Synthesis and chiral recognition ability of a novel fullerene-functionalized cellulose derivative

Article abstract of DOI:10.1246/cl.150637

The fullerene-functionalized cellulose derivative 1 was synthesized and coated onto silica gel as chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC). The chiral recognition ability of the obtained chiral packing material (CPM) was evaluated by HPLC with ten types of racemates 2-11. This CPM could be used in the eluents including chloroform and terahydrofuran (THF), which are usually unsuitable solvents for conventional coating-type CPMs. Hence the scope of application of this CPM is wider than conventional coating CPM.

Full text of DOI:10.1246/cl.150637

Received: July 2, 2015 | Accepted: July 31, 2015 | Web Released: August 12, 2015
CL-150637
Synthesis and Chiral Recognition Ability of a Novel Fullerene-functionalized Cellulose Derivative
Bo Gao,1,# Zeyu Xu,1,2,# Luan Fan,2 Xiaodong Xu,2 Jianwei Bai,2 and Xiande Shen*1
1School of Material Science and Engineering, Changchun University of Science and Technology, Changchun 130022, P. R. China
2Polymer Materials Research Center, Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education,
College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001, P. R. China
(E-mail: shenxiande@cust.edu.cn)
The fullerene-functionalized cellulose derivative 1 was
synthesized and coated onto silica gel as chiral stationary phase
(CSP) for high-performance liquid chromatography (HPLC).
The chiral recognition ability of the obtained chiral packing
material (CPM) was evaluated by HPLC with ten types of
racemates 2-11. This CPM could be used in the eluents
including chloroform and terahydrofuran (THF), which are
usually unsuitable solvents for conventional coating-type CPMs.
Hence the scope of application of this CPM is wider than
conventional coating CPM.
Figure 1. Structure of cellulose derivative 1 used as CPM.
In recent years, direct enantioseparation with chiral sta-
tionary phases (CSPs) by high-performance liquid chromatog-
raphy (HPLC) has attracted much attention.1-4 In particular,
CSPs, based on derivatives of cellulose and amylose, have been
intensively studied because they are capable of separating nearly
90% of racemates.5-8 Among these CSPs, most of them have
been prepared by coating the polysaccharide derivatives on
macroporous silica gel, which means the commonly used
solvents like chloroform and THF can hardly be used as eluents
because they will dissolve or swell the polymers.9-12 However,
Figure 2. A synthetic route for 1 from the starting compound of
cellulose.
the use of these prohibited eluents may result in higher solubility
for many enantiomers, a better resolution, and reversed elution
order of the enantiomers, which are important factors for the
efficient separation of enantiomers by HPLC. Therefore, CSPs
enabling use of these prohibited eluents are of great interest as
well as practice.13-16
reported by Okamoto.9 A3 was then transformed to A4 by
reacting itself with 6-bromocaproic acid (4 equiv relative to 6-
position OH) in the presence of a catalytic amount of DMAP
under the conditions of DMAc as solvent at room temperature
for 24 h. Consequently, A4 was reacted with NaN3 (10 equiv
relative to 6-position Br) in DMSO at r.t. for 24 h to afford A5.
1 was finally obtained by reacting A5 with fullerene (C60) in
DMSO at 80 °C for 24 h under a N2 atmosphere. For purification,
the product 1 was dialyzed against THF. 1 was constantly kept
in a THF solution because it was only slightly soluble in DMSO,
Based on this background, we are making efforts in
developing new material for CSPs as to improve the solvent
resistance. As a new type of material, fullerenes have been
widely used in superconductivity, semiconductor physics,
biology, catalysis, and other fields.17-21 However, their applica-
tion to chiral separation material has been rarely examined and
reported. This chiral packing material (CPM) with fullerene
cellulose derivative could be used in eluents including chloro-
form and terahydrofuran (THF), which are usually unsuitable
solvents for conventional coating-type CPMs. And this CPM
possesses superlong service life due to its rather low solubility in
common solvents. So the scope of application of this CPM is
wider than conventional coating CPM. Here, this study describes
the preparation of a new type of cellulose-based CSP and gives
insight into the effect of newly-introduced fullerene moiety on
chiral recognition ability.
1
THF, and CHCl3 when it existed in a solid state. The H NMR
spectrum of A5 is shown in Figure 3 and the IR spectra of
A5 and 1 are shown in Figure 4. As shown in Figure 3, the
characteristic main chain signals were clearly observed at 3.4-
5.3 ppm due to the glucose units, and those for side groups at
1.0-1.6, 1.8-2.3, 3.2-3.3, 6.4-7.2, and 8.4-9.3 ppm due to
(CH2)4CH2N3, CH3-Ph, (CH2)4CH2N3, aromatic H, and -NH-.
1
Unfortunately, we could not obtain the H NMR spectrum of
1 due to its low solubility in deuterated solvents. However,
it is reasonable for us to assume that 1 should have a rather
similar 1H NMR spectrum with that of A5 because C60 does not
contain any hydrogen atoms. In the IR spectra of A5 and 1
In the present study, the new cellulose-based CSP (1,
Figure 1), which bears a fullerene moiety at the 6-position, was
prepared by introducing two 3,5-dimethylphenylcarbamate sub-
stitutes onto 2- and 3-positions and fullerene onto the 6-postion
of cellulose, as shown in Figure 2. In greater detail, the cellulose
derivative, A3, was initially synthesized according to a method
¹1
(Figure 4), the characteristic trenching signals at ca. 2100 cm
due to the N3 group in A5 completely disappeared after reacting
A5 with C60, indicating the quantitative introduction of C60
into 1.22
Chem. Lett. 2015, 44, 1479–1481 | doi:10.1246/cl.150637
© 2015 The Chemical Society of Japan | 1479

Table 1. Resolution of racemates in eluent of hexane/2-propanola
DMSO
H/I = 90/10
H/I = 95/5
C
H
3
Racemates
H
O
2
k1¤
¡
k1¤
¡
2
3
4
5
6
7
8
9
10
11
0.35
0.14
1.01
0.28
0.63
0.25
0.46
0.04
1.68
1.00
ca. 1 (+)
ca. 1 (+)
1.25 (+)
1.35 (¹)
1.75 (¹)
1.38 (¹)
ca. 1 (¹)
1.00
0.54
0.13
2.49
0.70
3.59
1.29
1.29
0.54
6.66
1.25
1.16 (+)
1.56 (+)
1.23 (+)
1.28 (¹)
1.87 (¹)
1.24 (¹)
ca. 1 (¹)
ca. 1 (¹)
1.12 (+)
1.16 (+)
Ph-
H
OC(C
H )
C
H
2
N
2 4
3
glucose-
H
TMS
N-
H
10
8
6
4
2
0
δ (ppm)
1.15 (+)
1.18 (+)
Figure 3. 1H NMR (500 MHz) spectrum of the cellulose derivative
A5 in DMSO-d6 at 80 °C.
aColumn: 25 cm © 0.20cm i.d. Eluent: H: hexane, I: 2-propanol.
Flow rate: 0.1 mL min¹1. The signs in parentheses represent the optical
rotation the first-eluted enantiomer.
a
b
Table 2. Resolution of racemates in different mixture eluentsa
H/I = 90/10
k1¤
H/I/C = 89/1/10 H/I/T = 89/1/10
k1¤ k1¤
0.80 ca. 1 (+)
1.42 (+) 0.33 ca. 1 (+)
Racemates
¡
¡
¡
2
3
0.35 ca. 1 (+) 1.10
0.14 ca. 1 (+) 0.14
1.00
4
5
6
7
1.01
0.28
0.63
0.25
1.25 (+) 1.69
1.35 (¹) 0.28
1.75 (¹) 5.10
1.25 (+) 1.40
1.33 (¹) 0.44
2.08 (¹) 0.61
1.25 (+)
1.17 (¹)
1.36 (¹)
1.30 (¹)
1.00
1.38 (¹) 0.61 ca. 1 (¹) 1.07
4000
3500
3000
2500
2000
1500
1000
500
8
0.46 ca. 1 (¹) 0.56 ca. 1 (¹) 0.62
-1
Wavenumber/cm
9
10
11
0.04
1.68
1.00
1.00
1.15 (+) 6.90
1.18 (+) 0.80
0.31 ca. 1 (¹) 0.14
1.00
1.07 (¹) 1.56 ca. 1 (¹)
1.31 (+) 1.40 ca. 1 (+)
Figure 4. IR spectra of A5 (a) and 1 (b).
aColumn: 25 cm © 0.20cm i.d. Eluent: H: hexane, I: 2-propanol,
C: chloroform, T: THF. Flow rate: 0.1 mL min¹1. The signs in
parentheses represent the optical rotation the first-eluted enantiomer.
Table 1 shows the resolution of the racemates under
different hexane/2-propanol (H/I) proportions. The CSP
showed chiral separation ability for almost all of the enantiom-
ers, among which the racemates 4, 5, 6, 7, 10, and 11 could be
separated by the CSP in a mixture eluent of H/I = 90/10. On
the contrary, the racemates 2 and 3 could be separated in a
mixture eluent of H/I = 95/5, but could not be separated in that
of H/I = 90/10. As the hexane proportion in H/I was increased
to 95%, the baseline separation of racemate 4 was achieved,
and the separation factor as well as resolution of racemate 6
became greater. This was mainly due to the change of polarity of
the solvents. As the proportion of 2-propanol changed to 5%,
the polarity of the eluent declined, the retention time of the
racemates became longer, better separation effect was achieved.
Since the CSP was almost insoluble in most solvents, THF
and CHCl3 were thus selected as the polar eluents in this study.
Table 2 shows the resolution results of the racemates with
different eluents having the same solvent proportions, i.e., H/I/
C = 89/1/10 and H/I/T = 89/1/10. In comparison to the case
using a standard H/I = 90/10, the results in Table 2 suggest
that the ¡ values for some racemates 3, 6, and 11 in H/I/
C = 89/1/10 were greater than those in H/I = 90/10 and H/I/
T = 89/1/10. Typically, Figure 6 shows a chromatogram of the
resolution of racemate 6 in H/I/C = 89/1/10, in which a more
perfect baseline separation for racemate 6 was achieved. This
was mainly due to the different hydrogen-bonding force. The
Figure 5. Structures of racemates.
To prepare the CPM, a THF solution of 1 (0.2 g) was first
coated onto silica gel (0.8 g) according to a previous method.6
The coated silica gel was then washed with THF before packing
into a stainless-steel tube (25 cm © 0.20 cm i.d.) to ensure that
no uncoated CSP elutes out during the test. The plate number
of the packed column was estimated to be ca. 2100 for benzene
using a hexane/2-propanol (90/10, v/v) mixture as the eluent at
the flow rate of 0.1 mL min¹1 at 25 °C. The dead time (t0) of the
column was estimated using 1,3,5-tri-tert-butylbenzene.
The chiral recognition ability of the homemade CSP was
evaluated by HPLC using ten kinds of racemates 2-11, as shown
in Figure 5. The separation factor (¡) was calculated based on
an equation as:
¡ ¼ k2=k1
ð1Þ
Here, k1 and k2 are the capacity factors, which can be figured out
by equations: k1 = (t1 ¹ t0)/t0 and k2 = (t2 ¹ t0)/t0.
1480 | Chem. Lett. 2015, 44, 1479–1481 | doi:10.1246/cl.150637
© 2015 The Chemical Society of Japan

recognition ability toward most racemates, which is of great
potential as a nice candidate material for chiral separation by
HPLC.
t1
CH OH
CF3
This work was supported by the National Natural Science
Foundation of China (Nos. 51103030 and 21204082), the
Natural Science Foundation of Jilin Province, China (No.
20140101098JC), the Fundamental Research Funds for the
Central Universities of Harbin Engineering University (Nos.
HEUCFT1009 and HEUCF201403008) and Daicel Corporation
(Tokyo, Japan).
t2
6
t0
0
40
80
120
160
Elution time/min
Supporting Information is available electronically on J-STAGE.
Figure 6. Chromatogram for the resolution of 6 in H/I/C = 89/
1/10.
References
#
These authors contributed equally to this work and should
be considered as co-first authors.
Table 3. Resolution of racemates in different mixture eluentsa
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H/E = 95/5
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¡
¡
k1¤
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3
4
5
6
7
8
9
10
11
0.54
0.13
2.49
0.70
3.59
1.29
1.16 (+) 0.87 1.10 (+) 1.07
1.56 (+) 0.19 1.26 (+) 0.30
1.23 (+) 2.34 1.21 (+) 1.86
1.18 (+)
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1.26 (¹)
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1.77
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6.66
1.25
1.12 (+) 5.09 1.14 (+) 3.63
1.16 (+) 1.34 1.17 (+) 1.90
1.15 (+)
1.17 (+)
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was much stronger than chloroform. With the addition of
chloroform, the retention time became much longer than before.
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In this study, a new type of fullerene-functionalized
cellulose derivative was prepared as CSP to evaluate its chiral
recognition ability in HPLC using ten racemates. The newly-
developed CSP shows better solvent resistance when compared
with conventional coating type chromatographic columns.
Importantly, chloroform, THF, and other prohibited solvents
can be used in this coating type chromatographic column, which
is significantly different from the conventionally reported ones.
So the scope of application of this CPM is wider than
conventional coating CPM. And this CPM possesses long
service life due to its rather low solubility in common solvents.
In addition, the CSP reported here also showed strong chiral
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Chem. Lett. 2015, 44, 1479–1481 | doi:10.1246/cl.150637
© 2015 The Chemical Society of Japan | 1481