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Acta Crystallogr Sect E Struct Rep Online. 2009 February 1; 65(Pt 2): o239.
Published online 2009 January 8. doi:  10.1107/S1600536808044036
PMCID: PMC2968206

1,2,3,6,7,8-Hexahydro­cinnolino[5,4,3-cde]cinnoline

Abstract

The title compound, C12H12N4, was synthesized by the reaction of hydrazine hydrate and 9-methyl-3,4,6,7-tetra­hydro-2H-xanthene-1,8(5H,9H)-dione in ethanol. In the crystal, the mol­ecule lies across an inversion centre. The pyridazine rings are coplanar and the C6 rings adopt envelope conformations.

Related literature

For the biological properties of cinnoline and its derivatives, see: Abdelrazek et al. (2006 [triangle]); Gomtsyan et al. (2005 [triangle]); Inoue et al. (1993 [triangle]); Lewgowd & Stanczak (2007 [triangle]); Lewgowd et al. (2005 [triangle]); Singh et al. (2003 [triangle]); Stefanska et al. (2003 [triangle]); Tutsumi et al. (1992 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-0o239-scheme1.jpg

Experimental

Crystal data

  • C12H12N4
  • M r = 212.26
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-0o239-efi1.jpg
  • a = 9.698 (5) Å
  • b = 5.875 (3) Å
  • c = 10.023 (5) Å
  • β = 117.314 (6)°
  • V = 507.4 (4) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 298 (2) K
  • 0.55 × 0.41 × 0.09 mm

Data collection

  • Bruker SMART CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 1996 [triangle]) T min = 0.953, T max = 0.992
  • 2508 measured reflections
  • 890 independent reflections
  • 575 reflections with I > 2σ(I)
  • R int = 0.028

Refinement

  • R[F 2 > 2σ(F 2)] = 0.041
  • wR(F 2) = 0.123
  • S = 1.01
  • 890 reflections
  • 97 parameters
  • All H-atom parameters refined
  • Δρmax = 0.16 e Å−3
  • Δρmin = −0.15 e Å−3

Data collection: SMART (Bruker, 1998 [triangle]); cell refinement: SAINT (Bruker, 1999 [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: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808044036/ci2750sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808044036/ci2750Isup2.hkl

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

supplementary crystallographic information

Comment

It is well known that six-membered nitrogen-containing heterocycles are abundant in numerous natural products that exhibit important biological properties. For example, cinnolines and their derivatives exhibit a diverse range of biological properties (Lewgowd & Stanczak, 2007) such as molluscicidal activity (Abdelrazek et al., 2006), cytotoxic activity (Lewgowd et al., 2005), transient receptor potential vanilloid 1 (TRPV1) receptor antagonists (Gomtsyan et al., 2005), and topoisomerase I (TOP1)-targeting activity and cytotoxicity (Singh et al., 2003). They also acted as anticancer agents active on a multidrug resistant cell line (Stefanska et al., 2003). They can also be used as bactericides in pharmaceutical industry (Inoue et al., 1993; Tutsumi et al.,1992). The chemistry of cinnolines has received much attention based on the above facts.

The title molecule lies across an inversion centre (Fig. 1). The two pyridazine rings (C1/C2/C2A/C3A/N2/N1 and C1A/C2A/C2/C3/N2A/N1A) are conjugated and are coplanar. The two cyclohexene rings (C1—C6 and C1A—C6A) adopt envelope conformations, with atoms C5 and C5A deviate from the C1/C2/C3/C4/C6 and C1A/C2A/C3A/C4A/C6A planes by 0.656 (3) and 0.656 (3) Å, respectively.

A view of the crystal packing is shown in Fig.2.

Experimental

The title compound was prepared by the reaction of 3,4,6,7-tetrahydro -9-methyl-2H-xanthene-1,8(5H,9H)-dione (2 mmol) and hydrazine hydrate 80% (8 mmol) in ethanol (8 ml) stirring at 353 K (yield 84%; m.p. 543–544 K). Single crystals suitable for X-ray diffraction were obtained from an ethanol solution by slow evaporation.

Refinement

All H atoms were located in a difference Fourier map and refined freely [C-H = 0.95 (2)-1.04 (2) Å].

Figures

Fig. 1.
The molecular structure of the title compound, showing 50% probability displacement ellipsoids and the atom-numbering scheme. Atoms labelled with the suffix A are generated by the symmetry operation (1-x, -y, 1-z).
Fig. 2.
Molecular packing in the title compound, viewed approximately along the a axis.

Crystal data

C12H12N4F(000) = 224
Mr = 212.26Dx = 1.389 Mg m3
Monoclinic, P21/cMelting point = 543–544 K
Hall symbol: -P 2ybcMo Kα radiation, λ = 0.71073 Å
a = 9.698 (5) ÅCell parameters from 734 reflections
b = 5.875 (3) Åθ = 2.4–26.3°
c = 10.023 (5) ŵ = 0.09 mm1
β = 117.314 (6)°T = 298 K
V = 507.4 (4) Å3Plate, colourless
Z = 20.55 × 0.41 × 0.09 mm

Data collection

Bruker SMART CCD area-detector diffractometer890 independent reflections
Radiation source: fine-focus sealed tube575 reflections with I > 2σ(I)
graphiteRint = 0.028
[var phi] and ω scansθmax = 25.0°, θmin = 4.1°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)h = −11→11
Tmin = 0.953, Tmax = 0.992k = −6→6
2508 measured reflectionsl = −11→11

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)] = 0.041Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.123All H-atom parameters refined
S = 1.01w = 1/[σ2(Fo2) + (0.0655P)2 + 0.0552P] where P = (Fo2 + 2Fc2)/3
890 reflections(Δ/σ)max = 0.001
97 parametersΔρmax = 0.16 e Å3
0 restraintsΔρmin = −0.15 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
N10.7159 (2)−0.2597 (3)0.65617 (19)0.0547 (6)
N20.5861 (2)−0.3398 (3)0.66438 (18)0.0555 (6)
C10.7050 (2)−0.0820 (4)0.5729 (2)0.0466 (6)
C20.56377 (19)0.0384 (3)0.49395 (18)0.0390 (5)
C30.5474 (2)0.2352 (3)0.4062 (2)0.0450 (5)
C40.6864 (3)0.3211 (5)0.3949 (3)0.0581 (7)
C50.8354 (3)0.2567 (4)0.5326 (3)0.0647 (7)
C60.8445 (3)0.0004 (4)0.5597 (3)0.0621 (7)
H10.682 (2)0.250 (4)0.305 (3)0.065 (6)*
H20.678 (2)0.487 (4)0.382 (2)0.076 (7)*
H30.930 (3)0.308 (4)0.522 (3)0.086 (8)*
H40.839 (3)0.340 (4)0.623 (3)0.079 (7)*
H50.846 (2)−0.086 (4)0.470 (2)0.072 (7)*
H60.936 (3)−0.039 (4)0.649 (3)0.081 (7)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N10.0567 (12)0.0508 (12)0.0500 (10)0.0164 (9)0.0187 (9)0.0061 (8)
N20.0652 (12)0.0458 (11)0.0474 (11)0.0115 (9)0.0189 (9)0.0086 (8)
C10.0501 (12)0.0467 (12)0.0395 (10)0.0102 (10)0.0175 (9)−0.0019 (10)
C20.0445 (11)0.0386 (11)0.0306 (9)0.0072 (8)0.0146 (8)−0.0029 (8)
C30.0574 (13)0.0386 (12)0.0351 (10)0.0051 (10)0.0178 (9)−0.0010 (9)
C40.0737 (17)0.0505 (15)0.0555 (14)−0.0061 (12)0.0344 (13)−0.0027 (12)
C50.0595 (15)0.0680 (17)0.0681 (16)−0.0087 (13)0.0306 (13)−0.0101 (13)
C60.0484 (14)0.0707 (18)0.0650 (16)0.0111 (11)0.0242 (13)−0.0033 (12)

Geometric parameters (Å, °)

N1—C11.310 (3)C4—C51.518 (3)
N1—N21.381 (2)C4—H10.98 (2)
N2—C3i1.309 (3)C4—H20.98 (2)
C1—C21.417 (3)C5—C61.526 (3)
C1—C61.499 (3)C5—H31.01 (2)
C2—C2i1.373 (3)C5—H41.01 (2)
C2—C31.417 (3)C6—H51.04 (2)
C3—N2i1.309 (3)C6—H60.95 (2)
C3—C41.492 (3)
C1—N1—N2120.01 (17)C5—C4—H2111.0 (13)
C3i—N2—N1120.67 (18)H1—C4—H2109.4 (18)
N1—C1—C2121.89 (19)C4—C5—C6111.2 (2)
N1—C1—C6120.07 (18)C4—C5—H3111.1 (13)
C2—C1—C6118.0 (2)C6—C5—H3109.2 (14)
C2i—C2—C3118.3 (2)C4—C5—H4108.6 (14)
C2i—C2—C1117.8 (2)C6—C5—H4110.1 (13)
C3—C2—C1123.94 (17)H3—C5—H4106.5 (19)
N2i—C3—C2121.33 (19)C1—C6—C5110.70 (19)
N2i—C3—C4120.3 (2)C1—C6—H5107.1 (12)
C2—C3—C4118.39 (18)C5—C6—H5110.5 (12)
C3—C4—C5111.3 (2)C1—C6—H6109.2 (14)
C3—C4—H1105.8 (12)C5—C6—H6111.1 (15)
C5—C4—H1110.6 (12)H5—C6—H6108.2 (19)
C3—C4—H2108.6 (13)

Symmetry codes: (i) −x+1, −y, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: CI2750).

References

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  • Inoue, S., Yasaki, A., Mochizuki, H., Tutsumi, H., Murata, M. & Sakane, K. (1993). Japanese Patent No. 05213951.
  • Lewgowd, W. & Stanczak, A. (2007). Arch. Pharm.340, 65–80. [PubMed]
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