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

Abstract

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 ▶); Wang et al. (2009 ▶). For a related crystal structure, see: Zhu et al. (2007 ▶).

Experimental  

Crystal data  

• C₁₂H₁₃ClF₃NO

• M _r = 279.68

• Monoclinic,

• a = 5.8850 (12) Å

• b = 21.955 (4) Å

• c = 10.307 (2) Å

• β = 104.50 (3)°

• V = 1289.3 (5) ų

• 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 ▶) T _min = 0.910, T _max = 0.969

• 2599 measured reflections

• 2364 independent reflections

• 1477 reflections with I > 2σ(I)

• R _int = 0.052

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

Refinement  

• R[F ² > 2σ(F ²)] = 0.061

• wR(F ²) = 0.192

• S = 1.00

• 2364 reflections

• 163 parameters

• H-atom parameters constrained

• Δρ_max = 0.38 e Å⁻³

• Δρ_min = −0.38 e Å⁻³

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1989 ▶); cell refinement: CAD-4 EXPRESS; 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 ▶).

Supplementary Material

Supplementary material file. DOI: 10.1107/S1600536812031650/pk2427Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

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

supplementary crystallographic information

Comment

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.

Experimental

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

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 U_iso(H) were included at 1.5U_eq(C) for the methyl groups and 1.2U_eq for all other hydrogen atoms.

Figures

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.

Fig. 2.

A packing plot of (I), viewed down the a-axis of the unit cell.

Crystal data

C12H13ClF3NO	F(000) = 576
Mr = 279.68	Dx = 1.441 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 25 reflections
a = 5.8850 (12) Å	θ = 10–13°
b = 21.955 (4) Å	µ = 0.32 mm−1
c = 10.307 (2) Å	T = 293 K
β = 104.50 (3)°	Block, colorless
V = 1289.3 (5) Å3	0.30 × 0.20 × 0.10 mm
Z = 4

Data collection

Enraf–Nonius CAD-4 diffractometer	1477 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.052
Graphite monochromator	θmax = 25.4°, θmin = 1.9°
ω/2θ scans	h = 0→7
Absorption correction: ψ scan (North et al., 1968)	k = 0→26
Tmin = 0.910, Tmax = 0.969	l = −12→12
2599 measured reflections	3 standard reflections every 200 reflections
2364 independent reflections	intensity decay: 1%

Refinement

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)] = 0.061	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.192	H-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 parameters	Δρmax = 0.38 e Å−3
0 restraints	Δρmin = −0.38 e Å−3

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
Cl	0.8303 (2)	0.49337 (6)	0.12942 (14)	0.0873 (5)
O	0.1944 (5)	0.25926 (12)	0.2729 (2)	0.0647 (8)
N	0.2134 (5)	0.27644 (13)	0.0605 (3)	0.0494 (7)
H0A	0.1632	0.2645	−0.0211	0.059*
F1	0.7046 (6)	0.47123 (13)	0.3967 (3)	0.1021 (10)
C1	0.4957 (8)	0.46500 (17)	0.3095 (4)	0.0639 (11)
F2	0.3471 (6)	0.44832 (12)	0.3808 (3)	0.1073 (11)
C2	0.5006 (6)	0.42126 (16)	0.1992 (3)	0.0483 (9)
F3	0.4298 (5)	0.52091 (10)	0.2663 (3)	0.0797 (8)
C3	0.3567 (6)	0.37039 (15)	0.1826 (3)	0.0474 (9)
H3A	0.2576	0.3643	0.2389	0.057*
C4	0.3598 (6)	0.32856 (15)	0.0826 (3)	0.0444 (8)
C5	0.5033 (7)	0.33915 (17)	−0.0024 (3)	0.0540 (9)
H5A	0.5024	0.3120	−0.0718	0.065*
C6	0.6482 (7)	0.38958 (19)	0.0147 (4)	0.0623 (11)
H6A	0.7468	0.3957	−0.0420	0.075*
C7	0.6471 (6)	0.43065 (17)	0.1149 (4)	0.0542 (9)
C8	0.1439 (6)	0.24321 (15)	0.1556 (3)	0.0442 (8)
C9	0.0085 (6)	0.18476 (15)	0.1083 (3)	0.0463 (8)
C10	0.1853 (9)	0.1369 (2)	0.0953 (7)	0.107 (2)
H10A	0.2984	0.1321	0.1798	0.161*
H10B	0.2638	0.1493	0.0284	0.161*
H10C	0.1063	0.0989	0.0694	0.161*
C11	−0.1150 (11)	0.1652 (3)	0.2130 (5)	0.110 (2)
H11A	−0.0022	0.1605	0.2976	0.165*
H11B	−0.1931	0.1270	0.1872	0.165*
H11C	−0.2283	0.1955	0.2210	0.165*
C12	−0.1714 (9)	0.1921 (2)	−0.0249 (5)	0.0984 (18)
H12A	−0.0938	0.2042	−0.0923	0.148*
H12B	−0.2838	0.2226	−0.0166	0.148*
H12C	−0.2504	0.1540	−0.0500	0.148*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
Cl	0.0823 (8)	0.0705 (8)	0.1155 (10)	−0.0271 (6)	0.0370 (7)	−0.0055 (7)
O	0.107 (2)	0.0532 (16)	0.0354 (13)	−0.0215 (15)	0.0202 (13)	−0.0028 (11)
N	0.074 (2)	0.0427 (16)	0.0316 (13)	−0.0087 (14)	0.0141 (13)	−0.0051 (12)
F1	0.136 (3)	0.078 (2)	0.0703 (16)	0.0004 (17)	−0.0147 (17)	−0.0234 (14)
C1	0.095 (3)	0.043 (2)	0.055 (2)	−0.011 (2)	0.021 (2)	−0.0062 (18)
F2	0.196 (3)	0.0666 (17)	0.0886 (18)	−0.0380 (19)	0.090 (2)	−0.0322 (14)
C2	0.062 (2)	0.0390 (19)	0.0420 (18)	0.0023 (16)	0.0098 (16)	0.0041 (15)
F3	0.105 (2)	0.0383 (13)	0.0994 (18)	0.0013 (12)	0.0319 (15)	−0.0087 (12)
C3	0.068 (2)	0.0380 (19)	0.0395 (17)	−0.0036 (16)	0.0199 (16)	0.0009 (14)
C4	0.060 (2)	0.0382 (18)	0.0355 (17)	0.0003 (15)	0.0126 (15)	0.0012 (14)
C5	0.074 (2)	0.046 (2)	0.0458 (19)	0.0035 (18)	0.0225 (18)	−0.0040 (16)
C6	0.070 (3)	0.060 (2)	0.067 (2)	−0.004 (2)	0.035 (2)	0.002 (2)
C7	0.058 (2)	0.043 (2)	0.061 (2)	−0.0044 (17)	0.0159 (18)	0.0035 (18)
C8	0.060 (2)	0.0380 (18)	0.0351 (18)	0.0023 (15)	0.0136 (15)	0.0013 (14)
C9	0.057 (2)	0.0368 (18)	0.0441 (18)	−0.0022 (15)	0.0118 (15)	0.0005 (15)
C10	0.082 (3)	0.048 (3)	0.186 (6)	0.002 (2)	0.021 (4)	−0.032 (3)
C11	0.144 (5)	0.113 (4)	0.088 (3)	−0.075 (4)	0.056 (3)	−0.027 (3)
C12	0.106 (4)	0.073 (3)	0.090 (3)	−0.028 (3)	−0.026 (3)	0.009 (3)

Geometric parameters (Å, º)

Cl—C7	1.732 (4)	C6—C7	1.372 (5)
O—C8	1.222 (4)	C6—H6A	0.9300
N—C8	1.364 (4)	C8—C9	1.525 (5)
N—C4	1.416 (4)	C9—C11	1.506 (6)
N—H0A	0.8600	C9—C10	1.508 (6)
F1—C1	1.336 (5)	C9—C12	1.518 (5)
C1—F2	1.326 (5)	C10—H10A	0.9600
C1—F3	1.330 (4)	C10—H10B	0.9600
C1—C2	1.494 (5)	C10—H10C	0.9600
C2—C7	1.385 (5)	C11—H11A	0.9600
C2—C3	1.386 (5)	C11—H11B	0.9600
C3—C4	1.384 (4)	C11—H11C	0.9600
C3—H3A	0.9300	C12—H12A	0.9600
C4—C5	1.379 (5)	C12—H12B	0.9600
C5—C6	1.382 (5)	C12—H12C	0.9600
C5—H5A	0.9300
C8—N—C4	126.6 (3)	O—C8—N	120.9 (3)
C8—N—H0A	116.7	O—C8—C9	122.5 (3)
C4—N—H0A	116.7	N—C8—C9	116.6 (3)
F2—C1—F3	105.3 (4)	C11—C9—C10	109.4 (4)
F2—C1—F1	106.2 (3)	C11—C9—C12	109.0 (4)
F3—C1—F1	105.8 (3)	C10—C9—C12	109.5 (4)
F2—C1—C2	112.6 (3)	C11—C9—C8	108.6 (3)
F3—C1—C2	113.4 (3)	C10—C9—C8	107.3 (3)
F1—C1—C2	112.8 (4)	C12—C9—C8	113.0 (3)
C7—C2—C3	119.9 (3)	C9—C10—H10A	109.5
C7—C2—C1	121.1 (3)	C9—C10—H10B	109.5
C3—C2—C1	119.0 (3)	H10A—C10—H10B	109.5
C4—C3—C2	120.4 (3)	C9—C10—H10C	109.5
C4—C3—H3A	119.8	H10A—C10—H10C	109.5
C2—C3—H3A	119.8	H10B—C10—H10C	109.5
C5—C4—C3	119.0 (3)	C9—C11—H11A	109.5
C5—C4—N	118.6 (3)	C9—C11—H11B	109.5
C3—C4—N	122.3 (3)	H11A—C11—H11B	109.5
C4—C5—C6	120.7 (3)	C9—C11—H11C	109.5
C4—C5—H5A	119.6	H11A—C11—H11C	109.5
C6—C5—H5A	119.6	H11B—C11—H11C	109.5
C7—C6—C5	120.2 (3)	C9—C12—H12A	109.5
C7—C6—H6A	119.9	C9—C12—H12B	109.5
C5—C6—H6A	119.9	H12A—C12—H12B	109.5
C6—C7—C2	119.7 (3)	C9—C12—H12C	109.5
C6—C7—Cl	117.8 (3)	H12A—C12—H12C	109.5
C2—C7—Cl	122.4 (3)	H12B—C12—H12C	109.5
F2—C1—C2—C7	−179.3 (4)	C5—C6—C7—C2	0.2 (6)
F3—C1—C2—C7	61.3 (5)	C5—C6—C7—Cl	−179.2 (3)
F1—C1—C2—C7	−59.1 (5)	C3—C2—C7—C6	0.3 (5)
F2—C1—C2—C3	0.2 (5)	C1—C2—C7—C6	179.8 (4)
F3—C1—C2—C3	−119.2 (4)	C3—C2—C7—Cl	179.7 (3)
F1—C1—C2—C3	120.5 (4)	C1—C2—C7—Cl	−0.8 (5)
C7—C2—C3—C4	0.5 (5)	C4—N—C8—O	4.8 (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—C11	19.1 (5)
C2—C3—C4—N	−179.0 (3)	N—C8—C9—C11	−162.8 (4)
C8—N—C4—C5	148.6 (3)	O—C8—C9—C10	−99.1 (5)
C8—N—C4—C3	−34.1 (5)	N—C8—C9—C10	79.0 (4)
C3—C4—C5—C6	2.3 (5)	O—C8—C9—C12	140.2 (4)
N—C4—C5—C6	179.6 (3)	N—C8—C9—C12	−41.7 (5)
C4—C5—C6—C7	−1.5 (6)

Hydrogen-bond geometry (Å, º)

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