Crown ether functionalized magnetic hydroxyapatite as eco-friendly microvessel inorganic-organic hybrid nanocatalyst in nucleophilic substitution reactions: an approach to benzyl thiocyanate, cyanide, azide and acetate derivatives

Article abstract of DOI:10.1002/aoc.4046

In this paper, high catalytic activity of 4′,4″-diformyl dibenzo-18-crown-6 anchored onto the functionalized magnetite hydroxyapatite (γ-Fe₂O₃@HAp–Crown) as a new, versatile and magnetically recoverable catalyst, was prepared. It evaluated as phase-transfer catalyst and molecular host system for nucleophilic substitution reactions of benzyl halides with thiocyanate, cyanide, azide and acetate anions in water. No evidence for the formation of by-products was observed and the products obtained in pure form without further purification. The nanocomposite was easily removed from solution via application of a magnetic field, allowing straightforward recovery and reuse. The synthesized nanocomposite was characterized by several techniques such as FT-IR, TGA-DTG, EDX, XRD, BET, FE-SEM, TEM and VSM.

Full text of DOI:10.1002/aoc.4046

Received: 22 June 2017
DOI: 10.1002/aoc.4046
Revised: 21 July 2017
Accepted: 23 July 2017
F U L L P A P E R
Crown ether functionalized magnetic hydroxyapatite as eco‐
friendly microvessel inorganic‐organic hybrid nanocatalyst
in nucleophilic substitution reactions: an approach to benzyl
thiocyanate, cyanide, azide and acetate derivatives
Maedeh Azaroon1
| Ali Reza Kiasat1,2
1 Chemistry Department, College of
Science, Shahid Chamran University of
Ahvaz, Ahvaz, Iran
2 Petroleum Geology and Geochemistry
Research Centre, (PGGRC), Shahid
Chamran University of Ahvaz, Ahvaz,
Iran
In this paper, high catalytic activity of 4′,4″‐diformyl dibenzo‐18‐crown‐6
anchored onto the functionalized magnetite hydroxyapatite (γ‐Fe2O3@HAp–
Crown) as a new, versatile and magnetically recoverable catalyst, was prepared.
It evaluated as phase‐transfer catalyst and molecular host system for nucleo-
philic substitution reactions of benzyl halides with thiocyanate, cyanide, azide
and acetate anions in water. No evidence for the formation of by‐products
was observed and the products obtained in pure form without further purifica-
tion. The nanocomposite was easily removed from solution via application of a
magnetic field, allowing straightforward recovery and reuse. The synthesized
nanocomposite was characterized by several techniques such as FT‐IR, TGA‐
DTG, EDX, XRD, BET, FE‐SEM, TEM and VSM.
Correspondence
Maedeh Azaroon, Chemistry Department,
College of Science, Shahid Chamran
University of Ahvaz, Ahvaz, Iran.
Email: m‐azaroon@phdstu.scu.ac.ir
KEYWORDS
4′,4″‐diformyl dibenzo‐18‐crown‐6, Fe2O3@HAp‐crown, nucleophilic substitution reaction, phase‐
transfer catalyst
1 | INTRODUCTION
neutral host for charged metal ions in its narrow cavity
and activation of anion species in many circum-
The unique structure and properties of macrocyclic crown
ethers (CEs) have made them a popular choice for a wide
range of investigations and applications over the past few
decades. They play major roles in many disciplines such
as supramolecular chemistry, analytical chemistry, cataly-
sis and phase‐transfer catalysis.[1–4] CEs serve as simple
receptor models and are well‐suited as hosts because of
their conformational flexibility, hydrophilic cavity and
the presence of multiple binding sites that endow them
with a special ability to accommodate many organic com-
pounds by inclusion complexation because they can be
linked both non‐covalently and covalently.[5–7] In addi-
tion, the rather high selectivity of the many interesting
chemical reactions in the presence of crown ethers was
achieved due to their excellent ability as a selective
stances.[8–11]
Nowadays, magnetic nanoparticles have attracted con-
siderable interest due to their easy separation and also
their remarkable physical and chemical properties.[12–15]
To avoid the aggregation of nanoparticles and to improve
their chemical stability, the surface of the nanoparticles
has been coated with different materials, such as silica,
MCM‐41, polymer and hydroxyapatite.[16–23] Among
them hydroxyapatite, a mineral form of calcium apatite,
which is shown by Ca10(PO4)6(OH)2 has several unique
properties such as lower cost of production, availability
and environment friendly nature which can make
hydroxyapatite‐encapsulated magnetic nanocrystallites
an excellent support for the preparation of heterogeneous
catalysts in organic chemistry.[24–38]
Appl Organometal Chem. 2017;e4046.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
1 of 11
https://doi.org/10.1002/aoc.4046

2 of 11
AZAROON AND KIASAT
Crown ethers performing as excellent phase‐transfer
investigated with a vibrating magnetometer (Meghnatis
Daghigh Kavir Co., Kashan, Iran).
catalyst in asymmetric reactions have been reported in
several papers, with high enantioselectivities and yields
observed applying these compounds; in this work,
hydroxyapatite coated uniform γ‐Fe2O3 core‐shell parti-
cles were synthesized and crown ether immobilized on
an insoluble support presents can lead to the formation
of novel nanocomposites, which combines and enhances
the characteristics of the components, such as the elec-
tronic, thermal, and catalytic properties and molecular
recognition of the macrocyclic hosts. With this goal in
mind and in continuation of ongoing research into the
employment of grafted diformyl dibenzo‐18‐crown‐6
ether as a stationary micro‐vessel and heterogeneous
catalyst in organic transformations,herein, we report
our results on the preparation and characterization of
a novel organic–inorganic magnetic nanocomposite,
γ‐Fe2O3@HAp‐Crown, and explored its application in
the nucleophilic substitution reactions as a proficient,
harmless to the environment, recyclable and magnetic
powerful solid catalyst with good stability.
2.2 | Preparation of mesoporous
magnetite–hydroxyapatite nanoparticles
anchored dibenzo‐18‐crown‐6 ether, γ‐
Fe2O3@HAp –crown
2.2.1 | Preparation of aminopropyl conju-
gated mesoporous magnetite–
hydroxyapatite
First, the mixture of FeCl2.4H2O (1.85 mmol) and
FeCl3.6H2O (3.7 mmol) were dissolved in deionized water
(30 ml) under Ar atmosphere at room temperature and
the resulting solution was added to a 25 wt % NH4OH
solution (10 ml) with vigorous mechanical stirring. A
black precipitate of Fe3O4 was produced instantly. In
order to obtain small and uniform Fe3O4 particles, the
drop rate of NH4OH was controlled precisely by a con-
stant dropper and the drop rate was 1 ml min−1. After
15 min, 100 ml of Ca(NO3)2.4H2O (33.7 mmol, 0.5 M)
and (NH4)2HPO4 (20 mmol, 3.0 M) solutions adjusted to
pH 11 were added drop‐wise to the obtained precipitate
over 30 min with mechanical stirring. The resulting milky
solution was heated to 90 °C. After 2 h, the mixture was
cooled to room temperature and aged overnight. The dark
brown precipitate formed was filtered, washed repeatedly
with deionized water until the water was neutral, and
then air‐dried under vacuum at room temperature. The
synthesized sample was calcinated at 300 °C for 3 h, giv-
ing a reddish‐brown powder. Then for the linkage of
aminopropyl unit to the surface of support, 1 g of the
obtained γ‐Fe2O3 coated HAp, γ‐Fe2O3@HAP, was dis-
persed in anhydrous toluene (100 ml), with
ultrasonication for 15 min and 3‐aminopropyl
trimthoxysilane (10 mmol) was added. The mixture was
heated under reflux conditions for 24 h under Argon
protection. The suspended substance was collected by a
magnet and rinsed thoroughly with toluene, and dried
under vacuum to give pure 3‐aminopropyl‐modified
magnetite–hydroxyapatite, γ‐Fe2O3@HAP‐NH2.
2 | EXPERIMENTAL
2.1 | General remarks
Iron (II) chloride tetrahydrate (99%), iron (III) chloride
hexahydrate (98%), 3,4‐Dihydroxy benzaldehyde, benzyl
halides, and other chemicals were purchased from Fluka
and Merck companies and used without further purifica-
tion. NMR spectra were recorded in CDCl3 on a
Bruker Advance DPX 400 MHz instrument spectrometer
using TMS as internal standard The purity determination
of the products and reaction monitoring were accom-
plished by TLC on silica gel. Products were characterized
by comparison of their physical and spectral data
(1H NMR, 13C NMR and FT‐IR spectra) with those
reported in the literature.
The surface area and pore size distribution of the sup-
port was measured by the nitrogen adsorption–desorption
method (Belsorp mini II). FT‐IR (Fourier transform
infrared) spectra were recorded on a Perkin‐Elmer
(IL74XB3GV5) spectrometer. X‐ray diffraction (XRD)
patterns of catalyst were taken on Philips X‐ray diffraction
model Research (PANalytical Company). The field emis-
sion scanning electron micrograph (FE‐SEM) was
obtained by FE‐SEM instrumentation (MIRA3TESCAN‐
XMU). Energy‐Dispersive X‐ray spectroscopy (EDX)
analysis was obtained by MIRA3TESCAN‐XMU instru-
ment. Transmission electron microscope (TEM) images
were obtained using Zeiss – EM10C –80 kV instrument.
The TGA curve was recorded on a PC Luxx 409 at heating
rates of 10 °C min−1. The magnetic properties were
2.2.2 | Synthesis of 4′,4″‐diformyl dibenzo‐
18‐crown‐6 ether
Diethylene glycol ditosylate, DEDT, was firstly synthe-
sized and used as precursor for the synthesis of benzo
crown ether according to Pederson's method with suitable
adaptation[39,40]; Briefly for the preparation of DEDT[41]
;
diethylene glycol (14.86 g, 140 mmol) was dissolved in
THF (80 ml). Meanwhile, an aqueous solution of sodium
hydroxide (16 g, 400 mmol) in water (80 ml) was

AZAROON AND KIASAT
3 of 11
prepared. Two solutions were mixed and cooled on ice
bath with magnetic stirring. To the above mixture was
added drop wise tosyl chloride (48.6 g, 260 mmol) in
THF (80 ml) over 2 h with continuous stirring and cooling
of mixture below 5 °C. The solution was stirred at 0–5 °C
for additional 2 h, after this, the mixture was poured into
ice‐water (250 ml). The DEDT product was filtered,
washed with distilled water, dried and recrystallized
twice from methanol to give a pure product in 80%
isolated yield.
Then for the synthesis of 4′,4″‐diformyl dibenzo‐18‐
crown‐6 ether, DFBCE, a mixture of 3,4‐dihydroxy benz-
aldehyde (8.28 g, 60 mmol), and sodium hydroxide pellets
(2.44 g, 60 mmol) in 1‐butanol (40 ml) was refluxed under
argon for 30 min to ensure complete dissolution of
sodium hydroxide. A solution of DEDT (12.36 g, 30 mmol)
in 1‐butanol (20 ml) was added slowly over 1 h, and the
mixture was refluxed for 1 h. The temperature was
lowered to 90 °C and sodium hydroxide pellets (2.44 g)
was added. Refluxing was continued for 30 min and
DEDT (12.36 g, 30 mmol) in 1‐butanol (20 ml) was added
slowly over 1 h. Refluxing was continued for 16 h. Con-
centrated hydrochloric acid (1 ml) was slowly added,
and then 1/3 of solvent was rapidly removed by distilla-
tion. The distillation was continued but the volume in
the flask was kept constant by the steady addition
of water until the vapor temperature reached 100 °C.
The mixture was filtered, washed with 200 mL of
water, and sucked dry. The DFBCE product was
dispersed in 200 ml of acetone, stirred for 30 min,
filtered, washed with 50 ml of acetone, and dried in an
oven at 100 °C.
2.2.4 | General procedure for the nucleo-
philic substitution reaction catalyzed by
Fe2O3@HAp‐crown nanocomposite in
water
In a typical experiment, to a mixture of the benzyl halide
(1.0 mmol) and NaY (Y: SCN, N3, OAc, CN) (2 mmol) in
water (5 ml), Fe2O3@HAp‐Crown (0.08 g) was added
and heated under stirring condition at 80 °C for the time
specified in Table 3. After complete consumption of
starting material as judged by TLC (n‐hexane–ethyl ace-
tate), the catalyst was separated on the sidewall of the
reaction vessel using an external magnet, the aqueous
phase was separated by decantation and extracted with
diethyl ether (3 × 5 ml). After extraction, the organic layer
was dried with CaCl2 and evaporated in vacuum to give
corresponding product in 75–95% yields. The residual cat-
alyst in the reaction vessel was washed and dried and then
subjected to the next run directly.
3 | RESULTS AND DISCUSSION
Dibenzo‐18‐crown‐6‐ether
supported
on
HAp‐
encapsulated‐γ‐Fe2O3, Fe2O3@HAp‐Crown, was synthe-
sized according to the procedure shown in Scheme 1 and 2.
Maghemite‐nanoparticles are commonly synthesized by
coprecipitation of ferrous and ferric ions in a basic aqueous
solution followed by thermal treatment. Because of the
sensitivity of the γ‐Fe2O3, its surface was first coated with
hydroxyapatite. For grafting dibenzo‐18‐crown‐6‐ether
moieties onto the surface of the γ‐Fe2O3@HAp, the
aminopropyl groups were preliminarily bonded onto the
surface of magnetic hydroxyapatite. After that, the
dibenzo‐18‐crown‐6‐ether was covalently grafted onto the
surface of the core/shell magnetic nanostructure by simple
condensation reaction (Scheme 1 and 2).
2.2.3 | Preparation of magnetite–hydroxy-
apatite anchored dibenzo‐18‐crown‐6 ether
DFBCE (0.624 g, 1.5 mmol) was dissolved in CHCl3(50 ml)
and refluxed to complete dissolving of crown ether. γ‐
Fe2O3@HAP‐NH2 (1 g) was added to the mixture and
refluxed for 24 h. The precipitate, γ‐Fe2O3@HAp –Crown,
was washed and redispersed with deionized water and
ethanol several times. The particles were finally collected
using a magnet and dried at 50–60 °C for 12 h.
To characterize the nanocomposite, and to confirm the
immobilization of the active components on the pore
surface of magnetite–hydroxyapatite, Fourier transform
infrared spectroscopy (FT‐IR) was utilized. Figure 1a‐d
shows the FT‐IR spectra of the Fe2O3@HAp (a),
Fe2O3@HA‐NH2 (b), Fe2O3@HAp‐Crown (c) and DFBCE
(d), respectively. According to the spectra, characteristic
SCHEME 1 Synthetic procedure of
4′,4″‐diformyl dibenzo‐18‐crown‐6

4 of 11
AZAROON AND KIASAT
SCHEME 2 Synthetic route for
preparation of γ‐Fe2O3@HAp‐Cown
FIGURE 1 The FT‐IR spectra of (a) γ‐
Fe2O3@HAp, (b) γ‐Fe2O3@HAp‐NH2, (c)
γ‐Fe2O3@HAp‐crown and (d) DFBCE
absorption bands due to the bending vibration mode of ‐O–
P–O surface phosphate groups in the Hydroxyapatite were
observed at 566 and 603 cm−1 which overlap with Fe–O
bonds stretching, the adsorption band at 1035 cm−1 can be
attributed to the stretching of the P–O bond (Figure 1a‐c).
The peaks at 3571 and 632 cm−1 are due to OH− ions. The
broad Bands in 3420 cm−1 and around 1639 cm−1arise from
Fe2O3@HAp‐Crown with little shift (Figure 1c). The peak
at 1688 cm−1 was assigned to imin band in γ‐Fe2O3@HAp‐
Crown, show DFBCE was covalently grafted onto the
surface of Fe2O3@HAp‐NH2 (Figure 1d). The result pro-
vides direct evidence that the conjugation occurs.
Thermo‐gravimetric analysis‐ Derivative thermo‐
gravimetric Analysis (TGA‐DTG) is a useful method for
the determination of the presence or absence of residual
components of the catalysts. It is based on the observation
of the mass loss of individual components. The stability of
γ‐Fe2O3@HAp‐Crown was examined by TGA‐DTG were
shown in Figure 2.
water, the 1415 cm−1 peak are from CO3 ions. For
2−
Fe2O3@HAp‐NH2 (Figure 1b), peaks at 2930 cm−1 and
1631 cm−1 were assigned to stretching vibration of C‐H
bonds of the propyl‐amine groups and ‐NH stretching
vibrations. The spectrum of DFBCE (Figure 1d) displayed
characteristic peaks at 1270 cm−1, 1513 cm−1 and
1587 cm−1 were also observed in spectrum of γ‐
The curves show that three distinct steps of weight loss
in the combined TGA‐DTG curves. The first weight loss of

AZAROON AND KIASAT
5 of 11
FIGURE 2 A typical TGA curve of γ‐
Fe2O3@HAp‐crown catalyst
0.5% below 200 °C which might be due to the loss of the
adsorbed water as well as dehydration of the surface OH
groups. The second weight loss step of about 30% in the
region of 380–780 °C come from the decomposition of
organic substances in Fe2O3@HAp‐Crown composite.
After that, there was a weight loss from 800 °C to 1000 °C
due to the decomposition of calcium carbonate to calcium
oxide which verified the presence of hydroxyapatite.
γ‐Fe2O3@HAp and γ‐Fe2O3@HAp‐Crown nanocom-
posite were subject to further structural characterization
with Energy Dispersive X‐ray spectroscopy (EDX) spec-
trum (Figure 3). As clearly observed, in addition of Ca,
P, O and Fe elements, which are present in the magne-
tite–hydroxyapatite (Figure 3a), presence of C, N and Si
are indicated on the γ‐Fe2O3@HAp‐Crown (Figure 3b).
The results proved that DFBCE were successfully grafted
onto the surface of γ‐Fe2O3@HAp.
Typical X‐ray diffraction (XRD) patterns of the γ‐
Fe2O3@HAp‐Crown catalyst are shown Figure 4 The
peaks at 2θ = 35.7°, 43.6°, 53.3°, 57.1° and 63.1° are attrib-
uted to γ‐Fe2O3 (marked ), in agreement with the stan-
dard reflection peaks (JCPOS card 25–1402),
Hydroxyapatite also shows typical diffraction peaks,
(marked O), at 2θ = 25.7°, 31.8°, 32.9°, 34.1°, 39.8°,
46.8°, and 49.4° (PDF‐2‐no. [084–1998] (ICDD)).[27] The
functionalization process on the surface of γ‐Fe2O3@HAp
to produce γ‐Fe2O3@HAp‐Crown nanocomposite have no
obvious effect on the formation of well crystallized solid
with sharp and strong peaks. This result indicates that
supporting of DFBCE on γ‐Fe2O3@HAp does not change
the support structure.
FIGURE
Fe2O3@HAp‐crown(b)
3
EDX spectrum of γ‐Fe2O3@HAp(a) and γ‐
distributions of γ‐Fe2O3@HAp and γ‐Fe2O3@HAp‐Crown
samples which exhibit a type IV curve with a hysteresis
loop. Type IV isotherms correspond to a mesoporous
material. According to the report in Table 1 about
Brunauer–Emmett–Teller (BET) surface area, pore
Figure 5 represent the low temperature nitrogen
adsorption–desorption isotherms and pore size

6 of 11
AZAROON AND KIASAT
FIGURE 4 XRD patterns of γ‐
Fe2O3@HAp and γ‐Fe2O3@HAp‐crown
FIGURE 5 Nitrogen adsorption/desorption isotherms (left) and pore size distributions curves (right) of γ‐Fe2O3@HAp and γ‐Fe2O3@HAp‐
crown
TABLE 1 Comparison of the textural properties of γ‐Fe2O3@HAp and γ‐Fe2O3@HAp‐crown
Samples
BET surface area [m2/g]
Pore volume [cm3/g]
Pore size [nm]
γ‐Fe2O3@HAp
143.97
0.57
15.98
γ‐Fe2O3@HAp‐crown
113.53
0.20
7.22
volume and pore size of Fe2O3@HAp (BET: 143.97 m2/g,
pore volume: 0.57 cm3/g and pore size: 15.98 nm),
decrease in these values after loading crown ethers on
Fe2O3@HAp is due to this fact that the crown ethers
unites were deposited inside the cavities and dispersed
on the surface of magnetite–hydroxyapatite.
The morphology and size details were investigated by
field emission scanning electron microscopy (FE‐SEM)
measurement. The FE‐SEM images of the γ‐Fe2O3@HAp
and γ‐Fe2O3@HAp‐Crown are presented in Figure 6,
clearly shown that the particles have nano size range and
their morphology has a round shape. As shown in
Figure 6, grafting DFBCE onto the hydroxyapatite shell
did not lead to the significant change in the structure and
morphology of nanoparticles, indicating that the magnetic
core remained intact during the immobilization and
functionalization process on the surface of nanocomposite.
The transmission electron microscopy (TEM) images
of the as‐prepared Fe2O3@HAp‐Crown (Figure 7) was
clearly shown that the γ‐Fe2O3@HAp‐Crown has a spher-
ical‐shaped morphology with slight aggregation. The
images indicate that γ‐Fe2O3 (dark spots) was encapsu-
lated by Hap, and particles exhibit a size distribution of
25–30 nm, similar to the sizes obtained from the FE‐
SEM measurements.
Magnetic properties of γ‐Fe2O3@HAp, γ‐Fe2O3@HAp‐
Crown and Fe3O4 were investigated using a vibrating
sample magnetometer (VSM) with a field of −10000 Oe

AZAROON AND KIASAT
7 of 11
FIGURE 7 TEM image of γ‐Fe2O3@HAp‐crown
FIGURE 6 FE‐SEM images of γ‐Fe2O3@HAp (a), γ‐Fe2O3@HAp‐
crown (b)
to 10000 Oe at room temperature. As shown in Figure 8,
the M(H) hysteresis loop for the three samples was
completely
reversible,
which
indicated
their
superparamagnetic characteristics. The catalysts γ‐
Fe2O3@HAp and γ‐Fe2O3@HAp‐Crown demonstrated
saturation magnetization values of 8.13 emu. g−1 and
5.56 emu. g−1, respectively, while the Fe3O4 nanoparticle
had the value of 54.94 emu. g−1. The reason may be
FIGURE 8 Hysteresis loops of Fe3O4 (a), γ‐Fe2O3@HAp (b) and
γ‐Fe2O3@HAp‐crown (c)

8 of 11
AZAROON AND KIASAT
attributed to the grafting of DFBCE over γ‐Fe2O3@HAp.
However, the lower value of Figure 8b and Figure 8c is
still enough to ensure the readily recovery of the catalysts
from reaction mixture using external magnetic force.
In order to investigate the possible catalytic properties
of the γ‐Fe2O3@HAp‐Crown nanocatalyst in the nucleo-
philic substitution reaction, the reaction of benzyl halides
with thiocyanate anion in water was investigated. Ini-
tially, the mixture of benzyl bromide and NaSCN in water
was chosen as model reaction to determine whether the
use of phase transfer catalyst was efficient and to investi-
gate the optimized reaction conditions (Table 2).
Fe2O3@HAp‐Crown (0.08 g) in water under thermal con-
ditions (80 °C), is the best conditions and after stirring for
5 min, the corresponding thiocyanohydrine was obtained
in high isolated yield. The collected data for the nucleo-
philic substitution of thiocyanate anion with various
benzyl halides under optimized reaction conditions were
shown in Table 3.
This catalyst acted very efficiently and, in all cases, a
clean reaction was observed. It is noteworthy that no evi-
dence for the formation of by‐products such as alcohols or
isothiocyanates was observed and the products were
obtained in pure form without further purification. 13C
resonance of the −SCN and −NCS groups at ~111 and
~145 ppm, respectively, are very characteristic for thiocy-
anate and isothiocyanate functionalities.[42] The struc-
tures of all of the benzyl thiocyanate and thiocyanate
products were determined from their analytical and spec-
tral (IR, 1H and 13C NMR) data and by direct comparison
with authentic samples.
After several set of tests, it was found that the use of 2
equiv. of SCN per benzyl bromide in the presence of the γ‐
TABLE 2 Optimization of the amount of the γ‐Fe2O3@HAp‐
crown nanocomposite in the proposed reaction
Entry
Catalyst (g)
Time (min)
Yield (%)
1
‐
360
Trace
1HNMR spectra of the crude products clearly showed
the formation of thiocyanate and no evidence for the
hydrolysis of benzyl halides to the alcohols was observed,
which proved that the reactions proceeded cleanly. On the
2
4
5
0.05
0.08
0.1
30
5
60
95
95
5
TABLE 3 Nucleophilic substitution reaction of benzyl halides with different anions in water catalyzed by γ‐Fe2O3@HAp‐crown
Entry
Benzyl halide
Product
Nucleophile (Y)
Time (min)
Yield (%)a
1
SCN
N3
CN
5
92
90
88
80
10
30
55
OAc
2
3
4
5
6
SCN
N3
CN
5
87
85
80
76
15
30
50
OAc
SCN
N3
CN
80
90
85
120
85
85
82
73
OAc
SCN
N3
CN
45
60
80
130
78
75
72
68
OAc
SCN
N3
CN
15
20
30
50
80
82
78
70
OAc
SCN
N3
CN
40
50
40
90
82
85
80
78
OAc
aAll the reactions are carried out under refluxed using 1 mmol of benzyl halide, 2 mmol of different anions, 5 mL of H2O, 0.08 g of γ‐Fe2O3@HAp‐Crown.

AZAROON AND KIASAT
9 of 11
other hand, in the absence of γ‐Fe2O3@HAp‐Crown, the
reaction was sluggish and even after prolonged reaction
reaction, the product was extracted by diethyl ether and
so the remained mixture containing 1 mmol of NaSCN
and catalyst was reused for another run by adding 1 mmol
of NaSCN and benzyl bromide (1 mmol).
The reusability of catalysts is one of the most
important benefits of heterogeneous catalytic systems
time,
a considerable amount of starting material
remained. It is due to this fact that the cavity size of
dibenzo‐18‐crown‐6 conforming to the Na+ size, therefore
the nucleophilicity of SCN− anion was improved and so
the reaction time reduced (Scheme 3).
With these promising results in hand and establishing
the advantages of γ‐Fe2O3@HAp‐Crown as nanomagnetic
phase‐transfer catalyst and molecular host system, we
focused our attention on another nucleophilic substitu-
tion reaction. The conversion of various benzyl halides
with electron‐withdrawing and electron‐donating groups
to the corresponding benzyl thiocyanates, cyanides,
azides and acetates were also investigated and the results
were shown in Table 3, which indicate that the desired
products were formed in high yields and no side products
were observed.
The most ideal synthetic methodology could be defined
as a system wherein 100% atom economy as preserved, the
catalyst is recycled, and excess of reagent remains through-
out in the medium and does not lose activity for several
runs. As shown in Scheme 4, after completion of the
FIGURE 9 Recyclability of catalyst
SCHEME 3 Operation of catalyst in
presence of nucleophile salt
SCHEME 4 Facile nucleophilic
substitution reaction of benzyl bromide in
the atom economical method

10 of 11
AZAROON AND KIASAT
TABLE 4 A comparisons of the results of the present system with the some recently reported procedures
Substrate/
Time Yield
Entry nucleophile
Catalyst and conditions
(h)
(%)
Ref.
[43]
−
−
1
2
3
4
Benzyl bromide/N3
Tetramethylammonium bromide pillared clays/petroleum ether water/100 °C
6
84
[44]
[45]
[46]
Benzyl bromide/N3
Surfactant pillared clay materials and sonochemistry/hexane–water/5 °C
2.5
1
87
80
88
Benzyl bromide/SCN− Tetramethylammonium bromide/water/40 °C
Benzyl chloride/CN−
Poly [N‐(2‐aminoethyl) acrylamido] trimethyl ammonium chloride/water/
6.5
100 °C
[11]
[4]
5
Benzyl chloride/CN−
Ph3P. Pd(OAc)2/K4[Fe(CN)6], Na2CO3/140 °C
10
1
87
98
6
Benzyl bromide/SCN− n‐Bu4NF‐TMSNCS/THF/r.t.
Benzyl bromide/SCN− MNPs‐β CD/water/90 °C
Benzylbromide/SCN− Fe3O4@SiO2/DABCO/100 °C
Benzyl bromide/SCN− β‐CDPU‐MNPs/water/100 °C
Benzyl bromide/SCN− γ‐Fe2O3@HAp‐crown/80 °C
[17]
[47]
[42]
7
0.25 94
91
8
1
9
0.08 89
0.08 90
10
This work
from economic, and environmentally point of view. The
recyclability of nanocatalyst was investigated for the
nucleophilic substitution reaction between benzyl
bromide with thiocyanate anion by carrying out four con-
secutive cycles using the same reaction conditions. After
each run, the catalyst was recovered without filtration
since the γ‐Fe2O3@HAp‐Crown was rapidly concentrated
as soon as an external magnet was set close to the sidewall
of the reaction vessel, then washed with Et2O (5 ml) and
n‐hexane (5 ml). The solid catalyst dried under vacuum
after each cycle, and then reused for the next reaction
(Figure 9).
cyanides and acetates in water by nucleophilic substitu-
tion reactions.
ACKNOWLEDGEMENTS
This work was supported by the Research Council at the
Shahid Chamran University of Ahvaz.
ORCID
Maedeh Azaroon http://orcid.org/0000-0002-6867-3418
To demonstrate the superiority of γ‐Fe2O3@HAp‐
Crown over the reported catalysts, the reaction of Benzyl
bromide and nucleophile was considered as a representa-
tive example (Table 4). While in all of these cases,
comparative yields of the desired product were obtained
following the γ‐Fe2O3@HAp‐Crown catalyzed procedure.
These results clearly demonstrate that the nanocomposite
is an equally or more efficient catalyst for this reaction.
REFERENCES
[1] P. L. Sóti, L. Telkes, Z. Rapi, A. Tóth, T. Vigh, Z. K. Nagy, P. Bakó,
G. Marosi, J. Inorg. Organomet. Polym. Mater. 2014, 24, 713.
[2] A. Mishra, N. Mishra, V. K. Tiwari, J. Carbohydr. Chem. 2016,
35, 238.
[3] W. Bin Yi, J. J. Ma, L. Q. Jiang, C. Cai, W. Zhang, J. Fluorine
Chem. 2014, 157, 84.
[4] D. Landini, F. Montanari, F. M. Pirisi, J. Chem. Soc., Chem.
Commun. 1974, 879.
4 | CONCLUSION
[5] B. Gao, S. Wang, Z. Zhang, J. Inclusion Phenom. Macrocyclic
Chem. 2010, 68, 475.
In the present work, the diformyl dibenzo‐18‐crown‐6
ether was successfully grafted on magnetite–hydroxyapa-
tite nanoparticles and its efficiency as solid–liquid
phase‐transfer catalyst for nucleophilic substitution reac-
tions of benzyl halides in water was also investigated.
With the host effects of DFBCE and superparamagnetism
of iron oxide, γ‐Fe2O3@HAp‐Crown is expected to have
higher potential applications in substitution reactions of
benzyl halides. In conclusion, we have developed the easy
way to operate, short reaction times, simplicity in
operation, high catalytic activity, safe and cost‐effective
method for the preparation of benzyl thiocyanates, azides,
[6] G. H. Rounaghi, M. H. Zavar, R. M. Z. Kakhki, Russ. J. Coord.
Chem. 2008, 34, 167.
[7] W. Taleb Bendiab, F. Hamza Reguig, S. Hamad, B. Martínez‐
Haya, A. M. Krallafa, J. Inclusion Phenom. Macrocyclic Chem.
2016, 85, 83.
[8] M. J. Pugia, A. Czech, B. P. Czech, R. A. Bartsch, J. Org. Chem.
1986, 51, 2945.
[9] S. F. Lee, X. M. Zhu, Y. X. J. Wang, S. H. Xuan, Q. You, W. H.
Chan, C. H. Wong, F. Wang, J. C. Yu, C. H. K. Cheng, K. C. F.
Leung, ACS Appl. Mater. Interfaces 2013, 5, 1566.
[10] W. C. Guida, D. J. Mathre, J. Org. Chem. 1980, 45, 3172.

AZAROON AND KIASAT
11 of 11
[11] P. E. Stott, J. S. Bradshaw, W. W. Parish, J. Am. Chem. Soc. 1980,
102, 4810.
[33] J. A. Ramos Guivar, E. A. Sanches, F. Bruns, E. Sadrollahi, M. A.
Morales, E. O. López, F. J. Litterst, Appl. Surf. Sci. 2016, 389, 721.
[12] L. H. Reddy, J. L. Arias, J. Nicolas, P. Couvreur, Chem. Rev.
2012, 112, 5818.
[34] H. Liu, F. Chen, P. Xi, B. Chen, L. Huang, J. Cheng, C. Shao, J.
Wang, D. Bai, Z. Zeng, J. Phys. Chem. C 2011, 115, 18538.
[13] D. Ramimoghadam, S. Bagheri, S. B. Abd Hamid, Colloids Surf.,
B 2014, 133, 388.
[35] N. H. A. Camargo, S. A. de Lima, E. Gemelli, Am. J. Biomed.
Eng. 2012, 2, 41.
[14] R. Mrówczyński, A. Nan, J. Liebscher, RSC Adv. 2014, 4,
[36] M. Sarvestani, R. Azadi, Appl. Organomet. Chem. 2017, https://
5927.
doi.org/10.1002/aoc.3906.
[15] D. Saberi, M. Sheykhan, K. Niknam, A. Heydari, Catal. Sci.
Technol. 2013, 3, 2025.
[37] A. Shaabani, H. Afaridoun, S. Shaabani, Appl. Organomet.
Chem. 2016, 30, 772.
[16] A. R. Kiasat, S. Nazari, J. Inclusion Phenom. Macrocyclic Chem.
2013, 76, 363.
[38] L. Fu, W. Deng, L. Liu, Y. Peng, Appl. Organomet. Chem. 2017,
https://doi.org/10.1002/aoc.3853.
[17] J. Davarpanah, A. R. Kiasat, Catal. Commun. 2013, 42, 98.
[39] C. J. Pedersen, J. Am. Chem. Soc. 1967, 89, 7017.
[40] S. Yousefi, A. R. Kiasat, RSC Adv. 2015, 5, 92387.
[18] G. D. Venkatasubbu, S. Ramasamy, G. S. Avadhani,
V. Ramakrishnan, J. Kumar, Powder Technol. 2013, 235, 437.
[41] M. Ough, Y. Inoue, Y. Liu, S. Nagamune, S. Nakamur, K. Wada,
[19] J. Liu, S. Z. Qiao, Q. H. Hu, G. Q. Lu, Small 2011, 7, 425.
T. Hakushi, Bull. Chem. Soc. Jpn. 1990, 63, 1260.
[20] A. Ying, H. Hou, S. Liu, G. Chen, J. Yang, S. Xu, ACS Sustain.
Chem. Eng. 2016, 4, 625.
[42] A. R. Kiasat, S. Nazari, J. Mol. Catal. A: Chem. 2012, 365, 80.
[43] R. S. Varma, K. P. Naicker, Tetrahedron Lett. 1998, 39, 2915.
[21] M. J. Nasab, A. R. Kiasat, RSC Adv. 2016, 6, 41871.
[44] R. S. Varma, K. P. Naicker, D. Kumar, J. Mol. Catal. A: Chem.
1999, 149, 153.
[22] M. B. Gawande, A. Goswami, T. Asefa, H. Guo, A. V. Biradar,
D.‐L. Peng, R. Zboril, R. S. Varma, Chem. Soc. Rev. 2015,
44, 7540.
[45] A. R. Kiasat, R. Badri, S. Sayyahi, Chinese Chem. Lett. 2008, 19,
1301.
[23] D. Azarifar, M. Ghaemi, Appl. Organomet. Chem. 2017, https://
[46] B. Tamami, S. Ghasemi, J. Iran. Chem. Soc. 2008, 5, S26.
doi.org/10.1002/aoc.3834.
[47] A. R. Kiasat, J. Davarpanah, J. Mol. Catal. A: Chem. 2013, 373, 46.
[24] S. Igder, A. R. Kiasat, M. R. Shushizadeh, Res. Chem. Intermed.
2015, 41, 7227.
SUPPORTING INFORMATION
[25] Z. Zarei, B. Akhlaghinia, RSC Adv. 2016, 6, 106473.
Additional Supporting Information may be found online
in the supporting information tab for this article.
[26] A. Mouradzadegun, L. Ma'mani, M. Mahdavi, Z. Rashid, A.
Foroumadi, S. Dianat, RSC Adv. 2015, 4, 1166.
[27] Z. Zhang, J. Zhen, B. Liu, K. Lv, K. Deng, Green Chem. 2015,
17, 1308.
[28] Y. D. Kwon, D. H. Yang, D. W. Lee, J. Biomed. Nanotechnol.
2015, 11, 1007.
How to cite this article: Azaroon M, Kiasat AR.
Crown ether functionalized magnetic
[29] A. Michelot, S. Sarda, C. Audin, E. Deydier, E. Manoury, R.
hydroxyapatite as eco‐friendly microvessel
inorganic‐organic hybrid nanocatalyst in
nucleophilic substitution reactions: an approach to
benzyl thiocyanate, cyanide, azide and acetate
derivatives. Appl Organometal Chem. 2017;e4046.
https://doi.org/10.1002/aoc.4046
Poli, C. Rey, J. Mater. Sci. 2015, 50, 5746.
[30] C. S. Goonasekera, K. S. Jack, J. J. Cooper‐White, L. Grøndahl,
J. Mater. Chem. B 2013, 1, 5842.
[31] Z. Zhang, Z. Yuan, D. Tang, Y. Ren, K. Lv, B. Liu,
ChemSusChem 2014, 7, 3496.
[32] Y. Zhang, Z. Li, W. Sun, C. Xia, Catal. Commun. 2008,
10, 237.