N-(4-Fluoro­phen­yl)-2,2-dimethyl­propan­amide

Fang, Z.; Zhang, F.; Zou, B.; Guo, K.

doi:10.1107/S1600536812020570

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 68| Part 6| June 2012| Page o1757

doi:10.1107/S1600536812020570

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N-(4-Fluorophenyl)-2,2-dimethylpropanamide

Zheng Fang,^a Feng Zhang,^a Bao-hua Zou ^a and Kai Guo ^b ^*

^aSchool of Pharmaceutical Sciences, Nanjing University of Technology, Puzhu South Road No. 30 Nanjing, Nanjing 210009, People's Republic of China, and ^bCollege of Life Science and Pharmaceutical Engineering, Nanjing University of Technology, Puzhu South Road No. 30 Nanjing, Nanjing 210009, People's Republic of China
^*Correspondence e-mail: kaiguo@njut.edu.cn

(Received 13 April 2012; accepted 7 May 2012; online 16 May 2012)

The crystal packing in the title compound, C₁₁H₁₄FNO, features N—H⋯O hydrogen bonds, resulting in chains of molecules running parallel to the c axis. The dihedral angle between the ring and the amide group is 39.1 (3)°.

Related literature

The title compound is an intermediate in the synthesis of ezetimibe, which inhibits the absorption of cholesterol from the intestine, see: Rosenblum et al. (1998 ). For the synthesis, see: Wang et al. (2008 ). For a related structure, see: Gowda et al. (2007 ).

Experimental

Crystal data

C₁₁H₁₄FNO
M_r = 195.23
Monoclinic, P 2₁ /c
a = 9.5750 (19) Å
b = 13.027 (3) Å
c = 8.8340 (18) Å
β = 92.07 (3)°
V = 1101.2 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.09 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 = 0.974, T_max = 0.991
4219 measured reflections
2025 independent reflections
1091 reflections with I > 2σ(I)
R_int = 0.082
3 standard reflections every 200 reflections intensity decay: 1%

Refinement

R[F² > 2σ(F²)] = 0.062
wR(F²) = 0.155
S = 1.00
2025 reflections
128 parameters
H-atom parameters constrained
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N—H0A⋯Oⁱ	0.86	2.17	2.990 (3)	159
Symmetry code: (i) $[x, -y+{\script{3\over 2}}, z-{\script{1\over 2}}]$ .

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

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536812020570/pv2534sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812020570/pv2534Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812020570/pv2534Isup3.cml

checkCIF report

Comment top

Ezetimibe is a biologically active molecule and reasearch has shown it to have the useful property of inhibiting the absorption of cholesterol from the intestine (Rosenblum et al., 1998). As a part of our studies on the synthesis of Ezetimibe, the title compound (fIG. 1) which is one of the derivates of an intermediate, has been synthesized and its crystal structure is reported in this paper. The crystal structure of the title compound is stabilized by N—H0A···O hydrogen bonds resulting in chains of molecules running parallel to the c-axis (Fig. 1 and Tab. 1). The bond distances and angles in the title molecule are in excellent agreement with the corresponding bond distances and angles reported for its chloro-analogue (Gowda et al., 2007).

Related literature top

The title compound is an intermediate in the synthesis of ezetimibe, which inhibits the absorption of cholesterol from the intestine, see: Rosenblum et al. (1998). For the synthesis, see: Wang et al. (2008). For a related structure, see: Gowda et al. (2007).

Experimental top

To a solution of 4-fluoroaniline (13.32 g, 0.12 mol) in CH₂Cl₂(20 ml) were added 4-dimethylaminopyridine (1.2 g, 0.01 mol) and Et₃N (42.3 ml, 0.31 mol) and cooled the reaction mixture to 273 K. A solution of pivaloyl chloride (14.4 g, 0.12 mol) in CH₂Cl₂ (150 ml) was added dropwise over 1 h and the mixture was heated to reflux. After 12 h, H₂O and H₂SO₄ (2 N, 75 ml) were added, separated the layers and washed the organic layer sequentially with NaOH (10%), NaCl (satd.) and water. The organic layer was dried over MgSO₄ and concentrated to obtain the title compound as a yellow solid product in pure form following the procedure reported earlier (Wang et al., 2008). Crystals of the title compound suitable for X-ray diffraction were obtained by slow evaporation of an ethanol solution.

Computing details top

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

	Fig. 1. The molecular structure of the title compound with the atom numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are presented as small spheres of arbitrary radius.
	Fig. 2. A view of the N—H···O hydrogen bonds (dotted lines) in the crystal structure of the title compound. H atoms non-participating in hydrogen- bonding were omitted for clarity.

N-(4-Fluorophenyl)-2,2-dimethylpropanamide top

Crystal data top

C₁₁H₁₄FNO	F(000) = 416
M_r = 195.23	D_x = 1.178 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 25 reflections
a = 9.5750 (19) Å	θ = 10–13°
b = 13.027 (3) Å	µ = 0.09 mm⁻¹
c = 8.8340 (18) Å	T = 293 K
β = 92.07 (3)°	Block, yellow
V = 1101.2 (4) Å³	0.30 × 0.20 × 0.10 mm
Z = 4

Data collection top

Enraf–Nonius CAD-4 diffractometer	1091 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.082
Graphite monochromator	θ_max = 25.4°, θ_min = 2.1°
ω/2θ scans	h = −11→11
Absorption correction: ψ scan (North et al., 1968)	k = −15→15
T_min = 0.974, T_max = 0.991	l = 0→10
4219 measured reflections	3 standard reflections every 200 reflections
2025 independent reflections	intensity decay: 1%

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.062	H-atom parameters constrained
wR(F²) = 0.155	w = 1/[σ²(F_o²) + (0.065P)²] where P = (F_o² + 2F_c²)/3
S = 1.00	(Δ/σ)_max < 0.001
2025 reflections	Δρ_max = 0.20 e Å⁻³
128 parameters	Δρ_min = −0.20 e Å⁻³
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.020 (5)

Crystal data top

C₁₁H₁₄FNO	V = 1101.2 (4) Å³
M_r = 195.23	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 9.5750 (19) Å	µ = 0.09 mm⁻¹
b = 13.027 (3) Å	T = 293 K
c = 8.8340 (18) Å	0.30 × 0.20 × 0.10 mm
β = 92.07 (3)°

Data collection top

Enraf–Nonius CAD-4 diffractometer	1091 reflections with I > 2σ(I)
Absorption correction: ψ scan (North et al., 1968)	R_int = 0.082
T_min = 0.974, T_max = 0.991	3 standard reflections every 200 reflections
4219 measured reflections	intensity decay: 1%
2025 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.062	0 restraints
wR(F²) = 0.155	H-atom parameters constrained
S = 1.00	Δρ_max = 0.20 e Å⁻³
2025 reflections	Δρ_min = −0.20 e Å⁻³
128 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

	x	y	z	U_iso*/U_eq
O	0.55665 (18)	0.65320 (14)	0.18951 (19)	0.0619 (6)
F	0.01604 (17)	0.92797 (16)	0.1759 (2)	0.1032 (7)
N	0.4924 (2)	0.74067 (17)	−0.0211 (2)	0.0588 (7)
H0A	0.5136	0.7547	−0.1126	0.071*
C1	0.2795 (3)	0.7359 (2)	0.1236 (3)	0.0638 (8)
H1A	0.2982	0.6683	0.1514	0.077*
C2	0.1603 (3)	0.7837 (3)	0.1726 (4)	0.0728 (9)
H2A	0.0995	0.7493	0.2349	0.087*
C3	0.1340 (3)	0.8806 (3)	0.1284 (3)	0.0693 (9)
C4	0.2195 (3)	0.9346 (2)	0.0395 (3)	0.0731 (9)
H4A	0.1981	1.0016	0.0110	0.088*
C5	0.3409 (3)	0.8869 (2)	−0.0081 (3)	0.0640 (8)
H5A	0.4019	0.9225	−0.0687	0.077*
C6	0.3705 (3)	0.7878 (2)	0.0339 (3)	0.0507 (7)
C7	0.5775 (3)	0.6763 (2)	0.0568 (3)	0.0496 (7)
C8	0.7023 (3)	0.6356 (2)	−0.0266 (3)	0.0560 (7)
C9	0.8029 (3)	0.7255 (3)	−0.0500 (4)	0.0864 (11)
H9A	0.8316	0.7537	0.0465	0.130*
H9B	0.7565	0.7775	−0.1102	0.130*
H9C	0.8834	0.7014	−0.1011	0.130*
C10	0.7752 (4)	0.5529 (3)	0.0688 (4)	0.1008 (13)
H10A	0.7121	0.4967	0.0829	0.151*
H10B	0.8036	0.5809	0.1657	0.151*
H10C	0.8560	0.5289	0.0181	0.151*
C11	0.6568 (3)	0.5904 (2)	−0.1808 (3)	0.0759 (10)
H11A	0.5945	0.5338	−0.1662	0.114*
H11B	0.7375	0.5669	−0.2321	0.114*
H11C	0.6097	0.6422	−0.2408	0.114*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O	0.0662 (12)	0.0774 (14)	0.0430 (11)	0.0127 (10)	0.0146 (9)	0.0049 (10)
F	0.0656 (12)	0.1364 (17)	0.1092 (15)	0.0362 (11)	0.0246 (11)	−0.0114 (13)
N	0.0603 (14)	0.0756 (15)	0.0418 (12)	0.0164 (13)	0.0204 (11)	0.0052 (12)
C1	0.0579 (17)	0.071 (2)	0.0637 (18)	0.0048 (15)	0.0160 (15)	0.0065 (15)
C2	0.0509 (17)	0.099 (3)	0.070 (2)	0.0022 (18)	0.0194 (15)	0.0051 (19)
C3	0.0507 (17)	0.095 (2)	0.0631 (18)	0.0197 (18)	0.0119 (15)	−0.0072 (18)
C4	0.073 (2)	0.073 (2)	0.073 (2)	0.0218 (18)	0.0069 (17)	0.0059 (17)
C5	0.0660 (19)	0.071 (2)	0.0564 (17)	0.0073 (16)	0.0177 (14)	0.0078 (15)
C6	0.0519 (15)	0.0640 (18)	0.0370 (13)	0.0053 (14)	0.0113 (12)	−0.0002 (13)
C7	0.0537 (16)	0.0574 (17)	0.0384 (14)	0.0016 (13)	0.0114 (12)	−0.0005 (13)
C8	0.0548 (16)	0.0679 (19)	0.0461 (15)	0.0087 (14)	0.0119 (12)	−0.0050 (14)
C9	0.0548 (18)	0.112 (3)	0.093 (3)	−0.0102 (18)	0.0193 (18)	−0.023 (2)
C10	0.097 (2)	0.125 (3)	0.082 (2)	0.059 (2)	0.022 (2)	0.014 (2)
C11	0.080 (2)	0.082 (2)	0.067 (2)	0.0074 (18)	0.0224 (16)	−0.0181 (17)

Geometric parameters (Å, º) top

O—C7	1.233 (3)	C5—H5A	0.9300
F—C3	1.366 (3)	C7—C8	1.522 (3)
N—C7	1.342 (3)	C8—C10	1.522 (4)
N—C6	1.420 (3)	C8—C11	1.533 (4)
N—H0A	0.8600	C8—C9	1.535 (4)
C1—C6	1.376 (4)	C9—H9A	0.9600
C1—C2	1.383 (4)	C9—H9B	0.9600
C1—H1A	0.9300	C9—H9C	0.9600
C2—C3	1.343 (4)	C10—H10A	0.9600
C2—H2A	0.9300	C10—H10B	0.9600
C3—C4	1.352 (4)	C10—H10C	0.9600
C4—C5	1.397 (4)	C11—H11A	0.9600
C4—H4A	0.9300	C11—H11B	0.9600
C5—C6	1.371 (4)	C11—H11C	0.9600

C7—N—C6	125.9 (2)	C7—C8—C10	109.3 (2)
C7—N—H0A	117.1	C7—C8—C11	111.2 (2)
C6—N—H0A	117.1	C10—C8—C11	109.3 (2)
C6—C1—C2	120.4 (3)	C7—C8—C9	107.9 (2)
C6—C1—H1A	119.8	C10—C8—C9	109.7 (3)
C2—C1—H1A	119.8	C11—C8—C9	109.4 (2)
C3—C2—C1	118.7 (3)	C8—C9—H9A	109.5
C3—C2—H2A	120.6	C8—C9—H9B	109.5
C1—C2—H2A	120.6	H9A—C9—H9B	109.5
C2—C3—C4	123.1 (3)	C8—C9—H9C	109.5
C2—C3—F	118.9 (3)	H9A—C9—H9C	109.5
C4—C3—F	117.9 (3)	H9B—C9—H9C	109.5
C3—C4—C5	118.2 (3)	C8—C10—H10A	109.5
C3—C4—H4A	120.9	C8—C10—H10B	109.5
C5—C4—H4A	120.9	H10A—C10—H10B	109.5
C6—C5—C4	120.2 (3)	C8—C10—H10C	109.5
C6—C5—H5A	119.9	H10A—C10—H10C	109.5
C4—C5—H5A	119.9	H10B—C10—H10C	109.5
C5—C6—C1	119.3 (2)	C8—C11—H11A	109.5
C5—C6—N	118.6 (2)	C8—C11—H11B	109.5
C1—C6—N	122.0 (3)	H11A—C11—H11B	109.5
O—C7—N	121.6 (2)	C8—C11—H11C	109.5
O—C7—C8	122.1 (2)	H11A—C11—H11C	109.5
N—C7—C8	116.3 (2)	H11B—C11—H11C	109.5

C6—C1—C2—C3	1.4 (5)	C7—N—C6—C5	142.3 (3)
C1—C2—C3—C4	−0.9 (5)	C7—N—C6—C1	−39.9 (4)
C1—C2—C3—F	179.7 (3)	C6—N—C7—O	−1.2 (4)
C2—C3—C4—C5	0.0 (5)	C6—N—C7—C8	−179.9 (2)
F—C3—C4—C5	179.4 (2)	O—C7—C8—C10	9.3 (4)
C3—C4—C5—C6	0.5 (4)	N—C7—C8—C10	−172.0 (3)
C4—C5—C6—C1	0.0 (4)	O—C7—C8—C11	130.1 (3)
C4—C5—C6—N	177.8 (2)	N—C7—C8—C11	−51.3 (3)
C2—C1—C6—C5	−0.9 (4)	O—C7—C8—C9	−110.0 (3)
C2—C1—C6—N	−178.7 (2)	N—C7—C8—C9	68.7 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N—H0A···Oⁱ	0.86	2.17	2.990 (3)	159
C1—H1A···O	0.93	2.49	2.904 (3)	107

Symmetry code: (i) x, −y+3/2, z−1/2.

Experimental details

Crystal data
Chemical formula	C₁₁H₁₄FNO
M_r	195.23
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	9.5750 (19), 13.027 (3), 8.8340 (18)
β (°)	92.07 (3)
V (Å³)	1101.2 (4)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.30 × 0.20 × 0.10

Data collection
Diffractometer	Enraf–Nonius CAD-4 diffractometer
Absorption correction	ψ scan (North et al., 1968)
T_min, T_max	0.974, 0.991
No. of measured, independent and observed [I > 2σ(I)] reflections	4219, 2025, 1091
R_int	0.082
(sin θ/λ)_max (Å⁻¹)	0.603

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.062, 0.155, 1.00
No. of reflections	2025
No. of parameters	128
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.20, −0.20

Computer programs: CAD-4 Software (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···A	D—H	H···A	D···A	D—H···A
N—H0A···Oⁱ	0.86	2.17	2.990 (3)	159

Symmetry code: (i) x, −y+3/2, z−1/2.

Acknowledgements

This research was supported financially by the College of Life Science and Pharmaceutical Engineering, Nanjing University of Technology, the 973 project (2012CB725204) and the Key Basic Research Program of China.

References

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