Selective nanocatalyst for an efficient Ugi reaction: Magnetically recoverable Cu(acac)2/NH2-T/SiO2atFe3O4 nanoparticles

Article abstract of DOI:10.1007/s12039-013-0506-7

A novel, magnetically recoverable nanocatalyst is fabricated through simple immobilization of copper(II) acetylacetonate on the surface of amine-terminated silica-coated Fe3O4 nanoparticles: Cu(acac)2/NH2-T/SiO2@Fe3O4NPs. Unambiguous bonding of Cu to the terminal amine is indicated by Xray photoelectron spectroscopy (XPS). Further characterizations are carried out by different techniques. Selectivity of this catalyst is demonstrated through one-pot synthesis of fourteen a-aminoacyl amides using Ugi four-component reaction of cyclohexyl isocyanide, acetic acid, amines and various aldehydes. Interestingly, all aromatic aldehydes react with short reaction times and high yields, but heteroaromatic aldehydes do not yield any product. Catalyst efficiency remains unaltered through three consecutive experiments. Indian Academy of Sciences.

Full text of DOI:10.1007/s12039-013-0506-7

c
J. Chem. Sci. Vol. 125, No. 6, November 2013, pp. 1347–1357. ꢀ Indian Academy of Sciences.
A selective nanocatalyst for an efficient Ugi reaction: Magnetically
recoverable Cu(acac)2/NH2-T/SiO2@Fe3O4 nanoparticles
MONIREH GHAVAMI, MARYAM KOOHI and MOHAMMAD ZAMAN KASSAEE∗
Department of Chemistry, Tarbiat Modares University, P.O. Box 14155-4838, Tehran, Iran
e-mail: kassaeem@modares.ac.ir
MS received 13 April 2013; revised 13 August 2013; accepted 13 August 2013
Abstract. A novel, magnetically recoverable nanocatalyst is fabricated through simple immobiliza-
tion of copper(II) acetylacetonate on the surface of amine-terminated silica-coated Fe3O4 nanoparticles:
Cu(acac)2/NH2-T/SiO2@Fe3O4NPs. Unambiguous bonding of Cu to the terminal amine is indicated by X-
ray photoelectron spectroscopy (XPS). Further characterizations are carried out by different techniques. Selec-
tivity of this catalyst is demonstrated through one-pot synthesis of fourteen α-aminoacyl amides using Ugi
four-component reaction of cyclohexyl isocyanide, acetic acid, amines and various aldehydes. Interestingly, all
aromatic aldehydes react with short reaction times and high yields, but heteroaromatic aldehydes do not yield
any product. Catalyst efficiency remains unaltered through three consecutive experiments.
Keywords. Nano; Fe3O4; copper(II) acetylacetonate; Ugi reaction; nanocatalyst.
1. Introduction
(HMS),5 and activated carbon.14,15 These materials have
acted as recoverable and reusable heterogeneous cata-
lysts for the aziridination of olefins. In the first
case, the copper(II) complex is microencapsulated in
polystyrene, and in the second, a hexagonal meso-
porous silica (HMS) is chosen to anchor copper(II)
acetylacetonate. In the latter, it is anchored onto an
amine-functionalized activated carbon.14 All three hete-
rogeneous catalysts present similar catalytic parameters
as those obtained in homogeneous-phase reaction using
[Cu(acac)2]. Under similar experimental conditions, no
significant metal complex leaching is observed after the
catalytic reactions.13,15 However, in the case where acti-
vated carbon is used as support, inherent diffusion lim-
itations are observed due to the porous structure of the
support. Thus, a decrease in the initial activity (TOF)
and an increase in the reaction time are observed.15
Furthermore, the spectroscopic characterization of new
carbon-based heterogeneous catalysts proved to be dif-
ficult and impossible, respectively, due to the highly
absorbing carbon matrix, which limits the gathering of
information about the copper(II) complex forms on the
surface of the amine-functionalized activated carbon.
Magnetite Fe3O4 nanoparticles (Fe3O4NPs) have re-
cently emerged as promising supports for immobilization
because Fe3O4-supported catalysts can be separated from
the reaction medium by an external magnet.16–23 This
circumvents time-consuming and laborious separation
steps, and allows for practical continuous catalysis. In
particular, Fe3O4NPs coated with a thin-layer of silica
Transition-metal-catalysed reactions have contributed
greatly to the straightforward and facile construction
of carbon-carbon or carbon-heteroatom bonds.1 Sig-
nificant progress in this area has been achieved with
a variety of homogeneous copper catalysts.2 Copper
complexes are extensively used as efficient catalysts
in multicomponent reactions.3 Nevertheless, homoge-
neous catalysis suffers from the problematic separation
of catalyst from the product for reuse.4 This problem
is of particular environmental and economic concerns
in large-scale syntheses. Heterogeneity of the existing
homogeneous copper catalysts could be an attractive
solution to this problem.5,6 In fact, the last decade has
witnessed a growing interest in the heterogenization of
homogeneous metal complexes using several types of
supports and many immobilization strategies.7–10 Ini-
tially, the complexes are just ion-exchanged or adsorbed
on the porous supports and could be susceptible to
leaching.11,12 More recently, various grafting and teth-
ering procedures have been developed for covalent
attachment of transition-metal complexes to organic
polymers, silica, zeolites as well as other micro- and
mesoporous inorganic materials.7–10
Copper(II) acetylacetonate has already been immo-
bilized in a polymer,13 hexagonal mesoporous silica
∗For correspondence
1347

1348
Monireh Ghavami et al.
O
FeCl3 + FeCl2, 4H2O
a
O
O
Si
Si
Si
O
O
Si
Si
Si
O
N
O
O
Cu
Fe3O4 NPs
Si
Si
Si
O
O
Fe3O4 NPs
Si
O
Si
O
Si
O
O
Fe3O4 NPs
Cu(acac)2/NH2-T/SiO2@Fe3O4 NPs
d
b
O
HO
OH
O
O
HO
Si
Si
Si
Si
Si
O
Si
OH
Si
O
HO
Si
Si
Si
Si
Si
c
Fe3O4 NPs
NH2
Si
Si
Si
O
Fe3O4 NPs
Si
OH
OH
O
HO
Si
Si
OH
Si
Si
O
Si Si
O
Si
HO
O
HO
O
NH2-T/SiO2@Fe3O4 NPs
SiO2@Fe3O4 NPs
Scheme 1. Stepwise synthesis of our magnetic nanocatalyst (Cu(acac)2/NH2-
T/SiO2@Fe3O4NPs): (a) aqueous ammonia (25%), rt; (b) tetraethyl orthosili-
cate, EtOH, aqueous ammonia (10%), rt, 10 h then 40◦C, 12 h; (c) (3-
aminopropyl)triethoxysilane, toluene, 105◦C, 24 h; (d) Cu(acac)2, toluene,
105◦C, 5 h.
have beneficial properties such as invariant catalytic combinational strategy.27 Thus, we present herein the
activity and stability.24
possibility of a new U-4CR design, using a novel
On the other hand, Ugi four-component reaction (U- catalyst, for decreasing reaction time and increas-
4CR) is arguably one of the most important isocyanide- ing selectivity. In this context, we are reporting a
based multicomponent reactions, IMCRs.25–27 It is a facile route for synthesis of our magnetic nanocata-
valuable method for generating α-aminoacyl amide lyst, Cu(acac)2/NH2-T/SiO2@Fe3O4NPs (scheme 1);
derivatives in a very straightforward manner by con- followed by examination of its feasibility as a heteroge-
densing an aldehyde, amine, carboxylic acid, and iso- neous catalyst in U-4CR (scheme 2).
cyanide in one-pot reaction.25 Lewis acids are not
Catalytic activity of the heterogeneous copper
required for majority of the reported IMCRs, but they complex is compared with the parent-free complex
have been applied as catalyst for U-4CR.28–37 Yet, [Cu(acac)2]. In this context, the former heterogeneous
conventional U-4CR gives good yields, but shows no catalyst showed similar catalytic efficiency, turnover
selectivity, taking 24–72 h to complete at room tempe- numbers (TON) and turnover frequency (TOF), com-
rature.26 Due to the great diversity of products which pared to the free [Cu(acac)2] in the homogeneous phase,
can be obtained by the post-modifications of the U- under similar experimental conditions.
4CR with other reactions, selectivity and the time
of this reaction remain as important parameters in
2. Experimental
2.1 Chemicals and instruments
O
NC
R2
Reagents and solvents used in this study are obtained
O
O
N
cat 0.85 mol%
R2 NH2
H
from Fluka or Merck and used without any further
purification. Nanostructures are characterized using a
Holland Philips Xpert X-ray powder diffraction (XRD)
diffractometer (Cu Kα, radiation, λ = 1.54 Å), at a
scanning speed of 2◦/min from 10◦ to 80◦ (2θ). Particle
size and morphology are investigated by PHILIPS
(EM208S, The Netherlands) transmission electron
+
+
H3C
+
N
MeOH, rt.,
4 h
R1
H
OH
R1
O
I
Scheme 2. One-pot catalytic synthesis of α-aminoacyl
amides (I) through Ugi reaction via Cu(acac)2/NH2-
T/SiO2@Fe3O4NPs.

Magnetically recoverable Cu(acac)2/NH2-T/SiO2@Fe3O4 NPs
1349
microscopy (TEM) at 100 kV of acceleration voltage 12 h. Consequently, the iron oxide nanoparticles with a
and scanning electron microscopy (SEM) of a Holland thin-layer of silica (SiO2@Fe3O4NPs) are separated by
Philips XL30 microscope with an accelerating volt- an external magnet and washed thrice with ethanol and
age of 25 kV. Fourier transform infrared (FTIR) mea- dried under vacuum.
surements are performed using KBr disc on a Thermo
1
IR-100 spectrometer (Nicolet). H- and 13C-spectra
are measured at 500.1 and 125.7 MHz, respectively,
on a Bruker DRX 500-Avance NMR instrument with
CDCl3 or DMSO-d6 as the solvent. Melting points are
measured on an Electrothermal 9100 apparatus. X-ray
photoelectron spectroscopy (XPS) experiment is carried
out on a TWIN ANODE XR3E2 X-RAY source sys-
tem with Al Kα radiation (hν = 1486.6 eV). Thermo-
gravimetric analysis (TGA) curves are recorded using
a PL-TGA device, manufactured by Polymer Laborato-
ries. Magnetic properties of Fe3O4NPs and Cu(acac)2/
NH2-T/SiO2@Fe3O4NPs are measured as a function of
the applied magnetic field H using a LDJ 9600 vibrat-
ing sample magnetometer (VSM) (AGFM-Meghnatis
Daghigh Kavir Co.) with a maximum applied mag-
netic field of 10 kOe. Hysteresis of the magnetiza-
tion is obtained by varying H between +10000 and
−10000 Oe at 300 K.
2.4 Functionalization of the SiO2@Fe3O4NPs
with APTES (NH2-T/SiO2@Fe3O4NPs)
SiO2@Fe3O4NPs is ultrasonically dispersed in a
solution containing 20 ml toluene. 3-aminopropyl-
triethoxysilane (APTES) (1 ml) is added drop-wise into
the bottle under magnetic stirring. After hydrolysing
for 24 h at room temperature, the particles are collected
by an external magnet and washed with toluene sev-
eral times with the help of an external magnet, then
dried under vacuum. Thus, silica-coated Fe3O4NPs,
functionalized by –NH2 groups are obtained: NH2-
T/SiO2@Fe3O4NPs.
2.5 Synthesis of Cu(acac)2/NH2-T/SiO2@Fe3O4NPs
Synthesized NH2-T/SiO2@Fe3O4NPs (1.0 g) is added
to 50 ml of a solution of [Cu(acac)2] (4 mmol) in
toluene, the mixture is refluxed for 5 h. A progres-
sive disappearance of solution colour is observed. The
resulting material (Cu(acac)2/NH2-T/SiO2@Fe3O4NPs)
is extensively washed with toluene and then dried at
50◦C for 13 h.
2.2 Synthesis of Fe3O4NPs
In the formation of Fe3O4NPs, 2 g FeCl3 and 1.2 g of
FeCl2.4H2O, with molar ratio of (Fe3+ : Fe2+ = 2 : 1)
are dissolved in aqueous hydrochloride acid (2 M,
25 ml), then sonicated until the salts dissolve com-
pletely. Aqueous ammonia (25%, 20 ml) is added
slowly over 20 min to the solution with vigorous stirring
under argon atmosphere at room temperature followed
by stirring for about 30 min with mechanical stirrer. The
Fe3O4NPs are separated by external magnet and washed
thrice with deionized water and ethanol. The final pro-
duct could either be obtained after drying under vac-
uum, or stored as a suspension in ethanol in refrigerator,
for future use.
2.6 General procedure for Ugi four-component
reaction (U-4CR)
Butylamine (1 mmol) is added to a solution of alde-
hyde (1 mmol) and Cu(acac)2/NH2-T/SiO2@Fe3O4NPs
(0.85 mol%) in methanol (5 ml), and the reaction mix-
ture is stirred at room temperature for 1 h. Then,
acetic acid (1 mmol) is added and stirring is con-
tinued for 15 min. Cyclohexyl isocyanide (1 mmol)
is added and stirring is continued for 4 h until the
reaction is completed (indication by thin layer chro-
matography (TLC)). The catalyst is recovered after
placing a magnet on the reactor wall and decanting
2.3 Synthesis of silica-coated Fe3O4 nanoparticles
(SiO2@Fe3O4NPs)
SiO2@Fe3O4NPs is produced by hydrolysis of the reaction mixture which contains the product in
tetraethylorthosilicate (TEOS) on the surfaces of the either insoluble or soluble form. Filtration and/or col-
Fe3O4NPs. The precipitate Fe3O4 is ultrasonically re- umn chromatography of the reaction mixture on sili-
dispersed in a solution containing 35 ml ethanol and ca (ethyl acetate/hexane) affords the pure product. The
6 ml water. The pH value is adjusted to 9 with an ammo- recovered catalyst is washed twice with methanol and
nia solution, then 1.5 ml 3-aminopropyltriethoxysilane dried at 50◦C, then reused in the next run. Loss of the
(APTES) is added under vigorous stirring for 10 h. To catalyst, in the process of separation, appears minimal
further hydrolyse, the ferro-fluid is heated at 50◦C for and is negligible.

1350
Monireh Ghavami et al.
SEM and TEM (figure 1). In accord with TEM, which
3. Results and discussion
provides rather more accurate information on the par-
ticle size than SEM, average diameter of the core is
around 9.8 nm (figure 1b and c). Using BET method,
surface area (SBET) and the total pore volume (Vp)
appear fairly ideal for active Cu(acac)2/NH2-T/SiO2
@Fe3O4NPs, with 29 m2 g−1 and 0.12 cm3 g−1, respec-
tively. Owing to the remarkable increase in parti-
cle size during functionalization of Fe3O4 NPs, spe-
cific surface area is greatly reduced from Fe3O4NPs
(221.5 m2 g−1) to SiO2@Fe3O4NPs (58.1 m2 g−1), NH2-
T/SiO2@Fe3O4NPs (42 m2 g−1), and Cu(acac)2/NH2-
T/SiO2@Fe3O4NPs (29 m2 g−1). These results confirm
Fe3O4NPs functionalizations.
In this section, complete characterization of our
nanocatalyst (Cu(acac)2/NH2-T/SiO2@Fe3O4NPs) is
followed by its synthetic application. In the following
subsections, morphology and particle size of con-
stituting Fe3O4NPs are characterized by SEM and
TEM. Surface area of the catalyst is estimated by
Brunauer-Emmet-Teller (BET). Evidence for the effec-
tive irreversible attachment of [Cu(acac)2] on the sur-
face of NH2-T/SiO2@Fe3O4NPs is indicated by colour
change and confirmed by XRD, XPS, Inductively cou-
pled plasma (ICP), FTIR, and TGA analyses. Mag-
netic properties of Fe3O4NPs and Cu(acac)2/NH2-
T/SiO2@Fe3O4NPs are determined by VSM. Subse-
quently, the applicability, selectivity, efficiency, and
reusability of the catalyst are discussed in light of one-
pot synthesis of α-aminoacyl amides (I) using Ugi four-
component reaction (U-4CR) of cyclohexyl isocyanide,
acetic acid, various amines and aldehydes.
3.2 Structural analysis of the catalyst and its
components (via XRD)
The XRD patterns are compared and contrasted for
Fe3O4NPs, SiO2@Fe3O4NPs, NH2-T/SiO2@Fe3O4NPs,
and Cu(acac)2/NH2-T/SiO2@Fe3O4NPs (figure 2).
The position and relative intensities of all peaks coin-
cide with standard XRD pattern of Fe3O4 (JCPDS card
No. 19-0629), indicating retention of the crystalline
structure during functionalization of Fe3O4NPs. Average
Fe3O4NPs core diameter is calculated to be 10 nm from
3.1 Morphology, particle size and surface area (via
SEM, TEM and BET)
The Fe3O4 magnetic nanoparticles (Fe3O4NPs) come
into view with an approximate spherical shape in
(a)
Acc. V Spot Magn Det WD
500 nm
17.0 kV 1.0 30000x SE 8.8 S2 28nm
(c)
(b)
Figure 1. (a) SEM, (b) TEM images, and (c) Particle size histogram of our F3O4 NPs.

Magnetically recoverable Cu(acac)2/NH2-T/SiO2@Fe3O4 NPs
1351
confirm the structure of our catalyst, Cu(acac)2/NH2-
T/SiO2@Fe3O4NPs (table 1, figure 3).
For carbon spectra, the main change is the appear-
ance of a new shoulder around 288.0 eV in Cu(acac)2/
NH2-T/SiO2@Fe3O4NPs (figure 3, C 1s, S4), which
could be attributed to the C=N, C–N, and C=O
groups, indicating the anchoring of Cu(acac)2 in NH2-
T/SiO2@Fe3O4NPs.
Oxygen anions in the lattice of Fe3O4NPs give the O
1s peak at 528 eV (figure 3, C 1s, S1).41 Oxygen anions
in SiO2@Fe3O4NPs and NH2-T/SiO2@Fe3O4NPs sam-
ples give a shoulder at 528 eV (figure 3, O1s, S2 and
S3), while the region near 530 eV (figure 3, O 1s, S2, S3,
and S4) could be attributed to either C–O and/or C=O
and Si–O surface species.42 As XPS can only measure
the elements on the most outer surface, there is no sig-
nal at 528 eV in (Cu(acac)2/NH2-T/SiO2@Fe3O4NPs)
(figure 3, O 1s, S4). This is in agreement with the BET
results.
The Si 2p spectra consist of major peaks centred
at approximately 103 eV (Si-O) (figure 3, Si 2p S2).
Both NH2-T/SiO2@Fe3O4NPs and Cu(acac)2/NH2-
T/SiO2@Fe3O4NPs give similar spectra. XPS results
of the two samples show a new weak shoulder around
101.1 eV,43 which could be attributed to the C-Si-O3,
indicating the grafting of the APTES to SiO2@Fe3O4NPs
(figure 3, Si 2p S3 and S4).
Specifically, deconvolution of C 1s into five com-
ponents indicates C-Si (A), hydrocarbon or hydrocar-
bon groups (B), C=N (C), C–N (D), and C=O (E) at
283.22, 284.71, 285.61, 286.38, and 288.32 eV, respec-
tively (figure 4).44 The latter binding energy estab-
lishes unambiguous formation of C=N bond and hence
the anchorage of Cu(acac)2 onto the surface of NH2-
T/SiO2@Fe3O4NPs. Similarly N 1s peak is deconvo-
luted into peaks with maxima at 398.31 and 399.45 eV,
corresponding to C–N and C=N, respectively (not
shown here). The C=N binding energies extracted from
Figure 2. XRD patterns of (a) Fe3O4NPs, (b) SiO2@Fe3
O4NPs, (c) NH2-T/SiO2@Fe3O4NPs and (d) Cu(acac)2/
NH2-T/SiO2@Fe3O4NPs.
the XRD results by Scherrer’s equation, D = kλ/βcosθ,
where k is a constant (generally considered as 0.94), λ
is the wavelength of Cu Ka (1.54 Å), β is the corrected
diffraction line full-width at half-maximum (FWHM),
and θ is Bragg’s angle,38 which is in good accordance
with its TEM. A weak broad band at 2θ = 18–27◦
could be assigned to the amorphous silane shell formed
around the magnetic cores (figure 2b and c).39 The
XRD pattern of Cu(acac)2/NH2-T/SiO2@Fe3O4NPs
indicates an effective anchorage of Cu(acac)2 onto the
surface of NH2-T/SiO2@Fe3O4NPs, with lines at 2θ =
11.70, 15.55, 17.12, 24.73 and 27.27 (figure 2d).40
3.3 Structural characterization of the catalyst (via
XPS and ICP)
The XPS binding energy of C 1s, O 1s, Si 2p, N 1s and
Cu 2p, along with the corresponding atomic % data,
Table 1. Structural characterization by XPS data; Cu amounts (wt.%) obtained by ICP and XPS
analyses.
Atoms and C-bonds
BE (eV)
Atomic (%)
Bond (%)
%CuXPS
%CuICP
CuXPS/ CuICP
C
O
Si
N
285.18
533.44
101.11
398.2
932.47
952.92
283.22
284.71
285.61
286.38
288.32
49.8
36.5
9.8
1.5
1.2
1.2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
5.4
-
-
-
-
1.9
Cu 2p3/2
Cu 2p1/2
C–Si
C–C, C–H
C=N
C–N
C=O
10.2
-
19.3
43.5
9.9
18.4
8.9
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-

1352
Monireh Ghavami et al.
Figure 3. XPS spectra of Fe3O4 NPs (S1), SiO2@Fe3O4NPs (S2), NH2-
T/SiO2@Fe3O4NPs (S3), and Cu(acac)2/NH2-T/SiO2@Fe3O4NPs (S4) in the
regions of C 1s, O 1s, Si 2p, N 1s, and Cu 2p.
C 1s and N 1s (285.61, and 399.45 eV, respectively) tence of unpaired electrons in Cu(acac)2, and are con-
belong to the same range as those reported for organic sistent with literature values of 932.6 and 952.2 eV,
molecules, e.g. pyridine (285.5 and 400.6 eV), poly- respectively.47,48 The ICP and XPS copper content
acronitrile (286.4 and 399.57 eV) and hexamethylenete- of our catalyst are 5.4% and 10.2%, respectively
tramine (286.9 and 398.8 eV).45,46 In the XPS spectrum (table 2). The ratio of CuXPS/CuICP, with its value
of Cu(acac)2, a doublet structure appears at 932.47 and of 1.9, indicates that the Cu(acac)2 is approximately
952.92 eV, which correspond to Cu 2p3/2 and Cu 2p1/2 homogeneously distributed on the surface of NH2-
(figure 3e). These peaks are associated with the exis- T/SiO2@Fe3O4NPs.49
3.4 Structural analysis of the catalyst
and its components (via FTIR)
Comparing FTIR spectra of Fe3O4NPs, SiO2@Fe3O4NPs,
NH2-T/SiO2@Fe3O4NPs and Cu(acac)2/NH2-T/SiO2@
Fe3O4NPs appears instructive (figure 5). The two bands
at 600.08 and 437.55 cm−1 are attributed to the stretch-
ing vibrations of Fe–O in Fe3O4 nanoparticles (com-
posed of FeO and Fe2O3). Owing to the size reduction
in the nano structure, these vibrations are red-shifted
compared to those observed in the bulk Fe3O4 sam-
ples (570 and 375 cm−1, respectively).50,51 FTIR spectra
Figure 4. Deconvoluted spectrum of C 1s.

Magnetically recoverable Cu(acac)2/NH2-T/SiO2@Fe3O4 NPs
1353
Table 2. Optimization of the amount of catalyst in Ugi reaction of benzaldehyde, aniline,
acetic acid and cyclohexyl isocyanide (scheme 2).a
Entry
Catalyst (mol%)
Yield (%)
TONb
TOFc
1
2
3
4
5
6
7
-
10
54
82
98
98
98
96
12
63
96
115
115
115
112
3
16
24
29
29
29
28
Cu(acac)2/NH2-T/SiO2@Fe3O4NPs (0.25)
Cu(acac)2/NH2-T/SiO2@Fe3O4NPs (0.45)
Cu(acac)2/NH2-T/SiO2@Fe3O4NPs (0.85)
Cu(acac)2/NH2-T/SiO2@Fe3O4NPs (1)
Cu(acac)2/NH2-T/SiO2@Fe3O4NPs (1.2)
Cu(acac)2 (0.85)
aReaction conditions: aldehyde (1 mmol), amine (1 mmol), Cu(acac)2/NH2-T/SiO2@Fe3O4 NPs
(0.85 mol%), methanol (5 ml), RT, 1 h, then acetic acid (1 mmol), 15 min, then cyclohexyl iso-
cyanide (1 mmol), 4 h
bTON (turnover number): mols of product obtained per mol of the catalyst
cTOF (turnover frequency) for 4 h of reaction
of SiO2@Fe3O4NPs, NH2-T/SiO2@Fe3O4NPs and is confirmed by C–H stretchings at 2928 cm−1. Spec-
Cu(acac)2/NH2-T/SiO2@Fe3O4NPs show Fe-O vibra- trum of Cu(acac)2/NH2-T/SiO2@Fe3O4NPs exhibits
tions in the same vicinity. It was reported that Fe3O4 well-defined bands at about 1593 and 1418 cm−1 due
nanoparticles can take up extensive hydroxyl groups on to ν(C=O and/or C=N) and ν(C=C), respectively
their surface upon contact with aqueous phase through (figure 1d). This is a strong evidence for anchoring of
adsorption of OH− on Fe and H+ on O.52 This is [Cu(acac)2] on the surface of NH2-T/SiO2@Fe3O4NPs
confirmed by the broad O–H stretching band at through the Schiff condensation of −NH2 and −CO
3399 cm−1. The Si–O–Si asymmetric stretching vibra- groups.
tion at 1082 cm−1 and symmetric stretching vibration
at 796 cm−1 appear in all the samples, but Fe3O4NPs,
which indicates that silica is successfully coated on
the surface of Fe3O4 nanocrystals upon hydrolysis
3.5 Structural analysis of the catalyst
and its components (via TGA)
of TEOS. Introduction of APTES to the surface of
Thermogravimetric analysis curves of the SiO2@
Fe3O4NPs is confirmed by the band at 1082 cm−1,
Fe3O4NPs, NH2-T/SiO2@Fe3O4NPs and Cu(acac)2/
which is assigned to the Si–O stretching vibration. The
NH2-T/SiO2@Fe3O4NPs show the mass loss of organic
broad band at 3404 cm−1 corresponds to N–H stretch-
materials as they decompose upon heating (figure 6).
ing vibration.53 Presence of anchored propyl group
Initial weight loss from the SiO2@Fe3O4NPs up to
126◦C is due to the removal of physically adsorbed
Figure 5. Comparative FTIR spectra for (a) Fe3O4NPs,
(b) SiO2@Fe3O4NPs, (c) NH2-T/SiO2@Fe3O4NPs, (d)
Cu(acac)2/NH2-T/SiO2@Fe3O4NPs and (e) recovered cata-
lyst after usage.
Figure 6. TGA curve of (a) SiO2@Fe3O4NPs, (b) NH2-
T/SiO2@Fe3O4NPs and (c) Cu(acac)2/NH2-T/SiO2@
Fe3O4NPs.

1354
Monireh Ghavami et al.
there is a well-defined mass weight loss of 21.3%
60
(a)
(b)
between 135◦ and 282◦C related to the breakdown of
the Cu(acac)2 moieties. On the basis of these results, the
well grafting of APTES and Cu(acac)2 groups on the
Fe3O4NPs is verified.
40
20
0
-20
-40
-60
3.6 Magnetic properties of Fe3O4NPs and Cu(acac)2/
NH2-T/SiO2@Fe3O4NPs (via VSM)
Super-paramagnetic behaviour is attributed to both
Fe3O4NPs precursor and Cu(acac)2/NH2-T/SiO2@
Fe3O4NPs for exhibiting VSM magnetization values
of 60.0 and 23.0 emu/g, respectively56 (figure 7). Evi-
dently, lower magnetization of the latter is due to the
extensive silica coatings of the magnetic core and its
functionalizations. Yet, decrease in magnetization does
not prevent Cu(acac)2/NH2-T/SiO2@Fe3O4NPs from
being readily separated by conventional magnets.
-10000 -8000 -6000 -4000 -2000
0
2000 4000 6000 8000 10000
Applied Field (Oe)
Figure 7. Magnetization curves for (a) Fe3O4NPs and (b)
Cu(acac)2/NH2-T/SiO2@Fe3O4NPs at room temperature.
solvent and surface hydroxyl groups. Weight loss of
about 1.67% between 192◦ and 310◦C may be asso-
ciated with the thermal crystal phase transformation
from Fe3O4 to γ -Fe2O3 (figure 6a and b).49 High rate
of weight loss in the temperature ranging from 250–
600◦C for SiO2@Fe3O4NPs may be attributed to the
condensation of silanol groups in SiO2@Fe3O4NPs.55
Weight loss of APTES-modified Fe3O4NPs is about
3.06% at 379–568◦C, which is contributed to the
thermal decomposition of the 3-aminopropyl groups
(figure 6b). For Cu(acac)2/NH2-T/SiO2@Fe3O4NPs,
3.7 Evaluation of catalyst activity through U-4CR
In order to evaluate the catalytic activity of our
Cu(acac)2/NH2-T/SiO2@Fe3O4NPs, it is applied to
U-4CR25 for generating α-aminoacyl amide derivatives
by condensing an aldehyde, amine, carboxylic acid and
isocyanide.
Table 3. Ugi one-pot catalytic synthesis of α-aminoacyl amides (I, scheme 2) via
Cu(acac)2/NH2-T/SiO2@Fe3O4NPs.a
Entry
R1
R2
Time (h)
Catalyst
Yield (% I)
√
√
√
√
√
√
√
√
√
√
√
√
√
√
1
2
3
4
5
6
7
8
Phenyl
n-Butyl
n-Butyl
n-Butyl
n-Butyl
n-Butyl
n-Butyl
n-Butyl
Phenyl
Phenyl
Phenyl
n-Butyl
n-Butyl
n-Butyl
n-Butyl
n-Butyl
Phenyl
Phenyl
4
4
4
4
4
4
4
4
4
89
95
94
87
92
85
93
98
96
76
—
—
—
—
54
68
75
2-Methylphenyl
4-Methylphenyl
2-Chlorophenyl
4-Bromophenyl
4-Hydroxyphenyl
4-Trifluoromethylphenyl
Phenyl
2-Methylphenyl
Ethyl
Pyridine-2-yl
Pyridine-3-yl
Pyridine-4-yl
Pyrrole-2-yl
9
10
11
12
13
14
15
16
17
4
24
24
24
24
24
24
24
Phenyl
Phenyl
2-Methylphenyl
—
—
—
aReaction conditions: aldehyde (1 mmol), amine (1 mmol), Cu(acac)2/NH2-T/SiO2@Fe3O4 NPs
(0.85 mol%), methanol (5 ml), RT, 1 h, then acetic acid (1 mmol), 15 min, then cyclohexyl
isocyanide (1 mmol), 4 h

Magnetically recoverable Cu(acac)2/NH2-T/SiO2@Fe3O4 NPs
1355
H
R1
R2
N
O
NH2
H2O
Cy
O
O
R1
R2
N
H
R1
H
NR2
H
O
COOH
COO
O
H3C
H3C
N
Cy
NH
H
H
R2
R1
COO
R1
HN
R2
R2
H3C
C
NH
H
N
Cy
C
R1
N
Cy
Scheme 3. A provisional mechanism for the role of Cu(acac)2/NH2-T/SiO2@Fe3O4NPs in U-4CR.
In order to optimize amount of catalyst, Ugi reaction selectivity between aromatic and heteroaromatic alde-
is carried out using benzaldehyde, aniline, acetic acid hydes. While aromatic (and aliphatic) aldehydes render
and cyclohexyl isocyanide, in MeOH at room tempera- pure products in good to high yields, within 4 h (entry
ture. In the absence of the catalyst, about 10% of pro- 1–10, table 3); heteroaromatic aldehydes do not pro-
duct is obtained after 4 h (table 2, entry 1). The yield duce any product, even with an extended reaction time
of product is increased with increase of the amount of of 24 h (entry 11–14, table 3). In the absence of catalyst,
nanocatalyst from 0.25 to 0.85 mol% (table 2, entries
2–4). However, greater amounts than 0.85 mol% have
no significant effect on the yield (table 2, entries
5 and 6). So, the optimum amount of catalyst is
0.85 mol%/mmol of benzaldehyde which resulted in
98% yield of the product after 4 h.
The Cu(acac)2/NH2-T/SiO2@Fe3O4 NPs acts as a
heterogeneous catalyst in Ugi reaction, with TON and
TOF similar to the ones obtained with homogeneous
phase reaction performed with [Cu(acac)2], under com-
parable experimental conditions (table 2, entries 4
and 7).
Products of various aromatic as well as aliphatic
aldehydes and amines are isolated by filtration or
column chromatography, in good to excellent yields
(table 3). Purity and structural analysis of the pro-
ducts are mainly established by NMR, IR and mass
spectroscopy (supporting information). Reaction time
decreases to the unprecedented 4 h, which is a notice-
Figure 8. Efficiency of catalyst in Ugi reaction of ben-
zaldehyde, aniline, acetic acid and cyclohexyl isocyanide
(scheme 2) after each run.
able improvement from the previously reported 24–
72 h.26 Another advantage of our new catalyst is its

1356
Monireh Ghavami et al.
similar reactions result in low yields with long reaction
times (entry 15–17, table 3).
8. Fan Q-H, Li Y-M and Chan A S C 2002 Chem. Rev. 102
3385
9. Esmaeilpour M, Sardarian A R and Javidi J 2012 Appl.
Catal. A: Gen. 28 359
10. Leadbeater N E and Marco M 2002 Chem. Rev. 102 3217
11. Rafelt J S and Clark J H 2000 Catal. Today 57 33
12. Arends I W C E and Sheldon R A 2001 Appl. Catal. A:
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13. Kantam M L, Kavita B, Neeraja V, Haritha Y, Chaudhuri
M K and Dehury S K 2003 Tetrahedron Lett. 44 9029
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The role of our catalyst may be explained in light
of its ability to provide a suitable surface for perform-
ing U-4CR (scheme 3). Sequentially, Cu(acac)2/NH2-
T/SiO2@Fe3O4NPs facilitates the formation of imine,
by increasing the electrophilicity of the carbonyl group
of the aldehyde. The reaction proceeds via activation
of resulting imine, by the nanocatalyst and its further
reaction with acetic acid and cyclohexyl isocyanide to
form an intermediate, which in turn rearranges to the
α-aminoacyl amide. On the other hand, heteroaromatic
aldehydes seem to poison the catalyst giving no pro-
duct at all. This adds to the value of the nanocatalyst for
making it highly selective.
16. Cano R, Yus M and Ramón D J 2011 Tetrahedron 67
8079
17. Khoobia M, Ma’mania L, Rezazadehb F, Zareieb Z,
Foroumadia A, Ramazanib A and Shafiee A 2012 J. Mol.
Catal. A: Chem. 356 74
18. Kong A, Wang P, Zhang H, Yanga F, Huang S and Shan
Y 2012 Appl. Catal. A: Gen. 417–418 183
19. Claesson E M, Mehendale N C, Gebbink R J M K,
Koten G V and Philipse A P 2007 J. Magn. Magn. Mater.
311 41
Preservation of structural integrity of the catalyst is
suggested by the minimal changes in its efficiency after
three runs (figure 8) and confirmed by the comparison
of its FTIR spectra before and after its implementation
(figure 5d vs. e).
20. Masteri-Farahani M and Kashef Z 2012 J. Magn. Magn.
Mater. 324 1431
21. Bagheri M, Masteri-Farahani M and Ghorbani M 2013
J. Magn. Magn. Mater. 327 58
22. Masteri-Farahani M and Tayyebi N 2011 J. Mol. Catal.
A: Chem. 348 83
23. Masteri-Farahani M, Movassagh J, Taghavi F, Eghbali P
and Salimi F 2012 Chem. Eng. J. 184 342
24. Deng Y, Qi D, Deng C, Zhang X and Zhao D 2008
J. Am. Chem. Soc. 130 28
4. Conclusion
We have successfully prepared a new magnetically
recoverable nanocatalyst (Cu(acac)2/NH2-T/SiO2@
Fe3O4NPs), which is applied to one-pot synthesis of α-
aminoacyl amides, through Ugi four-component reac-
tion (U-4CRs). This investigation clearly shows that
our catalytic system drastically decreases reaction time,
increases yield, and more importantly exhibits a high
selectivity for aromatic aldehydes, to the extent that it
forms no product from the heteroaromatic ones.
25. Dömling A and Ugi I 2000 Angew. Chem. Int. Ed. 39
3169
26. Krasavin M, Parchinsky V, Shumsky A, Konstantinov I
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29. Kunz H and Pfrengle W 1988 Tetrahedron 44 5487
30. Kunz H, Pfrengle W and Sager W 1989 Tetrahedron
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Supporting information
Data of NMR and IR spectra are given as supporting
information and can be seen at www.ias.ac.in/chemsci
website.
31. Kunz H, Pfrengle W, Rück K and Sager W 1991 Synthe-
sis 11 1039
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