2-Amino-4,5,6,7-tetra­hydro­benzo[b]thio­phene-3-carbonitrile

Silva, W.L.; Lima, M. do C.A. de; Galdino, S.L.; Pitta, I.R.; De Simone, C.A.

doi:10.1107/S1600536811045338

organic compounds

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ISSN: 2056-9890

Volume 67| Part 12| December 2011| Page o3161

https://doi.org/10.1107/S1600536811045338

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2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile

Willams L. Silva,^a Maria do Carmo A. de Lima,^b Suely L. Galdino,^b Ivan R. Pitta ^b and Carlos A. De Simone ^c ^*

^aLaboratório de Síntese e Vetorização de Moléculas, Bioativas., Universidade Estadual da Paraíba, 58020-540 João Pessoa, PB, Brazil, ^bLaboratório de Síntese e Planejamento de Fármacos, Departamento de Antibióticos, Universidade Federal de Pernambuco, 50670-910 Recife, PE, Brazil, and ^cDepartamento de Física e Informática, Instituto de Física de São Carlos, Universidade de São Paulo - USP, 13560-970 São Carlos, SP, Brazil
^*Correspondence e-mail: casimone@ifsc.usp.br

(Received 26 October 2011; accepted 28 October 2011; online 2 November 2011)

The title compound, C₉H₁₀N₂S, was synthesized according to Gewald procedures by the reaction of cyclohexanone with malonitrile and sulfur in the presence morpholine. The cyclohexane ring adopts a half-chair conformation and the thiophene ring is essentially planar (r.m.s. deviation = 0.05 Å). The crystal packing is stabilized by two intermolecular N—H⋯N hydrogen bonds, which link the molecules into centrosymmetric rings with graph-set motif R₂²(12).

Related literature

For background to 2-amino thiophenes, see: Puterová et al. (2009 ). For antiarrhythmic and serotonin antagonist properties of 2-substituted thiophene derivatives, see: Amr et al. (2010 ). For their analgesic or anti-inflammatory activity, see: Hafez & El-Gazzar (2008 ). For the synthesis of 2-amino thiophenes, see: Gewald et al. (1966 ); Wang et al. (2010 ). For similar structures, see: Larson & Simonsen (1988 ); Mendonça Junior et al. (2010 ). For puckering parameters, see: Cremer & Pople (1975 ). For hydrogen-bond motifs, see: Bernstein et al. (1995 ).

Experimental

Crystal data

C₉H₁₀N₂S
M_r = 178.25
Monoclinic, P 2₁ /c
a = 10.4274 (3) Å
b = 8.1487 (3) Å
c = 13.2342 (4) Å
β = 126.937 (2)°
V = 898.81 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.30 mm⁻¹
T = 295 K
0.22 × 0.22 × 0.20 mm

Data collection

Nonius KappaCCD diffractometer
12462 measured reflections
2058 independent reflections
1630 reflections with I > 2σ(I)
R_int = 0.052

Refinement

R[F² > 2σ(F²)] = 0.045
wR(F²) = 0.137
S = 1.04
2058 reflections
109 parameters
H-atom parameters constrained
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.36 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2A⋯N1ⁱ	0.86	2.28	3.121 (2)	166
N2—H2B⋯N1ⁱⁱ	0.86	2.42	3.225 (3)	155
Symmetry codes: (i) -x, -y-1, -z; (ii) $[x, -y-{\script{1\over 2}}, z+{\script{1\over 2}}]$ .

Data collection: COLLECT (Nonius, 1997 ); cell refinement: SCALEPACK (Otwinowski & Minor, 1997 ); data reduction: DENZO (Otwinowski & Minor, 1997) and SCALEPACK; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ); software used to prepare material for publication: WinGX (Farrugia, 1999 ).

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536811045338/bx2379sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536811045338/bx2379Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S1600536811045338/bx2379Isup3.cml

checkCIF report

Comment top

Thiophenes and their fused heterocyclic ring systems possess a wide spectrum of biological activities, as antiarrhythmic and serotonin antagonist (Amr et al., 2010) and analgesic or anti-inflammatory activities (Hafez & El-Gazzar, 2008). In this work, the title compound was obtained according Gewald procedures, by the reaction of cyclohexanone with malonitrile and sulfur in the presence morpholine (Gewald et al., 1966; Wang et al., 2010). In the title compound, the cyclohexane ring adopts a half-chair conformation with calculated puckering parameters of: Q_T= 0.487 (1) Å, θ = 50.6 (1)°, φ = 148.6 (2)° (Cremer & Pople, 1975). The crystal packing is stabilized by two intermolecular N—H···N hydrogen bonds, which links the molecules into rings with graph-set notation R₂²(12), Table 1 & Fig.2.

Related literature top

For background to 2-amino thiophenes, see: Puterová et al. (2009). For antiarrhythmic and serotonin antagonist of 2-substituted thiophene derivatives, see: Amr et al. (2010). For their analgesic or anti-inflammatory activity, see: Hafez & El-Gazzar (2008). For the synthesis of 2-amino thiophenes, see: Gewald et al. (1966); Wang et al. (2010). For similar structures, see: Larson & Simonsen (1988); Mendonça Junior et al. (2010). For puckering parameters, see: Cremer & Pople (1975).

For hydrogen-bond motifs, see: Bernstein et al. (1995).

Experimental top

Crystals suitable for single-crystal X-ray diffraction were grown by slow evaporation at room temperature of a solution from ethanol/water.

Structure description top

For hydrogen-bond motifs, see: Bernstein et al. (1995).

Computing details top

Data collection: COLLECT (Nonius, 1997); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

	Fig. 1. The structure of (I), showing the atom-labelling scheme. Displacement ellipsoids are shown at the 50% probability level.
	Fig. 2. Part of the crystal structure showing the formation of centrosymmetric dimers R²₂(12) rings. [Symmetry codes: (i) -x, -y-1, -z; (ii) x, -y-1/2, z+1/2.]

2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile top

Crystal data top

C₉H₁₀N₂S	F(000) = 376
M_r = 178.25	D_x = 1.317 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 6505 reflections
a = 10.4274 (3) Å	θ = 2.6–27.5°
b = 8.1487 (3) Å	µ = 0.30 mm⁻¹
c = 13.2342 (4) Å	T = 295 K
β = 126.937 (2)°	Prism, yellow
V = 898.81 (5) Å³	0.22 × 0.22 × 0.20 mm
Z = 4

Data collection top

Nonius KappaCCD diffractometer	1630 reflections with I > 2σ(I)
Radiation source: Enraf–Nonius FR590	R_int = 0.052
Horizonally mounted graphite crystal monochromator	θ_max = 27.5°, θ_min = 3.1°
Detector resolution: 9 pixels mm^-1	h = −13→13
CCD rotation images,thick slices scans	k = −10→10
12462 measured reflections	l = −17→17
2058 independent reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.045	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.137	H-atom parameters constrained
S = 1.04	w = 1/[σ²(F_o²) + (0.1P)²] where P = (F_o² + 2F_c²)/3
2058 reflections	(Δ/σ)_max = 0.001
109 parameters	Δρ_max = 0.19 e Å⁻³
0 restraints	Δρ_min = −0.36 e Å⁻³

Crystal data top

C₉H₁₀N₂S	V = 898.81 (5) Å³
M_r = 178.25	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 10.4274 (3) Å	µ = 0.30 mm⁻¹
b = 8.1487 (3) Å	T = 295 K
c = 13.2342 (4) Å	0.22 × 0.22 × 0.20 mm
β = 126.937 (2)°

Data collection top

Nonius KappaCCD diffractometer	1630 reflections with I > 2σ(I)
12462 measured reflections	R_int = 0.052
2058 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.045	0 restraints
wR(F²) = 0.137	H-atom parameters constrained
S = 1.04	Δρ_max = 0.19 e Å⁻³
2058 reflections	Δρ_min = −0.36 e Å⁻³
109 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
S1	0.22127 (5)	0.01327 (5)	0.27769 (4)	0.0543 (2)
N1	0.0577 (2)	−0.37778 (18)	−0.07760 (14)	0.0648 (4)
N2	0.07860 (18)	−0.28276 (18)	0.20995 (14)	0.0603 (4)
H2A	0.0428	−0.3698	0.1640	0.072*
H2B	0.0719	−0.2727	0.2713	0.072*
C1	0.16686 (17)	−0.15535 (17)	0.09245 (13)	0.0426 (3)
C2	0.24712 (19)	−0.00893 (18)	0.09686 (15)	0.0445 (4)
C3	0.2917 (2)	0.0288 (2)	0.01054 (17)	0.0532 (4)
H3A	0.1965	0.0603	−0.0720	0.064*
H3B	0.3365	−0.0684	0.0002	0.064*
C4	0.4146 (2)	0.1681 (2)	0.06489 (19)	0.0662 (5)
H4A	0.5188	0.1265	0.1345	0.079*
H4B	0.4235	0.2079	0.0003	0.079*
C5	0.3678 (2)	0.3083 (2)	0.1112 (2)	0.0690 (5)
H5A	0.2627	0.3485	0.0419	0.083*
H5B	0.4439	0.3974	0.1389	0.083*
C6	0.3640 (2)	0.2565 (2)	0.22012 (18)	0.0641 (5)
H6A	0.4725	0.2486	0.2975	0.077*
H6B	0.3068	0.3380	0.2325	0.077*
C7	0.28162 (17)	0.0932 (2)	0.19015 (15)	0.0499 (4)
C8	0.14543 (17)	−0.16192 (19)	0.18582 (13)	0.0451 (4)
C9	0.10751 (18)	−0.27940 (19)	−0.00076 (14)	0.0477 (4)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0624 (3)	0.0552 (3)	0.0567 (3)	−0.01030 (17)	0.0419 (3)	−0.01544 (17)
N1	0.0984 (12)	0.0474 (8)	0.0663 (9)	−0.0081 (8)	0.0589 (9)	−0.0091 (7)
N2	0.0834 (10)	0.0550 (9)	0.0623 (8)	−0.0155 (7)	0.0543 (8)	−0.0106 (6)
C1	0.0474 (7)	0.0386 (7)	0.0442 (7)	0.0030 (6)	0.0288 (6)	−0.0003 (6)
C2	0.0430 (8)	0.0457 (8)	0.0457 (8)	0.0023 (6)	0.0271 (7)	0.0008 (6)
C3	0.0579 (10)	0.0550 (10)	0.0544 (9)	0.0025 (7)	0.0378 (8)	0.0051 (7)
C4	0.0629 (10)	0.0718 (13)	0.0748 (11)	−0.0065 (9)	0.0472 (9)	0.0060 (9)
C5	0.0694 (11)	0.0575 (11)	0.0780 (12)	−0.0141 (9)	0.0432 (10)	−0.0016 (9)
C6	0.0630 (10)	0.0561 (10)	0.0719 (11)	−0.0175 (8)	0.0398 (9)	−0.0164 (8)
C7	0.0469 (8)	0.0497 (9)	0.0539 (8)	−0.0047 (6)	0.0308 (7)	−0.0056 (7)
C8	0.0466 (7)	0.0441 (8)	0.0468 (8)	0.0014 (6)	0.0292 (7)	−0.0020 (6)
C9	0.0618 (9)	0.0409 (8)	0.0500 (8)	0.0028 (6)	0.0387 (7)	0.0026 (6)

Geometric parameters (Å, º) top

S1—C8	1.7280 (15)	C3—H3A	0.9700
S1—C7	1.7432 (17)	C3—H3B	0.9700
N1—C9	1.145 (2)	C4—C5	1.509 (3)
N2—C8	1.351 (2)	C4—H4A	0.9700
N2—H2A	0.8600	C4—H4B	0.9700
N2—H2B	0.8600	C5—C6	1.526 (3)
C1—C8	1.383 (2)	C5—H5A	0.9700
C1—C9	1.417 (2)	C5—H5B	0.9700
C1—C2	1.438 (2)	C6—C7	1.502 (2)
C2—C7	1.346 (2)	C6—H6A	0.9700
C2—C3	1.502 (2)	C6—H6B	0.9700
C3—C4	1.530 (2)

C8—S1—C7	92.09 (7)	H4A—C4—H4B	108.0
C8—N2—H2A	120.0	C4—C5—C6	111.88 (16)
C8—N2—H2B	120.0	C4—C5—H5A	109.2
H2A—N2—H2B	120.0	C6—C5—H5A	109.2
C8—C1—C9	121.99 (14)	C4—C5—H5B	109.2
C8—C1—C2	113.48 (13)	C6—C5—H5B	109.2
C9—C1—C2	124.47 (13)	H5A—C5—H5B	107.9
C7—C2—C1	112.23 (14)	C7—C6—C5	109.33 (15)
C7—C2—C3	122.47 (14)	C7—C6—H6A	109.8
C1—C2—C3	125.29 (14)	C5—C6—H6A	109.8
C2—C3—C4	110.43 (14)	C7—C6—H6B	109.8
C2—C3—H3A	109.6	C5—C6—H6B	109.8
C4—C3—H3A	109.6	H6A—C6—H6B	108.3
C2—C3—H3B	109.6	C2—C7—C6	125.82 (15)
C4—C3—H3B	109.6	C2—C7—S1	111.97 (12)
H3A—C3—H3B	108.1	C6—C7—S1	122.20 (13)
C5—C4—C3	111.65 (15)	N2—C8—C1	128.53 (14)
C5—C4—H4A	109.3	N2—C8—S1	121.26 (11)
C3—C4—H4A	109.3	C1—C8—S1	110.21 (11)
C5—C4—H4B	109.3	N1—C9—C1	178.84 (18)
C3—C4—H4B	109.3

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···N1ⁱ	0.86	2.28	3.121 (2)	166
N2—H2B···N1ⁱⁱ	0.86	2.42	3.225 (3)	155

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

Experimental details

Crystal data
Chemical formula	C₉H₁₀N₂S
M_r	178.25
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	295
a, b, c (Å)	10.4274 (3), 8.1487 (3), 13.2342 (4)
β (°)	126.937 (2)
V (Å³)	898.81 (5)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.30
Crystal size (mm)	0.22 × 0.22 × 0.20

Data collection
Diffractometer	Nonius KappaCCD
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	12462, 2058, 1630
R_int	0.052
(sin θ/λ)_max (Å⁻¹)	0.649

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.045, 0.137, 1.04
No. of reflections	2058
No. of parameters	109
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.19, −0.36

Computer programs: COLLECT (Nonius, 1997), DENZO and SCALEPACK (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···N1ⁱ	0.86	2.28	3.121 (2)	166
N2—H2B···N1ⁱⁱ	0.86	2.42	3.225 (3)	155

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

Acknowledgements

This work has received partial support from CNPq, CAPES, FACEPE and FINEP.

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