2-(1H-Imidazol-1-yl)-4-[3-(trifluoro­meth­yl)phen­yl]-1,3-thia­zole

Kudryavtsev, K.V.; Churakov, A.V.; Guh, J.-H.

doi:10.1107/S1600536813000615

organic compounds

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Volume 69| Part 2| February 2013| Page o238

doi:10.1107/S1600536813000615

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2-(1H-Imidazol-1-yl)-4-[3-(trifluoromethyl)phenyl]-1,3-thiazole

Konstantin V. Kudryavtsev,^a,^b ^* Andrei V. Churakov ^c and Jih-Hwa Guh ^d

^aDepartment of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory 1/3, Moscow 119991, Russian Federation, ^bInstitute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, Moscow Region, Russian Federation, ^cInstitute of General and Inorganic Chemistry, Russian Academy of Sciences, Leninskii prosp. 31, Moscow 119991, Russian Federation, and ^dSchool of Pharmacy, National Taiwan University, Taipei 100, Taiwan
^*Correspondence e-mail: kudr@org.chem.msu.ru

(Received 4 January 2013; accepted 7 January 2013; online 16 January 2013)

The title compound, C₁₃H₈F₃N₃S, consists of three linked aromatic rings. The whole molecule (except for the three F atoms) is planar to within 0.225 (2) Å. In the crystal, adjacent molecules are linked into chains along the ac diagonal by weak C—H⋯N interactions.

Related literature

For general background to the synthesis of imidazolothiazoles by copper-catalysed coupling, see: Zhu et al. (2007 ).

Experimental

Crystal data

C₁₃H₈F₃N₃S
M_r = 295.28
Monoclinic, P 2₁ /c
a = 8.4152 (7) Å
b = 19.2403 (15) Å
c = 8.4105 (7) Å
β = 114.210 (1)°
V = 1241.98 (18) Å³
Z = 4
Mo Kα radiation
μ = 0.29 mm⁻¹
T = 150 K
0.40 × 0.20 × 0.10 mm

Data collection

Bruker SMART APEXII diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ) T_min = 0.893, T_max = 0.972
9797 measured reflections
2716 independent reflections
2164 reflections with I > 2σ(I)
R_int = 0.049

Refinement

R[F² > 2σ(F²)] = 0.041
wR(F²) = 0.103
S = 1.07
2716 reflections
213 parameters
All H-atom parameters refined
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.27 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C9—H9⋯N3ⁱ	0.95 (2)	2.34 (2)	3.278 (2)	169.4 (18)
Symmetry code: (i) x+1, y, z+1.

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

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536813000615/ff2095sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536813000615/ff2095Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536813000615/ff2095Isup3.cml

checkCIF report

Comment top

The title compound, C₁₃H₈F₃N₃S, which is a potential anticancer agent, consists of the three linked aromatic and heteroaromatic cycles, which were condensed by copper-catalyzed method (Fig. 1). The whole molecule (except three fluorine atoms) is planar within 0.225 (2) Å (Fig. 2).

In the crystal, the adjacent molecules are combined in chains along ac-diagonal by weak C—H···N interactions (Fig. 3). The C···N separation is equal to 3.278 (2) Å and C—H···N angle is close to linear (169 (2) °).

Related literature top

For general background to the synthesis of imidazolothiazoles by copper-catalysed coupling, see: Zhu et al. (2007).

Experimental top

2-Bromo-4-(3-(trifluoromethyl)phenyl)thiazole (0.800 g, 2.60 mmol) was added to a stirred suspension of imidazole (0.345 g, 5.07 mmol), CuI (0.209 g, 1.10 mmol) and Cs₂CO₃ (1.830 g, 5.62 mmol) in 30 ml of DMF under argon atmosphere. The reaction mixture was stirred for 8 h at rt and then for 7 h at 115 °C. After cooling to the ambient temperature the reaction mixture was filtered and precipitate was washed with 30 ml of DMF. The solution was concentrated under vacuum and residue was diluted with 80 ml of ethyl acetate. Organic phase was washed with water (2 x 10 ml) and saturated solution of NH₄Cl (1 x 10 ml), dried over Na₂SO₄, concentrated and purified by column chromatography on silica gel 60 (particle size 0.040–0.063 mm) using CHCl₃—MeOH (gradient from 1:0 to 50:1) as eluent. 2-(1H-Imidazol-1-yl)-4-(3-(trifluoromethyl)phenyl)thiazole, yield 368 mg (48%), yellowish crystals, mp 99–100°C. ¹H NMR (400 MHz, CDCl₃/DMSO-d₆ 5:1): δ 7.16 (s, 1H), 7.52–7.56 (m, 2H), 7.67 (s, 1H), 7.75 (s, 1H), 8.09–8.11 (m, 1H), 8.15 (s, 1H), 8.40 (s, 1H). ¹³C NMR (100 MHz, CDCl₃/DMSO-d₆ 5:1): δ 111.88, 118.24, 122.95, 122.98, 125.00, 125.03, 129.59, 129.66, 130.17, 130.62, 134.35, 135.63, 150.89, 157.05. Found, %: C, 52.95; H, 2.69; N, 14.20. C₁₃H₈F₃N₃S. Calculated, %: C, 52.88; H, 2.73; N, 14.23. The crystals were obtained by slow evaporation of the CDCl₃/DMSO-d₆ (5:1) solution.

Computing details top

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

Figures top

	Fig. 1. Reaction scheme.
	Fig. 2. The molecular structure of the title compound, showing the numbering scheme adopted. Displacement ellipsoids are shown at the 50% probability level.
	Fig. 3. Chains along ac-diagonal in the structure of the title compound. C—H···N interactions are shown as dashed lines. [Symmetry codes: (i) 1 + x, y, 1 + z; (ii) -1 + x, y, -1 + z.]

2-(1H-Imidazol-1-yl)-4-[3-(trifluoromethyl)phenyl]-1,3-thiazole top

Crystal data top

C₁₃H₈F₃N₃S	F(000) = 600
M_r = 295.28	D_x = 1.579 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 1717 reflections
a = 8.4152 (7) Å	θ = 3.1–24.5°
b = 19.2403 (15) Å	µ = 0.29 mm⁻¹
c = 8.4105 (7) Å	T = 150 K
β = 114.210 (1)°	Block, colourless
V = 1241.98 (18) Å³	0.40 × 0.20 × 0.10 mm
Z = 4

Data collection top

Bruker SMART APEXII diffractometer	2716 independent reflections
Radiation source: fine-focus sealed tube	2164 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.049
ω scans	θ_max = 27.0°, θ_min = 2.1°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −10→9
T_min = 0.893, T_max = 0.972	k = −24→24
9797 measured reflections	l = −10→10

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)] = 0.041	Hydrogen site location: difference Fourier map
wR(F²) = 0.103	All H-atom parameters refined
S = 1.07	w = 1/[σ²(F_o²) + (0.0429P)² + 0.2754P] where P = (F_o² + 2F_c²)/3
2716 reflections	(Δ/σ)_max < 0.001
213 parameters	Δρ_max = 0.27 e Å⁻³
0 restraints	Δρ_min = −0.27 e Å⁻³

Crystal data top

C₁₃H₈F₃N₃S	V = 1241.98 (18) Å³
M_r = 295.28	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 8.4152 (7) Å	µ = 0.29 mm⁻¹
b = 19.2403 (15) Å	T = 150 K
c = 8.4105 (7) Å	0.40 × 0.20 × 0.10 mm
β = 114.210 (1)°

Data collection top

Bruker SMART APEXII diffractometer	2716 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2008)	2164 reflections with I > 2σ(I)
T_min = 0.893, T_max = 0.972	R_int = 0.049
9797 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.041	0 restraints
wR(F²) = 0.103	All H-atom parameters refined
S = 1.07	Δρ_max = 0.27 e Å⁻³
2716 reflections	Δρ_min = −0.27 e Å⁻³
213 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	0.22949 (6)	0.55985 (2)	0.40649 (6)	0.02492 (15)
N1	0.0577 (2)	0.44567 (7)	0.36963 (19)	0.0214 (3)
N2	−0.0844 (2)	0.52744 (7)	0.14612 (18)	0.0207 (3)
N3	−0.3431 (2)	0.52646 (9)	−0.0761 (2)	0.0306 (4)
F1	0.62622 (19)	0.32402 (8)	1.15343 (17)	0.0571 (4)
F2	0.64762 (19)	0.22590 (6)	1.0452 (2)	0.0571 (4)
F3	0.74065 (16)	0.31841 (7)	0.97113 (19)	0.0530 (4)
C1	0.2432 (2)	0.37530 (9)	0.6250 (2)	0.0215 (4)
C2	0.4056 (3)	0.36375 (10)	0.7611 (2)	0.0234 (4)
C3	0.4358 (3)	0.30371 (9)	0.8600 (2)	0.0250 (4)
C4	0.3055 (3)	0.25486 (10)	0.8277 (3)	0.0277 (4)
C5	0.1440 (3)	0.26582 (10)	0.6924 (3)	0.0288 (5)
C6	0.1129 (3)	0.32528 (10)	0.5908 (3)	0.0256 (4)
C7	0.6105 (3)	0.29265 (10)	1.0058 (3)	0.0331 (5)
C8	0.2102 (2)	0.43953 (9)	0.5201 (2)	0.0204 (4)
C9	0.3176 (3)	0.49573 (9)	0.5588 (2)	0.0240 (4)
C10	0.0540 (2)	0.50577 (9)	0.2999 (2)	0.0205 (4)
C11	−0.2399 (3)	0.49374 (10)	0.0647 (2)	0.0285 (5)
C12	−0.2503 (3)	0.58436 (11)	−0.0854 (3)	0.0286 (4)
C13	−0.0922 (3)	0.58620 (10)	0.0485 (2)	0.0266 (4)
H9	0.425 (3)	0.5042 (10)	0.656 (3)	0.028 (5)*
H6	0.004 (3)	0.3331 (10)	0.496 (3)	0.028 (5)*
H2	0.489 (3)	0.3964 (11)	0.783 (3)	0.031 (6)*
H11	−0.263 (3)	0.4517 (11)	0.113 (3)	0.035 (6)*
H5	0.053 (3)	0.2292 (11)	0.670 (3)	0.040 (6)*
H4	0.328 (3)	0.2144 (11)	0.900 (3)	0.037 (6)*
H12	−0.298 (3)	0.6159 (12)	−0.176 (3)	0.043 (7)*
H13	0.002 (3)	0.6192 (12)	0.080 (3)	0.044 (7)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0198 (3)	0.0248 (2)	0.0255 (3)	−0.00220 (19)	0.00454 (19)	0.00161 (18)
N1	0.0189 (8)	0.0255 (8)	0.0196 (8)	0.0012 (6)	0.0077 (6)	−0.0024 (6)
N2	0.0192 (8)	0.0238 (7)	0.0172 (7)	0.0011 (6)	0.0055 (6)	−0.0012 (6)
N3	0.0268 (9)	0.0364 (9)	0.0214 (8)	−0.0014 (7)	0.0028 (7)	0.0014 (7)
F1	0.0494 (9)	0.0731 (10)	0.0318 (7)	0.0124 (8)	−0.0007 (6)	−0.0037 (7)
F2	0.0446 (9)	0.0321 (7)	0.0713 (10)	0.0094 (6)	0.0003 (7)	0.0201 (6)
F3	0.0223 (7)	0.0689 (10)	0.0589 (9)	0.0053 (6)	0.0076 (6)	0.0279 (7)
C1	0.0230 (10)	0.0223 (9)	0.0209 (9)	0.0020 (7)	0.0107 (8)	−0.0022 (7)
C2	0.0210 (10)	0.0251 (9)	0.0244 (10)	0.0001 (8)	0.0096 (8)	−0.0013 (7)
C3	0.0256 (11)	0.0233 (9)	0.0250 (10)	0.0028 (8)	0.0094 (8)	0.0007 (7)
C4	0.0315 (11)	0.0222 (9)	0.0319 (11)	0.0007 (8)	0.0155 (9)	0.0025 (8)
C5	0.0257 (11)	0.0260 (10)	0.0361 (11)	−0.0043 (8)	0.0142 (9)	−0.0040 (8)
C6	0.0214 (10)	0.0273 (10)	0.0270 (10)	−0.0003 (8)	0.0088 (8)	−0.0046 (8)
C7	0.0315 (12)	0.0276 (10)	0.0357 (12)	0.0029 (9)	0.0092 (9)	0.0084 (8)
C8	0.0176 (9)	0.0250 (9)	0.0186 (9)	0.0028 (7)	0.0074 (7)	−0.0018 (7)
C9	0.0198 (10)	0.0267 (10)	0.0229 (9)	0.0014 (8)	0.0059 (8)	0.0008 (7)
C10	0.0179 (9)	0.0257 (9)	0.0176 (9)	0.0005 (7)	0.0068 (7)	−0.0029 (7)
C11	0.0274 (11)	0.0297 (10)	0.0220 (10)	−0.0044 (8)	0.0037 (8)	−0.0012 (8)
C12	0.0307 (11)	0.0316 (10)	0.0224 (10)	0.0043 (9)	0.0099 (8)	0.0034 (8)
C13	0.0259 (11)	0.0282 (10)	0.0255 (10)	−0.0005 (8)	0.0104 (8)	0.0036 (8)

Geometric parameters (Å, º) top

S1—C9	1.7128 (19)	C2—C3	1.385 (3)
S1—C10	1.7266 (18)	C2—H2	0.90 (2)
N1—C10	1.291 (2)	C3—C4	1.384 (3)
N1—C8	1.390 (2)	C3—C7	1.494 (3)
N2—C11	1.367 (2)	C4—C5	1.385 (3)
N2—C13	1.383 (2)	C4—H4	0.96 (2)
N2—C10	1.403 (2)	C5—C6	1.387 (3)
N3—C11	1.307 (2)	C5—H5	1.00 (2)
N3—C12	1.381 (3)	C6—H6	0.95 (2)
F1—C7	1.337 (3)	C8—C9	1.360 (3)
F2—C7	1.331 (2)	C9—H9	0.95 (2)
F3—C7	1.339 (3)	C11—H11	0.96 (2)
C1—C2	1.394 (3)	C12—C13	1.346 (3)
C1—C6	1.397 (3)	C12—H12	0.93 (2)
C1—C8	1.477 (2)	C13—H13	0.96 (2)

C9—S1—C10	88.27 (9)	F2—C7—F1	106.30 (17)
C10—N1—C8	109.34 (15)	F2—C7—F3	106.36 (18)
C11—N2—C13	106.72 (15)	F1—C7—F3	104.87 (18)
C11—N2—C10	125.71 (16)	F2—C7—C3	113.16 (17)
C13—N2—C10	127.57 (16)	F1—C7—C3	112.79 (18)
C11—N3—C12	105.01 (17)	F3—C7—C3	112.71 (17)
C2—C1—C6	118.77 (17)	C9—C8—N1	115.14 (16)
C2—C1—C8	120.30 (17)	C9—C8—C1	125.36 (16)
C6—C1—C8	120.93 (17)	N1—C8—C1	119.50 (16)
C3—C2—C1	120.20 (18)	C8—C9—S1	110.65 (14)
C3—C2—H2	121.4 (13)	C8—C9—H9	130.2 (12)
C1—C2—H2	118.4 (13)	S1—C9—H9	119.0 (12)
C4—C3—C2	120.85 (18)	N1—C10—N2	122.77 (16)
C4—C3—C7	119.88 (17)	N1—C10—S1	116.59 (13)
C2—C3—C7	119.25 (17)	N2—C10—S1	120.64 (13)
C3—C4—C5	119.30 (18)	N3—C11—N2	111.68 (18)
C3—C4—H4	119.6 (14)	N3—C11—H11	128.1 (13)
C5—C4—H4	121.1 (14)	N2—C11—H11	120.2 (13)
C4—C5—C6	120.36 (19)	C13—C12—N3	111.19 (17)
C4—C5—H5	117.8 (13)	C13—C12—H12	128.0 (14)
C6—C5—H5	121.8 (13)	N3—C12—H12	120.8 (14)
C5—C6—C1	120.50 (18)	C12—C13—N2	105.38 (17)
C5—C6—H6	121.5 (12)	C12—C13—H13	131.8 (14)
C1—C6—H6	118.0 (12)	N2—C13—H13	122.8 (14)

C6—C1—C2—C3	−0.1 (3)	C2—C1—C8—N1	170.46 (17)
C8—C1—C2—C3	179.52 (17)	C6—C1—C8—N1	−9.9 (3)
C1—C2—C3—C4	−1.0 (3)	N1—C8—C9—S1	0.5 (2)
C1—C2—C3—C7	−179.66 (18)	C1—C8—C9—S1	−178.79 (15)
C2—C3—C4—C5	1.2 (3)	C10—S1—C9—C8	−0.46 (15)
C7—C3—C4—C5	179.87 (19)	C8—N1—C10—N2	−179.81 (16)
C3—C4—C5—C6	−0.3 (3)	C8—N1—C10—S1	−0.2 (2)
C4—C5—C6—C1	−0.8 (3)	C11—N2—C10—N1	9.5 (3)
C2—C1—C6—C5	1.0 (3)	C13—N2—C10—N1	−171.01 (18)
C8—C1—C6—C5	−178.61 (18)	C11—N2—C10—S1	−170.05 (15)
C4—C3—C7—F2	26.1 (3)	C13—N2—C10—S1	9.4 (3)
C2—C3—C7—F2	−155.26 (19)	C9—S1—C10—N1	0.41 (16)
C4—C3—C7—F1	−94.6 (2)	C9—S1—C10—N2	180.00 (16)
C2—C3—C7—F1	84.0 (2)	C12—N3—C11—N2	−0.4 (2)
C4—C3—C7—F3	146.84 (19)	C13—N2—C11—N3	0.4 (2)
C2—C3—C7—F3	−34.5 (3)	C10—N2—C11—N3	180.00 (17)
C10—N1—C8—C9	−0.2 (2)	C11—N3—C12—C13	0.2 (2)
C10—N1—C8—C1	179.13 (16)	N3—C12—C13—N2	0.0 (2)
C2—C1—C8—C9	−10.3 (3)	C11—N2—C13—C12	−0.3 (2)
C6—C1—C8—C9	169.30 (18)	C10—N2—C13—C12	−179.81 (18)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C9—H9···N3ⁱ	0.95 (2)	2.34 (2)	3.278 (2)	169.4 (18)

Symmetry code: (i) x+1, y, z+1.

Experimental details

Crystal data
Chemical formula	C₁₃H₈F₃N₃S
M_r	295.28
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	150
a, b, c (Å)	8.4152 (7), 19.2403 (15), 8.4105 (7)
β (°)	114.210 (1)
V (Å³)	1241.98 (18)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.29
Crystal size (mm)	0.40 × 0.20 × 0.10

Data collection
Diffractometer	Bruker SMART APEXII diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2008)
T_min, T_max	0.893, 0.972
No. of measured, independent and observed [I > 2σ(I)] reflections	9797, 2716, 2164
R_int	0.049
(sin θ/λ)_max (Å⁻¹)	0.639

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.041, 0.103, 1.07
No. of reflections	2716
No. of parameters	213
H-atom treatment	All H-atom parameters refined
Δρ_max, Δρ_min (e Å⁻³)	0.27, −0.27

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

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C9—H9···N3ⁱ	0.95 (2)	2.34 (2)	3.278 (2)	169.4 (18)

Symmetry code: (i) x+1, y, z+1.

Acknowledgements

This study was partially supported by the Russian Foundation for Basic Research (project Nos. 11–03-00630_a and 12–03-92005-NSC_a) and by the National Science Council of the Republic of China (NSC101–2923-B-002–008-MY3).

References

Bruker (2008). APEX2, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
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Zhu, L., Guo, P., Li, G., Lan, J., Xie, R. & You, J. (2007). J. Org. Chem. 72, 8535–8538. Web of Science CrossRef PubMed CAS Google Scholar