Hydrogen-bonding patterns in rac-1-acetyl-5-methyl-2-thioxoimidazolidin-4- one

Article abstract of DOI:10.1107/S0108270107038012

In the title compound, C6H8N2O2S, also known as N-acetyl-2-thio-hydantoin- alanine, the mol-ecules are joined by N - H...O hydrogen bonds, forming centrosymmetric R 2 ²(8) dimers; these dimers are linked by C - H...O inter-actions to form R 2 ²(10) rings, thus forming C 2 ²(10) chains that run along the [101] direction. International Union of Crystallography 2007.

Full text of DOI:10.1107/S0108270107038012

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
group, which implies that l-alanine suffered an amino acid
racemization produced by the use of acetic acid in the
synthesis (Yamada et al., 1983; Yoshioka, 2007).
ISSN 0108-2701
All bond distances and angles are normal (Allen, 2002) and
in agreement with the average values found in 31 entries with
3
6 thiohydantoin ring fragments found in a search of the
Hydrogen-bonding patterns in
rac-1-acetyl-5-methyl-2-thioxo-
imidazolidin-4-one
a
a
a
Maria E. Sulbaran, Gerzon E. Delgado, * Asilo e J. Mora,
b
c
Ali Bahsas, Hector Novoa de Armas ³ and Norbert
c
Blaton
Cambridge Structural Database (CSD; Version 5.28; Allen,
a
Laboratorio de Cristalograf Âõ a, Departamento de Qu Âõ mica, Facultad de Ciencias,
3
2002), with atoms N1 and N3 unsubstituted and sp -hybridi-
zation at atom C5. The thiohydantoin ring is essentially planar,
b
Universidad de Los Andes, M e rida 5101, Venezuela, Laboratorio de Resonancia
Magn e tica Nuclear, Departamento de Qu Âõ mica, Facultad de Ciencias, Universidad
c
Ê
with maximum deviations of 0.020 (1) A for atom N3 and
de Los Andes, M e rida 5101, Venezuela, and Laboratory for Biocrystallography,
Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, Campus
Gasthuisberg ± O & N2, Herestraat 49, Box 822, 3000 Leuven, Belgium
Correspondence e-mail: gerzon@ula.ve
Ê
0.019 (2) A for atom C4. The N1ÐC2ÐS2 angle is greater
�
than the N3ÐC2ÐS2 angle (Table 1). This difference is also
observed in the two N-acetylthiohydantoin compounds
reported in the CSD [refcodes KOMGUO (Mackay et al.,
Received 31 July 2007
Accepted 2 August 2007
Online 17 August 2007
ꢀ
1992), with angles of 130.6 and 123.4 , and NIFHIT (Casas et
ꢀ
al., 1998), with angles of 132.0 and 121.9 ]. The average values
for the same angle in the 36 fragments searched above are
In the title compound, C H N O S, also known as N-acetyl-2-
8
ꢀ
6
2
2
1
agrees with the average value of 1.646 A found for the 36
27.7 and 125.2 , respectively. The C2ÐS2 distance (Table 1)
Ê
thiohydantoin±alanine, the molecules are joined by NÐHÁ Á ÁO
2
hydrogen bonds, forming centrosymmetric R (8) dimers; these
2
fragments, with minimum and maximum reported values of
Ê
2
2
dimers are linked by CÐHÁ Á ÁO interactions to form R (10)
1
.519 and 1.696 A, respectively. The acetyl group is almost
2
rings, thus forming C (10) chains that run along the [101]
direction.
2
coplanar with the thiohydantoin ring, and the dihedral angle
between the least-squares plane through the acetyl atoms N1,
ꢀ
C6, O6 and C7 and the thiohydantoin ring is 13.6 (6) . This
ꢀ
Comment
value agrees with the equivalent in KOMGUO (12 ; Mackay
ꢀ
et al., 1992) and is greater than the value of 6.7 found in
2
-Thioxoimidazolidin-4-ones, or 2-thiohydantoins, are sulfur
NIFHIT (Casas et al., 1998), indicating that the substitution at
atom C5 produces a major separation of the acetyl group with
regard to the thiohydantoin ring.
The molecular structure and crystal packing of (I) are
stabilized by intermolecular NÐHÁ Á ÁO and CÐHÁ Á ÁO
analogs of imidazolidine-2,4-diones, or hydantoins. These
compounds are constituted by two ®ve-membered hetero-
cyclic systems with a very reactive nucleus, which provides
four possible points of diversity. Both heterocycles represent
signi®cant building blocks for combinatorial chemistry
libraries (Boeijen et al., 1998; Park et al., 2001; Lin & Sun,
2
003; Zhang et al., 2006). In recent years, there has been much
interest in the search for new synthetic routes for the
preparation of hydantoins and thiohydantoins, via solution or
solid-state reactions (Kleinpeter, 1997, Muccioli et al., 2003;
Ganesan, 2003; V a zquez et al., 2004; Alsina et al., 2005; Dubey,
2
006; Wang et al., 2006; Reyes & Burgess, 2006).
We are interested in the N-carbamoyl, hydantoin and
thiohydantoin derivatives of natural amino acids (Seijas et al.,
006, 2007; Delgado et al., 2007), and report here the structure
2
of the title compound, (I), the N-acetylthiohydantoin deriva-
tive of the natural amino acid l-alanine, which is an inter-
mediate in the preparation of 2-thiohydantoin±alanine.
Compound (I) (Fig. 1) crystallizes in a centrosymmetric space
Figure 1
³
Present address: Johnson
&
Johnson Pharmaceutical Research and
The molecular structure of the title compound, showing the atomic
numbering scheme. Displacement ellipsoids are drawn at the 50%
probability level and H atoms are shown as spheres of arbitrary radii.
Development, a division of Janssen Pharmaceutica NV, Pharmaceutical
Sciences Department, Turnhoutseweg 30, 2340 Beerse, Belgium.
Acta Cryst. (2007). C63, o543±o545
DOI: 10.1107/S0108270107038012
# 2007 International Union of Crystallography o543

organic compounds
hydrogen bonds (Table 2). The NÐHÁ Á ÁO hydrogen bond
Re®nement
2
2
2
2
generates centrosymmetric R (8) (Etter, 1990) rings (Fig. 2).
R[F > 2ꢅ(F )] = 0.041
wR(F ) = 0.105
S = 1.02
H-atom parameters constrained
Ê
� 3
Áꢆmax = 0.21 e A
2
This motif constitutes a typical amide±amide hydrogen bond
joining pairs of molecules, and is also observed in the thio-
hydantoins THHYDT01 (Devillanova et al., 1987) and
KUWDOW (Cristiani et al., 1992). These dimers are parallel
Áꢆmin = � 0.23 e AÊ
� 3
1779 re¯ections
102 parameters
linked through the CÐHÁ Á ÁO hydrogen bond to form a
Table 2
Ê
ꢀ
Hydrogen-bond geometry (A, ).
2
2
second centrosymmetric ring motif, of R (10) type (Fig. 2).
2
The combination of these rings produces C (10) chains, which
2
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
run along the [101] direction.
i
N3ÐH3Á Á ÁO4
0.86
0.98
1.99
2.38
2.824 (3)
3.271 (4)
164
151
ii
C5ÐH5Á Á ÁO6
Symmetry codes: (i) � x ‡ 1;� y ‡ 1;� z ‡ 1; (ii) � x;� y ‡ 1;� z.
All H atoms were placed at calculated positions and treated using
Ê
a riding model, with CÐH distances of 0.96±0.98 A and an NÐH
Ê
distance of 0.86 A. The Uiso(H) parameters were ®xed at 1.2Ueq(C,N)
or 1.5Ueq(methyl C).
Data collection: DIF4 (Stoe & Cie, 1992); cell re®nement: DIF4;
data reduction: REDU4 (Stoe & Cie, 1992); program(s) used to solve
structure: SIR2004 (Burla et al., 2005); program(s) used to re®ne
structure: SHELXL97 (Sheldrick, 1997); molecular graphics:
DIAMOND (Brandenburg, 2001); software used to prepare material
for publication: PLATON (Spek, 2003).
Figure 2
A partial packing view of (I). Hydrogen bonds are shown as dashed lines.
H atoms not involved in hydrogen bonding have been omitted for clarity.
Symmetry codes: (i) � x + 1, � y + 1, � z + 1; (ii) � x, � y + 1, � z.]
[
Experimental
4
l-Alanine (500 mg, 3.0 mmol) and NH SCN (228 mg, 3.0 mmol) were
dissolved in a mixture of acetic anhydride (9 ml) and acetic acid
1 ml). This solution was warmed, with agitation, to 363 K over a
This work was supported by CDCHT±ULA (grant Nos.
C-1416-06-08-B and C-1485-07-08-F) and FONACIT (grant
No. LAB-97000821).
(
period of 30 min, and then cooled in ice/water and stored in a freezer
overnight. The resulting white solid was collected by ®ltration and
washed with cold water (m.p. 430±432 K). Crystals of (I) suitable for
single-crystal X-ray diffraction were obtained by slow evaporation of
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: GD3133). Services for accessing these data are
described at the back of the journal.
6
a solution in 1:1 ethanol±methanol. NMR (MSO-d ): ꢀ(H) 12.66 (H3,
s), 4.68 (H5, q), 2.72 (H7A = H7B = H7C, s), 1.43 (H8A = H8B = H8C,
d); ꢀ(C) 182 (C2), 173.9 (C4), 169.7 (C6), 58.7 (C5), 27.3 (C7), 15.9
(C8).
References
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ꢀ
ꢃ= 107.764 (7)
3
C
M
6
H
8
N
2
O
2
S
= 171.21
Ê
r
V = 389.3 (6) A
Z = 2
3135.
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ꢀ
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(EMPIR; Stoe & Cie, 1992)
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every 100 re¯ections
intensity decay: none
T
474 measured re¯ections
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min = 0.860, Tmax = 0.940
2
1
Table 1
Selected geometric parameters (A, ).
Ê
ꢀ
C2ÐN3
C2ÐS2
1.371 (3)
1.642 (2)
C4ÐO4
O6ÐC6
1.211 (3)
1.205 (3)
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N1ÐC2ÐS2
N3ÐC2ÐS2
131.47 (16)
122.19 (16)
O4ÐC4ÐN3
O4ÐC4ÐC5
126.1 (2)
126.77 (19)
1307.
ꢁ
o544 Sulbaran et al.
C H N O
6 8 2 2
S
Acta Cryst. (2007). C63, o543±o545

organic compounds
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1
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Sulbaran et al.
6 8 2 2
C H N O S
o545