Enantioselective extraction of fenvaleric acid enantiomers by two-phase (W/O) recognition chiral extraction

Article abstract of DOI:10.1007/s10847-010-9784-6

To establish an extraction method for fenvaleric acid (FA) enantiomers using l-iso-butyl-l-tartaric esters and hydroxypropyl-β-cyclodextrin (HP-β-CD) as chiral selector, the distribution of FA enantiomers was examined in methanol aqueous solution containing HP-β-CD and 1,2-dichloroethane organic solution containing l-iso-butyl-l-tartaric esters. The influences of the concentration of l-iso-butyl-l-tartaric esters and HP-β-CD, organic diluent, pH, extraction temperature and the concentration of methanol aqueous solution on the partition coefficient (k) and separation factor (α) of FA were investigated. The experiment results showed that the complex formed by l-iso-butyl-l-tartaric esters with S-enantiomer is stabler than that with R-enantiomer. With the increase of the concentration of l-iso-butyl-l-tartaric ester, k and α increased; With the increase of the concentration of HP-β-CD, k increased firstly, and then decreased, but α increased all the while, k was the highest when the concentration of HP-β-CD was 4 mmol L^-1. 1,2-dichloroethane organic diluent was better than the others. With the increase of pH, k and α decreased; with further increasing concentration of methanol aqueous solution, k and α decreased, k and α were the highest when the concentration of methanol aqueous solution was 10%. The extraction temperature had a great influence on k and α, too.

Full text of DOI:10.1007/s10847-010-9784-6

J Incl Phenom Macrocycl Chem (2010) 68:271–275
DOI 10.1007/s10847-010-9784-6
ORIGINAL ARTICLE
Enantioselective extraction of fenvaleric acid enantiomers
by two-phase (W/O) recognition chiral extraction
•
•
•
Jian Min Yi Sai Jin Huang Yu Ren Jiang
Ke Wen Tang
Received: 19 November 2009 / Accepted: 8 April 2010 / Published online: 4 June 2010
Ó Springer Science+Business Media B.V. 2010
Abstract To establish an extraction method for fenvaleric
acid (FA) enantiomers using L-iso-butyl-L-tartaric esters and
hydroxypropyl-b-cyclodextrin (HP-b-CD) as chiral selector,
the distribution of FA enantiomers was examined in meth-
anol aqueous solution containing HP-b-CD and 1,2-dichlo-
roethane organic solution containing L-iso-butyl-L-tartaric
esters. The influences of the concentration of L-iso-butyl-L-
tartaric esters and HP-b-CD, organic diluent, pH, extraction
temperature and the concentration of methanol aqueous
solution on the partition coefficient (k) and separation factor
(a) of FA were investigated. The experiment results showed
that the complex formed by L-iso-butyl-L-tartaric esters with
S-enantiomer is stabler than that with R-enantiomer. With
the increase of the concentration of L-iso-butyl-L-tartaric
ester, k and a increased; With the increase of the concen-
tration of HP-b-CD, k increased firstly, and then decreased,
but a increased all the while, k was the highest when the
concentration of HP-b-CD was 4 mmol L-1. 1,2-dichloro-
ethane organic diluent was better than the others. With the
increase of pH, k and a decreased; with further increasing
concentration of methanol aqueous solution, k and a
decreased, k and a were the highest when the concentration
of methanol aqueous solution was 10%. The extraction
temperature had a great influence on k and a, too.
Keywords Chiral extraction ꢀ L-iso-butyl-L-tartaric
esters ꢀ HP-b-CD ꢀ Fenvaleric acid enantiomers
Introduction
At present, the gain of optically pure medicine, pesticide,
perfume, essence, food additives, and new materials have
been a research focus in corresponding fields [1–4]. Chiral
pesticide used in the market are produced and used mostly in
the form of racemate, but different enantiomers have big
differencesactiveactionfor target organism, asweareknown,
so if we produce optically pure and high active pesticide, it
will improve pesticide effect, save cost, and reduce the pol-
lution in the environment [5–8]. And it is an important sig-
nificance for us to gain optically pure compound.
Hydroxypropyl-b-cyclodextrin (HP-b-CD) and L-iso-
butyl-L-tartaric esters as the chiral electors are a research
focus in the resolution of chiral enantiomers [9, 10]. If we
use HP-b-CD and L-iso-butyl-L-tartaric esters as chiral
selector simultaneously, comparing with L-iso-butyl-L-tar-
taric esters as chiral selectors individually, we expect to get
the better extraction efficiency.
J. M. Yi ꢀ K. W. Tang
Fenvaleric acid (FA), 3-methyl-2-(4-chlorophenyl) buty-
rate, is an important intermediate for synthesis of chrysan-
themum ester. The stereostructure of fenvaleric acid can be
seeninFig. 1, whichisenantiomers, andR-fenvalericacidhas
high active action for target organism [11]. In this paper, the
extraction and distribution of FA was studied, using L-iso-
butyl-L-tartaric esters and HP-b-CD as chiral selectors, the
influences of the concentration of chiral selectors, organic
diluent, pH and the concentration of methanol aqueous
Department of Chemistry and Chemical Engineering, Hunan
Institute of Science and Technology, 414000 Yueyang, China
S. J. Huang (&)
Department of Chemistry Engineering, Hunan Institute
of Engineering, 411104 Xiangtan, China
e-mail: huangsaijinpp@163.com
Y. R. Jiang
College of Chemistry and Chemical Engineering,
Central South University, 410083 Changsha, China
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J Incl Phenom Macrocycl Chem (2010) 68:271–275
H3C
esters in organic diluents. Equal volume (5 mL) solutions
were placed in a centrifugal tube and stirred for 0.5 h at
room temperature. After phase separation, the concentra-
tion of R- and S-enantiomer in methanol aqueous solution
was determined by HPLC, then the concentration in
organic diluents calculated by CO = C - CW, where C is
the concentration in the methanol aqueous solution before
extraction, and CW, CO is the concentration in the methanol
aqueous solution and organic diluents after extraction, and
the change of the volume was ignored. The partition
coefficients (kR and kS) can be expressed as kR = CRO/CRW
and kS = CSO/CSW, where CRO, CSO is the concentration of
R-and S-enantiomer in organic diluents and CRW, CSW is
the concentration of R- and S-enantiomer in the methanol
aqueous solution. The separation factor a is the ratio of
partition coefficients of kS to kR [13].
CH3
CH
CH
Cl
COOH
Fig. 1 Stereostructure of FA
solutiononthepartitioncoefficient(k)andseparationfactor(a)
of FA were investigated.
Experimental
Apparatus and chemicals
HPLC were taken on Agilent 1200, which have Photodiode
Array Detector chiral column (150 9 4.6 mm ID, Daicel,
made in Japan). Fenvaleric acid is purchased in Nanjin, All
chemicals reagents used are of analytical pure grade.
Results and discussion
Effect of different organic diluents on extraction
Chromatographic conditions
The extraction performance of different organic diluents
for fenvaleric acid enantiomers on k and a was listed in
Table 1, which other conditions kept no change. Organic
diluents such as halogenated hydrocarbon, alkane, alcohol,
ester were investigated. And the results indicates that
extraction and separation performance is the best if using
1,2-dichloroethane as organic diluents alkane and ester
have the best extraction performance, but the separation
performance is very bad, so it is no good choice.
Chromatographic conditions was referred to Ref. [12]:
mobile phases was acetonitrile, water (volume ratio:
90:10), which contained 3% acetate, and controlled the
pH = 6.0 using ammonia. Analysis was accomplished at a
constant flow rate of 0.65 mL min-1 with the detection
wavelength at 230 nm, and column temperature at 25 °C.
Chromatogram of fenvaleric acid enantiomers were
showed as Fig. 2.
Partition experiments
Effect of concentration of L-iso-butyl-L-tartaric esters
on k and a
A certain concentration of fenvaleric acid enantiomers was
prepared in methanol aqueous solution dissolving the
extractant of HP-b-CD, and the pH was adjusted with
Na2HPO4–H3PO4 buffer solution. An organic solution was
prepared by dissolving the extractant L-iso-butyl-L-tartaric
The influence of concentration of L-iso-butyl-L-tartaric
esters on k and a was investigated. It is found from Fig. 3
that the partition coefficients k and separation factor a
increase with the increase of concentration of L-iso-butyl-L-
Table 1 Effect of different organic diluent on extraction
Organic diluent
kR
kS
a
1,2-Dichloroethane
n-Heptane
2.0848
3.0428
1.4595
1.0458
1.2272
1.1865
1.0757
1.0448
3.3675
4.0325
15.3044
1.1344
4.1326
4.7844
16.4625
Chloroform
n-Hexyl alcohol
Ethyl acetate
Extraction condition: 0.1 g L-1 fenvaleric acid enantiomers was
prepared in 20% methanol aqueous solution containing 2 mmol L-1
HP-b-CD at pH = 4, the organic solution was prepared by dissolving
0.3 mol L-1 concentration of L-iso-butyl-L-tartaric esters in different
organic diluent
Fig. 2 Chromatogram of fenvaleric acid enantiomers on CHIR-
ALPAK QN-AX column
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273
1.8
1.6
1.4
1.2
1.0
6
5
4
3
2
1
1.9
1.8
1.7
1.6
1.5
1.4
1.3
1.2
7
kS
kR
a
6
5
4
3
2
1
0
kS
kR
a
0.1
0.2
0.3
0.4
0.5
0.6
C(mol/L)
0
1
2
3
4
5
6
7
Fig. 3 Effect of concentration of L-iso-butyl-L-tartaric esters on
extraction. Extraction condition: 0.1 g L-1 fenvaleric acid enantio-
mers was prepared in 20% methanol aqueous solution containing
2 mmol L-1 HP-b-CD at pH = 4, the organic solution was prepared
by dissolving different concentration of L-iso-butyl-L-tartaric esters in
1,2-dichloroethane
C(mmol/L)
Fig. 4 Effect of HP-b-CD concentration on extraction. Extraction
condition: 0.1 g L-1 fenvaleric acid enantiomers was prepared in
20% methanol aqueous solution containing different concentration of
HP-b-CD at pH = 4, the organic solution was prepared by dissolving
0.3 mol L-1 L-iso-butyl-L-tartaric esters in 1,2-dichloroethane
tartaric esters, and kS is always bigger than kR in the range
of experimental concentration. It can be explained that
L-iso-butyl-L-tartaric esters can form diastereomeric com-
plexes with S- and R-fenvaleric acid enantiomers in
the process of extraction, but L-iso-butyl-L-tartaric esters
forms a more stable complex with S-enantiomer than
R-enantiomer.
Effect of pH of aqueous phase on k and a
Fenvaleric acid have a carboxy group, which can be seen in
Fig. 1, so it is necessary to investigate the effect of pH on k
and a. It is found from Fig. 5 that k and a decrease with the
increase of pH. This may be because the fenvaleric acid in
ionic state increase, decrease in molecularity, with the
increase of pH. The difference of the partition coefficient
of fenvaleric acid in two phase indicated that the selectivity
between chiral selectors and enantiomers are different.
Effect of concentration of HP-b-CD on k and a
Hydroxypropyl-b-cyclodextrin (HP-b-CD) has special
chemical structure, good water solubility, which can form
inclusion compounds with fenvaleric acid enantiomers, but
are different for R-and S- enantiomers in hydrogen bond-
ing, the inclusion effect, hydrophobic interaction, Van der
Waals interactions and so on [14]. The effect of concen-
tration of HP-b-CD on the partition coefficient k and sep-
aration factor a was investigated. It is found from Fig. 4
that the partition coefficients k increase with the increase of
concentration of HP-b-CD, when concentration of HP-b-
CD reach to 4 mmol L-1, k reaches the maximum. With
the further increasing of the HP-b-CD, k begins to
decrease, this may be related to diastereomeric complexes
with fenvaleric acid enantiomers in the process of extrac-
tion, but separation factor a increase with the increase of
concentration of HP-b-CD. And the separation factor a is
1.2, when only using 0.3 mol L-1 L-iso-butyl-L-tartaric
esters as chiral selectors, but the separation factor a is up to
1.8, when using the same concentration L-iso-butyl-L-tar-
taric esters and HP-b-CD as chiral selectors, so it can be
seen that biphasic chiral extraction is better than single
chiral extraction, and the mechanism is under way.
1.8
1.6
1.4
1.2
1.0
8
6
4
2
kS
kR
a
2
3
4
5
6
7
pH
Fig. 5 Effect of pH of aqueous phase on extraction. Extraction condition:
0.1 g L-1 fenvaleric acid enantiomers was prepared in 20% methanol
aqueous solution containing 2 mmol L-1 HP-b-CD in the range of pH =
2.50–6.50, the organic solution was prepared by dissolving 0.3 mol L-1
L-iso-butyl-L-tartaric esters in 1,2-dichloroethane
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J Incl Phenom Macrocycl Chem (2010) 68:271–275
8
7
6
5
4
3
5
4
3
2
1
1.8
1.6
1.4
1.2
1.0
1.6
kS
kR
a
kS
1.5
kR
1.4
a
1.3
1.2
1.1
1.0
10
15
20
25
30
10
20
30
40
50
60
T(°C)
V(CH3OH)%
Fig. 6 Effect of temperature on extraction. Extraction condition:
0.1 g L-1 fenvaleric acid enantiomers was prepared in 20% methanol
aqueous solution containing 2 mmol L-1 HP-b-CD in the range of
pH = 4.0, the organic solution was prepared by dissolving 0.3 mol L-1
L-iso-butyl-L-tartaric esters in 1,2-dichloroethane
Fig. 7 Effect of concentration of methanol on extraction. Extraction
condition: 0.1 g L-1 fenvaleric acid enantiomers was prepared in
10–80%methanolaqueoussolutioncontaining2 mmol L-1 HP-b-CD in
the range of pH = 4.0, the organic solution was prepared by dissolving
0.3 mol L-1 L-iso-butyl-L-tartaric esters in 1,2-dichloroethane
Effect of extraction temperature on k and a
The temperature on the separation of fenvaleric acid
enantiomers was investigated. It is found from Fig. 6 that
the partition coefficient increases with the increase of
temperature, but the separation factor decrease, because the
solubility of R- and S-enantiomers increase with the
increase of temperature, but the interactions such as
hydrogen bonding, the inclusion effect, hydrophobic
interaction, Van der Waals interactions and so on between
chiral selectors and R- and S-enantiomers are different, and
decrease with the increase of temperature.
Acknowledgments This work is supported by the National Natural
Science Foundation (20676028) and Office of Education-funded
research projects in Hunan Province (06A022).
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