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

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

doi:10.1107/S160053680902039X

organic compounds

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ISSN: 2056-9890

Volume 65| Part 7| July 2009| Page o1483

doi:10.1107/S160053680902039X

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

Qin-Pei Wu,^a ^* Da-Xin Shi,^a Hao Wang ^b and Qing-Shan Zhang ^a

^aSchool of Chemical Engineering and Environment, Beijing Institute of Technology, Beijing 100081, People's Republic of China, and ^bSchool of Life Science, Beijing Institute of Technology, Beijing 100081, People's Republic of China
^*Correspondence e-mail: qpw@bit.edu.cn

(Received 14 April 2009; accepted 28 May 2009; online 6 June 2009)

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.

Related literature

The title compound is a precursor for the preparation of an important nucleoside drug. For applications of nucleosides in the fields of biology, drugs and chemistry, see: Goodyear et al. (2005 ); Simons (2001 ); Vittori et al. (2006 ).

Experimental

Crystal data

C₈H₁₂O₄S
M_r = 204.24
Monoclinic, P 2₁
a = 6.5528 (13) Å
b = 9.4029 (19) Å
c = 7.9240 (16) Å
β = 106.60 (3)°
V = 467.89 (16) Å³
Z = 2
Mo Kα radiation
μ = 0.33 mm⁻¹
T = 293 K
0.50 × 0.20 × 0.15 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005 ) T_min = 0.859, T_max = 0.952
1941 measured reflections
1705 independent reflections
1275 reflections with I > 2σ(I)
R_int = 0.056

Refinement

R[F² > 2σ(F²)] = 0.042
wR(F²) = 0.129
S = 1.01
1705 reflections
119 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.20 e Å⁻³
Absolute structure: Flack (1983 ), 593 Friedel pairs
Flack parameter: −0.01 (13)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C1—H1A⋯O3ⁱ	0.97	2.58	3.428 (4)	146
C1—H1B⋯O2ⁱⁱ	0.97	2.41	3.306 (6)	153
C3—H3⋯O2ⁱⁱⁱ	0.98	2.55	3.265 (4)	129
Symmetry codes: (i) x, y, z-1; (ii) $[-x+2, y+{\script{1\over 2}}, -z+1]$ ; (iii) x-1, y, z.

Data collection: RAPID-AUTO (Rigaku/MSC, 2005); cell refinement: RAPID-AUTO; 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.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053680902039X/wn2324sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S160053680902039X/wn2324Isup2.hkl

checkCIF report

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.

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

	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.
	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

C₈H₁₂O₄S	F(000) = 216
M_r = 204.24	D_x = 1.450 Mg m⁻³
Monoclinic, P2₁	Mo Kα radiation, λ = 0.71073 Å
a = 6.5528 (13) Å	Cell parameters from 1941 reflections
b = 9.4029 (19) Å	θ = 2.7–27.5°
c = 7.9240 (16) Å	µ = 0.33 mm⁻¹
β = 106.60 (3)°	T = 293 K
V = 467.89 (16) Å³	Block, colourless
Z = 2	0.50 × 0.20 × 0.15 mm

Data collection top

Rigaku Saturn CCD area-detector diffractometer	1705 independent reflections
Radiation source: fine-focus sealed tube	1275 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.056
Detector resolution: 10.00 pixels mm^-1	θ_max = 27.5°, θ_min = 2.7°
Ω scans	h = −8→8
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)	k = −12→11
T_min = 0.859, T_max = 0.952	l = −10→10
1941 measured reflections

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.042	w = 1/[σ²(F_o²) + (0.088P)²] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.129	(Δ/σ)_max < 0.001
S = 1.01	Δρ_max = 0.24 e Å⁻³
1705 reflections	Δρ_min = −0.20 e Å⁻³
119 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
1 restraint	Extinction coefficient: 0.102 (15)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), 593 Friedel pairs
Secondary atom site location: difference Fourier map	Absolute structure parameter: −0.01 (13)

Crystal data top

C₈H₁₂O₄S	V = 467.89 (16) Å³
M_r = 204.24	Z = 2
Monoclinic, P2₁	Mo Kα radiation
a = 6.5528 (13) Å	µ = 0.33 mm⁻¹
b = 9.4029 (19) Å	T = 293 K
c = 7.9240 (16) Å	0.50 × 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)
T_min = 0.859, T_max = 0.952	R_int = 0.056
1941 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.042	H-atom parameters constrained
wR(F²) = 0.129	Δρ_max = 0.24 e Å⁻³
S = 1.01	Δρ_min = −0.20 e Å⁻³
1705 reflections	Absolute structure: Flack (1983), 593 Friedel pairs
119 parameters	Absolute structure 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

	x	y	z	U_iso*/U_eq
S1	0.57296 (17)	0.19608 (12)	0.31212 (10)	0.0733 (4)
O1	0.7766 (4)	0.0255 (3)	0.5605 (3)	0.0514 (6)
O2	1.1103 (4)	0.0457 (3)	0.5630 (4)	0.0734 (8)
O3	0.8026 (4)	0.1607 (2)	0.9331 (3)	0.0560 (6)
O4	0.7352 (4)	0.2936 (2)	0.6920 (3)	0.0482 (5)
C1	0.8546 (6)	0.1980 (5)	0.3737 (4)	0.0612 (9)
H1A	0.9049	0.1803	0.2718	0.073*
H1B	0.9075	0.2899	0.4225	0.073*
C2	0.9307 (6)	0.0859 (4)	0.5061 (4)	0.0502 (8)
C3	0.5800 (5)	0.1011 (4)	0.5101 (4)	0.0509 (8)
H3	0.4622	0.0328	0.4851	0.061*
C4	0.5669 (5)	0.1947 (4)	0.6584 (4)	0.0486 (7)
H4	0.4302	0.2451	0.6269	0.058*
C5	0.5987 (5)	0.1192 (5)	0.8312 (4)	0.0567 (9)
H5A	0.4914	0.1477	0.8871	0.068*
H5B	0.5915	0.0169	0.8144	0.068*
C6	0.8418 (5)	0.2954 (4)	0.8756 (4)	0.0486 (8)
C7	1.0731 (6)	0.3117 (5)	0.9004 (6)	0.0742 (11)
H7A	1.1010	0.4044	0.8614	0.111*
H7B	1.1201	0.2405	0.8330	0.111*
H7C	1.1483	0.3006	1.0228	0.111*
C8	0.7487 (7)	0.4089 (5)	0.9608 (5)	0.0743 (12)
H8A	0.7778	0.5000	0.9182	0.111*
H8B	0.8106	0.4046	1.0861	0.111*
H8C	0.5975	0.3954	0.9332	0.111*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0745 (6)	0.0908 (9)	0.0459 (4)	−0.0108 (6)	0.0034 (4)	0.0026 (5)
O1	0.0541 (13)	0.0404 (12)	0.0659 (14)	−0.0020 (10)	0.0269 (11)	−0.0011 (11)
O2	0.0606 (17)	0.0628 (18)	0.107 (2)	0.0052 (14)	0.0402 (16)	−0.0045 (16)
O3	0.0649 (15)	0.0446 (14)	0.0563 (12)	0.0047 (11)	0.0139 (10)	0.0108 (11)
O4	0.0566 (12)	0.0465 (12)	0.0411 (10)	−0.0113 (11)	0.0132 (9)	0.0000 (9)
C1	0.082 (2)	0.053 (2)	0.0589 (18)	−0.012 (2)	0.0367 (17)	−0.0009 (17)
C2	0.059 (2)	0.0397 (17)	0.0597 (18)	−0.0016 (15)	0.0293 (16)	−0.0084 (14)
C3	0.0457 (16)	0.0508 (19)	0.0557 (17)	−0.0117 (15)	0.0134 (14)	−0.0050 (16)
C4	0.0389 (14)	0.0522 (19)	0.0563 (15)	−0.0025 (15)	0.0163 (12)	0.0032 (17)
C5	0.0558 (19)	0.060 (2)	0.062 (2)	−0.0076 (17)	0.0287 (17)	0.0027 (16)
C6	0.0548 (19)	0.0429 (18)	0.0453 (16)	0.0041 (15)	0.0100 (14)	0.0022 (13)
C7	0.058 (2)	0.065 (3)	0.088 (3)	−0.0082 (19)	0.004 (2)	−0.004 (2)
C8	0.106 (3)	0.057 (2)	0.063 (2)	0.015 (2)	0.027 (2)	−0.0093 (18)

Geometric parameters (Å, º) top

S1—C1	1.769 (4)	C3—H3	0.9800
S1—C3	1.795 (4)	C4—C5	1.504 (5)
O1—C2	1.333 (4)	C4—H4	0.9800
O1—C3	1.425 (4)	C5—H5A	0.9700
O2—C2	1.195 (4)	C5—H5B	0.9700
O3—C6	1.395 (4)	C6—C8	1.483 (5)
O3—C5	1.405 (4)	C6—C7	1.480 (5)
O4—C4	1.408 (4)	C7—H7A	0.9600
O4—C6	1.423 (4)	C7—H7B	0.9600
C1—C2	1.470 (5)	C7—H7C	0.9600
C1—H1A	0.9700	C8—H8A	0.9600
C1—H1B	0.9700	C8—H8B	0.9600
C3—C4	1.490 (5)	C8—H8C	0.9600

C1—S1—C3	89.97 (16)	O3—C5—C4	104.7 (3)
C2—O1—C3	113.9 (3)	O3—C5—H5A	110.8
C6—O3—C5	107.4 (3)	C4—C5—H5A	110.8
C4—O4—C6	109.3 (2)	O3—C5—H5B	110.8
C2—C1—S1	107.7 (3)	C4—C5—H5B	110.8
C2—C1—H1A	110.2	H5A—C5—H5B	108.9
S1—C1—H1A	110.2	O3—C6—O4	103.9 (3)
C2—C1—H1B	110.2	O3—C6—C8	111.5 (3)
S1—C1—H1B	110.2	O4—C6—C8	109.2 (3)
H1A—C1—H1B	108.5	O3—C6—C7	109.1 (3)
O2—C2—O1	119.9 (3)	O4—C6—C7	108.8 (3)
O2—C2—C1	126.4 (3)	C8—C6—C7	113.8 (4)
O1—C2—C1	113.7 (3)	C6—C7—H7A	109.5
O1—C3—C4	109.0 (3)	C6—C7—H7B	109.5
O1—C3—S1	106.8 (2)	H7A—C7—H7B	109.5
C4—C3—S1	113.7 (3)	C6—C7—H7C	109.5
O1—C3—H3	109.1	H7A—C7—H7C	109.5
C4—C3—H3	109.1	H7B—C7—H7C	109.5
S1—C3—H3	109.1	C6—C8—H8A	109.5
O4—C4—C3	108.7 (2)	C6—C8—H8B	109.5
O4—C4—C5	104.0 (3)	H8A—C8—H8B	109.5
C3—C4—C5	114.5 (3)	C6—C8—H8C	109.5
O4—C4—H4	109.8	H8A—C8—H8C	109.5
C3—C4—H4	109.8	H8B—C8—H8C	109.5
C5—C4—H4	109.8

C3—S1—C1—C2	19.2 (3)	S1—C3—C4—O4	−57.3 (3)
C3—O1—C2—O2	168.2 (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—O2	171.1 (3)	C6—O3—C5—C4	28.4 (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—O3	106.7 (3)
C2—O1—C3—S1	27.2 (3)	C5—O3—C6—O4	−33.7 (3)
C1—S1—C3—O1	−26.0 (3)	C5—O3—C6—C8	83.8 (3)
C1—S1—C3—C4	94.2 (3)	C5—O3—C6—C7	−149.6 (3)
C6—O4—C4—C3	−130.9 (3)	C4—O4—C6—O3	25.9 (3)
C6—O4—C4—C5	−8.5 (3)	C4—O4—C6—C8	−93.2 (4)
O1—C3—C4—O4	61.7 (3)	C4—O4—C6—C7	142.0 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1A···O3ⁱ	0.97	2.58	3.428 (4)	146
C1—H1B···O2ⁱⁱ	0.97	2.41	3.306 (6)	153
C3—H3···O2ⁱⁱⁱ	0.98	2.55	3.265 (4)	129

Symmetry codes: (i) x, y, z−1; (ii) −x+2, y+1/2, −z+1; (iii) x−1, y, z.

Experimental details

Crystal data
Chemical formula	C₈H₁₂O₄S
M_r	204.24
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	293
a, b, c (Å)	6.5528 (13), 9.4029 (19), 7.9240 (16)
β (°)	106.60 (3)
V (Å³)	467.89 (16)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.33
Crystal size (mm)	0.50 × 0.20 × 0.15

Data collection
Diffractometer	Rigaku Saturn CCD area-detector diffractometer
Absorption correction	Multi-scan (CrystalClear; Rigaku/MSC, 2005)
T_min, T_max	0.859, 0.952
No. of measured, independent and observed [I > 2σ(I)] reflections	1941, 1705, 1275
R_int	0.056
(sin θ/λ)_max (Å⁻¹)	0.649

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.042, 0.129, 1.01
No. of reflections	1705
No. of parameters	119
No. of restraints	1
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.24, −0.20
Absolute structure	Flack (1983), 593 Friedel pairs
Absolute structure parameter	−0.01 (13)

Computer programs: RAPID-AUTO (Rigaku/MSC, 2005), CrystalStructure (Rigaku/MSC, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1A···O3ⁱ	0.97	2.58	3.428 (4)	146
C1—H1B···O2ⁱⁱ	0.97	2.41	3.306 (6)	153
C3—H3···O2ⁱⁱⁱ	0.98	2.55	3.265 (4)	129

Symmetry codes: (i) x, y, z−1; (ii) −x+2, y+1/2, −z+1; (iii) x−1, y, z.

Acknowledgements

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

References

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