Copper-amino group complexes supported on silica-coated magnetite nanoparticles: Efficient catalyst for oxidative amidation of methyl arenes

Article abstract of DOI:10.1039/c7nj02257c

Magnetite nanoparticles coated with mesoporous silica, Fe₃O₄@SiO₂, were prepared. Surface functionalization of this core-shell nanocomposite with (3-aminopropyl)trimethoxysilane (APTMS) followed by its reaction with Cu(OAc)₂ was used to develop a new heterogeneous copper complex (Fe₃O₄@SiO₂-APTMS-Cu). The structure and composition of the synthesized nanocatalyst were characterized by FTIR, SEM, VSM, TEM, XRD, and ICP analyses. The catalytic activity of the synthesized catalyst was probed in the oxidative amidation reaction of methyl arenes with amine hydrochloride salts. Various primary, secondary, and tertiary amides were prepared by this method. The magnetic properties of this catalyst lead to easy separation as well as providing significant catalyst recyclability. The catalyst is reusable 6 times without significant decrease in its catalytic activity.

Full text of DOI:10.1039/c7nj02257c

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ISSN 1144-0546
PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
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Copper-Amino Groups Complex Supported on Silica Coated
Magnetite Nanoparticles: Efficient Catalyst for Oxidative
Amidation of Methyl Arenes
Received 00th January 20xx,
Accepted 00th January 20xx
Meghdad Karimia,*, Leila Ghandia, Dariush Saberib, Akbar Heydaria,*
DOI: 10.1039/x0xx00000x
Abstract
www.rsc.org/
Magnetite nanoparticles coated with mesoporous silica, Fe3O4@SiO2, were prepared. Surface
functionalization of this core-shell nanocomposite with (3-aminopropyl) trimethoxysilane (APTMS)
followed by its reaction with Cu(OAc)2 was resulted to develop a new heterogeneous copper complex
(Fe3O4@SiO2-APTMS-Cu). The structure and composition of synthesized nanocatalyst were characterized
by FTIR, SEM, VSM, TEM, XRD, and ICP analyses. Catalytic activity of the synthesized catalyst was probed in
oxidative amidation reaction of methyl arenes with amine hydrochloride salts. Various primary, secondary,
and tertiary amides were prepared by this method. Magnetic properties of this catalyst lead to easy
separation as well as providing significant recyclability of it. The catalyst is reusable for 6 times without
significant decrease in its catalytic activity.
Keywords: Oxidative Amidation, Magnetic Nanoparticles, Methyl anenes, Copper, Magnetic separation.
amide functionality, particularly waste-free and suitable for
fragment coupling, are in great demand.
1. Introduction
Reaction between carboxylic acids and amines without change in
the oxidation level is traditional approaches for amide synthesis. It
can be achieved through direct condensation reaction of carboxylic
acids with amines, associated with available compounds, water as
a side product and needs very high temperature.
The amide bond plays a major role in the elaboration and
composition of biological systems. It is one of the key structural
units in a wide range of biological compounds, such as peptides,
proteins, natural products agrochemicals and pharmaceuticals, and
is also widely employed in synthetic polymers, chemical
intermediates, intensifiers of perfume, anti-block reagents,
detergents, lubricants and color pigments for inks [1]. Being
present in 25% of available drugs, with amidation reactions being
among the most commonly used reactions in medicinal chemistry.
A recent report by the American Chemical Society Green Chemistry
Institute Pharmaceutical Roundtable (ACS GCIPR) has found that
amide formation, avoiding poor atom economy reagents, is the
priority area of research for the pharmaceutical industry [2].
Furthermore, the favorable properties of amides, such as high
polarity, stability and conformational diversity, make it one of the
most popular and reliable functional groups in all branches of
organic chemistry. Improved methods for the synthesis of an
On the other hand carboxylic acid and the amine can be coupled
directly by using a stoichiometric amount of activating agents like
carbodiimides [3] or in activated form (such as acid chlorides and
anhydrides) or rearrangement reactions induced by an acid or
base[4].
However, these all produce a stoichiometric amount of waste by-
product. To address these challenging problems, a number of
elegant methods have been developed affording innovative
strategies for amide fabrication, including Staudinger reaction [5],
the Schmidt reaction [6], Beckmann rearrangement [7],
hydroamination of alkynes [8], transamidation of primary amides
[9], amino carbonylation of haloarenes [10], catalytic acylation of
amines with carboxylic acids [11], dehydrogenative amidation of
alcohols [12], and oxidative amidation reactions [13]. Of the above
methods, oxidative amidation is more attractive than other
traditional procedures, as it provides a direct route for the
synthesis of carboxamides. In this regard, direct amidation of
aldehydes and alcohols with amines [14], carboxylic acids, azoles,
and alcohols with formamides [15], and alkynes with amines (or
azides) [16] have been reported. Bantreil et al. used an iron-
catalyzed system for benzamide synthesis from benzyl alcohol [17].
aChemistry Department, Tarbiat Modare University, Tehran, Iran
P.O. Box 14155-4838 Tehran, Iran, Tel: (+98) 21-82883444
E-mail: heydar_a@modares.ac.ir, meghdadkarimi1365@gmail.com
bFisheries and Aquaculture Department, College of Agriculture and Natural Resources,
Persian Gulf University, Bushehr 75169, Iran.
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Recently, Mizuno and co-workers demonstrated the direct aerobic
oxidative amidation of methylarenes using urea as the amine
source in the presence of amorphous MnO2 as the catalyst [18].
Also, Vanjari et al. established a new procedure for amide bond
formation through a C-H activation strategy [19]. Following on
from this research, and as part of our ongoing research on
oxidative amidation reactions [20], the use of catalytic reactants
with higher selectivity is one of the 12 principles of green
chemistry. As is well documented, catalytic methods are greener
than approaches in which stoichiometric reagents are exploited
[21]. Owing to improved efficacy, homogeneous catalysis has
grabbed more attention and interest than heterogeneous
approaches [22]. Given the cost and toxicity associated with metals
used as catalysts in homogeneous methods, together with the loss
of catalyst after one run, despite being widely used in academia,
these approaches have scarcely been utilized in industry. To
compensate for the deficiencies related to homogeneous catalysts,
the use of either heterogeneous catalysis or heterogenized
homogeneous catalysts [23] (tethering of homogeneous catalyst on
organic or inorganic supports in the liquid phase) has prevailed
[24]. Today, heterogeneous catalysis has opened up a new avenue
to chemists as a fundamental procedure from the standpoint of
recovery and product purification; especially in the production of
fine chemicals [25]. It is also worth mentioning that the use of
catalyst in more than one run is environmentally and economically
advantageous. In this content, here, we are going to report the
synthesis and characterization of a new magnetic heterogeneous
nanocatalyst, Fe3O4@SiO2-APTMS-Cu, and employed as a catalyst
in amide bond formation via oxidative amidation of methylarenes.
performed using thermal analyzer with a heating rate of 20 °C
min−1 over a temperature range of 25–1100 °C under flowing
compressed nitrogen. Transmission electron microscopy (TEM)
measurements were carried out at 120 kV (Philips, model CM120).
2.2. Preparation of the magnetic Fe3O4 (MNPs) coated by silica
nanoparticles (MNPs-SiO2)
Procedure for catalyst synthesis has been reported previously [26].
Briefly, 5 mmol FeCl3.6H2O and 2.5 mmol FeCl2.4H2O salts were
dissolved in 100 mL deionized water under vigorous stirring (800
rpm) then NH4OH solution (25%, w/w, 30 mL) was added to the
above mixture at room temperature until the pH was raised to 11.
The addition of NH4OH solution followed to maintain the reaction
pH between 11 and 12 at which a black suspension was formed.
The resulting black dispersion was continuously stirred for 1 h at
room temperature and then refluxed for 6 h. Coating of a layer of
silica on the surface of the Fe3O4 nanoparticles was achieved by
adding ethanol (40 mL) to purified nanoparticles then heated for 1
h at 40oC. Subsequently, tetraethyl orthosilicate (TEOS, 10 mL) was
charged to the reaction vessel, and the mixture was continuously
stirred for 24 h. The silica-coated nanoparticles were collected by a
magnet, followed by washing five times with EtOH, diethyl ether
and drying at 100ºC in vacuum for 12h.
2.3. Synthesis of n-propylamine-copper complex (APTMS-Cu)
A
mixture of 3-aminopropyl trimethoxysilane (8 mmol) and
Cu(OAc)2.2H2O (4 mmol) in methanol (20 mL) was stirred at room
temperature under an argon atmosphere. After 1 hour of reaction
time, the resulting complex was formed.
2.4. Synthesis of covalently anchored APTMS-Cu complex on the
surface of silica-modified magnetite nanoparticles (Fe3O4@SiO2-
APTMS-Cu)
2. Experimental section
2.1. General
All materials were purchased from Merck Company and used with
no more purification. The reaction was precisely monitored by
analytical thin layer chromatography (TLC) using ethyl acetate and
n-hexane as eluents. Due to needs for achieving final pure and
isolated target molecules, a scaled-up thin layer chromatography
was Merck 0.2mm of silica gel 60F-254 Al-plates.
Fe3O4@SiO2 (1 g) added to a solution of APTMS-Cu complex (2
mmol) in methanol (20 mL), and then stirred at room temperature
and under an argon atmosphere for 24 hours. Afterward, the
desired copper complex was magnetically separated and washed
thoroughly with ethanol and dried at room temperature under
vacuum.
Spectral analysis performed with aid of Infrared spectra (IR) on a
Shimadzu FT-IR-8400S spectrometer and in following for definite
1
2.5. General procedure for the oxidative amidation of
methylarenes with amine hydrochloride salts
characterization of all first-made products with H NMR (500 MHz)
and 13C NMR (125 MHz) spectra recorded on Bruker DRX-500
Avance spectrometers with CHCl3 and DMSO as solvent at ambient
temperature(relative to TMS as internal standard). Primary results
for reaction progress were obtained by Gas Chromatography (GC)
(Yonglin 6100; BP-5; 30m×0.25×mm×0.25μm) with toluene as
general solvent for injection and nitrogen as inert carrier gas. All
yields referred to the isolated products. The mentioned catalyst
EDX spectra were recorded on an Oxford Instrumental® and also
SEM images were obtained on Zeiss-Sigma VP 500. The magnetic
To a mixture of catalyst (40 mg, 0.5 mol%), amine hydrochloride
salt (1 mmol), toluene (0.5 mL), and CaCO3 (1.1 equiv.) in
acetonitrile (2 mL) were added TBHP (70 wt % in H2O, 8 equiv.)
drop wise under argon atmosphere at room temperature. The
reaction vessel was capped and allowed to stir at 80 °C for 10 h.
The progress of the reaction was monitored by TLC. After
completion, the reaction mixture was allowed to cool down at
room temperature. The reaction mixture was diluted with ethyl
acetate and the catalyst was easily separated from the reaction
mixture by using an external magnet and washed twice with ethyl
acetate. The combined organic layers were concentrated in
properties
were
measured
with
a
vibrating
magnetometer/alternating gradient force magnetometer (MD Co.,
Iran, www.mdk-magnetic.com). Thermogravimetric analysis was
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vacuum and the resulting residue was purified by column
chromatography. All compounds were identified by melting point
(in some cases), IR, CHN, Mass, 1H-NMR and 13C-NMR. The spectral
data of known compounds were compared with those reported in
literatures.
stretching vibrations appeared at about 2923cm−1 (C–H stretching
vibrations) in the FT-IR spectrum. The signals appeared at
1407.44cm−1 region can be assigned to the N–H bending and
1647.61cm−1
.
3. Results and discussions
As shown in scheme 1, APTMS-Cu complex covalently on the
surface of silica-modified magnetite nanoparticles was prepared in
three steps. At first, Fe3O4@SiO2 core-shell nanoparticles were
prepared by the chemical co-precipitation method for making
magnetite nanoparticles followed by the deposition of SiO2 shell on
the magnetite core with the Stober method. (Scheme 1, A). On the
other hand, the reaction between 3-aminopropyl trimethoxysilane
and Cu(OAc)2 resulted to the APTMS-Cu complex (Scheme 1, B).
The final structure of the catalyst was obtained via the reaction of
A with B (for details see experimental section).
Fig.1. FT-IR spectra of Fe3O4 (Black), Fe3O4@SiO2 (red), and Fe3O4@SiO2-APTMS-Cu2+
(blue)
3.1.2. Vibrating sample magnetometry (VSM)
The synthesized core-shell catalyst possesses sufficient
superparamagnetic characteristic for practical applications.
Magnetic hysteresis measurements were done in an applied
magnetic field at r.t, with the field sweeping from −10000 to
+10000 Oe using a vibrating sample magnetometer (VSM) as a
scientific instrument for measuring magnetic properties. As shown
in Fig. 2, the M (H) hysteresis loop for the samples was completely
reversible. The magnetic saturation values of functionalized
nanoparticles are 32.71, 10.41 and 7.24 for Fe3O4, Fe3O4@SiO2 and
Fe3O4@SiO2-APTMS-Cu2+ respectively.
Scheme.1. Schematic synthesis of Fe3O4@SiO2-APTMS-Cu
3.1. Characterization of heterogenized Cu catalyst
After Preparation, some different microscopic and spectroscopic
techniques such as XRD, FT-IR, VSM, ICP, TGA, SEM and TEM were
used to confirm the structure of the catalyst.
3.1.1. FT-IR spectroscopy
FT-IR spectra of the Fe3O4 (black), Fe3O4@SiO2 (red), and
Fe3O4@SiO2-APTMS-Cu2+ (blue) are depicted in Fig. 1. On the
spectrum region from 3650 cm-1 to 3200 cm-1 and a band appears
at 3424 cm-1 due to O-H vibrations of water [26].
For Fe3O4, the analysis indicated absorption peaks at 578 cm−1
and 493 cm−1 corresponding to the Fe–O vibration related to
the magnetite phase [27]. This result strongly supposed to
assignment of the synthesized iron oxide nanoparticle cluster
as Fe3O4.
Fig.2. VSM curves of Fe3O4 (Black), Fe3O4@SiO2 (red), and Fe3O4@SiO2-APTMS-Cu2+
(blue)
3.1.3. Thermogravimetric/differential thermal analyses
(TGA/DTA)
Quantitative determination of the organic groups loaded on the
surface of nanoparticles was studied by thermo-gravimetric
analysis (Fig. 3). The two main peaks can be seen in this spectrum:
The first one, appeared below 200 ºC, shows a weight loss of 3.9%
and is probably related to the physically adsorbed water on the
catalyst surface. The second one has appeared in the temperature
range of 400-600 ºC that is related to the organic groups
immobilized on inorganic support. This peak shows a weight loss of
3.5% that is equivalent to 0.48 mmol of APTMS per gram of
The covalent bond between silane and magnetite surface in
Fe3O4@SiO2 (red line) is underlined by the appearance of the band
at 1090cm−1 characteristic for Si–O groups. In more details,
absorption bands at 800-900cm−1 are associated to vibrating bands
for Si–O–Si groups. These results indicate that SiO2 layer is formed
on the surfaces of Fe3O4. The presence of anchored propyl groups
about Fe3O4@SiO2-APTMS-Cu2+ (blue), that were confirmed by
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catalyst. Through the inductively coupled plasma atomic emission
spectroscopy (ICPAES), the Cu loading for Fe3O4@SiO2-APTMS-Cu2+
was found to be 0.5 mmol per gram.
Fig.5. TEM micrographs of Fe3O4@SiO2-APTMS-Cu2+
3.1.6. Energy-Dispersive X-ray spectroscopy (EDX) analysis
To identify the elemental composition of Fe3O4@SiO2-APTMS-Cu2+,
an energy-dispersive X-ray spectroscopy (EDX) was obtained. As
can be seen in Fig. 6, EDX pattern obviously approves the well-
dispersion of Fe3O4 nanoparticles. Chemical characterization of the
typical sample showed it was consisted of iron (6.67 % mol), silicon
(3.73% mol), oxygen (54.10% mol), copper (1.31% mol) and carbon
(39.25% mol).
Fig.3. Thermogravimetric and differential thermogravimetric analysis of the catalyst
3.1.4. Scanning Electron Microscopy (SEM) analysis
As illustrated in Fig. 4, the particle size was studied by scanning
electron microscopy (SEM) and the identification of Fe3O4 (a),
Fe3O4@SiO2 (b) and Fe3O4@SiO2-APTMS-Cu2+ (c) before and after
(d) reaction was based on the analysis of SEM images (Fig.4.). It
was confirmed that the catalyst was made up of nanometer-sized
particles distributed between 40 nm to 150nm in size. It also shows
that the Fe3O4@SiO2-APTMS-Cu2+ nanoparticles have a core-shell
structure and spherical morphology and after 5cycle this
morphology is stable.
Fig.6. (a) EDX pattern of surface elements of functionalized nanoparticles; (b) Weight
percent of various elements on the surface of Fe3O4@SiO2-APTMS-Cu2+ NPs from EDX
analysis.
3.1.7. X-ray Powder Diffraction (XRD) patterns
X-ray diffraction (XRD) was used to determine the crystalline
structure of the magnetic nanoparticles obtained by hydrothermal
method. (Fig.7.) shows the results of X-ray diffraction analysis for
the catalyst. Diffraction peaks at around 30.13o, 37.29o, 43.73o,
53.61o, 57.01o, 65.09o and 76.81o which can be indexed as {220},
{311}, {400}, {422}, {511} and {440} lattice planes of cubic
magnetite, respectively (JCPDS 19-629). Diffraction peak at 21o can
be indexed to (223) reflection of the SiO2. The average crystallite
size D was calculated using the Debye–Sherrer formula D =
Kλ/(βCosθ), where K, λ, β and θ denote to Sherrer constant, X- ray
wavelength, the peak width of half-maximum, and the Bragg
Fig.4. SEM Analysis of the Fe3O4 (a), Fe3O4@SiO2 (b) and Fe3O4@SiO2-APTMS-Cu2+
before (c) and after reaction (d)
3.1.5. Transmission electron microscopy (TEM)
Transmission electron microscopy (TEM) confirmed the formation
of single-phase Fe3O4 nanoparticles, with spherical morphology
and a size range of 15 nm (Fig.5.).
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diffraction angle. The crystallite size thus obtained from this
equation was found to be about 37.06 nm.
Fig. 9 BJH desorption dV/dD Pore Volume plot
3.2. Application of Fe3O4@SiO2-APTMS-Cu2+ NPs for the oxidative
amidation reaction
Fig.7. XRD pattern of Fe3O4 (Black) Fe3O4@SiO2 (red) and Fe3O4@SiO2-APTMS-Cu2+
(blue)
3.2.1. General survey to investigate the best primary condition of
reaction
3.1.8. Brunauer–Emmett–Teller (BET) analysis
In order to acquire the optimal reaction conditions, the reaction of
oxidative amidation toluene, different experiments were carried out
for selection of the most ideal solvent, oxidant, base, most assorted
running temperature and also the shortest time for optimal
The specific surface area was measured using the BET method and
the pore size distribution was calculated using the classical
Barrett–Joyner–Halenda model. As shown in Fig. 8, the adsorption
desorption curves for the composite displayed the type IV
adsorption–desorption isotherms, which is the typical
characteristics of mesoporous materials. And the BET specific
surface area is calculated 28m2/g. The composite also showed the
narrow pore size distribution, and the pore size is 4.1 nm
condition (Scheme.2). The synthesized of
N-morpholine benzamide
(compound 1l) was chosen as model reaction to optimize the
oxidative amidation conditions (Scheme 2). The first reaction was
carried out under the following conditions: 20 mg catalyst, CaCO3 as
base, TBHP as oxidant at room temperature under Ar atmosphere for
8 h in different solvents (2 ml) and CH3CN/Toluene (4/1) chosen as
suitable solvent for the reaction according to yield of transformation
(20%, Fig.10).
Scheme.2. Model reaction for oxidative amidation of morpholine
Fig.8. N2 adsorption–desorption isotherms of functionalized magnetic nanoparticles
Sample showed middle average pore diameter (12.3 nm), however
a close look to BJH desorption dV/dD pore volume plot reveals a
sharp peak with narrow pore size distribution centered at
∼12.3
nm (Fig. 9). This might be uniform distribution of silica layer since
linker steady functionalization follows it.
Fig.10. Checking the effect of different solvents on reaction yield (reaction was run
with 20 mg catalyst, morpholine hydrochloride salt (1 mmol), CaCO3 (2.2 equiv.),
solvent/Toluene (2 ml, in a ratio of 4/1 respectively), TBHP (8 equiv.), 8 h at room
temperature under Ar atmosphere. Yield determined by GC-FID spectroscopy with an
internal standard).
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Screening a range of bases revealed that Ca2CO3 performed the
best among the other bases including Na2CO3, K2CO3, NaOH, Et3N,
CaCO3, and Cs2CO3 (20%, Fig.11).
Fig. 13. Checking the effect of different oxidants on reaction yield (reaction was run
with 20 mg catalyst, morpholine hydrochloride salt (1 mmol), CaCO3 (2.2 equiv.),
oxidant (8 equiv.), 6 h in CH3CN/Toluene (2 ml, in a ratio of 4/1 respectively) as
solvent. Yield determined by GC-FID spectroscopy with an internal standard).
The reaction was carried out in the presence of 10, 20, 30, 40 and
50 mg of catalyst at the same conditions, separately, in which
resulted a serious improvement of the capitulate (91%, Fig. 14).
Fig. 11. Checking the effect of different bases on reaction yield (reaction was run with
20 mg catalyst, morpholine hydrochloride salt (1 mmol), base (2.2 equiv.),
CH3CN/Toluene (2 ml, in a ratio of 4/1 respectively), TBHP (8 equiv.), 8 h at room
temperature under Ar atmosphere. Yield determined by GC-FID spectroscopy with an
internal standard).
Role of the temperature was probed. It was observed that the
increment of the temperature to 80 °C enhances the yield to a
small amount, whereas reducing it to room temperature, leads to a
significant reduction in the efficiency of the reaction (61%, Fig.12).
Fig. 14. Checking the amount of catalysis on reaction yield (reaction was run with
different mass of catalyst, morpholine hydrochloride salt (1 mmol), CaCO3 (2.2 equiv.),
TBHP (8 equiv.), 6 h in CH3CN/Toluene (2 ml, in a ratio of 4/1 respectively) as solvent.
Yield determined by GC-FID spectroscopy with an internal standard).
To understand the substrate scope of this reaction, a wide range of
aldehydes and amine hydrochloride salts were allowed to react
under the following conditions: (1 mmol), amine hydrochloride salt
(1 equiv.), CH3CN/Toluene (2 ml, in a ratio of 4/1 respectively),
CaCO3 (2.2 equiv.), TBHP (8 equiv.), Catalyst (40 mg, 2 mol%), at 80
°C under Ar. atmosphere (91%, Table 1).
Fig. 12. Checking the effect of temperature on reaction yield (reaction was run with 20
mg catalyst, morpholine hydrochloride salt (1 mmol), CaCO3 (2.2 equiv.),
CH3CN/Toluene (2 ml, in a ratio of 4/1 respectively), TBHP (8 equiv.), 8 h at different
temperatures under Ar atmosphere. Yield determined by GC-FID spectroscopy with an
internal standard).
A series of primary, secondary and tertiary amides was synthesized
by reaction of various amine hydrochloride salts (aliphatic and
aromatic) with different methylarenes. As can be seen in Table 1,
Hence, the reaction was carried out in the presence of several
oxidizing reagent such as
mCPBA, H2O2, UHP, NaOCl as well as
aliphatic amines such as ethyl, butyl, 2-amino-1-butanol and tert
-
trying oxidant-free conditions. But in neither case was observed
amide formation (61%, Fig.13).
butyl amines were converted into the corresponding amides in
good yields (48%, 71%, 60% and 55%, respectively). Notably no
oxidation of the alcoholic function occurred in 1d. Benzylamine and
(S)-α-methylbenzylamine were subjected to the amidation with
toluene and the corresponding amides were produced in 84% (1f)
and 80% (1g) yields, respectively. Tertiary amides were also
synthesized from various secondary amines (cyclic and aliphatic) in
moderate to goodn yields (1j-p).
Steric factors are often the most important in decreasing the
product yields in some cases. In the case of imidazole and O-benzyl
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Table 1: Preparation of various amides in the presence of Fe3O4@SiO2-APTMS-Cu2+ a
O
R1
R1
Cat. (40mg), CaCO3 (2.2eq), TBHP(8eq)
N
N.HH2Cl
R2
CH3CN / Toluene
R2
4 / 1
80 °C
O
O
O
O
OH
N
N
N
H
NH2
H
H
(63%)c
1d
1c
(60%)
(71%)
(48%)
1b
1a
(yellow oil)
TON = 98.95
O
(mp 73-76 °C)
TON = 91.17
O
(mp 71-72 °C)
TON = 56.13
O
(
mp 128-131 °C)
TON = 60.02
O
Fig. 15. Visualization of the Fe3O4@SiO2-APTMS-Cu2+ collection process using an
external magnet after 2 (a), 10(b), 20(c) and 30 (d) seconds respectively.
N
H
N
H
N
N
H
1g
1h
(55%)
(62%)
1e
(80%)
1f
(80%)
(mp 43-45 °C)
Reusability of the catalyst was evaluated in the synthesis of N-
(mp 96-98 °C)
TON = 141.6
O
(mp 134-136 °C)
(mp 104-106 °C)
TON = 132.8
O
TON = 79.95
TON = 72.73
morpholine benzamide (Fig. 15, 16). After completing the reaction;
the catalyst was removed by an external magnet, washed with
ethanol and dried for reuse. Fe3O4@SiO2-APTMS-Cu2+ was recycled
6 times in the oxidative amidation reaction without significant loss
of its activity.
O
O
N
N
N
OBz
N
H
O
1l (91%)
(colorless oil)
TON = 136.85
1k
1j
(70%)
(39%)
1i (0%)
(colorless oil)
TON = 104.16
(yellow oil)
TON = 71.54
O
O
O
O
N
O
N
O
N
N
1o (70%)
(mp 62-79 °C)
TON = 128.42
1p
1n
(55%)
(35%)
1m (63%)
(yellow oil)
TON = 99.72
(mp 94-96 °C)
TON = 130.35
(yellow oil)
TON = 69.72
O
O
O
O
NH2
N
H
NH2
N
N
O
1q
(0%)
1s
1r (60%)
(63%)
1t (60%)
(mp 162-163 °C)
TON = 93.06
(mp 94-96 °C)
TON = 66.96
(mp 164-167 °C)
TON = 71.33
Fig. 16. Catalyst reusability(reaction was run catalyst (40mg), morpholine
hydrochloride salt (1 mmol), CaCO3 (2.2 equiv.), TBHP (8 equiv.), 6 h in CH3CN/Toluene
O
O
O
O
N
H
ph
N
H
ph
NH2
N
H
ph
Cl
(2 ml, in
a ratio of 4/1 respectively) as solvent. Yield determined by GC-FID
spectroscopy with an internal standard).
Cl
O
1x (60%)
1w
1u (70%)
(70%)
1v (70%)
(mp 137-138 °C)
TON = 85.98
In order to gain insight into the heterogeneous nature of catalyst, a
leaching test was carried out. As indicated in Figure 17, no further
reaction took place without catalyst after initiation of the oxidative
amidation reaction at 210 min. This finding indicates that no
leaching of the catalytically active sites occurs and that
Fe3O4@SiO2-APTMS-Cu2+ exhibits a typical heterogeneous catalyst
nature.
(mp 133-135 °C)
TON = 90.94
(mp 131-132 °C)
TON = 98.10
(mp 172-175 °C)
TON = 85.4
aReaction conditions: (1 mmol), amine hydrochloride salt (1 equiv.),
CH3CN/Toluene (2 ml, in a ratio of 4/1 respectively), CaCO3 (2.2
equiv.), TBHP (8 equiv.), Catalyst (40 mg, 2 mol%), at 80 °C under Ar.
b
atmosphere. No racemization occurred during the synthesis of 1i
and 1q. c The yields refer to the isolated pure products.
hydroxylamine, the reactions were troublesome and amides 1i and
1q were not observed. Next, various arylarenes were used in this
reaction (1s-x).
p-Methylanisole, p-xylene and p-chlorotoluene
were chosen as the arylarenes and the corresponding amides were
obtained in good yields. All the products were characterized by
recording their melting points (in some cases), and from their IR,
1H-NMR and 13C-NMR spectra.
Fig. 17. Leaching test for catalytic oxidation based on 2.
The mechanism of this reaction can be assumed to be similar to
those in related reports.16 Toluene is oxidized to benzyl alcohol
This journal is © The Royal Society of Chemistry 20xx
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ARTICLE
Journal Name
Table 2. Summary of the Reported oxidative amidation reactions Using different
and subsequently benzaldehyde by Cu(II)/TBHP. The reaction then
proceeds via a hemiaminal intermediate that is oxidized to the
amide via a free-radical mechanism. (Scheme 3)
Catalysts and comparison with this work.
Time
(min)
Temp.
(˚C)
mol
%
Yield
(%)
Catalyst
Oxidant
Precursor
Ref.
[15f]
[13a]
[14v]
[14z]
[14f]
[15c]
[15i]
[20]
I2
KI
TBHP
TBHP
O2
Benzyl alcohol
Benzaldhyde
Benzyl alcohol
Benzyl alcohol
Benzaldhyde
Benzyl alcohol
Toluene
1320
900
720
240
1200
240
600
720
240
360
480
80
80
10
5
84
75
61
80
25
87
80
85
93
87
80
Gold/DNA
CuO
50
3.8
2
TBHP
ꢀ
80
[Rh(COD)2]
BF4·2PPh3
140
80
2.5
10
10
20
1.6
3.5
2
NaI
FeSO4.7H2O
KI
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
80
Toluene
100
80
Fe3O4@
EDTAꢀCu2+
Fe3O4@
[14a]
[15h]
Benzyl alcohol
Benzyl alcohol
Toluene
80
Fe(OH)3
Fe3O4@SiO2ꢀ
this
work
80
APTMSꢀCu2+
Scheme 3: Plausible mechanism for the oxidative amidation of toluene with
hydrochloric salts of amines in the presence of Cu(II)-TBHP
Acknowledgements
In comparison with other reported homogenous and
heterogeneous catalytic systems for the oxidative amidation,
Fe3O4@SiO2-APTMS-Cu2+ showed good catalytic performance in
terms of activity and reusability (Table 2).
We acknowledge Tarbiat modares University for partial support of
this work.
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Copper-Amino Groups Complex Supported on Silica Coated Magnetite
Nanoparticles: Efficient Catalyst for Oxidative Amidation of Methyl Arenes
Meghdad Karimia,*, Leila Ghandia, Dariush Saberib, Akbar Heydaria,*