Resolution of racemic trans-1,2-cyclohexanediol with tartaric acid

Article abstract of DOI:10.1016/j.tetasy.2008.06.023

A simple method for the resolution of racemic trans-1,2-cyclohexanediol enantiomers is presented in this paper. The chiral discrimination was performed by tartaric acid via diastereomeric complex formation. The diastereomeric complexes were formed by adding the resolving agent to the racemic diol in a 0.5:1 molar ratio. The (2R,3R)-(+)-tartaric acid forms stable diastereomeric complex with (1R,2R)-(-)-cyclohexanediol. Supercritical carbon dioxide extraction was applied to the separation of the mixture of diastereomeric complexes and uncomplexed diol enantiomers. We found unexpected optimal conditions according to the 3² factorial design on the resolution efficiency within the studied range of the extraction pressure and temperature. In the best cases, the (1S,2S)- and (1R,2R)-diol enantiomers were obtained with ee_(1S,2S) = 62% and ee_(1R,2R) = 93% enantiomeric excess in one equilibrium stage, respectively.

Full text of DOI:10.1016/j.tetasy.2008.06.023

Tetrahedron: Asymmetry 19 (2008) 1587–1592
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Resolution of racemic trans-1,2-cyclohexanediol with tartaric acid
a
a
a
a,*
b
b
Péter Molnár , Paul Thorey , György Bánsághi , Edit Székely , László Poppe , Anna Tomin ,
a
b
a
Sándor Kemény , Elemér Fogassy , Béla Simándi
Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, H-1521 Budapest, Hungary
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1521 Budapest, Hungary
a
b
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple method for the resolution of racemic trans-1,2-cyclohexanediol enantiomers is presented in this
paper. The chiral discrimination was performed by tartaric acid via diastereomeric complex formation.
The diastereomeric complexes were formed by adding the resolving agent to the racemic diol in a
Received 1 May 2008
Accepted 18 June 2008
Available online 16 July 2008
0
.5:1 molar ratio. The (2R,3R)-(+)-tartaric acid forms stable diastereomeric complex with (1R,2R)-(ꢀ)-
cyclohexanediol. Supercritical carbon dioxide extraction was applied to the separation of the mixture
of diastereomeric complexes and uncomplexed diol enantiomers. We found unexpected optimal condi-
2
tions according to the 3 factorial design on the resolution efficiency within the studied range of the
extraction pressure and temperature. In the best cases, the (1S,2S)- and (1R,2R)-diol enantiomers were
obtained with ee(1S,2S) = 62% and ee(1R,2R) = 93% enantiomeric excess in one equilibrium stage,
respectively.
Ó 2008 Elsevier Ltd. All rights reserved.
1
. Introduction
The optical purity (op) and yields (Y) for the corresponding diol
enantiomers were
The applicability of supercritical fluid extraction (SFE) as an
effective and green technique for enantioseparations is already
op
¼ 97%;
Y
ð1S;2SÞꢀ1 ¼ 46%; op
¼ 96%;
ð1S;2SÞꢀ1
ð1R;2RÞꢀ1
1
–5
23
known.
In these processes, diastereomeric salts or complexes
Y
ð1R;2RÞꢀ1 ¼ 41%; respectively:
of the racemic compounds and resolving agents are formed before
the extraction step. The selected resolving agent is added in less
than stoichiometric ratio to the racemic compound. The unreacted
enantiomers are extracted with the supercritical solvent, and are
collected as a powder after depressurization of the solution.
The cis- and trans-1,2-cyclohexanediols are the topic of many
Examples of enzyme-catalysed kinetic resolutions have been de-
24,25
scribed in the literature.
Bódai et al. studied the kinetic resolu-
tion of the monoacetates of trans-1,2-cycloalkanediols by acylation
26
with vinyl acetate.
Enantiomers of trans-1,2-cyclohexanediol
were produced from their bisacetylated derivatives by enantio-
selective hydrolysis with recombinant lipases obtained from Bacil-
6
–12
publications because of their importance as building blocks
27
lus subtilis.
1
3,14
or chiral auxiliaries.
The binary phase diagram for the trans-
Apart from these techniques, asymmetric hydrogenation is an
alternative method for producing cyclohexanediol enantiomers
from cyclohexane-1,2-dione by using a cinchonidine-modified
1
,2-cyclohexanediol 1 enantiomers was determined by Leitão
15
et al. Several publications can be found in the literature dealing
with the chiral derivatization or resolution of racemic trans-1,2-
28
platinum catalyst.
1
6–21
cyclohexanediol.
In a few cases, high enantiomeric purity
Among the aforementioned enantioseparation methods, the
kinetic resolution of the diol by lipases gave the best ee values,
although enzymatic transformation of the racemic compounds
usually resulted in a complex mixture of more than two products,
or required partial esterification before the kinetic resolution. In
addition, the long reaction times (>24 h) and the considerable price
of the enzymes are obvious disadvantages. Although the scale-up
of the chiral derivatization or resolution techniques by non-enzy-
matic methods are more realizable, the ee values of the products
are remarkably lower (<80%) in most of the cases. The chiral aux-
iliaries and selectors used were produced in laborious syntheses,
which required different organic reagents and solvents in signifi-
cant amounts, moreover, these enantioseparations are based on
was achieved. Lainé et al. resolved racemic trans-1,2-cyclohexane-
diol via the formation of dispiroketals. After removing the protect-
ing auxiliary, the subsequent oxidation gave the corresponding
diacetates of the diol in an enantiomeric excess (ee) of 95% and
2
2
yield of 36–45%.
Among the different optically active acids,
Chatterjee et al. found that O-acetyl mandelic acid is a favourable
agent for the esterification of the racemic trans-1,2-cyclohexanediol.
*
Corresponding author. Tel.: +36 1 463 2658/3096; fax: +36 1 463 3197.
E-mail address: sz-edit@mail.bme.hu (E. Székely).
Yield is calculated in regard to the amount of the racemic compound.
0
957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.06.023

1
588
P. Molnár et al. / Tetrahedron: Asymmetry 19 (2008) 1587–1592
Nomenclature
a, b
c, d
e, f
constants in Brunner’s equation
p
P
rac
rt
scCO
T
significance level of the experimental design
pressure, MPa
racemic
room temperature
supercritical carbon dioxide
temperature, °C
constants in the Hyperbolic equation
constants in the Parabolic diffusion model
constants in the Power law model
g, h
rel
CO2
relative amount of carbon dioxide to the rac-1, g/g (Eq.
2
(2.5))
ee
F
enantiomeric excess, %
resolution efficiency, separation efficiency, resolvability
Y
yield, % regarding the amount of the racemic compound
(Eqs. (2.1) and (2.2))
(Eq. (2.3))
q
density of the supercritical carbon dioxide, g/ml
m
m
m
Extr
mass of enantiomeric mixture in the extract
mass of enantiomeric mixture in the raffinate
mass of the racemic trans-1,2-cyclohexanediol in the
extractor
Raff
Subscripts
Extr
Rac
racꢀ1
extract
racemic trans-1,2-cyclohexanediol
mr
ee
molar ratio of the resolving agent (Eq. (2.4))
enantiomeric excess, %
Raff
raffinate
covalent bond formation with the racemic compound. Therefore,
additional process steps are required to form and remove the pro-
tecting/derivatizing agents from the diol, increasing the time and
the organic solvent demands of the processes and decreasing the
achievable yields.
Herein, we report a new and simple resolution for the enantio-
mers of trans-1,2-cyclohexanediol 1 by diastereomeric complex
formation and subsequent supercritical fluid extraction, and show
the influence of the extraction parameters on the resolution
efficiency.
where ‘n’ is the molar amount of the compounds. The relative
rel
amount of the carbon dioxide ðCO2 Þ in the extractions was calcu-
lated according to the following term:
m
m
CO2
rel
CO2
¼
:
ð2:5Þ
Rac
As a result of the rapid screening of resolving agents, tartaric acid
4
was found to be a suitable resolving agent for trans-1,2-cyclohex-
anediol. Successful resolutions were achieved with both of the pure
tartaric acid enantiomers (2R,3R)-(+)-4 and (2S,3S)-(ꢀ)-4, in accor-
dance with the Marckwald principle. For lack of acidic or basic func-
tional groups on the racemic compound, the resolution of rac-1 by 4
is performed via diastereomeric complex formation.
2
2
. Results and discussion
.1. Resolution of trans-1,2-cyclohexanediol enantiomers by
The enantiomer of (1R,2R)-(ꢀ)-1 was in excess in the more sta-
supercritical fluid extraction
ble diastereomer with (2R,3R)-(+)-4. Kassai et al. reported that
0
O,O -(ꢀ)-dibenzoyl-(2R,3R)-tartaric acid 2 is a sufficient resolving
Tartaric acid and its derivatives are widely used as chiral agents
in resolutions through diastereomeric complex or salt forma-
agent for several racemic alcohols with a structure related to 1;
moreover, they found that the (S,S)-enantiomers of the alcohols
were mainly in excess in the more stable supramolecular com-
2
9–34
tion.
These compounds provide the advantages of wide avail-
3
6
ability and low cost as chiral agents. The resolution of racemic
plexes. In all cases, both the racemic alcohol and the resolving
agent contain the two stereogenic centres at neighbouring carbon
atoms. The Fisher and absolute configurations of the molecules are
depicted in Scheme 1.
trans-1,2-cyclohexanediol 1 was first attempted with three com-
0
pounds: O,O -(ꢀ)-dibenzoyl-(2R,3R)-tartaric acid monohydrate 2,
0
O,O -(ꢀ)-di-p-toluyl-(2R,3R)-tartaric acid 3 and tartaric acid 4.
In general, the ratio of half a molar equivalent of resolving agent
to the racemic compound gives the best separation efficiency
The configurations of the alcohol enantiomers in the more stable
diastereomeric complexes with different resolving agents are col-
lected in Table 2. Due to the absolute configurations, these molecule
regions are mirror images of each other in certain diastereomers
3
5
(
Pope–Peachy method ) in the resolutions, therefore the resolving
agents and rac-1 were reacted in 1:2 molar ratios in an ethanol
solvent. The resolutions were performed according to the method
described in Section 4.2. The results of the preliminary resolutions
of rac-1 are collected in Table 1. The yield (Y) and the resolution
efficiency (F) are defined as follows:
(Table 2, compounds 5–8; Scheme 1a), and are not in a few other
diastereomers (Table 2, compounds 1, 9, 10; Scheme 1b). Although,
molecules have the opposite structures according to the Fisher
projection. Thus the (R,R)-alcohol:(R,R)-acid (D-alcohol:L-acid) con-
formation can be regarded as quasi racemic structures.
m
Extr
Y
Y
Extr
Raff
¼
¼
ꢁ
ꢁ
100;
100;
ð2:1Þ
The observed phenomenon indicates that the structurally
related racemic compounds cannot be resolved in every case with
those resolving agents which have a similar chiral structure, even if
the resolving agents have different substituents. Additionally, the
configuration of the more stable diastereomeric complexes cannot
be definitely predicted, even when structurally related racemic
compounds and resolving agents are reacted.
m
Rac
Raff
Rac
m
m
ð2:2Þ
ð2:3Þ
F ¼ YExtr ꢂ eeExtr þ YRaff ꢂ eeRaff
where the subscripts ‘Extr’, ‘Raff’ and ‘Rac’ indicate the data corre-
sponding to the extract, raffinate or to the racemic diol, respec-
tively. The mass of the materials is signed by ‘m’. The
concentration of the resolving agent is expressed by the term of
molar ratio (mr), as follows:
The trans-2-halogen-cyclohexane-1-ols were successfully
resolved with 2 via supercritical fluid extraction too, where the
complex formation is based both on hydrogen bonds and disper-
sion interactions between the racemic compound and the resolving
n
resolving agent
37
agent. In the case of the resolution of rac-1 with 4, however,
mr ¼
;
ð2:4Þ
n
Rac
the complex formation should be based primarily on hydrogen-

P. Molnár et al. / Tetrahedron: Asymmetry 19 (2008) 1587–1592
1589
Table 1
0
0
Preliminary resolutions of rac-1 with O,O -(ꢀ)-dibenzoyl-(2R,3R)-tartaric acid monohydrate 2, O,O -(ꢀ)-di-p-toluyl-(2R,3R)-tartaric acid 3 and tartaric acid enantiomers 4;
rel
2
P = 15 MPa, T = 48 °C, acid : rac-1 molar ratio = 1:2, average value of CO ¼ 770 g=g
Run
Resolving agent
Extract
Raffinate
F
eeExt (%)
Configuration
eeRaff (%)
Configuration
1
2
3
4
2
3
<1
<1
54.2
42.4
(1S,2S)-1
(1S,2S)-1
(1S,2S)-1
(1R,2R)-1
<5
<5
70.4
66.1
(1R,2R)-1
(1R,2R)-1
(1R,2R)-1
(1S,2S)-1
0.03
0.05
0.54
0.44
(2R,3R)-(+)-4
(2S,3S)-(ꢀ)-4
Scheme 1. Structures of different alcohol:resolving agent complexes according to the Fisher projection. The absolute configurations of the stereogenic centres are indicated
by (S) or (R) and are incorporated within the dashed line. Vertical line represents the plane of the mirror. (a) No mirror image-shaped molecule regions. (b) Mirror image-
shaped molecule regions.
Table 2
0
Configurations of different 2-substituted-cyclohexane-1-ol derivatives in the more stable diastereomeric complex formed with O,O -(ꢀ)-dibenzoyl-(2R,3R)-tartaric acid
monohydrate 2 or tartaric acid 4
Racemic compound
X
R
Cahn–Ingold–Prelog configurationa
Fisher projectiona
5
Cl
(1S,2S)-5:(2R,3R)-2
L
-5:
L-2
O
6
7
Br
I
(1S,2S)-6:(2R,3R)-2
(1S,2S)-7:(2R,3R)-2
L
L
-6:
-7:
L
-2
-2
O
O
L
O
8
9
(1S,2S)-8:(2R,3R)-2
(1R,2R)-9:(2R,3R)-2
L
-8:
L
-2
O
O
O
D
-9:L-2
O
O
1
1
0
(1R,2R)-10 : (2R,3R)-2
(1R,2R)-1:(2R,3R)-4
D-10:L-2
OH
H
D-1:L-4
a
The configurations given represent the alcohol:resolving agent stereochemistry of the more stable diastereomer.
bond formation. This shows that the cyclohexanol derivatives can
be generally resolved by supercritical fluid extraction with tartaric
acid or its derivatives.
A new process was developed for the enantioseparation of the
racemic diol 1 by the formation of diastereomeric complexes with
extraction, as depicted in Figure 1. The resolution process is based
on three steps. In the first step, a solid mixture is formed contain-
ing the uncomplexed diol enantiomers, the diastereomeric com-
plexes and an inert support. This mixture is treated by
supercritical carbon dioxide in the second step with a (1S,2S)-(+)-
1 rich enantiomeric mixture being extracted. The (1R,2R)-(ꢀ)-1
2
tartaric acid and subsequent supercritical carbon dioxide (scCO )

1
590
P. Molnár et al. / Tetrahedron: Asymmetry 19 (2008) 1587–1592
OH
O
H
OH
O
OH
+
OH
HO
H
OH
(
2R,3R)-(+)-4 in EtOH
rac-1 in EtOH
+
inert support,
evaporation of EtOH
OH
OH
OH
OH
+
HO
Figure 2. Extraction yield data of the unreacted diol enantiomers at P = 10 MPa,
T = 33 °C (s); and P = 15 MPa, T = 48 °C, (d); mr = 0.50. Extraction points are linked
by a spline fit.
O
H
H
HO
O
OH
OH
The extraction data in Figure 2 indicate that the diastereomers
formed are stable enough to allow the separation of the uncom-
plexed diol enantiomers and complexes by supercritical fluid
extraction, moreover, all of the unreacted 1 enantiomers were dis-
uncomplexed enantiomeric mixture
diastereomeric complexes
2
solved by scCO . The stoichiometric ratio in the diastereomeric
complex is diol:acid = 1:1.
SFE
Step 3.
decomposition
by Na CO
Step 2. P = 10-20 MPa,
o
2
3
2.2. Experimental design
T = 33-63 C
Twelve resolutions were carried out within a full factorial 32
type experimental design at nine different combinations of the
extraction pressure and temperature to study their influence on
the values of the enantiomeric excess, yield and resolution effi-
ciency and to quantify the effects of the extraction parameters with
OH
OH
OH
OH
0
.05 significance level. All experiments were carried out at an
(
1S,2S)-(+)-1 rich
(1R,2R)-(–)-1 rich
mr = 0.50 ratio. Four repetitions were performed at the centre
point. With this setup, the linear and quadratic effects of the pres-
sure and temperature, as well as the effects of their interactions
could be analysed statistically. The evaluation of the experimental
data was performed by STATISTICA software (StatSoft, Inc., version
enantiomeric mixture
in the extract
enantiomeric mixture
in the raffinate
Figure 1. Resolution of racemic trans-1,2-cyclohexanediol
tartaric acid 4 via diastereomeric complex formation and subsequent supercritical
fluid extraction (SFE).
1
with (2R,3R)-(+)-
7
.1). The factors and level values of the experimental design are
collected in Table 4.
The linear (L) effects of the pressure and temperature were
found to be significant for eeExtr, eeRaff, YExtr and YRaff and addition-
ally, the enantiomeric excess and yield of the extracts were also
influenced by the linear interaction of the pressure and tempera-
ture. The fitted surfaces of the experimental design are shown in
Figure 3.
The extraction pressure and temperature have reverse effects
on the enantiomeric excesses and yields of the extracts and raffi-
nates. The minimum value of the eeExtr = 38.7% as well as the max-
imum value of the eeRaff = 93.1% were achieved at P = 20 MPa and
T = 63 °C. We assume that a slight decomplexation of the diastereo-
mers, under these conditions, plays a primary role on the values
studied. The release of an enantiomeric mixture from the complex
leads to a decrease in the purity of the extracts, although it
enhances the purity of the raffinates. Thus, the yield of the extracts
rich raffinate enantiomeric mixture is recovered after the decom-
position of the remaining complexes in the last step.
Several empirical equations,38 which are generally applicable to
modelling the extraction kinetics, were tested to describe the
rel
extraction yields as a function of CO . However, the Brunner’s
2
3
9
2
equation gave a satisfactory value of R , and none of the equa-
tions used showed a reliable fit for the extraction data. The empir-
ical equations and R values of the fitted extraction curves are
2
collected in Table 3. The yield data at two different settings of
the extraction pressures and temperatures are shown in Figure 2.
Table 3
2
Fitted empirical equations and R values on the extraction data of unreacted diol
enantiomers
Fitting
Equation
R2a
R2b
rel
Brunner
Hyperbolic
Parabolic diffusion
Power law
Y
Y
Y
Y
Extr ¼ a ꢂ ð1 ꢀ expðꢀb ꢂ CO ÞÞ
0.988
0.978
0.941
0.942
0.984
0.974
0.943
0.942
Table 4
2
rel
2
rel
Extr ¼ c ꢂ CO =ð1 þ d ꢂ CO
Þ
Factors and levels of the experimental design, mr = 0.50
2
rel 1=2
Extr ¼ e þ f ꢂ ðCO
Þ
2
rel
2
h
Factor
Lowest level
Center level
Highest level
Extr ¼ g ꢂ ðCO
Þ
Pressure, MPa
Temperature, °C
10
33
15
48
20
63
a
Extraction at P = 10 MPa, T = 33 °C.
Extraction at P = 15 MPa, T = 48 °C.
b

P. Molnár et al. / Tetrahedron: Asymmetry 19 (2008) 1587–1592
1591
Figure 3. Fitted surfaces of the experimental design (a) eeExtr; (b) eeRaff; (c) YExtr; (d) YRaff; (e) F.
increases against the yield of the raffinates. As a result of the
observed influences, the fitted surface of the resolution efficiency
parameter is saddle-shaped, as shown in Figure 3e. It should be
case. Significantly lower resolution efficiencies were achieved at
P = 10 MPa, T = 33 °C, = 0.738 g/ml, F = 0.50; and at P = 20 MPa,
T = 63 °C, = 0.705 g/ml, F = 0.44, respectively.
q
q
2
noted that no verifiable influence of the density of scCO (q) on
the F parameter was found, despite the density being clearly
dependent on the pressure and temperature. The best resolutions
3
. Conclusion
In this study, a new and effective process has been proposed for
(
F ffi 0.6) within the range of the experimental design were
achieved under the following conditions: P = 10 MPa, T = 63 °C,
= 0.275 g/ml, eeExtr = 61.4%, eeRaff = 91.9%, F = 0.61; or P =
0 MPa, T = 33 °C, = 0.876 g/ml, eeExtr = 62.1%, eeRaff = 81.9%, F =
.59; respectively. A lesser amount of CO is necessary in the latter
the resolution of trans-1,2-cyclohexanediol. This is the first resolu-
tion for rac-1 which does not require formation of any new cova-
lent bond. The separation of the enantiomers is performed by
q
2
0
q
2

1
592
P. Molnár et al. / Tetrahedron: Asymmetry 19 (2008) 1587–1592
molecular complex formation, most likely stabilized by hydrogen
bonds. The enantiomeric mixtures were obtained over 60% ee for
the extracted (1S,2S)-1 and over 90% ee for the raffinate (1R,2R)-
TBDPM (25 m ꢁ 0.25 mm ꢁ 0.25
lm film with permethylated
b-cyclodextrin, Macherey & Nagel, No.: 21519/11) column. The
analysis was performed at isotherm conditions (130 °C), carrier
gas: hydrogen, head pressure: 12 psi, 1:50 split ratio, detector:
FID at 250 °C, injector temperature at 250 °C.
1
enantiomers. The resolution of trans-1,2-cyclohexanediol with
tartaric acid by SFE is a competitive technique with any already
published methods due to the following advantages:
Acknowledgements
ꢃ short overall process time (<6 h), including the sample prepara-
tion, the extraction with scCO
2
and the decomposition step;
The authors are grateful for the support of the Hungarian
Research Grant (OTKA K72861) and for the Marie Curie Fellowship
Programme (MEST-CT-2004 007767).
ꢃ the tartaric acid is a non-toxic, cheap and efficient resolving
agent that does not require any structural modifications before
use;
ꢃ the scCO
2
—as a green solvent—is a suitable media for the sepa-
ration of the uncomplexed enantiomers and diastereomeric
complexes;
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052–2053.
5
chased from Sigma–Aldrich Corp., (Budapest), Hungary. Perfil
P250 as inert support (expanded and milled perlite for use as a fil-
tering aid, specific surface area is 2.89 m /g) was kindly given by
Baumit Co., (Budapest), Hungary. Carbon dioxide (99.5 w/w% pure)
is the product of Linde Ltd, (Budapest), Hungary. Ethanol, methanol
and trichloromethane were provided by Reanal Ltd, (Budapest),
Hungary.
1
TM
2
2
2
1
2
17. Maki, B. E.; Chan, A.; Phillips, E. M.; Scheidt, K. A. Org. Lett. 2007, 9, 371–
374.
18. Vedejs, E.; Daugulis, O.; Diver, S. T. J. Org. Chem. 1996, 61, 430–431.
19. Yamada, S.; Katsumata, H. J. Org. Chem. 1999, 64, 9365–9373.
20. Brunner, H.; Obermann, U.; Wimmer, P. Organometallics 1989, 8, 821–826.
21. Clarke, I. D.; Hodge, P. Chem. Commun. 1997, 15, 1395–1396.
22. Lainé, D.; Fujita, M.; Ley, S. V. J. Chem. Soc., Perkin Trans. 1 1999, 12, 1639–1645.
23. Chatterjee, A.; Sasikumar, M.; Joshi, N. N. Synth. Commun. 2007, 37, 1727–1733.
24. Baldassarre, F.; Bertoni, G.; Chiappe, C.; Marioni, F. J. Mol. Catal. B: Enzym. 2000,
11, 55–58.
4
.2. Methods
Racemic trans-1,2-cyclohexanediol 1 (1 g, 8.609 mmol) and
(
2R,3R)-(+)-tartaric acid (0.6463 g, 4.306 mmol) were dissolved
separately in 15 ml of abs. ethanol and were combined. Inert sup-
port, Perfil P250 was added (1.5 g) to the solution. The ethanol
then was evaporated at 40–50 °C in 30 mbar vacuum. The solid
sample was left to dry overnight at room temperature. The sample
was extracted the next day under different conditions (P = 10–
TM
25. Seemayer, R.; Schneider, M. P. J. Chem. Soc., Chem. Commun. 1991, 1, 49–50.
26. Bódai, V.; Orovecz, O.; Szakács, Gy.; Novák, L.; Poppe, L. Tetrahedron:
Asymmetry 2003, 14, 2605–2612.
27. Detry, J.; Rosenbaum, T.; Lütz, S.; Hahn, D.; Jaeger, K.-E.; Müller, M.; Eggert, T.
Appl. Microbiol. Biotechnol. 2006, 72, 1107–1116.
2
2
8. Sonderegger, O. J.; Bürgi, T.; Baiker, A. J. Catal. 2003, 215, 116–121.
9. Noda, H.; Sakai, K.; Murakami, H. Tetrahedron: Asymmetry 2002, 13, 2649–
2652.
2
0 MPa, T = 33–63 °C) with approx. 660 g CO
tions were performed with a laboratory scale supercritical unit.
The (1S,2S)-(+)-1 rich mixture was collected in the separator at
MPa and 40 °C. The raffinate was removed from the extractor
2
/g rac-1. The extrac-
4
0
3
3
0. Tan, B.; Luo, G.; Qi, X.; Wang, J. Sep. Purif. Technol. 2006, 49, 186–191.
1. Bálint, J.; Egri, G.; Kiss, V.; Gajáry, A.; Juvancz, Z.; Fogassy, E. Tetrahedron:
Asymmetry 2001, 12, 3435–3439.
4
and 40 ml of methanol was added to it, in order to dissolve the
remaining diastereomeric complexes. After 1 h of stirring, the inert
support was filtered and the methanol was evaporated at
32. Fujii, A.; Fujima, Y.; Harada, H.; Ikunaka, M.; Inoue, T.; Katoa, S.; Matsuyama, K.
Tetrahedron: Asymmetry 2001, 12, 3235–3240.
3
3
3. Han, Z.; Krishnamurthy, D.; Fang, Q. K.; Wald, A. S.; Senanayake, C. H.
Tetrahedron: Asymmetry 2003, 14, 3553–3556.
4. Kmecz, I.; Simándi, B.; Székely, E.; Lovász, J.; Fogassy, E. Chirality 2007, 19, 430–
433.
4
0-50 °C in 30 mbar vacuum. The complex was decomposed by a
saturated aqueous solution of Na CO (6 ml) during the stirring
for 15 min. The water then was evaporated from the residue at
0–80 °C in 30 mbar vacuum. The solid particles were crushed
2
3
3
3
5. Pope, W. J.; Peachey, S. J. J. Chem Soc. 1899, 75, 1066–1093.
6. Kassai, Cs.; Juvancz, Z.; Bálint, J.; Fogassy, E.; Kozma, D. Tetrahedron 2000, 56,
7
8
355–8359.
37. Székely, E.; Simándi, B.; Fogassy, E.; Kemény, S.; Kmecz, I. Chirality 2003, 15,
83–786.
and 20 ml of trichloromethane was added to it. After 30 min of
stirring, the sodium-tartrate salt was filtered out and the organic
phase was evaporated. The product obtained contains the
7
3
8. Kitanovi c´ , S.; Milenovi c´ , D.; Veljkovi c´ , V. B. Biochem. Eng. J. 2008, doi:10.1016/
j.bej.2008.02.010, in press.
(
1R,2R)-(ꢀ)-1 in excess.
39. Brunner, G. Ber. Bunsen-Ges. Phys. Chem. 1984, 88, 887–891.
40. Székely, E.; Simándi, B.; Illés, R.; Molnár, P.; Gebefügi, I.; Kmecz, I.; Fogassy, E. J.
The enantiomeric excesses were determined by GC analysis
Supercrit. Fluids 2004, 31, 33–40.
with an Agilent 4890D chromatograph using Hydrodex-b-6-