A magnetic nanoparticle-catalyzed regioselective ring opening of epoxides by aromatic amines

Article abstract of DOI:10.1002/aoc.3450

Sulfonic acid-functionalized silica-coated magnetic Fe₃O₄ nanoparticles were synthesized and applied as a green catalyst for an efficient and environmentally friendly ring opening of epoxides with aromatic amines in good to excellent

Full text of DOI:10.1002/aoc.3450

Full paper
Received: 7 November 2015
Revised: 26 December 2015
Accepted: 10 January 2016
Published online in Wiley Online Library: 11 March 2016
(wileyonlinelibrary.com) DOI 10.1002/aoc.3450
A magnetic nanoparticle-catalyzed
regioselective ring opening of epoxides by
aromatic amines
Najmedin Azizi*, Parisa Kamrani and Mostafa Saadat
Sulfonic acid-functionalized silica-coated magnetic Fe3O4 nanoparticles were synthesized and applied as a green catalyst for an
efficient and environmentally friendly ring opening of epoxides with aromatic amines in good to excellent yields with high
chemoselectivity. Clean aminolysis of various aliphatic and aromatic epoxides in ethanol generates β-hydroxyamines under mild
reaction conditions. The synthesized acidic magnetic nanoparticles were recovered using a simple external magnet and success-
fully reused for five runs without any appreciable loss of catalytic activity. Copyright © 2016 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web site.
Keywords: magnetic Fe3O4 nanoparticle; epoxide; aromatic amine; nanocatalyst
emulsions. To overcome these limitations, the development of a
better catalyst for the activation of epoxides rendering them more
Introduction
In recent years, magnetic nanostructured materials with desirable
functional groups have been topics of overwhelming interest in view
of vast applications in targeted drug delivery, magnetic resonance
imaging, separation techniques and organic synthesis.[1,2] Magnetic
nanoparticles play a key role in various organic transformations as
environmentally benign reusable catalysts because of their high
liquid dispersibility, remarkable catalytic activity, ease of preparation
and surface modification, low cost and ease of separation from
reaction mixtures with the use of an external magnet compared to
filtration or centrifugation.[3,4] Furthermore, magnetic separation is
of overwhelming interest as an alternative to porous/mesoporous
catalyst supports, because it reduces the separation problems and
environmental issues and makes the recovery and reusability of
magnetic catalysts easier after completion of a reaction with the
minimum amount of production waste.[5,6] In this context, a variety
of functional magnetic nanoparticles have received increasing atten-
tion for a wide range of applications in diverse classes of organic
transformations from laboratory to large-scale operations.[7–12]
β-Amino alcohols are versatile intermediates in the synthesis of a
vast variety pharmacologically interesting compounds, and biolog-
ically active natural and synthetic products.[13,14] They also play a
significant role as chiral auxiliaries in asymmetric transforma-
tions.[15,16] Aminolysis of epoxides with excess amine at elevated
temperatures is a common synthetic tool for construction of
β-amino alcohols.[17,18] High temperature may not be appropriate
for certain complex and sensitive functional groups and, as a conse-
quence, a variety of catalysts and promoters have been introduced
for the cleavage of epoxides at room temperature.[19–31] Even
though these catalysts or promoters have improved the scope
and yields of these reactions considerably, there are still some lim-
itations with the method reported in the literature. For example,
some Lewis acid catalysts require prolonged reaction times and re-
actions involve large amounts of expensive catalysts, hazardous
solvents and the formation of bis-adducts. Furthermore, some of
these catalysts have work-up problems due to formation of
susceptible to nucleophilic attack under mild conditions with an ef-
ficient and general method is of great interest.
Experimental
Materials and equipment
All starting materials and solvents were commercially available and
were purchased and used without further purification. All amines
and epoxides were commercially available. Water and other sol-
vents were double distilled before use. Melting points and boiling
points were recorded with a Buchi 535 melting point apparatus
and are uncorrected. Fourier transform infrared (FT-IR) spectra were
obtained with a Bruker Vector-22 infrared spectrometer using KBr
1
discs. H NMR spectra were recorded at room temperature with
on a Bruker FT-NMR Ultra Shield™ (500 MHz) instrument using
CDCl3 as a solvent. Chemical shifts were measured in ppm down-
field from tetramethylsilane.
Preparation of sulfonic acid-functionalized silica-coated mag-
netic Fe3O4 nanoparticles (MNP-SiO2/SO3H)
The magnetic Fe3O4 nanoparticles were synthesized through a
modified co-precipitation reaction according to a previously re-
ported method.[32] FeCl2Á7H2O (5 mmol) and FeCl3Á6H2O (10 mmol)
were dissolved in deionized water (50 ml) and stirred mechanically
at 80°C for 15 min under a nitrogen atmosphere. This was followed
by dropwise addition (about 10 min) of NaOH (40 mmol) solution to
the reaction mixture which was stirred for 2 h at 80°C. Then the
*
Correspondence to: Najmedin Azizi, Chemistry and Chemical Engineering Research
Center of Iran, PO Box 14335-186, Tehran, Iran. E-mail: azizi@ccerci.ac.ir
Chemistry and Chemical Engineering Research Center of Iran, PO Box 14335-186
Tehran, Iran
Appl. Organometal. Chem. 2016, 30, 431–434
Copyright © 2016 John Wiley & Sons, Ltd.

N. Azizi, P. Kamrani and M. Saadat
precipitate was collected using a strong permanent magnet and
washed with deionized water to pH = 7. The collected precipitate
was washed twice with ethanol and dried under vacuum at 60°C
overnight to afford Fe3O4 nanoparticles.
To prepare silica-coated Fe3O4 (Fe3O4@SiO2) nanoparticles,
200 mg of Fe3O4 nanoparticles was suspended in 150 ml of ethanol
under ultrasonic irradiation for 30 min under nitrogen. This was
followed by dropwise addition of 11 ml of NH3 (28%) and 400 μl
of tetraethylorthosilicate (TEOS) to the Fe3O4 suspension which
was sonicated for another 2 h. The resulting Fe3O4@SiO2 nanopar-
ticles were thoroughly washed with ethanol (3 × 30 ml) and col-
lected using magnetic separation, followed by drying at 60°C
under vacuum for 4 h.
peak at 571 cmÀ1 is attributed to the stretching vibration of Fe–O
bond and the peak at 1155 cmÀ1 corresponds to the Si–O
stretching vibration in MNPs, indicating the successful coating of
silica on the magnetite surface. There are two peaks at 1155 and
1219 cmÀ1 which are assigned to the stretching vibration of S–O
group. O–H stretching vibrations at about 3434 and at 1646 cmÀ1
are due to the SO3H moiety and water molecules in MNPs.
The X-ray diffraction (XRD) pattern is depicted in Fig. 2, and
clearly reveals that the diffraction peaks are found to be similar to
reported values. The peaks indexed as planes 220, 311, 400, 511
and 440 correspond to a cubic unit cell, characteristic of crystalline
Fe3O4. Therefore, it is confirmed that the crystalline structure of the
MNP-SiO2/SO3H obtained agrees with the structure of an inverse
spinel type oxide. The crystallite size of Fe3O4 nanoparticles was de-
termined using the Debye–Scherrer equation and they are found to
have an average diameter of 35 nm.
MNP-SiO2/SO3H was prepared by surface functionalization of
0.5 g of Fe3O4@SiO2 nanoparticles using chlorosulfuric acid
(0.5 ml) in anhydrous CH2Cl2 (20 ml) in a three-necked flask under
standard conditions.[32]
TGA curves were obtained to quantitatively determine the com-
position as well as the thermal stability of the magnetic catalyst
(Fig. 3). The initial weight loss from the MNP-SiO2/SO3H up to
150°C is due to physically adsorbed water and surface hydroxyl
groups in the magnetic catalyst. The second weight loss, which ap-
pears at around 150–400°C, is related to the decomposition of SO3H
General procedure
A test tube, equipped with a magnetic stir bar, was charged with
epoxide (1.0 mmol), amine (1.0 mmol), MNP-SiO2/SO3H (10 mg)
and ethanol (2 ml). The resulting mixture was stirred at room tem-
perature (at 60°C for cyclohexene oxide) until the reaction was com-
pleted. The crude reaction mixture was then diluted with ethyl
acetate and washed with water. After separation of MNPs with an
external magnet, the organic layer was dried over Na2SO4 and
evaporated under vacuum. In some cases, the crude products were
purified using flash chromatography with a silica gel column or re-
crystallization from ethanol or diethyl ether to afford pure products.
All the products are known compounds and the characterizations
of these compounds are identical to literature reports.
Figure 1. FT-IR spectrum of MNP-SiO2/SO3H.
60
50
40
30
20
10
0
Results and discussion
Because of our interest in developing green and biocompatible
methodologies,[33,34] herein we report a facile and efficient synthe-
sis of β-amino alcohols by ring opening of epoxides using aromatic
amines in the presence of the acidic magnetic nanoparticles.
The procedure for the fabrication of sulfonic acid groups on the
MNPs is illustrated in Scheme 1. First, Fe3O4 nanoparticles were eas-
ily prepared via a co-precipitation method (modified solvothermal
reaction). Second, the Stöber method was used to grow SiO2 shells
around the Fe3O4 particles to protect the MNP morphology, pre-
vent aggregation and facilitate functionalization with sulfonic acid
groups. Finally, the abundant hydroxyl groups on the SiO2 reacted
rapidly with chlorosulfuric acid to afford MNP-SiO2/SO3H.
20
30
40
50
60
70
80
2-Theta - Scale
Figure 2. XRD pattern of MNP-SiO2/SO3H.
The morphology of the core–shell MNPs was characterized by
means of FT-IR and energy-dispersive X-ray (EDX) spectroscopies,
thermogravimetric analysis (TGA) and scanning electron micros-
copy and the data are found to be in agreement with the reported
procedure. The functional groups of the catalyst were analysed
using FT-IR spectroscopy and the results are shown in Fig. 1. The
Scheme 1. Synthesis of MNP-SiO2/SO3H catalyst.
Figure 3. TGA curve of MNP-SiO2/SO3H.
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Copyright © 2016 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2016, 30, 431–434

Regioselective ring opening of epoxides in the presence of MNP-SO3H
groups. Compared with Fe3O4@SiO2, the excess weight loss of
MNP-SiO2/SO3H is 18%, indicating that the SO3H groups are grafted
on the magnetic catalyst.
Table 1. Optimization of reaction conditions
A typical EDX spectrum of MNP-SiO2/SO3H is shown in Fig. 4.
Peaks associated with Fe, Si, O, Cl and S in the structure of the mag-
netic catalyst can be further confirmed.
The relation between the applied magnetic field (H; Oe) and the
magnetization (M; emu gÀ1) of MNP-SiO2/SO3H shows that the sat-
uration magnetization of Fe3O4 is 49.12 emu gÀ1 (Fig. 5).
Entry
Solvent
Temp. (°C)
Yield (%)a
1
EtOH
EtOH
r.t.
40
60
60
60
60
60
60
60
60
60
60
60
60
40
65
2
The MNP-supported sulfonic acid was next evaluated in the
model reaction of aniline and cyclohexene oxide for the synthesis
of β-amino alcohols. As evident from Table 1, the model reaction
occurs smoothly in the presence of 10 mg of catalyst in ethanol,
affording the corresponding trans-2-(phenylamino)cyclohexanol
in 40% yield at room temperature after 4 h. On increasing the
temperature to 60°C, higher yields of the corresponding product
are obtained. Regarding the use of solvent, ethanol is found to be
more suitable, and a more homogeneous dispersion of MNPs is ob-
served (Table 1, entry 3). Other solvents such as water, CH3CN,
dimethylformamide (DMF), poly(ethylene glycol) (PEG), tetrahydro-
furan (THF) and CH2Cl2 are found to be inferior in terms of yield and
time taken for completion of the reaction. To check the influence of
MNP-SiO2/SO3H, model reactions were carried out in the presence
of Fe3O4 and SiO2-coated Fe3O4 under the same conditions, giving
the desired product in 42 and 48% yield, respectively (Table 1, en-
tries 11 and 12). Without MNP-SiO2/SO3H catalyst under the same
reaction conditions, a trace amount of product (10% yield) is ob-
served (Table 1, entry 13). This clearly confirms the requirement of
MNP-supported SO3H for catalytic activity in terms of yield and re-
action time. Furthermore, a decrease in the amount of catalyst to
5 mg results in a lower yield (Table 1, entry 14).
3
EtOH
85
4
H2O
55
5
DMF
76
6
CH3CN
CH2Cl2
Ethyl acetate
THF
78
7
54
8
62
9
52
10
11b
12c
13d
14e
PEG
74
EtOH
42
EtOH
48
EtOH
Trace
52
EtOH
a
Isolated yields.
b
c
Nano-Fe3O4 catalyst.
Fe3O4-SiO2 catalyst.
Without catalyst.
d
e
5 mg MNP-SiO2/SO3H.
with several structurally diverse aniline and epoxide derivatives
for the ring-opening reaction (Table 2). Thus cyclohexene oxide
was treated with various aromatic amines such as aniline,
4-methylaniline, 4-chloroaniline, 3,4-dichloroaniline, 4-chloroaniline
and 4-isopropylaniline to isolate the corresponding β-amino alco-
hols in good to high yields. The trans stereochemistry of the prod-
uct is deduced from the relevant coupling constants of the peaks
at 3.22 ppm (ddd, J = 10.8, 10.1, 3.5 Hz, HNHPh) and 3.37 ppm
(ddd, J = 10.8, 10.2, 3.9 Hz, CHOH) in the 1H NMR spectra.
Having identified the choice of MNPs and the optimized reaction
conditions, we turned our attention to the scope of reaction
We next evaluated the outcome of selective ring-opening reac-
tions of commercial aliphatic epoxides such as glycidyl phenyl
ether, allyl 2,3-epoxypropyl ether and 1,2-epoxybutane with diverse
aniline derivatives under the same reaction conditions. Aniline,
4-bromoaniline, 4-butylaniline, 4-methylaniline, 2-methylaniline
and 4-isopropylaniline react well with aliphatic epoxides and in all
cases the corresponding amino alcohols are isolated in good yields
(Table 2). The regioselectivity in the reaction of unsymmetric epox-
ides is governed by both steric and electronic effects. Attack of ali-
phatic amines occurs mainly on the less substituted carbon of
unsymmetric aliphatic epoxides, affording a corresponding product
in good to high yields. Aniline undergoes the reaction with styrene
oxide in a regioselective manner to give two regioisomers and with
preferential nucleophilic attack at the benzylic position (Table 2, en-
try 14). All reactions are clean at room temperature and regioselec-
tive affording high yields of products in a short reaction time. All
products were characterized from 1H NMR, FT-IR and mass spectro-
metric data and also by comparison with authentic samples.
The reusability of the catalyst is an important factor in view of in-
dustrial purposes, and thus the reusability of the catalyst in the model
reaction under optimized conditions was tested (Table 1, entry 3). In
order to regenerate and reuse the catalyst, after each run it was sep-
arated by a simple magnetic decantation using an external magnet,
washed with ethyl acetate and ethanol, dried in vacuum at 60°C
Figure 4. EDX pattern MNP-SiO2/SO3H.
Figure 5. Magnetization curve of Fe3O4 nanoparticles.
Appl. Organometal. Chem. 2016, 30, 431–434
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N. Azizi, P. Kamrani and M. Saadat
Table 2. Aminolysis of epoxides in ethanol in the presence of MNP-SiO2/SO3H catalyst
Entry
Epoxide
Ar
Product
Temp. (°C)
Time (h)
Yield (%)a
Ratio of A:B
1
E1
E1
E1
E1
E1
E2
E2
E2
E2
E3
E3
E3
E4
E5
Ph
3a
3b
3c
3d
3e
3f
60
60
60
60
60
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
4
4
5
5
5
5
5
5
5
5
5
5
5
3
85
79
75
69
70
72
65
77
80
82
80
81
78
82
—
2
4-MePh
4-i-PrPh
4-ClPh
3,4-diCl2Ph
Ph
—
3
—
4
—
5
—
6
98:2
95:5
92:8
95:5
90:10
94:6
97:3
92:8
15:85
7
4-MePh
4-BrPh
2-MePh
Ph
3g
3h
3i
8
9
10
11
12
13
14
3j
4-i-PrPh
4-n-BuPh
Ph
3k
3l
3m
3n
Ph
a
Isolated yields.
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and reused in the subsequent run cycles without any significant loss
in catalytic activity (85%, 85%, 83, 83 and 80%), respectively.
Summary
[15] J. Seyden-Penne, Chiral Auxiliaries and Ligands in Asymmetric Synthesis,
John Wiley, New York, 1995, pp. 457–458.
We have demonstrated an efficient and environmentally friendly
method for the aminolysis of epoxides with aromatic amines using
recoverable and reusable acidic MNPs as an efficient promoter. In
light of its operational simplicity, use of an inexpensive and easily
accessed catalyst at low loading, simple experimental and purifica-
tion procedure, and high yields, this protocol is superior to existing
methods. Furthermore, the preparation and application of the sul-
fonic acid-functionalized magnetically separable MNPs are easier,
faster and cheaper than heterogeneous solid catalysts. In addition,
the catalyst could be easily recovered from the reaction mixture
with an external magnet and could be recycled, showing compara-
ble catalytic activity for up to six runs.
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Additional supporting information may be found in the online ver-
sion of this article at the publisher’s web site.
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Copyright © 2016 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2016, 30, 431–434