4-Hydrazinyl-1-isobutyl-1H-imidazo[4,5-c]quinoline

Wan-Sin Loh; Hoong-Kun Fun; Reshma Kayarmar; S Viveka; G K Nagaraja

doi:10.1107/S1600536811001553

. 2011 Jan 15;67(Pt 2):o406. doi: 10.1107/S1600536811001553

4-Hydrazinyl-1-isobutyl-1H-imidazo[4,5-c]quinoline

Wan-Sin Loh ^a,^‡, Hoong-Kun Fun ^a,^*,^§, Reshma Kayarmar ^b, S Viveka ^b, G K Nagaraja ^b

PMCID: PMC3051739 PMID: 21523078

Abstract

In the title compound, C₁₄H₁₇N₅, the 1H-imidazo[4,5-c]quinoline ring system is essentially planar, with a maximum deviation of 0.0325 (7) Å. In the crystal, a pair of intermolecular N—H⋯N hydrogen bonds link neighbouring molecules, forming an inversion dimer and generate an R ₂ ²(10) ring motif. These dimers are further connected into a chain along the b axis via intermolecular C—H⋯N hydrogen bonds, resulting in an R ₂ ²(14) ring motif.

Related literature

For background to quinolines and their microbial activity, see: Roth & Fenner (2000 ▶); Miller et al. (1999 ▶); Hirota et al. (2002 ▶). For bond-length data, see: Allen et al. (1987 ▶). For a related structure, see: Loh et al. (2011 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₁₄H₁₇N₅
M _r = 255.33
Triclinic,
a = 5.4735 (2) Å
b = 9.1275 (3) Å
c = 13.3814 (5) Å
α = 98.076 (1)°
β = 101.787 (1)°
γ = 96.269 (1)°
V = 641.35 (4) Å³
Z = 2
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 100 K
0.68 × 0.42 × 0.09 mm

Data collection

Bruker SMART APEXII DUO CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.945, T _max = 0.992
20646 measured reflections
5797 independent reflections
4836 reflections with I > 2σ(I)
R _int = 0.023

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.137
S = 1.12
5797 reflections
240 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.53 e Å⁻³
Δρ_min = −0.32 e Å⁻³

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 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811001553/is2657sup1.cif

e-67-0o406-sup1.cif^{(19.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811001553/is2657Isup2.hkl

e-67-0o406-Isup2.hkl^{(283.8KB, 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
N4—H1N4⋯N3ⁱ	0.883 (16)	2.130 (15)	2.9429 (9)	152.9 (15)
C5—H5⋯N5ⁱⁱ	1.012 (12)	2.437 (11)	3.3700 (10)	152.9 (10)

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

Acknowledgments

HKF and WSL thank Universiti Sains Malaysia (USM) for the Research University Grant (1001/PFIZIK/811160). WSL also thanks the Malaysian Government and USM for the award of a Research Fellowship.

supplementary crystallographic information

Comment

The quinoline scaffold is present in many classes of biologically active compounds (Roth & Fenner, 2000), as for example, in 1H-imidazo-[4,5-c]quinolines that induce IFN, as well as other cytokines, in mice, rats, guinea pigs, monkeys and humans (Miller et al., 1999). This initiated the syntheses of a series of compounds with differing substitution at N-1, C-2, C-4 and on substitution on the benzene ring. Phenoxymethyl and benzyl groups at C-2 increase the activity. All other C-4 substituents investigated fail to induce IFN production. This investigation encouraged us to substitute C-4 by- NHNH₂ in continuation of our research to explore novel series of immune response modifiers in an effort to find small molecules that treat diseases involving the immune system (Hirota et al., 2002).

In the title compound (Fig. 1), the 1H-imidazo[4,5-c]quinoline ring (C1–C6/N1/C7/C8/N3/C10/N2/C9) is approximately planar with a maximum deviation of 0.0325 (7) Å at atom C1. The torsion angle formed between this ring system and the isobutyl moiety, C10–N2–C11–C12, is 101.17 (8)°. Bond lengths (Allen et al., 1987) and angles are within the normal ranges and are comparable to the related structure (Loh et al., 2011).

In the crystal packing (Fig. 2), intermolecular N4—H1N4···N3 hydrogen bonds (Table 1) link the neighbouring molecules to form dimers and generate R₂²(10) ring motifs (Bernstein et al., 1995). These dimers are further connected into chains down the b axis via intermolecular C5—H5···N5 hydrogen bonds (Table 1), resulting in R₂²(14) ring motifs (Bernstein et al., 1995).

Experimental

4-Chloro-1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolone (10 g, 0.0385 mole) and hydrazine-hydrate (80%, 19.3 g, 0.385 mole) in ethanol was refluxed for 9 h during which white solids separated out. After cooling to room temperature, the resulting 4-hydrazinyl-1-(2-methylpropyl)-1H-imidazo[4,5-c]quinoline was filtered off, dried and crystallized from ethanol. Yield, 7.4 g (74%). Crystals suitable for X-ray analysis were obtained from ethanol by slow evaporation.