Organic/inorganic Fe3O4@MCM-41@Zr-piperazine: An impressive magnetite nanocatalyst for N-Tert-Butoxycarbonylation of amines

Article abstract of DOI:10.1166/jnn.2019.16291

Fe₃O₄@MCM-41@Zirconium magnetic nanoparticles modified with piperazine (Fe₃O₄@MCM-41@Zr-piperazine), as a newly reported catalyst, shows excellent catalytic activity in N-tertbutoxycarbonylation of amines under the mild and solvent-free conditions. Accordingly, different derivatives of N-tert-butylcarbamates owning diverse aliphatic, aromatic and heteroaromatic amines were prepared efficiently. Good performance of this method for the majority of used complex or acidsensitive substrates and facile separation of this nanocatalyst due to its superparamagnetic nature from the reaction mixture via an external magnetic field for several times are the most important striking features of this protocol.

Full text of DOI:10.1166/jnn.2019.16291

Article
Journal of
Nanoscience and Nanotechnology
Vol. 19, 3859–3870, 2019
Copyright © 2019 American Scientific Publishers
All rights reserved
www.aspbs.com/jnn
Printed in the United States of America
Organic/Inorganic Fe3O4@MCM-41@Zr-Piperazine:
An Impressive Magnetite Nanocatalyst for
N-Tert-Butoxycarbonylation of Amines
Reyhaneh Pourhasan-Kisomi1, Farhad Shirini1ꢀ∗, and Mostafa Golshekan2
1Department of Chemistry, College of Sciences, University of Guilan, Rasht, 41335-19141, Iran
2Institute of Medical Advanced Technologies, Guilan University of Medical Science, Rasht, 41335-19141, Iran
Fe3O4@MCM-41@Zirconium magnetic nanoparticles modified with piperazine (Fe3O4@MCM-
41@Zr-piperazine), as a newly reported catalyst, shows excellent catalytic activity in N-tert-
butoxycarbonylation of amines under the mild and solvent-free conditions. Accordingly, different
derivatives of N-tert-butylcarbamates owning diverse aliphatic, aromatic and heteroaromatic amines
were prepared efficiently. Good performance of this method for the majority of used complex or acid-
sensitive substrates and facile separation of this nanocatalyst due to its superparamagnetic nature
from the reaction mixture via an external magnetic field for several times are the most important
striking features of this protocol.
Keywords: Fe3O4@MCM-41@Zr-MNPs, Piperazine, Superparamagnetic, N-Ter t-Butoxycarbonylation,
IP: 46.148.112.246 On: Mon, 18 Mar 2019 05:40:47
Amine.
Copyright: American Scientific Publishers
Delivered by Ingenta
1. INTRODUCTION
procedures are included. Moreover, being very costly and
nonrecoverablity of the previously reported catalysts are as
the main disadvantages of most of the existing methods.10
These negative points prevent such procedures from being
perfect. Therefore, the introduction of new catalytic sys-
tems which in them the above-mentioned difficulties be
excluded is still in demand.
Silica mesoporous compounds are defined as natural and
artificial compounds having a pore size of 2–50 nm, classi-
fied between the two micro and macroporous classes. The
reason for the focus of many studies by researchers and
scientists on silica mesoporous materials like MCM-41 is
their exclusive characteristics such as high surface area
(∼1000 m2 · g−1ꢁ, large pore size (2–50 nm), narrow
pore size distribution, high thermal stability and the fea-
sibility of using them in a broad variety of applications
such as catalization, sensors, photocatalysis, isolation,
absorption, etc.15–23
The susceptibility of transition elements to mediate
organic synthesis develops one of the most effective strate-
gies to achieve both selectivity and efficiency in synthetic
chemistry.24 Possessing a high coordinating ability of zir-
conium (IV) compounds due to the higher charge-to-size
value of Zr4+ in contrast with most of the metal ions
leads to displaying a good Lewis acid behavior and high
The problem of incompatibility of functional groups in the
synthesis of complex organic structures is very important,
which makes these syntheses often comprise protection-
deprotection steps, so that by incorporation of an appro-
priate protecting group that can later be easily separated,
an active functional group can be temporarily disabled.
This is especially important in designing and manufactur-
ing molecules with a large number of functionalities.
The presence of amine groups in the synthesis of various
biological structures such as amino acids, peptides, gly-
copeptides, aminoglycosides, ꢀ-lactams, nucleosides and
alkaloids is very important due to their considerable nucle-
ophilicity and basicity. Therefore, the protection of amine
groups is of great importance. Amines are effectively
protected as N-tert-butylcarbamates derivatives through
N-tert-butoxycarbonylation, which can be related to the
stability of N-tert-butylcarbamates against nucleophiles,
bases, racemization and catalytic hydrogenation.1–5
In this regard, different reagents and methods were
introduced,6–14 in which despite their improvement,
some deficiencies such as extended reaction times, low
yields, use of organic solvents and tedious work-up
∗Author to whom correspondence should be addressed.
J. Nanosci. Nanotechnol. 2019, Vol. 19, No. 7
1533-4880/2019/19/3859/012
doi:10.1166/jnn.2019.16291
3859

Organic/Inorganic Fe3O4@MCM-41@Zr-Piperazine: An Impressive Magnetite Nanocatalyst
Pourhasan-Kisomi et al.
catalytic activity. Besides, many zirconium salts are now
commercially accessible or reported in the literature.25ꢂ26
Notwithstanding its advantages, in contrast with other tran-
sition metals, the utility of zirconium (IV) compounds as
Lewis acids for organic reactions has not been utilized to
a greater extent mainly.27–29 In last decade, due to grow-
ing environmental concerns and the necessity for efficient
and green Lewis acid catalysts for different useful organic
transformations, zirconium and its compounds has been
more interesting.30
As a proposal way to increase the accessibility of active
sites of zirconium to compensate its low surface area, zir-
conium can be introduced into the framework of molec-
ular sieves during their synthesis as co-condensation or
direct ones, by comparison with what had been made with
many other elements. In this sort of mesoporous mixed
metal materials, metals are extremely dispersed and more
active sites can be provided.31ꢂ32 Furthermore, the ther-
mal and hydrothermal stability can be improved.33 More-
over, to increase zirconium catalytic activity in organic
reactions, functionalization by organic amine groups like
piperazine as a basic functional group looks to be a good
idea.
bromide (CTAB), NaOH, NaF, ZrOCl2 ·8H2O, piperazine,
amine derivatives, di-tert-butyl pyrocarbonate (Boc)2O,
were purchased with high purity from Merck chemi-
cal company (Munich). All solvents were prepared from
Merck (Munich) and besides getting distilled before being
used, they were kept sealed in airtight bottles as well, to
minimize the absorption of atmosphere moisturize.
2.2. Characterization Techniques
All obtained products were characterized by comparing
their physical constants, and IR and NMR spectroscopy
with genuine samples and those reported in the litera-
ture. The purity determination of the substrate and reaction
monitoring was accompanied by thin-layer chromatogra-
phy (TLC) on a silica gel Polygram SILG/UV 254 plate.
Measuring Melting points were accomplished by apply-
ing electrothermal IA9100 melting point device in cap-
illary tubes. The composition and quality of pelletized
samples of synthesized nanoparticles were identified via
Fourier transform infrared spectroscopy (FT-IR) measure-
ments by Perkin-Elmer Spectrum BX series in the range
of 400–4000 cm−1. Analyzing the crystal phases and
crystallinity of synthesized MNPs were accomplished by
Philips PW1730 (Netherlands) instrument in the range of
0.7ꢀ–80ꢀ (2ꢃ). Iron Scanning electron microphotographs
(FESEM) and Energy Dispersive Spectrometer (EDS) was
performed on a TESCAN MIRA II (Czech) device to
study the size and morphology of particles. The pore vol-
ume, the BET surface area, and the average pore size
obtained before and after the modification was character-
ized bꢀy N2 adsorption/desorption which was carried out
at 77 K on a BELSORP-mini II apparatus using nitro-
gen. The samples were outgassed at 393 ꢀK and 1 mPa for
12 h before adsorption measurements. Thermogravimet-
ric analysis (TGA) and differential thermal analysis (DTA)
was carried out with a Q600 TGA analyzer under argon
On the other hand, the modification of methods that can
develop and reuse these nanocomposites at low concen-
trations in complex matrices will be strongly needed in
order to protect the environment and to prevent the attain-
IP: 46.148.112.246 On: Mon, 18 Mar 2019 05:40:47
ment of filtration and refinement catalysts. To do this, by
Copyright: American Scientific Publishers
heterogenization of the catalyst in the form of magnetic
Delivered by Ingenta
nanoparticles, the catalyst can be recovered using an exter-
nal magnetic field and increased the performance of the
nanocatalysis in subsequent reuses.
Accordingly, very recently we have introduced
and identified “piperazine-functionalized Fe3O4@MCM-
41@Zironium magnetic nanoparticles (Fe3O4@MCM-
41@Zr-piperazine-MNPs)” as a new stable and highly
active superparamagnetic nanocatalyst and inspected its
susceptibility in preparing a variety of tetrahydro-4H-
chromene and pyrano[2,3-d] pyrimidinone derivatives.34 In
continuance of this study and our prior reports on the
application of various acidic and basic catalysts, espe-
cially zirconium based and supported reagents in organic
transformations,34–38 and on the basis of the previously
mentioned deficiencies in the N-Boc protection techniques
which means there is a necessity to introduce more effec-
tive, applicable and environmentally benign method for
the synthesis of these compounds, we were interested
to investigate the applicability of Fe3O4@MCM-41@Zr-
piperazine-MNPs in the promotion of the synthesis of
N-tert-butylcarbamate molecules.
ꢀ
atmꢀosphere from 25 to 1200 C with a heating rate of
20 C · min−1 over. The magnetic properties were deter-
mined using vibrating sample magnetometry (VSM; Lake
Shore 7200 at 300 kVsm).
2.3. Preparation of Piperazine-Functionalized
Fe3O4@MCM-41@Zr-MNPs
According to our newly reported literature,34 after
synthesizing Fe3O4@MCM-41@Zr-MNPs and function-
alizing with piperazine, the intended nanocatalyst was
successfully prepared and characterized by a variety of
techniques such as FT-IR, XRD, TEM, EDX, VSM, TGA.
The results validate the structural correctness and justify
the accurate performance of the catalyst (Fig. 1).
2. EXPERIMENTAL DETAILS
2.1. Material
2.4. General Procedure for
N-tert-Butoxycarbonylation of Amines
All chemicals including FeCl3 · 6H2O, FeCl2 · 4H2O,
In a round-bottom flask (10 mL), 1 mmol of the
amine as the substrate was added to a magnetically
tetraethylorthosilicate (TEOS), cetyl trimethylammonium
3860
J. Nanosci. Nanotechnol. 19, 3859–3870, 2019

Pourhasan-Kisomi et al.
Organic/Inorganic Fe3O4@MCM-41@Zr-Piperazine: An Impressive Magnetite Nanocatalyst
IP: 46.148.112.246 On: Mon, 18 Mar 2019 05:40:47
Copyright: American Scientific Publishers
Delivered by Ingenta
Figure 1. Preparation of Fe3O4@MCM-41@Zr-piperazine-MNPs.
stirred mixture of di-tert-butyldicarbonate [(Boc)2O]
(1 mmol, 0.218 g) and Fe3O4@MCM-41@Zr-piperazine
nanocatalyst (0.03 g) at ambient temperature. When the
reaction was fulfilled, as indicated by TLC (n-hexane:
ethyl acetate; 7:3), the mixture was purified with ethanol.
Afterward, in the presence of a magnetic stirrer bar,
Fe3O4@MCM-41@Zr-piperazine nanocatalyst was sepa-
rated, concurrently turning clear the reaction mixture.
Eventually, after washing the organic phase with 10%
aqueous solution of sodium bicarbonate (2 × 20 mL), it
was dried over Na2SO4. The solvent was removed under
reduced pressure to acquire the favorable product in good
to high yields.
2.5. Characterization of the Catalyst
2.5.1. FT-IR Analysis
Comparison of the FT-IR spectra of the Fe3O4-MNPs,
Fe3O4@MCM-41@Zr-MNPs and Fe3O4@MCM-41@Zr-
piperazine-MNPs confirm the structure of the synthesized
nanoparticles (Fig. 2). For the bare MNPs, Fe3O4 usually
shows bands at ∼560 and 450 cm−1, from Fe–O vibra-
tions at tetrahedral and octahedral sites, respectively.39 In
the FT-IR spectra of the finally prepared reagent, there
are stretching vibrations of O–H bonds at ∼3435 cm−1
and bending vibrations of these bonds at 1635 cm−1 23
An
.
intense peak at 1000–1250 cm−1 corresponded to the Si–O
stretching vibrations in the amorphous silica shell.32 Also,
J. Nanosci. Nanotechnol. 19, 3859–3870, 2019
3861

Organic/Inorganic Fe3O4@MCM-41@Zr-Piperazine: An Impressive Magnetite Nanocatalyst
Pourhasan-Kisomi et al.
obvious diffraction peak around 0.8ꢀ–1ꢀ, characteristic of
the Bragg plane reflection (100), and one poorly resolved
diffraction peak around 2ꢀ–4ꢀ, indexed as (110) reflection,
which indicates the presence of ordered mesostructure and
the incorporation of Zr4+ in the framework of MCM-41
as a sufficient evidence.42ꢂ45 As a more precisely descrip-
tion, consistent with Yang et al. findings,32 after incorpo-
ration of ZrOCl2 into the gels, ordered Zr-MCM-41 was
obtained, with the explanation that the peak intensity of
(100) plane gradually decreased and the diffraction peaks
of (110) and (200) planes gradually disappeared with intro-
ducing of Zr, which meant that the ordering of Zr-MCM-41
samples decreased when Zr was introduced into the frame-
work of Fe3O4@MCM-41-MNPs. With loading of piper-
azine, there is decrease of peak intensity as well as a shift of
the (100) peak for Fe3O4@MCM-41@Zr-MNPs to the low
angle degree for Fe3O4@MCM-41@Zr-piperazine-MNPs.
The results are similar to that observed by Xu et al.46 upon
the loading of polyethyleneimine (PEI) onto MCM-41.
Accordingly, the diffraction patterns of MCM-41 did not
change after the piperazine was loaded, which indicated
that the structure of MCM-41 was preserved. However, the
intensity of the diffraction peaks of MCM-41 did change.
After loading of piperazine, the intensity of the diffraction
peaks of Fe3O4@MCM-41@Zr-MNPs decreased, which
was possibly caused by the pore filling by piperazine.
Figure 2. The FT-IR spectra of (a) Fe3O4-MNPs (b) Fe3O4@MCM-
41@Zr-MNPs and (c) Fe3O4@MCM-41@Zr-Piperazine-MNPs.
the external vibrations of SiO4 chains can be observed at
∼1200 and 800 cm−1 23
.
In this spectra, the angular bend-
ing of Si–O units (450 cm−1ꢁ is overlapped with the Fe–O
vibrations.40ꢂ41 The band at 980 cm−1 shows the funda-
mental vibrations of Zr–O–Si which overlaps with the Si–
OH vibrations of Fe3O4@MCM-41 nanoparticles.42 The
broad strong bond which appears at 3230 cm−1 is related
to the N–H bond of piperazine and the bands at 2810 cm−1
and 2950 cm−1 are due to CH2 stretching vibrations.43
IP: 46.148.112.246 On: Mon, 18 Mar 2019 05:40:47
2.5.2. Powder X-ray Diffraction (XRD) Analysis
2.5.3. BET Analysis
Copyright: American Scientific Publishers
X-ray diffraction (XRD) patterns of the mesoporous Fe3O4-
The nitrogen adsorption/desorption isotherms of
Fe3O4@MCM-41@Zr-MNPs before and after modifica-
tion with piperazine are shown in Figure 4. The isotherms
correspond to type IV (in the IUPAC classification), which
is typical of mesoporous materials,47 and further confirm
that the piperazine was loaded into the pore channels
of the MCM-41 support. The Brunauer-Emmet-Teller
(BET) surface areas, total pore volume and Barret-Joyne-
Delivered by Ingenta
MNPs showed peaks that could be indexed both meso-
porous structure and MNPs (Fig. 3). The Fe3O4-MNPs
indicated peaks with 2ꢃ at 29.72ꢀ, 35.57ꢀ, 43.17ꢀ, 57.15ꢀ
and 62.77ꢀ which are characteristic peaks of Fe3O4 and
matched well with the XRD pattern of the standard Fe3O4
from Joint Committee on Powder Diffraction Standards
(JCPDS No. 19-692).44 The three peaks with 2ꢃ at 1.5ꢀ–10ꢀ
are characteristic peaks of MCM-41.22 The peaks resem-
ble those of magnetite, indicates the presence of magnetite
in the caves of the synthesized nanocomposites. In low
angle region, Fe3O4@MCM-41@Zr-MNPs displayed an
Halendu (BJH) pore diameter were 597.42 m2 · g−1
,
0.3912 cm3 ·g−1, and 2.6196 nm, respectively. After load-
ing of piperazine, the mesoporous pores were filled with
piperazine, restricting the access of nitrogen into the pores
at the liquid nitrogen temperature.46ꢂ48 The surface area
was estimated to be 219.57 m2 ·g−1 and the residual pore
volume of the Fe3O4@MCM-41@Zr-piperazine-MNPs
is only 0.3072 cm3 · g−1. These results correlate with
the pore filling effect of the piperazine which was also
reflected by the XRD characterization. As we can see,
the adsorption curve is identical to the desorption curve,
which indicates that materials possess broad mesoporous
structure.49 Although after piperazine impregnation, the
BET surface and total pore volume area were reduced,
high surface areas and total pore volume were observed in
Fe3O4@MCM-41@Zr supported materials. Consequently,
it could be concluded that well-organized mesoporous
Fe3O4@MCM-41@Zr-piperazine-MNPs catalyst with a
high surface area could be obtained in the present study.
Figure 3. The XRD patterns of (a) Fe3O4@MCM-41@Zr-MNPs and
(b) Fe3O4@MCM-41@Zr-piperazine-MNPs.
3862
J. Nanosci. Nanotechnol. 19, 3859–3870, 2019

Pourhasan-Kisomi et al.
Organic/Inorganic Fe3O4@MCM-41@Zr-Piperazine: An Impressive Magnetite Nanocatalyst
Figure 4. The N2 adsorption/desorption isotherm of (a) Fe3O4@MCM-41@Zr-MNPs and (b) Fe3O4@MCM-41@Zr-piperazine-MNPs.
2.5.4. Transmission Electron Microscopy
surrounded by lighter amorphous silica shells bearing met-
als nanoparticles.22ꢂ50
(TEM) Analysis
The TEM images of the prepared functionalized
Fe3O4@MCM-41@Zr-MNPs are shown in Figure 5. The
TEM images disclosed the spherical-like particles of all
samples including agglomeration of dark MNPs cores
2.5.5. EDX Analysis
The EDX results of Fe3O4@MCM-41@Zr-piperazine-
MNPs are depicted in Figure 6 indicating the presence of
IP: 46.148.112.246 On: Mon, 18 Mar 2019 05:40:47
Copyright: American Scientific Publishers
Delivered by Ingenta
Figure 5. The TEM images of Fe3O4@MCM-41@Zr-piperazine-MNPs.
J. Nanosci. Nanotechnol. 19, 3859–3870, 2019
3863

Organic/Inorganic Fe3O4@MCM-41@Zr-Piperazine: An Impressive Magnetite Nanocatalyst
Pourhasan-Kisomi et al.
Figure 6. The EDX profiles of Fe3O4@MCM-41@Zr-piperazine-
MNPs.
Figure 8. The magnetic hysteresis curves of Fe3O4@MCM-41@Zr-
MNPs and Fe3O4@MCM-41@Zr-piperazine-MNPs.
all expected elements (Fe, Si, Zr, N and O). The existence
of Zr and N elements demonstrates the successful loading
of Zr and piperazine in the next step, onto the surface of
the materials.
comparison with Fe3O4@MCM-41@Zr-piperazine-MNPs
(Figs. 7(a, b)).
Since more than 90% of the structure of Fe3O4@MCM-
41@Zr-MNPs consists of iron, silica, and zirconium, so
there will be no particular weight loss in this range of
temperature and the observed change can be related to the
desorption of the physically adsorbed water and removal of
2.5.6. TGA Analysis
Thermogravimetric analysis (TGA) was performed
for characterization of Fe3O4@MCM-41@Zr-MNPs in
IP: 46.148.112.246 On: Mon, 18 Mar 2019 05:40:47
OH groups of the MCM network. However, in the case of
Copyright: American Scientific Publishers
Delivered by Ingenta
Fe3O4@MCM-41@Zr-piperazine-MNPs, due to the addi-
tion of piperazine as an organic compound, a larger weight
loss is observed, which confirms the catalyst structure.
2.5.7. VSM Analysis
Figure 8 represents the obtained magnetic hystere-
sis curves of MNPs. Both Fe3O4@MCM-41@Zr-MNPs
and Fe3O4@MCM-41@Zr-piperazine-MNPs exhibit typi-
cal superparamagnetic behavior, as evidenced by a zero
remanence and coercively on the magnetization loop.23
The large saturation magnetization values of
Fe3O4@MCM-41@Zr-MNPs and Fe3O4@MCM-41@Zr-
piperazine-MNPs were 27.85 emu/g and 35.21 emu/g,
respectively, which is sufficiently high for magnetic sepa-
ration using a conventional magnet. it is deduced that the
decrease in saturation magnetization of Fe3O4@MCM-
41@Zr-piperazine-MNPs is due to the grafted nonmag-
netic organic group, piperazine.
3. RESULTS AND DISCUSSION
3.1. Catalytic Activity
According to the high-grade performance of our newly
reported nanocatalyst in different organic transformations
and due to the lack of an effective catalyst in the
N-tert-butoxycarbonylation of amines in a method with
minimal disadvantages compared to formerly reported
Figure 7. The TGA curves of (a) Fe3O4@MCM-41@Zr-MNPs and
(b) Fe3O4@MCM-41@Zr-piperazine-MNPs.
3864
J. Nanosci. Nanotechnol. 19, 3859–3870, 2019

Pourhasan-Kisomi et al.
Organic/Inorganic Fe3O4@MCM-41@Zr-Piperazine: An Impressive Magnetite Nanocatalyst
Table I. N-tert-butoxycarbonylation of amines catalyzed by Fe3O4@MCM-41@Zr-piperazine-MNPs.
Entry
1
Amine
Product
Time (min)
20
Yield (%)a
80
NH2
NHBoc
2
3
31
25
81
79
NH2
NHBoc
Me
Me
NH2
NHBoc
OMe
OMe
4
5
17
21
85
78
NH2
NHBoc
H
N
Boc
N
IP: 46.148.112.246 On: Mon, 18 Mar 2019 05:40:47
Copyright: American Scientific Publishers
Delivered by Ingenta
6
NH2
NHBoc
20
75
Note: aIsolated yields.
catalysts, we were interested to check the efficacy of this
catalyst on the aforesaid reaction.
most effective reaction conditions, the reaction of aniline
(1 mmol) and di-tert-butyldicarbonate (Boc)2O (1 mmol)
was chosen as an instance reaction and the various condi-
tions including the quantities of the catalyst, solvent and
temperature were tested. eventually, the best conditions are
selected on the basis of these outcomes as represented in
Scheme 1. Any further increase in the catalyst or temper-
ature did not upgrade the reactions times and yields. The
obtained results were tabulated in Table II.
In this line, at first, the efficiency of Fe3O4@MCM-
41@Zr in the begetting of tert-butyl phenylcarbamate and
some other derivatives was surveyed under optimized con-
ditions tabulating in Table I. Due to the weak obtained
results of these reactions that were lower than expected and
in order to improve the mentioned reactions to proceeding
more efficiently, we decided to investigate the influence
of Fe3O4@MCM-41@Zr functionalized with piperazine
in the aforementioned syntheses. In this regard, to pre-
pare these vintages in a more efficient way with slight-
est amount of the catalyst and generally for finding the
Table II. Optimization of the amount of the catalyst, temperature
and solvent in the N-tert-butoxycarbonylation of aniline catalyzed by
Fe3O4@MCM-41@Zr-piperazine-MNPs.
Amount of
catalyst (g)
Temp.
(ꢀC)
Time
(min.)
Entry
Solvent
Conversion
1
2
3
4
5
20
30
40
30
30
–
–
–
–
H2O
50
50
50
rt.
9
7
6
10
11
100
100
100
100
100
Scheme 1. N-tert-butoxycarbonylation of amines catalyzed by
Fe3O4@MCM-41@Zr-piperazine-MNPs.
50
J. Nanosci. Nanotechnol. 19, 3859–3870, 2019
3865

Organic/Inorganic Fe3O4@MCM-41@Zr-Piperazine: An Impressive Magnetite Nanocatalyst
Pourhasan-Kisomi et al.
In order to generalize the best conditions, differ-
ent derivatives of N-tert-butylcarbamates owning diverse
aliphatic, aromatic and heteroaromatic amines were pre-
pared and the results were summarized in Table III. After
termination of the reaction, a small amount of the products
wasted through the work-up process and the percentage
yields got less than conversion yields. By comparison of
the mass of the pure product, we got from the chemi-
cal reaction (actual yield) and the theoretical maximum
(predicted) yield which was calculated from the balanced
equation, the percentage of the product efficiency (per-
centage yield) was calculated. Importantly, note that the
Table III. N-tert-butoxycarbonylation of amines catalyzed by Fe3O4@MCM-41@Zr-piperazine-MNPs.
Entry
1
Amine
Product
Time (min.)
4
Yield (%)a
94
NH2
NHBoc
2
3
4
5
7
9
93
94
90
NH2
NHBoc
NH2
NHBoc
NH2
NHBoc
NH2
NHBoc
5
22
87
IP: 46.148.112.246 On: Mon, 18 Mar 2019 05:40:47
MeO
MeO
Copyright: American Scientific Publishers
OMe
OMe
Delivered by Ingenta
H
N
Boc
N
6
7
8
10
9
91
89
94
H
N
Boc
N
NH2
NHBoc
NHBoc
7
NH2
9
8
91
85
OMe
OMe
NHBoc
10
32
NH2
OMe
OMe
3866
J. Nanosci. Nanotechnol. 19, 3859–3870, 2019

Pourhasan-Kisomi et al.
Organic/Inorganic Fe3O4@MCM-41@Zr-Piperazine: An Impressive Magnetite Nanocatalyst
Table III. Continued.
Entry
11
Amine
Product
Time (min.)
30
Yield (%)a
80
NHBoc
NH2
Br
Br
12
14
91
NH2
NHBoc
Me
Me
13
45
75
NH2
NHBoc
NO2
NO2
14
15
8
85
86
NH2
NHBoc
IP: 46.148.112.246 On: Mon, 18 Mar 2019 05:40:47
Boc
N
29
H
N
Copyright: American Scientific Publishers
Delivered by Ingenta
N
S
N
S
16
17
60
20
65
92
NH2
NHBoc
N
N
NHBoc
NH2
NHBoc
NH2
18
19
20
90
90
90
0
0
0
N
H
N
Boc
N
H
N
Boc
H
N
Boc
N
J. Nanosci. Nanotechnol. 19, 3859–3870, 2019
3867

Organic/Inorganic Fe3O4@MCM-41@Zr-Piperazine: An Impressive Magnetite Nanocatalyst
Pourhasan-Kisomi et al.
Table III. Continued.
Entry
21
Amine
Product
NHBoc
Time (min.)
90
Yield (%)a
0
NH2
22
NHBoc
90
0
NH2
NHBoc
NH2
Note: aIsolated yields.
superparamagnetic nature of the synthesized nanocata-
lyst, as a beneficial and valuable feature, made the iso-
lation and reuse of this catalyst very easy. As is shown
in Figure 9, in the presence of an external magnet,
Fe3O4@MCM-41@Zr-piperazine-MNPs was easily sepa-
rated from its aqueous suspension in a few minutes.
However, as indicated in Table III, primary and
secondary aliphatic amines gave the relevant tert-
butoxycarbonylated products in 87–94% yields in
4–22 min. (entries 1–7). Aromatic amines bearing vari-
ous electron-releasing substituents such as Me, OMe and
Br groups were converted to their N-tert-butylcarbamates
derivatives efficiently in 75–94% yields in 7–45 min.
IP: 46.148.112.246 On: Mon, 18 Mar 2019 05:40:47
(entries 8–14). Aromatic amines owning electron-
Copyright: American Scientific Publishers
withdrawing groups such as 4-nitroaniline (entry 13) pro-
Delivered by Ingenta
ceeded sluggishly in low yield under the stated conditions.
Heterocyclic amines like imidazole (entry 15) obtained the
favorable products in quantitative yields and the protec-
tion of amino groups attached aromatic heterocycle went
on temperately (entry 16) and preserving the acid sensitive
moieties such as methoxy group is due to enough mild-
ness of the reaction conditions (entries 5, 9 and 10). Also,
amines containing two adjacent amino groups were favor-
ably protected (entry 17). No isocyanate or urea formation
Figure 9. Photographs of an aqueous suspension of Fe3O4@MCM-
41@Zr-piperazine-MNPs before (a) and after (b) magnetic capture.
Table IV. Comparison of the proficiency of Fe3O4@MCM-41@Zr-piperazine-MNPs in the N-tert-butoxycarbonylation of aniline with previously
reported catalysts in the studied reactions.
Entry
Catalyst
Amount
Condition
Time (min)
Yield (%)
[Ref.]
1
2
3
4
5
6
7
8
Nano-Fe3O4
Yttria-zirconia
ZrCl4
Iodine
ꢀ-Cyclodextrine
RiH
0.03 mol
0.02 Wt
0.1 mol
0.1 mol
0.1 mol
0.05 g
0.1 mol
0.2 mmol
0.1 mol
0.1 mol
0.1 mol
0.2 mmol
0.03 g
EtOH/r.t.
CH3CN/r.t.
CH3CN/r.t.
Solvent-free/r.t.
H2O/r.t.
Solvent-free/r.t.
EtOH/30–40 ꢀC
n-Hexane/r.t.
EtOH/r.t.
20
14 (h)
3
30
150
10
8
60
15
300
40
99
90
95
95
75
95
95
97
90
80
95
95
94
[51]
[52]
[53]
[54]
[55]
[56]
[57]
[58]
[59]
Thioglycolic acid
Saccharin sulfonic acid
[Dsim]HSOa4
9
10
11
12
13
[H2-cryptand 222](Br3ꢁ2b
Thiourea
CH3CN/r.t.
[60]
[61]
[62]
Toluene/60–70 ꢀC
Solvent-free/r.t.
Solvent-free/50 ꢀC
[Py][OTf]c
25
7
Fe3O4@MCM-41@Zr-piperazine
[This work]
Notes: a1,3-Disulfonic acid imidazolium hydrogen sulfate, bA kind of macrobicyclic crown ethers, cPyridinium 2,2,2- trifluoroacetate.
3868
J. Nanosci. Nanotechnol. 19, 3859–3870, 2019

Pourhasan-Kisomi et al.
Organic/Inorganic Fe3O4@MCM-41@Zr-Piperazine: An Impressive Magnetite Nanocatalyst
products, (vi) the modest to excellent yields of the syn-
thesized products, (vii) good performance of this method
for different substrates including the majority of com-
plex or acid-sensitive ones, and (viii) facile separation of
this superparamagnetic catalyst from the reaction mixture
using an external magnetic field.
Having such superiorities of our newly proposed cata-
lyst makes it a useful substitute to the former methodolo-
gies for the scale-up of these reactions. We are probing
further applications of this superparamagnetic nanocatalyst
for the other sorts of organic reactions in our laboratory.
Figure 10. Reusability of Fe3O4@MCM-41@Zr-piperazine-MNPs in
the N-tert-butoxycarbonylation of aniline.
Acknowledgments: We are thankful to the Research
Council of the University of Guilan for the partial support
of this research.
was observed at all (according to IR and NMR spectro-
scopies). In this methodology, no rearrangement and elim-
ination by-products were perceived at all. It is notable
that bearing low nucleophilicity of some amines due to
the probability of strong withdrawing electron and steric
impression, cause them to resistant to this conversion and
being preserved in the reaction mixture (entries 18–22).
In order to reveal the proficiency of Fe3O4@MCM-
41@Zr-piperazine-MNPs as a catalyst, this method was
compared with previously reported data in terms of
gained results and applied reaction conditions for N-tert-
butoxycarbonylation of aniline (Table IV). Accordingly, it
References and Notes
1. P. J. Kocienski and G. T. Verlag, Protecting Groups, Stuttgart, New
York (2000); T. W. Greene and P. G. M. Wuts, Protective Groups in
Organic Synthesis, 2nd edn., Wiley, New York (1999); C. W. Jones,
K. Tsuji, and M. E. Davis, Nature 393, 52 (1998).
2. R. Neelarapu and P. A. Petukhov, Tetrahedron 68, 7056 (2012).
3. D. J. Upadhyaya, A. Barge, R. Stefania, and G. Cravotto, Tetrahe-
dron Lett. 48, 8318 (2007).
4. M. Oliverio, M. Nardi, P. Costanzo, M. L. Di Gioia, and A. Procopio,
Sustainability 10, 721 (2018).
5. G. Sartori, R. Ballini, F. Bigi, G. Bosica, R. Maggi, and P. Righi,
Chem. Rev. 104, 199 (2004); B. J. Melde, B. T. Holland, C. F.
Blanford, and A. Stein, Chem. Mater. 11, 3302 (1999).
is deduced that the proposed procedure using our men-
IP: 46.148.112.246 On: Mon, 18 Mar 2019 05:40:47
6. P. Saravanan and V. K. Singh, Tetrahedron Lett. 40, 2611 (1999).
Copyright: American Scientific Publishers
tioned nanocatalyst is preferable in yields, reaction times
Delivered by 7In. gSe. Knt.aDe, Tetrahedron Lett. 45, 2919 (2004).
and catalyst amount in addition to compatibility with the
environment and easy separation via an external magnetic
field.
8. S. Sunitha, S. Kanjilal, S. P. Reddy, and B. N. Prasad, Tetrahedron
Lett. 49, 2527 (2008).
9. A. Sarkar, S. R. Roy, N. Parikh, and A. K. Chakraborti, J. Org.
Chem. 76, 7132 (2011).
10. F. Shirini, S. V. Atghia, and M. Ghazi Jirdehi, Chin. Chem. Lett.
24, 34 (2013).
3.2. Reusability of the Catalyst
11. F. Shirini, S. Akbari-Dadamahaleh, A. Mohammad-Khah, and
A. Aliakbar, C. R. Chim. 17, 164 (2014).
12. F. Shirini, S. Akbari-Dadamahaleh, and A. Mohammad-Khah, Phos-
phorus, Sulfur Silicon Relat. Elem. 189, 577 (2014).
13. M. Seddighi, F. Shirini, and O. Goli-Jolodar. C. R. Chim. 19, 1003
(2016).
14. T. Ghauri Koodehi, F. Shirini, and O. GoliJolodar, J. Iran Chem.
Soc. 14, 443 (2017).
15. V. Polshettiwar and R. S. Varma, Green Chem. 12, 743 (2010).
16. G. Q. Lu and X. S. Zhao, Nanoporous Materials, Science and Engi-
neering, Series of Chemical Engineering, Imperial College Press,
London, UK (2004), Vol. 4.
To investigate the recyclability of the catalyst, it was
reused five times in the N-tert-butoxycarbonylation of ani-
line. The catalyst was magnetically recovered after each
run, washed with ethanol, dried in air prior to use and
tested for its activity in the subsequent run. This proce-
dure was repeated five times and each time the mentioned
product was obtained by the recovered catalyst with the
slight change in the reaction time and yield as shown in
Figure 10.
17. M. Sharifi, J. Schneider, and M. Wark, Microporous Mesoporous
Mater. 151, 506 (2012); A. Mobinikhaledi and M. A. Bodaghi Fard,
Acta Chim. Slov. 57, 931 (2010).
18. A. I. Carrillo, E. Serrano, R. Luque, and J. Garcia-Martinez, Appl.
Catal. A 483, 383 (2013).
4. CONCLUSION
In conclusion, Fe3O4@MCM-41@Zr modified with piper-
azine, a stable and highly active superparamagnetic
nanocatalyst, has been used to surveying its capability
in N-tert-butoxycarbonylation of amines. According to
the obtained results, this protocol was done successfully
and has the following advantages: (i) preparing a vari-
ety of N-tert-butylcarbamates derivatives under the mild
and solvent-free conditions. (ii) moderately short reaction
times, (iii) obtaining pure products, (iv) high chemos-
electivity, (v) not observing the formation of any side
19. T. Conesa, R. Mokaya, J. M. Campelo, and A. A. Romero, Chem.
Commun. 17, 1839 (2006).
20. D. Kumar, K. Schumacher, C. du Fresne von Hohenesche, M. Grün,
and K. K. Unger, Colloid Surface A 187, 109 (2001).
21. N. I. Cuello, V. R. Elías, C. E. Rodriguez Torres, M. E. Crivello,
M. I. Oliva, and G. A. Eimer, Microporous Mesoporous Mater.
203, 106 (2015).
22. N. Saadatjoo, M. Golshekan, S. Shariati, H. Kefayati, and P. Azizi,
J. Mol. Catal. A: Chem. 377, 173 (2013).
J. Nanosci. Nanotechnol. 19, 3859–3870, 2019
3869

Organic/Inorganic Fe3O4@MCM-41@Zr-Piperazine: An Impressive Magnetite Nanocatalyst
Pourhasan-Kisomi et al.
23. H. Kefayati, M. Golshekan, S. Shariati, and M. Bagheri, Chin.
J. Catal. 36, 572 (2015).
45. Zh. Miao, L. Xu, H. Song, H. Zhao, and L. Chou, Catal. Sci. Tech-
nol. 3, 1942 (2013).
24. B. M. Trost, M. Beller, C. Bolm (eds.), Transition Metal for
Organic Reaction, WILEY-VCH Verlag GmbH, D-69469, Weinheim,
Germany (1998).
25. A. K. Chakraborti and R. Gulhane, Synlett. 4, 627 (2004).
26. S. Z. M. Shamshuddin, Synlett. 2, 361 (2005).
27. M. Beller and C. Bolm, Transition Metals for Organic Synthesis,
Wiley-VCH, Weinheim (2004).
46. X. Xu, C. Song, J. M. Andresen, B. G. Miller, and A. W. Scaroni,
Energy and Fuels 16, 1463 (2002).
47. N. La-Salvia, J. J. Lovón-Quintana, and G. P. Valença, Braz.
J. Chem. Eng. 32, 489 (2015).
48. M. Manzano, V. Aina, C. O. Arean, F. Balas, V. Cauda, M. Colilla,
M. R. Delgado, and M. Vallet-Reg, Chem. Eng. J. 137, 30
(2008).
28. C. M. Vogels and S. A. Westcott, Curr. Org. Chem. 9, 687 (2005).
29. B. C. G. Soderberg, Coord. Chem. Rev. 248, 1085 (2004).
30. Z.-H. Zhang and T.-S. Li, Current Org. Chem. 13, 1 (2009).
31. X. X. Wang, F. Lefebvre, P. Patarin, and J. M. Basset, Microporous
Mesoporous Mater. 42, 269 (2001).
32. X. Yang, L. Zhou, C. Chen, and J. Xu, Mater. Chem. Phys. 120, 42
(2010).
33. W.-H. Zhang, J.-L. Shi, L.-Z. Wang, and D.-S. Yan, Mater. Lett.
46, 35 (2000).
34. R. Pourhasan-Kisomi, F. Shirini, and M. Golshekan, Appl.
Organomet. Chem. https://doi.org/10.1002/aoc.4371.
35. F. Shirini, M. A. Zolfigol, and E. Mollarazi, Synth. Commun.
36, 2307 (2006).
36. F. Shirini, M. A. Zolfigol, and A. Pourhabib, Russ. J. Org. Chem.
39, 1191 (2003).
37. F. Shirini and F. Kamali, Appl. Organomet. Chem. 32, 1 (2017).
38. F. Shirini, M. A. Zolfigol, and A. Safari, J. Chem. Res. (S) 2006, 154
(2006).
49. L. Li., S. Yu, F. Liu, J. Yang, and S. Zhaug, Catal. Lett. 100, 227
(2005).
50. M. Abdollahi-Alibeik and G. Ahmadi, Res. Chem. Intermed.
41, 8173 (2015).
51. M. A. Zolfigol, A. R. Moosavi-Zare, P. Moosavi, V. Khakyzadeh,
and A. Zare, C. R. Chim. 16, 962 (2013).
52. R. K. Pandey, S. P. Dagade, R. K. Upadhyay, M. K. Dongar, and
P. Kumara, Arch. Org. Chem. 7, 28 (2002).
53. G. V. M. Sharma, J. Janardhan Reddy, P. Sree Lakshmi, and P. Radha
Krishna, Tetrahedron Lett. 45, 6963 (2004).
54. R. Varala, S. Nuvula, and S. R. Adapa, J. Org. Chem. 71, 8283
(2006).
55. M. S. Reddy, M. Narender, Y. V. D. Nageswar, and K. R. Rao,
Synlett 1110 (2006).
56. F. Shirini, S. Akbari-Dadamahaleh, A. Mohammad-Khah, and A. R.
Aliakbar, C. R. Chim. 17, 164 (2014).
57. S. Khaskar, S. M. Vahdat, M. Tajbakhsh, F. Jahani, and A. Heydari,
Tetrahedron Lett. 51, 6388 (2010).
39. A. Pradeep and G. Chandrasekaran, Mater. Lett. 60, 371 (2006).
40. W. Que, Y. Zhou, Y. L. Lam, Y. C. Chan, and C. H. Kam, Thin Solid
Films 358, 16 (2000).
41. A. V. Rao, R. R. Kalesh, and G. M. Pajonk, J. Mater. Sci. 38, 4407
(2003).
58. F. Shirini, M. A. Zolfigol, and M. Abedini, J. Iran. Chem. Soc. 7, 603
(2010).
59. M. A. Zolfgol, V. Khakyzadeh, A. R. Moosavi-Zare, G. Chehardoli,
F. Derakhshan-Panah, A. Zare, and O. Khaledian, Sci. Iran 19, 1584
(2012).
42. S. Ghodke, R. Patel, and U. Chudasama, Inter. J. Innov. Res. Sci.
60. Gh. Chehardoli, M. A. Zolfigol, V. Khakyzadeh, R. Golbedaghi,
N. A. Hall, and A. G. Blackman, J. Chin. Chem. Soc. 58, 538
IP: 46.148.112.246 On: Mon, 18 Mar 2019 05:40:47
Eng. Tech. 4, 18735 (2015).
43. O. Alver, C. Parlak, and M. Senyel, Spectrochim. Acta MDole. Bliivoemroel.d by Ingenta
Copyright: American Scientific Publishers
(2011).
Spectrosc. 67, 793 (2007).
61. S. Khaksar, A. Heydari, M. Tajbakhsh, and S. M. Vahdat, Tetrahe-
44. J. H. Jang, H. B. Lim, Microchem, L. Chou, Catal. Sci. Technol.
3, 1942 (2013).
dron Lett. 49, 3527 (2008).
62. S. Karimian and H. Tajik, Chin. Chem. Lett. 25, 218 (2014).
Received: 19 May 2018. Accepted: 15 June 2018.
3870
J. Nanosci. Nanotechnol. 19, 3859–3870, 2019