Sulfamic acid heterogenized on hydroxyapatite-encapsulated γ-Fe 2O3 nanoparticles as a magnetic green interphase catalyst

Article abstract of DOI:10.1016/j.molcata.2010.12.004

A highly efficient and green system is introduced to chemical synthesis. Magnetic nanoparticle-supported propylsulfamic acid deposited onto hydroxyapatite [γ-Fe₂O₃-HAp-(CH₂) ₃-NHSO₃H] synthesized as a

Full text of DOI:10.1016/j.molcata.2010.12.004

Journal of Molecular Catalysis A: Chemical 335 (2011) 253–261
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Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Sulfamic acid heterogenized on hydroxyapatite-encapsulated ␥-Fe2O3
nanoparticles as a magnetic green interphase catalyst
Mehdi Sheykhana, Leila Ma’manib, Ali Ebrahimia, Akbar Heydaria,∗
a Chemistry Department, Tarbiat Modares University, P.O. Box 14155-4838, Tehran, Iran
b Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 October 2010
Received in revised form 6 December 2010
Accepted 8 December 2010
Available online 17 December 2010
A highly efficient and green system is introduced to chemical synthesis. Magnetic nanoparticle-supported
propylsulfamic acid deposited onto hydroxyapatite [␥-Fe2O3-HAp-(CH2)3-NHSO3H] synthesized as a
unique heterogeneous acid catalyst of excellent activity and recyclable for at least 10 reaction runs with-
out significant loss of activity. The facile recovery of the catalyst is carried out by applying an external
magnet device. It is both “green” and efficient. The catalyst was fully characterized by spectroscopic, mag-
netic, adsorptive and thermal techniques (TEM, SEM, FTIR, TGA, XRD, BET, elemental analysis (CHNOS)
and VSM).
Dedicated to memory of Noor Ali
Shooshtari.
© 2010 Elsevier B.V. All rights reserved.
Keywords:
Catalysis
Immobilization
Inorganic–organic hybrid
Magnetic recovery
Sulfamic acid
Magnetic core
1. Introduction
ery of the solid and eventually its reuse. The highest level of
evolution in the surface immobilization strategy is the cova-
Following the successful applications of magnetic nanoparti-
cles in designing of new catalytic supports [1], there is now a
growing interest in the further development of this type of cata-
lyst supports. So, magnetic catalytic systems have been introduced
as vastly powerful and clean recoverable supports for a variety
of catalytic reactions. The use from nano-particles as catalyst has
some problems. One of them is their high active surface which
leads to the agglomeration of the catalyst particles. Coating the
catalyst surface with an organic or an inorganic shell is an appro-
priate strategy to prevent agglomeration [2–7]. Hydroxyapatite
has been demonstrated to be preferable in terms of versatility
in surface modification, thermal and chemical stability and bio-
compatibility as one of the ideal materials for encapsulation of
iron oxide nanoparticles [8,9]. A general trend in catalysis is to
convert a homogeneous catalyst into a heterogeneous catalytic
system [10–22]. The immobilization of homogeneous catalysts
on solid supports opens up new avenues for design and engi-
neering of new and stimulating catalysts. These structures are
easily separable from the reaction mixture, allowing the recov-
lent attachment of the organic compound or ligand to the solid
surface [23]. While immobilizing a homogeneous catalyst on a
surface, diffusion of the reactants to the catalyst site may take
place with difficulty [24], resulting in decreased catalytic activ-
ity. To overcome this problem and enhance the availability of the
active catalyst sites, materials with porous structures such as zeo-
lites have been utilized [25–29] or by other procedures, smaller
sized particles of catalyst were produced [3]. The incorporation
of organic moieties with pendant attached chains, either on the
external part or on the internal surface, is an applicable modi-
fying manner to change the physical and chemical properties of
natural or synthesized materials. It can improve the ability of the
new multifunctional materials – considered as “inorganic–organic
hybrids” – to act in a variety of academic or technological activ-
ities [30]. An obvious advantage of such hybrids is the favorable
combination of both organic and inorganic properties in one nano-
material [31]. The inorganic–organic hybrids can combine the novel
inorganic properties like mechanical, thermal or structural sta-
bility as well as the organic features such as tendency toward
water, leakage from water, reactivity and also can be modified of
bulk characteristics such as mechanical and optical properties (by
the designing different organo-functionalization onto the surface)
[32].
∗
Corresponding author. Tel.: +98 21 82883444; fax: +98 21 82883455.
E-mail address: akbar.heydari@gmx.de (A. Heydari).
1381-1169/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.molcata.2010.12.004

254
M. Sheykhan et al. / Journal of Molecular Catalysis A: Chemical 335 (2011) 253–261
With respect to their high selectivity, resulting from the
were estimated by assuming two hydroxyl groups per formula
of phosphate. The mixture was refluxed under Ar atmosphere at
100 ◦C for 48 h. The product was separated by filtration, washed
with ethanol, and dried under vacuum for 24 h at 50 ◦C after soxh-
let extraction by hot ethanol to give the solid surface bonded amine
group at a loading 0.75 mmol g−1 (calculated by the back-titration
analysis).
extended surface, the usage of catalysts supported on nano struc-
tural has been increasing [33]. The extended surface (caused by the
nanosized structure) also improves the loading of the catalyst dur-
ing immobilization process [34]. In other words, as the particle size
decreases filtration becomes increasingly more difficult. Therefore,
despite many advantages, catalyst recovery remains as challenge.
Thus some of the drawbacks of the traditional procedures are the
tedious recycling via lengthy filtration and the inevitable loss of
solid catalyst during the separation process [35–37]. Receive to the
green aspect requires the use of a more effective recovery method
for these types of catalysts.
Among various magnetic nanoparticles, ␥-Fe2O3 (maghemite),
owing to its good thermal and chemical stability coated with
hydroxyapatite, has been considered as an ideal candidate. It
has a high surface area, surface modification ability, easily syn-
thesized, low toxicity and an important biocompatible inorganic
catalyst support [38]. Hydroxyapatite-encapsulated magnetic ␥-
Fe2O3 [␥-Fe2O3@HAp] nanocrystallities have been recently used
as a high-performance heterogeneous catalytic supports [33]. On
the basis of the above considerations, we report our efforts to
immobilizing the n-propyl sulfamic acid onto hydroxyapatite-
encapsulated superparamagnetic ␥-Fe2O3 nanoparticles, affording
high catalytic activity and excellent durability that can be reused
properly by external magnet for at least 10 times.
2.3. Synthesis of n-propylsulfamic acid supported on
HAp-encapsulated-ꢀ-Fe2O3 [ꢀ-Fe2O3@HAp-Si-(CH2)3-NHSO3H]
The [␥-Fe2O3@HAp-Si-(CH2)3-NH2] (0.75 mmol g−1, 10 g) was
allowed to react with chlorosulfonic acid (ClSO3H) (8.6 mmol, 1 g)
at r.t over 30 min. The mixture was mechanically stirred vigorously
for 6 h until HCl gas evolution was stopped. The resulted mag-
netic nanoparticles were separated by an external magnet device
and were washed with hot ethanol and deionized water until neu-
tral to remove the unreacted chlorosulfonic acid. It washed twice
with diethyl ether (100 mL) and then dried under vacuum at r.t
to give the corresponding solid surface bonded n-propylsulfamic
acid group (Scheme 1) at a loading 0.7 mmol g−1 (calculated by
TGA, back-titration and ion exchange pH analysis). To ensure that
no dissolution happened under reaction conditions, the ratio of
Fe2O3/HAp (w/w) in Fe2O3@HAp was determined based on Fe/Ca
(w/w) ratio using energy dispersive X-ray spectroscopy analysis,
equal to 0.46. The ratio did not have change before and after react-
ing with chlorosulfonic acid because the reaction done in room
temperature and also with short time.
2. Experimental
2.1. Synthesis of nano HAp-encapsulated-ꢀ-Fe2O3
[ꢀ-Fe2O3@HAp]
2.4. pH analysis of [ꢀ-Fe2O3@HAp-Si-(CH2)3NHSO3H]
To an aqueous solution of NaCl (1 M, 25 mL) with an initial
pH = 5.93, the ␥-Fe2O3@HAp-Si (CH2)3NHSO3H (50 mg) was added
and the resulting mixture stirred for 3 h after which the pH of
solution decreased to 2.85. This result confirmed by back-titration
analysis of the catalyst: To this analysis we added 10 mL of a stan-
dard 0.1 M sodium hydroxide solution to 100 mg of the synthesized
catalyst in a 50 mL Erlenmeyer flask. Excess amount of the base
was neutralized by addition of a standard 0.1 M HCl solution to the
equivalence point of titration. The required volume of HCl to this
Preparation of HAp-encapsulated ␥-Fe2O3 was carried out
according to the previously reported method [39–41]. A mixture
of FeCl2·4H2O (368 mg, 1.85 mmol) and FeCl3·6H2O (1 g, 3.7 mmol)
were dissolved in 30 mL deionized water (DW) under Ar atmo-
sphere at r.t, then a 25% NH4OH solution (10 mL) was added to
the resulting solution with vigorous mechanical stirring (700 rpm).
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 constant dropper, and the drop rate
was 1 mL/min. After 15 min, 100 mL of Ca(NO3)2·4H2O (7.95 g,
33.7 mmol) and (NH4)2HPO4 (2.64 g, 20 mmol) solutions adjusted
to pH = 11 were added drop-wise to the obtained precipitate over
30 min with mechanical stirring. The resultant milky solution was
heated to 90 ◦C. After 2 h, the mixture was cooled up to r.t and aged
overnight. The dark brown precipitate formed was filtered, washed
repeatedly with DW until neutral, and air dried under vacuum at r.t.
The as-synthesized sample was calcined at 300 ◦C for 3 h, resulted
in a reddish-brown powder (␥-Fe2O3@HAp).
point was 9.3 mL. This is equal to a loading 0.7 mmol NHSO3H g−1
.
2.5. Elemental analysis of [ꢀ-Fe2O3@HAp-Si-(CH2)3NHSO3H]
For confirmation of catalyst loading obtained from several above
methods, elemental analysis was carried out using a Vario EL-III
CHNOS elemental analyzer. Characterization of new magnetic cata-
lyst showed 3.65% C and 2.36% S (= 0.76 mmol NHSO3H g−1). Results
confirmed other data.
2.2. Synthesis of n-propylamine covalently supported on
2.6. General procedure for one-pot synthesis of quinolines
HAp-encapsulated-ꢀ-Fe2O3 [ꢀ-Fe2O3@HAp-Si-(CH2)3-NH2]
␥-Fe2O3@HAp-Si-(CH2)3NHSO3H (10 mg, 0.7 mol%) was added
to a mixture of a 2-aminoaryl ketone (1 mmol) and a ketone hav-
ing ␣-methylene group (1.2 mmol) and allowed to stirred at r.t
(Scheme 2). The progress was monitored by TLC (see Table 1). The
catalyst separated by a magnet device, washed with diethyl ether
and dried to reuse in the next run. All isolated products gave sat-
A
sample of magnetic hydroxyapatite (500 mg) was pre-
activated by heating under vacuum for 48 h at 120 ◦C and
suspended in mixture of 150 mL of dry toluene con-
taining stoichiometric amount (92 mg, 0.5 mmol) of 3-
aminopropyltrimethoxysilane. The used amounts of this agent
a
a
Scheme 1. Preparation of the ␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H.

M. Sheykhan et al. / Journal of Molecular Catalysis A: Chemical 335 (2011) 253–261
255
Table 1
Catalyzed Friedlander reaction of 2-aminoaryl ketones with ketones.
c
Entry
R1/R2
R3/R4
Product 3
Time (h)
Yielda (%)
TONb
132.8
TOF (h−1
)
CH3
CO2Et
CH3
a
–H/–CH3
–CH3/–CO2Et
3
93
44.3
N
CH3
O
b
c
d
e
f
–H/–CH3
–H/–CH3
–H/–C6H5
–H/–C6H5
–H/–C6H5
–H/–C6H5
–CH3/–COCH3
–CH2(CH2)2CO–
–CH3/–CO2Et
–CH3/–CO2Me
–CH3/–CO2tBu
–CH3/–COCH3
3
95
96
94
95
93
91
135.7
137.1
134.3
135.7
132.8
130
45.2
91.4
44.8
45.2
44.3
37.1
N
CH3
CH3
O
1.5
N
Ph
CO2Et
CH3
3
N
Ph
CO2Me
CH3
3
N
Ph
t
CO2 Bu
3
N
CH3
O
Ph
g
3.5
N
CH3
O
Ph
h
–H/–C6H5
–H/–C6H5
–H/–C6H5
–H/–C6H5
–CH2(CH2)2CO–
–CH2C(CH3)2CH2CO–
–(CH2)4–
3
3
3
3
93
93
96
95
132.8
132.8
137.1
135.7
44.3
44.3
45.7
45.2
N
Ph
O
i
N
Ph
j
N
Ph
k
–(CH2)3–
N

256
M. Sheykhan et al. / Journal of Molecular Catalysis A: Chemical 335 (2011) 253–261
Table 1 (Continued)
c
Entry
R1/R2
R3/R4
Product 3
Time (h)
1.5
Yielda (%)
TONb
138.6
TOF (h−1
)
Ph
N
Cl
CO2Et
CH3
l
–Cl/–C6H5
–CH3/–CO2Et
97
92.4
Ph
Cl
CO2Me
CH3
m
–Cl/–C6H5
–CH3/–CO2Me
1.5
97
138.6
92.4
N
Reaction conditions: 2-aminoaryl ketone (1 mmol), carbonyl compound (1.1 mmol), ␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H (10 mg, 0.7 mol%); quenched after mentioned times.
For entry (a) the catalyst was recycled and used for 10 cycles (each of them 2 h) with conversion of >85% in all the cycles.
a
The yields refer to pure isolated products characterized by spectral data.
Turnover number (average number of product molecules produced per mole of the catalyst).
Turnover frequency (turnover number per time).
b
c
R2
R2
R1
O
R1
R4
R3
O
cat.(0.7 mol%)
neat, r.t.
R4
+
R3
N
NH2
1
2
3
Scheme 2. ␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H catalyzed Friedlander reaction.
Table 2
3. Results and discussion
Friedlander annulation of 2-amino acetophenone and ethylacetoacetate with differ-
ent catalysts. Reaction conditions: free solvent, r.t, 0.7 mol% catalyst quenched after
3 h.
Magnetic sulfamic acid heterogenized on hydroxyapatite-
encapsulated ␥-Fe2O3 was synthesized according to the procedure
shown in Scheme 1. ␥-Fe2O3 nanocrystallities are commonly syn-
Entry
Catalyst
Yield
thesized by coprecipitation of ferrous (Fe+2) and ferric (Fe+3
)
1
2
3
4
5
No catalyst
␥-Fe2O3@HAp
␥-Fe2O3@HAp-SO3H
Homogeneous sulfamic acid
␥-Fe2O3@HAp-Si-(CH2)3NHSO3H
N.R.
N.R.
57%
17%
93%
ions in a basic aqueous solution followed by thermal treat-
ment. We employed the coprecipitation approach because basic
aqueous media permit subsequent crystallization of the hydrox-
yapatite phase and lead to coating of the ␥-Fe2O3 nanoparticles
by hydroxyapatite (␥-Fe2O3@HAp). The nanocrystallites of ␥-
Fe2O3@HAp were reacted with 3-aminopropyltrimethoxysilane
to produce an organic–inorganic hybrid. Then, this synthe-
sized hybrid was affected by chlorosulfonic acid. After 6 h
the brown powder washed by deionized water and diethyl
ether and dried under vacuum which led to the formation
of the n-propylsulfamic acid moiety functionalized core–shell
catalyst (␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H). [␥-Fe2O3@HAp-Si-
(CH2)3-NHSO3H] nanocrystallites were fully characterized by TEM
(Fig. 1a and b), SEM (Fig. 1c), TGA (Fig. 1d), FTIR (Fig. 1e), XRD
(Fig. 1f) and ion exchange pH-analysis. Due to the superpara-
magnetic nature of its core, nuclear magnetic resonance (NMR)
technique could not be used to confirm surface modification of the
Si-(CH2)3NHSO3H. Instead, acid-base back titration and FTIR were
used to characterization of the organic functional group. The load-
ing of sulfamic acid moiety on surface was determined by means
of ion-exchange pH-analysis and TGA analysis. In FTIR, charac-
isfactory spectral data (1H NMR and 13C NMR) and compared with
those reported in literature [42].
2.7. General procedure for one-pot synthesis of
˛-aminophosphonate
␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H (10 mg, 0.7 mol%) was added
to a mixture of aldehyde (1.0 mmol) and amine (1.0 mmol) at
r.t (Scheme 3). The mixture was stirred for 10 min and then
dimethylphosphite (1.1 mmol) was added. Reaction proceeds at r.t
and completion of the reaction indicated by TLC. Then the cata-
lyst was separated by an external magnet, washed with diethyl
ether and dried to reuse. The organic phase was evaporated under
reduced pressure and all isolated products gave satisfactory spec-
tral data (1H NMR and 13C NMR) compared with those reported in
literature (Table 3) [43].
NR2R3
O
O
O
cat.(0.7 mol%)
neat, r.t.
R1
P
+
R2R3NH
+
OCH3
OCH3
P
R1
H
H
OCH3
H3CO
4
5
6
7
Scheme 3. One-pot three-component procedure for the synthesis of ˛-aminophosphonates catalyzed by ␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H.

M. Sheykhan et al. / Journal of Molecular Catalysis A: Chemical 335 (2011) 253–261
257
Fig. 1. (a–b) TEM micrograph, (c) SEM image, (d) TGA diagram, (e) FTIR spectrum and (f) XRD spectrum of the ␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H.
teristic absorption bands due to the bending vibration mode of
O–P–O surface phosphate groups in the hydroxyapatite shell were
observed at 567 and 607 cm−1 which were in overlap with Fe–O
stretching. Also the stretching of P–O bond appeared at 1041 cm−1
overlapped with S–O stretching peak. The S O stretching band of
sulfamic group appeared at 1377 cm−1. The stretching and out of
plane bending of acidic O–H group observed at 2700–3500 and
815 cm−1, respectively. ␥-Fe2O3@HAp was subject to the further
structural characterization with XRD, Fig. 1f. Diffraction peaks at
around 18.4◦, 30.2◦, 35.7◦, 43.6◦, 56.2◦ and 63.1◦ corresponding
to the (1 1 1), (2 2 0), (3 1 1), (4 0 0), (4 4 0) and (5 1 1) are readily
recognized from the XRD pattern. The observed diffraction peaks
agree well with that of the tetragonal structure of ␥-Fe2O3 (1999
JCPDS file No. 13-0458). No other phase except the maghemite is
detectable [8]. Both the scanning electron microscopy (SEM) and
TEM showed that the encapsulated nanoparticles were present as
uniform particles and the size of encapsulated nanoparticles was
less than 50 nm. The obtained histogram (Fig. 2) confirmed the fact
that the size of distribution for 75 observed nanoparticles was a
narrow normal one with a 69 nm average value and a 2.1 nm stan-
dard deviation. The theoretical curve of standard distribution from
our studies (Fig. 2) was calculated by means of origin program.
Quantitative determination of the functional group loaded on
the surface of ␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H was performed
utilizing thermo-gravimetric analysis (TGA) and a loading of
0.73 0.01 mmol g−1 was obtained. The analysis showed two

258
M. Sheykhan et al. / Journal of Molecular Catalysis A: Chemical 335 (2011) 253–261
Fig. 2. The histogram of ␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H nanoparticles sizes by means of the SEM image (left) and the isotherm plot of ␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H
(right).
90
80
70
60
50
40
30
20
10
0
Fig. 3. VSM curve of ␥-Fe2O3@HAp (line) and ␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H
1
2
3
4
5
6
7
8
9
10
(dotted line) at r.t.
Run number
Fig. 5. The recycling experiment of catalyst in friedlander reaction for entry a;
carried out at r.t for 3 h.
peaks. First peak appears due to desorption of the water (centered
at 110 ◦C). This is followed by a second peak at 425 ◦C, corre-
sponding to loss of the organic spacer group. These results are in
agreement with those of ion-exchange pH and back-titration anal-
yses.
Nitrogen adsorption–desorption isotherms are shown in Fig. 2
and reveal that the adsorption–desorption process is not reversible.
This is a result of the hysteresis loops due to capillary condensation.
The surface area was calculated using BET method, and a value of
122 m2 g−1 was found for synthetic hydroxyapatite coated mag-
netic nanoparticle (␥-Fe2O3@HAp). This average was reduced to
97 m2 g−1 for n-propyl sulfamic acid functionalized hydroxyapatite
coated magnetic nanoparticle powder (␥-Fe2O3@HAp-Si-(CH2)3-
NHSO3H). The synthetic powder showed a type (IV) nitrogen
adsorption–desorption isotherm (Fig. 2).
the ␥-Fe2O3@HAp and ␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H nanopar-
ticles were done in an applied magnetic field at r.t, with the field
sweeping from −8000 to +8000 Oersted. As shown in Fig. 3, the
M (H) hysteresis loop for the samples was completely reversible,
showing that the nanoparticles exhibit superparamagnetic char-
acteristics. The hysteresis loops of them reached saturation up to
the maximum applied magnetic field. The magnetic saturation val-
ues of the ␥-Fe2O3@HAp and ␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H are
7.24 and 4.49 emu g−1 at r.t, respectively. Lower magnetic satura-
tion of latter nanoparticles can be explained by the influence of
the functional group. Both particles showed high permeability in
magnetization and their magnetization was sufficient for magnetic
separation with a conventional magnet (Fig. 4). The reversibil-
ity in hysteresis loop confirms that no aggregation impose to the
nanoparticles in the magnetic fields.
It is of great importance that the core/shell material should
possess sufficient magnetic and superparamagnetic properties for
its practical applications. Magnetic hysteresis measurements for
Fig. 4. Catalyst ability to effective recovery at the end of reactions.

M. Sheykhan et al. / Journal of Molecular Catalysis A: Chemical 335 (2011) 253–261
259
Catalysis 1: The polysubstituted quinolines are common struc-
tural motifs in a wide range of biologically active compounds
including antimalaria, antitumor and antibacterial agents [44]. The
Friedlander annulation (condensation followed by a cyclodehydra-
tion between 2-aminoaryl ketone and a second carbonyl compound
including a reactive methylene group) has attracted considerable
attention from the view point of combinatorial chemistry [42] and
is one of the simplest and easiest methods for the synthesis of
quinolines skeleton. Generally, this reaction is carried out by reflux-
ing an aqueous or an alcoholic solution of reactants in the presence
of an acid or base at high temperature. However, the classic Fried-
lander reaction or modified procedures have significant downsides
Table 3
Catalyzed ␣-aminophosphonates syntheses.
Entry
Substrate 4
Time (min)
Product 7
Yielda (%)
TON
TOF (h−1
)
H
N
CHO
a
40
95
135.7
203.5
O
P
OMe
MeO
H
N
CHO
Cl
b
60
94
134.3
134.3
O
P
Cl
OMe
MeO
H
N
CHO
c
60
94
134.3
134.3
O
P
OMe
MeO
H
N
d
35
97
138.6
237.6
CHO
O
P
O
O
OMe
MeO
O
N
CHO
e
45
60
94
94
134.3
134.3
179.1
134.3
O
P
OMe
MeO
O
CHO
N
f
O
P
OMe
MeO
O
N
g
35
45
98
94
140
240
O
CHO
O
P
O
OMe
MeO
O
N
CHO
h
134.3
179.1
O
P
OMe
MeO

260
M. Sheykhan et al. / Journal of Molecular Catalysis A: Chemical 335 (2011) 253–261
Table 3 (Continued)
Entry
Substrate 4
Time (min)
Product 7
Yielda (%)
TON
TOF (h−1
)
O
P
CHO
N
i
40
95
135.7
203.5
O
OMe
MeO
Reaction conditions: aldehyde (1 mmol), amine (1 mmol), dimethylphosphite (1.1 mmol), ␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H (10 mg, 0.7 mol%); quenched after mentioned
times. For entry (a) the catalyst was recycled and used for 10 cycles (each of them 1 h) with conversion of >90% in all the cycles.
a
The yields refer to pure isolated products characterized by spectral data.
Table 4
such as low yields, long reaction time, harsh reaction conditions,
The one-pot three-component coupling reaction of benzaldehyde, aniline and
dimethylphosphite in the presence of different catalysts. Reaction conditions: free
solvent, r.t, 0.7 mol% catalyst quenched after 40 min.
difficulties in workup and the use of stoichiometric and/or rel-
atively expensive catalysts. Moreover, the main disadvantage of
almost all existing methods is that the catalysts are destroyed in
Entry
Catalyst
Yield
the workup and cannot be recovered and reused, which do not
conform to environmental standards. Consequently, the develop-
ment of water stable acidic catalysts for quinoline synthesis is
quite desirable. On the basis of the optimal conditions established
(0.7 mol% ␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H, air, r.t), we examined
the reaction of 2-aminoaryl ketones with various ketones in aque-
ous medium. As shown in Scheme 2 the reactions proceed smoothly
and corresponding quinolines could be obtained in high yields.
At the end of the reaction, to determine the applicability of
catalyst recovery, we decanted the vessel by use of an external
magnet and remained catalyst was washed with diethyl ether to
remove residual product, dried under vacuum and reused in a
subsequent reaction. The reaction in entry a resulted in the cor-
responding quinoline 3a in 93% isolated yield. In 10 consecutive
runs, the conversion stayed with no detectable loss, higher than
85%. To contradiction any contribution of homogeneous catalysis,
we tested the reaction leached (after 8 min from the beginning and
removal of catalyst) and observed that the reaction did not com-
plete even after 24 h. This clearly confirmed that no active species
were present in the supernatant.
1
2
3
4
5
No catalyst
ꢀ-Fe2O3@HAp
ꢀ-Fe2O3@HAp-SO3H
Homogeneous sulfamic acid
ꢀ-Fe2O3@HAp-Si-(CH2)3NHSO3H
N.R.
42%
68%
21%
95%
reaction conditions like inert atmosphere or long time, no reac-
tion with secondary amines and low yields [57–60]. To overcome
the drawbacks mentioned above, especially from the standpoint
of green chemistry, there is a need to introduce a high flexible
way for the synthesis of ␣-aminophosphonates. With this aim, we
tested one-pot three-component procedure for the synthesis of
␣-aminophosphonates by use of our magnetic inorganic-organic
hybrid catalyst, ␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H. One-pot three-
component reactions are very attractive since they significantly
lower the cost of the synthetic routes as well as reducing the
amount of waste and solvents. In the presence of 0.7 mol% of
␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H, the three component coupling
reaction involving carbonyl compounds, amines and dialkylphos-
phite successively proceeded smoothly at r.t to afford the
corresponding ␣-aminophosphonate. Reusability test of the cat-
alyst was also performed successfully in all of 10 recycle runs.
Comparison of catalytic efficiencies presents in Table 4.
We have found that no special handling precaution regard-
ing exposure to air/moisture is needed to be taken in use of
␥-Fe2O3@HAp-Si-(CH2)3-NHSO3H. Table 2 compares new mag-
netic interphase catalyst with other analogues.
Catalysis 2: Due to their biological activities, phosphonate-
containing molecules received much attention in organic syntheses
[45]. The utilities of ␣-aminophosphonates as HIV protease [46],
EPSP synthase [47], plant growth regulators [48], anti-thrombotic
agents [49], as well as peptidases and proteinases [50] are well
documented. ␣-Aminophosphonates have many biological effects
and medicinal importance [51] and therefore many procedures for
the synthesis of them have been developed, especially, the nucle-
ophilic addition of phosphates to imines is of the most convenient
methods, which is usually promoted by the base [52], Brønsted
[53], or variety of Lewis acids [54,55]. However, all of these meth-
ods have limitations due to the hygroscopic properties of imines
which cause them not to be sufficiently stable for isolation. Using
Lewis acids as catalysts and dialkylphosphite and trialkylphosphite
as phosphorous reagents, this conversion can proceed in smooth
rate. The common used catalysts have some drawbacks for exam-
ple, reactions require a long time and when starting from aliphatic
amines, reactions give non-characterizable products [56]. Addi-
tionally, some of these catalysts are either expensive or somewhat
difficult to prepare. In many cases the acids were trapped by the
basic nitrogen and the reaction require stoichiometric amounts
of Lewis acids. These afforded the use of heterogeneous cata-
lysts. Some limitations of the previous methods consist of: harsh
4. Conclusion
The preparation and characterization of n-propyl sulfamic acid
covalently supported on hydroxyapatite-encapsulated magnetic
nanoparticles was described. Synthesized material acts as a power-
ful and “green” heterogeneous interphase catalyst for preparation
of substituted quinolines and ␣-aminophosphonates derivatives.
We believe that most of the interesting supported organic acid cat-
alysts reported previously have harmful ingredients for human and
environment. Hydroxyapatite is found in teeth and bones within
the human body. Thus, it is commonly uses as a filler to replace
amputated bone or as a coating to promote bone in growth into
prosthetic implants. It contains more than 60% of mammalian
hard tissues and in addition it has unique biocompatibility feature
among phosphate groups. One of the reasons to use of this biocom-
patible material as catalyst support was that it has no pollution
and is in the context of “green chemistry”. This can make our new
magnetic catalyst distinct from all of its present analogues. Besides,
this new magnetic catalyst has higher activity in comparison with
␥-Fe2O3@HAp-SO3H, due to its far catalytic active sites from solid
surface and therefore less steric hindrance and less mass trans-
port limitations. The present method requires remarkably small

M. Sheykhan et al. / Journal of Molecular Catalysis A: Chemical 335 (2011) 253–261
261
amounts of non-toxic and green (environmentally friendly) [␥-
Fe2O3@HAp-(CH2)3-NHSO3H] as catalyst (0.7 mol%). The recovered
catalyst was recycling in subsequent runs without observation sig-
nificant decrease in activity even after 10 runs. For example, the
reaction of 2-aminoacetophenone and ethylacetoacetate gave sub-
stituted quinoline (Table 1, entry a) in sequenced 10 runs (Fig. 5).
The mild reaction conditions, excellent yields, operational simplic-
ity, practicability, applicability to various substrates, product purity
and therefore cost efficiency are of advantages of this protocol.
Besides that, the new catalyst can be effectively reused. With regard
to observed satisfactory catalytic properties, it is expected that it
can be potential substitute for some commercial catalysts.
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