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

Won Ki Hong; You-Soon Lee; Byung Hee Han; Sung Kwon Kang; Chang Keun Sung

doi:10.1107/S1600536808003590

. 2008 Feb 6;64(Pt 3):o564. doi: 10.1107/S1600536808003590

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

Won Ki Hong ^a, You-Soon Lee ^a, Byung Hee Han ^a, Sung Kwon Kang ^a,^*, Chang Keun Sung ^b

PMCID: PMC2960874 PMID: 21201907

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 ▶); Dawley et al. (1993 ▶); Nerya et al. (2003 ▶); Lee et al. (2007 ▶); Ha et al. (2007 ▶); Hong et al. (2008 ▶); Yan et al. (2007 ▶).

Experimental

Crystal data

C₁₆H₁₅F₂NO₃
M _r = 307.29
Monoclinic,
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
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.19 e Å⁻³

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 ▶); 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: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

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

e-64-0o564-sup1.cif^{(16.2KB, cif)}

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

e-64-0o564-Isup2.hkl^{(129.4KB, hkl)}

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
N7—H7⋯O9ⁱ	0.89 (5)	1.98 (5)	2.846 (5)	163 (5)

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Symmetry code: (i) Inline graphic .

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.