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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 68| Part 8| August 2012| Page o2534
https://doi.org/10.1107/S1600536812031650

N-[4-Chloro-3-(tri­fluoro­meth­yl)phen­yl]-2,2-di­methyl­propanamide

Yu Zhou,a Lili Ren,a Yongyu Lu,a Feng Zhanga and Guoguang Chena*

aSchool of Pharmaceutical Sciences, Nanjing University of Technology, Puzhu South Road No. 30 Nanjing, Nanjing 210009, People's Republic of China
*Correspondence e-mail: guoguangchen@163.com

(Received 21 June 2012; accepted 11 July 2012; online 25 July 2012)

In the title compound, C12H13ClF3NO, the C—C—N—C torsion angle between the benzene ring and the pivaloyl group is −33.9 (5)°. In the crystal, molecules are linked via N—H⋯O hydrogen bonds to form chains running parallel to the c axis. Weak van der Waals inter­actions are also observed.

Related literature

For background information on related compounds, see: Rosenblum et al. (1998[Rosenblum, S. B., Huynh, T., Afonso, A., Davis, H. R., Yumibe, N., Clader, J. W. & Burnett, D. A. (1998). J. Med. Chem. 41, 973-980.]); Wang et al. (2009[Wang, Y., Zhang, H., Huang, W., Kong, J., Zhou, J. & Zhang, B. (2009). Eur. J. Med. Chem. 44, 1638-1643.]). For a related crystal structure, see: Zhu et al. (2007[Zhu, N., Tran, P., Bell, N. & Stevens, C. L. K. (2007). J. Chem. Crystallogr. 37, 670-683.]).

[Scheme 1]

Experimental

Crystal data

  • C12H13ClF3NO

  • Mr = 279.68

  • Monoclinic, P 21 /c

  • a = 5.8850 (12) Å

  • b = 21.955 (4) Å

  • c = 10.307 (2) Å

  • β = 104.50 (3)°

  • V = 1289.3 (5) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.32 mm−1

  • T = 293 K

  • 0.30 × 0.20 × 0.10 mm
Data collection

  • Enraf–Nonius CAD-4 diffractometer

  • Absorption correction: ψ scan (North et al., 1968[North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351-359.]) Tmin = 0.910, Tmax = 0.969

  • 2599 measured reflections

  • 2364 independent reflections

  • 1477 reflections with I > 2σ(I)

  • Rint = 0.052

  • 3 standard reflections every 200 reflections intensity decay: 1%
Refinement

  • R[F2 > 2σ(F2)] = 0.061

  • wR(F2) = 0.192

  • S = 1.00

  • 2364 reflections

  • 163 parameters

  • H-atom parameters constrained

  • Δρmax = 0.38 e Å−3

  • Δρmin = −0.38 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N—H0A⋯O 0.86 2.24 3.041 (4) 155

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1989[Enraf-Nonius (1989). CAD-4 Software. Enraf-Nonius, Delft, The Netherlands.]); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995[Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536812031650/pk2427sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536812031650/pk2427Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S1600536812031650/pk2427Isup3.cml

checkCIF report


Comment top

Ezetimibe is a biologically active molecule, and research has shown it to have the useful property of inhibiting the absorption of cholesterol in the intestine (Rosenblum et al., 1998). As part of our studies into the synthesis of Ezetimibe, the title compound, 4-chloro-3-(trifluoromethyl)-N-pivaloylaniline (I), which is a derivate formed as an intermediate, was synthesized (Wang et al., 2009). In the crystal structure, N—H···O hydrogen bonding interactions (Table 1) link the molecules (Fig. 2) into chains running parallel to the c axis.

Related literature top

For background information on related compounds, see: Rosenblum et al. (1998); Wang et al. (2009). For a related crystal structure, see: Zhu et al. (2007).

Experimental top

4-chloro-3-(trifluoromethyl)aniline (C7H5ClF3N, 23.40 g, 0.12 mol) in CH2Cl2 (40 ml) was added to 4-dimethylaminopyridine (C7H10N2, 1.2 g, 0.01 mol), and Et3N (42.3 ml, 0.31 mol) and the reaction was cooled to 273 K. A solution of pivaloyl chloride (C5H9ClO, 14.4 g, 0.12 mol) in CH2Cl2 (150 ml) was added dropwise over 1 h and the mixture was then heated to reflux. After 12 h, H2O and H2SO4 (2 N, 75 ml) were added, the layers were separated, and the organic layer was washed sequentially with NaOH (10%), NaCl (satd) and water. The organic layer was dried over MgSO4 and concentrated to obtain the product as a pure yellow solid (Wang et al., 2009). Crystals suitable for X-ray diffraction were obtained by slow evaporation of an ethanolic solution.

Refinement top

All H atoms were positioned geometrically and refined using a riding model, with C—H = 0.93 and 0.97 Å, for aryl and methylene H-atoms respectively, and 0.86 Å for N—H. The Uiso(H) were included at 1.5Ueq(C) for the methyl groups and 1.2Ueq for all other hydrogen atoms.

Structure description top

Ezetimibe is a biologically active molecule, and research has shown it to have the useful property of inhibiting the absorption of cholesterol in the intestine (Rosenblum et al., 1998). As part of our studies into the synthesis of Ezetimibe, the title compound, 4-chloro-3-(trifluoromethyl)-N-pivaloylaniline (I), which is a derivate formed as an intermediate, was synthesized (Wang et al., 2009). In the crystal structure, N—H···O hydrogen bonding interactions (Table 1) link the molecules (Fig. 2) into chains running parallel to the c axis.

For background information on related compounds, see: Rosenblum et al. (1998); Wang et al. (2009). For a related crystal structure, see: Zhu et al. (2007).

Computing details top

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1989); cell refinement: CAD-4 EXPRESS (Enraf–Nonius, 1989); data reduction: XCAD4 (Harms & Wocadlo, 1995); 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: PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I). Displacement ellipsoids are drawn at the 50% probability level. H atoms are shown as small spheres of arbitrary radius.
[Figure 2] Fig. 2. A packing plot of (I), viewed down the a-axis of the unit cell.
N-[4-Chloro-3-(trifluoromethyl)phenyl]-2,2-dimethylpropanamide top
Crystal data top
C12H13ClF3NOF(000) = 576
Mr = 279.68Dx = 1.441 Mg m−3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 25 reflections
a = 5.8850 (12) Åθ = 10–13°
b = 21.955 (4) ŵ = 0.32 mm−1
c = 10.307 (2) ÅT = 293 K
β = 104.50 (3)°Block, colorless
V = 1289.3 (5) Å30.30 × 0.20 × 0.10 mm
Z = 4
Data collection top
Enraf–Nonius CAD-4
diffractometer		1477 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.052
Graphite monochromatorθmax = 25.4°, θmin = 1.9°
ω/2θ scansh = 0→7
Absorption correction: ψ scan
(North et al., 1968)		k = 0→26
Tmin = 0.910, Tmax = 0.969l = −12→12
2599 measured reflections3 standard reflections every 200 reflections
2364 independent reflections intensity decay: 1%
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.061Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.192H-atom parameters constrained
S = 1.00 w = 1/[σ2(Fo2) + (0.1P)2 + 0.6P]
where P = (Fo2 + 2Fc2)/3
2364 reflections(Δ/σ)max < 0.001
163 parametersΔρmax = 0.38 e Å−3
0 restraintsΔρmin = −0.38 e Å−3
Crystal data top
C12H13ClF3NOV = 1289.3 (5) Å3
Mr = 279.68Z = 4
Monoclinic, P21/cMo Kα radiation
a = 5.8850 (12) ŵ = 0.32 mm−1
b = 21.955 (4) ÅT = 293 K
c = 10.307 (2) Å0.30 × 0.20 × 0.10 mm
β = 104.50 (3)°
Data collection top
Enraf–Nonius CAD-4
diffractometer		1477 reflections with I > 2σ(I)
Absorption correction: ψ scan
(North et al., 1968)		Rint = 0.052
Tmin = 0.910, Tmax = 0.9693 standard reflections every 200 reflections
2599 measured reflections intensity decay: 1%
2364 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0610 restraints
wR(F2) = 0.192H-atom parameters constrained
S = 1.00Δρmax = 0.38 e Å−3
2364 reflectionsΔρmin = −0.38 e Å−3
163 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
xyzUiso*/Ueq
Cl0.8303 (2)0.49337 (6)0.12942 (14)0.0873 (5)
O0.1944 (5)0.25926 (12)0.2729 (2)0.0647 (8)
N0.2134 (5)0.27644 (13)0.0605 (3)0.0494 (7)
H0A0.16320.2645−0.02110.059*
F10.7046 (6)0.47123 (13)0.3967 (3)0.1021 (10)
C10.4957 (8)0.46500 (17)0.3095 (4)0.0639 (11)
F20.3471 (6)0.44832 (12)0.3808 (3)0.1073 (11)
C20.5006 (6)0.42126 (16)0.1992 (3)0.0483 (9)
F30.4298 (5)0.52091 (10)0.2663 (3)0.0797 (8)
C30.3567 (6)0.37039 (15)0.1826 (3)0.0474 (9)
H3A0.25760.36430.23890.057*
C40.3598 (6)0.32856 (15)0.0826 (3)0.0444 (8)
C50.5033 (7)0.33915 (17)−0.0024 (3)0.0540 (9)
H5A0.50240.3120−0.07180.065*
C60.6482 (7)0.38958 (19)0.0147 (4)0.0623 (11)
H6A0.74680.3957−0.04200.075*
C70.6471 (6)0.43065 (17)0.1149 (4)0.0542 (9)
C80.1439 (6)0.24321 (15)0.1556 (3)0.0442 (8)
C90.0085 (6)0.18476 (15)0.1083 (3)0.0463 (8)
C100.1853 (9)0.1369 (2)0.0953 (7)0.107 (2)
H10A0.29840.13210.17980.161*
H10B0.26380.14930.02840.161*
H10C0.10630.09890.06940.161*
C11−0.1150 (11)0.1652 (3)0.2130 (5)0.110 (2)
H11A−0.00220.16050.29760.165*
H11B−0.19310.12700.18720.165*
H11C−0.22830.19550.22100.165*
C12−0.1714 (9)0.1921 (2)−0.0249 (5)0.0984 (18)
H12A−0.09380.2042−0.09230.148*
H12B−0.28380.2226−0.01660.148*
H12C−0.25040.1540−0.05000.148*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl0.0823 (8)0.0705 (8)0.1155 (10)−0.0271 (6)0.0370 (7)−0.0055 (7)
O0.107 (2)0.0532 (16)0.0354 (13)−0.0215 (15)0.0202 (13)−0.0028 (11)
N0.074 (2)0.0427 (16)0.0316 (13)−0.0087 (14)0.0141 (13)−0.0051 (12)
F10.136 (3)0.078 (2)0.0703 (16)0.0004 (17)−0.0147 (17)−0.0234 (14)
C10.095 (3)0.043 (2)0.055 (2)−0.011 (2)0.021 (2)−0.0062 (18)
F20.196 (3)0.0666 (17)0.0886 (18)−0.0380 (19)0.090 (2)−0.0322 (14)
C20.062 (2)0.0390 (19)0.0420 (18)0.0023 (16)0.0098 (16)0.0041 (15)
F30.105 (2)0.0383 (13)0.0994 (18)0.0013 (12)0.0319 (15)−0.0087 (12)
C30.068 (2)0.0380 (19)0.0395 (17)−0.0036 (16)0.0199 (16)0.0009 (14)
C40.060 (2)0.0382 (18)0.0355 (17)0.0003 (15)0.0126 (15)0.0012 (14)
C50.074 (2)0.046 (2)0.0458 (19)0.0035 (18)0.0225 (18)−0.0040 (16)
C60.070 (3)0.060 (2)0.067 (2)−0.004 (2)0.035 (2)0.002 (2)
C70.058 (2)0.043 (2)0.061 (2)−0.0044 (17)0.0159 (18)0.0035 (18)
C80.060 (2)0.0380 (18)0.0351 (18)0.0023 (15)0.0136 (15)0.0013 (14)
C90.057 (2)0.0368 (18)0.0441 (18)−0.0022 (15)0.0118 (15)0.0005 (15)
C100.082 (3)0.048 (3)0.186 (6)0.002 (2)0.021 (4)−0.032 (3)
C110.144 (5)0.113 (4)0.088 (3)−0.075 (4)0.056 (3)−0.027 (3)
C120.106 (4)0.073 (3)0.090 (3)−0.028 (3)−0.026 (3)0.009 (3)
Geometric parameters (Å, º) top
Cl—C71.732 (4)C6—C71.372 (5)
O—C81.222 (4)C6—H6A0.9300
N—C81.364 (4)C8—C91.525 (5)
N—C41.416 (4)C9—C111.506 (6)
N—H0A0.8600C9—C101.508 (6)
F1—C11.336 (5)C9—C121.518 (5)
C1—F21.326 (5)C10—H10A0.9600
C1—F31.330 (4)C10—H10B0.9600
C1—C21.494 (5)C10—H10C0.9600
C2—C71.385 (5)C11—H11A0.9600
C2—C31.386 (5)C11—H11B0.9600
C3—C41.384 (4)C11—H11C0.9600
C3—H3A0.9300C12—H12A0.9600
C4—C51.379 (5)C12—H12B0.9600
C5—C61.382 (5)C12—H12C0.9600
C5—H5A0.9300
C8—N—C4126.6 (3)O—C8—N120.9 (3)
C8—N—H0A116.7O—C8—C9122.5 (3)
C4—N—H0A116.7N—C8—C9116.6 (3)
F2—C1—F3105.3 (4)C11—C9—C10109.4 (4)
F2—C1—F1106.2 (3)C11—C9—C12109.0 (4)
F3—C1—F1105.8 (3)C10—C9—C12109.5 (4)
F2—C1—C2112.6 (3)C11—C9—C8108.6 (3)
F3—C1—C2113.4 (3)C10—C9—C8107.3 (3)
F1—C1—C2112.8 (4)C12—C9—C8113.0 (3)
C7—C2—C3119.9 (3)C9—C10—H10A109.5
C7—C2—C1121.1 (3)C9—C10—H10B109.5
C3—C2—C1119.0 (3)H10A—C10—H10B109.5
C4—C3—C2120.4 (3)C9—C10—H10C109.5
C4—C3—H3A119.8H10A—C10—H10C109.5
C2—C3—H3A119.8H10B—C10—H10C109.5
C5—C4—C3119.0 (3)C9—C11—H11A109.5
C5—C4—N118.6 (3)C9—C11—H11B109.5
C3—C4—N122.3 (3)H11A—C11—H11B109.5
C4—C5—C6120.7 (3)C9—C11—H11C109.5
C4—C5—H5A119.6H11A—C11—H11C109.5
C6—C5—H5A119.6H11B—C11—H11C109.5
C7—C6—C5120.2 (3)C9—C12—H12A109.5
C7—C6—H6A119.9C9—C12—H12B109.5
C5—C6—H6A119.9H12A—C12—H12B109.5
C6—C7—C2119.7 (3)C9—C12—H12C109.5
C6—C7—Cl117.8 (3)H12A—C12—H12C109.5
C2—C7—Cl122.4 (3)H12B—C12—H12C109.5
F2—C1—C2—C7−179.3 (4)C5—C6—C7—C20.2 (6)
F3—C1—C2—C761.3 (5)C5—C6—C7—Cl−179.2 (3)
F1—C1—C2—C7−59.1 (5)C3—C2—C7—C60.3 (5)
F2—C1—C2—C30.2 (5)C1—C2—C7—C6179.8 (4)
F3—C1—C2—C3−119.2 (4)C3—C2—C7—Cl179.7 (3)
F1—C1—C2—C3120.5 (4)C1—C2—C7—Cl−0.8 (5)
C7—C2—C3—C40.5 (5)C4—N—C8—O4.8 (5)
C1—C2—C3—C4−179.0 (3)C4—N—C8—C9−173.3 (3)
C2—C3—C4—C5−1.8 (5)O—C8—C9—C1119.1 (5)
C2—C3—C4—N−179.0 (3)N—C8—C9—C11−162.8 (4)
C8—N—C4—C5148.6 (3)O—C8—C9—C10−99.1 (5)
C8—N—C4—C3−34.1 (5)N—C8—C9—C1079.0 (4)
C3—C4—C5—C62.3 (5)O—C8—C9—C12140.2 (4)
N—C4—C5—C6179.6 (3)N—C8—C9—C12−41.7 (5)
C4—C5—C6—C7−1.5 (6)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N—H0A···O0.862.243.041 (4)155

Experimental details

Crystal data
Chemical formulaC12H13ClF3NO
Mr279.68
Crystal system, space groupMonoclinic, P21/c
Temperature (K)293
a, b, c (Å)5.8850 (12), 21.955 (4), 10.307 (2)
β (°) 104.50 (3)
V (Å3)1289.3 (5)
Z4
Radiation typeMo Kα
µ (mm−1)0.32
Crystal size (mm)0.30 × 0.20 × 0.10
Data collection
DiffractometerEnraf–Nonius CAD-4
Absorption correctionψ scan
(North et al., 1968)
Tmin, Tmax0.910, 0.969
No. of measured, independent and
observed [I > 2σ(I)] reflections		2599, 2364, 1477
Rint0.052
(sin θ/λ)max (Å−1)0.603
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.061, 0.192, 1.00
No. of reflections2364
No. of parameters163
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å−3)0.38, −0.38

Computer programs: CAD-4 EXPRESS (Enraf–Nonius, 1989), XCAD4 (Harms & Wocadlo, 1995), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008), PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N—H0A···O0.862.243.041 (4)155
 

Acknowledgements

This research work was financially supported by the College of Life Science and Pharmaceutical Engineering, Nanjing University of Technology, `973' project (2011CB710803), and the Key Basic Research Program of China, `973' project (2012CB721104).

References

First citationEnraf–Nonius (1989). CAD-4 Software. Enraf–Nonius, Delft, The Netherlands.  Google Scholar
 First citationHarms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.  Google Scholar
 First citationNorth, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.  CrossRef IUCr Journals Web of Science Google Scholar
 First citationRosenblum, S. B., Huynh, T., Afonso, A., Davis, H. R., Yumibe, N., Clader, J. W. & Burnett, D. A. (1998). J. Med. Chem. 41, 973–980.  Web of Science CrossRef CAS PubMed Google Scholar
 First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationWang, Y., Zhang, H., Huang, W., Kong, J., Zhou, J. & Zhang, B. (2009). Eur. J. Med. Chem. 44, 1638–1643.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationZhu, N., Tran, P., Bell, N. & Stevens, C. L. K. (2007). J. Chem. Crystallogr. 37, 670–683.  Web of Science CSD CrossRef Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 68| Part 8| August 2012| Page o2534
https://doi.org/10.1107/S1600536812031650
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