2-Chloro-1-(4,5,6,7-tetrahydro­thieno[3,2-c]pyridin-5-yl)ethanone

Yang, C.-W.; Yang, M.; Liu, D.-K.; Wang, P.-B.

doi:10.1107/S1600536810046805

organic compounds

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ISSN: 2056-9890

Volume 66| Part 12| December 2010| Page o3214

https://doi.org/10.1107/S1600536810046805

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2-Chloro-1-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)ethanone

Chuan-Wei Yang,^a Miao Yang,^b Deng-Ke Liu ^b ^* and Ping-Bao Wang ^b

^aSchool of Pharmacy, Henan University, Henan, 475004, 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 8 November 2010; accepted 12 November 2010; online 17 November 2010)

In the title compound, C₉H₁₀ClNOS, the dihedral angle between the planar thiophene ring and 2-chloroethane moiety (r.m.s deviations of 0.003 and 0.015 Å, respectively) is 45.79 (6)°. The tetrahydropyridine ring adopts a half-chair conformation. The crystal packing reveals intermolecular C—H⋯O interactions.

Related literature

The title compound is an intermediate in the synthesis of thienopyridine compounds, which are characterized by antiplatelet activity. For background to thienopyridine derivatives, see: Kam & Nethery (2003 ). For bond-length data, see: Allen et al. (1987 ). For ring conformational analysis, see: Cremer & Pople (1975 ). For the preparation of 4,5,6,7-tetrahydro-thieno[3,2-c]pyridine hydrochloride, see: Lodewijk & Khatri (1989 ).

Experimental

Crystal data

C₉H₁₀ClNOS
M_r = 215.69
Orthorhombic, P c a 2₁
a = 10.5753 (4) Å
b = 10.8291 (4) Å
c = 8.0679 (3) Å
V = 923.94 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.59 mm⁻¹
T = 113 K
0.26 × 0.24 × 0.18 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005 ) T_min = 0.861, T_max = 0.901
8326 measured reflections
1927 independent reflections
1850 reflections with I > 2σ(I)
R_int = 0.026

Refinement

R[F² > 2σ(F²)] = 0.020
wR(F²) = 0.057
S = 1.09
1927 reflections
119 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.20 e Å⁻³
Absolute structure: Flack (1983 ), 755 Friedel pairs
Flack parameter: 0.02 (5)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C9—H9A⋯O1ⁱ	0.99	2.55	3.356 (2)	138
Symmetry code: (i) $[-x+{\script{1\over 2}}, y, z-{\script{1\over 2}}]$ .

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) and PLATON (Spek, 2009 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536810046805/kp2289sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810046805/kp2289Isup2.hkl

checkCIF report

Comment top

The thienopyridines ticlopidine and clopidogrel are inhibitors of platelet function in vivo. They are effective in preventing atherothrombotic events in cardiovascular, cerebrovascular, and peripheral vascular disease (Kam & Nethery, 2003). The crystal structure of the title compound, 2-chloro-1-(6,7-dihydrothieno [3,2-c]pyridin-5(4H)-yl)ethanone (I), an intermediate in the synthesis of some of the thienopyridines, is reported here.

In the title compound (Fig. 1) all bond lengths and angles in (I) are within normal ranges (Allen et al., 1987). The thiophene ring is planar (r.m.s. deviation 0.003 Å for C8/C9/N1/O1/Cl1). The half chair conformation of the tetrahydropyridine ring is defined by the puckering parameter of φ₂=217.5 (2) ° and QT=0.5052 (15) Å (Cremer & Pople, 1975). The packing is realised by intermolecular C—H···O (Table 1) interactions.

Related literature top

The title compound is an intermediate in the synthesis of thienopyridine compounds, which are characterized by antiplatelet activity. For background to thienopyridine derivatives, see: Kam & Nethery (2003). For bond-length data, see: Allen et al. (1987). For ring conformational analysis, see: Cremer & Pople (1975). For the preparation of 4,5,6,7-tetrahydro-thieno[3,2-c]pyridine hydrochloride, see: Lodewijk & Khatri (1989).

Experimental top

The synthesis of 4,5,6,7-tetrahydro-thieno[3,2-c]pyridine hydrochloride was reported by Lodewijk & Khatri (1989). In our experiment, 4,5,6,7-tetrahydro-thieno[3,2-c]pyridine was released from 4,5,6,7-tetrahydrothieno[3,2,c]pyridine hydrochloride (5.0 g, 29 mmol) by reaction with NaHCO₃ (7.3 g, 87 mmol) in the presence of CH₂Cl₂ (50 mL) and water (15 mL), stirred for 4 h at 273 K. The organic phase was washed with water and evaporated off under reduced pressure to get yellow oil (3.9 g, 28 mmol). The oil was dissolved in CH₂Cl₂ (50 mL) and 2-chloroacetyl chloride (3.5 g, 31 mmol) was added dropwise into the mixture. The mixture was stirred at 268 K for 5 h, the organic phase was washed with water and evaporated off under reduced pressure to get yellow oil (5.7 g) as a crude product. The product was dissolved in a mixture of petroleum ether (40 mL) and acetone (10 mL) at 273 K, and white crystals were grown slowly.

Structure description top

The title compound is an intermediate in the synthesis of thienopyridine compounds, which are characterized by antiplatelet activity. For background to thienopyridine derivatives, see: Kam & Nethery (2003). For bond-length data, see: Allen et al. (1987). For ring conformational analysis, see: Cremer & Pople (1975). For the preparation of 4,5,6,7-tetrahydro-thieno[3,2-c]pyridine hydrochloride, see: Lodewijk & Khatri (1989).

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: SHELXL97 (Sheldrick, 2008); software used to prepare material for publication: CrystalStructure (Rigaku/MSC, 2005) and PLATON (Spek, 2009).

Figures top

Fig. 1. The molecular structure of (I), Displacement ellipsoids are drawn at the 50% probability level.

2-Chloro-1-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)ethanone top

Crystal data top

C₉H₁₀ClNOS	F(000) = 448
M_r = 215.69	D_x = 1.551 Mg m⁻³
Orthorhombic, Pca2₁	Mo Kα radiation, λ = 0.71070 Å
Hall symbol: P 2c -2ac	Cell parameters from 3069 reflections
a = 10.5753 (4) Å	θ = 1.9–27.9°
b = 10.8291 (4) Å	µ = 0.59 mm⁻¹
c = 8.0679 (3) Å	T = 113 K
V = 923.94 (6) Å³	Block, colourless
Z = 4	0.26 × 0.24 × 0.18 mm

Data collection top

Rigaku Saturn CCD area detector diffractometer	1927 independent reflections
Radiation source: rotating anode	1850 reflections with I > 2σ(I)
Confocal monochromator	R_int = 0.026
Detector resolution: 7.31 pixels mm^-1	θ_max = 27.9°, θ_min = 1.9°
ω and φ scans	h = −13→13
Absorption correction: multi-scan CrystalClear	k = −14→14
T_min = 0.861, T_max = 0.901	l = −10→8
8326 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)] = 0.020	w = 1/[σ²(F_o²) + (0.0393P)²] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.057	(Δ/σ)_max = 0.001
S = 1.09	Δρ_max = 0.23 e Å⁻³
1927 reflections	Δρ_min = −0.20 e Å⁻³
119 parameters	Extinction correction: SHELXL, Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
1 restraint	Extinction coefficient: 0.035 (5)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), 743 Friedel pairs
Secondary atom site location: difference Fourier map	Absolute structure parameter: 0.02 (5)

Crystal data top

C₉H₁₀ClNOS	V = 923.94 (6) Å³
M_r = 215.69	Z = 4
Orthorhombic, Pca2₁	Mo Kα radiation
a = 10.5753 (4) Å	µ = 0.59 mm⁻¹
b = 10.8291 (4) Å	T = 113 K
c = 8.0679 (3) Å	0.26 × 0.24 × 0.18 mm

Data collection top

Rigaku Saturn CCD area detector diffractometer	1927 independent reflections
Absorption correction: multi-scan CrystalClear	1850 reflections with I > 2σ(I)
T_min = 0.861, T_max = 0.901	R_int = 0.026
8326 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.020	H-atom parameters constrained
wR(F²) = 0.057	Δρ_max = 0.23 e Å⁻³
S = 1.09	Δρ_min = −0.20 e Å⁻³
1927 reflections	Absolute structure: Flack (1983), 743 Friedel pairs
119 parameters	Absolute structure parameter: 0.02 (5)
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
Cl1	0.26658 (4)	−0.10564 (3)	0.20010 (5)	0.02247 (11)
S1	0.01605 (3)	0.55872 (3)	0.34620 (6)	0.01748 (10)
O1	0.35771 (11)	0.10076 (10)	0.39637 (14)	0.0196 (3)
N1	0.17029 (11)	0.18603 (10)	0.47077 (16)	0.0144 (3)
C1	0.14078 (15)	0.62110 (13)	0.4538 (2)	0.0186 (3)
H1	0.1563	0.7072	0.4633	0.022*
C2	0.21493 (14)	0.53226 (13)	0.52392 (19)	0.0171 (3)
H2	0.2877	0.5491	0.5891	0.021*
C3	0.17003 (14)	0.41084 (12)	0.48778 (19)	0.0141 (3)
C4	0.06333 (14)	0.40982 (12)	0.39463 (19)	0.0136 (3)
C5	−0.01059 (13)	0.29663 (11)	0.3500 (3)	0.0162 (3)
H5A	0.0058	0.2734	0.2333	0.019*
H5B	−0.1023	0.3123	0.3631	0.019*
C6	0.03142 (13)	0.19294 (12)	0.4661 (2)	0.0160 (3)
H6A	−0.0015	0.2086	0.5790	0.019*
H6B	−0.0035	0.1133	0.4269	0.019*
C7	0.22995 (14)	0.29303 (12)	0.5499 (2)	0.0161 (3)
H7A	0.3215	0.2936	0.5246	0.019*
H7B	0.2198	0.2873	0.6717	0.019*
C8	0.24161 (16)	0.10101 (12)	0.3917 (2)	0.0156 (3)
C9	0.16586 (13)	0.00648 (13)	0.29136 (19)	0.0171 (3)
H9A	0.1180	0.0496	0.2032	0.021*
H9B	0.1043	−0.0352	0.3649	0.021*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0279 (2)	0.01909 (17)	0.02041 (19)	0.00927 (14)	−0.00056 (18)	−0.00199 (16)
S1	0.01631 (18)	0.01532 (16)	0.02081 (19)	0.00237 (13)	−0.00046 (18)	0.00111 (16)
O1	0.0134 (6)	0.0224 (5)	0.0229 (6)	0.0025 (4)	0.0001 (4)	0.0021 (4)
N1	0.0134 (6)	0.0131 (5)	0.0167 (6)	−0.0018 (4)	0.0003 (5)	0.0000 (5)
C1	0.0198 (8)	0.0159 (6)	0.0201 (8)	−0.0039 (5)	0.0037 (6)	−0.0013 (6)
C2	0.0161 (8)	0.0189 (7)	0.0163 (8)	−0.0033 (5)	0.0011 (6)	−0.0025 (6)
C3	0.0130 (7)	0.0162 (6)	0.0131 (7)	−0.0011 (5)	0.0024 (6)	0.0005 (5)
C4	0.0114 (7)	0.0138 (6)	0.0157 (8)	0.0014 (5)	0.0033 (5)	−0.0002 (5)
C5	0.0116 (6)	0.0170 (6)	0.0198 (7)	−0.0001 (5)	−0.0018 (6)	−0.0029 (7)
C6	0.0127 (7)	0.0140 (6)	0.0214 (8)	−0.0023 (5)	0.0043 (6)	−0.0021 (6)
C7	0.0155 (7)	0.0150 (6)	0.0179 (8)	−0.0019 (5)	−0.0036 (6)	0.0002 (6)
C8	0.0193 (8)	0.0146 (6)	0.0128 (7)	0.0020 (5)	0.0005 (6)	0.0049 (5)
C9	0.0173 (7)	0.0165 (6)	0.0175 (7)	0.0043 (5)	0.0001 (6)	−0.0016 (5)

Geometric parameters (Å, º) top

Cl1—C9	1.7751 (14)	C3—C7	1.5103 (18)
S1—C1	1.7173 (17)	C4—C5	1.4977 (18)
S1—C4	1.7329 (14)	C5—C6	1.528 (2)
O1—C8	1.2283 (19)	C5—H5A	0.9900
N1—C8	1.3503 (19)	C5—H5B	0.9900
N1—C7	1.4658 (17)	C6—H6A	0.9900
N1—C6	1.4710 (18)	C6—H6B	0.9900
C1—C2	1.364 (2)	C7—H7A	0.9900
C1—H1	0.9500	C7—H7B	0.9900
C2—C3	1.4280 (19)	C8—C9	1.532 (2)
C2—H2	0.9500	C9—H9A	0.9900
C3—C4	1.356 (2)	C9—H9B	0.9900

C1—S1—C4	91.75 (7)	N1—C6—C5	110.08 (11)
C8—N1—C7	120.29 (12)	N1—C6—H6A	109.6
C8—N1—C6	125.47 (13)	C5—C6—H6A	109.6
C7—N1—C6	113.62 (11)	N1—C6—H6B	109.6
C2—C1—S1	111.95 (11)	C5—C6—H6B	109.6
C2—C1—H1	124.0	H6A—C6—H6B	108.2
S1—C1—H1	124.0	N1—C7—C3	110.02 (12)
C1—C2—C3	111.93 (13)	N1—C7—H7A	109.7
C1—C2—H2	124.0	C3—C7—H7A	109.7
C3—C2—H2	124.0	N1—C7—H7B	109.7
C4—C3—C2	113.42 (13)	C3—C7—H7B	109.7
C4—C3—C7	121.76 (12)	H7A—C7—H7B	108.2
C2—C3—C7	124.78 (13)	O1—C8—N1	123.06 (14)
C3—C4—C5	125.05 (13)	O1—C8—C9	122.51 (13)
C3—C4—S1	110.95 (10)	N1—C8—C9	114.41 (13)
C5—C4—S1	123.83 (11)	C8—C9—Cl1	111.26 (10)
C4—C5—C6	107.60 (13)	C8—C9—H9A	109.4
C4—C5—H5A	110.2	Cl1—C9—H9A	109.4
C6—C5—H5A	110.2	C8—C9—H9B	109.4
C4—C5—H5B	110.2	Cl1—C9—H9B	109.4
C6—C5—H5B	110.2	H9A—C9—H9B	108.0
H5A—C5—H5B	108.5

C4—S1—C1—C2	−0.19 (13)	C7—N1—C6—C5	67.73 (16)
S1—C1—C2—C3	0.67 (18)	C4—C5—C6—N1	−48.83 (16)
C1—C2—C3—C4	−1.0 (2)	C8—N1—C7—C3	126.36 (14)
C1—C2—C3—C7	−178.84 (14)	C6—N1—C7—C3	−45.10 (16)
C2—C3—C4—C5	−174.63 (15)	C4—C3—C7—N1	10.1 (2)
C7—C3—C4—C5	3.3 (2)	C2—C3—C7—N1	−172.22 (13)
C2—C3—C4—S1	0.80 (17)	C7—N1—C8—O1	7.9 (2)
C7—C3—C4—S1	178.75 (12)	C6—N1—C8—O1	178.27 (14)
C1—S1—C4—C3	−0.36 (13)	C7—N1—C8—C9	−170.49 (12)
C1—S1—C4—C5	175.15 (15)	C6—N1—C8—C9	−0.1 (2)
C3—C4—C5—C6	16.2 (2)	O1—C8—C9—Cl1	4.40 (19)
S1—C4—C5—C6	−158.65 (11)	N1—C8—C9—Cl1	−177.22 (11)
C8—N1—C6—C5	−103.21 (16)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C9—H9A···O1ⁱ	0.99	2.55	3.356 (2)	138

Symmetry code: (i) −x+1/2, y, z−1/2.

Experimental details

Crystal data
Chemical formula	C₉H₁₀ClNOS
M_r	215.69
Crystal system, space group	Orthorhombic, Pca2₁
Temperature (K)	113
a, b, c (Å)	10.5753 (4), 10.8291 (4), 8.0679 (3)
V (Å³)	923.94 (6)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.59
Crystal size (mm)	0.26 × 0.24 × 0.18

Data collection
Diffractometer	Rigaku Saturn CCD area detector
Absorption correction	Multi-scan CrystalClear
T_min, T_max	0.861, 0.901
No. of measured, independent and observed [I > 2σ(I)] reflections	8326, 1927, 1850
R_int	0.026
(sin θ/λ)_max (Å⁻¹)	0.657

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.020, 0.057, 1.09
No. of reflections	1927
No. of parameters	119
No. of restraints	1
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.23, −0.20
Absolute structure	Flack (1983), 743 Friedel pairs
Absolute structure parameter	0.02 (5)

Computer programs: CrystalClear(Rigaku/MSC, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), CrystalStructure (Rigaku/MSC, 2005) and PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C9—H9A···O1ⁱ	0.99	2.55	3.356 (2)	138

Symmetry code: (i) −x+1/2, y, z−1/2.

Acknowledgements

The authors thank Mr Hai-Bin Song, Nankai University, for helpful discussions.

References

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