Magnetic magnetite nanoparticals catalyzed selective oxidation of Α-hydroxy ketones with air and one-pot synthesis of benzilic acid and phenytoin derivatives

Article abstract of DOI:10.1016/j.mcat.2018.05.013

A clean and efficient protocol for selective oxidation of α-hydroxy ketones using magnetic magnetite nanoparticals (Fe₃O₄·MNPs) as catalyst with air as green oxidant has been developed. Application of Fe₃O₄·MNPs was also proved to be successful in one-pot synthesis of benzilic acid and phenytoin derivatives. The facile one-pot procedure enhanced the production efficiency, shortened the reaction time and minimized the chemical waste. Notably, the catalyst can be reused at least for five times without any appreciable loss of its activity.

Full text of DOI:10.1016/j.mcat.2018.05.013

MolecularCatalysis454(2018)63–69
Contents lists available at ScienceDirect
Molecular Catalysis
journal homepage: www.elsevier.com/locate/mcat
Magnetic magnetite nanoparticals catalyzed selective oxidation of α-
hydroxy ketones with air and one-pot synthesis of benzilic acid and
phenytoin derivatives
Xiaona Lia,1, Dandan Xiac,1, Zhiyong Wena, Bowen Gongb, Maolin Suna, Yue Wua, Jie Zhanga,
Jun Suna, Yang Wua, Kai Baob,⁎⁎, Weige Zhanga,⁎
a
Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Benxi 117004, China
Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China
Department of Inorganic Chemistry, Shenyang Pharmaceutical University, Benxi 117004, China
b
c
A R T I C L E I N F O
A B S T R A C T
Keywords:
Fe3O4·MNPs
Selective oxidation
α-Hydroxy ketones
1,2-Diketones
A clean and efficient protocol for selective oxidation of α-hydroxy ketones using magnetic magnetite nano-
particals (Fe3O4·MNPs) as catalyst with air as green oxidant has been developed. Application of Fe3O4·MNPs was
also proved to be successful in one-pot synthesis of benzilic acid and phenytoin derivatives. The facile one-pot
procedure enhanced the production efficiency, shortened the reaction time and minimized the chemical waste.
Notably, the catalyst can be reused at least for five times without any appreciable loss of its activity.
One-pot synthesis
1. Introduction
It has been reported that Fe3O4·MNPs catalyzed aerobic oxidation of
alcohols in the solvent of toluene [23], which is an effective protocol for
1,2-Diketones are important materials that utilized as bioactive
compounds [1–3], photoinitiators [4] and versatile organic inter-
mediates [5–7]. Numerous methods are applied for their synthesis
[8–13], of which selective oxidation of easily available α-hydroxy ke-
tones is one of the most straightforward and effective methods. Various
oxidants have been successfully employed for the oxidation of α-hy-
droxy ketones, however, these methods usually suffered from the poor
atom economy and environmental pollution [14–17]. Some innovative
and effective methodologies employing air or oxygen as oxidant have
been explored, while the separation and recovery of the catalysts re-
quired tedious operation [18–21]. Thus, the development of new
methods to improve the simplicity, greenness and sustainability of the
oxidation processes is still in great demand.
aerobic oxidation of benzyl alcohols including 2-hydroxy-1,2-dipheny-
lethanone. In this study, we wish to report a clean, efficient, and sus-
tainable protocol for selective oxidation of α-hydroxy ketones by em-
ploying Fe3O4·MNPs as catalyst and air as oxidant in ethanol.
In addition, we speculated that Fe3O4·MNPs, prepared under alka-
line conditions, might keep its catalytic activity in the presence of KOH
or NaOH aqueous solution. Thus, its application was extended for the
one-pot synthesis of benzilic acid and phenytoin derivatives from α-
hydroxy ketones via in suit oxidation and rearrangement/condensation.
2. Experimental section
2.1. General information
Among the typical oxidants, FeCl3 attracted our attention because of
its activity during the conversion of α-hydroxy ketones to 1,2-diketones
[17], and the oxidation of resulted Fe2+ ion to Fe3+ ion in the presence
of air. Inspired by the phenomenon, we hypothesized that Fe3O4·MNPs
might furnish the oxidation of α-hydroxy ketones in the presence of
oxygen or air. Due to eco-friendliness, biocompatibility as well as facile
recovery of Fe3O4·MNPs [22], this process was expected to maximize
the resource efficiency and minimize the chemical waste.
All the solvents and chemical materials were directly used as pur-
chased without further treatment unless otherwise specified. Silica gel
GF254 and H (200–300 mesh) for preparative thin-layer chromato-
graphy and column chromatography was purchased from Qingdao
Ocean Chemicals (Qingdao, Shandong, China). 1H and 13C NMR spectra
were recorded on a Bruker Avance spectrometer using CDCl3 or DMSO-
d6 as the NMR solvent and TMS as internal standard (1H at 400 or
⁎
Corresponding author at: 46 Mail Box, Shenyang Pharmaceutical University, 85 Hongliu Road, Benxi, 117004, China.
⁎⁎
Corresponding author at: 46 Mail Box, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
E-mail addresses: baokai@syphu.edu.cn (K. Bao), zhangweige@syphu.edu.cn (W. Zhang).
These two authors contributed equally to this work.
1
https://doi.org/10.1016/j.mcat.2018.05.013
Received 28 August 2017; Received in revised form 24 April 2018; Accepted 10 May 2018
2468-8231/©2018ElsevierB.V.Allrightsreserved.

X. Li et al.
MolecularCatalysis454(2018)63–69
Fig. 1. Characterization of Fe3O4·MNPs. (a) XRD spectra; (b) IR spectra.
600 MHz, 13C at 100 or 150 MHz). Chemical shifts (δ) are reported in
ppm, and the following abbreviations are used: singlet (s), doublet (d),
triplet (t), multiplet (m). Mass spectra (MS) data were obtained on
Agilent 1100 LC–MS in ESI mode or Agilent Technologies 6890 N-5975
GC/MS in EI mode from Agilent Co., Ltd. The catalyst structure was
characterized using X-ray diffraction (Bruker D8 ADVANCE, CuKa,
40 kV, 40 mA). The size and surface morphologies were examined using
a scanning electron microscopy (Zeiss Ultra Plus, Germany) equipped
with an energy-dispersive spectroscope (EDS, X-Max 50, Oxford). IR
spectral analysis was performed via Equinox 55 instrument. The ICP
analysis was performed via Inductively Coupled Plasma Optical
Emission Spectrometer (DV4300ICP-OES). HPLC analysis was detected
by HPLC (HPLC-LC-20AT, Shimadzu) using SPD-20A UV as the de-
tector.
2.5. General procedure for one-pot synthesis of phenytoin derivatives
To a mixture of 1,2-diketone (0.2 mmol), urea (0.26 mol), Fe3O4 (30
mol%) and 50% ethanol (v/v, 0.5 mL), 20% NaOH aq. (0.15 mL) was
added. The reaction mixture was heated to 80 °C in the presence of air.
After completion of reaction, the catalyst was separated magnetically.
The mixture was filtered, and the filtrate was acidized by 5% hydro-
chloric acid solution until solid completely precipitated. After filtration,
the crude product was purified by preparative thin-layer chromato-
graphy with dichloromethane-methanol (v/v = 50:1).
2.6. Recovery of the catalyst
The recovery of the synthesized Fe3O4·MNPs was tested in the oxi-
dation and one-pot reactions utilizing 2-hydroxy-1,2-diphenylethanone
as the substrates under the aforementioned conditions. In each cycle,
the catalyst can be easily separated from the products by an external
magnet, and the remaining catalyst was washed by ethanol and water,
and dried in the air before using for the next cycle.
2.2. General procedure for preparation of Fe3O4
FeCl3·6H2O (0.54 g, 2 mmol) and urea (0.36 g, 6 mmol) were dis-
solved in distilled water (20 mL). The resulting solution was stirred at
87 °C for 2 h, then added FeSO4·7H2O (0.28 g, 1 mmol). After stirring at
87 °C for another 2 h, 0.1 M NaOH was added until pH 10. Cooled to
room temperature, the mixture was treated by ultrasound in a sealed
flask at 32 °C for 30 min. After ageing for 5 h, the obtained Fe3O4 were
washed by distilled water and ethanol, dried at room temperature
under vacuum. The dry black powders were further treated at 200 °C
under an N2 atmosphere for 6 h to afford the final catalyst.
3. Results and discussions
3.1. Characterization of the catalyst
In this work, Fe3O4·MNPs were prepared through a modified co-
precipitation method [24]. The crystalline structure of Fe3O4 was
characterized by X-ray diffraction (XRD). As shown in Fig. 1a, XRD
patterns of the catalyst was indexed to inverse spinel Fe3O4 with a face-
centred cubic structure (PDF#99-0073). Fig. 1b shows the Fourier
transform infrared (FT–IR) spectra of Fe3O4. The absorbance band at
582.7 cm−1 is attributed to the FeeO stretching vibration, which is
typical for spinel Fe3O4 [25]. Besides, the bands at around 3500-3000
and 2000–1500 cm−1 refer to the absorbed H2O or OH− on the surface
of catalyst [26]. These results indicated the catalyst was Fe3O4. The size
and morphology of Fe3O4 were examined by scanning electron micro-
scope (SEM) (Fig. 2a), which shows the synthesized Fe3O4 particles
were almost spherical and the diameter is about 20–50 nm. Further-
more, a typical energy-dispersive spectroscope (EDS) spectrum of Fe3O4
is shown in Fig. 2b. Peaks associated with Fe and O in the structure of
the magnetic catalyst can be further confirmed.
The characterization of the catalyst after using five times was car-
ried out. The SEM image of reused catalyst can be seen in Fig. 2c.
Compared with the SEM image of fresh catalyst (Fig. 2a), no prominent
change was observed after the catalyst had been used for five times. The
EDS pattern of the reused catalyst was shown as Fig. 2d. Comparing
Fig. 2d with Fig. 2b, we noticed that there was no visible difference in
the content of Fe between the reused catalyst and fresh catalyst. This
result indicated the catalyst was stable under the reaction conditions.
2.3. General procedure for oxidation of α-hydroxy ketones
A mixture of α-hydroxy ketone (0.2 mmol), Fe3O4·MNPs (30 mol%)
and ethanol (1.5 mL) were placed in a sealed tube. The reaction mixture
was heated at 80 °C. After completion of reactions, monitored by thin
layer chromatography, the catalyst was separated magnetically. The
reaction solution was concentrated under reduced pressure and the
crude material was purified by preparative thin-layer chromatography
with petroleum ether-EtOAc as eluent.
2.4. General procedure for one-pot synthesis of benzilic acid derivatives
KOH (0.6 mmol), water (0.1 mL), 1,2-diketone (0.2 mmol),
Fe3O4·MNPs (30 mol%) and 95% ethanol (0.3 mL) were added into a
sealed tube. The reaction mixture was heated to 80 °C in the presence of
air. After completion of reaction, the catalyst was separated magneti-
cally. The mixture was acidized by 5% hydrochloric acid solution until
pH was about 2.0. Then the solution was extracted with ethyl acetate,
and the combined organic phases were washed with brine, dried with
anhydrous sodium sulfate, evaporated under vacuum. The crude pro-
duct was purified by preparative thin-layer chromatography with di-
chloromethane-methanol (v/v = 50:1).
64

X. Li et al.
MolecularCatalysis454(2018)63–69
ethanol. To our delight, the oxidation of 2-hydroxy-1,2-diphenyletha-
none under O2 generated 1,2-diphenyl-1,2-diketone in close to quan-
titative yield compared to 15% yield in the absence of catalyst (Table 1,
entries 1 and 3). In addition, bulk-Fe3O4 (2.3 μm) was found to show
limited effects on the reaction (Table 1, entry 2). These results clearly
demonstrated the efficiency of our synthesized Fe3O4·MNPs. The
amount of catalyst exhibited significant influence on the reaction rate.
Decrease the amount of Fe3O4·MNPs from 30% to 10% resulting in a
reduction of reaction rates (Table 1, entries 3–5).
Subsequently, the influence of solvents, atmosphere, temperature
and reaction time on the yields was investigated. Generally, polar sol-
vents were found to be more efficient than less polar solvents (Table 1,
entries 3, 6–10) and the poor solubility of the substrate in water led to
the low yield of product with the unreacted starting material (Table 1,
entry 10). The effect of temperature showed that lowering the tem-
perature to 60 °C, the yield decreased obviously even extended the re-
action time (Table 1, entry 11). Considering the fact that air is more
convenient and costless compared with oxygen, we tried to replace O2
with air under the same conditions, and found that the yield kept same
as the one under the O2 atmosphere (Table 1, entry 12). In addition, the
pressure of the air could also affect the rate and yield, as the sealed
vessel conditions gave better yield than open vessel conditions (Table 1,
entry 13). Thus, the optimized reaction conditions were confirmed as:
30 mol% Fe3O4·MNPs/air in ethanol at 80 °C.
In the use of heterogeneous Fe catalysts for the oxidation reactions,
the leaching of Fe species to the solution often occurs. In order to clarify
whether the reaction occurs heterogeneously or homogeneously, a
comparison was carried out by using a simple magnetic separation of
the catalyst during the course of the reaction. With the removal of the
catalyst, if the reaction continued it indicated that the leaching of Fe3O4
to the solution occurred.
The solution of our reaction was separated with the catalyst by an
external magnet after stirring for 2 h, and transferred into a new reactor
vessel for another 7 h at 80 °C. The yield of product at different time
intervals was monitored by using HPLC and the results were shown in
Fig. 3. Compared with the curve of 30% Fe3O4, the leaching test curve
nearly showed no further reaction after the removal of catalyst from the
reaction mixture. Furthermore, the ICP analysis was carried out by
using Inductively Coupled Plasma Optical Emission Spectrometer
(DV4300ICP-OES). The ICP result showed that the content of Fe was
less than the limit of detection – 0.01 mg/L, which was consistent with
the leaching test and further indicated that the reaction was hetero-
geneous.
3.3. Substrates scope
With the optimized conditions in hand, we next applied them for the
synthesis of various 1,2-diketones from corresponding α-hydroxy ke-
tones. As summarized in Table 2, our synthesized Fe3O4·MNPs could
furnish the oxidation of aryl substituted α-hydroxy ketones in moderate
to excellent yields (2a–2h). Among them, the yields of phenyl sub-
stituted α-hydroxy ketones were normally better than those of other
aromatic substituted α-hydroxy ketones (2a–2b, 2e–2f). α-Hydroxy
ketones with aliphatic substitution were also examined, and the pro-
ducts were obtained in moderate yields (2i–2m). With the increase of
the length of aliphatic substituent, the oxidation products could be still
obtained in acceptable yields if extended the reaction time accordingly
(2k–2m).
To investigate the selectivity of the synthesized Fe3O4·MNPs be-
tween α-hydroxy ketones and benzyl alcohols, various benzyl alcohols
were applied as the substrates under the optimized conditions
(Table 2). Surprisingly, no oxidation products were observed even
prolonging time to 15 h (4a–4c). Similar selectivity was observed with
3e (1,2-diphenylethane-1,2-diol, the reduction product of 1a) and 3d
(n-hexanol) as substrates. We also performed intermolecular competi-
tion experiment with an equimolar mixture of 1a and 3a. The reaction
Fig. 2. SEM and EDS of Fe3O4·MNPs. (a) SEM image of fresh Fe3O4·MNPs; (b)
EDS pattern of fresh Fe3O4·MNPs; (c) SEM image of Fe3O4·MNPs after using five
times; (d) EDS pattern of Fe3O4·MNPs after using five times.
3.2. Optimization of α-hydroxy ketones oxidation conditions
2-Hydroxy-1,2-diphenylethanone was chosen as the model substrate
to investigate the catalytic activity of Fe3O4·MNPs (Table 1). Initially,
the reaction was carried out with/without 30 mol% Fe3O4·MNPs in
65

X. Li et al.
MolecularCatalysis454(2018)63–69
Table 1
Optimization of reaction conditions for the synthesis of 1,2-diphenyl-1,2-diketonea.
Entry
Catalyst (mol%)
Solvent
T (°C)
O2/air
Time (h)
Yieldb (%)
Conversionc (%)
1
2
3
4
5
6
7
8
None
EtOH
EtOH
EtOH
EtOH
EtOH
DCM
EtOAc
Acetone
CH3CN
H2O
80
80
80
80
80
40
80
55
80
100
60
80
80
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
Air
Air
9
9
9
12
15
9
9
9
9
9
9
9
15
30d
92
90
85
30
53
14
82
50
75
92
86e
20
38d
95
94
89
34
59
17
86
54
79
95
89e
Bulk Fe3O4 (30%)
Fe3O4·MNPs (30%)
Fe3O4·MNPs (20%)
Fe3O4·MNPs (10%)
Fe3O4·MNPs (30%)
Fe3O4·MNPs (30%)
Fe3O4·MNPs (30%)
Fe3O4·MNPs (30%)
Fe3O4·MNPs (30%)
Fe3O4·MNPs (30%)
Fe3O4·MNPs (30%)
Fe3O4·MNPs (30%)
9
10
11
12
13
EtOH
EtOH
EtOH
12
a
Reaction conditions: 2-hydroxy-1,2-diphenylethanone (0.2 mmol), solvents (1.5 mL) in a sealed vessel.
Yields were based on HPLC analysis.
By-products < 5%.
The bulk-Fe3O4 (2.3 μm, product number: 310069) was purchased from Sigma-Aldrich.
The reaction was carried out under an air atmosphere in an open vessel.
b
c
d
e
benactyzine and antiepileptic drug respectively, usually are obtained
via two-step reaction that includes the oxidation of α-hydroxy ketones
and the rearrangement/condensation of 1,2-diketones. Next, we tried to
apply the method to a one-pot tandem oxidation and subsequent re-
arrangement reaction between α-hydroxy ketones and potassium hy-
droxide for the synthesis of benzilic acid derivatives. As summarized in
Table 3, all the benzilic acid derivatives were successfully obtained
from corresponding α-hydroxy ketones in the presence of Fe3O4·MNPs
within 1 h to 1.5 h (entries 2–4, conversion rates > 97%). On the con-
trary, removal of the catalyst resulted in a dramatic decrease in the
yield of benzilic acid (entry 1), along with mass byproduct benzoic acid.
Increasing the reaction time to 6 h and the temperature to 100 °C, the
yield of 5a kept unchanged.
Encouraged by the success in one-pot synthesis of benzylic acid
derivatives, we further applied our method to the one-pot synthesis of
phenytoin derivatives with α-hydroxy ketones as the substrates
(Table 4). In the p resence of the Fe3O4·MNPs, all the materials could
be successfully converted into the corresponding phenytoin deriva-
tives in decent yields within 1 h to 1.5 h (conversion rates > 97%).
The yield of 6a kept unchanged when the reaction time was increased
to 6 h and the temperature was raised to 100 °C. The efficiency of the
Fe3O4·MNPs and one-pot strategy not only enhanced the production
efficiency, shortened the reaction time but also minimized the che-
mical waste.
Fig. 3. Leaching test of Fe species to the reaction solution. The yield of product
at different time intervals was monitored by HPLC.
with 30 mol% Fe3O4·MNPs for 9 h led to 2a in 92% yield and the 95%
unreacted 3a was recovered. Along with the decrease of the particle
size of the catalyst, the catalytic activity generally increases with the
cost of selectivity for substrates [27]. In the reported 10-nm sized
Fe3O4·MNPs catalytic system, benzyl alcohols including 2-hydroxy-1,2-
diphenylethanone were readily oxidized [23]. On the other hand, our
synthesized Fe3O4·MNPs were proved to be more sensitive when the α-
hydroxy ketones were applied as the substrates. In addition, the
greenness of the oxidation system was significantly improved by using
ethanol as the solvent. These facts indicated that the size of Fe3O4·MNPs
has significant effects on the catalytic activity and oxidation selectivity
of α-hydroxy ketones and benzyl alcohols. Comparing the oxidation
yield of 1a (92%) with 3e (no oxidation product was observed), we
conjectured that the carbonyl in the α-hydroxy ketones could co-
ordinate with Fe3O4 (Lewis acid) [28], which facilitated the oxidation
and then promoted the selectivity.
3.5. The recovery of catalyst
Finally, the recovery of the synthesized Fe3O4·MNPs was tested in
the oxidation and one-pot reactions utilizing 2-hydroxy-1,2-dipheny-
lethanone as the substrates under the aforementioned conditions. In
each cycle, the catalyst can be easily separated from the products by an
external magnet, and the remaining catalyst was washed by ethanol and
dried in the air before using for the next cycle. As shown in Fig. 4, the
catalyst could be reused at least for five times without significant loss of
its activity.
3.4. One-pot synthesis of benzilic acid and phenytoin derivatives
4. Conclusion
One-pot synthesis is a powerful strategy in the field of medicinal
chemistry and organic chemistry [29–31], which not only can cir-
cumvent intermediates separation and purification, minimize chemical
waste but also improve “atom economy” [32] and “step economy” [33]
to a great extent.
In summary, a selective oxidation of α-hydroxy ketones under
aerobic conditions catalyzed by cost-effective and reusable Fe3O4·MNPs
in ethyl alcohol has been developed. Easy separation and high reusa-
bility of catalyst made this procedure great potential in the application
of the synthesis of 1,2-diketones in a green, simple and efficient
manner. Available evidences indicate that the catalytic activity and
Benzilic acid and phenytoin derivatives, used as the intermediate of
66

X. Li et al.
MolecularCatalysis454(2018)63–69
Table 2
Selective oxidation of α-hydroxy ketones in the presence of Fe3O4·MNPs under an air atmospherea.
Substrate
Product
R1(R3)
R2(R4)
Time (h)
Yieldb (%)
Conversionc (%)
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
3a
3b
3c
3d
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2j
2k
2l
phenyl
phenyl
4-OMe-C6H4
3-OMe-C6H4
4-Me-C6H4
4-F-C6H4
2-F-C6H4
2-naphthyl
2-Thienyl
Me
Me
Me
Et
n-propyl
n-hexyl
phenyl
Me
H
H
9
9
9
12
9
9
12
9
9
9
92
95
80
80
93
90
85
73
60
70
70
62
65
67
–
95
98
83
86
96
92
89
78
67
76
70
67
72
74
–
4-OMe-C6H4
3-OMe-C6H4
4-Me-C6H4
4-F-C6H4
2-F-C6H4
2-naphthyl
2-Thienyl
phenyl
4-OMe-C6H4
4-OMe-C6H4
phenyl
phenyl
phenyl
9
12
12
12
15
15
15
15
2m
4a
4b
4c
4d
phenyl
phenyl
phenyl
n-pentyl
–
–
–
–
–
–
a
Reaction conditions: substrates (0.2 mmol), ethanol (1.5 mL), Fe3O4·MNPs (30 mol%) at 80 °C in a sealed vessel.
Isolated yields.
By-products < 5%.
b
c
selectivity of Fe3O4·MNPs are closely associated with the size of
Fe3O4·MNPs maintained a high efficiency till the 5th run without spe-
cial treatment. Efforts to further apply these Fe3O4·MNPs to the con-
struction of other potentially valuable organic molecules are currently
underway.
Fe3O4 particles, although further study is needed to understand the
detailed mechanism. Applications of the Fe3O4·MNPs in the one-pot
synthesis of benzilic acid and phenytoin derivatives from readily
available α-hydroxy ketones were proved to be successful. The reusable
Table 3
One-pot synthesis of benzilic acid derivativesa.
Entry
Product
R1(R2)
Fe3O4 (mol%)
T (°C)
Time (h)
Yield (%)b
1
2
3
4
5
6
5a
5a
5a
5a
5c
5f
phenyl
phenyl
phenyl
phenyl
3-OMe-C6H4
2-F-C6H4
0
80
80
80
100
80
80
1
1
6
1
1.5
1
8
30
30
30
30
30
70
70
70
52
50
a
Conditions: substrates (0.2 mmol), Fe3O4·MNPs (30 mol%), 95% ethanol (0.3 mL), water (0.1 mL), KOH (0.6 mmol) at 80 °C in a sealed vessel.
Isolated yields.
b
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X. Li et al.
MolecularCatalysis454(2018)63–69
Table 4
One-pot synthesis of phenytoin derivativesa.
Product
R1
R2
Fe3O4 (mol%)
T (°C)
Time (h)
Yield (%)b
6a
6a
6a
6a
6d
6f
phenyl
phenyl
phenyl
phenyl
4-Me-C6H4
2-F-C6H4
phenyl
phenyl
phenyl
phenyl
4-Me-C6H4
2-F-C6H4
0
80
80
100
80
80
80
1
1
1
6
1.5
1.5
10
70
70
70
60
62
30
30
30
30
30
a
Conditions: substrates (0.2 mmol), urea (0.26 mmol), Fe3O4·MNPs (30 mol%), 50% ethanol (v/v, 0.5 mL), 20% NaOH aq. (0.15 mL) at 80 °C in a sealed vessel.
Isolated yields.
b
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We thank the National Natural Science Foundation of China
(81673293, 81502932 and 81602969) and the Natural Science
Foundation of Liaoning Province (201602687 and 201610163L10) for
the financial support. This work was also supported by program
for young researchers from Shenyang Pharmaceutical University
(51120214) and Industry Development & Applied Basic Research from
Shenyang Technology Bureau (170449).
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Appendix A. Supplementary data
Supplementary data associated with this article can be found, in the
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