A simple, rapid and effective protocol for synthesis of bis(pyrazolyl)methanes using nickel–guanidine complex immobilized on MCM-41

Article abstract of DOI:10.1007/s11164-019-04073-y

Abstract: In this paper, a rapid, easy and very efficient method for the synthesis of bis(pyrazolyl)methanes has been reported in the presence of nickel–guanidine complex immobilized on MCM-41 (MCM-41@Gu@Ni) as a recyclable nanocatalyst. This mesoporous s

Full text of DOI:10.1007/s11164-019-04073-y

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-019-04073-y
A simple, rapid and efective protocol for synthesis
of bis(pyrazolyl)methanes using nickel–guanidine complex
immobilized on MCM‑41
Alireza Kohzadian, et al. [full author details at the end of the article]
Received: 3 October 2019 / Accepted: 30 December 2019
© Springer Nature B.V. 2020
Abstract
In this paper, a rapid, easy and very efcient method for the synthesis of
bis(pyrazolyl)methanes has been reported in the presence of nickel–guanidine com-
plex immobilized on MCM-41 (MCM-41@Gu@Ni) as a recyclable nanocatalyst.
This mesoporous silica catalyst was efective for the one-pot multi-component reac-
tion of arylaldehydes, phenylhydrazine and ethyl acetoacetate in ethanol solvent.
The current synthesis shows attractive features, for example the use of recoverable
and reusable nanocatalyst (5 times), easy workup, suitable one-pot procedure, short
reaction times, good to excellent yields and moderate reaction conditions.
Graphic abstract
EtOH, 60 °C
PhHN
NH2
OEt
EtO
OH
HO
Ph
Ph
O
O
O
O
N
N
N
N
Ar
CHO
NH2
Ar
PhHN
Time = 25-50 min
Yield = 82-96%
HN
Ni
NH2
1
4
-
O
O
O
M
Si
N
The nanocatalyst =
C
H
M
MCM–41@Gu@Ni
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-019-04073-y) contains supplementary material, which is available to authorized users.
Vol.:(0123456789)
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A. Kohzadian et al.
Keywords Nanocatalyst · Nickel–guanidine complex immobilized on MCM-
41 (MCM-41@Gu@Ni) · Bis(pyrazolyl)methanes · Phenylhydrazine · Ethyl
acetoacetate · Arylaldehyde
Introduction
Today, the evolution of technology has become directly linked to the smaller dimen-
sions of particles, so nanoscience has attracted considerable attention [1, 2]. Nano-
catalysts are very important tools in this feld, because they have diferent chemical
and physical properties compared to bulk materials [3, 4]. In fact, with the transi-
tion of microparticles to nanoparticles we confront two fundamental changes: (1)
increase the surface-to-volume ratio [5]; (2) enter the particle sizes into the realm
of mechanical efects and view the unusual properties resulting from the nanoscale
(magnetic, optical, etc.) [6]. Some others of the characteristics of nanoparticles
which make them attractive as a catalyst include: improved energy efciency and
economy, minimum chemical waste, easy functionalization, high mechanical stabil-
ity, low density and high permeability [7–12].
A domino reaction is a method including at least two bond-forming transforma-
tions under identical conditions without increasing excess catalysts and reagents [13,
14]. In this process, the subsequent reactions are the result of the formation of func-
tional groups in the previous stages, so these reactions are an important tool in the
modern total synthesis to produce macromolecules [15, 16]. Domino reactions have
remarkable advantages compared to conventional reactions, such as saving resources
by minimizing waste and reducing the reaction time by minimizing the steps to
reach the target molecule [16, 17].
One of the most active classes of compounds with a wide range of approved bio-
logical activities are the heterocycles containing pyrazole core [18]. For example,
pyrazole derivatives such as bis(pyrazolyl)methanes being used as antiviral [19],
anti-infammatory [20], antihypertensive [21], antioxidant [21], antidepressant [22],
antimicrobial [23], gastric secretion stimulatory [24], antibacterial [25], anticancer
[26], anti-HIV [27], antipyretic [28], antimalarial [29] and antiflarial activities [30].
Additionally, these derivatives are applied as pesticides [31], dyestufs [32], extract-
ing reagents and chelating for diverse metal ions [32] and important intermediates
in organic synthesis [33]. The common method for the synthesis of bis(pyrazolyl)
methanes is pseudo-three-component condensation reaction of arylaldehydes with
3-methyl-1-phenyl-1H-pyrazol-5(4H)-one. This protocol has been reported in
the attendance of various catalysts, for example alpha-casein [34], Cu–ZnO [35],
morpholinium glycolate [36], silica-bonded n-propyl-4-aza-1-azoniabicyclo[2.2.2]
octane hydrogen sulfate ((SB-DABCO)HSO4) [37], N,2-dibromo-6-chloro-3,4-
dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide (DCDBTSD)
[38], N,N,N′,N′-tetramethylethylenediaminium-N,N′-disulfonic acid hydrogen sul-
fate ([TMEDSA][HSO4]2) [39], 1,3-disulfonic acid imidazolium trifuoroacetate
([Dsim][TFA]) [40], ʟ-proline [41] and silica-bonded N-propylpiperazine sulfamic
acid (SBPPSA) [42]. Anyway, some of these reported procedures sufer from
defects such as tedious work-up methods, strongly acidic or basic conditions, longer
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A simple, rapid and efective protocol for synthesis of…
reaction time, low yield, corrosive and toxic solvent, expensive catalysts or reagents,
large amounts of catalysts, non-recyclable catalysts and poor selectivity or com-
mercial unavailability. However, restricted ways have been reported for the produc-
tion of these compounds by one-pot pseudo-fve-component condensation reaction
of ethyl acetoacetate, phenylhydrazine derivatives and arylaldehydes. So, due to of
the signifcance of these derivatives, the presentation of a quicker, easier and more
environmentally friendly method joined with higher efciency is quite required. We
report here efectual protocol for the synthesis of bis(pyrazolyl)methanes via one-
pot pseudo-fve-component domino reaction of ethyl acetoacetate (2 eq.) and phenyl
hydrazine (2 eq.) with aromatic aldehydes (1 eq.) at 60 °C in ethanol solvent.
Results and discussion
Nickel–guanidine complex immobilized on MCM-41 (MCM-41@Gu@Ni) was
synthesized according to Scheme 1 [43]. The FE-SEM (feld emission scanning
electron microscopy) and TEM (transmission electron microscopy) micrographs of
the nanocatalyst are shown in Figs. 1 and 2. The exact amount of nickel in catalyst
which was obtained by inductively coupled plasma (ICP) technique was found to be
1.6×10−3 mol g−1 [43].
The low-angle powder X-ray difraction patterns of both MCM-41 and MCM-
41@Gu@Ni samples are shown in Fig. 3. The pattern of the MCM-41 shows
three refection peaks corresponding to d100, d110 and d200 which are typical
CPTMS
n–Hexane, 80 oC
OH
OH
OH
NaOH
80 oC
O
O
CTAB
TEOS
+
Si
Cl
O
24h
MCM–41
CPTMS = 3-chloropropyltriethoxysilane
MCM-41@CPTMS
–
+
NH
O
2
NH
NH2
N
O
H N
NH
O
2
2
O
O
MCM-41@CPTMS
O
Si
N
H
Toluene, Na2CO3, 24h
MCM-41@Guanidine
HN
Ni
Ni(NO3)2.6H2O
O
O
MCM-41@Guanidine
Si
N
H
N
O
EtOH, 18 h, Reflux
H2
MCM-41@Gu@Ni
Scheme 1 The production of MCM-41@Gu@Ni
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A. Kohzadian et al.
Fig. 1 The FE-SEM image of
MCM-41@Gu@Ni
Fig. 2 The TEM micrograph of
MCM-41@Gu@Ni
confrming the presence of the ordered hexagonal mesoporous structure of MCM-
41. However, upon post-synthetic grafting, the d110 and d200 refections are no
longer observed and an overall decrease in intensity of d100 is observed. This is
probably due to the diference in scattering contrast of the pores and the walls, and
to the irregular immobilization of nickle complex on nano-channels.
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A simple, rapid and efective protocol for synthesis of…
Fig. 3 The low-angle XRD patterns of MCM-41 and MCM-41@Gu@Ni
N2 adsorption–desorption isotherms of MCM-41 and MCM-41@Gu@Ni are
shown in Fig. 4. Based on the IUPAC classifcation, the samples exhibit the type
IV curves, which is corresponded to mesoporous materials. The nitrogen adsorp-
tion–desorption isotherms exhibit the surface area of MCM-41 and MCM-41@
Gu@Ni which is 902.23 and 428.25 m2 g−1, respectively. The pore diameter and
pore volume of the mesoporous materials indicate a marked decrease as a result
of grafting organic layers and nickel complex on the surface of the MCM-41.
These results indicate that due to the presence of the large organic moieties within
the pore channels of mesoporous silica, the nickel complex loading appears as a
thin layer on the inner surface of MCM-41. The surface properties of the synthe-
sized materials are summarized in Table 1.
Catalytic activity of MCM-41@Gu@Ni was investigated in the synthesis of
bis(pyrazolyl)methanes (Scheme 2). At frst, the condensation of arylaldehydes,
phenylhydrazine and ethyl acetoacetate for the synthesis of bis(pyrazolyl)meth-
anes has been selected as the model reaction (Scheme 2). Afterward, the reac-
tion conditions for the synthesis of bis(pyrazolyl)methanes have been optimized
for diverse factors (Table 2). For this purpose, the efect of diverse amounts of
Fig. 4 N2 adsorption–desorption isotherms of MCM-41 (a) and MCM-41@Gu@Ni (b)
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A. Kohzadian et al.
Table 1 Surface properties
of MCM-41 and MCM-41@
Gu@Ni
Sample
SBET (m2/g) Pore diameter by Pore
BJH method (nm) volume
(cm3/g)
MCM-41
MCM-41@Gu@Ni 428.25
902.23
3.3
1.29
0.8265
0.61
OH HO
CHO
Ph
Ph
EtO
N
N
N
N
O
O
MCM-41@Gu@Ni
Different condions
2PhHN NH2
+
2
+
Cl
Cl
Scheme 2 The model reaction
Table 2 The results of optimizing the catalyst quantity, temperature and solvent on the reaction of arylal-
dehydes, phenylhydrazine and ethyl acetoacetate
Entry Catalyst
Catalyst
amount
(g)
Temp. (°C) Solvents Solvent
Time (min) Yielda (%)
amount
(mL)
1
2
3
4
5
6
7
8
MCM-41@Gu@Ni
0.02
0.03
0.02
0.02
0.01
0.03
0.02
0.02
0.02
0.02
110
90
Refux
60
60
–
–
–
–
2
2
2
2
2
2
2
2
2
2
60
80
25
25
35
25
35
40
360
360
360
360
60
40
98
96
84
96
90
87
Trace
Trace
Trace
Trace
MCM-41@Gu@Ni
MCM-41@Gu@Ni
MCM-41@Gu@Ni
MCM-41@Gu@Ni
MCM-41@Gu@Ni
MCM-41@Gu@Ni
MCM-41@Gu@Ni
MCM-41
EtOH
EtOH
EtOH
EtOH
EtOAc
CH3CN
EtOH
EtOH
EtOH
EtOH
60
Refux
Refux
Refux
Refux
Refux
Refux
9
10
11
12
Guanidine
MCM-41@guanidine 0.02
Ni(NO3)2. 6H2O 0.02
aYield of isolated product
MCM-41@Gu@Ni catalyst, reaction temperature and solvent type, in the model
reaction, was examined (Table 2). The best results were obtained in 2 mL ethanol
as solvent using 0.02 g of MCM-41@Gu@Ni at 60 °C (Table 2, entry 4). Further-
more, performing the reaction under solvent-free conditions did not aford good
results (Table 2, entries 1–2). The reaction was also checked in the presence of
the components for the synthesis of MCM-41@Gu@Ni, i.e., MCM-41, guanidine,
MCM-41@guanidine and nickel(II) nitrate hexahydrate (Table 2, entries 9–12).
1 3

A simple, rapid and efective protocol for synthesis of…
As it is shown in Table 2, the starting substances could not efectively catalyze the
reaction; these results confrmed that our design for immobilization of guanidine
and nickel metal on MCM-41 surface in order to prepare MCM-41 was reasonable
and successful.
After determining the optimal conditions, in order to identify performance
and generality of MCM-41@Gu@Ni, synthesis of diverse derivatives such as
bis(pyrazolyl)methanes was tested by various arylaldehydes (including benzalde-
hyde and arylaldehydes having electron-acceptor, halogen and electron–donor sub-
stituents); the corresponding results are displayed in Table 3. As it can be observed
in this table, all arylaldehydes worked well in the reaction and obtained the related
derivatives in short times and with excellent yields.
An admissible mechanism, considered by the literature [35], is shown in
Scheme 3. Initially, the carbonyl group in the ethyl acetoacetate was activated by the
nanocatalyst nickel for attack of lone pair of nitrogen form phenylhydrazine to form
intermediate pyrazolone I. In the next step, the activated aromatic aldehyde by nano-
catalyst nickel undergone a tandem reaction with intermediate II (which is the tau-
tomer of intermediate I) leads to intermediate III after removal of a H2O molecule
(the nanocatalyst also helps removing H2O). The next step is a Michael addition of
Table 3 The production of bis(pyrazolyl)methanes using MCM-41@Gu@Ni
OH HO
Ph
Ph
EtO
2
N
N
N
N
O
O
MCM-41@Gu@Ni (0.02 gr)
EtOH, 60 °C
2 PhHN NH2
+
Ar CHO
Ar
Comp. no
Ar
Time (min)
Yielda (%)
Mp (°C)
Found
Reported
1
C6H5
25
40
35
40
35
30
50
30
30
25
35
35
50
90
90
91
88
90
92
87
86
90
96
90
96
82
167–169
221–219
149–151
227–229
198–200
173–175
190–192
222–224
241–243
210–212
176–178
250–252
215–217
166–168 [39]
221–223 [44]
148–150 [39]
229–231 [39]
198–200 [39]
174–176 [39]
191–193 [39]
224–226 [39]
240–242 [39]
208–210 [39]
175–177 [44]
251–253 [39]
213–216 [45]
2
2-O2NC6H4
3-O2NC6H4
4-O2NC6H4
4-MeC6H4
4-MeOC6H4
3,4-(MeO)2C6H3
2,4-(Cl)2C6H3
2-ClC6H4
4-ClC6H4
4-FC6H4
2-BrC6H4
4-OHCC6H4
3
4
5
6
7
8
9
10
11
12
13b
aIsolated yield
bReaction conditions: terephthalaldehyde (1 mmol), ethyl acetoacetate (4 mmol), phenylhydrazine
(4 mmol), MCM-41@Gu@Ni (0.02 g) and EtOH (2 ml)
1 3

A. Kohzadian et al.
Ni
Ph
Ph
O
O
N
N
N
N
Ph-NHNH2
+
Me
OEt
O
Me
HO
Me
Ni
(I)
(II)
l
n
e
o
Ni
i
g
t
a
a
n
s
O
e
n
O
O
v
e
Ni
= Nanocatalyst Nickel = MCM-41@Gu@Ni
e
d
o
n
Ar
N
H
n
o
Me
OEt
K
c
Me
Me
Ar
Ph
N
Michael addition
N
N
N
N
Ni
O
Me
Ph
Ph
Ph
N N
Ni
OH
O
Ar
HO
Me
(III)
Ni
(IV)
Me
(II)
Me
Ar
N
N
N
N
Ph
N
N
Ph
Ph
OH HO
O
Me
Ni
bis(pyrazolyl)methanes
(I)
Scheme 3 The suggested mechanism for the preparation of bis(pyrazolyl)methanes
another intermediate of III to II to form intermediate IV. In the last step, after the
tautomeric proton shift, aford bis(pyrazolyl)methanes.
To display the superiority of our catalyst in comparison with other catalysts
used in the synthesis of bis(pyrazolyl)methanes via one-pot pseudo-fve-compo-
nent, these catalysts were compared in factors of the turnover frequency (TOF)
and turnover number (TON), reaction yield, time and temperature, in the synthe-
sis of compound 10; the results are illustrated in Table 4. According to the table
data, MCM-41@Gu@Ni was superior to other catalysts at least in four items of
comparison items.
The recovery capability of MCM-41@Gu@Ni was considered for the reaction
of phenylhydrazine, ethyl acetoacetate and 4-chlorobenzaldehyde to produce com-
pound 10. Recycling the nanocatalyst was obtained by the stated method in the
experimental section; it was reusable for 5 times with insignifcant loss of its activ-
ity (Fig. 5). The recycled MCM-41@Gu@Ni was also characterized by low-angle
powder X-ray difraction. The XRD pattern of recycled MCM-41@Gu@Ni (Fig. 6)
was slightly diferent relative to the fresh catalyst (the sharp peaks have decreased);
this can attributed to aggregation of the nanoparticles and increment of their sizes,
during recycling and reusing.
For the purpose of catalyst leaching, hot fltration experiment has been per-
formed in the reaction of phenylhydrazine, ethyl acetoacetate and 4-chloroben-
zaldehyde. In this test, 55% of the product was obtained after half-time of the
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A simple, rapid and efective protocol for synthesis of…
Table 4 Comparison results of MCM-41@Gu@Ni with other catalysts reported in the literature
Catalyst
Conditions
Time (min) Yield (%) TON
TOF (min−1
)
Ref.
MCM-41@Gu@Ni
Alpha-casein
EtOH, 60 °C
25
15
96
94
29.6
4.7
1.18
0.31
–
[34]
EtOH/H2O (2:1),
60 °C
Cu–ZnO NPs
EtOH, refux
Solvent-free, 80 °C
90
5
93
96
3.7
6.4
0.04
1.28
[35]
[36]
Morpholinium gly-
colate
(SB-DABCO)HSO4
DCDBTSD
EtOH, refux
Solvent-free, 80 °C
EtOH, 70 °C
EtOH, refux
EtOH, refux
40
40
30
30
55–80
35–60
70
88
80
93
93
84–95
80–93
90
14.7
8
18.6
13.3
0.37
0.20
0.62
0.44
[37]
[38]
[39]
[40]
[41]
[42]
[45]
[TMEDSA][HSO4]2
[Dsim][TFA]
ʟ-prolinea
4.2–4.8 0.05–0.10
9.2–10.7 0.04–0.30
–
SBPPSAb
Solvent-free, 80 °C
SSAc
EtOH/H2O (1:1),
–
70 °C
a,bIn this work, product 11 has not been synthesized; thus, we have tabulated the range of times and
yields
cIn this work, mol% of the catalyst has not been reported; thus, we could not calculate TON and TOF of
the catalyst
Time (min)
94
Yield (%)
94
96
96
100
90
80
70
60
50
40
30
20
10
0
92
90
30
27
27
25
25
25
Run 1
Run 2
Run 3
Run 4
Run 5
Run 6
Fig. 5 The recycling experiment of MCM-41@Gu@Ni in the production of bis(pyrazolyl)methanes
reaction. Moreover, the same reaction was repeated and after the half-time of
the reaction (after 12 min), the catalyst was removed and fltrated mixture was
allowed to run until the 25 min. In this step, 57% of the product was obtained.
These experiments verify that leaching of nickel does not occur.
1 3

A. Kohzadian et al.
Fig. 6 The low-angle powder X-ray pattern of recycled MCM-41@Gu@Ni
Conclusions
In summary, we have reported the synthesis of bis(pyrazolyl)methanes using
MCM-41@Gu@Ni as a heterogeneous and reusable catalyst in a recyclable
media. The advantages of this protocol are the use of a commercially available
materials, efciency, high yield, relatively short reaction time, low cost, cleaner
reaction profle, ease of product isolation and simplicity. Also, all products were
obtained in high yields without formation of by-product.
Experimental
Materials and apparatuses
All chemicals were purchased from Merck or Fluka Chemical Companies. All
known compounds were identifed by comparison of their melting points and/or
spectral data with those reported in the literature. Reaction progress was moni-
tored by thin-layer chromatography (TLC) on silica gel SIL G/UV 254 plates.
Melting points were recorded on a Büchi B-545 apparatus in open capillary
1
tubes. H NMR (500 MHz) and 13C NMR (125 MHz) were run on a Bruker
Avance DPX, FT-NMR spectrometers. The morphologies and particles sizes
of samples were characterized by feld emission scanning electron microscopy
(FE-SEM), model TESCAN MIRA3 LMH. A transmission electron micro-
scope (TEM), model Philips CM200, was used to measure the size and shape of
particles.
Procedure for the production of MCM‑41@Gu@Ni
Initially, nanosized MCM-41 was prepared using the sol–gel method with CTAB
(cetyltrimethylammonium bromide) as the template, TEOS (tetraethyl orthosilicate)
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A simple, rapid and efective protocol for synthesis of…
as the silicon source and sodium hydroxide as pH control agent. In a typical proce-
dure, CTAB (2.74 mmol, 0.1 g) was added to a solution of deionized water (480 ml)
and NaOH (2 M, 3.5 ml) at 80 °C. When the solution became homogeneous (after
complete dissolution), TEOS (5 ml) was added dropwise to the solution under con-
tinuous stirring at 80 °C, and the obtained gel was aged under refux for 2 h. The
mixture was allowed to cool to room temperature, and the resulting product was fl-
tered and washed with distilled water. The obtained material was calcined at 550 °C
in air for 5 h and is designated as MCM-41.
Then, mesoporous MCM-41 modifed by 3-chloropropyltrimethoxysilane (MCM-
41@nPrCl) was synthesized according to our previous reported method [41]. For
immobilization of the guanidine on the surface of MCM-41@nPrCl, guanidine
nitrate (2 mmol) and Na2CO3 (2 mmol) were added to mixture of MCM-41@nPrCl
(1 g) in toluene (10 ml), and the reaction mixture was stirred for 24 h at 100 °C. The
obtained MCM-41@nPr-guanidine was fltered and washed with ethanol for sev-
eral times and then dried under air atmosphere. In the fnal step, immobilization of
nickel onto MCM-41@nPr-guanidine was performed by mixing the MCM-41@nPr-
guanidine (1 g) and Ni(NO3)2·6H2O (2 mmol) in ethanol. The resulted mixture was
stirred for 20 h under refux conditions. The obtained MCM-41@nPr-guanidine@
Ni was fltered and washed with ethanol for several times and, then, dried under air
atmosphere (Scheme 1) [43]. Moreover, the exact amount of nickel in catalyst which
was obtained by ICP technique was found to be 1.6×10−3 mol g−1. The FE-SEM
and TEM micrographs of the nanocatalyst are shown in Figs. 1 and 2.
General procedure for the production of bis(pyrazolyl)methanes
A mixture of phenylhydrazine (2 mmol), ethyl acetoacetate (2 mmol) and MCM-
41@Gu@Ni (0.02 g, 3.24 mol%) was stirred for 2 min at 60 °C. After this time, the
arylaldehydes (1 mmol) and EtOH (2 mL) were added and stirred at 60 °C. The pro-
gress of the reaction was monitored by TLC. After the completion of reaction, EtOH
(7 mL) was added, and the resulting mixture was stirred for 2 min at 60 °C, followed
by centrifugation and decanting to separate the nanocatalyst. The recovered catalyst
was washed with EtOH (2×2 mL), dried (at 90 °C under vacuum condition) and
reused for the same reaction. The EtOH resulted from the decanting was evaporated,
and the solid crude product was recrystallized from hot ethanol (95%) to aford the
bis(pyrazolyl)methane as a pure product.
Selected spectral data of the products
1
Product 5 H NMR (250 MHz, DMSO-d6): δ (ppm) 2.10 (s, 3H, –CH3), 3.16 (s,
6H, 2CH3), 4.78 (s, 1H, CH, methine), 7.07 (d, J=8.1, 2H, HAr), 7.15 (d, J=8.1, 2H,
HAr), 7.22 (t, J=8.1, 2H, HAr), 7.43 (t, J=7.6, 4H, HAr), 7.73 (d, J=7.7, 4H, HAr),
11.97 (br, 1H, OH), 14.44 (s, 1H, OH) (Supplementary Material, Fig. S1 and S2);
13C NMR (62.50 MHz, DMSO-d6): δ (ppm) 22.9, 34.4, 117.9, 123.0, 128.4, 131.2,
131.3, 137.3, 139.3, 141.6, 146.5 (Supplementary Material, Fig. S3).
1 3

A. Kohzadian et al.
1
Product 10 H NMR (500 MHz, DMSO-d6): δ (ppm) 2.28 (s, 6H, 2-CH3), 4.93 (s,
1H, CH, methine), 7.17–7.23 (m, 4H, HAr), 7.29 (d, J=8.6, 2H, HAr), 7.39 (t, J=8.0,
4H, HAr), 7.66 (d, J=7.9, 4H, HAr), 12.48 (br, 1H, OH), 13.85 (s, 1H, OH) (Supple-
mentary Material, Fig. S4 and S5); 13C NMR (125 MHz, DMSO-d6): δ (ppm) 12.3,
33.1, 121.1, 126.2, 128.6, 129.5, 129.7, 131.1, 141.7, 146.8 (Supplementary Mate-
rial, Fig. S6).
1
Product 12 H NMR (500 MHz, DMSO-d6): δ (ppm) 2.33 (s, 6H, 2CH3), 5.16 (s,
1H, CH, methine), 7.14 (t, J=7.3 Hz, 1H, HAr), 7.24 (t, J=7.4 Hz, 2H, HAr), 7.35
(t, J=7.3 Hz, 1H, HAr), 7.44 (t, J=8.0 Hz, 4H, HAr), 7.57 (d, J=7.6 Hz, 1H, HAr),
7.73 (d, J=8.0 Hz, 4H, HAr), 7.87 (d, J=7.2 Hz, 1H, HAr), 12.72 (br, 1H, OH),
13.81 (s, 1H, OH) (Supplementary Material, Fig. S7 and S8); 13C NMR (125 MHz,
DMSO-d6): δ (ppm) 12.5, 34.9, 104.4, 121.1, 123.4, 126.0, 128.0, 128.8, 129. 3,
131.1, 133.2, 137.7, 141.6, 146.6 (Supplementary Material, Fig. S9).
Acknowledgements A. Kohzadian thanks IlamFarashimi Company for the support of this work. A. Zare
and Z. Kordrostami thank the Research Council of Payame Noor University for supporting this work. H.
Filian and A. Ghorbani-Choghamarani gratefully acknowledge the fnancial support through the start-up
funds from the Islamic Azad University, Ahvaz and Ilam University, Iran, respectively.
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maps and institutional afliations.
Afliations
Alireza Kohzadian1 · Hossein Filian2 · Zahra Kordrostami3 · Abdolkarim Zare3 ·
Arash Ghorbani‑Choghamarani4
*
Alireza Kohzadian
akohzadian@yahoo.com
1
2
IlamFarashimi Co, Industrial Estate of Ilam, PO Box 69315-451, Ilam, Iran
Department of Chemistry, Khuzestan Science and Research Branch, Islamic Azad University,
Ahvaz, Iran
3
4
Department of Chemistry, Payame Noor University, PO Box 19395-3697, Tehran, Iran
Department of Chemistry, Faculty of Science, Ilam University, PO Box 69315516, Ilam, Iran
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