organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2414-3146

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

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.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

Efavirenz is a potent HIV-1 reverse transcriptase inhibitor and an important anti­retroviral drug (Young et al., 1995[Young, S. D., Britcher, S. F., Tran, L. O., Payne, L. S., Lumma, W. C., Lyle, T. A., Huff, J. R., Anderson, P. S., Olsen, D. B. & Carroll, S. S. (1995). Antimicrob. Agents Chemother. 39, 2602-2605.]) for the treatment of AIDS (Vrouenraets, et al., 2007[Vrouenraets, S. M. E., Wit, F. W. N. M., van Tongeren, J. & Lange, J. M. A. (2007). Expert Opin. Pharmacother. 8, 851-871.]). One of the inter­mediates for the preparation of efavirenz (Nicolaou et al., 2009[Nicolaou, K. C., Krasovskiy, A., Majumder, U., Trépanier, V. É. & Chen, D. Y.-K. (2009). J. Am. Chem. Soc. 131, 3690-3699.]; Li & Ma, 2015[Li, S. & Ma, J.-A. (2015). Chem. Soc. Rev. 44, 7439-7448.]) 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[Allendörfer, N., Es-Sayed, M., Nieger, M. & Bräse, S. (2012). Tetrahedron Lett. 53, 388-391.]).

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[link]). In the crystal, N—H⋯F and N—H⋯O hydrogen bonds connect the mol­ecules into [010] chains (Fig. 1[link]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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]
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[link].

Table 2
Experimental details

Crystal data
Chemical formula C8H5ClF3NO
Mr 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)
V3) 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[Bruker. (2005). APEX2 , SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.304, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections 8037, 1934, 1374
Rint 0.091
(sin θ/λ)max−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
Δρmax, Δρmin (e Å−3) 0.37, −0.32
Computer programs: APEX2 and SAINT (Bruker, 2005[Bruker. (2005). APEX2 , SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXS97 and SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. A71, 3-8.]) and DIAMOND (Brandenburg, 1999[Brandenburg, K. (1999). DIAMOND. Crystal Impact GbR, Bonn, Germany.]).

Structural data


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
C8H5ClF3NOF(000) = 448
Mr = 223.58Dx = 1.759 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 12.7307 (16) ÅCell parameters from 2386 reflections
b = 9.0363 (12) Åθ = 2.8–27.3°
c = 7.4742 (9) ŵ = 0.46 mm1
β = 100.924 (4)°T = 120 K
V = 844.24 (19) Å3Block, yellow
Z = 40.20 × 0.10 × 0.02 mm
Data collection top
Bruker APEXII CCD
diffractometer
1374 reflections with I > 2σ(I)
φ and ω scansRint = 0.091
Absorption correction: multi-scan
(SADABS; Bruker, 2005)
θmax = 27.5°, θmin = 3.3°
Tmin = 0.304, Tmax = 0.746h = 1615
8037 measured reflectionsk = 1111
1934 independent reflectionsl = 99
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.043H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.113 w = 1/[σ2(Fo2) + (0.0262P)2 + 0.5023P]
where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max < 0.001
1934 reflectionsΔρmax = 0.37 e Å3
135 parametersΔρmin = 0.32 e Å3
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
xyzUiso*/Ueq
Cl10.52355 (5)0.71433 (7)0.54712 (9)0.0274 (2)
F20.19882 (12)0.37800 (16)0.46110 (19)0.0281 (4)
F30.26469 (12)0.36210 (16)0.7480 (2)0.0283 (4)
F10.09924 (13)0.31042 (16)0.6487 (2)0.0293 (4)
O10.05780 (14)0.5844 (2)0.6915 (2)0.0257 (4)
N10.0944 (2)0.8744 (3)0.6703 (3)0.0273 (5)
C20.1916 (2)0.8337 (3)0.6426 (3)0.0202 (5)
C70.1467 (2)0.5662 (3)0.6533 (3)0.0197 (5)
C60.3249 (2)0.6482 (3)0.5988 (3)0.0198 (5)
H60.3451800.5477560.5895680.024*
C10.2214 (2)0.6819 (3)0.6294 (3)0.0183 (5)
C40.3678 (2)0.9071 (3)0.5960 (3)0.0242 (6)
H40.4179900.9830130.5860130.029*
C80.1775 (2)0.4030 (3)0.6273 (3)0.0226 (6)
C50.3962 (2)0.7580 (3)0.5822 (3)0.0206 (5)
C30.2680 (2)0.9429 (3)0.6238 (3)0.0249 (6)
H30.2494301.0442900.6307770.030*
H1A0.051 (2)0.814 (3)0.689 (4)0.022 (8)*
H1B0.084 (3)0.961 (4)0.684 (4)0.045 (10)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0210 (4)0.0319 (4)0.0306 (4)0.0025 (3)0.0077 (3)0.0007 (3)
F20.0373 (10)0.0229 (8)0.0252 (8)0.0002 (7)0.0089 (7)0.0039 (6)
F30.0246 (8)0.0256 (8)0.0320 (8)0.0029 (6)0.0012 (7)0.0063 (7)
F10.0278 (9)0.0211 (8)0.0395 (9)0.0051 (6)0.0076 (7)0.0037 (7)
O10.0215 (10)0.0261 (10)0.0300 (10)0.0009 (8)0.0064 (8)0.0000 (8)
N10.0274 (14)0.0222 (14)0.0338 (13)0.0007 (11)0.0096 (11)0.0012 (11)
C20.0233 (14)0.0234 (12)0.0135 (11)0.0016 (11)0.0027 (10)0.0002 (10)
C70.0202 (13)0.0218 (13)0.0163 (11)0.0003 (10)0.0018 (10)0.0006 (10)
C60.0237 (14)0.0194 (13)0.0157 (11)0.0007 (10)0.0027 (10)0.0005 (10)
C10.0202 (13)0.0198 (12)0.0145 (11)0.0000 (10)0.0021 (10)0.0006 (9)
C40.0288 (15)0.0229 (13)0.0212 (13)0.0059 (11)0.0053 (11)0.0013 (10)
C80.0228 (14)0.0228 (13)0.0221 (12)0.0017 (11)0.0041 (11)0.0010 (10)
C50.0211 (13)0.0258 (13)0.0151 (12)0.0007 (11)0.0039 (10)0.0003 (10)
C30.0341 (16)0.0168 (13)0.0251 (13)0.0001 (11)0.0086 (12)0.0004 (10)
Geometric parameters (Å, º) top
Cl1—C51.736 (3)C7—C11.447 (3)
F2—C81.340 (3)C7—C81.548 (3)
F3—C81.343 (3)C6—C51.366 (4)
F1—C81.334 (3)C6—C11.413 (3)
O1—C71.229 (3)C6—H60.9500
N1—C21.344 (3)C4—C31.364 (4)
N1—H1A0.81 (3)C4—C51.404 (4)
N1—H1B0.81 (4)C4—H40.9500
C2—C31.411 (4)C3—H30.9500
C2—C11.432 (3)
C2—N1—H1A121 (2)C3—C4—C5119.9 (2)
C2—N1—H1B117 (2)C3—C4—H4120.0
H1A—N1—H1B121 (3)C5—C4—H4120.0
N1—C2—C3119.7 (2)F1—C8—F2107.0 (2)
N1—C2—C1122.4 (2)F1—C8—F3106.72 (19)
C3—C2—C1117.9 (2)F2—C8—F3106.9 (2)
O1—C7—C1126.0 (2)F1—C8—C7111.7 (2)
O1—C7—C8115.0 (2)F2—C8—C7112.2 (2)
C1—C7—C8119.0 (2)F3—C8—C7112.0 (2)
C5—C6—C1121.0 (2)C6—C5—C4120.3 (2)
C5—C6—H6119.5C6—C5—Cl1120.3 (2)
C1—C6—H6119.5C4—C5—Cl1119.3 (2)
C6—C1—C2119.0 (2)C4—C3—C2121.9 (2)
C6—C1—C7121.3 (2)C4—C3—H3119.1
C2—C1—C7119.7 (2)C2—C3—H3119.1
C5—C6—C1—C20.1 (3)O1—C7—C8—F2121.2 (2)
C5—C6—C1—C7177.9 (2)C1—C7—C8—F258.0 (3)
N1—C2—C1—C6179.5 (2)O1—C7—C8—F3118.6 (2)
C3—C2—C1—C60.1 (3)C1—C7—C8—F362.2 (3)
N1—C2—C1—C72.4 (4)C1—C6—C5—C40.2 (4)
C3—C2—C1—C7178.1 (2)C1—C6—C5—Cl1179.28 (18)
O1—C7—C1—C6175.3 (2)C3—C4—C5—C60.8 (4)
C8—C7—C1—C65.6 (3)C3—C4—C5—Cl1179.91 (19)
O1—C7—C1—C22.7 (4)C5—C4—C3—C21.1 (4)
C8—C7—C1—C2176.4 (2)N1—C2—C3—C4179.8 (2)
O1—C7—C8—F11.1 (3)C1—C2—C3—C40.7 (4)
C1—C7—C8—F1178.2 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···O10.81 (3)2.07 (3)2.672 (3)131 (3)
N1—H1A···F1i0.81 (3)2.45 (3)3.084 (3)136 (3)
N1—H1B···O1i0.81 (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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First citationBrandenburg, K. (1999). DIAMOND. Crystal Impact GbR, Bonn, Germany.  Google Scholar
First citationBruker. (2005). APEX2 , SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationLi, S. & Ma, J.-A. (2015). Chem. Soc. Rev. 44, 7439–7448.  CrossRef CAS PubMed Google Scholar
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First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
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