Enantioseparation of 1-arylethanols via a supramolecular chiral host consisting of N-(2-naphthoyl)-l-aspartic acid and an achiral diamine

Article abstract of DOI:10.1039/c2ob06475h

A supramolecular chiral host consisting of N-(2-naphthoyl)-l-aspartic acid (L-1) and meso-1,2-diphenylethylenediamine (2) is effective in enantioseparation of 1-arylethanols (up to 96% ee with 100% inclusion ratio). Here we report three different methods to prepare the inclusion crystals and discuss the chiral recognition mechanism on the basis of X-ray crystallography results.

Full text of DOI:10.1039/c2ob06475h

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PAPER
Enantioseparation of 1-arylethanols via a supramolecular chiral host
consisting of N-(2-naphthoyl)-L-aspartic acid and an achiral diamine†
Koichi Kodama,* Ayaka Kanno, Eriko Sekine and Takuji Hirose*
Received 29th August 2011, Accepted 5th December 2011
DOI: 10.1039/c2ob06475h
A supramolecular chiral host consisting of N-(2-naphthoyl)-L-aspartic acid (L-1) and meso-1,2-
diphenylethylenediamine (2) is effective in enantioseparation of 1-arylethanols (up to 96% ee with 100%
inclusion ratio). Here we report three different methods to prepare the inclusion crystals and discuss the
chiral recognition mechanism on the basis of X-ray crystallography results.
different target racemates.4 Recently, the carboxylic acid/primary
amine combination has been often used to construct supramole-
Introduction
Enantiomeric separation via diastereomeric salt formation is
simple and easily scaled up, making it one of the most useful
and practical methods of preparing optically active compounds.1
However, this method cannot be directly applied to neutral com-
pounds such as alcohols and sulfoxides because of their weaker
intermolecular interaction sites. Instead, host–guest inclusion
complexation has been found to be a useful alternative and is
therefore gaining popularity.2 Diastereomeric inclusion crystals
are formed by selective incorporation of one guest enantiomer
into asymmetric voids created by chiral host compounds and no
strong interactions between host and guest molecules are essen-
tial to obtain inclusion crystals. A further advantage is that
several methods have already been developed to prepare
inclusion crystals: i) crystallization from the host/guest solution,
ii) suspension of host/guest in a solvent, and iii) direct mixing
and cogrinding of host/guest compounds.3 However, for highly
enantioselective inclusion complexation, appropriate design of
the chiral host compound is essential and the key factor is the
extent of host complementarity to one enantiomer of the guest
compound. Consequently, the best host compound for the
purpose will depend on the structure of the guest. In other
words, a new host compound must be designed and synthesized
in an enantiopure form for each target racemate.
cular materials because of the strong ionic hydrogen bonds
between them.5 We previously reported that acid–base supramo-
lecular chiral host systems composed of dibenzoyl-L-tartaric acid
and some achiral diamines are effective in enantioselective
inclusion of chiral benzylic and aliphatic alcohols.6 It is note-
worthy that L-tartaric acid is an easily available chiral source and
its chiral recognition ability can be successfully controlled by
changing the achiral diamine.
In this study, we focused on expanding the utility of these
systems by using natural amino acids as the chiral components.
They are quite common and inexpensive chiral sources and also
have more structural variety than tartaric acid. In addition to
their wide commercial availability, they are easy to derivatize
into both acidic and basic compounds by an appropriate modifi-
cation of the amino and carboxyl groups, respectively. Moreover,
it has been reported that several dipeptides derived from
α-amino acids can be applied to enantioselective inclusion of
alcohols and sulfoxides.7
We selected N-acylated L-aspartic acid, a chiral dicarboxylic
acid, because of its simple structure and synthetic accessibility.
The target guest compounds selected were 1-arylalkanols
because they can act as both hydrogen-bonding donors and
acceptors. In the preliminary screening of the host systems, four
achiral diamines including those employed in our previous study
were tested.6 All the tested diamines have simple and symmetri-
cal structures to avoid complicated polymorphs. In addition, they
have rigid aromatic rings to give appropriate cavities. Fortu-
nately, it was found that the combination of N-(2-naphthoyl)-L-
aspartic acid (L-1) and meso-1,2-diphenylethylenediamine (2)
was a good candidate for enantioselective inclusion of 1-aryl-
ethanols. Compound 2 is an achiral meso-form of a diamine with
two stereogenic centers. Here we report the chiral recognition
ability of L-1·2 in three different techniques: crystallization
(Method A), re-precipitation (Method B), and suspension
(Method C). In order to understand the chiral recognition
This disadvantage has led to increased attention on the use of
supramolecular chiral hosts, comprising several different types of
molecules, because simple replacement of their components
allows modification of inclusion and recognition sites to match
Graduate School of Science and Engineering, Saitama University,
255 Shimo-Okubo, Sakura-ku, Saitama 338-8570, Japan.
E-mail: kodama@mail.saitama-u.ac.jp; Fax: +81-48-858-9548;
Tel: +81-48-858-9548
†Electronic supplementary information (ESI) available: Copies of 1H
NMR spectra of synthesized compounds. CCDC reference numbers
842304–842305. For ESI and crystallographic data in CIF or other elec-
tronic format see DOI: 10.1039/c2ob06475h
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mechanism, crystallographic analyses of the ternary inclusion
crystals were carried out. On the basis of the results, we discuss
the effects of the hydrogen-bonding networks, molecular
packing mode, and the structures of the guest compounds.
inclusion ratios and selectivities for the 1-arylethanols with
halogen groups at the para-position indicate that the electron-
withdrawing effect of the substituents had little influence on the
inclusion phenomenon. That is, the inclusion efficiency was
mainly determined by the size and shape of the guest com-
pounds (entries 8 and 9).
However, as seen in entry 10, bulky alkyl group at the stereo-
genic center of the target arylalkanol drastically hampered the
formation of inclusion crystals. This means the void around the
stereogenic center of incorporated 3 is small and less flexible. A
bulky alcohol, 1-(2-naphthyl)ethanol (3k), suffered a low
inclusion ratio and selectivity, probably because the 2-naphthyl
group was too large for inclusion and chiral recognition by L-
1·2. Despite the limitations shown above, various 1-phenyletha-
nols were included by L-1·2 in a highly efficient and enantio-
selective manner, and in particular the combination was found to
be suitable for meta- and para-substituted 1-phenylethanols.
Results and discussion
Enantioselective inclusion of 1-arylalkanols by L-1·2 via
crystallization (Method A)
Enantioselective inclusion of 1-arylethanols by L-1·2 via
re-precipitation (Method B) and suspension (Method C)
In this method, equimolar amounts of L-1 and 2 were dissolved
in an aqueous acetonitrile solution of racemic 3, followed by
crystallization of the inclusion complexes. The results in Table 1
clearly show that the (R)-enantiomer of each guest was preferen-
tially incorporated but the efficiency depended on the structure
of the alcohols: the chiral host efficiently included (R)-3a of
88% ee in 83% yield with 100% inclusion ratio as a L-1 : 2 : 3a
= 1 : 1 : 1 complex (entry 1). For the positional isomers of 1-
(methylphenyl)ethanols, a drastic decrease in enantiomeric
excess to 28% (in 90% yield) was observed for the ortho-isomer
3b (entry 2), whereas the highest enantioselectivity (91% ee)
with 100% inclusion was obtained for the meta-isomer 3c (entry
3). The good results for 1-(3-chlorophenyl)ethanol (3d) suggest
that substituents such as methyl and chloro groups are acceptable
at the meta-position of a phenyl group but not at the ortho-pos-
ition. For the para-isomer 3e, a moderate yield and selectivity
(76% ee in 85% yield) was achieved (entry 5).
As stated above, several methods have been used to prepare
inclusion crystals and they can afford different results. Method A
(crystallization) is the most reliable and commonly used strategy;
however, it is usually time-consuming (usually takes more than 3
days to obtain the inclusion crystals) and requires a large amount
of solvent. To further examine the applicability of the present
host system and improve the enantioselectivities for 3, Methods
B and C were also tested to prepare inclusion crystals L-1·2·3
and the results compared for four 1-arylethanols; the results are
summarized in Table 2. In these methods, the host was sus-
pended in hexane and the pre-organized crystals may have
played some role in preventing the inclusion of the undesired
enantiomer.
As seen in Method A, 3a–c and 3e were included by L-1·2
using Methods B and C, although the inclusion ratio was slightly
lower. Furthermore, as in Method A, (R)-enantiomers of 3a, 3c,
and 3e were predominantly selected. Furthermore, improved
enantioselectivity was observed for 3e in both Method B and
Method C (93% and 96% ee, respectively). The powder XRD
patterns of L-1·2·3a prepared by the three methods were almost
identical, which indicated that the structures of the inclusion
The greater the length of the alkyl group at the para-position
of the phenyl group, the lower was the enantiomeric excess,
although the yield and the inclusion ratio remained high (entries
5–7). This result suggests the supramolecular host has some
adaptability with regard to the molecular sizes of the para-sub-
stituted 1-phenylethanol derivatives. The comparably higher
Table 1 Enantioselective inclusion of 1-arylalkanols by inclusion complexation with L-1·2 using Method A
Entry
1-Arylalkanol
R
Ar
Yielda (%)
Inclusion ratiob (%)
eec (%)
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
3g
3h
3i
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
Ph
83
85
83
90
85
90
94
94
100
90
88 (R)
28 (R)
91 (R)
81 (R)
76 (R)
72 (R)
64 (R)
74 (R)
85 (R)
o-MePh
m-MePh
m-ClPh
p-MePh
p-EtPh
p-nPrPh
p-FPh
p-ClPh
Ph
2-Naphthyl
100
100
100
100
100
90
9
10
11
88
100
3j
3k
Not crystallized
77
Me
60
13 (R)
a Yield was determined on the basis of molar ratio of L-1·2 salt. b Inclusion ratio of 3 was determined by 1H NMR. c Enantiomeric excess was
determined by HPLC analysis.
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Table 2 Comparison of the three methods for enantioselective inclusion of 1-arylethanols
Method A (Crystallization)
Method B (Re-precipitation)
Method C (Suspension)
Entry 1-Arylethanol Ar
Yielda (%) Inc.b (%) Eec (%) Yielda (%) Inc.b (%) Eec (%) Yielda (%) Inc.b (%) Eec (%)
1
2
3
4
3a
3b
3c
3e
Ph
o-MePh
m-MePh 83
p-MePh 85
83
85
100
90
100
100
88 (R)
28 (R)
91 (R)
76 (R)
89
22d
90
90
50d
90
92 (R)
rac.
91 (R)
93 (R)
82
87
90
85
95
65
90
88 (R)
30 (R)
91 (R)
96 (R)
90
100
100
a Yield was determined on the basis of the molar amount of L-1·2. b Inclusion ratio was determined by 1H NMR. c Enantiomeric excess was
determined by HPLC analysis. d Yield and inclusion ratio were determined on the basis of the molar amount of 2.
Fig. 2 Crystal structure of L-1·2·(R)-3a (1 : 1 : 1, enantiomeric excess
of (R)-3a was 84%) viewed from the ac plane. The hydrogen bonds are
shown by dashed lines.
suspended in hexane in the presence of rac-3a. The resultant
inclusion crystal was filtered and heated under reduced pressure
to afford (R)-enriched 3a (2.56 mmol, 95% ee) in high yield and
enantiopurity. Thus, it has been shown that this method is
Fig. 1 Powder XRD patterns of the inclusion crystals L-1·2·3a
obtained by a) crystallization (Method A), b) re-precipitation (Method
B), and c) suspension (Method C).
readily applicable to the preparative-scale enantioseparation of 3.
Crystallographic analyses of the ternary inclusion crystals
L-1·2·3
crystals and their chiral recognition mechanisms were similar
(Fig. 1). Therefore, the higher enantioselectivities in Methods B
and C could probably be attributed to greater effectiveness of
pre-organized and suspended hosts in the preferential inclusion
of (R)-enantiomers from a dilute guest solution. However, both
methods afforded unacceptably low inclusion ratios and/or enan-
tioselectivities for 3b (entry 2). Considering the fact that Method
A was not effective either, the steric hindrance of the ortho-
methyl group seems have strongly affected the inclusion process
To examine the chiral recognition mechanism of 3 in detail, crys-
tallographic analyses of the inclusion crystals L-1·2·3 prepared
by Method A were carried out. Single crystals suitable for the
analysis were fortunately obtained from aqueous acetonitrile sol-
ution of L-1·2 in the presence of racemic 3a or 3e.
For both guest compounds, it was confirmed that the inclusion
crystals consisted of a 1 : 1 : 1 mixture of L-1, 2, and 3. In
addition, only (R)-isomers of 3 were incorporated, which is in
accordance with the results of the inclusion experiments. Fig. 2
shows the hydrogen bonds between the three components of the
L-1·2·(R)-3a inclusion crystals. There are two kinds of hydrogen
bonds in the host, that is, between L-1 and 2: one is between car-
boxylate oxygens of L-1 and ammonium nitrogens of 2 and the
other is between an amide oxygen of L-1 and an ammonium
nitrogen of 2. They constitute a 2D sheet-like hydrogen-bonding
1
in Methods B and Method C as well. In fact, H NMR analysis
indicated that the molar ratio of the precipitate obtained by
Method B was L-1 : 2 : 3b = 3.3 : 1 : 0.5, suggesting that the pre-
cipitate was a mixture of the expected inclusion crystals and the
uncomplexed host compounds.
Next, we applied Method B to a large-scale preparation of
enantioenriched 3a. The mixture of L-1 and 2 (4.71 mmol) was
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Fig. 3 Crystal structure of L-1·2·(R)-3a (1 : 1 : 1; 84% ee for (R)-3a). (a) Perspective view of the inclusion crystal. (b) Enlarged anterior view of
dashed square in (a). (c) Enlarged posterior view of dashed square in (a).
network along the ac plane (Fig. 3a). The guest molecules (R)-
3a are sandwiched between the two 2D-sheet structures of the
host. There are two hydrogen bonds involving the hydroxy
group of (R)-3a and the host: one is with a carboxylate oxygen
of L-1 and the other is with an ammonium nitrogen of 2. There
are no additional weak intermolecular interactions such as π–π or
CH–π interactions.8
In the solid state, the conformation of 2 was fixed by the inter-
actions with L-1 and the desymmetrized molecules 2 efficiently
afforded an asymmetric environment around them. As seen in
the space-filling models in Fig. 3b and 3c, the guest molecule
(R)-3a is located in the void created by two phenyl groups of 2
and two naphthyl groups of L-1. During the inclusion process of
3, the hydroxyl group of 3 is first captured by the two aforemen-
tioned hydrogen bonds between the hosts. Thereafter, the phenyl
group, methyl group, and the hydrogen atom seem to be
arranged to fill the asymmetric void according to their sizes.
Comparing the crystal structures of L-1·2·(R)-3a and L-
1·2·(R)-3e (Fig. 4), it is apparent that the 2D sheet-like hydro-
gen-bonding networks and the molecular arrangements are
almost identical, but the distance between the two networks
increases from 14.904 Å for L-1·2·(R)-3a to 15.456 Å for L-
1·2·(R)-3e because the methyl group of (R)-3e is oriented per-
pendicular to the sheet structures. Thus, it may be concluded that
because the hydrogen-bonding networks are almost identical,
similar yields and inclusion ratios were obtained for 3a and 3e
(entries 1 and 5 in Table 1). This high flexibility between the
two sheet structures may explain the high adaptability for para-
substituted 1-phenylethanols 3e–i. Moreover, it appears that the
enantioselectivities were gradually lowered because the para-
substituted, longer guests 3e–g increased the network distance,
which reduced the molecular packing density, allowing the
incorporation of the unfavored enantiomers.
The remarkably lower inclusion ratios and enantioselectivities
Fig. 4 Comparison of the crystal structures of (a) L-1·2·(R)-3a and (b)
for 3b and 3j can be attributed to the insufficient flexibility of
the void around the stereogenic center of 3 along the direction
parallel to the sheet structures.
L-1·2·(R)-3e.
can successfully serve as a supramolecular chiral host for enan-
tioselective inclusion of (R)-1-arylethanols (3). The inclusion
crystals could be prepared by all three different methods, but re-
precipitation and suspension, in particular, afforded higher selec-
tivity for (R)-3e (up to 96% ee). The suspension method was
Conclusions
We have demonstrated that the combination of N-(2-naphthoyl)-
L-aspartic acid (L-1) and meso-1,2-diphenylethylenediamine (2)
1880 | Org. Biomol. Chem., 2012, 10, 1877–1882
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successfully applied to a practical scale enantioseparation.
X-Ray crystallographic analyses revealed that 2D sheet-like
hydrogen-bonding networks formed in L-1·2, and 3 was incor-
porated in the asymmetric voids between two sheet structures.
The chiral recognition mechanism can be explained by the
matching between the (R)-isomer of 3 and the flexibility of the
asymmetric voids.
These host components are easily accessible from commer-
cially available compounds, allowing various host combinations
to be prepared without elaborate synthesis. The development of
other potential supramolecular host systems from chiral amino
acids is currently under investigation.
(MALDI-TOF, matrix; dithranol): m/z calcd for [M + H]+;
288.09 found 288.00, [M + Na]+; 310.07 found 310.00. Elemen-
tal analysis: Found: C, 62.90; H, 4.55; N, 4.58. Calc. for
C15H13NO5: C, 62.72; H, 4.56; N, 4.88%.
1,2-Diphenyl-N-phenylmethylene-N′-benzoyl-1,2-diaminoethane.9
A mixture of benzaldehyde (76.2 ml, 754 mmol) and ammonium
acetate (165 g) was heated to 120 °C and stirred at this tempera-
ture for 3 h. After cooling to room temperature, the precipitate
was collected, washed with water and hot ethanol to obtain a
white solid (39 g, 97 mmol, 52% yield).
1
Mp: 262.5–263.5 °C. H NMR (300 MHz, DMSO-d6) δ 8.85
(d, J = 9.6 Hz, 1H), 8.00 (s, 1H), 7.62–7.10 (m, 20H), 5.61 (t, J
= 9.6 Hz, 1H), 4.79 (d, J = 9.6 Hz, 1H). IR (KBr): 3381, 1636,
1523 cm−1
.
Experimental
meso-1,2-Diphenylethylenediamine (2).9
A
mixture of
Materials and general methods
1,2-diphenyl-N-phenylmethylene-N′-benzoyl-1,2-diaminoethane
(37.9 g, 93.5 mmol), 98 ml of conc. H2SO4, and 303 ml of
water was refluxed for 24 h, then the solid materials were filtered
off. The resultant acidic aqueous solution was basified with 6 N
NaOH aq. The light yellow precipitate was filtered and recrystal-
lized from hexane to obtain yellow needle-like crystals (10.7 g,
50.4 mmol, 54% yield). Mp: 122.3–123.2 °C. 1H NMR
(300 MHz, CD3OD) δ 7.42–7.27 (m, 10H), 4.01 (s, 2H). IR
Diamine 2 was synthesized according to the literature.9 All the
1-arylalkanols except for 3a were prepared by reduction of the
corresponding ketones. 1H NMR spectra of the inclusion crystals
in CDCl3/CD3OD were recorded on a Bruker AVANCE 300 or
AVANCE 500 spectrometer. IR spectra were measured on a
JASCO FT/IR-460 spectrometer by the KBr method at room
temperature. Melting points were measured on a MEL-TEMP
apparatus and reported uncorrected. Optical rotation was
measured by a JASCO DIP-370 polarimeter with a Hg lamp and
interference filter at 435 nm. Mass spectra were obtained using a
Bruker autoflex III matrix-assisted laser desorption ionization
mass spectrometer. Enantiomeric excesses and absolute configur-
ations of the alcohols were determined by HPLC analyses with a
Daicel Chiralcel OB-H, OD-3, or OJ column with detection at
254 nm. Powder X-ray diffractions were obtained with a Rigaku
RINT UltimaIII diffractometer using graphite-monochromated
Cu-Kα radiation at room temperature. Single crystals for the
X-ray diffraction analysis were prepared by slow evaporation of
a solution of L-1·2 in the presence of racemic 3.
(KBr) 3346, 3274 (br), 1592, 1493, 1452, 915, 699 cm−1
.
General procedures for the preparation of inclusion crystals
The inclusion crystals were prepared according to the following
three methods.
Method A (crystallization method): A H2O–CH3CN solution
of L-1 (66 μmol), 2 (66 μmol), and 3 (1.32 mmol) was left
standing at ambient temperature until the solvent had evaporated
to afford the inclusion compound. The crystals were washed
with hexane and collected.
Method B (re-precipitation method): To a solution of 2
(66 μmol) and 3 (1.32 mmol) in hexane (5 mL), L-1 (66 μmol)
was added in solid form and the mixture was stirred at rt for one
day. Usually L-1 appeared to dissolve slowly and re-precipitate
quickly as the inclusion compound. (It is expected that the par-
tially-organized salt formed a suspension to recognize and
include the guest molecules.)
Method C (suspension method): L-1·2 salt was prepared by
concentration of the methanol solution containing equimolar
amounts of their mixture in advance. To the suspension of L-1·2
salt (66 μmol) in hexane (5 mL), 3 (1.32 mmol) was added and
stirred at rt for one day to obtain the inclusion compound. (It is
expected that the host components are pre-organized before
inclusion of guest molecules.)
Synthesis
N-(2-Naphthoyl)-L-aspartic acid (L-1). A solution of 2-
naphthoyl chloride (9.9 g, 52 mmol, 1.5 equiv.) in Et2O (45 ml)
was added to a solution of L-aspartic acid (4.6 g, 35 mmol) in 4
N NaOH aq. (43 ml) at 0 °C. The resulting biphasic mixture was
vigorously stirred at room temperature overnight. The Et2O layer
was then discarded and the basic aqueous layer was washed with
Et2O (2 × 30 ml). Then the aqueous phase was acidified at 0 °C
with conc. HCl soln. to pH 1. The precipitated product was col-
lected and dissolved in a minimum amount of methanol and
water was carefully added until the solution became slightly
cloudy. The mixture was heated to afford a clear solution and
allowed to cool to obtain colorless needle crystals (3.5 g,
23
12 mmol, 35% yield). Mp: 172.7–173.3 °C. [α] −2.70 (c 1.0
435
Large scale preparation of the enantio-enriched 1-phenylethanol
by re-precipitation method
in MeOH). 1H NMR (300 MHz, CD3OD) δ 8.40 (s, 1H),
7.99–7.87 (m, 4H), 7.62–7.53 (m, 2H), 5.01 (dd, J1 = 7.0 Hz, J2
= 5.6 Hz, 1H), 3.04 (dd, J1 = 16.7 Hz, J2 = 5.6 Hz, 1H), 2.95
(dd, J1 = 16.7 Hz, J2 = 7.0 Hz, 1H). 13C NMR (125 MHz,
CD3OD) δ 175.1, 175.0, 170.9, 137.3, 134.9, 133.3, 130.9,
130.2, 129.9, 129.8, 129.7, 128.8, 125.8, 51.9, 37.7. IR (KBr)
3277, 3064 (br), 1738, 1704, 1634, 1537, 1409, 1250 cm−1. MS
According to Method B described above, L-1 (1.35 g,
4.71 mmol) was added to a hexane solution of 2 (1.00 g,
4.71 mmol) and 3a (11.5 g, 94.2 mmol), and the mixture was
stirred at rt for a day. The precipitated white solid (2.21 g) was
filtered and washed with hexane followed by characterization by
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1H NMR analysis (L-1 : 2 : 3a = 1.5 : 1 : 1). The solid obtained
was heated at 100–140 °C under reduced pressure (10 mmHg) to
give (R)-3a (0.312 g, 2.56 mmol, 95% ee) as a colorless oil.
was 0.1544 (I > 2σ(I)). Crystal data for L-1·2·3e: C38H41N3O6,
M = 635.74, triclinic, a = 5.660(2), b = 9.583(4), c = 15.456(6)
Å, α = 94.113(5), β = 92.683(5), γ = 96.361(5)°, V = 829.8(5)
Å3, T = 100 K, space group P1, Z = 1, 3764 reflections
measured, 3208 independent reflections (Rint
The final R1 was 0.0863 (I > 2σ(I)) and wR (F2) was 0.2314
(I > 2σ(I)).†
= 0.1348).
The conditions of HPLC analyses for enantiomer separations of
the alcohols
Absolute configuration of the alcohols was determined by com-
parison of the HPLC elution order with that of the literature
data.4d,6,10
Acknowledgements
This work was financially supported by the Ministry of Edu-
cation, Culture, Sports, Science and Technology, Japan (Grant-
in-Aid for Young Scientists (B) No. 22750119).
1-Phenylethanol (3a).6 Determination of the ee by HPLC
analysis: Chiralcel OD-3, n-hexane/2-propanol (95 : 5), 0.8 mL
min−1; tr (S) = 13.7 min; tr (R) = 11.3 min.
1-(2-Methylphenyl)ethanol (3b).6 Determination of the ee by
HPLC analysis: Chiralcel OB-H, n-hexane/2-propanol (95 : 5),
0.8 mL min−1; tr (S) = 17.4 min; tr (R) = 22.7 min.
Notes and references
1 (a) J. Jacques, A. Collet and S. H. Wilen, Enantiomers, Racemates, and
Resolutions, Krieger Publishing Company, Malabar, Florida, 1994;
(b) D. Kozma, Optical Resolutions via Diastereomeric Salt Formations,
CRC Press, London, 2002; (c) F. Faigl, E. Fogassy, M. Nógrádi,
E. Pálovics and J. Schindler, Tetrahedron: Asymmetry, 2008, 19, 519–
536.
1-(3-Methylphenyl)ethanol (3c).6 Determination of the ee by
HPLC analysis: Chiralcel OB-H, n-hexane/2-propanol (98 : 2),
0.8 mL min−1; tr (S) = 17.9 min; tr (R) = 28.3 min.
1-(3-Chlorophenyl)ethanol (3d).10 Determination of the ee by
HPLC analysis: Chiralcel OB-H, n-hexane/2-propanol (98 : 2),
0.8 mL min−1; tr (S) = 23.9 min; tr (R) = 31.3 min.
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1-(4-Methylphenyl)ethanol (3e).6 Determination of the ee by
HPLC analysis: Chiralcel OJ, n-hexane/2-propanol (98 : 2),
0.8 mL min−1; tr (S) = 25.7 min; tr (R) = 29.2 min.
1-(4-Ethylphenyl)ethanol (3f).4d Determination of the ee by
HPLC analysis: Chiralcel OD-3, n-hexane/2-propanol (99 : 1),
0.8 mL min−1; tr (S) = 30.9 min; tr (R) = 27.4 min.
1-(4-Propylphenyl)ethanol (3g).4d Determination of the ee by
HPLC analysis: Chiralcel OD-3, n-hexane/2-propanol (98 : 2),
1.0 mL min−1; tr (S) = 16.3 min; tr (R) = 13.7 min.
1-(4-Fluorophenyl)ethanol (3h).6 3h was derivatized to its
acetyl ester to determine enantiomeric excess by HPLC analysis:
Chiralcel OJ, n-hexane/2-propanol (98 : 2), 0.8 mL min−1; tr (S)
= 17.4 min; tr (R) = 14.5 min.
1-(4-Chlorophenyl)ethanol (3i).6 Determination of the ee by
HPLC analysis: Chiralcel OD-3, n-hexane/2-propanol (98 : 2),
0.8 mL min−1; tr (S) = 22.2 min; tr (R) = 24.1 min.
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and S. Matsumoto, Tetrahedron, 2011, 67, 2844–2848.
1-(2-Naphthyl)ethanol (3k).4d Determination of the ee by
HPLC analysis: Chiralcel OB-H, n-hexane/2-propanol (93 : 7),
0.5 mL min−1; tr (S) = 26.8 min; tr (R) = 30.8 min.
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Single crystal X-ray analyses of the inclusion crystals
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11 A. Altomare, M. C. Burla, M. Camalli, G. L. Cascarano, C. Giacovazzo,
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12 G. M. Sheldrick, SHELXL-97, program for the refinement of crystal
structures, Germany, University of Gottingen, 1997
X-Ray crystallographic data were collected on a Bruker Smart
APEX II diffractometer with graphite monochromated Mo-Kα
radiation. The structures were solved by a direct method using
SIR 9711 and refined by SHELXL-97 programs.12 Crystal data
for L-1·2·3a: C37H39N3O6, M = 621.71, triclinic, a = 5.7098(9),
b = 9.5517(15), c = 14.904(2) Å, α = 87.425(2), β = 89.606(2),
γ = 82.942(2)°, V = 805.9(2) Å3, T = 100 K, space group P1, Z
= 1, 3862 reflections measured, 3236 independent reflections
(Rint = 0.1402). The final R1 was 0.0587 (I > 2σ(I)) and wR (F2)
1882 | Org. Biomol. Chem., 2012, 10, 1877–1882
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