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Acta Crystallogr Sect E Struct Rep Online. 2010 July 1; 66(Pt 7): o1559–o1560.
Published online 2010 June 5. doi:  10.1107/S1600536810020465
PMCID: PMC3006765

3-Chloro-N-(4-sulfamoylphen­yl)propanamide

Abstract

In the title compound, C9H11ClN2O3S, the dihedral angle between the benzene ring and the amido –NHCO– plane is 15.0 (2)°. An intra­molecular C—H(...)O hydrogen bond generates an S(6) ring motif. In the crystal structure, the amino NH2 group is involved in inter­molecular N—H(...)O hydrogen bonds, which connect the mol­ecules into a double layer structure expanding parallel to the bc plane. The layers are further linked by an amido N—H(...)O hydrogen bond. Between the layers, a weak π–π inter­action with a centroid–centroid distance of 3.7447 (12) Å is also observed.

Related literature

For the anti­bacterial and pharmacological properties of sulfonamides and their derivatives, see: Albala et al. (1994 [triangle]); Mann & Keilin (1940 [triangle]); Maren (1976 [triangle]); Pastorekova et al. (2004 [triangle]); Reynolds (1996 [triangle]); Silverman (1992 [triangle]); Supuran & Scozzafava (2001 [triangle], 2002 [triangle]); Supuran et al. (2003 [triangle], 2004 [triangle]); Türkmen et al. (2005 [triangle]). For graph-set notation, see: Bernstein et al. (1995 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o1559-scheme1.jpg

Experimental

Crystal data

  • C9H11ClN2O3S
  • M r = 262.72
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o1559-efi1.jpg
  • a = 7.7554 (4) Å
  • b = 14.8191 (8) Å
  • c = 9.7482 (5) Å
  • β = 94.181 (4)°
  • V = 1117.36 (10) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.52 mm−1
  • T = 296 K
  • 0.78 × 0.45 × 0.22 mm

Data collection

  • Stoe IPDS2 diffractometer
  • Absorption correction: integration (X-RED32; Stoe & Cie, 2002 [triangle]) T min = 0.754, T max = 0.892
  • 6023 measured reflections
  • 2294 independent reflections
  • 2007 reflections with I > 2σ(I)
  • R int = 0.040

Refinement

  • R[F 2 > 2σ(F 2)] = 0.038
  • wR(F 2) = 0.106
  • S = 1.08
  • 2294 reflections
  • 153 parameters
  • 2 restraints
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.28 e Å−3
  • Δρmin = −0.44 e Å−3

Data collection: X-AREA (Stoe & Cie, 2002 [triangle]); cell refinement: X-AREA (Stoe & Cie, 2002 [triangle]); data reduction: X-RED32 (Stoe & Cie, 2002 [triangle]); program(s) used to solve structure: SIR97 (Altomare et al., 1999 [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: WinGX (Farrugia, 1999 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810020465/is2555sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810020465/is2555Isup2.hkl

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

Acknowledgments

The authors acknowledge the Faculty of Arts and Sciences, Ondokuz Mayıs University, Turkey, for the use of the Stoe IPDS2 diffractometer (purchased under grant F.279 of the University Research Fund).

supplementary crystallographic information

Comment

Sulfanilamide is a sulfonamide antibacterial. Chemically, it is a molecule containing the sulfonamide functional group attached to an aniline. As an antibiotic, it functions by competitively inhibiting (i.e, by acting as a substrate analogue) enzymatic reactions involving. Inhibition of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) with sulfonamides may be exploited clinically for the treatment and prevention of a multitude of diseases (Pastorekova et al., 2004; Supuran et al., 2004; Mann & Keilin, 1940). With the early report that sulfanilamide acts as an inhibitor of CA, a great scientific adventure initiated, leading to the development of several classes of drugs based on the sulfonamide motif.

Sulfonamides and their derivatives have been the subject of investigation for many reasons. The amides are important constituent of many biologically significant compounds. The chemistry of sulfonamides is of interest as they show distinct physical, chemical and biological properties. The sulfonamide derivatives are known for their numerous pharmacological activities, antibacterial, antitumor, insulin-release stimulation and antithyroid properties (Maren, 1976). In addition, the unsubstituted aromatic/heterocyclic sulfonamides act as carbonic anhydrase inhibitors (Supuran & Scozzafava, 2001; Türkmen et al., 2005; Supuran et al., 2003) whereas other types of derivatives show diuretic activity (high-ceiling diuretics or thiadiazine diuretics), hypoglycemic activity and anti- cancer properties (Supuran & Scozzafava, 2002). Although sulfonamides are best known as bacteriostatic (Silverman, 1992) and antimalarial agents (Albala et al., 1994), there is now a range of drugs, possessing very different pharmacological activities, in which the sulfonamide group is present (Reynolds, 1996). Due to their significant pharmacology applications and widespread use in medicine, these compounds have gained attention in bio-inorganic and metal-based drug chemistry. In this work we report the crystal structure of 3-chloro-N-(4-sulfamoylphenyl)propanamide.

In the title molecule (I), (Fig. 1), the S═O distances [1.4302 (14) and 1.4349 (16) Å] and the O═S═O angle [118.21 (9)°] are within the normal range as the values of the other geometric parameters of the molecule. The dihedral angle between the benzene ring and the amido –NHCO– plane is 15.0 (2)°.

The crystal structure is stabilized by N—H···O type hydrogen bonds (Table 1, Fig. 2). N1—H1A···O1 and N1—H1B···O3 generate the two-dimensional network (double layer structure), but N2—H2A···O2 links the layers into a three-dimensional network. An intramolecular hydrogen contact C3—H3···O3 generates a ring of graph-set motif S(6) (Bernstein et al., 1995) (Table 1). Furthermore, crystal packing is influenced by weak π–π stacking interactions between nearby aromatic rings of the adjacent molecules, [Cg···Cgiv = 3.7447 (12) Å; Cg is the centroid of the C1–C6 ring; symmetry code: (iv) 1 - x, 1 - y, 1 - z].

Experimental

Sulfanilamide (2.00 g, 0.011 mol) and N-ethylmaleimide (NEM) (1.566 g, 0.016 mol) were stirred in tetrahydrofuran (THF) (200 ml) until most of the starting material had dissolved. 3-Chloropropanoylchloride (1.782 g, 0.014 mol) in THF was slowly added to the reaction mixture. The reaction was stirred at 258 K for 4 h under anhydrous conditions. After warming to room temperature the white precipitate of NEM/HCl salt filtered off. The THF was removed in vacuo and the resulting white solid dissolved in ethyl acetate. The organic extract was washed with 3M hydrochloric acid (20 ml) then with saturated sodium bicarbonate solution (20 ml) and finally with brine. Drying over magnesium sulfate and evaporation yielded a white solid which was recrystallized from water to give the title compound (yield: 70%, m.p: 501–503 K).

Refinement

The H-atoms of the NH2 group were located in a difference Fourier map, and were refined with distance restraints of N—H = 0.86 (2) Å; their temperature factors were freely refined. The other H-atoms were placed in calculated positions with C—H = 0.93–0.97 Å and N—H = 0.86 Å, and were included in the refinement in the riding model approximation, with Uiso(H) = 1.2Ueq(C, N).

Figures

Fig. 1.
The title molecule with the atom numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 50% probability level.
Fig. 2.
The packing of the molecules of (I) linked by of N—H···O hydrogen bonds, viewed down the c axis. All hydrogen atoms not involved in hydrogen bonding have been omitted for clarity. Hydrogen bonds are indicated by dotted ...

Crystal data

C9H11ClN2O3SF(000) = 544
Mr = 262.72Dx = 1.562 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 8775 reflections
a = 7.7554 (4) Åθ = 2.1–28.0°
b = 14.8191 (8) ŵ = 0.52 mm1
c = 9.7482 (5) ÅT = 296 K
β = 94.181 (4)°Prism, colourless
V = 1117.36 (10) Å30.78 × 0.45 × 0.22 mm
Z = 4

Data collection

Stoe IPDS2 diffractometer2294 independent reflections
Radiation source: sealed X-ray tube, 12 x 0.4 mm long-fine focus2007 reflections with I > 2σ(I)
plane graphiteRint = 0.040
Detector resolution: 6.67 pixels mm-1θmax = 26.5°, θmin = 2.5°
ω scansh = −8→9
Absorption correction: integration (X-RED32; Stoe & Cie, 2002)k = −16→18
Tmin = 0.754, Tmax = 0.892l = −12→12
6023 measured reflections

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)] = 0.038Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.106H atoms treated by a mixture of independent and constrained refinement
S = 1.08w = 1/[σ2(Fo2) + (0.0602P)2 + 0.351P] where P = (Fo2 + 2Fc2)/3
2294 reflections(Δ/σ)max < 0.001
153 parametersΔρmax = 0.28 e Å3
2 restraintsΔρmin = −0.44 e Å3

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles
Refinement. Refinement on F2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The observed criterion of F2 > σ(F2) is used only for calculating -R-factor-obs 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
Cl10.18392 (12)−0.00186 (4)0.38004 (9)0.0791 (3)
S10.31196 (6)0.73280 (3)0.40392 (4)0.0330 (1)
O10.2882 (2)0.75787 (10)0.54296 (14)0.0471 (5)
O20.4665 (2)0.76199 (10)0.34461 (15)0.0445 (5)
O30.1258 (2)0.28706 (10)0.52407 (19)0.0571 (6)
N10.1520 (2)0.77368 (12)0.31092 (18)0.0398 (5)
N20.3009 (2)0.33382 (11)0.36141 (18)0.0419 (5)
C10.3044 (2)0.61415 (12)0.39403 (17)0.0331 (5)
C20.2424 (3)0.56420 (15)0.4978 (2)0.0499 (7)
C30.2372 (4)0.47119 (15)0.4898 (2)0.0530 (7)
C40.2965 (2)0.42797 (13)0.37652 (19)0.0360 (5)
C50.3592 (3)0.47919 (15)0.2722 (2)0.0508 (7)
C60.3617 (3)0.57169 (15)0.2792 (2)0.0488 (7)
C70.2202 (3)0.27011 (13)0.4329 (2)0.0389 (6)
C80.2583 (3)0.17489 (14)0.3889 (2)0.0448 (6)
C90.1263 (4)0.10957 (16)0.4265 (4)0.0725 (10)
H1A0.153 (4)0.7665 (17)0.2235 (18)0.053 (7)*
H1B0.055 (3)0.7636 (17)0.342 (3)0.051 (7)*
H20.203400.593100.574300.0600*
H2A0.363100.314000.298400.0500*
H30.194000.437700.560300.0640*
H50.400200.450500.196200.0610*
H60.401500.605500.207600.0590*
H8A0.265400.173700.290000.0540*
H8B0.369900.156700.431400.0540*
H9A0.015600.125200.380000.0870*
H9B0.114900.112300.524900.0870*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl10.1120 (6)0.0337 (3)0.0982 (6)−0.0094 (3)0.0520 (5)−0.0065 (3)
S10.0424 (3)0.0302 (2)0.0276 (2)−0.0060 (2)0.0106 (2)−0.0011 (2)
O10.0702 (10)0.0434 (8)0.0294 (7)−0.0105 (7)0.0146 (6)−0.0057 (5)
O20.0459 (8)0.0452 (8)0.0440 (8)−0.0140 (6)0.0142 (6)0.0000 (6)
O30.0628 (10)0.0383 (8)0.0757 (11)−0.0035 (7)0.0427 (9)−0.0018 (7)
N10.0471 (10)0.0372 (9)0.0367 (9)0.0024 (7)0.0131 (7)0.0019 (7)
N20.0504 (10)0.0315 (8)0.0466 (9)0.0014 (7)0.0233 (7)−0.0011 (7)
C10.0382 (10)0.0295 (9)0.0323 (8)0.0002 (7)0.0075 (7)0.0012 (6)
C20.0740 (15)0.0352 (10)0.0443 (11)0.0005 (10)0.0310 (10)0.0001 (8)
C30.0814 (16)0.0348 (11)0.0473 (11)0.0008 (11)0.0354 (11)0.0060 (9)
C40.0383 (10)0.0315 (9)0.0394 (9)0.0021 (8)0.0116 (8)0.0022 (7)
C50.0732 (15)0.0387 (10)0.0447 (11)−0.0035 (10)0.0323 (11)−0.0041 (9)
C60.0712 (15)0.0377 (10)0.0410 (10)−0.0061 (10)0.0278 (10)0.0009 (8)
C70.0385 (10)0.0335 (10)0.0461 (11)−0.0008 (8)0.0126 (8)0.0004 (8)
C80.0500 (12)0.0344 (10)0.0520 (11)−0.0010 (9)0.0176 (9)−0.0027 (8)
C90.0714 (18)0.0328 (11)0.118 (2)−0.0020 (12)0.0382 (17)−0.0012 (13)

Geometric parameters (Å, °)

Cl1—C91.778 (3)C3—C41.384 (3)
S1—O11.4302 (14)C4—C51.385 (3)
S1—O21.4349 (16)C5—C61.373 (3)
S1—N11.6012 (17)C7—C81.510 (3)
S1—C11.7617 (18)C8—C91.475 (4)
O3—C71.218 (3)C2—H20.9300
N2—C41.404 (3)C3—H30.9300
N2—C71.354 (3)C5—H50.9300
N1—H1A0.859 (18)C6—H60.9300
N1—H1B0.85 (2)C8—H8A0.9700
N2—H2A0.8600C8—H8B0.9700
C1—C21.369 (3)C9—H9A0.9700
C1—C61.385 (3)C9—H9B0.9700
C2—C31.381 (3)
Cl1···N1i3.3993 (19)C3···O32.889 (3)
Cl1···C9ii3.543 (3)C7···O2vi3.173 (3)
Cl1···H9Bii3.0400C8···O2vi3.372 (3)
S1···O1iii3.5128 (14)C9···Cl1ii3.543 (3)
O1···N1iv2.926 (2)C7···H32.7900
O1···S1iv3.5128 (14)C8···H6x3.0400
O1···O2iv3.171 (2)H1A···O1iii2.14 (2)
O2···N2v2.992 (2)H1A···H2iii2.5800
O2···C8vi3.372 (3)H1B···O3vii2.12 (3)
O2···O1iii3.171 (2)H2···O12.5500
O2···C7vi3.173 (3)H2···H1Aiv2.5800
O3···N1vii2.923 (2)H2A···H52.2800
O3···C32.889 (3)H2A···H8A2.2100
O1···H6iv2.6900H2A···O2x2.1300
O1···H1Aiv2.14 (2)H3···O32.3200
O1···H22.5500H3···C72.7900
O2···H8Av2.8600H5···H2A2.2800
O2···H62.7100H6···O22.7100
O2···H2Av2.1300H6···C8v3.0400
O2···H8Bvi2.7200H6···H8Bv2.4300
O3···H9A2.8800H6···O1iii2.6900
O3···H9B2.5900H8A···H2A2.2100
O3···H32.3200H8A···O2x2.8600
O3···H1Bvii2.12 (3)H8A···O3xi2.8000
O3···H8Aviii2.8000H8B···H6x2.4300
N1···Cl1ix3.3993 (19)H8B···O2vi2.7200
N1···O3vii2.923 (2)H9A···O32.8800
N1···O1iii2.926 (2)H9B···O32.5900
N2···O2x2.991 (2)H9B···Cl1ii3.0400
O1—S1—O2118.21 (9)N2—C7—C8113.46 (18)
O1—S1—N1106.87 (9)O3—C7—C8122.71 (18)
O1—S1—C1107.76 (8)C7—C8—C9112.9 (2)
O2—S1—N1107.05 (9)Cl1—C9—C8110.8 (2)
O2—S1—C1107.72 (8)C1—C2—H2120.00
N1—S1—C1108.98 (9)C3—C2—H2120.00
C4—N2—C7128.58 (17)C2—C3—H3120.00
S1—N1—H1A117 (2)C4—C3—H3120.00
S1—N1—H1B113.8 (19)C4—C5—H5120.00
H1A—N1—H1B114 (3)C6—C5—H5119.00
C4—N2—H2A116.00C1—C6—H6120.00
C7—N2—H2A116.00C5—C6—H6120.00
S1—C1—C2120.76 (14)C7—C8—H8A109.00
S1—C1—C6119.09 (14)C7—C8—H8B109.00
C2—C1—C6120.15 (18)C9—C8—H8A109.00
C1—C2—C3120.56 (19)C9—C8—H8B109.00
C2—C3—C4119.8 (2)H8A—C8—H8B108.00
N2—C4—C5117.07 (17)Cl1—C9—H9A109.00
C3—C4—C5119.15 (19)Cl1—C9—H9B109.00
N2—C4—C3123.77 (18)C8—C9—H9A110.00
C4—C5—C6121.01 (19)C8—C9—H9B109.00
C1—C6—C5119.32 (19)H9A—C9—H9B108.00
O3—C7—N2123.84 (18)
O1—S1—C1—C214.47 (18)C2—C1—C6—C5−1.5 (3)
O2—S1—C1—C2143.03 (16)C6—C1—C2—C30.4 (3)
N1—S1—C1—C2−101.16 (17)C1—C2—C3—C40.6 (4)
O1—S1—C1—C6−165.74 (15)C2—C3—C4—N2178.1 (2)
O2—S1—C1—C6−37.18 (17)C2—C3—C4—C5−0.5 (3)
N1—S1—C1—C678.63 (17)N2—C4—C5—C6−179.24 (19)
C7—N2—C4—C315.1 (3)C3—C4—C5—C6−0.6 (3)
C7—N2—C4—C5−166.4 (2)C4—C5—C6—C11.6 (3)
C4—N2—C7—O31.0 (3)O3—C7—C8—C921.5 (3)
C4—N2—C7—C8−178.99 (18)N2—C7—C8—C9−158.5 (2)
S1—C1—C2—C3−179.80 (19)C7—C8—C9—Cl1−177.00 (18)
S1—C1—C6—C5178.75 (17)

Symmetry codes: (i) x, y−1, z; (ii) −x, −y, −z+1; (iii) x, −y+3/2, z−1/2; (iv) x, −y+3/2, z+1/2; (v) −x+1, y+1/2, −z+1/2; (vi) −x+1, −y+1, −z+1; (vii) −x, −y+1, −z+1; (viii) x, −y+1/2, z+1/2; (ix) x, y+1, z; (x) −x+1, y−1/2, −z+1/2; (xi) x, −y+1/2, z−1/2.

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1A···O1iii0.859 (18)2.14 (2)2.926 (2)151 (3)
N1—H1B···O3vii0.85 (2)2.12 (3)2.923 (2)158 (3)
N2—H2A···O2x0.862.132.991 (2)175
C3—H3···O30.932.322.889 (3)120

Symmetry codes: (iii) x, −y+3/2, z−1/2; (vii) −x, −y+1, −z+1; (x) −x+1, y−1/2, −z+1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: IS2555).

References

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