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

Jiang, H.; Li, H.; Sun, H.

doi:10.1107/S1600536810007087

organic compounds

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ISSN: 2056-9890

Volume 66| Part 4| April 2010| Page o820

doi:10.1107/S1600536810007087

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

Hongshi Jiang,^a ^* Hui Li ^a and Hong Sun ^a

^aDepartment of Applied Chemistry, Yuncheng University, Yuncheng, Shanxi 044000, People's Republic of China
^*Correspondence e-mail: jianghongshi555@126.com

(Received 26 January 2010; accepted 24 February 2010; online 13 March 2010)

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 ).

Experimental

Crystal data

C₁₄H₁₇ClO₇S
M_r = 364.79
Orthorhombic, P 2₁ 2₁ 2₁
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 ) 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[F² > 2σ(F²)] = 0.061
wR(F²) = 0.160
S = 0.96
3708 reflections
210 parameters
H-atom parameters constrained
Δρ_max = 0.39 e Å⁻³
Δρ_min = −0.35 e Å⁻³
Absolute structure: Flack (1983 ), 1491 Friedel pairs
Flack parameter: 0.14 (12)

Data collection: CrystalClear (Rigaku/MSC, 2005); cell refinement: CrystalClear; data reduction: CrystalClear; 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: CrystalStructure (Rigaku/MSC, 2005).

Supporting information

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

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

checkCIF report

Comment top

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.

Related literature top

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

Experimental top

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).

Computing details top

Data collection: CrystalClear (Rigaku/MSC, 2005); cell refinement: CrystalClear (Rigaku/MSC, 2005); data reduction: CrystalClear (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: CrystalStructure (Rigaku/MSC, 2005).

Figures top

	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).

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

Crystal data top

C₁₄H₁₇ClO₇S	F(000) = 760
M_r = 364.79	D_x = 1.453 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 3922 reflections
a = 5.3103 (11) Å	θ = 1.4–27.2°
b = 10.996 (2) Å	µ = 0.39 mm⁻¹
c = 28.559 (6) Å	T = 113 K
V = 1667.6 (6) Å³	Prism, colorless
Z = 4	0.16 × 0.04 × 0.02 mm

Data collection top

Rigaku Saturn CCD diffractometer	3708 independent reflections
Radiation source: rotating anode	2350 reflections with I > 2σ(I)
Multilayer monochromator	R_int = 0.081
Detector resolution: 14.63 pixels mm^-1	θ_max = 27.4°, θ_min = 1.4°
ω and ϕ scans	h = −6→6
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)	k = −14→12
T_min = 0.941, T_max = 0.992	l = −36→36
10486 measured reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.061	H-atom parameters constrained
wR(F²) = 0.160	w = 1/[σ²(F_o²) + (0.0761P)²] where P = (F_o² + 2F_c²)/3
S = 0.96	(Δ/σ)_max < 0.001
3708 reflections	Δρ_max = 0.39 e Å⁻³
210 parameters	Δρ_min = −0.35 e Å⁻³
0 restraints	Absolute structure: Flack (1983), 1491 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.14 (12)

Crystal data top

C₁₄H₁₇ClO₇S	V = 1667.6 (6) Å³
M_r = 364.79	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 5.3103 (11) Å	µ = 0.39 mm⁻¹
b = 10.996 (2) Å	T = 113 K
c = 28.559 (6) Å	0.16 × 0.04 × 0.02 mm

Data collection top

Rigaku Saturn CCD diffractometer	3708 independent reflections
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)	2350 reflections with I > 2σ(I)
T_min = 0.941, T_max = 0.992	R_int = 0.081
10486 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.061	H-atom parameters constrained
wR(F²) = 0.160	Δρ_max = 0.39 e Å⁻³
S = 0.96	Δρ_min = −0.35 e Å⁻³
3708 reflections	Absolute structure: Flack (1983), 1491 Friedel pairs
210 parameters	Absolute structure parameter: 0.14 (12)
0 restraints

Special details top

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) top

	x	y	z	U_iso*/U_eq
S1	1.4386 (2)	0.10450 (10)	0.24656 (4)	0.0343 (3)
Cl1	−0.0628 (2)	0.49619 (10)	0.49439 (4)	0.0422 (3)
O1	1.5556 (6)	0.1924 (3)	0.27718 (10)	0.0405 (8)
O2	1.2922 (6)	0.1486 (3)	0.20756 (10)	0.0425 (8)
O3	1.2518 (5)	0.0213 (3)	0.27563 (10)	0.0354 (8)
O4	0.9138 (5)	−0.0285 (3)	0.35800 (10)	0.0344 (7)
O5	1.0908 (6)	−0.1751 (3)	0.40778 (11)	0.0432 (8)
O6	0.8593 (6)	0.2219 (3)	0.37504 (10)	0.0372 (8)
O7	0.8825 (6)	0.4043 (3)	0.33985 (11)	0.0438 (8)
C1	1.6668 (9)	−0.0004 (4)	0.22686 (16)	0.0409 (11)
H1A	1.7917	0.0419	0.2076	0.061*
H1B	1.5848	−0.0639	0.2082	0.061*
H1C	1.7507	−0.0375	0.2539	0.061*
C2	1.3140 (8)	−0.0092 (4)	0.32470 (14)	0.0364 (11)
H2	1.4918	0.0121	0.3327	0.044*
C3	1.2591 (9)	−0.1449 (4)	0.33224 (17)	0.0442 (13)
H3A	1.2336	−0.1866	0.3019	0.053*
H3B	1.4002	−0.1846	0.3490	0.053*
C4	1.0188 (8)	−0.1493 (4)	0.36168 (15)	0.0369 (11)
H4	0.8989	−0.2119	0.3495	0.044*
C5	1.1255 (8)	0.0530 (4)	0.35708 (16)	0.0344 (10)
H5	1.1994	0.0578	0.3892	0.041*
C6	0.8817 (12)	−0.1738 (5)	0.43964 (17)	0.0660 (18)
H6A	0.8109	−0.0916	0.4411	0.099*
H6B	0.9391	−0.1983	0.4709	0.099*
H6C	0.7524	−0.2306	0.4287	0.099*
C7	1.0480 (9)	0.1795 (4)	0.34171 (15)	0.0345 (10)
H7A	1.1953	0.2347	0.3417	0.041*
H7B	0.9765	0.1772	0.3097	0.041*
C8	0.7876 (9)	0.3383 (4)	0.36835 (15)	0.0333 (10)
C9	0.5748 (9)	0.3752 (4)	0.40003 (14)	0.0341 (10)
C10	0.4615 (9)	0.2920 (4)	0.43100 (14)	0.0347 (10)
H10	0.5206	0.2106	0.4324	0.042*
C11	0.2639 (9)	0.3286 (5)	0.45937 (15)	0.0398 (12)
H11	0.1832	0.2722	0.4796	0.048*
C12	0.1858 (9)	0.4488 (4)	0.45785 (15)	0.0349 (10)
C13	0.2946 (9)	0.5324 (5)	0.42730 (15)	0.0389 (11)
H13	0.2350	0.6138	0.4260	0.047*
C14	0.4913 (9)	0.4948 (4)	0.39879 (15)	0.0392 (11)
H14	0.5695	0.5514	0.3783	0.047*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0263 (5)	0.0336 (6)	0.0429 (6)	−0.0003 (5)	−0.0009 (5)	0.0002 (5)
Cl1	0.0340 (6)	0.0454 (7)	0.0473 (6)	0.0034 (6)	0.0002 (5)	−0.0041 (5)
O1	0.0359 (17)	0.0371 (18)	0.0485 (18)	−0.0078 (16)	−0.0019 (16)	−0.0060 (15)
O2	0.0409 (19)	0.045 (2)	0.0421 (19)	−0.0024 (17)	−0.0071 (15)	0.0032 (15)
O3	0.0274 (17)	0.0376 (19)	0.0413 (17)	−0.0057 (14)	−0.0010 (13)	0.0050 (14)
O4	0.0238 (15)	0.0308 (17)	0.0485 (18)	−0.0014 (14)	−0.0039 (14)	0.0003 (13)
O5	0.0414 (19)	0.0372 (19)	0.0511 (19)	0.0062 (17)	0.0016 (16)	0.0043 (14)
O6	0.0388 (19)	0.0297 (17)	0.0431 (18)	0.0019 (14)	0.0032 (13)	−0.0001 (13)
O7	0.0443 (19)	0.0324 (18)	0.055 (2)	0.0036 (16)	0.0098 (16)	0.0077 (15)
C1	0.034 (2)	0.043 (3)	0.046 (3)	0.009 (2)	0.003 (2)	−0.003 (2)
C2	0.023 (2)	0.052 (3)	0.035 (2)	0.005 (2)	−0.0005 (18)	0.007 (2)
C3	0.040 (3)	0.038 (3)	0.055 (3)	0.009 (2)	0.006 (2)	0.008 (2)
C4	0.033 (3)	0.029 (2)	0.048 (3)	0.006 (2)	−0.003 (2)	0.0000 (19)
C5	0.028 (2)	0.033 (2)	0.042 (3)	−0.0045 (19)	0.0035 (19)	0.0022 (19)
C6	0.077 (4)	0.062 (4)	0.059 (3)	0.029 (3)	0.031 (3)	0.015 (3)
C7	0.034 (2)	0.030 (2)	0.039 (2)	0.002 (2)	0.008 (2)	−0.0056 (18)
C8	0.033 (2)	0.033 (3)	0.033 (2)	0.002 (2)	−0.0060 (19)	0.0012 (19)
C9	0.034 (2)	0.030 (2)	0.038 (2)	0.003 (2)	−0.003 (2)	0.0003 (18)
C10	0.032 (2)	0.033 (2)	0.040 (2)	0.001 (2)	−0.003 (2)	0.0006 (19)
C11	0.034 (3)	0.040 (3)	0.045 (3)	−0.004 (2)	0.000 (2)	0.000 (2)
C12	0.032 (2)	0.036 (3)	0.036 (3)	0.003 (2)	−0.005 (2)	−0.0027 (19)
C13	0.036 (3)	0.039 (3)	0.042 (3)	0.007 (2)	0.000 (2)	−0.003 (2)
C14	0.043 (3)	0.030 (2)	0.044 (3)	−0.001 (2)	−0.004 (2)	0.004 (2)

Geometric parameters (Å, º) top

S1—O2	1.442 (3)	C3—H3B	0.9900
S1—O1	1.444 (3)	C4—H4	1.0000
S1—O3	1.585 (3)	C5—C7	1.516 (6)
S1—C1	1.765 (4)	C5—H5	1.0000
Cl1—C12	1.761 (5)	C6—H6A	0.9800
O3—C2	1.479 (5)	C6—H6B	0.9800
O4—C5	1.438 (5)	C6—H6C	0.9800
O4—C4	1.444 (5)	C7—H7A	0.9900
O5—C4	1.400 (5)	C7—H7B	0.9900
O5—C6	1.435 (6)	C8—C9	1.504 (6)
O6—C8	1.349 (5)	C9—C14	1.388 (6)
O6—C7	1.458 (5)	C9—C10	1.408 (6)
O7—C8	1.201 (5)	C10—C11	1.386 (6)
C1—H1A	0.9800	C10—H10	0.9500
C1—H1B	0.9800	C11—C12	1.386 (6)
C1—H1C	0.9800	C11—H11	0.9500
C2—C5	1.524 (6)	C12—C13	1.393 (6)
C2—C3	1.535 (6)	C13—C14	1.388 (6)
C2—H2	1.0000	C13—H13	0.9500
C3—C4	1.529 (6)	C14—H14	0.9500
C3—H3A	0.9900

O2—S1—O1	118.33 (19)	O4—C5—H5	108.9
O2—S1—O3	105.14 (18)	C7—C5—H5	108.9
O1—S1—O3	109.79 (18)	C2—C5—H5	108.9
O2—S1—C1	110.1 (2)	O5—C6—H6A	109.5
O1—S1—C1	109.6 (2)	O5—C6—H6B	109.5
O3—S1—C1	102.7 (2)	H6A—C6—H6B	109.5
C2—O3—S1	119.2 (3)	O5—C6—H6C	109.5
C5—O4—C4	105.8 (3)	H6A—C6—H6C	109.5
C4—O5—C6	112.5 (4)	H6B—C6—H6C	109.5
C8—O6—C7	113.9 (3)	O6—C7—C5	106.9 (3)
S1—C1—H1A	109.5	O6—C7—H7A	110.3
S1—C1—H1B	109.5	C5—C7—H7A	110.3
H1A—C1—H1B	109.5	O6—C7—H7B	110.3
S1—C1—H1C	109.5	C5—C7—H7B	110.3
H1A—C1—H1C	109.5	H7A—C7—H7B	108.6
H1B—C1—H1C	109.5	O7—C8—O6	123.5 (4)
O3—C2—C5	109.1 (3)	O7—C8—C9	124.0 (4)
O3—C2—C3	108.1 (4)	O6—C8—C9	112.5 (4)
C5—C2—C3	103.1 (3)	C14—C9—C10	119.7 (4)
O3—C2—H2	112.0	C14—C9—C8	118.7 (4)
C5—C2—H2	112.0	C10—C9—C8	121.6 (4)
C3—C2—H2	112.0	C11—C10—C9	120.2 (4)
C4—C3—C2	105.4 (4)	C11—C10—H10	119.9
C4—C3—H3A	110.7	C9—C10—H10	119.9
C2—C3—H3A	110.7	C10—C11—C12	119.0 (4)
C4—C3—H3B	110.7	C10—C11—H11	120.5
C2—C3—H3B	110.7	C12—C11—H11	120.5
H3A—C3—H3B	108.8	C11—C12—C13	121.6 (4)
O5—C4—O4	111.1 (3)	C11—C12—Cl1	119.2 (4)
O5—C4—C3	107.2 (4)	C13—C12—Cl1	119.1 (4)
O4—C4—C3	104.7 (4)	C14—C13—C12	118.9 (4)
O5—C4—H4	111.2	C14—C13—H13	120.5
O4—C4—H4	111.2	C12—C13—H13	120.5
C3—C4—H4	111.2	C13—C14—C9	120.5 (4)
O4—C5—C7	111.4 (4)	C13—C14—H14	119.8
O4—C5—C2	104.2 (3)	C9—C14—H14	119.8
C7—C5—C2	114.5 (4)

O2—S1—O3—C2	−162.0 (3)	C8—O6—C7—C5	174.5 (4)
O1—S1—O3—C2	−33.7 (3)	O4—C5—C7—O6	59.2 (4)
C1—S1—O3—C2	82.8 (3)	C2—C5—C7—O6	177.1 (3)
S1—O3—C2—C5	112.1 (3)	C7—O6—C8—O7	−5.1 (6)
S1—O3—C2—C3	−136.5 (3)	C7—O6—C8—C9	174.2 (3)
O3—C2—C3—C4	−106.4 (4)	O7—C8—C9—C14	−4.3 (7)
C5—C2—C3—C4	9.0 (4)	O6—C8—C9—C14	176.4 (4)
C6—O5—C4—O4	62.4 (5)	O7—C8—C9—C10	176.4 (5)
C6—O5—C4—C3	176.2 (4)	O6—C8—C9—C10	−2.9 (6)
C5—O4—C4—O5	79.2 (4)	C14—C9—C10—C11	1.4 (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—O4	15.6 (4)	C10—C11—C12—C13	2.4 (7)
C4—O4—C5—C7	166.4 (3)	C10—C11—C12—Cl1	−179.2 (3)
C4—O4—C5—C2	42.4 (4)	C11—C12—C13—C14	−2.0 (7)
O3—C2—C5—O4	84.0 (4)	Cl1—C12—C13—C14	179.6 (3)
C3—C2—C5—O4	−30.7 (4)	C12—C13—C14—C9	1.3 (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—C13	179.7 (4)

Experimental details

Crystal data
Chemical formula	C₁₄H₁₇ClO₇S
M_r	364.79
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	113
a, b, c (Å)	5.3103 (11), 10.996 (2), 28.559 (6)
V (Å³)	1667.6 (6)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.39
Crystal size (mm)	0.16 × 0.04 × 0.02

Data collection
Diffractometer	Rigaku Saturn CCD diffractometer
Absorption correction	Multi-scan (CrystalClear; Rigaku/MSC, 2005)
T_min, T_max	0.941, 0.992
No. of measured, independent and observed [I > 2σ(I)] reflections	10486, 3708, 2350
R_int	0.081
(sin θ/λ)_max (Å⁻¹)	0.647

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.061, 0.160, 0.96
No. of reflections	3708
No. of parameters	210
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.39, −0.35
Absolute structure	Flack (1983), 1491 Friedel pairs
Absolute structure parameter	0.14 (12)

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

Acknowledgements

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

References

Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Li, J. L. & Yan, L. (2009). Chin. Patent No. 101376667 Google Scholar
Rigaku/MSC (2005). CrystalClear and CrystalStructure. Rigaku/MSC Inc., The Woodlands, Texas, USA. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

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