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Acta Crystallogr Sect E Struct Rep Online. 2009 April 1; 65(Pt 4): o900–o901.
Published online 2009 March 28. doi:  10.1107/S1600536809010058
PMCID: PMC2968962

N-(3,4-Dimethyl­phen­yl)-4-hydr­oxy-2-methyl-2H-1,2-benzothia­zine-3-carboxamide 1,1-dioxide

Abstract

1,2-Benzothia­zines similar to the title compound, C18H18N2O4S, are well known in the literature for their biological activities and are used as medicines in the treatment of inflammation and rheumatoid arthritis. 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 arrange themselves into centrosymmetric dimers by means of pairs of weak inter­molecular N—H(...)O hydrogen bonds.

Related literature

For the synthesis of related mol­ecules, see: Siddiqui et al. (2007 [triangle]); Zia-ur-Rehman et al. (2005 [triangle]). For the biological activity of 1,2-benzothia­zine-1,1-dioxides, see: Turck et al. (1996 [triangle]); Zia-ur-Rehman et al. (2006 [triangle], 2009 [triangle]). For related structures, see: Golič & Leban (1987 [triangle]). For the pharmacological background to 1,2-benzothia­zine-3-carboxamide 1,1-dioxide derivatives, see Gennari et al. (1994 [triangle]); Bihovsky et al. (2004 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-0o900-scheme1.jpg

Experimental

Crystal data

  • C18H18N2O4S
  • M r = 358.40
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-0o900-efi1.jpg
  • a = 7.5458 (4) Å
  • b = 8.0214 (3) Å
  • c = 14.4832 (7) Å
  • α = 89.864 (3)°
  • β = 79.530 (2)°
  • γ = 73.812 (3)°
  • V = 826.78 (7) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.22 mm−1
  • T = 120 K
  • 0.27 × 0.13 × 0.03 mm

Data collection

  • Bruker–Nonius CCD camera on κ-goniostat diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 2007 [triangle]) T min = 0.942, T max = 0.993
  • 13798 measured reflections
  • 3783 independent reflections
  • 2808 reflections with I > 2σ(I)
  • R int = 0.055

Refinement

  • R[F 2 > 2σ(F 2)] = 0.048
  • wR(F 2) = 0.119
  • S = 1.05
  • 3783 reflections
  • 230 parameters
  • H-atom parameters constrained
  • Δρmax = 0.27 e Å−3
  • Δρmin = −0.45 e Å−3

Data collection: COLLECT (Hooft, 1998 [triangle]); cell refinement: DENZO (Otwinowski & Minor, 1997 [triangle]) and COLLECT; data reduction: DENZO and COLLECT; 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 and local programs.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809010058/bt2906sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809010058/bt2906Isup2.hkl

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

Acknowledgments

The authors are grateful to the Higher Education Commission of Pakistan for a grant.

supplementary crystallographic information

Comment

In order to discover new useful therapeutic agents, many new compounds are continuously being synthesized. Owing to their applications as non-steroidal anti-inflammatory compounds (Turck et al., 1996), considerable attention has been given to 1,2-benzothiazine 1,1-dioxides and their precursor intermediates (Golič & Leban, 1987). Some of the 1,2-benzothiazines 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). 1,2-Benzothiazines are also found to be used for the treatment of rheumatoid arthritis, ankylosing spondylitis, osteoarthrosis and other inflammatory rheumatic and non- rheumatic processes, including onsets and traumatologic lesions (Gennari et al., 1994). As part of a research program synthesizing various bioactive benzothiazines (Siddiqui et al., 2007, Zia-ur-Rehman et al., 2005, 2006, 2009), we herein report the crystal structure of the title compound (Scheme and figure 1). The thiazine ring, involving two double bonds, exhibits a distorted half-chair conformation. The enolic hydrogen on O1 is involved in intramolecular hydrogen bonding giving rise to a six-membered hydrogen bond ring (Table 1). The molecules form centrosymmetric dimers through intermolecular N—H···O hydrogen bonds.

Experimental

A mixture of methyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide (2.693 g; 10.0 mmoles), 3,4-dimethyl aniline (1.818 g; 15.0 mmoles) and xylene (25.0 ml) was refluxed under nitrogen atmosphere in a Soxhlet apparatus having Linde type 4Å molecular sieves. Three fourth of the xylene was then distilled off and the remaining contents were allowed to stand overnight at room temperature. Settled solids were filtered off, washed with diethyl ether and crystallized from ethanol. Yield: 79.5%.

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 refined. The following distances were used: Cmethyl—H 0.98 Å; Caromatic—H 0.95 Å; O—H 0.84 Å. U(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 three-dimensional crystal packing showing hydrogen-bonded interactions (dashed lines). H atoms not involved in hydrogen bonding have been omitted for clarity.

Crystal data

C18H18N2O4SZ = 2
Mr = 358.40F(000) = 376
Triclinic, P1Dx = 1.440 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 7.5458 (4) ÅCell parameters from 8399 reflections
b = 8.0214 (3) Åθ = 2.9–27.5°
c = 14.4832 (7) ŵ = 0.22 mm1
α = 89.864 (3)°T = 120 K
β = 79.530 (2)°Slab, colourless
γ = 73.812 (3)°0.27 × 0.13 × 0.03 mm
V = 826.78 (7) Å3

Data collection

Bruker–Nonius CCD camera on κ-goniostat diffractometer3783 independent reflections
Radiation source: Bruker–Nonius FR591 Rotating Anode2808 reflections with I > 2σ(I)
graphiteRint = 0.055
Detector resolution: 9.091 pixels mm-1θmax = 27.5°, θmin = 3.0°
[var phi] and ω scans to fill the asymmetric unith = −9→9
Absorption correction: multi-scan (SADABS; Sheldrick, 2007)k = −10→10
Tmin = 0.942, Tmax = 0.993l = −18→18
13798 measured reflections

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.048Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.119H-atom parameters constrained
S = 1.05w = 1/[σ2(Fo2) + (0.0504P)2 + 0.2877P] where P = (Fo2 + 2Fc2)/3
3783 reflections(Δ/σ)max < 0.001
230 parametersΔρmax = 0.27 e Å3
0 restraintsΔρmin = −0.45 e Å3

Special details

Experimental. SADABS was used to perform the Absorption correction Estimated minimum and maximum transmission: 0.6504 0.7456 The given Tmin and Tmax were generated using the SHELX SIZE command
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
S10.31447 (7)0.72556 (6)0.43102 (3)0.01788 (15)
O10.3403 (2)0.73723 (17)0.52605 (9)0.0238 (3)
O20.1712 (2)0.65260 (17)0.41180 (10)0.0212 (3)
O30.6047 (2)0.46253 (18)0.12076 (10)0.0272 (4)
O40.4283 (2)0.78465 (18)0.13671 (9)0.0239 (3)
H40.48340.68730.10880.036*
N10.5143 (2)0.6143 (2)0.36582 (11)0.0176 (4)
N20.6598 (2)0.3138 (2)0.25259 (12)0.0194 (4)
H20.64330.32590.31420.023*
C10.2807 (3)0.9323 (2)0.38337 (14)0.0171 (4)
C20.1944 (3)1.0828 (2)0.43980 (15)0.0201 (4)
H2A0.15761.07730.50580.024*
C30.1629 (3)1.2423 (2)0.39801 (15)0.0215 (5)
H30.10291.34680.43540.026*
C40.2191 (3)1.2483 (3)0.30167 (15)0.0222 (5)
H4A0.19771.35760.27370.027*
C50.3058 (3)1.0979 (3)0.24565 (14)0.0202 (4)
H50.34241.10450.17970.024*
C60.3397 (3)0.9359 (2)0.28595 (14)0.0177 (4)
C70.4321 (3)0.7733 (2)0.22839 (14)0.0181 (4)
C80.5104 (3)0.6205 (2)0.26674 (13)0.0176 (4)
C90.5948 (3)0.4596 (3)0.20776 (14)0.0193 (4)
C100.7520 (3)0.1427 (2)0.21235 (14)0.0180 (4)
C110.7367 (3)0.0876 (3)0.12370 (15)0.0212 (4)
H110.66280.16660.08710.025*
C120.8283 (3)−0.0820 (3)0.08799 (14)0.0201 (4)
C130.9391 (3)−0.1984 (2)0.14171 (14)0.0190 (4)
C140.9516 (3)−0.1413 (2)0.23036 (14)0.0198 (4)
H141.0254−0.21970.26730.024*
C150.8592 (3)0.0269 (2)0.26607 (14)0.0191 (4)
H150.86920.06280.32690.023*
C160.6865 (3)0.6405 (3)0.39200 (16)0.0245 (5)
H16A0.79750.55640.35570.037*
H16B0.68290.62380.45930.037*
H16C0.69240.75870.37820.037*
C170.8062 (3)−0.1375 (3)−0.00753 (15)0.0282 (5)
H17A0.7218−0.0405−0.03340.042*
H17B0.7532−0.2363−0.00180.042*
H17C0.9292−0.1716−0.04950.042*
C181.0438 (3)−0.3820 (3)0.10461 (16)0.0273 (5)
H18A1.1256−0.43840.14780.041*
H18B1.1202−0.37930.04250.041*
H18C0.9536−0.44720.09950.041*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.0253 (3)0.0134 (2)0.0139 (3)−0.0045 (2)−0.0023 (2)0.00043 (18)
O10.0374 (9)0.0178 (7)0.0141 (8)−0.0048 (7)−0.0048 (7)−0.0002 (6)
O20.0253 (8)0.0165 (7)0.0218 (8)−0.0081 (6)−0.0015 (6)0.0003 (6)
O30.0358 (9)0.0250 (8)0.0154 (8)−0.0022 (7)−0.0013 (7)−0.0013 (6)
O40.0338 (9)0.0206 (7)0.0137 (8)−0.0032 (7)−0.0027 (7)0.0004 (6)
N10.0201 (9)0.0172 (8)0.0142 (9)−0.0028 (7)−0.0038 (7)−0.0003 (7)
N20.0233 (10)0.0179 (8)0.0139 (9)−0.0021 (7)−0.0012 (7)−0.0036 (7)
C10.0180 (10)0.0165 (9)0.0182 (11)−0.0057 (8)−0.0057 (8)0.0011 (8)
C20.0251 (11)0.0179 (9)0.0182 (11)−0.0074 (9)−0.0038 (9)−0.0006 (8)
C30.0246 (11)0.0146 (9)0.0254 (12)−0.0050 (9)−0.0060 (9)−0.0013 (8)
C40.0267 (12)0.0158 (10)0.0267 (12)−0.0078 (9)−0.0088 (9)0.0056 (8)
C50.0236 (11)0.0224 (10)0.0173 (11)−0.0103 (9)−0.0049 (9)0.0048 (8)
C60.0179 (10)0.0181 (10)0.0184 (11)−0.0066 (8)−0.0045 (8)0.0013 (8)
C70.0199 (11)0.0203 (10)0.0151 (10)−0.0082 (9)−0.0021 (8)0.0014 (8)
C80.0204 (11)0.0188 (10)0.0131 (10)−0.0057 (8)−0.0020 (8)0.0003 (8)
C90.0186 (11)0.0220 (10)0.0155 (11)−0.0046 (9)−0.0007 (8)−0.0005 (8)
C100.0165 (10)0.0183 (10)0.0178 (11)−0.0050 (8)0.0000 (8)−0.0022 (8)
C110.0225 (11)0.0194 (10)0.0209 (11)−0.0033 (9)−0.0066 (9)0.0010 (8)
C120.0222 (11)0.0223 (10)0.0164 (11)−0.0085 (9)−0.0017 (9)−0.0026 (8)
C130.0204 (11)0.0172 (9)0.0187 (11)−0.0056 (8)−0.0013 (9)−0.0010 (8)
C140.0204 (11)0.0194 (10)0.0204 (11)−0.0054 (9)−0.0063 (9)0.0019 (8)
C150.0215 (11)0.0227 (10)0.0143 (10)−0.0084 (9)−0.0033 (8)−0.0013 (8)
C160.0247 (12)0.0264 (11)0.0249 (12)−0.0087 (9)−0.0090 (9)0.0017 (9)
C170.0380 (14)0.0252 (11)0.0190 (11)−0.0041 (10)−0.0071 (10)−0.0043 (9)
C180.0330 (13)0.0203 (10)0.0265 (12)−0.0032 (10)−0.0071 (10)−0.0033 (9)

Geometric parameters (Å, °)

S1—O11.4317 (14)C7—C81.368 (3)
S1—O21.4326 (14)C8—C91.467 (3)
S1—N11.6427 (17)C10—C151.389 (3)
S1—C11.7646 (19)C10—C111.394 (3)
O3—C91.249 (2)C11—C121.395 (3)
O4—C71.336 (2)C11—H110.9500
O4—H40.8400C12—C131.405 (3)
N1—C81.441 (2)C12—C171.506 (3)
N1—C161.485 (3)C13—C141.392 (3)
N2—C91.350 (3)C13—C181.511 (3)
N2—C101.425 (2)C14—C151.387 (3)
N2—H20.8800C14—H140.9500
C1—C21.387 (3)C15—H150.9500
C1—C61.403 (3)C16—H16A0.9800
C2—C31.392 (3)C16—H16B0.9800
C2—H2A0.9500C16—H16C0.9800
C3—C41.388 (3)C17—H17A0.9800
C3—H30.9500C17—H17B0.9800
C4—C51.383 (3)C17—H17C0.9800
C4—H4A0.9500C18—H18A0.9800
C5—C61.400 (3)C18—H18B0.9800
C5—H50.9500C18—H18C0.9800
C6—C71.473 (3)
O1—S1—O2118.91 (8)O3—C9—C8120.03 (18)
O1—S1—N1108.79 (9)N2—C9—C8116.48 (17)
O2—S1—N1107.59 (8)C15—C10—C11119.54 (18)
O1—S1—C1109.51 (9)C15—C10—N2117.23 (17)
O2—S1—C1108.75 (9)C11—C10—N2123.23 (18)
N1—S1—C1101.94 (9)C10—C11—C12120.92 (19)
C7—O4—H4109.5C10—C11—H11119.5
C8—N1—C16114.78 (16)C12—C11—H11119.5
C8—N1—S1112.57 (13)C11—C12—C13119.55 (18)
C16—N1—S1115.69 (13)C11—C12—C17119.35 (18)
C9—N2—C10127.93 (17)C13—C12—C17121.10 (18)
C9—N2—H2116.0C14—C13—C12118.72 (18)
C10—N2—H2116.0C14—C13—C18120.17 (18)
C2—C1—C6122.11 (18)C12—C13—C18121.12 (18)
C2—C1—S1121.06 (15)C15—C14—C13121.66 (19)
C6—C1—S1116.80 (14)C15—C14—H14119.2
C1—C2—C3118.78 (19)C13—C14—H14119.2
C1—C2—H2A120.6C14—C15—C10119.61 (18)
C3—C2—H2A120.6C14—C15—H15120.2
C4—C3—C2119.89 (18)C10—C15—H15120.2
C4—C3—H3120.1N1—C16—H16A109.5
C2—C3—H3120.1N1—C16—H16B109.5
C5—C4—C3121.17 (18)H16A—C16—H16B109.5
C5—C4—H4A119.4N1—C16—H16C109.5
C3—C4—H4A119.4H16A—C16—H16C109.5
C4—C5—C6120.08 (19)H16B—C16—H16C109.5
C4—C5—H5120.0C12—C17—H17A109.5
C6—C5—H5120.0C12—C17—H17B109.5
C5—C6—C1117.96 (18)H17A—C17—H17B109.5
C5—C6—C7121.49 (18)C12—C17—H17C109.5
C1—C6—C7120.55 (17)H17A—C17—H17C109.5
O4—C7—C8122.55 (18)H17B—C17—H17C109.5
O4—C7—C6115.15 (17)C13—C18—H18A109.5
C8—C7—C6122.27 (18)C13—C18—H18B109.5
C7—C8—N1120.84 (17)H18A—C18—H18B109.5
C7—C8—C9120.78 (18)C13—C18—H18C109.5
N1—C8—C9118.37 (16)H18A—C18—H18C109.5
O3—C9—N2123.49 (18)H18B—C18—H18C109.5
O1—S1—N1—C8−170.25 (12)C6—C7—C8—N1−3.3 (3)
O2—S1—N1—C859.69 (14)O4—C7—C8—C9−0.2 (3)
C1—S1—N1—C8−54.62 (14)C6—C7—C8—C9177.62 (17)
O1—S1—N1—C16−35.53 (16)C16—N1—C8—C7−91.7 (2)
O2—S1—N1—C16−165.58 (13)S1—N1—C8—C743.5 (2)
C1—S1—N1—C1680.10 (15)C16—N1—C8—C987.5 (2)
O1—S1—C1—C2−31.1 (2)S1—N1—C8—C9−137.36 (16)
O2—S1—C1—C2100.31 (18)C10—N2—C9—O31.4 (3)
N1—S1—C1—C2−146.23 (17)C10—N2—C9—C8−178.11 (17)
O1—S1—C1—C6150.83 (15)C7—C8—C9—O33.8 (3)
O2—S1—C1—C6−77.72 (17)N1—C8—C9—O3−175.38 (18)
N1—S1—C1—C635.73 (17)C7—C8—C9—N2−176.68 (18)
C6—C1—C2—C31.0 (3)N1—C8—C9—N24.2 (3)
S1—C1—C2—C3−176.88 (15)C9—N2—C10—C15159.47 (19)
C1—C2—C3—C4−0.6 (3)C9—N2—C10—C11−21.5 (3)
C2—C3—C4—C50.3 (3)C15—C10—C11—C12−0.3 (3)
C3—C4—C5—C6−0.5 (3)N2—C10—C11—C12−179.32 (18)
C4—C5—C6—C10.9 (3)C10—C11—C12—C13−0.7 (3)
C4—C5—C6—C7−179.85 (18)C10—C11—C12—C17179.17 (19)
C2—C1—C6—C5−1.2 (3)C11—C12—C13—C141.1 (3)
S1—C1—C6—C5176.80 (15)C17—C12—C13—C14−178.73 (19)
C2—C1—C6—C7179.56 (19)C11—C12—C13—C18−178.68 (19)
S1—C1—C6—C7−2.4 (3)C17—C12—C13—C181.5 (3)
C5—C6—C7—O4−19.6 (3)C12—C13—C14—C15−0.6 (3)
C1—C6—C7—O4159.62 (18)C18—C13—C14—C15179.19 (19)
C5—C6—C7—C8162.50 (19)C13—C14—C15—C10−0.4 (3)
C1—C6—C7—C8−18.3 (3)C11—C10—C15—C140.8 (3)
O4—C7—C8—N1178.98 (17)N2—C10—C15—C14179.89 (17)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O4—H4···O30.841.802.545 (2)146
N2—H2···O1i0.882.393.231 (2)161

Symmetry codes: (i) −x+1, −y+1, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BT2906).

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