3-Di­fluoro­methyl-5-[4-(tri­fluoro­meth­yl)phen­yl]isoxazole

Zhao, H.

doi:10.1107/S2414314618004455

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 3| Part 4| April 2018| x180445

https://doi.org/10.1107/S2414314618004455

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3-Difluoromethyl-5-[4-(trifluoromethyl)phenyl]isoxazole

Hui Zhao ^a ^*

^aAnhui Engineering Technology Research Center for Extraction and Isolation of Active Components, Anhui Academy of Applied Technology, Hefei, 230031, People's Republic of China
^*Correspondence e-mail: zh1986@iccas.ac.cn

Edited by J. Simpson, University of Otago, New Zealand (Received 8 March 2018; accepted 16 March 2018; online 6 April 2018)

The title molecule, C₁₁H₆F₅NO, lies on a mirror plane in the orthorhombic unit cell, with only two F atoms each of the difluoro and trifluoromethyl substituents lying out of the plane. In the crystal, molecules are linked by C—H⋯O, C—H⋯N and C—H⋯F hydrogen bonds, forming a layer structure parallel to the (001) plane. Weak π–π interactions promote the formation of a three-dimensional network.

Keywords: crystal structure; fluoroalkylated isoxazoles; hydrogen bonds; π–π interactions.

CCDC reference: 1577897

Structure description

Nitrogen heterocycles are important scaffolds in bioactive natural and synthesized compounds (Fried et al., 2001 ; Baraldi et al., 2008 ; Vitaku et al., 2014 ). Moreover, organic molecules with fluoroalkyl substituents often impart desirable physical and biological properties (Wang et al., 2014 ).

The title compound crystallizes in the orthorhombic space group Pbcm with most atoms of the molecule in the mirror plane (Fig. 1). Only the F1 and F3 atoms of the difluoro and trifluoromethyl substituents lie out of this plane. In the crystal, molecules are linked by a combination of C—H⋯O, C—H⋯N and C—H⋯F hydrogen bonds (Table 1) together with a weak π–π stacking interaction between C5–C10 rings [centroid–centroid separation = 3.904 (2) Å] (Fig. 2). In more detail, a chain running along the [010] direction forms through C3—H3⋯O1 and C3—H3⋯N1 hydrogen bonds, Table 1. These [010] chains are joined by the C1—H1⋯F2 hydrogen bonds, forming a layer structure parallel to the (001) plane. Finally, molecules in these (001) layers are linked by the weak π–π stacking interactions to generate a three-dimensional network.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C3—H3⋯O1ⁱ	0.93	2.69	3.581 (7)	160
C3—H3⋯N1ⁱ	0.93	2.62	3.534 (6)	170
C1—H1⋯F2ⁱⁱ	0.98	2.65	3.258 (6)	121
Symmetry codes: (i) $[-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) x+1, y, z.

Figure 1
The structure of the title compound, with displacement ellipsoids drawn at the 50% probability level. [Symmetry code: (i) x, y, −z + $[{1\over 2}]$ .]

Figure 2
Overall packing of the title compound viewed along the c-axis direction. Hydrogen bonds are drawn as dashed lines.

Synthesis and crystallization

The title compound was synthesized by a one-pot `click synthesis' of fluoroalkylated isoxazoles from commercially avalilable 1-ethynyl-4-(trifluoromethyl)benzene and 2,2-difluoroethanamine, and the isolation and characterization have been reported previously (Zhang et al., 2018 ). Crystals for X-ray data collection were obtained by slow evaporation of a petroleum ether/ethylacetate (v:v = 100:1) solution.

Refinement

Crystal data, data collection, and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₁H₆F₅NO
M_r	263.17
Crystal system, space group	Orthorhombic, Pbcm
Temperature (K)	293
a, b, c (Å)	13.1081 (13), 11.1491 (13), 7.1798 (11)
V (Å³)	1049.3 (2)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.17
Crystal size (mm)	0.24 × 0.22 × 0.20

Data collection
Diffractometer	Rigaku Oxford Diffraction SuperNova, Dual, Cu at zero, Atlas
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2015 $[Rigaku OD (2015). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ )
T_min, T_max	0.961, 0.967
No. of measured, independent and observed [I > 2σ(I)] reflections	5659, 1066, 707
R_int	0.027
(sin θ/λ)_max (Å⁻¹)	0.605

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.079, 0.292, 1.07
No. of reflections	1066
No. of parameters	103
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.24, −0.49
Computer programs: CrysAlis PRO (Rigaku OD, 2015 $[Rigaku OD (2015). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ ), SHELXS97 and SHELXL97 (Sheldrick, 2008 ) and OLEX2 (Dolomanov et al. 2009 ).

Structural data

CCDC reference: 1577897

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314618004455/sj4168sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314618004455/sj4168Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314618004455/sj4168Isup3.cdx

Supporting information file. DOI: https://doi.org/10.1107/S2414314618004455/sj4168Isup4.cml

checkCIF report

Computing details top

Data collection: CrysAlis PRO (Rigaku OD, 2015); cell refinement: CrysAlis PRO (Rigaku OD, 2015); data reduction: CrysAlis PRO (Rigaku OD, 2015); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al. 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al. 2009).

3-Difluoromethyl-5-[4-(trifluoromethyl)phenyl]isoxazole top

Crystal data top

C₁₁H₆F₅NO	D_x = 1.666 Mg m⁻³
M_r = 263.17	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pbcm	Cell parameters from 1887 reflections
a = 13.1081 (13) Å	θ = 3.7–26.4°
b = 11.1491 (13) Å	µ = 0.17 mm⁻¹
c = 7.1798 (11) Å	T = 293 K
V = 1049.3 (2) Å³	Block, colourless
Z = 4	0.24 × 0.22 × 0.20 mm
F(000) = 528

Data collection top

Rigaku Oxford Diffraction SuperNova, Dual, Cu at zero, Atlas diffractometer	1066 independent reflections
Radiation source: fine-focus sealed tube	707 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.027
Detector resolution: 8.0353 pixels mm^-1	θ_max = 25.5°, θ_min = 3.6°
ω scans	h = −15→15
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2015)	k = −13→12
T_min = 0.961, T_max = 0.967	l = −7→8
5659 measured reflections

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)] = 0.079	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.292	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ²(F_o²) + (0.1997P)² + 0.0686P] where P = (F_o² + 2F_c²)/3
1066 reflections	(Δ/σ)_max < 0.001
103 parameters	Δρ_max = 0.24 e Å⁻³
0 restraints	Δρ_min = −0.49 e Å⁻³

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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
N1	0.5503 (3)	0.1715 (3)	0.2500	0.0724 (13)
O1	0.4442 (3)	0.1696 (2)	0.2500	0.0689 (11)
F1	0.7082 (2)	0.3834 (2)	0.3982 (4)	0.1078 (12)
C4	0.4094 (4)	0.2842 (3)	0.2500	0.0544 (12)
C5	0.2998 (4)	0.3006 (4)	0.2500	0.0542 (12)
C3	0.4895 (4)	0.3580 (4)	0.2500	0.0650 (14)
H3	0.4882	0.4414	0.2500	0.078*
C9	0.1574 (4)	0.4343 (5)	0.2500	0.0844 (17)
H9	0.1312	0.5118	0.2500	0.101*
C8	0.0914 (4)	0.3356 (4)	0.2500	0.0794 (16)
C6	0.2315 (4)	0.2038 (4)	0.2500	0.0683 (14)
H6	0.2568	0.1259	0.2500	0.082*
C10	0.2593 (4)	0.4164 (4)	0.2500	0.0704 (15)
H10	0.3031	0.4821	0.2500	0.084*
C11	−0.0320 (6)	0.3614 (6)	0.2500	0.0780 (19)
C7	0.1293 (5)	0.2218 (4)	0.2500	0.0797 (17)
H7	0.0851	0.1565	0.2500	0.096*
C1	0.6860 (4)	0.3158 (5)	0.2500	0.0734 (15)
H1	0.7276	0.2428	0.2500	0.088*
C2	0.5753 (4)	0.2845 (4)	0.2500	0.0607 (13)
F2	−0.0709 (6)	0.2549 (10)	0.2500	0.327 (7)
F3	−0.0478 (5)	0.3962 (6)	0.3638 (11)	0.260 (5)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.066 (3)	0.053 (3)	0.098 (3)	0.0016 (18)	0.000	0.000
O1	0.064 (2)	0.0454 (19)	0.097 (3)	−0.0009 (14)	0.000	0.000
F1	0.0887 (19)	0.124 (2)	0.111 (2)	−0.0307 (14)	−0.0063 (14)	−0.0265 (15)
C4	0.073 (3)	0.043 (2)	0.047 (2)	−0.0011 (19)	0.000	0.000
C5	0.064 (3)	0.048 (2)	0.050 (2)	0.003 (2)	0.000	0.000
C3	0.074 (3)	0.041 (2)	0.080 (3)	−0.004 (2)	0.000	0.000
C9	0.079 (4)	0.055 (3)	0.118 (5)	0.005 (2)	0.000	0.000
C8	0.066 (3)	0.072 (4)	0.100 (4)	0.009 (3)	0.000	0.000
C6	0.078 (4)	0.047 (3)	0.080 (3)	−0.009 (2)	0.000	0.000
C10	0.066 (3)	0.053 (3)	0.092 (4)	−0.001 (2)	0.000	0.000
C11	0.058 (4)	0.060 (3)	0.115 (6)	−0.021 (3)	0.000	0.000
C7	0.074 (4)	0.062 (3)	0.103 (4)	−0.014 (3)	0.000	0.000
C1	0.070 (3)	0.063 (3)	0.088 (4)	−0.015 (3)	0.000	0.000
C2	0.069 (3)	0.051 (3)	0.062 (3)	−0.005 (2)	0.000	0.000
F2	0.127 (6)	0.223 (8)	0.63 (2)	0.010 (7)	0.000	0.000
F3	0.101 (3)	0.264 (6)	0.414 (15)	−0.013 (4)	−0.016 (5)	−0.005 (5)

Geometric parameters (Å, º) top

N1—C2	1.302 (5)	C8—C7	1.363 (7)
N1—O1	1.392 (6)	C8—C11	1.643 (10)
O1—C4	1.356 (5)	C6—C7	1.354 (8)
F1—C1	1.336 (3)	C6—H6	0.9300
C4—C3	1.334 (7)	C10—H10	0.9300
C4—C5	1.449 (7)	C11—F3ⁱ	0.928 (8)
C5—C10	1.395 (6)	C11—F3	0.928 (8)
C5—C6	1.402 (7)	C11—F2	1.293 (13)
C3—C2	1.393 (7)	C7—H7	0.9300
C3—H3	0.9300	C1—F1ⁱ	1.336 (3)
C9—C10	1.351 (7)	C1—C2	1.492 (7)
C9—C8	1.400 (7)	C1—H1	0.9800
C9—H9	0.9300	F3—F3ⁱ	1.634 (16)

C2—N1—O1	105.4 (3)	C9—C10—H10	119.6
C4—O1—N1	108.8 (3)	C5—C10—H10	119.6
C3—C4—O1	108.5 (5)	F3ⁱ—C11—F3	123.3 (15)
C3—C4—C5	134.6 (4)	F3ⁱ—C11—F2	107.2 (7)
O1—C4—C5	116.9 (4)	F3—C11—F2	107.2 (7)
C10—C5—C6	118.0 (5)	F3ⁱ—C11—C8	107.1 (8)
C10—C5—C4	119.6 (4)	F3—C11—C8	107.1 (8)
C6—C5—C4	122.4 (4)	F2—C11—C8	103.1 (6)
C4—C3—C2	105.8 (4)	C6—C7—C8	119.9 (5)
C4—C3—H3	127.1	C6—C7—H7	120.1
C2—C3—H3	127.1	C8—C7—H7	120.1
C10—C9—C8	119.7 (5)	F1—C1—F1ⁱ	105.6 (4)
C10—C9—H9	120.2	F1—C1—C2	110.1 (3)
C8—C9—H9	120.2	F1ⁱ—C1—C2	110.1 (3)
C7—C8—C9	120.5 (5)	F1—C1—H1	110.3
C7—C8—C11	121.5 (5)	F1ⁱ—C1—H1	110.3
C9—C8—C11	118.1 (4)	C2—C1—H1	110.3
C7—C6—C5	121.2 (5)	N1—C2—C3	111.5 (5)
C7—C6—H6	119.4	N1—C2—C1	118.1 (4)
C5—C6—H6	119.4	C3—C2—C1	130.4 (4)
C9—C10—C5	120.8 (5)	C11—F3—F3ⁱ	28.3 (7)

C2—N1—O1—C4	0.0	C7—C8—C11—F3	112.9 (8)
N1—O1—C4—C3	0.0	C9—C8—C11—F3	−67.1 (8)
N1—O1—C4—C5	180.0	C7—C8—C11—F2	0.0
C3—C4—C5—C10	0.0	C9—C8—C11—F2	180.0
O1—C4—C5—C10	180.0	C5—C6—C7—C8	0.0
C3—C4—C5—C6	180.0	C9—C8—C7—C6	0.0
O1—C4—C5—C6	0.0	C11—C8—C7—C6	180.0
O1—C4—C3—C2	0.0	O1—N1—C2—C3	0.0
C5—C4—C3—C2	180.0	O1—N1—C2—C1	180.0
C10—C9—C8—C7	0.0	C4—C3—C2—N1	0.0
C10—C9—C8—C11	180.0	C4—C3—C2—C1	180.0
C10—C5—C6—C7	0.0	F1—C1—C2—N1	−122.0 (3)
C4—C5—C6—C7	180.0	F1ⁱ—C1—C2—N1	122.0 (3)
C8—C9—C10—C5	0.0	F1—C1—C2—C3	58.0 (3)
C6—C5—C10—C9	0.0	F1ⁱ—C1—C2—C3	−58.0 (3)
C4—C5—C10—C9	180.0	F2—C11—F3—F3ⁱ	−125.1 (18)
C7—C8—C11—F3ⁱ	−112.9 (8)	C8—C11—F3—F3ⁱ	124.8 (15)
C9—C8—C11—F3ⁱ	67.1 (8)

Symmetry code: (i) x, y, −z+1/2.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C3—H3···O1ⁱⁱ	0.93	2.69	3.581 (7)	160
C3—H3···N1ⁱⁱ	0.93	2.62	3.534 (6)	170
C1—H1···F2ⁱⁱⁱ	0.98	2.65	3.258 (6)	121

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

Funding information

Funding for this research was provided by: National Natural Science Foundation of China (award No. 21502076); Natural Science Foundation of Jiangxi Province (award No. 20161BAB213068); Hundred–Talent Program (Hefei); Outstanding Young Talent Program of Jiangxi Province (award No. 2017BCB23039).

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