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Acta Crystallogr Sect E Struct Rep Online. 2009 March 1; 65(Pt 3): o644–o645.
Published online 2009 February 28. doi:  10.1107/S1600536809006837
PMCID: PMC2968491

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

Abstract

In the crystal structure of the title compound, C18H18N2O4S, the thia­zine ring adopts a distorted half-chair conformation. 1,2-Benzothia­zines of this kind have a wide range of biological activities and are mainly used as medicines in the treatment of inflammation and rheumatoid arthritis. The enolic H atom is involved in an intra­molecular O—H(...)O hydrogen bond, forming a six-membered ring. The mol­ecules arrange themselves into centrosymmetric dimers by means of inter­molecular N—H(...)O hydrogen bonds. A weak inter­molcular C—H(...)O inter­action is also present.

Related literature

For the synthesis of related mol­ecules, see: Siddiqui, Ahmad, Khan et al. (2007 [triangle]); Zia-ur-Rehman et al. (2006 [triangle]); For the biological activity of 1,2-benzothia­zine-1,1-dioxides, see: Zia-ur-Rehman et al. (2009 [triangle]). For related structures, see: Siddiqui et al. (2008 [triangle]); Siddiqui, Ahmad, Siddiqui et al. (2007 [triangle]). For the pharmacological background to 1,2-benzothia­zine-3-carboxamide 1,1-dioxide derivatives, see Gennari et al. (1994 [triangle]); Lombardino & Wiseman (1972 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-0o644-scheme1.jpg

Experimental

Crystal data

  • C18H18N2O4S
  • M r = 358.40
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-0o644-efi1.jpg
  • a = 10.2461 (3) Å
  • b = 8.5421 (2) Å
  • c = 19.8944 (5) Å
  • β = 104.832 (1)°
  • V = 1683.20 (8) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.22 mm−1
  • T = 120 K
  • 0.30 × 0.10 × 0.10 mm

Data collection

  • Bruker–Nonius CCD camera on κ-goniostat diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 2007 [triangle]) T min = 0.855, T max = 0.978
  • 18371 measured reflections
  • 3828 independent reflections
  • 3000 reflections with I > 2σ(I)
  • R int = 0.055

Refinement

  • R[F 2 > 2σ(F 2)] = 0.045
  • wR(F 2) = 0.114
  • S = 1.06
  • 3828 reflections
  • 234 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.27 e Å−3
  • Δρmin = −0.57 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/S1600536809006837/bt2887sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809006837/bt2887Isup2.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

1,2-Benzothiazine-3-carboxamide 1,1-dioxide derivatives belonging to oxicams, a class of non-steroidal anti-inflammatory drugs (NSAIDs), are well known as analgesic and anti-inflammatory agents since the introduction of Piroxicam (Lombardino & Wiseman, 1972) in the United States in 1982 where it gained immediate acceptance and remained among the top fifty prescription drugs for several years. Besides having anti-inflammatory activity, these have also been 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).

In continuation of our work on the synthesis (Siddiqui, Ahmad, Khan et al., 2007, Zia-ur-Rehman et al., 2006, biological activity (Zia-ur-Rehman et al, 2009) and crystal structures (Siddiqui, Ahmad, Siddiqui et al., 2007, Siddiqui et al., 2008) of various 1,2-benzothiazine-1,1-dioxides, we herein report the synthesis and crystal structure of the title compound (I) (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. In addition, the crystal packing is stabilized by weak C—H···O contacts.

Experimental

A mixture of methyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide (2.693 g; 10.0 mmoles), 2,3-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: 78%.

Refinement

All hydrogen atoms were identified in the difference map. Those bonded to O and C were 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: Methyl C—H 0.98 Å. ° Aromatic C—H 0.95 Å. ° Hydroxyl O—H 0.84 Å. U(H) was set to 1.2Ueq of the parent atoms or 1.5Ueq for methyl groups. The H atom bonded to N was freely refined.

Figures

Fig. 1.
The molecular structure of the title compound 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

C18H18N2O4SF(000) = 752
Mr = 358.40Dx = 1.414 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 10340 reflections
a = 10.2461 (3) Åθ = 2.9–27.5°
b = 8.5421 (2) ŵ = 0.22 mm1
c = 19.8944 (5) ÅT = 120 K
β = 104.832 (1)°Block, colourless
V = 1683.20 (8) Å30.30 × 0.10 × 0.10 mm
Z = 4

Data collection

Bruker–Nonius CCD camera on κ-goniostat diffractometer3828 independent reflections
Radiation source: Bruker Nonius FR591 Rotating Anode3000 reflections with I > 2σ(I)
graphiteRint = 0.055
Detector resolution: 9.091 pixels mm-1θmax = 27.5°, θmin = 3.2°
[var phi] and ω scans to fill the asymmetric unith = −13→11
Absorption correction: multi-scan (SADABS; Sheldrick, 2007)k = −11→9
Tmin = 0.855, Tmax = 0.978l = −25→24
18371 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)] = 0.045Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.114H atoms treated by a mixture of independent and constrained refinement
S = 1.06w = 1/[σ2(Fo2) + (0.0495P)2 + 0.8901P] where P = (Fo2 + 2Fc2)/3
3828 reflections(Δ/σ)max = 0.001
234 parametersΔρmax = 0.27 e Å3
0 restraintsΔρmin = −0.57 e Å3

Special details

Experimental. SADABS was used to perform the Absorption correction Parameter refinement on 11612 reflections reduced R(int) from 0.0681 to 0.0328 Ratio of minimum to maximum apparent transmission: 0.867291 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
S10.65769 (5)0.38059 (5)0.08727 (2)0.01787 (14)
O20.85778 (13)0.51574 (15)−0.10128 (6)0.0190 (3)
O10.93907 (13)0.27205 (16)−0.03046 (7)0.0208 (3)
H1O0.93100.3360−0.06330.031*
N20.70234 (16)0.67387 (18)−0.06965 (8)0.0162 (3)
N10.73387 (15)0.51959 (17)0.05471 (8)0.0155 (3)
O30.55860 (13)0.31248 (15)0.03050 (7)0.0207 (3)
O40.61656 (14)0.44317 (17)0.14534 (7)0.0255 (3)
C60.88260 (18)0.2273 (2)0.07631 (9)0.0173 (4)
C90.78894 (18)0.5530 (2)−0.05975 (9)0.0154 (4)
C100.67298 (17)0.7818 (2)−0.12596 (9)0.0166 (4)
C70.87323 (18)0.3265 (2)0.01508 (9)0.0162 (4)
C10.78842 (19)0.2430 (2)0.11619 (9)0.0187 (4)
C180.8113 (2)0.6356 (2)0.10495 (10)0.0226 (4)
H18A0.89110.58510.13480.034*
H18B0.75420.67640.13360.034*
H18C0.83970.72200.07950.034*
C50.98373 (19)0.1138 (2)0.09600 (10)0.0216 (4)
H51.04800.10000.06950.026*
C80.80079 (18)0.4615 (2)0.00417 (9)0.0151 (4)
C140.61045 (19)1.0447 (2)−0.16562 (11)0.0226 (4)
C160.6568 (2)0.9831 (2)−0.03662 (10)0.0233 (4)
H16A0.58960.9260−0.01900.035*
H16B0.64101.0959−0.03440.035*
H16C0.74750.9578−0.00820.035*
C40.9901 (2)0.0215 (2)0.15404 (11)0.0266 (5)
H41.0594−0.05490.16720.032*
C150.64525 (18)0.9363 (2)−0.11082 (10)0.0181 (4)
C120.6398 (2)0.8437 (2)−0.24637 (10)0.0246 (4)
H120.64020.8140−0.29230.030*
C110.67017 (19)0.7340 (2)−0.19320 (9)0.0203 (4)
H110.68870.6283−0.20250.024*
C30.8966 (2)0.0393 (2)0.19319 (11)0.0294 (5)
H30.9024−0.02460.23290.035*
C130.6091 (2)0.9960 (2)−0.23262 (10)0.0248 (4)
H130.58651.0692−0.26970.030*
C20.7944 (2)0.1507 (2)0.17439 (10)0.0258 (4)
H20.72990.16330.20090.031*
C170.5769 (2)1.2125 (3)−0.15299 (12)0.0350 (5)
H17A0.55291.2691−0.19730.052*
H17B0.65551.2624−0.12170.052*
H17C0.50061.2151−0.13170.052*
H1N0.657 (2)0.683 (3)−0.0397 (12)0.026 (6)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.0187 (2)0.0193 (3)0.0181 (2)−0.00080 (18)0.00918 (18)−0.00048 (18)
O20.0210 (7)0.0221 (7)0.0160 (6)0.0015 (5)0.0085 (5)0.0000 (5)
O10.0218 (7)0.0229 (7)0.0208 (7)0.0045 (6)0.0112 (6)0.0014 (5)
N20.0159 (8)0.0182 (8)0.0155 (8)0.0018 (6)0.0062 (6)0.0012 (6)
N10.0162 (8)0.0170 (8)0.0151 (7)−0.0005 (6)0.0073 (6)−0.0023 (6)
O30.0156 (7)0.0230 (7)0.0245 (7)−0.0022 (5)0.0072 (5)−0.0032 (6)
O40.0325 (8)0.0269 (8)0.0232 (7)0.0000 (6)0.0183 (6)−0.0027 (6)
C60.0168 (9)0.0173 (9)0.0163 (9)−0.0034 (7)0.0018 (7)−0.0016 (7)
C90.0157 (9)0.0163 (9)0.0136 (8)−0.0038 (7)0.0028 (7)−0.0017 (7)
C100.0121 (8)0.0192 (9)0.0170 (9)−0.0021 (7)0.0013 (7)0.0026 (7)
C70.0130 (8)0.0187 (9)0.0171 (9)−0.0023 (7)0.0041 (7)−0.0018 (7)
C10.0223 (9)0.0172 (9)0.0161 (9)−0.0019 (7)0.0037 (7)−0.0020 (7)
C180.0263 (10)0.0227 (10)0.0197 (10)−0.0050 (8)0.0075 (8)−0.0057 (8)
C50.0192 (10)0.0194 (10)0.0243 (10)0.0010 (7)0.0020 (8)−0.0008 (8)
C80.0147 (8)0.0179 (9)0.0134 (9)−0.0015 (7)0.0049 (7)−0.0016 (7)
C140.0180 (9)0.0190 (10)0.0273 (10)−0.0014 (8)−0.0003 (8)0.0024 (8)
C160.0267 (11)0.0192 (10)0.0250 (10)0.0004 (8)0.0083 (9)−0.0035 (8)
C40.0292 (11)0.0210 (10)0.0246 (10)0.0028 (8)−0.0023 (9)0.0033 (8)
C150.0140 (9)0.0193 (9)0.0199 (9)−0.0028 (7)0.0025 (7)−0.0007 (7)
C120.0275 (11)0.0277 (11)0.0163 (9)−0.0036 (8)0.0015 (8)0.0010 (8)
C110.0235 (10)0.0196 (10)0.0168 (9)−0.0011 (8)0.0034 (8)−0.0005 (7)
C30.0429 (13)0.0229 (11)0.0187 (10)−0.0008 (9)0.0013 (9)0.0054 (8)
C130.0250 (11)0.0249 (11)0.0211 (10)−0.0024 (8)−0.0005 (8)0.0073 (8)
C20.0353 (12)0.0248 (10)0.0190 (10)−0.0030 (9)0.0101 (9)0.0017 (8)
C170.0428 (14)0.0220 (11)0.0361 (13)0.0039 (9)0.0029 (11)0.0019 (9)

Geometric parameters (Å, °)

S1—O41.4308 (13)C5—C41.386 (3)
S1—O31.4345 (14)C5—H50.9500
S1—N11.6424 (15)C14—C131.393 (3)
S1—C11.7639 (19)C14—C151.405 (3)
O2—C91.257 (2)C14—C171.510 (3)
O1—C71.344 (2)C16—C151.504 (3)
O1—H1O0.8400C16—H16A0.9800
N2—C91.343 (2)C16—H16B0.9800
N2—C101.422 (2)C16—H16C0.9800
N2—H1N0.85 (2)C4—C31.389 (3)
N1—C81.442 (2)C4—H40.9500
N1—C181.485 (2)C12—C131.383 (3)
C6—C51.400 (3)C12—C111.388 (3)
C6—C11.404 (3)C12—H120.9500
C6—C71.467 (3)C11—H110.9500
C9—C81.471 (2)C3—C21.394 (3)
C10—C111.392 (3)C3—H30.9500
C10—C151.399 (3)C13—H130.9500
C7—C81.359 (3)C2—H20.9500
C1—C21.389 (3)C17—H17A0.9800
C18—H18A0.9800C17—H17B0.9800
C18—H18B0.9800C17—H17C0.9800
C18—H18C0.9800
O4—S1—O3119.46 (8)C7—C8—C9120.66 (16)
O4—S1—N1108.44 (8)N1—C8—C9118.12 (15)
O3—S1—N1107.14 (8)C13—C14—C15118.96 (18)
O4—S1—C1109.98 (9)C13—C14—C17119.71 (18)
O3—S1—C1108.17 (8)C15—C14—C17121.33 (18)
N1—S1—C1102.26 (8)C15—C16—H16A109.5
C7—O1—H1O109.5C15—C16—H16B109.5
C9—N2—C10127.78 (16)H16A—C16—H16B109.5
C9—N2—H1N115.6 (16)C15—C16—H16C109.5
C10—N2—H1N116.6 (16)H16A—C16—H16C109.5
C8—N1—C18115.56 (14)H16B—C16—H16C109.5
C8—N1—S1112.65 (12)C5—C4—C3120.83 (19)
C18—N1—S1116.30 (12)C5—C4—H4119.6
C5—C6—C1118.36 (17)C3—C4—H4119.6
C5—C6—C7121.28 (17)C10—C15—C14118.67 (17)
C1—C6—C7120.36 (17)C10—C15—C16119.51 (17)
O2—C9—N2123.99 (16)C14—C15—C16121.80 (17)
O2—C9—C8119.87 (16)C13—C12—C11120.17 (18)
N2—C9—C8116.14 (15)C13—C12—H12119.9
C11—C10—C15121.91 (17)C11—C12—H12119.9
C11—C10—N2120.98 (17)C12—C11—C10118.68 (18)
C15—C10—N2117.10 (16)C12—C11—H11120.7
O1—C7—C8122.29 (16)C10—C11—H11120.7
O1—C7—C6114.99 (16)C4—C3—C2120.22 (19)
C8—C7—C6122.71 (16)C4—C3—H3119.9
C2—C1—C6121.79 (18)C2—C3—H3119.9
C2—C1—S1121.16 (15)C12—C13—C14121.55 (18)
C6—C1—S1117.01 (14)C12—C13—H13119.2
N1—C18—H18A109.5C14—C13—H13119.2
N1—C18—H18B109.5C1—C2—C3118.73 (19)
H18A—C18—H18B109.5C1—C2—H2120.6
N1—C18—H18C109.5C3—C2—H2120.6
H18A—C18—H18C109.5C14—C17—H17A109.5
H18B—C18—H18C109.5C14—C17—H17B109.5
C4—C5—C6120.06 (18)H17A—C17—H17B109.5
C4—C5—H5120.0C14—C17—H17C109.5
C6—C5—H5120.0H17A—C17—H17C109.5
C7—C8—N1121.22 (16)H17B—C17—H17C109.5
O4—S1—N1—C8169.35 (12)C6—C7—C8—C9−176.92 (16)
O3—S1—N1—C8−60.45 (14)C18—N1—C8—C794.4 (2)
C1—S1—N1—C853.19 (14)S1—N1—C8—C7−42.6 (2)
O4—S1—N1—C1832.66 (15)C18—N1—C8—C9−85.4 (2)
O3—S1—N1—C18162.85 (13)S1—N1—C8—C9137.60 (14)
C1—S1—N1—C18−83.51 (14)O2—C9—C8—C7−7.7 (3)
C10—N2—C9—O2−1.0 (3)N2—C9—C8—C7172.23 (16)
C10—N2—C9—C8179.07 (16)O2—C9—C8—N1172.09 (16)
C9—N2—C10—C1135.7 (3)N2—C9—C8—N1−8.0 (2)
C9—N2—C10—C15−145.22 (18)C6—C5—C4—C30.3 (3)
C5—C6—C7—O118.7 (2)C11—C10—C15—C141.6 (3)
C1—C6—C7—O1−160.50 (16)N2—C10—C15—C14−177.46 (16)
C5—C6—C7—C8−162.85 (18)C11—C10—C15—C16−176.85 (17)
C1—C6—C7—C818.0 (3)N2—C10—C15—C164.1 (2)
C5—C6—C1—C20.7 (3)C13—C14—C15—C10−2.1 (3)
C7—C6—C1—C2179.90 (17)C17—C14—C15—C10178.91 (18)
C5—C6—C1—S1−176.97 (14)C13—C14—C15—C16176.29 (18)
C7—C6—C1—S12.2 (2)C17—C14—C15—C16−2.7 (3)
O4—S1—C1—C232.47 (18)C13—C12—C11—C10−2.0 (3)
O3—S1—C1—C2−99.61 (17)C15—C10—C11—C120.5 (3)
N1—S1—C1—C2147.51 (16)N2—C10—C11—C12179.45 (17)
O4—S1—C1—C6−149.86 (14)C5—C4—C3—C20.1 (3)
O3—S1—C1—C678.06 (16)C11—C12—C13—C141.4 (3)
N1—S1—C1—C6−34.82 (16)C15—C14—C13—C120.6 (3)
C1—C6—C5—C4−0.7 (3)C17—C14—C13—C12179.7 (2)
C7—C6—C5—C4−179.94 (17)C6—C1—C2—C3−0.2 (3)
O1—C7—C8—N1−178.38 (15)S1—C1—C2—C3177.33 (16)
C6—C7—C8—N13.3 (3)C4—C3—C2—C1−0.2 (3)
O1—C7—C8—C91.4 (3)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O1—H1O···O20.841.792.5320 (18)147
N2—H1N···O3i0.85 (2)2.26 (2)2.972 (2)141 (2)
C3—H3···O4ii0.952.493.352 (3)150

Symmetry codes: (i) −x+1, −y+1, −z; (ii) −x+3/2, y−1/2, −z+1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BT2887).

References

  • Gennari, C., Salom, B., Potenza, D. & Williams, A. (1994). Angew. Chem. Int. Ed. Engl 33, 2067–2069.
  • Hooft, R. W. W. (1998). COLLECT Nonius BV, Delft, The Netherlands.
  • Lombardino, J. G. & Wiseman, E. H. (1972). J. Med. Chem.15, 848–849. [PubMed]
  • Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307–326. New York: Academic Press.
  • Sheldrick, G. M. (2007). SADABS Bruker AXS Inc., Madison, Wisconsin, USA.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Siddiqui, W. A., Ahmad, S., Khan, I. U., Siddiqui, H. L. & Weaver, G. W. (2007). Synth. Commun 37, 767–773.
  • Siddiqui, W. A., Ahmad, S., Siddiqui, H. L., Tariq, M. I. & Parvez, M. (2007). Acta Cryst. E63, o4585.
  • Siddiqui, W. A., Ahmad, S., Tariq, M. I., Siddiqui, H. L. & Parvez, M. (2008). Acta Cryst. C64, o4-o6. [PubMed]
  • Zia-ur-Rehman, M., Anwar, J., Ahmad, S. & Siddiqui, H. L. (2006). Chem. Pharm. Bull 54, 1175–1178. [PubMed]
  • Zia-ur-Rehman, M., Choudary, J. A., Elsegood, M. R. J., Siddiqui, H. L. & Khan, K. M. (2009). Eur. J. Med. Chem 44, 1311–1316. [PubMed]

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