PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2009 October 1; 65(Pt 10): o2451.
Published online 2009 September 12. doi:  10.1107/S1600536809036204
PMCID: PMC2970237

Piperidinium 4-hydr­oxy-3-methoxy­carbon­yl-1,2-benzothia­zin-2-ide 1,1-dioxide

Abstract

In the anion of the title compound, C5H12N+·C10H8NO5S, the thia­zine ring adopts a distorted half-chair conformation and the enolic H atom is involved in an intra­molecular O—H(...)O hydrogen bond, forming a six-membered ring. The anions and cations are connected via N—H(...)N and N—H(...)O inter­actions.

Related literature

For the synthesis of related mol­ecules, see: Zia-ur-Rehman et al. (2005 [triangle], 2006 [triangle]); Braun (1923 [triangle]). For the biological activity of 1,2-benzothia­zine1,1-dioxides, see: Bihovsky et al. (2004 [triangle]); Turck et al. (1996 [triangle]); Zia-ur-Rehman et al. (2009 [triangle]). For related structures, see: Golič & Leban (1987 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o2451-scheme1.jpg

Experimental

Crystal data

  • C5H12N+·C10H8NO5S
  • M r = 340.39
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o2451-efi1.jpg
  • a = 12.0423 (5) Å
  • b = 9.1791 (3) Å
  • c = 14.5193 (5) Å
  • β = 90.556 (2)°
  • V = 1604.85 (10) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.23 mm−1
  • T = 296 K
  • 0.39 × 0.33 × 0.29 mm

Data collection

  • Bruker KAPPA APEXII CCD diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker 2007 [triangle]) T min = 0.921, T max = 0.940
  • 16000 measured reflections
  • 3690 independent reflections
  • 2896 reflections with I > 2σ(I)
  • R int = 0.025

Refinement

  • R[F 2 > 2σ(F 2)] = 0.036
  • wR(F 2) = 0.103
  • S = 1.03
  • 3690 reflections
  • 216 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.30 e Å−3
  • Δρmin = −0.34 e Å−3

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, New_Global_Publ_Block. DOI: 10.1107/S1600536809036204/bt5055sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809036204/bt5055Isup2.hkl

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

Acknowledgments

The authors are grateful to PCSIR Laboratories Complex, Lahore, for the provision of necessary facilities to complete this work.

supplementary crystallographic information

Comment

Owing to their application as non-steroidal anti-inflammatory agents (Turck et al., 1996), considerable attention has been given to synthetic and structural investigations of 1,2-benzothiazine1,1-dioxides and their precursor intermediates (Golič & Leban, 1987). These are known to possess a versatile range of biological activities and have been synthesized continuously since the very first synthesis (Braun, 1923). Among these, Piroxicam (Zia-ur-Rehman et al., 2005), and Meloxicam (Turck et al., 1996) are familiar for their analgesic action and are being used world wide as non-steroidal anti-inflammatory drugs (NSAIDs). Besides, 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. Some of the 3,4-dihydro-1,2-benzothiazine-3-carboxylate 1,1-dioxide α-ketomide and P(2)—P(3) peptide mimetic aldehyde compounds act as potent calpain I inhibitors (Bihovsky et al., 2004) while 1,2-benzothiazin-3-yl-quinazolin-4(3H)-ones possess anti-bacterial properties (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 (Scheme and figure 1). The asymmetric unit contains one piperidinum cation and one 4-hydroxy-3-(methoxycarbonyl)-1,2-benzothiazin-2-ide 1,1-dioxide anion. The piperidinium cation displays a typical chair conformation. The thiazine ring of the anion, involving two double bonds, exhibits a distorted half-chair conformation and the enolic hydrogen on O1 is involved in intramolecular hydrogen bonding giving rise to a six membered hydrogen bond ring (Table 1). Both the ions are linked together through N—H···N and N—H···O interactions. Adjacent asymmetric units are linked through intermolecular N—H···O hydrogen bonds, resulting in zigzag chains lying along the b axis (Figure 2).

Experimental

A mixture of methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide (2.693 g; 10.0 mmoles), piperidine (1.02 g, 12.0 mmoles) and toluene (25.0 ml) was heated to reflux for an hour. Solvent and excess piperdine were removed under vacuum and the resulting solids were dried 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. The following distances were used: Methyl C—H 0.98 Å. °, aromatic C—H 0.95 Å and O—H 0.84 Å. U(H) was set to 1.2Ueq of the parent atoms or 1.5Ueq for methyl groups. The coordinates of the H atom bonded to N were refined.

Figures

Fig. 1.
The molecular structure of the title compound, with displacement ellipsoids at the 50% probability level. Hydrogen atoms bonded to C omitted for clarity.
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

C5H12N+·C10H8NO5SF(000) = 720
Mr = 340.39Dx = 1.409 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 6881 reflections
a = 12.0423 (5) Åθ = 2.6–27.4°
b = 9.1791 (3) ŵ = 0.23 mm1
c = 14.5193 (5) ÅT = 296 K
β = 90.556 (2)°Needle, white yellow
V = 1604.85 (10) Å30.39 × 0.33 × 0.29 mm
Z = 4

Data collection

Bruker KAPPA APEXII CCD diffractometer3690 independent reflections
Radiation source: fine-focus sealed tube2896 reflections with I > 2σ(I)
graphiteRint = 0.025
[var phi] and ω scansθmax = 27.5°, θmin = 2.2°
Absorption correction: multi-scan (SADABS; Bruker 2007)h = −15→15
Tmin = 0.921, Tmax = 0.940k = −11→11
16000 measured reflectionsl = −18→18

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)] = 0.036Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.103H atoms treated by a mixture of independent and constrained refinement
S = 1.03w = 1/[σ2(Fo2) + (0.0492P)2 + 0.5427P] where P = (Fo2 + 2Fc2)/3
3690 reflections(Δ/σ)max = 0.001
216 parametersΔρmax = 0.30 e Å3
0 restraintsΔρmin = −0.34 e Å3

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
S10.46805 (3)0.74091 (4)0.76725 (3)0.02947 (12)
O10.48950 (11)0.80132 (14)0.85705 (8)0.0461 (3)
O20.38877 (9)0.62124 (13)0.76755 (8)0.0388 (3)
O30.51396 (13)0.69087 (18)0.47854 (8)0.0570 (4)
H30.47060.74290.44970.085*
O40.36167 (13)0.88585 (17)0.45879 (8)0.0598 (4)
O50.30030 (10)1.00194 (13)0.58304 (8)0.0428 (3)
N10.33595 (12)0.12173 (16)0.77625 (10)0.0354 (3)
H2N0.2658 (17)0.113 (2)0.7631 (13)0.042*
H1N0.3719 (16)0.041 (2)0.7515 (13)0.042*
N20.43544 (11)0.86485 (14)0.69844 (9)0.0334 (3)
C10.59021 (13)0.64809 (18)0.62624 (12)0.0358 (4)
C20.67446 (15)0.5623 (2)0.58853 (15)0.0502 (5)
H2A0.67680.54740.52520.060*
C30.75373 (15)0.4998 (2)0.64477 (17)0.0576 (6)
H3A0.80790.44050.61910.069*
C40.75421 (15)0.5235 (2)0.73845 (17)0.0536 (5)
H40.81040.48430.77520.064*
C50.67134 (14)0.60531 (19)0.77759 (14)0.0425 (4)
H50.67110.62160.84080.051*
C60.58827 (12)0.66317 (17)0.72195 (11)0.0322 (3)
C70.50910 (14)0.72383 (19)0.56940 (11)0.0359 (4)
C80.43901 (13)0.82600 (18)0.60482 (10)0.0319 (3)
C90.36534 (14)0.90591 (19)0.54163 (11)0.0366 (4)
C100.22478 (18)1.0821 (2)0.52354 (13)0.0553 (5)
H10A0.17491.01540.49340.083*
H10B0.26641.13420.47810.083*
H10C0.18291.14990.55970.083*
C110.37737 (15)0.25674 (18)0.73166 (12)0.0396 (4)
H11A0.33540.33990.75340.047*
H11B0.36700.24980.66550.047*
C120.49815 (17)0.2779 (2)0.75380 (14)0.0483 (5)
H12A0.52420.36670.72490.058*
H12B0.54040.19710.72920.058*
C130.51701 (19)0.2874 (2)0.85636 (15)0.0592 (6)
H13A0.48150.37430.88000.071*
H13B0.59600.29450.86940.071*
C140.47016 (19)0.1542 (2)0.90404 (13)0.0560 (5)
H14A0.51430.06970.88800.067*
H14B0.47580.16760.97020.067*
C150.35025 (17)0.1258 (2)0.87800 (13)0.0517 (5)
H15A0.32680.03360.90400.062*
H15B0.30380.20200.90330.062*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.0313 (2)0.0288 (2)0.0283 (2)0.00206 (15)−0.00296 (14)0.00160 (15)
O10.0628 (8)0.0457 (7)0.0298 (6)0.0067 (6)−0.0103 (5)−0.0026 (5)
O20.0301 (6)0.0365 (6)0.0498 (7)−0.0018 (5)0.0027 (5)0.0071 (5)
O30.0690 (10)0.0707 (10)0.0313 (7)0.0207 (8)0.0058 (6)−0.0064 (6)
O40.0770 (10)0.0738 (10)0.0285 (6)0.0239 (8)−0.0077 (6)0.0021 (6)
O50.0503 (7)0.0440 (7)0.0339 (6)0.0158 (6)−0.0076 (5)0.0031 (5)
N10.0295 (7)0.0335 (8)0.0431 (8)0.0014 (6)−0.0020 (6)−0.0021 (6)
N20.0425 (7)0.0295 (7)0.0280 (6)0.0070 (6)−0.0034 (5)−0.0003 (5)
C10.0305 (8)0.0330 (8)0.0439 (9)−0.0015 (7)0.0060 (7)0.0023 (7)
C20.0409 (10)0.0493 (11)0.0606 (12)0.0078 (9)0.0150 (9)−0.0001 (10)
C30.0320 (9)0.0491 (12)0.0918 (17)0.0096 (9)0.0121 (10)0.0026 (11)
C40.0289 (9)0.0453 (11)0.0863 (16)0.0027 (8)−0.0118 (9)0.0105 (11)
C50.0342 (8)0.0358 (9)0.0573 (11)−0.0029 (7)−0.0120 (8)0.0066 (8)
C60.0258 (7)0.0268 (8)0.0438 (9)−0.0035 (6)−0.0018 (6)0.0021 (7)
C70.0375 (9)0.0401 (9)0.0301 (8)−0.0004 (7)0.0038 (6)0.0003 (7)
C80.0350 (8)0.0322 (8)0.0284 (7)−0.0001 (7)−0.0011 (6)0.0022 (6)
C90.0417 (9)0.0363 (9)0.0317 (8)−0.0004 (8)−0.0021 (7)0.0030 (7)
C100.0630 (13)0.0602 (13)0.0426 (10)0.0239 (10)−0.0116 (9)0.0095 (9)
C110.0444 (9)0.0312 (9)0.0430 (9)−0.0001 (7)−0.0060 (7)0.0015 (7)
C120.0467 (10)0.0394 (10)0.0589 (12)−0.0109 (8)−0.0033 (9)0.0003 (9)
C130.0645 (14)0.0474 (12)0.0653 (13)−0.0078 (10)−0.0238 (11)−0.0101 (10)
C140.0728 (14)0.0560 (13)0.0389 (10)0.0058 (11)−0.0160 (9)−0.0044 (9)
C150.0611 (12)0.0534 (12)0.0409 (10)0.0075 (10)0.0129 (9)0.0001 (9)

Geometric parameters (Å, °)

S1—O11.4379 (12)C4—H40.9300
S1—O21.4554 (12)C5—C61.385 (2)
S1—N21.5618 (13)C5—H50.9300
S1—C61.7483 (16)C7—C81.366 (2)
O3—C71.3553 (19)C8—C91.467 (2)
O3—H30.8200C10—H10A0.9600
O4—C91.217 (2)C10—H10B0.9600
O5—C91.327 (2)C10—H10C0.9600
O5—C101.449 (2)C11—C121.499 (3)
N1—C151.486 (2)C11—H11A0.9700
N1—C111.487 (2)C11—H11B0.9700
N1—H2N0.87 (2)C12—C131.507 (3)
N1—H1N0.93 (2)C12—H12A0.9700
N2—C81.4063 (19)C12—H12B0.9700
C1—C61.397 (2)C13—C141.516 (3)
C1—C21.400 (2)C13—H13A0.9700
C1—C71.450 (2)C13—H13B0.9700
C2—C31.375 (3)C14—C151.512 (3)
C2—H2A0.9300C14—H14A0.9700
C3—C41.377 (3)C14—H14B0.9700
C3—H3A0.9300C15—H15A0.9700
C4—C51.376 (3)C15—H15B0.9700
O1—S1—O2113.61 (8)O4—C9—O5122.16 (16)
O1—S1—N2109.94 (7)O4—C9—C8123.95 (16)
O2—S1—N2113.00 (7)O5—C9—C8113.88 (14)
O1—S1—C6110.88 (8)O5—C10—H10A109.5
O2—S1—C6103.81 (7)O5—C10—H10B109.5
N2—S1—C6105.11 (7)H10A—C10—H10B109.5
C7—O3—H3109.5O5—C10—H10C109.5
C9—O5—C10115.92 (14)H10A—C10—H10C109.5
C15—N1—C11112.06 (15)H10B—C10—H10C109.5
C15—N1—H2N108.9 (12)N1—C11—C12110.10 (15)
C11—N1—H2N108.1 (13)N1—C11—H11A109.6
C15—N1—H1N110.7 (11)C12—C11—H11A109.6
C11—N1—H1N109.6 (11)N1—C11—H11B109.6
H2N—N1—H1N107.3 (17)C12—C11—H11B109.6
C8—N2—S1115.08 (11)H11A—C11—H11B108.2
C6—C1—C2117.64 (16)C11—C12—C13110.86 (17)
C6—C1—C7120.06 (14)C11—C12—H12A109.5
C2—C1—C7122.27 (17)C13—C12—H12A109.5
C3—C2—C1120.25 (19)C11—C12—H12B109.5
C3—C2—H2A119.9C13—C12—H12B109.5
C1—C2—H2A119.9H12A—C12—H12B108.1
C2—C3—C4121.11 (18)C12—C13—C14110.59 (16)
C2—C3—H3A119.4C12—C13—H13A109.5
C4—C3—H3A119.4C14—C13—H13A109.5
C5—C4—C3119.85 (18)C12—C13—H13B109.5
C5—C4—H4120.1C14—C13—H13B109.5
C3—C4—H4120.1H13A—C13—H13B108.1
C4—C5—C6119.40 (19)C15—C14—C13112.54 (17)
C4—C5—H5120.3C15—C14—H14A109.1
C6—C5—H5120.3C13—C14—H14A109.1
C5—C6—C1121.54 (16)C15—C14—H14B109.1
C5—C6—S1122.21 (14)C13—C14—H14B109.1
C1—C6—S1115.89 (12)H14A—C14—H14B107.8
O3—C7—C8123.54 (15)N1—C15—C14110.74 (15)
O3—C7—C1114.31 (15)N1—C15—H15A109.5
C8—C7—C1122.03 (15)C14—C15—H15A109.5
C7—C8—N2124.26 (14)N1—C15—H15B109.5
C7—C8—C9118.70 (14)C14—C15—H15B109.5
N2—C8—C9116.99 (14)H15A—C15—H15B108.1
O1—S1—N2—C8165.08 (12)C2—C1—C7—O37.3 (2)
O2—S1—N2—C8−66.84 (13)C6—C1—C7—C89.0 (3)
C6—S1—N2—C845.69 (13)C2—C1—C7—C8−168.87 (17)
C6—C1—C2—C3−2.0 (3)O3—C7—C8—N2−177.84 (16)
C7—C1—C2—C3175.93 (18)C1—C7—C8—N2−2.0 (3)
C1—C2—C3—C4−2.0 (3)O3—C7—C8—C9−0.5 (3)
C2—C3—C4—C53.1 (3)C1—C7—C8—C9175.28 (15)
C3—C4—C5—C6−0.1 (3)S1—N2—C8—C7−29.7 (2)
C4—C5—C6—C1−4.0 (3)S1—N2—C8—C9152.98 (12)
C4—C5—C6—S1168.73 (14)C10—O5—C9—O4−0.2 (3)
C2—C1—C6—C55.0 (2)C10—O5—C9—C8−179.11 (16)
C7—C1—C6—C5−172.97 (16)C7—C8—C9—O40.8 (3)
C2—C1—C6—S1−168.17 (13)N2—C8—C9—O4178.31 (17)
C7—C1—C6—S113.8 (2)C7—C8—C9—O5179.66 (15)
O1—S1—C6—C528.75 (16)N2—C8—C9—O5−2.8 (2)
O2—S1—C6—C5−93.61 (15)C15—N1—C11—C1259.0 (2)
N2—S1—C6—C5147.50 (14)N1—C11—C12—C13−58.6 (2)
O1—S1—C6—C1−158.11 (12)C11—C12—C13—C1455.4 (2)
O2—S1—C6—C179.53 (13)C12—C13—C14—C15−52.5 (2)
N2—S1—C6—C1−39.36 (14)C11—N1—C15—C14−55.5 (2)
C6—C1—C7—O3−174.80 (15)C13—C14—C15—N152.2 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O3—H3···O40.821.862.577 (2)145
N1—H1N···N2i0.932 (19)1.951 (19)2.881 (2)175.4 (18)
N1—H2N···O2ii0.87 (2)1.91 (2)2.7739 (18)172.4 (18)

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BT5055).

References

  • Bihovsky, R., Tao, M., Mallamo, J. P. & Wells, G. J. (2004). Bioorg. Med. Chem. Lett 14, 1035–1038. [PubMed]
  • Braun, J. (1923). Chem. Ber 56, 2332–2343.
  • Bruker (2007). APEX2, SAINT and SADABS Bruker AXS Inc., Madison, Wisconsin, USA.
  • Farrugia, L. J. (1999). J. Appl. Cryst.32, 837–838.
  • Golič, L. & Leban, I. (1987). Acta Cryst. C43, 280–282.
  • Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst.39, 453–457.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]
  • Turck, D., Busch, U., Heinzel, G., Narjes, H. & Nehmiz, G. (1996). J. Clin. Pharmacol 36, 79–84. [PubMed]
  • Zia-ur-Rehman, M., Choudary, J. A. & Ahmad, S. (2005). Bull. Korean Chem. Soc 26,1771–1775.
  • Zia-ur-Rehman, M. Z., Choudary, J. A., 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]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography