Application of novel nanostructured dinitropyrazine molten salt catalyst for the synthesis of sulfanylpyridines via anomeric based oxidation

Article abstract of DOI:10.1007/s13738-017-1123-z

1,4-Dinitropyrazine-1,4-diium trinitromethanide {[1,4-pyrazine-NO₂][C(NO₂)₃]₂} as a novel nanostructured molten salt (NMS) catalyzed the synthesis of 2-amino-3,5-dicarbonitrile-6-sulfanylpyridine derivatives via

Full text of DOI:10.1007/s13738-017-1123-z

J IRAN CHEM SOC
DOI 10.1007/s13738-017-1123-z
ORIGINAL PAPER
Application of novel nanostructured dinitropyrazine molten salt
catalyst for the synthesis of sulfanylpyridines via anomeric based
oxidation
Mohammad Ali Zolfgol1 · Maliheh Safaiee2 · Bahar Ebrahimghasri1 ·
Saeed Baghery1 · Saied Alaie1 · Mahya Kiafar1 · Avat Taherpour3,4 · Yadollah Bayat5 ·
Asiye Asgari5
Received: 10 November 2016 / Accepted: 13 April 2017
© Iranian Chemical Society 2017
Abstract 1,4-Dinitropyrazine-1,4-diium trinitromethanide
{[1,4-pyrazine-NO2][C(NO2)3]2} as a novel nanostructured
molten salt (NMS) catalyzed the synthesis of 2-amino-
3,5-dicarbonitrile-6-sulfanylpyridine derivatives via the
one-pot three-component condensation reaction between
several aromatic aldehyde, malononitrile and benzyl mer-
captan at room temperature under solvent-free conditions.
The synthesized NMS catalyst was fully characterized
that the proposed mechanism has potential for entering into
the graduate text book in the future.
Keywords Anomeric based oxidation · 2-Amino-3,5-
dicarbonitrile-6-sulfanylpyridine · 1,4-Dinitropyrazine-1,4-
diium trinitromethanide {[1,4-pyrazine-NO2][C(NO2)3]2} ·
Nanostructured molten salt · Theoretical study
1
by FTIR, H NMR, 13CNMR, mass, thermal gravimetric,
X-ray diffraction patterns, scanning electron microscopy
and transmission electron microscopy analysis. The major
advantages of described methodology are mildness, ease of
separation, good yields and short reaction times. A rational
mechanism was suggested for the fnal step of the 2-amino-
3,5-dicarbonitrile-6-sulfanylpyridines synthesis. We think
Introduction
The pyridine ring plays a major role in various biological
processes, most notably in the oxidation/reduction cofac-
tors such as NADH, NADPH, NADH and NAD+; the vita-
min niacin is required for its biosynthesis [1, 2]. Pyridoxine
(vitamin B6) plays a key role as the coenzyme in transami-
nases enzymatic behavior. Nicotine, a highly toxic alka-
loid, is the major active component in tobacco and the most
addictive drug known. To the best of our knowledge, het-
erocyclic derivatives with pyridine moiety display pharma-
cological activities such as isoniazide as an antituberculosis
agent and sulfapyridine one of the sulfonamide antibacte-
rials. Herbicides such as paraquat and fungicides (davicil)
have also pyridine moieties in their structures (Fig. 1) [3].
3,5-Dicyanopyridines have been used as intermedi-
ates in the synthesis of pyrido[2,3-d]pyrimidines as
antihistaminic agents [4], pyridothieno- and pyrido-
dithienotriazines endowed with antihistaminic and cyto-
toxic activity [5], 3,4,6-triazabenz[d,e]anthracene and
3,4,6,9-tetrazabenz[d,e]anthracene that are DNA inserting
agents [6] and acyclo-3-deazapyrimidine S-nucleosides that
are active toward HIV [7]. Various kinds of reagent systems
such as Et2NH/C2H5OH/r.t. [8], microporous molecular
sieves (zeolites)/H2O [9], CaO NPs/50 °C [10], CuI NPs/
C2H5OH/H2O/refux [11], Et3N/C2H5OH/refux [12, 13],
Electronic supplementary material The online version of this
article (doi:10.1007/s13738-017-1123-z) contains supplementary
material, which is available to authorized users.
* Mohammad Ali Zolfgol
zolf@basu.ac.ir; mzolfgol@yahoo.com
* Maliheh Safaiee
azalia_s@yahoo.com
1
Department of Organic Chemistry, Faculty of Chemistry, Bu-
Ali Sina University, Hamedan 6517838683, Iran
2
Department of Medicinal Plants Production, Nahavand
University, Nahavand 6593139565, Iran
3
Department of Organic Chemistry, Razi University, P.O. Box:
67149-67346, Kermanshah, Iran
4
Medical Biology Research Center, Kermanshah University
of Medical Sciences, Kermanshah, Iran
5
Faculty of Chemistry and Chemical Engineering, Malek
Ashtar University of Technology, Tehran, Iran
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J IRAN CHEM SOC
On the other hand, we know that the anomeric effect is
a fundamental concept in organic chemistry. It includes an
important interaction between the lone pair electrons of
heteroatom and the antibonding orbitals of adjacent bonds,
which can control reaction mechanism in appropriate sys-
tems [22, 23]. In this regard, we have introduced a new
term entitled “anomeric based oxidation” (ABO) for unu-
sual hydride releasing from carbon [24–27]. With this aim,
we decided to join both of these research areas for the sys-
tematic development of ABO concept in organic synthesis.
Experimental
General
Fig. 1 Some bioactive compounds with pyridine moiety
The materials were purchased from Merck, Fluka and
Sigma-Aldrich companies and were applied without any
additional purifcation. All reactions were checked out by
thin-layer chromatography (TLC) on gel F254 plates. (1H
NMR 400 MHz and 13C NMR 100 MHz) spectroscopy in
pure deuterated DMSO with tetramethylsilane (TMS) as an
internal standard. The prepared NMS catalyst was identi-
SnO NPs/C2H5OH/refux [14], borax/C2H5OH/refux [15]
and silica nanoparticle [16] have been used to catalyze
these reactions.
Molten salts (MSs) and ionic liquids (ILs) are both liq-
uids mainly composed of ions. Mainly, ILs and MSs are
defned as those fused salts with a melting point less than
100 °C, with salts with higher melting points mentioned to
as molten salts [17]. Combination of various cations and
anions allows preparing a wide range of ILs and/or MSs for
different purposes. Thus, the terms “designer” and “task-
specifc” ILs and MSs have been applied for these classes
of compounds [18, 19]. Very recently, Atkin et al. [20] have
extensively reviewed the chemical and physical proper-
ties of nanostructured ILs and MSs. Nowadays, energetic
materials have attracted interest [21]; therefore, we decided
to design and synthesize a novel, task-specifc and bifunc-
tional energetic salt. Thus, 1,4-dinitropyrazine-1,4-di-
1
fed by FTIR, H NMR, 13CNMR, mass, X-ray diffraction
patterns (XRD), scanning electron microscopy (SEM),
transmission electron microscopy (TEM) and thermogravi-
metric (TG) analysis. X-ray diffraction (XRD) patterns of
catalyst were achieved on a APD 2000, Ital structure with
Cu K_ radiation (k = 0.1542 nm) operating at 50 kV and
20 mA in a 2-h range of 5°–90° with step size 0.01° and
time step 1.0 s to assess the crystallinity of the catalyst.
Fourier transform-infrared spectra of the samples were
recorded on a Perkin-Elmer FTIR spectrometer 17,259
using KBr disks. Thermogravimetric analyses by a Perkin-
Elmer TGA were attained on catalyst. The SEM analyses
were done with a TESCAN/MIRA with a maximum accel-
eration voltage of the primary electrons between 10 and
15 kV. Transmission electron microscopy and TEM meas-
urements were examined on a Philips CM10 analyzer.
ium
trinitromethanide{[1,4-pyrazine-NO2][C(NO2)3]2}
as a unique and safe energetic nanostructured molten salt
(NMS) was prepared (Scheme 1).
Scheme 1 Synthesis of
1,4-dinitropyrazine-1,4-diium
trinitromethanide {[1,4-pyra-
zine-NO2][C(NO2)3]2}
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J IRAN CHEM SOC
General procedure for the synthesis
of 1,4-dinitropyrazine-1,4-diium trinitromethanide
{[1,4-pyrazine-NO2][C(NO2)3]2} as nanostructured
molten salt catalyst
from the other materials (the reaction mixture was insoluble
in water and the catalyst was soluble in water). The organic
layer was removed, and the crude product was purifed by
recrystallization from ethanol/water (10:1) to yield pure
products. More purifcation can be happened by recrystalli-
zation in n-hexane. In this investigation, NMS catalyst was
recycled and reused for fve times without important loss of
its catalytic activity (spectral data analysis for compounds
refers to supplementary data).
To a round-bottomed fask (50 mL) containing a solution of
pyrazine (3 mmol; 0.240 g) in CH3CN (5 mL), was drop-
wise added tetranitromethane (6 mmol; 1.176 g) and stirred
over a period of 120 min at room temperature. Then, the
solvent was removed through distillation under reduced
pressure and the product was dried under vacuum at 80 °C
for 120 min. The orange solid product was fltered, washed
with diethyl ether for three times and then dried under
vacuum conditions. {[1,4-Pyrazine-NO2][C(NO2)3]2} was
Results and discussion
In continuation of our previous investigation related to
the knowledge-based development of task-specifc nano-
structured ionic liquids (NILs), molten salts (NMSs)
and their applications in multi-component reactions
(MCRs) [28–33], we wish to report the synthesis of a
novel task-specifc nanostructured molten salt (NMS),
namely 1,4-dinitropyrazine-1,4-diium trinitromethanide
{[1,4-pyrazine-NO2][C(NO2)3]2} in acetonitrile at room
temperature (Scheme 1). The catalytic application of the
described NMS in the synthesis of 2-amino-3,5-dicarboni-
trile-6-sulfanylpyridines via the one-pot condensation reac-
tion between aromatic aldehydes, malononitrile and benzyl
mercaptan at room temperature and solvent-free conditions
was examined (Scheme 2).
1
characterized by FTIR, H NMR, 13CNMR, mass, thermal
gravimetry (TG), X-ray diffraction patterns (XRD), scan-
ning electron microscopy (SEM) and transmission electron
microscopy (TEM) analysis (Scheme 2).
1,4-Dinitropyrazine-1,4-diium
trinitromethanide
{[1,4-Pyrazine-NO2][C(NO2)3]2}: orange solid; M.p: 128–
130 °C; Yield: 95% (1.346 g); IR (KBr): υ 3481, 3289,
1
3152, 1768, 1677, 1422, 1153 cm−1; H NMR (400 MHz,
DMSO-d6): δppm 8.68 (s, 4H, ArH); 13C NMR (100 MHz,
DMSO-d6): δppm 122.8, 145.7; MS: m/z = 472 [M]+.
General procedure for the synthesis
of 2-amino-3,5-dicarbonitrile-6-sulfanylpyridines
{[1,4-Pyrazine-NO2][C(NO2)3]2} (2 mol%; 0.009 g) was
added and mixed to a mixture of aldehydes (1 mmol),
malononitrile (2.5 mmol; 0.165 g) and benzyl mercaptan
(1 mmol; 0.124 g) under solvent-free conditions and at
room temperature for the appropriate time (Table 4). After
completion of the reaction, which was monitored by TLC
(n-hexane/ethyl acetate: 5/2), the resulting mixture was
washed with water (10 mL) and fltered to separate catalyst
Characterization of 1,4-dinitropyrazine-1,4-diium
trinitromethanide {[1,4-pyrazine-NO2][C(NO2)3]2}
as nanostructured molten salt catalyst
Characterization of nanostructured molten salt catalyst was
confrmed by using analytical approaches including FTIR,
1H NMR, 13C NMR, mass, TG, XRD, SEM and TEM
analysis.
Scheme 2 Synthesis of
2-amino-3,5-dicarbonitrile-
6-sulfanylpyridines using
{[1,4-pyrazine-NO2]
[C(NO2)3]2}
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J IRAN CHEM SOC
In the FTIR spectrum of {[1,4-pyrazine-NO2]
[C(NO2)3]2}, the absorption bond at 1677 and 1422 cm−1
is conformed to vibrational modes of –NO2 bonds. Also,
the peak identifed at 3152 cm−1 linked to C–H stretching
group on 1,4-dinitropyrazine-1,4-diium ring. The IR spec-
trum changes of {[1,4-pyrazine-NO2][C(NO2)3]2} in com-
parison with pyrazine and tetranitromethane presented for-
mation of described molten salt catalyst (Fig. 2).
aromatic hydrogen’s of 1,4-dinitropyrazine-1,4-diium ring.
The H NMR chemical shift changes of {[1,4-pyrazine-
1
NO2][C(NO2)3]2} in comparison with pyrazine showed cre-
ation of nanostructured molten salt catalyst (Fig. 3).
Appearance of two signals in the 13C NMR is in agree-
ment with the {[1,4-pyrazine-NO2][C(NO2)3]2} structure.
Also the 13C NMR chemical shift changes of {[1,4-pyra-
zine-NO2][C(NO2)3]2} in comparison with pyrazine and
tetranitromethane clearly displayed formation of nanostruc-
tured molten salt catalyst (Fig. 4).
The 1H NMR spectrum of the {[1,4-pyrazine-NO2]
[C(NO2)3]2} displays a singlet at 8.68 ppm linked to the
Fig. 2 The FTIR spectrum of
tetranitromethane (a), pyra-
zine (b), {[1,4-pyrazine-NO2]
[C(NO2)3]2} (c)
Fig. 3 The 1H NMR spec-
trum of {[1,4-pyrazine-NO2]
[C(NO2)3]2}
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J IRAN CHEM SOC
Fig. 4 The 13C NMR spec-
trum of {[1,4-pyrazine-NO2]
[C(NO2)3]2}
Abundance
Scan 129 (1.272 min): 3001251438.D
154
160000
150000
140000
130000
120000
110000
100000
90000
127
80000
70000
60000
44
50000
40000
30000
20000
10000
0
81
198
296
237
362
350
264
327
392
400
495 522
500
580
552
550
449
450
104
100
50
150
200
250
300
m/z-->
Fig. 5 The mass spectrum of {[1,4-pyrazine-NO2][C(NO2)3]2}
The mass spectrum of the {[1,4-pyrazine-NO2]
[C(NO2)3]2} is in accordance with the structure of the cata-
lyst. The signifcant peak of mass spectrum of nanostruc-
tured molten salt catalyst is related to trinitromethanide
counter ion which is known at 300 m/z and connected peak
at 172 m/z is related to 1,4-dinitropyrazine-1,4-diium ring
(Fig. 5).
The thermal gravimetric analysis (TGA) curves of
{[1,4-pyrazine-NO2][C(NO2)3]2} display mass loss of
organic materials as they decompose upon heating. The
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J IRAN CHEM SOC
TGA curve of catalyst (Fig. 6) shows an initial weight loss
of 25% around 80–110 °C which is owing to residual phy-
sisorbed water and organic solvents, which were used in
the course of catalyst synthesis. Thermal degradation of the
catalyst occurred after 300 °C which reveal the high ther-
mostability of catalyst. The second weight loss of 75% in
the range of 110–300 °C was due to the thermal decom-
position of the organic residues. The thermal gravimetric
analysis of the described NMS catalyst offered signif-
cant loss in two steps and decomposed after 300 °C. Ionic
chemical bonds afford the catalyst high thermal stability, so
it is probable that the catalyst could be applied for high-
temperature uses.
Described NMS catalyst was considered by X-ray
diffraction (XRD) pattern (Fig. 7), scanning electron
microscopy (SEM) and transmission electron microscopy
(TEM) (Fig. 8). In this regard, to approve the structure of
{[1,4-pyrazine-NO2][C(NO2)3]2}, frstly, its XRD pat-
tern was studied. As shown in Fig. 7, the XRD patterns of
NMS catalyst expose peaks at 2θ ≈ 18.30°, 18.90°, 22.20°,
23.50°, 25.10°, 27.60°, 28.90°, 31.70°, 37.10°, 54.10°,
61.80° and 66.90°, correspondingly, which was confrmed
through the described value of scanning electron micros-
copy (SEM) and transmission electron microscopy (TEM)
(Fig. 8). Peak width (FWHM), size and interplanar distance
related to XRD pattern of {[1,4-pyrazine-NO2][C(NO2)3]2}
were investigated in the 18.30°–66.90° degree, and the
achieved results is summarized in Table 1. The average
crystallite size D was studied using the Scherrer formula:
D = Kλ/(βcosθ). The average size of the NMS catalyst,
subsequently, attained from this equation was found to be
about 5.88–71.22 nm, which is basically in a good agree-
ment with the scanning electron microscopy and transmis-
sion electron microscopy (Fig. 8).
Application of 1,4-dinitropyrazine-1,4-diium
trinitromethanide {[1,4-pyrazine-NO2][C(NO2)3]2} as a
nanostructured molten salt catalyst
The synthesis of 2-amino-3,5-dicarbonitrile-6-sulfa-
nylpyridines was attained by the one-pot, three-com-
ponent condensation of aromatic aldehydes, malononi-
trile and benzyl mercaptan using {[1,4-pyrazine-NO2]
[C(NO2)3]2} under solvent-free conditions at room tem-
perature to give products in high yields (Scheme 2).
For optimization of reaction conditions, the reaction
Fig. 6 The thermal gravimetric analysis (TGA) of {[1,4-pyrazine-
NO2][C(NO2)3]2}
Fig. 7 The XRD pattern
of {[1,4-pyrazine-NO2]
[C(NO2)3]2}
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J IRAN CHEM SOC
Fig. 8 Scanning electron
microscopy (SEM) (a, b), trans-
mission electron microscopy
(TEM) (c, d) of {[1,4-pyrazine-
NO2][C(NO2)3]2}
Table 1 The XRD data for
the {[1,4-pyrazine-NO2]
[C(NO2)3]2}as a nanostructured
molten salt catalyst
Entry
2θ
Peak width (FWHM) (degree)
Size (nm)
Interplanar distance (nm)
1
18.30
18.90
22.20
23.50
25.10
27.60
28.90
31.70
37.10
54.10
61.80
66.90
0.23
0.13
1.03
1.38
0.65
0.50
0.97
0.87
0.89
0.27
0.13
0.23
34.99
61.95
7.86
0.484216
0.468977
0.399954
0.378115
0.354362
0.322806
0.308574
0.281927
0.242038
0.169317
0.149939
0.139693
2
3
4
5.88
5
12.52
16.07
8.46
6
7
8
9.49
9
9.42
10
11
12
33.04
71.22
41.40
between 4-chlorobenaldehyde, malononitrile and benzyl
mercaptan was selected as a model reaction for examin-
ing the effect of different solvents. As shown in Table 2,
the solvent-free condition is the most effective condi-
tions for this reaction. In this condition, the reaction was
happened very fast. Although, for this reaction, studying
the research in laboratory not in industry, the same results
were achieved by carrying out the reaction at room tem-
perature in ethanol for 25 min (yield of 91%) using
2 mol% of NMS catalyst.
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Table 2 Solvent effect
in the reaction between
4-chlorobenaldehyde,
malononitrile and benzyl
mercaptan
Solvent
Solvent-free
H2O
C2H5OH
CH2Cl2
CH3CN
CH3CO2Et
Reaction time (min)
Yield (%)a
25
91
60
53
25
91
45
81
45
87
60
75
Reaction condition: 4-chlorobenaldehyde (1 mmol), malononitrile (2.5 mmol) benzyl mercaptan (1 mmol),
NMS catalyst (2 mol%), solvent (2 mL)
a
Isolated yield
Table 3 Optimization reaction between 4-chlorobenaldehyde, malo-
nonitrile and benzyl mercaptan
obviously show that reactions can tolerate a broad range of
differently substituted aromatic aldehydes. Also, by using
terephthaldehyde as a bifunctional aldehyde, bispyridine
product was produced (Table 4, entry 9). A slight excess of
the malononitrile was known to be favorable, and hence,
the molar ratio of aromatic aldehyde and benzyl mercaptan
to malononitrile was investigated at 1:1:2.5.
Entry Catalyst amount Temperature
Time (min) Yield (%)a
(mol%)
(°C)
1
–
r.t.
180
180
60
60
45
45
25
25
25
25
25
25
7
10
25
27
57
57
91
91
87
87
91
87
2
–
100
r.t.
3
0.5
0.5
1
According to the previously reported process [22–26], an
appropriate mechanism for the synthesis of 2-amino-3,5-di-
carbonitrile-6-sulfanylpyridines (4) by {[1,4-pyrazine-NO2]
[C(NO2)3]2} as a NMS catalyst was proposed (Scheme 3).
Initially, we considered that the reaction happens via a
Knoevenagel condensation between activated malononi-
trile (2) and aromatic aldehyde (1). Then, the consequent
Michael-type addition of the second molecule of activated
malononitrile (2) to the Knoevenagel adduct (5) causes the
synthesis of the intermediate (6). In the other step by thi-
olate addition to cyanide group of the intermediate (6) and
cyclization, dihydropyridine (7) was synthesized and tau-
tomerized to dihydropyridine (8) [8–15]. Finally, dihydro-
pyridine (8) via anomeric-based oxidation was converted
to its corresponding 2-amino-3,5-dicarbonitrile-6-sulfa-
nylpyridine (4). Previously reported investigations have
proposed an aerobic auto-oxidation of intermediate (8) to
its corresponding 2-amino-3,5-dicarbonitrile-6-sulfanylpyr-
idines (4). In contrast to the previously reported mecha-
nistic description for the fnal step of the above-described
organic synthesis, we proposed that this step might be pro-
gressed by unusual hydride transfer as well as Cannizzaro
reaction (Scheme S1) [34] and H2 releasing from tricyclic
orthoamide (Scheme S2) [35–37]. As mentioned in Intro-
duction part, we have suggested an anomeric-based oxida-
tion (ABO) for the fnal step in mechanistic pathways in
the synthesis of 1,4-dihydropyrano-[2,3-c]-pyrazole [24],
2,4,6-triarylpyridine derivatives [25], 2-amino-3-cyanopyr-
idines [26] and 2-substituted benz-(imida, oxa and othia)-
zole derivatives [27] (Schemes S3–S6). For approving of
aforementioned idea, reaction was happened/done under
nitrogen atmosphere and in the absence of any molecular
oxygen. It was identifed that the reaction proceeded under
atmosphere of nitrogen as well as normal reaction condi-
tion (under air atmosphere). By considering the above-men-
tioned evidence, conversion of intermediate (8) to its cor-
responding 2-amino-3,5-dicarbonitrile-6-sulfanylpyridines
4
100
r.t.
5
6
1
100
r.t.
7
2
8
2
50
9
2
75
10
11
12
2
100
r.t.
5
5
100
Reaction condition: 4-chlorobenaldehyde (1 mmol), malononitrile
(2.5 mmol) benzyl mercaptan (1 mmol)
a
Isolated yield
The scope of this procedure was extended to the synthe-
sis of 2-amino-3,5-dicarbonitrile-6-sulfanylpyridines. The
three-component condensation reaction of 4-chlorobenal-
dehyde, malononitrile and benzyl mercaptan was selected
as a model reaction, and the effect of different amounts of
catalyst and temperature was studied under solvent-free
conditions (Table 3). Table 3 clearly recognizes that in the
absence of the catalyst, product was attained in low yield
after 3 h (Table 3, entries 1 and 2). The good results were
obtained in the presence of 2 mol% of NMS catalyst at
25 °C that affect temperature in terms of reaction time and
obtained yield (Table 3, entry 7). Increasing the reaction
temperature and catalyst loading did not improve the rate
of the reaction (Table 3, entries 8–12).
Subsequently, a series of different 2-amino-3,5-dicarbo-
nitrile-6-sulfanylpyridines were synthesized successfully
from different aldehydes bearing electron-withdrawing
and electron-donating groups, malononitrile and benzyl
mercaptan under solvent-free conditions at room tempera-
ture. Electron-withdrawing groups such as 3-nitro and
4-nitro reacted faster than electron-donating groups such as
4-Me and 4-OMe under optimized conditions. The results
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J IRAN CHEM SOC
Table 4 Synthesis of
Entry Product
1
Time (min) Yield (%)a M.p (°C) (Lit.) (Refs.) (color)
2-amino-3,5-dicarbonitrile-
6-sulfanylpyridines using
{[1,4-pyrazine-NO2]
[C(NO2)3]2} as a nanostructured
molten salt catalyst under
solvent-free conditions
20
25
30
93
91
89
202–204 (210–212) [15] (red solid)
2
3
298–300 [15] (green solid)
249–251 [15] (yellow solid)
4
5
25
30
90
89
242–243 (brown solid)
166–168 (yellow solid)
6
7
25
30
91
89
223–225 (brown solid)
205–207 (214–215) [12] (brown solid)
8
9
30
35
89
87
202–204 (orange solid)
268–270 (cream solid)
10
25
90
197–199 (brown solid)
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J IRAN CHEM SOC
Time (min) Yield (%)a M.p (°C) (Lit.) (Refs.) (color)
Table 4 continued
Entry Product
11
25
90
213–215 (brown solid)
12
35
85
218–220 (brown solid)
13
14
15
40
40
40
83
83
83
208–210 (224–226) [8] (brown solid)
214–216 (brown solid)
191–193 (brown solid)
16
17
30
40
89
83
255–257 [15] (yellow solid)
228–230 (cream solid)
Reaction condition: aldehyde (1 mmol), malononitrile (2.5 mmol) benzyl mercaptan (1 mmol), NMS cata-
lyst (2 mol%)
a
Isolated yield
(4) might be occurred through uncommon hydride transfer
and releasing of molecular hydrogen (H2). The C–H bond
is so weaken via electron donation from the nitrogen lone
pairs into the antibonding of C–H (σ*C–H orbital) which
can be broken via reaction with a proton to provide molec-
ular hydrogen. We have entitled this phenomenon “Ano-
meric Based Oxidation” (ABO). The major reason of ABO
is driving force of aromatization which will be supported
via stereoelectronic and/or anomeric effect (the experimen-
tal and theoretical study refers to supplementary data [38]).
The probability of recycling the {[1,4-pyrazine-NO2]
[C(NO2)3]2}as a NMS catalyst was investigated by the
reaction between 4-chlorobenaldehyde, malononitrile
and benzyl mercaptan under the optimized conditions.
Upon completion of the reaction, the reaction mixture was
washed with water and ethyl acetate to separate catalyst
from other materials (the product is soluble in hot ethyl
acetate and NMS catalyst is soluble in water). The recov-
ered catalyst was dried and reused for consequent runs. The
recycled catalyst could be reused ffth times without any
additional treatment. There was no observation of any per-
ceptible loss in the catalytic activity. The recycled catalyst
was also characterized by FTIR spectrum after its applica-
tion in the reaction. This spectrum was identical to those
of the fresh catalyst. The deactivation of the NMS catalyst
is low. The reaction was scaled up to 20 mmol of malon-
onitrile and 10 mmol of 4-chlorobenaldehyde and benzyl
mercaptan in the presence of 20 mol% of NMS catalyst at
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J IRAN CHEM SOC
Scheme 3 The suggested mechanism for the synthesis of 2-amino-3,5-dicarbonitrile-6-sulfanylpyridines using {[1,4-pyrazine-NO2][C(NO2)3]2}
1 3

J IRAN CHEM SOC
room temperature. The yield of the reaction was 91% after
25 min and 83% after the fourth run. The results are sum-
marized in Fig. 9.
catalysts for the synthesis of 3,5-dicarbonitrile-6-sulfa-
nylpyridines, we have organized the results of these cata-
lysts in Table 6. Table 6 shows that {[1,4-pyrazine-NO2]
[C(NO2)3]2} has strangely improved the synthesis of
3,5-dicarbonitrile-6-sulfanylpyridines in different terms
(reaction condition, time and yield). The reaction time
was shorter, and the yields were higher with our described
catalyst.
In addition to the usage of {[1,4-pyrazine-NO2]
[C(NO2)3]2} as a NMS catalyst in the synthesis of 2-amino-
3,5-dicarbonitrile-6-sulfanylpyridines, we studied the eff-
ciency of numerous catalysts for confrming ABO proposed
mechanism. To optimize the reaction conditions, the reac-
tion between 4-chlorobenaldehyde, malononitrile and ben-
zyl mercaptan under N2 atmosphere at room temperature
was used as a model reaction (Table 5).
Conclusion
To compare the effcacy of {[1,4-pyrazine-NO2]
[C(NO2)3]2} as a NMS catalyst with other reported
In summary, a reusable 1,4-dinitropyrazine-1,4-diium
trinitromethanide {[1,4-pyrazine-NO2][C(NO2)3]2} as an
energetic task-specifc nanostructured molten salt (NMS)
1
was designed and completely characterized by FTIR, H
NMR, 13CNMR, mass, thermal gravimetric (TG), X-ray
diffraction patterns (XRD), scanning electron microscopy
(SEM) and transmission electron microscopy (TEM)
analysis. Catalytic application of {[1,4-pyrazine-NO2]
[C(NO2)3]2} was investigated in the synthesis of 2-amino-
3,5-dicarbonitrile-6-sulfanylpyridines via the three-com-
ponent condensation reaction between aromatic aldehyde,
malononitrile and benzyl mercaptan under solvent-free
conditions at room temperature. Numerous noteworthy
advantages of this study are relatively cleaner reaction
profle, simplicity of product isolation, low cost, high
yield, short reaction time, reusability of the NMS catalyst
and agreement with the green chemistry disciplines. An
anomeric based oxidation mechanistic process was also
proposed for the fnal step of the 2-amino-3,5-dicarboni-
trile-6-sulfanylpyridines synthesis which was supported
Fig. 9 Reusability studies of {[1,4-pyrazine-NO2][C(NO2)3]2} as a
nanostructured molten salt catalyst for the reaction between 4-chlo-
robenaldehyde, malononitrile and benzyl mercaptan in 25 min
Table 5 The reaction
Entry
Catalyst
Catalyst loading (mol%)
Time (min)
Yield (%)a
between 4-chlorobenaldehyde,
malononitrile and benzyl
mercaptan using various
catalysts for approving of ABO
proposed mechanism
1
{[1,4-pyrazine-NO2][C(NO2)3]2}
HBF4
2
5
25
30
45
45
45
45
45
45
30
30
30
30
91
83
65
57
53
50
48
45
89
85
88
82
2
3
Zn(HSO4)2
5
4
Oxone
5
5
Ce(HSO4)3·7H2O
Bi(HSO4)3
5
6
10
10
10
2
7
CeO2
8
PbO2
9
[MIMPS]3PW12O40
Nano-ZnO
10
11
12
2
[MSIM]Cl
2
H3PW12O40
2
Reaction conditions: 4-chlorobenzaldehyde (1 mmol), malononitrile (2.5 mmol), benzyl mercaptan
(1 mmol), under N2 atmosphere, r.t.
a
Isolated yield
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J IRAN CHEM SOC
Table 6 Comparison of the results in the synthesis of 1,4-dihydropyridines catalyzed by [3,6-DOMDA]OTf with those other reported catalysts
Entry
Reaction condition
Time (min)
Yield (%) (Refs.)
1
2
{[1,4-Pyrazine-NO2][C(NO2)3]2} (2 mol%), solvent-free, r.t.
Diethylamine, ethanol, r.t.
40
83 (This work)
77 [8]
270
3
4
5
{[1,4-Pyrazine-NO2][C(NO2)3]2} (2 mol%), solvent-free, r.t.
30
89 (This work)
44 [12]
Et3N, ethanol, refux, aldehyde/malononitrile/thiol in a ratio of 1:2:1
Et3N, ethanol, refux, aldehyde/malononitrile/thiol in a ratio of 1:1.5:0.5
150–180
150–180
88 [13]
6
7
{[1,4-Pyrazine-NO2][C(NO2)3]2} (2 mol%), solvent-free, r.t.
25
60
91 (This work)
84 [15]
Borax, ethanol, refux
8
9
{[1,4-Pyrazine-NO2][C(NO2)3]2} (2 mol%), solvent-free, r.t.
20
93 (This work)
81 [15]
Borax, ethanol, refux
150
10
11
{[1,4-Pyrazine-NO2][C(NO2)3]2} (2 mol%), solvent-free, r.t.
30
60
89 (This work)
84 [15]
Borax, ethanol, refux
by theoretical investigations. Subsequently, we think that
the suggested mechanism has potential for entering into
the graduate text book in the future.
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