Magnetic Metal-Organic Framework CoFe2O4@SiO2@IRMOF-3 as an Efficient Catalyst for One-Pot Synthesis of Functionalized Dihydro-2-oxopyrroles

Article abstract of DOI:10.1055/s-0036-1588924

A magnetic metal-organic framework-based catalyst CoFe₂O₄@SiO₂@IRMOF-3 was prepared and identified as an efficient catalyst for the synthesis of a variety of functionalized dihydro-2-oxopyrroles by a one-pot, four-component reaction of a dialkyl acetylenedicarboxylate, an aryl amine, formaldehyde, and optionally a second amine or diamine at room temperature. The catalyst was magnetically separated and recovered without significant loss of its catalytic efficiency, even after eight reaction cycles.

Full text of DOI:10.1055/s-0036-1588924

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© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–G
letter
A
J.-N. Zhang et al.
Letter
Synlett
Magnetic Metal–Organic Framework CoFe2O4@SiO2@IRMOF-3 as
an Efficient Catalyst for One-Pot Synthesis of Functionalized Dihy-
dro-2-oxopyrroles
Jia-Nan Zhang
Xiu-Huan Yang
Wei-Jie Guo
R2
HN
O
CO2R1
ArNH2
R2NH2
HCHO
CoFe2O4@SiO2@IRMOF-3
MeOH, r.t.
+
N
Ar
R1O2C
Bo Wang
CO2R1
Zhan-Hui Zhang*
35 examples
81–92%
College of Chemistry and Material Science, Hebei Normal
University, Shijiazhuang 050024, P. R. of China
zhanhui@hebtu.edu.cn
Received: 22.10.2016
Accepted after revision: 20.11.2016
Published online:
ated methods have drawbacks such as narrow substrate
scope, poor product yield, long reaction time, tedious puri-
fication protocols, or the use of expensive or nonrecyclable
catalysts. Therefore, the development of more efficient cat-
alytic systems for the construction of these heterocyclic
compounds under environmentally benign conditions is
still an attractive option.
DOI: 10.1055/s-0036-1588924; Art ID: st-2016-w0719-l
Abstract A magnetic metal–organic framework-based catalyst
CoFe2O4@SiO2@IRMOF-3 was prepared and identified as an efficient
catalyst for the synthesis of a variety of functionalized dihydro-2-oxopyr-
roles by a one-pot, four-component reaction of a dialkyl acetylenedicar-
boxylate, an aryl amine, formaldehyde, and optionally a second amine
or diamine at room temperature. The catalyst was magnetically sepa-
rated and recovered without significant loss of its catalytic efficiency,
even after eight reaction cycles.
Metal–organic frameworks (MOFs) constructed from
metal ions or metallic clusters and multidirectional organic
linkers have attracted considerable attention as an emerg-
ing class of potentially useful porous crystalline materials
for several reasons: their large specific surface areas; tun-
able pore distributions; abundant aromatic ligands; out-
standing thermal, mechanical, and solvent stabilities; high
acid–base catalytic activities; and ease of functionalization
and design.20 By virtue of these special properties, MOFs
have unquestionable potential for practical applications in
a wide range of fields, such as gas adsorption/storage,21
separations,22 chemical sensors,23 thin-film devices,24 pho-
toluminescence,25 drug carriers,26 or biomedical imaging.27
Although the use of MOFs as heterogeneous catalysts in or-
ganic synthesis is still in its infancy, there has been signifi-
cant growth in relevant research work.28 Recently, MOFs
based on Cu, Fe, Co, Zr, or Al have been shown to be effec-
tive and reusable heterogeneous catalysts for several reac-
tions such as oxidation,29 coupling,30 condensation,31 epoxi-
dation,32 cycloaddition,33 hydroxylation,34 cyclization,35 ac-
etalization,36 ring-opening,37 cyanosilylation,38 Friedel–
Crafts reactions,39 or Friedländer reactions,40 as well as
multicomponent reactions.41 Unfortunately, it is difficult to
ensure complete separation and recycling of MOF-based
heterogeneous catalysts from the reaction solutions. How-
ever, if MOFs are combined with magnetic components, the
resulting magnetic MOFs will show magnetic susceptibility,
which permits separation of the catalyst from the reaction
medium simply by applying an external magnet after the
Key words magnetic separation, metal–organic framework, nano-
structures, multicomponent reactions, dihydropyrroles, cobalt catalysis
Dihydro-2-oxopyrroles are an important class of hetero-
cycles that constitute the structural cores of many natural
products, synthetic bioactive compounds, and functional
materials. They exhibit a range of biological and pharmaco-
logical activities, and have been recognized as quorum-
sensing inhibitors,1 signal-regulating kinase 1 (ASK1) inhib-
itors,2 DRAK2 inhibitors,3 caspase-3 inhibitors,4 potential
cytotoxic agents,5 or antibiofilm agents.6 Consequently, the
high demand for dihydro-2-oxopyrroles has stimulated rig-
orous research into the development of efficient methods
for the construction of this skeleton. Among the numerous
methods that provide access to dihydro-2-oxopyrroles, the
one-pot, four-component reaction of amines, dialkyl acety-
lenedicarboxylates, and formaldehyde is among the most
important strategies for the construction of highly substi-
tuted dihydro-2-oxopyrroles. A careful survey of the litera-
ture revealed that this conversion is promoted by such cata-
lysts as Cu(OAc)2·H2O,7 InCl3,8 maltose,9 sucrose,10 xylose,11
nanoparticulate TiCl4/SiO2,12 Bu4NHSO4,13 TsOH,14 ZrCl4,15
UiO-66-SO3H metal–organic framework,16 BF3/nanopartic-
ulate sawdust,17 trityl chloride,18 or molecular iodine.19 De-
spite the effectiveness of these catalysts, some of the associ-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–G

B
J.-N. Zhang et al.
Letter
Synlett
Zn(NO3)2•6H2O
2-aminoterephthalic acid
FeCl3
NH4OH
TEOS
NaOH
+
DMF
CoCl2
CoFe2O4
CoFe2O4@SiO2@IRMOF-3
CoFe2O4@SiO2
Scheme 1 Synthesis of CoFe2O4@SiO2@IRMOF-3
reaction;42 the catalyst can then be regenerated and reused
without filtration or centrifugation operations, and without
loss of catalytic activity. Nevertheless, there are few exam-
ples of syntheses or applications of magnetic MOFs.43
By taking account of the above reports, and as a part of
our ongoing research into the design of magnetic nanocata-
lysts44 and the development of environmentally friendly
approaches for the construction of heterocyclic mole-
cules,45 we prepared a highly active and easily recyclable
reaction of a dialkyl acetylenedicarboxylate, an aryl amine,
formaldehyde, and optionally a second amine at room tem-
perature.
Magnetic nanocomposite particles CoFe2O4@SiO2@IR-
MOF-3, containing the basic isoreticular MOF IRMOF-3,
were prepared in a three-step procedure (Scheme 1) by us-
ing CoFe2O4 as a magnetic core, Zn2+ ion as a connector, and
2-aminoterephthalic acid (H2NH2BDC) as a linker.46 First,
CoFe2O4 particles were synthesized by chemical co-precipi-
tation from FeCl3 and CoCl2. Secondly, the CoFe2O4 particles
were modified with a layer of SiO2 by stirring them in sus-
pension in an aqueous alkaline solution of tetraethyl ortho-
silicate (TEOS). Finally, IRMOF-3 MOFs were deposited on
MOF-based
porous
magnetic
core–shell
material
(CoFe2O4@SiO2@IRMOF-3) by a simple approach, and we
used it as an efficient catalyst for the synthesis of function-
alized dihydro-2-oxopyrroles in a one-pot, four-component
Table 1 Optimization of the Conditions for the Synthesis of 4ha
CO2Me
CO2Me
NH
N
catalyst
+ 2
Br
NH2
+
HCHO
O
r. t.
Br
CO2Me
4h
Br
Entry
Catalyst
Solvent
Time (h)
Yieldb (%)
1
2
–
MeOH
MeOH
MeOH
MeOH
EtOH
10 h
3 h
3 h
3 h
3 h
3 h
3 h
3 h
3 h
3 h
3 h
3 h
3 h
3 h
3 h
3 h
3 h
trace
36
33
92
85
45
75
72
52
59
66
77
63
82
86
92
93
CoFe2O4
3
CoFe2O4@SiO2
4
CoFe2O4@SiO2@IRMOF-3
CoFe2O4@SiO2@IRMOF-3
CoFe2O4@SiO2@IRMOF-3
CoFe2O4@SiO2@IRMOF-3
CoFe2O4@SiO2@IRMOF-3
CoFe2O4@SiO2@IRMOF-3
CoFe2O4@SiO2@IRMOF-3
CoFe2O4@SiO2@IRMOF-3
CoFe2O4@SiO2@IRMOF-3
CoFe2O4@SiO2@IRMOF-3
CoFe2O4@SiO2@IRMOF-3 (10 mg)
CoFe2O4@SiO2@IRMOF-3 (15 mg)
CoFe2O4@SiO2@IRMOF-3 (30 mg)
CoFe2O4@SiO2@IRMOF-3
5
6
H2O
7
CH2Cl2
MeCN
THF
8
9
10
11
12
13
14
15
16
17c
DMF
toluene
PEG 400
ChCl–glycerine
MeOH
MeOH
MeOH
MeOH
a Experimental conditions: DMAD (1 mmol), 4-bromoaniline (1 mmol), HCHO (1.5 mmol), solvent (3 ml), catalyst (20 mg unless otherwise stated), r.t.
b Isolated yield.
c The reaction was carried out on a 10 mmol scale.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–G

C
J.-N. Zhang et al.
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Synlett
the CoFe2O4@SiO2 microspheres by dispersing the micro-
spheres in a solution of zinc(II) nitrate hexahydrate and
H2NH2BDC in DMF, and heating the mixture at 100 °C in a
Teflon-lined steel autoclave. The morphology, structure,
and composition of the thus-prepared CoFe2O4@SiO2@IR-
MOF-3 nanocomposites were investigated by various tech-
niques.
7–13). Next, the catalyst loading was optimized, and 20 mg
of catalyst was found to give the maximum product yield
(entry 3). Increasing the amount of catalyst did not improve
the results (entries 14–16), whereas decreasing the amount
of catalyst resulted in a lower yield of product 4h. Note that
the efficiency of the reaction was unaffected by scaling up;
for example, the model reaction of DMAD (10 mmol), 4-
bromoaniline (20 mmol), and formaldehyde (15 mmol)
gave the pure product 4h in 93% yield (entry 17).
Next, we examined the substrate scope and limitations
of this domino four-component reaction under the opti-
mized conditions.47 Representative results are given in Ta-
ble 2. Generally, most anilines bearing electron-rich, elec-
tron-neutral, or electron-deficient substituents reacted
successfully with DMAD and formaldehyde to give the cor-
responding highly substituted dihydropyrrol-2-one deriva-
tives in good to excellent yields (entries 2–5). The position
of the substituents on the phenyl ring had some effect on
yield of the product. An ortho-substituted aniline gave a
lower yield of the product compared with the correspond-
ing meta- or para-substituted anilines, possibly due to ste-
ric hindrance (entries 6–8). However, almost none of the
desired product was formed when an aniline with a strong-
ly electron-deficient 4-trifluoromethyl substituent was
used as a substrate (not shown). Unfortunately, 2-aminopy-
ridine was also incompatible with reaction conditions (not
The activity of the prepared catalyst was probed in the
model reaction of dimethyl acetylenedicarboxylate (DMAD;
1 mmol), 4-bromoaniline (2 mmol), and formaldehyde (1.5
mmol). Almost no target product was detected when the
reaction mixture was stirred for ten hours in MeOH at room
temperature in the absence of a catalyst (Table 1, entry 1).
The reaction proceeded well in the presence of
CoFe2O4@SiO2@IRMOF-3, affording pyrrolidinone 4h as the
sole product in 92% yield (Table 1, entry 4). In contrast,
magnetic CoFe2O4 also catalyzed the reaction, but its effi-
ciency was much lower than that of CoFe2O4@SiO2@IRMOF-
3 (entries 2 and 3). Next, we examined the effect of the sol-
vent. Among the various solvents screened, MeOH was
found to be the solvent of choice. The use of EtOH decreased
the yield of 4h (entry 5). An inferior result was also ob-
served when the model reaction was performed in H2O (en-
try 6). The use of CH2Cl2, MeCN, THF, DMF, toluene, po-
ly(ethylene glycol) (PEG 400) and choline chloride (ChCl)–
glycerine gave the desired product in 52–77% yield (entries
Table 2 Synthesis of Pyrrolidinones from Various Aromatic Amines
Ar
O
HN
CO2R1
CoFe2O4@SiO2@IRMOF-3
MeOH, r.t.
+
2 ArNH2
+
HCHO
N
Ar
R1O2C
CO2R1
3
2
4
1
Entry
R1
ArNH2
Product
Time (h)
Yield (%)
Mp (°C)
Found
Lit.
154–1558
1
2
Me
Ph
4a
4b
4c
4d
4e
4f
3
3
3
3
3
5
4
3
3
3
3
3
3
3
90
88
89
92
93
82
88
91
92
87
88
91
93
90
154–155
175–177
175–176
165–166
173–174
165–166
143–144
165–167
139–140
153–154
129–130
172–173
166–167
166–167
Me
Me
Me
Me
Me
Me
Me
Et
4-MeOC6H4
4-Tol
176–1789
177–1798
163–1658
170–1729
–
3
4
4-FC6H4
4-ClC6H4
2-BrC6H4
3-BrC6H4
4-BrC6H4
Ph
5
6
7
4g
4h
4i
–
8
165–1679
136–1388
152–1548
128–1308
170–1729
167–1708
167–1698
9
10
11
12
13
14
Et
4-MeOC6H4
4-Tol
4j
Et
4k
4l
Et
4-FC6H4
4-ClC6H4
4-BrC6H4
Et
4m
4n
Et
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–G

D
J.-N. Zhang et al.
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Synlett
Table 3 Synthesis of Polysubstituted Dihydropyrrol-2-ones from Two Different Amines
R2
HN
CO2R1
O
CoFe2O4@SiO2@IRMOF-3
MeOH, r.t.
R2NH2
+
+
ArNH2
+
HCHO
N
Ar
R1O2C
CO2R1
1
2
5
3
6
Entry
R1
Ar
R2
Product
Time (h)
Yield (%)a
Mp (°C)
Found
Lit.
–
1
2
Me
4-MeOC6H4
4-MeC6H4
4-ClC6H4
4-BrC6H4
4-O2NC6H4
Ph
Ph
6a
6b
6c
6d
6e
6f
3.0
3.0
3.0
3.0
3.0
2.0
3.0
2.0
1.5
1.5
1.5
1.5
1.5
1.0
1.0
1.5
81
83
89
88
85
85
83
88
90
88
92
91
89
90
81
86
120–121
153–154
149–150
152–153
146–147
137–139
128–129
119–120
96–97
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
Ph
154–1567
3
Ph
–
4
Ph
–
5
Ph
–
6
Bn
Bn
Bn
Cy
140–1417
129–13019
119–1218
96–9719
128–12919
120–12214
124–1269
–
7
4-MeOC6H4
4-BrC6H4
Ph
6g
6h
6i
8
9
10
11
12
13
14
15
16
4-MeOC6H4
4-ClC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-O2NC6H4
Cy
6j
127–128
123–124
124–125
90–92
Cy
6k
6l
Cy
c-Pent
Bu
6m
6n
6o
6p
107–108
59–60
108–1109
–
Me(CH2)5NH2
Cy
143–144
–
a Isolated yield.
shown), probably due to inactivation of the catalyst by co-
ordination. When the corresponding reactions of DEAD
were evaluated, similar results were obtained, as expected
(entries 9–14).
Encouraged by these results, we examined the multi-
component reaction with two different amines to further
explore the scope of the protocol. The reactions of various
anilines with DMAD, formaldehyde, and aniline, benzyl-
amine, cyclohexylamine, butylamine, or hexylamine under
the optimized conditions proceeded smoothly to give the
corresponding dihydropyrrol-2-one derivatives 6a–p in
good to high yields (Table 3, entries 1–16).48
The recovery and reuse of the catalyst is an important
economic benefit and an ecological requirement. Therefore,
the reusability of CoFe2O4@SiO2@IRMOF-3 was investigated
in the model reaction of DMAD, 4-bromoaniline, and form-
aldehyde. After completion of the reaction, the catalyst was
simply and efficiently recovered from the reaction mixture
by using an external magnet, then washed with EtOAc,
Finally, we extended the scope of the method to include
the synthesis of substituted bisdihydropyrrol-2-ones. The
four-component (pseudo-seven-component) reaction of
propane-1,3-diamine (1 equiv), DMAD (2 equiv), various
aromatic amines (2 equiv), and formaldehyde (2 equiv) was
conducted under the optimized conditions. As expected,
the desired bis-N-aryl-3-aminodihydropyrrol-2-one-4-car-
boxylates 8 were generated in high yields (Table 4).48 The
structures of the products were confirmed by FTIR, 1H
NMR, and 13C NMR spectroscopy and mass spectrometry.
Figure 1 Reusability of the CoFe2O4@SiO2@IRMOF-3
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–G

E
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Table 4 Synthesis of Substituted Bisdihydropyrrol-2-ones
NH2
CO2Me
CO2Me MeO2C
CoFe2O4@SiO2@IRMOF-3
MeOH, r.t., 4 h
+
2
+
H2N
N
N
HCHO
NH2
+ 2
CO2Me
2
R
R
N
N
H
H
O
O
R
2
8
3
7
1
Entry
R
Product
Yield (%)a
Mp (°C)
1
2
3
4
5
H
8a
8b
8c
8d
8e
89
91
90
88
87
104–105
135–136
109–110
163–164
168–170
4-MeO
4-Me
4-Cl
4-Br
a Isolated yield.
dried under vacuum to remove residual solvent, and reused.
The catalyst could be recycled seven times without signifi-
cant loss of its activity (Figure 1).
(10) Hazeri, N.; Sajadikhah, S. S.; Maghsoodlou, M. T.; Mohamadian-
Souri, S.; Norouzi, M.; Moein, M. J. Chin. Chem. Soc. (Taipei) 2014,
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Acknowledgment
This research was supported by the National Natural Science Founda-
tion of China (No. 21272053) and by the Natural Science Foundation
of Hebei Province (No. B2015205182).
(15) Sajadikhah, S. S.; Maghsoodlou, M. T.; Hazeri, N.; Mohamadian-
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Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588924.
S
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p
p
ortioInfgrmoaitn
S
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ortiInfogrmoaitn
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was then transferred to a Teflon-lined steel autoclave, which
was sealed and kept at 100 °C for 20 h. The resulting brown
solid was collected with a permanent magnet, washed with
EtOH, and dried under vacuum at 60 °C for 6 h.
(47) Pyrrolidinones 4a–h; General Procedure
(35) Ho, S. L.; Yoon, I. C.; Cho, C. S.; Choi, H.-J. J. Organomet. Chem.
2015, 791, 13.
(36) Dhakshinamoorthy, A.; Alvaro, M.; Garcia, H. Adv. Synth. Catal.
2010, 352, 3022.
(37) Wee, L. H.; Bonino, F.; Lamberti, C.; Bordiga, S.; Martens, J. A.
Green Chem. 2014, 16, 1351.
(38) Zhang, Z.; Chen, J.; Bao, Z.; Chang, G.; Xing, H.; Ren, Q. RSC Adv.
2015, 5, 79355.
A mixture of the dialkyl acetylenedicarboxylate 1 (1 mmol),
aromatic amine 2 (2 mmol), 37% aq HCHO (3, 5 mmol), and
CoFe2O4@SiO2@IRMOF-3 (0.02 g) in MeOH (3 mL) was stirred at
r.t. for the appropriate time (Table 2). When the reaction was
complete (TLC), the catalyst was separated by using a bar
magnet, and the product was collected by filtration and washed
with EtOH.
Methyl
1-(2-Bromophenyl)-4-[(2-bromophenyl)amino]-5-
(39) Jiang, S.; Yan, J.; Habimana, F.; Ji, S. Catal. Today 2016, 264, 83.
(40) Pérez-Mayoral, E.; Čejka, J. ChemCatChem 2011, 3, 157.
(41) Puthiaraj, P.; Ramu, A.; Pitchumani, K. Asian J. Org. Chem. 2014,
3, 784.
(42) (a) Azizi, K.; Azarnia, J.; Karimi, M.; Yazdani, E.; Heydari, A.
Synlett 2016, 27, 1810. (b) Fujita, K.-i.; Fujii, A.; Sato, J.; Yasuda,
H. Synlett 2016, 27, 1941. (c) Ghanbaripour, R.; Samadizadeh,
M.; Honarpisheh, G.; Abdolmohammadi, M. Synlett 2015, 26,
2117.
oxo-2,5-dihydro-1H-pyrrole-3-carboxylate (4f)
White solid; yield: 482 mg (82%); mp 165–166 °C. IR (KBr):
3330, 1686, 1635, 1446, 1298, 825 cm–1 1H NMR (500 MHz,
.
CDCl3): δ = 3.80 (s, 3 H), 4.48 (s, 2 H), 7.03 (t, J = 7.5 Hz, 1 H),
7.18 (t, J = 7.0 Hz, 1 H), 7.33–7.36 (m, 5 H), 7.49–7.51 (m, 1 H),
8.40 (s, 1 H). 13C NMR (125 MHz, CDCl3): δ = 49.7, 51.5, 106.7,
124.3, 125.1, 126.4, 126.5, 127.8, 129.2, 129.6, 129.7, 130.6,
132.4, 135.0, 135.4, 142.6, 164.1, 165.0. HRMS (ESI): m/z
[M + H]+ calcd for C18H14Br2N2O3: 464.9449; found: 464.9455.
(48) Pyrrolidinones 6a–p and Bipyrrolidinones 8a–e; General
Procedure
(43) (a) Li, X.; Zhang, W.; Liu, Y.; Li, R. ChemCatChem 2016, 8, 1111.
(b) Wang, R.; Zhang, C.; Wang, S.; Zhou, Y. Huaxue Jinzhan 2015,
27, 945; DOI: 10.7536/PC150110.
A mixture of the aromatic amine 3 (1 mmol for product 6; 2
mmol for product 8) and dialkyl acetylenedicarboxylate (1
mmol for product 6; 2 mmol for product 8) in MeOH (3 mL) was
stirred at r.t. for 20 min. Amine 5 (1 mmol) or propane-1,3-
diamine (7, 1 mmol), 37% aq HCHO (1.5 mmol for product 6; 3.0
mmol for product 8), and CoFe2O4@SiO2@IRMOF-3 (0.02 g) were
added successively, and the mixture was stirred at r.t. for the
appropriate time (Tables 3 and 4). When the reaction was com-
plete (TLC), the catalyst was separated with a bar magnet, and
the product was collected by filtration and washed with EtOH.
(44) (a) Li, P.-H.; Li, B.-L.; An, Z.-M.; Mo, L.-P.; Cui, Z.-S.; Zhang, Z.-H.
Adv. Synth. Catal. 2013, 355, 2952. (b) Lu, J.; Li, X.-T.; Ma, E.-Q.;
Mo, L.-P.; Zhang, Z.-H. ChemCatChem 2014, 6, 2854. (c) Li, B.-L.;
Zhang, M.; Hu, H.-C.; Du, X.; Zhang, Z.-H. New J. Chem. 2014, 38,
2435. (d) Lu, J.; Ma, E.-Q.; Liu, Y.-H.; Li, Y.-M.; Mo, L.-P.; Zhang,
Z.-H. RSC Adv. 2015, 5, 59167. (e) Zhang, M.; Lu, J.; Zhang, J.-N.;
Zhang, Z.-H. Catal. Commun. 2016, 78, 26. (f) Zhao, X.-N.; Hu, H.-
C.; Zhang, F.-J.; Zhang, Z.-H. Appl. Catal., A 2014, 482, 258.
(g) Zhao, X.-N.; Hu, G.-F.; Tang, M.; Shi, T.-T.; Guo, X.-L.; Li, T.-T.;
Zhang, Z.-H. RSC Adv. 2014, 4, 51089.
Methyl
1-(4-Methoxyphenyl)-5-oxo-4-(phenylamino)-2,5-
(45) (a) Li, B.-L.; Li, P.-H.; Fang, X.-N.; Li, C.-X.; Sun, J.-L.; Mo, L.-P.;
Zhang, Z.-H. Tetrahedron 2013, 69, 7011. (b) Guo, R.-Y.; Wang,
P.; Wang, G.-D.; Mo, L.-P.; Zhang, Z.-H. Tetrahedron 2013, 69,
2056. (c) Guo, R.-Y.; An, Z.-M.; Mo, L.-P.; Yang, S.-T.; Liu, H.-X.;
Wang, S.-X.; Zhang, Z.-H. Tetrahedron 2013, 69, 9931. (d) Liu, P.;
Hao, J.; Zhang, Z. Chin. J. Chem. 2016, 34, 637. (e) Li, X.-T.; Liu, Y.-
H.; Liu, X.; Zhang, Z.-H. RSC Adv. 2015, 5, 25625. (f) Li, X.-T.;
Zhao, A.-D.; Mo, L.-P.; Zhang, Z.-H. RSC Adv. 2014, 4, 51580.
(g) Guo, R.-Y.; An, Z.-M.; Mo, L.-P.; Wang, R.-Z.; Liu, H.-X.; Wang,
S.-X.; Zhang, Z.-H. ACS Comb. Sci. 2013, 15, 557.
dihydro-1H-pyrrole-3-carboxylate (6a)
White solid; yield: 273 mg (81%); mp 120–121 °C. IR (KBr):
3279, 1711, 1688, 1510, 1201, 823 cm–1 1H NMR (500 MHz,
.
CDCl3): δ = 3.74 (s, 3 H), 3.80 (s, 3 H), 4.49 (s, 2 H), 6.84–6.86 (m,
1 H), 6.91 (d, J = 9.0 Hz, 2 H), 7.09 (d, J = 8.5 Hz, 1 H), 7.13–7.15
(m, 1 H), 7.28–7.32 (m, 2 H), 7.64–7.67 (m, 2 H), 8.02 (s, 1 H). 13
C
NMR (125 MHz, CDCl3): δ = 48.7, 51.3, 55.5, 100.8, 113.6, 114.3,
119.3, 121.1, 122.8, 124.6, 125.1, 128.3, 157.1, 163.5, 165.1.
HRMS (ESI): m/z [M + H]+ calcd for C19H19N2O4: 339.1345;
found: 339.1353.
(46) Magnetic CoFe2O4@SiO2@IRMOF-3 Nanoparticles
CoFe2O4 magnetic nanoparticles (NPs) were synthesized by
chemical co-precipitation from FeCl3·6H2O and CoCl2·6H2O. The
surface of the CoFe2O4 NPs was coated with a layer of SiO2 by
adding distilled H2O (80 mL) to the purified CoFe2O4 NPs (1 g),
heating for 1 h at 40 °C, adding concd aq NH3 (1.5 mL), stirring
at 40 °C for 30 min, adding TEOS (1.0 mL), and stirring continu-
ously for 24 h. The mixture was then cooled to r.t. and the silica-
coated NPs were collected by using a permanent magnet,
washed three times with distilled H2O and EtOH, and dried at
60 °C under vacuum for 6 h.
Methyl 1-(4-Bromophenyl)-4-(cyclopentylamino)-5-oxo-2,5-
dihydro-1H-pyrrole-3-carboxylate (6m)
White solid; yield: 336 mg (89%); mp 90–92 °C. IR (KBr): 3335,
1713, 1683, 1259, 844 cm–1 1H NMR (500 MHz, CDCl3): δ =
.
1.45–1.50 (m, 2 H), 1.60–1.65 (m, 3 H), 1.71–1.75 (m, 2 H),
2.02–2.07 (m, 2 H), 3.78 (s, 3 H), 4.37 (s, 2 H), 5.03 (s, 1 H), 7.49-
7.51 (m, 2 H), 7.67–7.69 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ
= 23.7, 34.8, 47.8, 50.9, 54.1, 95.9, 117.7, 120.5, 128.8, 132.0,
137.9, 164.4, 165.5. HRMS (ESI): m/z [M + H]+ calcd for C17H20Br-
N2O3: 379.0657; found: 379.0661.
Dimethyl 4,4'-[Propane-1,3-diylbis(azanediyl)]bis(5-oxo-1-
phenyl-2,5-dihydro-1H-pyrrole-3-carboxylate) (8a)
A versatile step-by-step assembly strategy was used to fabricate
the porous CoFe2O4@SiO2@IRMOF-3 core–shell nanoparticles.
Briefly, the CoFe2O4@SiO2 NPs (0.5 g) were dispersed in a solu-
tion of Zn(NO3)2 (1.7 g) and H2NH2BDC (0.4 g) in dry DMF (50
mL), and the mixture was stirred at r.t. for 20 min. The solution
White solid; yield: 445 mg (89%); mp 104–105 °C. IR (KBr):
3314, 2950, 1706, 1686, 1499, 1259, 762 cm–1 1H NMR (500
.
MHz, CDCl3): δ = 1.92–1.97 (m, 2 H), 3.78 (s, 6 H), 3.97–4.01 (m,
4 H), 4.39 (s, 4 H), 7.10 (t, J = 7.5 Hz, 2 H), 7.37 (t, J = 8.0 Hz, 4 H),
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–G

G
J.-N. Zhang et al.
Letter
Synlett
7.74 (d, J = 8.0 Hz, 4 H). 13C NMR (125 MHz, CDCl3): δ = 33.2,
40.3, 48.0, 51.0, 118.2, 119.4, 125.0, 129.1, 129.3, 138.8, 164.5,
165.5. HRMS (ESI): m/z [M + H]+ calcd for C27H29N4O6: 505.2087;
found: 505.2093.
HRMS (ESI): m/z [M + H]+ calcd for C29H33N4O6: 533.2400;
found: 533.2406.
4,4'-[Propane-1,3-diylbis(azanediyl)]bis[1-(4-bromophenyl)-
5-oxo-2,5-dihydro-1H-pyrrole-3-carboxylate] (8e)
Yellow solid; yield: 574 mg (87%); mp 168–170 °C. IR (KBr):
Dimethyl 4,4'-[Propane-1,3-diylbis(azanediyl)]bis[5-oxo-1-
(p-tolyl)-2,5-dihydro-1H-pyrrole-3-carboxylate] (8c)
White solid; yield: 479 mg (90%); mp 135–136 °C. IR (KBr):
3324, 2941, 1703, 1687, 1645, 1430, 1290, 1200, 759 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 1.87–1.90 (m, 2 H), 3.73 (s, 6 H),
3.93-3.95 (m, 4 H), 4.28 (s, 4 H), 7.40–7.45 (m, 4 H), 7.59 (d, J =
9.0 Hz, 4 H). 13C NMR (125 MHz, CDCl3): δ = 33.0, 40.1, 47.8,
51.1, 117.7, 119.3, 119.6, 120.5, 132.0, 137.8, 164.5, 165.5.
HRMS (ESI): m/z [M + H]+ calcd for C27H27Br2N4O6: 661.0297;
found: 661.0292.
3401, 2951, 1659, 1636, 1455, 1258, 820 cm–1 1H NMR (500
.
MHz, CDCl3): δ = 1.93–1.95 (m, 2 H), 2.34 (s, 6 H), 3.77 (s, 6 H),
3.97–4.01 (m, 4 H), 4.36 (s, 4 H), 7.17 (d, J = 8.5 Hz, 4 H), 7.60 (d,
J = 8.5 Hz, 4 H). 13C NMR (125 MHz, CDCl3): δ = 20.9, 29.7, 40.0,
47.4, 51.0, 119.4, 129.6, 129.7, 132.4, 134.7, 136.3, 161.9, 164.3.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–G