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Acta Crystallogr Sect E Struct Rep Online. 2010 November 1; 66(Pt 11): o3019.
Published online 2010 October 31. doi:  10.1107/S1600536810043904
PMCID: PMC3009207

4,5,6,7,8,9-Hexahydro-2H-cyclo­octa[c]pyrazol-1-ium-3-olate

Abstract

The title compound, C9H14N2O, exists in the zwitterionic form in the crystal. The cyclo­octane ring adopts a twisted boat-chair conformation. In the crystal, inter­molecular N—H(...)O hydrogen bonds link the mol­ecules into sheets lying parallel to bc. The structure is also stabilized by π–π inter­actions, with a centroid-to-centroid distance of 3.5684 (8) Å.

Related literature

For pyrazole derivatives and their microbial activities, see: Ragavan et al. (2009 [triangle], 2010 [triangle]). For a related structure, see: Xiong et al. (2007 [triangle]). For the stability of the temperature controller used for data collection, see: Cosier & Glazer (1986 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o3019-scheme1.jpg

Experimental

Crystal data

  • C9H14N2O
  • M r = 166.22
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o3019-efi1.jpg
  • a = 12.8078 (2) Å
  • b = 6.7758 (1) Å
  • c = 10.7096 (2) Å
  • β = 111.620 (1)°
  • V = 864.03 (2) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 100 K
  • 0.54 × 0.24 × 0.11 mm

Data collection

  • Bruker SMART APEXII CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2009 [triangle]) T min = 0.956, T max = 0.991
  • 6990 measured reflections
  • 1680 independent reflections
  • 1474 reflections with I > 2σ(I)
  • R int = 0.026

Refinement

  • R[F 2 > 2σ(F 2)] = 0.037
  • wR(F 2) = 0.095
  • S = 1.05
  • 1680 reflections
  • 117 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.25 e Å−3
  • Δρmin = −0.25 e Å−3

Data collection: APEX2 (Bruker, 2009 [triangle]); cell refinement: SAINT (Bruker, 2009 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810043904/fj2356sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810043904/fj2356Isup2.hkl

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

Acknowledgments

HKF and CSY thank USM for a Research University Grant (No. 1001/PFIZIK/811160). VV is grateful to DST-India for funding through the Young Scientist Scheme (Fast Track Proposal).

supplementary crystallographic information

Comment

Antibacterial and antifungal activities of the azoles are most widely studied and some of them are in clinical practice as anti-microbial agents. However, the azole-resistant strains led to the development of new antimicrobial compounds. In particular pyrazole derivatives are extensively studied and used as antimicrobial agents. Pyrazole is an important class of heterocyclic compounds and many pyrazole derivatives are reported to have a broad spectrum of biological properties such as anti-inflammatory, antifungal, herbicidal, anti-tumour, cytotoxic, molecular modelling and antiviral activities. Pyrazole derivatives also act as antiangiogenic agents, A3 adenosine receptor antagonists, neuropeptide YY5 receptor antagonists, kinase inhibitor for treatment of type 2 diabetes, hyperlipidemia, obesity, and thrombopiotinmimetics. Recently urea derivatives of pyrazoles have been reported as potent inhibitors of p38 kinase. Since the high electronegativity of halogens (particularly chlorine and fluorine) in the aromatic part of the drug molecules play an important role in enhancing their biological activity, we are interested to have 4-fluoro or 4-chloro substitution in the aryls of 1,5-diaryl pyrazoles. As part of our on-going research aiming on the synthesis of new antimicrobial compounds, we have reported the synthesis of novel pyrazole derivatives and their microbial activities (Ragavan et al., 2009, 2010).

The title compound exists in an zwitterionic form (Fig. 1). The cyclooctane ring adopts a twisted boat-chair conformation which similar to Xiong et al. (2007). In the crystal structure, intermolecular N1—H1N1···O1 and N2—H1N2···O1 hydrogen bonds linked the molecules into planes parallel to the bc plane (Fig. 2). The structure is stabilized by the π–π interactions [Cg1···Cg1iii = 3.5684 (8) Å; Cg1 is centroid of N1–N2–C1–C8–C9 ring; (iii) 1 - x, 1 - y, 1 - z].

Experimental

The compound has been synthesized using the method available in the literature Ragavan et al., (2010) and recrystallized using the ethanol–chloroform 1:1 mixture. Yield: 74%. m.p. 221.6–228.8 °C.

Refinement

The N-bound H atoms were located from difference Fourier map and refined freely. The rest of H atoms were positioned geometrically [C—H = 0.97 Å] and refined using a riding model [Uiso(H) = 1.2Ueq].

Figures

Fig. 1.
The molecular structure of the title compound with atom labels and 50% probability ellipsoids for non-H atoms.
Fig. 2.
The crystal packing of title compound, viewed down b axis, showing the molecules linked into planes parallel to the bc plane. Intermolecular hydrogen bonds are shown as dashed lines.

Crystal data

C9H14N2OF(000) = 360
Mr = 166.22Dx = 1.278 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 3802 reflections
a = 12.8078 (2) Åθ = 3.5–30.1°
b = 6.7758 (1) ŵ = 0.09 mm1
c = 10.7096 (2) ÅT = 100 K
β = 111.620 (1)°Plate, colourless
V = 864.03 (2) Å30.54 × 0.24 × 0.11 mm
Z = 4

Data collection

Bruker SMART APEXII CCD area-detector diffractometer1680 independent reflections
Radiation source: fine-focus sealed tube1474 reflections with I > 2σ(I)
graphiteRint = 0.026
[var phi] and ω scansθmax = 26.0°, θmin = 1.7°
Absorption correction: multi-scan (SADABS; Bruker, 2009)h = −15→15
Tmin = 0.956, Tmax = 0.991k = −8→8
6990 measured reflectionsl = −13→12

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)] = 0.037Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.095H atoms treated by a mixture of independent and constrained refinement
S = 1.05w = 1/[σ2(Fo2) + (0.047P)2 + 0.3516P] where P = (Fo2 + 2Fc2)/3
1680 reflections(Δ/σ)max < 0.001
117 parametersΔρmax = 0.25 e Å3
0 restraintsΔρmin = −0.25 e Å3

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K.
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
O10.41579 (8)0.06094 (13)0.31883 (8)0.0190 (2)
N10.44456 (9)0.21181 (16)0.52370 (10)0.0160 (3)
N20.41423 (9)0.38447 (16)0.56789 (11)0.0154 (3)
C10.34257 (10)0.48051 (18)0.46046 (12)0.0149 (3)
C20.28502 (11)0.66563 (19)0.47482 (13)0.0177 (3)
H2A0.27110.74760.39610.021*
H2B0.33350.73840.55250.021*
C30.17257 (11)0.6209 (2)0.49123 (12)0.0189 (3)
H3A0.18830.57340.58180.023*
H3B0.13060.74300.48070.023*
C40.09909 (11)0.4691 (2)0.39200 (12)0.0185 (3)
H4A0.02950.45550.40750.022*
H4B0.13710.34260.41130.022*
C50.07002 (11)0.5164 (2)0.24164 (12)0.0191 (3)
H5A−0.01050.50250.19540.023*
H5B0.08880.65340.23390.023*
C60.12881 (11)0.38840 (19)0.16907 (12)0.0189 (3)
H6A0.09050.40650.07310.023*
H6B0.12020.25100.18890.023*
C70.25452 (11)0.42986 (19)0.20469 (12)0.0177 (3)
H7A0.27950.35810.14240.021*
H7B0.26400.56950.19180.021*
C80.32877 (10)0.37496 (19)0.34518 (12)0.0153 (3)
C90.39626 (10)0.20329 (18)0.38724 (12)0.0150 (3)
H1N10.4969 (14)0.125 (3)0.5823 (17)0.030 (4)*
H1N20.4229 (14)0.397 (3)0.6572 (19)0.037 (5)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0272 (5)0.0181 (5)0.0123 (4)0.0062 (4)0.0082 (4)0.0006 (3)
N10.0201 (6)0.0158 (5)0.0122 (5)0.0031 (4)0.0061 (4)0.0007 (4)
N20.0181 (6)0.0167 (5)0.0122 (5)0.0012 (4)0.0065 (4)−0.0012 (4)
C10.0149 (6)0.0163 (6)0.0150 (6)−0.0015 (5)0.0072 (5)0.0013 (5)
C20.0214 (7)0.0155 (6)0.0166 (6)−0.0001 (5)0.0076 (5)−0.0017 (5)
C30.0204 (7)0.0207 (7)0.0165 (6)0.0025 (5)0.0078 (5)−0.0021 (5)
C40.0179 (7)0.0212 (7)0.0182 (6)0.0003 (5)0.0090 (5)−0.0014 (5)
C50.0179 (7)0.0217 (7)0.0163 (7)0.0025 (5)0.0045 (5)−0.0006 (5)
C60.0223 (7)0.0203 (7)0.0130 (6)0.0034 (5)0.0051 (5)0.0004 (5)
C70.0227 (7)0.0192 (6)0.0126 (6)0.0053 (5)0.0082 (5)0.0035 (5)
C80.0165 (6)0.0168 (6)0.0144 (6)0.0001 (5)0.0078 (5)0.0012 (5)
C90.0168 (6)0.0172 (6)0.0118 (6)−0.0001 (5)0.0061 (5)0.0011 (5)

Geometric parameters (Å, °)

O1—C91.2902 (15)C4—C51.5467 (17)
N1—C91.3622 (16)C4—H4A0.9700
N1—N21.3708 (15)C4—H4B0.9700
N1—H1N10.939 (18)C5—C61.5343 (17)
N2—C11.3459 (16)C5—H5A0.9700
N2—H1N20.925 (19)C5—H5B0.9700
C1—C81.3807 (17)C6—C71.5377 (18)
C1—C21.4912 (17)C6—H6A0.9700
C2—C31.5438 (17)C6—H6B0.9700
C2—H2A0.9700C7—C81.5007 (17)
C2—H2B0.9700C7—H7A0.9700
C3—C41.5283 (18)C7—H7B0.9700
C3—H3A0.9700C8—C91.4199 (17)
C3—H3B0.9700
C9—N1—N2109.39 (10)H4A—C4—H4B107.4
C9—N1—H1N1128.4 (10)C6—C5—C4115.83 (11)
N2—N1—H1N1121.9 (10)C6—C5—H5A108.3
C1—N2—N1107.96 (10)C4—C5—H5A108.3
C1—N2—H1N2128.7 (11)C6—C5—H5B108.3
N1—N2—H1N2119.5 (11)C4—C5—H5B108.3
N2—C1—C8109.65 (11)H5A—C5—H5B107.4
N2—C1—C2121.73 (11)C5—C6—C7115.82 (11)
C8—C1—C2128.51 (11)C5—C6—H6A108.3
C1—C2—C3111.34 (10)C7—C6—H6A108.3
C1—C2—H2A109.4C5—C6—H6B108.3
C3—C2—H2A109.4C7—C6—H6B108.3
C1—C2—H2B109.4H6A—C6—H6B107.4
C3—C2—H2B109.4C8—C7—C6114.98 (10)
H2A—C2—H2B108.0C8—C7—H7A108.5
C4—C3—C2114.47 (10)C6—C7—H7A108.5
C4—C3—H3A108.6C8—C7—H7B108.5
C2—C3—H3A108.6C6—C7—H7B108.5
C4—C3—H3B108.6H7A—C7—H7B107.5
C2—C3—H3B108.6C1—C8—C9106.16 (11)
H3A—C3—H3B107.6C1—C8—C7126.38 (11)
C3—C4—C5115.79 (11)C9—C8—C7127.44 (11)
C3—C4—H4A108.3O1—C9—N1122.31 (11)
C5—C4—H4A108.3O1—C9—C8130.92 (11)
C3—C4—H4B108.3N1—C9—C8106.76 (11)
C5—C4—H4B108.3
C9—N1—N2—C12.98 (13)C2—C1—C8—C9−175.54 (12)
N1—N2—C1—C8−2.13 (13)N2—C1—C8—C7178.99 (11)
N1—N2—C1—C2174.25 (11)C2—C1—C8—C72.9 (2)
N2—C1—C2—C3−89.09 (14)C6—C7—C8—C1−77.60 (16)
C8—C1—C2—C386.55 (15)C6—C7—C8—C9100.55 (14)
C1—C2—C3—C4−46.15 (14)N2—N1—C9—O1176.18 (11)
C2—C3—C4—C5−55.64 (15)N2—N1—C9—C8−2.61 (13)
C3—C4—C5—C6108.08 (13)C1—C8—C9—O1−177.37 (13)
C4—C5—C6—C7−72.87 (15)C7—C8—C9—O14.2 (2)
C5—C6—C7—C868.15 (15)C1—C8—C9—N11.29 (13)
N2—C1—C8—C90.52 (14)C7—C8—C9—N1−177.16 (11)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1N1···O1i0.938 (19)1.757 (19)2.6900 (14)173.0 (19)
N2—H1N2···O1ii0.925 (19)1.789 (19)2.7056 (14)170.1 (18)

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: FJ2356).

References

  • Bruker (2009). APEX2, SAINT and SADABS Bruker AXS Inc., Madison, Wisconsin, USA.
  • Cosier, J. & Glazer, A. M. (1986). J. Appl. Cryst.19, 105–107.
  • Ragavan, R. V., Vijayakumar, V. & Kumari, N. S. (2009). Eur. J. Med. Chem.44, 3852–3857. [PubMed]
  • Ragavan, R. V., Vijayakumar, V. & Kumari, N. S. (2010). Eur. J. Med. Chem.45, 1173–1180. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]
  • Xiong, Y., Gao, W.-Y., Deng, K.-Z., Chen, H.-X. & Wang, S.-J. (2007). Acta Cryst. E63, o333–o334.

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