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

In the title compound, C₆H₈N₂O₂S, also known as N-acetyl-2-thio­hydantoin–alanine, the mol­ecules are joined by N—H...O hydrogen bonds, forming centrosymmetric R₂²(8) dimers; these dimers are linked by C—H...O inter­actions to form R₂²(10) rings, thus forming C₂²(10) chains that run along the [101] direction.

S1. Comment

2-Thioxo-imidazolidin-4-ones, or 2-thiohydantoins, are sulfur analogs of imidazolidine-2,4-diones, or hydantoins. These compounds are constituted by two five-membered heterocyclic systems with a very reactive nucleus, which provides four possible points of diversity. Both heterocycles represent significant building blocks for combinatorial chemistry libraries (Boeijen et al., 1998; Park et al., 2001; Lin & Sun, 2003; 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; Vázquez et al., 2004; Alsina et al., 2005; Dubey, 2006; 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., 2006, 2007; Delgado et al., 2007), and we report here the structure of the title compound, (I), the N-acetyl thiohydantoin derivative of the natural amino acid L-alanine, which is an intermediate in the preparation of 2-thiohydantoin–alanine. Compound (I) (Fig. 1) crystallizes in a centrosymmetric space 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).

All bond distances and angles are normal (Allen, 2002) and are in agreement with the average values found in 31 entries with 36 thiohydantoin ring fragments found in a search of the Cambridge Structural Database (CSD; Version 5.28; Allen, 2002), with atoms N1 and N3 unsubstituted and sp³-hybridization at atom C5. The thiohydantoin ring is essentially planar, with maximum deviations of 0.020 (1) Å for atom N3 and -0.019 (2) Å for atom C4. The N1—C2—S2 bond angle is greater than N3—C2—S2 angle (Table 1). This difference is also observed in the two N-acetyl thiohydantoin compounds reported in the CSD [refcodes KOMGUO (Mackay et al., 1992), with angle values 130.6 and 123.4°, and NIFHIT (Casas et al., 1998) with angles 132.0° and 121.9°]. The average values for the same angle in the 36 fragments searched above are 127.7 and 125.2°, respectively. The C2—S2 distance (Table 1) agrees with the average value of 1.646 Å found for the 36 fragments found in the CSD, with minimum and maximum reported values of 1.519 and 1.696 Å, respectively. The acetyl group is almost planar 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 value agrees with the same plane in KOMGUO (Mackay et al., 1992) of 12°, and it is greater than the 6.7° found in NIFHIT (Casas et al., 1998), indicating that the substitution in atom C5 atom 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 N—H···O and C—H···O intermolecular hydrogen bonds (Table 2). The N—H···O hydrogen bond generates centrosymmetric R₂²(8) (Etter, 1990) rings (Fig. 2). This motif constitutes a typical amide–amide hydrogen bond joining pairs of molecules, and is also observed in the thiohydantoins THHYDT01 (Devillanova et al., 1987) and KUWDOW (Cristiani et al., 1992). These dimers are parallel linked through the C—H···O hydrogen bond to form a second centrosymmetric ring motif, of R₂²(10) type (Fig. 2). The combination of these rings produces C₂²(10) chains, which run along the [101] direction.

Related literature

For related literature, see: Allen (2002); Alsina et al. (2005); Boeijen et al. (1998); Casas et al. (1998); Cristiani et al. (1992); Delgado et al. (2007); Devillanova et al. (1987); Dubey (2006); Etter (1990); Ganesan (2003); Kleinpeter (1997); Lin & Sun (2003); Mackay et al. (1992); Muccioli et al. (2003); Park et al. (2001); Reyes & Burgess (2006); Seijas et al. (2006, 2007); Vázquez et al. (2004); Wang et al. (2006); Yamada et al. (1983); Yoshioka (2007); Zhang et al. (2006).

S2. Experimental

L-Alanine (500 mg, 3.0 mmol) and NH₄SCN (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 period of 30 min, and then cooled in ice/water and stored in a freezer overnight. The resulting white solid was collected by filtration 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 a solution in 1:1 ethanol–methanol. NMR (MSO-d₆): δ(H) 12.66 (H3, s), 4.68 (H5, q), 2.72 (H7A = H7B = H7C, s), 1.43 (H8A = H8B = H8C, d); δ(C) 182 (C2), 173.9 (C4), 169.7 (C6), 58.7 (C5), 27.3 (C7), 15.9 (C8).

S3. Refinement

All H atoms were placed at calculated positions and treated using a riding model, with C—H distances of 0.96–0.98 Å and an N—H distance of 0.86 Å. The U_iso(H) parameters were fixed at 1.2U_eq(C, N) or 1.5U_eq(methyl C). (Geometric details for H3 and H5 are missing from the _geom_··· loops in the CIF.)

Computing details

Data collection: DIF4 (Stoe & Cie, 1992); cell refinement: DIF4; data reduction: REDU4 (Stoe & Cie, 1992); program(s) used to solve structure: SIR2004 (Burla et al., 2005); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: DIAMOND (Brandenburg, 2001); software used to prepare material for publication: PLATON (Spek, 2003).

Figures

	Fig. 1. The molecular structure of the title compound, with the atomic numering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as spheres of arbitrary radii.
	Fig. 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].

rac-1-acetyl-5-methyl-2-thioxoimidazolidin-4-one

Crystal data

C6H8N2O2S	Z = 2
Mr = 171.21	F(000) = 180
Triclinic, P1	Dx = 1.469 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71069 Å
a = 7.001 (6) Å	Cell parameters from 24 reflections
b = 7.210 (6) Å	θ = 7.5–12.0°
c = 8.102 (7) Å	µ = 0.37 mm^−1
α = 91.085 (7)°	T = 295 K
β = 91.052 (7)°	Prism, colourless
γ = 107.764 (7)°	0.57 × 0.34 × 0.15 mm
V = 389.3 (6) Å^3

Data collection

Stoe Stadi-4 diffractometer	1322 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.018
Graphite monochromator	θmax = 27.5°, θmin = 2.5°
/w scans	h = −9→9
Absorption correction: ψ scan (EMPIR; Stoe & Cie, 1992)	k = −9→2
Tmin = 0.860, Tmax = 0.940	l = −10→10
2474 measured reflections	3 standard reflections every 100 reflections
1779 independent reflections	intensity decay: none

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.041	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.105	H-atom parameters constrained
S = 1.02	w = 1/[σ^2(Fo^2) + (0.0556P)^2 + 0.0336P] where P = (Fo^2 + 2Fc^2)/3
1779 reflections	(Δ/σ)max < 0.001
102 parameters	Δρmax = 0.21 e Å^−3
0 restraints	Δρmin = −0.23 e Å^−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
N1	−0.0211 (2)	0.2663 (2)	0.27240 (19)	0.0356 (4)
C2	0.0313 (3)	0.2719 (3)	0.4371 (2)	0.0354 (4)
S2	−0.10342 (9)	0.19453 (9)	0.60004 (7)	0.04819 (19)
N3	0.2335 (2)	0.3661 (2)	0.44895 (19)	0.0390 (4)
H3	0.3018	0.3806	0.5402	0.047*
C4	0.3160 (3)	0.4345 (3)	0.3025 (2)	0.0389 (4)
O4	0.4900 (2)	0.5251 (2)	0.28167 (18)	0.0537 (4)
C5	0.1528 (3)	0.3708 (3)	0.1725 (2)	0.0381 (4)
H5	0.1287	0.4849	0.1230	0.046*
C6	−0.2109 (3)	0.1935 (3)	0.1918 (3)	0.0416 (5)
O6	−0.2258 (2)	0.2424 (3)	0.0519 (2)	0.0578 (5)
C7	−0.3787 (3)	0.0546 (4)	0.2770 (3)	0.0604 (7)
H7A	−0.4285	0.1233	0.3601	0.091*
H7B	−0.3318	−0.0432	0.3279	0.091*
H7C	−0.4844	−0.0063	0.1982	0.091*
C8	0.2064 (3)	0.2452 (4)	0.0400 (3)	0.0539 (6)
H8A	0.2108	0.1251	0.0866	0.081*
H8B	0.3354	0.3130	−0.0026	0.081*
H8C	0.1071	0.2181	−0.0478	0.081*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0333 (8)	0.0372 (9)	0.0336 (8)	0.0061 (7)	0.0034 (6)	0.0086 (7)
C2	0.0393 (10)	0.0316 (10)	0.0351 (9)	0.0104 (8)	0.0052 (8)	0.0037 (8)
S2	0.0519 (3)	0.0530 (4)	0.0376 (3)	0.0117 (3)	0.0146 (2)	0.0081 (2)
N3	0.0376 (9)	0.0443 (9)	0.0293 (8)	0.0040 (7)	−0.0005 (6)	0.0041 (7)
C4	0.0391 (10)	0.0383 (11)	0.0336 (10)	0.0033 (9)	0.0025 (8)	0.0039 (8)
O4	0.0395 (8)	0.0680 (11)	0.0381 (8)	−0.0069 (7)	0.0010 (6)	0.0050 (7)
C5	0.0350 (10)	0.0400 (11)	0.0322 (10)	0.0004 (8)	0.0025 (7)	0.0078 (8)
C6	0.0349 (10)	0.0436 (11)	0.0447 (11)	0.0092 (9)	−0.0001 (8)	0.0081 (9)
O6	0.0467 (9)	0.0669 (11)	0.0510 (10)	0.0039 (8)	−0.0096 (7)	0.0185 (8)
C7	0.0372 (11)	0.0733 (17)	0.0607 (15)	0.0008 (11)	0.0021 (10)	0.0162 (13)
C8	0.0446 (12)	0.0691 (16)	0.0370 (11)	0.0015 (11)	0.0049 (9)	−0.0072 (11)

Geometric parameters (Å, º)

N1—C2	1.374 (3)	C6—C7	1.483 (3)
N1—C6	1.413 (3)	C7—H7A	0.9600
N1—C5	1.485 (3)	C7—H7B	0.9600
C2—N3	1.371 (3)	C7—H7C	0.9600
C2—S2	1.642 (2)	C8—H8A	0.9600
N3—C4	1.363 (3)	C8—H8B	0.9600
C4—O4	1.211 (3)	C8—H8C	0.9600
C4—C5	1.497 (3)	N3—H3	0.8600
O6—C6	1.205 (3)	C5—H5	0.9800
C5—C8	1.516 (3)
C2—N1—C6	130.25 (17)	C6—C7—H7B	109.5
C2—N1—C5	111.40 (17)	H7A—C7—H7B	109.5
C6—N1—C5	118.11 (16)	C6—C7—H7C	109.5
N1—C2—N3	106.31 (17)	H7A—C7—H7C	109.5
N1—C2—S2	131.47 (16)	H7B—C7—H7C	109.5
N3—C2—S2	122.19 (16)	C5—C8—H8A	109.5
C4—N3—C2	113.66 (18)	C5—C8—H8B	109.5
O4—C4—N3	126.1 (2)	H8A—C8—H8B	109.5
O4—C4—C5	126.77 (19)	C5—C8—H8C	109.5
N3—C4—C5	107.12 (17)	H8A—C8—H8C	109.5
N1—C5—C4	101.37 (16)	H8B—C8—H8C	109.5
N1—C5—C8	114.23 (18)	C4—N3—H3	123.2
C4—C5—C8	110.93 (19)	C2—N3—H3	123.2
O6—C6—N1	117.4 (2)	N1—C5—H5	110.0
O6—C6—C7	122.8 (2)	C4—C5—H5	110.0
N1—C6—C7	119.73 (19)	C8—C5—H5	110.0
C6—C7—H7A	109.5

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···O4^i	0.86	1.99	2.824 (3)	164
C5—H5···O6^ii	0.98	2.38	3.271 (4)	151

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x, −y+1, −z.