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

Fun, H.-K.; Yeap, C.S.; Ragavan, R.V.; Vijayakumar, V.; Sarveswari, S.

doi:10.1107/S1600536810043904

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 66| Part 11| November 2010| Page o3019

https://doi.org/10.1107/S1600536810043904

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

Hoong-Kun Fun,^a ^*‡ Chin Sing Yeap,^a § R. Venkat Ragavan,^b V. Vijayakumar ^b and S. Sarveswari ^b

^aX-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia, and ^bOrganic Chemistry Division, School of Advanced Sciences, VIT University, Vellore 632 014, India
^*Correspondence e-mail: hkfun@usm.my

(Received 19 October 2010; accepted 27 October 2010; online 31 October 2010)

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 the bc plane. 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 , 2010 ). For a related structure, see: Xiong et al. (2007 ). For the stability of the temperature controller used for data collection, see: Cosier & Glazer (1986 ).

Experimental

Crystal data

C₉H₁₄N₂O
M_r = 166.22
Monoclinic, P 2₁ /c
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 ) 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[F² > 2σ(F²)] = 0.037
wR(F²) = 0.095
S = 1.05
1680 reflections
117 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.25 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N1⋯O1ⁱ	0.938 (19)	1.757 (19)	2.6900 (14)	173.0 (19)
N2—H1N2⋯O1ⁱⁱ	0.925 (19)	1.789 (19)	2.7056 (14)	170.1 (18)
Symmetry codes: (i) -x+1, -y, -z+1; (ii) $[x, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ .

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

Supporting information

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

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810043904/fj2356Isup2.hkl

checkCIF report

Comment top

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 link 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].

Related literature top

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

Experimental top

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.

Structure description top

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

Computing details top

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

Figures top

	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 are linked into planes parallel to the bc plane. Intermolecular hydrogen bonds are shown as dashed lines.

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

Crystal data top

C₉H₁₄N₂O	F(000) = 360
M_r = 166.22	D_x = 1.278 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 3802 reflections
a = 12.8078 (2) Å	θ = 3.5–30.1°
b = 6.7758 (1) Å	µ = 0.09 mm⁻¹
c = 10.7096 (2) Å	T = 100 K
β = 111.620 (1)°	Plate, colourless
V = 864.03 (2) Å³	0.54 × 0.24 × 0.11 mm
Z = 4

Data collection top

Bruker SMART APEXII CCD area-detector diffractometer	1680 independent reflections
Radiation source: fine-focus sealed tube	1474 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.026
φ and ω scans	θ_max = 26.0°, θ_min = 1.7°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −15→15
T_min = 0.956, T_max = 0.991	k = −8→8
6990 measured reflections	l = −13→12

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.037	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.095	H atoms treated by a mixture of independent and constrained refinement
S = 1.05	w = 1/[σ²(F_o²) + (0.047P)² + 0.3516P] where P = (F_o² + 2F_c²)/3
1680 reflections	(Δ/σ)_max < 0.001
117 parameters	Δρ_max = 0.25 e Å⁻³
0 restraints	Δρ_min = −0.25 e Å⁻³

Crystal data top

C₉H₁₄N₂O	V = 864.03 (2) Å³
M_r = 166.22	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 12.8078 (2) Å	µ = 0.09 mm⁻¹
b = 6.7758 (1) Å	T = 100 K
c = 10.7096 (2) Å	0.54 × 0.24 × 0.11 mm
β = 111.620 (1)°

Data collection top

Bruker SMART APEXII CCD area-detector diffractometer	1680 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2009)	1474 reflections with I > 2σ(I)
T_min = 0.956, T_max = 0.991	R_int = 0.026
6990 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.037	0 restraints
wR(F²) = 0.095	H atoms treated by a mixture of independent and constrained refinement
S = 1.05	Δρ_max = 0.25 e Å⁻³
1680 reflections	Δρ_min = −0.25 e Å⁻³
117 parameters

Special details top

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) top

	x	y	z	U_iso*/U_eq
O1	0.41579 (8)	0.06094 (13)	0.31883 (8)	0.0190 (2)
N1	0.44456 (9)	0.21181 (16)	0.52370 (10)	0.0160 (3)
N2	0.41423 (9)	0.38447 (16)	0.56789 (11)	0.0154 (3)
C1	0.34257 (10)	0.48051 (18)	0.46046 (12)	0.0149 (3)
C2	0.28502 (11)	0.66563 (19)	0.47482 (13)	0.0177 (3)
H2A	0.2711	0.7476	0.3961	0.021*
H2B	0.3335	0.7384	0.5525	0.021*
C3	0.17257 (11)	0.6209 (2)	0.49123 (12)	0.0189 (3)
H3A	0.1883	0.5734	0.5818	0.023*
H3B	0.1306	0.7430	0.4807	0.023*
C4	0.09909 (11)	0.4691 (2)	0.39200 (12)	0.0185 (3)
H4A	0.0295	0.4555	0.4075	0.022*
H4B	0.1371	0.3426	0.4113	0.022*
C5	0.07002 (11)	0.5164 (2)	0.24164 (12)	0.0191 (3)
H5A	−0.0105	0.5025	0.1954	0.023*
H5B	0.0888	0.6534	0.2339	0.023*
C6	0.12881 (11)	0.38840 (19)	0.16907 (12)	0.0189 (3)
H6A	0.0905	0.4065	0.0731	0.023*
H6B	0.1202	0.2510	0.1889	0.023*
C7	0.25452 (11)	0.42986 (19)	0.20469 (12)	0.0177 (3)
H7A	0.2795	0.3581	0.1424	0.021*
H7B	0.2640	0.5695	0.1918	0.021*
C8	0.32877 (10)	0.37496 (19)	0.34518 (12)	0.0153 (3)
C9	0.39626 (10)	0.20329 (18)	0.38724 (12)	0.0150 (3)
H1N1	0.4969 (14)	0.125 (3)	0.5823 (17)	0.030 (4)*
H1N2	0.4229 (14)	0.397 (3)	0.6572 (19)	0.037 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0272 (5)	0.0181 (5)	0.0123 (4)	0.0062 (4)	0.0082 (4)	0.0006 (3)
N1	0.0201 (6)	0.0158 (5)	0.0122 (5)	0.0031 (4)	0.0061 (4)	0.0007 (4)
N2	0.0181 (6)	0.0167 (5)	0.0122 (5)	0.0012 (4)	0.0065 (4)	−0.0012 (4)
C1	0.0149 (6)	0.0163 (6)	0.0150 (6)	−0.0015 (5)	0.0072 (5)	0.0013 (5)
C2	0.0214 (7)	0.0155 (6)	0.0166 (6)	−0.0001 (5)	0.0076 (5)	−0.0017 (5)
C3	0.0204 (7)	0.0207 (7)	0.0165 (6)	0.0025 (5)	0.0078 (5)	−0.0021 (5)
C4	0.0179 (7)	0.0212 (7)	0.0182 (6)	0.0003 (5)	0.0090 (5)	−0.0014 (5)
C5	0.0179 (7)	0.0217 (7)	0.0163 (7)	0.0025 (5)	0.0045 (5)	−0.0006 (5)
C6	0.0223 (7)	0.0203 (7)	0.0130 (6)	0.0034 (5)	0.0051 (5)	0.0004 (5)
C7	0.0227 (7)	0.0192 (6)	0.0126 (6)	0.0053 (5)	0.0082 (5)	0.0035 (5)
C8	0.0165 (6)	0.0168 (6)	0.0144 (6)	0.0001 (5)	0.0078 (5)	0.0012 (5)
C9	0.0168 (6)	0.0172 (6)	0.0118 (6)	−0.0001 (5)	0.0061 (5)	0.0011 (5)

Geometric parameters (Å, º) top

O1—C9	1.2902 (15)	C4—C5	1.5467 (17)
N1—C9	1.3622 (16)	C4—H4A	0.9700
N1—N2	1.3708 (15)	C4—H4B	0.9700
N1—H1N1	0.939 (18)	C5—C6	1.5343 (17)
N2—C1	1.3459 (16)	C5—H5A	0.9700
N2—H1N2	0.925 (19)	C5—H5B	0.9700
C1—C8	1.3807 (17)	C6—C7	1.5377 (18)
C1—C2	1.4912 (17)	C6—H6A	0.9700
C2—C3	1.5438 (17)	C6—H6B	0.9700
C2—H2A	0.9700	C7—C8	1.5007 (17)
C2—H2B	0.9700	C7—H7A	0.9700
C3—C4	1.5283 (18)	C7—H7B	0.9700
C3—H3A	0.9700	C8—C9	1.4199 (17)
C3—H3B	0.9700

C9—N1—N2	109.39 (10)	H4A—C4—H4B	107.4
C9—N1—H1N1	128.4 (10)	C6—C5—C4	115.83 (11)
N2—N1—H1N1	121.9 (10)	C6—C5—H5A	108.3
C1—N2—N1	107.96 (10)	C4—C5—H5A	108.3
C1—N2—H1N2	128.7 (11)	C6—C5—H5B	108.3
N1—N2—H1N2	119.5 (11)	C4—C5—H5B	108.3
N2—C1—C8	109.65 (11)	H5A—C5—H5B	107.4
N2—C1—C2	121.73 (11)	C5—C6—C7	115.82 (11)
C8—C1—C2	128.51 (11)	C5—C6—H6A	108.3
C1—C2—C3	111.34 (10)	C7—C6—H6A	108.3
C1—C2—H2A	109.4	C5—C6—H6B	108.3
C3—C2—H2A	109.4	C7—C6—H6B	108.3
C1—C2—H2B	109.4	H6A—C6—H6B	107.4
C3—C2—H2B	109.4	C8—C7—C6	114.98 (10)
H2A—C2—H2B	108.0	C8—C7—H7A	108.5
C4—C3—C2	114.47 (10)	C6—C7—H7A	108.5
C4—C3—H3A	108.6	C8—C7—H7B	108.5
C2—C3—H3A	108.6	C6—C7—H7B	108.5
C4—C3—H3B	108.6	H7A—C7—H7B	107.5
C2—C3—H3B	108.6	C1—C8—C9	106.16 (11)
H3A—C3—H3B	107.6	C1—C8—C7	126.38 (11)
C3—C4—C5	115.79 (11)	C9—C8—C7	127.44 (11)
C3—C4—H4A	108.3	O1—C9—N1	122.31 (11)
C5—C4—H4A	108.3	O1—C9—C8	130.92 (11)
C3—C4—H4B	108.3	N1—C9—C8	106.76 (11)
C5—C4—H4B	108.3

C9—N1—N2—C1	2.98 (13)	C2—C1—C8—C9	−175.54 (12)
N1—N2—C1—C8	−2.13 (13)	N2—C1—C8—C7	178.99 (11)
N1—N2—C1—C2	174.25 (11)	C2—C1—C8—C7	2.9 (2)
N2—C1—C2—C3	−89.09 (14)	C6—C7—C8—C1	−77.60 (16)
C8—C1—C2—C3	86.55 (15)	C6—C7—C8—C9	100.55 (14)
C1—C2—C3—C4	−46.15 (14)	N2—N1—C9—O1	176.18 (11)
C2—C3—C4—C5	−55.64 (15)	N2—N1—C9—C8	−2.61 (13)
C3—C4—C5—C6	108.08 (13)	C1—C8—C9—O1	−177.37 (13)
C4—C5—C6—C7	−72.87 (15)	C7—C8—C9—O1	4.2 (2)
C5—C6—C7—C8	68.15 (15)	C1—C8—C9—N1	1.29 (13)
N2—C1—C8—C9	0.52 (14)	C7—C8—C9—N1	−177.16 (11)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N1···O1ⁱ	0.938 (19)	1.757 (19)	2.6900 (14)	173.0 (19)
N2—H1N2···O1ⁱⁱ	0.925 (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.

Experimental details

Crystal data
Chemical formula	C₉H₁₄N₂O
M_r	166.22
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	100
a, b, c (Å)	12.8078 (2), 6.7758 (1), 10.7096 (2)
β (°)	111.620 (1)
V (Å³)	864.03 (2)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.54 × 0.24 × 0.11

Data collection
Diffractometer	Bruker SMART APEXII CCD area-detector
Absorption correction	Multi-scan (SADABS; Bruker, 2009)
T_min, T_max	0.956, 0.991
No. of measured, independent and observed [I > 2σ(I)] reflections	6990, 1680, 1474
R_int	0.026
(sin θ/λ)_max (Å⁻¹)	0.617

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.095, 1.05
No. of reflections	1680
No. of parameters	117
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.25, −0.25

Computer programs: APEX2 (Bruker, 2009), SAINT (Bruker, 2009), SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N1···O1ⁱ	0.938 (19)	1.757 (19)	2.6900 (14)	173.0 (19)
N2—H1N2···O1ⁱⁱ	0.925 (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

‡Thomson Reuters ResearcherID: A-3561-2009.

§Thomson Reuters ResearcherID: A-5523-2009.

Acknowledgements

HKF and CSY thank Universiti Sains Malaysia (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).

References

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