Ethyl 3-bromo-4-cyano-5-[(2-eth­oxy-2-oxoeth­yl)sulfan­yl]thio­phene-2-carboxyl­ate

Li, X.; Jia, X.; Li, J.

doi:10.1107/S1600536813010611

organic compounds

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ISSN: 2056-9890

Volume 69| Part 6| June 2013| Page o848

doi:10.1107/S1600536813010611

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Ethyl 3-bromo-4-cyano-5-[(2-ethoxy-2-oxoethyl)sulfanyl]thiophene-2-carboxylate

Xiuping Li,^a ^* Xiaochuan Jia ^a and Jing Li ^a

^aTianjin Entry–Exit Inspection and Quarantine Bureau, Youyi road No. 33, Tianjin, People's Republic of China
^*Correspondence e-mail: xpli0705@163.com

(Received 14 March 2013; accepted 18 April 2013; online 11 May 2013)

The title compound, C₁₂H₁₂BrNO₄S₂, was obtained by the Sandmeyer reaction from ethyl 3-amino-4-cyano-5-[(2-ethoxy-2-oxoethyl)sulfanyl]thiophene-2-carboxylate. The dihedral angle between the thiophene ring and linked CO₂ ester group is 2.0 (5)°.

Related literature

For background literature on the use of 3-amino-4-cyano-5-ethoxycarbonylmethylsulfanyl-thiophene-2-carboxylic acid ethyl ester as an important intermediate compound for the synthesis of thienopyrimidine derivatives, which are thought to be potential biologically active compounds or pharmaceuticals, see: Liu et al. (2008 ). For a related compound, see: Padmavathi et al. (2011 ).

Experimental

Crystal data

C₁₂H₁₂BrNO₄S₂
M_r = 378.26
Monoclinic, P 2₁ /c
a = 8.5896 (17) Å
b = 10.837 (2) Å
c = 16.584 (3) Å
β = 99.44 (3)°
V = 1522.8 (5) Å³
Z = 4
Mo Kα radiation
μ = 2.98 mm⁻¹
T = 293 K
0.20 × 0.18 × 0.12 mm

Data collection

Rigaku Saturn diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005 ) T_min = 0.587, T_max = 0.716
15211 measured reflections
3596 independent reflections
2224 reflections with I > 2σ(I)
R_int = 0.067

Refinement

R[F² > 2σ(F²)] = 0.052
wR(F²) = 0.157
S = 1.00
3596 reflections
184 parameters
H-atom parameters constrained
Δρ_max = 0.43 e Å⁻³
Δρ_min = −0.71 e Å⁻³

Data collection: CrystalClear (Rigaku, 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: SHELXTL.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536813010611/zj2102sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536813010611/zj2102Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536813010611/zj2102Isup3.cml

checkCIF report

Comment top

3-Amino-4-cyano-5-ethoxycarbonylmethylsulfanyl-thiophene-2-carboxylic acid ethyl ester is an important intermediate compound for sythesis of thienothienopyrimidines derivatives, which are thought to be potential biological active compounds or pharmaceuticals (Liu, et al.,2008). We obtained the title compound by the Sandmeyer reaction from compound 3-Amino-4-cyano-5-ethoxycarbonylmethylsulfanyl-thiophene-2-carboxylic acid ethyl ester.The crystal for X-ray crystal structure analysis was obtained by recrystallizing the title compound in petroleum ether. In the crystal, the thiophene ring together with its four adjoint groups, i.e. CN, Br, S—CH₂ and COO–,was located at one perfect plane, which is consistent with the crystal of 3-Amino-4-cyano-5-ethoxycarbonylmethylsulfany- thiophene-2-carboxylic acid ethyl ester reported in the literature (Padmavathi et al., 2011). The title compound cyrstal demonstrated a crystal system of monoclinic and a spce group of P2(1)/c. There existed hydrogen bond with length of 2.554 Å between one of –SCH₂ H atom and the O atom of carbonyl adjoined with thiophene ring of neighbor molecule.

Related literature top

For background literature on the use of 3-amino-4-cyano-5-ethoxycarbonylmethylsulfanyl-thiophene-2-carboxylic acid ethyl ester as an important intermediate compound for the synthesis of thienothienopyrimidines derivatives, which are thought to be potential biologically active compounds or pharmaceuticals, see: Liu et al. (2008). For a related compound, see: Padmavathi et al. (2011).

Experimental top

To a solution of 3-Amino-4-cyano-5-ethoxycarbonylmethylsulfanyl -thiophene-2-carboxylic acid ethyl ester (1.57 g, 5 mmol) in 70% H₂SO₄ (13 mL) was added NaNO₂ (0.4 g,5,7 mmol) in 5 minutes under ice water temperature. After addition, the solution was stirred for 30 min at room temperature. Then, the reaction mixture was transfered to HBr solution containing CuBr (1 g, 7 mmol). After standing overnight, water (100 mL) was added. The precipitate was collected by filtration and recrystallized from petroleum ether to afford the title compound as colourless crystals, yield 50%.

Computing details top

Data collection: CrystalClear (Rigaku, 2005); cell refinement: CrystalClear (Rigaku, 2005); data reduction: CrystalClear (Rigaku, 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: SHELXTL (Sheldrick, 2008).

Figures top

	Fig. 1. The structure of the title compound showing 30% probability ellipsoids.
	Fig. 2. Packing structure of the title compound.

Ethyl 3-bromo-4-cyano-5-[(2-ethoxy-2-oxoethyl)sulfanyl]thiophene-2-carboxylate top

Crystal data top

C₁₂H₁₂BrNO₄S₂	F(000) = 760
M_r = 378.26	D_x = 1.650 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 3404 reflections
a = 8.5896 (17) Å	θ = 3.1–27.9°
b = 10.837 (2) Å	µ = 2.98 mm⁻¹
c = 16.584 (3) Å	T = 293 K
β = 99.44 (3)°	Block, colorless
V = 1522.8 (5) Å³	0.20 × 0.18 × 0.12 mm
Z = 4

Data collection top

Rigaku Saturn diffractometer	3596 independent reflections
Radiation source: rotating anode	2224 reflections with I > 2σ(I)
Confocal monochromator	R_int = 0.067
ω scans	θ_max = 27.9°, θ_min = 3.1°
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005)	h = −11→11
T_min = 0.587, T_max = 0.716	k = −14→14
15211 measured reflections	l = −21→21

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)] = 0.052	H-atom parameters constrained
wR(F²) = 0.157	w = 1/[σ²(F_o²) + (0.0817P)²] where P = (F_o² + 2F_c²)/3
S = 1.00	(Δ/σ)_max = 0.003
3596 reflections	Δρ_max = 0.43 e Å⁻³
184 parameters	Δρ_min = −0.71 e Å⁻³
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.018 (2)

Crystal data top

C₁₂H₁₂BrNO₄S₂	V = 1522.8 (5) Å³
M_r = 378.26	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 8.5896 (17) Å	µ = 2.98 mm⁻¹
b = 10.837 (2) Å	T = 293 K
c = 16.584 (3) Å	0.20 × 0.18 × 0.12 mm
β = 99.44 (3)°

Data collection top

Rigaku Saturn diffractometer	3596 independent reflections
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005)	2224 reflections with I > 2σ(I)
T_min = 0.587, T_max = 0.716	R_int = 0.067
15211 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.052	0 restraints
wR(F²) = 0.157	H-atom parameters constrained
S = 1.00	Δρ_max = 0.43 e Å⁻³
3596 reflections	Δρ_min = −0.71 e Å⁻³
184 parameters

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
Br1	1.34684 (5)	−0.05401 (5)	0.13435 (3)	0.0723 (3)
S1	0.95059 (11)	0.19092 (9)	0.04312 (6)	0.0421 (3)
S2	0.75972 (12)	0.13383 (10)	0.17935 (7)	0.0505 (3)
O1	1.3519 (4)	0.1042 (3)	−0.0246 (2)	0.0703 (9)
O2	1.1477 (3)	0.2261 (3)	−0.07630 (18)	0.0577 (8)
O3	0.4240 (3)	0.3685 (3)	0.10494 (18)	0.0559 (8)
O4	0.4796 (4)	0.2478 (3)	0.2147 (2)	0.0744 (10)
N1	1.0569 (5)	−0.0869 (4)	0.2904 (3)	0.0784 (13)
C1	1.3411 (7)	0.3617 (5)	−0.1215 (3)	0.0825 (16)
H1A	1.2890	0.4277	−0.0980	0.124*
H1B	1.3794	0.3912	−0.1692	0.124*
H1C	1.4282	0.3325	−0.0823	0.124*
C2	1.2285 (6)	0.2598 (5)	−0.1446 (3)	0.0667 (13)
H2A	1.1510	0.2847	−0.1911	0.080*
H2B	1.2845	0.1885	−0.1607	0.080*
C3	1.2245 (5)	0.1481 (4)	−0.0215 (3)	0.0468 (10)
C4	1.1325 (4)	0.1209 (3)	0.0445 (2)	0.0420 (9)
C5	1.1667 (5)	0.0433 (3)	0.1088 (3)	0.0440 (9)
C6	1.0474 (4)	0.0400 (3)	0.1587 (2)	0.0427 (9)
C7	0.9215 (4)	0.1161 (3)	0.1300 (2)	0.0390 (8)
C8	1.0542 (5)	−0.0323 (4)	0.2309 (3)	0.0551 (11)
C9	0.6413 (4)	0.2381 (4)	0.1105 (2)	0.0473 (10)
H9A	0.7050	0.3072	0.0979	0.057*
H9B	0.6003	0.1960	0.0599	0.057*
C10	0.5069 (4)	0.2838 (4)	0.1508 (3)	0.0464 (10)
C11	0.2964 (6)	0.4242 (5)	0.1395 (3)	0.0632 (13)
H11A	0.3373	0.4630	0.1914	0.076*
H11B	0.2205	0.3617	0.1488	0.076*
C12	0.2186 (6)	0.5190 (5)	0.0800 (4)	0.0903 (18)
H12A	0.2957	0.5782	0.0691	0.135*
H12B	0.1371	0.5603	0.1029	0.135*
H12C	0.1733	0.4791	0.0299	0.135*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Br1	0.0499 (4)	0.0728 (4)	0.0911 (5)	0.0186 (2)	0.0023 (3)	0.0000 (3)
S1	0.0381 (5)	0.0419 (5)	0.0472 (6)	0.0045 (4)	0.0093 (4)	0.0038 (4)
S2	0.0452 (6)	0.0526 (6)	0.0570 (7)	0.0040 (5)	0.0186 (5)	0.0114 (5)
O1	0.0539 (19)	0.088 (2)	0.075 (2)	0.0161 (18)	0.0267 (16)	0.0067 (19)
O2	0.0532 (18)	0.0659 (19)	0.0574 (18)	0.0027 (15)	0.0195 (14)	0.0111 (16)
O3	0.0464 (16)	0.0658 (19)	0.0585 (19)	0.0130 (15)	0.0177 (14)	−0.0037 (15)
O4	0.074 (2)	0.088 (2)	0.070 (2)	0.0212 (18)	0.0363 (18)	0.0164 (19)
N1	0.073 (3)	0.077 (3)	0.087 (3)	0.012 (2)	0.020 (2)	0.035 (3)
C1	0.100 (4)	0.089 (4)	0.064 (3)	−0.022 (3)	0.030 (3)	0.002 (3)
C2	0.076 (3)	0.072 (3)	0.056 (3)	−0.004 (3)	0.022 (2)	0.008 (2)
C3	0.040 (2)	0.049 (2)	0.052 (2)	−0.0011 (19)	0.0102 (18)	−0.005 (2)
C4	0.034 (2)	0.039 (2)	0.054 (2)	0.0016 (16)	0.0101 (17)	−0.0058 (18)
C5	0.036 (2)	0.041 (2)	0.054 (2)	−0.0013 (16)	0.0032 (18)	−0.0033 (18)
C6	0.041 (2)	0.039 (2)	0.047 (2)	−0.0030 (17)	0.0034 (18)	0.0045 (17)
C7	0.036 (2)	0.0346 (19)	0.046 (2)	−0.0006 (16)	0.0064 (16)	−0.0012 (16)
C8	0.045 (2)	0.051 (2)	0.070 (3)	0.006 (2)	0.011 (2)	0.011 (2)
C9	0.036 (2)	0.059 (3)	0.048 (2)	0.0034 (19)	0.0114 (18)	0.003 (2)
C10	0.039 (2)	0.053 (2)	0.049 (2)	0.0003 (19)	0.0099 (18)	−0.003 (2)
C11	0.050 (3)	0.070 (3)	0.074 (3)	0.018 (2)	0.023 (2)	−0.008 (3)
C12	0.068 (3)	0.097 (4)	0.108 (5)	0.036 (3)	0.021 (3)	0.015 (4)

Geometric parameters (Å, º) top

Br1—C5	1.864 (4)	C2—H2A	0.9700
S1—C7	1.707 (4)	C2—H2B	0.9700
S1—C4	1.734 (4)	C3—C4	1.480 (6)
S2—C7	1.735 (4)	C4—C5	1.352 (5)
S2—C9	1.798 (4)	C5—C6	1.418 (6)
O1—C3	1.202 (5)	C6—C7	1.381 (5)
O2—C3	1.335 (5)	C6—C8	1.425 (6)
O2—C2	1.468 (5)	C9—C10	1.509 (5)
O3—C10	1.323 (5)	C9—H9A	0.9700
O3—C11	1.449 (5)	C9—H9B	0.9700
O4—C10	1.188 (5)	C11—C12	1.504 (7)
N1—C8	1.147 (6)	C11—H11A	0.9700
C1—C2	1.477 (7)	C11—H11B	0.9700
C1—H1A	0.9600	C12—H12A	0.9600
C1—H1B	0.9600	C12—H12B	0.9600
C1—H1C	0.9600	C12—H12C	0.9600

C7—S1—C4	92.15 (19)	C5—C6—C8	124.7 (4)
C7—S2—C9	100.55 (18)	C6—C7—S1	111.1 (3)
C3—O2—C2	116.1 (3)	C6—C7—S2	123.1 (3)
C10—O3—C11	115.6 (3)	S1—C7—S2	125.8 (2)
C2—C1—H1A	109.5	N1—C8—C6	177.4 (5)
C2—C1—H1B	109.5	C10—C9—S2	108.6 (3)
H1A—C1—H1B	109.5	C10—C9—H9A	110.0
C2—C1—H1C	109.5	S2—C9—H9A	110.0
H1A—C1—H1C	109.5	C10—C9—H9B	110.0
H1B—C1—H1C	109.5	S2—C9—H9B	110.0
O2—C2—C1	111.0 (4)	H9A—C9—H9B	108.4
O2—C2—H2A	109.4	O4—C10—O3	125.0 (4)
C1—C2—H2A	109.4	O4—C10—C9	124.4 (4)
O2—C2—H2B	109.4	O3—C10—C9	110.6 (4)
C1—C2—H2B	109.4	O3—C11—C12	108.0 (4)
H2A—C2—H2B	108.0	O3—C11—H11A	110.1
O1—C3—O2	124.9 (4)	C12—C11—H11A	110.1
O1—C3—C4	123.6 (4)	O3—C11—H11B	110.1
O2—C3—C4	111.4 (3)	C12—C11—H11B	110.1
C5—C4—C3	129.3 (3)	H11A—C11—H11B	108.4
C5—C4—S1	111.1 (3)	C11—C12—H12A	109.5
C3—C4—S1	119.5 (3)	C11—C12—H12B	109.5
C4—C5—C6	113.1 (3)	H12A—C12—H12B	109.5
C4—C5—Br1	126.6 (3)	C11—C12—H12C	109.5
C6—C5—Br1	120.4 (3)	H12A—C12—H12C	109.5
C7—C6—C5	112.6 (3)	H12B—C12—H12C	109.5
C7—C6—C8	122.7 (4)

C3—O2—C2—C1	−83.9 (5)	C5—C6—C7—S1	−0.2 (4)
C2—O2—C3—O1	−0.4 (6)	C8—C6—C7—S1	179.4 (3)
C2—O2—C3—C4	179.9 (3)	C5—C6—C7—S2	−178.6 (3)
O1—C3—C4—C5	−2.5 (7)	C8—C6—C7—S2	0.9 (6)
O2—C3—C4—C5	177.2 (4)	C4—S1—C7—C6	−0.1 (3)
O1—C3—C4—S1	179.4 (4)	C4—S1—C7—S2	178.3 (3)
O2—C3—C4—S1	−1.0 (5)	C9—S2—C7—C6	−178.3 (3)
C7—S1—C4—C5	0.4 (3)	C9—S2—C7—S1	3.5 (3)
C7—S1—C4—C3	178.9 (3)	C7—C6—C8—N1	−36 (12)
C3—C4—C5—C6	−178.9 (4)	C5—C6—C8—N1	144 (11)
S1—C4—C5—C6	−0.6 (4)	C7—S2—C9—C10	−169.7 (3)
C3—C4—C5—Br1	0.6 (6)	C11—O3—C10—O4	3.5 (6)
S1—C4—C5—Br1	178.9 (2)	C11—O3—C10—C9	−176.8 (4)
C4—C5—C6—C7	0.5 (5)	S2—C9—C10—O4	−5.4 (6)
Br1—C5—C6—C7	−179.0 (3)	S2—C9—C10—O3	174.9 (3)
C4—C5—C6—C8	−179.0 (4)	C10—O3—C11—C12	178.9 (4)
Br1—C5—C6—C8	1.5 (5)

Experimental details

Crystal data
Chemical formula	C₁₂H₁₂BrNO₄S₂
M_r	378.26
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	8.5896 (17), 10.837 (2), 16.584 (3)
β (°)	99.44 (3)
V (Å³)	1522.8 (5)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	2.98
Crystal size (mm)	0.20 × 0.18 × 0.12

Data collection
Diffractometer	Rigaku Saturn diffractometer
Absorption correction	Multi-scan (CrystalClear; Rigaku, 2005)
T_min, T_max	0.587, 0.716
No. of measured, independent and observed [I > 2σ(I)] reflections	15211, 3596, 2224
R_int	0.067
(sin θ/λ)_max (Å⁻¹)	0.658

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.052, 0.157, 1.00
No. of reflections	3596
No. of parameters	184
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.43, −0.71

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

Acknowledgements

The authors appreciate the help of Dr Haibin Song in Nankai University for the crystal X-ray measurement.

References

Liu, M. G., Hu, Y. G. & Ding, M. W. (2008). Tetrahedron, 64, 9052–9059. Web of Science CSD CrossRef CAS Google Scholar
Padmavathi, V., Reddy, G. D., Reddy, S. N. & Mahesh, K. (2011). Eur. J. Med. Chem. 46, 1367–1373. Web of Science CSD CrossRef CAS PubMed Google Scholar
Rigaku (2005). CrystalClear. Rigaku Corporation, Tokyo, Japan. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

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