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Acta Crystallogr Sect E Struct Rep Online. 2009 August 1; 65(Pt 8): o1939.
Published online 2009 July 22. doi:  10.1107/S1600536809027962
PMCID: PMC2977360

N-(2,5-Dimethoxy­phen­yl)-4-nitro­benzene­sulfonamide

Abstract

The title compound, C14H14N2O6S, is an inter­mediate for the synthesis of β-3-adrenergic receptor agonists. The two meth­oxy groups are approximately coplanar with the attached benzene ring [C—O—C—C = −2.7 (4) and 9.4 (4)°]. The dihedral angle between the two aromatic rings is 67.16 (12)°. An intra­molecular N—H(...)O hydrogen bond is observed. In the crystal, mol­ecules are linked into chains along the c axis by C—H(...)O hydrogen bonds.

Related literature

For biological activity of β-3-adrenergic receptors, see: Bardou et al. (1998 [triangle]); Hu et al. (2001 [triangle]); Klaus et al. (2001 [triangle]); Margareto et al. (2001 [triangle]); Ok et al. (2000 [triangle]); Parmee et al. (1998 [triangle], 2000 [triangle]); Tonello et al. (1998 [triangle]); Weber et al. (1998 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o1939-scheme1.jpg

Experimental

Crystal data

  • C14H14N2O6S
  • M r = 338.33
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-65-o1939-efi1.jpg
  • a = 14.532 (4) Å
  • b = 12.375 (4) Å
  • c = 17.311 (4) Å
  • V = 3113.2 (14) Å3
  • Z = 8
  • Mo Kα radiation
  • μ = 0.24 mm−1
  • T = 292 K
  • 0.48 × 0.44 × 0.42 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: for a sphere (WinGX; Farrugia, 1999 [triangle]) T min = 0.893, T max = 0.906
  • 4003 measured reflections
  • 2877 independent reflections
  • 1790 reflections with I > 2σ(I)
  • R int = 0.004
  • 3 standard reflections every 200 reflections intensity decay: 0.9%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.040
  • wR(F 2) = 0.121
  • S = 1.06
  • 2877 reflections
  • 214 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.20 e Å−3
  • Δρmin = −0.32 e Å−3

Data collection: DIFRAC (Gabe & White, 1993 [triangle]); cell refinement: DIFRAC; data reduction: NRCVAX (Gabe et al., 1989 [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 (Farrugia, 1997 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809027962/ci2846sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809027962/ci2846Isup2.hkl

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

supplementary crystallographic information

Comment

The beta 3-adrenergic receptor has been shown to mediate various pharmacological and physiological effects such as lipolysis in white adipocyte tissue, thermogenesis in brown adipocyte tissue (Tonello et al., 1998; Ok et al., 2000; Parmee et al., 1998, 2000) and relaxation of urinary bladder detrusor tissue (Hu et al., 2001; Parmee et al., 1998; Weber et al., 1998). Consequently, several pharmaceutical firms, including ourselves, are engaged in developing potent and selective beta 3-adrenergic receptor agonists for the treatment of obesity, type II diabetes, and frequent urination (Margareto et al., 2001; Bardou et al., 1998; Klaus et al., 2001). In our synthetic work of beta 3-adrenergic receptor agonists, we obtained the title compound. Its crystal structure is reported here.

The two methoxy groups are approximately coplanar with the attached benzene ring [C7—O1—C3—C4 = -2.7 (4)° and C8—O2—C6—C5 9.4 (4)°]. The nitro group is coplanar with the C9-C14 benzene ring. The dihedral angle between the two aromatic rings is 67.16 (12)°. An intramolecular N—H···O hydrogen bond is observed.

The crystal packing of the title compound shows that the molecules are linked by C—H···.O hydrogen bonds (Table 1) to form chains along the c axis.

Experimental

2,5-Dimethoxybenzenamine (10 mmol) and excess pyridine were dissolved in dichloromethane (20 ml) and a solution of 4-nitrobenzene-1-sulfonyl chloride (13 mmol) in dichloromethane (20 ml) was added dropwise with vigorous stirring at 273 K. After 1 h, the reaction was quenched by addition of water and the oil was washed with diluted HCl. The organic layer separated was evaporated to give the crude product, which was recrystallized from n-hexane -dichloromethane (5:1). Colourless crystals suitable for X-ray analysis were obtained by slow evaporation in n-hexane-dichloromethane at room temperature.

Refinement

Atom H1N was located in a difference map and was refined freely. All other H atoms were positioned geometrically (C-H = 0.93–0.96 Å) and refined using a riding model, with Uiso(H) = 1.2–1.5Ueq(C).

Figures

Fig. 1.
The molecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level.
Fig. 2.
A packing diagram for the title compound.

Crystal data

C14H14N2O6SF(000) = 1408
Mr = 338.33Dx = 1.444 Mg m3
Orthorhombic, PbcaMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2abCell parameters from 32 reflections
a = 14.532 (4) Åθ = 4.3–7.5°
b = 12.375 (4) ŵ = 0.24 mm1
c = 17.311 (4) ÅT = 292 K
V = 3113.2 (14) Å3Block, colourless
Z = 80.48 × 0.44 × 0.42 mm

Data collection

Enraf–Nonius CAD-4 diffractometer1790 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.004
graphiteθmax = 25.4°, θmin = 2.4°
ω/2θ scansh = −17→10
Absorption correction: for a sphere (WinGX; Farrugia, 1999)k = −2→14
Tmin = 0.893, Tmax = 0.906l = −11→20
4003 measured reflections3 standard reflections every 200 reflections
2877 independent reflections intensity decay: 0.9%

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.040Hydrogen site location: mixed
wR(F2) = 0.121H atoms treated by a mixture of independent and constrained refinement
S = 1.06w = 1/[σ2(Fo2) + (0.0632P)2 + 0.3387P] where P = (Fo2 + 2Fc2)/3
2877 reflections(Δ/σ)max = 0.001
214 parametersΔρmax = 0.20 e Å3
0 restraintsΔρmin = −0.32 e Å3

Special details

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)

xyzUiso*/Ueq
S10.06666 (4)0.69183 (6)0.38224 (3)0.0473 (2)
N10.05816 (14)0.7151 (2)0.28983 (13)0.0530 (6)
H1N0.0834 (18)0.669 (2)0.2672 (16)0.057 (10)*
N2−0.23262 (16)0.3748 (2)0.44664 (14)0.0662 (7)
O1−0.20633 (15)0.94720 (18)0.27633 (11)0.0854 (7)
O20.00947 (13)0.61834 (17)0.16246 (10)0.0731 (6)
O30.15329 (11)0.63919 (17)0.39190 (10)0.0624 (5)
O40.04683 (13)0.78981 (14)0.42213 (10)0.0615 (5)
O5−0.30528 (13)0.40717 (19)0.47199 (13)0.0831 (7)
O6−0.21642 (16)0.28124 (19)0.43150 (18)0.1057 (9)
C1−0.02551 (15)0.7501 (2)0.25371 (14)0.0452 (6)
C2−0.07889 (17)0.8326 (2)0.28188 (15)0.0549 (7)
H2−0.06180.86810.32700.066*
C3−0.15884 (18)0.8634 (2)0.24300 (15)0.0569 (7)
C4−0.18336 (17)0.8124 (2)0.17588 (15)0.0562 (7)
H4−0.23660.83290.14990.067*
C5−0.12900 (19)0.7305 (2)0.14695 (15)0.0576 (7)
H5−0.14560.69660.10110.069*
C6−0.04991 (17)0.6982 (2)0.18527 (14)0.0495 (6)
C7−0.2851 (2)0.9874 (3)0.23675 (18)0.0916 (11)
H7A−0.26881.00470.18440.137*
H7B−0.30711.05120.26230.137*
H7C−0.33250.93340.23680.137*
C8−0.0013 (2)0.5726 (3)0.08822 (16)0.0856 (11)
H8A−0.05710.53120.08660.128*
H8B0.05010.52630.07720.128*
H8C−0.00410.62920.05040.128*
C9−0.02178 (15)0.59843 (19)0.40462 (12)0.0392 (5)
C10−0.00660 (16)0.4902 (2)0.39088 (14)0.0518 (6)
H100.04980.46700.37160.062*
C11−0.07563 (18)0.4167 (2)0.40591 (15)0.0542 (7)
H11−0.06640.34320.39780.065*
C12−0.15815 (16)0.4544 (2)0.43310 (14)0.0474 (6)
C13−0.17421 (17)0.5610 (2)0.44706 (15)0.0536 (7)
H13−0.23100.58380.46570.064*
C14−0.10508 (15)0.6342 (2)0.43313 (15)0.0494 (6)
H14−0.11440.70730.44280.059*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.0389 (3)0.0590 (4)0.0440 (3)−0.0088 (3)−0.0050 (3)0.0049 (3)
N10.0418 (12)0.0706 (17)0.0467 (12)−0.0002 (12)0.0015 (9)0.0032 (12)
N20.0512 (15)0.0693 (18)0.0780 (16)−0.0135 (13)−0.0120 (12)0.0180 (14)
O10.0911 (14)0.0898 (16)0.0751 (13)0.0359 (14)−0.0083 (11)−0.0015 (12)
O20.0859 (14)0.0786 (14)0.0547 (12)0.0178 (12)−0.0074 (10)−0.0102 (11)
O30.0344 (9)0.0884 (14)0.0645 (11)−0.0040 (9)−0.0062 (8)0.0152 (10)
O40.0738 (12)0.0565 (11)0.0541 (11)−0.0146 (10)−0.0101 (9)−0.0053 (10)
O50.0478 (11)0.0999 (18)0.1017 (16)−0.0122 (12)0.0057 (11)0.0330 (14)
O60.0880 (17)0.0563 (15)0.173 (3)−0.0261 (13)−0.0048 (17)0.0040 (16)
C10.0409 (12)0.0526 (14)0.0422 (12)−0.0101 (13)−0.0033 (11)0.0099 (13)
C20.0566 (15)0.0624 (18)0.0458 (13)−0.0020 (14)−0.0048 (12)0.0002 (13)
C30.0563 (15)0.0618 (17)0.0525 (15)0.0030 (14)0.0020 (12)0.0101 (14)
C40.0475 (14)0.0632 (18)0.0577 (15)−0.0060 (14)−0.0077 (12)0.0131 (15)
C50.0602 (17)0.0620 (18)0.0505 (15)−0.0190 (15)−0.0130 (12)0.0054 (14)
C60.0533 (14)0.0506 (15)0.0446 (13)−0.0061 (13)0.0019 (11)0.0057 (13)
C70.082 (2)0.105 (3)0.088 (2)0.036 (2)0.0062 (18)0.030 (2)
C80.128 (3)0.078 (2)0.0505 (17)0.016 (2)−0.0012 (17)−0.0066 (17)
C90.0350 (12)0.0436 (13)0.0389 (12)0.0026 (11)−0.0008 (9)0.0004 (11)
C100.0390 (12)0.0553 (16)0.0612 (16)0.0061 (12)0.0085 (11)−0.0058 (13)
C110.0547 (15)0.0425 (14)0.0653 (16)0.0039 (13)0.0012 (12)−0.0019 (13)
C120.0391 (13)0.0484 (15)0.0548 (14)−0.0044 (12)−0.0053 (11)0.0091 (12)
C130.0360 (13)0.0545 (16)0.0703 (17)0.0073 (12)0.0093 (12)0.0041 (14)
C140.0427 (13)0.0409 (14)0.0646 (15)0.0075 (12)0.0074 (12)0.0013 (13)

Geometric parameters (Å, °)

S1—O41.4249 (19)C4—H40.93
S1—O31.4273 (18)C5—C61.386 (3)
S1—N11.630 (2)C5—H50.93
S1—C91.771 (2)C7—H7A0.96
N1—C11.434 (3)C7—H7B0.96
N1—H1N0.78 (3)C7—H7C0.96
N2—O61.210 (3)C8—H8A0.96
N2—O51.212 (3)C8—H8B0.96
N2—C121.482 (3)C8—H8C0.96
O1—C31.373 (3)C9—C101.378 (4)
O1—C71.424 (3)C9—C141.380 (3)
O2—C61.370 (3)C10—C111.379 (3)
O2—C81.413 (3)C10—H100.93
C1—C21.372 (3)C11—C121.371 (3)
C1—C61.393 (3)C11—H110.93
C2—C31.396 (3)C12—C131.360 (3)
C2—H20.93C13—C141.374 (3)
C3—C41.370 (4)C13—H130.93
C4—C51.379 (4)C14—H140.93
O4—S1—O3120.67 (12)C5—C6—C1119.0 (2)
O4—S1—N1108.06 (13)O1—C7—H7A109.5
O3—S1—N1105.22 (11)O1—C7—H7B109.5
O4—S1—C9107.61 (11)H7A—C7—H7B109.5
O3—S1—C9108.45 (11)O1—C7—H7C109.5
N1—S1—C9105.95 (11)H7A—C7—H7C109.5
C1—N1—S1123.06 (17)H7B—C7—H7C109.5
C1—N1—H1N114 (2)O2—C8—H8A109.5
S1—N1—H1N109 (2)O2—C8—H8B109.5
O6—N2—O5124.4 (3)H8A—C8—H8B109.5
O6—N2—C12117.4 (3)O2—C8—H8C109.5
O5—N2—C12118.3 (3)H8A—C8—H8C109.5
C3—O1—C7117.8 (2)H8B—C8—H8C109.5
C6—O2—C8118.8 (2)C10—C9—C14120.9 (2)
C2—C1—C6120.1 (2)C10—C9—S1118.70 (18)
C2—C1—N1123.3 (2)C14—C9—S1120.34 (19)
C6—C1—N1116.6 (2)C9—C10—C11119.5 (2)
C1—C2—C3120.2 (2)C9—C10—H10120.3
C1—C2—H2119.9C11—C10—H10120.3
C3—C2—H2119.9C12—C11—C10118.4 (2)
C4—C3—O1125.0 (2)C12—C11—H11120.8
C4—C3—C2120.0 (3)C10—C11—H11120.8
O1—C3—C2115.0 (2)C13—C12—C11122.8 (2)
C3—C4—C5119.9 (2)C13—C12—N2119.4 (2)
C3—C4—H4120.1C11—C12—N2117.8 (2)
C5—C4—H4120.1C12—C13—C14118.9 (2)
C4—C5—C6120.9 (2)C12—C13—H13120.6
C4—C5—H5119.6C14—C13—H13120.6
C6—C5—H5119.6C13—C14—C9119.5 (2)
O2—C6—C5126.3 (2)C13—C14—H14120.3
O2—C6—C1114.7 (2)C9—C14—H14120.3
O4—S1—N1—C1−61.0 (2)N1—C1—C6—C5−178.5 (2)
O3—S1—N1—C1168.9 (2)O4—S1—C9—C10−162.61 (19)
C9—S1—N1—C154.1 (2)O3—S1—C9—C10−30.5 (2)
S1—N1—C1—C247.4 (3)N1—S1—C9—C1082.0 (2)
S1—N1—C1—C6−134.8 (2)O4—S1—C9—C1419.3 (2)
C6—C1—C2—C31.3 (4)O3—S1—C9—C14151.32 (19)
N1—C1—C2—C3179.0 (2)N1—S1—C9—C14−96.1 (2)
C7—O1—C3—C4−2.7 (4)C14—C9—C10—C11−0.1 (4)
C7—O1—C3—C2175.8 (3)S1—C9—C10—C11−178.18 (19)
C1—C2—C3—C4−1.0 (4)C9—C10—C11—C121.0 (4)
C1—C2—C3—O1−179.7 (2)C10—C11—C12—C13−1.1 (4)
O1—C3—C4—C5178.6 (2)C10—C11—C12—N2178.1 (2)
C2—C3—C4—C50.1 (4)O6—N2—C12—C13178.0 (3)
C3—C4—C5—C60.6 (4)O5—N2—C12—C13−2.0 (4)
C8—O2—C6—C59.4 (4)O6—N2—C12—C11−1.3 (4)
C8—O2—C6—C1−170.3 (2)O5—N2—C12—C11178.7 (2)
C4—C5—C6—O2−180.0 (2)C11—C12—C13—C140.2 (4)
C4—C5—C6—C1−0.3 (4)N2—C12—C13—C14−179.0 (2)
C2—C1—C6—O2179.1 (2)C12—C13—C14—C90.7 (4)
N1—C1—C6—O21.2 (3)C10—C9—C14—C13−0.8 (4)
C2—C1—C6—C5−0.7 (4)S1—C9—C14—C13177.25 (19)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1N···O20.78 (3)2.20 (3)2.607 (3)113 (2)
C8—H8C···O4i0.962.553.414 (4)150

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: CI2846).

References

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