WEB (water extract of banana): An efficient natural base for one-pot multi-component synthesis of 2-amino-3,5-dicarbonitrile-6-thio-pyridines

Article abstract of DOI:10.1080/10426507.2020.1835905

One-pot multi-component synthesis of 2-amino-3,5-dicarbonitrile-6-thio-pyridines derivatives using WEB (water extract of banana peels ash) as a green catalyst is described. A variety of aromatic aldehydes (with electron-donating and electron-withdrawing groups) in conjunction with aromatic and aliphatic thiols are known to tolerate this reaction condition using WEB. The reaction has simple work up procedure without using toxic solvents.

Full text of DOI:10.1080/10426507.2020.1835905

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/gpss20
WEB (water extract of banana): An efficient natural
base for one-pot multi-component synthesis of 2-
amino-3,5-dicarbonitrile-6-thio-pyridines
Alireza Allahi & Batool Akhlaghinia
To cite this article: Alireza Allahi & Batool Akhlaghinia (2020): WEB (water extract of
banana): An efficient natural base for one-pot multi-component synthesis of 2-amino-3,5-
dicarbonitrile-6-thio-pyridines, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI:
10.1080/10426507.2020.1835905
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PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2020.1835905
WEB (water extract of banana): An efficient natural base for one-pot multi-
component synthesis of 2-amino-3,5-dicarbonitrile-6-thio-pyridines
Alireza Allahi and Batool Akhlaghinia
Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
ABSTRACT
ARTICLE HISTORY
Received 27 July 2020
Accepted 8 October 2020
One-pot multi-component synthesis of 2-amino-3,5-dicarbonitrile-6-thio-pyridines derivatives using
WEB (water extract of banana peels ash) as a green catalyst is described. A variety of aromatic
aldehydes (with electron-donating and electron-withdrawing groups) in conjunction with aromatic
and aliphatic thiols are known to tolerate this reaction condition using WEB. The reaction has sim-
ple work up procedure without using toxic solvents.
KEYWORDS
2-amino-35-dicarbonitrile-6-
thio-pyridines; aldehydes;
malononitrile; one-pot
multi-component reaction;
thiophenol; WEB (Water
Extract of Banana)
GRAPHICAL ABSTRACT
Introduction
anti-prion,[2,7,8] anti-hepatitis B virus,[4] anti-bacterial,[9] and
anti-cancer[3] agents and as potassium channel openers for
the treatment of urinary incontinence.[6] Also, the import-
ance of this class of compounds can be recognized as poten-
tial targets for the development of new drugs for the
treatment of Parkinson’s disease, hypoxia, asthma, kidney
disease, epilepsy, cancer,[10] and Creutzfeldt-Jacob dis-
ease.[7,8,11] Therefore, with the aim of developing new drug
molecules, the synthesis or structure modifications of highly
functionalized pyridine derivatives have attracted huge atten-
tion from both synthetic and medicinal chemists.[10]
Recently several scientists have used the multi-component
reaction (MCR) strategy as one of the most prominent
existing procedure to synthesize 2-amino-3,5-dicarbonitrile-
Among the nitrogen containing heterocycles, the pyridine
nucleus as a key structural subunit in a range of bioactive
compounds, both naturally occurring and synthetic is of
considerable interest.[1] Substituted pyridine derivatives par-
ticularly 2-amino-3,5-dicarbonitrile-6-thio-pyridines, are
among the most promising candidates for demonstrating
biological activity, and are also considered as medicinally
‘privileged scaffold’[2] for developing pharmaceutical agents
due to their potential therapeutic applications.[2–11] These
pyridine skeletons were reported to inhibit PrPSc accumula-
tion in scrapie-infected mouse neuroblastoma cells
(ScN2a),[8] MAPK-activated PK-2,[3] IKK-2 for treating
HBV infection,[4] and modulate androgen receptor func-
tion.[5] Additionally, these compounds are often used as 6-thio-pyridines via the cyclocondensation of aldehyde,
CONTACT Batool Akhlaghinia
akhlaghinia@um.ac.ir
Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad
9177948974, Iran.
Supplemental data for this article is available online at https://doi.org/10.1080/10426507.2020.1835905.
ß 2020 Taylor & Francis Group, LLC

2
A. ALLAHI AND B. AKHLAGHINIA
Scheme 1. Synthesis of structurally different 2-amino-3,5-dicarbonitrile-6-thio-pyridines using WEB.
malononitrile and thiol. Much attention has been paid to believed that various chemical processes could be catalyzed
one-pot multicomponent reactions particularly for the devel-
opment of the library heterocyclic compounds[12–17] due to
atom economy, green conditions, procedural simplicity, and
cost-effectiveness over conventional multistep synthesis.
Various synthetic methods with their own merits and
demerits have been developed for the construction of these
compounds following this route with intervention of differ-
ent basic (KOH,[18] K2CO3,[19,20] DBU,[21] Na2SiO3,[22]
TBAB/Cs2CO3,[23] MgO,[24] Et3N,[25] DABCO,[25] ZrOCl2/
NaNH2,[26] piperidine,[11] silica-bonded N-propyldiethylene-
triamine,[27] TBAF,[28] CH3COONa,[29] 2-HEAA,[30] KF/
Al2O3,[31] molecular sieves 4 Å,[32] [bmIm]OH,[33]
[bmim][Br],[34] CaO NPs[35]) as well as acidic catalysts
(c-Fe2O3-2-HEAS,[36] Sc(OTf)3,[37] silica NPs,[38] CuI
NPs,[39] boric acid,[40] Zn(II) and Cd(II) MOFs,[41] phospho-
tungstic acid/CTAB,[42] ZnCl2,[43] o-iodoxybenzoic acid[44]).
Nevertheless, some of the previously reported methods
suffer from one or more drawbacks such as using toxic or
expensive catalyst and reagent[21,23] and exotic reaction con-
ditions (use of microwave irradiation or an ionic
liquid).[29,33,34] Therefore, continuing interest in developing
an environmentally safer, green and practical synthetic route
using a readily available and inexpensive catalyst for the syn-
thesis of the pyridine derivatives has remained a significant
challenge. With respect to the role of green chemistry to
reduce or eliminate the use or generation of hazardous sub-
stances, significant awareness has been increased to using
natural feedstocks as available, nontoxic, and metal-free
reagents in greener catalytic processes under mild and con-
venient reaction conditions.[45–51]
using banana peels (WEB) (based on their basic behavior
upon the presence of sodium carbonate and potassium car-
bonate), which supplied long-term economic and environ-
mental impacts in the near future.
Results and discussion
From the economic and environmental points of view, the
use of an inexpensive and environmentally friendly natural
feedstock extract without purification or characterization is
very appealing and has been an active area of research. In
this research, a one-pot multi component reaction of alde-
hydes, malononitrile and thiols was conducted using WEB
as internal base to produce 2-amino-3,5-dicarbonitrile-6-
thio-pyridines. In search for the best experimental reaction
conditions,
benzaldehyde
(0.25 mmol),
malonitrile
(0.5 mmol) and thiophenol (0.25 mmol) in refluxing EtOH
were adopted as the model substrates for investigating the
multi-component synthesis of 2-amino-3,5-dicarbonitrile-4-
phenyl-6-(phenylthio)pyridine using WEB under different
reaction conditions. The results of the optimizations are
summarized in Table 1. It was found that in the absence of
WEB, only Knoevenagel adduct (I) (see Scheme 2) was
obtained alongside a trace amount of product after 24 h
(Table 1, entry 1). But when the reaction was conducted in
the presence of WEB (0.5 mL) the reaction was completed
(yielding 90%) in 20 min (Table 1, entry 2). Increasing the
amount of WEB up to 1 mL afforded the desired product as
the same as using 0.5 mL of WEB (Table 1, entry 3), but
lower amount of WEB (0.4 mL) produced 2-amino-3,5-
dicarbonitrile-4-phenyl-6-(phenylthio)pyridine in a lower
yield (80%) even after 60 min (Table 1, entry 4). To verify
the effect of temperature, by applying 0.5 and 0.4 mL of
WEB, in two separate flasks the model reaction was per-
formed at 65 ꢀC (Table 1, entries 5–6). It was evident from
Table 1 that using 0.4 mL of WEB at 65 ꢀC afforded lower
yield of the desired product. Additionally, the effect of other
temperatures (55 and 60 ꢀC) was also screened on the model
reaction (Table 1, entries 7–8). It was found that the reac-
tion prolonged with very poor yields at 55 and 60 ꢀC. Based
on the obtained results, reaction proceeds smoothly toward
completion in excellent yield (90%) using 0.5 mL of WEB at
65 ꢀC. After finalizing the amount of catalyst and tempera-
In the past few years, Sonogashira and Suzuki-Miyaura
cross-coupling reactions have been reported using Pd(OAc)2
and ‘Water Extract of Banana’ (WEB).[52,53] Moreover,
greener Dakin oxidation under metal catalyst, base and solv-
ent free reaction conditions has been performed employing
H2O2-WEB system.[54]
Based on the previous reports[52–54] and in continuation
of our recent studies,[55–84] with the aim of reducing the
environmental impacts, this is the first report for the one-
pot multicomponent synthesis of 2-amino-3,5-dicarbonitrile-
6-thio-pyridines employing WEB as a natural feedstock
without the help of any toxic reagent, external base, transi-
tion metal catalyst, external additives, and organic solvent
(Scheme 1). In this study, the water extract of banana has
been prepared by an aqueous extract of banana peels. It is ture for this reaction, the next target was to choose proper

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
solvent. Various solvents like CH3CN, CH3OH, THF, CHCl3 present one-pot multicomponent condensation reaction with
and toluene have been tested and compared their results satisfactory yields.
with EtOH mediated reaction (Table 1, entries 10–14). Prior
to using solvents, the reaction was examined under neat
conditions, but reaction failed to afford more than 60% yield
in 60 min (Table 1, entry 9). Comparatively, in all tested sol-
vents, reaction was carried out but afforded lower yields.
Reaction in CH3CN proceeded smoothly in agreement with
EtOH, but because of safety and economic considerations,
EtOH was chosen for further experiments. The toxicity and
the hazardous nature of CH3CN confined its use for this
one-pot multi component reaction.
Most of the synthesized molecules are known (a–h &
j–p) and were characterized by 1H NMR, 13C NMR, and
mass spectrometry and comparison of their melting points
with known compounds. Novel compounds (i & q) were
fully characterized with the help of the usual spectroscopic
1
techniques including FT-IR, H NMR, 13C NMR, mass spec-
troscopies and elemental analysis.
The HPLC trace and LC-MS method have high sensitiv-
ity, good linearity, and feasibility, which are used to con-
After optimization the reaction conditions, we turned our
firmed the structure of compounds as well. For this
attention to investigate the scope and general applicability of
purpose, the structure of two selected products (g & h) were
this methodology by carrying out the one-pot multi compo-
recorded by LC-MS analysis and also, the purity of another
nent reaction of variety of electronically divergent aldehydes
two derivates (a & f) were determined by high performance
with respect to thiols using WEB (Table 2). As is evident
liquid chromatography (HPLC). The results can be seen in
from the results shown in Table 2, aryl aldehydes as well as
the Supplemental Materials file.
heteroaryl aldehydes (pyridine-4-carbaldehyde and thio-
FT-IR spectroscopy of the purified products revealed two
phene-2-carbaldehyde) were found to be highly compatible
absorption bands at 3465–3453 and 3328–3322 cmꢁ1 due to
with the optimized reaction conditions and gave the desired
N–H stretching vibrations and also one absorption band at
products in excellent yields (Table 2, entries 12–13). A var-
2218 cmꢁ1 for –CꢂN stretching. An absorption band about
iety of electron-donating or electron-withdrawing groups,
757 cmꢁ1 is mainly attributed to thioether linkage. In add-
such as OH, OMe, CH3, Br, Cl, F and NO2 groups were
ition, the disappearance of the band at about 1720 cmꢁ1
used to obtain the corresponding products with excellent
attributed to the carbonyl group is evidence for the product
yield.[24,26] The results shown that, aromatic aldehydes bear-
ing electron-donating or electron-withdrawing groups con-
densed with malononitrile and thiols very smoothly and
produced the corresponding 2-amino-3,5-dicarbonitrile-6-
thio-pyridines in short reaction times (Table 2, entries 7–11
vs entries 2–6).
Surprisingly it was found that 2-naphthaldehyde, as a
bulky aldehyde, was suitable to obtain the corresponding
1
formations. In the H-NMR spectra (in DMSO) of the prod-
ucts, the NH2 protons were observed downfield as a singlet
(2H) at about d ¼ 8 ppm and protons of the aromatic ring
were appeared as multiplet at d ¼ 7.5–7.7 ppm.[25,32,40] All
the aromatic carbon atoms of compounds exhibited signals
at d ¼ 115–166 ppm in the 13C NMR spectra. The C-3 and
C-5 carbon atoms of the pyridine ring, attached to the
nitrile group, exhibited signals at d ¼ 88 and 94 ppm,
pyridine derivative in the present one-pot multicomponent
reaction (Table 2, entry 14). Thereafter, various thiols were
tested under the optimized reaction conditions. As given in
respectively. The mass spectra detected the expected
Table 2, both aromatic and aliphatic thiols can undergo the
Table 2. One-pot multi-component synthesis of 2-amino-3,5-dicarbonitrile-6-
thio-pyridines using WEB.
Time
Isolated
Table 1. Reaction condition optimizations for preparation of 2-amino-3,5-
dicarbonitrile-4-phenyl-6-(phenylthio)pyridine.
Entry
R1
R2
Product (min) yield (%)
Ref.
1
2
3
4
5
6
7
8
C6H5
4-HOC6H4
3-HOC6H4
4-H3COC6H4
3-H3CC6H4
4-H3CC6H4
3-BrC6H4
4-ClC6H4
2-ClC6H4
4-FC6H4
4-O2NC6H4
4-NC5H4
2-SC4H3
2-C10H7
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
–C6H5
A
B
C
D
E
20
45
40
35
40
40
25
25
25
20
10
20
25
30
20
30
35
90
80
85
80
85
90
85
90
85
85
90
90
85
80
90
85
80
20
86
39
87
39
30
37
86
Novel
86
88
89
19
30
20
30
Novel
Catalyst
(mL)
Temperature
(ꢀC)
Time
(min)
Isolated
yield (%)
Entry
Solvent
1
2
3
4
5
6
7
8
–
0.5
1
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
–
CH3CN
CH3OH
THF
CHCl3
Toluene
Reflux
Reflux
Reflux
Reflux
65
65
55
60
65
65
65
65
65
24 (h)
20/60
20/60
20/60
20/60
20/60
20/60
20/60
20/60
20/60
20/60
20/60
20/60
20/60
Trace
90/90
90/90
60/80
90/90
40/60
50/65
60/80
30/60
50/70
40/50
30/40
40/60
30/40
F
0.4
0.5
0.4
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
G
H
I
J
K
L
M
N
O
P
Q
9
10
11
12
13
14
15
16
17
9
10
11
12
13
14
–C6H5
C6H5
C6H5
C6H5
4-ClC6H4
CH3(CH2)2CH2
CH3(CH2)6CH2
65

4
A. ALLAHI AND B. AKHLAGHINIA
molecular ion signals corresponding to the respective most stable tautomeric form (IV, V, VI). Finally, 2-amino-
molecular formula of the synthesized compounds. 3,5-dicarbonitrile-6-thio-pyridine (VIII) was obtained upon
Based on a literature report[32] a proposed mechanism air oxidative aromatization.
for the synthesis of 2-amino-3,5-dicarbonitrile-6-thio-pyri-
dines using WEB is depicted in Scheme 2.
In another variation, the catalytic ability of WEB in a
one-pot multicomponent preparation of 2-amino-3,5-dicar-
Previously, it was found that potassium carbonate, bonitrile-6-thio-pyridine derivatives is compared with that
sodium carbonate, potassium chloride, and sodium chloride of catalysts reported by others previously. We have tabulated
are the major constituents of WEB along with a host of the results of some commonly basic and acidic catalysts in
other trace elements.[85] The mechanistic approach involves the literature for the same transformation in Table 3. As
the Knoevenagel condensation of aldehyde with malononi- Table 3 indicates, despite the merits of most of the previ-
trile in basic media forming Knoevenagel adduct (I). In the ously reported methods, the newly developed catalytic sys-
following steps, the Michael addition of the second molecule tem acts better rather than other ones from the aspect of
of malononitrile on Knoevenagel adduct (I) and subsequent economic and environmental factors.[52–54] The current
nucleophilic addition of thiolate to CN afforded intermedi- study is much superior to almost all of them in terms of the
ates II and III respectively. Thereafter, intramolecular cyc- reaction time (entries 2, 4–11, 13–14), solvent (entry 5) as
lization lead to formation of dihydropyridine (VII) as the well as price and toxicity.
Scheme 2. Proposed mechanism for the WEB mediated preparation of 2-amino-3,5-dicarbonitrile-6-thio-pyridines.

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
5
Table 3. Comparison of the catalytic activity of WEB with some literature precedents using other catalysts for synthesis of 2-amino-3,5-dicarbonitrile-4-phenyl-6-
(phenylthio)pyridine.
Time
(min)
Yield
(%)
Entry
Catalyst
Substrates and reagents
Explanations
1
–
–
–
KOH, EtOH (solvent), reflux[18]
K2CO3, PEG-400 (solvent), 40 ꢀC[19]
DBU, 10% aqueous ethanol (solvent), 35 ꢀC[21]
EtOH (solvent), r.t[22]
Low yield, using 10 mol% base
Long reaction time, using 10 mol% base
Low yield, expensive base (DBU)
Long reaction time, using toxic base, low yield
Long reaction time, expensive reagents
Long reaction time, low yield
Long reaction time, low yield
Long reaction time, low yield
Long reaction time, using toxic reagent
Corrosive and highly flammable liquid
and vapor reagent
Long reaction time, using ionic base
Low yield, expensive catalyst
30
60
15
60
3 h
86
92
80
78
92
78
35
45
43
92
2
3a
4
Na2SiO3
TBAB/Cs2CO3
MgO NPs
5b
6
MeOH (solvent), r.t[23]
EtOH (solvent), reflux[24]
5 h
7
–
–
–
–
Et3N, EtOH (solvent), reflux[25]
DABCO, EtOH (solvent), reflux[25]
Piperidine, EtOH (solvent), reflux[11]
TBAF, H2O (solvent), 80 ꢀC[28]
2.5 h
2.5 h
27 h
50
8c
9
10d
11
12
13
14
15
[bmIm]OH
Sc(OTf)3
Silica NPs
CuI NPs
Zn(II) and
Cd(II) MOFs
WEB
EtOH (solvent), r.t[33]
1.1 h
15
3 h
100
30
92
85
70
90
86
EtOH (solvent), reflux[37]
EtOH (solvent), reflux[38]
EtOH/H2O (solvent), reflux[39]
Solvent-free, 100 ꢀC[41]
Long reaction time, low yield
Long reaction time
High temperature, using expensive catalyst
16
EtOH (solvent), 65 ꢀC
Excellent yield, short reaction time, using
feedstock, mild reaction conditions,
easy work-up
20
90
a1,8-Diazabicyclo[5.4.0]undec-7-ene.
bTetrabutylammonium bromide.
c1,4-Diazabicyclo[2.2.2]octane.
dTetra-n-butyl ammonium fluoride.
to TMS. Coupling constants
J
are given in Hz.
Conclusion
Abbreviations used for 1H-NMR signals are: s ¼ singlet,
d ¼ doublet, t ¼ triplet, q ¼ quartet, m ¼ multiplet. Mass
spectra were recorded with a CH7A Varianmat Bremem
instrument at 70 eV electron impact ionization, in m/z (rel
%) (Germany). Chromatographic separation was conducted
on a HPLC system (Waters 600, USA). The HPLC instrument
consisted of an In-line degasser AF, a smart line pump 600,
with a 50-lL loop and with a 2487 Dual k Absorbance
Detector. Chromatographic separations were carried out using
a Thermo-C18 column (USA) packed with octadecyl bonded
silica with Column Dimensions 4.6ꢃ 250 mm and 175 Å pore
size at 30 ꢀC. Mobile phase was in isocratic elution mode with
a mixture of acetonitrile/water (80:20, v/v), flow rate of 1.0 mL/
min. The sample injection volume was 50 mL and analytes
were monitored at 365 nm. The samples were filtered through
0.45 mm, 13 mm cellulose acetate syringe filters prior to injec-
tion. The LC/MS experiments were also performed on the
Agilent 6410 triple quadrupole LC/MS system with the Agilent
1200 series (Column: Agilent Eclipse XDB-C18, 4.6 ꢃ 150 mm,
5mm). All yields refer to isolated products after purification by
recrystallization from EtOH. The Supplemental Materials con-
We have reported an efficient synthetic method for 2-
amino-3,5-dicarbonitrile-6-thio-pyridine derivatives by suc-
cessive one-pot multi-component reactions of various alde-
hydes and thiols with malononitrile using WEB as a green
catalyst. The WEB as a natural feedstock has a basic nature
which helps the reaction proceed under the mild reaction con-
ditions. The scope of using WEB is broad with respect to a
range of aromatic/and hetero aromatic aldehydes with elec-
tron-donating and electron-withdrawing groups in conjunction
with aromatic as well as aliphatic thiols. It has also been shown
that the yields are high and reaction completion time is within
10–45 min. Short reaction times, good to excellent yields, safe
process and simple work-up (without using toxic solvents)
make this method an attractive and useful contribution to the
present organic synthesis for the preparation of 2-amino-3,5-
dicarbonitrile-6-thio-pyridine derivatives.
Experimental
General
1
tains sample H, 13C NMR and mass spectra of the products
The purity determinations of the products and the progress
of the reactions were accomplished by TLC on silica gel
polygram STL G/UV 254 plates (Merck, Germany). The
melting points of products were determined with an
Electrothermal Type 9100 melting point apparatus (UK).
The Fourier transform infrared (FT-IR) spectra were
recorded on an Avatar 370 FT-IR Therma Nicolet spectrom-
eter (USA). Elemental analyses were performed using a
Thermofinnigan Flash EA1112 CHNO-S Series analyzer and
agreed with the calculated values.
a–q (Figures S1–S41).
Preparation of WEB (water extract of banana)
WEB (Water Extract of Banana) (scientific name: Musa bal-
bisiana Colla; family: Musaceae; species: Musa balbisiana)
was obtained according the method reported previously.[52]
Firstly, banana peels ash was obtained by drying the banana
peels followed by burning it into ash. Afterwards, the
obtained ash (5 g) was suspended in of distilled H2O
The nuclear magnetic resonance (NMR) spectra were
provided on Brucker Avance 300 MHz instruments in
DMSO-d6 (Germany). Chemical shifts are given in d relative (100 mL), magnetically stirred for 10 min at room

6
A. ALLAHI AND B. AKHLAGHINIA
Dicarbonitriles as Potential Prion Disease Therapeutics. J. Med.
Chem. 2006, 49, 607–615. DOI: 10.1021/jm050610f.
temperature and then filtered through sintered glass cru-
cible. The filtrate is termed WEB.
[8] Perrier, V.; Wallace, A. C.; Kaneko, K.; Safar, J.; Prusiner, S. B.;
Cohen, F. E. Mimicking Dominant Negative Inhibition of Prion
Replication through Structure-Based Drug Design. Proc. Natl.
Acad. Sci. USA 2000, 97, 6073–6078. DOI: 10.1073/pnas.97.11.
6073.
Typical procedure for preparation of 2-amino-3,5-
dicarbonitrile-4-phenyl-6-(phenylthio)pyridine using WEB
[9] Mamaghani, M.; Tabatabaeian, K.; Bayat, M.; Nia, R. H.; Rassa, M.
Regioselective Synthesis and Antibacterial Evaluation of a New
Class of Substituted Pyrazolo[3,4-B]Pyridines. J. Chem. Res. 2013,
37, 494–498. DOI: 10.3184/174751913X13735444714766.
[10] Fredholm, B. B.; Ijzerman, A. P.; Jacobson, K. A.; Klotz, K. N.;
Linden, J. International Union of Pharmacology. XXV.
Nomenclature and Classification of Adenosine Receptors. J.
Pharmacol. Rev. 2001, 53, 527–552.
[11] Guo, K.; Mutter, R.; Heal, W.; Reddy, T. R. K.; Cope, H.; Pratt,
S.; Thompson, M. J.; Chen, B. Synthesis and Evaluation of a
Focused Library of Pyridine Dicarbonitriles against Prion
Disease. Eur. J. Med. Chem. 2008, 43, 93–106. DOI: 10.1016/j.
ejmech.2007.02.018.
To
a
magnetically stirred solution of benzaldehyde
(0.25 mmol, 0.0265 g), malononitrile (0.5 mmol, 0.0330 g),
and thiophenol (0.25 mmol, 0.025 mL) in EtOH (2 mL),
WEB (0.5 mL) was added. The reaction mixture was stirred
at 65 ꢀC for 20 min in the open air. The progress of the reac-
tion was monitored by TLC. After completion of the reaction,
the reaction mixture was gradually cooled to room temperature
and diluted with distilled water (5 mL). Afterwards, the result-
ing solid product was collected by simple filtration and washed
several times with distilled water and dried. Pure product was
then obtained from the resulting solid by recrystallization from
EtOH (90% yield, 0.295 g).
[12] Weber, L.; Illgen, K.; Almstetter, M. Discovery of New Multi
Component Reactions with Combinatorial Methods. Synlett
1999, 1999, 366–374. DOI: 10.1055/s-1999-2612.
[13] Ugi, I.; Heck, S. The Multicomponent Reactions and Their
Libraries for Natural and Preparative Chemistry. Comb. Chem.
High Throughput Screen. 2001, 4, 1–34. DOI: 10.2174/
1386207013331291.
Funding
[14] Orru, R. V. A.; de Greef, M. Recent Advances in Solution-
Phase Multicomponent Methodology for the Synthesis of
Heterocyclic Compounds. Synthesis 2003, 10, 1471–1499. DOI:
10.1055/s-2003-40507.
The authors gratefully acknowledge the partial support of this study by
Ferdowsi University of Mashhad Research Council (Grant no. p/
3/50460).
[15] Hulme, C.; Gore, V. Multi-component Reactions: Emerging
Chemistry in Drug Discovery from Xylocain to Crixivan. Curr.
Med. Chem. 2003, 10, 51–80. DOI: 10.2174/0929867033368600.
ORCID
ꢀ
[16] Ramon, D. J.; Yus, M. Asymmetric Multicomponent Reactions
(AMCRS): The New Frontier. Angew. Chem. Int. Ed. Engl.
2005, 44, 1602–1634. DOI: 10.1002/anie.200460548.
Batool Akhlaghinia
http://orcid.org/0000-0002-9940-5045
[17] Gerencse, ꢀR. J.; Dorman, G.; Darvas, F. Meldrum’s Acid in
Multicomponent Reactions: Applications to Combinatorial and
Diversity-Oriented Synthesis. QSAR Comb. Sci. 2006, 25,
439–448. DOI: 10.1002/qsar.200540212.
[18] Nasim Khan, M.; Pal, S.; Parvin, T.; Choudhury, L. H. A
Simple and Efficient Method for the Facile Access of Highly
Functionalized Pyridines and Their Fluorescence Property
Studies. RSC Adv. 2012, 2, 12305–12314. DOI: 10.1039/
c2ra21385k.
[19] Kidwai, M.; Chauhan, R. K2CO3 Catalyzed Green and Rapid
Access to 2-Amino-3,5- Dicarbonitrile-6-Thio-Pyridines. J. Iran.
Chem. Soc. 2014, 11, 1005–1013. DOI: 10.1007/s13738-013-
0368-4.
[20] Mishra, S.; Ghosh, R. K2CO3-Mediated, One-Pot, Multicomponent
Synthesis of Medicinally Potent Pyridine and Chromeno[2,3-B]
Pyridine Scaffolds. Synth. Commun. 2012, 42, 2229–2244. DOI: 10.
1080/00397911.2011.555284.
[21] Mamgain, R.; Singh, R.; Rawat, D. S. DBU-Catalyzed Three-
Component One-Pot Synthesis of Highly Functionalized
Pyridines in Aqueous Ethanol. J. Heterocyclic Chem. 2009, 46,
69–73. DOI: 10.1002/jhet.32.
[22] Heravi, M. M.; Khorshidi, M.; Beheshtia, Y. S.; Baghernejad, B.
Sodium Silicate-Catalyzed Multicomponent Synthesis of
Pyridine Dicarbonitriles. Bull. Korean Chem. Soc. 2010, 31,
1343–1344. DOI: 10.5012/bkcs.2010.31.5.1343.
[23] Kamble, V. T.; Atkore, S. T.; Pisal, P. M.; Sadaf, M.; Thakre,
R. V. Tetrabutylammonium Bromide-Cesium Carbonate: New
Reagent System for the Synthesis of Substituted Pyridines at
Room Temperature. Iran. Chem. Commun. 2016, 4, 186–196.
[24] Kantam, M.; Mahendar, K.; Bhargava, S. One-Pot, Three-
Component Synthesis of Highly Substituted Pyridines and 1,4-
Dihydropyridines by Using Nanocrystalline Magnesium Oxide. J.
Chem. Sci. 2010, 122, 63–69. DOI: 10.1007/s12039-010-0007-x.
References
[1] Boger, D. L.; Nakahara, S. Diels-Alder Reactions of N-Sulfonyl-
L-Aza-1,3-Butadienes: Development of a Synthetic Approach to
the Streptonigrone C Ring. J. Org. Chem. 1991, 56, 880–886.
DOI: 10.1021/jo00002a077.
[2] May, B. C. H.; Zorn, J. A.; Witkop, J.; Sherrill, J.; Wallace,
A. C.; Legname, G.; Prusiner, S. B.; Cohen, F. E. Structure-
Activity Relationship Study of Prion Inhibition by 2-
Aminopyridine-3,5-dicarbonitrile-based Compounds: Parallel
Synthesis, Bioactivity, and In Vitro Pharmacokinetics. J. Med.
Chem. 2007, 50, 65–73. DOI: 10.1021/jm061045z.
[3] Anderson, D. R.; Hegde, S.; Reinhard, E.; Gomez, L.; Vernier,
W. F.; Lee, L.; Liu, S.; Sambandam, A.; Snider, P. A.; Masih, L.
Aminocyanopyridine Inhibitors of Mitogen Activated Protein
Kinase-Activated Protein Kinase 2 (MK-2). Bioorg. Med. Chem.
Lett. 2005, 15, 1587–1590. DOI: 10.1016/j.bmcl.2005.01.067.
[4] Zhang, F.; Wang, G. A Review of Non-Nucleoside Anti-
Hepatitis
B Virus Agents. Eur. J. Med. Chem. 2014, 75,
267–281. DOI: 10.1016/j.ejmech.2014.01.046.
[5] Cadilla, R.; Turnbull, P. Selective Androgen Receptor
Modulators in Drug Discovery: Medicinal Chemistry and
Therapeutic Potential. Curr. Top. Med. Chem. 2006, 6, 245–270.
DOI: 10.2174/156802606776173456.
[6] Zhang, X.; Qiu, Y.; Li, X.; Bhattacharjee, S.; Woods, M.; Kraft,
P.; Lundeen, S. G.; Sui, Z. Discovery and Structure-Activity
Relationships of a Novel Series of Benzopyran-Based K(ATP)
Openers for Urge Urinary Incontinence. Bioorg. Med. Chem.
2009, 17, 855–866. DOI: 10.1016/j.bmc.2008.11.055.
[7] Reddy, T. R. K.; Mutter, R.; Heal, W.; Guo, K.; Gillet, V. J.; Pratt,
S.; Chen, B. Library Design, Synthesis, and Screening: Pyridine

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
7
[25] Evdokimov, N. M.; Kireev, A. S.; Yakovenko, A. A.; Antipin, [40] Shinde, P. V.; Sonar, S. S.; Shingate, B. B.; Shingare, M. S. Boric
Acid Catalyzed Convenient Synthesis of 2-Amino-3,5-
Dicarbonitrile-6-Thio-Pyridines in Aqueous Media. Tetrahedron
Lett. 2010, 51, 1309–1312. DOI: 10.1016/j.tetlet.2009.12.146.
[41] Shinde, P. V.; Sonar, S. S.; Shingate, B. B.; Shingare, M. S.
Multi-Component Synthesis of 2-Amino-6-(Alkylthio)Pyridine-
3,5-Dicarbonitriles Using Zn(II) and Cd(II) Metal–Organic
Frameworks (MOFs) Under Solvent Free Conditions.
Tetrahedron Lett. 2012, 53, 4870–4872. DOI: 10.1016/j.tetlet.
2012.06.139.
[42] Su, M. S.; Ji, X. J.; Zhao, B. B.; Tian, M.; Ma, J. J.
Phosphotungstic Acid Catalyzed One-Pot Synthesis of 2-
Amino-3,5-Dicarbonitrile-6-Thio-Pyridines in Aqueous Media.
J. Chem. Soc. Pak. 2015, 37, 1130–1134.
M. Y.; Magedov, I. V.; Kornienko, A. One-Step Synthesis of
Heterocyclic Privileged Medicinal Scaffolds by
Multicomponent Reaction of Malononitrile with Aldehydes and
Thiols. J. Org. Chem. 2007, 72, 3443–3453. DOI: 10.1021/
jo070114u.
a
[26] Poor Heravi, M. R.; Fakhr, F. Ultrasound-Promoted Synthesis of
2-Amino-6-(Arylthio)-4-Arylpyridine-3,5-Dicarbonitriles
Using
ZrOCl2ꢄ8H2O/NaNH2 as the Catalyst in the Ionic Liquid
[Bmim]BF4 at Room Temperature. Tetrahedron Lett. 2011, 52,
6779–6782. DOI: 10.1016/j.tetlet.2011.10.031.
[27] Niknam, K.; Hosseini, A. R. Synthesis of 2-Amino-3,5-
Dicarbonitrile-6-Thiopyridines
Propyldiethylenetriamine as
Using
Silica-Bonded
N-
a
Heterogeneous Solid Base
[43] Sridhar, M.; Ramanaiah, B. C.; Narsaiah, C.; Mahesh, B.;
Kumaraswamy, M.; Mallu, K. K. R.; Ankathi, V. M.; Rao, P. Sh.
Novel ZnCl2-Catalyzed One-Pot Multicomponent Synthesis of
2-Amino-3,5-Dicarbonitrile-6-Thio-Pyridines. Tetrahedron Lett.
2009, 50, 3897–3900. DOI: 10.1016/j.tetlet.2009.04.051.
Catalyst. Org. Chem. Res. 2017, 3, 16–24. DOI: 10.22036/org.
chem.2017.41100.
[28] Pravin, V.; Bapurao, B.; Murlidhar, S. Facile and Rapid Access
to Polyfunctionalized Pyridine Derivatives. Chin. J. Chem. 2011,
29, 1049–1054. DOI: 10.1002/cjoc.201190178.
[29] Pandharpatte, M. S.; Osman, H. A.; Osman, A. M.; Nazeruddin,
G. M. Microwave Promoted Sodium Acetate Catalyzed One Pot
Synthesis of Highly Functionalized Pyridine Derivatives. Chem.
Sci. Trans. 2017, 6, 1–7. DOI: 10.7598/cst2017.1277.
[30] Sobhani, S.; Honarmand, M. 2-Hydroxyethylammonium
Acetate: A Reusable Task-Specific Ionic Liquid Promoting One-
[44] Takale, S.; Patil, J.; Padalkar, V.; Pisal, R.; Chaskar, A. O-
Iodoxybenzoic Acid in Water: Optimized Green Alternative for
Multicomponent
One-Pot
Synthesis
of
2-Amino-3,5-
Dicarbonitrile-6-Thiopyridines. J. Braz. Chem. Soc. 2012, 23,
966–969. DOI: 10.1590/S0103-50532012000500024.
[45] Keith, L. H.; Gron, L. U.; Young, J. L. Green Analytical
Methodologies. Chem. Rev. 2007, 107, 2695–2708. DOI: 10.
1021/cr068359e.
[46] Anastas, P. T. Green Chemistry and the Role of Analytical
Methodology Development. Crit. Rev. Anal. Chem. 1999, 29,
167–175. DOI: 10.1080/10408349891199356.
[47] Sheldon, R. A. Green and Sustainable Manufacture of
Chemicals from Biomass: State of the Art. Green Chem. 2014,
16, 950–963. DOI: 10.1039/C3GC41935E.
[48] Sheldon, R. A. Green Solvents for Sustainable Organic
Synthesis: State of the Art. Green Chem. 2005, 7, 267–278. DOI:
10.1039/b418069k.
Pot,
Three-Component
Synthesis
of
2-Amino-3,5-
Dicarbonitrile-6-Thio-Pyridines. C. R. Chim. 2013, 16, 279–286.
DOI: 10.1016/j.crci.2012.10.011.
[31] Das, B.; Ravikanth, B.; Kumar, A. S.; Kanth, B. S. An Efficient
Procedure for the Synthesis of Substituted Pyridines Using
KF.Al2O3. J. Heterocyclic Chem. 2009, 46, 1208–1212. DOI: 10.
1002/jhet.206.
[32] Shinde, P. V.; Labade, V. B.; Shingate, B. B.; Shingare, M. S.
Application of Unmodified Microporous Molecular Sieves for
the Synthesis of Polyfunctionalized Pyridine Derivatives in
Water. J. Mol. Catal. A Chem. 2011, 336, 100–105. DOI: 10.
1016/j.molcata.2011.01.005.
[33] Ranu, B. C.; Jana, R.; Sowmiah, S. An Improved Procedure for
the Three-Component Synthesis of Highly Substituted Pyridines
Using Ionic Liquid. J. Org. Chem. 2007, 72, 3152–3154. DOI:
10.1021/jo070015g.
[34] Davoodnia, A.; Attar, P.; Eshghi, H.; Morsali, A.; Tavakoli-
Hoseini, N.; Tavakoli-Nishaburi, A. Ionic Liquid, [Bmim]Br, as
an Efficient Promoting Medium for Synthesis of 2-Amino-3,5-
Dicarbonitrile-6-Thiopyridines. Asian J. Chem. 2011, 23,
1273–1275.
[49] Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and
Practice; Oxford University Press: New York, 1998.
[50] Saikia, B.; Boruah, P. R.; Ali, A. A.; Sarma, D. On-Water
Organic Synthesis: A Green, Highly Efficient, Low Cost and
Reusable Catalyst System for Biaryl Synthesis under Aerobic
Conditions at Room Temperature. RSC Adv. 2015, 5,
50655–50659. DOI: 10.1039/C5RA09102K.
[51] Boruah, P. R.; Ali, A. A.; Chetia, M.; Saikia, B.; Sarma, D.
Pd(OAc)2 in WERSA: A Novel Green Catalytic System for
Suzuki-Miyaura
Cross-Coupling
Reactions
at
Room
Temperature. Chem. Commun. (Camb) 2015, 51, 11489–11492.
DOI: 10.1039/C5CC04561D.
[35] Safaei-Ghomi, J.; Ghasemzadeh, M. A.; Mehrabi, M. Calcium
Oxide Nanoparticles Catalyzed One-Step Multicomponent
Synthesis of Highly Substituted Pyridines in Aqueous Ethanol
Media. Sci. Iran. C 2013, 20, 549–554. DOI: 10.1016/j.scient.
2012.12.037.
[52] Boruah, P. R.; Ali, A. A.; Saikia, B.; Sarma, D. A Protocol for
Ligand Free Suzuki–Miyaura Cross-Coupling Reactions in WEB
at Room Temperature. Green Chem. 2015, 17, 1442–1445. DOI:
10.1039/C4GC02522A.
[53] Dewan, A.; Sarmah, M.; Bora, U.; Thakur, A. J. A Green
Protocol for Ligand, Copper and Base Free Sonogashira
Crosscoupling Reaction. Tetrahedron Lett. 2016, 57, 3760–3763.
DOI: 10.1016/j.tetlet.2016.07.021.
[54] Saikia, B.; Borah, P.; Barua, N. C. H2O2 in WEB: A Highly
Efficient Catalyst System for Dakin Reaction. Green Chem.
2015, 17, 4533–4536. DOI: 10.1039/C5GC01404B.
[55] Razavi, N.; Akhlaghinia, B. Cu(II) Immobilized on Aminated
Epichlorohydrin Activated Silica (CAES): As a New, Green and
Efficient Nanocatalyst for Preparation of 5-Substituted-1H-
Tetrazoles. RSC Adv. 2015, 5, 12372–12381. DOI: 10.1039/
C4RA15148H.
[36] Sobhani, S.; Honarmand, S. M. Ionic Liquid Immobilized on
c-Fe2O3 Nanoparticles:
A
New Magnetically Recyclable
Heterogeneous Catalyst for One-Pot Three-Component
Synthesis of 2-Amino-3,5-Dicarbonitrile-6-Thio-Pyridines. Appl.
Catal. A Gen. 2013, 467, 456–462. DOI: 10.1016/j.apcata.2013.
08.006.
[37] Kottawar, S. S.; Siddiqui, S. A.; Bhusare, S. R. Scandium
Triflate-Catalyzed One-Pot Multi-Component Synthesis of 2-
Amino-6-Thiopyridine-3,5-Dicarbonitriles.
Heterocycl.
Commun. 2012, 18, 249–252. DOI: 10.1515/hc-2012-0103.
[38] Banerjee, S.; Sereda, G. One-Step, Three-Component Synthesis
of Highly Substituted Pyridines Using Silica Nanoparticle as
Reusable Catalyst. Tetrahedron Lett. 2009, 50, 6959–6962. DOI:
10.1016/j.tetlet.2009.09.137.
[39] Safaei-Ghomi, J.; Ghasemzadeh, M. A. Cu(I) Nanoparticles: A
Highly Active and Easily Recyclable Catalyst for the Synthesis
of 2-Amino-3,5-Dicyano-6-Sulfanyl Pyridines. J. Sulfur Chem.
2013, 34, 233–241. DOI: 10.1080/17415993.2012.728220.
[56] Ghodsinia, S. S. E.; Akhlaghinia, B. A Rapid Metal Free
Synthesis of 5-Substituted-1H-Tetrazoles Using Cuttlebone as a
Natural High Effective and Low Cost Heterogeneous Catalyst.
RSC Adv. 2015, 5, 49849–49860. DOI: 10.1039/C5RA08147E.
[57] Zarghani, M.; Akhlaghinia, B. Copper Immobilized on
Aminated Ferrite Nanoparticles by 2-Aminoethyl Dihydrogen

8
A. ALLAHI AND B. AKHLAGHINIA
Phosphate (Fe3O4@AEPH2-Cu(II)) Catalyses the Conversion of
Aldoximes to Nitriles. Appl. Organometal. Chem. 2015, 29,
683–689. DOI: 10.1002/aoc.3351.
Novel, Green and Magnetically Recyclable Bifunctional
Nanocatalyst for One-Pot Multi-Component Synthesis of
Acridinediones Under Solvent-Free Conditions. New J. Chem.
2017, 41, 15485–15500. DOI: 10.1039/C7NJ03281A.
[58] Jahanshahi, R.; Akhlaghinia, B. Expanded Perlite: An
Inexpensive Natural Efficient Heterogeneous Catalyst for the
Green and Highly Accelerated Solvent-Free Synthesis of 5-
Substituted 1H-Tetrazoles Using [Bmim]N3 and Nitriles. RSC
Adv. 2015, 5, 104087–104094. DOI: 10.1039/C5RA21481E.
[71] Jahanshahi, R.; Akhlaghinia, B. Thiophene Methanimine-
Palladium Schiff Base Complex Anchored on Magnetic
Nanoparticles:
A Novel, Highly Efficient and Recoverable
Nanocatalyst for Cross-Coupling Reactions in Mild and
Aqueous Media. Catal. Lett. 2017, 147, 2640–2655. DOI: 10.
1007/s10562-017-2170-x.
[59] Siavashi, N. Y.; Akhlaghinia, B.; Zarghani, M. Sulfonated
Nanohydroxyapatite
Functionalized
with
2-Aminoethyl
Dihydrogen Phosphate (HAP@AEPH2-SO3H) as a Reusable
Solid Acid for Direct Esterification of Carboxylic Acids with
Alcohols. Res. Chem. Intermed. 2016, 42, 5789–5806. DOI: 10.
1007/s11164-015-2404-8.
[72] Mohammadian, N.; Akhlaghinia, B. Calcined Oyster Shell
Nanoparticles (COS NPs): A New, Efficient and Reusable
Catalyst for One-Pot Rapid Preparation of 1,8-Dioxo-
Octahydroxanthenes under Solvent-Free Conditions. Res. Chem.
Intermed. 2018, 42, 1085–1103. DOI: 10.1007/s11164-017-3153-7.
[73] Zarei, Z.; Akhlaghinia, B. Cu(II) Immobilized on
Fe3O4@Agarose Nanomagnetic Catalyst Functionalized with
[60] Jahanshahi, R.; Akhlaghinia, B. Cu(II) Immobilized on
Guanidinated Epibromohydrin Functionalized c-Fe2O3@TiO2
(c-Fe2O3@TiO2-EG-Cu(II)): A Novel Magnetically Recyclable
Heterogeneous Nanocatalyst for the Green One-Pot Synthesis
of 1,4-Disubstituted 1,2,3-Triazoles through Alkyne-Azide
Cycloaddition in Water. RSC Adv. 2016, 6, 29210–29219. DOI:
10.1039/x0xx00000x.
[61] Zarghani, M.; Akhlaghinia, B. Magnetically Separable
Fe3O4@Chitin as an Eco-Friendly Nanocatalyst with High
Efficiency for Green Synthesis of 5-Substituted-1H-Tetrazoles
under Solvent-Free Conditions. RSC Adv. 2016, 6,
31850–31860. DOI: 10.1039/C6RA07252F.
[62] Zarghani, M.; Akhlaghinia, B. Fe3O4 Magnetic Nanoparticles
(MNPs) as an Efficient Catalyst for Selective Oxidation of
Benzylic and Allylic C-H Bonds to Carbonyl Compounds with
tert-Butyl Hydroperoxide. RSC Adv. 2016, 6, 38592–38601.
DOI: 10.1002/chin.201635035.
Ethanolamine Phosphate Salicylaldehyde Schiff Base:
A
Magnetically Reusable Nanocatalyst for Preparation of 2-
Substituted Imidazolines, Oxazolines, and Thiazolines. Turk. J.
Chem. 2018, 42, 170–191. DOI: 10.3906/kim-1704-53.
[74] Ghasemzadeh, M. S.; Akhlaghinia, B. 2-Aminoethanesulfonic
Acid Immobilized on Epichlorohydrin Functionalized
Fe3O4@WO3 (Fe3O4@WO3-EAE-SO3H): A Novel Magnetically
Recyclable Heterogeneous Nanocatalyst for the Green One-Pot
Synthesis of 1-Substituted-1H-1,2,3,4-Tetrazoles in Water. Bull.
Chem. Soc. Jpn. 2017, 90, 1119–1128. DOI: 10.1246/bcsj.
20170148.
[75] Ghasemzadeh, M. S.; Akhlaghinia, B. c-Fe2O3@SiO2-EC-Zn(II):
A
Magnetic Recyclable Nanocatalyst for the Synthesis of
Spiro[Indoline-3,9-Xanthene]Trione Derivatives in Aqueous
Media. ChemistrySelect 2018, 3, 3161–3170. DOI: 10.1002/slct.
201703189.
[63] Masjed, S. M.; Akhlaghinia, B.; Zarghani, M.; Razavi, N. Direct
Synthesis of Nitriles from Aldehydes and Hydroxylamine
Hydrochloride
Catalyzed
by
a
HAP@AEPH2-SO3H
[76] Zamani, M.; Akhlaghinia, B.; Mohammadinezhad, A. Selective,
Efficient and Gram-Scale Oxidation of Alcohols Using
Household Bleach in the Presence of Fe3O4@Boehmite-NH2-
Co(II) Nanoparticles. ChemistrySelect 2018, 3, 9431–9442. DOI:
10.1002/slct.201802124.
[77] Ghasemzadeh, M. S.; Akhlaghinia, B. C-P Bond Construction
Catalyzed by Ni(II) Immobilized on Aminated Fe3O4@TiO2
Yolk-Shell NPs Functionalized by (3-Glycidyloxypropyl)
Trimethoxysilane (Fe3O4@TiO2 YS-GLYMO-UNNi(II)) in
Green Media. New J. Chem. 2019, 43, 5341–5356. DOI: 10.
1039/C9NJ00352E.
[78] Mohammadinezhad, A.; Akhlaghinia, B. Co(II) Immobilized on
Aminated Magnetic Metal-Organic Framework Catalyzed C-N
and C-S Bond Forming Reactions: A Journey for the Mild and
Efficient Synthesis of Arylamines and Arylsulfides. New J.
Chem. 2019, 43, 15525–15538. DOI: 10.1039/C9NJ03400E.
[79] Pakdel, S.; Akhlaghinia, B.; Mohammadinezhad, A.
Fe3O4@Boehmite-NH2-Co(II) NPs: An Environment Friendly
Nanocatalyst for Solvent Free Synthesis of Coumarin
Derivatives through Pechmann Condensation Reaction. Chem.
Africa 2019, 2, 367–376. DOI: 10.1007/s42250-019-00042-5.
[80] Mohammadian, N.; Akhlaghinia, B. Magnetic Calcined Oyster
Shell Functionalized with Taurine Immobilized on B-
Cyclodextrin (Fe3O4/COS@B-CD-SO3H NPs) as Green and
Magnetically Reusable Nanocatalyst for Efficient and Rapid
Synthesis of Spirooxindoles. Res. Chem. Intermed. 2019, 45,
4737–4756. DOI: 10.1007/s11164-019-03860-x.
Nanocatalyst. Aust. J. Chem. 2017, 70, 33–43. DOI: 10.1071/
CH16126.
[64] Zarghani, M.; Akhlaghinia, B. Green and Efficient Procedure
for Suzuki-Miyaura and Mizoroki-Heck Coupling Reactions
Using Palladium Catalyst Supported on Phosphine
Functionalized ZrO2 NPs (ZrO2@ECP-Pd) as a New Reusable
Nanocatalyst. Bull. Chem. Soc. Jpn. 2016, 89, 1192–1200. DOI:
10.1246/bcsj.20160163.
[65] Zarei, Z.; Akhlaghinia, B. Zn(II) Anchored on to the Magnetic
Natural Hydroxyapatite (Zn(II)/HAP/Fe3O4): as a Novel, Green
and Recyclable Catalyst for A3-Coupling Reaction towards
Propargylamine Synthesis under Solvent-Free Conditions. RSC
Adv. 2016, 6, 106473–106484. DOI: 10.1039/C6RA20501A.
[66] Razavi, N.; Akhlaghinia, B.; Jahanshahi, R. Aminophosphine
Palladium(0) Complex Supported on ZrO2 Nanoparticles
(ZrO2@AEPH2-PPh2-Pd(0)) as an Efficient Heterogeneous
Catalyst for Suzuki–Miyaura and Heck–Mizoroki Reactions in
Green Media. Catal. Lett. 2017, 147, 360–373. DOI: 10.1007/
s10562-016-1944-x.
[67] Jahanshahi, R.; Akhlaghinia, B. Cu(II)-Grafted SBA-15
Functionalized S-Methylisothiourea Aminated Epibromohydrin
(SBA-15/E-SMTU-Cu(II)): A Novel and Efficient Heterogeneous
Mesoporous Catalyst. New J. Chem. 2017, 41, 7203–7219. DOI: 10.
1039/C7NJ00849J.
[68] Mohammadinezhad, A.; Akhlaghinia, B. Nanofibre Sepiolite
Catalyzed Green and Rapid Synthesis of 2-Amino-4H-Chromene
Derivatives. Aust. J. Chem. 2018, 71, 32–46. DOI: 10.1071/
CH17093.
[81] Ghodsinia, S. S.; Akhlaghinia, B. Cu(I) Anchored onto
Mesoporous SBA-16 Functionalized by Aminated 3-
Glycidyloxypropyltrimethoxysilane with Thiosemicarbazide (SBA-
16/GPTMS-TSC-Cu(I)): a Heterogeneous Mesostructured Catalyst
for S-Arylation Reaction under Solvent-Free Conditions. Green
Chem. 2019, 21, 3029–3049. DOI: 10.1039/C8GC03931C.
[82] Ghasemzadeh, M. S.; Akhlaghinia, B. Fmmwcnts@CPA@
SMTU@Pd(II) NPs: As a Versatile Ferromagnetic Nanostructured
Catalyst for Sonogashira-Hagihara Cross-Coupling Reaction in
[69] Mohammadinezhad, A.; Akhlaghinia, B. Co(II) Immobilized on
Aminated Fe3O4@Boehmite Nanoparticles (Fe3O4@Boehmite-
NH2-Co(II) NPs): A Novel, Inexpensive and Highly Efficient
Heterogeneous Magnetic Nanocatalyst for Suzuki–Miyaura and
Heck–Mizoroki Cross-Coupling Reactions in Green Media.
Green Chem. 2017, 19, 5625–5641. DOI: 10.1039/C7GC02647A.
[70] Zarei, Z.; Akhlaghinia, B. Zn(II) Doped and Immobilized on
Functionalized Magnetic Hydrotalcite (Fe3O4/HT-SMTU-Zn(II)): A

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
9
Solvent-Free Conditions. ChemistrySelect 2019, 4, 1542–1555. DOI: [86] Chavan, A. S.; Kharat, A. S.; Bhosle, M. R.; Mane, R. A. A
10.1002/slct.201803453.
Convenient Baker Yeast Accelerated, One-Potsynthesis of
Pentasubstituted Thiopyridines. Synth. Commun. 2017, 47,
1777–1782. DOI: 10.1080/00397911.2017.1350982.
[83] Ghasemzadeh, M. S.; Akhlaghinia, B. Pd(II) Immobilized on
Ferromagnetic Multi-Walled Carbon Nanotubes Functionalized
by Aminated 2-Chloroethylphosphonic Acid with S-
Methylisothiourea (Fmmwcnts@CPA@SMTU@Pd(II) NPs)
Applied as a Highly Efficient and Recyclable Nanostructured
Catalyst for Suzuki–Miyaura and Mizoroki–Heck Cross-
Coupling Reactions in Solvent-Free Conditions. Aust. J. Chem.
2019, 72, 674–692. DOI: 10.1071/CH19117.
[84] Akhlaghinia, B.; Sanati, P.; Mohammadinezhad, A.; Zarei, Z.
The Magnetic Nanostructured Natural Hydroxyapatite (Hap/
Fe3O4 NPs): An Efficient, Green and Recyclable Nanocatalyst
for the Synthesis of Biscoumarin Derivatives under Solvent-Free
Conditions. Res. Chem. Intermed. 2019, 45, 3215–3235. DOI:
10.1007/s11164-019-03788-2.
[87] Norouzi, M.; Ghorbani-Choghamarani, A.; Nikoorazm, M.
Heterogeneous Cu(II)/L-His@Fe3O4 Nanocatalyst:
A Novel,
Efficient and Magnetically Recoverable Catalysts for Organic
Transformations in Green Solvents. RSC Adv. 2016, 6,
92387–92401. DOI: 10.1039/C6RA19776K.
[88] Hao, D.; Yun-Lei, Z.; Xiao-Peng, S.; Yang Jin-Ming, Y.; Dong,
F. Synthesis of 2-Amino-4-Phenyl-6-(Phenylsulfanyl)-3,5-
Dicyanopyridines by Tandem Reaction. Res. Chem. Intermed.
2014, 40, 587–594. DOI: 10.1007/s11164-012-0984-0.
[89] Manna, P.; Maiti, P. K. First Report of Multiple Metal Ions
Containing Glass Ceramic Material as a Heterogeneous Ditopic
Catalyst for the Chromatography Free Synthesis of 2-Amino-3,
5-Dicarbonitrile-6-Arylthio-Pyridines in Water. Tetrahedron
Lett. 2015, 56, 5094–5098. DOI: 10.1016/j.tetlet.2015.07.038.
[85] Deka, D. C.; Talukdar, N. N. Chemical and Spectroscopic
Investigation of Kolakharand Its Commercial Importance.
Indian J. Tradit. Know 2007, 6, 72–78.