A poly(hydroxyethyl methacrylate)-immobilized chiral manganese(III)salen catalyst for asymmetric epoxidation of α-methylstyrene

Article abstract of DOI:10.1016/S1872-2067(11)60345-8

Phenylalaninol was introduced in the C5 and C5′ position of a chiral Mn(III)salenCl compound, and the catalyst was then immobilized on poly(hydroxyethyl methacrylate) (pHEMA) by axial coordination. The catalytic system, with (R,R)(R,R)pHEMA-immobilized Mn(III)salenCl as catalyst and [bmim]PF₆ as reaction medium, gave excellent catalytic activity and enantioselectivity with 80-91 ee values and 84-92 yields for the asymmetric epoxidation of α-methylstyrene. The catalyst can be reused several times without significant loss of catalytic activity. This was due to a chiral synergy between the chiral carbons of the amino alcohol and the chiral carbons of (R,R)-diaminocyclohexane.

Full text of DOI:10.1016/S1872-2067(11)60345-8

CHINESE JOURNAL OF CATALYSIS
Volume 33, Issue 3, 2012
Online English edition of the Chinese language journal
Cite this article as: Chin. J. Catal., 2012, 33: 473–477.
ARTICLE
A Poly(hydroxyethyl methacrylate)-Immobilized Chiral
Manganese(III)salen Catalyst for Asymmetric Epoxidation
of ꢀ-Methylstyrene
XU Guojin1,2, WEI Saili2, FAN Yingguo1, ZHU Libo1, TANG Yuhai2,*, ZHENG Yuansuo2
1Environment Monitoring Center of Ningbo, Ningbo 315012, Zhejiang, China
2Institute of Analytical Sciences, School of Science, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China
Abstract: Phenylalaninol was introduced in the C5 and C5ꢀ position of a chiral Mn(III)salenCl compound, and the catalyst was then im-
mobilized on poly(hydroxyethyl methacrylate) (pHEMA) by axial coordination. The catalytic system, with
(R,R)(R,R)pHEMA-immobilized Mn(III)salenCl as catalyst and [bmim]PF6 as reaction medium, gave excellent catalytic activity and en-
antioselectivity with 80%–91% ee values and 84%–92% yields for the asymmetric epoxidation of ꢁ-methylstyrene. The catalyst can be
reused several times without significant loss of catalytic activity. This was due to a chiral synergy between the chiral carbons of the amino
alcohol and the chiral carbons of (R,R)-diaminocyclohexane.
Key words: poly(hydroxyethyl methacrylate); immobilized Mn(III)salen; asymmetric epoxidation; ꢁ-methylstyrene; ionic liquid
Metal catalyzed oxidation of organic substrates is of im-
mense importance for chemical and biochemical syntheses.
Schiff-base compounds which mimics cytochrome P-450 [1,2]
have been developed as catalysts for various asymmetric reac-
tions [3–7]. Various researchers have studied these chiral
Mn(III)salen species from the aspects of the design and syn-
thesis of salen ligands and the investigation of steric and elec-
tronic effects of the catalyst structure on stereoselectivity and
the mechanism of the asymmetric induction [8]. Many epox-
ides have been successful reacted due to the remarkable
stereoselective activity of the chiral diamine of the
Jacobsen-like catalyst, but the oxidation catalyzed by a chiral
amino alcohol accompanying the chiral diamine of
Jacobsen-like derivatives has appeared only recently [9,10]. In
our study, we have incorporated chiral phenylalaninol into a
Mn(III)salen compound as a homogeneous catalyst.
active species has the advantages of ease of handling, recov-
ery, separation, and recycling [13,14]. Our group has used
poly(hydroxyethyl methacrylate) (pHEMA) as the solid car-
rier because it contains abundant hydroxyls, which are highly
polar and active. The salen monomer was incorporated onto
pHEMA by a coordinate bond similar to that reported in the
literature from other methods including non-covalent immobi-
lization, inorganic graft, and copolymerization [15].
The solid-immobilized catalyst can suffer some loss from
some catalyst leached from the solid carrier in the catalytic
cycle. In order to prevent the small loss of catalyst, an ionic
liquid ([bmim]PF6) as a ‘liquid carrier’was used as the reaction
medium. The catalytic system, which was the Mn(III)salen
compound grafted onto pHEMA by coordinate bonds and then
dispersed into the ionic liquid, effectively prevented catalyst
loss. To make up for the lower activity of the supported catalyst
as compared with the homogeneous catalyst, a chiral amino
alcohol (phenylalaninol) was introduced into the Mn(III)salen
compound to increase the enantioselective epoxidation of
ꢁ-methylstyrene. The synergy between the chiral carbon of the
amino alcohol present in the C5 and C5ꢀ positions and the
chiral carbon of diaminocyclohexane was investigated.
While a homogeneous catalyst often gives the best enanti-
oselectivity, a heterogeneous catalyst offers the advantages of
simplified product purification and recycling of the catalyst.
To allow recovery for reuse, a number of supports with high
molecular weights have been synthesized and studied [11,12].
Among the many solid supports, a polymer to support the
Received 8 September 2011. Accepted 22 November 2011.
*Corresponding author. Tel/Fax: +86-29-82655399; E-mail: weipaopao2012@sina.cn
Copyright © 2012, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier BV. All rights reserved.
DOI: 10.1016/S1872-2067(11)60345-8

XU Guojin et al. / Chinese Journal of Catalysis, 2012, 33: 473–477
1 Experimental
CHO
OH
CHO
CHO
OH
(RS or R)
H
ClH C
OH
PhH C C HN H C
2
2
2
(R,R)-1,2-diaminocyclohexane,
3-tert-butyl-2-hydroxy-
CH OH
2
benzaldehyde, and tin(IV)tetrachloride was obtained from Alfa
Aesar Chemical Co. Paraformaldehyde, manganese acetate,
and 2-amino-3-phenyl-1-propanol were laboratory grade re-
agents from local suppliers. All other chemicals were reagent
grade and used as received.
1
2
3
R
N
R
N
(RS or R)
CH NHCHCH
2 2
(RS or R)
2
HO
PhCH CHNHCH
OH
C5
C5'
2
Ph
UV-Vis and Fourier transform infrared (FT-IR) spectra, re-
spectively, were recorded from 200 to 800 nm on a UV-3310
spectrophotometer and from 400 to 4000 cm–1 on a Nicolet
AVATAR 330 FT-IR spectrometer (using KBr pellets). The
high performance liquid chromatography (HPLC) analysis was
carried out on a Shimadzu instrument (system controller:
LC-10AT VP; UV-Vis detector: SPD-10A VP) and the chiral
stationary phase column was Daicel Chiralcel OD-H manu-
CH OH
HOH C
2
2
4
R
N
R
N
Mn
(RS or R)
(RS or R)
O
CH NHCHCH
2 2
PhCH CHNHCH
O
C5
C5'
2
2
Cl
1
factured by Daicel Chemical Industries Ltd. H NMR spectra
Ph
CH OH
HOH C
2
2
were obtained on a Bruker MSL300 spectrometer operating at
400 MHz.
Mn(III)salenCl
Catalyst 1 = (R,R)(RS,RS)Mn(III)salenCl
Catalyst 2 = (R,R)(R,R)Mn(III)salenCl
1.1 Catalyst preparation
Scheme 1. Route for the preparation of the chiral Mn(III)salenCl com-
pound.
The chiral Mn(III)salenCl catalyst 1 and 2 were obtained by
the synthesis sequence given in Scheme 1. A mixture of
3-tert-butyl-2-hydroxybenzaldehyde (1, 17.98 mmol), para-
formaldehyde (39.39 mmol), and tetrabutylammonium bro-
mide (1.72 mmol) in 12 ml of concentrated hydrochloric acid
was stirred vigorously at 40 °C for 72 h [16]. The reaction
mixture was repeatedly extracted with ethyl acetate (15 ml × 5)
and the organic phase was washed with 5% NaHCO3 (10 ml ×
5) and brine (10 ml × 2), then dried by MgSO4. The solvent was
removed by vacuum and 3-tert-butyl-5-chloromethyl-2-hy-
droxybenzaldehyde (2) was isolated as a yellow crystalline
solid. 1H NMR (CDCl3, 400 MHz): ꢀ 1.33 (s, 9H), 4.62 (s, 2H),
7.41 (s, 1H), 7.43 (s, 1H), 10.24 (s, 1H). 13C NMR (CDCl3, 400
MHz): ꢀ 30.5, 31.9, 46.9, 128, 129, 130, 133, 138,157, 192.
3-tert-Butyl-5-chloromethyl-2-hydroxybenzaldehyde (16
mmol), 2-amino-3-phenyl-1-propanol (16 mmol), and
triethylamine (16 mmol) in 100 ml of toluene was stirred under
refluxing for 8 h. The reaction mixture was allowed to cool
down to room temperature and then it was poured into water
(100 ml). The solution was extracted with dichloromethane (15
ml × 5). The organic layer was washed with brine (10 ml × 2),
dried by MgSO4, and concentrated and purified by column
chromatography (SiO2, petroleum/acetic ether = 5/1, v/v) to
generate a dark yellow oily compound 3 of 3-tert-butyl-2-hy-
droxy-5-((1-hydroxy-3-phenylpropan-2-ylamino)methyl)benz
aldehyde. 1H NMR (CDCl3, 400 MHz): ꢀ 1.33 (s, 9H), 2.66 (d,
2H), 3.10 (m, 1H), 3.59 (m, 2H), 3.82 (s, 2H), 7.08–7.24 (m,
7H), 10.24 (s, 1H). 13C NMR (CDCl3, 400 MHz): ꢀ 30.5, 31.9,
52.9, 58.1, 66.3, 126–128, 133, 138, 156, 192.
heated to reflux (75–80 °C) and a solution of compound 3 (12
mmol) in ethanol was added in a steady stream. The yellow
solution was refluxed for 8 h with stirring. The reaction mix-
ture was cooled to room temperature and collected by vacuum
filtration. The crude solid was redissolved in dichloromethane
(50 ml) and washed with deionized water (15 ml × 2) and brine
(10 ml × 2). After drying over MgSO4, the solvent was con-
centrated and purified by column chromatography (SiO2, pe-
troleum/acetic ether = 1/5, v/v) to generate a dark yellow oily
1
chiral compound 4. H NMR (CDCl3, 400 MHz): ꢀ 1.33 (s,
8H), 1.39–1.88 (m, 8H), 2.66 (d, 2H), 3.05 (m, 2H), 3.10 (m,
2H), 3.59 (m, 4H), 3.82 (s, 4H), 6.95–7.21 (m, 14H). 8.18 (s,
2H). 13C NMR (CDCl3, 400 MHz): ꢀ 23, 25, 30.5, 31.9, 40,
52.9, 58.1, 60, 66.3, 126–128, 136, 138, 156, 161.
Under vigorous stirring, 15 ml of ethanol containing 8 mmol
of manganese acetate was added dropwise to 15 ml of ethanol
solution containing 4 mmol of chiral compound 4 under ni-
trogen protection. The mixture was refluxed for 5 h, then 10 ml
of ethanol containing 24 mmol of lithium chloride was added to
the mixture under stirring for 3 h. After the reaction was over,
the crude product was collected by filtration, redissolved in
dichloromethane (50 ml), and washed with distilled water (15
ml × 2) and brine (10 ml × 2). After the solvent was concen-
trated, chiral Mn(III)salenCl was obtained and dried under
vacuum. FT-IR (KBr, cmꢂ1): v 3520, 3120, 3040, 2610, 1612,
1540, 1490, 1280, 1175, 990, 460, 310.
The pHEMA-immobilized Mn(III)salenCl compound
(Scheme 2) was prepared as follows. pHEMA powder (1.10 g)
was refluxed in an aqueous solution of sodium hydroxide (100
(R,R)-1,2-diaminocyclohexane (6 mmol) and K2CO3 (12.3
mmol) in ethanol were stirred. The resulting mixture was

XU Guojin et al. / Chinese Journal of Catalysis, 2012, 33: 473–477
CH
2
m
Catalyst
O
+
O
NaClO
[bmim]PF
6
O
Scheme 3.
Enantioselective epoxidation of ꢁ-methylstyrene in
[bmim]PF6.
O
O
reaction products were analyzed by HPLC using UV-detection
at wavelength 254 nm; eluent agent: n-hexane/i-PrOH = 99/1,
v/v; flow rate: 0.8 ml/min; column pressure: 2.0–3.0 MPa;
column temperature: 25 °C.
H C
2
CH
2
m
m
O
O
t-Bu
t-Bu
(RS or R)
(RS or R)
2
O
2 Results and discussion
PhH CHCHNH C
O
O
CH NHCHCH Ph
2
2
2
Mn
HOH C
2
CH OH
2
N
R
N
R
2.1 FT-IR spectra
The FT-IR spectrum of Na(pHEMA) in Fig. 1 showed one
peak characteristic of the alcoholic group at 3475 cm–1
(stretching C–O). Ester groups were identified by the peaks at
1728 cm–1 (C=O stretching) and 1175 cm–1 (C–O stretching).
The other peaks were C–C and C–H vibrations of –CH3 and
–CH2 groups. The peak at 519 cm–1 of pHEMA-immobilized
Mn(III)salen was due to the Mn–N bond. The FT-IR spectrum
of pHEMA-immobilized Mn(III)salen also showed an absorp-
tion band at 1578 cm–1, which was assigned to the C=N vibra-
tions of the imines present in the Mn(III)salenCl compound.
This proved that the Mn(III)salenCl was successfully immobi-
lized onto the Na(pHEMA) [17].
Catalyst 3 = (R,R)(RS,RS)pHEMA-immobilized Mn(III)salenCl
Catalyst 4 = (R,R)(R,R)pHEMA-immobilized Mn(III)salenCl
Scheme 2.
Route for preparation of the chiral pHEMA-immobilized
Mn(III)salen compound.
ml, 13.3 mmol/g) for 3 h. The solid was filtrated and washed
with distilled water until pH 7, and dried at 120 oC in an oven.
A white powder was obtained under vacuum, which was des-
ignated as Na(pHEMA).
A mixture of Mn(III)salenCl (1.0 mmol) and Na(pHEMA)
(2.0 g) was added into ethanol (60 ml) and stirred for 8 h under
refluxing. The suspension was then filtrated, washed thor-
oughly with ethanol and CH2Cl2 to produce pHEMA-immo-
bilized Mn(III)salenCl as small yellow powder particles. The
CH2Cl2 filtrate was examined by FT-IR until there was no
Mn(III)salenCl (with CH2Cl2 as reference) peak. FT-IR (KBr,
cmꢂ1): v 3520, 3120, 3040, 2610, 1728, 1725, 1627, 1540,
1490, 1280, 1175, 990, 471, 310.
2.2 UV-Vis spectra
The UV-Vis spectra of neat chiral Mn(III)salenCl and
pHEMA-immobilized Mn(III)salenCl are shown in Fig. 2. The
peak at 433 nm was assigned to charge-transfer transitions
between the metal and ligand. The peak at 508 nm was as-
signed to the d-d transitions in the Mn(III)salenCl compound
[18]. pHEMA-immobilized Mn(III)salenCl, in which the
pHEMA was attached by the direct axial coordination of the
metal center, exhibited a red shift in the wavelength ranges
1.2 Enantioselective epoxidation of unfunctionalized
ꢀ-methylstyrene
The enantioselective epoxidation of ꢁ-methylstyrene
(Scheme 3) was performed by the following procedure. First, 2
mmol of ꢁ-methylstyrene and 0.4 mmol of axial base NH4OAc
were added to 4 ml of [bmim]PF6 containing 0.2 mmol of
catalyst (10 mol% based on the mol of the ꢁ-methylstyrene)
under stirring at 0 °C. A solution of Na2HPO4 (0.05 mol/L) was
added to a pre-cooled solution of aqueous NaClO (0.58 mol/L)
as an oxidant. The pH value of this mixed solution was accu-
rately adjusted to 11.3 by the slow addition of HCl (1 mol/L) or
NaOH (1 mol/L). After the reaction, 20 ml of n-hexane was
directly added to the reaction mixture. The n-hexane phase was
separated and concentrated under reduced pressure, then the
residue was purified by column chromatography (SiO2, petro-
leum ether/CH2Cl2 = 2/1, v/v) to obtain the epoxides. The ionic
liquid containing the catalyst was separated for recycling. The
(1)
20
(2)
ꢀ
Mn N
ꢀ
C O
C=N
(3)
4000 3500 3000 2500 2000 1500 1000 500
Wavenumber (cmꢀ1)
Fig. 1. FT-IR spectra of different compounds. (1) Na(pHEMA); (2)
pHEMA-immobilized Mn(III)salenCl; (3) Mn(III)salenCl.

XU Guojin et al. / Chinese Journal of Catalysis, 2012, 33: 473–477
catalyst from the ionic liquid in the recycling, which resulted in
0.5
0.4
0.3
0.2
0.1
0.0
-0.1
433
the low ee values and yields of ꢁ-methylstyrene epoxide after
the ionic liquid [bmim]PF6 containing Mn(III)salenCl catalyst
was recycled only three times.
In order to reduce catalyst loss, the Mn(III)salenCl catalyst
was immobilized on the pHEMAby coordinate bonds, and then
dispersed in the ionic liquid. This catalytic system, named as a
double-immobilized system, effectively prevented catalyst
loss. The catalytic performance of the heterogeneous catalyst
was compared with the corresponding ee values of the homo-
geneous catalyst (catalyst 1 vs catalyst 3, catalyst 2 vs catalyst
4). In the five recycles, the ee values were only slightly de-
graded (70% < ee < 79% by catalyst 3, 80% < ee < 91% by
catalyst 4). This showed that the recycle ability of the dou-
ble-immobilized system was improved and catalytic activity
was well maintained.
With respect to increasing the ee value, it was evident that
the catalytic performance of catalyst 4 was improved as com-
pared to catalyst 3, with the yield increased from 86% to 92%
and ee value increased from 79% to 91% in cycle 1. Mean-
while, the ee value still reached 80% in the fifth recycle. The
increase in activity and selectivity was attributed to the chiral
synergy between the chiral carbons of (R)-phenylalaninol and
the chiral carbons of (R,R)-diamino-cyclohexane. The ex-
perimental data showed that the catalytic system with
(R,R)(R,R)-pHEMA-immobilized Mn(III)salenCl as catalyst
and [bmim]PF6 as reaction medium for the asymmetric ep-
oxidation of ꢁ-methylstyrene exhibited excellent catalytic
activity and enantioselectivity with 91%–80% ee values and
92%–84% yields, and the catalyst can be reused several times
without significant loss of catalytic activity.
447
508
(1)
(2)
520
400 420 440 460 480 500 520 540 560 580
Wavelength (nm)
Fig. 2. UV-Vis spectra of Mn(III)salenCl (1) and pHEMA-immobilized
Mn(III)salenCl (2).
from 433 to 447 nm and from 508 to 520 nm, which were due
to the strong coordination between the metal center and the
hydroxy group of the pHEMA. These findings proved that the
Mn(III)salenCl was bonded onto the pHEMA compound.
Table 1 summarizes the catalytic performance of the
pHEMA-immobilized Mn(III)salenCl and Mn(III)salenCl in
the enantioselective epoxidation of unfunctionalized
ꢁ-methylstyrene. In the chiral induction, the first cycle results
of catalyst 1 for asymmetric epoxidation of ꢁ-methylstyrene in
pure [bmim]PF6 gave the ee value of 80% and yield of 85%.
However, in the third recycle, the ee value decreased to 56%.
Chiral (R)-phenylalaninol was added in the C5 and C5ꢀ position
of catalyst 1 and (R,R)(R,R) Mn(III)salenCl named catalyst 2
was obtained. Compared with catalyst 1, the catalytic per-
formance of catalyst 2 was better, with the yield increased from
85% to 90% and ee value increased from 80% to 93% in cycle
1. Overall, the change from the racemic phenylalaninol of
catalyst 1 to (R)-phenylalaninol of catalyst 2 gave increases in
the yield and ee value of the epoxide. However, the ee values
for epoxidation catalyzed by catalyst 2 reduced rapidly from
93% to 64% over three recycles. n-Hexane as an extractant was
detected by FT-IR. FT-IR spectra of the extraction solvent in
the second and third recycles showed the characteristic ab-
sorption peak of the Mn(III)salenCl catalyst. This proved that
the process had the problem of the loss of Mn(III)salenCl
3 Conclusions
A pHEMA-immobilized Mn(III)salenCl catalyst in the ionic
liquid [bmim]PF6 for the asymmetric epoxidation of
ꢁ-methylstyrene exhibited excellent catalytic activity and en-
antioselectivity with 91%–80% ee values and 92%–84%
yields. The polymer-immobilized Mn(III)salenCl catalyst can
be easily recycled by simply filtration and was relatively stable
in activity and enantioselectivity after three recycles. Catalyst 2
and 4 containing four chiral carbons as compared to the catalyst
1 and 3 gave better yields and ee values of epoxides. This was
possibly due to the chiral synergy between the chiral carbons of
amino alcohol and the chiral carbons of (R,R)-diamino-
cyclohexane.
Table 1 Epoxidation of ꢁ-methylstyrene catalyzed by Mn(III)salenCl
and pHEMA-immobilized Mn(III)salenCl with ionic liquid [bmim]PF6 as
reaction medium
eea/yieldb (%)
Catalyst
Cycle 1
80/85
93/90
79/86
91/92
Cycle 2
72/72
85/78
76/84
89/90
Cycle 3
56/50
64/61
74/83
87/89
Cycle 4
—
Cycle 5
—
—
70/79
80/84
Catalyst 1
Catalyst 2
Catalyst 3
Catalyst 4
—
72/81
83/87
Acknowledgments
Reaction conditions: ꢁ-methylstyrene 2 mmol, catalyst 0.2 mmol (10
mol%), NaClO 5.8 mmol, NH4OAc 0.4 mmol (20 mol%).
aDetermined by HPLC over a chiral OD-H column.
bYield of the isolated epoxide.
XU Guojin is grateful to the Chairperson Foundation of
Environment Monitoring Center of Ningbo for financial sup-
port.

XU Guojin et al. / Chinese Journal of Catalysis, 2012, 33: 473–477
2006, 86: 803
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