Copper immobilized on aminated ferrite nanoparticles by 2-aminoethyl dihydrogen phosphate (Fe3O4@AEPH2-CuII) catalyses the conversion of aldoximes to nitriles

Article abstract of DOI:10.1002/aoc.3351

Cu^II immobilized on aminated ferrite nanoparticles by 2-aminoethyl dihydrogen phosphate (Fe₃O₄@AEPH₂-Cu^II) was prepared and characterized using FT-IR, TGA, TEM, EDX, VSM, XRD, CHN and ICP techniques. The easily prepared heterogeneous nanocatalyst demonstrated a significant catalytic performance for the transformation of aldoximes to nitriles that is far superior to previously reported methods. The reaction allows for the conversion of a wide variety of aldoximes including aromatic, aliphatic and heterocyclic aldoximes in good to excellent yields (50-98%). High efficiency, mild reaction conditions, easy work-up, operational simplicity, simple purification of products and safe handling of the catalyst are important advantages of this method. In addition, the environmentally benign heterogeneous nanocatalyst can be easily recovered from reaction mixtures using an external magnet and reused several times without any loss of activity.

Full text of DOI:10.1002/aoc.3351

Full paper
Received: 13 May 2015
Revised: 10 June 2015
Accepted: 14 June 2015
Published online in Wiley Online Library: 7 August 2015
(wileyonlinelibrary.com) DOI 10.1002/aoc.3351
Copper immobilized on aminated ferrite
nanoparticles by 2-aminoethyl dihydrogen
II
phosphate (Fe3O4@AEPH2-Cu ) catalyses the
conversion of aldoximes to nitriles
Monireh Zarghani and Batool Akhlaghinia*
CuII immobilized on aminated ferrite nanoparticles by 2-aminoethyl dihydrogen phosphate (Fe3O4@AEPH2-CuII) was prepared and
characterized using FT-IR, TGA, TEM, EDX, VSM, XRD, CHN and ICP techniques. The easily prepared heterogeneous nanocatalyst
demonstrated a significant catalytic performance for the transformation of aldoximes to nitriles that is far superior to previously
reported methods. The reaction allows for the conversion of a wide variety of aldoximes including aromatic, aliphatic and hetero-
cyclic aldoximes in good to excellent yields (50–98%). High efficiency, mild reaction conditions, easy work-up, operational simplic-
ity, simple purification of products and safe handling of the catalyst are important advantages of this method. In addition, the
environmentally benign heterogeneous nanocatalyst can be easily recovered from reaction mixtures using an external magnet
and reused several times without any loss of activity. Copyright © 2015 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web-site.
Keywords: Fe3O4@AEPH2-CuII; Fe3O4 NPs; 2-aminoethyl dihydrogen phosphate (AEPH2); aldoximes; nitriles
PtCl4(EtCN)2,[44] Ga(OTf)3,[45] Bi(OTf)3,[46] W–Sn hydroxide,[47]
Introduction
SnCl4,[48] Pd(OAc)2 in the presence of PPh3,[49] Pd(en)(NO3)2,[50]
molecular sieve modified with copper(II),[51] CoCl2/NaF,[52] Raney
Nitriles are an important class of compounds in chemistry as well as
biology.[1] They serve as a versatile precursor for various functional
nickel,[53] cetyltrimethylammonium dichromate,[54] AlCl3ꢀ6H2O/
group transformations[2] and heterocyclic synthesis.[3] Moreover, ni-
triles as key components of numerous natural products are industri-
ally important for the production of agrochemicals, pharmaceuticals,
polymers, dyes and pigments.[4–9] There are a variety of synthetic
routes to nitriles from diverse chemical precursors reported in the
literature, including Sandmeyer reaction,[10] ammoxidation of
aldehydes,[11] metal-catalysed cyanation of aryl halides, nucleophilic
substitution of alkyl halides with cyanides, oxidation of
amines,[12] hydrocyanation of alkenes,[13] Kolbe nitrile
synthesis,[14] Rosenmund–von Braun reaction[15] and dehydration
of amides and aldoximes.[16] Among these, the dehydration of
aldoximes into nitriles is one of the most suitable candidate reac-
tions for clean nitrile synthesis, because of the availability of
starting materials and the avoidance of very toxic cyanide ion.
At first, the aldoxime–nitrile transformation was investigated by
Gabriel and Meyer.[17] In the recent past, a number of efficient
KI/H2O/CH3CN,[55] (La3+, Ce3+, Re3+, Sm3+) Na–Y zeolites,[56] In
(NO3)3[57] and Zn(OTf)2[58] have been used to carry out the same
transformation. The reported methods have paid much attention
to the activation of the hydroxyl group in aldoxime as leaving
group for the subsequent 1,2- elimination to give nitrile.[59]
Despite the development of dehydration methods for conversion
of aldoximes to nitriles, it is still an interesting topic to current or-
ganic chemists. Also, the reported methods may have limitations
in some respects such as harsh reaction conditions, low yields,
lack of generality and use of high-cost or less readily available re-
agents, high microwave power and high temperature. Therefore,
to overcome the mentioned limitations, we decided to apply a
new reaction medium for the conversion of aldoximes to nitriles.
Our aim was to prepare an amino-functionalized Fe3O4 nanopar-
ticle (NP) carrier, using 2-aminoethyl dihydrogen phosphate
(AEPH2) as a bifunctional short-chained organic molecule that has
both a phosphate group and an amino group. Because there is a
relatively high affinity between phosphate ions and hydrated oxide
particles, in particular iron(III) oxides,[60,61] the phosphate group of
AEPH2 is useful for binding with Fe3O4 NPs. As the amino group
reagents and conditions have been described for the dehydration
of aldoximes, such as NCS/PPh3,
(NCS/Py),[19] Ph3P/I2,[20] Ph3PO/
[18]
(COCl)2,[21] thionyl chloride-benzotriazole,[22] N-(p-toluenesulfonyl)
imidazole,[23] Vilsmeier reagent,[24] Burgess reagent,[25] cyanuric
chloride,[26] S,S-dimethyl dithiocarbonate,[27] sulfonyl chlorides,[28] triflyl
imidazole,[29] bromodimethylsulfonium bromide,[30] 8-bromocaffeine,[31]
tetrachloropyridine,[32] PEG-SO3H,[33] silica gel,[34] phthalic
anhydride,[35] clay,[36] ethyl 2-cyano-2-(hydroxyimino)acetate[37]
and Ac2O/K2CO3/dimethylsulfoxide.[38] In recent decades several
metal catalysts such as [RuCl2(p-cymene)]2/molecular sieves,[39]
rhenium(VII)oxo complexes,[40] InCl3,[41] TiCl3(OTf),[42] Cu salts,[43]
*
Correspondence to: Batool Akhlaghinia, Department of Chemistry, Faculty of
Sciences, Ferdowsi University of Mashhad, Mashhad 9177948974, Iran. E-mail:
akhlaghinia@um.ac.ir
Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad,
Mashhad 9177948974, Iran
Appl. Organometal. Chem. 2015, 29, 683–689
Copyright © 2015 John Wiley & Sons, Ltd.

M. Zarghani and B. Akhlaghinia
Preparation of Fe3O4@AEPH2-CuII
can also work as an anchoring point for bonding of several metal
ions,[62] immobilization of CuII on aminated Fe3O4 NPs
(Fe3O4@AEPH2-CuII) was investigated. The catalytic activity of
Fe3O4@AEPH2-CuII, as a new magnetically recoverable heteroge-
neous catalyst, was studied in the conversion of aldoximes to
nitriles.
Cu(OAc)2ꢀH2O (0.2 g, 1 mmol) was added to a suspension of
Fe3O4@AEPH2 (1 g) in ethanol (50 ml). The mixture was refluxed with
vigorous stirring. After 24 h, the resulting Fe3O4@AEPH2-CuII product
was collected using an external magnet and washed repeatedly
with ethanol and then dried at room temperature in vacuo for 6 h.
Experimental
Typical procedure for preparation of nitriles
General procedure
To a solution of 4-nitrobenzaldoxime (0.08 g, 1.00 mmol) in dry ace-
tonitrile (2ml), Fe3O4@AEPH2-CuII (0.088 g, 8 mol%) was added with
stirring. The reaction mixture was refluxed for 1 h. The progress of
reaction was monitored using TLC. After completion of the reaction
and separation of the catalyst using a magnetic field, the residue
was purified using flash column chromatography on silica gel with
n-hexane–ethyl acetate (4:1) as eluent to afford 4-nitrobenzonitrile
(0.144 g, 98%).
The purity determinations of the products were accomplished
using TLC on silica gel polygram STL G/UV 254 plates. The melting
points of products were determined with an Electrothermal type
9100 melting point apparatus. Fourier transform infrared (FT-IR)
spectra were recorded with a Nicolet Avatar 370 FT-IR Therma spec-
trometer. NMR spectra were obtained with Brucker AMX 100 and
400 MHz instruments in CDCl3. Elemental analyses were performed
using a Thermo Finnegan Flash EA 1112 series instrument. Mass
spectra were recorded with Agilent Technologies (HP) 5973 Network
Mass Selective Detector and Shimadzu GC-MS-QP 5050 instruments
at 70 eV. Thermogravimetric analysis (TGA) was performed with a
Shimadzu thermogravimetric analyser (TG-50) under air atmosphere
at a heating rate of 10°C minꢁ1. Transmission electron microscopy
(TEM) was performed with a Leo 912 AB (120 kV) microscope (Zeiss,
Germany). Inductively coupled plasma (ICP) analysis was carried
out with a Varian VISTA-PRO, CCD (Australia). Elemental compositions
were determined with energy-dispersive X-ray analysis (EDX; model
7353, Oxford Instruments, UK), with 133 eV resolution.
The crystal structure of the catalyst was analysed using X-ray
diffraction (XRD) with a Bruker D8 ADVANCE diffractometer using
a Cu target (λ = 1.54 Å). The magnetic property of the catalyst was
measured using vibrating sample magnetometry (VSM; model
7400, Lake Shore). All of the products were known compounds
and characterized using FT-IR spectroscopy, mass spectrometry
and comparison of their melting points with known compounds.
The structure of selected products was further confirmed using
1H NMR spectroscopy.
Results and discussion
Synthesis and characterization of Fe3O4@AEPH2-CuII
Recently, heterogeneous and magnetically recoverable catalysts
with reagents immobilized on solid supports have been widely
used in organic reactions, because of their advantages over con-
ventional solution-phase reactions, such as good dispersion of ac-
tive reagent sites, better selectivity and easier work-up. Also,
recyclability of these solid-supported reagents renders these pro-
cesses truly eco-friendly green protocols. In continuation of our
study to design efficient heterogeneous catalysts,[64] we have pre-
pared Fe3O4@AEPH2-CuII as an efficient, heterogeneous and mag-
netically recoverable catalyst which has been characterized using
FT-IR spectroscopy, TGA, TEM, EDX, VSM, XRD, elemental analysis
and ICP techniques. Initially, Fe3O4 NPs were prepared and purified
using the method described in the literature[63] (Scheme 1).
To confirm the existence of the bonded species, the catalyst
structure was defined using FT-IR spectroscopy. Figure 1 illustrates
the FT-IR spectra of Fe3O4 NPs, Fe3O4@AEPH2 and Fe3O4@AEPH2-
CuII. The principal bands for Fe3O4 NPs (Fig. 1(a)) are observed at
3250–3400 cmꢁ1 (as a broad absorption band attributed to
stretching frequencies of hydroxyl groups and bound water on the
Preparation of Fe3O4 NPs
In a 500 ml three-necked round-bottom flask, a mixture of
FeCl3ꢀ6H2O (46 mmol, 12.4 g) and FeSO4ꢀ7H2O (23 mmol, 6.3 g)
was dissolved in 150ml of deionized water. Argon was imported
for 3 min to exclude air. Then 20 ml of ammonium hydroxide
(25%) was added quickly into the iron solution under vigorous stir-
ring. After 30 min, 3 ml of oleic acid was added into the reaction
mixture. The mixture was heated at 75°C under argon atmosphere.
After 1 h, the reaction mixture was cooled to room temperature.
The Fe3O4 NPs were collected through magnetic separation and
washed with deionized water and ethanol three times each. The
Fe3O4 NPs were then dried under vacuum conditions.[63]
Preparation of aminated Fe3O4 NPs (Fe3O4@AEPH2)
To a suspension of Fe3O4 NPs (1.15 g, 5 mmol) in deionized wa-
ter (20 ml), AEPH2 (0.7g, 5 mmol) was added portion by potion
at room temperature. The flask was swept with argon for
3 min to exclude air and then closed. The closed flask was then
shaken for 48 h. The resulting Fe3O4@AEPH2 product was iso-
lated using an external magnet, washed with distilled water
and dried in vacuo at 50°C for 6 h.
Scheme 1. Preparation of CuII immobilized on aminated Fe3O4 NPs
(Fe3O4@AEPH2-CuII).
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Appl. Organometal. Chem. 2015, 29, 683–689

Conversion of aldoximes to nitriles by Fe3O4@AEPH2-CuII
Figure 2. TGA thermogram of Fe3O4@AEPH2-CuII.
reveals the amount of AEPH2 combined on Fe3O4 NPs to be 6.2%
(w/w). So, the elevated temperature for pendent organic group re-
moval indicates the high thermal stability of Fe3O4@AEPH2-CuII.
This high thermal stability of Fe3O4@AEPH2-CuII confirms the
covalent bonding of AEPH2 on the surface of Fe3O4 NPs.
Figure 1. FT-IR spectra of (a) Fe3O4 NPs, (b) Fe3O4@AEPH2 and
(c) Fe3O4@AEPH2-CuII.
In addition to the structural confirmation of the catalyst using
FT-IR spectroscopy and TGA, quantitative determination of cova-
lently bonded AEPH2 on the surface of Fe3O4 NPs was performed
using elemental analysis. The elemental analysis of Fe3O4@AEPH2-CuII
shows the carbon and nitrogen contents to be 1.71 and 0.948%,
respectively. The results of elemental analysis of Fe3O4@AEPH2-CuII
are in good agreement with those of TGA. The elemental analysis
data for the catalyst reveal that 0.75 mmol of AEPH2 is incorpo-
rated into 1.000 g of Fe3O4@AEPH2-CuII.
surface of Fe3O4 NPs), 2927, 2856, 1573 and 1436 cmꢁ1 (asymmetric
and symmetric vibrational frequencies of CH2 and carboxylate group
of the adsorbed oleate anion), 1060 and 847 cmꢁ1 (asymmetric and
symmetric stretching vibrations characteristic of Fe–O–H bond) and
580–620 cmꢁ1 (attributed to vibrational frequency of Fe–O bond).
Upon the reaction of Fe3O4 NPs with AEPH2, all the oleate anions
are replaced by phosphonate groups. Thus in the FT-IR spectrum of
Fe3O4@AEPH2, absorption bands at 1573 and 1436 cmꢁ1 (asym-
metric and symmetric vibrational frequencies of carboxylate group
of the adsorbed oleate anion) are removed completely (Fig. 1(b)).
The characteristic band of Fe3O4@AEPH2 appears at 1153 cmꢁ1
due to stretching vibration of P¼O. The presence of P–O–Fe bond
is confirmed by two absorption bands at 1012 and 987 cmꢁ1 (asym-
metric and symmetric stretching vibrations). Also, absorption bands
at 1099, 981 and 570–604 cmꢁ1 correspond to the asymmetric and
symmetric stretching and bending vibrations of O–P–O bond,
respectively. The latter absorption band is covered by the broad
characteristic band of Fe–O at around 580–620 cmꢁ1. Two absorp-
tion bands at 3457 and 3415 cmꢁ1 are attributed to –NH2 stretching
frequencies and, furthermore, two other absorption bands at 1619
and 1238 cmꢁ1 are assigned to –NH bending vibration and –CN
stretching vibration, respectively (Fig. 1(b)).
The copper content of Fe3O4@AEPH2-CuII is found, using ICP
analysis, to be 58 320 ppm, 0.057 g or 0.91 mmol of Cu per 1.000 g
of Fe3O4@AEPH2-CuII.
TEM micrographs and size distributions (25nm) of Fe3O4 NPs and
Fe3O4@AEPH2-CuII are shown in Fig. 3. TEM images indicate that
most of the prepared Fe3O4 NPs (Figs 3(a) and (b)) and
Fe3O4@AEPH2-CuII (Figs 3(c) and (d)) are spherical in shape and
have sizes of 10–20 nm. The TEM results reveal that incorporation
of AEPH2 on the surface of Fe3O4 NPs and immobilization of CuII
on Fe3O4@AEPH2 do not change the particle size of Fe3O4 NPs.
XRD was used to identify the crystalline structure of Fe3O4 NPs
and Fe3O4@AEPH2-CuII. As shown in Fig. 4, all the diffraction peaks
can be indexed to (2, 2, 0), (3, 1, 1), (4, 0, 0), (4, 2, 2), (5, 1, 1) and (4, 4, 0)
reflections, matching well with the characteristic peaks of
In the FT-IR spectrum of Fe3O4@AEPH2-CuII, coordination of CuII
on aminated Fe3O4 NPs is confirmed by the presence of an absorp-
tion band at 428 cmꢁ1. This absorption due to Cu–N vibration is cov-
ered by structural vibrations of Fe3O4 NPs (Fig. 1(c)). The intensities
of –NH2 stretching bands (3457 and 3415 cmꢁ1) are decreased
significantly upon coordination of CuII on aminated Fe3O4 NPs. Also,
coordination of CuII moves the –NH bending absorption band to
lower frequency (1619 to 1590 cmꢁ1). A broad absorption band with
rather low intensity at around 1455–1580 cmꢁ1 is attributed to the
asymmetric and symmetric stretching vibrations of acetate ions
(OAc) which confirms that the acetate ions are still connected to CuII.
The TGA thermogram of Fe3O4@AEPH2-CuII (Fig. 2) shows two
main weight losses. The first one (2.4%, 27–200°C) is accounted
for by physically and hydrogen bonded water in the structure of
Fe3O4@AEPH2-CuII. The second one which occurs at 200–500°C
(6.2%) is related to the decomposition of organic segment an-
chored to the Fe3O4 NP surface. This part of the thermogram
Figure 3. TEM images of (a, b) Fe3O4 NPs and (c, d) Fe3O4@AEPH2-CuII.
Appl. Organometal. Chem. 2015, 29, 683–689
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M. Zarghani and B. Akhlaghinia
Figure 6. Magnetization curves of (a) Fe3O4 NPs and (b) Fe3O4@AEPH2-CuII.
Figure 4. XRD patterns of (a) Fe3O4@AEPH2-CuII, (b) Fe3O4 NPs and
(c) standard reference (JCPDS 19–0629).
cubicstructure (JCPDS 19–0629). The average crystallite sizes, d,
of Fe3O4 NPs and Fe3O4@AEPH2-CuII calculated using the
Debye–Scherrer equation d = K λ/β cos θ are about 16.5 and
13 nm, respectively. As the peak positions of Fe3O4 NPs (Fig. 4(b))
are unchanged during the production of Fe3O4@AEPH2-CuII
(Fig. 4(a)), we can conclude that the crystalline structure of
Fe3O4 NPs is conserved after the surface modification with
AEPH2 and CuII.
Scheme 2. Synthesis of
a variety of nitriles in the presence of
Fe3O4@AEPH2-CuII.
EDX indicates the presence of C, O, P, Fe and Cu elements (Fig. 5).
This analysis confirms that CuII is supported on aminated Fe3O4 NPs.
The M–H hysteresis curves of Fe3O4 NPs and Fe3O4@AEPH2-CuII
are shown in Fig. 6. The magnetization curves measured at room
temperature show that Fe3O4 NPs and Fe3O4@AEPH2-CuII are
superparamagnetic. This is because the diameters of Fe3O4 NPs
and Fe3O4@AEPH2-CuII are smaller than 25 nm. It can be seen that
the saturation magnetizations of Fe3O4 NPs and Fe3O4@AEPH2-CuII
are 54.6 and 45.0 emu gꢁ1, respectively. The decrease in the satura-
tion magnetization of Fe3O4@AEPH2-CuII indicates the presence of
surface-bound AEPH2-CuII.
In order to achieve the maximum yield and efficiency for the
synthesis of various nitrile compounds, the experimental conditions
must be carefully optimized. Conversion of 4-nitrobenzaldoxime to
4-nitrobenzonitrile as a model reaction was studied in the presence
of Fe3O4@AEPH2-CuII and acetonitrile as dehydrating agent and
subjected to a series of reaction conditions (applying various
amounts of catalyst at various temperatures). The obtained results
are summarized in Table 1. The best results are obtained using
8 mol% (0.0880g) of Fe3O4@AEPH2-CuII (containing 0.08 mmol of
Cu) in refluxing acetonitrile (Table 1, entry 2). When the reaction is
carried out at lower temperatures, the rate of reaction is reduced
considerably with the formation of 4-nitrobenzamide as by-product
(Table 1, entry 1). Higher catalyst loading (16 mol%, 0.1760 g
containing 0.16 mmol of Cu) has no significant influence on the
reaction rate, while a lower amount of Fe3O4@AEPH2-CuII decreases
the reaction rate (Table 1, entries 4 and 5). To improve the reaction
conditions, conversion of 4-nitrobenzaldoxime to 4-nitrobenzonitrile
was performed with stoichiometric amount of acetonitrile (1:1 molar
ratio of 4-nitrobenzaldoxime to CH3CN) in the presence of 8 mol%
(0.0880 g) of Fe3O4@AEPH2-CuII (Table 1, entry 3). As can be seen,
stoichiometric amount of acetonitrile reduces the catalytic activity
of Fe3O4@AEPH2-CuII efficiently, and 4-nitrobenzamide is produced
as by-product.
Catalytic conversion of aldoximes to nitriles
In continuation of our recent studies of the application of CuII in
organic reactions,[64–67] after preparation and characterization
of Fe3O4@AEPH2-CuII, its catalytic activity as a new magnetic
nanocatalyst was investigated in the preparation of a library of ni-
triles through dehydration of aldoximes by acetonitrile (Scheme 2).
The major role of Fe3O4@AEPH2-CuII as a catalyst in the conver-
sion of aldoximes to nitriles was established by performing the
model reaction in the absence of Fe3O4@AEPH2-CuII. After a long
reaction time (24 h), the reaction proceeds to only 10% conversion
(trace amount of 4-nitrobenzonitrile and 8% yield of 4-
nitrobenzamide) and no additional conversion is obtained even
after a longer reaction time (Table 1, entry 6). Similarly, performing
the model reaction in the presence of Fe3O4@AEPH2 and Fe3O4 NPs
gives the same results (Table 1, entries 7 and 8).
In the presence of the optimized amount of CuII (0.0051 g,
0.08 mmol), using 0.0159 g (7mol%) of Cu(OAc)2ꢀH2O, the
Figure 5. EDX trace of Fe3O4@AEPH2-CuII.
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Appl. Organometal. Chem. 2015, 29, 683–689

Conversion of aldoximes to nitriles by Fe3O4@AEPH2-CuII
Table 1. Conversion of 4-nitrobenzaldoxime to 4-nitrobenzonitrile in the presence of various amounts of Fe3O4@AEPH2-CuII and 2 ml
of acetonitrile, and at various temperatures
Entry
Catalyst (mol%)
Temp. (°C)
Time (h)
Conversion (%)
4-Nitrobenzonitrile (%)
4-Nitrobenzamide (%)
1
8 (0.0880 g)
8 (0.0880 g)
8 (0.0880 g)
16 (0.1760 g)
4 (0.0440 g)
None
60
2
1
50
100
30
40
100
10
0
2
3a
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
1
10
20
0
4
0.83
3
100
90
100
5
85
5
6
24
24
24
1
10
Trace
Trace
Trace
60
8
7b
8c
9d
8 (0.0168 g)
8 (0.0180 g)
7 (0.0159 g)
10
8
10
8
90
30
a1:1 molar ratio of 4-nitrobenzaldoxime to acetonitrile.
bIn the presence of Fe3O4@AEPH2.
cIn the presence of Fe3O4NPs.
dIn the presence of Cu(OAc)2ꢀH2O.
Table 2. Dehydration of various aldoximes in the presence of
Fe3O4@AEPH2-CuII and acetonitrile
Entry
R
Time (h)
Isolated
M.p. (°C)
yield (%)
1
C6H5
2
90
98
50
95
95
85
95
90
85
90
95
96
85
98
75
90
98
95
95
75
90
98
95
Oil[68]
2
3a
4-OHC6H4
2-OHC6H4
4-OMeC6H4
3-OMeC6H4
2-MeC6H4
4-MeC6H4
4-iso-PrC6H4
4-(Me2N)C6H4
2-ClC6H4
1
108–110[46]
92–94[33]
56–58[48]
Oil[49]
4
4
1
5
2
6
4
Oil[69]
26–27[70]
Oil[46]
7
2
8
2
9
2
70–72[71]
40–41[48]
92–93[72]
89–90[48]
140–143[32]
112–113[70]
106–108[48]
114–115[73]
146–148[73]
218–220[72]
32-34[74]
Oil[68]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
4
3-ClC6H4
1.5
1
4-ClC6H4
2,6-(Cl)2C6H3
4-BrC6H4
4
1
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
4-CNC6H4
1-Naphthyl
1-Pyridyl
4
Scheme 3. Proposed mechanism of conversion of aldoximes to nitriles in
2
the presence of Fe3O4@AEPH2-CuII.
1
1
2
3
3-Pyridyl
3
46–50[75]
Oil[21]
Oil[76]
C6H4CH¼CH2
C6H12
1.5
1
aIn the presence of equimolar amount of triethylamine.
dehydration reaction of 4-nitrobenzaldoxime is completed after 1 h
with the formation of 60% of 4-nitrobenzonitrile and 30% of
4-nitrobenzamide (Table 1, entry 9). Therefore, we may conclude
that immobilization of CuII on the surface of Fe3O4@AEPH2 not only
increases the catalytic activity but also improves the selective
formation of 4-nitrobenzonitrile (compare entries 2 and 9).
Figure 7. Dehydration of 4-nitrobenzaldoxime the presence of reused
Fe3O4@AEPH2-CuII.
Appl. Organometal. Chem. 2015, 29, 683–689
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M. Zarghani and B. Akhlaghinia
Table 3. Comparison of various catalysts in conversion of aldoximes to nitriles
Entry
Catalyst
Solvent
Temperature (°C)
Time (h)
Yield (%)
Ref.
1
2
3
4
5
6
7
8
9
SnCl4
—
90
0.5
8
92
70
82
90
90
95
96
88
98
48
S,S-Dimethyl dithiocarbonate
Ga(OTf)3
Dioxane
90
27
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
120
16
5
45
PEG-SO3H
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
33
Pd(OAc)2/PPh3
Bi(OTf)3
3
49
46
16
8
Cu(II)/MS 4 Å
Cu(OAc)2
Fe3O4@AEPH2-CuII
51
1
43
1
This study
Based on the optimized reaction conditions, 0.0880 g of the
catalyst (containing 0.08 mmol of Cu) in refluxing acetonitrile, to
extend the scope and versatility of the present findings, different
aldoximes possessing a wide range of functional groups (Scheme 2)
were dehydrated and the corresponding nitriles are produced
within 1–4 h with good to excellent yields. The results are summa-
rized in Table 2. Aromatic aldoximes containing both electron-
withdrawing and electron-donating groups undergo conversion
smoothly. This means that aldoximes appear to be insensitive to
substitution. The difference in dehydration rate of ortho-substituted
aldoximes and the other aromatic aldoximes can be rationalized
by the steric effect (compare entries 3, 6, 10, 13, 15 with the other
aromatic aldoximes in Table 2). Under the same reaction conditions,
salicylaldoxime cannot be dehydrated. It is well known that strong
intramolecular hydrogen bonding between the aldoxime nitrogen
and the o-hydroxyl group in salicylaldoxime can hinder the complex
formation of the oxime with CuII and leads to weak reactivity of
salicylaldoxime (Table 2, entry 3). To improve the dehydration
tendency of salicylaldoxime, triethyamine should be added to the
reaction mixture to disrupt this hydrogen bonding. Conversion
of 50% is obtained with equimolar amount of triethylamine.
Additional amount of triethylamine does not lead to complete
conversion of salicylaldoxime to o-hydroxybenzonitrile after a long
reaction time because of steric hindrance. 1-Naphthaldehydeoxime,
and also 2-pyridinealdoxime and 3-pyridinealdoxime as
heteroaromatic oximes are dehydrated the same as the other
oximes (Table 2, entries 19–21). The present method was further
examined for dehydration of aliphatic aldoximes. Comparatively,
aliphatic aldoximes undergo this reaction with equal efficiency
as aromatic aldoximes (Table 2, entries 22 and 23).
In our experiments, the completion of the reaction is confirmed by
the disappearance of the aldoximes using TLC followed by the disap-
pearance of OH and C¼N stretching frequencies at 3570–3600 and
1480–1690 cmꢁ1 in the FT-IR spectra. Also, the appearance of ab-
sorption bands at 2200–2260 cmꢁ1 due to CN group of nitriles in
the FT-IR spectra confirms the formation of nitriles. All of the prod-
ucts are known compounds and characterized using FT-IR spectros-
copy, mass spectrometry and comparison of their melting points
with known compounds. See the supporting information for details.
According to these observations and by analogy with previous
reports,[64] we propose the mechanism shown in Scheme 3. In the
absence of Fe3O4@AEPH2-CuII a trace amount of product is ob-
served in dehydration of 4-nitrobenzaldoxime after a long reaction
time (Table 1, entry 6). Although the role of Fe3O4@AEPH2-CuII in
dehydration of aldoximes is not clear definitively, it is speculated
that the Lewis acidity of the CuII complex plays an essential role in
dehydration reaction of aldoximes. Initially, interaction of nitrogen
atom of aldoxime and acetonitrile with CuII forms I which facilitates
the nucleophilic addition of oxygen atom of aldoxime to activated
acetonitrile. Then, hydrogen shift leads to the formation of interme-
diate II. Cleavage of II leads to fast extrusion of nitrile and
acetamide. The catalyst re-enters the catalytic cycle by making
the active sites for further turnovers. Further investigation of the
elucidation of the mechanism and scope of this reaction is currently
underway in our laboratory.
Catalyst reusability was assessed in the dehydration of 4-
nitrobenzaldoxime. The reaction was stopped after 1 h (i.e. at
100% conversion) and the catalyst retrieved from the reaction
mixture using an external magnet and washed with ethyl acetate
several times to remove the products, followed by drying at room
temperature under vacuum for 6 h. Figure 7 shows the results
obtained after six reuse cycles. As can be seen, no significant loss
of activity of the catalyst is observed. ICP analysis shows that freshly
prepared Fe3O4@AEPH2-CuII contains 58 320 ppm, 0.057 g or
0.91 mmol of Cu per 1.000 g of Fe3O4@AEPH2-CuII, while
Fe3O4@AEPH2-CuII after six cycles contains 29 850 ppm, 0.0295 g
or 0.4680 mmol of Cu per 1.000 g of Fe3O4@AEPH2-CuII. In
other words, during the recovery process of the catalyst the
catalytic activity is maintained effectively after six reuses of
Fe3O4@AEPH2-CuII. No significant loss of activity of the catalyst is
observed, in spite of some leaching of CuII during the recovery
process of the catalyst.
To obtain a better idea about the efficiency of the present cata-
lyst in the dehydration of aldoximes to nitriles, the model reaction
was compared with previously reported methods in the literature
(Table 3). As is evident from Table 3, some of the reported methods,
in addition to using expensive, hazardous or corrosive reagents
and tedious work-up procedures, require longer reaction times to
achieve reasonable yields. In comparison, Fe3O4@AEPH2-CuII, as
a new and environmentally benign heterogeneous nanocatalyst,
is an efficient catalyst for the conversion of aldoximes to nitriles
under mild reaction conditions. More importantly, this catalyst
can be easily removed from the reaction mixture using an external
magnet.
Conclusions
In summary, we presented here a simple and effective method for
the synthesis of nitriles from aldoximes using Fe3O4@AEPH2-CuII
as a new, heterogeneous and magnetically reusable catalyst.
Fe3O4@AEPH2-CuII is easily prepared and stable to air. Selective
dehydration of various aldoximes to nitriles can be performed in
the presence of the magnetic and nano-sized heterogeneous
catalyst with excellent catalytic performance. Simple separation of
the magnetic nanocatalyst from the reaction mixture offers easy
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Copyright © 2015 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2015, 29, 683–689

Conversion of aldoximes to nitriles by Fe3O4@AEPH2-CuII
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Acknowledgments
The authors gratefully acknowledge the partial support of this study
by the Ferdowsi University of Mashhad Research Council (grant no.
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Appl. Organometal. Chem. 2015, 29, 683–689
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