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The title compound, C12H12N2O3S, is a strict pyridine analogue of nimesulide, a selective inhibitor of cyclooxygen­ase-2. The structure is characterized by a pyridinium ring with a deprotonated sulfon­amide group. An intermolecular charge-assisted hydrogen bond between these two groups is observed within the crystal packing, linking the mol­ecules into an infinite chain running along the b-axis direction.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270101018595/sk1503sup1.cif
Contains datablocks I, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270101018595/sk1503Isup2.hkl
Contains datablock I

CCDC reference: 182026

Comment top

N-(3-Phenoxy-4-pyridyl)methanesulfonamide, also known as FJ1, (I), a strict pyridine analogue of nimesulide, has been structurally studied to compare it with nimesulide, (II), a selective inhibitor of cyclooxygenase-2 (COX-2) (Dupont, Pirotte et al., 1995), and to try to understand its unexpected inactivity towards the cyclooxygenases (Julémont, 2001). \sch

The molecular structure of (I) is shown in Fig. 1. The pyridine group appears as a pyridinium nucleus and the sulfonamide group is deprotonated. Bond lengths and angles (Table 1), in particular C11—N10—C9 [120.59 (12)°, greater than in the pyridine ring, between 116 and 118°] and C13—N14 [1.354 (2) Å], agree with a zwitterionic structure where N14 is deprotonated and N10 protonated. Such a structure was also observed in a pyridylsulfonylcyanoguanidine compound, where the main bond lengths and angles are comparable (Dupont, Masereel et al., 1995).

A geometry optimization by an ab initio 6–31g* method at the B3LYP level using GAUSSIAN98 (Frisch et al., 1998) was performed on the zwitterionic form of (I), (a), and the neutral form, (b). The results are as follows: form (a) C—N—C 120.54° and C—N 1.313 Å; form (b) C—N—C 116.96° and C—N 1.401 Å. After optimization, the bond lengths and angles of (a) are the closest to those in the crystal structure. In nimesulide, where the sulfonamide group is not deprotonated, the C13—N14 bond length is longer [1.409 (4) Å] than that in (I) [1.354 (2) Å] because of the weaker delocalization.

Unlike nimesulide, (I) does not show any strong intramolecular hydrogen bonds. The crystal cohesion comes principally from van der Waals interactions and an intermolecular charge-assisted (Giacovazzo et al., 1992) and strongly directional N10—H10···N14 hydrogen bond (Table 2).

In the Cambridge Structural Database (CSD; Version 5.21; Allen & Kennard, 1993), 31 structures possess a pyridinium group and intermolecular hydrogen bonds are observed. Strongly directional hydrogen bonds are found in only nine structures; the others have weaker hydrogen bonds and less directionality. The acceptor changes from structure to structure and is either neutral or charged: –COO-, –CO-, –OH, –PO3H-, –N- or –N (pyridine group).

The crystal packing of (I) also involves four C—H···O interactions (Fig. 2) that may be classified as weak donor-strong acceptor hydrogen bonds (Desiraju & Steiner, 1999). Indeed, H···A lengths are between 2 and 3 Å, D···A lengths between 3 and 4 Å and X—H···A angles between 90 and 180° (Table 2). The two rings and the sulfone of (I) are involved in these. One of these is an intramolecular hydrogen bond (C12—H12···O16) that should partly contribute to the molecular conformation of the sulfonamide group of (I).

In conclusion, (I) appears structurally different from nimesulide in its zwitterionic form and its interactions within the crystal packing. Consequently,binding of (I) onto the COX-2 enzyme will be also different. The positive charge on the pyridine group would lead to unfavourable interaction. The loss of the intramolecular hydrogen bond in (I) induces a different position of the phenoxy group with regard to nimesulide.

Experimental top

Slow evaporation of a solution of (I) in methanol gave colourless crystals suitable for X-ray analysis.

Computing details top

Data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: CAD-4 Software; data reduction: HELENA (Spek, 1997); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 1990); software used to prepare material for publication: SHELXL97.

Figures top
[Figure 1] Fig. 1. A view of the molecular structure of (I) with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms have been omitted, except for N—H.
[Figure 2] Fig. 2. A packing diagram for (I), illustrating the hydrogen-bonding network.
N-(3-phenoxy-4-pyridyl)methanesulfonamide top
Crystal data top
C12H12N2O3SF(000) = 1104
Mr = 264.30Dx = 1.453 Mg m3
Orthorhombic, PbcaCu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ac 2abCell parameters from 25 reflections
a = 8.059 (1) Åθ = 30–40°
b = 12.116 (1) ŵ = 2.42 mm1
c = 24.744 (2) ÅT = 293 K
V = 2416.1 (4) Å3Needle, colourless
Z = 80.64 × 0.31 × 0.19 mm
Data collection top
Enraf-Nonius CAD-4
diffractometer
2257 reflections with I > 2σ(I)
Radiation source: long fine-focus sealed tubeRint = 0.011
Graphite monochromatorθmax = 71.9°, θmin = 3.6°
θ/2θ scansh = 99
Absorption correction: analytical
(North et al., 1968)
k = 014
Tmin = 0.306, Tmax = 0.656l = 030
4729 measured reflections3 standard reflections every 200 reflections
2366 independent reflections intensity decay: 3%
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.032All H-atom parameters refined
wR(F2) = 0.096 w = 1/[σ2(Fo2) + (0.0635P)2 + 0.4886P]
where P = (Fo2 + 2Fc2)/3
S = 1.07(Δ/σ)max = 0.001
2366 reflectionsΔρmax = 0.24 e Å3
212 parametersΔρmin = 0.31 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0029 (2)
Crystal data top
C12H12N2O3SV = 2416.1 (4) Å3
Mr = 264.30Z = 8
Orthorhombic, PbcaCu Kα radiation
a = 8.059 (1) ŵ = 2.42 mm1
b = 12.116 (1) ÅT = 293 K
c = 24.744 (2) Å0.64 × 0.31 × 0.19 mm
Data collection top
Enraf-Nonius CAD-4
diffractometer
2257 reflections with I > 2σ(I)
Absorption correction: analytical
(North et al., 1968)
Rint = 0.011
Tmin = 0.306, Tmax = 0.6563 standard reflections every 200 reflections
4729 measured reflections intensity decay: 3%
2366 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0320 restraints
wR(F2) = 0.096All H-atom parameters refined
S = 1.07Δρmax = 0.24 e Å3
2366 reflectionsΔρmin = 0.31 e Å3
212 parameters
Special details top

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) top
xyzUiso*/Ueq
C10.6341 (3)0.22801 (16)0.02154 (9)0.0642 (5)
C20.7231 (3)0.15945 (16)0.05550 (8)0.0601 (5)
C30.7953 (2)0.06568 (16)0.03440 (7)0.0565 (4)
C40.7806 (2)0.04045 (13)0.01998 (6)0.0475 (4)
C50.69306 (17)0.11064 (11)0.05346 (6)0.0374 (3)
C60.6196 (2)0.20474 (14)0.03275 (8)0.0536 (4)
O70.67108 (13)0.09362 (8)0.10838 (4)0.0404 (3)
C80.74286 (17)0.00172 (10)0.13191 (5)0.0330 (3)
C90.65682 (19)0.09512 (12)0.13105 (7)0.0429 (3)
N100.71742 (18)0.18453 (9)0.15635 (5)0.0461 (3)
C110.8617 (2)0.17949 (12)0.18302 (6)0.0465 (4)
C120.9512 (2)0.08399 (11)0.18597 (6)0.0407 (3)
C130.89577 (16)0.01331 (10)0.15974 (5)0.0301 (3)
N140.97024 (14)0.11339 (8)0.15794 (4)0.0324 (3)
S151.13367 (4)0.13824 (3)0.193283 (12)0.03378 (15)
O161.12025 (13)0.09799 (9)0.24791 (4)0.0439 (3)
O171.16398 (16)0.25480 (9)0.18717 (4)0.0504 (3)
C181.3016 (2)0.06796 (18)0.16336 (8)0.0565 (4)
H90.555 (3)0.1052 (16)0.1134 (7)0.051 (5)*
H121.044 (2)0.0837 (15)0.2055 (7)0.046 (4)*
H60.559 (3)0.2483 (18)0.0572 (8)0.068 (6)*
H30.862 (3)0.0198 (19)0.0583 (9)0.068 (6)*
H40.830 (3)0.0222 (18)0.0340 (8)0.060 (5)*
H10.584 (4)0.295 (2)0.0362 (11)0.091 (8)*
H20.729 (3)0.1757 (19)0.0926 (9)0.071 (6)*
H18A1.399 (3)0.082 (2)0.1859 (9)0.080 (7)*
H18B1.317 (3)0.095 (2)0.1277 (10)0.074 (7)*
H110.899 (2)0.2409 (18)0.1997 (7)0.052 (5)*
H18C1.269 (4)0.014 (2)0.1650 (9)0.086 (7)*
H100.651 (3)0.247 (2)0.1541 (9)0.071 (6)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0764 (13)0.0436 (9)0.0727 (12)0.0033 (8)0.0258 (9)0.0143 (8)
C20.0692 (12)0.0586 (10)0.0523 (9)0.0138 (9)0.0179 (8)0.0100 (8)
C30.0609 (10)0.0587 (10)0.0500 (9)0.0022 (8)0.0063 (7)0.0035 (8)
C40.0534 (9)0.0394 (7)0.0498 (8)0.0096 (6)0.0075 (7)0.0012 (6)
C50.0342 (6)0.0296 (6)0.0485 (7)0.0003 (5)0.0111 (6)0.0003 (5)
C60.0588 (10)0.0356 (8)0.0664 (11)0.0109 (7)0.0153 (8)0.0002 (7)
O70.0426 (5)0.0286 (5)0.0501 (6)0.0107 (4)0.0051 (4)0.0029 (4)
C80.0368 (6)0.0216 (6)0.0405 (6)0.0024 (5)0.0020 (5)0.0014 (5)
C90.0397 (7)0.0312 (7)0.0577 (9)0.0052 (5)0.0041 (6)0.0087 (6)
N100.0581 (8)0.0220 (5)0.0581 (7)0.0103 (5)0.0114 (6)0.0033 (5)
C110.0758 (11)0.0205 (6)0.0432 (7)0.0001 (6)0.0033 (7)0.0054 (5)
C120.0559 (9)0.0232 (6)0.0428 (7)0.0021 (6)0.0087 (6)0.0041 (5)
C130.0374 (6)0.0197 (6)0.0332 (6)0.0009 (5)0.0037 (5)0.0000 (4)
N140.0361 (6)0.0196 (5)0.0415 (6)0.0004 (4)0.0013 (4)0.0021 (4)
S150.0371 (2)0.0272 (2)0.0370 (2)0.00319 (11)0.00110 (11)0.00497 (11)
O160.0584 (7)0.0361 (5)0.0372 (5)0.0017 (4)0.0028 (4)0.0033 (4)
O170.0632 (7)0.0316 (6)0.0564 (6)0.0170 (5)0.0009 (5)0.0021 (4)
C180.0377 (8)0.0718 (12)0.0600 (10)0.0033 (8)0.0017 (7)0.0227 (9)
Geometric parameters (Å, º) top
C1—C61.377 (3)C9—H90.94 (2)
C1—C21.382 (3)N10—C111.338 (2)
C1—H10.97 (3)N10—H100.92 (2)
C2—C31.379 (3)C11—C121.366 (2)
C2—H20.94 (2)C11—H110.90 (2)
C3—C41.385 (2)C12—C131.418 (2)
C3—H30.97 (2)C12—H120.893 (19)
C4—C51.381 (2)C13—N141.354 (2)
C4—H40.92 (2)N14—S151.6094 (11)
C5—C61.383 (2)S15—O161.4411 (10)
C5—O71.3859 (17)S15—O171.4412 (11)
C6—H60.94 (2)S15—C181.7623 (17)
O7—C81.3833 (15)C18—H18A0.98 (3)
C8—C91.363 (2)C18—H18B0.95 (2)
C8—C131.418 (2)C18—H18C1.03 (3)
C9—N101.343 (2)
C6—C1—C2120.93 (16)C11—N10—C9120.6 (1)
C6—C1—H1119.8 (16)C11—N10—H10124.5 (14)
C2—C1—H1119.2 (16)C9—N10—H10114.9 (14)
C3—C2—C1118.94 (17)N10—C11—C12121.61 (14)
C3—C2—H2121.4 (15)N10—C11—H11118.6 (13)
C1—C2—H2119.6 (14)C12—C11—H11119.8 (13)
C2—C3—C4120.88 (17)C11—C12—C13120.89 (14)
C2—C3—H3118.3 (13)C11—C12—H12118.4 (12)
C4—C3—H3120.8 (13)C13—C12—H12120.7 (12)
C5—C4—C3119.40 (15)N14—C13—C12128.31 (12)
C5—C4—H4119.9 (13)N14—C13—C8117.26 (11)
C3—C4—H4120.7 (13)C12—C13—C8114.43 (12)
C4—C5—C6120.26 (15)C13—N14—S15120.84 (9)
C4—C5—O7124.19 (12)O16—S15—O17116.28 (6)
C6—C5—O7115.55 (14)O16—S15—N14112.64 (6)
C1—C6—C5119.58 (17)O17—S15—N14105.37 (6)
C1—C6—H6123.9 (13)O16—S15—C18106.76 (9)
C5—C6—H6116.5 (13)O17—S15—C18107.41 (9)
C8—O7—C5118.63 (10)N14—S15—C18108.05 (7)
C9—C8—O7118.27 (13)S15—C18—H18A107.2 (15)
C9—C8—C13122.33 (12)S15—C18—H18B108.9 (15)
O7—C8—C13119.20 (11)H18A—C18—H18B111 (2)
N10—C9—C8120.14 (14)S15—C18—H18C104.7 (16)
N10—C9—H9115.5 (12)H18A—C18—H18C110 (2)
C8—C9—H9124.4 (12)H18B—C18—H18C113.7 (19)
C6—C1—C2—C31.1 (3)C8—C9—N10—C110.6 (2)
C1—C2—C3—C40.5 (3)C9—N10—C11—C120.6 (2)
C2—C3—C4—C50.4 (3)N10—C11—C12—C131.3 (2)
C3—C4—C5—C60.6 (2)C11—C12—C13—N14178.87 (14)
C3—C4—C5—O7179.77 (14)C11—C12—C13—C80.8 (2)
C2—C1—C6—C50.9 (3)C9—C8—C13—N14179.88 (12)
C4—C5—C6—C10.0 (2)O7—C8—C13—N145.20 (17)
O7—C5—C6—C1179.63 (15)C9—C8—C13—C120.44 (19)
C4—C5—O7—C81.08 (19)O7—C8—C13—C12175.13 (11)
C6—C5—O7—C8179.28 (13)C12—C13—N14—S156.85 (19)
C5—O7—C8—C986.36 (15)C8—C13—N14—S15173.52 (9)
C5—O7—C8—C1398.74 (14)C13—N14—S15—O1644.58 (12)
O7—C8—C9—N10175.86 (12)C13—N14—S15—O17172.32 (10)
C13—C8—C9—N101.1 (2)C13—N14—S15—C1873.10 (13)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N10—H10···N14i0.93 (2)1.96 (2)2.878 (2)172 (2)
C2—H2···O17ii0.94 (2)2.54 (2)3.453 (2)163 (2)
C11—H11···O16iii0.90 (2)2.35 (2)3.195 (2)156 (1)
C12—H12···O160.89 (2)2.51 (2)3.011 (2)116 (1)
C18—H18A···O16iv0.98 (2)2.43 (2)3.398 (2)171 (2)
Symmetry codes: (i) x+3/2, y1/2, z; (ii) x1/2, y+1/2, z; (iii) x+2, y1/2, z+1/2; (iv) x+1/2, y, z+1/2.

Experimental details

Crystal data
Chemical formulaC12H12N2O3S
Mr264.30
Crystal system, space groupOrthorhombic, Pbca
Temperature (K)293
a, b, c (Å)8.059 (1), 12.116 (1), 24.744 (2)
V3)2416.1 (4)
Z8
Radiation typeCu Kα
µ (mm1)2.42
Crystal size (mm)0.64 × 0.31 × 0.19
Data collection
DiffractometerEnraf-Nonius CAD-4
diffractometer
Absorption correctionAnalytical
(North et al., 1968)
Tmin, Tmax0.306, 0.656
No. of measured, independent and
observed [I > 2σ(I)] reflections
4729, 2366, 2257
Rint0.011
(sin θ/λ)max1)0.616
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.032, 0.096, 1.07
No. of reflections2366
No. of parameters212
H-atom treatmentAll H-atom parameters refined
Δρmax, Δρmin (e Å3)0.24, 0.31

Computer programs: CAD-4 Software (Enraf-Nonius, 1989), CAD-4 Software, HELENA (Spek, 1997), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 1990), SHELXL97.

Selected geometric parameters (Å, º) top
C8—C91.363 (2)C11—C121.366 (2)
C8—C131.418 (2)C12—C131.418 (2)
C9—N101.343 (2)C13—N141.354 (2)
N10—C111.338 (2)
C11—N10—C9120.6 (1)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N10—H10···N14i0.93 (2)1.96 (2)2.878 (2)172 (2)
C2—H2···O17ii0.94 (2)2.54 (2)3.453 (2)163 (2)
C11—H11···O16iii0.90 (2)2.35 (2)3.195 (2)156 (1)
C12—H12···O160.89 (2)2.51 (2)3.011 (2)116 (1)
C18—H18A···O16iv0.98 (2)2.43 (2)3.398 (2)171 (2)
Symmetry codes: (i) x+3/2, y1/2, z; (ii) x1/2, y+1/2, z; (iii) x+2, y1/2, z+1/2; (iv) x+1/2, y, z+1/2.
Selected bond lengths and angles in the (a) and (b) forms of (I) after geometry optimisation in 6-31g*. top
C-N-C (°)C-N (Å)
(a)120.541.313
(b)116.961.401
 

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