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Acta Crystallogr Sect E Struct Rep Online. 2009 December 1; 65(Pt 12): o3025.
Published online 2009 November 7. doi:  10.1107/S1600536809046236
PMCID: PMC2972157

Methyl 4-hydr­oxy-2-propyl-2H-1,2-benzothia­zine-3-carboxyl­ate 1,1-dioxide

Abstract

In the title compound, C13H15NO5S, the thia­zine ring adopts a distorted half-chair conformation. The enolic H atom is involved in an intra­molecular O—H(...)O hydrogen bond, forming a six-membered ring. In the crystal, mol­ecules are linked through weak inter­molecular C—H(...)O hydrogen bonds, resulting in zigzag chains lying along the c axis.

Related literature

For the syntheses of related compounds, see: Bihovsky et al. (2004 [triangle]); Braun (1923 [triangle]); Lombardino et al. (1971 [triangle]); Zia-ur-Rehman et al. (2005 [triangle], 2009 [triangle]). For the biological activity of benzothia­zines, see: Turck et al. (1996 [triangle]); Zia-ur-Rehman et al. (2006 [triangle]). For related structures, see: Fabiola et al. (1998 [triangle]); Zia-ur-Rehman et al. (2007 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o3025-scheme1.jpg

Experimental

Crystal data

  • C13H15NO5S
  • M r = 297.32
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-65-o3025-efi1.jpg
  • a = 12.4398 (6) Å
  • b = 8.7538 (5) Å
  • c = 12.7288 (7) Å
  • V = 1386.11 (13) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.25 mm−1
  • T = 296 K
  • 0.39 × 0.36 × 0.11 mm

Data collection

  • Bruker APEXII CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 1996 [triangle]) T min = 0.908, T max = 0.973
  • 8843 measured reflections
  • 3252 independent reflections
  • 2540 reflections with I > 2σ(I)
  • R int = 0.028

Refinement

  • R[F 2 > 2σ(F 2)] = 0.036
  • wR(F 2) = 0.094
  • S = 1.03
  • 3252 reflections
  • 184 parameters
  • 1 restraint
  • H-atom parameters constrained
  • Δρmax = 0.16 e Å−3
  • Δρmin = −0.22 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 1451 Friedel pairs
  • Flack parameter: −0.08 (8)

Data collection: APEX2 (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: PLATON (Spek, 2009 [triangle]) and Mercury (Macrae et al., 2006 [triangle]); software used to prepare material for publication: WinGX (Farrugia, 1999 [triangle]) and PLATON.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809046236/is2482sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809046236/is2482Isup2.hkl

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

Acknowledgments

The authors are grateful to the Higher Education Commission of Pakistan and PCSIR Laboratories Complex for the provision of the diffractometer and chemicals, respectively.

supplementary crystallographic information

Comment

Benzothiazine1,1-dioxides are known to possess a versatile range of biological activities and have been synthesized continuously since the very first synthesis in 1923 (Braun, 1923). Among these, Piroxicam (Lombardino et al., 1971; Zia-ur-Rehman et al., 2005), and Meloxicam (Turck et al., 1996) are familiar for their analgesic and anti-inflammatory activities and are being used world wide as non-steroidal anti-inflammatory drugs (NSAIDs). Few of its derivatives are also known as potent calpain I inhibitors (Bihovsky et al., 2004), while benzothiaine-3-yl-quinazolin-4-ones showed marked activity against Bacillus subtilis (Zia-ur-Rehman et al., 2006). As part of a research program synthesizing various bioactive benzothiazines (Zia-ur-Rehman et al., 2005, 2006, 2009), we herein report the crystal structure of the title compound, (I).

In the molecule of the title compound (Fig. 1), the thiazine ring exhibits a distorted half-chair conformation with S1/C1/C6/C7 atoms lying in a plane and N1 showing significant departure from the plane due to its pyramidal geometry projecting the propyl group approximately perpendicular to the ring. Like other 1,2-benzothiazine 1,1-dioxide derivatives (Fabiola et al., 1998; Zia-ur-Rehman et al., 2007), the enolic hydrogen on O3 is involved in intramolecular hydrogen bonding (Table1). Also, C7—C8 bond length [1.346 (3) Å] (very close to normal C—C bond 1.36 Å) indicates a partial double-bond character indicating the dominance of enolic form in the molecule. The C1—S1 bond distance [1.759 (3) Å] is as expected for typical C(sp2)—S bond (1.751 Å). Each molecule is linked to neighbouring molecules via weaker C—H···O=S interactions giving rise to zigzag chains along the c axis (Fig. 2).

Experimental

Propyl iodide (5.10 g, 30.0 mmol) was added drop wise to the mixture of methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide (3.83 g, 15.0 mmol), anhydrous potassium carbonate (1.68 g, 30.0 mmol) and dimethylformamide (20.0 ml) in a round bottom flask. Contents were stirred at room temperature for 7 h under nitrogen atmosphere and poured over ice cooled water (300 ml) resulting in an immediate formation of a white solid, which was filtered and washed with cold water. Crystallization from methanol yielded pure compound.

Refinement

All hydrogen atoms were identified in the difference map and subsequently fixed in ideal positions and treated as riding on their parent atoms. In the case of the methyl and hydroxyl H atoms the torsion angles were freely refined. The following distances were used: C—H = 0.98 Å for methyl, C—H = 0.95 Å for aromatic and O—H = 0.84 Å for hydroxyl. Uiso(H) was set to 1.2Ueq of the parent atoms or 1.5Ueq for methyl groups.

Figures

Fig. 1.
The molecular structure of (I), with displacement ellipsoids at the 50% probability level.
Fig. 2.
Perspective view of the crystal packing showing C—H···O hydrogen-bonded interactions (dashed lines). H atoms not involved in hydrogen bonding have been omitted for clarity.

Crystal data

C13H15NO5SF(000) = 624
Mr = 297.32Dx = 1.425 Mg m3
Orthorhombic, Pca21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2acCell parameters from 2980 reflections
a = 12.4398 (6) Åθ = 2.3–25.3°
b = 8.7538 (5) ŵ = 0.25 mm1
c = 12.7288 (7) ÅT = 296 K
V = 1386.11 (13) Å3Rods, yellow
Z = 40.39 × 0.36 × 0.11 mm

Data collection

Bruker APEXII CCD area-detector diffractometer3252 independent reflections
Radiation source: fine-focus sealed tube2540 reflections with I > 2σ(I)
graphiteRint = 0.028
[var phi] and ω scansθmax = 28.3°, θmin = 2.9°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)h = −16→10
Tmin = 0.908, Tmax = 0.973k = −11→11
8843 measured reflectionsl = −16→15

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.036H-atom parameters constrained
wR(F2) = 0.094w = 1/[σ2(Fo2) + (0.0496P)2] where P = (Fo2 + 2Fc2)/3
S = 1.03(Δ/σ)max < 0.001
3252 reflectionsΔρmax = 0.16 e Å3
184 parametersΔρmin = −0.22 e Å3
1 restraintAbsolute structure: Flack (1983), 1451 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: −0.08 (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
C10.58950 (17)0.7963 (3)0.8319 (2)0.0442 (5)
C20.66903 (18)0.8114 (3)0.7577 (2)0.0565 (6)
H20.73910.78160.77260.068*
C30.6434 (2)0.8714 (3)0.6609 (3)0.0703 (8)
H30.69670.88290.61030.084*
C40.5396 (2)0.9145 (3)0.6385 (2)0.0622 (7)
H40.52300.95360.57250.075*
C50.45981 (19)0.9001 (3)0.71319 (19)0.0509 (6)
H50.39000.93080.69760.061*
C60.48305 (15)0.8403 (3)0.81103 (17)0.0407 (5)
C70.39979 (15)0.8187 (3)0.89165 (18)0.0398 (5)
C80.40966 (15)0.7206 (2)0.97246 (19)0.0389 (5)
C90.32273 (17)0.7043 (3)1.04807 (18)0.0443 (5)
C100.2568 (3)0.5866 (3)1.2006 (3)0.0755 (8)
H10A0.19550.54551.16450.113*
H10B0.23780.68251.23220.113*
H10C0.27940.51651.25420.113*
C110.50112 (17)0.4660 (3)0.9658 (2)0.0493 (5)
H11A0.44650.42141.01070.059*
H11B0.56950.42040.98480.059*
C120.4761 (2)0.4257 (3)0.8530 (2)0.0589 (7)
H12A0.52790.47480.80720.071*
H12B0.40520.46390.83500.071*
C130.4794 (3)0.2548 (3)0.8355 (3)0.0812 (10)
H13A0.42970.20570.88230.122*
H13B0.55070.21780.84900.122*
H13C0.46000.23250.76410.122*
N10.50637 (13)0.6325 (2)0.98684 (13)0.0423 (5)
O10.70303 (11)0.6188 (2)0.95391 (16)0.0633 (5)
O20.62415 (13)0.8534 (2)1.02728 (17)0.0676 (6)
O30.31275 (12)0.90699 (18)0.87688 (13)0.0532 (4)
H3A0.26710.88610.92110.080*
O40.23788 (13)0.7728 (2)1.03972 (15)0.0586 (5)
O50.34308 (13)0.60963 (19)1.12699 (13)0.0547 (4)
S10.61649 (4)0.72551 (7)0.95848 (6)0.04848 (16)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0361 (10)0.0384 (12)0.0580 (13)−0.0019 (9)0.0015 (10)−0.0081 (10)
C20.0407 (13)0.0523 (15)0.0765 (17)−0.0002 (11)0.0107 (12)−0.0006 (13)
C30.0666 (18)0.0632 (18)0.081 (2)0.0040 (15)0.0342 (15)0.0044 (15)
C40.0709 (17)0.0561 (17)0.0595 (16)0.0069 (13)0.0155 (14)0.0104 (13)
C50.0502 (13)0.0437 (14)0.0587 (15)0.0032 (10)0.0017 (11)0.0047 (11)
C60.0369 (10)0.0354 (12)0.0499 (13)−0.0005 (9)0.0016 (9)−0.0056 (10)
C70.0322 (10)0.0402 (12)0.0471 (12)0.0021 (8)−0.0027 (9)−0.0072 (9)
C80.0315 (8)0.0412 (11)0.0439 (14)0.0042 (8)−0.0029 (9)−0.0057 (10)
C90.0403 (12)0.0447 (12)0.0480 (12)0.0016 (10)0.0004 (10)−0.0040 (11)
C100.0678 (16)0.095 (2)0.0642 (17)0.0176 (16)0.0203 (13)0.0219 (18)
C110.0443 (10)0.0444 (12)0.0592 (13)0.0112 (9)−0.0031 (11)0.0016 (13)
C120.0590 (14)0.0499 (16)0.0677 (17)−0.0024 (11)−0.0011 (13)−0.0091 (12)
C130.077 (2)0.059 (2)0.107 (3)−0.0003 (14)0.0020 (18)−0.0210 (19)
N10.0350 (9)0.0465 (11)0.0455 (12)0.0077 (7)−0.0061 (7)−0.0044 (8)
O10.0354 (7)0.0806 (12)0.0740 (11)0.0161 (7)−0.0059 (9)−0.0045 (11)
O20.0468 (10)0.0802 (14)0.0760 (12)−0.0004 (8)−0.0149 (8)−0.0329 (11)
O30.0378 (8)0.0548 (10)0.0669 (11)0.0137 (7)0.0065 (7)0.0114 (8)
O40.0413 (9)0.0678 (11)0.0669 (11)0.0144 (8)0.0100 (8)0.0109 (9)
O50.0484 (9)0.0677 (11)0.0480 (9)0.0105 (8)0.0071 (7)0.0092 (8)
S10.0309 (2)0.0583 (3)0.0562 (3)0.0046 (2)−0.0086 (3)−0.0146 (3)

Geometric parameters (Å, °)

C1—C21.374 (3)C10—O51.439 (3)
C1—C61.404 (3)C10—H10A0.9600
C1—S11.759 (3)C10—H10B0.9600
C2—C31.376 (4)C10—H10C0.9600
C2—H20.9300C11—N11.483 (3)
C3—C41.375 (4)C11—C121.511 (4)
C3—H30.9300C11—H11A0.9700
C4—C51.380 (3)C11—H11B0.9700
C4—H40.9300C12—C131.513 (4)
C5—C61.382 (3)C12—H12A0.9700
C5—H50.9300C12—H12B0.9700
C6—C71.470 (3)C13—H13A0.9600
C7—O31.344 (2)C13—H13B0.9600
C7—C81.346 (3)C13—H13C0.9600
C8—N11.441 (3)N1—S11.6339 (19)
C8—C91.455 (3)O1—S11.4268 (15)
C9—O41.219 (3)O2—S11.425 (2)
C9—O51.327 (3)O3—H3A0.8200
C2—C1—C6121.5 (2)H10A—C10—H10C109.5
C2—C1—S1121.76 (19)H10B—C10—H10C109.5
C6—C1—S1116.72 (17)N1—C11—C12114.2 (2)
C1—C2—C3119.0 (2)N1—C11—H11A108.7
C1—C2—H2120.5C12—C11—H11A108.7
C3—C2—H2120.5N1—C11—H11B108.7
C4—C3—C2120.5 (2)C12—C11—H11B108.7
C4—C3—H3119.7H11A—C11—H11B107.6
C2—C3—H3119.7C11—C12—C13111.4 (2)
C3—C4—C5120.5 (3)C11—C12—H12A109.3
C3—C4—H4119.8C13—C12—H12A109.3
C5—C4—H4119.8C11—C12—H12B109.3
C4—C5—C6120.4 (2)C13—C12—H12B109.3
C4—C5—H5119.8H12A—C12—H12B108.0
C6—C5—H5119.8C12—C13—H13A109.5
C5—C6—C1118.1 (2)C12—C13—H13B109.5
C5—C6—C7122.04 (19)H13A—C13—H13B109.5
C1—C6—C7119.8 (2)C12—C13—H13C109.5
O3—C7—C8123.2 (2)H13A—C13—H13C109.5
O3—C7—C6113.3 (2)H13B—C13—H13C109.5
C8—C7—C6123.46 (18)C8—N1—C11117.79 (16)
C7—C8—N1120.99 (19)C8—N1—S1113.92 (15)
C7—C8—C9120.03 (18)C11—N1—S1119.13 (14)
N1—C8—C9118.98 (19)C7—O3—H3A109.5
O4—C9—O5122.6 (2)C9—O5—C10115.99 (19)
O4—C9—C8122.6 (2)O2—S1—O1119.30 (11)
O5—C9—C8114.85 (18)O2—S1—N1108.17 (11)
O5—C10—H10A109.5O1—S1—N1108.37 (10)
O5—C10—H10B109.5O2—S1—C1107.40 (13)
H10A—C10—H10B109.5O1—S1—C1109.72 (11)
O5—C10—H10C109.5N1—S1—C1102.59 (9)
C6—C1—C2—C30.1 (4)N1—C8—C9—O51.8 (3)
S1—C1—C2—C3−178.3 (2)N1—C11—C12—C13176.1 (2)
C1—C2—C3—C4−0.5 (4)C7—C8—N1—C11−108.9 (2)
C2—C3—C4—C50.9 (4)C9—C8—N1—C1172.3 (3)
C3—C4—C5—C6−0.9 (4)C7—C8—N1—S137.8 (3)
C4—C5—C6—C10.5 (3)C9—C8—N1—S1−141.04 (17)
C4—C5—C6—C7−178.1 (2)C12—C11—N1—C863.6 (3)
C2—C1—C6—C5−0.1 (3)C12—C11—N1—S1−81.3 (2)
S1—C1—C6—C5178.34 (18)O4—C9—O5—C102.7 (3)
C2—C1—C6—C7178.5 (2)C8—C9—O5—C10−177.5 (2)
S1—C1—C6—C7−3.0 (3)C8—N1—S1—O261.60 (18)
C5—C6—C7—O3−21.8 (3)C11—N1—S1—O2−152.19 (18)
C1—C6—C7—O3159.7 (2)C8—N1—S1—O1−167.73 (15)
C5—C6—C7—C8158.4 (2)C11—N1—S1—O1−21.5 (2)
C1—C6—C7—C8−20.2 (3)C8—N1—S1—C1−51.72 (16)
O3—C7—C8—N1−177.71 (19)C11—N1—S1—C194.49 (18)
C6—C7—C8—N12.1 (3)C2—C1—S1—O2100.0 (2)
O3—C7—C8—C91.1 (3)C6—C1—S1—O2−78.46 (19)
C6—C7—C8—C9−179.1 (2)C2—C1—S1—O1−31.1 (2)
C7—C8—C9—O42.6 (3)C6—C1—S1—O1150.46 (17)
N1—C8—C9—O4−178.5 (2)C2—C1—S1—N1−146.1 (2)
C7—C8—C9—O5−177.1 (2)C6—C1—S1—N135.43 (19)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O3—H3A···O40.821.842.558 (2)145
C3—H3···O2i0.932.483.358 (3)158

Symmetry codes: (i) −x+3/2, y, z−1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: IS2482).

References

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