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Acta Crystallogr Sect E Struct Rep Online. 2009 July 1; 65(Pt 7): o1667.
Published online 2009 June 24. doi:  10.1107/S1600536809023022
PMCID: PMC2969438

N-(4-Hydroxy­phen­yl)-2-(1,1,3-trioxo-2,3-di­hydro-1,2-benzothia­zol-2-yl)­acet­amide

Abstract

In the title compound, C15H12N2O5S, the benzisothia­zole group is approximately planar (r.m.s. deviation excluding H atoms and the two O atoms bonded to S = 0.023 Å). The dihedral angle between the benzisothia­zole ring and the terminal phenol ring is 84.9 (1)°. In the crystal, mol­ecules are joined by N—H(...)O and O—H(...)O hydrogen bonds, and π-stacking inter­actions are observed between alternating phenol and benzisothia­zole rings [centroid–centroid distances = 3.929 (3) and 3.943 (3) Å].

Related literature

For background literature related to analgesics, see: Slattery et al. (1996 [triangle]); McGoldrick & Bailie (1997 [triangle]); Watkins et al. (2006 [triangle]). For the synthesis and biological activity of the title compound, see: Vaccarino et al. (2007 [triangle]); González-Martin et al. (1998 [triangle]); Bazan & Alvarez-Builla (1996a [triangle],b [triangle]). For related structures, see: Arshad et al. (2009a [triangle],b [triangle],c [triangle]); Siddiqui et al. (2008a [triangle],b [triangle]; 2007 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o1667-scheme1.jpg

Experimental

Crystal data

  • C15H12N2O5S
  • M r = 332.33
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-65-o1667-efi1.jpg
  • a = 16.3588 (10) Å
  • b = 9.6451 (6) Å
  • c = 9.9603 (6) Å
  • V = 1571.56 (17) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.23 mm−1
  • T = 230 K
  • 0.60 × 0.20 × 0.20 mm

Data collection

  • Bruker SMART 1K CCD diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2007 [triangle]) T min = 0.832, T max = 0.954
  • 19429 measured reflections
  • 3580 independent reflections
  • 3283 reflections with I > 2σ(I)
  • R int = 0.033

Refinement

  • R[F 2 > 2σ(F 2)] = 0.039
  • wR(F 2) = 0.084
  • S = 1.07
  • 3580 reflections
  • 257 parameters
  • 1 restraint
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.28 e Å−3
  • Δρmin = −0.38 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 1681 Friedel pairs
  • Flack parameter: 0.02 (8)

Data collection: SMART (Bruker, 2007 [triangle]); cell refinement: SAINT (Bruker, 2007 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809023022/bi2377sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809023022/bi2377Isup2.hkl

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

Acknowledgments

Helpful discussions with Professor M. L. Trudell, University of New Orleans, are gratefully acknowledged.

supplementary crystallographic information

Comment

Analgesics currently in use have high incidence of adverse reactions and can cause potentially lethal effects like hepatotoxicity and nephrotoxicity (Slattery et al., 1996; McGoldrick & Bailie, 1997; Watkins et al., 2006). A series of compounds bearing the acetaminophen (Tylenol) fragment linked to different lipophilic heterocyclic moieties were synthesized with a view to modulate its pharmacokinetic profile (Bazan & Alvarez-Builla, 1996a,b6; Vaccarino et al., 2007). Of these new derivatives, the title compound (commonly called SCP-1) has a similar profile to that of acetaminophen but with shorter elimination half-life and clearance.

Experimental

The title compound was synthesized following the procedure described by Vaccarino et al. (2007) and colourless needles suitable for X-ray analysis were obtained by recrystallization from an ethanol-water (8:1) mixture.

Refinement

All H atoms were located in a difference density map and their positional parameters and Uiso included in the full-matrix least-squares refinement. Observed C—H bond lengths are in the range 0.91 (3)–0.97 (3) Å.

Figures

Fig. 1.
The asymmetric unit of the title compound. Displacement ellipsoids are drawn at the 50% probability level.
Fig. 2.
Perspective view of the contents of the unit cell showing the parallel stacking of the aromatic rings in layers perpendicular to the a axis.

Crystal data

C15H12N2O5SF(000) = 688
Mr = 332.33Dx = 1.405 Mg m3
Orthorhombic, Pna21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2nCell parameters from 17706 reflections
a = 16.3588 (10) Åθ = 2.5–30.5°
b = 9.6451 (6) ŵ = 0.23 mm1
c = 9.9603 (6) ÅT = 230 K
V = 1571.56 (17) Å3Needle, colourless
Z = 40.60 × 0.20 × 0.20 mm

Data collection

Bruker SMART 1K CCD diffractometer3580 independent reflections
Radiation source: fine-focus sealed tube3283 reflections with I > 2σ(I)
graphiteRint = 0.033
[var phi] and ω scansθmax = 27.5°, θmin = 2.5°
Absorption correction: multi-scan (SADABS; Bruker, 2007)h = −21→21
Tmin = 0.832, Tmax = 0.954k = −12→12
19429 measured reflectionsl = −12→12

Refinement

Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.039w = 1/[σ2(Fo2) + (0.0183P)2 + 1.0724P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.084(Δ/σ)max < 0.001
S = 1.07Δρmax = 0.28 e Å3
3580 reflectionsΔρmin = −0.38 e Å3
257 parametersExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraintExtinction coefficient: 0.0063 (8)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack (1983), 1681 Friedel pairs
Secondary atom site location: difference Fourier mapFlack parameter: 0.02 (8)

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
S10.11997 (4)0.20573 (6)0.93772 (6)0.03830 (15)
O10.10058 (12)0.3352 (2)1.0007 (2)0.0534 (5)
N20.09100 (11)0.0757 (2)1.0375 (2)0.0339 (4)
O20.08966 (13)0.1841 (2)0.80485 (18)0.0554 (5)
C30.15368 (14)0.0026 (2)1.0986 (2)0.0320 (5)
O30.14167 (11)−0.0882 (2)1.17895 (19)0.0451 (4)
C40.31014 (15)0.0065 (3)1.0784 (3)0.0467 (6)
H40.3137 (16)−0.067 (3)1.135 (3)0.034 (7)*
C4A0.23289 (14)0.0552 (3)1.0467 (2)0.0353 (5)
C50.37621 (17)0.0677 (4)1.0128 (4)0.0608 (9)
H50.430 (2)0.035 (4)1.032 (4)0.081 (11)*
C60.36573 (17)0.1721 (4)0.9215 (4)0.0640 (9)
H60.4123 (19)0.209 (3)0.873 (4)0.065 (9)*
C7A0.22384 (13)0.1609 (3)0.9562 (3)0.0398 (5)
C70.2887 (2)0.2225 (3)0.8913 (3)0.0561 (8)
H70.283 (2)0.295 (3)0.830 (3)0.058 (9)*
C80.00639 (14)0.0545 (3)1.0733 (2)0.0346 (5)
H8B−0.0203 (16)0.141 (3)1.072 (3)0.038 (7)*
H8A0.0067 (16)0.018 (3)1.162 (3)0.035 (7)*
C9−0.03588 (12)−0.0469 (2)0.9791 (2)0.0298 (4)
O90.00080 (9)−0.11209 (18)0.89225 (16)0.0379 (4)
N10−0.11625 (11)−0.0573 (2)1.0033 (2)0.0331 (4)
H10−0.1339 (17)−0.008 (3)1.070 (3)0.045 (8)*
C11−0.17479 (12)−0.1418 (2)0.9368 (2)0.0295 (4)
C12−0.25630 (14)−0.1228 (3)0.9725 (3)0.0391 (6)
H12−0.2690 (17)−0.049 (3)1.033 (3)0.047 (8)*
C13−0.31719 (13)−0.2010 (3)0.9129 (3)0.0407 (6)
H13−0.3736 (19)−0.187 (3)0.933 (4)0.066 (9)*
C14−0.29711 (13)−0.2994 (2)0.8175 (2)0.0320 (5)
O14−0.35473 (10)−0.3808 (2)0.75619 (19)0.0442 (5)
H14−0.397 (2)−0.378 (3)0.802 (4)0.060 (10)*
C15−0.21627 (14)−0.3179 (3)0.7811 (2)0.0341 (5)
H15−0.2007 (16)−0.386 (3)0.716 (3)0.040 (7)*
C16−0.15511 (13)−0.2396 (3)0.8404 (2)0.0320 (5)
H16−0.1000 (17)−0.255 (3)0.814 (3)0.041 (7)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.0371 (3)0.0407 (3)0.0371 (3)−0.0060 (2)−0.0064 (3)0.0063 (3)
O10.0547 (11)0.0422 (10)0.0633 (12)0.0011 (9)−0.0100 (10)0.0011 (9)
N20.0253 (9)0.0422 (11)0.0343 (10)−0.0052 (8)−0.0035 (7)0.0048 (9)
O20.0640 (12)0.0651 (13)0.0371 (10)−0.0036 (11)−0.0141 (9)0.0105 (9)
C30.0288 (11)0.0366 (12)0.0306 (11)−0.0023 (9)−0.0040 (9)−0.0026 (10)
O30.0430 (10)0.0481 (11)0.0443 (10)0.0011 (8)−0.0010 (8)0.0133 (9)
C40.0312 (12)0.0594 (17)0.0496 (15)0.0012 (12)−0.0040 (11)−0.0117 (14)
C4A0.0278 (11)0.0438 (13)0.0343 (11)−0.0037 (10)−0.0027 (10)−0.0065 (10)
C50.0260 (13)0.081 (2)0.075 (2)−0.0045 (14)−0.0007 (13)−0.0239 (19)
C60.0398 (14)0.081 (2)0.072 (2)−0.0244 (15)0.0125 (16)−0.009 (2)
C7A0.0312 (11)0.0480 (13)0.0401 (14)−0.0085 (10)0.0011 (10)−0.0019 (11)
C70.0491 (16)0.065 (2)0.0547 (18)−0.0222 (15)0.0078 (13)0.0049 (15)
C80.0256 (10)0.0460 (14)0.0323 (12)−0.0015 (10)−0.0004 (9)−0.0030 (11)
C90.0246 (9)0.0372 (11)0.0275 (10)−0.0002 (9)−0.0012 (8)0.0020 (9)
O90.0238 (7)0.0520 (10)0.0379 (9)−0.0013 (7)0.0043 (6)−0.0089 (8)
N100.0249 (9)0.0425 (11)0.0319 (10)−0.0037 (8)0.0045 (8)−0.0087 (9)
C110.0240 (8)0.0352 (10)0.0293 (9)−0.0040 (8)0.0016 (9)−0.0002 (10)
C120.0276 (10)0.0465 (14)0.0432 (14)−0.0007 (10)0.0078 (10)−0.0145 (11)
C130.0219 (10)0.0511 (13)0.0492 (16)−0.0017 (10)0.0059 (10)−0.0093 (12)
C140.0254 (10)0.0402 (12)0.0304 (11)−0.0067 (9)0.0012 (9)0.0024 (9)
O140.0284 (9)0.0613 (12)0.0427 (10)−0.0135 (9)0.0038 (8)−0.0150 (9)
C150.0296 (11)0.0408 (13)0.0319 (11)−0.0023 (10)0.0053 (9)−0.0044 (10)
C160.0216 (10)0.0401 (12)0.0343 (12)−0.0010 (9)0.0055 (9)−0.0010 (10)

Geometric parameters (Å, °)

S1—O21.4286 (19)C8—H8B0.94 (3)
S1—O11.433 (2)C8—H8A0.95 (3)
S1—N21.668 (2)C9—O91.226 (3)
S1—C7A1.763 (2)C9—N101.340 (3)
N2—C31.386 (3)N10—C111.421 (3)
N2—C81.444 (3)N10—H100.87 (3)
C3—O31.203 (3)C11—C161.384 (3)
C3—C4A1.484 (3)C11—C121.392 (3)
C4—C4A1.385 (3)C12—C131.383 (3)
C4—C51.394 (4)C12—H120.95 (3)
C4—H40.91 (3)C13—C141.383 (3)
C4A—C7A1.369 (4)C13—H130.95 (3)
C5—C61.367 (5)C14—O141.370 (3)
C5—H50.96 (4)C14—C151.383 (3)
C6—C71.384 (4)O14—H140.82 (3)
C6—H60.97 (3)C15—C161.385 (3)
C7A—C71.377 (4)C15—H150.96 (3)
C7—H70.93 (3)C16—H160.95 (3)
C8—C91.522 (3)
O2—S1—O1117.12 (13)N2—C8—H8B108.3 (16)
O2—S1—N2110.07 (11)C9—C8—H8B110.3 (16)
O1—S1—N2109.35 (12)N2—C8—H8A106.1 (16)
O2—S1—C7A113.30 (13)C9—C8—H8A109.9 (16)
O1—S1—C7A112.41 (12)H8B—C8—H8A110 (2)
N2—S1—C7A91.57 (11)O9—C9—N10124.6 (2)
C3—N2—C8121.9 (2)O9—C9—C8122.84 (19)
C3—N2—S1115.73 (16)N10—C9—C8112.52 (19)
C8—N2—S1121.75 (17)C9—N10—C11128.3 (2)
O3—C3—N2122.8 (2)C9—N10—H10115.0 (19)
O3—C3—C4A128.6 (2)C11—N10—H10116.6 (19)
N2—C3—C4A108.6 (2)C16—C11—C12119.3 (2)
C4A—C4—C5117.2 (3)C16—C11—N10123.88 (19)
C4A—C4—H4117.7 (17)C12—C11—N10116.8 (2)
C5—C4—H4125.0 (17)C13—C12—C11120.6 (2)
C7A—C4A—C4120.1 (2)C13—C12—H12121.3 (17)
C7A—C4A—C3112.9 (2)C11—C12—H12117.9 (17)
C4—C4A—C3127.0 (2)C12—C13—C14119.9 (2)
C6—C5—C4121.8 (3)C12—C13—H13122 (2)
C6—C5—H5120 (2)C14—C13—H13118 (2)
C4—C5—H5119 (2)O14—C14—C15117.9 (2)
C5—C6—C7121.2 (3)O14—C14—C13122.4 (2)
C5—C6—H6120.3 (19)C15—C14—C13119.7 (2)
C7—C6—H6118 (2)C14—O14—H14108 (2)
C4A—C7A—C7123.2 (2)C14—C15—C16120.6 (2)
C4A—C7A—S1110.83 (17)C14—C15—H15121.2 (16)
C7—C7A—S1126.0 (2)C16—C15—H15118.1 (16)
C7A—C7—C6116.6 (3)C11—C16—C15119.9 (2)
C7A—C7—H7123 (2)C11—C16—H16121.3 (16)
C6—C7—H7120 (2)C15—C16—H16118.8 (16)
N2—C8—C9111.95 (19)
O2—S1—N2—C3121.36 (18)O2—S1—C7A—C763.0 (3)
O1—S1—N2—C3−108.64 (18)O1—S1—C7A—C7−72.6 (3)
C7A—S1—N2—C35.82 (19)N2—S1—C7A—C7175.7 (3)
O2—S1—N2—C8−67.6 (2)C4A—C7A—C7—C60.1 (5)
O1—S1—N2—C862.4 (2)S1—C7A—C7—C6179.4 (2)
C7A—S1—N2—C8176.87 (19)C5—C6—C7—C7A−0.9 (5)
C8—N2—C3—O34.5 (4)C3—N2—C8—C9−96.0 (3)
S1—N2—C3—O3175.5 (2)S1—N2—C8—C993.5 (2)
C8—N2—C3—C4A−176.0 (2)N2—C8—C9—O96.7 (3)
S1—N2—C3—C4A−5.0 (2)N2—C8—C9—N10−174.0 (2)
C5—C4—C4A—C7A−1.1 (4)O9—C9—N10—C11−0.2 (4)
C5—C4—C4A—C3177.2 (3)C8—C9—N10—C11−179.5 (2)
O3—C3—C4A—C7A−179.5 (3)C9—N10—C11—C166.3 (4)
N2—C3—C4A—C7A1.0 (3)C9—N10—C11—C12−173.7 (2)
O3—C3—C4A—C42.1 (4)C16—C11—C12—C130.3 (4)
N2—C3—C4A—C4−177.4 (2)N10—C11—C12—C13−179.8 (2)
C4A—C4—C5—C60.3 (4)C11—C12—C13—C140.3 (4)
C4—C5—C6—C70.7 (5)C12—C13—C14—O14179.3 (2)
C4—C4A—C7A—C70.9 (4)C12—C13—C14—C15−0.7 (4)
C3—C4A—C7A—C7−177.6 (3)O14—C14—C15—C16−179.4 (2)
C4—C4A—C7A—S1−178.4 (2)C13—C14—C15—C160.6 (4)
C3—C4A—C7A—S13.1 (3)C12—C11—C16—C15−0.4 (3)
O2—S1—C7A—C4A−117.6 (2)N10—C11—C16—C15179.7 (2)
O1—S1—C7A—C4A106.8 (2)C14—C15—C16—C11−0.1 (4)
N2—S1—C7A—C4A−5.0 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N10—H10···O14i0.87 (3)2.23 (3)3.078 (3)165 (3)
O14—H14···O9ii0.82 (3)1.91 (3)2.725 (2)173 (3)

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BI2377).

References

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