N-(5-Chloro-1,3-thia­zol-2-yl)-2,4-difluoro­benzamide

Liu, X.-W.; Li, J.-Y.; Zhang, H.; Yang, Y.-J.; Zhang, J.-Y.

doi:10.1107/S1600536812022477

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 68| Part 6| June 2012| Page o1857

doi:10.1107/S1600536812022477

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N-(5-Chloro-1,3-thiazol-2-yl)-2,4-difluorobenzamide

Xi-Wang Liu,^a Jian-Yong Li,^a ^* Han Zhang,^a Ya-Jun Yang ^a and Ji-Yu Zhang ^a

^aKey Laboratory of the New Animal Drug Project, Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou Institute of Animal Science and Veterinary Pharmaceutics of CAAS, Lanzhou 730050, People's Republic of China
^*Correspondence e-mail: lijy1971@163.com

(Received 27 March 2012; accepted 17 May 2012; online 23 May 2012)

The title compound, C₁₀H₅ClF₂N₂OS, was obtained by linking an amino heterocycle and a substituted benzoyl chloride. The dihedral angle between the two rings is 41.2 (2)° and the equalization of the amide C—N bond lengths reveals the existence of conjugation between the benzene ring and the thiazole unit. In the crystal, pairs of N—H⋯N hydrogen bonds link molecules into inversion dimers. Non-classical C—H⋯F and C—H⋯O hydrogen bonds stabilize the crystal structure.

Related literature

For synthesis and the biological activity of thiazolides, see: Ballard et al. (2011 ).

Experimental

Crystal data

C₁₀H₅ClF₂N₂OS
M_r = 274.68
Triclinic, $[P \overline 1]$
a = 6.929 (2) Å
b = 7.330 (2) Å
c = 12.179 (4) Å
α = 101.669 (3)°
β = 98.277 (3)°
γ = 111.796 (3)°
V = 545.9 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.55 mm⁻¹
T = 296 K
0.35 × 0.33 × 0.27 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ) T_min = 0.831, T_max = 0.866
3930 measured reflections
1998 independent reflections
1693 reflections with I > 2σ(I)
R_int = 0.028

Refinement

R[F² > 2σ(F²)] = 0.047
wR(F²) = 0.136
S = 1.06
1998 reflections
155 parameters
H-atom parameters constrained
Δρ_max = 1.25 e Å⁻³
Δρ_min = −0.33 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯N2ⁱ	0.86	2.15	2.988 (3)	166
C4—H4⋯F2ⁱⁱ	0.93	2.38	3.127 (4)	137
C4—H4⋯O3ⁱⁱ	0.93	2.56	3.329 (4)	140
Symmetry codes: (i) -x+2, -y+1, -z+1; (ii) x+1, y, z.

Data collection: APEX2 (Bruker, 2008 ); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT; 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 I, global. DOI: 10.1107/S1600536812022477/rk2350sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812022477/rk2350Isup3.hkl

Supporting information file. DOI: 10.1107/S1600536812022477/rk2350Isup3.cml

checkCIF report

Comment top

Nitazoxanide, (2-acetyloloxy-N-(5-nitro-2-thiazolyl)benzamide), belonged to nitrothiazole analogue, was developed as a promising compound to treat both human and animal diseases (Ballard et al., 2011). In this paper, we report the synthesis and structure of the title compound, which is a derivative of nitazoxanide. The conjugation between benzene ring and thiazole moiety confirmed the existance of amide anion, which is considered to directly inhibit the PFOR enzyme (key enzyme of central intermidiary matabolism in anaerobic organisms). The classical intermolecular hydrogen bonds N1—H1···N2ⁱ forms centrosymmetrical dimers (Table 1). The non-classical intermolecular hydrogen bonds C4—H4···F2ⁱⁱ and C4—H4···O3ⁱⁱ stabilize molecular packing in crystal. Symmetry codes: (i) -x+2, -y+1, -z+1; (ii) x+1, y, z.

Related literature top

For synthesis and the biological activity of thiazolides, see: Ballard et al. (2011).

Experimental top

The title compound was obtained according to routine method: to a solution of 5-chlorothiazol-2-amine (1 mmol) in distilled pyridine was added a equimolar amount of 2,4-difluorobenzoyl chloride with stirring. When addition was complete, the reaction mixture was allowed to stand at room temperature and stirred over night. The reaction was judged complete by TLC analysis. The crude product then seperated on dilution was filtered out, washed with 10% NaHCO₃ solution, then several times with water. The dry solid was purified by chromatography to give pure compound and the crystals were obtained by recrystalization from CH₃OH.

Computing details top

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); 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 molecular structure of title compound with the atom labels. Displacement ellipsoids are drawn at the 30% probability level. H atoms are presented as a small spheres of arbitrary radius.

N-(5-Chloro-1,3-thiazol-2-yl)-2,4-difluorobenzamide top

Crystal data top

C₁₀H₅ClF₂N₂OS	Z = 2
M_r = 274.68	F(000) = 276
Triclinic, P1	D_x = 1.671 Mg m⁻³
Hall symbol: -P 1	Melting point = 428–429 K
a = 6.929 (2) Å	Mo Kα radiation, λ = 0.71073 Å
b = 7.330 (2) Å	Cell parameters from 2870 reflections
c = 12.179 (4) Å	θ = 3.1–28.2°
α = 101.669 (3)°	µ = 0.55 mm⁻¹
β = 98.277 (3)°	T = 296 K
γ = 111.796 (3)°	Block, colourless
V = 545.9 (3) Å³	0.35 × 0.33 × 0.27 mm

Data collection top

Bruker APEXII CCD diffractometer	1998 independent reflections
Radiation source: fine-focus sealed tube	1693 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.028
ϕ– and ω–scans	θ_max = 25.5°, θ_min = 3.1°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −8→8
T_min = 0.831, T_max = 0.866	k = −8→8
3930 measured reflections	l = −14→14

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)] = 0.047	H-atom parameters constrained
wR(F²) = 0.136	w = 1/[σ²(F_o²) + (0.0689P)² + 0.4949P] where P = (F_o² + 2F_c²)/3
S = 1.06	(Δ/σ)_max < 0.001
1998 reflections	Δρ_max = 1.25 e Å⁻³
155 parameters	Δρ_min = −0.33 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: 0.53 (3)

Crystal data top

C₁₀H₅ClF₂N₂OS	γ = 111.796 (3)°
M_r = 274.68	V = 545.9 (3) Å³
Triclinic, P1	Z = 2
a = 6.929 (2) Å	Mo Kα radiation
b = 7.330 (2) Å	µ = 0.55 mm⁻¹
c = 12.179 (4) Å	T = 296 K
α = 101.669 (3)°	0.35 × 0.33 × 0.27 mm
β = 98.277 (3)°

Data collection top

Bruker APEXII CCD diffractometer	1998 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	1693 reflections with I > 2σ(I)
T_min = 0.831, T_max = 0.866	R_int = 0.028
3930 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.047	0 restraints
wR(F²) = 0.136	H-atom parameters constrained
S = 1.06	Δρ_max = 1.25 e Å⁻³
1998 reflections	Δρ_min = −0.33 e Å⁻³
155 parameters

Special details top

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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
C1	1.0517 (5)	0.7233 (5)	0.9365 (3)	0.0438 (7)
C2	1.2260 (5)	0.8083 (5)	1.0282 (3)	0.0494 (8)
H2	1.2296	0.8968	1.0958	0.059*
C3	1.3958 (5)	0.7579 (5)	1.0168 (3)	0.0467 (8)
C4	1.3945 (5)	0.6268 (5)	0.9182 (3)	0.0464 (7)
H4	1.5116	0.5954	0.9126	0.056*
C5	1.2153 (5)	0.5432 (5)	0.8280 (3)	0.0413 (7)
H5	1.2120	0.4530	0.7612	0.050*
C6	1.0387 (4)	0.5896 (4)	0.8336 (2)	0.0358 (6)
C7	0.8392 (5)	0.4900 (4)	0.7407 (2)	0.0390 (7)
C8	0.6940 (4)	0.3522 (4)	0.5350 (2)	0.0365 (6)
C9	0.5284 (5)	0.2099 (5)	0.3514 (3)	0.0505 (8)
H9	0.5166	0.1733	0.2722	0.061*
C10	0.3587 (5)	0.1551 (4)	0.3969 (3)	0.0447 (7)
Cl1	0.09389 (14)	0.01753 (14)	0.32522 (8)	0.0662 (4)
F1	1.5714 (3)	0.8434 (3)	1.10528 (18)	0.0673 (6)
F2	0.8890 (3)	0.7783 (4)	0.9458 (2)	0.0796 (8)
N1	0.8646 (4)	0.4602 (4)	0.62983 (19)	0.0376 (6)
H1	0.9916	0.5106	0.6191	0.045*
N2	0.7224 (4)	0.3246 (4)	0.4302 (2)	0.0449 (6)
O3	0.6609 (3)	0.4314 (4)	0.75914 (18)	0.0553 (6)
S1	0.43196 (11)	0.24360 (11)	0.54607 (6)	0.0421 (3)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0358 (15)	0.0438 (16)	0.0480 (17)	0.0122 (13)	0.0149 (13)	0.0095 (13)
C2	0.0483 (18)	0.0462 (17)	0.0386 (16)	0.0079 (14)	0.0089 (14)	0.0038 (13)
C3	0.0365 (15)	0.0494 (18)	0.0420 (16)	0.0035 (13)	0.0018 (12)	0.0198 (14)
C4	0.0377 (15)	0.0559 (19)	0.0504 (18)	0.0196 (14)	0.0119 (14)	0.0236 (15)
C5	0.0396 (15)	0.0447 (16)	0.0393 (15)	0.0156 (13)	0.0128 (12)	0.0123 (13)
C6	0.0329 (13)	0.0370 (14)	0.0339 (14)	0.0084 (11)	0.0107 (11)	0.0119 (11)
C7	0.0377 (15)	0.0413 (15)	0.0368 (15)	0.0135 (12)	0.0117 (12)	0.0121 (12)
C8	0.0339 (13)	0.0349 (14)	0.0372 (14)	0.0094 (11)	0.0101 (11)	0.0110 (11)
C9	0.0490 (18)	0.0455 (17)	0.0361 (16)	0.0020 (14)	0.0049 (13)	0.0052 (13)
C10	0.0414 (16)	0.0335 (15)	0.0440 (16)	0.0049 (12)	0.0006 (13)	0.0066 (12)
Cl1	0.0435 (5)	0.0572 (6)	0.0666 (6)	−0.0003 (4)	−0.0052 (4)	0.0058 (4)
F1	0.0444 (11)	0.0784 (14)	0.0528 (12)	0.0031 (10)	−0.0082 (9)	0.0204 (10)
F2	0.0495 (12)	0.0830 (16)	0.0895 (17)	0.0280 (11)	0.0141 (11)	−0.0104 (13)
N1	0.0304 (11)	0.0443 (13)	0.0336 (12)	0.0099 (10)	0.0091 (10)	0.0111 (10)
N2	0.0423 (13)	0.0449 (14)	0.0341 (13)	0.0058 (11)	0.0096 (11)	0.0062 (11)
O3	0.0349 (11)	0.0801 (17)	0.0385 (12)	0.0114 (11)	0.0119 (9)	0.0125 (11)
S1	0.0327 (4)	0.0449 (5)	0.0426 (5)	0.0098 (3)	0.0088 (3)	0.0114 (3)

Geometric parameters (Å, º) top

C1—F2	1.343 (4)	C7—O3	1.220 (3)
C1—C2	1.366 (4)	C7—N1	1.371 (4)
C1—C6	1.393 (4)	C8—N2	1.306 (4)
C2—C3	1.374 (5)	C8—N1	1.379 (4)
C2—H2	0.9300	C8—S1	1.729 (3)
C3—F1	1.348 (3)	C9—C10	1.334 (5)
C3—C4	1.374 (5)	C9—N2	1.378 (4)
C4—C5	1.376 (4)	C9—H9	0.9300
C4—H4	0.9300	C10—Cl1	1.719 (3)
C5—C6	1.394 (4)	C10—S1	1.730 (3)
C5—H5	0.9300	N1—H1	0.8600
C6—C7	1.480 (4)

F2—C1—C2	117.5 (3)	O3—C7—N1	120.7 (3)
F2—C1—C6	119.1 (3)	O3—C7—C6	123.3 (3)
C2—C1—C6	123.4 (3)	N1—C7—C6	116.0 (2)
C1—C2—C3	117.4 (3)	N2—C8—N1	121.3 (2)
C1—C2—H2	121.3	N2—C8—S1	115.8 (2)
C3—C2—H2	121.3	N1—C8—S1	122.9 (2)
F1—C3—C4	119.0 (3)	C10—C9—N2	115.1 (3)
F1—C3—C2	118.5 (3)	C10—C9—H9	122.5
C4—C3—C2	122.5 (3)	N2—C9—H9	122.5
C3—C4—C5	118.3 (3)	C9—C10—Cl1	127.8 (3)
C3—C4—H4	120.9	C9—C10—S1	111.6 (2)
C5—C4—H4	120.9	Cl1—C10—S1	120.56 (19)
C4—C5—C6	122.0 (3)	C7—N1—C8	122.4 (2)
C4—C5—H5	119.0	C7—N1—H1	118.8
C6—C5—H5	119.0	C8—N1—H1	118.8
C1—C6—C5	116.4 (3)	C8—N2—C9	110.0 (3)
C1—C6—C7	120.8 (3)	C8—S1—C10	87.44 (14)
C5—C6—C7	122.6 (3)

F2—C1—C2—C3	−177.5 (3)	C1—C6—C7—N1	145.0 (3)
C6—C1—C2—C3	0.2 (5)	C5—C6—C7—N1	−40.5 (4)
C1—C2—C3—F1	178.6 (3)	N2—C9—C10—Cl1	178.5 (2)
C1—C2—C3—C4	−0.3 (5)	N2—C9—C10—S1	−0.6 (4)
F1—C3—C4—C5	−179.1 (3)	O3—C7—N1—C8	−4.4 (4)
C2—C3—C4—C5	−0.1 (5)	C6—C7—N1—C8	173.7 (2)
C3—C4—C5—C6	0.8 (4)	N2—C8—N1—C7	−179.6 (3)
F2—C1—C6—C5	178.1 (3)	S1—C8—N1—C7	−0.1 (4)
C2—C1—C6—C5	0.4 (4)	N1—C8—N2—C9	179.1 (3)
F2—C1—C6—C7	−7.1 (4)	S1—C8—N2—C9	−0.4 (3)
C2—C1—C6—C7	175.2 (3)	C10—C9—N2—C8	0.7 (4)
C4—C5—C6—C1	−0.9 (4)	N2—C8—S1—C10	0.1 (2)
C4—C5—C6—C7	−175.6 (3)	N1—C8—S1—C10	−179.4 (3)
C1—C6—C7—O3	−37.0 (4)	C9—C10—S1—C8	0.3 (3)
C5—C6—C7—O3	137.5 (3)	Cl1—C10—S1—C8	−178.9 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N2ⁱ	0.86	2.15	2.988 (3)	166
C4—H4···F2ⁱⁱ	0.93	2.38	3.127 (4)	137
C4—H4···O3ⁱⁱ	0.93	2.56	3.329 (4)	140

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

Experimental details

Crystal data
Chemical formula	C₁₀H₅ClF₂N₂OS
M_r	274.68
Crystal system, space group	Triclinic, P1
Temperature (K)	296
a, b, c (Å)	6.929 (2), 7.330 (2), 12.179 (4)
α, β, γ (°)	101.669 (3), 98.277 (3), 111.796 (3)
V (Å³)	545.9 (3)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.55
Crystal size (mm)	0.35 × 0.33 × 0.27

Data collection
Diffractometer	Bruker APEXII CCD diffractometer
Absorption correction	Multi-scan (SADABS; Sheldrick, 1996)
T_min, T_max	0.831, 0.866
No. of measured, independent and observed [I > 2σ(I)] reflections	3930, 1998, 1693
R_int	0.028
(sin θ/λ)_max (Å⁻¹)	0.606

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.047, 0.136, 1.06
No. of reflections	1998
No. of parameters	155
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	1.25, −0.33

Computer programs: APEX2 (Bruker, 2008), SAINT (Bruker, 2008), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N2ⁱ	0.86	2.15	2.988 (3)	166.3
C4—H4···F2ⁱⁱ	0.93	2.38	3.127 (4)	137.1
C4—H4···O3ⁱⁱ	0.93	2.56	3.329 (4)	139.7

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

Acknowledgements

This research was supported by the earmarked fund for the China Agriculture Research System (CARS-38) and the open fund of the Key Laboratory of the New Animal Drug Project of Gansu Province and the Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture (1610322011011).

References

Ballard, T. E., Wang, X., Olekhnovich, I., Koerner, T., Seymour, C., Salamoun, J., Warthan, M., Hoffman, P. S. & Macdonald, T. L. (2011). ChemMedChem, 6, 362–377. Web of Science CrossRef CAS PubMed Google Scholar
Bruker (2008). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar