Magnetically separable graphene oxide anchored sulfonic acid: a novel, highly efficient and recyclable catalyst for one-pot synthesis of 3,6-di(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitriles in deep eutectic solvent under microwave irradiation

Article abstract of DOI:10.1039/c6ra19579b

Magnetically separable graphene oxide anchored sulfonic acid (Fe₃O₄-GO-SO₃H) nanoparticles were prepared and characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (T

Full text of DOI:10.1039/c6ra19579b

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Graphical Abstract:
Magnetically separable graphene oxide anchored sulfonic acid: a novel, high efficient and recyclable
catalyst for one-pot synthesis of 3,6-di(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitriles in
deep eutectic solvent under microwave irradiation
Mo Zhang, Peng Liu, YuꢀHeng Liu,* ZeꢀRen Shang, HaiꢀChuan Hu, ZhanꢀHui Zhang*
A magnetic separable graphene oxide anchored sulfonic acid catalyst was prepared and applied for the
synthesis of 3,6ꢀdi(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolo[3,4ꢀb]pyridineꢀ5ꢀcarbonitriles via oneꢀpot, threeꢀcomponent
reaction of 1ꢀphenylꢀ3ꢀ(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolꢀ5ꢀamine with 3ꢀoxoꢀ3ꢀ(pyridinꢀ3ꢀyl)propanenitrile and
aldehydes in choline chloride/glycerol under microwave irradiation.
1

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Magnetically separable graphene oxide anchored sulfonic acid: a novel, high
efficient and recyclable catalyst for one-pot synthesis of
3,6-di(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitriles in deep
eutectic solvent under microwave irradiation
Mo Zhang,a Peng Liu,a YuꢀHeng Liu,*a,b ZeꢀRen Shang,a HaiꢀChuan Hu,a ZhanꢀHui
Zhang*a
Magnetically separable graphene oxide anchored sulfonic acid (Fe3O4ꢀGOꢀSO3H) nanoparticles were
prepared and characterized by Xꢀray diffraction (XRD), scanning electron microscopy (SEM), transmission
electron microscope (TEM), and vibrating sample magnetometry (VSM) techniques. The synthesized
heterogeneous material was found to exhibit high catalytic activity for synthesis of
3,6ꢀdi(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolo[3,4ꢀb]pyridineꢀ5ꢀcarbonitriles via oneꢀpot, threeꢀcomponent reaction of
1ꢀphenylꢀ3ꢀ(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolꢀ5ꢀamine with 3ꢀoxoꢀ3ꢀ(pyridinꢀ3ꢀyl)propanenitrile and aldehydes
using choline chloride (ChCl)/glycerol as a green solvent under microwave irradiation. The catalytic system
can be successfully reused eight times with no significant loss of its catalytic performance.
___________________________________________________________________________
a College of Chemistry and Material Science, Hebei Normal University, Shijiazhuang 050024, P. R. China.
Eꢀmail: zhanhui@mail.nankai.edu.cn
b College of Preclinical Medicine, Hebei Medical University, Shijiazhuang 050017, P. R. China.
2

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Introduction
Pyrazolo[3,4ꢀb]pyridines are a promising class of heterocyclic compounds and have received much
attention due to their promising applications in diverse areas, such as pharmaceuticals,1 dyes2 and
luminescence materials.3 In addition, the compounds with pyrazolo[3,4ꢀb]pyridine scaffold have also been
reported to possess diverse biological activities, such as antimicrobial,4 antiꢀbiofilm,5 antimicrobial,6 and
antioxidant7, and they are also used as FGFR kinase inhibitors,8 cꢀMet inhibitors,9 potent dual orexin
receptor antagonists,10 anticancer agents11 as well as corrosion inhibitors for metals and alloys in acid
medium.12 Several synthetic methods for the construction of these compounds and their structural
analogues have been developed,13 for example (1) condensation of pyrazoleꢀ5ꢀamine derivatives and
activated carbonyl groups in refluxing acetic acid,1 (2) threeꢀcomponent reaction of aminopyrazoles,
aldehydes,
and
(a)
cycloketones,14
(b)
1,3ꢀdicarbonyl
compounds,15
(c)
Nꢀmethylꢀ1ꢀ(methylthio)ꢀ2ꢀnitropropꢀ1ꢀenꢀ1ꢀamine,16 (d) 3ꢀ(cyanoacetyl)indole,17 (e) ethyl cyanoacetate,18
(3) threeꢀcomponent reaction of aminopyrazole, isatin, and alkyl cyanoacetate using Et3N as catalyst,19 (4)
fourꢀcomponent reaction of pyrazolꢀ5ꢀamines, aromatic amines, 4ꢀhydroxyꢀ6ꢀmethylꢀ2Hꢀpyranꢀ2ꢀone, and
cyclohexaneꢀ1,3ꢀdiones in the presence of acetic acid,20 (5) A pseudo sixꢀcomponent reaction of ethyl
acetoacetate, aldehyde, hydrazine and ammonium acetate.21 Based on the importance of these structural
frameworks, the further development of a versatile, more environmentally benign and practical protocol for
synthesis of functionalized pyrazolo[3,4ꢀb]pyridines using simple and readily available starting materials is
highly desirable and valuable.
Due to its intriguing properties such as large surface area, high mechanical strength, unique layered
structure, excellent physicochemical stability, strong covalent character and high flexibility, graphene oxide
(GO) has been demonstrated to be good catalyst support for many catalytic applications.22 The availability
of oxygenꢀcontaining functional groups, such as hydroxyl, carboxyl, epoxide and carboxylic acid, on the
GO sheets allows them to be functionalized with various organic and inorganic materials in covalent or
nonꢀcovalent approaches. These oxygen functional groups in GO afford mild acidic and oxidative
properties, and further functionalization of GO can make stronger acid sites on these carbons.23 In this
regard, sulfonic acidꢀfunctionalized GO materials have been developed and successfully used in organic
transformations.24ꢀ27 Despite their excellent catalytic performance in some organic reactions, traditional
separation methods such as filtration or centrifugation were usually required for the recycling of catalysts. In
address this issue, magnetic separation occurred as a feasible solution because it reduces loss of catalyst and
makes the recovery and reusability of catalyst easier by magnetic force upon completion of the reaction.28ꢀ31
Therefore, the incorporation of magnetic components on GO is most favoured and will provide high catalytic
activity and improve separation efficiency.32ꢀ33 Also, since conventional harmful organic solvents make
several troubles relating to environmental pollution, replacement of these toxic solvents by green and
environmentally benign media is also of key relevance.34 Recently, deep eutectic solvents (DESs) have
emerged as viable alternatives to traditional volatile organic solvents due to their advantages of low melting
points, negligible vapour pressure, low flammability, biodegradable, simple and inexpensive preparation as
well as ease of recyclability.35ꢀ36 In addition, microwaveꢀassisted organic reaction has become particularly
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popular in recent years due to them offering the shorter reaction time and efficient routes for a large number
of organic reactions.37
In consideration of these superiorities and based on our research interest in developing
environmentally benign synthetic methodologies,38ꢀ39 herein, we report for the first time, magnetically
separable graphene oxide anchored sulfonic acid as catalyst for the synthesis of
3,6ꢀdi(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolo[3,4ꢀb]pyridineꢀ5ꢀcarbonitriles via oneꢀpot, threeꢀcomponent reaction of
1ꢀphenylꢀ3ꢀ(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolꢀ5ꢀamine with 3ꢀoxoꢀ3ꢀ(pyridinꢀ3ꢀyl)propanenitrile and aldehydes in
choline chloride (ChCl)/glycerol under microwave irradiation (Scheme 1).
Scheme 1 Synthesis of 3,6ꢀdi(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolo[3,4ꢀb]pyridineꢀ5ꢀcarbonitrile derivatives.
Results and discussion
As shown in Scheme 2, the catalyst CoFe2O4ꢀGOꢀSO3H was prepared in a threeꢀstep process. At first,
graphene oxide (GO) was synthesized by oxidation of graphite powder according to a slightly modified
Hummer’s method. Then, the synthesized graphene oxide was suspended into water and treated with FeCl3,
CoCl2 to obtain CoFe2O4/GO nanocomposites. High specific surface area of GO along with easily accessible
oxygenꢀconating groups on GO sheets provided a better support for anchoring of CoFe2O4 NPs. Further the
addition of chlorosulfonic acid into the CoFe2O4/GO suspension in dichloromethane yielded magnetically
separable CoFe2O4ꢀGOꢀSO3H nanocomposites.
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HO
HO
HO
O
O
OH
O
H2SO4
FeCl3, CoCl2
NH4OH
KMnO4, H2O2
HO
O
O
HO
HO
Graphene
GO
HO
O
HO
HO
OSO3H
HO
HO3SO
O
O
O
OH
O
OH
ClSO3H
CH2Cl2, r. t.
O
HO
O
HO
O
O
O
HO
HO3SO
HO
CoFe2O4-GO
HO3SO
CoFe2O4-GO-SO3H
Scheme 2 Preparation of CoFe2O4ꢀGOꢀSO3H
The Xꢀray diffraction pattern of the CoFe2O4ꢀGOꢀSO3H nanoparticles is shown in Fig. 1. The main
peaks in CoFe2O4ꢀGOꢀSO3H located at 2θ = 18.20o, 30.10o, 35.50o, 43.10o, 57.00o and 62.60o can be
indexed to (111), (220), (311), (400), (511) and (440) planes of the cubic CoFe2O4 spinel structure (JCPDS
22ꢀ1086).40 It is apparent that the crystal structure of the CoFe2O4 core was still wellꢀmaintained after
functionalization.41 However, no GO peaks were observed in XRD spectrum of CoFe2O4ꢀGOꢀSO3H
indicating that GO was exfoliated due to crystal growth of CoFe2O4 between interlayer of GO sheets.26 The
prepared particle diameter are found to be 28.6 nm using the Debye–Scherrer’s equation: d = 0.89λ/βcosθ,
which was derived from fullꢀwidth at halfꢀmaximum of the most intense peak corresponding to the (311)
plane located at 43.10o. The elemental composition of the CoFe2O4ꢀGOꢀSO3H sample was determined by
energy dispersive spectrum (EDS) analysis. As it can be seen in Fig. 2, Fe, Co, O, C and S species have
been observed in the catalyst. The content of the CoFe2O4 in CoFe2O4ꢀGO and CoFe2O4ꢀGOꢀSO3H was
found to be 85.75% and 78.48 wt%, respectively, as determined by atomic absorption spectroscopy (AAS).
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12
10
8
6
4
2
0
10 20 30 40 50 60 70 80
2 Theta degree
Fig. 1 XRD pattern of graphite (a), GO (b), and Fe3O4/GOꢀMo (c).
Fig. 2 EDS spectrum of Fe3O4/GOꢀMo
The SEM and TEM images of CoFe2O4, CoFe2O4ꢀGO and CoFe2O4ꢀGOꢀSO3H are represented in Fig. 3
and Fig. 4, respectively. These images confirm the formation of nanoparticles and that these nanoparticles
are unevenꢀsized particles and most of the particles have a quasiꢀspherical shape. The TEM image of
CoFe2O4ꢀGO shows that CoFe2O4 nanoparticles distributed homogeneously throughout the graphene oxide
surface. The TEM image of the CoFe2O4ꢀGO shows that the graphene oxide sheets are decorated with large
quantity of CoFe2O4. The average diameter of magnetic cores was estimated to be about 28.0 nm, which was
in good agreement with the particle sizes calculated using the Debye–Scherrer’s equation by XRD data.
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Fig. 3 SEM images of CoFe2O4 (left), CoFe2O4ꢀGO (middle) and CoFe2O4ꢀGOꢀSO3H (right).
(A)
(B)
(C)
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Fig. 4 TEM image of CoFe2O4 (A), CoFe2O4ꢀGO (B) and CoFe2O4ꢀGOꢀSO3H (C).
The magnetic property of as synthesized CoFe2O4ꢀGOꢀSO3H was measured by using vibrating sample
magnetometery (VSM) at room temperature. Magnetic measurement indicates the supermagnetic nature of
the prepared CoFe2O4ꢀGOꢀSO3H and the saturation magnetization value is found to be 28.2 emu gꢀ1 (Fig. 5).
A suitable magnetic property of the prepared CoFe2O4ꢀGOꢀSO3H meets our objectives to design a more
efficient and easily separable catalyst for organic reactions.
Fig. 5 Magnetization curve of CoFe2O4ꢀGOꢀSO3H.
The catalytic activity of the prepared catalyst was then evaluated in the model reaction of
1ꢀphenylꢀ3ꢀ(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolꢀ5ꢀamine, benzaldehyde and 3ꢀoxoꢀ3ꢀ(pyridinꢀ3ꢀyl)propanenitrile. As
shown in Table 1, the desired product 4a was obtained in 78% yield in the presence of CoFe2O4ꢀGOꢀSO3H in
EtOH for 10 min under microwave irradiation (Table 1, entry 2). To further improve the yield, various
reaction parameters such as solvents, microwave power, the amount of catalyst and temperature were
evaluated systematically. Various solvents, including water, glucose, ChCl/L-(+)ꢀtartaric acid, ChCl/glucose,
ChCl/urea, ChCl/citric acid, ChCl/itaconic acid, ChCl/glycerol were investigated in the model reaction.
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When glycerol was used, 4a was obtained in 46% yield (entry 5). The yield of desired product was
improved when deep eutectic solvent ChCl/glycerol was used. And, the product yield increased with the
increasing proportion of glycerol in the deep eutectic solvent. We were pleased to find that ChCl/glycerol
(1:3) was optimal and the reaction was completed with 10 min to give 95% yield of desired product (entry
13). Control experiments confirmed that, in the absence of any catalyst or the presence of CoFe2O4 or GO,
the targeted product was obtained in very low yields, indicating that the acid catalyst was still playing the
key role in the reaction. In addition, we found that the reaction is significantly accelerated when using
microwave irradiation. The reaction under conventional heating condition needed longer time and the yield
of the expected product was lower than under microwave irradiation (entry 17). The effect of microwave
power on the reaction was also examined. The results showed that 700 W was the appropriate power for this
reaction. Further examination of the amount of the catalyst revealed that 50 mg was the best loading for the
reaction. Reducing the amount of catalyst to 30 mg led to slightly lower yield. A further increase the amount
of catalyst to 80 mg did not affect the yield. A survey of the temperature was also conducted. The desired
product 4a was formed in 83% yield at 70 oC. And decreasing the temperature to room temperature did affect
the reaction efficiency and the expected product was obtained in 35% yield (entry 22), while a higher
temperature (90 oC, entry 26) was not advantageous for the yield either. Thus, the best result was obtained
o
in ChCl/glycerol (1:3) at 80 C in the presence of 50 mg CoFe2O4ꢀGOꢀSO3H under microwave irradiation
(700 W).
As a further proof of the practical applicability of this methodology, the model reaction was scaled up to
50 mmol. The result indicated that the reaction proceeded successfully and the desired product 4a could be
obtained without decreasing the reaction efficiency (Table 1, entry 29).
Table 1 The effect of reaction condition on the reaction of 1ꢀphenylꢀ3ꢀ(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolꢀ5ꢀamine,
benzaldehyde and 3ꢀoxoꢀ3ꢀ(pyridinꢀ3ꢀyl)propanenitrilea
Entry Catalyst
Solvent
MW (W) Temp (oC) Time (min)
Yield (%)b
1
2
3
4
5
6
no
ChCl/glycerol (1:3)
700
700
700
700
700
700
80
30
30
10
10
10
10
13
12
78
25
46
37
CoFe2O4/GOꢀSO3H no
80
CoFe2O4/GOꢀSO3H EtOH
CoFe2O4/GOꢀSO3H H2O
CoFe2O4/GOꢀSO3H Glucose
reflux
80
80
CoFe2O4/GOꢀSO3H ChCl/
L-(+)ꢀtartaric acid (2:1)
80
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7
CoFe2O4/GOꢀSO3H ChCl/glucose
700
700
700
700
700
700
700
700
700
700
0
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
20
30
50
70
90
80
80
80
10
10
10
10
10
10
10
20
20
10
120
40
15
15
10
60
60
20
10
10
10
10
10
10
62
27
15
71
80
95
26
40
52
86
91
91
93
95
35
42
68
83
95
75
95
94
8
CoFe2O4/GOꢀSO3H ChCl/urea (1:2)
CoFe2O4/GOꢀSO3H ChCl/citric acid (1:2)
CoFe2O4/GOꢀSO3H ChCl/itaconic acid (1:1)
CoFe2O4/GOꢀSO3H ChCl/glycerol(1:1)
CoFe2O4/GOꢀSO3H ChCl/glycerol(1:2)
CoFe2O4/GOꢀSO3H ChCl/glycerol(1:3)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27c
28d
29e
CoFe2O4
GO
ChCl/glycerol(1:3)
ChCl/glycerol(1:3)
ChCl/glycerol(1:3)
CoFe2O4/GO
CoFe2O4/GOꢀSO3H ChCl/glycerol(1:3)
CoFe2O4/GOꢀSO3H ChCl/glycerol(1:3)
CoFe2O4/GOꢀSO3H ChCl/glycerol(1:3)
CoFe2O4/GOꢀSO3H ChCl/glycerol(1:3)
CoFe2O4/GOꢀSO3H ChCl/glycerol(1:3)
CoFe2O4/GOꢀSO3H ChCl/glycerol(1:3)
CoFe2O4/GOꢀSO3H ChCl/glycerol(1:3)
CoFe2O4/GOꢀSO3H ChCl/glycerol(1:3)
CoFe2O4/GOꢀSO3H ChCl/glycerol(1:3)
CoFe2O4/GOꢀSO3H ChCl/glycerol(1:3)
CoFe2O4/GOꢀSO3H ChCl/glycerol(1:3)
CoFe2O4/GOꢀSO3H ChCl/glycerol(1:3)
CoFe2O4/GOꢀSO3H ChCl/glycerol(1:3)
400
500
600
800
700
700
700
700
700
700
700
700
a Reaction was performed with 1ꢀphenylꢀ3ꢀ(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolꢀ5ꢀamine (1 mmol), benzaldehyde (1
mmol) and 3ꢀoxoꢀ3ꢀ(pyridinꢀ3ꢀyl)propanenitrile (1 mmol), catalyst (50 mg) in 1 ml solvent otherwise
specified in the Table; b Isolated yields; c Catalyst (30 mg); d Catalyst (80 mg); e The reaction was carried out
in 50 mmol scale.
With the optimized reaction conditions established, the scope and limitation of this protocol were
further explored and representative results are summarized in Table 2. The CoFe2O4ꢀGOꢀSO3Hꢀcatalyzed
threeꢀcomponent reaction showed good functional group tolerance and has proved to be a general method
for the synthesis of 3,6ꢀdi(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolo[3,4ꢀb]pyridineꢀ5ꢀcarbonitriles. A number of
benzaldehydes, whether substituted by electronꢀrich or electronꢀpoor groups on aromatic ring, reacted with
1ꢀphenylꢀ3ꢀ(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolꢀ5ꢀamine and 3ꢀoxoꢀ3ꢀ(pyridinꢀ3ꢀyl)propanenitrile to furnish the
desired products 4aꢀ4l in high yields. Compared with the result of 4ꢀmethoxybenzaldehyde (4d, 95% yield),
the yield of the reaction with 2ꢀmethoxybenzaldehyde (4b, 85% yield) was lower, which may be attributed
to the steric hindrance. Delightfully, heteroaryl aldehydes, such as thiopheneꢀ2ꢀcarbaldehyde,
isonicotinaldehyde and 1Hꢀindoleꢀ3ꢀcarbaldehyde, were also suitable for this reaction, providing the
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corresponding products 4mꢀ4o in high yields. Unfortunately, aliphatic aldehydes, such as
cyclohexanecarbaldehyde and butyraldehyde, was also tested for this threeꢀcomponent reaction, the target
product was not formed under same reaction conditions.
Table 2 Synthesis of 3,6ꢀdi(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolo[3,4ꢀb]pyridineꢀ5ꢀcarbonitriles
Entry
1
R
Product
4a
Time (min)
Yield (%)a
mp (oC)
PhCHO
10
15
10
10
10
10
10
10
10
15
10
10
94
85
93
95
94
93
95
95
95
84
94
93
134ꢀ135
2
2ꢀMeOC6H4CHO
3ꢀMeOC6H4CHO
4ꢀMeOC6H4CHO
4ꢀMeC6H4CHO
3ꢀClC6H4CHO
4ꢀClC6H4CHO
3ꢀBrC6H4CHO
4ꢀBrC6H4CHO
2ꢀNO2C6H4CHO
3ꢀNO2C6H4CHO
4ꢀNO2C6H4CHO
256ꢀ257
4b
4c
3
246ꢀ247
230ꢀ232 (231ꢀ233)6
4
4d
4e
5
188ꢀ190
6
220ꢀ221
4f
7
223ꢀ225
4g
8
229ꢀ230
4h
4i
9
138ꢀ139
10
11
12
258ꢀ259
4j
230ꢀ231
4k
4l
118ꢀ120
S
13
14
10
10
89
90
127ꢀ128
198ꢀ199
4m
4n
O
15
10
88
230ꢀ231
4o
a Isolated yield.
A
plausible
mechanism
for
the
formation
of
3,6ꢀdi(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolo[3,4ꢀb]pyridineꢀ5ꢀcarbonitriles (4) in the presence of CoFe2O4ꢀGOꢀSO3H
is depicted in Scheme 3. The formation of these products can be visualised by initial Knoevenagel
condensation of aldehyde (2) and 3ꢀoxoꢀ3ꢀ(pyridinꢀ3ꢀyl)propanenitrile (3) to afford the intermediate (I).
The CoFe2O4ꢀGOꢀSO3H activated intermediate I, which subsequently undergoes Michael addition of
1ꢀphenylꢀ3ꢀ(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolꢀ5ꢀamine (1) via attack of the nucleophilic Cꢀ4 of the pyrazolamine,
followed by cyclization and loss of H2O to afford the desired products 4. It is pertinent to note that
CoFe2O4ꢀGOꢀSO3H catalyses the above transformation efficiently, whilst either CoFe2O4 or GO give the
product in low yield (Table 1). This suggests that the presence of sulfonic acid functional group in the
catalyst molecule is crucial for the success of this transformation.
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CoFe2O4/GO-SO3H
O
O
CN
R
O
CN
CoFe2O4/GO-SO3H
CN
CoFe2O4/GO-SO3H
RCHO
+
I
N
Knoevenagel Condensation
- H2O
1
N
N
R
NH2
2
3
N
N
N
R
R
CN
CN
H
N
N
N
N
O
HO+
N
N
N+
H
N
H
N
N
H
CoFe2O4/GO-SO3H
CoFe2O4/GO-SO3H
R
R
CN
N
CN
- H2O
N
OH
4
N
- CoFe2O4/GO-SO3H
N
N
N
H
O
CoFe2O4/GO-SO3H
N
N
NH2
N
Scheme 3 Plausible mechanism for synthesis of 4
Finally, the recovery and reusability of catalytic system were investigated in model reaction under the
optimized reaction conditions. After completion of the reaction, the reaction mixture was cooled to room
temperature, then, the catalyst was separated magnetically, and washed with ethyl acetate and water, dried
under vacuum. Then, water was added to reaction mixture to dissolve DES. The formed solid product was
collected by filtration. The water of the aqueous phase containing the DES, was evaporated under reduced
pressure in order to recover the DES. The recover DES and catalyst were reused in model reaction to the next
round. The catalytic system was found to be effective for up to eight consecutive runs without any
significant loss in its catalytic activity and stability (Fig. 6).
100
90
80
70
60
50
40
30
20
10
0
1
2
3
4 5
Cycles
6
7
8
Fig. 6 Reusability of the CoFe2O4ꢀGOꢀSO3H in ChCl/glycerol catalytic system in the model reaction.
12

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Conclusion
In summary, a novel magnetically separable graphene oxide anchored sulfonic acid catalyst has been
successfully prepared and used as an efficient heterogeneous catalyst for synthesis of
3,6ꢀdi(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolo[3,4ꢀb]pyridineꢀ5ꢀcarbonitriles via oneꢀpot, threeꢀcomponent reaction of
1ꢀphenylꢀ3ꢀ(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolꢀ5ꢀamine, 3ꢀoxoꢀ3ꢀ(pyridinꢀ3ꢀyl)propanenitrile and aldehydes in ChCl/
glycerol under microwave irradiation. The main highlights of this methodology are simplicity in the catalyst
preparation, high yields, short reaction times, ecoꢀfriendliness, an easy workꢀup procedure, avoidance of
toxic solvent, and applicability for largeꢀscale synthesis. Particularly, catalytic system could be easily
recovered and reused eight successive times without considerable loss of its activity, conferring great
potential for industrial application.
Experimental section
General information
All reagents and materials used in this work were obtained from commercial sources and utilized as
received without further purification. Microwave irradiation was carried out with a XHꢀ300A Microwave
Synthesizers from Beijing Science and Technology Development Co., Ltd, China. Melting points were
1
measured with an Xꢀ5 apparatus and were uncorrected. H NMR and 13C NMR (500 and 125 MHz,
respectively) spectra were acquired on a Bruker Avance III 500 spectrometer using TMS as internal standard.
The nanostructures were characterized by a PANalytical X’Pert Pro Xꢀray power diffraction (XRD)
o
diffractormeter employing a scanning rate of 0.05 /s from 20 to 80º using CuꢀKα radiation as the Xꢀray
source. Transmission electron microscope (TEM) and energy dispersive Xꢀray spectroscopy (EDX) analyses
were carried out on a Hitachi Hꢀ7650 instrument operating at 80 KV. Scanning electron microscope (SEM)
images of samples were obtained from a Hitachi Sꢀ4800 instrument. Magnetic properties of the samples were
measured using a Physical Property Measurement System (PPMSꢀ6700).
Preparation of graphene oxide (GO)42
Graphene oxide was prepared by the modified procedure reported by Hummers and Offeman.43 In a typical
procedure, 36.0 mL of concentrated H2SO4 (95%) was added into a roundꢀbottomed flask and cooled in an
ice bath. Then, 1 g of graphite powder and 300 mg of NaNO3 were added with vigorous stirring to avoid
agglomeration. After the graphite powder was well dispersed, 5.0 g of KMnO4 was slowly added over 2 h
under stirring at 8–10°C. The ice bath was then removed and the mixture was stirred at room temperature for
8 h. After that, 45 mL of distilled water was added, and the temperature was maintained at 95 °C for 1 h. After
the temperature was reduced to 50 °C, 10.0 mL of 30 % H2O2 was added to the mixture so as to eliminate the
ꢀ
excess MnO4 . The resulting GO was separated by filtration, washed successively with distilled water and
5% HCl solution repeatedly until sulfate could not be detected with BaCl2, and then finally dried under
vacuum at 50 °C for 24 h.
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Synthesis of CoFe2O4-GO nanocomposite
0.1 g GO was dispersed into 100 mL of deionized water with sonication for 30 min. Then, the aqueous
solution of 2.70 g of FeCl3·6H2O and 1.19 g of CoCl2·6H2O (50 ml) was slowly added into the mixture.
The mixture was stirred strongly at 80 °C for 2 h, and then 25 % ammonia solution was added until the pH
increased to 12. The reaction mixture was then continually stirred under refluxing condition for 1 h. After
cooling the solution to room temperature, the CoFe2O4ꢀGO NPs were collected using a permanent magnet
and washed with water and ethanol, then dried under vacuum at 60 oC for 24 h.
Preparation of CoFe2O4-GO-SO3H
CoFe2O4ꢀGOꢀSO3H was prepared by the reaction of CoFe2O4ꢀGO and chlorosulfonic acid. In an ice bath,
CoFe2O4ꢀGO (1.0 g) was suspended in dichloromethane (5 mL) in a 100 mL round bottom flask equipped
with a gas outlet tube and a dropping funnel containing a solution of chlorosulfonic acid (0.5 g, 4.3 mmol)
in dichloromethane (15 mL). With continuous stirring, chlorosulfonic acid solution was added dropwise to
the mixture during 30 min. After the complete of the addition, the mixture was stirred for 1 h at room
temperature until all HCl was removed from reaction vessel. Then, the catalyst was separated by magnetic
decantation and washed several times with CH2Cl2 and ethanol, and dried under vacuum at 60 °C for 2 h.
General procedure for synthesis of 3,6-di(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitriles
A
mixture
of
1ꢀphenylꢀ3ꢀ(pyridinꢀ3ꢀyl)ꢀ1Hꢀpyrazolꢀ5ꢀamine
(1
mmol),
3ꢀoxoꢀ3ꢀ(pyridinꢀ3ꢀyl)propanenitrile (1 mmol), and aldehydes (1 mmol) and Fe3O4ꢀGOꢀSO3H (50 mg) in
ChCl/glycerol (1:2, 1 ml) was stirred under microwave irradiation at 80 °C for an appropriate time. After
completion of the reaction (monitored by TLC), the mixture was cooled to room temperature. The catalyst
was separated using an external magnet and washed with ethyl acetate followed by water, and dried under
vacuum and reused directly for the next round of reaction. After that, water (5 mL) was added to reaction
mixture to dissolve DES. The formed solid product was collected by filtration and recrystallized from ethanol
to afford the pure product.
Characterization data
1,4-Diphenyl-3,6-di(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4a). Light yellow
1
crystals; H NMR (DMSOꢀd6, 500 MHz) δ = 7.15 (dd, J = 7.5, 4.5 Hz, 1H), 7.33 (t, J = 7.5 Hz, 2H),
7.44ꢀ7.47 (m, 5H), 7.65ꢀ7.70 (m, 3H), 8.30 (d, J = 7.5 Hz, 2H), 8.35 (s, 1H), 8.44ꢀ8.47 (m, 2H), 8.83 (d, J =
4.5 Hz, 1H), 9.21 (d, J = 2.0 Hz, 1H) ppm; 13C NMR (DMSOꢀd6, 125 MHz) δ = 103.1, 113.0, 117.6, 122.4,
123.1, 124.0, 127.8, 128.7, 129.9, 130.5, 133.4, 133.9, 136.5, 137.4, 138.4, 144.6, 149.6, 150.2, 150.3, 151.5,
152.8, 158.4 ppm; HRMS (ESI, m/z): calcd. for C29H19N6 [M+H]+: 451.1671; found: 451.1665.
4-(2-Methoxyphenyl)-1-phenyl-3,6-di(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4b).
Light yellow crystals; 1H NMR (DMSOꢀd6, 500 MHz) δ = 3.36 (s, 3H), 6.82 (d, J = 8.5 Hz, 1H), 7.06 (t, J =
7.5 Hz, 1H), 7.16 (dd, J = 7.5, 4.5 Hz, 1H), 7.43ꢀ7.51 (m, 4H), 7.64ꢀ7.69 (m, 3H), 8.29 (d, J = 8.0 Hz, 2H),
8.39 (s, 1H), 8.44 (d, J = 8.0 Hz, 1H), 8.48 (d, J = 4.5 Hz, 1H), 8.81 (d, J = 4.5 Hz, 1H), 9.20 (s, 1H) ppm;
13C NMR (DMSOꢀd6, 125 MHz) δ = 55.6, 103.7, 111.7, 113.3, 121.1, 122.5, 123.0, 124.0, 127.9, 130.0,
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131.2, 132.7, 134.0, 136.1, 137.5, 138.4, 145.0, 149.2, 149.8, 150.2, 151.4, 156.2, 158.5 ppm; HRMS (ESI,
m/z): calcd. for C30H21N6O [M+H]+: 481.1777; found: 481.1817.
4-(3-Methoxyphenyl)-1-phenyl-3,6-di(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile
(4c). Yellow crystals; 1H NMR (DMSOꢀd6, 500 MHz) δ = 3.54 (s, 3H), 6.94 (s, 1H), 7.00 (d, J = 8.0 Hz, 1H),
7.10 (d, J = 7.5 Hz, 1H), 7.19 (dd, J = 7.5, 4.5 Hz, 1H), 7.31 (t, J = 8.0 Hz, 1H), 7.46ꢀ7.49 (m, 2H),
7.64ꢀ7.70 (m, 3H), 8.28 (d, J = 8.0 Hz, 2H), 8.38 (s, 1H), 8.45 (d, J = 8.0 Hz, 1H), 8.49 (d, J = 8.0 Hz, 1H),
8.82 (d, J = 4.5 Hz, 1H), 9.21 (s, 1H) ppm; 13C NMR (DMSOꢀd6, 125 MHz) δ = 55.6, 103.0, 115.4, 116.7,
122.1, 122.5, 123.1, 124.0, 127.9, 130.0, 134.0, 134.5, 136.5, 137.5, 138.4, 144.6, 149.5, 149.7, 150.3, 151.5,
152.5, 158.5, 159.3 ppm; HRMS (ESI, m/z): calcd. for C30H21N6O [M+H]+: 481.1777; found: 481.1801.
4-(4-Methoxyphenyl)-1-phenyl-3,6-di(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile
1
(4d). Light brown crystals; H NMR (DMSOꢀd6, 500 MHz) δ = 3.79 (s, 3H), 6.87 (d, J = 8.0 Hz, 2H),
7.20ꢀ7.24 (m, 1H), 7.37 (d, J = 8.0 Hz, 2H), 7.45ꢀ7.51 (m, 2H), 7.63ꢀ7.70 (m, 3H), 8.29 (d, J = 8.0 Hz, 2H),
8.36 (s, 1H), 8.44 (d, J = 7.5 Hz, 1H), 8.50 (d, J = 4.5 Hz, 1H), 8.62 (d, J = 4.5 Hz, 1H), 9.21 (s, 1H) ppm;
13C NMR (DMSOꢀd6, 125 MHz) δ = 55.9, 114.2, 117.9, 122.3, 123.1, 124.0, 125.3, 127.7, 127.9, 129.9,
131.7, 134.0, 136.6, 137.5, 138.4, 144.6, 149.6, 150.2, 151.4, 152.7, 158.5, 161.2 ppm; HRMS (ESI, m/z):
calcd. for C30H21N6O [M+H]+: 481.1777; found: 481.1797.
1-Phenyl-3,6-di(pyridin-3-yl)-4-(p-tolyl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4e). Dark
1
yellow crystals; H NMR (DMSOꢀd6, 500 MHz) δ = 2.33 (s, 3H), 7.12ꢀ7.13 (m, 3H), 7.42ꢀ7.46 (m, 2H),
7.63ꢀ7.65 (m, 3H), 7.83 (d, J = 7.0 Hz, 2H), 8.29ꢀ8.35 (m, 3H), 8.45ꢀ8.48 (m, 2H), 8.82 (s, 1H), 9.20 (s, 1H)
ppm; 13C NMR (DMSOꢀd6, 125 MHz) δ = 21.6, 103.0, 113.1, 117.7, 122.4, 123.0, 127.8, 128.6, 129.2, 129.5,
129.9, 130.5, 134.0, 136.5, 137.4, 138.5, 140.4, 143.4, 144.6, 149.6, 150.2, 151.4, 153.0, 158.4, 167.7 ppm;
HRMS (ESI, m/z): calcd. for C30H21N6 [M+H]+: 465.1777; found: 465.1750.
4-(3-Chlorophenyl)-1-phenyl-3,6-di(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4f).
Light yellow crystals; 1H NMR (DMSOꢀd6, 500 MHz) δ = 7.21 (dd, J = 7.5, 4.5 Hz, 1H), 7.38 (t, J = 7.5 Hz,
1H), 7.45ꢀ7.53 (m, 5H), 7.62ꢀ7.68 (m, 3H), 8.27 (d, J = 8.0 Hz, 2H), 8.33 (s, 1H), 8.44 (d, J = 8.0 Hz, 1H),
8.49 (d, J = 8.0 Hz, 1H), 8.80 (d, J = 4.5 Hz, 1H), 9.29 (s, 1H) ppm; 13C NMR (DMSOꢀd6, 125 MHz) δ =
103.0, 112.9, 117.5, 122.4, 123.2, 124.0, 127.6, 127.9, 128.7, 130.0, 133.6, 133.8, 135.1, 136.6, 137.5, 138.3,
144.5, 149.9, 150.2, 151.0, 151.6, 158.4 ppm; HRMS (ESI, m/z): calcd. for C29H18ClN6 [M+H]+: 485.1281;
found: 485.1292.
4-(4-Chlorophenyl)-1-phenyl-3,6-di(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4g).
Light yellow crystals; 1H NMR (DMSOꢀd6, 500 MHz) δ = 7.24 (dd, J = 8.0, 5.0 Hz, 1H), 7.41 (d, J = 8.0 Hz,
2H), 7.47ꢀ7.50 (m, 3H), 7.54 (d, J = 8.0 Hz, 1H), 7.65ꢀ7.71 (m, 3H), 8.30 (d, J = 8.0 Hz, 2H), 8.36 (s, 1H),
8.46 (d, J = 8.0 Hz, 1H), 8.53 (dd, J = 4.5, 1.5 Hz, 1H), 8.83 (dd, J = 4.5, 1.5 Hz, 1H), 9.21 (d, J = 1.5 Hz,
1H) ppm; 13C NMR (DMSOꢀd6, 125 MHz) δ = 103.1, 113.1, 117.5, 122.5, 123.1, 124.0, 127.7, 127.9, 128.8,
130.0, 131.8, 132.2, 133.9, 135.6, 136.7, 137.4, 138.4, 144.5, 149.8, 150.2, 151.5, 158.4 ppm; HRMS (ESI,
m/z): calcd. for C29H17ClN6Na [M+Na]+: 507.1101; found: 507.1065.
4-(3-Bromophenyl)-1-phenyl-3,6-di(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4h).
Yellow crystals; 1H NMR (DMSOꢀd6, 500 MHz) δ = 7.24 (dd, J = 8.0, 4.5 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H),
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7.46ꢀ7.51 (m, 3H), 7.61ꢀ7.10 (m, 5H), 8.28 (d, J = 8.0 Hz, 2H), 8.36 (s, 1H), 8.45 (d, J = 8.0 Hz, 1H), 8.52
(d, J = 4.5 Hz, 1H), 8.83 (d, J = 4.5 Hz, 1H), 9.21 (s, 1H) ppm; 13C NMR (DMSOꢀd6, 125 MHz) δ = 103.0,
112.9, 117.6, 122.5, 123.2, 124.1, 128.0, 130.0, 130.8, 131.4, 132.2, 132.9, 133.3, 135.3, 136.1, 136.7, 138.2,
144.5, 149.6, 150.0, 150.2, 150.9, 151.6, 158.4 ppm; HRMS (ESI, m/z): calcd. for C29H18BrN6 [M+H]+:
529.0776; found: 529.0742.
4-(4-Bromophenyl)-1-phenyl-3,6-di(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4i).
Light yellow crystals; 1H NMR (DMSOꢀd6, 500 MHz) δ = 7.23 (dd, J = 8.0, 4.5 Hz, 1H), 7.41 (d, J = 8.0 Hz,
2H), 7.49 (t, J = 8.0 Hz, 1H), 7.51ꢀ7.55 (m, 3H), 7.64ꢀ7.70 (m, 3H), 8.30 (d, J = 8.0 Hz, 2H), 8.35 (s, 1H),
8.45 (d, J = 8.0 Hz, 1H), 8.53 (d, J = 4.5 Hz, 1H), 8.83 (d, J = 4.5 Hz, 1H), 9.21 (s, 1H) ppm; 13C NMR
(DMSOꢀd6, 125 MHz) δ = 103.0, 113.0, 117.5, 122.4, 123.2, 124.0, 127.7, 127.9, 129.9, 131.0, 132.0, 132.5,
133.8, 136.7, 137.4, 138.3, 144.5, 149.8, 150.2, 151.6, 158.4 ppm; HRMS (EI, m/z): calcd. for C29H17BrN6
[M]+: 528.0698; found: 528.0715.
4-(2-Nitrophenyl)-1-phenyl-3,6-di(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4j).
Light yellow crystal; 1H NMR (DMSOꢀd6, 500 MHz) δ = 7.19 (dd, J = 8.0, 4.5 Hz, 1H), 7.49 (t, J = 8.0 Hz,
1H), 7.49ꢀ7.51 (m, 1H), 7.61ꢀ7.68 (m, 4H), 7.97 (d, J = 7.5 Hz, 1H), 8.12ꢀ8.29 (m, 5H), 8.40 (dd, J = 5.0,
1.5 Hz, 1H), 8.42ꢀ8.45 (m, 1H), 8.79 (dd, J = 5.0, 1.5 Hz, 1H), 9.19 (d, J = 2.0 Hz, 1H) ppm; 13C NMR
(DMSOꢀd6, 125 MHz) δ = 103.0, 113.1, 117.5, 122.5, 123.3, 124.1, 125.2, 125.3, 127.5, 128.0, 130.0, 130.7,
133.8, 134.5, 136.5, 136.9, 137.5, 138.3, 144.3, 147.5, 149.8, 149.9, 150.0, 150.2, 151.7, 158.4 ppm;
HRMS (ESI, m/z): calcd. for C29H18N7O2 [M+H]+: 496.1522; found: 496.1442.
4-(3-Nitrophenyl)-1-phenyl-3,6-di(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4k).
Light brown crystals; 1H NMR (DMSOꢀd6, 500 MHz) δ = 7.17 (dd, J = 7.5, 4.5 Hz, 1H), 7.47 (t, J = 7.5 Hz,
1H), 7.52 (d, J = 7.5 Hz, 1H), 7.63ꢀ7.70 (m, 4H), 8.00 (d, J = 7.5 Hz, 1H), 8.24ꢀ8.31 (m, 5H), 8.42 (d, J =
4.0 Hz, 1H), 8.46 (d, J = 7.5 Hz, 1H), 8.81 (d, J = 4.5 Hz, 1H), 9.21 (s, 1H) ppm; 13C NMR (DMSOꢀd6, 125
MHz) δ = 103.0, 113.1, 117.5, 122.5, 123.3, 124.1, 125.2, 125.4, 127.5, 128.0, 130.0, 130.7, 133.8, 134.5,
136.5, 136.9, 137.5, 138.3, 144.3, 147.5, 149.8, 149.9, 150.0, 150.2, 151.7, 158.4 ppm; HRMS (ESI, m/z):
calcd. for C29H18N7O2 [M+H]+: 496.1522; found: 496.1512.
4-(4-Nitrophenyl)-1-phenyl-3,6-di(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4l).
Dark yellow crystals; 1H NMR (DMSOꢀd6, 500 MHz) δ = 7.21 (dd, J = 8.0, 5.0 Hz, 1H), 7.48ꢀ7.53 (m, 2H),
7.68 (t, J = 7.5 Hz, 2H), 7.72 (t, J = 5.0 Hz, 1H), 7.76 (d, J = 8.5 Hz, 2H), 8.18 (d, J = 8.5 Hz, 2H), 8.30 (d,
J = 7.5 Hz, 2H), 8.34 (d, J = 2.0 Hz, 1H), 8.46 (dd, J = 4.5, 2.0 Hz, 2H), 8.53 (dd, J = 4.5, 2.0 Hz, 1H), 9.22
(d, J = 2.0 Hz, 1H) ppm; 13C NMR (DMSOꢀd6, 125 MHz) δ = 102.8, 113.0, 117.2, 121.2, 122.4, 123.2, 123.6,
124.0, 127.5, 127.9, 130.0, 131.7, 133.7, 136.7, 137.4, 138.3, 139.8, 144.3, 148.7, 149.7, 149.9, 150.2, 150.4,
151.6, 158.3 ppm; HRMS (ESI, m/z): calcd. for C29H18N7O2 [M+H]+: 496.1522; found: 496.1535.
1-Phenyl-3,6-di(pyridin-3-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4m).
Dark green crystal; 1H NMR (DMSOꢀd6, 500 MHz) δ = 7.17 (dd, J = 5.0, 4.5 Hz, 1H), 7.26 (dd, J = 7.5, 4.5
Hz, 1H), 7.32 (d, J = 2.5 Hz, 1H), 7.35 (t, J = 7.5 Hz, 1H), 7.59ꢀ7.67 (m, 4H), 7.78 (d, J = 4.5 Hz, 1H), 8.24
(d, J = 7.5 Hz, 2H), 8.41 (d, J = 7.5 Hz, 1H), 8.44 (d, J = 1.5 Hz, 1H), 8.52 (dd, J = 4.5, 1.5 Hz, 1H), 8.79
(dd, J = 4.5, 1.5 Hz, 1H), 9.16 (d, J = 1.5 Hz, 1H) ppm; 13C NMR (DMSOꢀd6, 125 MHz) δ = 102.9, 113.0,
117.2, 121.2, 122.4, 123.0, 123.6, 124.1, 127.4, 130.7, 131.6, 133.7, 136.8, 137.6, 139.8, 144.3, 149.0, 150.1,
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150.3, 151.5, 158.4 ppm; HRMS (EI, m/z): calcd. for C27H16N6S [M]+: 456.1157; found: 456.1169.
1-Phenyl-3,4,6-tri(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4n). Light yellow
crystal; 1H NMR (DMSOꢀd6, 500 MHz) δ = 7.16 (dd, J = 7.5, 4.5 Hz, 1H), 7.43ꢀ7.46 (m, 3H), 7.51 (dt, J =
8.0, 2.0 Hz, 1H), 7.61ꢀ7.67 (m, 3H), 8.24 (d, J = 8.0 Hz, 2H), 8.35 (d, J = 2.0 Hz, 1H), 8.41 (dt, J = 8.0, 2.0
Hz, 1H), 8.46 (dd, J = 4.5, 2.0 Hz, 1H), 8.50ꢀ8.51 (m, 2H), 8.79 (dd, J = 5.0, 2.0 Hz, 1H), 9.17 (d, J = 2.0
Hz, 1H) ppm; 13C NMR (DMSOꢀd6, 125 MHz) δ = 102.7, 103.0, 117.2, 122.5, 123.2, 124.0, 124.3, 127.4,
128.0, 130.0, 133.7, 136.7, 137.4, 138.2, 141.1, 144.4, 149.7, 149.9, 150.2, 151.6, 158.3 ppm; HRMS (EI,
m/z): calcd. for C28H17N7 [M]+: 451.1545; found: 451.1549.
1-Phenyl-3,6-di(pyridin-3-yl)-4-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile
(4o).
Dark green crystal; 1H NMR (DMSOꢀd6, 500 MHz) δ = 7.31ꢀ7.44 (m, 3H), 7.58ꢀ7.66 (m, 5H), 8.26ꢀ8.29 (m,
3H), 8.37 (d, J = 8.0 Hz, 1H), 8.59 (d, J = 8.0 Hz, 1H), 8.73 (d, J = 4.5 Hz, 1H), 8.78 (d, J = 4.0 Hz, 1H),
9.12 (s, 1H), 9.38 (s, 1H), 9.61 (s, 1H), 11.70 (brs, 1H) ppm; 13C NMR (DMSOꢀd6, 125 MHz) δ = 115.0,
121.4, 122.1, 124.7, 126.5, 126.9, 127.2, 128.4, 129.8, 131.1, 131.5, 134.9, 136.1, 139.2, 141.7, 148.2, 150.2,
150.3, 150.7, 169.1 ppm; HRMS (EI, m/z): calcd. for C31H19N7 [M]+: 489.1702; found: 489.1700.
Acknowledgments
This work was financially supported by the National Natural Science Foundation of China (21272053), the
Natural Science Foundation of Hebei Province (B2015205182 and H2015206393) and the Natural Science
Foundation of Hebei Education Department (QN 2014126).
References
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