2-(Thio­phen-2-yl)ethyl 4-methyl­benzene­sulfonate

Liang, Y.-S.; Liu, B.-N.; Liu, M.; Liu, D.-K.

doi:10.1107/S1600536811023907

organic compounds

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ISSN: 2056-9890

Volume 67| Part 7| July 2011| Page o1787

doi:10.1107/S1600536811023907

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2-(Thiophen-2-yl)ethyl 4-methylbenzenesulfonate

Yan-Shu Liang,^a Bing-Ni Liu,^b ^* Mo Liu ^b and Deng-Ke Liu ^b

^aTianjin University of Commerce, Tianjin 300134, People's Republic of China, and ^bTianjin Institute of Pharmaceutical Research, Tianjin 300193, People's Republic of China
^*Correspondence e-mail: liudk@tjipr.com

(Received 31 May 2011; accepted 18 June 2011; online 25 June 2011)

In the title molecule, C₁₃H₁₄O₃S₂, the thiophene and benzene rings form a dihedral angle of 13.86 (13)°. In the crystal, weak intermolecular C—H⋯O hydrogen bonds link the molecules into layers parallel to the ab plane.

Related literature

The title compound is an intermediate in the synthesis of the antiplatelet agent clopidogrel (systematic name (+)-(S)-methyl 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetate). For background to the bioactivity and applications of clopidogrel, see: Raju et al. (2008 ). For the synthesis of the title compound, see: Sajja et al. (2007 ).

Experimental

Crystal data

C₁₃H₁₄O₃S₂
M_r = 282.36
Monoclinic, P 2₁
a = 8.6130 (9) Å
b = 5.9961 (4) Å
c = 13.1284 (12) Å
β = 97.935 (19)°
V = 671.52 (10) Å³
Z = 2
Mo Kα radiation
μ = 0.39 mm⁻¹
T = 113 K
0.20 × 0.18 × 0.10 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005 ) T_min = 0.926, T_max = 0.962
6939 measured reflections
3167 independent reflections
2365 reflections with I > 2σ(I)
R_int = 0.048

Refinement

R[F² > 2σ(F²)] = 0.035
wR(F²) = 0.088
S = 0.83
3167 reflections
164 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.39 e Å⁻³
Δρ_min = −0.38 e Å⁻³
Absolute structure: Flack (1983 ), 1405 Friedel pairs
Flack parameter: 0.00 (8)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C2—H2⋯O2ⁱ	0.95	2.58	3.523 (3)	174
C6—H6B⋯O2ⁱⁱ	0.99	2.41	3.161 (3)	132
C13—H13A⋯O3ⁱⁱⁱ	0.98	2.58	3.496 (3)	155
Symmetry codes: (i) $[-x+1, y+{\script{1\over 2}}, -z+1]$ ; (ii) x, y+1, z; (iii) x-1, y, z.

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 global, I. DOI: 10.1107/S1600536811023907/cv5113sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811023907/cv5113Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536811023907/cv5113Isup3.cdx

Supporting information file. DOI: 10.1107/S1600536811023907/cv5113Isup4.cml

checkCIF report

Comment top

Clopidogrel, a thienopyridine class inhibitor of P2Y12 ADP platelet receptor, has been found to be particularly useful in the treatment of coronary artery disease, peripheral vascular disease and cerebrovascular disease (Raju et al., 2008). Herewith we present the crystal structure of the title compound (I) used as an intermediate in the synthesis of clopidogrel (Sajja et al., 2007).

In (I) (Fig. 1), the dihedral angle formed between the benzene ring plane (r.m.s. deviation 0.0029 Å) and the thiophene ring plane (r.m.s. deviation 0.0025 Å) is 13.86 (13)°. The packing of the crystal is consolidated by the weak C—H···O interactions (Table 1).

Related literature top

The title compound is an intermediate of the antiplatelet agent clopidogrel (systematic name (+)-(S)-methyl 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetate). For background to the bioactivity and applications of clopidogrel, see: Raju et al. (2008). For the synthesis of the title compound, see: Sajja et al. (2007).

Experimental top

5 g of 4-Methylbenzene-1-sulfonyl chloride and 30 ml of toluene were charged into a clean and dry reactor followed by cooling to about 5 °C. 3.4 g 2-(Thiophen-2-yl)ethanol was added at about 5 °C over about 20 minutes, followed by addition of 4.5 g of triethylamine over about 6 h. The reaction mixture temperature was raised to about 30 °C, followed by stirring for about 9 h. The reaction mass was filtered through a Nutsche filter and washed with 50 ml of toluene, and then, the reaction filtrate was transferred into another reactor followed by washing with 80 ml of water. Organic and aqueous layers were separated and the organic layer was distilled completely at about below 70 °C to afford 6.3 g of off-white solid as crude product. The solid was dissolved in methanol 30 ml at 20 °C, then colourless crystals were generated slowly.

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), with the atom-numbering scheme and 50% probability displacement ellipsoids.

2-(Thiophen-2-yl)ethyl 4-methylbenzenesulfonate top

Crystal data top

C₁₃H₁₄O₃S₂	F(000) = 296
M_r = 282.36	D_x = 1.396 Mg m⁻³
Monoclinic, P2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 2573 reflections
a = 8.6130 (9) Å	θ = 2.4–27.9°
b = 5.9961 (4) Å	µ = 0.39 mm⁻¹
c = 13.1284 (12) Å	T = 113 K
β = 97.935 (19)°	Prism, colourless
V = 671.52 (10) Å³	0.20 × 0.18 × 0.10 mm
Z = 2

Data collection top

Rigaku Saturn CCD area-detector diffractometer	3167 independent reflections
Radiation source: rotating anode	2365 reflections with I > 2σ(I)
Multilayer monochromator	R_int = 0.048
Detector resolution: 14.63 pixels mm^-1	θ_max = 27.9°, θ_min = 2.4°
ω and ϕ scans	h = −11→11
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)	k = −7→7
T_min = 0.926, T_max = 0.962	l = −17→13
6939 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)] = 0.035	H-atom parameters constrained
wR(F²) = 0.088	w = 1/[σ²(F_o²) + (0.0455P)²] where P = (F_o² + 2F_c²)/3
S = 0.83	(Δ/σ)_max = 0.021
3167 reflections	Δρ_max = 0.39 e Å⁻³
164 parameters	Δρ_min = −0.38 e Å⁻³
1 restraint	Absolute structure: Flack (1983), 1405 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.00 (8)

Crystal data top

C₁₃H₁₄O₃S₂	V = 671.52 (10) Å³
M_r = 282.36	Z = 2
Monoclinic, P2₁	Mo Kα radiation
a = 8.6130 (9) Å	µ = 0.39 mm⁻¹
b = 5.9961 (4) Å	T = 113 K
c = 13.1284 (12) Å	0.20 × 0.18 × 0.10 mm
β = 97.935 (19)°

Data collection top

Rigaku Saturn CCD area-detector diffractometer	3167 independent reflections
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)	2365 reflections with I > 2σ(I)
T_min = 0.926, T_max = 0.962	R_int = 0.048
6939 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.035	H-atom parameters constrained
wR(F²) = 0.088	Δρ_max = 0.39 e Å⁻³
S = 0.83	Δρ_min = −0.38 e Å⁻³
3167 reflections	Absolute structure: Flack (1983), 1405 Friedel pairs
164 parameters	Absolute structure parameter: 0.00 (8)
1 restraint

Special details top

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	0.19325 (6)	0.31172 (10)	0.75706 (4)	0.02115 (14)
S2	0.22445 (7)	0.29779 (13)	0.39671 (4)	0.03087 (17)
O1	0.15911 (18)	0.3941 (3)	0.64203 (11)	0.0213 (4)
O2	0.1803 (2)	0.0753 (3)	0.75046 (13)	0.0330 (5)
O3	0.33583 (19)	0.4105 (3)	0.80406 (12)	0.0278 (4)
C1	0.3827 (2)	0.3018 (6)	0.33242 (16)	0.0278 (5)
H1	0.4116	0.1822	0.2915	0.033*
C2	0.4623 (3)	0.4953 (5)	0.34661 (18)	0.0275 (6)
H2	0.5542	0.5244	0.3163	0.033*
C3	0.3976 (2)	0.6547 (4)	0.41104 (16)	0.0193 (5)
H3	0.4385	0.7991	0.4282	0.023*
C4	0.2621 (3)	0.5599 (4)	0.44481 (16)	0.0201 (5)
C5	0.1556 (3)	0.6739 (4)	0.51055 (16)	0.0263 (6)
H5A	0.1611	0.8368	0.4993	0.032*
H5B	0.0465	0.6263	0.4870	0.032*
C6	0.1919 (3)	0.6291 (4)	0.62353 (17)	0.0221 (5)
H6A	0.3035	0.6624	0.6477	0.027*
H6B	0.1265	0.7255	0.6617	0.027*
C7	0.0366 (3)	0.4163 (4)	0.81555 (16)	0.0202 (5)
C8	0.0527 (3)	0.6179 (4)	0.86654 (16)	0.0207 (5)
H8	0.1479	0.6996	0.8707	0.025*
C9	−0.0732 (3)	0.7003 (4)	0.91203 (16)	0.0232 (5)
H9	−0.0638	0.8400	0.9465	0.028*
C10	−0.2126 (3)	0.5795 (5)	0.90745 (16)	0.0269 (6)
C11	−0.2247 (3)	0.3748 (4)	0.85539 (17)	0.0261 (6)
H11	−0.3190	0.2912	0.8518	0.031*
C12	−0.1017 (2)	0.2926 (5)	0.80928 (15)	0.0233 (5)
H12	−0.1110	0.1540	0.7739	0.028*
C13	−0.3486 (3)	0.6686 (5)	0.9550 (2)	0.0415 (8)
H13A	−0.4457	0.6455	0.9078	0.062*
H13B	−0.3336	0.8284	0.9687	0.062*
H13C	−0.3554	0.5901	1.0197	0.062*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0254 (3)	0.0184 (3)	0.0206 (3)	0.0022 (3)	0.0066 (2)	0.0007 (3)
S2	0.0249 (3)	0.0325 (4)	0.0362 (3)	−0.0035 (4)	0.0080 (2)	−0.0007 (4)
O1	0.0264 (9)	0.0206 (9)	0.0176 (8)	−0.0047 (7)	0.0059 (7)	−0.0013 (6)
O2	0.0464 (11)	0.0142 (11)	0.0429 (12)	0.0044 (8)	0.0224 (9)	0.0026 (8)
O3	0.0240 (9)	0.0355 (11)	0.0228 (9)	0.0015 (8)	−0.0004 (7)	0.0032 (8)
C1	0.0266 (12)	0.0343 (14)	0.0230 (11)	0.0024 (15)	0.0053 (9)	−0.0027 (15)
C2	0.0210 (13)	0.0330 (16)	0.0301 (13)	0.0011 (11)	0.0097 (10)	0.0086 (12)
C3	0.0179 (11)	0.0230 (15)	0.0163 (11)	0.0085 (10)	0.0000 (8)	0.0010 (10)
C4	0.0235 (12)	0.0206 (14)	0.0160 (11)	0.0033 (10)	0.0018 (9)	0.0051 (10)
C5	0.0282 (13)	0.0274 (16)	0.0245 (12)	0.0073 (11)	0.0080 (10)	0.0070 (11)
C6	0.0246 (12)	0.0189 (14)	0.0236 (12)	−0.0014 (10)	0.0056 (9)	−0.0005 (10)
C7	0.0245 (13)	0.0214 (14)	0.0149 (11)	0.0018 (10)	0.0032 (9)	0.0009 (10)
C8	0.0277 (13)	0.0196 (14)	0.0149 (11)	−0.0032 (10)	0.0041 (9)	0.0017 (9)
C9	0.0317 (13)	0.0192 (13)	0.0185 (11)	0.0031 (11)	0.0026 (9)	−0.0029 (11)
C10	0.0283 (14)	0.0343 (17)	0.0182 (12)	0.0025 (12)	0.0036 (10)	−0.0009 (11)
C11	0.0251 (13)	0.0309 (17)	0.0225 (12)	−0.0049 (10)	0.0039 (10)	−0.0049 (10)
C12	0.0300 (12)	0.0200 (13)	0.0196 (10)	−0.0027 (13)	0.0023 (8)	−0.0010 (12)
C13	0.0290 (14)	0.059 (2)	0.0373 (15)	0.0042 (15)	0.0080 (11)	−0.0180 (16)

Geometric parameters (Å, º) top

S1—O2	1.4236 (19)	C6—H6A	0.9900
S1—O3	1.4250 (17)	C6—H6B	0.9900
S1—O1	1.5776 (15)	C7—C8	1.379 (3)
S1—C7	1.758 (2)	C7—C12	1.396 (3)
S2—C1	1.700 (2)	C8—C9	1.399 (3)
S2—C4	1.708 (3)	C8—H8	0.9500
O1—C6	1.464 (3)	C9—C10	1.396 (3)
C1—C2	1.347 (4)	C9—H9	0.9500
C1—H1	0.9500	C10—C11	1.402 (4)
C2—C3	1.438 (3)	C10—C13	1.500 (3)
C2—H2	0.9500	C11—C12	1.382 (3)
C3—C4	1.423 (3)	C11—H11	0.9500
C3—H3	0.9500	C12—H12	0.9500
C4—C5	1.507 (3)	C13—H13A	0.9800
C5—C6	1.497 (3)	C13—H13B	0.9800
C5—H5A	0.9900	C13—H13C	0.9800
C5—H5B	0.9900

O2—S1—O3	119.74 (12)	C5—C6—H6A	110.0
O2—S1—O1	104.53 (10)	O1—C6—H6B	110.0
O3—S1—O1	108.65 (9)	C5—C6—H6B	110.0
O2—S1—C7	108.87 (12)	H6A—C6—H6B	108.4
O3—S1—C7	109.28 (11)	C8—C7—C12	121.5 (2)
O1—S1—C7	104.69 (10)	C8—C7—S1	119.52 (18)
C1—S2—C4	92.64 (13)	C12—C7—S1	119.0 (2)
C6—O1—S1	116.46 (14)	C7—C8—C9	119.0 (2)
C2—C1—S2	111.8 (2)	C7—C8—H8	120.5
C2—C1—H1	124.1	C9—C8—H8	120.5
S2—C1—H1	124.1	C10—C9—C8	120.8 (2)
C1—C2—C3	115.0 (2)	C10—C9—H9	119.6
C1—C2—H2	122.5	C8—C9—H9	119.6
C3—C2—H2	122.5	C9—C10—C11	118.7 (2)
C4—C3—C2	108.6 (2)	C9—C10—C13	120.9 (3)
C4—C3—H3	125.7	C11—C10—C13	120.3 (2)
C2—C3—H3	125.7	C12—C11—C10	121.1 (2)
C3—C4—C5	126.0 (2)	C12—C11—H11	119.5
C3—C4—S2	111.98 (17)	C10—C11—H11	119.5
C5—C4—S2	121.96 (18)	C11—C12—C7	118.9 (3)
C6—C5—C4	115.19 (19)	C11—C12—H12	120.5
C6—C5—H5A	108.5	C7—C12—H12	120.5
C4—C5—H5A	108.5	C10—C13—H13A	109.5
C6—C5—H5B	108.5	C10—C13—H13B	109.5
C4—C5—H5B	108.5	H13A—C13—H13B	109.5
H5A—C5—H5B	107.5	C10—C13—H13C	109.5
O1—C6—C5	108.57 (19)	H13A—C13—H13C	109.5
O1—C6—H6A	110.0	H13B—C13—H13C	109.5

O2—S1—O1—C6	−169.41 (15)	O3—S1—C7—C8	22.3 (2)
O3—S1—O1—C6	−40.48 (18)	O1—S1—C7—C8	−93.96 (19)
C7—S1—O1—C6	76.18 (17)	O2—S1—C7—C12	−25.2 (2)
C4—S2—C1—C2	0.0 (2)	O3—S1—C7—C12	−157.67 (17)
S2—C1—C2—C3	−0.4 (3)	O1—S1—C7—C12	86.1 (2)
C1—C2—C3—C4	0.7 (3)	C12—C7—C8—C9	−0.6 (3)
C2—C3—C4—C5	−177.6 (2)	S1—C7—C8—C9	179.48 (17)
C2—C3—C4—S2	−0.6 (2)	C7—C8—C9—C10	0.9 (3)
C1—S2—C4—C3	0.37 (17)	C8—C9—C10—C11	−0.6 (3)
C1—S2—C4—C5	177.50 (18)	C8—C9—C10—C13	−179.2 (2)
C3—C4—C5—C6	−94.9 (3)	C9—C10—C11—C12	0.0 (3)
S2—C4—C5—C6	88.4 (2)	C13—C10—C11—C12	178.6 (2)
S1—O1—C6—C5	178.83 (14)	C10—C11—C12—C7	0.3 (3)
C4—C5—C6—O1	−67.3 (3)	C8—C7—C12—C11	0.0 (3)
O2—S1—C7—C8	154.71 (18)	S1—C7—C12—C11	179.91 (17)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2···O2ⁱ	0.95	2.58	3.523 (3)	174
C6—H6B···O2ⁱⁱ	0.99	2.41	3.161 (3)	132
C13—H13A···O3ⁱⁱⁱ	0.98	2.58	3.496 (3)	155

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

Experimental details

Crystal data
Chemical formula	C₁₃H₁₄O₃S₂
M_r	282.36
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	113
a, b, c (Å)	8.6130 (9), 5.9961 (4), 13.1284 (12)
β (°)	97.935 (19)
V (Å³)	671.52 (10)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.39
Crystal size (mm)	0.20 × 0.18 × 0.10

Data collection
Diffractometer	Rigaku Saturn CCD area-detector diffractometer
Absorption correction	Multi-scan (CrystalClear; Rigaku/MSC, 2005)
T_min, T_max	0.926, 0.962
No. of measured, independent and observed [I > 2σ(I)] reflections	6939, 3167, 2365
R_int	0.048
(sin θ/λ)_max (Å⁻¹)	0.658

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.035, 0.088, 0.83
No. of reflections	3167
No. of parameters	164
No. of restraints	1
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.39, −0.38
Absolute structure	Flack (1983), 1405 Friedel pairs
Absolute structure parameter	0.00 (8)

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

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2···O2ⁱ	0.95	2.58	3.523 (3)	174
C6—H6B···O2ⁱⁱ	0.99	2.41	3.161 (3)	132
C13—H13A···O3ⁱⁱⁱ	0.98	2.58	3.496 (3)	155

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

Acknowledgements

The authors thank Mr Hai-Bin Song of Nankai University for the X-ray crystal structure determination and helpful suggestions.

References

Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Raju, N. C., Eikelboom, J. W. & Hirsh, J. (2008). Nat. Clin. Pract. Cardiovasc. Med. 5, 766–780. Web of Science CrossRef PubMed CAS Google Scholar
Rigaku/MSC (2005). CrystalClear and CrystalStructure. Rigaku/MSC Inc., The Woodlands, Texas, USA. Google Scholar
Sajja, E. S., Anumula, R. R., Gilla, G. & Madivada, L. R. (2007). US Patent No. 0 225 320. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar