7,9-Dichloro-6H,12H-indolo[2,1-b]quinazoline-6,12-dione

Peter Grundt; Kelsi A Douglas; Bogdana Krivogorsky; Victor N Nemykin

doi:10.1107/S1600536810018969

. 2010 May 29;66(Pt 6):o1474–o1475. doi: 10.1107/S1600536810018969

7,9-Dichloro-6H,12H-indolo[2,1-b]quinazoline-6,12-dione

Peter Grundt ^a, Kelsi A Douglas ^a, Bogdana Krivogorsky ^a, Victor N Nemykin ^a,^*

PMCID: PMC2979507 PMID: 21579542

Abstract

There are two independent molecules in the asymmetric unit of the title compound, C₁₅H₆Cl₂N₂O₂. The conjugated four-ring system is essentially planar in each molecule [maximum deviation = 0.089 (2) Å]. In the crystal, weak intermolecular C—H⋯Cl, C—H⋯O and C—H⋯·N interactions help to stabilize the packing.

Related literature

For the synthesis, chemistry, and biological activity of the title compound see: Krivogorsky et al. (2008 ▶). For chemistry and biological activity of the natural product tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione) and its derivatives and for related structures, see: Honda et al. (1979 ▶); Mitscher & Baker (1998 ▶); Kataoka et al. (2001 ▶); Bandekar et al. (2010 ▶); Sharma et al. (2002 ▶); Motoki et al. (2005 ▶); Yu et al. (2009 ▶); Bhattacharjee et al. (2002 ▶); Scovill et al. (2002 ▶); Bhattacharjee et al. (2004 ▶); Pitzer et al. (2000 ▶). For the extinction correction, see: Larson (1970 ▶).

Experimental

Crystal data

C₁₅H₆Cl₂N₂O₂
M _r = 317.13
Triclinic,
a = 7.0179 (2) Å
b = 10.7276 (3) Å
c = 17.2338 (12) Å
α = 94.908 (7)°
β = 96.709 (7)°
γ = 107.395 (8)°
V = 1219.66 (12) Å³
Z = 4
Mo Kα radiation
μ = 0.54 mm⁻¹
T = 100 K
0.54 × 0.48 × 0.35 mm

Data collection

Rigaku R-AXIS RAPID-II imaging plate diffractometer
Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ▶) T _min = 0.633, T _max = 0.899
31502 measured reflections
5585 independent reflections
4830 reflections with I > 2σ(I)
R _int = 0.049

Refinement

R[F ² > 2σ(F ²)] = 0.034
wR(F ²) = 0.082
S = 1.00
5571 reflections
416 parameters
84 restraints
All H-atom parameters refined
Δρ_max = 0.53 e Å⁻³
Δρ_min = −0.36 e Å⁻³

Data collection: CrystalClear (Rigaku Americas, 2009 ▶); cell refinement: HKL-2000 (Otwinowski & Minor, 1997 ▶); data reduction: CrystalClear; program(s) used to solve structure: SHELXS86 (Sheldrick, 2008 ▶); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003 ▶); molecular graphics: CAMERON (Watkin et al., 1996 ▶); software used to prepare material for publication: CRYSTALS.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810018969/jj2032sup1.cif

e-66-o1474-sup1.cif^{(22KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810018969/jj2032Isup2.hkl

e-66-o1474-Isup2.hkl^{(278.8KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C1B—H1B⋯Cl1Aⁱ	0.94 (2)	2.73 (2)	3.637 (2)	162 (1)
C2A—H2A⋯O1Bⁱⁱ	0.93 (2)	2.54 (2)	3.264 (3)	135 (1)
C4B—H4B⋯N5Aⁱⁱⁱ	0.94 (2)	2.56 (2)	3.422 (3)	154 (1)
C10A—H6A⋯Cl2B^iv	0.94 (2)	2.67 (2)	3.585 (2)	165 (1)

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) .

Acknowledgments

This study was supported by Stanley Medical Research Institute (grant 08R-2032) and the NSF (grant CHE-0922366 for X-ray diffractometer).

supplementary crystallographic information

Comment

The natural product tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione) and its derivatives have been shown to possess antibacterial (Honda et al., 1979), Mitscher & Baker, 1998, Kataoka et al., 2001, Bandekar et al., 2010) and antitumor Sharma et al., 2002, Motoki et al., 2005, Yu et al., 2009) properties. Of particular interest is the discovery by several groups that this class of compounds also inibits the growth of parasites such as Leishmania donovani (Bhattacharjee et al., 2002), Trypanosoma brucei (Scovill et al., 2002), and Plasmodium falciparum (Bhattacharjee et al., 2004, Pitzer et al., 2000), and more recently by our laboratory, Toxoplasma gondii (Krivogorsky et al., 2008). In our continued interest to characterize the structure-activity-relationship of this class of compounds and to reveal the underlying mechanism, we have synthesized the 7,9-dichloro analog of tryptanthrin.

The title compound, (I), C₁₅H₆Cl₂N₂O₂, crystallizes in the P-1 space group with two independent molecules in the asymmetric unit cell. It consists of a 7,9-dichloroindolo ring fused to a quinazoline ring with a dione group at the 6 and 12 poisitions (IUPAC nomenclature). C—Cl bond distances have been observed between 1.7272 (19) and 1.7358 (19) Å with Cl1—C7 distances being slightly shorter as compared to Cl2—C9 bond lengths. C=O bonds have clear double bond character and were observed between 1.211 (2) and 1.221 (2) Å with C=O bonds in the five-membered ring being slightly shorter as compared to those at the six-membered rings. N5—C14 bond distances in molecules A and B have clear double bond character. Four weak intermolecular interactions are observed in (I), (Table 2) that help stabilize crystal packing.

Experimental

The title compound was prepared by condensation of isatoic anhydride and 4,6-dichloroisatin in refluxing benzene with triethylamine as a co-solvent (Krivogorsky et al., 2008). Crystals suitable for single-crystal X-ray diffraction were grown by slow evaporation of an acetone solution of the compound.