Microwave assisted one-pot pseudo four-component synthesis of 2,4,6-trisubstituted pyridines using γ-MnO2 nanoparticles

Article abstract of DOI:10.1007/s00706-016-1698-6

This work described an efficient, one-pot pseudo four-component synthesis of 2,4,6-triarylpyridines. This reaction was performed under microwave irradiation and solvent-free conditions in the presence of γ-MnO₂ nanoparticles. Herein 2,4,6-triarylpyridines were synthesized via a simple reaction between benzyl alcohols, acetophenone, and ammonium acetate in the presence of γ-MnO₂ nanoparticles in good to excellent yields. Eco friendly, excellent yields of the product, short reaction times, inexpensive and readily available starting material are the main advantages of this method. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-016-1698-6

Monatsh Chem
DOI 10.1007/s00706-016-1698-6
ORIGINAL PAPER
Microwave assisted one-pot pseudo four-component synthesis
of 2,4,6-trisubstituted pyridines using c-MnO2 nanoparticles
Bagher Mohammadi1
Received: 26 December 2015 / Accepted: 7 February 2016
Ó Springer-Verlag Wien 2016
Abstract This work described an efficient, one-pot
pseudo four-component synthesis of 2,4,6-triarylpyridines.
This reaction was performed under microwave irradiation
and solvent-free conditions in the presence of c-MnO2
nanoparticles. Herein 2,4,6-triarylpyridines were synthe-
sized via a simple reaction between benzyl alcohols,
acetophenone, and ammonium acetate in the presence of c-
MnO2 nanoparticles in good to excellent yields. Eco
friendly, excellent yields of the product, short reaction
times, inexpensive and readily available starting material
are the main advantages of this method.
Introduction
The nitrogen containing heterocyclic systems are one of the
most important motifs in natural products and many syn-
thetic compounds of pharmaceutical interest. Pyridine
heterocycles are part of the most interesting heterocyclic
organic compounds which represent chemical and phar-
macological interest such as antiviral [1], antitumor [2],
anticancer [3, 4], antibacterial [5, 6], and other biological
activity [7–19]. Pyridines and their nucleoside analog
showed intense cytotoxicity against several human cancer
cell [20], influential and selective farnesyltransferase
inhibitions [21], and inhibitors of HCV NS5B polymerase
inhibitions [22], as well as antimicrobial [23] and
antimycobacterial activities [24].
Graphical abstract
O
O2
Ar'
CH3
NH4OAc
H
O
O
H
H
Transition metals oxide nanoparticles such as MnO2
nanoparticles could catalyze organic reactions efficiently in
a mild and environment friendly manner [25–31]. Use of
minimum of reagent and energy, high yield of products
easy reaction, simple work-up procedure and minimize
byproduct, efficiency and recyclability are the main
advantages of these catalysts. In recent decades many
synthetic methods have been developed for the preparation
of MnO2 nanoparticles for example: reduction of potassium
permanganate with aniline at ambient condition [32], use
of hydrothermal method with longer hydrothermal reaction
time [33, 34], by the incipient wetness impregnation
method [2], by hydrothermal treatment and sequential
thermal decomposition without employing any template or
surfactant [35], via a facile quick-precipitation procedure at
a low temperature (about 83 °C) without using any tem-
plates or surfactants [36] and by an sodium dodecyl
sulphate (SDS)-assisted hydrothermal treatment method
[37] or by reaction between MnSO4, (NH4)2S2O8, and
Na2SO4 [38].
Ar'
CH3
Ar
Ar
N
O2
MW
600 watts
−
γ
Mn
O2
Ar'
Ar'
nano
3 min
=
nano γ-MnO2
Keywords Multi-component reaction Á Microwave Á
Nano c-MnO2 Á Triarylpyridine Á Benzyl alcohols
& Bagher Mohammadi
Bagher.mohammadi@yahoo.com
1
Department of Chemistry, Payame Noor University, Tehran,
P. O. Box 19395-3697, Iran
123

B. Mohammadi
Scheme 1
Table 1 Pseudo four-component synthesis of 2,4,6-trisubstituted
pyridines 3 in the presence of nano c-MnO2
As part of our study aimed at developing efficient and
straightforward methods to prepare organic compounds
from readily available building blocks and simple catalyst
[39–45], herein we report a simple and efficient method for
the synthesis of 2,4,6-trisubstituted pyridines using c-
MnO2 nanoparticles as catalyst, under microwave and
solvent-free conditions (Scheme 1).
Product
Ar
Ar0
Yielda/%
3a
3b
3c
3d
3e
3f
3g
3h
3i
Ph
Ph
95
78
86
83
84
79
78
80
87
85
89
Ph
4-MePh
2-MePh
4-OMePh
4-Cl-Ph
4-F-Ph
4-NO2-Ph
4-Me-Ph
4-Cl-Ph
4-OMePh
Ph
Ph
Ph
Ph
Ph
Results and discussion
Ph
4-Me-Ph
4-Me-Ph
4-Me-Ph
4-Me-Ph
Aryl alcohol, acetophenone, and ammonium acetate in the
presence of air and nano c-MnO2 under microwave irra-
diation produced 2,4,6-triphenylpyridines 3a–3k in
78–95 % yields (Table 1). This reaction was carried out as
a pseudo four-component reaction under microwave and
solvent-free conditions.
3j
3k
a
Isolated yields
1
ZnO and ZnFe2O4 nanoparticles to the reaction yields were
tested. Finally, the reaction temperature was optimized.
The results of these experiments are displayed in the
Tables 2 and 3. All of these tests were done in solvent-free
conditions. The effect of microwave power to the reaction
yields was tested and indicated in Table 2. As can be seen
from Table 2, at low and high temperatures, the reaction
yields were low. It may be because of low reaction rate and
being incomplete at low temperatures and formation of the
other byproducts at high powers. According to Tables 2
and 3, the highest yield was obtained in the presence of
10 mol% of nano c-MnO2 under microwave irradiation
600 W power for 3 min (Tables 2, 3).
The H NMR spectrum of 3f exhibited two triplets at
d = 7.45 and 7.54 ppm due to the 8 CH groups, a doublet
3
of doublet signal at 7.74 with JFH = 8.7 and
3JHH = 7.2 Hz is due to the two CH groups and one singlet
at 7.85 ppm is due to the two CH groups of pyridine ring.
One distinctive doublet at 8.22 ppm with J = 7.2 Hz is due
to the four ortho CH of phenyl groups.
A mechanistic pathway for the reaction is provided in
Scheme 2, it is reasonable to assume that the first step may
involve oxidation of benzyl alcohol 1 to corresponding
nano c-MnO2 activated aryl aldehyde 4 by O2 and then
condensation with nano c-MnO2 activated acetophenone
will form nano c-MnO2 activated chalcone 5. The reaction
of an ammonia molecule with a nano c-MnO2 activated
chalcone 5 and Michael addition of another ammonia to a
second nano c-MnO2 activated chalcone 5 leading to 2,4-
diaryl-1-azadiene 6 and 1:1 adduct 7. Azadiene 6 and
adduct 7 probably undergo a formal [4?2] cycloaddition
reaction to form tetrahydropyridine intermediate 8. Elimi-
nation of OH- and nano c-MnO2 gives dihydropyridine
intermediate 9. Finally oxidative removal of benzylamin
forms 2,4,6-triarylpyridine 3 (Scheme 2).
Conclusion
In conclusion, we have developed a simple and efficient
synthesis of 2,4,6-trisubstituted pyridines in the presence of
c-MnO2 nanoparticles under microwave irradiation in
solvent-free conditions. Excellent yields of products, short
reaction times and mild reaction conditions, use of simple
chemicals, eco-friendly, inexpensive and readily available
starting chemicals, and high atomic economy are the main
advantages of this method.
To optimize this reaction, the 3a preparation was
selected as a model, then the effects of nano c-MnO2
amounts and the effects of the other Lewis acids such as
123

Microwave assisted one-pot pseudo four-component synthesis of 2,4,6-trisubstituted pyridines…
Scheme 2
Table 2 Synthesis of 3a in the presence of various nano-catalysts under
microwave irradiation power 600 W for 3 min
Experimental
Entry Nano ZnFe2O4/
mol %
Nano a-Fe2O3/
mol %
Nano c-MnO2/
mol %
Yielda/
%
All starting materials and solvents were obtained from
Merck (Germany) and Fluka (Switzerland) and were used
without further purification. c-MnO2 nanoparticles were
synthesized via dissolving MnSO4, (NH4)2S2O8, and Na2-
SO4 with a molar ratio of 1:1:1 in deionized water at room
temperature [36]. To confirm nano structure of nano c-
MnO2 the SEM image were carried out (Fig. 1).
1
2
0
0
0
0
0
1
6
17
23
40
66
85
95
95
35
80
78
3
0
0
2
4
0
0
4
5
0
0
6
6
0
0
8
The progress of the reaction was monitored by TLC.
7
0
0
10
12
10b
0
Melting points were measured on an Electro-thermal 9100
1
8
0
0
apparatus. H NMR and 13C NMR spectra (CDCl3) were
9
0
0
recorded on a BRUKER DRX-300 AVANCE spectrometer
at 300.1 and 75.4 MHz, respectively. Elemental analyses for
C, H and N were performed using a CHN-O-Rapid analyzer
and the instrument model was Eager 300 for EA11112. The
experiments were performed using a microwave oven
10
11
a
10
0
0
10
0
Isolated yields
b
Commercial MnO2
123

B. Mohammadi
(1 mmol), and 0.077 g ammonium acetate (1 mmol) in the
presence of 0.001 g c-MnO2 nanoparticles (0.010 mmol)
then heating them under microwave irradiation at 600 W
for 3 min in solvent-free condition. Reaction monitoring by
TLC clearly indicated formation of the corresponding
2,4,6-triarylpyridines. Upon completion, the reaction mix-
ture was cooled to room temperature and c-MnO2
nanoparticles were separated by dissolving the reaction
mixture in boiling ethanol and then it was centrifuged.
After over flowing the solution the titled product was
separated as a light yellow crystal in solution. The solvent
was removed and the product was recrystallized from n-
hexane–EtOAc (1:1). The structures of the isolated prod-
ucts 3a–3k were confirmed by their 1H and 13C NMR
spectral data and their melting point values [39].
Table 3 Synthesis of 3a at various microwave powers and time in
the presence of 10 mol % nano c-MnO2
Entry
Microwave power/W
Time/min
Yielda/%
1
2
3
4
5
6
7
8
9
a
100
180
300
450
600
600
600
900
900
2
2
2
2
2
3
4
2
3
23
35
46
54
67
95
93
72
65
Isolated yields
Acknowledgements I gratefully acknowledge the financial support
from the Research Council of Payame Noor University (PNU),
Tehran-Iran.
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