Environmentally friendly and highly efficient synthesis of benzoxazepine and malonamide derivatives using HPA/TPI-Fe3O4 nanoparticles as recoverable catalyst in aqueous media

Article abstract of DOI:10.1002/aoc.3603

A magnetic inorganic–organic nanohybrid material (HPA/TPI-Fe₃O₄ NPs) was produced as an efficient, highly recyclable and eco-friendly catalyst for the one-pot multi-component synthesis of malonamide and 2,3,4,5-tetrahydrobenzo[b][1,4]oxazepine derivatives with high yields in short reaction times (25–35?min) in aqueous media at room temperature. The nanohybrid catalyst was prepared by the chemical anchoring of H₆P₂W₁₈O₆₂ onto the surface of modified Fe₃O₄ nanoparticles (NPs) with N-[3-(triethoxysilyl)propyl]isonicotinamide (TPI) linker. The magnetic recoverable catalyst was easily recycled at least ten times without any loss of catalytic activity.

Full text of DOI:10.1002/aoc.3603

Received: 28 March 2016
DOI 10.1002/aoc.3603
Revised: 19 July 2016
Accepted: 8 August 2016
F U L L PA P E R
Environmentally friendly and highly efficient synthesis of
benzoxazepine and malonamide derivatives using HPA/TPI‐Fe3O4
nanoparticles as recoverable catalyst in aqueous media
1
2
2
*
Esmail Vessally | Rahim Hosseinzadeh‐Khanmiri | Mirzaagha Babazadeh
Ebrahim Ghorbani‐Kalhor2 | Ladan Edjlali2
|
1 Department of Chemistry, Payame Noor
A magnetic inorganic–organic nanohybrid material (HPA/TPI‐Fe3O4 NPs) was
produced as an efficient, highly recyclable and eco‐friendly catalyst for the one‐pot
multi‐component synthesis of malonamide and 2,3,4,5‐tetrahydrobenzo[b][1,4]
oxazepine derivatives with high yields in short reaction times (25–35 min) in
aqueous media at room temperature. The nanohybrid catalyst was prepared by the
chemical anchoring of H6P2W18O62 onto the surface of modified Fe3O4
nanoparticles (NPs) with N‐[3‐(triethoxysilyl)propyl]isonicotinamide (TPI) linker.
The magnetic recoverable catalyst was easily recycled at least ten times without
any loss of catalytic activity.
University, Tehran, Iran
2 Department of Chemistry, Tabriz Branch, Islamic
Azad University, Tabriz, Iran
Correspondence
Mirzaagha Babazadeh, Department of Chemistry,
Tabriz Branch, Islamic Azad University, Tabriz,
Iran.
Email: babazadeh@iaut.ac.ir
KEYWORDS
2,3,4,5‐tetrahydrobenzo[b][1,4]oxazepine, green chemistry, HPA/TPI‐Fe3O4 NPs,
malonamide
1
|
INTRODUCTION
with supported dodecatungstophosphoric acid (HPW), such
as HPW/C,[5] HPW/CNTs,[6] HPW/TiO2,[7] HPW/SnO2,[8]
HPW/C‐Al2O3,[9] HPW/Nb2O5,[10] HPW/ZrO2,[11] HPW/
hydrous zirconia[12] and HPW/SiO2,[13] have been studied.
Paramagnetic Fe3O4 nanoparticles (NPs) have attracted
worldwide attention and have been studied extensively due
to their technological and biological applications such as in
drug delivery, bioseparation, biomolecular sensors and mag-
netic resonance imaging.[14,15]
Benzoxazepine derivatives are important scaffolds in
medicinal chemistry with various biological activities,[16] and
attractive compounds of growing pharmaceutical interest as
documented by many publications. Among compounds
containing this fragment are a non‐nucleoside histamine recep-
tor agonist,[17] HIV‐1 reverse transcriptase inhibitor[18] and
calcium antagonists,[19] as well as analgesics[20] and antide-
pressants.[21] The benzo[b][1,4]oxazepine derivatives demon-
strate various forms of bioactivity such as antidepressant and
anxiolytic activity,[22] they are used for treating bronchial
asthma and allergic bronchitis[23] and they show
antiserotoninergic and antihistaminic effects,[24] and
tetrahydrobenzo[b][1,4]oxazepines are progesterone receptor
Today, most emphasis of chemical synthesis is on the
development of green synthetic routes with heterogeneous
catalysts and aqueous media.[1] Multi‐component reactions
(MCRs) are chemical transformations in which three or more
different starting materials react to generate a final complex
product in a one‐pot reaction.[2]
Heteropolyacids (HPAs) are water‐soluble complex
metal‐oxo structures which have been extensively exploited
as catalysts in various homogeneous and heterogeneous
organic transformations in applications ranging from fine
chemical industries to pharmaceuticals and food industries.[3]
The advantages afforded by applying Keggin‐type HPA reac-
tions include strong acidities, lower proportion of side reac-
tions and production of non‐toxic wastes. The use of HPAs,
as catalysts for fine organic synthetic processes, is to develop
and synthesize antioxidants, medicinal preparations, vitamins
and biologically active substances as reported previously.[4]
Recently, science and technology are shifting emphasis to
environmentally friendly and sustainable resources and pro-
cesses. For these reasons several heterogeneous materials
Appl Organometal Chem 2016; 1–7
wileyonlinelibrary.com/journal/aoc
Copyright © 2016 John Wiley & Sons, Ltd.
1

2
VESSALLY ET AL.
agonists[25] and show anticancer activity against breast cancer
cells.[26]
Melting points were measured with an Electrothermal
9100 apparatus.
Malonamide derivatives are some of the most important
targets in synthetic chemistry because they display a number
of interesting properties in various fields.[27] In medicinal and
pharmaceutical chemistry, their derivatives are identified as
selective γ‐opioid receptor agonists,[28] as a γ‐secretase
inhibitor in treatment of Alzheimer’s disease[29] and as a
potent c‐Met/VEGFR2 multi‐targeted kinase inhibitor for
cancer therapy.[30] Recent studies have also shown that some
malonamides can act as gelators where their gelling proper-
ties strongly depend on their stereochemistry.[31,32] Because
of the broad range of applications that these compounds have,
new and simple synthetic methods for their preparation are
warranted, and recently MCRs have provided practical syn-
thetic routes.[33]
2.2 | General procedure for preparation of malonamide
(4a–h) and 2,3,4,5‐tetrahydrobenzo[b][1,4]oxazepine
(5a–h) derivatives
A solution of 2‐amino‐4‐methylphenol (1.00 or 2.00 mmol),
isocyanide derivatives (1.00 mmol) and Meldrum’s acid
(1.00 mmol) was stirred in the presence of HPA/TPI‐Fe3O4
NPs (0.02 g) in 3 ml of water as solvent at room temperature.
After completion of the reaction, as indicated by TLC (ethyl
acetate–n‐hexane, 1:1), ethanol (3 ml) was added and the
resulting mixture was heated at 60°C. The catalyst was recov-
ered using an external magnet. Then, the solution crystallized
to give products 4a–h and 5a–h.
Shaabani et al. have reported novel routes for the synthe-
sis of benzoxazepines and malonamide derivatives in the
absence of catalyst in CH2Cl2 solvent and with long reaction
times using isocyanide‐based MCRs.[33]
2.3 | Preparation of H6P2W18O62·24H2O
In view of our current studies on MCRs,[34] and consider-
ing our previous results, herein we report a highly versatile,
eco‐friendly and efficient one‐pot three‐component heteroge-
neous protocol for the synthesis of benzoxazepines and
malonamide derivatives in the presence of a catalytic amount
of H6P2W18O62/pyridino‐Fe3O4 NPs in water as a solvent at
room temperature (Scheme 1).
H6P2W18O62⋅24H2O was prepared from an α/β‐
K6P2W18O62⋅10H2O isomer mixture.[35–37] Concentrated
phosphoric acid in a 4:1 acid‐to‐salt ratio was added to a boil-
ing aqueous solution of Na2WO4⋅2H2O and the mixture was
kept boiling in a reflux system for 12 h. The salt was precip-
itated by adding KCl, then purified by recrystallization and
cooled overnight to 5°C. The product consisting of a mixture
of the α‐ and β‐isomers, was filtered, washed and then vac-
uum‐dried for 10 h. The acid was obtained from an aqueous
solution of α/β‐K6P2W18O62⋅10H2O salt, which was treated
with ether and concentrated HCl (37%) solution. The acid
so released formed an addition compound with ether, which
allowed it to be separated from the solution. Then, the ether
was eliminated by dry air and the remaining solution was
crystallized in a vacuum desiccator.
2
| EXPERIMENTAL
2.1 | General considerations
All reagents and solvents were obtained from Merck
(Germany) and used without further purification.
2.4 | Synthesis of N‐[3‐(Triethoxysilyl)propyl]
isonicotinamide (TPI)‐functionalized Fe3O4
Fe3O4 NPs were synthesized according to previously
reported methods.[38,39] FeCl3⋅6H2O (5.2 g) and FeCl2⋅4H2O
(2.0 g) were added to a three‐necked flask containing deion-
ized water (50 ml) and heated at 80°C under nitrogen gas
blowing. Then, NH3 aqueous solution (8 ml, 32%) was added
dropwise to the reaction mixture. After 15 min, the obtained
NPs were separated using an external magnet and washed
three times with brine solution. The pyridine‐functionalized
Fe3O4 NPs were obtained using a dispersion of Fe3O4 NPs
(0.5 g) in dry toluene (50 ml), the mixture being stirred for
1 h. Then, TPI (1 ml) was added and the mixture and refluxed
for 24 h. The TPI‐Fe3O4 NPs were collected using a strong
magnet, washed with toluene and ethanol and then dried at
ambient temperature.
SCHEME 1 Synthesis of malonamide and 2,3,4,5‐tetrahydrobenzo[b][1,4]
oxazepine derivatives.

VESSALLY ET AL.
3
2.5 | Immobilization of H6P2W18O62·24H2O on TPI‐
Fe3O4 NPs
structure in the 750–1010 cm−1 region confirms the loading
of H6P2W18O62 onto the surface of TPI‐Fe3O4 NPs
(Figure 1).[40]
HPA/TPI‐Fe3O4 NPs was synthesized according to a
previously reported procedure.[40] The immobilization of
H6P2W18O62⋅24H2O onto the TPI‐Fe3O4 NPs was done in
3.1.2
| XRD analysis
methanol solution (100 ml) containing 0.6
g
of
The crystallinity of H6P2W18O62/TPI‐Fe3O4 NPs was investi-
gated by XRD method.[40] The positions and relative intensi-
ties of all diffraction peaks match well with those from the
JCPDS card (75–1610). The XRD pattern of Fe3O4
(Figure 2) exhibited (220), (311), (400), (422), (511) and
(440) reflections.[38] The spinel structure of Fe3O4 is retained
after functionalization with TPI and immobilization of
H6P2W18O62 onto TPI‐Fe3O4 NPs. Moreover, the sample is
crystalline and Fe3O4 NPs with a spinel structure is the only
obtained phase together with some additional peaks,
indicated by star marks in Figure 2, associated with the
Wells–Dawson‐structured H6P2W18O62.[39]
H6P2W18O62⋅24H2O and TPI‐Fe3O4 NPs (1.2 g), and the
mixture was refluxed for 3 h. Then, the heterogeneous cata-
lyst was collected and extracted in a Soxhlet extractor using
methanol for 12 h and thereafter was dried at 105°C at
reduced pressure.
A schematic for the preparation of HPA/TPI‐Fe3O4
NPs is shown in Scheme 2. All of the synthesized
nanoparticles were characterized using Fourier transform
infrared (FT‐IR) spectroscopy, X‐ray diffraction (XRD),
thermal analysis (DTA/TGA), transmission electron
microscopy (TEM) and scanning electron microscopy
(SEM).
3.1.3
| TEM and SEM analyses
The size and morphology of the HPA/TPI‐Fe3O4 NPs were
investigated using TEM. The micrographs (Figure 3) illus-
trate that the Fe3O4 NP core is coated with a TPI shell uni-
formly, and particles have semi‐spherical morphology with
3
| RESULTS AND DISCUSSION
3.1 | Structural characterization of HPA/TPI‐Fe3O4
NPs
3.1.1
| FT‐IR spectroscopy
FT‐IR spectroscopy was used to characterize the HPA/TPI‐
Fe3O4 NPs. The FT‐IR spectrum of H6P2W18O62/TPI‐
Fe3O4 NPs has a distinct band with shoulders at about
1035 cm−1, confirming a strong interaction of the pyridine‐
modified Fe3O4 NPs with H6P2W18O62. In addition, observa-
tion of the fingerprinting FT‐IR bands of the Wells–Dawson
FIGURE 1 FT‐IR spectra of Fe3O4, TPI‐Fe3O4 and H6P2W18O62/TPI‐
Fe3O4 NPs.
FIGURE 2 XRD patterns of Fe3O4, TPI‐Fe3O4 and H6P2W18O62/TPI‐
SCHEME 2 Preparation of HPA/TPI‐Fe3O4 NPs.
Fe3O4 NPs.

4
VESSALLY ET AL.
3.2 | Catalytic study
The catalytic efficiency of the HPA/TPI‐Fe3O4 NPs
heterogeneous catalytic system was studied for the prepara-
tion of malonamide and 2,3,4,5‐tetrahydrobenzo[b][1,4]
oxazepine derivatives (Scheme 1). To illustrate the need for
a catalyst for these reactions, in a typical experiment, one or
two equivalents of 2‐amino‐4‐methylphenol (1) with
cyclohexylisocyanide (2a) and Meldrum’s acid (3) as a model
system were stirred in water at room temperature in the
absence of catalyst. The yield in this case was a trace amount
after 12 h showing that catalyst is an important part of the
reaction.
TABLE 1 Optimization of catalyst for synthesis of 2,3,4,5‐tetrahydrobenzo
[b][1,4]oxazepine and malonamidea
FIGURE 3 TEM and SEM images of Fe3O4 and H6P2W18O62/TPI‐Fe3O4
NPs.
narrow size distributions and an average diameter of approx-
imately 40 nm. According to the SEM images (Figure 3), the
morphology of HPA/TPI‐Fe3O4 NP surface clearly indicates
the homogeneity of the material and also shows that
H5PW10V2O40 is well dispersed in TPI‐Fe3O4 NPs.
3.1.4
| Thermal analyses
The thermal stability of HPA/TPI‐Fe3O4 NPs was investi-
gated by carrying out TGA/DTA analysis (Figure 4). The
DTA profile exhibits a wide endothermic peak from 25 to
200°C which is attributed to the elimination of adsorbed
water molecules. A weight loss occurs between 200 and
500°C which is accompanied by a broad exothermic peak
between 350 and 450°C in the DTA curve, corresponding
to the oxidative decomposition of the organic part (TPI). As
can be seen in TGA curve, the 3% decrease of mass of the
catalyst from 200 to 500°C is related to the modification by
TPI on the sorbent. Also, the prepared HPA/TPI‐Fe3O4 NPs
are stable up to 200°C.[40]
Catalyst
Time (min)
Yield (%)b
Yield (%)c
HPA
25
25
25
25
64
33
52
90
69
36
57
95
Fe3O4 NPs
TPI‐Fe3O4 NPs
HPA/TPI‐Fe3O4 NPs
aReaction conditions: 1 (1.00 or 2.00 mmol), 2a (1.00 mmol), 3 (1.00 mmol) and
catalyst (0.02 g) in H2O as solvent at room temperature.
bIsolated yields from 4a.
cIsolated yields from 5a.
TABLE 2 Optimization of solvent for synthesis of 2,3,4,5‐tetrahydrobenzo
[b][1,4]oxazepine and malonamidea
Entry
Solvent
H2O
Time (min)
Yield (%)b
Yield (%)c
1
2
3
4
5
6
7
25
25
25
25
25
25
25
90
91
91
45
89
89
84
95
96
92
48
94
91
85
EtOH
CH3CN
C7H8
CH2Cl2
CHCl3
Tetrahydrofuran
aReaction conditions:
1 (1.00 mmol or 2.00 mmol), 2a (1.00 mmol), 3
(1.00 mmol) and HPA/TPI‐Fe3O4 NPs (0.02 g), solvent (3.00 ml), at room
temperature.
bIsolated yields from 4a.
cIsolated yields from 5a.
FIGURE 4 TGA and DTA curves of HPA/TPI‐Fe3O4 NPs.

VESSALLY ET AL.
5
TABLE 3 Effect of catalyst amount on reaction of 2,3,4,5‐tetrahydrobenzo
[b][1,4]oxazepine and malonamidea
acetonitrile give similar yields. Furthermore, water was
selected as the solvent due to its accordance with green
chemistry principles.
Catalyst
(g)
Time
(min)
Yield (%)
Yield
(%)c
b
Entry
The catalytic efficiency can be influenced by the amount
of catalyst. Therefore, a set of experiments using various
amounts of catalyst was conducted using the reaction of one
or two equivalents of 1 with 2a and 3 in water at room tem-
perature (Table 3). The optimum catalyst amount is 0.02 g f
HPA/TPI‐Fe3O4 NPs leading to 90 and 95% yields of com-
pounds 4a and 5a, respectively. Lower amounts of catalyst
result in a decrease in the efficiency of the reaction, while
higher amounts lead to complete conversion in a short reac-
tion time.
HPA
0.02
0.01
0.04
0.02
0.01
0.02
0.01
0.02
0.01
25
25
25
25
25
25
25
25
25
64
44
38
32
24
52
39
90
78
69
49
43
37
29
57
44
95
83
HPA
Fe3O4 NPs
Fe3O4 NPs
Fe3O4 NPs
TPI‐Fe3O4 NPs
TPI‐Fe3O4 NPs
HPA/TPI‐Fe3O4 NPs
HPA/TPI‐Fe3O4 NPs
The generality of the process was studied using a range of
isocyanides and 2‐aminophenol derivatives for the synthesis
of 4a–h and 5a–h in the presence of HPA/TPI‐Fe3O4 NPs
as catalyst (Table 4).
aReaction conditions: 1 (1.00 or 2.00 mmol), 2a (1.00 mmol), 3 (1.00 mmol) and
catalyst in H2O as solvent at room temperature.
bIsolated yields from 4a.
cIsolated yields from 5a.
The catalyst is very active, stable, non‐toxic and inexpen-
sive. To explore the reusability of the HPA/TPI‐Fe3O4 NPs
catalyst, it was easily separated from the reaction medium
using an external magnet and washed thoroughly with
CH2Cl2. The catalyst was then dried in air and activated in
a vacuum oven at 70°C for 4 h. Finally, the recycled catalyst
was reused for another condensation reaction. The results
indicate the same catalytic activity as the fresh catalyst, with-
out any loss of its activity. In addition, to ensure reproduc-
ibility of the transformation, repeated typical experiments
were carried out under identical reaction conditions
(Table 5).
In a pilot experiment, one or two equivalents of 1
with 2a and 3 were stirred in water at room temperature
using each of HPA, Fe3O4 NPs, TPI‐Fe3O4 NPs and
HPA/TPI‐Fe3O4 NPs as catalyst. Table 1 summarizes the
catalytic performance for the synthesis of compounds 4a
and 5a. The catalytic activity decreased in the order:
HPA/TPI‐Fe3O4 NPs > HPA > TPI‐Fe3O4 NPs > Fe3O4
NPs.
In order to obtain the best synthesis conditions, one or
two equivalents of 1 with 2a and 3 in the presence of
HPA/TPI‐Fe3O4 NPs in various protic and aprotic solvents
were allowed to react at room temperature (Table 2). It is
important to note that organic solvents such as ethanol and
The changes in the structure of the recovered HPA/TPI‐
Fe3O4 NPs were determined using FT‐IR spectroscopy. As
can be seen in Figure 5, the structure of the recycled catalyst
TABLE 4 Synthesis of 2,3,4,5‐tetrahydrobenzo[b][1,4]oxazepine (4a–h) and malonamide (5a–h) derivatives in absence and presence of HPA/TPI‐Fe3O4 NPsa
M.p. (°C)
Time
(min)
Yield
(%)b
Product
R1
R2
Foundb
Reported
4a
4b
4c
c‐Hex
c‐Hex
t‐Bu
4‐CH3
4‐Cl
H
25
30
35
25
30
35
25
25
25
25
35
25
30
30
30
30
90
88
87
92
89
93
93
92
95
92
91
93
91
92
89
87
250–252
229–231
151–153
227–229
212–214
171–173
221–223
264–266
221–223
228–230
244–246
232–234
172–174
151–153
245–247
216–218
249–251[34]
228–230[33]
151–153[33]
227–229[33]
214–216[33]
169–171[33]
220–223[34]
264–267[34]
220–222[33]
227–229[33]
242–244[33]
233–235[33]
172–174[33]
151–153[33]
245–247[34]
215–218[34]
4d
4e
t‐Bu
4‐CH3
H
1,1,3,3‐Tetramethylbutyl
c‐Hex
4f
H
4 g
4 h
5a
5b
5c
2,6‐Dimethylphenyl
2,6‐Dimethylphenyl
c‐Hex
H
4‐CH3
4‐CH3
4‐CH3
H
1,1,3,3‐Tetramethylbutyl
2,6‐Dimethylphenyl
2,6‐Dimethylphenyl
4‐Methylphenylsulfonyl
4‐Methylphenylsulfonyl
c‐Hex
5d
5e
4‐CH3
H
5f
4‐CH3
4‐Cl
4‐CH3
5 g
5 h
t‐Bu
aReaction conditions: 1 (1.00 mmol or 2.00 mmol), 2 (1.00 mmol), 3 (1.00 mmol) and HPA/TPI‐Fe3O4 NPs (0.02 g) in H2O as solvent at room temperature.
bIsolated yields from 4a and 5a.

6
VESSALLY ET AL.
TABLE 5 Recycling of catalysta
REFERENCES
[1] B. K. Min, C. M. Friend, Chem. Rev. 2007, 107, 2709.
Cycle
Catalyst (g)
Yield (%)b
Yield (%)c
[2] J. Zhu, H. Bienayme, Multicomponent Reactions, Wiley, Weinheim 2005.
[3] M. N. Timofeeva, Appl. Catal. A 2003, 256, 19.
1
2
3
4
5
6
7
8
9
10
0.020
0.020
0.020
0.019
0.019
0.019
0.019
0.018
0.018
0.018
90
90
90
90
89
89
89
89
88
87
95
95
95
94
94
93
93
92
92
91
[4] T. Okuhara, N. Mizuno, M. Misono, Adv. Catal. 1996, 41, 221.
[5] P. Ferreira, I. M. Fonseca, A. M. Ramos, J. Vital, J. E. Castanheiro, Catal.
Commun. 2011, 12, 573.
[6] A. Micek‐Ilnicka, E. Bielańska, L. Lityńska‐Dobrzyńska, A. Bielański, Appl.
Catal. A 2012, 421, 91.
[7] K. M. Su, Z. H. Li, B. W. Cheng, L. Zhang, M. L. Zhang, J. Ming, J. Fuel
Process. Technol. 2011, 92, 2011.
[8] A. E. R. S. Khder, Appl. Catal. A 2008, 343, 109.
[9] E. Caliman, J. A. Dias, S. C. L. Dias, A. D. S. Prado, Catal. Today 2005,
816, 107.
aReaction conditions: 1 (1.00 mmol or 2.00 mmol), 2 (1.00 mmol), 3 (1.00 mmol)
and HPA/TPI‐Fe3O4 NPs in H2O as solvent at room temperature.
bIsolated yields from 4a.
cIsolated yields from 5a.
[10] A. M. Alsalme, E. F. Kozhevnikova, I. V. Kozhevnikov, Appl. Catal. A 2010,
390, 219.
[11] B. M. Devassy, F. Lefebvre, S. B. Halligudi, J. Catal. 2005, 231, 1.
[12] L. M. Somavilla, J. E. Zorzi, G. Machado, G. R. Ramos, C. L. G. de
Amorim, C. A. Perottoni, J. Am. Ceram. Soc. 2011, 94, 2640.
[13] V. V. Costa, K. A. D. Rocha, I. V. Kozhevnikovb, E. V. Gusevskaya, Appl.
Catal. A 2010, 383, 217.
[14] M. Babazadeh, R. Hosseinzadeh‐Khanmiri, J. Abolhasani, E. Ghorbani‐
Kalhor, A. Hassanpour, RSC Adv. 2015, 5, 19884.
[15] E. Ghorbani‐Kalhor, R. Hosseinzadeh‐Khanmiri, J. Abolhasani, M.
Babazadeh, A. Hassanpour, J. Sep. Sci. 2015, 38, 1179.
[16] F. Bihel, J. L. Kraus, Org. Biomol. Chem. 2003, 1, 793.
[17] R. A. Smits, H. D. Lim, B. Stegink, R. A. Bakker, I. J. P. de Esch, R. Leurs,
J. Med. Chem. 2006, 49, 4512.
[18] X. L. Xing, J. L. Wu, J. L. Luo, W. Dai, Synlett 2006, 13, 2099.
[19] R. Li, P. S. Farmer, J. Wang, R. J. Boyd, T. S. Cameron, M. A. Quilliam,
J. A. Walter, S. E. Howlett, Drug Des. Discovery 1995, 12, 337.
[20] J. Wu, Y. Jiang, W. M. Dai, Synlett 2009, 7, 1162.
[21] K. Nagarajan, J. David, Y. S. Kulkarni, S. B. Hendi, S. J. Shenoy,
FIGURE 5 FT‐IR spectrum of recovered HPA/TPI‐Fe3O4 NPs.
P. Upadhyaya, Eur. J. Med. Chem. Chim. Ther. 1986, 21, 21.
[22] W. J. Van der Burg, Chem. Abstr. 1974, 81, 3986, DE2347727.
[23] G. Walther, C. S. Schneider, K. H. Weber, A. Fuegner, Chem. Abstr. 1982,
96, 6777, DE3008944.
does not change, and a very slight decrease in the reaction
yield may be due to the covering of the surface of the catalyst
by impurities.
[24] F. G. Sulman, Y. Pfeifer, E. Superstine, Arzneimittelforschung 1981, 31, 109.
[25] P. P. M. A. Dols, B. J. B. Folmer, H. Hamersma, C. W. Kuil, H. Lucas, L.
Ollero, J. B. M. Rewinkel, P. H. H. Hermkens, Bioorg. Med. Chem. Lett.
2008, 18, 1461.
[26] M. Díaz‐Gavilán, F. Rodríguez‐Serrano, J. A. Gómez‐Vidal, J. A. Marchal,
A. Aránega, M. Á. Gallo, A. Espinosa, J. M. Campos, Tetrahedron 2004,
60, 11547.
4
| CONCLUSIONS
We report HPA/TPI‐Fe3O4 NPs as a new and efficient solid
acid catalyst for the synthesis of 2,3,4,5‐tetrahydrobenzo[b]
[1,4]oxazepine and malonamide derivatives upon mixing
readily available substrates in short reaction times at room
temperature. Recyclability of the catalyst with no loss in
its activity, mild reaction conditions and product isolation,
use of non‐toxic materials and excellent yields are impor-
tant features of this new protocol for the preparation of
2,3,4,5‐tetrahydrobenzo[b][1,4]oxazepine and malonamide
derivatives.
[27] S. A. Ansari, P. K. Mohapatra, V. K. Manchanda, Talanta 2007, 73, 878.
[28] G. H. Chu, M. Gu, J. A. Cassel, S. Belanger, T. M. Graczyk, R. N. DeHaven,
N. Conway‐James, M. Koblish, P. J. Little, D. L. DeHaven‐Hundkins, R. E.
Dolle, Bioorg. Med. Chem. Lett. 2007, 17, 1951.
[29] J.‐U. Peters, G. Galley, H. Jacobsen, C. Czech, P. David‐Pierson, A. E. Kitas,
L. Ozmen, Bioorg. Med. Chem. Lett. 2007, 17, 5918.
[30] F. Gaudette, S. Raeppel, H. Nguyen, N. Beaulieu, C. Beaulieu, I. Dupont,
A. R. Macleod, J. M. Besterman, A. Vaisburg, Bioorg. Med. Chem. Lett.
2010, 20, 848.
[31] H. F. Chow, K. N. Lau, M. C. Chan, Chem. – Eur. J. 2011, 17, 8395.
[32] S. K. Lee, K. Kim, S. Jang, J. Kang, Tetrahedron Lett. 2011, 52, 1977.
[33] A. Shaabani, H. Mofakham, A. Maleki, F. Hajishaabanha, J. Comb. Chem.
2010, 12, 630.
ACKNOWLEDGMENTS
The authors thank Tabriz Branch, Islamic Azad University
for the financial support of this research.
[34] M. Babazadeh, R. Hosseinzadeh‐Khanmiri, S. Zakhireh, Appl. Organomet.
Chem. 2016, 30, 514.

VESSALLY ET AL.
7
[35] D. Lyon, W. Miller, T. Novet, P. Domaille, E. Evitt, D. Johnson, R. Finke,
J. Am. Chem. Soc. 1991, 113, 7209.
How to cite this article: Vessally, E., Hosseinzadeh‐
Khanmiri, R., Babazadeh, M., Ghorbani‐Kalhor, E.,
and Edjlali, L. (2016), Environmentally friendly and
highly efficient synthesis of benzoxazepine and
malonamide derivatives using HPA/TPI‐Fe3O4
nanoparticles as recoverable catalyst in aqueous media,
Appl. Organometal. Chem., doi: 10.1002/aoc.3603
[36] G. Baronetti, L. Briand, U. Sedran, H. Thomas, Appl. Catal. A 1998,
173, 265.
[37] G. P. Romanellia, D. M. Ruiza, H. P. Bideberripea, J. C. Autinob, G. T.
Baronetti, H. J. Thomasa, ARKIVOC 2007, 16, 1.
[38] X. Liu, Z. Ma, J. Xing, H. Liu, J. Magn. Magn. Mater. 2004, 270, 1.
[39] A. Tarlani, M. Abedini, M. Khabaz, M. M. Amini, J. Colloid Interface, Sci.
2005, 292, 486.
[40] R. Tayebee, M. Kargar Razi, Res. Rev.: J. Mater. Sci. 2014, 2, 13.