PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2010 October 1; 66(Pt 10): o2663.
Published online 2010 September 30. doi:  10.1107/S1600536810038158
PMCID: PMC2983257

4-Amino-N-(3-meth­oxy­pyrazin-2-yl)benzene­sulfonamide

Abstract

The overall mol­ecular geometry of the title compound, C11H12N4O3S, is bent, with a dihedral angle of 89.24 (5)° between the best planes through the two aromatic rings. Each mol­ecule behaves as a hydrogen-bond donor toward three different mol­ecules, through its amidic and the two aminic H atoms, and it behaves as a hydrogen-bond acceptor from two other mol­ecules via one of its sulfonamidic O atoms. In the crystal, mol­ecules linked by N—H(...)N and N—H(...)O hydrogen bonds form kinked layers parallel to (001), adjacent layers being connected by van der Waals inter­actions.

Related literature

The title compound is a prolonged-action drug known as sulfameth­oxy­pyrazine or sulfalene, traditionally used for the treatment of urinary tract infections and chronic bronchitis. It is also presently employed in combination with other drugs for the treatment of malaria and other diseases. For the pharmacological applications of the title compound, see: Adam & Hagelnur (2009 [triangle]); Penali & Jansen (2008 [triangle]). For the structure of a related anti­cancer drug, see: Liu et al. (1994 [triangle]). For hydrogen-bond motifs, see: Bernstein et al. (1995 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o2663-scheme1.jpg

Experimental

Crystal data

  • C11H12N4O3S
  • M r = 280.31
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-66-o2663-efi1.jpg
  • a = 10.7589 (2) Å
  • b = 9.5652 (2) Å
  • c = 24.5586 (4) Å
  • V = 2527.35 (8) Å3
  • Z = 8
  • Cu Kα radiation
  • μ = 2.40 mm−1
  • T = 150 K
  • 0.60 × 0.10 × 0.10 mm

Data collection

  • Oxford Diffraction Xcalibur PX Ultra CCD diffractometer
  • Absorption correction: multi-scan (ABSPACK; Oxford Diffraction, 2006 [triangle]) T min = 0.477, T max = 1.000
  • 5771 measured reflections
  • 2373 independent reflections
  • 2103 reflections with I > 2σ(I)
  • R int = 0.016

Refinement

  • R[F 2 > 2σ(F 2)] = 0.032
  • wR(F 2) = 0.103
  • S = 1.14
  • 2373 reflections
  • 184 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.29 e Å−3
  • Δρmin = −0.41 e Å−3

Data collection: CrysAlis PRO CCD (Oxford Diffraction, 2006 [triangle]); cell refinement: CrysAlis PRO CCD; data reduction: CrysAlis PRO RED (Oxford Diffraction, 2006 [triangle]); program(s) used to solve structure: SIR2004 (Burla et al., 2005 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 (Farrugia, 1997 [triangle]) and PLATON (Spek, 2009 [triangle]); software used to prepare material for publication: SHELXL97, WinGX (Farrugia, 1999 [triangle]) and PARST (Nardelli, 1995 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810038158/fl2318sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810038158/fl2318Isup2.hkl

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

Acknowledgments

The authors acknowledge financial support from the Italian Ministero dell’Istruzione, dell’Universitá e della Ricerca. The availability of diffraction facilities at the CRIST Centre of the University of Florence is also acknowledged.

supplementary crystallographic information

Comment

The title compound (I), a drug known as sulfamethoxypyrazine or sulfalene, has been in use for a long time in the treatment of urinary tract infections and chronic bronchitis. Recently, due to the onset of Plasmodium falciparum resistance to many antimalarial drugs (e.g. chloroquine), the use of sulfamethoxypyrazine in combination with the dihydrofolate reductase inhibitor pyrimethamine has acquired great importance (Penali & Jansen, 2008). These formulations are also being tested against other deseases, like cutaneous leishmaniasis (Adam & Hagelnur, 2009).

In the structure of I there is one molecule of the title compound in the asymmetric unit of the orthorhombic unit cell. As a consequence of the arrangement of bonds around the sulfur atom, the overall molecular geometry is bent (Fig. 1), with an 89.24 (5) ° angle between the best planes through the two aromatic rings. The amidic N—H bond is almost parallel to the pyrazine plane, the H atom deviating by 0.28 (2) Å from that plane, and the plane of the aminic group is almost parallel to that of the phenyl ring, forming a 12 (2) ° angle with it. Each molecule behaves as a hydrogen bond donor toward three different molecules, through its amidic and the two aminic H atoms, and it behaves as a hydrogen bond acceptor from two other molecules via one of its sulfonamidic O atoms. The N—H···N and N—H···O interactions generate, respectively, a C(5) motif and a C21(4) binary graph set (Bernstein et al., 1995). Kinked layers of hydrogen–bonded molecules parallel to (001) are formed (Fig. 2), with no additional hydrogen bond interactions between layers. The structure of a somewhat related anticancer drug has been reported (Liu et al., 1994).

Experimental

Samples of I were kindly provided by SIMS (SIMS srl, Reggello, Firenze, Italy). Crystals of the compound, suitable for X-ray diffraction analysis, were obtained by slow evaporation from 1:1 ethanol:butanol solutions.

Refinement

In the final refinement cycles non-hydrogen atoms were assigned anisotropic thermal parameters and H atoms had Uiso(H) = 1.2 Ueq(C, N), or Uiso(H) = 1.5 Ueq(C) for methyl H atoms. Hydrogen atoms were placed in geometrically generated positions, riding, except for those linked to nitrogen atoms, whose positions were allowed to refine (final values: 0.85 (2) Å for amidic N—H and 0.90 (3)–0.91 (3) Å range for aminic N—H bonds), and for the methyl H atoms, which were refined as part of a group with idealized geometry, freely rotating about the C—C bond. Assigned C—H: aromatic CH 0.950 Å; primary CH 0.952 Å.

Figures

Fig. 1.
A view of the molecule forming the asymmetric unit of the title compound. Displacement ellipsoids are drawn at the 30% probability level.
Fig. 2.
The arrangement of molecules in the structure of I, viewed along the b direction. Only hydrogen atoms involved in the formation of hydrogen bonds are shown for clarity. Hydrogen bonds are denoted by dashed lines.

Crystal data

C11H12N4O3SF(000) = 1168
Mr = 280.31Dx = 1.473 Mg m3
Orthorhombic, PbcaCu Kα radiation, λ = 1.54180 Å
Hall symbol: -P 2ac 2abCell parameters from 4106 reflections
a = 10.7589 (2) Åθ = 4.5–71.1°
b = 9.5652 (2) ŵ = 2.40 mm1
c = 24.5586 (4) ÅT = 150 K
V = 2527.35 (8) Å3Elongated prism, colourless
Z = 80.60 × 0.10 × 0.10 mm

Data collection

Oxford Diffraction Xcalibur PX Ultra CCD diffractometer2373 independent reflections
Radiation source: fine-focus sealed tube2103 reflections with I > 2σ(I)
Oxford Diffraction, Enhance ULTRA assemblyRint = 0.016
Detector resolution: 8.1241 pixels mm-1θmax = 71.2°, θmin = 5.5°
ω scansh = −8→12
Absorption correction: multi-scan (ABSPACK; Oxford Diffraction, 2006)k = −7→11
Tmin = 0.477, Tmax = 1.000l = −28→29
5771 measured reflections

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.032H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.103w = 1/[σ2(Fo2) + (0.0536P)2 + 1.4166P] where P = (Fo2 + 2Fc2)/3
S = 1.14(Δ/σ)max = 0.001
2373 reflectionsΔρmax = 0.29 e Å3
184 parametersΔρmin = −0.41 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.00110 (16)

Special details

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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
S0.45913 (4)0.21136 (4)0.376497 (16)0.01994 (17)
O10.59274 (13)0.21818 (13)0.37730 (5)0.0254 (3)
O20.40093 (12)0.07918 (13)0.38690 (5)0.0263 (3)
N30.40614 (15)0.31297 (15)0.42568 (6)0.0221 (3)
H3N0.340 (2)0.283 (2)0.4404 (9)0.026*
C10.42548 (17)0.45781 (18)0.42714 (7)0.0217 (4)
C20.34037 (17)0.53944 (18)0.45771 (7)0.0214 (4)
N10.34155 (15)0.67589 (16)0.45622 (6)0.0258 (4)
C30.43419 (19)0.7358 (2)0.42669 (8)0.0299 (4)
H30.43770.83470.42390.036*
C40.52204 (19)0.6575 (2)0.40095 (9)0.0321 (5)
H40.58850.70350.38280.039*
N20.51757 (14)0.51529 (17)0.40040 (7)0.0272 (4)
O30.25850 (12)0.46696 (12)0.48767 (5)0.0255 (3)
C50.1764 (2)0.5454 (2)0.52249 (8)0.0326 (5)
H510.1171 (12)0.5941 (15)0.5008 (3)0.049*
H520.2235 (7)0.6108 (14)0.5432 (5)0.049*
H530.1343 (12)0.4832 (9)0.5465 (5)0.049*
C60.40661 (16)0.27630 (17)0.31414 (7)0.0209 (4)
C70.47006 (16)0.3858 (2)0.28819 (8)0.0242 (4)
H70.54090.42670.30490.029*
C80.42941 (17)0.43368 (19)0.23848 (7)0.0252 (4)
H80.47230.50830.22120.030*
C90.32573 (16)0.37426 (18)0.21290 (7)0.0230 (4)
C100.26457 (17)0.2631 (2)0.23915 (7)0.0262 (4)
H100.19530.22010.22200.031*
C110.30361 (17)0.21565 (18)0.28935 (8)0.0250 (4)
H110.26030.14180.30690.030*
N40.28793 (16)0.42195 (19)0.16322 (6)0.0282 (4)
H410.321 (2)0.501 (3)0.1502 (10)0.034*
H420.219 (2)0.387 (2)0.1469 (10)0.034*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S0.0234 (3)0.0165 (2)0.0200 (2)0.00331 (15)0.00297 (15)0.00145 (15)
O10.0264 (7)0.0259 (7)0.0240 (7)0.0062 (5)0.0027 (5)0.0034 (5)
O20.0363 (8)0.0165 (6)0.0262 (6)0.0009 (5)0.0048 (6)0.0012 (5)
N30.0267 (8)0.0169 (7)0.0225 (7)−0.0006 (6)0.0063 (6)−0.0002 (6)
C10.0259 (9)0.0183 (8)0.0209 (8)−0.0016 (7)−0.0015 (7)0.0012 (7)
C20.0265 (9)0.0189 (8)0.0189 (8)−0.0013 (7)−0.0027 (7)0.0007 (7)
N10.0320 (8)0.0175 (7)0.0278 (8)−0.0020 (6)−0.0023 (6)−0.0015 (6)
C30.0345 (10)0.0197 (9)0.0353 (10)−0.0051 (8)−0.0028 (8)−0.0001 (8)
C40.0319 (10)0.0261 (10)0.0385 (11)−0.0091 (8)0.0046 (8)0.0001 (9)
N20.0278 (8)0.0221 (8)0.0316 (9)−0.0051 (6)0.0046 (7)−0.0007 (7)
O30.0325 (7)0.0194 (6)0.0244 (6)0.0011 (5)0.0081 (5)−0.0001 (5)
C50.0431 (12)0.0291 (10)0.0255 (9)0.0060 (9)0.0122 (9)−0.0003 (8)
C60.0233 (9)0.0178 (8)0.0216 (9)0.0022 (6)0.0021 (7)0.0015 (7)
C70.0220 (9)0.0251 (9)0.0255 (9)−0.0018 (7)−0.0018 (7)0.0021 (8)
C80.0249 (9)0.0249 (9)0.0258 (9)−0.0021 (7)0.0008 (7)0.0048 (8)
C90.0241 (9)0.0228 (9)0.0222 (8)0.0029 (7)0.0010 (7)−0.0001 (7)
C100.0255 (9)0.0246 (9)0.0285 (9)−0.0037 (8)−0.0027 (8)−0.0002 (8)
C110.0263 (9)0.0205 (9)0.0282 (9)−0.0013 (7)0.0019 (7)0.0027 (7)
N40.0276 (8)0.0325 (9)0.0247 (8)−0.0050 (7)−0.0044 (7)0.0057 (7)

Geometric parameters (Å, °)

S—O21.4338 (13)C5—H510.9522
S—O11.4392 (14)C5—H520.9522
S—N31.6519 (15)C5—H530.9522
S—C61.7466 (17)C6—C111.391 (3)
N3—C11.401 (2)C6—C71.403 (3)
N3—H3N0.85 (2)C7—C81.375 (3)
C1—N21.310 (2)C7—H70.9500
C1—C21.418 (3)C8—C91.401 (3)
C2—N11.306 (2)C8—H80.9500
C2—O31.341 (2)C9—N41.365 (2)
N1—C31.359 (3)C9—C101.407 (3)
C3—C41.361 (3)C10—C111.379 (3)
C3—H30.9500C10—H100.9500
C4—N21.361 (3)C11—H110.9500
C4—H40.9500N4—H410.90 (3)
O3—C51.440 (2)N4—H420.91 (3)
O2—S—O1118.28 (8)H51—C5—H52109.5
O2—S—N3103.76 (8)O3—C5—H53109.5
O1—S—N3107.94 (8)H51—C5—H53109.5
O2—S—C6109.19 (8)H52—C5—H53109.5
O1—S—C6108.60 (8)C11—C6—C7120.01 (16)
N3—S—C6108.68 (8)C11—C6—S119.54 (13)
C1—N3—S123.30 (13)C7—C6—S120.41 (14)
C1—N3—H3N116.6 (15)C8—C7—C6119.81 (17)
S—N3—H3N113.7 (15)C8—C7—H7120.1
N2—C1—N3120.97 (16)C6—C7—H7120.1
N2—C1—C2121.51 (16)C7—C8—C9121.07 (17)
N3—C1—C2117.51 (16)C7—C8—H8119.5
N1—C2—O3122.59 (16)C9—C8—H8119.5
N1—C2—C1121.94 (17)N4—C9—C8120.18 (17)
O3—C2—C1115.46 (15)N4—C9—C10121.54 (17)
C2—N1—C3116.31 (17)C8—C9—C10118.27 (16)
N1—C3—C4121.68 (18)C11—C10—C9121.07 (17)
N1—C3—H3119.2C11—C10—H10119.5
C4—C3—H3119.2C9—C10—H10119.5
N2—C4—C3121.98 (18)C10—C11—C6119.76 (17)
N2—C4—H4119.0C10—C11—H11120.1
C3—C4—H4119.0C6—C11—H11120.1
C1—N2—C4116.19 (17)C9—N4—H41118.9 (15)
C2—O3—C5117.34 (14)C9—N4—H42121.1 (15)
O3—C5—H51109.5H41—N4—H42118 (2)
O3—C5—H52109.5
O2—S—N3—C1−170.84 (15)C1—C2—O3—C5175.49 (16)
O1—S—N3—C162.86 (16)O2—S—C6—C1113.30 (17)
C6—S—N3—C1−54.74 (17)O1—S—C6—C11143.57 (14)
S—N3—C1—N2−22.2 (2)N3—S—C6—C11−99.25 (15)
S—N3—C1—C2156.57 (13)O2—S—C6—C7−164.57 (14)
N2—C1—C2—N17.2 (3)O1—S—C6—C7−34.30 (17)
N3—C1—C2—N1−171.57 (16)N3—S—C6—C782.88 (16)
N2—C1—C2—O3−173.32 (16)C11—C6—C7—C80.6 (3)
N3—C1—C2—O37.9 (2)S—C6—C7—C8178.47 (14)
O3—C2—N1—C3176.25 (16)C6—C7—C8—C9−0.5 (3)
C1—C2—N1—C3−4.4 (3)C7—C8—C9—N4−179.05 (17)
C2—N1—C3—C4−1.1 (3)C7—C8—C9—C10−0.5 (3)
N1—C3—C4—N24.3 (3)N4—C9—C10—C11179.95 (17)
N3—C1—N2—C4174.85 (17)C8—C9—C10—C111.5 (3)
C2—C1—N2—C4−3.9 (3)C9—C10—C11—C6−1.3 (3)
C3—C4—N2—C1−1.5 (3)C7—C6—C11—C100.3 (3)
N1—C2—O3—C5−5.1 (2)S—C6—C11—C10−177.59 (14)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N3—H3N···N1i0.85 (2)2.24 (2)3.063 (2)164 (2)
N4—H42···O1ii0.91 (3)2.19 (3)3.033 (2)154 (2)
N4—H41···O1iii0.90 (3)2.37 (3)3.266 (2)176 (2)

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: FL2318).

References

  • Adam, I. & Hagelnur, A. A. (2009). Int. J. Antimicrob. Agents, 34, 380–381. [PubMed]
  • Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl.34, 1555–1573.
  • Burla, M. C., Caliandro, R., Camalli, M., Carrozzini, B., Cascarano, G. L., De Caro, L., Giacovazzo, C., Polidori, G. & Spagna, R. (2005). J. Appl. Cryst.38, 381–388.
  • Farrugia, L. J. (1997). J. Appl. Cryst.30, 565.
  • Farrugia, L. J. (1999). J. Appl. Cryst.32, 837–838.
  • Liu, M., Ruble, J. R. & Arora, S. K. (1994). Acta Cryst. C50, 2032–2033.
  • Nardelli, M. (1995). J. Appl. Cryst.28, 659.
  • Oxford Diffraction (2006). CrysAlis PRO CCD and CrysAlis PRO RED (including ABSPACK). Oxford Diffraction Ltd, Abingdon,England.
  • Penali, L. K. & Jansen, F. H. (2008). Int. J. Infect. Dis 12, 430–437. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography