Crystal structure of 2-amino-N-(2-fluoro­phen­yl)-4,5,6,7-tetra­hydro-1-benzo­thio­phene-3-carboxamide

In the title compound, C₁₅H₁₅FN₂OS, the dihedral angle between the planes of the benzo­thio­phene ring system and the fluoro­benzene ring is 3.74 (14)°. The six-membered ring of the benzo­thio­phene moiety adopts a half-chair conformation. The mol­ecular conformation is consolidated by intra­molecular N—H...F and N—H...O hydrogen bonds. In the crystal, mol­ecules are linked by N—H...O hydrogen bonds, generating C(6) [001] chains.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.038
• wR factor = 0.081
• Data-to-parameter ratio = 14.2

checkCIF/PLATON results

No syntax errors found



Alert level B
PLAT934_ALERT_3_B Number of (Iobs-Icalc)/SigmaW > 10 Outliers ....          2 Check

Alert level C
PLAT148_ALERT_3_C su on the      a  - Axis is (Too) Large ........      0.013 Ang.
PLAT148_ALERT_3_C su on the      b  - Axis is (Too) Large ........     0.0170 Ang.
PLAT148_ALERT_3_C su on the      c  - Axis is (Too) Large ........      0.015 Ang.
PLAT340_ALERT_3_C Low Bond Precision on  C-C Bonds ...............     0.0043 Ang.
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600          2 Report
PLAT915_ALERT_3_C Low Friedel Pair Coverage ......................         85 %

Alert level G
PLAT005_ALERT_5_G No _iucr_refine_instructions_details  in the CIF     Please Do !
PLAT007_ALERT_5_G Number of Unrefined Donor-H Atoms ..............          3 Report
PLAT128_ALERT_4_G Alternate Setting for Input Space Group  Cc         Ia      Note
PLAT199_ALERT_1_G Reported _cell_measurement_temperature ..... (K)        293 Check
PLAT200_ALERT_1_G Reported   _diffrn_ambient_temperature ..... (K)        293 Check
PLAT912_ALERT_4_G Missing # of FCF Reflections Above STh/L=  0.600          6 Note
PLAT953_ALERT_1_G Reported (CIF) and Actual (FCF) Hmax Differ by .          1 Units

   0 ALERT level A = Most likely a serious problem - resolve or explain
   1 ALERT level B = A potentially serious problem, consider carefully
   6 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   7 ALERT level G = General information/check it is not something unexpected

   3 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   7 ALERT type 3 Indicator that the structure quality may be low
   2 ALERT type 4 Improvement, methodology, query or suggestion
   2 ALERT type 5 Informative message, check

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S1. Comment

Thiophene nucleus has been established as a potential entity in the largely growing chemical world of heterocyclic compounds possessing promising pharmacological characteristics such as anti-HIV PR inhibitors (Bonini et al., 2005) and anti-breast cancer (Brault et al., 2005) activities. Particularly, benzothiophene derivative shows significant antimicrobial and anti- inflammatory activities (Isloora et al., 2010). In addition structures containing fluorine atoms plays a major role in intermolecular interactions (Choudhury et al., 2004). The title compound was prepared and characterized by single-crystal X-ray diffraction studies.

In the molecular structure of the title compound (Fig. 1), the dihedral angle between the flurobenzene (C1–C2–C3–C4–C5–C6) and benzothiophene (C11–C12–C13–S14–C15–C17–C18–C19–C20) ring is 3.74 (14)°. The benzothiophene moiety adopts a half chair conformation conformation with puckering parameter Q = 0.475 (3) Å and φ = 215.4 (5)°, and the maximum deviation found on the puckered atom at C18 is 0.372 (4) Å. The carboximidamide unit is in anti-periplanar conformation with respect to the benzothiophene moiety, as indicated by the torsion angle value of 161.9 (3)° (N8–C9–C11–C15). The crystal structure features intermolecular N—H···O hydrogen bonds. The packing diagram of the molecule viewed down the a axis as shown in Fig. 2.

Related literature

For background to thiophene derivatives, see: Bonini et al. (2005); Brault et al. (2005); Isloor et al. (2010). For intermolecular interactions involving F atoms, see: Choudhury et al. ( 2004).

S2. Experimental

Cyclohexanone (1 equiv.), 2-cyano-N-(2-fluorophenyl) acetamide (1.1 equiv.), elemental sulfur (1.2 equiv.), diethylamine (0.8 equiv.) was taken in ethanol and mixed thoroughly in a microwave tube. The tube was sealed and irradiated at 325 K for 15 min. After cooling ethyl acetate was added to the reaction mixture and solid residue was removed by filtration. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain yellow block shaped crystals.

S3. Refinement

H atoms were placed at idealized positions and allowed to ride on their parent atoms with N–H distance is equal to 0.86 and C–H distances in the range of 0.93 to 0.97 Å; U_iso(H) = 1.2–1.5U_eq(carrier atom) for all H atoms.

Computing details

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures

	Fig. 1. Perspective diagram of the molecule with 50% probability displacement ellipsoids.
	Fig. 2. Packing diagram of the molecule viewed down the 'a' axis.

2-Amino-N-(2-fluorophenyl)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide

Crystal data

C15H15FN2OS	F(000) = 608
Mr = 290.36	Dx = 1.413 Mg m^−3
Monoclinic, Cc	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C -2yc	Cell parameters from 2577 reflections
a = 11.213 (13) Å	θ = 2.5–26.4°
b = 14.231 (17) Å	µ = 0.25 mm^−1
c = 9.582 (15) Å	T = 293 K
β = 116.76 (3)°	Bolck, yellow
V = 1365 (3) Å^3	0.30 × 0.25 × 0.20 mm
Z = 4

Data collection

Bruker APEXII CCD area-detector diffractometer	Rint = 0.029
ω and φ scans	θmax = 26.4°, θmin = 2.5°
5264 measured reflections	h = −13→14
2577 independent reflections	k = −17→17
2363 reflections with I > 2σ(I)	l = −11→11

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.038	H-atom parameters constrained
wR(F^2) = 0.081	w = 1/[σ^2(Fo^2) + (0.010P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.84	(Δ/σ)max < 0.001
2577 reflections	Δρmax = 0.20 e Å^−3
182 parameters	Δρmin = −0.29 e Å^−3
2 restraints	Absolute structure: Flack (1983), ??? Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.06 (7)

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F² for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating -R-factor-obs 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 (Ų)

	x	y	z	Uiso*/Ueq
S14	0.42139 (7)	0.13494 (4)	1.08277 (7)	0.0586 (3)
F7	0.17969 (19)	0.42740 (10)	0.4264 (2)	0.0746 (6)
O10	0.2917 (2)	0.10081 (11)	0.56571 (19)	0.0568 (7)
N8	0.2299 (2)	0.25423 (14)	0.5376 (2)	0.0503 (7)
N16	0.3503 (2)	0.01559 (15)	0.8447 (3)	0.0674 (9)
C1	0.1812 (2)	0.26650 (18)	0.3762 (3)	0.0466 (9)
C2	0.1530 (3)	0.1953 (2)	0.2671 (3)	0.0588 (10)
C3	0.1087 (4)	0.2175 (3)	0.1106 (3)	0.0727 (11)
C4	0.0865 (3)	0.3097 (3)	0.0601 (4)	0.0735 (13)
C5	0.1109 (3)	0.3807 (2)	0.1661 (3)	0.0643 (11)
C6	0.1566 (3)	0.35800 (18)	0.3201 (3)	0.0519 (9)
C9	0.2880 (3)	0.17625 (17)	0.6279 (3)	0.0444 (9)
C11	0.3397 (2)	0.18699 (17)	0.7955 (3)	0.0423 (8)
C12	0.3705 (3)	0.27223 (17)	0.8901 (3)	0.0422 (8)
C13	0.4142 (3)	0.25543 (17)	1.0436 (3)	0.0478 (8)
C15	0.3637 (3)	0.10698 (17)	0.8869 (3)	0.0483 (9)
C17	0.3638 (3)	0.37266 (16)	0.8342 (3)	0.0497 (9)
C18	0.4470 (3)	0.43925 (17)	0.9684 (3)	0.0575 (10)
C19	0.4211 (4)	0.42420 (18)	1.1078 (3)	0.0665 (11)
C20	0.4583 (3)	0.32519 (19)	1.1743 (3)	0.0583 (10)
H2A	0.16370	0.13280	0.29880	0.0710*
H3A	0.09370	0.16960	0.03860	0.0870*
H4A	0.05520	0.32350	−0.04550	0.0880*
H5A	0.09670	0.44300	0.13370	0.0770*
H9A	0.22220	0.30220	0.58740	0.0600*
H15C	0.32330	0.00050	0.74820	0.0810*
H15D	0.36900	−0.02760	0.91420	0.0810*
H18A	0.55430	0.32090	1.23760	0.0700*
H18B	0.41570	0.31140	1.24040	0.0700*
H20A	0.32720	0.43510	1.07740	0.0800*
H20B	0.47240	0.46950	1.18820	0.0800*
H21A	0.54110	0.42920	0.99880	0.0690*
H21B	0.42570	0.50370	0.93290	0.0690*
H22A	0.27150	0.39340	0.78560	0.0600*
H22B	0.39610	0.37500	0.75590	0.0600*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S14	0.0914 (6)	0.0458 (4)	0.0421 (4)	0.0089 (4)	0.0332 (4)	0.0085 (3)
F7	0.1052 (14)	0.0470 (9)	0.0552 (10)	−0.0004 (8)	0.0217 (9)	−0.0020 (7)
O10	0.0853 (14)	0.0416 (10)	0.0432 (10)	0.0028 (9)	0.0286 (10)	−0.0026 (8)
N8	0.0726 (15)	0.0413 (11)	0.0362 (11)	0.0066 (10)	0.0239 (11)	−0.0015 (8)
N16	0.116 (2)	0.0397 (13)	0.0496 (13)	0.0007 (12)	0.0400 (13)	0.0038 (10)
C1	0.0467 (15)	0.0481 (16)	0.0397 (15)	0.0014 (11)	0.0147 (13)	0.0030 (11)
C2	0.073 (2)	0.0556 (17)	0.0419 (15)	0.0064 (14)	0.0206 (15)	0.0020 (12)
C3	0.087 (2)	0.080 (2)	0.0370 (15)	0.0112 (17)	0.0154 (15)	−0.0070 (15)
C4	0.095 (3)	0.083 (2)	0.0342 (15)	0.0095 (19)	0.0217 (16)	0.0113 (14)
C5	0.070 (2)	0.0614 (18)	0.0486 (18)	0.0004 (14)	0.0153 (15)	0.0137 (13)
C6	0.0546 (17)	0.0487 (16)	0.0459 (16)	−0.0034 (12)	0.0170 (13)	−0.0001 (12)
C9	0.0539 (17)	0.0385 (13)	0.0445 (14)	−0.0016 (12)	0.0255 (13)	0.0000 (11)
C11	0.0541 (17)	0.0391 (13)	0.0377 (13)	0.0027 (11)	0.0241 (13)	0.0029 (10)
C12	0.0534 (16)	0.0389 (13)	0.0379 (15)	0.0012 (11)	0.0238 (13)	0.0015 (10)
C13	0.0616 (16)	0.0414 (13)	0.0426 (15)	0.0068 (12)	0.0255 (14)	0.0037 (10)
C15	0.0671 (19)	0.0425 (14)	0.0408 (15)	0.0012 (12)	0.0293 (14)	0.0005 (11)
C17	0.0697 (17)	0.0404 (14)	0.0431 (13)	0.0014 (12)	0.0291 (12)	0.0014 (10)
C18	0.075 (2)	0.0433 (14)	0.0542 (16)	−0.0033 (13)	0.0292 (15)	−0.0045 (12)
C19	0.100 (2)	0.0474 (15)	0.059 (2)	0.0027 (16)	0.0418 (19)	−0.0082 (14)
C20	0.079 (2)	0.0536 (16)	0.0434 (16)	0.0055 (14)	0.0286 (15)	−0.0018 (12)

Geometric parameters (Å, º)

S14—C13	1.749 (4)	C12—C17	1.516 (4)
S14—C15	1.734 (4)	C12—C13	1.346 (4)
F7—C6	1.357 (4)	C13—C20	1.497 (4)
O10—C9	1.238 (4)	C17—C18	1.530 (4)
N8—C1	1.400 (4)	C18—C19	1.505 (5)
N8—C9	1.377 (4)	C19—C20	1.525 (4)
N16—C15	1.350 (4)	C2—H2A	0.9300
N8—H9A	0.8600	C3—H3A	0.9300
N16—H15C	0.8600	C4—H4A	0.9300
N16—H15D	0.8600	C5—H5A	0.9300
C1—C6	1.388 (4)	C17—H22A	0.9700
C1—C2	1.386 (4)	C17—H22B	0.9700
C2—C3	1.387 (4)	C18—H21A	0.9700
C3—C4	1.382 (6)	C18—H21B	0.9700
C4—C5	1.370 (5)	C19—H20A	0.9700
C5—C6	1.365 (4)	C19—H20B	0.9700
C9—C11	1.449 (4)	C20—H18A	0.9700
C11—C12	1.460 (4)	C20—H18B	0.9700
C11—C15	1.387 (4)
C13—S14—C15	91.95 (12)	C12—C17—C18	111.9 (2)
C1—N8—C9	129.3 (2)	C17—C18—C19	111.7 (3)
C9—N8—H9A	115.00	C18—C19—C20	112.1 (3)
C1—N8—H9A	115.00	C13—C20—C19	109.8 (2)
H15C—N16—H15D	120.00	C1—C2—H2A	120.00
C15—N16—H15D	120.00	C3—C2—H2A	120.00
C15—N16—H15C	120.00	C2—C3—H3A	119.00
C2—C1—C6	117.1 (2)	C4—C3—H3A	120.00
N8—C1—C2	125.8 (2)	C3—C4—H4A	120.00
N8—C1—C6	117.1 (2)	C5—C4—H4A	120.00
C1—C2—C3	119.9 (3)	C4—C5—H5A	121.00
C2—C3—C4	121.0 (3)	C6—C5—H5A	121.00
C3—C4—C5	119.8 (3)	C12—C17—H22A	109.00
C4—C5—C6	118.6 (3)	C12—C17—H22B	109.00
F7—C6—C5	119.4 (2)	C18—C17—H22A	109.00
C1—C6—C5	123.6 (2)	C18—C17—H22B	109.00
F7—C6—C1	117.0 (2)	H22A—C17—H22B	108.00
N8—C9—C11	116.8 (2)	C17—C18—H21A	109.00
O10—C9—N8	120.4 (2)	C17—C18—H21B	109.00
O10—C9—C11	122.8 (2)	C19—C18—H21A	109.00
C9—C11—C12	129.8 (2)	C19—C18—H21B	109.00
C9—C11—C15	118.7 (2)	H21A—C18—H21B	108.00
C12—C11—C15	111.5 (2)	C18—C19—H20A	109.00
C11—C12—C13	113.5 (2)	C18—C19—H20B	109.00
C13—C12—C17	119.3 (2)	C20—C19—H20A	109.00
C11—C12—C17	127.1 (2)	C20—C19—H20B	109.00
S14—C13—C20	120.30 (19)	H20A—C19—H20B	108.00
C12—C13—C20	128.1 (2)	C13—C20—H18A	110.00
S14—C13—C12	111.56 (19)	C13—C20—H18B	110.00
S14—C15—C11	111.52 (19)	C19—C20—H18A	110.00
N16—C15—C11	129.6 (2)	C19—C20—H18B	110.00
S14—C15—N16	118.8 (2)	H18A—C20—H18B	108.00
C15—S14—C13—C12	−0.1 (3)	N8—C9—C11—C12	−16.9 (5)
C15—S14—C13—C20	−178.1 (3)	N8—C9—C11—C15	161.9 (3)
C13—S14—C15—N16	178.9 (3)	C9—C11—C12—C13	178.4 (3)
C13—S14—C15—C11	−0.1 (3)	C9—C11—C12—C17	−4.5 (6)
C9—N8—C1—C2	16.1 (5)	C15—C11—C12—C13	−0.4 (4)
C9—N8—C1—C6	−165.1 (3)	C15—C11—C12—C17	176.8 (3)
C1—N8—C9—O10	−7.0 (5)	C9—C11—C15—S14	−178.6 (2)
C1—N8—C9—C11	174.7 (3)	C9—C11—C15—N16	2.4 (5)
N8—C1—C2—C3	−178.1 (3)	C12—C11—C15—S14	0.3 (4)
C6—C1—C2—C3	3.2 (5)	C12—C11—C15—N16	−178.6 (3)
N8—C1—C6—F7	−1.1 (4)	C11—C12—C13—S14	0.3 (4)
N8—C1—C6—C5	179.0 (3)	C11—C12—C13—C20	178.1 (3)
C2—C1—C6—F7	177.7 (3)	C17—C12—C13—S14	−177.1 (3)
C2—C1—C6—C5	−2.1 (5)	C17—C12—C13—C20	0.7 (6)
C1—C2—C3—C4	−2.8 (6)	C11—C12—C17—C18	−160.2 (3)
C2—C3—C4—C5	1.3 (6)	C13—C12—C17—C18	16.8 (5)
C3—C4—C5—C6	−0.2 (6)	S14—C13—C20—C19	−170.8 (3)
C4—C5—C6—F7	−179.2 (3)	C12—C13—C20—C19	11.5 (5)
C4—C5—C6—C1	0.6 (6)	C12—C17—C18—C19	−47.1 (4)
O10—C9—C11—C12	164.9 (3)	C17—C18—C19—C20	61.4 (4)
O10—C9—C11—C15	−16.4 (5)	C18—C19—C20—C13	−41.6 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N8—H9A···F7	0.86	2.26	2.643 (5)	107
N16—H15C···O10	0.86	2.16	2.733 (5)	124
N16—H15D···O10^i	0.86	2.25	2.986 (6)	143

Symmetry code: (i) x, −y, z+1/2.