Beruflich Dokumente
Kultur Dokumente
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, P.O. Box 87317-51167, Islamic Republic of Iran
Institute of Nano Science and Nano Technology, University of Kashan, Kashan, P. O. Box. 8731751167, Islamic Republic of Iran
KEYWORDS
Multicomponent reactions;
Nanoparticles;
Calcium oxide;
Poly functionalized
pyridines;
Heterogeneous catalyst;
One-pot.
1. Introduction
Multicomponent reactions (MCRs) are special types of synthetically useful organic reactions, in which three or more
various substrates react to give a final product in a one-pot
procedure [1]. Clearly, for multi-step synthetic pathways, a
number of reactions and purification steps are the most important criteria for the efficiency and ability of the process, and
should be as low as possible [2]. MCRs are powerful devices in
novel drug discovery procedures and allow the fast, automated
and high-throughput generation of organic compounds [3]. The
formation of CN, CO and CS bonds by MCRs is usual in numerous compounds with pharmaceutical, biological and material properties [4].
Because of significant biological and physiological activities, synthesis of pyridines has attracted much attention
Corresponding author. Tel.: +98 361 5912385; fax: +98 361 5912397.
E-mail address: safaei@kashanu.ac.ir (J. Safaei-Ghomi).
Peer review under responsibility of Sharif University of Technology.
in recent years [57]. Polyfunctionalized pyridine derivatives, known as medicinally privileged scaffolds, can inhibit
MAPK-activated PK-26 [8] and modulate androgen receptor
functions [9]. Among them, 2-amino-3,5-dicyano-6-sulfanyl
pyridines, in particular serve as a privileged scaffold due to
their potential therapeutic applications in the treatment of urinary incontinence [10], HBF infections [11], Creutzfeldt-Jacob
disease, Parkinsons disease, hypoxia/ischemia, asthma, kidney disease, epilepsy and cancer [1214]. Also, a 2-amino3,5-dicyano-6-sulfanyl pyridines skeleton is often used as an
anti-prion [15], anti-hepatitis B virus and anti-bacterial [16].
Consequently, synthesis of highly functionalized pyridine
derivatives, with the aim of developing new drug molecules,
has been an active area of research. Recently, much attention has been paid to the development of new methodologies for the preparation of pyridines. The synthetic routes for
preparation of substituted pyridines, mainly, are the Mannich
reaction of iminium salts and aldehydes [17], azaelectrocyclization of azatrienes [18], conversion of ketene dithioacetals
to substituted pyridines [19], reaction of 3-siloxy-1-aza1,3-butadiens and 2H-1,4-oxazinones with acetylenes [20],
conversion of conjugated oximes under Vilsmeier conditions [21], cycloisomerization of 3-azadienynes [22], VilsmeierHaack reaction of -hydroxyketenedithioacetals [23], and
the Diels-Alder cycloadditions of oximinosulfonates [24]. One
1026-3098 2013 Sharif University of Technology. Production and hosting by Elsevier B.V. Open access under CC BY-NC-ND license.
http://dx.doi.org/10.1016/j.scient.2012.12.037
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551
: 2.40 (s, 3H, CH3 ), 5.50 (s, 2H, NH2 ), 7.267.28 (d, J = 7.8 Hz,
2H, Ar-H), 7.437.45 (d, J = 8 Hz, 2H, Ar-H), 7.667.68 (d, J =
7.8 Hz, 2H, Ar-H), 8.39-8.41 (d, J = 8 Hz, 2H, Ar-H); 13 C NMR
(CDCl3 , 100 MHz) : 18.9, 86.8, 96.2, 115.1, 116.9, 125.3, 131.3,
132.9, 134.1, 134.9, 135.5, 136.2, 137.3, 156.1, 158.2, 165.1.;
Anal. Calcd for C20 H13 N5 O2 S : C, 62.01; H, 3.38; N, 18.08%.
Found: C, 61.85; H, 3.26; N, 18.16%.
2-Amino-4-(4-cyanophenyl)-6-(4-methylphenylsulfanyl)3,5-pyridinedicarbonitrile (4o)
White solid; mp 272 C; IR (KBr) v : 3479, 3352, 3215, 2218,
1634, 1551, 1498, 1256, cm1 ; 1 H NMR (CDCl3 , 400 MHz) :
2.41 (s, 3H, CH3 ), 5.50 (s, 2H, NH2 ), 7.287.30 (d, J = 8 Hz, 2H,
Ar-H), 7.377.51 (m, 4H, Ar-H), 7.717.73 (d, J = 8 Hz, 2H, ArH); 13 C NMR (CDCl3 , 100 MHz) : 87.2, 94.5, 114.9, 115.8, 128.1,
130.5, 131.5, 133.8, 134.1, 134.4, 135.7, 136.5, 155.4, 156.3,
165.1.; Anal. Calcd for C21 H13 N5 S : C, 68.65; H, 3.57; N, 19.06%.
Found: C: 68.78; H, 3.44; N, 18.95%.
3. Results and discussion
Initially, in order to investigate the morphology and particle
size of prepared CaO nanoparticles, a SEM image of CaO NPs is
presented in Figure 1. These results show that spherical calcium
oxide nanoparticles were obtained with particle size 3040 nm
using the thermal-decomposition method.
The XRD pattern of CaO nanoparticles has been shown in
Figure 2. All reflection peaks in Figure 2 can be readily indexed
to a pure cubic phase of CaO with a Fm-3m space group (JCDPS
No. 77-2376). The crystallite size diameter (D) of the CaO NPs
has been calculated by the DebyeScherrer equation (D =
K/ cos ), where FWHM (full-width at half-maximum or
half-width) is in radian and is the position of the maximum
of the diffraction peak. K is the so-called shape factor, which
usually takes a value of about 0.9, and is the X-ray wavelength
(1.5406 for Cu K ). The average crystallite size of CaO has been
found to be 35 nm.
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Table 2: One-pot synthesis of 2-Amino-4-phenyl-6-(phenylsulfanyl)-3,5pyridinedicarbonitrile (4a) in various solvents.a
Entrry
1
2
3
4
5
Toluene
Acetonitrile
Ethanol
Water
Water/Ethanol
a
b
Table
1:
Preparation
of
2-Amino-4-phenyl-6-(phenylsulfanyl)
-3,5-pyridinedicarbonitrile (4a) in different catalysts.a
Entrry
1
2
3
4
5
6
7
Catalyst
CuO NPs
Mn3 O4 NPs
MgO NPs
NiO NPs
SiO2 NPs
CaO NPs
CaO bulk
Time (min)
140
150
130
140
180
100
260
Yields
(%)b
60
55
70
65
40
85
40
a
1 mmol of benzaldehyde, 2.2 mmol of malononitrile and 1 mmol of
thiophenol under reflux conditions.
b
Isolated yields.
Solvent
Time (min)
240
180
120
140
100
Yields
(%)b
35
50
70
60
85
Reflux conditions.
Isolated yields.
J. Safaei-Ghomi et al. / Scientia Iranica, Transactions C: Chemistry and Chemical Engineering 20 (2013) 549554
553
Ar
Ph
m-MeC6 H4
p-MeC6 H4
m-HOC6 H4
p-HOC6 H4
p-MeOC6 H4
m-O2 NC6 H4
p-O2 NC6 H4
p-ClC6 H4
p-BrC6 H4
Ph
p-MeC6 H4
p-MeOC6 H4
p-O2 NC6 H4
p-NCC6 H4
Ar
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
p-MeC6 H4
p-MeC6 H4
p-MeC6 H4
p-MeC6 H4
p-MeC6 H4
Product
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
Time (min)
100
120
140
130
145
150
110
85
80
90
110
115
130
80
95
Yield (%)
85
85
90
80
85
92
78
75
80
80
82
80
85
70
78
mp (C)
218220
277279
208210
265267
314316
240242
218220
288290
221223
254256
248250
222224
229231
301303
272274
Lit. mp (C)
(220221)29
(278280)29
(206207)32
(315317)32
(241244)29
(219220)29
(289290)32
(221222)32
(255257)29
(246249)35
(230233)35
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