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Acta Cryst. (2009). E65, o1483    [ doi:10.1107/S160053680902039X ]

(R)-2-[(R)-2,2-Dimethyl-1,3-dioxolan-4-yl]-1,3-oxathiolan-5-one

Q.-P. Wu, D.-X. Shi, H. Wang and Q.-S. Zhang

Abstract top

In the title compound, C8H12O4S, the two five-membered rings both adopt envelope conformations. In the crystal, weak C-H...O interactions link neighbouring molecules.

Comment top

Nucleosides are a very important series of compounds in the fields of biology, drugs and chemistry (Simons, 2001); as an example, lamivudine is used as a drug for HIV and HBV diseases (Goodyear et al., 2005; Vittori et al., 2006). Studies of the synthesis of nucleoside mimetics are essential.

The purpose of this structure determination was to establish the molecular conformation of the title compound obtained by coupling (R)-(+)-2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde with 2-mercaptoacetic acid. The chirality at the 2-position (C3) is R; this satisfies our requirements for the preparation of corresponding L-nucleosides. All bond lengths and bond angles have expected values. The two 5-membered rings both adopt envelope conformations with atoms C3 and C6 at the flap. Three intermolecular C—H···O interactions link neighbouring molecules.

Related literature top

For applications of nucleosides in the fields of biology,

drugs and chemistry, see: Goodyear et al. (2005); Simons (2001); Vittori et al. (2006).

Experimental top

A solution of (R)-(+)-2,2-dimethyl -1,3-dioxolane-4-carboxaldehyde (6.51 g, 50.0 mmol) and 2-mercaptoacetic acid (4.20 ml, 60.0 mmol) in toluene (200 ml) was heated under reflux for 1.5 h. After the reaction mixture was cooled to room temperature, a saturated aqueous solution of NaHCO3 (30 ml) was added and these two layers were separated. The organic layer was washed with brine, dried (MgSO4) and concentrated under reduced pressure. The residue was isolated through short column chromatography on silica gel, which was eluted with EtOAc-petroleum to give the target compound (4.96 g, 48%). m.p. 75–77°C.

50 mg of the final product was dissolved in petroleum ether (5 ml) and the solution was kept at room temperature for 2 days to give colorless single crystals.

Refinement top

H atoms were included in the riding model approximation, with C—H distances 0.96–0.98 Å, and with Uiso(H) = kUeq(C), where k = 1.5 for methyl H and 1.2 for all other H atoms.

Computing details top

Data collection: RAPID-AUTO (Rigaku/MSC, 2005); cell refinement: RAPID-AUTO (Rigaku/MSC, 2005); data reduction: CrystalStructure (Rigaku/MSC, 2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. Molecular structure of the title compound with displacement ellipsoids drawn at the 30% probability level. Hydrogen atoms are drawn as spheres of arbitrary radius.
[Figure 2] Fig. 2. The crystal packing of the title compound, viewed along the a axis. Hydrogen bonds are shown as dashed lines.
(R)-2-[(R)-2,2-Dimethyl-1,3-dioxolan-4-yl]-1,3-oxathiolan-5-one top
Crystal data top
C8H12O4SF(000) = 216
Mr = 204.24Dx = 1.450 Mg m−3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
a = 6.5528 (13) ÅCell parameters from 1941 reflections
b = 9.4029 (19) Åθ = 2.7–27.5°
c = 7.9240 (16) ŵ = 0.33 mm−1
β = 106.60 (3)°T = 293 K
V = 467.89 (16) Å3Block, colourless
Z = 20.50 × 0.20 × 0.15 mm
Data collection top
Rigaku Saturn CCD area-detector
diffractometer		1705 independent reflections
Radiation source: fine-focus sealed tube1275 reflections with I > 2σ(I)
graphiteRint = 0.056
Detector resolution: 10.00 pixels mm-1θmax = 27.5°, θmin = 2.7°
Ω scansh = −8→8
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2005)		k = −12→11
Tmin = 0.859, Tmax = 0.952l = −10→10
1941 measured reflections
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.042 w = 1/[σ2(Fo2) + (0.088P)2]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.129(Δ/σ)max < 0.001
S = 1.01Δρmax = 0.24 e Å−3
1705 reflectionsΔρmin = −0.20 e Å−3
119 parametersExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraintExtinction coefficient: 0.102 (15)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack (1983), 593 Friedel pairs
Secondary atom site location: difference Fourier mapFlack parameter: −0.01 (13)
Crystal data top
C8H12O4SV = 467.89 (16) Å3
Mr = 204.24Z = 2
Monoclinic, P21Mo Kα radiation
a = 6.5528 (13) ŵ = 0.33 mm−1
b = 9.4029 (19) ÅT = 293 K
c = 7.9240 (16) Å0.50 × 0.20 × 0.15 mm
β = 106.60 (3)°
Data collection top
Rigaku Saturn CCD area-detector
diffractometer		1705 independent reflections
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2005)		1275 reflections with I > 2σ(I)
Tmin = 0.859, Tmax = 0.952Rint = 0.056
1941 measured reflectionsθmax = 27.5°
Refinement top
R[F2 > 2σ(F2)] = 0.042H-atom parameters constrained
wR(F2) = 0.129Δρmax = 0.24 e Å−3
S = 1.01Δρmin = −0.20 e Å−3
1705 reflectionsAbsolute structure: Flack (1983), 593 Friedel pairs
119 parametersFlack parameter: −0.01 (13)
1 restraint
Special details top

Experimental. 1H NMR(CDCl3,P.P.M.): 1.41 (d, 6 H), 3.58(d, 4 H), 3.77 (d, 1 H), 3.92 (dd, 1 H), 4.12 (dd, 1 H), 4.35 (m, 1 H), 5.45(d, 1 H).

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 (Å2) top
xyzUiso*/Ueq
S10.57296 (17)0.19608 (12)0.31212 (10)0.0733 (4)
O10.7766 (4)0.0255 (3)0.5605 (3)0.0514 (6)
O21.1103 (4)0.0457 (3)0.5630 (4)0.0734 (8)
O30.8026 (4)0.1607 (2)0.9331 (3)0.0560 (6)
O40.7352 (4)0.2936 (2)0.6920 (3)0.0482 (5)
C10.8546 (6)0.1980 (5)0.3737 (4)0.0612 (9)
H1A0.90490.18030.27180.073*
H1B0.90750.28990.42250.073*
C20.9307 (6)0.0859 (4)0.5061 (4)0.0502 (8)
C30.5800 (5)0.1011 (4)0.5101 (4)0.0509 (8)
H30.46220.03280.48510.061*
C40.5669 (5)0.1947 (4)0.6584 (4)0.0486 (7)
H40.43020.24510.62690.058*
C50.5987 (5)0.1192 (5)0.8312 (4)0.0567 (9)
H5A0.49140.14770.88710.068*
H5B0.59150.01690.81440.068*
C60.8418 (5)0.2954 (4)0.8756 (4)0.0486 (8)
C71.0731 (6)0.3117 (5)0.9004 (6)0.0742 (11)
H7A1.10100.40440.86140.111*
H7B1.12010.24050.83300.111*
H7C1.14830.30061.02280.111*
C80.7487 (7)0.4089 (5)0.9608 (5)0.0743 (12)
H8A0.77780.50000.91820.111*
H8B0.81060.40461.08610.111*
H8C0.59750.39540.93320.111*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0745 (6)0.0908 (9)0.0459 (4)−0.0108 (6)0.0034 (4)0.0026 (5)
O10.0541 (13)0.0404 (12)0.0659 (14)−0.0020 (10)0.0269 (11)−0.0011 (11)
O20.0606 (17)0.0628 (18)0.107 (2)0.0052 (14)0.0402 (16)−0.0045 (16)
O30.0649 (15)0.0446 (14)0.0563 (12)0.0047 (11)0.0139 (10)0.0108 (11)
O40.0566 (12)0.0465 (12)0.0411 (10)−0.0113 (11)0.0132 (9)0.0000 (9)
C10.082 (2)0.053 (2)0.0589 (18)−0.012 (2)0.0367 (17)−0.0009 (17)
C20.059 (2)0.0397 (17)0.0597 (18)−0.0016 (15)0.0293 (16)−0.0084 (14)
C30.0457 (16)0.0508 (19)0.0557 (17)−0.0117 (15)0.0134 (14)−0.0050 (16)
C40.0389 (14)0.0522 (19)0.0563 (15)−0.0025 (15)0.0163 (12)0.0032 (17)
C50.0558 (19)0.060 (2)0.062 (2)−0.0076 (17)0.0287 (17)0.0027 (16)
C60.0548 (19)0.0429 (18)0.0453 (16)0.0041 (15)0.0100 (14)0.0022 (13)
C70.058 (2)0.065 (3)0.088 (3)−0.0082 (19)0.004 (2)−0.004 (2)
C80.106 (3)0.057 (2)0.063 (2)0.015 (2)0.027 (2)−0.0093 (18)
Geometric parameters (Å, °) top
S1—C11.769 (4)C3—H30.9800
S1—C31.795 (4)C4—C51.504 (5)
O1—C21.333 (4)C4—H40.9800
O1—C31.425 (4)C5—H5A0.9700
O2—C21.195 (4)C5—H5B0.9700
O3—C61.395 (4)C6—C81.483 (5)
O3—C51.405 (4)C6—C71.480 (5)
O4—C41.408 (4)C7—H7A0.9600
O4—C61.423 (4)C7—H7B0.9600
C1—C21.470 (5)C7—H7C0.9600
C1—H1A0.9700C8—H8A0.9600
C1—H1B0.9700C8—H8B0.9600
C3—C41.490 (5)C8—H8C0.9600
C1—S1—C389.97 (16)O3—C5—C4104.7 (3)
C2—O1—C3113.9 (3)O3—C5—H5A110.8
C6—O3—C5107.4 (3)C4—C5—H5A110.8
C4—O4—C6109.3 (2)O3—C5—H5B110.8
C2—C1—S1107.7 (3)C4—C5—H5B110.8
C2—C1—H1A110.2H5A—C5—H5B108.9
S1—C1—H1A110.2O3—C6—O4103.9 (3)
C2—C1—H1B110.2O3—C6—C8111.5 (3)
S1—C1—H1B110.2O4—C6—C8109.2 (3)
H1A—C1—H1B108.5O3—C6—C7109.1 (3)
O2—C2—O1119.9 (3)O4—C6—C7108.8 (3)
O2—C2—C1126.4 (3)C8—C6—C7113.8 (4)
O1—C2—C1113.7 (3)C6—C7—H7A109.5
O1—C3—C4109.0 (3)C6—C7—H7B109.5
O1—C3—S1106.8 (2)H7A—C7—H7B109.5
C4—C3—S1113.7 (3)C6—C7—H7C109.5
O1—C3—H3109.1H7A—C7—H7C109.5
C4—C3—H3109.1H7B—C7—H7C109.5
S1—C3—H3109.1C6—C8—H8A109.5
O4—C4—C3108.7 (2)C6—C8—H8B109.5
O4—C4—C5104.0 (3)H8A—C8—H8B109.5
C3—C4—C5114.5 (3)C6—C8—H8C109.5
O4—C4—H4109.8H8A—C8—H8C109.5
C3—C4—H4109.8H8B—C8—H8C109.5
C5—C4—H4109.8
C3—S1—C1—C219.2 (3)S1—C3—C4—O4−57.3 (3)
C3—O1—C2—O2168.2 (3)O1—C3—C4—C5−54.1 (3)
C3—O1—C2—C1−13.0 (4)S1—C3—C4—C5−173.1 (2)
S1—C1—C2—O2171.1 (3)C6—O3—C5—C428.4 (3)
S1—C1—C2—O1−7.6 (4)O4—C4—C5—O3−11.8 (4)
C2—O1—C3—C4−96.1 (3)C3—C4—C5—O3106.7 (3)
C2—O1—C3—S127.2 (3)C5—O3—C6—O4−33.7 (3)
C1—S1—C3—O1−26.0 (3)C5—O3—C6—C883.8 (3)
C1—S1—C3—C494.2 (3)C5—O3—C6—C7−149.6 (3)
C6—O4—C4—C3−130.9 (3)C4—O4—C6—O325.9 (3)
C6—O4—C4—C5−8.5 (3)C4—O4—C6—C8−93.2 (4)
O1—C3—C4—O461.7 (3)C4—O4—C6—C7142.0 (3)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C1—H1A···O3i0.972.583.428 (4)146
C1—H1B···O2ii0.972.413.306 (6)153
C3—H3···O2iii0.982.553.265 (4)129
Symmetry codes: (i) x, y, z−1; (ii) −x+2, y+1/2, −z+1; (iii) x−1, y, z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C1—H1A···O3i0.972.583.428 (4)146
C1—H1B···O2ii0.972.413.306 (6)153
C3—H3···O2iii0.982.553.265 (4)129
Symmetry codes: (i) x, y, z−1; (ii) −x+2, y+1/2, −z+1; (iii) x−1, y, z.
Acknowledgements top

The authors thank the National Science Foundation of China (30340070) and the Ministry of Science and Technology of China (2006AA100216) for financial support.

references
References top

Flack, H. D. (1983). Acta Cryst. A39, 876–881.

Goodyear, M. D., Hill, M. L., West, J. P. & Whitehead, A. J. (2005). Tetrahedron Lett. 46, 8535–8538.

Rigaku/MSC (2005). CrystalClear, CrystalStructure and RAPID-AUTO. Rigaku/MSC Inc., The Woodlands, Texas, USA.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Simons, C. (2001). Nucleoside Mimetics, Their Chemistry and Biological Properties. Amsterdam: Gordon and Breach Science Publisher.

Vittori, S., Dal Ben, D., Lambertucci, C., Marucci, G., Volpini, R. & Cristalli, G. (2006). Curr. Med. Chem. 13, 3529–3552.