Aqueous asymmetric aldol reaction catalyzed by nanomagnetic solid acid SO42-/Zr(OH)4-Fe3O4

Article abstract of DOI:10.1016/S1872-2067(14)60222-9

Magnetic solid acid catalysts SO₄^2-/Zr(OH)₄-Fe₃O₄ were prepared using magnetic Fe₃O₄ nanoparticles, ZrOCl₂·8H₂O, and sulfuric acid as starting materials in

Full text of DOI:10.1016/S1872-2067(14)60222-9

Chinese Journal of Catalysis 36 (2015) 425–431
a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m
j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / c h n j c
Article
Aqueous asymmetric aldol reaction catalyzed by nanomagnetic solid
2−
acid SO4 /Zr(OH)4–Fe3O4
Tao Wu, Jingwei Wan, Xuebing Ma*
School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China
A R T I C L E I N F O
A B S T R A C T
Article history:
Magnetic solid acid catalysts SO42−/Zr(OH)4–Fe3O4 were prepared using magnetic Fe3O4 nanoparti‐
cles, ZrOCl2·8H2O, and sulfuric acid as starting materials in the calcination temperature range
110–650 °C. The properties of the magnetic solid acid, such as loaded SO42− content, acid distribu‐
tion, surface morphology, and porous structure, were characterized. In the aqueous asymmetric
aldol reaction of various benzaldehydes with strong electron‐withdrawing groups (R = NO2 and CN),
good to excellent catalytic performance (83%–100% yield, 86.0%–95.6% ee anti, and anti/syn =
88–96/12–4) was achieved. These nanomagnetic solid acids can be quantitatively recycled from the
reaction mixture using an external magnet and reused five times without significant loss of catalytic
activity.
Received 13 July 2014
Accepted 2 September 2014
Published 20 March 2015
Keywords:
Solid acid catalyst
Magnetism
Aldol reaction
Asymmetric catalysis
Aqueous phase
© 2015, Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
Published by Elsevier B.V. All rights reserved.
1. Introduction
adsorption processes owing to their unique superparam‐
agnetism, low toxicity, simple preparation, low cost, and ease of
The asymmetric aldol reaction is one of the most important
C–C bond‐forming reactions and creates the optically active
β‐hydroxy carbonyl structural unit found in many natural
products and drugs [1–4]. Most asymmetric aldol reactions
involve the directed aldol reaction in the presence of acidic
promoters, including organic and inorganic acids, which are
used to activate aldehydes electrophilically. Unfortunately,
organic acids such as TfOH and F3CCO2H have high solubility in
the organic phase, which results in impurities in the catalytic
products owing to difficult separation. Furthermore, liquid
inorganic acids are highly corrosive to industrial equipment.
Therefore, the choice of the solid acid in the aldol reaction is a
crucial decision [5–10].
recovery [11–13]. To combine the advantages of MNPs and
solid acids, magnetic solid acids have been developed and
widely applied in catalytic nitration [14], the Hantzsch reaction
[15], esterification [16,17], hydrolysis reactions [18,19], the
acetal reaction of benzaldehyde with ethylene glycol [20], and
coupling reactions of aryl bromides with heterocycles [21].
However, the application of magnetic solid acids in asymmetric
catalytic reactions is seldom reported.
In this paper, the nanomagnetic solid acids SO42−/Zr(OH)4–
Fe3O4 [22–24] were applied to the asymmetric aldol reaction of
cyclohexanone with various substituted benzaldehydes for the
first time. Good to excellent catalytic performance for the ben‐
zaldehydes with strong electron‐withdrawing groups (83%–
100% yield, 86.0%–95.6% ee anti, and anti/syn = 88–96/12–4)
was satisfactorily achieved. These magnetic solid acids can be
easily recovered in quantitative yield using an external magnet
Magnetic nanoparticles (MNPs) with large specific surface
areas and good textural properties are currently an area of
extensive research, particularly for applications in catalysis and
*Corresponding author. Tel/Fax: +86‐23‐68253237; E‐mail: zcj123@swu.edu.cn
This work was supported by the National Natural Science Foundation of China (21071116).
DOI: 10.1016/S1872‐2067(14)60222‐9 | http://www.sciencedirect.com/science/journal/18722067 | Chin. J. Catal., Vol. 36, No. 3, March 2015

426
Tao Wu et al. / Chinese Journal of Catalysis 36 (2015) 425–431
and possessed good tolerance in catalytic cycles with no signif‐
icant loss of catalytic performance.
Accurately weighed nanomagnetic solid acid (100.0 mg)
was soaked in 6 mol/L HCl (50 mL) under vigorous stirring for
3 h and filtered. Saturated BaCl2 was added to the filtrate and
BaSO4 precipitated out. After BaSO4 was filtered, dried under
2. Experimental
2−
reduced pressure, and accurately weighed, the SO4 content
2.1. Preparation of nanomagnetic solid acid
was calculated.
SO42−/Zr(OH)4–Fe3O4
2.4. General asymmetric aldol reaction
The suspension of nano‐Fe3O4 (2.32 g, 10.0 mmol, Aladdin,
99.5%) in distilled water (20 mL) was well stirred at 65 °C, and
aqueous ZrOCl2·8H2O solution (20 mL, Aladdin, 99.9%) with
molar ratios of ZrOCl2·8H2O:Fe3O4 = 0.2, 0.5, 1.0, 2.0, or 5.0 was
added dropwise. The pH of the reaction medium was adjusted
to 13 by ammonia spirit and stirred for another 4 h. The su‐
pernatant was decanted by magnetic separation using an ex‐
ternal magnet, and the obtained magnetic solids Zr(OH)4/Fe3O4
were washed with distilled water until the solution was neutral
and no Cl− ions were present and dried at 110 °C in vacuo. After
three nitrogen replacement, grinding, immersing in 0.5 mol/L
sulfuric acid for 3 h, and separating using an external magnet,
the samples were dried at 110 °C to obtain nanomagnetic solid
acids, which were designated as SZF1–5 for ZrOCl2·8H2O:Fe3O4
ratios of 0.2, 0.5, 1.0, 2.0, and 5.0, respectively [25,26]. SZF3 was
calcined in a muffle furnace at 300 or 650 °C for 3 h to give the
nanomagnetic solid acids SZF3‐300 and SZF3‐650, respectively.
9‐Amino‐9‐deoxy‐epi‐cinchonidine (epi‐CDNH2) was prepa‐
red according to a literature procedure [27]. In a vial (25 mL),
the mixture of nanomagnetic solid acid SZF3 (35.0 mg),
epi‐CDNH2 (11.0 mg, 0.0375 mmol), cyclohexanone (0.98 g,
10.0 mmol, Adamas‐beta, 99.5%), and deionized water (2.0
mL) was stirred at room temperature for 15 min. Then,
p‐nitrobenzaldehyde (76 mg, 0.50 mmol, Adamas‐beta, 99%)
was added and allowed to react at 25 °C for 48 h. After the re‐
action was complete, the SZF3 catalyst was magnetically sepa‐
rated using an external magnet and directly reused in the next
experiment. The resulting reaction mixture was extracted with
ethyl acetate (3 × 20 mL). The combined organic phases were
dried over anhydrous Na2SO4 and evaporated under reduced
pressure to give the crude product, which was purified by flash
column chromatography eluted with petroleum ether/ethyl
acetate (v/v = 10/1 to 2/1) to give pure 2‐(hydroxy(4‐meth‐
oxyphenyl)methyl)cyclohexanone. The anti/syn (Dr) ratio was
determined by 1H NMR in CDCl3, in which the chemical shifts of
syn‐ and anti‐CHOH protons were at δ = 5.32 ppm (d) with 3J =
1.3 Hz and δ = 4.74 ppm (d) with 3J = 8.8 Hz, respectively. The
enantiomeric excess (ee) was determined by high‐performance
liquid chromatography (HPLC) (Agilent Technologies 1200
Series) with a 254 nm UV‐vis detector using a Daicel chiralpak
Chiral OD column (4.6 mm × 250 mm), eluting with n‐hexane/
iso‐propanol (95/5) with a flow rate of 0.5 mL/min at 20 °C.
2.2. Characterization of catalysts
Magnetic hysteresis loops were measured on a vibrating
sample magnetometer (VSM, HH‐15, China) using Ni as the
standard substance. The powder was strongly pressed and
fixed in a small cylindrical plastic box for the magnetization
measurements. Thermogravimetry‐differential thermal analy‐
sis (TG‐DSC) spectra of the as‐synthesized samples were
measured on an SBTQ600 thermal analyzer (TA, USA) with a
heating rate of 20 °C/min from 40 to 800 °C under N2 (100
mL/min). The total acidity of the samples was determined by
temperature‐programmed desorption (TPD) of NH3. The
measurements were carried out by an automatic TPD appa‐
ratus (PCA‐1200, China). The sample was kept at 50 °C for 60
min in a flow of NH3. The amount of desorbed NH3 was deter‐
mined after heating the sample up to 700 °C with a heating rate
of 10 °C/min. N2 adsorption‐desorption analysis was per‐
formed at −196 °C on an Autosorb‐1 apparatus (Quantachrome,
USA). All samples were degassed at 130 °C for 12 h before
measurements, and the surface area and pore size distribution
were calculated by the BET and BJH models, respectively. After
being well‐dispersed in water (10 mg sample in 10 mL of H2O)
for 10 min under ultrasonic irradiation, sputtered over copper
wire, and evaporated under infrared radiation for 10 min, the
as‐synthesized samples were observed by transmission elec‐
tron microscopy (TEM) using a JEM 2100 transmission electron
microscope under an accelerating rate voltage of 200 kV to
show their surface morphologies (JEOL, Japan).
3. Results and discussion
3.1. Chemical composition of nanomagnetic solid acid
The chemical compositions of the magnetic solid acids
SZF1–5 are listed in Table 1. Although the molar ratios of
ZrOCl2:Fe3O4 in the preparation of Zr(OH)4–Fe3O4 varied great‐
ly in the range 0.2–5.0, the formed Zr(OH)4 could be loaded
onto nano‐Fe3O4 in 72%–75% yield. The content of Zr(OH)4 in
SZF1–5 determined by the inductively coupled plasma (ICP)
method increased from 13.9% to 71.2% with the increasing
Table 1
Chemical compositions of the various magnetic solid acids.
Molar ratio of Loaded Zr(OH)4 SO42− content
Entry Catalyst
ZrOCl2:Fe3O4
(wt%)
13.9
20.3
33.9
50.1
71.2
(wt%)
6.8
14.3
20.7
17.2
12.3
1
2
3
4
5
SZF1
SZF2
SZF3
SZF4
SZF5
1:5
1:2
1:1
2:1
5:1
2.3. Determination of SO42− content in nanomagnetic solid acid

Tao Wu et al. / Chinese Journal of Catalysis 36 (2015) 425–431
427
2−
molar ratio of ZrOCl2:Fe3O4. It is noteworthy that the SO4
100
96
92
88
84
DSC
DTG
contents in the magnetic solid acids SZF1–5 showed a close rela‐
tionship with the loaded Zr(OH)4. The immersed SO42− contents
in SZF1–5 first increased with increasing loaded amount of
Zr(OH)4. However, when the loaded Zr(OH)4 exceeded 33.9%,
the SO4 content gradually decreased owing to the accumula‐
tion of Zr(OH)4 on the outer surface of nano‐Fe3O4.
2.0
1.5
1.0
0.5
0.0
-0.5
6.08%
2.41%
2−
TG
8.06%
3.2. Magnetic properties
The magnetic properties of the representative solid acids
SZF1, SZF3, and SZF3ʹ (SZF3 reused five times) were examined
through vibrating sample magnetometry. Their hysteresis
loops at room temperature are shown in Fig. 1. VSM analysis
showed that the magnetic solid acids SZF1, SZF3, and SZF3ʹ pos‐
sessed saturated magnetization values of 55.58, 39.21, and
46.44 emu/g, respectively. The saturated magnetization values
of SZF1, SZF3, and SZF3ʹ were all sufficiently high to meet the
needs of magnetic separation. The zero coercivity and reso‐
nance of each magnetization loop confirmed the superpa‐
ramagnetism behavior at 25 °C for all of the samples, which is
very beneficial for the catalyst’s rapid dispersion and magnetic
separation. Unexpectedly, the magnetic susceptibility of SZF3ʹ
increased from 39.21 to 46.44 emu/g. The most likely reason
for this phenomenon is the decrease in SO42− content from 20.7
wt% (SZF3) to 12.8 wt% (SZF3ʹ), which was verified by the de‐
crease in the catalytic performance.
0
100 200 300 400 500 600 700 800
Temperature (oC)
Fig. 2. TG‐DSC curves of magnetic solid acid SZF3.
the tetragonal to the monoclinic phase [29]. Accompanied by an
endothermic peak centered at 721 °C in the DSC curve, the peak
with a sharp weight loss of 8.06% at 600–780 °C corresponded
to the removal of the SO42− group [14].
3.4. NH3‐TPD analysis
The NH3‐TPD profiles of the magnetic solid acids SZF3,
SZF3‐300, and SZF3‐650 are shown in Fig. 3. Magnetic solid acid
SZF3 with 0.952 mmol/g acidity showed a broad NH3 desorp‐
tion peak, including four peaks centered at 146, 257, 389, and
539 °C, which indicated that the surface acid strengths were
not homogeneously distributed. In general, the broad NH3 de‐
sorption peak was divided into two types of desorption peaks
based on Gaussian fitting: the first broad medium temperature
(MT) desorption signal in the range 100–300 °C, corresponding
to NH3 adsorbed on the acid sites at medium strengths; and the
second broad high‐temperature (HT) peak in the range of
300–650 °C, suggesting the presence of very strong acid sites
[29]. Unfortunately, the MT and HT desorption signals of
SZF3‐300 and SZF3‐650 sharply decreased with increasing cal‐
cination temperature from 110 to 650 °C for 3 h. Especially for
magnetic solid acid SZF3‐650, little NH3 adsorption demon‐
strated weak acidity (0.178 mmol/g), which was also evi‐
denced by its poor catalytic performance in the following
asymmetric aldol reaction.
3.3. TG analysis
Using solid acid SZF3 as an example, the thermal deco‐
mposition was characterized by TG‐DSC. From the TG‐DSC re‐
sults shown in Fig. 2, there are three types of peaks for SZF3. An
endothermic peak with a gradual weight loss of 6.08% below
200 °C, which was verified by the DSC curve, was mainly at‐
tributed to desorption of surface‐bound or intercalated water
in the pores. Another gradual weight loss peak of 2.41% at
200–600 °C resulted from the dehydration of Zr(OH)4 to form
amorphous ZrO2 [28] and the transformation of zirconia from
60
(1)
(3)
389
40
(2)
(1)

20
539
0
257
146
-1.0
-0.5
0.0
0.5
H (104 Oe)
1.0
(2)
(3)
-20
-40
-60
100
200
300
400
500
600
Temperature (oC)
Fig. 3. NH3‐TPD profiles of magnetic solid acids (1) SZF3, (2) SZF3‐300,
Fig. 1. Magnetization curves of the nanomagnetic solid acids (1) SZF1,
and (3) SZF3‐650.
(2) SZF3, and (3) SZF3ʹ.

428
Tao Wu et al. / Chinese Journal of Catalysis 36 (2015) 425–431
(a)
(b)
(3)
(2)
14 nm
21 nm
(1)
60
Fig. 4. TEM profiles of (a) nano‐Fe3O4 and (b) magnetic solid acid SZF3.
25
30
35
40
45
2/( o )
50
55
65
3.5. Surface morphology and porous structure
Fig. 6. Powder XRD patterns of (1) nano‐Fe3O4, (2) Zr(OH)4–Fe3O4, and
The TEM images of nano‐Fe3O4 and magnetic solid acid SZF3
are shown in Fig. 4. The micrograph of nano‐Fe3O4 clearly
shows uniform square crystallites of about 60–80 nm in diam‐
eter. After Fe3O4 was coated with Zr(OH)4 and immersed in 0.5
mol/L sulfuric acid, the obtained magnetic solid acid SZF3 with
80–100 nm in diameter shows about 10–20 nm growth of par‐
ticle size. The N2 adsorption‐desorption isotherm of magnetic
solid acid SZF3 (Fig. 5) is a type II isotherm in classic defini‐
tions, agreed well with the normal form obtained with a
non‐porous or macroporous adsorbent. This indicates that
magnetic solid acid SZF3 was a typical microporous material,
which was verified by its BJH pore size distribution plot (inset
of Fig. 5). Based on the multipoint BET method and the BJH
method, the BET specific surface area and pore volume of
magnetic solid acid SZF3 were calculated to be 15.8 m2/g and
0.029 mL/g, respectively.
(3) SO42−/Zr(OH)4–Fe3O4.
Å), (440) (d = 1.72 Å), and (533) (d = 1.48 Å) reflections, re‐
spectively [30]. After Zr(OH)4 and SO4 were consecutively
loaded on nano‐Fe3O4, there was no significant change in the
various characteristic diffraction peaks, which indicated that
Zr(OH)4 and SO42− were well‐dispersed on/in the internal and
external surfaces of nano‐Fe3O4.
2−
3.7. Catalytic performance in asymmetric aldol reaction
3.7.1. Effect of reaction temperature and magnetic solid acids
The asymmetric aldol reaction between 4‐nitrobenzal‐
dehyde and cyclohexanone was used as a model reaction to
investigate the catalytic performance of the as‐synthesized
magnetic solid acids [31,32]. From Fig. 7, the catalytic reaction
temperature had a great influence on the yield and enantiose‐
lectivity of the aldol adduct. With increasing reaction tempera‐
ture, the yield of the aldol adduct increased, whereas the enan‐
tioselectivity markedly decreased. Considering these two con‐
tradictory factors, the optimal temperature of 25 °C was chosen
for the following screening tests.
Furthermore, the catalytic performance of various magnetic
solid acids (SZF1–5) in the aldol reaction of 4‐nitrobenzaldehyde
with cyclohexanone was evaluated, and the results are listed in
Table 2. It was found that the SO4 content had a significant
influence on the yield of the aldol adduct. Magnetic solid acid
3.6. XRD results
Figure 6 shows the high‐angle powder XRD patterns of
nano‐Fe3O4, Zr(OH)4–Fe3O4, and SO42−/Zr(OH)4–Fe3O4. The XRD
pattern of nano‐Fe3O4 shows the typical peaks at 18.12°, 30.08°,
35.45°, 43.06°, 53.49°, 57.00°, 62.62°, and 74.05°, which corre‐
spond to the (111) (d = 5.68 Å), (220) (d = 3.44 Å), (311) (d =
2.94 Å), (400) (d = 2.44 Å), (422) (d = 1.99 Å), (511) (d = 1.87
2−
20
5
4
100
90
80
15
3
100
80
60
2
1
10
0
10
100
1000
Pore diameter (Å)
5
0
70
60
40
20
Desorption
Adsorption
0.0
0.2
0.4
0.6
0.8
1.0
-20 -10
0
10 20 30 40 50 60 70 80
Temperature (oC)
Relative pressure (p/p0)
Fig. 5. N2 adsorption‐desorption isotherms and pore size distribution
Fig. 7. Asymmetric aldol reaction of 4‐nitrobenzaldehyde with cyclo‐
(insert) of magnetic solid acid SZF3.
hexanone at different temperatures.

Tao Wu et al. / Chinese Journal of Catalysis 36 (2015) 425–431
429
3.7.2. Effect of calcination temperature and magnetic solid acid
amount
Table 2
Asymmetric aldol reaction catalyzed by various magnetic solid acids.
It is well known that the calcination temperature of the solid
acid strongly affects the form of the SO42− group [14]. To inves‐
tigate the influence of the calcination temperature and the
amount of SZF3, the aldol reaction was performed under the
optimized conditions. From Fig. 8, after calcining at 110 °C,
magnetic solid acid SZF3 gave the highest catalytic performance
(>99% yield, 92.1% ee anti, and anti/syn = 89/11). With in‐
creasing the calcination temperature from 110 to 650 °C, the
enantioselectivity and yield decreased for different amounts of
catalyst SZF3 (5.0–55.0 mg). In particular, the enantioselectivity
and yield of the aldol adduct sharply decreased when the calci‐
nation temperature reached 650 °C. The main reason might be
OH
O
O
CHO
+
Cat., rt
epi-CDNH (7.5 mol%)
O N
2
2
O N
2
Entry
Catalyst
SZF1
SZF2
SZF3
SZF4
SZF5
—
Isolated yield (%) ee anti c (%) Dr (anti/syn) c
1
2
3
4
5
6
7
8
9
74
85
96
87
80
84.0
84.3
83.1
82.9
85.1
20.4
90.8
96.8
91.2
81/19
79/21
81/19
81/19
82/18
70/30
91/9
54
a
SZF3
>99
>99
98
TfOH b
93/7
90/10
2–
Zr(OH)4/SO4
2−
the removal of the SO4 group with increasing temperature,
which was verified by the sharp mass loss at 600–780 °C (Fig.
2) and the decreased acidity of catalyst SZF3‐650 (Fig. 3).
Reaction conditions: Catalyst (20.0 mg), epi‐CDNH2 (11.0 mg, 0.0375
mmol), cyclohexanone (0.98 g, 10.0 mmol), p‐nitrobenzaldehyde (76.0
mg, 0.5 mmol), H2O (2.0 mL), 25 °C, 48 h.
a SZF3 (30.0 mg), 72 h. b TfOH (10.0 mg), 12 h.
c Determined by chiral HPLC (AD‐H column).
3.7.3. Reaction with various substituted benzaldehydes
Encouraged by the remarkable results under the above re‐
action conditions, the substrate scope was extended to a wide
variety of benzaldehydes with ortho, meta, and para substitu‐
ents. The catalytic results are summarized in Table 3. For the
benzaldehydes with strong electron‐withdrawing substituents
(R = NO2 and CN), the aldol reactions exhibited good to excel‐
lent enantioselectivity (86.0%–95.6% ee anti) and diastereose‐
lectivity (anti/syn = 88–96/12–4) with 83%–100% yield (en‐
tries 1–6). However, the benzaldehydes with weak elec‐
tron‐withdrawing substituents (R = Cl and Br) gave moderate
to good enantioselectivity (70.9%–85.9% ee anti) and disap‐
pointing yield (19%–76%) although good to excellent dia‐
stereoselectivity (anti/syn = 88–96/12–4) was achieved. Un‐
fortunately, the benzaldehydes with electron‐donating substit‐
uents (R = CH3 and OCH3) did not proceed smoothly.
2−
SZF3 with 20.7% SO4 content produced the highest yield
(96%, entry 3). However, the stereoselectivity was insensitive
to the SO4 content. The enantioselectivity (82.9%–85.1% ee
anti) and diastereoselectivity (anti/syn
2−
= 79–82/21–18)
2−
changed little when the SO4 content varied in the range
6.8%–20.7%. Unfortunately, in the absence of magnetic solid
acid, the aldol reaction afforded unsatisfactory catalytic results
(54% yield, 20% ee anti, and anti/syn = 70/30, entry 6). In par‐
ticular, compared with an organic acid (>99% yield, 96.8% ee
anti, and anti/syn = 93/7), magnetic solid acid SZF3 gave similar
diastereoselectivity (anti/syn = 91/9) and lower enantioselec‐
tivity (90.8% ee anti) in excellent yield (>99%) (entries 7 and
8). Considering the possible effect of the bonding interaction
between Zr(OH)4 and Fe3O4 on the catalytic performance,
Zr(OH)4/SO42− was prepared according to the same procedure
as SZF3 in the absence of Fe3O4. A similar yield and stereoselec‐
tivity of aldol products were obtained (entry 9), which indicat‐
ed that the bonding interaction between Zr(OH)4 and Fe3O4 had
little effect on the catalytic performance.
3.7.4. Recovery and reuse of catalyst
At the end of the catalytic aldol reaction, magnetic solid acid
SZF3 could be easily and quantitatively separated from the re‐
action mixture using an external magnet and directly reused in
(b)
(a)
Fig. 8. Effect of calcination temperature and amount of SZF3 used on the enantioselectivity (a) and yield (b) of the aldol adduct. Reaction conditions:
epi‐CDNH2 (11.0 mg, 0.0375 mmol), cyclohexanone (0.98 g, 10.0 mmol), p‐nitrobenzaldehyde (76 mg, 0.50 mmol), and 2.0 mL H2O.

430
Tao Wu et al. / Chinese Journal of Catalysis 36 (2015) 425–431
93.2% ee anti) was observed. After the completion of the aldol
Table 3
reaction, solid acid SZF3 was filtered for reuse. Furthermore,
epi‐CDNH2 was also recovered by extraction with dilute hy‐
drochloric acid (10%), alkalization with an excess of concent‐
rated ammonia, and extraction with CH2Cl2. The catalytic sys‐
tem could be reused and gave satisfactory results (87% yield,
anti/syn = 89/11, 90.4% ee anti) in the third cycle.
Asymmetric aldol reaction of various benzaldehydes with cycloh‐
exanone.
O
OH
O
CHO
+
Cat., rt
R
R
epi-CDNH2 (7.5 mol%)
Entry
1
2
3
4
5
6
7
8
R
Isolated yield (%) ee anti b (%) Dr (anti/syn) b
4‐NO2
3‐NO2
2‐NO2
4‐CN
3‐CN
2‐CN
4‐Cl a
3‐Cl a
2‐Cl a
2,4‐Cl a
4‐Br a
>99
95
83
91
94
92
76
67
38
39
19
92.1
90.9
95.9
92.5
86.0
87.4
72.8
82.2
81.9
85.9
70.9
89/11
81/19
96/4
84/16
88/12
88/12
94/6
96/4
93/7
89/11
88/12
4. Conclusions
With the purpose of realizing environmentally benign and
friendly processes in asymmetric reactions, a series of sulfated
zirconium hydroxide compounds loaded on nano‐Fe3O4 were
prepared, characterized, and applied in the aqueous asym‐
metric aldol reaction of various benzaldehydes with cyclohex‐
anone for the first time. These magnetic solid acids, which
could be easily and quantitatively separated from the reaction
mixture using an external magnet, showed good to excellent
catalytic performance for benzaldehydes with strong electron‐
withdrawing substituents and possessed good tolerance in five
consecutive runs without a significant loss of catalytic perfor‐
mance.
9
10
11
Reaction conditions: SZF3 (35.0 mg), epi‐CDNH2 (11.0 mg, 0.0375
mmol), cyclohexanone (0.98 g, 10.0 mmol), benzaldehyde (0.5 mmol),
H2O (2.0 mL), 25 °C, 48 h.
a Reaction time 72 h. b Determined by chiral HPLC (AD‐H column).
cycle tests. Figure 9 shows the catalytic results of reused mag‐
netic solid acid SZF3 in the aqueous asymmetric aldol reaction
of cyclohexanone with 4‐nitrobenzaldehyde. To our surprise,
the yield and enantioselectivity unexpectedly increased during
the first three cycles. In the third cycle, magnetic solid acid SZF3
produced the highest enantioselectivity (94.7% ee anti) owing
to the increased dispersion in the aqueous medium. It is note‐
worthy that 91.3% yield, 90.2% ee anti, and anti/syn = 78/22
were obtained in the fifth run. The slight decrease in catalytic
References
[1] Casiraghi G, Battistini L, Curti C, Rassu G, Zanardi F. Chem Rev,
2011, 111: 3076
[2] Adachi S, Harada T. Eur J Org Chem, 2009: 3661
[3] Markert M, Mahrwald R. Chem Eur J, 2008, 14: 40
[4] Palomo C, Oiarbide M, Garcia J M. Chem Soc Rev, 2004, 33: 65
[5] Zali A, Ghani K, Shokrolahi A, Keshavarz M H. Chin J Catal, 2008,
29: 602
[6] Garro R, Navarro M T, Primo J, Corma A. J Catal, 2005, 233: 342
[7] Climent M J, Corma A, Fornes V, Guil‐Lopez R, Iborra S. Adv Synth
Catal, 2002, 344: 1090
[8] Kawal M, Onaka M, Izumi Y. Bull Chem Soc Jpn, 1988, 61: 1237
[9] Bhupathi R S, Devi B R, Dubey P K. Asian J Chem, 2011, 23: 4215
[10] Demuynck A L W, Peng L, de Clippel F, Vanderleyden J, Jacobs P A,
Sels B F. Adv Synth Catal, 2011, 353: 725
[11] Polshettiwar V, Luque R, Fihri A, Zhu H B, Bouhrara M, Basset J M.
Chem Rev, 2011, 111: 3036
2−
performance was because of the loss of SO4 (20.7 to 12.8
wt%) in the catalytic process.
3.7.5. Large‐scale asymmetric aldol reaction
A large‐scale asymmetric aldol reaction between cycloh‐
exanone (9.8 g, 0.10 mol) and 4‐nitrobenzaldehyde (3.8 g,
25 mmol) was performed at 25 °C for 48‒72 h in the presence
of epi‐CDNH2 (110.0 mg, 0.375 mmol) and SZF3 (350.0 mg).
Good catalytic performance (96% yield, anti/syn = 90/10,
[12] Zhang D H, Zhou C, Sun Z H, Wu L Z, Tung C H, Zhang T R. Na‐
noscale, 2012, 4: 6244
[13] Gawande M B, Branco P S, Varma R S. Chem Soc Rev, 2013, 42:
3371
[14] Wang P C, Zhu J, Liu X, Lu T T, Lu M. ChemPlusChem, 2013, 78: 310
[15] Koukabi N, Kolvari E, Zolfigol M A, Khazaei A, Shaghasemi B S,
Fasahati B. Adv Synth Catal, 2012, 354: 2001
[16] Wang Q H, Zhao W C, Sun X H, Zhao W J. Catal Lett, 2008, 121: 324
[17] Zillillah, Tan G W, Li Z. Green Chem, 2012, 14: 3077
[18] Lai D M, Deng L, Guo Q X, Fu Y. Energy Environ Sci, 2011, 4: 3552
[19] Lai D M, Deng L, Li J, Liao B, Guo Q X, Fu Y. ChemSusChem, 2011, 4: 55
[20] Kong A G, Wang P, Zhang H Q, Yang F, Huang S P, Shan Y K. Appl
Catal A, 2012, 417‐418: 183
[21] Chouhan G, Wang D S, Alper H. Chem Commun, 2007: 4809
[22] Hino M, Kobayashi S, Arata K. J Am Chem Soc, 1979, 101: 6439
[23] Lei T, Hua W M, Tang Y, Yue Y H, Gao Z. Chem J Chin Univ, 2000, 21:
1697
120
100
80
60
40
20
0
10
8
ee anti
Yield
Dr
6
4
2
1
2
3
4
5
Reuse time
[24] Hu Z J, Ling L C, Lü C X, Liu L, Zhang B J. Chin J Catal, 1998, 19: 447
[25] Chang Z, Guo C X, Duan X, Zhang M L. Chin J Catal, 2003, 24: 47
Fig. 9. Reusability of magnetic solid acid SZF3 in cycle experiment.

Tao Wu et al. / Chinese Journal of Catalysis 36 (2015) 425–431
431
Graphical Abstract
Chin. J. Catal., 2015, 36: 425–431 doi: 10.1016/S1872‐2067(14)60222‐9
Aqueous asymmetric aldol reaction catalyzed by nanomagnetic solid acid SO42−/Zr(OH)4–Fe3O4
Tao Wu, Jingwei Wan, XuebingMa*
Southwest University
OH
O
O
CHO
+
Solid Cat., rt
R
R
epi-CDNH2 (7.5 mol%)
Organic phase
Aqueous phase
Cat.
83%-100% yield
86.0%-95.6% ee anti
anti/syn = 88-96/12-4
magnet
Sulfated zirconium hydroxide loaded on nano‐Fe3O4 was prepared and applied to the aqueous asymmetric aldol reaction with good to
excellent catalytic performance (83%–100% yield, 86.0%–95.6% ee anti, and anti/syn = 88–96/12–4).
[26] Zhang M L, Wang J, Mei C S, Jing X Y, Duan X. Chem J Chin Univ,
2002, 23: 1347
[30] Wan J W, Ding L, Wu T, Ma X B, Tang Q. RSC Adv, 2014, 4: 38323
[31] Zhou J Q, Wan J W, Ma X B, Wang W. Org Biomol Chem, 2012, 10:
[27] Wan J W, Ma X B, He R X, Li M. Chin Chem Lett, 2014, 25: 557
[28] Zhang J R, Gao L. Mater Lett, 2004, 58: 2730
4179
[32] Wang W, Ma X B, Wan J W, Cao J, Tang Q. Dalton Trans, 2012, 41:
[29] Ren B, Fan M Q, Wang J, Jing X Y. Solid State Sci, 2011, 13: 1594
5715