organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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

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[Puterová, Z., Krutosiková, A. & Végh, D. (2009). Nova Biotech. 9, 167-173.]). For anti­arrhythmic and serotonin antagonist properties of 2-substituted thio­phene derivatives, see: Amr et al. (2010[Amr, A. E. E., Sherif, M. H., Assy, M. G., Al-Omar, M. A. & Ragab, I. (2010). Eur. J. Med. Chem. 45, 5935-5942.]). For their analgesic or anti-inflammatory activity, see: Hafez & El-Gazzar (2008[Hafez, H. N. & El-Gazzar, A. B. A. (2008). Bioorg. Med. Chem. Lett. 18, 5222-5227.]). For the synthesis of 2-amino thio­phenes, see: Gewald et al. (1966[Gewald, K., Schinke, E. & Bottcher, H. (1966). Chem. Ber. 99, 99-100.]); Wang et al. (2010[Wang, T., Huang, X., Liu, J., Li, B., Wu, J., Chen, K., Zhu, W., Xu, X. & Zeng, B. (2010). Synthesis, 9, 1351-1354.]). For similar structures, see: Larson & Simonsen (1988[Larson, S. B. & Simonsen, S. H. (1988). Acta Cryst. C44, 2035-2037.]); Mendonça Junior et al. (2010[Mendonça Junior, F. J. B., Lima, M. do C. A. de, Galdino, S. L., Pitta, I. R. & Simone, C. A. de (2010). Acta Cryst. E66, o2543.]). For puckering parameters, see: Cremer & Pople (1975[Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358.]). For hydrogen-bond motifs, see: Bernstein et al. (1995[Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555-1573.]).

[Scheme 1]

Experimental

Crystal data
  • C9H10N2S

  • Mr = 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)

  • Rint = 0.052

Refinement
  • R[F2 > 2σ(F2)] = 0.045

  • wR(F2) = 0.137

  • S = 1.04

  • 2058 reflections

  • 109 parameters

  • H-atom parameters constrained

  • Δρmax = 0.19 e Å−3

  • Δρmin = −0.36 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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[Nonius (1997). COLLECT in KappaCCD Server Software for Windows. Nonius BV, Delft, The Netherlands.]); cell refinement: SCALEPACK (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.]); data reduction: DENZO (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.]) and SCALEPACK; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.]); software used to prepare material for publication: WinGX (Farrugia, 1999[Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837-838.]).

Supporting information


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: QT= 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.

Refinement top

All H atoms attached were fixed geometrically and treated as riding with C—H = 0.97 Å (methylene) and N—H = 0.86 Å and with Uiso(H) = 1.2Ueq(C or N).

Structure description 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: QT= 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.

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).

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
[Figure 1] Fig. 1. The structure of (I), showing the atom-labelling scheme. Displacement ellipsoids are shown at the 50% probability level.
[Figure 2] 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
C9H10N2SF(000) = 376
Mr = 178.25Dx = 1.317 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 6505 reflections
a = 10.4274 (3) Åθ = 2.6–27.5°
b = 8.1487 (3) ŵ = 0.30 mm1
c = 13.2342 (4) ÅT = 295 K
β = 126.937 (2)°Prism, yellow
V = 898.81 (5) Å30.22 × 0.22 × 0.20 mm
Z = 4
Data collection top
Nonius KappaCCD
diffractometer
1630 reflections with I > 2σ(I)
Radiation source: Enraf–Nonius FR590Rint = 0.052
Horizonally mounted graphite crystal monochromatorθmax = 27.5°, θmin = 3.1°
Detector resolution: 9 pixels mm-1h = 1313
CCD rotation images,thick slices scansk = 1010
12462 measured reflectionsl = 1717
2058 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.045Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.137H-atom parameters constrained
S = 1.04 w = 1/[σ2(Fo2) + (0.1P)2]
where P = (Fo2 + 2Fc2)/3
2058 reflections(Δ/σ)max = 0.001
109 parametersΔρmax = 0.19 e Å3
0 restraintsΔρmin = 0.36 e Å3
Crystal data top
C9H10N2SV = 898.81 (5) Å3
Mr = 178.25Z = 4
Monoclinic, P21/cMo Kα radiation
a = 10.4274 (3) ŵ = 0.30 mm1
b = 8.1487 (3) ÅT = 295 K
c = 13.2342 (4) Å0.22 × 0.22 × 0.20 mm
β = 126.937 (2)°
Data collection top
Nonius KappaCCD
diffractometer
1630 reflections with I > 2σ(I)
12462 measured reflectionsRint = 0.052
2058 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0450 restraints
wR(F2) = 0.137H-atom parameters constrained
S = 1.04Δρmax = 0.19 e Å3
2058 reflectionsΔρmin = 0.36 e Å3
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
xyzUiso*/Ueq
S10.22127 (5)0.01327 (5)0.27769 (4)0.0543 (2)
N10.0577 (2)0.37778 (18)0.07760 (14)0.0648 (4)
N20.07860 (18)0.28276 (18)0.20995 (14)0.0603 (4)
H2A0.04280.36980.16400.072*
H2B0.07190.27270.27130.072*
C10.16686 (17)0.15535 (17)0.09245 (13)0.0426 (3)
C20.24712 (19)0.00893 (18)0.09686 (15)0.0445 (4)
C30.2917 (2)0.0288 (2)0.01054 (17)0.0532 (4)
H3A0.19650.06030.07200.064*
H3B0.33650.06840.00020.064*
C40.4146 (2)0.1681 (2)0.06489 (19)0.0662 (5)
H4A0.51880.12650.13450.079*
H4B0.42350.20790.00030.079*
C50.3678 (2)0.3083 (2)0.1112 (2)0.0690 (5)
H5A0.26270.34850.04190.083*
H5B0.44390.39740.13890.083*
C60.3640 (2)0.2565 (2)0.22012 (18)0.0641 (5)
H6A0.47250.24860.29750.077*
H6B0.30680.33800.23250.077*
C70.28162 (17)0.0932 (2)0.19015 (15)0.0499 (4)
C80.14543 (17)0.16192 (19)0.18582 (13)0.0451 (4)
C90.10751 (18)0.27940 (19)0.00076 (14)0.0477 (4)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0624 (3)0.0552 (3)0.0567 (3)0.01030 (17)0.0419 (3)0.01544 (17)
N10.0984 (12)0.0474 (8)0.0663 (9)0.0081 (8)0.0589 (9)0.0091 (7)
N20.0834 (10)0.0550 (9)0.0623 (8)0.0155 (7)0.0543 (8)0.0106 (6)
C10.0474 (7)0.0386 (7)0.0442 (7)0.0030 (6)0.0288 (6)0.0003 (6)
C20.0430 (8)0.0457 (8)0.0457 (8)0.0023 (6)0.0271 (7)0.0008 (6)
C30.0579 (10)0.0550 (10)0.0544 (9)0.0025 (7)0.0378 (8)0.0051 (7)
C40.0629 (10)0.0718 (13)0.0748 (11)0.0065 (9)0.0472 (9)0.0060 (9)
C50.0694 (11)0.0575 (11)0.0780 (12)0.0141 (9)0.0432 (10)0.0016 (9)
C60.0630 (10)0.0561 (10)0.0719 (11)0.0175 (8)0.0398 (9)0.0164 (8)
C70.0469 (8)0.0497 (9)0.0539 (8)0.0047 (6)0.0308 (7)0.0056 (7)
C80.0466 (7)0.0441 (8)0.0468 (8)0.0014 (6)0.0292 (7)0.0020 (6)
C90.0618 (9)0.0409 (8)0.0500 (8)0.0028 (6)0.0387 (7)0.0026 (6)
Geometric parameters (Å, º) top
S1—C81.7280 (15)C3—H3A0.9700
S1—C71.7432 (17)C3—H3B0.9700
N1—C91.145 (2)C4—C51.509 (3)
N2—C81.351 (2)C4—H4A0.9700
N2—H2A0.8600C4—H4B0.9700
N2—H2B0.8600C5—C61.526 (3)
C1—C81.383 (2)C5—H5A0.9700
C1—C91.417 (2)C5—H5B0.9700
C1—C21.438 (2)C6—C71.502 (2)
C2—C71.346 (2)C6—H6A0.9700
C2—C31.502 (2)C6—H6B0.9700
C3—C41.530 (2)
C8—S1—C792.09 (7)H4A—C4—H4B108.0
C8—N2—H2A120.0C4—C5—C6111.88 (16)
C8—N2—H2B120.0C4—C5—H5A109.2
H2A—N2—H2B120.0C6—C5—H5A109.2
C8—C1—C9121.99 (14)C4—C5—H5B109.2
C8—C1—C2113.48 (13)C6—C5—H5B109.2
C9—C1—C2124.47 (13)H5A—C5—H5B107.9
C7—C2—C1112.23 (14)C7—C6—C5109.33 (15)
C7—C2—C3122.47 (14)C7—C6—H6A109.8
C1—C2—C3125.29 (14)C5—C6—H6A109.8
C2—C3—C4110.43 (14)C7—C6—H6B109.8
C2—C3—H3A109.6C5—C6—H6B109.8
C4—C3—H3A109.6H6A—C6—H6B108.3
C2—C3—H3B109.6C2—C7—C6125.82 (15)
C4—C3—H3B109.6C2—C7—S1111.97 (12)
H3A—C3—H3B108.1C6—C7—S1122.20 (13)
C5—C4—C3111.65 (15)N2—C8—C1128.53 (14)
C5—C4—H4A109.3N2—C8—S1121.26 (11)
C3—C4—H4A109.3C1—C8—S1110.21 (11)
C5—C4—H4B109.3N1—C9—C1178.84 (18)
C3—C4—H4B109.3
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2A···N1i0.862.283.121 (2)166
N2—H2B···N1ii0.862.423.225 (3)155
Symmetry codes: (i) x, y1, z; (ii) x, y1/2, z+1/2.

Experimental details

Crystal data
Chemical formulaC9H10N2S
Mr178.25
Crystal system, space groupMonoclinic, P21/c
Temperature (K)295
a, b, c (Å)10.4274 (3), 8.1487 (3), 13.2342 (4)
β (°) 126.937 (2)
V3)898.81 (5)
Z4
Radiation typeMo Kα
µ (mm1)0.30
Crystal size (mm)0.22 × 0.22 × 0.20
Data collection
DiffractometerNonius KappaCCD
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
12462, 2058, 1630
Rint0.052
(sin θ/λ)max1)0.649
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.045, 0.137, 1.04
No. of reflections2058
No. of parameters109
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)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···AD—HH···AD···AD—H···A
N2—H2A···N1i0.862.283.121 (2)166
N2—H2B···N1ii0.862.423.225 (3)155
Symmetry codes: (i) x, y1, z; (ii) x, y1/2, z+1/2.
 

Acknowledgements

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

References

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First citationBernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555–1573.  CrossRef CAS Web of Science Google Scholar
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