Room temperature aldol reactions using magnetic Fe3O 4@Fe(OH)3 composite microspheres in hydrogen bond catalysis

Article abstract of DOI:10.1039/b920009f

Fe₃O₄@Fe(OH)₃ composite microspheres are highly active, environmentally friendly and easy to recycle catalysts for aldol reactions, which are catalyzed by a solid-liquid interfacial hydrogen bond catalyst at room temperature.

Full text of DOI:10.1039/b920009f

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Room temperature aldol reactions using magnetic Fe3O4@Fe(OH)3
composite microspheres in hydrogen bond catalysisw
Fang Niu, Long Zhang, San-Zhong Luo and Wei-Guo Song*
Received (in Cambridge, UK) 30th September 2009, Accepted 4th December 2009
First published as an Advance Article on the web 23rd December 2009
DOI: 10.1039/b920009f
Fe3O4@Fe(OH)3 composite microspheres are highly active,
environmentally friendly and easy to recycle catalysts for aldol
reactions, which are catalyzed by a solid–liquid interfacial
hydrogen bond catalyst at room temperature.
Aldol reactions are among the most useful C–C bond forming
reactions in organic synthesis. It generally proceeds in
homogeneous acid or basic solutions through carbocation or
carbanion mechanisms.1 In recent years, several aldol
Fig. 1 TEM images of (a) Fe3O4 microspheres and (b) Fe3O4@Fe(OH)3
reactions using acid or base catalysts have been reported,2
composite microspheres.
including iron-catalyzed cross-aldol reactions,3 proline-loaded
catalysts for stereoselectivity,4–6 and aldol-type reactions of
In mechanistic studies, isotopic labeling experiments, in which
lithium enolate7 and silyl enolate.8 In our previous work, the
the hydrogen atoms on the surface hydroxyl groups are
replaced by deuterium atoms, show a secondary isotopic effect
aldol reaction between benzaldehyde and phenyl methyl
on the reaction rate, but no H/D exchange. A hydrogen
ketone was catalyzed by nanostructured magnesium oxide as
a solid basic catalyst.9 The reaction mechanisms of hetero-
bond-mediated catalytic mechanism at the solid–liquid interface
is proposed to explain the observations.
geneous catalysts are believed to be similar to those in homo-
Fe3O4 microspheres were prepared according to the
reported method with minor modifications.16 Fe3O4@Fe(OH)3
geneous systems, i.e. definite acidic or basic species must be
incorporated onto the catalysts for successful aldol reactions.
core–shell composite microspheres was self-prepared by
The leaching of such active species will lead to catalyst
depositing Fe(OH)3 gel on the Fe3O4 microspheres (see
deactivation, difficulty in further processing and environmental
experimental details in the ESIw). The as-prepared Fe3O4
microspheres are porous with an average diameter of about
implications.
In the so-called ‘‘on water’’ reaction, the free hydroxyl
300 nm and clear boundaries (Fig. 1a). The TEM image of the
group on water at the oil–water interface can enormously
Fe3O4@Fe(OH)3 composite microspheres (Fig. 1b) become
enhance the reaction rate of organic reactions through hydrogen
bond catalysis.10–12 We have shown hydrogen bond catalysis
denser and the diameter slightly enlarged. A thin and loose
Fe(OH)3 layer can be seen at the boundary of each sphere.
at the solid–liquid interface on metal oxide or metal hydroxide
XRD patterns (Fig. 2a) of Fe3O4 microspheres and
nanoparticles for several coupling reactions through solid–
liquid interfacial hydrogen bond catalysis.13,14 Surface hydroxyl
Fe3O4@Fe(OH)3 composite microspheres show only the
magnetite phase. No XRD signal was observed from the
groups are natural functional groups on metal hydroxides and
Fe(OH)3 phase, indicating that Fe(OH)3 component is
are environmentally benign. However, surface hydroxyl
amorphous. From the TGA results of Fe3O4 microspheres
groups on metal hydroxides are considered very weak acid
and Fe3O4@Fe(OH)3 composite microspheres under nitrogen
sites, and hydrogen bonds between surface hydroxyl groups
atmosphere (ESIw, Fig. S1), we determined that the composite
and the organic molecules do not generate the cationic or
anionic species necessary for traditional aldol reactions.15
consists of 17 wt% of Fe(OH)3 and 83 wt% Fe3O4. BET
analysis (Fig. 2b) gives a specific surface area of 32 m2 gÀ1 for
In this report, we will demonstrate that aldol reactions can
be catalyzed by the hydroxyl groups on the Fe(OH)3 shell
from Fe3O4@Fe(OH)3 core–shell composite microspheres.
This core–shell composite material shows high catalytic activity
from the Fe(OH)3 shell and the magnetic core makes it is
easy to recycle the catalyst from the reaction mixture.
Beijing National Laboratory for Molecular Sciences (BNLMS),
Laboratory for Molecular Nanostructures and Nanotechnology,
Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190,
P.R.China. E-mail: wsong@iccas.ac.cn; Fax: (+86) 10-62557908
w Electronic supplementary information (ESI) available: Preparation
and TGA results of materials; detailed product identification by NMR
and MS; aldol reaction using recovered catalysts. See DOI: 10.1039/
b920009f
Fig.
2 (a) XRD patterns for (1) Fe3O4 microspheres and
(2) Fe3O4@Fe(OH)3 composite microspheres; (b) N2 isotherm for (1)
Fe3O4 microspheres and (2) Fe3O4@Fe(OH)3 composite microspheres,
(red dots) N2 desorption curve, and (black dots) N2 adsorption curve.
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Table
and
composite microspheres
1
aromatic aldehydes catalyzed by Fe3O4@Fe(OH)3
Room temperature aldol reaction between acetone
Table 2 Aldol reaction between 4-chlorobenzaldehyde and ketones in
various solvents catalyzed by Fe3O4@Fe(OH)3 composite microspheres
Entrya
Ar–
Reaction time/h
Yields (%)
Reaction Yields
time/h
Entrya Ketone
Solvent
(%)
1
2
3
4
5
6
7
8
C6H5
4-NO2-C6H4
4-Cl-C6H4
24
24
24
24
24
24
24
24
120
24
3
18
60
88
82
51
77
76
40
1
2
3
4
5
6
7
8
Acetone
Butanone
Toluene
Toluene
Phenyl methyl ketone Toluene
20
20
20
20
20
20
3
24
24
24
24
24
20
38
82
65
22
70
18
24
18
11
28
23
88
4-Br-C6H4
4-CN-C6H4
4-CH3-C6H4
4-CH3O-C6H4
4-NH2-C6H4
4-HO-C6H4
3-CF3-C6H4
4-NO2-C6H4
Cyclopentanone
Cyclohexanone
Cycloheptanone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Toluene
Toluene
Toluene
Tolueneb
Ethanol
THF
DMF
CHCl3
Cyclohexane 20
9
10
11
Trace
40
9
99b
10
11
12
13
14
a
Reaction conditions: 2 ml acetone, 0.2 mmol of aromatic aldehydes,
128 mg of Fe3O4@Fe(OH)3 composite microspheres, room temperature.
p-Xylene
Acetone
20
24
b
Heated to 50 1C.
a
Reaction conditions: 0.2 mmol of 4-chlorobenzaldehyde, 1 mmol of
ketones, 128 mg of Fe3O4@ Fe(OH)3 composite microspheres in 2 ml
b
the Fe3O4 microspheres and 102 m2 gÀ1 for the Fe3O4@Fe(OH)3
composite microspheres, respectively. A rough estimation
based on the surface area data and the content of the composite
gives a 438 m2 gÀ1 net surface area of the Fe(OH)3 shell. Such
a high surface area value suggests abundant surface hydroxyl
groups on this composite material.
of solvent, room temperature. Heated to 50 1C.
As shown above, Fe3O4@Fe(OH)3 composite microspheres
are a good catalyst for the aldol reaction. However, the
hydroxyl groups on the Fe(OH)3 surface, like the silanol
groups on silica, are considered very weak acids, thus it is
unlikely that cationic or anionic intermediates are formed in
these Fe(OH)3-catalyzed reactions, especially considering that
these reactions were carried out at room temperature. The
weakly acidic surface hydroxyl groups often form hydrogen
bonds with oxygenates.17,18 We believed that H-bonds
catalyze the aldol reactions in this work, as illustrated in
Scheme 1. Several experiments were designed to confirm it.
We first studied the H/D exchange in reactions (1) and (2).
Fe3O4@Fe(OD)3 was prepared (see the ESIw) to repeat the
same experiments of reaction (1) and (2). The rationale behind
this H/D exchange experiment is that if Fe(OH)3 materials act
as a solid acid catalyst in a cationic mechanism, the O–H bond
of the surface hydroxyl groups will break and H/D exchange is
expected to form deuterium-labeled product, i.e. D2O or HDO
in reaction (1) and deuterium-labeled product 3 in reaction (2).
By GC-MS analysis, we do not observe any of these
The catalytic activity of Fe3O4@Fe(OH)3 composite
microspheres was tested in aldol reactions. In the first set of
trials, acetone was chosen for aldol condensation with
aromatic aldehydes (Table 1) at room temperature. The
reaction products were isolated through silica column
chromatography, and analyzed by HPLC, mass spectrometry
and NMR (detailed product identification by NMR and MS
can be seen in the ESIw). As shown in Table 1, most reactions
have good yields except when 4-hydroxybenzaldehyde is used
(Table 1, entry 9). When the reaction temperature was elevated
to 50 1C, a total conversion of 4-nitrobenzaldehyde in aldol
condensation was achieved in 3 h (Table 1, entry 11).
We then tested several aldol reactions between various
ketones and 4-chlorobenzaldehyde using Fe3O4@Fe(OH)3
composite microspheres as the catalyst (Table 2). Aldol
reactions with cyclopentanone and cyclohexanone show
conversions of 82% and 65%, respectively. For acetone,
butanone, phenyl methyl ketone, and cycloheptanone, lower
yields were achieved. The yields of reactions are kept moderate
by carrying out the reaction at room temperature.
One of the advantages of heterogeneous catalysis is the facile
catalyst recycling. This is more evident for Fe3O4@Fe(OH)3
composite microspheres as it can be conveniently separated
by magnet and reused. In this study, the catalyst was
reused five times with a constant yield of about 90% in the
aldol reaction between acetone and 4-chlorobenzaldehyde
(ESIw, Table S1, entry 3–7). In control experiments, we found
that Fe3O4 microspheres alone can not catalyze the reaction
(ESIw, Table S1, entry 9), indicating that the surface hydroxyl
group is the key factor for catalyzing the aldol reactions in
this work.
Scheme 1 Mechanism illustration of the aldol reaction catalyzed by
Fe3O4@Fe(OH)3 composite microspheres.
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Table 3 H/D exchange results for aldol reactions
activate the CQO bond of the 4-nitrobenzaldehydes by
inducing a more electron-depleted C atom, thus accelerating
the aldol reactions. In addition, the hydrogen bonds may
stabilize the reaction intermediate species or transition state
species.21,22
In summary, we prepared Fe3O4@Fe(OH)3 composite
microspheres, which are an excellent catalyst for several sets
of aldol reactions. A hydrogen bond-mediated catalytic
mechanism at the solid–liquid interface in heterogeneous
system is proposed, and is supported by isotopic labeling
experiments. Using Fe3O4@Fe(OH)3 composite microspheres
for hydrogen bond-catalyzed aldol reaction does not need
strong acid or base for cationic or anionic pathways and
broadens the scope of hydrogen bond catalysis for green and
environment friendly catalysis.
Deuterium
content in
products
Yields
(%)
Entrya
Reaction
Catalyst
(atom %)
1
2
1
2
Fe3O4@Fe(OD)3
Fe3O4@Fe(OD)3
30
25
0b
0c
a
Reaction conditions: 2 ml acetone, 0.2 mmol of aromatic aldehydes,
128 mg of Fe3O4@Fe(OD)3 composite microspheres, room temperature.
c
Based on the identical ion mass pattern of water. Based on the
We gratefully thank the National Natural Science Founda-
tion of China (NSFC 50725207, 20821003 and 20873156),
Ministry of Science and Technology (MOST 2007CB936400
and 2009CB930400) and the Chinese Academy of Sciences for
financial supports.
b
identical ion mass pattern of product 3.
deuterium-labeled products at all (see Table 3 and the ESIw,
Fig. S2 and S3) in reaction (1) or in reaction (2). In addition,
the 3/2D NMR spectrum of product 3 (ESIw, Fig. S4) shows no
deuterium signal from this product.
Notes and references
Interestingly, an isotope effect was observed: as shown in
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1 ml of p-xylene and stirred for 3 min, followed by a simple
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Chem. Commun., 2010, 46, 1109–1111 | 1111