MOF-5 as a highly efficient and recyclable catalyst for one pot synthesis of 2,4-disubstituted quinoline derivatives

Article abstract of DOI:10.1039/d0nj01301c

A MOF-5-catalyzed three-component coupling reaction was developed as an efficient approach for the synthesis of 2,4-disubstituted quinoline derivatives via a one pot three-component reaction of aromatic amines, aldehydes and alkynes with excellent yields. The easy recovery and reusability of the catalyst, broad substrate scope, short reaction time, high yields of products and solvent-free conditions make this protocol practical, environmentally friendly and economically attractive.

Full text of DOI:10.1039/d0nj01301c

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MOF-5 as a highly efficient and recyclable catalyst for one pot synthesis
of 2,4-disubstituted quinoline derivatives
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Song-Tao Xiao*1, Cui-Ting Ma2, Jia-Qi Di2 and Zhan-Hui Zhang*2
Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
D5 OI: 10.1039/b000000x
A MOF-5-catalyzed three-component coupling reaction was developed as an efficient approach for the synthesis of 2,4-
disubstituted quinoline derivatives via one pot three-component reaction of aromatic amine, aldehyde and alkyne with
excellent yields. The easy recovery of the catalyst and reusability, broad substrate scopes, short reaction time, high yields
of products and solvent-free conditions make this protocol practical, environmentally friendly and economically attractive.
Introduction
Heterogeneous catalysts have many advantages, such as easy
separation from the reaction mixture, recyclability and less
pollution in the final product. Metal-organic frameworks (MOFs),
an emerging new class of porous materials constructed by metal
ions and organic building units, have drawn significant attention
because of their applications in gas storage,15 separation,16
magnetics,17 sensing18 and heterogeneous biomimetic catalysis.19 In
particular, the specific porous structure of MOFs containing organic
and inorganic active sites and their ductility make them effective
heterogeneous catalysts.20 Furthermore, heterogeneous catalysts
based on MOFs have exhibited remarkable advantages with respect
to analogous homogeneous transition-metal catalysts because of
their zeolite-like properties, such as high internal surface area and
microporosity, and well-ordered porous structures. Applications of
MOFs in the synthesis of the organic compounds have also been
widely explored.20 However, the exploration of their applications in
different reactions is yet interesting.
Recently, some MOFs have been employed for the A3-coupling
reaction of alkyne, aldehyde and amine. Li and co-workers reported
sulfonate-based Cu(I) metal-organic framework (Cu(I)-MOF) as a
highly efficient and reusable catalyst for the synthesis of
propargylamine compounds via the three-component reaction of
aldehydes, alkynes and secondary amines under solvent-free
conditions (Scheme 1a).21 In 2018, Kassymova et al prepared a new
heterogeneous NHC catalyst (Ag-NHC-MOF) by the post-synthetic
modification of an azolium-containing metal–organic framework.
This catalyst showed an excellent activity towards above A3-
coupling reaction under ambient conditions (Scheme 1b).22 These
efforts focused on the coupling reaction of using secondary amines
to produce propargylamine. MOF-5, one of the most studied MOFs
prepared from Zn ions and 1,4-benzene dicarboxylic acid (H2BDC),
is a typical MOFs reported by Yaghi and co-workers and exhibits
considerable potential application in catalytic organic reaction
owing to its remarkably large pore volume, large surface area and
relatively high thermal stability.24 In continuation of our effort to
Nitrogen containing heterocycles are important natural products
and can be pharmaceutically active. In particular, quinolines and
their derivatives is present in many natural products,1 biologically
active molecules,2 and they play important roles in medicinal
chemistry, which have been found to be associated with wide
ranging pharmaceutical activities, such as, antitumor,3
antimalarial,4 antiasthmatic,5 antiinflammatory,6 and antidiabetic7
activities. The classical method for synthesis of quinoline is
Skraup’s procedure.8 Also, many methods of quinoline synthesis
have been developed,9 including Doebner-von Miller,10 Conrad-
Limpach,11 Friedländer,12 and Combes13 reactions. However, they
usually involve arduous processes, which are incompatible with the
environment, generate large amounts of waste, give relatively large
amounts of undesirable by-products. Recently, the A3-coupling
reaction of alkyne, aldehyde and amine was widely used to
synthesize 2,4-disubstitued-quinoline,14 which offers a number of
advantages: (i) simple materials, (ii) high atom economy, (iii)
reduce reaction steps, and (iv) easy work-up procedure. But the use
of corrosive, expensive and non-reusable catalysts limits the
usefulness of this method, especially for large scale operation and
leads to serious environmental and safety problems. Consequently,
the design of efficient, neat conditions, environmentally friendly
approach by using a reusable catalyst for the A3-coupling reaction
of alkyne, aldehyde and amine is in great demand.
_________________________________________________
Department of Radiochemistry, China Institute of Atomic Energy,
1
Beijing 102413, China. E-mail: 13331157677@126.com
2
Hebei Key Laboratory of Organic Functional Molecules, National
Demonstration Center for Experimental Chemistry Education, College of
Chemistry and Material Science, Hebei Normal University, Shijiazhuang
050024, China. E-mail: zhanhui@mail.nankai.edu.cn
†Electronic Supplementary Information (ESI) available: 1H NMR and 13
C
NMR spectra of all compounds. See DOI: 10.1039/b000000x/
This journal is © The Royal Society of Chemistry [year]
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develop efficient and reusable heterogeneous for green synthetic
method,25 herein, a MOF-5-catalyzed three-component coupling
reaction of aromatic amine, aldehyde and alkyne was developed
under solvent-free conditions. As far as we know, the present work
is the first example where the coupling reaction is followed by an
intramolecular hydroarylation/oxidative aromatization using MOF-
5 as an efficient catalyst, leading to 2,4-disubstituted quinoline
derivatives (Scheme 1c).
9
R2
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Li and co-workers
N
CHO
Cu(I)-MOF
(a)
NH
R2
+
R1
+
solvent-free, 80 °C
R1
Ref. 21
Kassymova and co-workers
R
Fig. 1 XRD pattern of MOF-5.
R1
Ag-NHC-MOF
CH2Cl2, r. t.
R3
R3
HN
+
+
RCHO
R2
R1
(b)
N
R2
Ref. 22
This work
R3
NH2
CHO
(c)
MOF-5
R1
R2
+
+
R3
R1
solvent-free, 110 °C
N
R2
Scheme 1 MOF catalyzed three-component reaction of amine, aldehyde
and alkyne
Results and discussion
Synthesis and crystal structure determination. Solvothermal
reaction of Zn(NO3)·6H2O and 1,4-benzenedicarboxylate in N,N-
dimethylformamide at 100 °C produced MOF-5. The powder XRD
pattern of the MOF-5 is given in Fig. 1, which basically
consisitented with the result reported by Howard.26 MOF-5 has
good thermal stability, as can be learned from the thermogram
shown in Fig. 2. The weight loss below 300°C resulted from the
occluded solvent DEF and water. MOF-5 began to decompose
above 450 °C, which is much higher than the reaction temperatures
of the A3-coupling reaction (110 °C). The FTIR spectrum of the
MOF-5 is provided in Fig. 3. IR spectra show the expected strong
characteristic adsorptions for the symmetrical stretching vibration
and the asymmetric stretching vibrations of the carboxyl group
which is one of the main functional group of 1,4-
benzenedicarboxylic (BDC) ligands (1375 and 1597 cm–1). The
broad absorption peak apparent around 3400 cm-1 corresponds to
the absorption peak of water molecules in the sample. As shown in
Fig. 4, the SEM of MOF-5 catalyst demonstrates that the particles
is highly crystalline cubic structure with a particle size of 2.0-3.0
µm, which was also in a good agreement with the results from
TEM (Fig. 5). The EDS elemental analysis indicates the presence
of O, C and Zn (Fig. 6). The nitrogen absorption–desorption
measurements indicates that the catalyst had a specific surface area
of 240 m2g-1 (Fig. 7).
Fig. 2 Thermogram of MOF-5.
Fig. 3 FTIR spectra of MOF-5.
2 | New J. Chem. 2020, 44, 00–00
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Fig. 4 SEM image of MOF-5.
the screening results implied that the use of these solvent resulted
in lower yields of the quinoline product 4a along with a mixture
of propargylamine product and unreacted starting materials (from
HPLC-MS) (Table 1, entry 2-7). Lowering the catalyst amount to
15 mg, the yield was decreased to 87% (Table 1, entry11). The
use of 5.0 wt% (5.3 mg) of MOF-5 resulted in a lower yield (82%)
even under a longer reaction (Table 1, entry12). Whereas an
increasing in catalyst amount to 25 mg did not produce better
results (Table 1, entry 13). It should be mentioned that the
presence of various Lewis acid catalysts led to a decreased yield
of product. Under similar reaction conditions, the use of 1:1:1 of
1a/2a/3a resulted in a slightly lower yield. (4a, 89%, Table 1;
entry 19). Therefore, the optimal reaction conditions for this
MOF-5-catalyzed A3-coupling reaction was use of 1:1:1.2 of 1a,
2a and 3a under solvent-free condition at 110 °C for 3 h.
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Fig. 5 TEM image of MOF-5.
Fig. 6 EDS spectrum of MOF-5.
Fig. 7 SEM image of MOF-5.
Table 1. Optimization of the Reaction Conditionsa
NH2
CHO
+
catalyst
solvent
+
N
1a
2a
3a
4a
Entry catalyst
Solvent Temperature (oC) Time/h Yield/%b
1
no
no
110
8
3
3
3
3
3
3
3
3
3
3
8
3
3
3
3
3
3
3
trace
34
35
28
29
31
trace
78
91
91
87
82
91
62
59
58
56
43
89
2
MOF-5
MOF-5
MOF-5
MOF-5
MOF-5
MOF-5
MOF-5
MOF-5
MOF-5
MOF-5
MOF-5
MOF-5
FeCl3
EtOH
reflux
3
MeOH reflux
CHCl3 reflux
4
5
DMF
reflux
6
EtOAc reflux
7
H2O
no
no
no
no
no
no
no
no
no
no
no
no
reflux
90
8
9
110
130
110
110
110
110
110
110
110
110
110
10
11c
12d
13e
14
15
16
17
18
19f
ZnCl2
CuCl2
AgNO3
MgO
The activity of the prepared catalyst was tested for the
reaction of benzaldehyde (1a, 1.0 mmol), aniline (2a, 1.0 mmol)
and phenyl acetylene (3a, 1.2 mmol) at 110 C. The reaction, as
MOF-5
a Reaction conditions: 1a (1.0 mmol), 2a (1.0 mmol), 3a (1.2 mmol) and
o
MOF-5 (20 mg, 18.9 wt%) in the solvent (2.0 mL) or neat condition for 3
c
d
h under air atmosphere. b Isolated yields. 15 mg catalyst was used. 5.3
mg catalyst (5.0 wt%) was used. e 25 mg catalyst was used. f Using 1:1:1
of 1a/2a/3a.
shown in Table 1, proceeded very slowly in the absence of
catalyst and only a trace of desired product was found after
heating for 8 h (Table 1, entry 1). As expected, the desired 2,4-
disubstitued-quinoline product 4a was isolated in 91% yield after
reaction at 110 °C for 3 h (Table 1, entry 9). Moreover, a higher
reaction temperature (130 °C) does not make an obvious
difference in the yield of the product (Table 1, entry 10), but
lowering the temperature to 70 °C resulted in a lower yield (Table
1, entry 8). A number of common solvents were examined and
Having the optimal conditions in hand, we investigated the
substrate scope of this reaction provided good yields between 78-
91% as summarized in Table 2. Phenyl acetylene and aniline
were initially used as substrates for exploring the scope of
aromatic aldehyde substrates with different substituents (para,
ortho, meta). All of aromatic aldehyde with electrondonating or
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Table 2 Substrate scope examination.
5
6
R3
7
8
9
NH2
CHO
MOF-5
R2
R1
R3
+
+
solvent-free, 110 °C
R1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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25
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1
2
3
N
R2
4
Br
Me
N
N
N
N
N
4e 82%
OMe
4a 91%
4c 87%
Me
4b 85%
4d 88%
Me
Br
N
N
N
N
N
4j 86%
Br
Br
CN
NO2
4i 84%
4f 84%
4g 86%
4h 87%
MeO
Br
Cl
F
N
N
N
N
N
4k 87%
4l 84%
4n 87%
Me
4m 85%
4o 84%
Cl
F
Br
Ph
N
4p 83%
N
N
N
N
4r 81%
NO2
4s 80%
Me
4q 85%
Me
4t 79%
Me
Br
Br
Br
Cl
N
Me
Br
N
N
N
4v 78%
N
OMe
4u 81%
Me
4y 81%
4w 79%
4x 82%
Reaction conditions: 1 (1.0 mmol), 2 (1.0 mmol), 3 (1.2 mmol), and 20 mg MOF-5 under solvent-free condition at 110 oC for 3 h. Isolated yield.
4 | New J. Chem. 2020, 44, 00–00
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CHO
Ph
weakly electron-withdrawing substituents were found to be
NH2
applicable to this reaction and gave the expected products in high
to excellent yields (4b-4g). Remarkably, strongly electron-poor
aromatic aldehyde such as 4-formylbenzonitrile and 4-
nitrobenzaldehyde afforded the desired product in high yields.
The position of substituents has no obvious effect (4e, 4f, 4g). To
our disappointment, under these reaction conditions, aliphatic
aldehyde such as cyclohexanal is not a suitable substrate, and an
inseparable mixture is formed.
Next, various substituted phenyl acetylene and anilines, such
as para substituents (F, Cl, Br, OMe and CH3), were examined.
Electronwithdrawing and electron-donating substituents were
generally well-tolerated, affording the desired products 4j−4q
bearing alkyl, halide, and alkoxyl functionalities in good yields.
15 Moreover, 4-ethynyl-1,1'-biphenyl was compatible in the reaction,
and product 4r was obtained. Stimulated by these results, the
reactions of substituted aromatic aldehydes or substituted anilines
was tested under the above optimal conditions and the
corresponding quinolines (4s-4y) were obtained in high yields.
The recyclability and reusability of the catalyst MOF-5 are
very important for commercial and industrial applications.
Finally, the reusability of the catalyst has been tested in the
reaction of benzaldehyde, aniline and phenyl acetylene. After
completion of the reaction, the mixture was cooled to room
O2
N
Ph
H2O
4a
5
Ph
N
N
Ph
A
C
10
12
13
14
15
MOF-5
H
N
H
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N
Ph
Ph
B
20
45 Scheme 2
derivative 4a.
A plausible mechanism for the synthesis of quinoline
Conclusions
25 temperature and diluted with cold ethyl acetate. The catalyst was
easily recovered by simple filtration and the recover catalyst was
washed with ethyl acetate, drying under vacuum and then reused
directly in model reaction for the next round without further
purification. As shown in Table 3, the catalyst can be reused at
30 least five times with essentially no loss of catalytic activity,
which indicates that the prepared catalyst possessed excellent
activity and reusability.
In summary, we have developed an efficient, selective and
green one-pot synthesis of quinolines using the recoverable MOF-5
catalyst under solvent-free condition. A variety of aromatic amine,
aldehyde and alkyne can be tolerated, giving the structural diversity
of quinolines in good to excellent yields. Besides, the catalyst could
be reused five times without significant loss of activity, showing
good potential for industrial application.
5
0
Table 3 Recycling of the catalyst
55 Experimental Section
Entry
Recycle
1st
Yield (%)a
General Methods: All solvents and chemicals were obtained
commercially and were used without further purification. X-ray
diffraction analysis was carried out using a PANalytical X’Pert
Pro X-ray diffractometer. The surface morphology and particle
60 size were studied using a Hitachi S-4800 SEM instrument.
Transmission electron microscopy (TEM) observation was
performed using a Hitachi H-7650 microscope at 80 kV. Melting
points were determined on X-5 apparatus and were uncorrected.
IR spectra were obtained with KBr pellets in the range of 400–
65 4000 cm-1 using a Thermo Fisher iS50 spectrometer. Elemental
compositions were determined using a Hitachi S-4800 scanning
electron microscope equipped with an INCA 350 energy
1
91
90
91
86
85
2
2nd
3rd
3
4
5
4th
5th
a Isolated yield.
In accordance with reports from the literature14b, a plausible
35 mechanism for the current MOF-5-catalyzed tandem reaction is
proposed (Scheme 2). Intermediate A is generated in situ from
aromatic aldehyde and aniline. The nitrogen atom of the
intermediate A is coordinated by the MOF-5 and enhances the
electrophilicity of the imine, and then addition of alkyne to
40 intermediate A forms the propargylamine intermediate B, which
then undergoes an intramolecular hydroarylation of alkyne to
give dihydroquinoline intermediate C, followed by oxidized
aromatization with O2 to afford the quinoline 4a.
dispersive spectrometer (SEM-EDS) presenting
a 133 eV
resolution at 5.9 keV. 1H NMR and 13C NMR spectra were
70 recorded on a Bruker AV III-500 or Zhongke Niujin AS 400
spectrometer using TMS as an internal standard. Mass spectra
were recorded on a 3200 Qtrap instrument with an ESI source.
High resolution mass spectra (HR-MS) were measured on a
Brukter Impact II instrument using ESI source.
75 Preparation of the MOF-5. In a typical preparation, a solid
mixture of zinc nitrate hexahydrate (Zn(NO3)2·6H2O) (0.1188 g,
0.4 mmol) and 1,4-benzenedicarboxylic acid (H2BDC) (0.0216 g,
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195-199; (i) M. Zhu, W. J. Fu, C. Xun and G. L. Zou, Bull. Korean
Chem. Soc., 2012, 33, 43-47; (j) C. Xu, X. Q. Hao, Z. Q. Xiao, Z. Q.
Wang, X. E. Yuan, W. J. Fu, B. M. Ji and M. P. Song, J. Org. Chem.,
2013, 78, 8730-8738.
0.13 mmol) was dissolved in N,N-dimethylformamide (10 ml) in
a 20 ml vial. The vial was tightly capped and heated at 100 ◦C in
an isothermal over for 24 h to yield pale yellow crystals. After
unassisted cooling of the vial to room temperature, the solid
product was removed by decanting with mother liquor and
washed with N,N-dimethylformamide (DMF) (3 × 10 ml). After
the solid product had been obtained, solvent exchange was
carried out with dichloromethane (DCM) (3 × 10 ml) at room
temperature. The product was then dried under vacuum at 125 ◦C
65 10 M. M. Heravi, S. Asadi and F. Azarakhshi, Curr. Org. Synth., 2014,
11, 701-731.
11 A. J. Hodgkinson and B. Staskun. J. Org. Chem. 1969, 34, 1709-
1713.
5
12 (a) P. Friedlaender. Chem. Ber. 1882, 15, 2572-2575; (b) F. P. Ma, G.
70
75
80
85
90
95
T. Cheng, Z. G. He and Z. H. Zhang, Aust. J. Chem., 2012, 65, 409-
416.
13 A. Combes. Bull. Soc. Chim. France 1888, 49, 89-92.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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50
51
52
53
54
55
56
57
58
59
60
14 (a) K.-M. Jiang, J.-A. Kang, Y. Jin and J. Lin. Org. Chem. Front.
2018, 5, 434-441; (b) K. Sapkotaa, S. S. Han. New J. Chem. 2017, 41,
5395-5403; (c) X. Mi, J. Chen and L. Xu. Eur. J. Org. Chem. 2015,
2015, 1415-1418; (d) Y. Zhang, P. Li and L. Wang. J. Heterocycl.
Chem. 2010, 48, 153-157; (e) K. Cao, F.-M. Zhang, Y.-Q. Tu, X.-T.
Zhuo and C.-A. Fan. Chem.-Eur. J. 2009, 15, 6332-6334; (f) S.
Kumar, A. Patel and N. Ahmed. RSC Adv. 2015, 5, 93067- 93080; (g)
L. Zhang, B. Wu, Y. Zhou, J. Xia, S. Zhou and S. Wang. Chin. J.
Chem. 2013, 31, 465-471; (h) A. De Andrade, G. Carvalho dos
Santos and L. C. da Silva-Filho. J. Heterocycl. Chem. 2015, 52, 273-
277; (i) X. Zhang, X. Xu, L. Yu and Q. Zhao. Asian J. Org. Chem.
2014, 3, 281-284; (j) H. Z. Syeda Huma, R. Halder, S. Singh Kalra, J.
Das and J. Iqbal. Tetrahedron Lett. 2002, 43, 6485-6488; (k) M. M.
Sarmah, D. Bhuyan and D. Prajapati. Synlett 2013, 24, 2245-2248; (l)
A. Kumar and V. K. Rao. Synlett 2012, 43, 2157-2162; (m) X. Zhang,
B. Liu, X. Shu, Y. Gao, H. Lv and J. Zhu. J. Org. Chem. 2012, 77,
501-510; (n) M. Zhang, T. Wang, B. Xiong, F. Yan, X. Wang, Y.
Ding and Q. Song. Heterocycles 2012, 85, 639-649; (o) C.Yao, B.
Qin, H. Zhang, J. Lu, D. Wang and S. Tu. RSC Adv. 2012, 2, 3759-
3764; (p) S. Anvar, I. Mohammadpoor-Baltork, S. Tangestaninejad,
M. Moghadam, V. Mirkhani, A. R. Khosropour and R. Kia. RSC Adv.
2012, 2, 8713-8720; (q) A. Kulkarni and B. Torok. Green Chem.
2010, 12, 875-878; (r) F. Xiao, Y. Chen, Y. Liu and J. Wang.
Tetrahedron 2008, 64, 2755-2761; (s) J. S. Yadav, B. V. S. Reddy, R.
S. Rao, V. Naveenkumar and K. Nagaiah. Synthesis 2003, 34, 1610-
1614; (t) R. J. Kalbasi and A. Khojastegi, ChemistrySelect, 2018, 3,
12666-12675.
10 for 6 h. X-ray diffraction patterns, thermograms, and FTIR
spectra of the MOF-5 prepared in this work agree well with those
reported by other authors.
General procedure for the synthesis of 2,4-disubstitued-
quinoline product 4a. The mixture of benzaldehyde (1.0 mmol),
15 aniline (1.0 mmol) and phenyl acetylene (1.2 mmol) and MOF-5
(20 mg) under solvent-free condition at 110 oC for 3 h (monitored
by TLC). Upon completion of the reaction, the reaction mixture
was cooled to room temperature and 5 ml of ethyl acetate was
added. The quinoline derivatives were dissolved in ethyl acetate
20 and the catalyst was separated by simple filtration, washed with
ethyl acetate, and used for subsequent cycles after drying under
vacuum. Pure products were obtained by evaporation of the
solvent, followed by column chromatography on silica gel using
ethyl acetate/hexane as the eluent.
25 Acknowledgements
This research was financially supported by the National Natural
Science Foundation of China (No. 21272053) and the Science and
Technology Research Foundation of Hebei Normal University 100 15 B. Moulton and M. J. Zaworotko, Chem. Rev. 2001, 101, 1629-1653.
16 P. K. Thallapally, J. Tian, M. R. Kishan, C. A. Fernandez, S. J.
(L2018Z06).
Dalgarno, P. B. McGrail, J. E. Warren and J. L. Atwood. J. Am.
Chem. Soc. 2008, 130, 16842.
17 O. Kahn, Acc. Chem. Res. 2000, 33, 647-662.
30 References
105 18 H. Xu, J. Gao, X. Qian, J. Wang, H. He, Y. Cui, Y. Yang, Z. Wang
and G. Qian. J. Mater. Chem A. 2016, 4, 11900-11905.
1
P. M. S. Chauhan and S. K. Srivastava. Curr. Med. Chem. 2001, 8,
1535-1541.
19 M. Zhao, S. Ou and C.-D. Wu. Acc. Chem. Res. 2014, 47, 1199-1207.
20 (a) A. Dhakshinamoorthy, M. Alvaro and H. Garcia. Chem. Commun.
2012, 48, 11275-11288; (b) L. H. Li, Z. J. Niu and Y. M. Liang,
2
3
V. R. Solomon and H. Lee. Curr. Med. Chem. 2011, 18, 1488-1508.
F. Pierre, S. E. O'Brien, M. Haddach, P. Bourbon, M. K. Schwaebe,
E. Stefan, L. Darjania, R. Stansfield, C. Ho, A. Siddiqui-Jain, N.
Streiner, W. G. Rice, K. Anderes and D. M. Ryckman. Med. Chem.
Lett. 2011, 21, 1687-1691.
35
110
115
120
Chem. Asian. J., 2020, 15, 231-241; (c) A. Dhakshinamoorthy, S.
Navalon, A. M. Asiri and H. Garcia, Chem. Commun., 2020, 56, 26-
45.
4
X. Z. Yang, Y. J. Feng, S. Duffy, V. M. Avery, D. Camp, R. J. Quinn
and R. A. Davis. Planta Med. 2011, 77, 1644-1647.
21 (a) Y.-B. Huang, J. Liang, X.-S. Wang and R. Cao. Chem. Soc. Rev.
2017, 46,126-157. (b) J. N. Zhang, X. H. Yang, W. J. Guo, B. Wang
and Z. H. Zhang, Synlett, 2017, 28, 734-740; (c) H. Y. Zhang, X. P.
Hao, L. P. Mo, S. S. Liu, W. B. Zhang and Z. H. Zhang. New J.
Chem. 2017, 41, 7108-7115; (d) M. J. Liu, J. Wu and H. W. Hou,
Chem. Eur. J., 2019, 25, 2935-2948.
22 P. Li, S. Regati, H. C. Huang, H. D. Arman, B. L. Chen and J. C. G.
Zhao, Chin. Chem. Lett., 2015, 26, 6-10.
23 M. Kassymova, A. de Mahieu, S. Chaemchuen, P. Demeyere, B.
Mousavi, S. Zhuiykov, M. S. Yusubov and F. Verpoort, Catal. Sci.
Technol., 2018, 8, 4129-4140.
40 5 D. Doube, M. Blouin, C. Brideau, C. Chan, C. Desmarais, D. Ethier,
J. P. Falgueyret, R. W. Friesen, M. Girard, Y. Girard, J. Guay, P.
Tagari and R. N. Young. Bioorg. Med. Chem. Lett. 1998, 8, 1255-
1260.
6
J. Liu, C. J. Li, L. Ni, J. Z. Yang, L. Li, C. X. Zang, X. Q. Bao, D.
Zhang and D. M. Zhang. RSC Adv. 2015, 5, 80553-80560.
45
50
55
60
7
D. Edmont, R. Rocher, C. Plisson and J. Chenault, Bioorg. Med.
Chem. Lett. 2000, 10, 1831-1834.
8
9
Z. H. Skraup. Ber. Dtsch. Chem. Ges. 1880, 13, 2086-2090.
(a) V. V. Kouznetsov, L. Y. V. Méndez and C. M. M. Gómez, Curr.
Org. Chem., 2005, 9, 141-161; (b) D. D. Xuan, Curr. Org. Synth.,
2019, 16, 671-708; (c) Y. Y. Liu, Arkivoc, 2014, i, 1-20; (d) Y. G.
Kappenberg, A. Ketzer, F. S. Stefanello, P. R. S. Salbego, T. V.
Acunha, B. L. Abbadi, C. V. Bizarro, L. A. Basso, P. Machado, M. A.
P. Martins, N. Zanatta, B. A. Iglesias and H. G. Bonacorso, New J.
Chem., 2019, 43, 12375-12384; (e) Y. Li, X. J. Cao, Y. Y. Liu and J.
P. Wan, Org. Biomol. Chem., 2017, 15, 9585-9589; (f) Y. J. Ma, X.
X. Jiang and Y. K. Lv, Chem. Asian. J., 2019, 14, 3515-3530; (g) B.
Wang, W. B. Ye, Z. C. Yan, C. F. Wan, H. Q. Hou and Z. Y. Wang,
Chin. J. Org. Chem., 2018, 38, 504-508; (h) M. Zhu, W. J. Fu, G. L.
Zou, C. Xun, D. S. Deng and B. M. Ji, J. Fluorine Chem., 2012, 135,
24 H. Li, M. Eddaoudi and O. M.Yaghi, Nature 1999, 402, 276-279.
125 25 (a) M. Zhang, Y. H. Liu, Z. R. Shang, H. C. Hu and Z. H. Zhang.
Catal. Commun. 2017, 88, 39-44; (b) M. Zhang, Q. Y. Fu, G. Gao, H.
Y. He, Y. Zhang, Y. S. Wu and Z. H. Zhang. ACS Sustainable Chem.
Eng. 2017, 5, 6175-6618; (c) M. Zhang, Y. Han, J. L. Niu and Z. H.
Zhang. Adv. Synth. Catal. 2017, 359, 3618-3625; (d) C. T. Ma, P. Liu,
130
W. Wu and Z. H. Zhang, J. Mol. Liq. 2017, 242, 606-611; (e) Y. Han,
M. Zhang, Y.-Q. Zhang and Z. H. Zhang. Green Chem. 2018, 20,
4891-4900; (f) M. Zhang, M. N. Chen and Z. H. Zhang, Adv. Synth.
Catal., 2019, 361, 5182-5190; (g) H. J. Wang, M. Zhang, W. J. Li, Y.
Ni, J. Lin and Z. H. Zhang, Adv. Synth. Catal., 2019, 361, 5018-5024;
6 | New J. Chem. 2020, 44, 00–00
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1
2
3
(h) G. Gao, P. Wang, P. Liu, W. H. Zhang, L. P. Mo and Z. H. Zhang,
Chin. J. Org. Chem., 2018, 38, 846-854.
26 E. C. Spencer, J. A. K. Howard, G. J. McIntyre, J. L. C. Rowsell and
O. M. Yaghic. Chem. Commun. 2006, 2006, 278-280.
4
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DOI: 10.1039/D0NJ01301C
Graphical Abstract:
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MOF-5 as a highly efficient and recyclable catalyst for one pot synthesis
of 2,4-disubstituted quinoline derivatives
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Song-Tao Xiao*, Cui-Ting Ma, Jia-Qi Di and Zhan-Hui Zhang*
An approach was developed for synthesis of 2,4-disubstituted quinoline derivatives
via one pot three-component reaction of aromatic amine, aldehyde and alkyne
catalyzed by MOF-5 under solvent-free condition.
R3
NH2
CHO
MOF-5
R2
R1
R1
R3
+
+
solvent-free, 110 °C
N
R2