst for the
synthesis of 2,4,6-triarylpyridines under solvent-free con-
ditions. Catalysis Communications, 8, 1973–1976. DOI:
10.1016/j.catcom.2007.08.003.
Conclusions
In conclusion, a simple, eco-friendly, and green pro-
cedure for the synthesis of 2,4,6-triaryl pyridines us-
ing nanocrystalline MgAl2O4 as a new nanocatalyst
is described. This method shows some advantages in-
cluding excellent yields, short reaction time, the use
of a new recyclable, and heterogeneous nanocatalyst,
simple operation, and work-up, and no volatile or haz-
ardous organic solvents.
Acknowledgements. We gratefully acknowledge financial
support from the Research Council of the University of Kashan,
Grant NO (159198/IV).
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