Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536801015823/wn6057sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536801015823/wn6057Isup2.hkl |
CCDC reference: 175998
Crystal source: slow evaporation of a solution of FJ6 with methanol at 277 K gave colorless crystals suitable for X-ray analysis.
Data collection: CAD-4 EXPRESS (Enraf-Nonius, 1992); cell refinement: CAD-4 EXPRESS; data reduction: PLATON (Spek, 2001); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON; software used to prepare material for publication: SHELXL97.
Fig. 1. Displacement ellipsoid (50% probability) representation of FJ6. | |
Fig. 2. Superposition of nimesulide (in black) and FJ6 (in grey). |
C14H14N2O5S | F(000) = 672 |
Mr = 322.33 | Dx = 1.423 Mg m−3 |
Monoclinic, P21/c | Cu Kα radiation, λ = 1.54178 Å |
a = 14.522 (1) Å | Cell parameters from 24 reflections |
b = 10.439 (1) Å | θ = 32–40° |
c = 10.523 (1) Å | µ = 2.16 mm−1 |
β = 109.460 (4)° | T = 293 K |
V = 1504.1 (2) Å3 | Polyhedral, colorless |
Z = 4 | 0.46 × 0.36 × 0.15 mm |
Nonius diffractometer | 2747 reflections with I > 2σ(I) |
Radiation source: long fine-focus sealed tube | Rint = 0.034 |
Graphite monochromator | θmax = 71.9°, θmin = 3.2° |
ω/θ scans | h = −17→0 |
Absorption correction: analytical (de Meulenaer & Tompa, 1965) | k = −11→12 |
Tmin = 0.411, Tmax = 0.743 | l = −12→12 |
5119 measured reflections | 3 standard reflections every 200 reflections |
2951 independent reflections | intensity decay: 5% |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.041 | H-atom parameters constrained |
wR(F2) = 0.118 | w = 1/[σ2(Fo2) + (0.061P)2 + 0.373P] where P = (Fo2 + 2Fc2)/3 |
S = 1.05 | (Δ/σ)max = 0.005 |
2951 reflections | Δρmax = 0.23 e Å−3 |
203 parameters | Δρmin = −0.31 e Å−3 |
0 restraints | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0139 (8) |
C14H14N2O5S | V = 1504.1 (2) Å3 |
Mr = 322.33 | Z = 4 |
Monoclinic, P21/c | Cu Kα radiation |
a = 14.522 (1) Å | µ = 2.16 mm−1 |
b = 10.439 (1) Å | T = 293 K |
c = 10.523 (1) Å | 0.46 × 0.36 × 0.15 mm |
β = 109.460 (4)° |
Nonius diffractometer | 2747 reflections with I > 2σ(I) |
Absorption correction: analytical (de Meulenaer & Tompa, 1965) | Rint = 0.034 |
Tmin = 0.411, Tmax = 0.743 | 3 standard reflections every 200 reflections |
5119 measured reflections | intensity decay: 5% |
2951 independent reflections |
R[F2 > 2σ(F2)] = 0.041 | 0 restraints |
wR(F2) = 0.118 | H-atom parameters constrained |
S = 1.05 | Δρmax = 0.23 e Å−3 |
2951 reflections | Δρmin = −0.31 e Å−3 |
203 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
S19 | 0.09820 (3) | 0.39270 (5) | 0.16659 (4) | 0.05765 (19) | |
O21 | 0.04416 (12) | 0.27815 (16) | 0.12467 (17) | 0.0850 (5) | |
O7 | 0.22028 (10) | 0.50640 (18) | 0.50900 (13) | 0.0797 (5) | |
O16 | 0.51319 (13) | 0.77639 (18) | 0.56081 (16) | 0.0869 (5) | |
O15 | 0.55160 (14) | 0.7375 (2) | 0.38477 (18) | 0.0973 (6) | |
O20 | 0.12730 (11) | 0.4642 (2) | 0.07183 (15) | 0.0857 (5) | |
N17 | 0.19856 (10) | 0.35423 (14) | 0.28886 (15) | 0.0552 (4) | |
N14 | 0.50130 (11) | 0.71966 (16) | 0.45550 (16) | 0.0618 (4) | |
C10 | 0.42369 (11) | 0.62339 (16) | 0.41260 (16) | 0.0491 (4) | |
C12$ | 0.33644 (13) | 0.46585 (18) | 0.25715 (17) | 0.0542 (4) | |
C8 | 0.28922 (11) | 0.52039 (17) | 0.44807 (16) | 0.0504 (4) | |
C13 | 0.27459 (11) | 0.44752 (16) | 0.33146 (15) | 0.0469 (3) | |
C9 | 0.36518 (12) | 0.60666 (17) | 0.49095 (16) | 0.0521 (4) | |
H9 | 0.3766 | 0.6523 | 0.5706 | 0.063* | |
C11 | 0.41069 (13) | 0.55540 (19) | 0.29531 (17) | 0.0563 (4) | |
H11 | 0.4507 | 0.5695 | 0.2436 | 0.068* | |
C3 | 0.31187 (16) | 0.4931 (2) | 0.7455 (2) | 0.0681 (5) | |
H3 | 0.3537 | 0.4333 | 0.7283 | 0.082* | |
C4 | 0.23891 (13) | 0.54821 (19) | 0.64109 (17) | 0.0567 (4) | |
C22 | 0.03142 (16) | 0.4925 (3) | 0.2367 (3) | 0.0801 (6) | |
H22A | 0.0673 | 0.5701 | 0.2678 | 0.120* | |
H22B | 0.0205 | 0.4496 | 0.3112 | 0.120* | |
H22C | −0.0302 | 0.5125 | 0.1697 | 0.120* | |
C1 | 0.26067 (18) | 0.6124 (2) | 0.9017 (2) | 0.0724 (6) | |
H1 | 0.2673 | 0.6329 | 0.9903 | 0.087* | |
C2 | 0.32242 (18) | 0.5271 (2) | 0.8760 (2) | 0.0719 (5) | |
H2 | 0.3724 | 0.4913 | 0.9471 | 0.086* | |
C5 | 0.17718 (15) | 0.6381 (2) | 0.6648 (2) | 0.0714 (5) | |
H5 | 0.1291 | 0.6777 | 0.5942 | 0.086* | |
C6 | 0.18948 (18) | 0.6677 (2) | 0.7993 (3) | 0.0796 (6) | |
H6 | 0.1478 | 0.7266 | 0.8184 | 0.095* | |
C18 | 0.18954 (18) | 0.2569 (2) | 0.3867 (3) | 0.0826 (7) | |
H18A | 0.2531 | 0.2380 | 0.4498 | 0.124* | |
H18B | 0.1613 | 0.1801 | 0.3395 | 0.124* | |
H18C | 0.1485 | 0.2894 | 0.4343 | 0.124* | |
H12 | 0.3296 | 0.4224 | 0.1782 | 0.071 (6)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
S19 | 0.0491 (3) | 0.0693 (3) | 0.0530 (3) | −0.00738 (17) | 0.01497 (18) | −0.00689 (18) |
O21 | 0.0707 (9) | 0.0824 (10) | 0.0943 (11) | −0.0200 (7) | 0.0170 (8) | −0.0286 (8) |
O7 | 0.0535 (7) | 0.1426 (14) | 0.0514 (7) | −0.0261 (8) | 0.0286 (6) | −0.0203 (8) |
O16 | 0.0821 (10) | 0.1003 (12) | 0.0759 (9) | −0.0309 (9) | 0.0229 (8) | −0.0212 (8) |
O15 | 0.0878 (11) | 0.1210 (14) | 0.0976 (11) | −0.0441 (10) | 0.0503 (9) | −0.0093 (10) |
O20 | 0.0648 (8) | 0.1299 (14) | 0.0572 (8) | −0.0108 (9) | 0.0132 (6) | 0.0203 (8) |
N17 | 0.0506 (7) | 0.0555 (8) | 0.0597 (8) | −0.0035 (6) | 0.0187 (6) | 0.0047 (6) |
N14 | 0.0523 (8) | 0.0684 (9) | 0.0625 (9) | −0.0063 (7) | 0.0164 (7) | 0.0074 (7) |
C10 | 0.0408 (7) | 0.0566 (9) | 0.0484 (8) | 0.0006 (6) | 0.0131 (6) | 0.0084 (6) |
C12$ | 0.0517 (9) | 0.0661 (10) | 0.0493 (8) | 0.0004 (7) | 0.0227 (7) | −0.0039 (7) |
C8 | 0.0428 (8) | 0.0678 (10) | 0.0434 (8) | 0.0027 (7) | 0.0183 (6) | 0.0053 (7) |
C13 | 0.0421 (7) | 0.0529 (8) | 0.0461 (8) | 0.0039 (6) | 0.0150 (6) | 0.0061 (6) |
C9 | 0.0467 (8) | 0.0653 (10) | 0.0445 (8) | 0.0025 (7) | 0.0155 (6) | −0.0002 (7) |
C11 | 0.0491 (8) | 0.0751 (11) | 0.0511 (8) | −0.0015 (8) | 0.0253 (7) | 0.0046 (8) |
C3 | 0.0701 (12) | 0.0756 (12) | 0.0620 (11) | 0.0078 (9) | 0.0268 (9) | −0.0037 (9) |
C4 | 0.0529 (9) | 0.0754 (11) | 0.0493 (8) | −0.0099 (8) | 0.0271 (7) | −0.0036 (8) |
C22 | 0.0548 (11) | 0.0934 (15) | 0.0839 (14) | 0.0104 (10) | 0.0122 (10) | −0.0186 (12) |
C1 | 0.0928 (15) | 0.0701 (12) | 0.0627 (11) | −0.0159 (11) | 0.0371 (11) | −0.0128 (9) |
C2 | 0.0870 (14) | 0.0734 (12) | 0.0548 (10) | −0.0037 (10) | 0.0229 (10) | 0.0033 (9) |
C5 | 0.0615 (11) | 0.0752 (12) | 0.0790 (13) | 0.0038 (9) | 0.0254 (10) | 0.0055 (10) |
C6 | 0.0859 (15) | 0.0712 (13) | 0.0953 (16) | 0.0028 (11) | 0.0484 (13) | −0.0201 (12) |
C18 | 0.0760 (13) | 0.0714 (13) | 0.0967 (16) | −0.0074 (10) | 0.0239 (12) | 0.0275 (11) |
S19—O21 | 1.4177 (15) | C11—H11 | 0.9300 |
S19—O20 | 1.4183 (16) | C3—C4 | 1.373 (3) |
S19—N17 | 1.6405 (15) | C3—C2 | 1.376 (3) |
S19—C22 | 1.745 (2) | C3—H3 | 0.9300 |
O7—C8 | 1.3647 (19) | C4—C5 | 1.377 (3) |
O7—C4 | 1.395 (2) | C22—H22A | 0.9600 |
O16—N14 | 1.217 (2) | C22—H22B | 0.9600 |
O15—N14 | 1.218 (2) | C22—H22C | 0.9600 |
N17—C13 | 1.428 (2) | C1—C6 | 1.349 (3) |
N17—C18 | 1.484 (2) | C1—C2 | 1.353 (3) |
N14—C10 | 1.465 (2) | C1—H1 | 0.9300 |
C10—C9 | 1.378 (2) | C2—H2 | 0.9300 |
C10—C11 | 1.381 (3) | C5—C6 | 1.400 (3) |
C12$—C11 | 1.382 (3) | C5—H5 | 0.9300 |
C12$—C13 | 1.387 (2) | C6—H6 | 0.9300 |
C12$—H12 | 0.9229 | C18—H18A | 0.9600 |
C8—C9 | 1.378 (2) | C18—H18B | 0.9600 |
C8—C13 | 1.399 (2) | C18—H18C | 0.9600 |
C9—H9 | 0.9300 | ||
O21—S19—O20 | 119.28 (11) | C4—C3—C2 | 119.3 (2) |
O21—S19—N17 | 107.01 (9) | C4—C3—H3 | 120.3 |
O20—S19—N17 | 106.58 (8) | C2—C3—H3 | 120.3 |
O21—S19—C22 | 107.87 (12) | C3—C4—C5 | 121.05 (18) |
O20—S19—C22 | 108.71 (13) | C3—C4—O7 | 120.55 (18) |
N17—S19—C22 | 106.74 (10) | C5—C4—O7 | 118.18 (18) |
C8—O7—C4 | 120.37 (13) | S19—C22—H22A | 109.5 |
C13—N17—C18 | 119.16 (15) | S19—C22—H22B | 109.5 |
C13—N17—S19 | 118.12 (11) | H22A—C22—H22B | 109.5 |
C18—N17—S19 | 116.83 (13) | S19—C22—H22C | 109.5 |
O16—N14—O15 | 123.36 (17) | H22A—C22—H22C | 109.5 |
O16—N14—C10 | 118.41 (15) | H22B—C22—H22C | 109.5 |
O15—N14—C10 | 118.22 (16) | C6—C1—C2 | 120.3 (2) |
C9—C10—C11 | 122.79 (16) | C6—C1—H1 | 119.8 |
C9—C10—N14 | 117.85 (15) | C2—C1—H1 | 119.8 |
C11—C10—N14 | 119.35 (15) | C1—C2—C3 | 120.5 (2) |
C11—C12$—C13 | 121.26 (16) | C1—C2—H2 | 119.7 |
C11—C12$—H12 | 115.7 | C3—C2—H2 | 119.7 |
C13—C12$—H12 | 123.0 | C4—C5—C6 | 117.5 (2) |
O7—C8—C9 | 123.26 (16) | C4—C5—H5 | 121.2 |
O7—C8—C13 | 115.68 (15) | C6—C5—H5 | 121.2 |
C9—C8—C13 | 120.91 (14) | C1—C6—C5 | 121.2 (2) |
C12$—C13—C8 | 118.82 (15) | C1—C6—H6 | 119.4 |
C12$—C13—N17 | 119.71 (15) | C5—C6—H6 | 119.4 |
C8—C13—N17 | 121.46 (14) | N17—C18—H18A | 109.5 |
C10—C9—C8 | 118.21 (15) | N17—C18—H18B | 109.5 |
C10—C9—H9 | 120.9 | H18A—C18—H18B | 109.5 |
C8—C9—H9 | 120.9 | N17—C18—H18C | 109.5 |
C10—C11—C12$ | 117.94 (15) | H18A—C18—H18C | 109.5 |
C10—C11—H11 | 121.0 | H18B—C18—H18C | 109.5 |
C12$—C11—H11 | 121.0 | ||
O21—S19—N17—C13 | 168.05 (13) | C18—N17—C13—C8 | −51.1 (2) |
O20—S19—N17—C13 | 39.39 (16) | S19—N17—C13—C8 | 101.08 (16) |
C22—S19—N17—C13 | −76.65 (16) | C11—C10—C9—C8 | −1.6 (3) |
O21—S19—N17—C18 | −39.15 (18) | N14—C10—C9—C8 | 177.13 (15) |
O20—S19—N17—C18 | −167.82 (17) | O7—C8—C9—C10 | −172.45 (16) |
C22—S19—N17—C18 | 76.14 (18) | C13—C8—C9—C10 | 2.9 (2) |
O16—N14—C10—C9 | 3.0 (2) | C9—C10—C11—C12$ | −0.9 (3) |
O15—N14—C10—C9 | −178.01 (18) | N14—C10—C11—C12$ | −179.59 (16) |
O16—N14—C10—C11 | −178.23 (17) | C13—C12$—C11—C10 | 2.2 (3) |
O15—N14—C10—C11 | 0.7 (3) | C2—C3—C4—C5 | 0.9 (3) |
C4—O7—C8—C9 | −20.3 (3) | C2—C3—C4—O7 | −173.58 (18) |
C4—O7—C8—C13 | 164.13 (17) | C8—O7—C4—C3 | −63.9 (3) |
C11—C12$—C13—C8 | −0.9 (3) | C8—O7—C4—C5 | 121.5 (2) |
C11—C12$—C13—N17 | 179.91 (16) | C6—C1—C2—C3 | −1.8 (3) |
O7—C8—C13—C12$ | 173.96 (16) | C4—C3—C2—C1 | 1.1 (3) |
C9—C8—C13—C12$ | −1.7 (2) | C3—C4—C5—C6 | −2.2 (3) |
O7—C8—C13—N17 | −6.9 (2) | O7—C4—C5—C6 | 172.44 (19) |
C9—C8—C13—N17 | 177.49 (15) | C2—C1—C6—C5 | 0.4 (4) |
C18—N17—C13—C12$ | 128.11 (19) | C4—C5—C6—C1 | 1.5 (3) |
S19—N17—C13—C12$ | −79.74 (18) |
Experimental details
Crystal data | |
Chemical formula | C14H14N2O5S |
Mr | 322.33 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 293 |
a, b, c (Å) | 14.522 (1), 10.439 (1), 10.523 (1) |
β (°) | 109.460 (4) |
V (Å3) | 1504.1 (2) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 2.16 |
Crystal size (mm) | 0.46 × 0.36 × 0.15 |
Data collection | |
Diffractometer | Nonius diffractometer |
Absorption correction | Analytical (de Meulenaer & Tompa, 1965) |
Tmin, Tmax | 0.411, 0.743 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 5119, 2951, 2747 |
Rint | 0.034 |
(sin θ/λ)max (Å−1) | 0.616 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.041, 0.118, 1.05 |
No. of reflections | 2951 |
No. of parameters | 203 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.23, −0.31 |
Computer programs: CAD-4 EXPRESS (Enraf-Nonius, 1992), CAD-4 EXPRESS, PLATON (Spek, 2001), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 1997), PLATON, SHELXL97.
The crystal structure of N-(4-nitro-2-phenoxyphenyl)methanesulfonamide, nimesulide, (I), has been previously described (Dupont et al., 1995). It is reported as a selective inhibitor of cyclooxygenase-2 (COX-2) (Tavares & Bishai, 1995). In order to study the importance of the NH proton, an analogue of nimesulide, N-methyl-N-(4-nitro-2-phenoxyphenyl)methanesulfonamide, (FJ6), (II), was synthesized and its structure solved (Fig. 1). FJ6 appeared to be inactive as a COX inhibitor (Julémont, 2001). The sole difference between the two compounds is that the sulfonamide N atom is protonated in nimesulide, while it is methylated in FJ6. The molecular conformation of nimesulide is stabilized by an intramolecular N17—H···O7 hydrogen bond, not available in FJ6. As a result, the orientation of the sulfonamide group differs from that in nimesulide, while the position of the phenoxy group remains unchanged. This can be seen in the superposition of the two compounds (Fig. 2). The inactivity of FJ6 could be partly explained by this change in orientation. Indeed, the displacement of one of the O atoms of the sulfonamide group (O20) could prevent the formation of an hydrogen bond inside the COX-2 active site and consequently yield a less stable enzyme–ligand complex. Furthermore, the two methyl groups in FJ6 could lead to steric clashes in the COX-2 enzyme. Moreover, S—O bond lengths are observed to be longer in nimesulide [1.431 (2) Å] than in FJ6 [1.418 (2) Å]. This suggests that electronic delocalization is more important for the O atoms of the sulfonamide group in nimesulide than in FJ6. Thus, O atoms of nimesulide will be able to form stronger hydrogen bonds with COX-2 residues, increasing the interaction between the inhibitor and the enzyme. In conclusion, the COX inactivity of the title compound could be partially related to its sulfonamide conformation and electronic properties, different from those observed in nimesulide.