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Acta Crystallogr Sect E Struct Rep Online. 2010 April 1; 66(Pt 4): o820.
Published online 2010 March 13. doi:  10.1107/S1600536810007087
PMCID: PMC2983765

Methyl 5-O-(4-chloro­benzo­yl)-2-de­oxy-3-O-methyl­sulfonyl-threo-pentofuran­oside

Abstract

In the chiral title compound, C14H17ClO7S, an inter­mediate in the synthesis of the AIDS treatment drug zidovudine, the threose ring adopts an envelope configuration, with the O atom at the flap position.

Related literature

For general background to the title compound, see: Li & Yan (2009 [triangle]).

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Object name is e-66-0o820-scheme1.jpg

Experimental

Crystal data

  • C14H17ClO7S
  • M r = 364.79
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o820-efi1.jpg
  • a = 5.3103 (11) Å
  • b = 10.996 (2) Å
  • c = 28.559 (6) Å
  • V = 1667.6 (6) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.39 mm−1
  • T = 113 K
  • 0.16 × 0.04 × 0.02 mm

Data collection

  • Rigaku Saturn CCD diffractometer
  • Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005 [triangle]) T min = 0.941, T max = 0.992
  • 10486 measured reflections
  • 3708 independent reflections
  • 2350 reflections with I > 2σ(I)
  • R int = 0.081

Refinement

  • R[F 2 > 2σ(F 2)] = 0.061
  • wR(F 2) = 0.160
  • S = 0.96
  • 3708 reflections
  • 210 parameters
  • H-atom parameters constrained
  • Δρmax = 0.39 e Å−3
  • Δρmin = −0.35 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 1491 Friedel pairs
  • Flack parameter: 0.14 (12)

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

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810007087/hb5317sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810007087/hb5317Isup2.hkl

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

Acknowledgments

We thank the College Research Program of Yuncheng University (2008112) for funding.

supplementary crystallographic information

Comment

Zidovudine is a nucleoside analog reverse transcriptase inhibitor, a type of antiretroviral drug. It is the first drug approved for the treatment of AIDS and HIV infection. The structure of the title compound, (I), a key intermediate in the synthesis of zidovudine, is reported here. Single-crystal X-ray diffraction analysis reveals that the title compound crystallizes in the orthorhombic space group P212121.

Experimental

A solution of methyl sulfonylchloride (21.7 g, 0.19 mol) in dichloromethane (50 ml) was added dropwise to a stirred mixture of methyl 5-O-p-chloro-benzoyl-2-deoxy-threo-pentofuranoside (45.9 g, 0.16 mol) in triethylamine (30.8 ml, 0.22 mol) at 273-278 K. After stirring for 1 h, ice water (200 ml) was added. After a further 1 h stirring, the organic layer was separated and washed sequentially with hydrochloric acid (5%, 200 ml), saturated aqueous sodium bicarbonate (200 ml) and brine solution (200 ml). The organic extracts were dried with sodium sulphate. The solvent was removed in vacuum and the crude residue purified by flash column chromatography on silica gel. Colourless prisms of (I) were obtained by slow vaporation of a solution in a mixture of ethylacetate and petroleum ether (1:4).

Refinement

C-bound H atoms were positioned geometrically and refined in the riding-model approximation, with C—H = 0.95-1.00 Å and Uiso(H) = 1.2 or 1.5Ueq(C).

Figures

Fig. 1.
The molecular structure of (I). Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radius.
Fig. 2.
The crystal packing for (I).

Crystal data

C14H17ClO7SF(000) = 760
Mr = 364.79Dx = 1.453 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 3922 reflections
a = 5.3103 (11) Åθ = 1.4–27.2°
b = 10.996 (2) ŵ = 0.39 mm1
c = 28.559 (6) ÅT = 113 K
V = 1667.6 (6) Å3Prism, colorless
Z = 40.16 × 0.04 × 0.02 mm

Data collection

Rigaku Saturn CCD diffractometer3708 independent reflections
Radiation source: rotating anode2350 reflections with I > 2σ(I)
multilayerRint = 0.081
Detector resolution: 14.63 pixels mm-1θmax = 27.4°, θmin = 1.4°
ω and [var phi] scansh = −6→6
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)k = −14→12
Tmin = 0.941, Tmax = 0.992l = −36→36
10486 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)] = 0.061H-atom parameters constrained
wR(F2) = 0.160w = 1/[σ2(Fo2) + (0.0761P)2] where P = (Fo2 + 2Fc2)/3
S = 0.96(Δ/σ)max < 0.001
3708 reflectionsΔρmax = 0.39 e Å3
210 parametersΔρmin = −0.35 e Å3
0 restraintsAbsolute structure: Flack (1983), 1491 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: 0.14 (12)

Special details

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

xyzUiso*/Ueq
S11.4386 (2)0.10450 (10)0.24656 (4)0.0343 (3)
Cl1−0.0628 (2)0.49619 (10)0.49439 (4)0.0422 (3)
O11.5556 (6)0.1924 (3)0.27718 (10)0.0405 (8)
O21.2922 (6)0.1486 (3)0.20756 (10)0.0425 (8)
O31.2518 (5)0.0213 (3)0.27563 (10)0.0354 (8)
O40.9138 (5)−0.0285 (3)0.35800 (10)0.0344 (7)
O51.0908 (6)−0.1751 (3)0.40778 (11)0.0432 (8)
O60.8593 (6)0.2219 (3)0.37504 (10)0.0372 (8)
O70.8825 (6)0.4043 (3)0.33985 (11)0.0438 (8)
C11.6668 (9)−0.0004 (4)0.22686 (16)0.0409 (11)
H1A1.79170.04190.20760.061*
H1B1.5848−0.06390.20820.061*
H1C1.7507−0.03750.25390.061*
C21.3140 (8)−0.0092 (4)0.32470 (14)0.0364 (11)
H21.49180.01210.33270.044*
C31.2591 (9)−0.1449 (4)0.33224 (17)0.0442 (13)
H3A1.2336−0.18660.30190.053*
H3B1.4002−0.18460.34900.053*
C41.0188 (8)−0.1493 (4)0.36168 (15)0.0369 (11)
H40.8989−0.21190.34950.044*
C51.1255 (8)0.0530 (4)0.35708 (16)0.0344 (10)
H51.19940.05780.38920.041*
C60.8817 (12)−0.1738 (5)0.43964 (17)0.0660 (18)
H6A0.8109−0.09160.44110.099*
H6B0.9391−0.19830.47090.099*
H6C0.7524−0.23060.42870.099*
C71.0480 (9)0.1795 (4)0.34171 (15)0.0345 (10)
H7A1.19530.23470.34170.041*
H7B0.97650.17720.30970.041*
C80.7876 (9)0.3383 (4)0.36835 (15)0.0333 (10)
C90.5748 (9)0.3752 (4)0.40003 (14)0.0341 (10)
C100.4615 (9)0.2920 (4)0.43100 (14)0.0347 (10)
H100.52060.21060.43240.042*
C110.2639 (9)0.3286 (5)0.45937 (15)0.0398 (12)
H110.18320.27220.47960.048*
C120.1858 (9)0.4488 (4)0.45785 (15)0.0349 (10)
C130.2946 (9)0.5324 (5)0.42730 (15)0.0389 (11)
H130.23500.61380.42600.047*
C140.4913 (9)0.4948 (4)0.39879 (15)0.0392 (11)
H140.56950.55140.37830.047*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.0263 (5)0.0336 (6)0.0429 (6)−0.0003 (5)−0.0009 (5)0.0002 (5)
Cl10.0340 (6)0.0454 (7)0.0473 (6)0.0034 (6)0.0002 (5)−0.0041 (5)
O10.0359 (17)0.0371 (18)0.0485 (18)−0.0078 (16)−0.0019 (16)−0.0060 (15)
O20.0409 (19)0.045 (2)0.0421 (19)−0.0024 (17)−0.0071 (15)0.0032 (15)
O30.0274 (17)0.0376 (19)0.0413 (17)−0.0057 (14)−0.0010 (13)0.0050 (14)
O40.0238 (15)0.0308 (17)0.0485 (18)−0.0014 (14)−0.0039 (14)0.0003 (13)
O50.0414 (19)0.0372 (19)0.0511 (19)0.0062 (17)0.0016 (16)0.0043 (14)
O60.0388 (19)0.0297 (17)0.0431 (18)0.0019 (14)0.0032 (13)−0.0001 (13)
O70.0443 (19)0.0324 (18)0.055 (2)0.0036 (16)0.0098 (16)0.0077 (15)
C10.034 (2)0.043 (3)0.046 (3)0.009 (2)0.003 (2)−0.003 (2)
C20.023 (2)0.052 (3)0.035 (2)0.005 (2)−0.0005 (18)0.007 (2)
C30.040 (3)0.038 (3)0.055 (3)0.009 (2)0.006 (2)0.008 (2)
C40.033 (3)0.029 (2)0.048 (3)0.006 (2)−0.003 (2)0.0000 (19)
C50.028 (2)0.033 (2)0.042 (3)−0.0045 (19)0.0035 (19)0.0022 (19)
C60.077 (4)0.062 (4)0.059 (3)0.029 (3)0.031 (3)0.015 (3)
C70.034 (2)0.030 (2)0.039 (2)0.002 (2)0.008 (2)−0.0056 (18)
C80.033 (2)0.033 (3)0.033 (2)0.002 (2)−0.0060 (19)0.0012 (19)
C90.034 (2)0.030 (2)0.038 (2)0.003 (2)−0.003 (2)0.0003 (18)
C100.032 (2)0.033 (2)0.040 (2)0.001 (2)−0.003 (2)0.0006 (19)
C110.034 (3)0.040 (3)0.045 (3)−0.004 (2)0.000 (2)0.000 (2)
C120.032 (2)0.036 (3)0.036 (3)0.003 (2)−0.005 (2)−0.0027 (19)
C130.036 (3)0.039 (3)0.042 (3)0.007 (2)0.000 (2)−0.003 (2)
C140.043 (3)0.030 (2)0.044 (3)−0.001 (2)−0.004 (2)0.004 (2)

Geometric parameters (Å, °)

S1—O21.442 (3)C3—H3B0.9900
S1—O11.444 (3)C4—H41.0000
S1—O31.585 (3)C5—C71.516 (6)
S1—C11.765 (4)C5—H51.0000
Cl1—C121.761 (5)C6—H6A0.9800
O3—C21.479 (5)C6—H6B0.9800
O4—C51.438 (5)C6—H6C0.9800
O4—C41.444 (5)C7—H7A0.9900
O5—C41.400 (5)C7—H7B0.9900
O5—C61.435 (6)C8—C91.504 (6)
O6—C81.349 (5)C9—C141.388 (6)
O6—C71.458 (5)C9—C101.408 (6)
O7—C81.201 (5)C10—C111.386 (6)
C1—H1A0.9800C10—H100.9500
C1—H1B0.9800C11—C121.386 (6)
C1—H1C0.9800C11—H110.9500
C2—C51.524 (6)C12—C131.393 (6)
C2—C31.535 (6)C13—C141.388 (6)
C2—H21.0000C13—H130.9500
C3—C41.529 (6)C14—H140.9500
C3—H3A0.9900
O2—S1—O1118.33 (19)O4—C5—H5108.9
O2—S1—O3105.14 (18)C7—C5—H5108.9
O1—S1—O3109.79 (18)C2—C5—H5108.9
O2—S1—C1110.1 (2)O5—C6—H6A109.5
O1—S1—C1109.6 (2)O5—C6—H6B109.5
O3—S1—C1102.7 (2)H6A—C6—H6B109.5
C2—O3—S1119.2 (3)O5—C6—H6C109.5
C5—O4—C4105.8 (3)H6A—C6—H6C109.5
C4—O5—C6112.5 (4)H6B—C6—H6C109.5
C8—O6—C7113.9 (3)O6—C7—C5106.9 (3)
S1—C1—H1A109.5O6—C7—H7A110.3
S1—C1—H1B109.5C5—C7—H7A110.3
H1A—C1—H1B109.5O6—C7—H7B110.3
S1—C1—H1C109.5C5—C7—H7B110.3
H1A—C1—H1C109.5H7A—C7—H7B108.6
H1B—C1—H1C109.5O7—C8—O6123.5 (4)
O3—C2—C5109.1 (3)O7—C8—C9124.0 (4)
O3—C2—C3108.1 (4)O6—C8—C9112.5 (4)
C5—C2—C3103.1 (3)C14—C9—C10119.7 (4)
O3—C2—H2112.0C14—C9—C8118.7 (4)
C5—C2—H2112.0C10—C9—C8121.6 (4)
C3—C2—H2112.0C11—C10—C9120.2 (4)
C4—C3—C2105.4 (4)C11—C10—H10119.9
C4—C3—H3A110.7C9—C10—H10119.9
C2—C3—H3A110.7C10—C11—C12119.0 (4)
C4—C3—H3B110.7C10—C11—H11120.5
C2—C3—H3B110.7C12—C11—H11120.5
H3A—C3—H3B108.8C11—C12—C13121.6 (4)
O5—C4—O4111.1 (3)C11—C12—Cl1119.2 (4)
O5—C4—C3107.2 (4)C13—C12—Cl1119.1 (4)
O4—C4—C3104.7 (4)C14—C13—C12118.9 (4)
O5—C4—H4111.2C14—C13—H13120.5
O4—C4—H4111.2C12—C13—H13120.5
C3—C4—H4111.2C13—C14—C9120.5 (4)
O4—C5—C7111.4 (4)C13—C14—H14119.8
O4—C5—C2104.2 (3)C9—C14—H14119.8
C7—C5—C2114.5 (4)
O2—S1—O3—C2−162.0 (3)C8—O6—C7—C5174.5 (4)
O1—S1—O3—C2−33.7 (3)O4—C5—C7—O659.2 (4)
C1—S1—O3—C282.8 (3)C2—C5—C7—O6177.1 (3)
S1—O3—C2—C5112.1 (3)C7—O6—C8—O7−5.1 (6)
S1—O3—C2—C3−136.5 (3)C7—O6—C8—C9174.2 (3)
O3—C2—C3—C4−106.4 (4)O7—C8—C9—C14−4.3 (7)
C5—C2—C3—C49.0 (4)O6—C8—C9—C14176.4 (4)
C6—O5—C4—O462.4 (5)O7—C8—C9—C10176.4 (5)
C6—O5—C4—C3176.2 (4)O6—C8—C9—C10−2.9 (6)
C5—O4—C4—O579.2 (4)C14—C9—C10—C111.4 (7)
C5—O4—C4—C3−36.2 (4)C8—C9—C10—C11−179.3 (4)
C2—C3—C4—O5−102.4 (4)C9—C10—C11—C12−2.1 (7)
C2—C3—C4—O415.6 (4)C10—C11—C12—C132.4 (7)
C4—O4—C5—C7166.4 (3)C10—C11—C12—Cl1−179.2 (3)
C4—O4—C5—C242.4 (4)C11—C12—C13—C14−2.0 (7)
O3—C2—C5—O484.0 (4)Cl1—C12—C13—C14179.6 (3)
C3—C2—C5—O4−30.7 (4)C12—C13—C14—C91.3 (6)
O3—C2—C5—C7−37.9 (5)C10—C9—C14—C13−1.0 (6)
C3—C2—C5—C7−152.6 (4)C8—C9—C14—C13179.7 (4)

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HB5317).

References

  • Flack, H. D. (1983). Acta Cryst. A39, 876–881.
  • Li, J. L. & Yan, L. (2009). Chin. Patent No. 101376667
  • Rigaku/MSC (2005). CrystalClear and CrystalStructure Rigaku/MSC Inc., The Woodlands, Texas, USA.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]

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