Salts of N,N'-oxalylbis(phenylglycine)s and 1-phenylethylamines: Structural variation of layered materials induced by stereochemistry

Article abstract of DOI:10.1016/S0040-4020(99)01059-5

Salts between (R,R)- or meso-N,N'-oxalylbis(phenylglycine) 1 and (R)-, (S)-, or (±)-1-phenylethylamine 2 construct three different layer structures depending on their stereochemistry. By X-ray crystallography, it is elucidated that the formation of a hydr

Full text of DOI:10.1016/S0040-4020(99)01059-5

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 753–761
Salts of N,N0-Oxalylbis(phenylglycine)s and 1-Phenylethylamines:
Structural Variation of Layered Materials Induced by
Stereochemistry
Motohiro Akazome,a Toshiaki Takahashi,b Naoyuki Ito,a Noriyuki Babaa and Katsuyuki Oguraa,
*
aDepartment of Materials Technology, Faculty of Engineering, Chiba University, 1-33 Yayoicho, Inageku, Chiba 263-8522, Japan
bGraduate School of Science and Technology, Chiba University, 1-33 Yayoicho, Inageku, Chiba 263-8522, Japan
Received 2 November 1999; accepted 8 December 1999
Abstract—Salts between (R,R)- or meso-N,N0-oxalylbis(phenylglycine) 1 and (R)-, (S)-, or (^)-1-phenylethylamine 2 construct three
different layer structures depending on their stereochemistry. By X-ray crystallography, it is elucidated that the formation of a hydrogen
bonding network between the amino and carboxyl groups and the planarity of the oxalyl functionality are important to construct the sheet
structure. The salt of (R,R)-1 and 2 forms a bilayer or puckered structure, whereas the salt of meso-1 and 2 constructs a monolayer structure.
᭧ 2000 Elsevier Science Ltd. All rights reserved.
Introduction
and (^)- or (R)-2, while the salt of meso-1 and (^)-2 formed
a monolayer structure.9 Furthermore, the salt of (R,R)-1 and
(S)-2 gave rise to the formation of another layer structure
which is called “a puckered layer”. These facts are in sharp
contrast with the case of organic salts between 1-phenyl-
ethylamine and such chiral carboxylic acids as cholic
acids,10 phenylpropionic acid11 and mandelic acids,12
which construct helical columnar structures.
In crystal engineering, two-dimensional inorganic networks
have been extensively studied from the standpoint of solid-
state supramolecular chemistry.1 Recently, two-dimensional
organic molecules were designed so as to control their
aggregation and, as a result, construct layer structures.2
Zaworotko et al. reported supramolecular synthesis of
organic laminates using affinity to aromatic guests.3 It was
also reported by Ward et al. that guanidium alkane- and
arenesulfonates construct a bilayer or monolayer structure
depending on the size of alkyl and aryl groups.4 Napthalene-
dicarboxamides were shown by Lewis et al. to form a mono-
layer or bilayer structure according to the position of their
Results and Discussion
Synthesis of (R,R)- or meso-1 and these salts
substituents.5 Furthermore, Aarkeroy et al. reported the
¨
hydrogen-bonding layers of hydrogen malate anions as
well as the influence of their counter ions on the geometry
and crystal packing.6
According to Scheme 1, (R,R)-1 was easily prepared by the
coupling of oxalyl chloride and (R)-phenylglycine benzyl
ester followed by hydrogenolysis to remove the protecting
benzyl groups. Some difficulties were encountered in a simi-
lar synthesis of meso-1 starting from racemic phenylglycine
benzyl ester to obtain the product in a pure state. Hence,
oxalyl chloride reacted with a 1:1 mixture of (R)-phenylgly-
cine benzyl ester and (S)-phenylglycine methyl ester to
afford a statistic mixture (1:2:1) of oxalyl amides. After
the separation of their differentially protected products
using column chromatography, stepwise deprotection of
the benzyl and the methyl groups was performed by hydro-
genolysis and acid-catalyzed hydrolysis, respectively, to
afford meso-1 in a pure form.
Our attention was focused on a salt of an optically active
amine and an N,N0-oxalylbis(a-amino acid) because the
latter is well-known to construct a two-dimensional sheet
structure, in which the central oxalamide unit adopts a
planar and trans configuration.7,8 Here we report that the
salt of N,N0-oxalylbis(phenylglycine) 1 and 1-phenylethyl-
amine 2 forms a monolayer or bilayer structure according to
the stereochemistry of each component, as summarized in
Chart 1: A bilayer structure was given by the salt of (R,R)-1
These (R,R)- or meso-1 reacted with (R)-, (S)-, or (^)-2 in
methanol to form a homogenous solution of the correspond-
ing salt. Slow evaporation of the methanol deposited the 1:2
salts of 1 and 2 in a crystalline state. In order to prepare the
Keywords: ammonium salts; amino acids; stereochemistry; X-ray crystal
structure.
* Corresponding author. Tel.: ϩ81-43-290-3388; fax: ϩ81-43-290-3402;
e-mail: katsu@planet.tc.chiba-u.ac.jp
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(99)01059-5

754
M. Akazome et al. / Tetrahedron 56 (2000) 753–761
Chart 1.
Scheme 1.
Table 1. Crystal data and data collection parameters
Data
Formula
(R,R)-1·(^)-2·H2O
C34H40N4O7
616.71
Monoclinic
P21
298
14.605(3)
10.034(3)
12.129(3)
(R,R)-1·(R)-2·H2O
C34H40N4O7
616.71
Monoclinic
P21
(R,R)-1·(S)-2
C34H38N4O6
598.70
Monoclinic
P21
173
19.946(6)
5.557(3)
14.580(5)
meso-1·(^)-2
C17H19N2O3
299.35
Formula weight
Crystal system
Space group
T (K)
Triclinic
¯
P1
298
173
˚
a (A)
14.747(3)
9.952(3)
12.251(3)
15.917(5)
10.345(4)
5.072(2)
86.13(3)
94.34(3)
74.76(3)
800.2(4)
2
˚
b (A)
˚
c (A)
a (Њ)
b (Њ)
g (Њ)
104.44(2)
106.27(2)
108.97(3)
3
˚
V (A )
1721.5(8)
2
1725.9(6)
2
1528(1)
2
Z
Dcalcd
1.19
1.186
Cu-Ka
0.684
3470
1.301
Cu-Ka
0.7325
3219
1.242
Radiation used
Cu-Ka
0.610
3468
Cu-Ka
0.6995
3074
m (mmϪ1
)
Measured reflections
Observed reflections
3040
2152
2786
1897
Criteria of I
3
3
3
1.5
R
wR
0.0446
0.0519
0.15, Ϫ0.22
0.040
0.043
0.20, Ϫ0.18
0.060
0.062
0.83, Ϫ0.54
0.074
0.066
0.22, Ϫ0.25
Residual electron density

M. Akazome et al. / Tetrahedron 56 (2000) 753–761
755
Figure 1. A bilayer structure of (R,R)-1·(R)-2·H2O (a–c plane). Alkyl and phenyl groups are colored white.
corresponding anhydrous salts, dry methanol was used as a
solvent and the crystallization process was performed in a
desiccator.
Bilayer structure: the salts of (R,R)-1 and (^)- or (R)-2
The crystal of (R,R)-1·(R)-2·H2O formed a bilayer structure
(Fig. 1), which is an isostructure of (R,R)-1·(^)-2·H2O (Fig.
3). In the bilayer structure, the half-layer consists of a hydro-
philic hydrogen bonding sheet and a hydrophobic part
containing phenyl and alkyl groups. Two half-layers are
paired via hydrogen bonding interaction between their
hydrophilic layers. The XRPD pattern showed a strong
X-Ray diffraction analysis for salts of 1 and 2
Among the possible combinations of 1 [(R,R)- or meso-1]
and 2 [(R)-, (S)-, or (^)-2], four kinds of salts, i.e. (R,R)-
1·(^)-2·H2O,9 (R,R)-1·(R)-2·H2O, (R,R)-1·(S)-2, and meso-
1·(^)-2 were obtained as single crystals. The data of
their single-crystal X-ray analyses are summarized in
Table 1.
˚
peak at 14.1 A, which corresponded to the layer distance
between the (100) planes in Fig. 1.
As seen in Fig. 2a, the hydrophilic hydrogen bonding
sheet shows that the conformation of an oxalyl linkage
is a somewhat distorted transoid13 (the torsion angle
of O2–C14–C17–O8ˆ168.9Њ). The salt formation
between the amino and carboxyl groups constructed a
In addition to the single-crystal analyses, X-ray powder
diffraction (XRPD) analyses gave us important information
about their layered structures. In all these salts, a strong
diffraction peak was observed at a lower range of 2Q
angle. This peak corresponds to a layer distance (vide infra).
12-membered ring;14 bond distances are 2.80 A for
˚
10
5
10
4
6
1
˚
˚
N ···O , 2.73 A for N ···O , 2.73 A for N ···O , and
6
3
˚
2.90 A for N ···O . By the aid of water molecules,
which bind simultaneously to the amino and carboxyl
groups (N ···O , 2.89 and O ···O , 2.83 A), the one-
dimensional backbones of the salts combine to form a
two-dimensional sheet structure.
The salts of (R,R)-1 and (^)- or (R)-2 included water, but
other salts were obtained as anhydrous salts even under
wet conditions. By carefully keeping anhydrous
conditions, anhydrous salts of (R,R)-1·(^)-2 and (R,R)-
1·(R)-2 could be prepared. In XRPD patterns of these
anhydrous salts, no characteristic strong peak was observed
(see Fig. 10).
6
9
ء5
9
˚
Two hydrophilic layers are combined by two hydrogen
Figure 2. (a) The hydrogen bonding layer of the salt of (R,R)-1·(R)-2·H2O (b–c plane). (b) The offset between two layers (b–c plane). Alkyl and phenyl groups
are omitted.

756
M. Akazome et al. / Tetrahedron 56 (2000) 753–761
Figure 3. A bilayer structure of (R,R)-1·(^)-2·H2O (a–c plane). Alkyl and phenyl groups are colored white.
Figure 4. (a) The hydrogen bonding layer of the salt of (R,R)-1·(^)-2·H2O (b–c plane). (b) The offset between two layers (b–c plane). Alkyl and phenyl groups
are omitted.
bonds (Fig. 1); one hydrogen bond is between the water and
a carboxylate (O ···O , 2.76 A) and the other is between a
The crystal of (R,R)-1·(^)-2·H2O9 also has a bilayer struc-
ture, which consists of (R,R)-1, (R)-2 and (S)-2, and water
(Fig. 3). The XRPD pattern shows a strong peak at 14.1 A
corresponding to the layer distance between the (100)
planes. The hydrogen bonding sheet (Fig. 4) of (R,R)-
1·(^)-2·H2O is very similar to that of (R,R)-1·(R)-2·H2O.
9
3
˚
˚
nitrogen of ammonium and an oxygen of the oxalyl group
10
2
˚
(N ···O , 2.88 A). The two hydrophilic layers stack in a
face-to-face manner to become the bilayer structure
(Fig. 2b).
Figure 5. Similarity of crystal packing. (a) (R,R)-1·(R)-2·H2O, (R)-2 in Regions I and II. (b) (R,R)-1·(^)-2·H2O, (S)-2 in Region I and (R)-2 in Region II.

M. Akazome et al. / Tetrahedron 56 (2000) 753–761
757
Figure 6. Puckered layer of (R,R)-1·(S)-2 (a–c plane). Alkyl and phenyl groups are colored white.
The hydrophobic parts of these two salts are shown in a
space filling model (Fig. 5). Region I is tolerant for the
stereochemistry of 2, but region II permitted only the R
form of 2. Therefore, it is assumed that, if (S)-2 is enclosed
instead of (R)-2, region II has to change its shape. Indeed,
the steric repulsion of region II compelled the structure of
(R,R)-1·(S)-2 to adopt a puckered layer (vide infra).
face of four benzene rings realize the puckered layer. Since
the conformation of an oxalyl linkage is a somewhat
distorted transoid13 (the torsion angle of O4–C14–C12–
O5ˆ176.2Њ), two phenyl groups of (R,R)-1 stand on one
side of the backbone of (R,R)-1.
In one monolayer structure (Fig. 7), the salt formation
between the amino and carboxyl groups constructed two
42
2
˚
different 10-membered rings; one has N ···O (2.70 A),
42 1 42 ء1
If (R)-2 molecules are included between such puckered
layers, they would undergo steric repulsion and, as a result,
the bilayer structure was constructed by the incorporation of
water.
˚
˚
N ···O (2.79 A), and N ···O (2.80 A), the other has
ء41
52
41
52
N52···O40 (2.69 A), N ···O (2.74 A), and N ···O
˚
˚
˚
(3.06 A). These 10-membered rings are often observed in
the helical hydrogen-bond columns (21-column) of amine
salts of carboxylic acids.12a,14a
Puckered layer structure: a salt of (R,R)-1 and (S)-2
Even when crystallization was performed in the presence of
water, the anhydrous salt of (R,R)-1 and (S)-2 was obtained.
Fig. 6 shows that the crystal structure has a puckered sheet
of (R,R)-1·(S)-2. One hydrophobic layer of (R,R)-1·(S)-2 has
two different modes of benzene–benzene packing, one is
“edge-to-face (tilted T)” and the other is “parallel stacking
(parallel stacked and displaced)” (A and B in Fig. 6).15 It is
Monolayer structure: a salt of meso-1 and (^)-2
Crystals of meso-1·(^)-2 did not include any water
molecule. The crystal structure of this salt has a center of
symmetry and shows a monolayer structure (Fig. 8). In
addition to salt formation, benzene–benzene interactions
were also observed, where the (R)- and (S)-phenylglycine
moieties of meso-1 interacted with the phenyl group of (R)-
and (S)-2, respectively. The XRPD pattern showed a strong
˚
also shown that a strong peak (13.5 A) of the XRPD pattern
¯
corresponds to the layer distance between the (101) planes.
˚
Between the puckered sheets, an edge-to-face interaction of
peak at 15.5 A, which corresponded to the layer distance
phenyl groups is also observed, where successive edge-to-
between the (100) planes.
Figure 7. (a) Hydrogen bonds of a puckered layer of (R,R)-1·(S)-2. (b) CPK model. Alkyl and phenyl groups of (R,R)-1 and (S)-2 or coloured white and gray,
respectively.

758
M. Akazome et al. / Tetrahedron 56 (2000) 753–761
Figure 8. A monolyer structure of meso-1·(^)-2 (a–b plane). Alkyl and phenyl groups are colored white.
Since the conformation of an oxalyl linkage is perfectly
transoid13 (the torsion angle of O4–C6–Cء6–Oء4ˆ180.0Њ)
and fixes the conformation of meso-1 to be flat, two phenyl
groups of meso-1 stand above and below the backbone
sheet.
Interestingly, after anhydrous (R,R)-1·(^)-2 and (R,R)-
1·(R)-2 were exposed to water vapor for a few weeks, hydra-
tion of these anhydrous salts occurred. The XRPD pattern of
these hydrated solids became similar to those of (R,R)-
1·(^)-2·H2O and (R,R)-1·(R)-2·H2O, respectively (Fig.
10). These results supported that the water molecules play
an important role in constructing the hydrogen bonding
network in the bilayer structures of (R,R)-1·(^)-2·H2O and
(R,R)-1·(R)-2·H2O.
Fig. 9a shows the salt formation and hydrogen bonding
network in the monolayer structure: N5···O2 (2.73 A),
˚
5
3
5
ء3
5
ء2
˚
˚
˚
N ···O (2.78 A), N ···O (2.94 A), and N ···O (2.99 A).
Phenyl groups of meso-1·(^)-2 construct a herringbone
motif via the edge-to-face interactions (Fig. 9b).
On the other hand, the water molecules were hardly
removed from both hydrated (R,R)-1·(R)-2 and (R,R)-
1·(^)-2 at room temperature. When hydrated salts were
heated, the dehydration occurred above 150ЊC to decom-
pose both the salts.
Another salt, meso-1·(R)-2, is also shown to include no
water molecule. Since its XRPD pattern and IR spectrum
are very similar to those of meso-1·(^)-2, the salt of meso-
1·(R)-2 can be assumed to be a monolayer structure.
Hydration of anhydrous (R,R)-1·2 salts: X-ray powder
diffraction analysis for these layers
Conclusion
In this paper, we demonstrated that the oxalyl functionality,
which combined two phenylglycine parts, makes the back-
bone of N,N0-oxalylbis(phenylglycine) fairly flat, and the
salt formation between 1 and 2 constructs a sheet structure
with the aid of hydrogen bonds.
As mentioned above, anhydrous salts [(R,R)-1·(^)-2 and
(R,R)-1·(R)-2] were prepared by crystallization from dry
methanol. Their compositions were also confirmed by
elemental analysis.
Figure 9. (a) Hydrogen bonds of a monolayer structure of meso-1·(^)-2. (b) CPK model. Alkyl and phenyl groups of meso-1 and (^)-2 are colored white and
gray, respectively.

M. Akazome et al. / Tetrahedron 56 (2000) 753–761
759
˚
Figure 10. Change of the powder X-ray diffraction by hydration of the salts: (a) (R,R)-1·(R)-2; (b) (R,R)-1·(^)-2. Selected distances (A) corresponding to 2u
values are shown on each peak.
Three different layer structures formed according to the
combination of the stereochemical isomers of 1 and 2.
The salt of (R,R)-1 and (^)- or (R)-2 included water
molecules, which construct a bilayer structure. These crystal
structures of the hydrated salts were isostructural. Under
anhydrous conditions, anhydrous (R,R)-1·(^)-2 and (R,R)-
1·(R)-2 were obtained. On the other hand, the salt of (R,R)-1
and (S)-2 showed quite a different structure, a puckered
layer. The salt of meso-1 and (^)-2 has a monolayer struc-
ture. Thus, it was found that the structural variation of these
layered materials depends on the stereochemistry of 1 and 2.
These results suggest that the stereochemistry of amino
acids takes an important role in crystal engineering. In
symmetric molecules bearing two chiral centers, d,l- and
Powder X-ray diffraction
All XRPD analyses were taken on a MAC Science MXP
powder diffractometer using graphite-monochromated
CuKa radiation (40 kV, 300 mA). The spectra were
measured between 2 and 50Њ in the 2u/u-scan mode with
steps of 0.01Њ in 2u and 4Њ/min.
X-Ray crystallography
Data collection was performed on a Mac Science MXC18
four-circle diffractometer with monochromated CuKa
˚
(lˆ1.54178 A) radiation using the 2u –v scan technique,
and the X-ray intensities were measured up to 2uˆ140Њ.
Three standard reflections were monitored every 100 reflec-
tions; there were no significant variations in intensities. The
structures were solved and refined on direct methods (SIR
9217 on a computer program package; crystan-gm ver.
6.2.1 or maXus ver. 1.1 from MAC Science Co. Ltd.)
Further detail data have been deposited with the Cambridge
Crystallographic Data Centre.18
¨
meso-forms are possible. Although Aakeroy et al. have
prepared salts between l- or meso-tartaric acid and (S)-2,
their crystal structures showed only a monolayer structure.16
Our design of phenylglycine derivatives based on the stereo-
chemistry will make it possible to adopt various two-
dimensional crystal arrangements.
Synthesis of (R,R)-N,N0-oxalylbis(phenylglycine)
[(R,R)-1]
Experimental
General
Oxalyl chloride (3.02 mL, 34.6 mmol) in dry diethyl ether
(80 mL) was added dropwise into a mixture of (R)-phenyl-
glycine benzyl ester p-tolenesulfonate19 (29.7 g,
71.8 mmol), triethylamine (19.5 mL, 140 mmol), and dry
diethyl ether (250 mL) over 40 min at 0ЊC, and stirred for
18 h at ambient temperature. After evaporation of the
solvent, ethyl acetate (400 mL) was added and insoluble
salts were filtered. Organic residue was washed by 0.6 M
aqueous HCl (100 mL×3), 5% NaHCO3 (200 mL×3), and
water (100 mL), dried over MgSO4 and evaporated. The
1H NMR spectra were recorded on a Varian Gemini 2000
spectrometer. The infrared spectra were recorded on a
JASCO Herschel FT/IR-350. The melting points were
measured on a hot-stage microscope apparatus (Yanagi-
moto) and are uncorrected. (R)-Phenylglycine (99% ee),
(S)-phenylglycine (99% ee), racemic 1-phenylethylamine,
(R)-1-phenylethylamine (99% ee) and (S)-1-phenylethyl-
amine (99% ee) were purchased from Tokyo Kasei Kogyo.

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M. Akazome et al. / Tetrahedron 56 (2000) 753–761
residue was recrystallized from hexane/ethyl acetate to give
O,O0-dibenzyl N,N0-oxalylbis(phenylglycine) (15.0 g,
27.9 mmol, 80%) as colorless crystals: mp 157–158ЊC;
[a]2D5ˆϪ123.5 (cˆ1.00, CHCl3); 1H NMR(300 MHz:
CDCl3) d 5.13 (d, Jˆ12.4 Hz, 2H), 5.22 (d, Jˆ12.4 Hz,
2H), 5.55 (d, Jˆ7.6 Hz, 2H), 7.16–7.32 (m, 20H), 8.25 (d,
Jˆ7.6 Hz, 2H); IR (KBr): 3300, 1740, 1660, 1538, 1506,
1454, 1314, 1172, 728, 696 cmϪ1. O,O0-Dibenzyl N,N0-
oxalylbis(phenylglycine) (10.5 g, 19.5 mmol) was dissolved
in MeOH (300 mL), and treated with hydrogen in the
presence of palladium black (prepared from PdCl2
902 mg) as a catalyst for 18 h. The catalyst was removed
by filtration, and concentration of the filtrate gave a solid.
Crystallization of the solid from methanol afforded (R,R)-1
(5.67 g, 15.9 mmol, 81%) as a colorless powder: mp 225ЊC
dec.; [a]2D5ˆϪ231.5 (cˆ1.01, methanol); 1H NMR
(300 MHz: d6-DMSO) d 5.42 (d, Jˆ7.7 Hz, 2H), 7.30–
7.42 (m, 10H), 9.02 (d, Jˆ7.7 Hz, 2H); IR (KBr): 3300,
3140, 2930, 1718, 1660, 1506, 1416, 1224, 1088, 1069,
726, 696 cmϪ1. Anal. Calcd for C18H16N2O6: C, 60.67; H,
4.53; N, 7.86. Found: C, 60.51; H, 4.44; N, 7.77.
General synthesis of salts between 1 and 2
To prepare salts of 1 (34 mg, 0.11 mmol) and 2 (37 mg,
0.33 mmol), both of them were dissolved in water
(2.0 mL) or dry methanol (2.0 mL) in a vial. The vial was
kept for a few days. For anhydrous salts, the vial was stored
over P2O5 in a desiccator under anhydrous conditions.
(R,R)-1·(^)-2·H2O: colorless plate crystals: mp 161ЊC dec.;
1H NMR (300 MHz: D2O) d 1.63 (d, Jˆ7.0 Hz, 6H), 4.51
(q, Jˆ7.0 Hz, 2H), 5.15 (s, 2H), 7.34–7.51 (m, 20H). IR
(KBr): 3384, 3345, 3168, 3060, 3023, 2945, 2100, 1671,
1577, 1476, 1377, 1236, 1172, 1066, 968, 699 cmϪ1
;
˚
˚
Powder X-ray Analysis (I/I0) 14.04 A (1.00), 7.04 A
˚
˚
˚
˚
(0.20), 4.70 A (0.02), 4.25 A (0.03), 3.53 A (0.13), 2.82 A
(0.06). Anal. Calcd for C34H40N4O7: C, 66,21; H, 6.54; N,
9.08. Found: C, 66.50; H, 6.49; N, 9.28.
Anhydrous (R,R)-1·(^)-2: colorless plate crystals: mp
152.5ЊC dec.; 1H NMR (300 MHz: D2O) d 1.61 (d,
Jˆ6.9 Hz, 6H), 4.48 (q, Jˆ6.9 Hz, 2H), 5.15 (s, 2H),
7.26–7.53 (m, 20H); IR (KBr): 3385, 3070, 3038, 2980,
2930, 2180, 1671, 1577, 1491, 1389, 1236, 1190, 1091,
1068, 1030, 700 cmϪ1; Powder X-ray Analysis (I/I0)
Synthesis of meso-N,N0-oxalylbis(phenylglycine)
[meso-1]
˚
˚
˚
˚
˚
17.42 A (0.44), 12.30 A (1.00), 8.17 A (0.28), 6.80 A
˚
˚
˚
(0.26), 4.90 A (0.20), 4.54 A (0.13), 4.20 A (0.38), 4.02 A
˚
˚
Oxalyl chloride (0.87 mL, 10.0 mmol) was added dropwise
into a mixture of (R)-phenylglycine benzyl ester p-toluene-
sulfonate19 (4.14 g, 10.0 mmol), (S)-phenylglycine methyl
ester hydrochloride20 (2.02 g, 10.0 mmol), triethylamine
(5.60 mL, 40.0 mmol), and dry THF (100 mL) over
30 min at 0ЊC, and stirred for 24 h at ambient temperature.
After evaporation of the solvent, ethyl acetate (300 mL) was
added and insoluble salts were filtered. Organic residue was
washed by 10% aqueous citric acid (100 mL×3), brine
(100 mL×3), and saturated NaHCO3 (100 mL×3), dried
over MgSO4, and evaporated. The crude products were
separated by careful silica gel column chromatography
(eluent, hexane/AcOEtˆ2:1) to give O-benzyl O0-methyl
meso-1 (1.81 g, 2.71 mmol, 44 %) as a colorless powder:
(0.89), 3.87 A (0.18), 3.65 A (0.36). Anal. Calcd for
C34H38N4O6: C, 68.21; H, 6.40; N, 9.36. Found: C, 68.17;
H, 6.41; N, 9.33.
(R,R)-1·(R)-2·H2O: colorless plate crystals: mp 174ЊC dec.;
1H NMR (300 MHz: d4-CD3OD) d 1.62 (d, Jˆ6.9 Hz, 6H),
4.48 (q, Jˆ6.9 Hz, 2H), 5.14 (s, 2H), 7.36–7.45 (m, 20H);
IR (KBr): 3386, 3343, 3068, 3038, 2960, 2162, 1663, 1580,
1492, 1387, 1236, 1089, 1065, 1028, 968, 701 cmϪ1
;
˚
˚
Powder X-ray Analysis (I/I0) 14.13 A (1.00), 7.06 A
˚
˚
˚
(0.15), 4.75 A (0.04), 4.04 A (0.13), 3.54 A (0.14). Anal.
Calcd for C34H40N4O7: C, 66.21; H, 6.54; N, 9.08. Found:
C, 66.16; H, 6.50; N, 9.16.
1
mp 170.8ЊC dec.; H NMR (300 MHz: CDCl3) d 3.73 (s,
Anhydrous (R,R)-1·(R)-2: colorless plate crystals: mp
158.2ЊC dec.; 1H NMR (300 MHz: D2O) d 1.62 (d,
Jˆ6.9 Hz, 6H), 4.48 (q, Jˆ6.9 Hz, 2H), 5.14 (s, 2H),
7.34–7.51(m, 20H); IR (KBr): 3373, 3036, 2978, 2937,
2170, 1676, 1577, 1476, 1386, 1234, 1188, 1066, 742,
3H), 5.12 (d, Jˆ14.0 Hz, 1H), 5.20 (d, Jˆ14.0 Hz, 1H),
5.51(d, Jˆ7.6 Hz, 1H), 5.55 (d, Jˆ7.6 Hz, 1H), 7.30–7.42
(m, 10H), 8.22 (d, Jˆ7.6 Hz, 1H), 8.24 (d, Jˆ7.6 Hz, 1H);
IR (KBr): 3316, 2362, 2344, 1736, 1662, 1508, 1173,
696 cmϪ1. Anal. Calcd for C24H24N2O6: C, 66.96; H, 5.62;
N. 6.51. Found: C, 66.85; H, 5.74; N. 6.40. O-Benzyl O0-
methyl meso-1 (223 mg, 0.48 mmol) was dissolved in
MeOH (80 mL), and treated with hydrogen in the presence
of palladium black (prepared from PdCl2 92 mg) as a
catalyst for 18 h. The catalyst was removed by filtration,
and concentration of the filtrate gave O-methyl meso-1
(173 mg, 0.46 mmol, 95%) as a colorless powder. To
O-methyl meso-1 in acetone (60 mL), 3 M aqueous HCl
(20 mL) was added and stirred under reflux conditions for
66 h. The concentration of the reaction mixture gave a solid
and crystallization from methanol afford meso-1 (136 mg,
697 cmϪ1; Powder X-ray Analysis (I/I0) 11.92 A (0.67),
˚
˚
˚
˚
˚
˚
˚
˚
11.34 A (0.29), 10.10 A (1.00), 6.82 A (0.23), 5.97 A
˚
˚
˚
(0.24), 5.85 A (0.65), 5.75 A (0.24), 5.15 A (0.77), 5.04 A
(0.23), 4.86 A (0.59), 4.42 A (0.56), 4.31 A (0.44), 4.00 A
(0.46), 3.94 A (0.73), 3.58 A (0.36), 3.41 A (0.34), 3.34 A
(0.28), 2.80 A (0.17). Anal. Calcd for C34H38N4O6: C, 68.21;
˚
˚
˚
˚
˚
˚
˚
H, 6.40; N, 9.36. Found: C, 68.09; H, 6.49; N, 9.31.
1
(R,R)-1·(S)-2: colorless plate crystals: mp 180ЊC dec.; H
NMR (300 MHz: D2O) d 1.64 (d, Jˆ6.9 Hz, 6H), 4.54 (d,
Jˆ6.9 Hz, 2H), 5.16 (s, 2H), 7.35–7.51 (m, 20H); IR (KBr):
3341, 3060, 3036, 2968, 2924, 2190, 1663, 1578, 1492,
1396, 1375, 1234, 1092, 1064, 770, 695 cmϪ1; Powder
1
0.38 mmol, 83%) as a white powder: mp 235ЊC dec.; H
NMR (300 MHz: d4-MeOH) d 5.46 (s, 2H), 7.31–7.48
(m, 10H); IR (KBr): 3286, 3934, 2921, 1719, 1664, 1520,
1420, 1220, 1093, 1068, 934, 723, 695 cmϪ1. Anal. Calcd
for C18H16N2O6: C, 60.67; H, 4.53; N. 7.86. Found: C,
60.50; H, 4.47; N. 7.69.
˚
˚
˚
X-ray Analysis (I/I0) 13.50 A (0.56), 6.74 A (1.00), 4.47 A
˚
(0.08), 3.36 A (0.38). Anal. Calcd for C34H38N4O6: C, 68.21;
H, 6.40; N, 9.36. Found: C, 68.26; H, 6.29; N, 9.31.
1
meso-1·(^)-2: colorless plate crystals: mp 180ЊC dec.; H

M. Akazome et al. / Tetrahedron 56 (2000) 753–761
761
¨
6. Aakeroy, C. B.; Nieuwenhuyzen, M. J. Am. Chem. Soc. 1994,
NMR (300 MHz: D2O) d 1.63 (d, Jˆ7.0 Hz, 6H), 4.52 (d,
Jˆ7.0 Hz, 2H), 5.18 (s, 2H), 7.30–7.51 (m, 20H); IR
(KBr): 3347, 3062, 3036, 2936, 2150, 1659, 1491, 1387,
1238, 1186, 1092, 1064, 758, 728, 699 cmϪ1; Powder
116, 10 983.
7. (a) Coe, S.; Kane, J. J.; Nguyen, T. L.; Toledo, L. M.; Wininger,
E.; Fowler, F. W.; Lauher, J. W. J. Am. Chem. Soc. 1997, 119, 86.
(b) Chang, Y.-L.; West, M.-A.; Fowler, F. W.; Lauher, J. W. J. Am.
Chem. Soc. 1993, 115, 5991. (c) Zhao, X.; Chang, Y.-L.; Fowler, F.
W.; Lauher, J. W. J. Am. Chem. Soc. 1990, 112, 6627.
8. (a) Karle, I. L.; Ranganathan, D.; Sha, K.; Vaish, N. K. Int. J.
Peptide Protein Res. 1994, 43, 160. (b) Karle, I. L.;
Ranganathan, D. Int. J. Peptide Protein Res. 1995, 46, 18. (c)
Karle, I. L.; Ranganathan, D. Biopolymers 1995, 36, 323.
9. For a preliminary accounts of this work, see: Akazome, M.;
Takahashi, T.; Ogura, K. Tetrahedron Lett. 1998, 39, 4839.
10. Sada, K.; Maeda, T.; Miyata, M. Chem. Lett. 1996, 837.
11. Brianso, P. M. C. Acta Cryst. 1984, B32, 3040.
12. (a) Kinbara, K.; Sakai, K.; Hashimoto, Y.; Nohira, H.; Saigo,
K. J. Chem. Soc., Perkin Trans. 2 1996, 2615. (b) de Diego, H. L.
Acta Chem. Scand. 1994, 48, 306. (c) Zingg, S. P.; Arnett, E. M.;
McPhail, A. T.; Brthner-By, A. A.; Gilkerson, W. R. J. Am. Chem.
Soc. 1988, 110, 1565. (d) Brianso, P. M.-C.; Leclercq, M.;
Jacques, J. Acta Cryst. 1979, B35, 2751.
˚
˚
˚
X-ray Analysis (I/I0) 15.49 A (1.00), 7.70 A (0.04), 5.12 A
˚
˚
(0.03), 3.84 A (0.17).3.07 A (0.03). Anal. Calcd for
C34H38N4O6: C, 68.21; H, 6.40; N, 9.36. Found: C, 67.93;
H, 6.26; N, 9.27.
1
meso-1·(R)-2: colorless plate crystals: mp 189.2ЊC dec.; H
NMR (300 MHz: d4-CD3OD) d 1.57 (d, Jˆ6.9 Hz, 6H),
4.37 (q, Jˆ6.9 Hz, 2H), 5.16 (s, 2H), 7.20–7.45 (m, 20H);
IR (KBr): 3344, 3031, 2925, 2132, 1658, 1592, 1494,
1384, 1240, 1198, 1093, 1066, 730, 698 cmϪ1; Powder
˚
˚
˚
X-ray Analysis (I/I0) 14.97 A (1.00), 7.52 A (0.05), 5.02 A
˚
(0.05), 3.77 A (0.17). Anal. Calcd for C34H38N4O6: C, 68.21;
H, 6.40; N, 9.36. Found: C, 67.88; H, 6.35; N, 9.27.
Acknowledgements
This work was supported by Grant-in-Aids for Research for
the Future Program (JSPS-RFTF96P00304) and Encourage-
ment of Young Scientists (No. 11750733) from the Japan
Society for the Promotion of Science.
13. The conformations of oxalyl groups in oxalylamide and N,N0-
dimethyloxamide are complete transoid. (a) Ayerst, E. M.; Duke,
J. R. C. Acta Crystallogr. 1954, 7, 588. (b) Adiwidjaja, G.; Voß, J.
Chem. Ber. 1977, 110, 1159.
14. Hydrogen bonding of 12-membered ring structure in several
ammonium carboxylates. For recent papers; (a) Kinbara, K.;
Hashimoto, Y.; Sukegawa, M.; Nohira, H.; Saigo, K. J. Am.
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