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Acta Crystallogr Sect E Struct Rep Online. 2009 December 1; 65(Pt 12): o3190–o3191.
Published online 2009 November 25. doi:  10.1107/S1600536809049460
PMCID: PMC2971766

4-(Pyrimidin-2-yl)-1-thia-4-aza­spiro­[4.5]decan-3-one

Abstract

The title compound, C12H15N3OS, features an envelope conformation for the 1,3-thia­zolidin-4-one ring with the S atom as the flap atom. The pyrimidine ring is almost orthogonal to the 1,3-thia­zolidin-4-one ring as indicated by the N—C—C—N torsion angle of −111.96 (18)°. Supra­molecular dimers are formed in the crystal structure through the agency of C—H(...)O contacts occurring between centrosymmetrically related mol­ecules. These are linked into supra­molecular tapes along [100] via C—H(...)S contacts.

Related literature

For the biological activity of thia­zolidinones, see: Cunico et al. (2008a [triangle]); Solomon et al. (2007 [triangle]); Kavitha et al. (2006 [triangle]); Sharma et al. (2006 [triangle]); Ravichandran et al. (2009 [triangle]); Rao et al. (2004 [triangle]). For background to the synthesis, see: Cunico et al. (2008b [triangle]); Rawal et al. (2008 [triangle]). For related studies on the synthesis and biological evaluation of thia­zolidinones, see: Cunico et al. (2006 [triangle], 2007 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o3190-scheme1.jpg

Experimental

Crystal data

  • C12H15N3OS
  • M r = 249.33
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o3190-efi1.jpg
  • a = 6.2466 (2) Å
  • b = 8.6748 (2) Å
  • c = 22.0439 (6) Å
  • β = 95.698 (1)°
  • V = 1188.61 (6) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.26 mm−1
  • T = 120 K
  • 0.26 × 0.22 × 0.14 mm

Data collection

  • Nonius KappaCCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 2003 [triangle]) T min = 0.658, T max = 0.746
  • 14004 measured reflections
  • 2661 independent reflections
  • 2227 reflections with I > 2σ(I)
  • R int = 0.054

Refinement

  • R[F 2 > 2σ(F 2)] = 0.038
  • wR(F 2) = 0.113
  • S = 1.14
  • 2661 reflections
  • 155 parameters
  • H-atom parameters constrained
  • Δρmax = 0.36 e Å−3
  • Δρmin = −0.40 e Å−3

Data collection: COLLECT (Hooft, 1998 [triangle]); cell refinement: DENZO (Otwinowski & Minor, 1997 [triangle]) and COLLECT; data reduction: DENZO and COLLECT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: DIAMOND (Brandenburg, 2006 [triangle]); software used to prepare material for publication: publCIF (Westrip, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809049460/hg2601sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809049460/hg2601Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

The use of the EPSRC X-ray crystallographic service at the University of Southampton, England and the valuable assistance of the staff there is gratefully acknowledged. JLW acknowledges support from FAPEMIG (Brazil).

supplementary crystallographic information

Comment

Thiazolidinones constitute an important group of heterocyclic compounds (Cunico et al., 2008a), having valuable biological uses, for example, as anti-malarial (Solomon et al., 2007), anti-microbial (Kavitha et al., 2006), anti-inflammatory (Sharma et al., 2006), and anti-viral agents, especially as anti-HIV agents (Ravichandran et al., 2009; Rao et al., 2004). The main synthetic routes to 1,3-thiazolidin-4-ones involve three components (an aldehyde, an amine and mercaptoacetic acid), either in a one- or two-step process (Cunico et al., 2008a; Rawal et al., 2006). In continuation of our research on thiazolidinones, (Cunico et al., 2006; Cunico et al., 2007: Cunico et al., 2008b), we report the structure of the title compound, 1-thia-4-azaspiro[4.5]decan-3-one, (I).

The molecule structure of (I) shows the five-membered 1,3-thiazolidin-4-one ring to adopt an envelope conformation with the S1 atom as the flap atom. The cyclohexyl ring adopts a regular chair conformation. The pyrimidine is twisted out of the plane of the 1,3-thiazolidin-4-one ring as seen in the value of the C4–N3–C11–N1 torsion angle of -111.96 (18) °. When viewed along the plane through the N1, C2, C4 and C5 atoms, the molecule, with the exception of the S1 atom, has approximate mirror symmetry.

In the crystal structure, centrosymmetric pairs associate via C—H···O contacts to form dimers, Table 1. The dimeric aggregates are linked into a supramolecular tape aligned along [1 0 0] via C—H···S contacts, Table 1 and Fig.2. The pivotal role of the C10-methylene group is noted in the stabilization of the crystal structure as each of the C10-bound H atoms forms a significant intermolecular contact.

Experimental

A mixture of 2-aminopyrimidine (1 mmol), cyclohexanone (2 mmol) and mercaptoacetic acid (3 mmol) in toluene (35 ml) was heated at 403 K with a Dean-Stark trap for 16 h. The reaction was cooled, washed with NaHCO3 (3 x 20 ml), and dried with MgSO4. The crude product was washed with a hot solvent mixture of hexane/ethyl acetate (9:1) and recrystallized from EtOH. Yield 80%. m. pt. 475–476 K. 1H NMR (200 MHz, CDCl3): δ 8.76 (s, 2H, aryl), 7.22 (s, 1H, aryl), 3.66 (s, 2H, H5), 2.21–1.57 (m, 10H, CH2) p.p.m. 13C NMR (100 MHz, CDCl3): δ 172.4 (CO), 158.5, 158.4, 119.3 (aryl), 75.7 (C2), 39.5 (CH2), 38.0 (CH2), 31.9 (C5), 24.4 (CH2), 23.6 (CH2) p.p.m.

Refinement

The C-bound H atoms were geometrically placed with C—H = 0.95–0.99 Å, and refined as riding with Uiso(H) = 1.2Ueq(C).

Figures

Fig. 1.
Molecular structure of (I) showing atom-labelling scheme and displacement ellipsoids at the 50% probability level.
Fig. 2.
Supramolecular tape formation in (I) whereby dimeric aggregates sustained by C—H···O (orange dashed lines) contacts are linked via C—H···S contacts (brown dashed lines) along [1 0 0].

Crystal data

C12H15N3OSF(000) = 528
Mr = 249.33Dx = 1.393 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 7514 reflections
a = 6.2466 (2) Åθ = 2.9–27.5°
b = 8.6748 (2) ŵ = 0.26 mm1
c = 22.0439 (6) ÅT = 120 K
β = 95.698 (1)°Block, colourless
V = 1188.61 (6) Å30.26 × 0.22 × 0.14 mm
Z = 4

Data collection

Nonius KappaCCD area-detector diffractometer2661 independent reflections
Radiation source: Enraf Nonius FR591 rotating anode2227 reflections with I > 2σ(I)
10 cm confocal mirrorsRint = 0.054
Detector resolution: 9.091 pixels mm-1θmax = 27.5°, θmin = 3.0°
[var phi] and ω scansh = −8→7
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)k = −10→11
Tmin = 0.658, Tmax = 0.746l = −28→28
14004 measured reflections

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.038H-atom parameters constrained
wR(F2) = 0.113w = 1/[σ2(Fo2) + (0.0508P)2 + 0.5459P] where P = (Fo2 + 2Fc2)/3
S = 1.14(Δ/σ)max < 0.001
2661 reflectionsΔρmax = 0.36 e Å3
155 parametersΔρmin = −0.40 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.012 (2)

Special details

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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 (Å2)

xyzUiso*/Ueq
S10.30913 (6)0.59301 (5)0.14394 (2)0.02184 (17)
O10.19102 (19)0.33684 (15)0.00174 (6)0.0215 (3)
N1−0.2660 (2)0.24603 (17)0.08348 (7)0.0189 (3)
N20.0587 (2)0.09881 (17)0.08941 (8)0.0206 (3)
N30.0732 (2)0.36704 (16)0.09593 (6)0.0147 (3)
C20.0699 (2)0.47007 (19)0.14937 (7)0.0143 (3)
C40.1922 (2)0.40748 (19)0.04984 (8)0.0161 (4)
C50.3225 (3)0.5513 (2)0.06440 (8)0.0207 (4)
H5A0.26300.63840.03900.025*
H5B0.47370.53490.05610.025*
C60.0987 (3)0.3792 (2)0.20899 (8)0.0194 (4)
H6A0.23530.32070.21100.023*
H6B−0.02040.30410.20980.023*
C70.1015 (3)0.4855 (2)0.26444 (8)0.0239 (4)
H7A0.10980.42240.30200.029*
H7B0.23110.55170.26650.029*
C8−0.0989 (3)0.5870 (2)0.26138 (8)0.0230 (4)
H8A−0.22660.52170.26550.028*
H8B−0.08520.66070.29590.028*
C9−0.1310 (3)0.6762 (2)0.20155 (8)0.0186 (4)
H9A−0.01290.75180.19990.022*
H9B−0.26830.73380.19960.022*
C10−0.1346 (2)0.5672 (2)0.14669 (8)0.0159 (4)
H10A−0.26120.49830.14610.019*
H10B−0.14860.62840.10860.019*
C11−0.0534 (2)0.22881 (19)0.08959 (8)0.0144 (3)
C12−0.3796 (3)0.1143 (2)0.07570 (9)0.0214 (4)
H12−0.53230.11940.07220.026*
C13−0.2817 (3)−0.0280 (2)0.07264 (8)0.0215 (4)
H13−0.3630−0.12000.06580.026*
C14−0.0591 (3)−0.0296 (2)0.08007 (9)0.0246 (4)
H140.0131−0.12560.07850.030*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.0154 (2)0.0251 (3)0.0259 (3)−0.00679 (16)0.00633 (17)−0.00990 (19)
O10.0249 (6)0.0233 (7)0.0168 (6)−0.0011 (5)0.0045 (5)−0.0020 (5)
N10.0163 (7)0.0159 (8)0.0243 (8)−0.0001 (5)0.0017 (6)−0.0026 (6)
N20.0177 (7)0.0163 (8)0.0279 (9)−0.0001 (5)0.0023 (6)−0.0012 (6)
N30.0144 (6)0.0138 (7)0.0161 (7)−0.0015 (5)0.0033 (5)−0.0025 (6)
C20.0123 (7)0.0152 (8)0.0154 (8)−0.0015 (6)0.0015 (6)−0.0035 (7)
C40.0137 (7)0.0186 (9)0.0161 (9)0.0030 (6)0.0016 (6)0.0023 (7)
C50.0195 (8)0.0224 (9)0.0204 (9)−0.0039 (7)0.0037 (7)0.0002 (8)
C60.0230 (8)0.0171 (9)0.0173 (9)0.0021 (7)−0.0019 (7)0.0006 (7)
C70.0331 (10)0.0221 (10)0.0156 (9)0.0008 (8)−0.0021 (7)0.0002 (8)
C80.0297 (9)0.0236 (10)0.0168 (9)−0.0026 (7)0.0071 (7)−0.0045 (8)
C90.0156 (7)0.0195 (9)0.0208 (9)0.0015 (6)0.0028 (6)−0.0026 (7)
C100.0133 (7)0.0171 (9)0.0173 (9)0.0016 (6)0.0017 (6)−0.0012 (7)
C110.0158 (7)0.0144 (8)0.0130 (8)−0.0010 (6)0.0015 (6)−0.0017 (6)
C120.0166 (8)0.0230 (10)0.0243 (10)−0.0034 (7)0.0008 (7)−0.0023 (8)
C130.0243 (9)0.0166 (9)0.0235 (10)−0.0050 (7)0.0017 (7)−0.0041 (7)
C140.0243 (9)0.0164 (9)0.0334 (11)0.0015 (7)0.0036 (8)−0.0018 (8)

Geometric parameters (Å, °)

S1—C51.8004 (19)C6—H6B0.9900
S1—C21.8494 (16)C7—C81.527 (3)
O1—C41.224 (2)C7—H7A0.9900
N1—C111.330 (2)C7—H7B0.9900
N1—C121.347 (2)C8—C91.525 (3)
N2—C111.328 (2)C8—H8A0.9900
N2—C141.339 (2)C8—H8B0.9900
N3—C41.363 (2)C9—C101.533 (2)
N3—C111.436 (2)C9—H9A0.9900
N3—C21.480 (2)C9—H9B0.9900
C2—C101.527 (2)C10—H10A0.9900
C2—C61.528 (2)C10—H10B0.9900
C4—C51.507 (2)C12—C131.382 (3)
C5—H5A0.9900C12—H120.9500
C5—H5B0.9900C13—C141.384 (2)
C6—C71.530 (3)C13—H130.9500
C6—H6A0.9900C14—H140.9500
C5—S1—C293.63 (8)H7A—C7—H7B108.0
C11—N1—C12115.20 (15)C9—C8—C7111.57 (14)
C11—N2—C14115.15 (15)C9—C8—H8A109.3
C4—N3—C11118.58 (14)C7—C8—H8A109.3
C4—N3—C2119.29 (14)C9—C8—H8B109.3
C11—N3—C2122.06 (13)C7—C8—H8B109.3
N3—C2—C10112.34 (13)H8A—C8—H8B108.0
N3—C2—C6111.29 (14)C8—C9—C10111.08 (15)
C10—C2—C6110.16 (13)C8—C9—H9A109.4
N3—C2—S1102.80 (10)C10—C9—H9A109.4
C10—C2—S1110.96 (12)C8—C9—H9B109.4
C6—C2—S1109.06 (11)C10—C9—H9B109.4
O1—C4—N3124.04 (15)H9A—C9—H9B108.0
O1—C4—C5123.77 (15)C2—C10—C9111.29 (13)
N3—C4—C5112.18 (15)C2—C10—H10A109.4
C4—C5—S1107.29 (12)C9—C10—H10A109.4
C4—C5—H5A110.3C2—C10—H10B109.4
S1—C5—H5A110.3C9—C10—H10B109.4
C4—C5—H5B110.3H10A—C10—H10B108.0
S1—C5—H5B110.3N2—C11—N1128.08 (15)
H5A—C5—H5B108.5N2—C11—N3115.10 (13)
C2—C6—C7111.52 (15)N1—C11—N3116.80 (14)
C2—C6—H6A109.3N1—C12—C13122.23 (16)
C7—C6—H6A109.3N1—C12—H12118.9
C2—C6—H6B109.3C13—C12—H12118.9
C7—C6—H6B109.3C12—C13—C14116.59 (16)
H6A—C6—H6B108.0C12—C13—H13121.7
C8—C7—C6111.59 (15)C14—C13—H13121.7
C8—C7—H7A109.3N2—C14—C13122.69 (17)
C6—C7—H7A109.3N2—C14—H14118.7
C8—C7—H7B109.3C13—C14—H14118.7
C6—C7—H7B109.3
C4—N3—C2—C10101.41 (16)C2—C6—C7—C854.95 (19)
C11—N3—C2—C10−75.57 (19)C6—C7—C8—C9−53.8 (2)
C4—N3—C2—C6−134.54 (15)C7—C8—C9—C1054.38 (19)
C11—N3—C2—C648.48 (19)N3—C2—C10—C9−178.32 (14)
C4—N3—C2—S1−17.93 (17)C6—C2—C10—C957.00 (18)
C11—N3—C2—S1165.09 (12)S1—C2—C10—C9−63.87 (16)
C5—S1—C2—N319.77 (12)C8—C9—C10—C2−56.35 (18)
C5—S1—C2—C10−100.52 (12)C14—N2—C11—N12.2 (3)
C5—S1—C2—C6137.96 (12)C14—N2—C11—N3−176.42 (16)
C11—N3—C4—O13.4 (2)C12—N1—C11—N2−0.6 (3)
C2—N3—C4—O1−173.65 (15)C12—N1—C11—N3177.99 (15)
C11—N3—C4—C5−177.71 (14)C4—N3—C11—N266.8 (2)
C2—N3—C4—C55.2 (2)C2—N3—C11—N2−116.21 (17)
O1—C4—C5—S1−170.17 (14)C4—N3—C11—N1−111.96 (18)
N3—C4—C5—S110.98 (18)C2—N3—C11—N165.0 (2)
C2—S1—C5—C4−18.17 (13)C11—N1—C12—C13−1.7 (3)
N3—C2—C6—C7178.46 (13)N1—C12—C13—C142.1 (3)
C10—C2—C6—C7−56.27 (18)C11—N2—C14—C13−1.6 (3)
S1—C2—C6—C765.74 (15)C12—C13—C14—N2−0.4 (3)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C10—H10a···S1i0.992.803.4765 (13)126
C10—H10b···O1ii0.992.443.361 (2)155

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HG2601).

References

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