The high catalytic activity and reusability of the proline functionalized cage-like mesoporous material SBA-16 for the asymmetric aldol reaction proceeding in methanol-water mixed solvent

Article abstract of DOI:10.1039/c3ra47262k

The cage-like mesoporous material SBA-16 has been successfully functionalized with l-4-hydroxyproline and characterized by Fourier transform infrared (FT-IR) spectroscopy, Small-angle X-ray powder diffraction (XRD), N₂ sorption detection, trans

Full text of DOI:10.1039/c3ra47262k

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The high catalytic activity and reusability of the
proline functionalized cage-like mesoporous
material SBA-16 for the asymmetric aldol reaction
proceeding in methanol–water mixed solvent†
Cite this: RSC Adv., 2014, 4, 9292
a
a
a
b
a
*
*
Honglei Yang, Xueyao Zhang, Shuwen Li, Xiaoyu Wang and Jiantai Ma
The cage-like mesoporous material SBA-16 has been successfully functionalized with L-4-hydroxyproline
and characterized by Fourier transform infrared (FT-IR) spectroscopy, Small-angle X-ray powder
diffraction (XRD), N2 sorption detection, transmission electron microscopy (TEM), elemental analysis and
thermo gravimetric analysis (TGA). This chiral non-metallic catalyst avoided heavy metal pollution during
the preparing and using process, and demonstrated high catalytic activity (up to 91%), diastereoselectivity
(up to 97 : 3) and enantioselectivity (up to 83%) in the asymmetric aldol reaction between aldehyde
acceptors and ketone donors with methanol–H2O as solvent. Moreover, the synthesized catalyst could
be easily separated from the reaction mixture by filtration and reused for up to five runs without any
obvious loss of activity, indicating its excellent recyclability.
Received 3rd December 2013
Accepted 23rd January 2014
DOI: 10.1039/c3ra47262k
www.rsc.org/advances
asymmetric aldol condensations,16 a signicant amount of
efforts have been devoted to immobilization and recycling of L-
proline.17–21 Different types of support materials, such as poly-
1. Introduction
The asymmetric aldol reaction is one of the most important
carbon–carbon bond-forming strategies in organic synthesis,
which can be used in the generation of various compounds with
biological and optical activities. Generally, there are three kinds
of catalysts for the aldol reaction, which are the biocatalysts,1–3
chiral metal complexes4,5 and metal-free small molecular orga-
nocatalysts.6–8 Among these catalysts, the third one has attrac-
ted intense attention in recent years owing to its economical
advantage, operationally simple and environmentally friendly
features. Since List et al.9 successfully demonstrated that L-
proline can highly catalyze the simple aldol reaction of acetone
and aldehydes, numerous highly-efficient small organic
molecular catalysts based on proline and its derivatives have
been designed for varieties of asymmetric reactions10–15 and
rapidly grown to their adolescence from infancy.
mer, ionic liquids, magnetite, carbon and silica materials have
been used in connection with the immobilization of proline.
Huerta et al.22 investigated the catalytic behaviors of a water-
soluble L-proline-functionalized catalytic polymer in the aldol
reaction. A kind of basic chiral ionic liquids on the basis of
commercially available (S)-proline was designed by Vasiloiu and
his co-workers,23 and utilized as organocatalyst in asymmetric
aldolization. Riente et al.24 immobilized the (S)-a,a-diphenyl-
prolinol trimethylsilyl ether onto superparamagnetic Fe3O4
nanoparticles and used it as a highly active, magnetically
recoverable and reusable catalyst for the asymmetric Michael
addition reaction. An effective heterogeneous L-proline catalyst
for the direct asymmetric aldol reaction using graphene oxide as
support was reported by Tan and his company.25 Hsiao et al.26
prepared the mesoporous SBA-15 modied with chiral proline
derivatives for catalyzing the addition of diethylzinc to
benzaldehyde.
Among various supports of the heterogeneous catalysts, the
mesoporous materials are very promising for their large specic
surface area and regularly arranged pore structure. Unlike the
widely-used channel-like materials MCM-41 or SBA-15, the
recently synthesized SBA-16 is a new type of ordered silicon
material with cage-like mesoporous framework, which is suit-
able for processing large molecules because of their unique
structure and pore connectivity. This mesoporous cage-like
material has tunable cage size (4–10 nm) and tunable
pore entrance size (generally less than 4 nm). The isolated
Compared with homogeneous catalysts, supported proline
can be easily recovered from the reaction mixture and keep
stable catalytic activity and selectivity aer being reused for
many times, which is meaningful for the environmental
protection and energy conservation. Since the PEG-supported
proline catalyst was successfully prepared and applied in the
aState Key Laboratory of Applied Organic Chemistry, College of Chemistry and
Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, P. R. China.
E-mail: majiantai@lzu.edu.cn; Fax: +86-931-891258; Tel: +86-931-8912577
bSchool of Earth Sciences, Lanzhou University, Lanzhou, Gansu, 730000, P. R. China.
E-mail: wangxiaoyu@lzu.edu.cn
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c3ra47262k
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nanocages are three-dimensionally interconnected by pore
entrances. Such architectures can probably eliminate pore
blocking and allow a fast transport of reactants and products.27
Recently, due to its excellent physical and chemical properties,
SBA-16 has played an important role in the immobilization of
catalysts.28–32
In our previous work, a kind of magnetic catalyst based on
proline as active component and Fe3O4@SiO2 as support was
successfully synthesized and demonstrated high catalytic
activity, diastereoselectivity and enantioselectivity in the direct
aldol reactions.33 Upon the consideration that the three-
dimensional mesoporous cage-like material SBA-16 has a
superior ability in reducing the diffusion resistance,28 which is
crucial factor for designing high-performance catalyst, another
heterogeneous catalyst, proline anchored into the cage-like
mesoporous material SBA-16 was designed, consequently
named SBA-16-Pro and conrmed by corresponding character-
ization means. Furthermore, the catalytic activity, stereo-
selectivity and reusability of the catalyst SBA-16-Pro were
evaluated in the asymmetric aldol reaction.
Scheme 1 Preparation of the catalyst SBA-16-Pro.
at room temperature under H2 atmosphere (3 atm). The
catalyst Pd/C was ltered off, and the ltrate was concentrated in
vacuo
yielding
(2S,4R)-2-carboxy-4-(3-triethoxysilylpropyla-
minocarboxy) pyrrolidine (compound 3) quantitatively as pale
yellow oil. No purication was possible due to the instability of
the product.
The solution of the proline derivative (compound 3, 1 g) in
toluene (20 mL) was added into the suspension of the inorganic
support of SBA-16 (1 g) in a mixture of toluene/water (40 mL/
40 mL). The mixture was reuxed for 24 h. The solid was
then ltered and washed with several solvents of different
polarity (MeOH, AcOEt, CH2Cl2, hexane and ether) abundantly,
to remove the remaining non-supported proline derivative.
The light yellow solid SBA-16-Pro was dried at 40 ꢀC under
vacuum.
2. Experimental
2.1. Preparation of the catalyst SBA-16-Pro
2.1.1. Synthesis of SBA-16. The mesoporous cage-like
material SBA-16 as support of catalyst was synthesized accord-
ing to the previously published methods.29
Pluronic F127 (EO106PO70EO106, 1.48 g) and Pluronic P123
(EO20PO70EO20, 0.24 g) were used as the templates. Aer the
mixed templates were completely dissolved in a solution of
60 mL of distilled water and 8.9 mL of concentrated hydro-
chloric acid (37%), the solution was further stirred at 40 ꢀC for
4 h. Then, 5.6 mL of tetraethylorthosilicate (TEOS) was added
2.2. Characterization of the catalyst SBA-16-Pro
dropwise to the solution. Aer being stirred for 40 min, the The synthesized catalyst SBA-16-Pro was conrmed by corre-
resultant suspension was transferred into an autoꢀ clave. The sponding characterization means. Fourier transform infrared
autoclave was placed under static conditions at 40 C for 24 h. (FT-IR) spectra were recorded on a Nicolet NEXUS 670 FTIR
Aer that, the temperature was raised up to 100 ꢀC and kept spectrometer with
a DTGS detector, and samples were
for 32 h. Aer the hydrothermal treatment, the precipitated measured with KBr pellets. Small-angle X-ray powder diffraction
solid was isolated by ltration and washed with distilled water (XRD) measurements were performed on a Rigaku D/max-2400
ꢀ
and ethanol, then dried in vacuum at 60 C for 24 h, yielding diffractometer using Cu-Ka radiation as the X-ray source in the
white solid powders. This powder sample was then subjected 2q range of 0.5–4ꢀ. N2 physical sorption was carried out on
to calcination at 550 ꢀC for 10 h, and the mesoporous cage-like micromeritics ASAP2020 volumetric adsorption analyzer (before
material SBA-16 was eventually obtained.
the measurements, samples were out gassed at 120 ꢀC for 6 h).
2.1.2. Preparation of SBA-16-Pro. Aer successful synthesis The Brunauer–Emmett–Teller (BET) surface area was evaluated
of SBA-16, the catalyst SBA-16-Pro was prepared by steps dis- from data in the relative pressure range from 0.05 to 0.20. The
played in Scheme 1.
total pore volume of each sample was estimated from the
The solution of (2S,4R)-1,2-dibenzyloxycarbonyl-4-hydroxy amount adsorbed at the highest P/P0 (above 0.99). Pore diam-
pyrrolidine, (compound 1, 10 mmol, 3.55 g), triethoxysilylpropyl eters were determined from the adsorption branch using Bar-
isocyanate (15 mmol, 3.71 g), and triethylamine (20 mmol, rett–Joyner–Halenda (BJH) method. The morphology and
2.02 g) in THF (25 mL) was reuxed for 24 h and then cooled to microstructure of SBA-16-Pro were characterized by trans-
room temperature. Aer removal of solvent under vaccum, the mission electron microscopy (TEM). The TEM images were
crude product was puried by column chromatography on silica obtained through Tecnai G2 F30 electron microscope operating
gel (hexane/AcOEt, 3 : 1) to give 4.99 g of (2S,4R)-1,2-dibenzy- at 300 kV. The C, H and N contents in SBA-16-Pro were deter-
loxycarbonyl-4-(3-triethoxysilylpropylaminocarboxy) pyrrolidine mined by Elementar Analysensysteme GmbH varioEL cube.
(compound 2) as a brown oil (yield 83%).
Thermal gravimetric analysis (TGA) was measured under
Compound 2 (2 mmol, 1.20 g) was hydrogenated over nitrogen atmosphere to 800 ꢀC with aꢁP1erkin Elmer Thermal
ꢀ
palladium on carbon (0.16 g, 10%) in methanol (40 mL) for 7 h Analyzer at a heating rate of 10 C min
.
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2.3. Reaction procedures for activity evaluation of catalyst
SBA-16-Pro in the direct aldol reaction
2.3.1. Optimization experiments of reaction conditions. 4-
Nitrobenzaldehyde (0.5 mmol, 76 mg), cyclohexanone (2 mmol,
196 mg) and corresponding kinds and amounts of catalysts
were added in the solvent. The reaction mixture was stirred for
12–96 h at room temperature. Aer separation of the catalyst,
the mixture was treated with 10 mL of saturated ammonium
chloride solution and extracted with ethyl acetate (3 ꢂ 10 mL).
The organic layer was dried over anhydrous Na2SO4, and
concentrated in vacuo. The products were isolated by column
chromatography on silica gel (hexane/AcOEt, 4 : 1). The dia-
stereomeric and enantiomeric excess of products was deter-
mined by chiral high performance liquid chromatography
(HPLC) using CHIRALPAK AD-H column with n-hexane and
isopropyl alcohol (95 : 5) as eluants.
Fig. 1 FT-IR spectra of (a) SBA-16, (b) SBA-16-Pro, (c) SBA-16-Pro
after five runs.
2.3.2. The direct aldol reactions between different alde-
hydes and ketones. The catalyst SBA-16-Pro (20 mol%) and
corresponding aldehyde (0.5 mmol) and ketone (2 mmol) were
stirred in 2 mL MeOH/H2O (v/v ¼ 10 : 1) for 24–72 h at room
temperature. Aer separation of the catalyst, the mixture was
treated with 10 mL of saturated ammonium chloride solution
and extracted with ethyl acetate (3 ꢂ 10 mL). The organic layer
was dried over anhydrous Na2SO4, and concentrated in vacuo.
The residue was puried by column chromatography on silica
gel, eluting with hexanes/ethyl acetate. The diastereomeric and
enantiomeric excess of products was determined by chiral
HPLC using CHIRALPAK AD-H and OB-H columns with n-
hexane and isopropyl alcohol as eluants.
2.3.3. Recycling tests of catalyst SBA-16-Pro. 4-Nitro-
benzaldehyde (0.5 mmol 76 mg), cyclohexanone (2 mmol, 196
mg), catalyst SBA-16-Pro (20 mol%) and 2 mL MeOH/H2O (v/v ¼
10 : 1) were mixed and stirred at room temperature for 48 h. The
catalyst SBA-16-Pro was removed by ltration, washed with
MeOH and AcOEt for several times and dried under vacuum.
Then another portion of reactants was added. The products in
every recycling test were isolated by column chromatography
and analyzed by chiral HPLC.
L-4-hydroxyproline and the original structure of the silicon
material SBA-16 was retained.
Small-angle powder XRD patterns of SBA-16 and SBA-16-Pro
were illustrated in Fig. 2. The synthesized SBA-16 showed an
intense peak at 0.85ꢀ attributable to the (110) reection and two
poorly resolved weak peaks at 1.2ꢀand 1.5ꢀ due to the (200) and
(211) reections, respectively.30 These results indicated that
SBA-16 was a kind of mesoporous material with the ordered
cubic Im3m structure. The SBA-16-Pro still kept the main
diffraction (110) peak, however, its intensity obviously
decreased and the diffraction (200) and (211) peaks completely
disappeared revealing that the proline was successfully graed
into the mesoporous SBA-16 and did not seriously destroy the
structure of SBA-16, which could be conrmed by N2 sorption
detection.
The nitrogen adsorption–desorption isotherms and pore size
distributions of corresponding samples were depicted in Fig. 3.
Both SBA-16 and SBA-16-Pro exhibited type IV isotherm patterns
with typical H2 hysteresis loop, demonstrating that the cage-
like structure of SBA-16 was maintained even aer graed with
proline. From the textural parameters determined by N2 sorp-
tion and listed in Table 1, the decreases in BET surface area,
3. Results and discussion
3.1. Characterizations of the catalyst SBA-16-Pro
The FT-IR spectra of SBA-16, SBA-16-Pro and SBA-16-Pro aer
ve runs were displayed in Fig. 1. The bands approximately at
960 cmꢁ1 and 1095 cmꢁ1 were assigned to the typical silanol
groups (Si–OH) stretching mode and Si–O–Si vibrations,
respectively, which were commonly found in the silica-based
materials. The band at 1640 cmꢁ1 observed in the spectra of
both SBA-16 and SBA-16-Pro was related to the water absorbed
on the solid surface.28 Compared to the spectrum of SBA-16,
there were three new peaks near 2970, 1710 and 1560 cmꢁ1
obviously appearing in that of SBA-16-Pro, corresponding to the
stretching vibrations of C–H, carboxylic C]O, and the bending
vibration of N–H in proline, respectively. These results
Fig. 2 Small-angle powder XRD patterns of (a) SBA-16 and (b) SBA-
demonstrated that SBA-16 was successfully functionalized by 16-Pro.
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Fig. 3 N2 sorption isotherms and pore size distributions of (a) SBA-16 and (b) SBA-16-Pro.
Table 1 Structural parameters of SBA-16 and SBA-16-Pro
silica materials. The weight of SBA-16 did not have an obvious
loss throughout the temperature rising process (Fig. 5a),
demonstrating that SBA-16 material as the support of catalyst
had a strong thermal stability. The TGA curve of SBA-16-Pro
(Fig. 5b) got a sharp drop at the temperature range of 200–600
ꢀC, and then became at above 600 ꢀC. This part of weight loss
was mainly caused by the decomposition of organic groups
from the graed proline. Through the TGA analysis, the total
weight loss of SBA-16-Pro was evaluated to be 35%, and the
proline content into the catalyst SBA-16-Pro was evaluated to be
1.62 mmol gꢁ1, which was close to the CHN elemental analysis
result (1.68 mmol gꢁ1). The little difference between the results
of the proline content in SBA-16-Pro was mainly attributed to
the difference of detection methods and the instrument error of
the two detection means.
BET surface
area (m2 gꢁ1
Pore volume
Pore size
(nm)
Samples
)
(cm3 gꢁ1
)
SBA-16
SBA-16-Pro
698.28
459.17
0.869
0.434
4.98
3.78
pore volume and pore size were observed for SBA-16-Pro. These
changes pointed to the fact that proline was not only immobi-
lized on the external surface of SBA-16, but also into the interior
of it.
The TEM images shown in Fig. 4 provided more information
about SBA-16, fresh and reused catalyst SBA-16-Pro. The support
material SBA-16 presented a cubic array of uniform channels
(Fig. 4a). Aer modications with proline, the ordered body-
centered cubic mesostructure was still well maintained
(Fig. 4b).
3.2. Activity evaluations of SBA-16-Pro
Through elemental analysis of C, H and N, the proline
With the synthesized catalyst SBA-16-Pro in hand, its catalytic
activity was evaluated in the asymmetric aldol reaction.
content of SBA-16-Pro was evaluated to be 1.68 mmol gꢁ1
.
SBA-16 and SBA-16-Pro were further characterized with TGA
(Fig. 5). It could be seen that the weight losses of both SBA-16
and SBA-16-Pro below 200 ꢀC were very slight, which should be
assigned to the release of physisorbed and chemisorbed water
existing on the surface and in the channels of the mesoporous
The well-documented aldol reaction between 4-nitro-
benzaldehyde and cyclohexanone was chosen as a model to
optimize the reaction conditions (Table 2). The solvent, amount
of catalyst, reaction temperature and time, as inuencing
factors for the reaction, were investigated one by one. In all
Fig. 4 TEM images of (a) SBA-16, (b) SBA-16-Pro and (c) SBA-16-Pro after five runs.
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cases, the desired aldol product was obtained as a mixture of
diastereomers.
Regrettably, H2O, as an environmentally friendly solvent,
could not be used directly in the reaction, because plenty of
water had a restraint for the activity of the catalyst34 (entry 1).
Meanwhile, the reaction proceeded with much higher yield in
alcohols (entries 2 and 3), especially in methanol, compared
with other kinds of solvent (entries 4 and 5), revealing that the
catalytic efficiency of SBA-16-Pro in hydrophilic solvent was
better than that in hydrophobic solvent. It could be observed
that when the reaction took place in singe solvent, the enan-
tioselectivity was generally non-ideal. It has been reported that
small amount of water is sometimes benecial in the proline-
catalyzed aldol reaction.35 Therefore, the mixed solvent
Methanol–H2O was tried to be used in place of single solvent
Methanol (entries 7 to 10), in which the catalyst solid had a good
dispersion. Interestingly, the reactions in Methanol–H2O
mixture exhibited a progressive increase of stereoselectivity as
the volume ratio of Methanol–H2O was changed from 100 : 1 to
10 : 1. However, when 1 : 1 of Methanol–H2O volume ratio was
used, the yield dropped drastically and the enantioselectivity
began to decrease. On the basis of these results, the mixed
Methanol–H2O, which was cheap and available, was chosen as
Fig. 5 TGA curves of (a) SBA-16 and (b) SBA-16-Pro.
Scheme
2 The reaction between 4-nitrobenzaldehyde and
cyclohexanone.
Table 2 Optimization conditions for the direct aldol reaction catalyzed by SBA-16-Pro
Entry Catalyst
Loading (mol%) Time (h) Temperature (ꢀC) Solvent
Yielda (%) drb (anti : syn) eeb (%)
1
2
3
4
5
6
7
8
SBA-16-Pro
20
20
20
20
20
20
20
20
20
20
—
—
20
20
5
10
30
40
20
20
20
20
20
20
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
12
24
72
96
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
40
H2O
MeOH
EtOH
CH2Cl2
CHCl3
No solvent
<5
97
82
47
50
69
n.d.c
n.d.
49
56
46
50
62
74
86
83
77
n.d.
n.d.
68
76
84
82
78
74
61
18
77
75
78
77
SBA-16-Pro
SBA-16-Pro
SBA-16-Pro
SBA-16-Pro
SBA-16-Pro
SBA-16-Pro
SBA-16-Pro
SBA-16-Pro
SBA-16-Pro
—
98 : 2
90 : 10
59 : 41
59 : 41
97 : 3
94 : 6
93 : 7
97 : 3
80 : 20
n.d.
MeOH/H2O (100 : 1) 95
MeOH/H2O (50 : 1)
MeOH/H2O (10 : 1)
MeOH/H2O (1 : 1)
MeOH/H2O (10 : 1)
MeOH/H2O (10 : 1)
MeOH/H2O (10 : 1)
MeOH/H2O (10 : 1)
MeOH/H2O (10 : 1)
MeOH/H2O (10 : 1)
MeOH/H2O (10 : 1)
MeOH/H2O (10 : 1)
MeOH/H2O (10 : 1)
MeOH/H2O (10 : 1)
MeOH/H2O (10 : 1)
MeOH/H2O (10 : 1)
MeOH/H2O (10 : 1)
MeOH/H2O (10 : 1)
94
91
44
n.d.
n.d.
98
70
62
82
94
92
86
63
33
71
93
91
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
d
SBA-16
n.d.
L-4-Hydroxyproline
SBA-16-Proe
SBA-16-Pro
SBA-16-Pro
SBA-16-Pro
SBA-16-Pro
SBA-16-Pro
SBA-16-Pro
SBA-16-Pro
SBA-16-Pro
SBA-16-Pro
SBA-16-Pro
82 : 18
95 : 5
95 : 5
80 : 20
82 : 18
98 : 2
>99 : 1
99 : 1
>99 : 1
96 : 4
90 : 10
>99 : 1
60
RT
RT
RT
RT
a
b
Isolated yield of mixture of all four diastereomers. Determined by chiral HPLC (Chiralpak AD-H column, 95 : 5 n-hexane/isopropanol,
1 mL minꢁ1, detected at 254 nm). n.d. ¼ not determined. The mass equal to 20 mol% SBA-16-Pro was added. Aer the reaction proceeded
c
d
e
for 24 h, the catalyst SBA-16-Pro was separated from the system by ltration and the le reaction mixture kept being stirring for another 24 h.
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Table 3 Evaluation of the catalyst SBA-16-Pro for the direct aldol reactions between different aromatic aldehydes and ketones
Entry
R1
R2
R3
Time (h)
Yielda (%)
drb (anti : syn)
eeb (%) anti (syn)
1
2
3
4
5
6
7
8
2-O2NC6H4–
3-O2NC6H4–
4-NCC6H4–
4-ClC6H4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)3–
–(CH2)5–
CH3
48
48
48
48
48
48
48
60
60
48
72
24
72
72
76
90
88
78
63
71
77
46
41
97
41
95
n.d.
n.d.
88 : 12
96 : 4
80 : 20
90 : 10
8 : 92
88 : 12
97 : 3
95 : 5
97 : 3
56 : 44
53 : 47
—
95
80
82
85
(93)
92
84
83
91
C6H5–
2-Thienyl–
2-Furanyl–
4-MeOC6H4–
4-MeC6H4–
4-O2NC6H4–
4-O2NC6H4–
4-O2NC6H4–
4-O2NC6H4–
4-O2NC6H4–
9
10
11
12
13
14
>99%
58
H
H
H
38c
n.d.
n.d.
C6H5–
4-O2NC6H4–
n.d.d
n.d.
a
Isolated yield of mixture of all four diastereomers. b Determined by chiral HPLC (Chiralpak AD-H column, 95 : 5 n-hexane/isopropanol, detected at
254 nm). Determined by chiral HPLC (Chiralpak OB-H column, 85 : 15 n-hexane/isopropanol, 1 mL minꢁ1, detected at 254 nm). n.d. ¼ not
c
d
determined.
the solvent of the reaction, and the volume ratio was 10 : 1. It (Scheme 2). The results of the aldol reactions proceeding for
was also noteworthy that excellent diastereoselectivity, difference time were summarized (entries 21 to 24). When the
moderate yield and enantioselectivity were obtained when the reaction time increased from 12 to 48 h, the yield had a
reaction proceeded in solvent-free condition. Several groups of signicant growth, and almost reached equilibrium aer 48 h.
controlled experiments were arranged to investigate the inu- Moreover, the enantiomeric excess value (ee values) of the
ence of the catalyst's amount for the reaction. It could be seen product obtained at 48 h was the best. So the optimum reac-
that when no catalyst or just the support material SBA-16 tion time was decided to be 48 h.
participating, the reaction almost hardly occurred (entries 11
Under the optimized conditions, the catalyst SBA-16-Pro was
and 12), which demonstrated that proline played a very tested in aldol reactions between a variety of aromatic aldehyde
important catalytic role in the asymmetric aldol reaction. On acceptors and ketone donors, and the results were summarized
the other hand, when the homogeneous proline was used as in Table 3. It was obvious that good yields with excellent ee
catalyst in the reaction, a superior yield was obtained, but its values were still obtained aer changing the substituting group
enantioselectivity was not as good as that of heterogeneous positions onto the aromatic aldehydes (entries 1 and 2).
catalyst SBA-16-Pro (entry 13). That is possibly because in some Meanwhile, 4-cyanobenzaldehyde and 4-chlorobenzaldehyde
cases, there is a strong interaction between active sites and were good acceptors and gave the desired anti products in good
supports which can improve the activity and stability of cata-
lysts.36 Compared with the heterogeneous catalyst, supported
catalyst has some special characteristics in the structure. The
Table 4 Recycling experiments of the catalyst SBA-16-Pro for the
aldol reaction between 4-nitrobenzaldehyde and cyclohexanone
steric hindrances of the active centers immobilized on the
support and the restrictions from the channels of the meso-
porous material SBA-16 were benecial for the chiral induc-
tion in the catalysis of the asymmetric aldol reaction.
Furthermore, the yield and enantioselectivity did not improve
apparently aer increasing the catalyst loading from 20 to
40 mol% (entries 17 and 18). And although good enantiose-
lectivities were still obtained, the yields were low when the
amount of catalyst was reduced to 5 and 10 mol% (entries 15
and 16). From an economical point of view, 20 mol% was the
preferred catalyst loading. With the reaction temperature
rising, not only the enantioselectivities, but also the yields
appreciably decreased (entries 19 and 20). The drop of yield
was mainly attributed to the occurrence of side reaction
Run
Yielda (%)
drb (anti : syn)
eeb (%)
1
2
3
4
5
91
92
88
87
90
97 : 3
98 : 2
99 : 1
95 : 5
92 : 8
83
77
78
81
81
a
b
Isolated yield of mixture of all four diastereomers. Determined by
chiral HPLC (Chiralpak AD-H column, 95 : 5 n-hexane/isopropanol, 1
mL minꢁ1, detected at 254 nm).
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yield with high diastereoselectivity and enantioselectivity
(entries 3 and 4), which indicated that the aromatic aldehydes
carrying electron withdrawing groups were good substrates for
the aldol reaction. Moreover, when benzaldehyde, 2-thenalde-
hyde and furfural were used as aldehyde acceptors, good ee
values were all obtained, and the yield gradually increased with
the aromaticity of aldehyde weakening (entries 5 to 7). The dr
and ee values were ideal, when the reaction proceeded between
cyclohexanone and benzaldehyde with electron donating group,
whereas the yield had an apparent decrease (entries 8 and 9).
The ee values were still good when other cyclic ketones
including cyclopentanone and cycloheptanone were used as
donors, although the increase of the carbon numbers onto the
cyclic ketones led the yields to have a signicant drop (entries
10 and 11). Acetone was also proved to be a suitable donor
providing excellent yield with moderate enantioselectivity (entry
12). However, attempts using acetophenone derivatives as
ketone donors in this reaction were unsuccessful. The corre-
sponding target products were almost not detected, so aceto-
phenone derivatives were not suitable substrates in this
reaction system (entries 13 and 14).
4. Conclusions
A new chiral metal-free organocatalyst based on proline as
active site and mesoporous cage-like material SBA-16 as support
has been successfully prepared and used in the asymmetric
aldol reaction between aromatic aldehydes and ketones.
Moderate to good yields, diastereoselectivities and enantiose-
lectivities exhibited in the activity evaluation experiments. This
synthesized catalyst avoided heavy metal pollution during the
preparing and using process, and had excellent mechanical
strength and reusability, evidenced by being extensively reused
without any substantial loss of activity.
Acknowledgements
This work was jointly supported by the Fundamental Research
Funds for the Central Universities (Grant no. lzujbky-2013-234
and lzujbky-2013-115) and the National Natural Science Foun-
dation of China (Grant no. 41371003).
The catalyst SBA-16-Pro can be easily separated from the
reaction media by ltration and subsequently reused in the next
cycle. The reusability of the synthesized catalyst in the reaction
between 4-nitrobenzaldehyde and cyclohexanone was studied.
As shown in Table 4, This SBA-16 material supported proline
could be reused up to ve runs without a signicant loss of
activity, proving that the catalyst had excellent mechanical
strength and recyclability. Through elemental analysis, the
catalyst SBA-16-Pro did not have an obvious change in proline
content (1.55 mmol gꢁ1), which still remained 92% of original
porline, aer being reused for ve times. The FT-IR spectrum of
SBA-16-Pro aer ve runs (Fig. 1c) still kept the characteristic
peaks of proline compared with that of fresh catalyst (Fig. 1b).
From the TEM images (Fig. 4c), it could be seen that the cage-
like structure of the reused catalyst was still observed although
the channel had a little collapse locally. For better exploring the
effect of the leached proline for the reaction result, another
experiment for comparison was arranged (Table 2, entry 14). 20
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