Molecular self-assembly and optical activity of chiral thionooxalamic acid esters

Article abstract of DOI:10.1016/j.tetasy.2007.06.019

Three chiral bisthionooxalamides were synthesized by acylation with ethyl or (1R)-menthyl chloroxoacetate of the corresponding diamines and subsequent thionation with Lawesson's reagent. Single crystal X-ray diffraction analysis revealed that products 4b-

Full text of DOI:10.1016/j.tetasy.2007.06.019

Tetrahedron: Asymmetry 18 (2007) 1486–1494
Molecular self-assembly and optical activity of
chiral thionooxalamic acid esters
a
a
b
a,
*
´
Barbara Piotrkowska, Maria J. Milewska, Maria Gdaniec and Tadeusz Połonski
aDepartment of Chemistry, Technical University, 80-952 Gdan´sk, Poland
bFaculty of Chemistry, A. Mickiewicz University, 60-780 Poznan´, Poland
Received 15 May 2007; accepted 18 June 2007
Abstract—Three chiral bisthionooxalamides were synthesized by acylation with ethyl or (1R)-menthyl chloroxoacetate of the corre-
sponding diamines and subsequent thionation with Lawesson’s reagent. Single crystal X-ray diffraction analysis revealed that products
4b–7b self-assemble in the solid state by the ring [N–Hꢀ ꢀ ꢀO@C, R22ð10Þ] or chain [N–Hꢀ ꢀ ꢀS@C, C(4)] hydrogen-bond motifs. Only in the
case of 4b was a helical superstructure formed. In racemic compound 6b, the molecules are connected via N–Hꢀ ꢀ ꢀS@C hydrogen bonds
into homochiral chains, similar to those formed in 7b. The solid state CD spectra of chiral bisthionooxalamides are characterized by
strong Cotton effects in the region of the thioamide n–p* transition. Their sign is determined by the helicity of the S@C–C@O unit.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
They can result in the formation of one-dimensional chains
or tapes, two-dimensional sheets or layers and various
three-dimensional structures.
The construction of complex supramolecular architectures
by the self-assembly of a molecular species via weak non-
covalent interactions in the solid state is the main goal of
crystal engineering.1 Particularly, attractive targets are heli-
cal assemblies that are indispensable structural elements in
biological systems. The helical organization of molecules is
an ubiquitous phenomenon in Nature and appears to play
a critical role in molecular recognition and information
storage.2 In view of the importance of helical chirality as
a structural motif, there have been many efforts to intro-
duce helicity into artificial systems.3 The construction of
such systems by self-assembly is a promising alternative
to a stepwise covalent synthesis. Among the variety of
intermolecular interactions, relatively strong and direc-
tional hydrogen bonds appear to be the most important
driving force for stabilizing a supramolecular structure.
To explore the possibility of a helix supramolecular archi-
tecture, we chose oxalamic esters due to their ability to
form self-complementary hydrogen-bonding interactions,
motif I,4 very similar to that known for simple oxalamides,5
which have found wide application as supramolecular
building blocks for construction of ordered solid state
assemblies,5,6 meso-helicate structures,7 and gelators yield-
ing thermo-reversible gels.8 A Cambridge Structural Data-
base (CSD)9 survey revealed that oxalamic esters also
readily form chain motif II10 involving only amide units.
In contrast to oxalamides organizing into polymeric tape
structures, simple oxalamic acid esters can form only di-
mers with the use of the hydrogen-bond motif I. Thus com-
pounds bearing at least two such functions are required for
O
N
OR
X
O
N
OR
X
O
N
OR
X
O
OR
X
NH
O
X
H
H
H
HN
RO
I
II
X = O or S
*
Corresponding author. Tel.: +48 58 3471528; fax: +48 58 3472694; e-mail: tadpol@chem.pg.gda.pl
0957-4166/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.06.019

B. Piotrkowska et al. / Tetrahedron: Asymmetry 18 (2007) 1486–1494
1487
the construction of polymeric assemblies with use of this
cyclic motif. We expected that upon acylation, trans-1,2-
diaminocyclohexane 1, 1,2-diphenylethylenediamine 2,
and 2,20-diaminobiphenyl 3 residues may serve as scaffolds
to create helical hydrogen-bonded structures. To assure us
of obtaining homochiral supramolecular assemblies, we
used optically active amines 1 and 2, whereas in the case
of 3, the acylation was carried out with the use of the chiral
acid chloride. We also anticipated that substitution of the
amide carbonyl oxygen by sulfur should enhance the acid-
ity of the amide proton making it a stronger hydrogen-
bond donor and additionally should promote formation
of the cyclic motif I since the thiocarbonyl sulfur atom is
a much weaker hydrogen-bond acceptor than the carbonyl
oxygen. Substitution of O for S, causes bathochromic shifts
of the corresponding UV and CD bands, facilitating the
spectroscoping measurements.11 Thus, we designed and
synthesized thionooxamides 4b–7b and examined their
ability to generate helical networks in the solid state by sin-
gle crystal X-ray analysis and CD measurements.
Within the molecule, the thionooxalamide groups are in
close contact and are oriented in an approximately anti-
parallel manner (Fig. 1a). The thioamide and ester parts
of these groups are significantly twisted along the C–C
bond with the S@C–C@O torsion angle of ꢁ156.8(1)°.
The thionoxalamide units generate the intermolecular
hydrogen-bond motif I through N–Hꢀ ꢀ ꢀO@C interaction
˚
[hydrogen-bond geometry: Nꢀ ꢀ ꢀO 2.968(2) A; N–Hꢀ ꢀ ꢀO
157(1)°] (Fig. 1c). The twisted conformation of the thiono-
oxalamide groups leads to the twisted motif I, and prevents
short intermolecular contacts, which would be formed be-
tween neighboring molecules of 4b if they were joined by
the planar motif I. Hydrogen-bonded molecules of 4b form
an extended right-handed helix of the 31 symmetry which
˚
runs along the c-axis and has a pitch of 18.3 A (Fig. 1b
and c).
Compound 5b crystallizes as a solvate in the orthorhombic
P212121 space group with two molecules of thioxalamic
acid ester and one molecule of toluene in the asymmetric
part of the unit cell. The molecules of 5b, which are located
in the crystal at general positions, adopt the conformation
of an approximate C2 symmetry, which is mostly broken by
the terminal ethyl substituents. Despite a similarity in the
molecular symmetry between 4b and 5b, a spatial arrange-
ment adopted by thionooxalamide groups is quite different
in the two crystal structures: in 5b the torsion angle along
the N–Csp3 bond of the thionooxalamide group is in the
range 155.8(4)–166.5(4)° whereas in 4b, the analogues tor-
sion angle is ꢁ94.5(2)°. The conformation adopted by 5b
allows the formation of discrete supramolecular assemblies
composed of two symmetry independent molecules joined
by a pair of strongly twisted cyclic motifs I. These hydro-
gen-bonded assemblies have an approximate D2 symmetry
(Fig. 2b). The non-planarity of the cyclic motif reflects a
strong twist of thionoxalamide units which most probably
results from the optimalization of intradimer hydrogen-
bonding interactions. The S@C–C@O torsion angle values
range from ꢁ146.7(3)° to ꢁ159.9(3)°.
X
X
NHCCO2Et
Ph
Ph
NHCCO2Et
NHCCO2Et
X
NHCCO2Et
X
5a, X = O
5b, X = S
4a, X = O
4b, X = S
X
X
NHCCO2Et
EtO2CCNH
OCOCNH
2
X
7a, X = O
7b, X = S
6a, X = O
6b, X = S
Whereas compounds 4b and 5b are chiral, bisthionooxal-
amide 6b is achiral and its orange needle-shaped crystals
obtained from toluene belong to the centrosymmetric space
ꢀ
2. Results and discussion
group P1. There are two symmetry independent molecules
of 6b in the crystal, both adopting similar asymmetric con-
formations with the phenyl rings rotated by 61.6(3)° and
57.5(3)° about the central C–C bond. One thionoxalamide
unit is nearly planar whereas the second one is significantly
twisted [the corresponding S@C–C@O torsion angles are of
177.6(4)°, 178.1(3)° for planar units and 137.0(3)°,
137.9(3)° for twisted units]. The chiral conformations of
the molecules are fixed by the intramolecular N–Hꢀ ꢀ ꢀS@C
hydrogen bond between the two thionoxalamide ester
groups, which in 6b are separated by three C–C bonds.
The N–H groups not involved in the intramolecular inter-
action act as donors in intermolecular N–Hꢀ ꢀ ꢀS@C hydro-
gen bonding, joining the homochiral molecules of 6b into
infinite chiral chains (Fig. 3b). Thus, in bisthionooxalamide
6b, only thionamide groups are involved in hydrogen-
bonding and motif II encompasses both intra- and inter-
molecular N–Hꢀ ꢀ ꢀS@C interactions. In the crystal, there
are two symmetry independent chiral chains but since the
Bisoxalamide esters 4a–6a were obtained by acylation of
the corresponding diamines with ethyl chlorooxoacetate.
Compound 7a was prepared via the use of (1R)-menthyl
chloroxoacetate obtained from (ꢁ)-menthol and oxalyl
chloride. Thionation of compounds 4a–7a with Lawesson’s
reagent12 in boiling toluene afforded bisthionooxalamides
4b–7b. The reaction occurred selectively at the amide car-
bonyl, since the ester group is much less reactive to Lawes-
son’s reagent.12b
Yellow needles of 4b were grown from toluene. X-ray
structural analysis revealed that crystals of 4b belong to
the hexagonal P6422 space group, with the molecule
located at the special position of the C2 symmetry. The
bisthionooxalamide molecule adopts a conformation in
which the equatorially oriented NH groups point up and
down with respect to the mean cyclohexane ring plane.

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B. Piotrkowska et al. / Tetrahedron: Asymmetry 18 (2007) 1486–1494
Figure 1. Crystal structure of 4b: (a) side view of the molecule showing anti-parallel arrangement of the thionooxalamide groups; (b) the right-handed
helix via hydrogen bonds—view along the c-axis; (c) view perpendicular to the helix axis. Hydrogen bonds are shown as dashed lines.
structure is centrosymmetric, the chains of the opposite
chirality co-exist within one crystal lattice.
it can be unequivocally assigned to the n–p* electronic tran-
sition. A much stronger absorption at 300 nm (e 11,000) is
only slightly dependent on the solvent polarity changes and
corresponds to the allowed p–p* excitation. Compounds 5b
and 7b behave in a similar manner. Interactions between
two carbonyl or thiocarbonyl groups result in the splitting
of the n, p, and p* levels.13 However, in monothiooxamides
the carbonyl and thiocarbonyl n as well as p levels have
rather different energies and their interaction is much
weaker.14 In fact, the two lowest energy transitions occur
at much shorter wavelengths than those observed in dithio-
oxamides and the UV–vis spectra of monothiooxamides
resemble those of simple thioamides. The twisted oxamide
and dithiooxamide systems are inherently chiral while the
sign of the CD band corresponding to the lowest energy
n–p* transition is determined by helicity of these chro-
mophores. Thus the right-handed chirality (P-helicity) of
the twisted chromophore should lead to the negative Cot-
ton effect at the region of the n–p* excitation and left-
handed chirality (M-helicity) to the positive one.13d,15 An
analogous behavior is also expected for monothioox-
amides. The solid state CD of 4b, measured in a KBr disk
shown in Figure 4, featured a strong positive Cotton effect
near 460 nm in accordance with the X-ray structure reveal-
ing the left-handed twist of the thionoxalamide unit. Obvi-
ously, upon dissolution of the crystal, the helical structure
Compound 7b (yellow prisms, space group P21) is the chi-
ral analogue of 6b with the ester ethyl groups changed to
chiral (1R,2S,5R)-menthyl units. The crystal structure of
7b reveals that the twist angle between the phenyl rings
of the core biphenyl, assuming the P-helicity, is of
61.2(2)°. Similar to 6b, the twisted conformation is stabi-
lized by an intramolecular N–Hꢀ ꢀ ꢀS@C interaction
(Fig. 3a) and molecules related by translation along the
b-axis are connected via hydrogen bonds into chiral chains
(Fig. 3b). In 7b, the intermolecular three-center hydrogen
bonds are formed between the CO and CS groups of the
cis-oriented thionoxalamide unit (the S@C–C@O dihedral
angle is of 13.5(2)°) and the NH hydrogen of the twisted
trans-thionoxalamide group [the S@C–C@O dihedral angle
is of 139.7(2)°] (Fig. 3b).
In order to obtain more information with regards to the
formation and helical organization of the aggregates, we
studied the UV–vis and CD spectra of the thionooxal-
amides 4b–7b in the solid state and in solution. The UV–
vis spectrum of 4b taken in the cyclohexane–CH2Cl2 (4:1)
shows a weak absorption near 440 nm (e 50), which shifts
to ca. 400 nm upon changing the solvent to methanol. Thus

B. Piotrkowska et al. / Tetrahedron: Asymmetry 18 (2007) 1486–1494
1489
450 and 400 nm in the solid state spectrum corresponding
to the n–p* transition in the nearly planar cis- and twisted
trans-thionooxalamide group, respectively, assuming P-
helicity. The solution spectra appeared to be extremely
sensitive to solvent polarity and feature an exciton cou-
plet16 in the region of the p–p* transition; a positive one
in cyclohexane–CH2Cl2 and a negative one in methanol.
They correspond to the right- and left-handed screwness,
respectively, of the transition moments of the chromo-
phores assuming two mutual different orientations induced
by solvent changes in the conformationally flexible mole-
cule of 7b.
3. Conclusion
In conclusion, our results have shown that bisthionooxal-
amides are supramolecular monomers with a potential to
self-associate through intermolecular hydrogen bonds into
helices in the solid state. Using optically active monomers
the crystalline homochiral, infinite as well as discrete supra-
molecular assemblies can be prepared. However, the inter-
molecular N–Hꢀ ꢀ ꢀO@C hydrogen bonds formed by two
oxalamide functions are generally weaker than those
involving two simple amide groups,17 which makes the pre-
diction and control of the three-dimensional structure of
the aggregates rather difficult. The long-wavelength
absorption of the thionooxalamide chromophore facilitates
the monitoring of the conformational changes within the
molecules with use of the solid state and solution CD
measurements.
4. Experimental
1H and 13C NMR spectra were obtained with a Varian
Unity Plus spectrometer at 500 and 125 MHz, respectively.
The deuteriated solvents were used as an internal lock for
1H and 13C NMR. FT-IR absorptions were taken with a
Bruker IFS66 spectrometer. CD spectra were recorded on
a JASCO J-715 dichrograph. The solid state CD spectra
were taken in freshly prepared KBr disk. A mixture of
3 mg of the sample and 200 mg of dried KBr was ground
and formed into a disk 0.5 mm thick and with a radius of
15 mm. The disk was rotated around the optical axis and
the CD recordings were made for several positions in order
to check a reproducibility of the spectrum. The solution
CD spectra were taken using 1 and 0.5 mm path lengths
and sample concentration of 0.001–0.005 mol Lꢁ1. The
UV–vis spectra were measured with Unicam SP-300
spectrophotometer.
Figure 2. Crystal structure of 5b: (a) conformation adopted one of the
symmetry independent molecules of 5b in the crystal and (b) hydrogen-
bonded dimeric assembly formed by the two symmetry independent
molecules of 5b showing an approximate D2 symmetry (with indicated
directions of pseudo twofold axes). Hydrogen bonds are shown as dashed
lines.
is lost which results in a decrease in the long-wavelength
CD signal, which moves to shorter wavelengths and inverts
the sign. The latter effect indicates that the P-helicity of the
chromophore predominates in solution. In contrast, a
strong positive Cotton effect at 450 nm exhibited by 5b in
the solid state also persists in solution (Fig. 5), which
means that the helical dimer structure is at least partially
preserved in solution. A moderately strong CD near
470 nm observed in a non-polar solvent splits into two
overlapping positive bands at 420 and 380 nm upon chang-
ing the solvent to methanol and that might be due to a con-
tribution from two species with different degree of the
chromophore twist. They are most likely responsible for
the two negative Cotton effects observed in the region of
the p–p* excitation.
4.1. (1S,2S)-N,N0-1,2-Cyclohexanediyl-bis-oxalamic acid
diethyl ester, 4a
To a solution of (1S,2S)-(+)-1,2-diaminocyclohexane 118
(2.09 g, 18.3 mmol) in chloroform (35 mL), ethyl chloro-
oxoacetate (4.07 mL, 36.7 mmol) and triethylamine
(5.7 mL, 41 mmol) were added and the mixture was kept
at room temperature overnight. The reaction mixture was
washed with water, dilute hydrochloric acid, and saturated
aqueous NaHCO3. The organic layer was dried over
The lack of helical organization of the molecules of bis-
thionooxalamide 7b results only in weak Cotton effects
in the solid state as well as in solution CD spectra
(Fig. 6). There are two weak negative CD bands near

1490
B. Piotrkowska et al. / Tetrahedron: Asymmetry 18 (2007) 1486–1494
Figure 3. Comparison of crystal structures of the biphenyl derivatives 6b and 7b: (a) asymmetric conformations with intramolecular hydrogen bonds (alkyl
substituents omitted for clarity)—the cis-oriented thionoxalamide group in 7b should be noted; (b) chiral chains in the racemic 6b (the two chains of
opposite chirality are symmetry independent) and in chiral 7b.
40
40
εx10-3
[Θ]x10-3
35
30
25
20
15
10
5
x10
20
0
OCH2CH3
S
NH
-20
-40
-60
-80
O
NH
S
O
OCH2CH3
x100
400
X100
0
200
300
500
600
λ[nm]
Figure 4. Solid state and solution CD and UV–vis spectra of 4b taken in a KBr disk, cyclohexane–CH2Cl2 (4:1) and MeOH (red, black, and blue lines,
respectively).
MgSO4 and then evaporated at reduced pressure. The
resulting solid was recrystallized from chloroform–hexane
1679 cmꢁ1. Anal. Calcd for C14H22N2O6 (314): C, 53.50;
H, 7.05; N, 8.91. Found: C, 53.38; H, 6.95; N, 8.82.
to obtain the product as white needles (3.5 g, 60%); mp
25
150.5–152 °C; ½aꢂD ¼ ꢁ31 (c 1.168, CHCl3); 1H NMR
4.2. (1S,2S)-N,N0-1,2-Cyclohexanediyl-bis-thiooxalamic
acid diethyl ester, 4b
(CDCl3) d 7.3 (br s, NH, 2H), 4.34 (m, 4H), 3.8 (s, 2H),
2.11 (d, J = 6.3 Hz, 2H), 1.83 (s, 2H), 1.38 (t, J = 7.1 Hz,
10H); 13C NMR (CDCl3) d 160.1, 156.8, 63.1, 53.5, 31.7,
24.3, 13.8; mmax (KBr) 3370, 3314, 1729, 1704, and
A mixture of 4a (0.985 g, 3.13 mmol) and Lawesson’s
reagent (1.267 g, 3.13 mmol) in toluene (60 mL) was

B. Piotrkowska et al. / Tetrahedron: Asymmetry 18 (2007) 1486–1494
1491
60
30
-3
x10
ε
-3
[Θ]
x10
20
10
50
40
30
20
10
0
x10
x5
0
-10
-20
-30
-40
-50
-60
OCH2CH3
S
O
Ph
Ph
NH
NH
S
O
OCH2CH3
x100
400
x100
200
300
500
600
λ[nm]
Figure 5. Solid state and solution CD and UV–vis spectra of 5b taken in a KBr disk, cyclohexane–CH2Cl2 (4:1) and MeOH (red, black, and blue lines,
respectively).
1.5
60
-3
x 10-3
[Θ]
x 10
ε
S
1.0
0.5
O
O
50
40
30
20
10
0
N
H
S
O
HN
O
x10
0.0
-0.5
-1.0
-1.5
-2.0
-2.5
x5
x100
x50
200
300
400
500
600
λ [nm]
Figure 6. Solid state and solution CD and UV–vis spectra of 7b taken in a KBr disk, cyclohexane–CH2Cl2 (4:1) and MeOH (red, black, and blue lines,
respectively).
refluxed for 0.5 h. After removal of the solvent, the residue
was purified by column chromatography on silica gel [elu-
tion with chloroform–hexane (1:1)]. The product was crys-
for C14H22N2O4S2 (346.5): C, 48.54; H, 6.39; N, 8.09; S,
18.51. Found: C, 48.54; H, 6.28; N, 8.02; S, 18.68.
4.3. (1R,2R)-N,N0-1,2-Diphenyl-1,2-ethanediyl-bis-oxalamic
acid diethyl ester, 5a
tallized from toluene–hexane to give the title compound as
25
yellow needles (0.73 g, 67%); mp 87–88 °C; ½aꢂD ¼ ꢁ442 (c
0.052, CHCl3); 1H NMR (CDCl3) d 9.18 (s, NH, 2H), 4.63
(br s, 2H), 4.35 (m, 4H), 2.29 (br s, 2H), 1.89 (br s, 2H),
1.45 (d, J = 7.8 Hz, 4H), 1.39 (t, J = 7.1 Hz, 6H); mmax
(KBr) 3293, 1702, 1528, 1269, and 1246 cmꢁ1. Anal. Calcd
Compound 5a was prepared from (1R,2R)-(+)-1,2-diphen-
ylethylenediamine 219 in a similar manner to that of com-
25
pound 4a in 78% yield; mp 178–180 °C; ½aꢂD ¼ ꢁ103:8 (c

1492
B. Piotrkowska et al. / Tetrahedron: Asymmetry 18 (2007) 1486–1494
0.106, CHCl3); 1H NMR (CDCl3) d 7.9 (s, NH, 2H), 7.28–
7.15 (m, 10H), 5.37 (dd, J = 5.86 Hz and 2.45 Hz, 2H), 4.35
(m, 4H), 1.38 (t, J = 7.3 Hz, 6H); 13C NMR (CDCl3) d
160.0, 156.8, 136.9, 128.6, 128.2, 127.5, 63.2, 58.8, 13.8;
mmax (KBr) 3591, 3299, 1742, and 1675 cmꢁ1. Anal. Calcd
for C22H24N2O6 (412): C, 64.07; H, 5.86; N, 6.79. Found:
C, 64.01; H, 5.94; N, 6.77.
the solvent was evaporated at reduced pressure. The
residue was distilled in vacuo; the fraction boiling at
120–125 °C (15 mmHg) was collected to give (1R,2S,5R)-
22
menthyl chlorooxoacetate;21 yield 70%, ½aꢂD ¼ ꢁ82:4
(neat).
Compound 7a was prepared from 2,20-diaminobiphenyl 3
and freshly prepared (1R,2S,5R)-menthyl chlorooxoacetate
4.4. (1R,2R)-N,N0-1,2-Diphenyl-1,2-ethanediyl-bis-thio-
oxalamic acid diethyl ester, 5b
in a similar manner to that of compound 4a in 60% yield;
25
mp 134–136 °C (CCl4); ½aꢂD ¼ ꢁ82:8 (c 0.169, CHCl3);
1H NMR (CDCl3) d 8.77 (s, NH, 2H), 8.59 (dd,
J = 8.1 Hz and 2.2 Hz, 2H), 7.56 (t, J = 7.6 Hz, 2H), 7.35
(m, 4H), 4.75 (t, J = 10.9 Hz, 2H), 1.95 (d, J = 8.3 Hz,
2H), 1.78–1.68 (m, 6H), 1.46 (br t, J = 10 Hz, 4H), 1.04
(q, J = 11.8 Hz, 4H), 0.91 (d, J = 6.3 Hz, 7H), 0.87 (t,
J = 6.3 Hz, 7H), 0.70 (t, J = 6.8 Hz, 6H); 13C NMR d
159.5, 159.3, 153.8, 134.6, 134.5, 130.1, 126.7, 126.6,
125.6, 121.0, 120.9, 78.4, 46.4, 46.3, 40.1, 39.9, 33.9, 33.8,
31.3, 26.0, 23.1, 21.8, 20.6, 16.0; mmax (KBr) 3308, 1794,
1715, 1700, and 1520 cmꢁ1. Anal. Calcd for C36H48N2O6
(605): C, 71.50; H, 8.00; N, 4.63. Found: C, 71.28; H,
7.97; N, 4.51.
Bisthionooxalamide 5b was obtained in a similar manner to
that of compound 4b. The product was isolated by chroma-
tography on silica gel with chloroform as an eluent and
after crystallization from toluene, was obtained as a 2:1 sol-
25
vate with toluene, yield 62%; mp 76–79 °C; ½aꢂD ¼ ꢁ155:6
1
(c 0.045, CHCl3); H NMR (CDCl3) d 9.67 (br s, NH,
2H), 7.31–7.24 (m, 10H), 6.19 (dd, J = 5.9 Hz and
2.9 Hz, 2H), 4.37 (m, 4H), 1.39 (t, J = 7.1 Hz, 6H); 13C
NMR (CDCl3) d 184.0, 158.7, 135.5, 128.9, 128.8, 128.0,
63.2, 63.1, 13.8; mmax (KBr) 3236, 1739, 1726, 1516, and
1270 cmꢁ1. Anal. Calcd for C22H24N2O4S2 (444.5): C,
59.44; H, 5.44; N, 6.30; S, 14.43. Found: C, 59.19; H,
5.44; N, 6.27; S, 14.51.
4.8. N,N0-Biphenyl-2,20-diyl-bis-thiooxalamic acid di-
(1R,2S,5R)-menthyl ester, 7b
4.5. N,N0-Biphenyl-2,20-diyl-bis-oxalamic acid diethyl ester,
6a
The bisthionooxalamide 7b was obtained in a similar man-
ner to that of compound 4b. The product was isolated by
column chromatography on silica gel with benzene as an
eluent. Yield 59%; mp 228–230 °C (toluene–hexane);
Compound 6a was prepared from 2,20-diaminobiphenyl 320
in a similar manner to that of compound 4a in 58% yield;
mp 143 °C (CH2Cl2–hexane); 1H NMR (CDCl3) d 8.73
(s, NH, 2H), 8.52 (d, J = 7.8 Hz, 2H), 7.56 (td,
J = 8.7 Hz and 1.9 Hz, 2H), 7.33 (td, J = 7.6 Hz and
1.1 Hz, 2H), 7.32 (dd, J = 7.8 Hz and 1.7 Hz, 2H), 4.29
(q, J = 7.2 Hz, 4H), 1.32 (t, J = 7.1 Hz, 6H); mmax (KBr)
cmꢁ1 3348, 1707, 1531, 1290 cmꢁ1. Anal. Calcd for
C20H20N2O6 (394): C, 62.50; H, 5.24; N, 7.29. Found: C,
62.39; H, 5.26; N, 7.20.
25
1
½aꢂD ¼ ꢁ150 (c 0.04, CHCl3); H NMR (CDCl3) d 10.27
(s, NH, 2H), 8.56 (d, J = 8.3 Hz, 1H), 8.37 (d,
J = 8.3 Hz, 1H), 7.54 (q, J = 7.5 Hz, 2H), 7.41 (q,
J = 7.3 Hz, 2H), 7.34 (t, J = 8.3 Hz, 2H), 4.73 (m, 2H),
1.96 (br t, J = 5.2 Hz, 2H), 1.62 (m, 6H), 1.45 (m, 4H),
1.05 (m, 4H), 0.9 (m, 8H), 0.88 (d, J = 6.8 Hz, 3H), 0.83
(d, J = 6.8 Hz, 3H), 0.72 (d, J = 6.8 Hz, 3H), 0.68 (d,
J = 6.8 Hz, 3H); mmax (KBr) 3476, 3179, 1747, 1718, 1512,
1275, and 1240 cmꢁ1. Anal. Calcd for C36H48N2O4S2
(637): C, 67.89; H, 7.60; N, 4.40; S, 10.06. Found: C,
67.66; H, 7.65; N, 4.46; S, 9.99.
4.6. N,N0-Biphenyl-2,20-diyl-bis-thiooxalamic acid diethyl
ester, 6b
Bisthionooxalamide 6b was obtained in a similar manner to
that of compound 4b. The product was isolated by chroma-
tography on silica gel with benzene as an eluent; yield 66%;
mp 139–140 °C (CH2Cl2–hexane); 1H NMR (CDCl3) d
10.27 (s, NH, 2H), 8.52 (d, J = 8.3 Hz, 2H), 7.54 (td,
J = 8.5 Hz and 1.5 Hz, 2H), 7.42 (td, J = 7.6 Hz and
0.98 Hz, 2H), 7.34 (dd, J = 7.8 Hz and 1.5 Hz, 2H), 4.28
(q, J = 7.1 Hz, 4H), 1.32 (t, J = 7.3 Hz, 6H); mmax cmꢁ1
3421, 3131, 1718, 1365, 1275, and 1261 cmꢁ1. Anal. Calcd
for C20H20N2O4S2 (416.5): C, 57.68; H, 4.84; N, 6.72; S,
15.40. Found: C, 57.43; H, 4.81; N, 6.75; S, 15.28.
4.9. X-ray structure analysis
Diffraction data were collected using a Kuma CCD diffrac-
tometer with graphite monochromated Mo Ka radiation
˚
(k = 0.71073 A). The structures were solved by direct meth-
ods with the program SHELXS-97.22 Full matrix least-
squares refinement was carried out with SHELXL-97.23
Crystal data for 4b: C14H22N2O4S2, M = 346.46, hexa-
gonal, space group P6422, a = b = 12.9170(5), c =
3
˚
˚
18.2939(7) A, V = 2643.38(18) A , T = 120 K, Z = 6,
l(Mo Ka) = 0.320 mmꢁ1, k = 0.71073 A, 15,300 reflec-
˚
4.7. N,N0-Biphenyl-2,20-diyl-bis-oxalamic acid di-
(1R,2S,5R)-menthyl ester, 7a
tions measured, 1800 unique (Rint = 0.0274). Final residu-
als for 104 parameters were R1 = 0.0260, wR2 = 0.0573
for 1782 reflections with I > 2r(I), and R1 = 0.0266,
wR2 = 0.0576 for all 1800 data; absolute structure Flack
parameter 0.02(8).
A solution of oxalyl chloride (2.1 mL, 25 mmol) in dichloro-
methane (10 mL) was cooled to ꢁ10 °C and (ꢁ)-menthol
(3.9 g, 25 mmol) in dichloromethane (10 mL) was then
added with stirring and cooling. The reaction mixture
was left to stand for 10 h at room temperature and then
Crystal data for 5b: (C22H24N2O4S2)2ÆC7H8, M = 981.28,
orthorhombic, space group P212121, a = 12.3362(15), b =

B. Piotrkowska et al. / Tetrahedron: Asymmetry 18 (2007) 1486–1494
1493
3
˚
˚
W., Ed.; CRC Press: Boca Raton, 1997; (e) Chin, D. N.;
Zerkowski, J. A.; MacDonald, J. C.; Whitesides, G. M. In
Organised Molecular Assemblies in the Solid State; Whitesell,
J. K., Ed.; Wiley: Chichester, 1999; Chapter 5; (f) Moulton,
B.; Zaworotko, M. J. Chem. Rev. 2001, 101, 1629.
12.3866(10), c = 34.3572(16) A, V = 5249.9(8) A , T =
120 K, Z = 4, l(Mo Ka) = 0.235 mmꢁ1, k = 0.71073 A,
˚
25,841 reflections measured, 9179 unique (Rint = 0.0785).
Final residuals for 605 parameters were R1 = 0.0508,
wR2 = 0.0945 for 9013 reflections with I > 2r(I), and
R1 = 0.0520, wR2 = 0.0949 for all 9179 data; absolute
structure Flack parameter 0.07(9). The structure was deter-
mined from a pseudo-merohedral twinned crystal with the
2. (a) Schulz, G. E.; Schirmer, R. H. Principles of Protein
Structure; Springer: New York, 1979; Chapter 5; (b) Saenger,
W. Principles of Nucleic Acid Protein Structure; Springer:
New York, 1984; Chapters 10 and 11.
twin matrix ½0
1
0
ꢁ1
0
0
0
0
1ꢂ . The diethyl
3. (a) Katz, T. J. Angew. Chem., Int. Ed. 2000, 39, 1921; (b) Hill,
D. J.; Mio, M. J.; Prince, R. B.; Hughes, T. S.; Moore, J. S.
Chem. Rev. 2001, 101, 3893; (c) Albrecht, M. Angew. Chem.,
Int. Ed. 2005, 44, 6448; (d) Piguet, C.; Bernardinelli, G.;
Hopfgartner, G. Chem. Rev. 1997, 97, 2005.
4. Garcia-Baez, E. V.; Gomez-Castro, C. Z.; Hopfl, H.; Mar-
tinez-Martinez, F. J.; Padilla-Martinez, I. I. Acta Crystallogr.,
Sect. C 2003, 59, o541; Blay, G.; Fernandez, I.; Pedro, J. R.;
Ruiz-Garcia, R.; Munoz, M. C.; Cano, J.; Carrasco, R. Eur.
J. Org. Chem. 2003, 1627.
5. (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) Nguyen, T. L.; Scott, A.; Dinkelmeyer, B.;
Fowler, F. W.; Lauher, J. W. New J. Chem. 1998, 129; (c)
Nguyen, T. L.; Fowler, F. W.; Lauher, J. W. J. Am. Chem.
Soc. 2001, 123, 11057.
6. (a) Simonov, Y. A.; Fonari, M. S.; Zaworotko, M. J.;
Abourahma, H.; Lipkowski, J.; Ganin, E. V.; Yavolovskii, A.
A. Org. Biomol. Chem. 2003, 1, 2922; (b) Fonari, M. S.;
Simonov, Y. A.; Croitoru, L.; Basok, S. S.; Ganin, E. V.;
Lipkowski, J. J. Mol. Struct. 2006, 794, 110; (c) Hsu, Y.-F.;
Chen, J.-D. Eur. J. Inorg. Chem. 2004, 1488.
ether solvate of 5b, (C22H24N2O4S2)2ÆC4H10O, is isostruc-
tural with 5b [space group P212121, a = 12.5950(13),
b = 12.6160(10),
T = 130 K], and also crystallizes as a pseudo-merohedral
twin.
3
˚
˚
c = 33.115(3) A,
V = 5262.0(8) A ,
Crystal data for 6b: C20H20N2O4S2, M = 416.50, triclinic,
ꢀ
space group P1, a = 9.7779(8), b = 14.1859(11), c =
˚
16.4021(14) A, a = 112.554(8), b = 100.510(7), c =
3
˚
91.130(6)°, V = 2055.8(3) A , T = 293 K, Z = 4, l(Mo
Ka) = 0.287 mmꢁ1, k = 0.71073 A, 22,047 reflections mea-
˚
sured, 7251 unique (Rint = 0.0498). Final residuals for 505
parameters were R1 = 0.0505, wR2 = 0.1026 for 3993
reflections with I > 2r(I), and R1 = 0.1121, wR2 = 0.1227
for all 7251 data.
Crystal data for 7b: C36H48N2O4S2, M = 636.88, mono-
clinic, space group P21, a = 12.8620(5), b = 9.5611(4),
3
˚
˚
c = 14.3594(5) A, b = 91.432(3)°, V = 1765.29(12) A , T =
100 K, Z = 2, l(Mo Ka) = 0.0190 mmꢁ1, k = 0.71073 A,
˚
7. Blay, G.; Fernandez, I.; Pedro, J. R.; Ruiz-Garcia, R.;
Carmen-Munoz, M.; Cano, J.; Carrasco, R. Eur. J. Org.
Chem. 2003, 1627.
14,930 reflections measured, 6267 unique (Rint = 0.0159).
Final residuals for 405 parameters were R1 = 0.0322,
wR2 = 0.0843 for 5869 reflections with I > 2r(I), and
R1 = 0.0346, wR2 = 0.0861 for all 6267 data; absolute
structure Flack parameter ꢁ0.05(5).
´
´
´
´
´
8. (a) Makarevic, J.; Jokic, M.; Peric, B.; Tomisic, V.; Kojic-
´
´
Prodic, B.; Zinic, M. Chem. Eur. J. 2001, 7, 3328; (b)
´
´
´
´
Makarevic, J.; Jokic, M.; Frkanec, L.; Katalenic, D.; Zinic,
´
´
M. Chem. Commun. 2002, 2238; (c) Makarevic, J.; Jokic, M.;
´
´
´
´
Raza, Z.; Stefanic, Z.; Kojic- Prodic, B.; Zinic, M. Chem. Eur.
Crystallographic data (excluding structure factors) for the
structures in this paper have been deposited with the Cam-
bridge Crystallographic Data Centre as supplementary
publication numbers CCDC 646359–646362. Copies of
the data can be obtained, free of charge, on application
to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK
[fax: +44(0)-1223-336033 or e-mail: deposit@ccdc.cam.
ac.uk].
J. 2003, 9, 5567.
9. Allen, F. H. Acta Crystallogr., Sect. B 2002, 58, 380.
10. (a) Kocienski, P.; Narquizian, R.; Raubo, P.; Smith, C.;
Farrugia, L. J.; Muir, K.; Boyle, F. T. J. Chem. Soc., Perkin.
Trans. 1 2000, 2357; (b) Hashmi, A. S. K.; Weyrauch, J. P.;
Frey, W.; Bats, J. W. Org. Lett. 2004, 6, 4391; (c) Padilla-
Martinez, I. I.; Chaparro-Huerta, M.; Martinez-Martinez, F.
J.; Hopfl, H.; Garcia-Baez, E. V. Acta Crystallogr., Sect. E
2003, 59, o825; (d) Martinez-Martinez, F. J.; Maya-Lugardo,
P.; Garcia-Baez, E. V.; Hopfl, H.; Hernandez-Diaz, J.;
Padilla-Martinez, I. I. Acta Crystallogr., Sect. E 2005, 61,
o2994.
Acknowledgments
11. (a) Clouthier, D. J.; Moule, D. C. Top. Curr. Chem. 1989,
150, 167; (b) Maciejewski, A.; Steer, R. P. Chem. Rev. 1993,
We are indebted to Dr. J. Frelek (IChO PAN, Warsaw) for
CD measurements with use of her JASCO J-715 instru-
ment. The financial support from the Committee of Scien-
tific Research (Project No. 3 T09A 030 29) is gratefully
acknowledged.
´
93, 67; (c) Połonski, T.; Milewska, M. J.; Konitz, A.;
Gdaniec, M. Tetrahedron: Asymmetry 1999, 10, 2591.
12. (a) Yde, B.; Yousif, N. M.; Pedersen, V.; Thomsen, J.;
Lawesson, S.-O. Tetrahedron 1984, 40, 2047; For a review see:
(b) Cava, M. P.; Levinson, M. J. Tetrahedron 1985, 41, 5061;
(c) Jesberger, M.; Davis, T. P.; Barner, L. Synthesis 2003,
1929.
13. (a) Larson, D. B.; McGlynn, S. P. J. Mol. Spectrosc. 1973, 47,
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