2′-Fluoro-3′,5′-dimethoxy­acetanilide

Xie, K.; Lou, Y.; Zheng, J.; Zhao, Q.; Wei, Y.

doi:10.1107/S1600536808042554

organic compounds

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ISSN: 2056-9890

Volume 65| Part 1| January 2009| Page o205

doi:10.1107/S1600536808042554

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2′-Fluoro-3′,5′-dimethoxyacetanilide

Kai Xie,^a Yuan-yuan Lou,^a Jin Zheng,^b Qing-jie Zhao ^b and Ya-bing Wei ^a ^*

^aCollege of Materials Science and Engineering, Nanjing University of Technology, Nanjing 210009, People's Republic of China, and ^bShanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People's Republic of China
^*Correspondence e-mail: ybwei@njut.edu.cn

(Received 24 November 2008; accepted 14 December 2008; online 24 December 2008)

Molecules of the title compound, C₁₀H₁₂FNO₃, are nearly planar considering all non-H atoms with a mean deviation of 0.0288 Å. Molecules are linked through intermolecular N—H⋯O and N—H⋯F hydrogen bonds.

Related literature

For bond-length data, see: Allen et al. (1987 ). For the synthesis, see: Borodkin et al. (2006 ); Stavber et al. (2002 ).

Experimental

Crystal data

C₁₀H₁₂FNO₃
M_r = 213.21
Monoclinic, P 2₁ /c
a = 9.741 (3) Å
b = 4.8439 (12) Å
c = 21.634 (6) Å
β = 98.082 (3)°
V = 1010.7 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.12 mm⁻¹
T = 296 (2) K
0.20 × 0.20 × 0.10 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2000 ) T_min = 0.977, T_max = 0.989
4791 measured reflections
1780 independent reflections
1434 reflections with I > 2σ(I)
R_int = 0.030

Refinement

R[F² > 2σ(F²)] = 0.046
wR(F²) = 0.121
S = 1.02
1780 reflections
139 parameters
H-atom parameters constrained
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O1ⁱ	0.86	2.61	3.246 (2)	131
N1—H1⋯F1ⁱ	0.86	2.47	3.3128 (19)	166
Symmetry code: (i) $[-x+1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Data collection: SMART (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT; 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: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808042554/bt2815sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808042554/bt2815Isup2.hkl

checkCIF report

Comment top

In our recent research for the synthesis of potential PDE5 inhitiors, 2-fluoro-3,5-dimethoxyanilide, (I), was synthesized as one of the structural units by fluorination (Stavber et al., 2002) of 3,5-dimethoxyanilide (Borodkin et al., 2006).

A view of the molecular structure of (I) is depicted in Fig. 1. In the molecule, almost all non-H atoms are in the same plane. All bond lengths and angles are normal (Allen et al., 1987). The molecules are linked via intermolecular hydrogen bonds in which the amide group acts as a donor to F and O atoms (Fig. 2 and Table 1).

Related literature top

For bond-length data, see: Allen et al. (1987). For the synthesis, see: Borodkin et al. (2006); Stavber et al. (2002).

Experimental top

To a solution of 3,5-dimethoxyanilide (195 mg, 1.0 mmol) in CH₃CN (5 ml), 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane-bis(tetrafluoroborate) (390 mg, 1.1 mmol) was added at 0°C. After 3 h, TLC showed that the reaction was complete, the mixture was evaporated to give an oil, then ethyl acetate was added, and the solution was washed with 5% aqueous sodium bicarbonate, dried and then concentrated by rotary evaporation. The crude product was purified by column chromatography over silica gel (CH₂Cl₂/MeOH = 100/1) to afford (I) (111 mg, 52%) as a white solid. Single crystals suitable for X-ray analysis (m.p. 403 K) were obtained by slow evaporation of a dichloromethane solution at 298 K.

Computing details top

Data collection: SMART (Bruker, 2000); cell refinement: SMART (Bruker, 2000); data reduction: SAINT (Bruker, 2000); 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: SHELXTL (Sheldrick, 2008).

Figures top

	Fig. 1. View of the molecule of (I) showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. The crystal packing of (I), viewed along the c-axis. Hydrogen bonds are shown as dashed lines.

2'-Fluoro-3',5'-dimethoxyacetanilide top

Crystal data top

C₁₀H₁₂FNO₃	F(000) = 448
M_r = 213.21	D_x = 1.401 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 9.741 (3) Å	Cell parameters from 2061 reflections
b = 4.8439 (12) Å	θ = 2.6–26.6°
c = 21.634 (6) Å	µ = 0.12 mm⁻¹
β = 98.082 (3)°	T = 296 K
V = 1010.7 (4) Å³	Block, colourless
Z = 4	0.20 × 0.20 × 0.10 mm

Data collection top

Bruker SMART CCD area-detector diffractometer	1780 independent reflections
Radiation source: fine-focus sealed tube	1434 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.030
ϕ and ω scans	θ_max = 25.1°, θ_min = 2.1°
Absorption correction: multi-scan (SADABS; Bruker, 2000)	h = −11→11
T_min = 0.977, T_max = 0.989	k = −5→5
4791 measured reflections	l = −23→25

Refinement top

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)] = 0.046	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.121	H-atom parameters constrained
S = 1.02	w = 1/[σ²(F_o²) + (0.058P)² + 0.3484P] where P = (F_o² + 2F_c²)/3
1780 reflections	(Δ/σ)_max < 0.001
139 parameters	Δρ_max = 0.20 e Å⁻³
0 restraints	Δρ_min = −0.18 e Å⁻³

Crystal data top

C₁₀H₁₂FNO₃	V = 1010.7 (4) Å³
M_r = 213.21	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 9.741 (3) Å	µ = 0.12 mm⁻¹
b = 4.8439 (12) Å	T = 296 K
c = 21.634 (6) Å	0.20 × 0.20 × 0.10 mm
β = 98.082 (3)°

Data collection top

Bruker SMART CCD area-detector diffractometer	1780 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2000)	1434 reflections with I > 2σ(I)
T_min = 0.977, T_max = 0.989	R_int = 0.030
4791 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.046	0 restraints
wR(F²) = 0.121	H-atom parameters constrained
S = 1.02	Δρ_max = 0.20 e Å⁻³
1780 reflections	Δρ_min = −0.18 e Å⁻³
139 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
F1	0.42666 (11)	0.1466 (2)	0.26102 (5)	0.0512 (3)
C1	0.31928 (18)	0.2862 (4)	0.22731 (8)	0.0397 (4)
C2	0.25035 (18)	0.4812 (4)	0.25813 (8)	0.0406 (4)
C3	0.14087 (19)	0.6226 (4)	0.22477 (9)	0.0446 (5)
H3	0.0918	0.7534	0.2443	0.053*
C4	0.10546 (18)	0.5662 (4)	0.16181 (9)	0.0430 (5)
C5	0.17582 (18)	0.3739 (4)	0.13084 (9)	0.0429 (5)
H5	0.1503	0.3404	0.0885	0.051*
C6	0.28642 (17)	0.2311 (4)	0.16492 (9)	0.0394 (4)
C7	0.3591 (2)	−0.0570 (4)	0.07947 (9)	0.0465 (5)
C8	0.4620 (2)	−0.2755 (5)	0.06870 (10)	0.0580 (6)
H8A	0.4152	−0.4232	0.0448	0.087*
H8B	0.5056	−0.3455	0.1081	0.087*
H8C	0.5311	−0.1978	0.0463	0.087*
C9	0.2337 (2)	0.7206 (5)	0.35272 (10)	0.0565 (6)
H9A	0.2418	0.8972	0.3334	0.085*
H9B	0.2777	0.7274	0.3953	0.085*
H9C	0.1375	0.6752	0.3516	0.085*
C10	−0.0414 (2)	0.6888 (6)	0.06772 (10)	0.0661 (7)
H10A	0.0364	0.7382	0.0473	0.099*
H10B	−0.1180	0.8085	0.0537	0.099*
H10C	−0.0673	0.5011	0.0578	0.099*
N1	0.36727 (16)	0.0327 (3)	0.13913 (7)	0.0458 (4)
H1	0.4313	−0.0427	0.1651	0.055*
O1	0.29930 (14)	0.5157 (3)	0.31975 (6)	0.0527 (4)
O2	−0.00485 (14)	0.7163 (3)	0.13322 (7)	0.0582 (4)
O3	0.27541 (18)	0.0299 (4)	0.03737 (7)	0.0754 (6)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0422 (6)	0.0570 (7)	0.0516 (7)	0.0111 (5)	−0.0030 (5)	0.0003 (5)
C1	0.0305 (9)	0.0417 (11)	0.0454 (10)	0.0019 (8)	0.0004 (7)	0.0042 (8)
C2	0.0344 (9)	0.0440 (11)	0.0435 (10)	−0.0049 (8)	0.0051 (8)	−0.0013 (8)
C3	0.0372 (10)	0.0453 (11)	0.0519 (11)	0.0029 (9)	0.0090 (8)	−0.0030 (9)
C4	0.0319 (9)	0.0460 (11)	0.0504 (11)	0.0038 (8)	0.0036 (8)	0.0051 (9)
C5	0.0367 (10)	0.0475 (12)	0.0437 (10)	0.0006 (8)	0.0029 (8)	−0.0001 (9)
C6	0.0328 (9)	0.0401 (10)	0.0454 (10)	−0.0004 (8)	0.0057 (7)	0.0000 (8)
C7	0.0445 (11)	0.0497 (12)	0.0451 (11)	0.0029 (9)	0.0060 (9)	−0.0001 (9)
C8	0.0587 (13)	0.0590 (14)	0.0574 (13)	0.0130 (11)	0.0120 (10)	−0.0077 (11)
C9	0.0553 (13)	0.0627 (14)	0.0526 (12)	−0.0030 (11)	0.0117 (10)	−0.0140 (10)
C10	0.0594 (14)	0.0814 (17)	0.0540 (13)	0.0227 (13)	−0.0048 (11)	0.0055 (12)
N1	0.0403 (8)	0.0511 (10)	0.0442 (9)	0.0121 (8)	−0.0005 (7)	−0.0014 (7)
O1	0.0464 (8)	0.0643 (10)	0.0461 (8)	0.0060 (7)	0.0022 (6)	−0.0097 (7)
O2	0.0490 (8)	0.0678 (10)	0.0555 (8)	0.0238 (7)	−0.0002 (6)	0.0008 (7)
O3	0.0767 (11)	0.0974 (14)	0.0481 (9)	0.0365 (10)	−0.0052 (8)	−0.0069 (9)

Geometric parameters (Å, º) top

F1—C1	1.367 (2)	C7—C8	1.498 (3)
C1—C6	1.369 (3)	C8—H8A	0.9600
C1—C2	1.383 (3)	C8—H8B	0.9600
C2—O1	1.362 (2)	C8—H8C	0.9600
C2—C3	1.382 (3)	C9—O1	1.425 (2)
C3—C4	1.384 (3)	C9—H9A	0.9600
C3—H3	0.9300	C9—H9B	0.9600
C4—O2	1.371 (2)	C9—H9C	0.9600
C4—C5	1.384 (3)	C10—O2	1.418 (3)
C5—C6	1.400 (2)	C10—H10A	0.9600
C5—H5	0.9300	C10—H10B	0.9600
C6—N1	1.407 (2)	C10—H10C	0.9600
C7—O3	1.209 (2)	N1—H1	0.8600
C7—N1	1.354 (2)

C6—C1—F1	119.01 (16)	C7—C8—H8B	109.5
C6—C1—C2	123.11 (17)	H8A—C8—H8B	109.5
F1—C1—C2	117.87 (16)	C7—C8—H8C	109.5
O1—C2—C1	115.39 (16)	H8A—C8—H8C	109.5
O1—C2—C3	126.06 (17)	H8B—C8—H8C	109.5
C1—C2—C3	118.55 (17)	O1—C9—H9A	109.5
C4—C3—C2	118.88 (17)	O1—C9—H9B	109.5
C4—C3—H3	120.6	H9A—C9—H9B	109.5
C2—C3—H3	120.6	O1—C9—H9C	109.5
O2—C4—C3	114.22 (16)	H9A—C9—H9C	109.5
O2—C4—C5	123.28 (17)	H9B—C9—H9C	109.5
C3—C4—C5	122.50 (17)	O2—C10—H10A	109.5
C4—C5—C6	118.32 (17)	O2—C10—H10B	109.5
C4—C5—H5	120.8	H10A—C10—H10B	109.5
C6—C5—H5	120.8	O2—C10—H10C	109.5
C1—C6—C5	118.62 (17)	H10A—C10—H10C	109.5
C1—C6—N1	117.25 (16)	H10B—C10—H10C	109.5
C5—C6—N1	124.13 (17)	C7—N1—C6	129.53 (16)
O3—C7—N1	123.31 (19)	C7—N1—H1	115.2
O3—C7—C8	121.59 (19)	C6—N1—H1	115.2
N1—C7—C8	115.10 (17)	C2—O1—C9	117.11 (15)
C7—C8—H8A	109.5	C4—O2—C10	118.15 (16)

C6—C1—C2—O1	−178.01 (17)	F1—C1—C6—N1	−0.4 (3)
F1—C1—C2—O1	0.8 (2)	C2—C1—C6—N1	178.37 (17)
C6—C1—C2—C3	1.6 (3)	C4—C5—C6—C1	0.5 (3)
F1—C1—C2—C3	−179.52 (16)	C4—C5—C6—N1	−179.38 (17)
O1—C2—C3—C4	178.88 (17)	O3—C7—N1—C6	0.5 (3)
C1—C2—C3—C4	−0.7 (3)	C8—C7—N1—C6	−179.28 (19)
C2—C3—C4—O2	179.66 (17)	C1—C6—N1—C7	−178.81 (19)
C2—C3—C4—C5	−0.2 (3)	C5—C6—N1—C7	1.1 (3)
O2—C4—C5—C6	−179.54 (17)	C1—C2—O1—C9	178.18 (17)
C3—C4—C5—C6	0.3 (3)	C3—C2—O1—C9	−1.4 (3)
F1—C1—C6—C5	179.65 (16)	C3—C4—O2—C10	174.96 (19)
C2—C1—C6—C5	−1.5 (3)	C5—C4—O2—C10	−5.2 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1ⁱ	0.86	2.61	3.246 (2)	131
N1—H1···F1ⁱ	0.86	2.47	3.3128 (19)	166

Symmetry code: (i) −x+1, y−1/2, −z+1/2.

Experimental details

Crystal data
Chemical formula	C₁₀H₁₂FNO₃
M_r	213.21
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	296
a, b, c (Å)	9.741 (3), 4.8439 (12), 21.634 (6)
β (°)	98.082 (3)
V (Å³)	1010.7 (4)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.12
Crystal size (mm)	0.20 × 0.20 × 0.10

Data collection
Diffractometer	Bruker SMART CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2000)
T_min, T_max	0.977, 0.989
No. of measured, independent and observed [I > 2σ(I)] reflections	4791, 1780, 1434
R_int	0.030
(sin θ/λ)_max (Å⁻¹)	0.596

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.046, 0.121, 1.02
No. of reflections	1780
No. of parameters	139
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.20, −0.18

Computer programs: SMART (Bruker, 2000), SAINT (Bruker, 2000), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1ⁱ	0.86	2.61	3.246 (2)	131.2
N1—H1···F1ⁱ	0.86	2.47	3.3128 (19)	165.8

Symmetry code: (i) −x+1, y−1/2, −z+1/2.

Acknowledgements

Acknowledgement is made to the crew of Topharman Shanghai Co Ltd for their active cooperation in this work. We also thank Instrument Analysis and Research Center of Shanghai University for structural confirmation.

References

Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19. CrossRef Web of Science Google Scholar
Borodkin, G. I., Zaikin, P. A. & Shubin, V. G. (2006). Tetrahedron Lett. 47, 15, 2639–2642. Google Scholar
Bruker (2000). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Stavber, S., Jereb, M. & Zupan, M. (2002). J. Phys. Org. Chem. 15, 1, 56–61. Google Scholar