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Acta Crystallogr Sect E Struct Rep Online. 2011 February 1; 67(Pt 2): o406.
Published online 2011 January 15. doi:  10.1107/S1600536811001553
PMCID: PMC3051739

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

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 [triangle]); Miller et al. (1999 [triangle]); Hirota et al. (2002 [triangle]). For bond-length data, see: Allen et al. (1987 [triangle]). For a related structure, see: Loh et al. (2011 [triangle]). For hydrogen-bond motifs, see: Bernstein et al. (1995 [triangle]). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 [triangle]).

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Object name is e-67-0o406-scheme1.jpg

Experimental

Crystal data

  • C14H17N5
  • M r = 255.33
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-67-0o406-efi1.jpg
  • 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 [triangle]) 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
  • Δρmax = 0.53 e Å−3
  • Δρmin = −0.32 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/S1600536811001553/is2657sup1.cif

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

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

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.

Refinement

All H atoms were located from difference Fourier map and were refined freely [N—H = 0.883 (15) to 0.909 (14) Å; C—H = 0.978 (13) to 1.037 (12) Å].

Figures

Fig. 1.
The molecular structure of the title compound, showing 50% probability displacement ellipsoids and the atom-numbering scheme.
Fig. 2.
The crystal packing of the title compound, showing the chains along the b axis. H atoms not involved in the intermolecular interactions (dashed lines) have been omitted for clarity.

Crystal data

C14H17N5Z = 2
Mr = 255.33F(000) = 272
Triclinic, P1Dx = 1.322 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 5.4735 (2) ÅCell parameters from 9851 reflections
b = 9.1275 (3) Åθ = 2.5–35.6°
c = 13.3814 (5) ŵ = 0.08 mm1
α = 98.076 (1)°T = 100 K
β = 101.787 (1)°Plate, yellow
γ = 96.269 (1)°0.68 × 0.42 × 0.09 mm
V = 641.35 (4) Å3

Data collection

Bruker SMART APEXII DUO CCD area-detector diffractometer5797 independent reflections
Radiation source: fine-focus sealed tube4836 reflections with I > 2σ(I)
graphiteRint = 0.023
[var phi] and ω scansθmax = 35.6°, θmin = 1.6°
Absorption correction: multi-scan (SADABS; Bruker, 2009)h = −8→8
Tmin = 0.945, Tmax = 0.992k = −14→14
20646 measured reflectionsl = −21→21

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)] = 0.040Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.137H atoms treated by a mixture of independent and constrained refinement
S = 1.12w = 1/[σ2(Fo2) + (0.0821P)2 + 0.0687P] where P = (Fo2 + 2Fc2)/3
5797 reflections(Δ/σ)max = 0.001
240 parametersΔρmax = 0.53 e Å3
0 restraintsΔρmin = −0.32 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
N30.66263 (12)0.41343 (6)0.40530 (5)0.01739 (12)
N20.83913 (11)0.28950 (6)0.28779 (4)0.01494 (11)
N10.29129 (11)0.04458 (6)0.39588 (4)0.01382 (11)
N40.27467 (12)0.27155 (7)0.49606 (5)0.01719 (12)
N50.09896 (12)0.21044 (7)0.54799 (5)0.01683 (11)
C90.66447 (12)0.18519 (7)0.31040 (5)0.01294 (11)
C10.58776 (12)0.02794 (7)0.27674 (5)0.01284 (11)
C20.68633 (13)−0.06582 (7)0.20610 (5)0.01545 (12)
C30.60210 (14)−0.21733 (7)0.18278 (5)0.01727 (13)
C40.41445 (14)−0.27919 (7)0.22854 (6)0.01769 (13)
C50.31322 (13)−0.19005 (7)0.29698 (5)0.01611 (12)
C60.39780 (12)−0.03437 (7)0.32402 (5)0.01301 (11)
C70.37122 (12)0.18938 (7)0.42576 (5)0.01334 (11)
C80.55945 (13)0.26428 (7)0.38309 (5)0.01385 (11)
C100.82902 (15)0.42279 (7)0.34703 (5)0.01813 (13)
C111.00391 (12)0.26889 (7)0.21544 (5)0.01498 (12)
C120.86854 (13)0.26095 (7)0.10230 (5)0.01536 (12)
C131.04956 (16)0.22187 (9)0.03277 (6)0.02337 (15)
C140.77216 (15)0.40809 (8)0.08500 (6)0.02100 (14)
H120.714 (2)0.1783 (13)0.0858 (9)0.022 (3)*
H50.188 (2)−0.2330 (14)0.3351 (9)0.023 (3)*
H11A1.082 (2)0.1765 (14)0.2249 (9)0.021 (3)*
H11B1.135 (2)0.3583 (12)0.2340 (8)0.016 (2)*
H30.684 (3)−0.2852 (15)0.1362 (10)0.030 (3)*
H14A0.647 (2)0.4297 (15)0.1284 (10)0.028 (3)*
H20.824 (3)−0.0234 (15)0.1744 (10)0.028 (3)*
H14B0.684 (2)0.4015 (15)0.0128 (10)0.027 (3)*
H13A1.198 (3)0.3048 (16)0.0476 (10)0.035 (3)*
H13B0.967 (3)0.2083 (16)−0.0425 (11)0.042 (4)*
H14C0.914 (3)0.4902 (15)0.1002 (10)0.027 (3)*
H2N5−0.034 (3)0.1553 (16)0.5007 (11)0.034 (3)*
H1N50.168 (2)0.1427 (14)0.5847 (9)0.026 (3)*
H40.351 (3)−0.3897 (15)0.2119 (11)0.033 (3)*
H1N40.338 (3)0.3668 (17)0.5163 (11)0.039 (4)*
H100.947 (2)0.5153 (13)0.3482 (9)0.023 (3)*
H13C1.111 (3)0.1258 (16)0.0456 (11)0.036 (3)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N30.0241 (3)0.0107 (2)0.0180 (2)−0.00015 (19)0.0094 (2)−0.00037 (18)
N20.0186 (2)0.0106 (2)0.0163 (2)−0.00019 (17)0.00804 (18)0.00044 (17)
N10.0166 (2)0.0107 (2)0.0146 (2)0.00162 (17)0.00618 (18)−0.00006 (16)
N40.0236 (3)0.0116 (2)0.0184 (2)0.00107 (19)0.0123 (2)−0.00060 (18)
N50.0190 (3)0.0158 (2)0.0174 (2)0.00174 (19)0.00878 (19)0.00190 (18)
C90.0160 (3)0.0101 (2)0.0132 (2)0.00083 (19)0.00551 (19)0.00118 (17)
C10.0152 (3)0.0103 (2)0.0134 (2)0.00142 (18)0.00501 (19)0.00076 (18)
C20.0191 (3)0.0117 (2)0.0168 (3)0.0018 (2)0.0085 (2)0.00019 (19)
C30.0211 (3)0.0121 (2)0.0196 (3)0.0017 (2)0.0096 (2)−0.0009 (2)
C40.0209 (3)0.0107 (2)0.0215 (3)0.0000 (2)0.0091 (2)−0.0015 (2)
C50.0180 (3)0.0112 (2)0.0195 (3)−0.0001 (2)0.0082 (2)−0.0001 (2)
C60.0145 (2)0.0109 (2)0.0140 (2)0.00148 (18)0.00531 (19)0.00056 (18)
C70.0164 (3)0.0112 (2)0.0131 (2)0.00201 (19)0.00547 (19)0.00073 (18)
C80.0180 (3)0.0106 (2)0.0135 (2)0.00126 (19)0.00616 (19)0.00052 (18)
C100.0244 (3)0.0108 (2)0.0195 (3)−0.0011 (2)0.0096 (2)−0.0006 (2)
C110.0157 (3)0.0136 (2)0.0166 (2)0.0008 (2)0.0067 (2)0.00201 (19)
C120.0174 (3)0.0133 (2)0.0162 (2)0.0012 (2)0.0064 (2)0.00193 (19)
C130.0275 (4)0.0252 (3)0.0210 (3)0.0058 (3)0.0129 (3)0.0032 (2)
C140.0244 (3)0.0170 (3)0.0226 (3)0.0049 (2)0.0055 (2)0.0048 (2)

Geometric parameters (Å, °)

N3—C101.3179 (9)C3—H31.020 (13)
N3—C81.3821 (8)C4—C51.3798 (9)
N2—C101.3687 (9)C4—H41.008 (14)
N2—C91.3828 (8)C5—C61.4170 (9)
N2—C111.4590 (9)C5—H51.011 (12)
N1—C71.3236 (8)C7—C81.4322 (9)
N1—C61.3820 (8)C10—H101.002 (12)
N4—C71.3484 (8)C11—C121.5315 (9)
N4—N51.4085 (9)C11—H11A0.999 (12)
N4—H1N40.883 (15)C11—H11B0.993 (11)
N5—H2N50.909 (14)C12—C141.5258 (10)
N5—H1N50.909 (13)C12—C131.5282 (10)
C9—C81.3854 (9)C12—H121.037 (12)
C9—C11.4314 (9)C13—H13A1.014 (14)
C1—C21.4138 (9)C13—H13B1.000 (14)
C1—C61.4302 (9)C13—H13C0.998 (14)
C2—C31.3795 (9)C14—H14A1.001 (13)
C2—H21.008 (14)C14—H14B0.978 (13)
C3—C41.4058 (10)C14—H14C0.985 (14)
C10—N3—C8103.93 (5)N1—C7—C8121.10 (6)
C10—N2—C9106.32 (6)N4—C7—C8117.90 (6)
C10—N2—C11124.73 (6)N3—C8—C9111.27 (6)
C9—N2—C11128.95 (5)N3—C8—C7128.47 (6)
C7—N1—C6118.55 (6)C9—C8—C7120.25 (6)
C7—N4—N5123.58 (6)N3—C10—N2113.44 (6)
C7—N4—H1N4118.2 (10)N3—C10—H10124.7 (7)
N5—N4—H1N4117.8 (10)N2—C10—H10121.7 (7)
N4—N5—H2N5109.3 (9)N2—C11—C12113.35 (6)
N4—N5—H1N5109.3 (8)N2—C11—H11A108.6 (7)
H2N5—N5—H1N5104.1 (12)C12—C11—H11A110.6 (7)
N2—C9—C8105.04 (5)N2—C11—H11B106.1 (6)
N2—C9—C1134.08 (6)C12—C11—H11B107.6 (6)
C8—C9—C1120.87 (6)H11A—C11—H11B110.5 (9)
C2—C1—C6119.84 (6)C14—C12—C13111.16 (6)
C2—C1—C9126.25 (6)C14—C12—C11110.90 (5)
C6—C1—C9113.89 (6)C13—C12—C11108.94 (6)
C3—C2—C1120.58 (6)C14—C12—H12107.7 (6)
C3—C2—H2119.1 (7)C13—C12—H12110.1 (7)
C1—C2—H2120.3 (7)C11—C12—H12108.0 (6)
C2—C3—C4119.88 (6)C12—C13—H13A109.6 (8)
C2—C3—H3120.0 (8)C12—C13—H13B112.4 (9)
C4—C3—H3120.0 (8)H13A—C13—H13B108.1 (11)
C5—C4—C3120.75 (6)C12—C13—H13C109.9 (8)
C5—C4—H4118.6 (8)H13A—C13—H13C109.8 (12)
C3—C4—H4120.6 (8)H13B—C13—H13C106.9 (12)
C4—C5—C6120.97 (6)C12—C14—H14A110.3 (7)
C4—C5—H5122.2 (7)C12—C14—H14B110.4 (8)
C6—C5—H5116.6 (7)H14A—C14—H14B106.7 (10)
N1—C6—C5116.69 (6)C12—C14—H14C110.4 (8)
N1—C6—C1125.32 (6)H14A—C14—H14C111.1 (11)
C5—C6—C1117.98 (6)H14B—C14—H14C107.9 (11)
N1—C7—N4120.99 (6)
C10—N2—C9—C8−0.05 (7)C6—N1—C7—N4−179.65 (6)
C11—N2—C9—C8−179.38 (6)C6—N1—C7—C81.52 (10)
C10—N2—C9—C1−178.69 (7)N5—N4—C7—N14.70 (11)
C11—N2—C9—C11.98 (12)N5—N4—C7—C8−176.43 (6)
N2—C9—C1—C20.80 (12)C10—N3—C8—C9−0.50 (8)
C8—C9—C1—C2−177.67 (6)C10—N3—C8—C7178.70 (7)
N2—C9—C1—C6178.97 (7)N2—C9—C8—N30.34 (8)
C8—C9—C1—C60.50 (9)C1—C9—C8—N3179.20 (6)
C6—C1—C2—C3−0.43 (10)N2—C9—C8—C7−178.94 (6)
C9—C1—C2—C3177.64 (6)C1—C9—C8—C7−0.07 (10)
C1—C2—C3—C40.77 (11)N1—C7—C8—N3179.87 (6)
C2—C3—C4—C5−0.14 (11)N4—C7—C8—N31.00 (11)
C3—C4—C5—C6−0.84 (11)N1—C7—C8—C9−0.99 (10)
C7—N1—C6—C5177.81 (6)N4—C7—C8—C9−179.86 (6)
C7—N1—C6—C1−1.08 (10)C8—N3—C10—N20.48 (8)
C4—C5—C6—N1−177.81 (6)C9—N2—C10—N3−0.28 (8)
C4—C5—C6—C11.16 (10)C11—N2—C10—N3179.09 (6)
C2—C1—C6—N1178.35 (6)C10—N2—C11—C12−101.17 (8)
C9—C1—C6—N10.05 (10)C9—N2—C11—C1278.06 (8)
C2—C1—C6—C5−0.52 (10)N2—C11—C12—C1463.65 (7)
C9—C1—C6—C5−178.82 (6)N2—C11—C12—C13−173.69 (6)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N4—H1N4···N3i0.883 (16)2.130 (15)2.9429 (9)152.9 (15)
C5—H5···N5ii1.012 (12)2.437 (11)3.3700 (10)152.9 (10)

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: IS2657).

References

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  • Bruker (2009). APEX2, SAINT and SADABSBruker AXS Inc., Madison, Wisconsin, USA.
  • Cosier, J. & Glazer, A. M. (1986). J. Appl. Cryst. 19, 105–107.
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  • Loh, W.-S., Fun, H.-K., Kayarmar, R., Viveka, S. & Nagaraja, G. K. (2011). Acta Cryst. E67, o405. [PMC free article] [PubMed]
  • Miller, R. L., Gerster, J. F., Owens, M. L., Slade, H. B. & Tomai, M. A. (1999). Int. J. Immunopharmacol. 21, 1–14. [PubMed]
  • Roth, H. J. & Fenner, H. (2000). Arzneistoffe, pp. 51–114.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]

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