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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 64| Part 6| June 2008| Page o994
doi:10.1107/S1600536808012610

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

Hyon Pil You,a Byung Hee Han,a* Sung Kwon Kang,a Chang Keun Sungb and Sang Ook Kangc

aDepartment of Chemistry, Chungnam National University, Daejeon 305-764, Republic of Korea, bDepartment of Food Science and Technology, Chungnam National University, Daejeon 305-764, Republic of Korea, and cDepartment of Materials Chemistry, Korea University, 208 Seochang, Chochidwon, Chungnam 339-700, Republic of Korea
*Correspondence e-mail: bhhan@cnu.ac.kr

(Received 3 April 2008; accepted 30 April 2008; online 3 May 2008)

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[Dawley, R. M. & Flurkey, W. H. (1993). J. Food Sci. 58, 609-610.]); Nerya et al. (2003[Nerya, O., Vaya, J., Musa, R., Izrael, S., Ben-Arie, R. & Tamir, S. (2003). J. Agric. Food Chem. 51, 1201-1207.]); Juana et al. (1994[Juana, C., Soledad, C. & Francisco, G. (1994). J. Pharm. Pharmacol. 46, 983-985.]); Briganti et al. (2003[Briganti, S., Camera, E. & Picardo, M. (2003). Pigment Cell Res. 16, 101-110.]). For the synthesis, see: Hussain et al. (2003[Hussain, H. H., Babic, G., Durst, T., Wright, J. S., Flueraru, M., Chichirau, A. & Chepelev, L. L. (2003). J. Org. Chem. 68, 7023-7032.]).

[Scheme 1]

Experimental

Crystal data

  • C14H13F2NO4S

  • Mr = 329.31

  • Monoclinic, P 21 /c

  • 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[Bruker (2002). SADABS, SAINT and SMART. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.928, Tmax = 0.957

  • 9690 measured reflections

  • 3308 independent reflections

  • 1700 reflections with I > 2σ(I)

  • Rint = 0.042
Refinement

  • R[F2 > 2σ(F2)] = 0.044

  • wR(F2) = 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

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N7—H7⋯O17i 0.76 (3) 2.48 (3) 3.180 (3) 155 (3)
N7—H7⋯O19i 0.76 (3) 2.61 (3) 3.256 (3) 144 (3)
Symmetry code: (i) [-x+2, y+{\script{1\over 2}}, -z+{\script{1\over 2}}].

Data collection: SMART (Bruker, 2002[Bruker (2002). SADABS, SAINT and SMART. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2002[Bruker (2002). SADABS, SAINT and SMART. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.]); software used to prepare material for publication: WinGX (Farrugia, 1999[Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837-838.]).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808012610/bh2170sup1.cif

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

checkCIF report


Comment top

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.

Related literature top

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

Experimental top

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 top

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.

Computing details top

Data collection: SMART (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT (Bruker, 2002); 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).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, showing the atom-numbering scheme and 30% probability ellipsoids.
N-(3,4-Difluorophenyl)-3,4-dimethoxybenzenesulfonamide top
Crystal data top
C14H13F2NO4SF(000) = 680
Mr = 329.31Dx = 1.516 Mg m−3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 1598 reflections
a = 12.2886 (10) Åθ = 2.8–23.5°
b = 8.5662 (7) ŵ = 0.26 mm−1
c = 14.5546 (12) ÅT = 295 K
β = 109.655 (2)°Block, colourless
V = 1442.8 (2) Å30.25 × 0.18 × 0.15 mm
Z = 4
Data collection top
Bruker SMART CCD area-detector
diffractometer		1700 reflections with I > 2σ(I)
ϕ and ω scansRint = 0.042
Absorption correction: multi-scan
(SADABS; Bruker, 2002)		θmax = 27.5°, θmin = 1.8°
Tmin = 0.928, Tmax = 0.957h = −15→14
9690 measured reflectionsk = −11→9
3308 independent reflectionsl = −18→18
Refinement top
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 Å−3
S = 0.99Δρmin = −0.21 e Å−3
3308 reflectionsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
204 parametersExtinction coefficient: 0.0349 (19)
0 restraints
Crystal data top
C14H13F2NO4SV = 1442.8 (2) Å3
Mr = 329.31Z = 4
Monoclinic, P21/cMo Kα radiation
a = 12.2886 (10) ŵ = 0.26 mm−1
b = 8.5662 (7) ÅT = 295 K
c = 14.5546 (12) Å0.25 × 0.18 × 0.15 mm
β = 109.655 (2)°
Data collection top
Bruker SMART CCD area-detector
diffractometer		3308 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2002)		1700 reflections with I > 2σ(I)
Tmin = 0.928, Tmax = 0.957Rint = 0.042
9690 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0440 restraints
wR(F2) = 0.126H atoms treated by a mixture of independent and constrained refinement
S = 0.99Δρmax = 0.19 e Å−3
3308 reflectionsΔρmin = −0.21 e Å−3
204 parameters
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
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) top
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, º) top
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, º) top
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 code: (i) −x+2, y+1/2, −z+1/2.

Experimental details

Crystal data
Chemical formulaC14H13F2NO4S
Mr329.31
Crystal system, space groupMonoclinic, P21/c
Temperature (K)295
a, b, c (Å)12.2886 (10), 8.5662 (7), 14.5546 (12)
β (°) 109.655 (2)
V (Å3)1442.8 (2)
Z4
Radiation typeMo Kα
µ (mm−1)0.26
Crystal size (mm)0.25 × 0.18 × 0.15
Data collection
DiffractometerBruker SMART CCD area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2002)
Tmin, Tmax0.928, 0.957
No. of measured, independent and
observed [I > 2σ(I)] reflections		9690, 3308, 1700
Rint0.042
(sin θ/λ)max (Å−1)0.650
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.044, 0.126, 0.99
No. of reflections3308
No. of parameters204
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)0.19, −0.21

Computer programs: SMART (Bruker, 2002), SAINT (Bruker, 2002), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).

Hydrogen-bond geometry (Å, º) top
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 code: (i) −x+2, y+1/2, −z+1/2.
 

Acknowledgements

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.

References

First citationBriganti, S., Camera, E. & Picardo, M. (2003). Pigment Cell Res. 16, 101–110.  Web of Science CrossRef PubMed Google Scholar
 First citationBruker (2002). SADABS, SAINT and SMART. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
 First citationDawley, R. M. & Flurkey, W. H. (1993). J. Food Sci. 58, 609–610.  CrossRef CAS Web of Science Google Scholar
 First citationFarrugia, L. J. (1997). J. Appl. Cryst. 30, 565.  CrossRef IUCr Journals Google Scholar
 First citationFarrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838.  CrossRef CAS IUCr Journals Google Scholar
 First citationHussain, H. H., Babic, G., Durst, T., Wright, J. S., Flueraru, M., Chichirau, A. & Chepelev, L. L. (2003). J. Org. Chem. 68, 7023–7032.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationJuana, C., Soledad, C. & Francisco, G. (1994). J. Pharm. Pharmacol. 46, 983–985.  Google Scholar
 First citationNerya, O., Vaya, J., Musa, R., Izrael, S., Ben-Arie, R. & Tamir, S. (2003). J. Agric. Food Chem. 51, 1201–1207.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 64| Part 6| June 2008| Page o994
doi:10.1107/S1600536808012610
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