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Acta Crystallogr Sect E Struct Rep Online. 2008 March 1; 64(Pt 3): o564.
Published online 2008 February 6. doi:  10.1107/S1600536808003590
PMCID: PMC2960874

N-(3,4-Difluoro­phen­yl)-2-(3,4-dimethoxy­phen­yl)acetamide

Abstract

In the title amide, C16H15F2NO3, the dihedral angle between the benzene rings is 53.7 (1)°. Mol­ecules are linked in the crystal structure by an inter­molecular N—H(...)O hydrogen bond involving N—H and C=O functionalities of the amide group. A one-dimensional network is thus formed along the [001] direction. No significant inter­chain contacts are observed.

Related literature

For general background, see: Maeda et al. (1991 [triangle]); Dawley et al. (1993 [triangle]); Nerya et al. (2003 [triangle]); Lee et al. (2007 [triangle]); Ha et al. (2007 [triangle]); Hong et al. (2008 [triangle]); Yan et al. (2007 [triangle]).

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Object name is e-64-0o564-scheme1.jpg

Experimental

Crystal data

  • C16H15F2NO3
  • M r = 307.29
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-0o564-efi1.jpg
  • a = 8.6440 (11) Å
  • b = 18.867 (6) Å
  • c = 9.4827 (13) Å
  • β = 111.019 (11)°
  • V = 1443.6 (5) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.12 mm−1
  • T = 295 (2) K
  • 0.26 × 0.26 × 0.23 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: none
  • 2855 measured reflections
  • 2689 independent reflections
  • 1089 reflections with I > 2σ(I)
  • R int = 0.050
  • 3 standard reflections every 400 reflections intensity decay: 3%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.076
  • wR(F 2) = 0.161
  • S = 0.99
  • 2689 reflections
  • 203 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.19 e Å−3
  • Δρmin = −0.19 e Å−3

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 [triangle]); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 [triangle]); software used to prepare material for publication: WinGX (Farrugia, 1999 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808003590/bh2160sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808003590/bh2160Isup2.hkl

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

Acknowledgments

The X-ray data were collected at the Center for Research Facilities, Chungnam National University. This work was partially supported by the fund of New University for Regional Innovation (grant No. 05-Na-A-01) from the Ministry of Education and Human Resources Department, Republic of Korea.

supplementary crystallographic information

Comment

Tyrosinase is the key enzyme (Ha et al., 2007) that converts tyrosine to melanin, and its inhibitors are the target molecules to develop and research anti-pigmentation agents for application to skin. The melanin formation is also accelerated by exposure under sunlight, especially U.V. (Ha et al., 2007; Yan et al., 2007). Therefore, treatments using potent inhibitory agents on tyrosinase and melanin formation may be cosmetically useful. Most of the whitening agents (Maeda et al., 1991; Dawley et al., 1993; Nerya et al., 2003) contain hydroxyl (Hong et al., 2008; Lee et al., 2007), aromatic, alkene, carbonyl, and ether groups in their structure, and act as a specific functional group to make the skin white by inhibiting the production of melanin.

During our work on developing potent whiting agents, in order to prevent the inadequacies of current whitening agents (poor skin penetration and toxicity) and maximize the inhibitory effects of melanin creation, we synthesized the title compound, (I), via a general chemical reaction, and studied its X-ray crystal structure.

The 3,4-dimethoxyphenyl moiety and 3,4-difluoroaniline group are essentially planar, with a mean deviation of 0.005 and 0.006 Å, respectively, from the corresponding least-squares planes. The dihedral angle between the benzene rings is 53.7 (1)°. The intermolecular N7—H7···O9i (symmetry code: (i) x, -y + 3/2, z - 1/2) hydrogen bond (involving the H atom of the amine and O atom of carbonyl) allows to form an extensive one-dimensional network along the c-axis, which stabilizes the crystal structure.

Experimental

3,4-Difluoroaniline and 3,4-dimethoxy phenyl acetyl chloride were purchased from Sigma Chemicals Co. Solvents used for organic synthesis were distilled before use. All other chemicals and solvents were of analytical grade and used without further purification. The title compound was prepared from the reaction of 3,4-difluoroaniline (1 mmol) and 3,4-dimethoxy phenyl acetyl chloride (1.2 mmol) by simple substitution (nucleophilic addition-elimination on carbonyl C atom) in THF. Removal of solvent gave a white solid. The solid was purified by column chromatography on silica gel (2:1 hexane/ethyl acetate) to give the title compound (92% yield). Colourless crystals (m.p. 393 K) were obtained by slow evaporation of an ethyl acetate solution at 298 K.

Refinement

Although diffraction data were collected using optimized parameters, a poor quality pattern resulted, which is reflected in the high final residuals. Atom H7 of the NH group was located in a differnce map and refined freely. Other H atoms were positioned geometrically and refined using a riding model, with C—H = 0.93–0.97 Å, and with Uiso(H) = 1.2Ueq(carrier C) for aromatic and CH2 groups, and 1.5Ueq(carrier C) for methyl H atoms.

Figures

Fig. 1.
The molecular structure of the title compound, showing the atom-numbering scheme and 30% probability ellipsoids.

Crystal data

C16H15F2NO3F000 = 640
Mr = 307.29Dx = 1.414 Mg m3
Monoclinic, P21/cMelting point: 393 K
Hall symbol: -P 2ybcMo Kα radiation λ = 0.71073 Å
a = 8.6440 (11) ÅCell parameters from 25 reflections
b = 18.867 (6) Åθ = 10.0–13.5º
c = 9.4827 (13) ŵ = 0.12 mm1
β = 111.019 (11)ºT = 295 (2) K
V = 1443.6 (5) Å3Block, colourless
Z = 40.26 × 0.26 × 0.23 mm

Data collection

Enraf–Nonius CAD-4 diffractometerθmin = 2.2º
non–profiled ω/2θ scansh = −10→9
Absorption correction: nonek = 0→22
2855 measured reflectionsl = 0→11
2689 independent reflections3 standard reflections
1089 reflections with I > 2σ(I) every 400 reflections
Rint = 0.050 intensity decay: 3%
θmax = 25.5º

Refinement

Refinement on F2H atoms treated by a mixture of independent and constrained refinement
Least-squares matrix: full  w = 1/[σ2(Fo2) + (0.0403P)2] where P = (Fo2 + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.076(Δ/σ)max < 0.001
wR(F2) = 0.161Δρmax = 0.19 e Å3
S = 1.00Δρmin = −0.19 e Å3
2689 reflectionsExtinction correction: none
203 parameters

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
C10.1632 (6)0.6519 (2)−0.2444 (5)0.0423 (12)
C20.0544 (6)0.6516 (3)−0.3939 (5)0.0492 (13)
H20.05780.6871−0.46060.059*
C3−0.0570 (7)0.5976 (3)−0.4396 (6)0.0581 (15)
C4−0.0637 (7)0.5447 (3)−0.3452 (6)0.0593 (15)
C50.0438 (7)0.5443 (3)−0.1995 (6)0.0671 (17)
H50.04070.5079−0.13460.081*
C60.1575 (6)0.5985 (3)−0.1487 (5)0.0531 (14)
H60.23060.5988−0.04890.064*
F1−0.1663 (4)0.59760 (17)−0.5842 (3)0.0941 (12)
F2−0.1777 (4)0.49215 (17)−0.3968 (4)0.0917 (12)
N70.2760 (5)0.7098 (2)−0.2001 (4)0.0446 (11)
H70.304 (6)0.729 (3)−0.273 (5)0.08 (2)*
C80.3307 (6)0.7408 (3)−0.0639 (5)0.0418 (12)
O90.2978 (4)0.71902 (17)0.0431 (3)0.0608 (11)
C100.4341 (6)0.8066 (3)−0.0549 (5)0.0566 (15)
H10A0.50550.7986−0.11220.068*
H10B0.36070.8457−0.10190.068*
C110.5399 (6)0.8276 (3)0.1044 (5)0.0464 (13)
C120.5239 (6)0.8935 (3)0.1612 (5)0.0502 (14)
H120.44630.92540.10070.06*
C130.6219 (6)0.9127 (3)0.3069 (5)0.0490 (14)
C140.7395 (6)0.8654 (3)0.3968 (5)0.0498 (13)
C150.7552 (6)0.8002 (3)0.3398 (5)0.0611 (16)
H150.83340.76820.39930.073*
C160.6557 (6)0.7815 (3)0.1945 (6)0.0599 (15)
H160.66770.7370.15750.072*
O170.6123 (4)0.97621 (19)0.3725 (4)0.0741 (12)
C180.4880 (7)1.0251 (3)0.2884 (6)0.0797 (19)
H18A0.49461.06710.34740.12*
H18B0.38071.00390.26430.12*
H18C0.5051.03730.19680.12*
O190.8299 (4)0.88921 (18)0.5388 (4)0.0679 (11)
C200.9656 (6)0.8464 (3)0.6292 (5)0.0686 (17)
H20A1.01950.8690.72510.103*
H20B1.04310.84080.57860.103*
H20C0.92520.80080.64460.103*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.047 (3)0.043 (3)0.037 (3)0.001 (3)0.015 (2)−0.006 (2)
C20.054 (3)0.045 (3)0.039 (3)0.000 (3)0.006 (3)0.006 (2)
C30.060 (4)0.062 (4)0.040 (3)0.001 (3)0.004 (3)−0.013 (3)
C40.061 (4)0.053 (4)0.060 (4)−0.007 (3)0.018 (3)−0.010 (3)
C50.092 (5)0.043 (4)0.066 (4)−0.010 (3)0.028 (4)0.001 (3)
C60.067 (4)0.047 (3)0.040 (3)0.002 (3)0.012 (3)0.006 (3)
F10.087 (3)0.103 (3)0.062 (2)−0.025 (2)−0.0110 (18)−0.010 (2)
F20.093 (3)0.073 (2)0.103 (3)−0.036 (2)0.028 (2)−0.024 (2)
N70.047 (3)0.053 (3)0.030 (2)−0.004 (2)0.010 (2)−0.003 (2)
C80.041 (3)0.053 (3)0.029 (3)−0.002 (3)0.010 (2)−0.003 (3)
O90.078 (3)0.073 (3)0.0360 (19)−0.027 (2)0.0258 (18)−0.0142 (18)
C100.056 (3)0.066 (4)0.045 (3)−0.009 (3)0.015 (3)−0.003 (3)
C110.045 (3)0.051 (3)0.041 (3)−0.004 (3)0.012 (2)−0.003 (3)
C120.044 (3)0.056 (4)0.044 (3)−0.001 (3)0.009 (3)0.004 (3)
C130.050 (3)0.049 (3)0.041 (3)0.000 (3)0.007 (3)−0.011 (3)
C140.041 (3)0.058 (4)0.041 (3)−0.001 (3)0.004 (2)−0.006 (3)
C150.056 (3)0.057 (4)0.054 (3)0.011 (3)0.000 (3)−0.014 (3)
C160.060 (4)0.059 (4)0.057 (3)0.000 (3)0.018 (3)−0.009 (3)
O170.069 (3)0.062 (3)0.062 (2)0.020 (2)−0.012 (2)−0.008 (2)
C180.074 (4)0.059 (4)0.083 (4)0.016 (3)0.000 (3)−0.006 (3)
O190.062 (2)0.070 (3)0.048 (2)0.019 (2)−0.0085 (19)−0.0103 (19)
C200.054 (3)0.078 (4)0.051 (3)0.010 (3)−0.009 (3)0.000 (3)

Geometric parameters (Å, °)

C1—C61.368 (6)C11—C161.369 (6)
C1—C21.392 (6)C11—C121.381 (6)
C1—N71.423 (6)C12—C131.386 (6)
C2—C31.362 (6)C12—H120.93
C2—H20.93C13—O171.367 (5)
C3—C41.356 (7)C13—C141.390 (6)
C3—F11.357 (5)C14—O191.368 (5)
C4—F21.359 (5)C14—C151.370 (6)
C4—C51.361 (6)C15—C161.383 (6)
C5—C61.380 (6)C15—H150.93
C5—H50.93C16—H160.93
C6—H60.93O17—C181.423 (5)
N7—C81.340 (5)C18—H18A0.96
N7—H70.89 (5)C18—H18B0.96
C8—O91.219 (5)C18—H18C0.96
C8—C101.515 (6)O19—C201.428 (5)
C10—C111.511 (6)C20—H20A0.96
C10—H10A0.97C20—H20B0.96
C10—H10B0.97C20—H20C0.96
C6—C1—C2120.0 (5)C16—C11—C10120.2 (5)
C6—C1—N7123.6 (4)C12—C11—C10121.0 (4)
C2—C1—N7116.4 (4)C11—C12—C13120.9 (5)
C3—C2—C1118.0 (5)C11—C12—H12119.6
C3—C2—H2121C13—C12—H12119.6
C1—C2—H2121O17—C13—C12124.6 (4)
C4—C3—F1119.2 (5)O17—C13—C14115.7 (4)
C4—C3—C2122.2 (5)C12—C13—C14119.7 (5)
F1—C3—C2118.5 (5)O19—C14—C15125.5 (4)
C3—C4—F2119.8 (5)O19—C14—C13115.3 (4)
C3—C4—C5119.9 (5)C15—C14—C13119.2 (4)
F2—C4—C5120.4 (5)C14—C15—C16120.5 (5)
C4—C5—C6119.5 (5)C14—C15—H15119.7
C4—C5—H5120.2C16—C15—H15119.7
C6—C5—H5120.2C11—C16—C15120.9 (5)
C1—C6—C5120.3 (5)C11—C16—H16119.5
C1—C6—H6119.9C15—C16—H16119.5
C5—C6—H6119.9C13—O17—C18118.1 (4)
C8—N7—C1125.9 (4)O17—C18—H18A109.5
C8—N7—H7118 (3)O17—C18—H18B109.5
C1—N7—H7116 (3)H18A—C18—H18B109.5
O9—C8—N7123.3 (5)O17—C18—H18C109.5
O9—C8—C10122.6 (4)H18A—C18—H18C109.5
N7—C8—C10114.1 (4)H18B—C18—H18C109.5
C11—C10—C8113.8 (4)C14—O19—C20117.5 (4)
C11—C10—H10A108.8O19—C20—H20A109.5
C8—C10—H10A108.8O19—C20—H20B109.5
C11—C10—H10B108.8H20A—C20—H20B109.5
C8—C10—H10B108.8O19—C20—H20C109.5
H10A—C10—H10B107.7H20A—C20—H20C109.5
C16—C11—C12118.8 (4)H20B—C20—H20C109.5
C6—C1—C2—C30.8 (7)C8—C10—C11—C1659.3 (6)
N7—C1—C2—C3−178.9 (4)C8—C10—C11—C12−121.7 (5)
C1—C2—C3—C4−0.6 (8)C16—C11—C12—C13−0.6 (7)
C1—C2—C3—F1178.5 (4)C10—C11—C12—C13−179.5 (4)
F1—C3—C4—F20.8 (8)C11—C12—C13—O17−178.9 (5)
C2—C3—C4—F2179.9 (5)C11—C12—C13—C140.8 (7)
F1—C3—C4—C5−179.3 (5)O17—C13—C14—O19−0.2 (7)
C2—C3—C4—C5−0.2 (9)C12—C13—C14—O19−180.0 (4)
C3—C4—C5—C60.8 (8)O17—C13—C14—C15179.1 (5)
F2—C4—C5—C6−179.3 (5)C12—C13—C14—C15−0.6 (8)
C2—C1—C6—C5−0.2 (7)O19—C14—C15—C16179.4 (5)
N7—C1—C6—C5179.5 (5)C13—C14—C15—C160.2 (8)
C4—C5—C6—C1−0.6 (8)C12—C11—C16—C150.1 (8)
C6—C1—N7—C8−34.1 (7)C10—C11—C16—C15179.1 (5)
C2—C1—N7—C8145.6 (5)C14—C15—C16—C110.1 (8)
C1—N7—C8—O95.3 (8)C12—C13—O17—C183.0 (7)
C1—N7—C8—C10−173.2 (4)C14—C13—O17—C18−176.8 (5)
O9—C8—C10—C1120.3 (7)C15—C14—O19—C208.1 (8)
N7—C8—C10—C11−161.2 (4)C13—C14—O19—C20−172.6 (4)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N7—H7···O9i0.89 (5)1.98 (5)2.846 (5)163 (5)

Symmetry codes: (i) x, −y+3/2, z−1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BH2160).

References

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