Crystallization-based optical resolution of 1,1′-binaphthalene-2,2′-dicarboxylic acid via 1-phenylethylamides: control by the molecular structure and dielectric property of solvent

Article abstract of DOI:10.1016/j.tetlet.2009.02.088

In the recrystallization of a diastereomeric mixture of amides (RS_a,S)-1 formed from racemic 1,1′-binaphthalene-2,2′-dicarboxylic acid and (S)-1-phenylethylamine, either of the diastereomers crystallizes out as a diastereomerically pure form, d

Full text of DOI:10.1016/j.tetlet.2009.02.088

Tetrahedron Letters 50 (2009) 1998–2002
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Crystallization-based optical resolution of 1,10-binaphthalene-2,20-dicarboxylic
acid via 1-phenylethylamides: control by the molecular structure
and dielectric property of solvent
Yuki Kato a, Yuichi Kitamoto a, Naoya Morohashi a, Yosuke Kuruma a,
Shuichi Oi b, Kenichi Sakai c, Tetsutaro Hattori a,
*
a Department of Environmental Studies, Graduate School of Environmental Studies, Tohoku University, 6-6-11 Aramaki-Aoba, Aoba-ku, Sendai 980-8579, Japan
b Environment Conservation Research Institute, Tohoku University, 6-6-11 Aramaki-Aoba, Aoba-ku, Sendai 980-8579, Japan
c Specialty Chemicals Technology Development Department, Toray Fine Chemicals Co., Ltd, 9-1 Oe-Cho, Minato-ku, Nagoya 455-8502, Japan
a r t i c l e i n f o
a b s t r a c t
In the recrystallization of a diastereomeric mixture of amides (RSa,S)-1 formed from racemic 1,10-binaph-
thalene-2,20-dicarboxylic acid and (S)-1-phenylethylamine, either of the diastereomers crystallizes out as
a diastereomerically pure form, depending on the solvent employed; sterically undemanding solvents,
acetone, dichloromethane, and acetonitrile, afford crystals formulated as (Sa,S)-1ꢀsolvent with an excep-
tion of ethanol, which affords (Ra,S)-1ꢀEtOH, while sterically bulkier solvents afford (Ra,S)-1 including no
solvent. The stereoselectivity can be rationalized by the crystal structures. A dielectrically controlled res-
olution (DCR) can also be carried out by using mixed solvents, which contain, for example, 25 vol % of ace-
tone and varying ratios of hexane and 1-propanol in total 75 vol %; (Sa,S)-1ꢀacetone is deposited as
Article history:
Received 10 January 2009
Revised 8 February 2009
Accepted 12 February 2009
Available online 15 February 2009
Keywords:
Solvent-controlled resolution
Dielectrically controlled resolution (DCR)
1,10-Binaphthalene-2,20-dicarboxylic acid
1-Phenylethylamine
crystals from the solvents with a dielectric constant (
from the solvents with 14.8 6 6 20.3.
e
) range 8.9 6
e 6 10.2, while (Ra,S)-1 is deposited
e
Ó 2009 Elsevier Ltd. All rights reserved.
Recrystallization-based optical resolutions are important ways
to obtain enantiopure compounds in both laboratories and indus-
tries because of the ease of operation and wide applicability.1 Meth-
ods that are based on novel principles or those which greatly
improve the efficiency of resolution, such as preferential enrich-
ment2 and Dutch resolution,3 have been developed. The diastereo-
meric salt formation method is the one that resolves one
enantiomer from its racemic mixture by crystallization after conver-
sion into diastereomeric salts with a chiral resolving agent. It has
been a common understanding in the resolution by this method that
when one enantiomer of a target molecule crystallizes out with the
(S)-enantiomer of a resolving agent as the less soluble diastereo-
meric salt, the antipode necessitates the (R)-enantiomer of the
resolving agent to be deposited as crystals from a racemic mixture.
During the course of the study on the development of an industrial
and higher
e
ranges (62–78), giving that formulated as (R)-ACLꢀ(S)-
TPA with up to 69% de.5 It is easily conceivable that the chiral mole-
cules are associated in solution by forming a hydrogen-bond net-
work. The DCR phenomenon has been interpreted as an outcome
of structural change in the hydrogen-bond network depending on
the dielectric property of solvent,6,7 although further experiments
have to be done to know how the chiral molecules are associated
in solution and how the association affects crystal structures. The
DCR phenomenon is not special for the ACL–TPA system but has
Table 1
Recrystallization of amides (RSa,S)-1 from various solvents
Entry Solvent
e
Yield (%)a de (%)b Absolute
Inclusion ratiob
configurationb (1:solvent)
process to resolve a-amino-e
-caprolactam (ACL),4 however, one of
c
c
1
2
3
4
5
6
7
8
Toluene
AcOEt
CH2Cl2
2-PrOH
1-PrOH
Acetone 20.7 23
EtOH
MeCN
2.4
6.0 24
8.9 27
18.3 15
20.1 30
5
100
100
100
100
100
100
100
100
Ra,S
Ra,S
Sa,S
Ra,S
Ra,S
Sa,S
Ra,S
Sa,S
—
—
us has found an interesting phenomenon that the enantiomer pref-
erentially crystallized with N-tosyl-(S)-phenylalanine [(S)-TPA] var-
ies depending on the dielectric property of the solvent employed;
1:0.87
c
—
—
c
(S)-ACL is selected in solvents with e values between 29 and 58, giv-
1:0.93
1:0.98
1:0.82
ing a diastereomeric salt formulated as (S)-ACLꢀ(S)-TPAꢀH2O with up
24.3 34
37.5 35
to 100% de, while (R)-ACL is selected in solvents with lower (5–27)
a
b
c
Isolated yield.
Determined by 1H NMR analysis.
No solvent inclusion was observed.
* Corresponding author. Tel.: +81 22 795 7262; fax: +81 22 795 7293.
E-mail address: hattori@orgsynth.che.tohoku.ac.jp (T. Hattori).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.088

Y. Kato et al. / Tetrahedron Letters 50 (2009) 1998–2002
1999
exploring such a chiral recognition system, we report herein that the
recrystallization of a diastereomeric mixture of amides (RSa,S)-1
formed from racemic 1,10-binaphthalene-2,20-dicarboxylic acid
and (S)-1-phenylethylamine can be controlled by the molecular
structure and dielectric property of the solvent employed.
CO2H
CONH
(RSa,S)-1
Previously, it was reported from our laboratory that one recrys-
tallization of a diastereomeric mixture of amides (RSa,S)-1 from
acetonitrile gave (Sa,S)-1 in 43% yield, and the mother liquid, after
concentration, was recrystallized twice from ethanol to give (Ra,S)-
1 in 40% yield; both of them were essentially diastereomerically
pure.10 This outstanding efficiency of the resolution for both the
diastereomers prompted us to examine solvent effects on the ste-
reoselectivity in this system. A 200 mg of 1:1 mixture of amides
Figure 1. Crystal structure of (Ra,S)-1. Molecules are color-coded according to their
orientations. Dotted lines indicate hydrogen bonds.
already been observed in five other resolutions via diastereomeric
salt formation.8,9 Moreover, we believe that the dielectric property
of solvent can play a decisive role in a wide variety of chiral discrim-
ination phenomena. As the first successful example of our efforts for
Figure 2. Hydrogen-bond network formed in the crystal. (a) (Ra,S)-1; (b) (Sa,S)-1ꢀacetone; (c) (Ra,S)-1ꢀEtOH.

2000
Y. Kato et al. / Tetrahedron Letters 50 (2009) 1998–2002
Figure 4. Crystal structure of (Sa,S)-1ꢀacetone.
helical structure to that observed for (Ra,S)-1 is created along the
b-axis (Fig. 2b); the bond lengths of the intra- and intermolecular
hydrogen bonds are 1.989 and 1.658 Å, respectively. The helices
are arranged parallel to each other along the a-axis to form a layer
(Fig. 5c), which is laminated along the c-axis (Fig. 5a and b); every
adjacent layers are turned 180° in the a–b plane. There are voids on
the layer surface, which are filled with acetone molecules (Fig. 5c).
The crystal density (
and should drop considerably (
q
= 1.222 g cmꢁ3) is lower than that of (Ra,S)-1
= 1.081 g cmꢁ3), if there were no
q
acetone molecules in the lattice. This suggests that the crystal
structure cannot be kept without the aid of the solvent molecules.
The crystals of (Sa,S)-1 that include dichloromethane and acetoni-
trile molecules (Table 1) are expected to have similar packing
Figure 3. Crystal packing of (Ra,S)-1. (a) Cross-section parallel to the b–c plane; (b)
layers separated along the c-axis; (c) surface of the separated layer.
(RSa,S)-1, prepared as reported previously,10 was dissolved in a sol-
vent at 50 °C by adding the solvent portionwise until it forms a
nearly saturated solution, which was allowed to cool to room tem-
perature and then kept overnight at 4 °C to induce recrystalliza-
tion. Table 1 lists the results of the recrystallization from various
solvents. Interestingly, under the conditions, either of the diaste-
reomers crystallized out with complete selectivity from individual
solvents employed, though the dependence on the dielectric prop-
erty of solvent was not clear. The crystals of (Sa,S)-1 included sol-
vent molecules in a molar ratio of about 1:1 (1:solvent), while
those of (Ra,S)-1 did not, except for ethanol.
In order to clarify the reasons why the crystallized diastereomer
varies depending on the solvents, X-ray crystallographic analyses
were carried out.11 Diastereomerically pure (Ra,S)-1 was recrystal-
lized from acetonitrile to give single crystals, including no solvent
molecules. The crystal belongs to the P21 space group (Z = 2)
(Fig. 1), in which a 21 helical structure is created along the b-axis
by intramolecular hydrogen bonds between the carbamoyl NH
and carboxy C@O groups (2.086 Å) and intermolecular hydrogen
bonds between the carboxy OH and carbamoyl C@O groups
(1.786 Å) (Fig. 2a). The helices are arranged parallel to each other
along the a-axis to form a layer (Fig. 3c), which is laminated along
the c-axis (Fig. 3a and b). Although the upper and bottom surfaces
of each layer are uneven, every bumps and hollows engage with
each other between two adjacent layers to form a tight packing
structure (q
= 1.233 g cmꢁ3).
On the other hand, single crystals formulated as (Sa,S)-1ꢀacetone
were obtained by slow diffusion of hexane vapor into an acetone
solution of diastereomerically pure (Sa,S)-1. The crystal belongs
to the P212121 space group (Z = 4) (Fig. 4), in which a similar 21
Figure 5. Crystal packing of (Sa,S)-1ꢀacetone. (a) Cross-section parallel to the b–c
plane; (b) layers separated along the c-axis; (c) surface of the separated layer.

Y. Kato et al. / Tetrahedron Letters 50 (2009) 1998–2002
2001
Figure 6. Crystal structure of (Ra,S)-1ꢀEtOH.
structures to this, considering the fact that these molecules are
similar to acetone in steric bulk.
in the order (Ra,S)-1ꢀEtOH > (Sa,S)-1ꢀsolvent (solvent = acetone,
CH2Cl2, or MeCN) > (Ra,S)-1.
In this connection, it is of interest to note that (Sa,S)-1ꢀEtOH was
not precipitated from ethanol. The X-ray analysis of (Ra,S)-1ꢀEtOH
prepared by recrystallization of diastereomerically pure (Ra,S)-1
from ethanol revealed that the crystal structure is very different
from the preceding ones, having P32 symmetry (Z = 3) (Fig. 6), in
which a 32 helical structure is created along the c-axis by intra-
and intermolecular hydrogen bonds (Fig. 2c). The intramolecular
hydrogen bond is formed between the carbamoyl NH and carboxy
C@O groups (2.143 Å) as observed in the above two crystal struc-
tures, while the intermolecular hydrogen bond between the car-
boxy OH and carbamoyl C@O groups is mediated by the hydroxy
group of ethanol as C@O–OHꢀꢀꢀOH (ethanol)ꢀꢀꢀO@C–NH, the bond
lengths being 1.687 and 1.893 Å, respectively. The helices are
As a solvent-dependent resolution system was in hand, we next
tried to control the resolution by the dielectric property of solvent.
The 18 solvents with different dielectric constants (Table 2) were
prepared by mixing the corresponding components in the indicated
volume ratios.12 Each solvent mixture contains a constant vol % of
acetone or dichloromethane that can be incorporated into the crys-
tal lattice of (Sa,S)-1ꢀsolvent. The mixed solvents were nearly satu-
rated with amides (RSa,S)-1 at 40–50 °C and kept at ꢁ2 °C for 2–
3 days to induce recrystallization. Figure 8 shows the dependence
of the diastereomeric excess of deposited amide 1 on the dielectric
constant of solvent. In the recrystallization from the hexane–1-pro-
panol-based solvents, the diastereomeric excess of deposited amide
1 drastically changed within a narrow
diastereomerically pure (Sa,S)-1ꢀsolvent and (Ra,S)-1 were depos-
ited from the solvents with lower and higher ranges, respectively.
e range (10.5 < e < 14.8), and
packed tightly (q
= 1.259 g cmꢁ3) as shown in Figure 7.
From these observations, we may conclude that (Sa,S)-1ꢀsolvent
crystallizes out in preference to (Ra,S)-1 from the solvents that have
suitable molecular size for being incorporated into the crystal lat-
tice formed by (Sa,S)-1. However, (Ra,S)-1ꢀEtOH, having the excep-
tional packing structure, crystallizes out in preference to (Sa,S)-
1ꢀEtOH. From the other solvents, (Ra,S)-1 crystallizes out in prefer-
ence to (Sa,S)-1ꢀsolvent. In short, the ease of crystal formation falls
e
This observation clearly indicates that the resolution can be con-
trolled by the dielectric property of solvent. However, a comparison
of the de change obtained from acetone–hexane–1-propanol with
that from acetone–toluene–1-propanol revealed that the dielectric
property of solvent does not solely determine the diastereoselectiv-
ity but it is also affected by the molecular structure of solvent. Sim-
Figure 7. Crystal packing of (Ra,S)-1ꢀEtOH. (a) Cross-section parallel to the a–b plane; (b) a 32 helix along the c-axis.

2002
Y. Kato et al. / Tetrahedron Letters 50 (2009) 1998–2002
Table 2
ment with thionyl chloride, followed by the alkaline hydrolysis
of the resulting 20-cyano-1,10-binaphthalene-2-carboxylic acid.10
Therefore, the solvent-controlled optical resolution of the diacid
via 1-phenylethylamides has been achieved.
Recrystallization oof amides (RSa,S)-1 from mixed solvents
Entry Components and volume ratio
of mixed solvent
e
Yield
(%)a
De
Absolute
(%)b
configurationb
In conclusion, we have shown here that the recrystallization of
a diastereomeric mixture of amides (RSa,S)-1 affords either of the
diastereomers as diastereomerically pure crystals, depending on
the solvent employed, and that the solvent dependence is attrib-
uted to the difference in crystal structure between the two diaste-
reomers and to the steric and electronic properties of the solvent.
In addition, we have succeeded in extending the DCR method to
a covalent diastereomer-based resolution. We believe that detailed
studies on this covalent diastereomer-based resolution, which is
more simple than existing diastereomeric salt systems, afford deep
insight into the chiral discrimination mechanisms that control the
DCR phenomena.
Acetone:hexane:1-PrOH
1
2
3
4
5
6
7
8
25:63:12
25:55:20
25:43:32
25:30:45
25:19:56
25:7:68
25:0:75
8.9 23
10.2 21
12.5 14
100
100
32
100
100
100
100
100
Sa,S
Sa,S
Ra,S
Ra,S
Ra,S
Ra,S
Ra,S
Ra,S
14.8
16.8
4
9
18.9 10
20.3
20.3 10
4
25:0:75
Acetone:toluene:1-PrOH
25:75:0
25:63:12
25:50:25
25:50:25
25:20:55
25:12:63
25:12:63
25:0:75
9
10
11
12
13
14
15
16
7.0
9.2
6
7
3
9
9
4
4
92
100
100
100
100
100
100
100
Sa,S
Ra,S
Ra,S
Ra,S
Ra,S
Ra,S
Ra,S
Ra,S
11.4
11.4
16.7
18.0
18.0
Acknowledgments
20.3 10
CH2Cl2:hexane:1-PrOH
25:63:12
25:37:38
25:25:50
25:20:55
This study was supported in part by a Grant-in-Aid for Scientific
Research on a Priority Area ‘Advanced Molecular Transformations
of Carbon Resources’ from the Ministry of Education, Culture,
Sports, Science and Technology, Japan. T. H. wishes to thank Toray
Fine Chemicals Co., Ltd for financial support.
17
18
19
20
21
22
6.0 12
10.5 15
12.8 26
100
100
20
84
100
100
Sa,S
Sa,S
Sa,S
Ra,S
Ra,S
Ra,S
13.7
7
25:12:63
25:0:75
15.0 11
17.3 11
a
Isolated yield.
b
Determined by 1H NMR analysis.
References and notes
1. (a) Jacques, J.; Collet, A.; Wilen, S. H. Enantiomers, Racemates, and Resolutions;
Wiley: New York, 1981; (b) Kozma, D. CRC Handbook of Optical Resolution via
Diastereomeric Salt Formation; CRC: Boca Raton, 2002.
2. Tamura, R.; Takahashi, H.; Fujimoto, D.; Ushio, T. Top. Curr. Chem. 2007, 269, 53.
3. Kellogg, R. M.; Kaptein, B.; Vries, T. R. Top. Curr. Chem. 2007, 269, 159.
4. Sakai, K.; Sakurai, R.; Yuzawa, A.; Hirayama, N. Tetrahedron: Asymmetry 2003,
14, 3713.
5. Sakai, K.; Sakurai, R.; Hirayama, N. Tetrahedron: Asymmetry 2004, 15, 1073.
6. Sakai, K.; Sakurai, R.; Akimoto, T.; Hirayama, N. Org. Biomol. Chem. 2005, 3, 360.
7. In this connection, effects of the dielectric constant of solvent on the specific
rotations of the diastereomeric salts have been studied: Taniguchi, K.; Sakurai,
R.; Sakai, K.; Yasutake, M.; Hirose, T. Bull. Chem. Soc. Jpn. 2006, 79, 1084.
8. Reviews: (a) Sakai, K.; Sakurai, R.; Nohira, H. Top. Curr. Chem. 2007, 269, 199; (b)
Sakai, K.; Sakurai, R.; Hirayama, N. Top. Curr. Chem. 2007, 269, 233.
9. (a) Sakai, K.; Sakurai, R.; Nohira, H.; Tanaka, R.; Hirayama, N. Tetrahedron:
Asymmetry 2004, 15, 3495; (b) Sakai, K.; Sakurai, R.; Hirayama, N. Tetrahedron:
Asymmetry 2006, 17, 1812; (c) Sakurai, R.; Yuzawa, A.; Sakai, K.; Hirayama, N.
Cryst. Growth Des. 2006, 6, 1606; (d) Taniguchi, K.; Aruga, M.; Yasutake, M.;
Hirose, T. Org. Biomol. Chem. 2008, 6, 458; (e) Hirose, T.; Begum, M.; Islam, Md.
S.; Taniguchi, K.; Yasutake, M. Tetrahedron: Asymmetry 2008, 19, 1641.
10. Oi, S.; Matsuzaka, Y.; Yamashita, J.; Miyano, S. Bull. Chem. Soc. Jpn. 1989, 62,
956.
11. Crystallographic data for (Ra,S)-1: C30H23NO3, fw = 445.49, T = 100(2) K,
monoclinic, P21, a = 9.202(2) Å, b = 14.170(3) Å, c = 9.299(2) Å, b = 98.369(6)°,
V = 1199.6(5) Å3, Z = 2, calcd = 1.233 g cmꢁ3, 5145 independent reflections, 3951
q
reflections were observed (I > 2r(I)), R1 = 0.0577, wR2 = 0.1276 (observed),
R1 = 0.0723, wR2 = 0.1333 (all data). Crystallographic data for (Sa,S)-1ꢀacetone:
C33H29NO4, fw = 505.37, T = 173(2) K, orthorhombic, P212121, a = 11.325(2) Å,
b = 13.892(2) Å, c = 17.405(3) Å, V = 2738.2(8) Å3, Z = 4,
6381 independent reflections, 4054 reflections were observed (I > 2
q
calcd = 1.222 g cmꢁ3
(I)),
,
r
Figure 8. Dependence of the diastereomeric excess of deposited amide 1 on the
dielectric constant of the solvent employed in the resolution; acetone–hexane–1-
propanol (d), acetone–toluene–1-propanol (j), CH2Cl2–hexane–1-propanol (N).
R1 = 0.0485, wR2 = 0.1071 (observed), R1 = 0.0972, wR2 = 0.1234 (all data).
Crystallographic data for (Ra,S)-1ꢀEtOH: C32H29NO4, fw = 491.56, T = 100 (2) K,
trigonal, P32, a = b = 14.8700(16) Å, c = 10.1538(16) Å, V = 1944.4(4) Å3, Z = 3,
q
calcd = 1.259 g cmꢁ3
observed (I > 2
,
5603 independent reflections, 4312 reflections were
ilar observations have been reported for the resolution of diastereo-
meric salts.9a,d,e
The diastereomerically pure amides (Sa,S)- and (Ra,S)-1 thus ob-
tained can be converted into 1,10-binaphthalene-2,20-dicarboxylic
acid without any appreciable loss of axial chirality by the treat-
r
(I)), R1 = 0.0430, wR2 = 0.1028 (observed), R1 = 0.0606,
wR2 = 0.1143 (all data). The details of the crystal data have been deposited
with CambridgeCrystallographic Data Centre as supplementary publication Nos.
CCDC 715192–715194.
12. The values of dielectric constants of mixed solvents were calculated as the
weighted average of dielectric constants of components. See Ref. 9a.