1-(2-Amino-5-chloro­phen­yl)-2,2,2-tri­fluoro­ethan-1-one

Gao, J.; Pan, Y.; Li, Y.; Li, Y.

doi:10.1107/S2414314619010253

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 4| Part 7| July 2019| x191025

https://doi.org/10.1107/S2414314619010253

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1-(2-Amino-5-chlorophenyl)-2,2,2-trifluoroethan-1-one

Jie Gao,^a Yangdan Pan,^b Yahong Li ^b ^* and Yafei Li ^b

^aTianqi Lithium (Jiangsu) Co., Ltd., Zhangjiagang, Jiangsu 215634, People's Republic of China, and ^bCollege of Chemistry, Chemical Engineering and Materials Science, Soochow, University, Suzhou 215123, People's Republic of China
^*Correspondence e-mail: liyahong@suda.edu.cn

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 1 July 2019; accepted 18 July 2019; online 23 July 2019)

In the title compound, C₈H₅ClF₃NO, the F—C—C=O grouping shows a syn conformation [torsion angle = 1.1 (3)°] and an intramolecular N—H⋯O hydrogen bond generates an S(6) ring. In the crystal, N—H⋯F and N—H⋯O hydrogen bonds link the molecules into [010] chains.

Keywords: crystal structure; efavirenz intermediate; hydrogen bonding.

CCDC reference: 1810647

Structure description

Efavirenz is a potent HIV-1 reverse transcriptase inhibitor and an important antiretroviral drug (Young et al., 1995 ) for the treatment of AIDS (Vrouenraets, et al., 2007 ). One of the intermediates for the preparation of efavirenz (Nicolaou et al., 2009 ; Li & Ma, 2015 ) is the title compound (1) and we now describe its crystal structure. The title compound was synthesized by employing 2-amino-5-chlorobenzoic acid as starting material (Allendörfer et al., 2012 ).

The F1—C8—C7=O1 grouping in (1) shows a syn conformation [torsion angle = 1.1 (3)°]. The average C—F bond distance is 1.338 Å and the C—Cl, C=O, and C—N bond lengths are 1.736 (3), 1.229 (3) and 1.344 (3) Å, respectively, which are all within their expected ranges. An intramolecular N—H⋯O hydrogen bond generates a S(6) ring; the same H atom also participates in a weak intermolecular N—H⋯F link (Table 1). In the crystal, N—H⋯F and N—H⋯O hydrogen bonds connect the molecules into [010] chains (Fig. 1).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯O1	0.81 (3)	2.07 (3)	2.672 (3)	131 (3)
N1—H1A⋯F1ⁱ	0.81 (3)	2.45 (3)	3.084 (3)	136 (3)
N1—H1B⋯O1ⁱ	0.81 (4)	2.45 (3)	3.030 (3)	130 (3)
Symmetry code: (i) $[-x, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

Figure 1
The molecular structure and hydrogen-bonding interactions of the title compound. Symmetry codes: (i) −x, $[{1\over 2}]$ + y, $[{3\over 2}]$ − z; (ii) −x, − $[{1\over 2}]$ + y, $[{3\over 2}]$ − z.

Synthesis and crystallization

To a solution of 2-amino-5-chlorobenzoic acid (0.86 g, 5.0 mmol) in toluene (25 ml), was added trimethylamine (1.52 g, 15 mmol) and acetic anhydride (1.53 g, 15 mmol). The reaction mixture was stirred at 110°C for 15 h. After the starting material had been consumed completely, the solvent was removed under reduced pressure. The resulting mixture was dissolved in water and extracted by ethyl acetate. The organic layer was dried over Na₂SO₄ and the solvent removed under reduced pressure. The 6-chloro-2-methyl-4H-benzo[d][1,3]oxazin-4-one product was used in the next step without further purification.

Under an argon atmosphere, 6-chloro-2-methyl-4H-benzo[d][1,3]oxazin-4-one (0.60 g, 3.0 mmol) was dissolved in dry DMSO. To the solution, (trifluoromethyl)trimethylsilane (TMS-CF₃; 0.87 g, 6.0 mmol) and tetra-n-butylammonium fluoride (TBAF; 0.37 ml) were added and the mixture was stirred at room temperature for 15 h. Then the reaction mixture was quenched with HCl (2 M) and further stirred for 1 h. The mixture was extracted with CH₂Cl₂. The organic layer was washed with brine and dried over Na₂SO₄. The solvent was removed under reduced pressure. The title compound was isolated by column chromatography and recrystallized from a solvent mixture of CH₃OH and CH₂Cl₂ (v:v = 1:1).

Refinement

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

Table 2
Experimental details

Crystal data
Chemical formula	C₈H₅ClF₃NO
M_r	223.58
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	120
a, b, c (Å)	12.7307 (16), 9.0363 (12), 7.4742 (9)
β (°)	100.924 (4)
V (Å³)	844.24 (19)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.46
Crystal size (mm)	0.20 × 0.10 × 0.02

Data collection
Diffractometer	Bruker APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2005 )
T_min, T_max	0.304, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections	8037, 1934, 1374
R_int	0.091
(sin θ/λ)_max (Å⁻¹)	0.650

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.043, 0.113, 1.06
No. of reflections	1934
No. of parameters	135
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.37, −0.32
Computer programs: APEX2 and SAINT (Bruker, 2005), SHELXS97 and SHELXTL (Sheldrick, 2008 ), SHELXL (Sheldrick, 2015 ) and DIAMOND (Brandenburg, 1999 ).

Structural data

CCDC reference: 1810647

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314619010253/hb4303sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314619010253/hb4303Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314619010253/hb4303Isup3.cml

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT (Bruker, 2005); data reduction: SAINT (Bruker, 2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL (Sheldrick, 2015); molecular graphics: SHELXTL (Sheldrick, 2008) and DIAMOND (Brandenburg, 1999); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

1-(2-Amino-5-chlorophenyl)-2,2,2-trifluoroethan-1-one top

Crystal data top

C₈H₅ClF₃NO	F(000) = 448
M_r = 223.58	D_x = 1.759 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 12.7307 (16) Å	Cell parameters from 2386 reflections
b = 9.0363 (12) Å	θ = 2.8–27.3°
c = 7.4742 (9) Å	µ = 0.46 mm⁻¹
β = 100.924 (4)°	T = 120 K
V = 844.24 (19) Å³	Block, yellow
Z = 4	0.20 × 0.10 × 0.02 mm

Data collection top

Bruker APEXII CCD diffractometer	1374 reflections with I > 2σ(I)
φ and ω scans	R_int = 0.091
Absorption correction: multi-scan (SADABS; Bruker, 2005)	θ_max = 27.5°, θ_min = 3.3°
T_min = 0.304, T_max = 0.746	h = −16→15
8037 measured reflections	k = −11→11
1934 independent reflections	l = −9→9

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.043	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.113	w = 1/[σ²(F_o²) + (0.0262P)² + 0.5023P] where P = (F_o² + 2F_c²)/3
S = 1.06	(Δ/σ)_max < 0.001
1934 reflections	Δρ_max = 0.37 e Å⁻³
135 parameters	Δρ_min = −0.32 e Å⁻³
0 restraints

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. All H atoms were positioned geometrically and refined using a riding model.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
Cl1	0.52355 (5)	0.71433 (7)	0.54712 (9)	0.0274 (2)
F2	0.19882 (12)	0.37800 (16)	0.46110 (19)	0.0281 (4)
F3	0.26469 (12)	0.36210 (16)	0.7480 (2)	0.0283 (4)
F1	0.09924 (13)	0.31042 (16)	0.6487 (2)	0.0293 (4)
O1	0.05780 (14)	0.5844 (2)	0.6915 (2)	0.0257 (4)
N1	0.0944 (2)	0.8744 (3)	0.6703 (3)	0.0273 (5)
C2	0.1916 (2)	0.8337 (3)	0.6426 (3)	0.0202 (5)
C7	0.1467 (2)	0.5662 (3)	0.6533 (3)	0.0197 (5)
C6	0.3249 (2)	0.6482 (3)	0.5988 (3)	0.0198 (5)
H6	0.345180	0.547756	0.589568	0.024*
C1	0.2214 (2)	0.6819 (3)	0.6294 (3)	0.0183 (5)
C4	0.3678 (2)	0.9071 (3)	0.5960 (3)	0.0242 (6)
H4	0.417990	0.983013	0.586013	0.029*
C8	0.1775 (2)	0.4030 (3)	0.6273 (3)	0.0226 (6)
C5	0.3962 (2)	0.7580 (3)	0.5822 (3)	0.0206 (5)
C3	0.2680 (2)	0.9429 (3)	0.6238 (3)	0.0249 (6)
H3	0.249430	1.044290	0.630777	0.030*
H1A	0.051 (2)	0.814 (3)	0.689 (4)	0.022 (8)*
H1B	0.084 (3)	0.961 (4)	0.684 (4)	0.045 (10)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0210 (4)	0.0319 (4)	0.0306 (4)	−0.0025 (3)	0.0077 (3)	−0.0007 (3)
F2	0.0373 (10)	0.0229 (8)	0.0252 (8)	−0.0002 (7)	0.0089 (7)	−0.0039 (6)
F3	0.0246 (8)	0.0256 (8)	0.0320 (8)	0.0029 (6)	−0.0012 (7)	0.0063 (7)
F1	0.0278 (9)	0.0211 (8)	0.0395 (9)	−0.0051 (6)	0.0076 (7)	0.0037 (7)
O1	0.0215 (10)	0.0261 (10)	0.0300 (10)	−0.0009 (8)	0.0064 (8)	0.0000 (8)
N1	0.0274 (14)	0.0222 (14)	0.0338 (13)	0.0007 (11)	0.0096 (11)	−0.0012 (11)
C2	0.0233 (14)	0.0234 (12)	0.0135 (11)	0.0016 (11)	0.0027 (10)	0.0002 (10)
C7	0.0202 (13)	0.0218 (13)	0.0163 (11)	0.0003 (10)	0.0018 (10)	0.0006 (10)
C6	0.0237 (14)	0.0194 (13)	0.0157 (11)	0.0007 (10)	0.0027 (10)	0.0005 (10)
C1	0.0202 (13)	0.0198 (12)	0.0145 (11)	0.0000 (10)	0.0021 (10)	−0.0006 (9)
C4	0.0288 (15)	0.0229 (13)	0.0212 (13)	−0.0059 (11)	0.0053 (11)	0.0013 (10)
C8	0.0228 (14)	0.0228 (13)	0.0221 (12)	−0.0017 (11)	0.0041 (11)	0.0010 (10)
C5	0.0211 (13)	0.0258 (13)	0.0151 (12)	−0.0007 (11)	0.0039 (10)	−0.0003 (10)
C3	0.0341 (16)	0.0168 (13)	0.0251 (13)	0.0001 (11)	0.0086 (12)	−0.0004 (10)

Geometric parameters (Å, º) top

Cl1—C5	1.736 (3)	C7—C1	1.447 (3)
F2—C8	1.340 (3)	C7—C8	1.548 (3)
F3—C8	1.343 (3)	C6—C5	1.366 (4)
F1—C8	1.334 (3)	C6—C1	1.413 (3)
O1—C7	1.229 (3)	C6—H6	0.9500
N1—C2	1.344 (3)	C4—C3	1.364 (4)
N1—H1A	0.81 (3)	C4—C5	1.404 (4)
N1—H1B	0.81 (4)	C4—H4	0.9500
C2—C3	1.411 (4)	C3—H3	0.9500
C2—C1	1.432 (3)

C2—N1—H1A	121 (2)	C3—C4—C5	119.9 (2)
C2—N1—H1B	117 (2)	C3—C4—H4	120.0
H1A—N1—H1B	121 (3)	C5—C4—H4	120.0
N1—C2—C3	119.7 (2)	F1—C8—F2	107.0 (2)
N1—C2—C1	122.4 (2)	F1—C8—F3	106.72 (19)
C3—C2—C1	117.9 (2)	F2—C8—F3	106.9 (2)
O1—C7—C1	126.0 (2)	F1—C8—C7	111.7 (2)
O1—C7—C8	115.0 (2)	F2—C8—C7	112.2 (2)
C1—C7—C8	119.0 (2)	F3—C8—C7	112.0 (2)
C5—C6—C1	121.0 (2)	C6—C5—C4	120.3 (2)
C5—C6—H6	119.5	C6—C5—Cl1	120.3 (2)
C1—C6—H6	119.5	C4—C5—Cl1	119.3 (2)
C6—C1—C2	119.0 (2)	C4—C3—C2	121.9 (2)
C6—C1—C7	121.3 (2)	C4—C3—H3	119.1
C2—C1—C7	119.7 (2)	C2—C3—H3	119.1

C5—C6—C1—C2	0.1 (3)	O1—C7—C8—F2	121.2 (2)
C5—C6—C1—C7	−177.9 (2)	C1—C7—C8—F2	−58.0 (3)
N1—C2—C1—C6	179.5 (2)	O1—C7—C8—F3	−118.6 (2)
C3—C2—C1—C6	0.1 (3)	C1—C7—C8—F3	62.2 (3)
N1—C2—C1—C7	−2.4 (4)	C1—C6—C5—C4	0.2 (4)
C3—C2—C1—C7	178.1 (2)	C1—C6—C5—Cl1	179.28 (18)
O1—C7—C1—C6	175.3 (2)	C3—C4—C5—C6	−0.8 (4)
C8—C7—C1—C6	−5.6 (3)	C3—C4—C5—Cl1	−179.91 (19)
O1—C7—C1—C2	−2.7 (4)	C5—C4—C3—C2	1.1 (4)
C8—C7—C1—C2	176.4 (2)	N1—C2—C3—C4	179.8 (2)
O1—C7—C8—F1	1.1 (3)	C1—C2—C3—C4	−0.7 (4)
C1—C7—C8—F1	−178.2 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O1	0.81 (3)	2.07 (3)	2.672 (3)	131 (3)
N1—H1A···F1ⁱ	0.81 (3)	2.45 (3)	3.084 (3)	136 (3)
N1—H1B···O1ⁱ	0.81 (4)	2.45 (3)	3.030 (3)	130 (3)

Symmetry code: (i) −x, y+1/2, −z+3/2.

Acknowledgements

The authors acknowledge financial support from Tianqi Lithium (Jiangsu) Co. Ltd (p110900617).

Funding information

Funding for this research was provided by: Science Bureau of Zhangjiaguang (grant No. N710912718v).

References

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