Ultrasound-Mediated Synthesis of 2,4,6-Triaryl-Pyridines Using MgAl2O4 Nanostructures

Article abstract of DOI:10.1007/s10593-015-1638-0

Nanocrystalline MgAl₂O₄ was found to be a highly efficient catalyst for the preparation of 2,4,6-triaryl-pyridines from the reaction of acetophenone derivatives, aryl aldehydes, and ammonium acetate under sonic condition for the first time. The present methodology offers several advantages, such as excellent yields, simple procedure, shorter reaction times, and milder conditions; the catalyst also exhibited remarkable reusable activity. This procedure is much simpler and faster than the protocols published to date.

Full text of DOI:10.1007/s10593-015-1638-0

DOI 10.1007/s10593-015-1638-0
Chemistry of Heterocyclic Compounds, Vol. 50, No. 12, March, 2015 (Russian Original Vol. 50, No. 12, December, 2014)
ULTRASOUND-MEDIATED SYNTHESIS OF 2,4,6-TRIARYL-
PYRIDINES USING MgAl2O4 NANOSTRUCTURES
1
1
1
*
Z. Zarnegar , J. Safari , and M. Borjian-borujeni
Nanocrystalline MgAl2O4 was found to be a highly efficient catalyst for the preparation of 2,4,6-triaryl-
pyridines from the reaction of acetophenone derivatives, aryl aldehydes, and ammonium acetate under
sonic condition for the first time. The present methodology offers several advantages, such as excellent
yields, simple procedure, shorter reaction times, and milder conditions; the catalyst also exhibited
remarkable reusable activity. This procedure is much simpler and faster than the protocols published to
date.
Keywords: nanocrystalline magnesium aluminate, 2,4,6-triarylpyridines, nanocatalyst, one-pot
synthesis, ultrasound irradiation.
Ultrasound-accelerated organic chemical reactions have been increasingly developed by researchers
across the globe for the synthesis of organic compounds. Ultrasound irradiation offers an alternative energy
source for organic synthesis which are ordinarily accomplished by heating. Ultrasound-mediated reactions
proceed by the formation, growth, and collapse of acoustic bubbles in the reaction medium. These directly help
in shortening the time span of reactions and increasing the yield of products [1].
The pyridine ring system is present in various natural compounds, and many pyridines exhibit a broard
range of biological activities [2]. Due to their π-stacking ability, some pyridine derivatives are used in
supramolecular chemistry [3]. Recently, these heterocyclic compounds have also evoked considerable attention,
being endowed with a wide range of pharmaceutical activities such as anticonvulsant, antimalarial, anesthetic,
vasodilator, and antiepileptic, and they have been used as agrochemicals such as pesticides, fungicides and
herbicides [4, 5]. Therefore, it is of continuous interest to develop procedures for the synthesis of 2,4,6-tri-
arylpyridines, Kröhnke pyridines. Since Kröhnke's original report on the preparation of 2,4,6-triarylpyridines
[6], there has been a plethora of research targeting their syntheses [7-12]. Recently, much effort has been
devoted to developing more efficient protocols for the synthesis of 2,4,6-triarylpyridines, for example solid-
phase synthesis [7], one-pot synthesis under microwave irradiation [8], and solvent-free reaction between
acetophenones, benzaldehydes, and ammonium acetate in the presence of various catalyst such as I2 [9],
heteropolyacid [10], HClO4–SiO2 [11], and ionic liquid [12]. However, many of these processes suffer from
drawbacks such as long reaction time, expensive catalyst, undesired side products in reaction with harsh
reagents, special care in handling and storing the reagents, cumbersome product isolation procedures
_______
*To whom correspondence should be addressed, e-mail: safari@kashanu.ac.ir.
1Laboratory of Organic Chemistry Research, Department of Organic Chemistry, College of Chemistry,
University of Kashan, P. O. Box, 87317-51167, Kashan, I. R. Iran.
_________________________________________________________________________________________
Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1832-1840, December, 2014.
Original article submitted August 2, 2014.
0009-3122/15/5012-1683©2015 Springer Science+Business Media New York
1683

and environmental pollution. Therefore, a need still exists for further development of versatile reaction
conditions in the synthesis of 2,4,6-triarylpyridine using an efficient, reusable, inexpensive, eco-friendly, and
selective catalyst.
In recent years, nanostructures have emerged as powerful catalysts in various organic synthesis such as
cobalt nanoparticles for synthesis of 1,4-dihydropyridines [13], nanocrystalline MgO for synthesis of 2,4,5-tri-
substituted imidazole derivatives [14], silica nanoparticles for the preparation of highly substituted pyridines
[15] and ZnO nanopowder for the preparation of 2,4,6-triarylpyridines [16]. In recent years, the use of MgAl2O4
nanostructures has become a significant area of research in organic reactions and has been shown to improve
yield and purity of the products. It has catalytic properties because of its unique properties such as chemical
inertness, high surface area, small crystallite size, and more active sites [17-19].
However, despite extensive studies on the synthesis of 2,4,6-triarylpyridines reported in the literature, to
the best of our knowledge there is no report focusing on the development of one-pot synthesis of Kröhnke
pyridines using nanocatalyst under ultrasound conditions. Therefore, this report describes a convenient and
facile synthesis of 2,4,6-triarylpyridines in high yields using nanocrystalline magnesium aluminate spinel as
nanocatalyst under ultrasound irradiation.
To achieve suitable conditions for the synthesis of 2,4,6-triarylpyridines, various reaction conditions have
been investigated in the reaction of acetophenone (1a), benzaldehyde (2a), ammonium acetate, and
nanocrystalline MgAl2O4 (4 mol%) as a model reaction. We examined the effect of different solvents such as
EtOH, DMSO, THF, DMF, AcOH, and MeCN on the model reaction under ultrasound irradiation (power
intensity 50 W) at 70°C (Table 1). Comparing the yields of 2,4,6-triphenylpyridine (3a), AcOH was chosen as
the best solvent for further experiments.
The reaction was performed in the presence of different amounts of catalyst (Table 2) with and without
ultrasonic irradiation. In all cases, the experimental results show that the reaction times are shorter and the
yields of the products are higher under ultrasound irradiation. With the application of ultrasound, compression
of the liquid is followed by rarefaction, in which a sudden pressure drop forms small, oscillating bubbles of the
gaseous substances. These bubbles are small and rapidly collapse, and they can be regarded as microreactors
that offer the opportunity of speeding up certain reactions and allowing mechanistically novel reactions to take
place in an absolutely safe manner [20]. The best results were obtained using 5 mol% of the nanocatalyst under
both conditions (Table 2, entry 6). As shown, in the absence of catalyst the yield of the product was found to be
low (Table 2, entry 1).
TABLE 1. Screening of the Solvent Effect on the Model Reaction
Ph
Ph
O
H
2a
Me
Me
Nanocrystalline MgAl2O4 (4 mol%)
+
sonication (50 W)
70°C, 70 min
Ph
O
O
Ph
Ph
N
Ph
1a
1a
NH4OAc
3a
Entry
Solvent
Yield, %
1
2
3
4
5
6
EtOH
DMSO
THF
50
60
60
68
72
48
DMF
AcOH
MeCN
1684

TABLE 2. Effect of the Catalyst Loading on Yields of the Model Reaction
with or without Sonication
Yield, %
Entry
Amount of catalyst, mol%
With sonication*
Without sonication*2
1
2
3
4
5
6
7
0
1
2
3
4
5
6
20
35
50
60
65
72
72
10
25
45
50
58
64
65
_______
*Reaction conditions: AcOH, ultrasonic irradiation (50 W), 70°C, 70 min.
*2Reaction conditions: AcOH, reflux, 100 min.
In order to further improve the yield of the reaction, we performed five experiments carrying out the
model reaction under ultrasound irradiation (50 W) at 30, 50, 70, 90, and 100°C. It was observed that lower
reaction temperature led to lower yield of the product. As shown in Table 3, increasing the reaction temperature
improves the reaction yield, with the best result obtained at 90°C (entry 4). So, further experiments were
performed at this temperature. In order to determine the effect of ultrasonic irradiation power on the reaction
course, the model reaction was also performed at irradiation power of 20, 40, 60, 80 and 100 W (Table 3, entries
6-10). Increase in ultrasonic power led to relatively higher yield and shorter reaction time until the ultrasound
power reached 80 W, at which further increase in ultrasound power to 100 W caused a slight decrease in yield
of the model reaction. These results indicated that there was a remarkable ultrasonic temperature effect on this
reaction.
Encouraged by the results obtained in the reaction of acetophenone (1a), benzaldehyde (2a), and
NH4OAc, we performed the reaction of acetophenones 1a,b with a series of aromatic aldehydes 2a-j (Table 4).
All the reactions proceeded very cleanly at the optimized reaction conditions, and no undesirable side reactions
were observed. The experimental results show that the course of this reaction obviously does not depend on the
substituent at the aromatic rings in both acetophenone and aldehyde: all the products 3a-p, including furyl-
substituted derivatives 3e,f,o, were obtained in high yields with short reaction time. Compared to other
methodologies reported for the synthesis of 2,4,6-triarylpyridines via one-pot reaction, the present methodology
offers suitable conditions with respect to reaction times and yields.
TABLE 3. Effect of the Reaction Conditions on Yields of the Model
Reaction (Solvent – AcOH, Catalyst Loading – 5 mol%)
Entry* Temperature, °C Yield, % Entry*2 Ultrasound power, W Time, min Yield, %
1
2
3
4
5
30
50
53
60
72
80
80
6
7
20
40
70
70
70
60
60
45
65
84
90
85
70
8
60
90
100
9
10
80
100
_______
*In entries 1-5, reaction time was 70 min.
*2In entries 6-10, reaction temperature was 90°C.
1685

TABLE 4. Nanocrystalline MgAl2O4-Catalyzed Synthesis of 2,4,6-Tri-
arylpyridines 3a-p under Sonic Conditions
Ar1
Nanocrystalline MgAl2O4
(5 mol%)
2 ArCOMe
+
Ar1CHO
+
NH4OAc
sonication (80 W)
AcOH, 90°C
1a,b
2a–j
Ar
N
Ar
3a–p
Aceto-
phenone
Time,
Yield,
Entry
Ar
Aldehyde
Ar1
Product
Mp, °C
min
%
90
97
1
2
Ph
Ph
Ph
60
135-137
(134-135 [21])
127-128
1a
2a
2b
3a
3b
4-ClC6H4
55
1a
(124-126 [22])
124-127
3
4
5
Ph
Ph
Ph
3-MeOC6H4
2-FC6H4
5-Methyl-
furan-2-yl
2-Furyl
60
55
60
91
96
92
1a
1a
1a
2c
2d
2e
3c
3d
3e
119-120
162-164
6
7
Ph
Ph
Ph
Ph
60
65
65
60
55
94
90
90
94
98
160-162
(164-165 [21])
119-120
(123-124 [22])
98-100
(99-101 [22])
137-139
1a
1a
1a
1a
1b
2f
2g
2h
2i
3f
3g
3h
3i
4-MeC6H4
4-MeOC6H4
4-Me2NC6H4
Ph
8
9
(136-138 [21])
175-178
10
4-ClC6H4
2a
3j
(188-190 [7])
190-191
11
12
13
14
15
16
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-MeOC6H4
2-MeOC6H4
3-MeOC6H4
2-FC6H4
55
60
70
60
60
70
97
93
85
94
95
84
1b
1b
1b
1b
1b
1b
2h
2j
2c
2d
2f
2i
3k
3l
164-166
159-160
3m
3n
3o
3p
144-148
2-Furyl
144-146
4-Me2NC6H4
139-140
On the other hand, ultrasound enhanced the rate of the reaction and, consequently, reduced energy
consumption. The driving force for the increased efficiency of formation of 2,4,6-triarylpyridines by ultrasound
is the increase in temperature due to the formation of hot spots, as well as the increase in reactant contact
surface area through a cavitation phenomenon. Upon irradiation with ultrasound, the formation, growth,
and implosive collapse of bubbles can create extreme chemical and physical conditions in solid/liquid systems,
leading to short-lived localized hotspots that produce relatively high temperature for this one-pot condensation
reaction to occur, and the rate of the reaction was well accelerated under sonic condition. Moreover, when
cavitation phenomenon occurs near the solid catalyst surface, cavity collapse is nonspherical, and as a result of
this, a liquid jet will be formed, which is targeted at the surface, and this effect is equivalent to a high-
pressure/high-velocity liquid. These jets activate the heterogeneous catalyst and increase the mass transfer to the
surface by disrupting the interfacial boundary layers as well as dislodging the material occupying the inactive sites
[23].
The suggested mechanism of the reaction is shown below. First, the aldol condensation of acetophenone
1 and aldehyde 2 occurred, and the second molecule of acetophenone 1 condensed with ammonia, forming
enamine. The Michael addition of the enamine to the aldol product followed by cyclization produced
dihydropyridine. Finally, air oxidation afforded the final product. The reaction involves three major stages:
aldol condensation, Michael addition, and cyclization and oxidation. Nanocrystalline MgAl2O4 facilitates aldol
condensation, Michael addition, and subsequent oxidation of dihydropyridine to the final product. An
1686

interesting point is that aromatic aldehydes carrying either electron-donating or electron-withdrawing
substituents reacted very well to give the corresponding products in moderate to excellent yields with high
purity.
O
O
Me
Ar
Me
Ar
NH3
1
1
2+
2+
.
Mg
.
Mg
.
.
.
.
O
OH
Ar
O
NH2
Ar
+
Ar1
H
H2C
Ar1
Ar
H2C
–H2O
2
.
Ar1
2+
Mg
.
Ar1
O
.
NH Ar1 OH
Ar
Ar
Ar
Ar
N
H
Ar
Ar
NH2
Ar1
[O]
Ar
N
Ar
3
The reusability of the catalyst is one of the most important benefits and makes it useful for commercial
applications: thus, the recovery and reusability of nano-MgAl2O4 as a heterogeneous catalyst was investigated.
For this purpose, the model reaction of acetophenone (1a) with benzaldehyde (2a) and NH4OAc was studied
under optimized conditions. After the completion of the reaction, the mixture was evaporated and then diluted
with hot ethanol. The catalyst was separated by filtration, washed with hot ethanol, and dried. The recovered
nano-MgAl2O4 was reused in subsequent reactions without significant decrease in activity even after six runs
(Fig. 1).
Fig. 1. Reusability of nano-MgAl2O4 for the synthesis of compound 3a.
In conclusion, we have developed a new and facile procedure for the one-pot synthesis of 2,4,6-tri-
arylpyridines in the presence of nano-MgAl2O4 as a heterogeneous nanocatalyst under ultrasonic condition. The
present methodology offers very attractive features such as shorter reaction time and higher yields and will have
wide applications in organic synthesis. This simple method combined with ease of recovery and reuse of the
nanocatalyst makes this protocol economic, benign, and a waste-free chemical process for the synthesis of 2,4,6-
triarylpyridines.
1687

EXPERIMENTAL
1
IR spectra were recorded on a Perkin–Elmer 781 spectrophotometer in KBr pellets. H and 13C NMR
spectra were recorded on a Bruker DPX-400 Avance spectrometer (400 and 100 MHz, respectively) in DMSO-d6,
internal standard was TMS. Elemental analysis (C, H, N) was performed on a Carlo Erba model EA 1108
analyzer or a Perkin–Elmer 240c analyzer. Melting points were determined on a Yanagimoto micromelting
point apparatus. The purity determination of the substrates and reaction monitoring were accomplished by TLC
on silica gel polygram SILG/UV 254 plates. Transmission electron microscopy (TEM) was performed with a
Jeol JEM-2100UHR apparatus operating at 200 kV. Sonication was performed in a Shanghai Branson-BUG40-
06 ultrasonic cleaner (with a frequency of 35 kHz and a nominal maximal power 100 W). A circulating water
bath (DC2006, Shanghai Hengping Apparatus Factory) with an accuracy of 0.1 K was adopted to keep the
reaction temperature constant.
Chemicals were purchased from Merck and Fluka in high purity. All of the materials were of
commercial reagent grade.
Preparation of Nanocrystalline MgAl2O4. Nanocrystalline magnesium aluminate spinel was
synthesized using a procedure reported in [18]. In short, stoichiometric amounts of magnesium nitrate and
aluminum nitrate and the desired amount of cetyl trimethylammonium bromide were added to well-stirred
deionized water. Then ammonia solution was added dropwise to the well-stirred slurry to adjust the pH value to
~9. After precipitation, the slurry was stirred for another 30 min and refluxed at 80°C for 24 h under continuous
stirring. The mixture was then cooled and filtered. The final product was dried at 100°C for 24 h under flowing
air and calcined at 700 and 800°C. The crystallite sizes of the magnesium aluminate determined by TEM
analysis at 700°C was 3-10 nm. The pore volume, calculated from the N2 adsorption/desorption isotherm, was
approximately 1.10 cm3·g-1. The surface area was determined as ~201 m2·g-1 [18]. The crystallite sizes of
MgAl2O4 increased to 4-12 nm after calcinations at 800°C. These results revealed that MgAl2O4 nanoparticles
have high thermal stability toward high temperatures. Moreover, the particles are closely sintered together, and
most of the particles have a slightly irregular, rounded shape [18].
Preparation of 2,4,6-Triarylpyridines 3a-p Using Nanocrystalline MgAl2O4 under Sonication
(General Method). A 25-ml Erlenmeyer flask was charged with acethophenone 1a,b (2 mmol), aromatic
aldehyde 2a-j (1 mmol), NH4OAc (308 mg, 4 mmol), nano-MgAl2O4 (7 mg, 5 mol%), and AcOH (5 ml). The
reaction flask was located in the ultrasonic bath, where the surface of the reactants was slightly lower than the
level of the water, and irradiated with ultrasound at 80 W power during 55-70 min (Table 4), keeping the
temperature inside the reactor at 90°C. The reaction was monitored by TLC (eluent petroleum ether – EtOAc,
7:3). After the reaction was completed, the reaction mixture was concentrated on a rotary evaporator under
reduced pressure, the obtained solid product was dissolved in hot EtOH, and the insoluble catalyst was filtered
off. The pure products were obtained by recrystallization from EtOH.
2,4,6-Triphenylpyridine (3a). White solid. IR spectrum, ν, cm-1: 3069, 1597, 1552, 1494, 1440, 1398,
1
1178, 1074, 1027, 867, 759, 692. H NMR spectrum, δ, ppm (J, Hz): 8.37 (2H, d, J = 7.2, H Ar); 8.33 (2H, d,
J = 7.5, H Ar); 8.20 (2H, s, H Ar); 8.06 (2H, d, J = 7.4, H Ar); 7.60-7.50 (9H, m, H Ar). 13C NMR spectrum, δ,
ppm: 157.0; 150.1; 139.3; 139.2; 129.7 (2C); 128.7; 128.4; 127.8; 127.4; 117.0. Found, %: C 89.82; H 5.55;
N 4.51. C23H17N. Calculated, %: C 89.87; H 5.57; N 4.56.
4-(4-Chlorophenyl)-2,6-diphenylpyridine (3b). White solid. IR spectrum, ν, cm-1: 3061, 1599, 1543,
1
1489, 1449, 1414, 1384, 1237, 1090, 1013, 825, 773, 692. H NMR spectrum, δ, ppm (J, Hz): 8.39 (2H, d,
J = 7.1, H Ar); 8.34 (2H, d, J = 7.8, H Ar); 8.14 (2H, s, H Ar); 7.81 (2H, d, J = 7.9, H Ar ); 7.62 (2H, d, J = 7.9,
13
H Ar); 7.56-7.53 (6H, m, H Ar). C NMR spectrum, δ, ppm: 157.1; 148.6; 139.2; 136.9; 134.7; 129.6; 129.5;
129.4; 129.2; 116.9. Found, %: C 80.75; H 4.70; N 4.08. C23H16ClN. Calculated, %: C 80.81; H 4.72; N 4.10.
4-(3-Methoxyphenyl)-2,6-diphenylpyridine (3c). White solid. IR spectrum, ν, cm-1: 3034, 2936, 1596,
1547, 1486, 1444, 1398, 1285, 1255, 1204, 1171, 1037, 872, 775, 692. 1H NMR spectrum, δ, ppm (J, Hz): 8.36
(2H, d, J = 7.5, H Ar); 8.30 (2H, d, J = 7.6, H Ar); 8.14 (2H, s, H Ar); 7.59-7.50 (8H, m, H Ar); 7.46 (1H, d,
1688

J = 7.4, H Ar); 6.89 (1H, t, J = 7.4, H Ar); 3.70 (3H, s, OCH3). 13C NMR spectrum, δ, ppm: 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. Found, %: C 85.39; H 5.59; N 4.12.
C24H19NO. Calculated, %: C 85.43; H 5.68; N 4.15.
4-(2-Fluorophenyl)-2,6-diphenylpyridine (3d). White solid. IR spectrum, ν, cm-1: 3031, 1591, 1544,
1490, 1451, 1395, 1288, 1209, 1204, 1114, 1074, 1025, 878, 759, 694. 1H NMR spectrum, δ, ppm (J, Hz): 8.36
(2H, d, J = 7.5, H Ar); 8.31 (2H, d, J = 7.3, H Ar); 8.10 (2H, s, H Ar); 7.85 (1H, d, J = 6.9, H Ar); 7.49-7.45
(8H, m, H Ar); 7.07 (1H, d, J = 7.9, H Ar). Found, %: C 84.85; H 4.85; N 4.23. C23H16FN. Calculated, %:
C 84.90; H 4.96; N 4.30.
4-(5-Methylfuran-2-yl)-2,6-diphenylpyridine (3e). Light-brown solid. IR spectrum, ν, cm-1: 3058,
2927, 1591, 1548, 1495, 1447, 1394, 1237, 1122, 1204, 1114, 1075, 1027, 878, 758, 691. 1H NMR spectrum, δ,
ppm (J, Hz): 8.35 (2H, d, J = 7.7, H Ar); 8.27 (2H, d, J = 7.5, H Ar); 8.18 (2H, s, H Ar); 7.57-7.47 (7H, m,
13
H Ar); 6.34 (1H, d, J = 7.9, H Ar); 2.50 (3H, s, CH3). C NMR spectrum, δ, ppm: 155.3; 151.4; 146.1; 136.2;
129.3; 127.6; 127.4; 118.6; 107.8; 101.8; 14.1. Found, %: C 84.83; H 5.45; N 4.45. C22H17NO. Calculated, %: C
84.86; H 5.50; N 4.50.
4-(Furan-2-yl)-2,6-diphenylpyridine (3f). Light-brown solid. IR spectrum, ν, cm-1: 3058, 1606, 1541,
1487, 1454, 1414, 1244, 1158, 1073, 1010, 868, 772, 690. 1H NMR spectrum, δ, ppm (J, Hz): 8.30 (2H, d, J = 7.6,
H Ar); 8.20 (2H, d, J = 7.5, H Ar); 8.14 (2H, s, H Ar); 7.96 (1H, s, H Ar); 7.57-7.47 (7H, m, H Ar); 6.75 (1H, d,
13
J = 8.1, H Ar). C NMR spectrum, δ, ppm: 157.0; 151.4; 145.2; 139.6; 130.0; 129.8; 129.2; 127.2; 113.1; 113.0;
110.9. Found, %: C 84.78; H 5.02; N 4.68. C21H15NO. Calculated, %: C 84.82; H 5.08; N 4.71.
4-(4-Methylphenyl)-2,6-diphenylpyridine (3g). White solid. IR spectrum, ν, cm-1: 3034, 2936, 1598,
1
1548, 1442, 1398, 1286, 1254, 1203, 1170, 1036, 871, 775, 691. H NMR spectrum, δ, ppm (J, Hz): 8.35 (2H, d,
J = 7.3, H Ar); 8.29 (2H, d, J = 7.5, H Ar); 8.14 (2H, s, H Ar); 7.93 (2H, d, J = 7.8, H Ar); 7.58 (2H, t, J = 7.6, H Ar);
13
7.50 (2H, t, J = 7.6, H Ar); 7.47 (2H, t, J = 7.7, H Ar); 7.35 (2H, d, J = 7.8, H Ar); 2.48 (3H, s, CH3). C NMR
spectrum, δ, ppm: 157.0; 149.0; 139.4; 135.2; 130.1; 129.6; 129.2; 127.5; 127.4; 116.7; 21.3. Found, %: C 89.63;
H 5.93; N 4.30. C24H19N. Calculated, %: C 89.68; H 5.96; N 4.36.
4-(4-Methoxyphenyl)-2,6-diphenylpyridine (3h). White solid. IR spectrum, ν, cm-1: 3035, 2936, 1596,
1547, 1486, 1444, 1398, 1285, 1255, 1204, 1171, 1037, 750, 691. 1H NMR spectrum, δ, ppm (J, Hz): 8.38 (2H, d,
J = 7.6, H Ar); 8.30 (2H, d, J = 7.3, H Ar); 8.14 (2H, s, H Ar); 8.03 (2H, d, J = 7.1, H Ar); 7.50 (4H, t, J = 6.8, H
Ar); 7.48 (2H, d, J = 7.3, H Ar); 7.10 (2H, d, J = 7.1, H Ar); 3.82 (3H, s, OCH3). 13C NMR spectrum, δ, ppm: 160.8;
156.9; 149.5; 139.4; 130.4; 130.3; 129.6; 129.1; 127.4; 116.4; 115.0; 55.8. Found, %: C 85.41; H 5.64; N 4.11.
C24H19NO. Calculated, %: C 85.43; H 5.68; N 4.15.
N,N-Dimethyl-4-(2,6-diphenylpyridin-4-yl)benzenamine (3i). Yellow solid. IR spectrum, ν, cm-1:
1
3037, 2936, 1598, 1525, 1489, 1442, 1398, 1352, 1233, 1199, 1168, 1066, 1023, 818, 773, 695. H NMR
spectrum, δ, ppm (J, Hz): 8.35 (2H, d, J = 7.4, H Ar); 8.20 (2H, d, J = 7.6, H Ar); 8.10 (2H, s, H Ar); 7.92 (2H,
d, J = 6.8, H Ar); 7.55-7.44 (6H, m, H Ar); 6.83 (2H, d, J = 7.4, H Ar); 3.19 (6H, s, N(CH3)2). 13C NMR
spectrum, δ, ppm: 155.2; 152.0; 150.1; 136.2; 129.3; 128.3; 127.6; 127.4; 118.0; 114.8; 40.2. Found, %:
C 85.65; H 6.28; N 7.95. C25H22N2. Calculated, %: C 85.68; H 6.33; N 7.99.
2,6-Bis(4-chlorophenyl)-4-phenylpyridine (3j). White solid. IR spectrum, ν, cm-1: 3052, 1598, 1544,
1
1490, 1449, 1413, 1384, 1239, 1174, 1091, 1012, 829, 761, 694. H NMR spectrum, δ, ppm (J, Hz): 8.42 (2H,
d, J = 7.6, H Ar); 8.33 (2H, d, J = 7.5, H Ar); 8.23 (2H, s, H Ar); 8.04 (2H, d, J = 7.7, H Ar); 7.61-7.50 (7H, m,
H Ar). 13C NMR spectrum, δ, ppm: 155.8; 150.3; 137.9; 134.7; 129.9; 129.6; 127.9; 117.3. Found, %: C 73.36;
H 4.01; N 3.67. C23H15Cl2N. Calculated, %: C 73.42; H 4.02; N 3.72.
2,6-Bis(4-chlorophenyl)-4-(4-methoxyphenyl)pyridine (3k). White solid. IR spectrum, ν, cm-1: 3052,
1
2928, 1602, 1543, 1512, 1489, 1426, 1381, 1291, 1247, 1177, 1088, 1011, 824. H NMR spectrum, δ, ppm (J,
Hz): 8.40 (2H, d, J = 7.6, H Ar); 8.29 (2H, d, J = 7.6, H Ar); 8.17 (2H, s, H Ar); 7.60 (2H, d, J = 6.8, H Ar);
7.50 (2H, d, J = 6.8, H Ar); 7.48 (2H, d, J = 7.3, H Ar); 7.12 (2H, d, J = 7.3, H Ar); 3.84 (3H, s, OCH3).
13C NMR spectrum, δ, ppm: 161.1; 155.8; 134.3; 132.9; 130.2; 129.3; 129.0; 128.4; 118.0; 114.8; 50.80. Found,
%: C 70.91; H 4.18; N 3.41. C24H17Cl2NO. Calculated, %: C 70.95; H 4.22; N 3.45.
1689

2,6-Bis(4-chlorophenyl)-4-(2-methoxyphenyl)pyridine (3l). White solid. IR spectrum, ν, cm-1: 3049,
2948, 1601, 1542, 1512, 1491, 1411, 1383, 1263, 1245, 1175, 1126, 1090, 1014, 827, 749. 1H NMR spectrum,
δ, ppm (J, Hz): 8.32 (2H, d, J = 7.6, H Ar); 8.20 (2H, d, J = 7.4, H Ar); 8.04 (2H, s, H Ar); 7.63 (1H, d, J = 7.9,
H Ar); 7.55-7.53 (4H, m, H Ar); 7.45 (1H, t, J = 7.2, H Ar); 7.22 (1H, d, J = 7.2, H Ar); 7.09 (1H, t, J = 7.9,
H Ar); 3.84 (3H, s, OCH3). 13C NMR spectrum, δ, ppm: 161.1; 155.8; 134.3; 132.9; 130.2; 129.3; 129.0; 128.4;
118.0; 114.8; 55.8. Found, %: C 71.03; H 4.18; N 3.51. C24H17Cl2NO. Calculated, %: C 70.95; H 4.22; N 3.45.
2,6-Bis(4-chlorophenyl)-4-(3-methoxyphenyl)pyridine (3m). White solid. IR spectrum, ν, cm-1: 3062,
2932, 1595, 1546, 1490, 1460, 1411, 1383, 1265, 1211, 1176, 1089, 1012, 833, 787. 1H NMR spectrum, δ, ppm
(J, Hz): 8.40 (2H, d, J = 7.5, H Ar); 8.31 (2H, d, J = 7.4, H Ar); 8.20 (2H, s, H Ar); 7.62 (2H, d, J = 7.6, H Ar);
7.55-7.52 (4H, m, H Ar); 7.42 (1H, d, J = 7.3, H Ar); 7.05 (1H, d, J = 7.4, H Ar); 3.88 (3H, s, OCH3). 13C NMR
spectrum, δ, ppm: 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. Found, %: C 70.93; H 4.20; N 3.48. C24H17Cl2NO. Calculated, %: C 70.95; H 4.22; N 3.45.
2,6-Bis(4-chlorophenyl)-4-(2-fluorophenyl)pyridine (3n). White solid. IR spectrum, ν, cm-1: 3061,
1
1599, 1543, 1490, 1460, 1411, 1383, 1265, 1211, 1176, 1089, 1012, 833, 787. H NMR spectrum, δ, ppm (J,
Hz): 8.38 (2H, d, J = 7.2, H Ar); 8.30 (2H, d, J = 7.5, H Ar); 8.18 (2H, s, H Ar); 7.59-7.55 (6H, m, H Ar);
7.35-7.43 (2H, m, H Ar). 13C NMR spectrum, δ, ppm: 116.0; 118.0; 124.9; 129.0; 129.3; 130.9; 132.8; 134.3;
152.0; 155.2; 158.2. Found, %: C 70.11; H 3.52; N 3.60. C23H14Cl2FN. Calculated, %: C 70.07; H 3.58; N 3.55
2,6-Bis(4-chlorophenyl)-4-(furan-2-yl)pyridine (3o). White solid. IR spectrum, ν, cm-1: 3061, 1609,
1544, 1488, 1422, 1374, 1265, 1216, 1176, 1090, 1012, 826, 736. 1H NMR spectrum, δ, ppm (J, Hz): 8.38 (2H,
d, J = 7.6, H Ar); 8.30 (2H, d, J = 7.5, H Ar); 8.21 (2H, s, H Ar); 7.96 (1H, s, H Ar); 7.68-7.52 (5H, m, H Ar);
13
6.76 (1H, d, J = 8.1, H Ar). C NMR spectrum, δ, ppm: 155.3; 154.0; 146.1; 142.9; 134.3; 132.9; 129.3; 129.0;
118.0; 107.0; 105.0. Found, %: C 68.86; H 3.54; N 3.75. C21H13Cl2NO. Calculated, %: C 68.87; H 3.58; N 3.82.
4-[2,6-Bis(4-chlorophenyl)pyridin-4-yl]-N,N-dimethylbenzenamine (3p). Yellow solid. IR spectrum, ν,
1
cm-1: 3061, 2932, 1597, 1527, 1432, 1359, 1265, 1201, 1189, 1090, 945, 814. H NMR spectrum, δ, ppm (J,
Hz): 8.38 (2H, d, J = 7.5, H Ar); 8.31 (2H, d, J = 7.3, H Ar); 8.12 (2H, s, H Ar); 7.95 (2H, d, J = 6.8, H Ar);
7.56 (2H, d, J = 7.5, H Ar); 7.52 (2H, d, J = 7.5, H Ar); 6.84 (2H, d, J = 6.8, H Ar); 2.98 (6H, s, N(CH3)2). 13C
NMR spectrum, δ, ppm: 155.2; 152.0; 150.1; 134.3; 132.9; 129.0; 128.3; 127.4; 118.0; 114.8; 40.2. Found, %:
C 71.55; H 4.78; N 6.63. C25H20Cl2N2. Calculated, %: C 71.60; H 4.81; N 6.68.
We gratefully acknowledge financial support from the Research Council of the University of Kashan,
grant No. 256722/28.
REFERENCES
1.
2.
3.
D. Nagargoje, P. Mandhane, S. Shingote, P. Badadhe, and C. Gill, Ultrason. Sonochem., 19, 94 (2012).
R. D. Allen and G. A. R. Johnston, Med. Res. Rev., 3, 91 (1983).
E. C. Constable, C. E. Housecroft, M. Neuburger, D. Phillips, P. R. Raithby, E. Schofield, E. Sparr,
D. A. Tocher, M. Zehnder, and Y. Zimmermann, J. Chem. Soc., Dalton Trans., 2219 (2000).
B. Y. Kim, J. B. Ahn, H. W. Lee, S. K. Kang, J. H. Lee, J. S. Shin, S. K. Ahn, C. I. Hong, and
S. S. Yoon, Eur. J. Med. Chem., 39, 433 (2004).
4.
5.
I. J. Enyedy, S. Sakamuri, W. A. Zaman, K. M. Johnson, and S. Wang, Bioorg. Med. Chem. Lett., 13,
513 (2003).
6.
7.
8.
9.
F. Kröhnke, Synthesis, 1 (1976).
C. Chiu, Z. Tang, and J. W. Ellingboe, J. Comb. Chem., 1, 73 (1999).
X. Q. Huang, H. X. Li, J. X. Wang, and X. F. Jia, Chin. Chem. Lett., 16, 607 (2005).
Y. M. Ren and C. Cai, Monatsh. Chem., 140, 49 (2009).
1690

10.
11.
M. M. Heravi, K. Bakhtiari, Z. Daroogheha, and F. F. Bamoharram, Catal. Commun., 8, 1991 (2007).
L. Nagarapu, Aneesa, R. Peddiraju, and S. Apuri, Catal. Commun., 8, 1973 (2007).
A. Davoodnia, M. Bakavoli, R. Moloudi, M. Khashi, and N. Tavakoli-Hoseini, Monatsh. Chem., 141,
867 (2010).
12.
13.
J. Safari, S. H. Banitaba, and S. Dehghan Khalili, Chin. J. Catal., 32, 1850 (2011).
J. Safari, S. Dehghan Khalili, M. Rezaei, S. H. Banitaba, and F. Meshkani, Monatsh. Chem., 141, 1339
(2010).
14.
15.
16.
17.
18.
19.
20.
S. Banerjee and G. Sereda, Tetrahedron Lett., 50, 6959 (2009).
M. Reza, M. Shafiee, R. Moloudi, and M. Ghashang, APCBEE Procedia, 1, 221 (2012).
J. Guo, H. Lou, H. Zhao, X. Wang, and X. Zheng, Mater. Lett., 58, 1920 (2004).
E. Navaei Alvar, M. Rezaei, and H. Navaei Alvar, Powder Technol., 198, 275 (2010).
N. Jeong, J. Yeo, and K. Song, Material. Lett., 109, 34 (2013).
D. Nagargoje, P. Mandhane, S. Shingote, P. Badadhe, and C. Gill, Ultrason. Sonochem., 19, 94 (2012).
B. Maleki, D. Azarifar, H. Veisi, S. F. Hojati, H. Salehabadi, and R. N. Yami, Chin. Chem. Lett., 21,
1346 (2010).
21.
22.
M. Adib, H. Tahermansouri, S. A. Koloogani, B. Mohammadi, and H. R. Bijanzadeh, Tetrahedron Lett.,
47, 5957 (2006).
J. Safari and Z. Zarnegar, Ultrason. Sonochem., 20, 740 (2013).
1691