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Acta Crystallogr Sect E Struct Rep Online. 2008 June 1; 64(Pt 6): o994.
Published online 2008 May 3. doi:  10.1107/S1600536808012610
PMCID: PMC2961509

N-(3,4-Difluoro­phen­yl)-3,4-dimethoxy­benzene­sulfonamide

Abstract

In the title sulfonamide derivative, C14H13F2NO4S, the dihedral angle between the benzene rings is 66.05 (9)°. The crystal structure is stabilized by weak inter­molecular N—H(...)O hydrogen bonds involving the amine and meth­oxy groups, which link the mol­ecules into a one-dimensional chain. No significant inter­chain contacts are observed.

Related literature

For general background on skin-whitening agents, see: Dawley & Flurkey (1993 [triangle]); Nerya et al. (2003 [triangle]); Juana et al. (1994 [triangle]); Briganti et al. (2003 [triangle]). For the synthesis, see: Hussain et al. (2003 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-64-0o994-scheme1.jpg

Experimental

Crystal data

  • C14H13F2NO4S
  • M r = 329.31
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-0o994-efi1.jpg
  • a = 12.2886 (10) Å
  • b = 8.5662 (7) Å
  • c = 14.5546 (12) Å
  • β = 109.655 (2)°
  • V = 1442.8 (2) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.26 mm−1
  • T = 295 (2) K
  • 0.25 × 0.18 × 0.15 mm

Data collection

  • Bruker SMART CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2002 [triangle]) T min = 0.928, T max = 0.957
  • 9690 measured reflections
  • 3308 independent reflections
  • 1700 reflections with I > 2σ(I)
  • R int = 0.042

Refinement

  • R[F 2 > 2σ(F 2)] = 0.044
  • wR(F 2) = 0.126
  • S = 0.99
  • 3308 reflections
  • 204 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.19 e Å−3
  • Δρmin = −0.21 e Å−3

Data collection: SMART (Bruker, 2002 [triangle]); cell refinement: SAINT (Bruker, 2002 [triangle]); data reduction: SAINT; 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/S1600536808012610/bh2170sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808012610/bh2170Isup2.hkl

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

Acknowledgments

This work was partially supported by Chungnam National University,, the Fund of New Universities for Regional Innovation (05-Na-A-01) from the Ministry of Education and Human Resources Department, Republic of Korea, and the DBIO Co. Ltd.

supplementary crystallographic information

Comment

Most skin whitening agents currently on the market (Dawley & Flurkey, 1993; Nerya et al., 2003) contain hydroquinone, ascorbic acid, kojic acid (Juana et al., 1994), arbutin, azealic acid, and glycyrrhetinic acid. They include aromatic, methoxy, hydroxyl and carbonyl functional groups in their structures. They are acting as a direct inhibitors of tyrosinase, the enzyme in the skin pigment cells (melanocytes) producing melanin.

Tyrosinase is the key enzyme converting the amino acid L-tyrosine to melanin, and its inhibitors are target molecules to develop anti-pigmentation agents for skin treatment after sunburn (Briganti et al. 2003). The melanin formation by the tyrosinase activity after sunlight exposure causes some dermatological disorders associated with freckles and melasma. Therefore, potent inhibitory agents on melanin formation and tyrosinase should be cosmetically useful for treatment of dermatological disorders.

However, most skin whitening agents have some problems, due to toxicity, low stability of formulation and poor skin permeation. In our work on the development of new whitening agents to complement the inadequacy of current whitening agents and maximize the inhibitory effects of melanin creation, we synthesized the title compound (Fig. 1), via a general chemical reaction (Hussain et al., 2003) of 3,4-difluoroaniline with aromatic sulfonyl chloride, and studied its X-ray crystal structure.

The 3,4-dimethoxybenzenesulfonyl and 3,4-difluoroaniline moieties are essentially planar, with a mean deviation of 0.004 Å and 0.010 Å, respectively, from the corresponding least-squares planes. The dihedral angle between benzene rings is 66.05 (9)°. The intermolecular N7—H7···O17i and O19i [symmetry code: (i) -x + 2, y + 1/2, -z + 1/2] hydrogen bonds (involving the H atom of the amine and O atoms of methoxy groups) allow to form an extensive one-dimensional network along the b axis, which stabilizes the crystal structure.

Experimental

3,4-difluoroaniline and 3,4-dimethoxy benzenesulfonyl chloride were purchased from Sigma Chemical Co. Solvents used for organic synthesis were redistilled before used. All other chemicals and solvents were of analytical grade and used without further purification. The title compound was prepared by the reaction of 3,4-difluoroaniline (1 mmol) with aromatic sulfonyl chloride (1.2 mmol) in triethylamine as a solvent, under stirring. Evaporation of solvent, treatment with water, extraction with methylene chloride and chromatography of the dried solution (MgSO4) on silica gel column (2 / 1 = hexane / ethyl acetate) gave the title compound in 56% yield. Colourless single crystals were obtained by slow evaporation from an ethyl acetate solution, at room temperature.

Refinement

The amine H atom H7 was located in a difference map and refined freely. The other H atoms were positioned geometrically and refined using a riding model, with C—H = 0.93 Å for aromatic H atoms and 0.96 Å for methyl H atoms, and with Uiso(H) = 1.2Ueq(C) for aromatic and 1.5Ueq(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

C14H13F2NO4SF000 = 680
Mr = 329.31Dx = 1.516 Mg m3
Monoclinic, P21/cMo Kα radiation λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 1598 reflections
a = 12.2886 (10) Åθ = 2.8–23.5º
b = 8.5662 (7) ŵ = 0.26 mm1
c = 14.5546 (12) ÅT = 295 (2) K
β = 109.655 (2)ºBlock, colourless
V = 1442.8 (2) Å30.25 × 0.18 × 0.15 mm
Z = 4

Data collection

Bruker SMART CCD area-detector diffractometerRint = 0.042
[var phi] and ω scansθmax = 27.5º
Absorption correction: multi-scan(SADABS; Bruker, 2002)θmin = 1.8º
Tmin = 0.928, Tmax = 0.957h = −15→14
9690 measured reflectionsk = −11→9
3308 independent reflectionsl = −18→18
1700 reflections with I > 2σ(I)

Refinement

Refinement on F2H atoms treated by a mixture of independent and constrained refinement
Least-squares matrix: full  w = 1/[σ2(Fo2) + (0.0426P)2 + 0.5561P] where P = (Fo2 + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.044(Δ/σ)max = 0.001
wR(F2) = 0.126Δρmax = 0.19 e Å3
S = 0.99Δρmin = −0.21 e Å3
3308 reflectionsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
204 parametersExtinction coefficient: 0.0349 (19)

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

xyzUiso*/Ueq
F10.37106 (16)0.1400 (3)−0.04021 (13)0.0975 (7)
F20.3788 (2)0.0318 (3)0.13264 (17)0.1271 (9)
C10.6212 (2)0.3457 (3)0.11332 (19)0.0492 (7)
C20.5338 (2)0.2966 (3)0.0306 (2)0.0584 (8)
H20.52880.3352−0.03040.07*
C30.4554 (2)0.1914 (4)0.0395 (2)0.0609 (8)
C40.4593 (3)0.1366 (4)0.1281 (2)0.0753 (10)
C50.5430 (3)0.1849 (5)0.2102 (2)0.0885 (12)
H50.54540.14750.27080.106*
C60.6248 (2)0.2906 (4)0.2030 (2)0.0692 (9)
H60.68260.32450.25910.083*
N70.7042 (2)0.4591 (3)0.1068 (2)0.0595 (7)
H70.738 (2)0.489 (4)0.158 (2)0.062 (10)*
S80.78080 (6)0.43912 (9)0.03547 (5)0.0595 (3)
O90.84833 (17)0.5777 (2)0.04834 (17)0.0802 (7)
O100.70295 (15)0.3991 (3)−0.05866 (13)0.0709 (6)
C110.8750 (2)0.2809 (3)0.07756 (18)0.0490 (7)
C120.9910 (2)0.3073 (3)0.13211 (17)0.0478 (6)
H121.01840.40870.14680.057*
C131.0644 (2)0.1829 (3)0.16380 (17)0.0472 (6)
C141.0231 (2)0.0296 (3)0.14189 (18)0.0480 (6)
C150.9086 (2)0.0050 (3)0.0875 (2)0.0559 (7)
H150.8809−0.09620.07240.067*
C160.8350 (2)0.1300 (3)0.0554 (2)0.0566 (7)
H160.75790.11280.01870.068*
O171.17904 (15)0.1936 (2)0.21844 (13)0.0614 (5)
C181.2333 (2)0.3419 (4)0.2277 (2)0.0669 (9)
H18A1.31290.33260.26810.1*
H18B1.19490.41410.25690.1*
H18C1.22880.37920.16430.1*
O191.10296 (15)−0.0832 (2)0.17753 (14)0.0599 (5)
C201.0682 (3)−0.2409 (3)0.1507 (2)0.0668 (8)
H20A1.132−0.30980.18050.1*
H20B1.0441−0.25140.08110.1*
H20C1.005−0.26740.17270.1*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
F10.0780 (12)0.1205 (18)0.0749 (12)−0.0470 (12)0.0005 (10)−0.0069 (11)
F20.1139 (17)0.160 (2)0.1037 (16)−0.0684 (17)0.0321 (14)0.0185 (15)
C10.0374 (13)0.0490 (16)0.0540 (17)0.0026 (12)0.0060 (12)−0.0074 (13)
C20.0499 (16)0.0634 (19)0.0522 (17)−0.0065 (14)0.0044 (13)0.0047 (14)
C30.0480 (16)0.069 (2)0.0555 (18)−0.0104 (15)0.0037 (14)−0.0058 (15)
C40.0615 (19)0.088 (3)0.075 (2)−0.0210 (18)0.0223 (17)0.0036 (19)
C50.074 (2)0.134 (4)0.057 (2)−0.015 (2)0.0207 (18)0.008 (2)
C60.0520 (17)0.096 (3)0.0530 (19)−0.0028 (17)0.0093 (14)−0.0121 (17)
N70.0462 (13)0.0581 (16)0.0618 (17)−0.0029 (12)0.0019 (12)−0.0102 (13)
S80.0460 (4)0.0573 (5)0.0647 (5)−0.0070 (4)0.0048 (3)0.0101 (4)
O90.0582 (12)0.0579 (14)0.1098 (18)−0.0137 (10)0.0090 (12)0.0198 (12)
O100.0543 (11)0.0896 (17)0.0556 (12)−0.0054 (10)0.0009 (9)0.0153 (11)
C110.0422 (14)0.0530 (17)0.0480 (15)−0.0059 (13)0.0102 (12)0.0031 (13)
C120.0480 (14)0.0453 (16)0.0459 (15)−0.0115 (12)0.0102 (12)−0.0005 (12)
C130.0420 (14)0.0526 (17)0.0427 (14)−0.0059 (13)0.0084 (11)0.0005 (12)
C140.0469 (14)0.0473 (17)0.0482 (15)−0.0036 (13)0.0138 (12)0.0015 (12)
C150.0509 (16)0.0509 (17)0.0643 (18)−0.0130 (14)0.0171 (14)−0.0060 (14)
C160.0418 (14)0.062 (2)0.0598 (18)−0.0137 (14)0.0092 (13)−0.0027 (15)
O170.0470 (10)0.0523 (12)0.0707 (13)−0.0082 (9)0.0010 (9)0.0051 (10)
C180.0486 (16)0.061 (2)0.078 (2)−0.0199 (14)0.0042 (14)0.0031 (16)
O190.0563 (11)0.0441 (12)0.0732 (13)−0.0037 (9)0.0138 (10)−0.0016 (9)
C200.0727 (19)0.0473 (18)0.081 (2)−0.0054 (16)0.0270 (17)−0.0061 (16)

Geometric parameters (Å, °)

F1—C31.343 (3)C11—C121.398 (3)
F2—C41.354 (3)C12—C131.372 (4)
C1—C61.375 (4)C12—H120.93
C1—C21.382 (3)C13—O171.369 (3)
C1—N71.434 (4)C13—C141.405 (4)
C2—C31.357 (4)C14—O191.350 (3)
C2—H20.93C14—C151.379 (3)
C3—C41.359 (4)C15—C161.378 (4)
C4—C51.352 (4)C15—H150.93
C5—C61.383 (4)C16—H160.93
C5—H50.93O17—C181.420 (3)
C6—H60.93C18—H18A0.96
N7—S81.628 (3)C18—H18B0.96
N7—H70.76 (3)C18—H18C0.96
S8—O101.424 (2)O19—C201.431 (3)
S8—O91.424 (2)C20—H20A0.96
S8—C111.754 (3)C20—H20B0.96
C11—C161.381 (4)C20—H20C0.96
C6—C1—C2119.3 (3)C13—C12—C11119.6 (2)
C6—C1—N7119.9 (2)C13—C12—H12120.2
C2—C1—N7120.7 (3)C11—C12—H12120.2
C3—C2—C1119.2 (3)O17—C13—C12125.1 (2)
C3—C2—H2120.4O17—C13—C14114.6 (2)
C1—C2—H2120.4C12—C13—C14120.3 (2)
F1—C3—C2120.1 (3)O19—C14—C15125.5 (2)
F1—C3—C4118.5 (3)O19—C14—C13114.9 (2)
C2—C3—C4121.4 (3)C15—C14—C13119.6 (3)
C5—C4—F2120.7 (3)C16—C15—C14120.1 (3)
C5—C4—C3120.4 (3)C16—C15—H15119.9
F2—C4—C3118.9 (3)C14—C15—H15119.9
C4—C5—C6119.3 (3)C15—C16—C11120.5 (2)
C4—C5—H5120.3C15—C16—H16119.8
C6—C5—H5120.3C11—C16—H16119.8
C1—C6—C5120.3 (3)C13—O17—C18118.3 (2)
C1—C6—H6119.8O17—C18—H18A109.5
C5—C6—H6119.8O17—C18—H18B109.5
C1—N7—S8123.2 (2)H18A—C18—H18B109.5
C1—N7—H7109 (2)O17—C18—H18C109.5
S8—N7—H7115 (2)H18A—C18—H18C109.5
O10—S8—O9120.03 (13)H18B—C18—H18C109.5
O10—S8—N7107.04 (13)C14—O19—C20117.3 (2)
O9—S8—N7105.36 (14)O19—C20—H20A109.5
O10—S8—C11107.51 (13)O19—C20—H20B109.5
O9—S8—C11108.15 (12)H20A—C20—H20B109.5
N7—S8—C11108.29 (13)O19—C20—H20C109.5
C16—C11—C12119.9 (2)H20A—C20—H20C109.5
C16—C11—S8120.0 (2)H20B—C20—H20C109.5
C12—C11—S8120.0 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N7—H7···O17i0.76 (3)2.48 (3)3.180 (3)155 (3)
N7—H7···O19i0.76 (3)2.61 (3)3.256 (3)144 (3)

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BH2170).

References

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  • Dawley, R. M. & Flurkey, W. H. (1993). J. Food Sci.58, 609–610.
  • Farrugia, L. J. (1997). J. Appl. Cryst.30, 565.
  • Farrugia, L. J. (1999). J. Appl. Cryst.32, 837–838.
  • Hussain, H. H., Babic, G., Durst, T., Wright, J. S., Flueraru, M., Chichirau, A. & Chepelev, L. L. (2003). J. Org. Chem.68, 7023–7032. [PubMed]
  • Juana, C., Soledad, C. & Francisco, G. (1994). J. Pharm. Pharmacol.46, 983–985.
  • Nerya, O., Vaya, J., Musa, R., Izrael, S., Ben-Arie, R. & Tamir, S. (2003). J. Agric. Food Chem.51, 1201–1207. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]

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