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

Abstract

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,

• 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) ų

• 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[F ² > 2σ(F ²)] = 0.047

• wR(F ²) = 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

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.

Supplementary Material

Supplementary material file. DOI: 10.1107/S1600536812022477/rk2350Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

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) ; (ii) .

supplementary crystallographic information

Comment

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.

Experimental

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.

Refinement

The positions of all H atoms were determined geometrically and refined using a riding model with C—H = 0.93Å, N—H = 0.86Å and U_iso(H) = 1.2U_eq(C, N).

Figures

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.

Crystal data

C10H5ClF2N2OS	Z = 2
Mr = 274.68	F(000) = 276
Triclinic, P1	Dx = 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

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

Refinement

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(Fo2) + (0.0689P)2 + 0.4949P] where P = (Fo2 + 2Fc2)/3
S = 1.06	(Δ/σ)max < 0.001
1998 reflections	Δρmax = 1.25 e Å−3
155 parameters	Δρmin = −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)

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
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 (Ų)

	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)

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)

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.