Crystal structures and vibrational spectra of racemic and chiral 4-phenyl-1,3-oxazolidine-2-thione

Article abstract of DOI:10.1023/A:1021169403084

The crystal structures of (rac)- and (R)-4-phenyl-1,3-oxazolidine-2-thione (4-POT) have been determined by X-ray diffraction. The structure of (rac)-4-POT is monoclinic P2₁/n with a = 11.9096(9) A, b = 5.9523(6) A, c = 12.3563(8) A, β = 91.054(

Full text of DOI:10.1023/A:1021169403084

C
Journal of Chemical Crystallography, Vol. 32, No. 12, December 2002 ( 2002)
Crystal structures and vibrational spectra of racemic
and chiral 4-phenyl-1,3-oxazolidine-2-thione
Soh-ichi Kitoh,(1) Ko-Ki Kunimoto,(1) Norio Funaki,(1) Hitoshi Senda,(1)
Akio Kuwae,(2) and Kazuhiko Hanai(3)
Received October 31, 2001
The crystal structures of (rac)- and (R)-4-phenyl-1,3-oxazolidine-2-thione (4-POT) have
been determined by X-ray diffraction. The structure of (rac)-4-POT is monoclinic
˚
˚
˚
P21/n with a = 11.9096(9) A, b = 5.9523(6) A, c = 12.3563(8) A, = 91.054(6) , V =
3
˚
875.8(1) A , and Z = 4. The structure of (R)-4-POT is orthorhombic P212121 with
3
˚
˚
˚
˚
a = 7.7197(6) A, b = 21.603(2) A, c = 5.4613(9) A, V = 910.8(2) A , and Z = 4. (rac)-
4-POT and (R)-4-POT crystals are shown to have different hydrogen-bonding patterns.
In the racemic crystals, the enantiomeric (R)- and (S)-4-POT molecules are connected to
form a cyclic dimer via the N
H
S hydrogen bond of the cis thioamide moiety [N
Si 176(2) ; symmetry code: (i) 1 x, 1 y, 1 z]. In the chiral
---
Si
---
˚
---
3.438(2) A, N
(R)-4-POT crystals, the N
around the twofold screw axis [N S 3.347(3) A, N
H
H
S intermolecular hydrogen bond forms a zigzag chain
ii
˚
---
H
Sii 161(3) ; symmetry code:
(ii) 1/2 + x, 1/2 y, 2 z]. Observed difference of 46 C in the melting points between
the (rac)-4-POT and (R)-4-POT crystals is correlated with difference in the crystal packing.
Vibrational spectra of (rac)- and (R)-4-POT crystals are discussed both in the solid state
and in solution.
KEY WORDS: Crystal structure; 4-phenyl-1,3-oxazolidine-2-thione; vibrational spectra; crystal packing;
intermolecular hydrogen bonds.
Introduction
have been developed as versatile and efficient
auxiliaries.1,2 Recent studies have shown that
Chiral auxiliary methodologies are prov-
usage of oxazolidine-2-thiones has some ad-
vantages as chiral auxiliaries compared to
their 2-oxo analogues.3–5 Enantiomerically pure
1,3-oxazolidine-2-thiones are usually obtained
through the reaction of chiral -aminoalcohols
and carbon disulfide.6,7 As an alternative route
to chiral 2-thioxo-O,N-heterocycles, we have
studied the optical resolution of racemic com-
pounds through preferential crystallization. This
methodology relies on the formation of con-
glomerate crystals, a separable mechanical mix-
ture of the two pure enantiomers. Conglomerates
ing to be increasingly useful for the asymmetric
synthesis of many classes of compounds.
Chiral 1,3-oxazolidine-2-ones and -2-thiones
(1) Department of Chemistry and Chemical Engineering, Faculty
of Technology, Kanazawa University, Kakuma-machi, Kanazawa
920-1192, Japan.
(2) Institute of Natural Sciences, Nagoya City University, Mizuho-ku,
Nagoya 467-8501, Japan.
(3) Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-
8585, Japan.
To whom correspondence should be addressed. E-mail: lee@
kenroku.kanazawa-u.ac.jp
547
C
1074-1542/02/1200-0547/0 2002 Plenum Publishing Corporation

548
Kitoh, Kunimoto, Funaki, Senda, Kuwae, and Hanai
usually show different physico-chemical behavior
between racemates and racemic compounds ow-
ing to different intermolecular forces.
sample position. All spectra were accumulated for
60 scans with a resolution of 4 cm .
1
In search for the crystallization condition,
we have found a difference of 46 C in the melt-
ing points between the (rac)- and the (R)-4-
POT crystals. In the present study, the crys-
tal structures of racemic and chiral 4-POT have
been analyzed by X-ray crystallography in or-
der to understand the intermolecular interactions
in the two crystal systems. IR and Raman spec-
tra of (rac)-4-POT and (R)-4-POT are measured
and correlated with the molecular and crystal
structures.
Summary of physical and spectroscopic data
(rac)-4-POT. m.p.: 171.0–172.0 C; Anal.
Calcd for C9H9NOS: C 60.31, H 5.06, N 7.81;
Found: C 60.38, H 5.14, N 7.83; IR (KBr, cm ):
1
---
---
---
3191 ( (N H)), 1511 ( (C N) + (N H)),
1
==
1178 ( (C S)); Raman (neat, cm ): 3171
---
---
---
( (N H)), 1505 ( (C N) + (N H)), 1168
1
==
( (C S)); H NMR (CDCl3): 4.49 (dd, 1H,
CH), 5.00 (t, 1H, CH2), 5.12 (dd, 1H, CH2), 7.36–
7.46 (m, 5H, phenyl), 7.49 (s, 1H, NH).
(R)-4-POT. m.p.: 125.0–126.0 C; [ ]25
:
D
32.00 (c 5.00, CHCl3); Anal. Calcd for
Experimental
C9H9NOS: C 60.31, H 5.06, N 7.81; Found: C
1
60.27, H 5.09, N 7.78; IR (KBr, cm ): 3183
Materials
---
---
---
( (N H)), 1522 ( (C N) + (N H)), 1171
1
==
---
( (C S)); Raman (neat, cm ): 3175 ( (N H)),
(R)- and (S)-4-POT were prepared through
the reaction of chiral phenylglycinol by using
the published procedure.7 The reaction products
were recrystallized from hot water several times.
(rac)-4-POT was prepared by mixing equimolar
(R)- and (S)-4-POT in acetone. The purities of
these compounds were checked by the elemental
analyses and 1H NMR spectra. (R)-( )- and (S)-
(+)-phenylglycinol were purchased from Aldrich
Chemical Co. Solvents and other chemicals were
of reagent grade.
1
---
---
==
1531 ( (C N) + (N H)), 1166 ( (C S)); H
NMR(CDCl3): 4.49 (dd, 1H, CH), 5.00 (t, 1H,
CH2), 5.12 (dd, 1H, CH2), 7.36–7.46 (m, 5H,
phenyl), 7.49 (s, 1H, NH).
X-ray crystal structure analysis
(rac)- and (R)-4-POT crystals suitable for
X-ray diffraction analysis were obtained by crys-
tallization from aqueous acetone at room temper-
ature. The absolute configuration of (R)-4-POT
crystals was determined based on the absolute
stereochemistry established previously.6,7 The
preliminary cell dimensions and space group sym-
metry were determined photographically. X-ray
diffraction data were obtained on a Rigaku AFC-
5R diffractometer with a graphite monochromated
Spectroscopic measurements
The IR spectra were recorded on a Perkin-
Elmer 1650 FT-IR spectrometer by averaging 64
scans with a resolution of 4 cm . The spectra
1
of solid samples were measured as KBr pellets
and Nujol mulls. Either a 0.11-mm or a 1.0-mm
path-length liquid cell with NaCl windows was
used for solution samples.
The FT-Raman spectra were obtained on a
Perkin-Elmer 2000R spectrometer equipped with
a quartz beam splitter and InGaAs detector. The
1064-nm line of a Spectron Laser System SL300
Nd:YAG laser was used as the exciting source
with an output power of about 200 mW at the
˚
Cu K radiation ( = 1.54178 A). Intensity data
were collected at room temperature (23 1 C)
with an ω–2 scan mode. An empirical absorption
correction, based on azimuthal scans of several re-
flections, was applied which resulted in transmis-
sion factors ranging from 0.91 to 1.00 for (rac)-
4-POT and from 0.76 to 1.00 for (R)-4-POT. The
data were corrected for both Lorentz and polariza-
tion effects. Table 1 summarizes the crystal data

4-Phenyl-1,3-oxazolidine-2-thione
549
Table 1. Crystal Data and Structure Refinement
(rac)-4-POT
Compound
(R)-4-POT
CCDC deposit no.
Color/shape
CCDC-1003/6159
Colorless/parallelepiped
C9H9NOS
179.24
296
Monoclinic
P21/n
CCDC-1003/6160
Colorless/parallelepiped
C9H9NOS
179.24
296
Chemical formula
Formula weight
Temperature, K
Crystal system
Space group
Orthorhombic
P212121
Unit cell dimensions
˚
a (A)
11.9096(9)
5.9523(6)
12.3563(8)
91.054(6)
7.7197(6)
21.603(2)
5.4613(9)
˚
b (A)
˚
c (A)
(deg)
3
˚
Volume, A
875.8(1)
910.8(2)
Z
4
4
Density(calculated), Mg/m3
Absorption coefficient, mm
Diffractometer/scan
1.359
2.808
Rigaku AFC-5R/ω–2
3.57–59.92
1530
1.307
2.700
Rigaku AFC-5R/ω–2
4.09–59.99
850
1
range for data collection, deg
Reflections measured
Independent reflections
Observed reflections
Data/restraints/parameters
Goodness of fit
1453 (Rint = 0.025)
1209 [I > 1.20 (I)]
1209/0/145
2.42
850
807 [I > 1.20 (I)]
807/0/145
2.23
Final R indices [I > 1.20 (I)]
R = 0.036, wR = 0.047
R = 0.034, wR = 0.042
3
˚
Largest diff. peak and hole, e/A
0.20, 0.32
0.13, 0.21
and experimental conditions for the crystal struc-
ture determination.
monoclinic and orthorhombic forms, respectively,
with four molecules in a unit cell. Bond lengths
and bond angles of (rac)-4-POT and (R)-4-POT
are very similar to each other and comparable
to that of nonsubstituted 1,3-oxazolidine-2-thione
The structure was solved by direct methods
using SIR88. Crystal structure analysis was per-
formed by using the teXsan crystallographic soft-
ware package.8 Non-hydrogen atoms were refined
anisotropically. All the hydrogen-atom positions
were found from a difference Fourier map and re-
fined isotropically.
(OT).9 However, the thiocarbonyl C(1) S(1)
---
bond lengths are shorter than that of OT [1.656(2)
˚
and 1.652(3) A for (rac)-4-POT and (R)-4-POT
˚
compared to 1.671(6) A for OT]. As shown in
Fig. 1, the oxazolidine ring conformations of the
two crystals are slightly different from each other:
Results and discussion
---
---
---
the S(1) C(1) O(1) C(3) fragment is almost
planar with the C(2) atom on the opposite side
of the ring. Thus the heterocyclic ring adopts the
envelope conformation with the torsional angle
Crystal structures of (rac)-4-POT and (R)-4-POT
The final positional and thermal parame-
ters of (rac)-4-POT and (R)-4-POT for non-H
atoms are presented in Table 2. Tables 3 and 4
summarize the bond lengths, bond angles, tor-
sion angles, and the hydrogen-bonding geome-
tries of the two crystals. As shown in Table 1,
(rac)-4-POT and (R)-4-POT are crystallized in the
---
---
---
S(1) C(1) N(1) C(2) of 171.9(1) for (rac)-
4-POT and 172.8(2) for (R)-4-POT.
The molecular packing in crystals is shown
in Fig. 2. In both cases a short intermolecular con-
tact between the H atom of one molecule and the
S atom of a neighboring molecule is observed.

550
Kitoh, Kunimoto, Funaki, Senda, Kuwae, and Hanai
Table 2. Fractional Atomic Coordinates and Equivalent Isotropic
˚
Table 3. Selected Bond Lengths (A), Bond Angles (Deg), and
Torsion Angles (Deg)a
Thermal Parameters
a
2
˚
Beq (A )
Atom
x
y
z
(rac)-4-POT
(R)-4-POT
(rac)-4-POT
S(1)
O(1)
N(1)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
Bond length
0.56633(4) 0.19455(9) 0.58045(4) 3.98(3)
----
S(1) C(1)
----
1.656(2)
1.345(2)
1.452(3)
1.310(3)
1.457(3)
1.528(3)
1.507(3)
1.652(3)
1.337(4)
1.452(4)
1.315(4)
1.456(4)
1.537(5)
1.508(4)
0.7690(1) 0.3336(2) 0.6294(1)
0.6661(1) 0.5942(3) 0.5536(1)
0.6676(2) 0.3852(3) 0.5866(1)
0.7756(2) 0.7032(4) 0.5585(2)
0.8391(2) 0.5333(4) 0.6292(2)
0.8247(1) 0.7372(3) 0.4482(2)
0.8802(2) 0.9341(4) 0.4238(2)
0.9295(2) 0.9621(5) 0.3244(2)
0.9232(2) 0.7966(5) 0.2481(2)
0.8667(2) 0.6017(5) 0.2706(2)
0.8180(2) 0.5718(4) 0.3697(2)
3.97(7)
3.53(8)
2.99(8)
3.39(9)
4.1(1)
3.03(8)
4.1(1)
5.2(1)
5.0(1)
4.6(1)
3.9(1)
O(1) C(1)
----
O(1) C(3)
----
N(1) C(1)
----
N(1) C(2)
----
C(2) C(3)
----
C(2) C(4)
Bond angle
----
----
----
C(1) O(1) C(3)
109.0(2)
113.8(2)
120.6(1)
129.1(2)
110.2(2)
99.3(2)
112.6(2)
114.2(2)
105.3(2)
109.5(2)
113.6(3)
121.6(2)
128.3(3)
110.0(3)
99.1(3)
113.7(2)
114.3(2)
104.3(3)
----
C(1) N(1) C(2)
---- ----
S(1) C(1) O(1)
---- ----
S(1) C(1) N(1)
---- ----
(R)-4-POT
S(1)
O(1)
N(1)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
O(1) C(1) N(1)
---- ----
0.4034(1) 0.18887(3) 0.9843(2)
0.2708(3) 0.25589(9) 0.6327(5)
0.5023(3) 0.2969(1) 0.7901(5)
0.3959(4) 0.2494(1) 0.7999(6)
0.4692(4) 0.3382(1) 0.5846(6)
0.2862(5) 0.3161(2) 0.516(1)
0.4805(3) 0.4059(1) 0.6497(5)
0.5704(3) 0.4456(1) 0.4997(6)
0.5794(4) 0.5082(1) 0.5528(6)
0.5003(4) 0.5308(1) 0.7573(6)
0.4095(4) 0.4915(1) 0.9098(6)
0.4003(4) 0.4291(1) 0.8565(5)
6.58(5)
6.5(1)
4.9(1)
4.9(1)
4.8(1)
6.5(2)
3.9(1)
4.6(1)
5.2(1)
5.1(1)
5.1(1)
4.6(1)
N(1) C(2) C(3)
---- ----
N(1) C(2) C(4)
---- ----
C(3) C(2) C(4)
----
----
O(1) C(3) C(2)
Torsion angle
----
----
----
S(1) C(1) O(1) C(3)
177.3(1)
171.9(1)
14.6(2)
7.6(2)
139.5(2)
42.0(3)
11.8(2)
3.2(2)
173.9(3)
172.8(2)
17.9(4)
7.4(3)
134.2(3)
46.6(3)
15.6(4)
5.9(4)
---- ---- ----
S(1) C(1) N(1) C(2)
---- ---- ----
O(1) C(3) C(2) N(1)
---- ---- ----
O(1) C(1) N(1) C(2)
---- ---- ----
N(1) C(2) C(4) C(5)
---- ---- ----
N(1) C(2) C(4) C(9)
---- ---- ----
C(1) O(1) C(3) C(2)
---- ---- ----
N(1) C(1) O(1) C(3)
---- ---- ----
P P
a Beq = (4/3)
i j ai aj (ai aj ).
j
C(1) N(1) C(2) C(3)
---- ---- ----
14.0(2)
108.1(2)
70.3(2)
16.1(3)
113.0(3)
66.2(4)
i
C(3) C(2) C(4) C(5)
---- ---- ----
C(3) C(2) C(4) C(9)
However, the hydrogen-bonding pattern is quite
different. In the crystal of (rac)-4-POT, the
aEstimatedstandarddeviationsintheleastsignificantfigurearegiven
in parentheses.
==
thioamide C S group of an enantiomeric
molecule is hydrogen-bonded to the thioamide
NH group of a antipode molecule to form
a centrosymmetric cyclic dimer [N(1) S(1)i
S(1)ii 161(3) ; symme-
˚
---
3.347(3) A, N(1) H
try code: (ii) 1/2 + x, 1/2 y, 2 z]. In con-
3.438(2) A, N(1) H
S(1)i 176(2) ; sym-
˚
---
---
sidering the D A distance and the D H
A
metry code: (i) 1 x, 1 y, 1 z]. On the
other hand, a zigzag chain is formed through
angle, (rac)-4-POT crystals may have slightly
more favorable hydrogen bonding than (R)-
4-POT crystals. However, this small differ-
ence in the hydrogen-bonding strength cannot
---
the N H
S intermolecular hydrogen bond-
ing in the (R)-4-POT crystals [N(1)
S(1)ii
Table 4. Hydrogen Bonding Geometry
˚
˚
˚
----
----
----
----
D H
Compound
D
H
A
D
H (A)
H
A (A)
D
A (A)
A (deg)
(rac)-4-POT
(R)-4-POT
N(1)
N(1)
H
H
S(1)i
S(1)ii
0.78(2)
0.86(4)
2.66(2)
2.53(4)
3.438(2)
3.347(3)
176(2)
161(3)
----
Note: Symmetry codes: (i) 1 x, 1 y, 1 z; (ii) 1/2 + x, 1/2 y, 2 z.

4-Phenyl-1,3-oxazolidine-2-thione
551
Fig. 1. ORTEP drawings of the (R)-4-POT molecules with the atom numbering: (a) in (rac)-4-POT crystals and
(b) (R)-4-POT crystals. Thermal ellipsoids are drawn at the 50% probability level.
account for a large difference in the melting
points (171.5 C for (rac)-4-POT and 125.5 C for
(R)-4-POT). Closer crystal packing in (rac)-4-
POT crystals is the main reason for the higher
melting point for the crystals (calculated densi-
ties of (rac)-4-POT and (R)-4-POT are 1.359 and
difference between the free and the associated
forms is often used as a measure of the hydrogen
bonding strength. However, it is hard to correlate
---
a frequency difference in the (N H) with the
H-bonding strength, since (rac)-4-POT and (R)-
4-POT have different intermolecular H-bonding
patterns as shown in the X-ray result. The
3
1.307 Mg m , respectively).
---
---
==
(C N) + (N H) and the (C S) bands are
observed at 1511 and 1178 cm 1 for (rac)-4-POT
IR and Raman spectra
1
and at 1522 and 1171 cm for (R)-4-POT. In
IR spectrum of the nonsubstituted OT was
first reported by Cristiani et al.10 They also carried
outnormalcoordinateanalysesofOTandits2-one
analogue to establish the band assignments.11
Similar to OT, (rac)- and (R)-4-POT exhibit IR
bands characteristic of the OT ring; the (NH), the
the Raman spectra, the corresponding bands are
observed at 1505 and 1168 cm 1 for (rac)-4-POT
and at 1531 and 1166 cm 1 for (R)-4-POT.
---
When dissolved in CHCl3, the (N H) band
of (rac)-4-POT is observed as a doublet at 3443
1
and 3189 cm . On decreasing the concentration
---
---
==
(C N) + (N H), and the (C S) bands are
from 0.1 to 0.01 M stepwise, the intensity of
the former gradually increases at the expense of
the latter. Thus, the former and the latter bands
1
observed in the 3200, 1500, and 1170 cm re-
gions, respectively. Assignment of the 1170 cm
1
==
---
band to (C S) is tentative, because the calcu-
are assigned to the (N H) of the free and
lation by Devillanova et al.11 indicates that the
the associated form, respectively. The band at
3189 cm undergoes a higher frequency shift to
the 3209 cm , while that of the free form remains
unshifted. This concentration dependence of the
1
==
C S stretching mode in OT does not give the
main contribution to the band at 1107 cm , but
to the band at 513 cm . In the solid-state IR
1
1
1
---
spectra, the (NH) bands of hydrogen-bonded
(N H) of the associated form suggests that the
(rac)-4-POT and (R)-4-POT are observed at 3191
and 3183 cm , respectively, close to that of
chain-type hydrogen bonding occurs in CHCl3 so-
lution in contrast with the association in the crys-
1
---
---
OT. In the Raman spectra, these bands occur at
tal. In CHCl3 solution, the (C N) + (N H)
3171 and 3175 cm , respectively. The (N H)
band around 1500 cm 1 is also split into a doublet
1
---

552
Kitoh, Kunimoto, Funaki, Senda, Kuwae, and Hanai
Fig. 2. Molecular packing (a) in (rac)-4-POT and (b) in (R)-4-POT crystals. The hydrogen bondings are indicated by
dashed lines.
1
1
---
at 1519 cm
(shoulder) and at 1480 cm
bands can be assigned to the (C N) + (NH)
1
(strong). Since the 1480 cm band gains its in-
tensityattheexpenseofthe1519cm 1 bandinten-
sity, the higher frequency and the lower frequency
mode of the associated and the free species,
respectively. (R)-4-POT in CHCl3 solution shows
similar IR spectra; the spectral behavior implies

4-Phenyl-1,3-oxazolidine-2-thione
553
4. Crimmins, M.T.; King, B.W. J. Am. Chem. Soc. 1998, 120, 9084.
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Kuroda, C. Tetrahedron Lett. 1991, 32, 1195.
that the molecule also assumes the chain-type
hydrogen bonding in concentrated solution.
6. Delaunay, D.; Toupet, L.; Le Corre, M. J. Org. Chem. 1995, 60,
6604.
7. Li, G.; Ohtani, T. Heterocycles, 1997, 45, 2471.
8. teXsan, Crystal Structure Analysis Package; Molecular Struc-
ture Corp.: The Woodlands, TX, 1985.
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II 1977, 324.
3. Fujita, E.; Nagao, Y. Adv. Heterocycl. Chem. 1989, 45, 1, and
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