Oxidative amidation of aromatic aldehydes with amine hydrochloride salts catalyzed by silica-coated magnetic carbon nanotubes (MagCNTs@SiO 2)-immobilized imine-Cu(I)

Article abstract of DOI:10.1002/aoc.3087

Mesoporous silica-coated magnetic carbon nanotubes were prepared; their surface functionalization, followed by reaction with CuI, were carried out to develop a Cu-grafted functionalized mesoporous material. This system is able to catalyze oxidative amidation of aromatic aldehydes with amine hydrochloride salts, generating amide derivatives in moderate to good yields. Magnetic properties of this catalyst led to easy separation as well as providing significant recyclability.

Full text of DOI:10.1002/aoc.3087

Full Paper
Received: 17 September 2013
Revised: 8 October 2013
Accepted: 8 October 2013
Published online in Wiley Online Library: 6 December 2013
(wileyonlinelibrary.com) DOI 10.1002/aoc.3087
Oxidative amidation of aromatic aldehydes
with amine hydrochloride salts catalyzed by
silica-coated magnetic carbon nanotubes
(MagCNTs@SiO2)-immobilized imine–Cu(I)
Dariush Saberi and Akbar Heydari*
Mesoporous silica-coated magnetic carbon nanotubes were prepared; their surface functionalization, followed by reaction
with CuI, were carried out to develop a Cu-grafted functionalized mesoporous material. This system is able to catalyze
oxidative amidation of aromatic aldehydes with amine hydrochloride salts, generating amide derivatives in moderate to good
yields. Magnetic properties of this catalyst led to easy separation as well as providing significant recyclability. Copyright ©
2013 John Wiley & Sons, Ltd.
Keywords: oxidative amidation; magnetic nanoparticles; carbon nanotubes; copper; heterogeneous catalysis
of alkynes,[11] transamidation of primary amides[12] and oxidative
Introduction
amidation of aldehydes.[13] Among these approaches, oxidative
There has been always a growing need for greener and more
sustainable processes in chemical industry. 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.[1] Owing to improved efficacy, homogeneous catalysis
has grabbed more attention and interest than heterogeneous
approaches.[2] 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[3] (tethering
of homogeneous catalyst on organic or inorganic supports in
the liquid phase) has prevailed.[4] 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.[5] It
is also worth mentioning that the use of catalyst in more than
one run is environmentally and economically advantageous.
Amide bonds have been ubiquitously found in the scaffold of
pharmaceuticals, agrochemicals, polymers, etc.[6] The conven-
tional procedure for amide formation involves the reaction of
an amine with either activated carboxylic acids or non-activated
carboxylic acids, mediated by a coupling reagent.[7] These
methods suffer from several common drawbacks such as poor
atom efficiency, use of hazardous reagents and generation of
wastes that not only reduce process efficiency but also pose
environmental problems. During past decades, a number of
elegant methodologies were developed affording innovative
strategies for amide fabrication, including catalytic acylation of
amines with carboxylic acid,[8] dehydrogenative amidation of
alcohols,[9] amino carbonylation of haloarenes,[10] hydroamination
amidation in which amines react with different aldehydes, is more
alluring than other traditional methods, since it provides a direct
method for the synthesis of carboxamides. Owing to wide
accessibility of starting materials, this procedure is of
tremendous value in industrial applications. This approach was
first reported by Nakagawa et al. in 1966 using stoichiometric
amounts of nickel peroxide as the oxidant.[13s] Subsequently,
other groups manipulated this reaction by introducing either
novel catalysts or new oxidants to directly convert aldehydes
to amides.[13] In this context, oxidative amidation of aldehydes
with amine hydrochloride salts reported by Li et al. in 2006
gained special attention,[13r] because they devised an efficient
method for amide formation by using CuIÀAgIO3 as the catalyst
and inexpensive aqueous tert-butyl hydroperoxide (T-Hydro) as
the oxidant, which was greener than previous method. However,
the reaction required a dual catalytic system and was only
applicable to the synthesis of secondary amides. Afterwards,
Chen et al. have reported oxidative amidation of aldehydes with
amine salts in the presence of copper catalyst and T-Hydro as the
oxidant.[14] This is a green method for the synthesis of different
types of amides, yet one of the most important principles of
green chemistry – catalyst recovery and reusability – still remains
a challenge.
To rise to this challenge and in pursuit of innovating new
magnetic heterogeneous catalysts for organic reactions,[15] we set
our minds to introducing a new heterogeneous catalytic system
consisting of CuI-grafted surface functionalized mesoporous silica
coated magnetic carbon nanotubes (MagCNTs@SiO2–linker–CuI)
*
Correspondence to: Akbar Heydari, Chemistry Department, Tarbiat Modares
University, PO Box 14155-4838, Tehran, Iran. Email: heydar_a@modares.ac.ir
Chemistry Department, Tarbiat Modares University, PO Box 14155-4838,
Tehran, Iran
Appl. Organometal. Chem. 2014, 28, 101–108
Copyright © 2013 John Wiley & Sons, Ltd.

D. Saberi and A. Heydari
as a highly efficient and magnetically separable catalyst in
oxidative amidation of aromatic aldehydes with amine
hydrochloride salts. Mesoporous silica-coated magnetic carbon
nanotubes were prepared as novel hybrid materials for the first
time by Yan et al. in 2011 which were used as absorbents for
the fast removal of microcystins.[16] In an innovative programme,
we improved this catalytic system via exploiting propylamine,
furfural and CuI in the form of a complex to obtain a heteroge-
neous catalytic system supported on carbon nanotubes. Lately,
carbon nanotubes have been commonly used as supports due
to their peerless attributes such as large specific surface area,
high oxidation stability and significant mechanical and thermal
stability.[17] Of the other virtues of this system is its magnetic
hallmark which gives rise to easy separation of catalyst from
reaction media and straightforward work-up.
heated at 200°C for 12 h. Finally the MagCNTs gained were
washed with EtOH and collected by magnetic separation–
redispersion cycle.
Synthesis of MagCNTs@SiO2
According to the reported method,[16] the mesoporous silica was
coated on the MagCNTs as follows: MagCNTs (200 mg) and CTAB
(2g) were well dispersed in 300ml deionized water with NaOH
(84 mg) by 3 h ultrasonication. After heating the mixture at 60°C
for half an hour, 12.9ml tetraethyl orthosilicate (TEOS) ethanol
solution (0.186 g mlÀ1) was added in three batches with the aid of
a mild shake. Then the mixture continued to be heated at 60°C
for 12 h to complete the coating process. Finally, the products of
MagCNTs@SiO2 were washed several times in warmed alcohol
(60°C) and collected by magnetic separation–redispersion cycle.
Synthesis of n-propylamine covalently anchored on MagCNTs@SiO2
3-Aminopropyl-functionalized MagCNTs@SiO2 was synthesized
by the reported procedure as described previously.[18] A sample
of MagCNTs@SiO2 (500 mg) was suspended in a mixture of
100 ml dry toluene containing an excess amount (179 mg,
1 mmol) of 3-aminopropyl trimethoxysilane (3-APTMS). The
mixture was refluxed under Ar atmosphere at 110°C for 24 h.
The product was separated using an external magnet, washed
with ethanol and dried under vacuum for 24 h at 50°C after
Soxhlet extraction by hot ethanol to give the solid surface-
bonded amine.
Experimental
Chemicals, Instrumentation and Analysis
All reagents were purchased from commercial suppliers and used
without further purification. Multi-wall carbon nanotubes used in
this work incorporate 3.06 wt% of OH with an external diameter
of 10–20 nm, internal diameter 5–10 nm and an approximate
length of 30 μm. All experiments were carried out under argon.
The catalyst was characterized using spectroscopic techniques
(FT-IR, X-ray diffraction (XRD), inductively coupled plasma (ICP),
vibrating sample magnetometry (VSM), thermal gravimetric anal-
ysis (TGA), scanning electron microscopy–energy-dispersive X-ray
analysis (SEM-EDX) and transmission electron microscopy (TEM)).
FT-IR spectra were obtained over the region 400–4000 cmÀ1 with
NICOLET IR100 FT-IR with spectroscopic-grade KBr. Powder X-ray
diffraction spectrum was recorded at room temperature by a
Philips X’pert 1710 diffractometer using Cu-Kα (α = 1.54056 Å) in
Bragg–Brentano geometry (θ–2θ). ICP analysis was accomplished
using a VISTA-PRO, CCD simultaneous ICP analyzer. Magnetic
properties of catalyst were obtained by vibrating sample magne-
tometer/Alternating Gradient Force Magnetometer (VSM/AGFM,
MDK Co, Iran, www.mdk-magnetic.com). TGA was performed on
a Thermal Analyzer with a heating rate of 20 °C min-1 over a tem-
perature range of 25–1000 °C under flowing compressed N2. SEM
images were observed using Philips XL 30 and S-4160
instruments with gold coating equipped with EDX. TEM
measurements were carried out at 120 kV (Philips model
CM120). 1H NMR and 13C NMR spectra were recorded on a Bruker
Avance (DRX 400 MHz) in pure deuterated CDCl3 solvent with
tetramethylsilane (TMS) as internal standard.
Synthesis of imine-functionalized MagCNTs@SiO2 (MagCNTs@SiO2–linker)
A solution of furfural in methanol (5 ml) was added dropwise to the
3-APTMS-functionalized MagCNTs@SiO2 material dispersed in meth-
anol (15 ml) under continuous stirring. When the addition was
completed, the reaction mixture was heated at reflux for about 6 h
at 60°C and then cooled to room temperature, and the final product
was collected by magnetic filtration, washed repeatedly with hot
methanol to remove unreacted aldehyde and then dried.[19]
Synthesis of Cu(I)-anchored imine-functionalized MagCNTs@SiO2
(MagCNTs@SiO2–linker– Cu(I))
MagCNTs@SiO2–linker–Cu(I) catalyst was synthesized by the
procedure reported previously.[20] The imine-functionalized
MagCNTs@SiO2 (1 g) in acetonitrile (20 ml) was treated with 5 ml
of a 1% (w/v) acetonitrile solution of copper iodide over a period
of nearly 30 min under constant stirring. The reaction mixture
was then refluxed for 24 h. The copper complex thus formed
was magnetic filtered, washed thoroughly with ethanol and dried
at room temperature under vacuum.
General Procedure for the Oxidative Amidation of Aldehydes
with Amine Hydrochloride Salts
Catalyst Preparation
Preparation of magnetic carbon nanotubes (MagCNTs)
To a mixture of catalyst (20 mg, 0.2 mol%), amine hydrochloride
salt (2 mmol) and Na2CO3 (212 mg, 2 mmol) in acetonitrile (1 ml)
were added aldehyde (1 mmol,) and T-Hydro (1.5 equiv.) under
argon atmosphere at room temperature. The reaction vessel
was capped and stirred at 60°C for 6 h. Progress of the reaction
was monitored by thin-layer chromatography. After completion,
the reaction mixture was allowed to cool to room temperature.
It was then diluted with ethyl acetate and the catalyst was easily
separated from the reaction mixture by using an external magnet
and washing twice with ethyl acetate. The combined organic
layers were concentrated under vacuum and the resulting
MagCNTs were prepared via a modified hydrothermal method
reported by Yan et al.[16] Multi-wall CNTs (1g, diameter 10–20 nm)
were dispersed in 100 ml concentrated nitric acid at 100°C with
magnetic stirring for 7 h. The pre-treated CNTs were collected
by washing with water five times and then drying under vacuum
at 50°C. The dried pre-treated CNTs (200 mg) and FeCl3.6H2O
(810 mg) were dispersed into 40 mL ethylene glycol solution
with trisodium citrate (0.15 g), sodium acetate (3.6 g) and poly
(ethylene glycol) 6000 (1.0 g) by ultrasonication and magnetic
stirring for 3 h. The mixture was sealed in an autoclave and
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Copyright © 2013 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2014, 28, 101–108

Oxidative amidation reaction catalyzed by Cu(I) supported on MagCNTs
Scheme 1. Pathway to preparation of MagCNTs@SiO2–linker–CuI.
Figure 3. Magnetization curve of the catalyst.
Figure 1. XRD pattern of the catalyst.
Figure 4. Thermogravimetric weight loss plots for the catalyst.
Figure 2. FT-IR spectra of (a) raw MWCNTs, (b) MagCNTs@SiO2, (c)
MagCNTs@SiO2–linker, (d) MagCNTs@SiO2–linker–CuI.
(R)-N-(1-Phenylethyl)benzamide (3 m): yield 83%, white solid,
m.p. 96–98°C. IR (KBr): ν = 3329, 2964, 2925, 1634, 1525, 1449,
1
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 the literature.
1080 cmÀ1. H NMR (400 MHz, CDCl3/TMS) δ (ppm): 1.64 (d, 3H,
3J = 7.2 Hz, CH3), 5.32–5.41 (m, 1H, CHCH3), 6.34 (d, 1H,
3J = 5.2 Hz, NH), 7.31–7.38 (m, 2H, 2CHmeta of ph), 7.39–7.41
(m, 1H, CHpara of ph), 7.41–7.43 (m, 2H, 2CHortho of ph), 7.45–7.47
Appl. Organometal. Chem. 2014, 28, 101–108
Copyright © 2013 John Wiley & Sons, Ltd.
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D. Saberi and A. Heydari
(m, 2H, 2CHortho of ph), 7.50–7.54 (m, 1H, CHpara of ph), 7.78–7.81
(m, 2H, 2CHmeta of ph). 13C NMR (100MHz, CDCl3/TMS) δ (ppm):
21.73 (CH3), 49.23 (CH), 126.28 (CHpara of ph), 126.94 (2CHortho of
ph), 127.48 (2CHortho of ph), 128.57 (2CHmeta of ph), 128.77 (2CHmeta
of ph), 131.47 (CHpara of ph), 134.61 (Cipso-C-O), 143.14 (Cipso-CH ),
166.57 (C-;O); MS (EI, 70 eV): m/z (%) = 225 (M+, 13), 210 (64),
105 (100), 91 (69), 77 (100). Anal. Calcd for C15H15NO (225.28):
C, 79.97; H, 6.71; N, 6.22; O, 7.10. Found: C, 79.92; H, 6.75; N,
6.28; O, 7.05
Anal. Calcd for C17H19NO (253.34): C, 80.60; H, 7.56; N, 5.53;
O, 6.32. Found: C, 80.67; H, 7.63; N, 5.48; O, 6.25.
Results and Discussion
As can be seen in Scheme 1, our magnetic catalytic system was
prepared in several steps (for details see Experimental section).
Prepared catalyst was then characterized using various
microscopic and spectroscopic techniques such as XRD, FT-IR,
VSM, ICP, TGA, SEM-EDX and TEM. XRD was used to determine
the crystalline structure of the magnetic nanoparticles obtained
by the hydrothermal method (Fig. 1). In particular, the peaks at
2θ equal 30.1°, 35.4°, 43.1°, 53.4°, 57.1° and 62.6°, which can be
indexed as (220), (311), (400), (511) and (440) lattice planes of
cubic magnetite, respectively (JCPDS 19-629). Diffraction peak
at 26.1° can be indexed to (022) reflection of the CNTs.
(R)-N-(1-hydroxybutan-2-yl)benzamide (3p): yield 68%, white
solid, m.p. 73–76°C. IR (KBr): ν = 3296, 2956, 2927, 2867, 1637,
1
1535, 1454, 1048 cmÀ1. H NMR (400 MHz, CDCl3/TMS) δ (ppm):
3
0.94 (t, 3H, J = 7.2 Hz, CH3), 1.51–1.67 (m, 2H, CHCH2CH3), 2.96
2
3
(brs, 1H, NH), 3.62 (dd, 1H, J = 10.7 Hz, J = 5.2 Hz, CH2OH), 3.71
2
3
(dd, 1H, J = 10.7 Hz, J = 2.8 Hz, CH2OH), 4.0 (brs, 1H, CHCH2OH),
6.36 (s, 1H, OH), 7.34 (dd, 2H, J = 7.6 Hz, J = 7.2 Hz, 2CHmeta of
3
3
3
3
ph), 7.42 (t, 1H, J = 7.2 Hz, CHpara of ph), 7.70 (d, 2H, J = 7.6 Hz,
2CHortho of ph). 13C NMR (100 MHz, CDCl3/TMS) δ (ppm): 10.71
(CH3), 24.33 (CH2), 53.73 (CH), 65.20 ( CH2OH), 127.00 (2CHortho
of ph), 128.60 (2CHmeta of ph), 131.61(CHpara of ph), 134.40
(Cipso of ph), 168.35 (C-;O); MS (EI, 70 eV): m/z (%) = 194 (M+, 16),
163 (100), 122 (95), 105 (66), 77 (58). Anal. Calcd for C11H15NO2
(193.24): C, 68.37; H, 7.82; N, 7.25; O, 16.56. Found: C, 68.32; H,
7.77; N, 7.31; O, 16.62.
N,N-Diallylbenzamide (3v): yield 68%, yellow oil. IR (neat):
1
ν = 3078, 2930, 2800, 1639, 1416, 1263 cmÀ1. H NMR (400 MHz,
CDCl3/TMS) δ (ppm): 3.84 (brs, 2H, CH2), 4.15 (brs, 2H, CH2),
5.18–5.26 (m, 4H, 2CH-CH2), 5.74 (brs, 1H, CH-CH2), 5.89 (brs, 1H,
CH-CH2), 7.36–7.41 (m, 3H, CH of ph), 7.43 (d, 2H, 3J = 7.2 Hz,
2CHortho of ph). 13C NMR (100 MHz, CDCl3/TMS) δ (ppm): 46.92
(CH2NH), 50.75 (CH2NH), 117.63 (2 CH-CH2), 126.61 (2CHortho
of ph), 128.44 (2CHmeta of ph), 129.63 (CHpara of ph), 132.8
(CH-CH2), 133.22 (CH-CH2), 136.3 (Cipso of ph), 171.85 (C-O); MS
(EI, 70 eV): m/z (%) = 201 (M+, 7), 172 (15), 121 (7), 105 (100), 91
(25), 77 (70). Anal. Calcd for C13H15NO (201.26): C, 77.58; H,
7.51; N, 6.96; O, 7.95. Found: C, 77.53; H, 7.58; N, 7.01; O, 7.99.
N,N-Dibenzylbenzamide (3y): yield 50%, white solid, m.p.
95–97°C. IR (KBr): ν = 3059, 2916, 1639, 1493, 1419, 1253 cmÀ1
.
1H NMR (400 MHz, CDCl3/TMS) δ (ppm): 4.42 (s, 2H, CH2), 4.72
(s, 2H, CH2), 7.16 (d, 2H, 3J = 7.2Hz, 2CHortho of ph), 7.31 (t, 2H,
3J = 6.8Hz, 2CHortho of ph), 7.35–7.40 (m, 7H, CH of ph), 7.39
(dd, 2H, 3J = 6.8Hz, 3J = 5.2Hz, 2CHmeta of ph), 7.51 (dd, 2H,
3J = 5.2Hz, 4J = 1.6Hz, CHortho of ph).13C NMR (100MHz, CDCl3/
TMS) δ (ppm): 46.93 (CH2), 51.53 (CH2), 126.71 (CHpara of Bn),
127.14 (CHpara of Bn ), 127.62 (2CHortho of ph), 127.75 (2CHortho
of Bn), 128.53 (2 CHortho of Bn), 128.62 (2CHmeta of ph), 128.75
(2CHmeta of Bn), 128.92 (2CHmeta of Bn), 129.74(CHpara of ph),
136.24 (Cipso of ph), 136.45 (Cipso of Bn), 136.93 (Cipso of Bn),
172.35 (C-O); MS (EI, 70 eV): m/z (%) = 301 (M+, 10), 210 (63),
105 (100), 91 (63), 77 (63). Anal. Calcd for C21H19NO (301.38):
C, 83.69; H, 6.35; N, 4.65; O, 5.31. Found: C, 83.64; H, 6.43; N,
4.73; O, 5.24.
N-Benzyl-N-isopropylbenzamide (3z): yield 70%, yellow oil, IR
(neat) ν = 3061, 2978, 1633, 1421, 1345, 1180 cmÀ1 1H NMR
.
(400 MHz, CDCl3/TMS) δ (ppm): 1.12 (brs, 6H, CH3), 4.15 (brs, 1H,
CH3CHCH3), 4.70 (s, 2H, CH2), 7.33–7.36 (m, 5H, CH of ph), 7.42–
7.45 (m, 5H, CH of ph). 13C NMR (100 MHz, CDCl3/TMS) δ (ppm):
21.53 (2CH3), 43.55 (CH), 50.82 (CH2), 126.24 (CHpara of Bn),
127.00 (CHortho of ph), 128.52 (CHortho of Bn), 128.65 (CHmeta of
ph), 129.23 (CHmeta of Bn), 129.9 4(CHpara of ph), 133.24 (Cipso
of ph), 137.32 (Cipso of Bn), 168.91 (C-O); MS (EI, 70 55 eV):
m/z (%) = 253 (M+, 81), 210 (82), 105 (100), 91 (54), 77 (66).
Figure 5. (a, b) TEM and (c) SEM images of the catalyst.
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Appl. Organometal. Chem. 2014, 28, 101–108

Oxidative amidation reaction catalyzed by Cu(I) supported on MagCNTs
FT-IR spectra of the pristine MWCNTs, intermediates and final
catalyst are depicted in Fig. 2. The spectrum in Fig. 2(a), related
to the raw CNTs, shows a band around 3436 cmÀ1 which can
be attributed to the hydroxyl groups (νOH). Bands around 2924
and 2855 cmÀ1 are due to asymmetric and symmetric C-H
stretching and the signal located around 1400–1600 cmÀ1 can
be attributed to the structure of graphite in MWCNTs. The FT-IR
spectrum of MagCNTs@SiO2 is shown in Fig. 2(b). Typical bands
assigned to the Fe-O stretching vibration appeared at around
400–600 cmÀ1 for MagCNTs@SiO2 and the strong band around
1070 cmÀ1 is consistent with the Si-O-Si stretching vibration
confirming that silica is well coated on the MagCNTs. In the IR
spectrum for furfural-functionalized MagCNTs@SiO2 the peak at
1638 cmÀ1 can be ascribed to the C-N band stretching frequency
(Fig. 2c). It is worth mentioning that in Cu-anchored mesoporous
MagCNTs@SiO2 material, the C-N stretching frequency is shifted
to a lower wavelength at ~1633 cmÀ1, indicating that C-N bond
is coordinated to copper through the lone pair of nitrogens in
the Schiff base (Fig. 2d).
The superparamagnetic feature of the catalyst, which accounts
for its easy recovery, is confirmed by VSM analysis (there is no
hysteresis loop and the ratio of magnetic remanence/magnetic
saturation (Ms) is about 0.0004, Ms = 25.0 emu gÀ1) (Fig. 3).
Quantitative determination of the organic functional groups
loaded on the surface of MagCNTs@SiO2 was performed utilizing
TGA and a loading of 0.38 mmol gÀ1 was obtained. The analysis
cps/eV
35
30
25
I
O Cu
Fe
C
Si
I
Fe
Cu
20
15
10
5
0
2
4
6
8
10
12
14
16
18
20
keV
Figure 6. EDX spectrum of the catalyst.
Table 1. Optimization of reaction conditions for amide bond formation in the presence of MagCNTs@SiO2–linker–CuI as catalyst
Entry
Solvent
Oxidant
Base
Catalyst (mg)
Temperature (°C)
Yield (%)
1
DMF
T-Hydro
T-Hydro
T-Hydro
T-Hydro
T-Hydro
mCPBA
H2O2
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
K2CO3
20
20
20
20
20
20
20
20
20
20
20
20
20
-
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
80
40
r.t.
10
55
35
68
40
—
—
—
—
—
20
60
50
<10
68
40
70
40
10
2
H2O
3
Toluene
CH3CN
DMSO
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
4
5
6
7
8
UHP
9
NaOCl
10
11
12
13
14
15
16
17
18
19
—
T-Hydro
T-Hydro
T-Hydro
T-Hydro
T-Hydro
T-Hydro
T-Hydro
T-Hydro
T-Hydro
CaCO3
Cs2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
30
15
20
20
20
Reaction conditions: benzaldehyde (1 mmol), ammonium chloride (2 equiv.), solvent (1 ml), base (2 equiv.), oxidant (1.5 equiv.), 6 h, under Ar
atmosphere.
Appl. Organometal. Chem. 2014, 28, 101–108
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D. Saberi and A. Heydari
showed three peaks (Fig. 4). The first peak appears due to
desorption of water (below 200°C). This is followed by a second
peak at 400°C, which agrees well with the loss of the organic
spacer groups. The last peak, at 700°C, is assigned to the
combustion of CNTs.
The SEM and TEM images of MagCNTs@SiO2–linker–CuI are
outlined in Fig. 5, denoting that CNTs were orderly decorated
with spherical particles with mean diameters of about 95 nm.
The decoration mostly occurred at either end of the tube, where
the density of carboxyl groups was supposed to be the highest.
Another finding was that both the magnetite beads and the
whole nanotubes were coated with a mesoporous silica shell of
~15 nm thickness.
R2
R3
O
O
Cat., T-Hydro, Na2CO3
CH3CN, 60 OC, 6 h
R2
R1
N
R3
+
N.HHCl
The EDX spectrum of the Cu-incorporated catalyst is outlined in
Fig. 6. Atoms such as Fe, I, Si, C and O, related to the catalyst
structure, are seen in this spectrum. The copper content of the
catalyst was found to be 0.1 mmol gÀ1 based on the EDX spec-
trum. Also, ICP analysis was used for this purpose, from which
R1
H
1 mmol
1
2 eq.
2
3
Scheme 2. Amide bond formation in the presence of the new catalyst.
the amount of catalyst obtained was 0.09 mmol gÀ1
.
After characterization, catalytic
activity of the catalyst was exam-
ined in the oxidative coupling of
the aromatic aldehydes with various
types of ammonium salts, an easy
method for the synthesis of amides.
First, we examined the oxidative
coupling of benzaldehyde with am-
monium chloride to give benzamide
under various conditions in order to
establish the optimal conditions
(Table 1). When the reaction was
carried out under the following con-
ditions – 20 mg catalyst (0.2 mol%),
DMF as solvent, Na2CO3 as base,
T-Hydro as oxidant at 60°C under
Ar atmosphere for 6 h – the forma-
tion of the desired amide product
was isolated in only 10% yield
(Table 1, entry 1). To improve the
efficiency of the reaction, first the
solvent effect was investigated. To
this end, some organic solvents as
well as H2O were examined (Table 1,
entries 2–5) and, as can be seen in
this table, in CH3CN the reaction
proceeded more efficiently than
with other solvents (Table 1, entry
4). Next, the effect of oxidant on
the yield of the reaction was taken
into account. Hence the reaction
was carried out in the presence of
several oxidizing reagents, such as
mCPBA, H2O2, UHP and NaOCl, as
well as attempted in oxidant-free
conditions. But in neither case was
amide formation (Table 1, entries
6–10). This shows that the presence
and type of oxidant are important
for this reaction. Screening a range
of bases revealed that Na2CO3
performed best among the other
bases, including K2CO3, CaCO3, and
Cs2CO3 (Table 1, entries 11–13). In
the absence of catalyst, less than
10% of product was isolated
(Table 1, entry 14). Increasing the
Figure 7. MagCNTs@SiO2–linker–CuI-catalyzed synthesis of primary, secondary and tertiary amides from al-
dehydes and amine hydrochloride salts. Reaction conditions: aldehyde (1mmol), amine hydrochloride salt (2
equiv.), CH3CN (1ml), Na2CO3 (2 equiv.), T-Hydro (1.5 equiv.), catalyst (20 mg), 60°C, under Ar atmosphere, 6 h. amount of catalyst to 30 mg made
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Copyright © 2013 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2014, 28, 101–108

Oxidative amidation reaction catalyzed by Cu(I) supported on MagCNTs
Reusability of the catalyst was studied in the preparation of
compound 3n. After completion of the reaction in the first
run, the catalyst was easily separated from the reaction
mixture by using an external magnet; it was washed twice
with ethyl acetate, dried at ambient temperature and immedi-
ately used in the next step. The reaction was repeated for up
to five consecutive runs without significant change in the
efficiency of the reaction (Scheme 3).
The heterogeneity of the reaction was studied by performing
the reaction between benzaldehyde and benzylamine
hydrochloride using MagCNTs@SiO2–linker–CuI as catalyst under
the present reaction conditions. After 45% conversion,
determined by gas chromatography, the catalyst was removed
from the reaction mixture using an external magnet, allowing
the reaction to continue in the absence of the catalyst. After
6 h, conversion was increased to 50%, suggesting that Cu atoms
are not leached from the support during the course of the
reaction, and ICP-AES showed the presence of 0.14 ppm Cu in
the filtrate. This shows that catalytic activity is carried out on
the solid phase and leaching of catalyst is negligible.
Scheme 3. Recycling of the catalyst in the preparation of compound 3n
carried out for 6 h.
no difference to the reaction yield. Conversely, the reduction in cat-
alyst loading to 15 mg gave rise to a significant drop in yield (Table 1,
entries 15 and 16). Finally, the role of temperature was probed. It
was observed that increasing the temperature to 80°C enhanced
the yield by a small amount, whereas reducing it to room tempera-
ture led to a significant reduction in the efficiency of the reaction
(Table 1, entries 17–19).
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: aldehyde (1 mmol),
amine hydrochloride salt (2 equiv.), CH3CN (1 ml), Na2CO3
(2 equiv.), T-Hydro (1.5 equiv.), catalyst (20 mg, 0.2 mol%), at 60°
C under Ar atmosphere (Scheme 2).
Conclusions
In summary, we have developed a novel protocol for the one-pot
oxidative amidation of different aldehydes with amine hydro-
chloride salts in the presence of furfural imine-functionalized
Cu-grafted magnetic CNTs as an effective heterogeneous catalyst
which possess magnetic characteristics. In the present protocol
only 0.2 mol% of catalyst was used for the preparation of
different derivatives of amides in moderate to good yield. The
magnetic properties of this catalyst help easy separation from
the reaction mixture. The introduced magnetically inorganic–
organic hybrid nanocatalyst supported on CNTs was stable
and could be reused in five successive runs with no significant
structural change or loss of activity.
Under the optimized conditions, various aromatic and hetero-
aromatic aldehydes were coupled with ammonium chloride salt
to prepare the primary amides with moderate to good yields
(Fig. 7, compounds 3a–3j). In general, electron-donating groups
on the aromatic ring such as methyl or methoxy give a better
yield than electron-withdrawing groups such as nitro or
chloro. Hetero-aromatic aldehydes such as furfural and thiophen
2-carbaldehyde were well coupled with ammonium chloride salt
to give the corresponding amide. Following successful synthesis
of the primary amides with this heterogeneous catalytic system,
we were encouraged to examine the synthesis of secondary
amides. At first, coupling of the benzaldehyde with ethyl amine
hydrochloride salt, under the optimized conditions for synthesis
of the primary amides, was carried out to prepare the
corresponding product. Under these conditions, ethyl benzamide
was obtained in 80% yield. By changing the influential
parameters of the reaction, little change occurred in the yield
and different derivatives of the secondary amides were
synthesized in good yield under the same conditions (Fig. 7,
compounds 3 k–3p). Chiral amine salts provided chiral amides
in high yield without detectable racemization when compared
with high-performance liquid chromatograms of the racemic
compounds (Fig. 7, compounds 3 m and 3p). Encouraged by the
facile synthesis of secondary amides from primary amine salts,
the scope of the reaction was extended to the formation of more
challenging tertiary amides. First, the synthesis of n,n-diethyl
benzamide (Fig. 7, compound 3q), under the above conditions,
was examined and the product was obtained in 70% yield. By
changing the effective parameters of the reaction, there was no
significant change in efficiency. However, the different salts of
secondary amines, under the reaction conditions, were converted
to the corresponding tertiary amide in good yield (Fig. 7,
compounds 3q–3z). In the case of dibenzylamine hydrochloride
salt the product yield was reduced to 50%, probably due to
steric effects.
Acknowledgment
We acknowledge Tarbiat Modares University for partial support
of this work.
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