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Acta Crystallogr Sect E Struct Rep Online. 2011 February 1; 67(Pt 2): o405.
Published online 2011 January 15. doi:  10.1107/S160053681100153X
PMCID: PMC3051498

1-Isobutyl-N,N-dimethyl-1H-imidazo[4,5-c]quinolin-4-amine

Abstract

In the title compound, C16H20N4, the 1H-imidazo[4,5-c]quinoline ring system is approximately planar, with a maximum deviation of 0.0719 (15) Å. An intra­molecular C—H(...)N hydrogen bond contributes to the stabilization of the mol­ecule, forming an S(6) ring motif. In the crystal, the mol­ecules are stacked along the b axis through weak aromatic π–π inter­actions between benzene and imidazole and benzene and pyridine rings [centroid–centroid distances = 3.6055 (10) and 3.5342 (10) Å, respectively].

Related literature

For background to quinolines and their microbial activity, see: Jampilek et al. (2005 [triangle]); Gershon et al. (2004 [triangle]); Dardari et al. (2004 [triangle]). For the syntheses of 1H-imidazo[4,5-c]quinolin-4-amines, see: Gabriel (1918 [triangle]); Izumi et al. (2003 [triangle]). For bond-length data, see: Allen et al. (1987 [triangle]). For hydrogen-bond motifs, see: Bernstein et al. (1995 [triangle]).

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Object name is e-67-0o405-scheme1.jpg

Experimental

Crystal data

  • C16H20N4
  • M r = 268.36
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-67-0o405-efi1.jpg
  • a = 9.2804 (2) Å
  • b = 18.5492 (6) Å
  • c = 8.5147 (2) Å
  • β = 101.051 (2)°
  • V = 1438.57 (7) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.08 mm−1
  • T = 296 K
  • 0.39 × 0.29 × 0.14 mm

Data collection

  • Bruker SMART APEXII CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2009 [triangle]) T min = 0.971, T max = 0.989
  • 13134 measured reflections
  • 3456 independent reflections
  • 2271 reflections with I > 2σ(I)
  • R int = 0.037

Refinement

  • R[F 2 > 2σ(F 2)] = 0.055
  • wR(F 2) = 0.146
  • S = 1.02
  • 3456 reflections
  • 185 parameters
  • H-atom parameters constrained
  • Δρmax = 0.26 e Å−3
  • Δρmin = −0.18 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/S160053681100153X/is2656sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S160053681100153X/is2656Isup2.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

Compounds bearing a quinoline moiety are well known due to their broad biological activity (Jampilek et al., 2005). For example, hydroxyquinoline and its derivatives were introduced as antifungal agents in clinical practice and the novel compounds of this type are still being investigated (Gershon et al., 2004; Dardari et al., 2004). 1H-imidazo[4,5-c]quinolin-4-amines were synthesized by using two main synthetic routes. The first route started with 4-hydroxy-3-nitro-1H-quinolin-2-one, employing a modification of the method of Gabriel (Gabriel, 1918) to give 2,4-dichloro-3-nitroquinoline. Alternatively, the chlorination can be accomplished using phenylphosphonicdichloride (Izumi et al., 2003). Reaction of the N-oxide with POCl3 in dichloromethane gave the 4-chloro-1H-imidazo[4,5-c]quinoline analogue, which was converted to 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine by treatment with NH3 in methanol at 150 °C. 1H-Imidazo-[4,5-c]quinolines are potential antiviral agents and also induce the production of cytokines, especially interferon (IFN). This promoted us to react 4-chloro-1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolone with dimethylformide to give 1-isobutyl-N,N-dimethyl-1H-imidazo[4,5-c]quinolin-4-amine.

In the title compound (Fig. 1), the 1H-imidazo[4,5-c]quinoline ring system (C1–C6/N1/C7/C8/N3/C10/N2/C9) is approximately planar with a maximum deviation of 0.0719 (15) Å at atom N3. The torsion angle, C10—N2—C11—C12, formed between this ring system and the isobutyl unit is 100.8 (2)°. An intramolecular C15—H15A···N3 hydrogen bond (Table 1) contributes to the stabilization of the molecule, forming an S(6) ring motif (Bernstein et al., 1995). Bond lengths (Allen et al., 1987) and angles are within the normal ranges.

There is no significant intermolecular hydrogen bond observed in the crystal packing (Fig. 2). The molecules are stacked along the b axis by way of weak aromatic π–π interactions of the benzene C1–C6 ring (centroid Cg3) with the imidazole N2/C9/C8/N3/C10 (centroid Cg1) and pyridine N1/C6/C1/C9/C8/C7 (centroid Cg2) rings [Cg3···Cg1 separation = 3.6055 (10) Å; Cg3···Cg2 separation = 3.5342 (10) Å].

Experimental

4-Chloro-1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolone (2 g, 0.00771 mole), methanol (30 ml) and 3.3 ml of DMF were heated to reflux for 72 h. The solid formed was separated, filtered off and washed with methanol. Yield, 1.99 g (58.5%). Crystals suitable for x-ray analysis were obtained from ethanol by slow evaporation.

Refinement

All H atoms were positioned geometrically (C—H = 0.93 to 0.98 Å) and refined using the riding model with Uiso(H) = 1.2 or 1.5 Ueq(C). A rotating group model was applied to the methyl groups.

Figures

Fig. 1.
The molecular structure of the title compound, showing 30% probability displacement ellipsoids and the atom-numbering scheme. The dashed line indicates the intramolecular hydrogen bond.
Fig. 2.
The crystal packing of the title compound, viewed along the b axis.

Crystal data

C16H20N4F(000) = 576
Mr = 268.36Dx = 1.239 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 3031 reflections
a = 9.2804 (2) Åθ = 2.2–27.4°
b = 18.5492 (6) ŵ = 0.08 mm1
c = 8.5147 (2) ÅT = 296 K
β = 101.051 (2)°Block, colourless
V = 1438.57 (7) Å30.39 × 0.29 × 0.14 mm
Z = 4

Data collection

Bruker SMART APEXII CCD area-detector diffractometer3456 independent reflections
Radiation source: fine-focus sealed tube2271 reflections with I > 2σ(I)
graphiteRint = 0.037
[var phi] and ω scansθmax = 28.0°, θmin = 2.2°
Absorption correction: multi-scan (SADABS; Bruker, 2009)h = −12→12
Tmin = 0.971, Tmax = 0.989k = −19→24
13134 measured reflectionsl = −10→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)] = 0.055Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.146H-atom parameters constrained
S = 1.02w = 1/[σ2(Fo2) + (0.0604P)2 + 0.3608P] where P = (Fo2 + 2Fc2)/3
3456 reflections(Δ/σ)max = 0.001
185 parametersΔρmax = 0.26 e Å3
0 restraintsΔρmin = −0.18 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
N10.44302 (15)0.08084 (8)0.74563 (17)0.0430 (4)
N30.31258 (17)0.18631 (8)0.3740 (2)0.0512 (4)
N20.51431 (15)0.14182 (8)0.30069 (17)0.0418 (4)
N40.22238 (16)0.14021 (9)0.68830 (19)0.0520 (4)
C70.35046 (18)0.12102 (9)0.6440 (2)0.0400 (4)
C60.57198 (17)0.05715 (9)0.7062 (2)0.0386 (4)
C50.66567 (19)0.01562 (10)0.8208 (2)0.0467 (5)
H5A0.63870.00590.91840.056*
C40.7957 (2)−0.01084 (11)0.7918 (2)0.0500 (5)
H4A0.8563−0.03780.86980.060*
C30.8376 (2)0.00247 (10)0.6460 (2)0.0499 (5)
H3A0.9262−0.01550.62690.060*
C20.74870 (18)0.04200 (9)0.5307 (2)0.0428 (4)
H2A0.77710.05000.43330.051*
C10.61517 (17)0.07070 (8)0.55699 (19)0.0358 (4)
C90.51360 (17)0.11474 (8)0.45202 (19)0.0363 (4)
C80.38711 (18)0.14192 (9)0.4938 (2)0.0395 (4)
C100.3921 (2)0.18403 (10)0.2632 (2)0.0510 (5)
H10A0.36770.20900.16700.061*
C110.61699 (19)0.12704 (10)0.1942 (2)0.0449 (4)
H11A0.56820.13620.08480.054*
H11B0.64340.07640.20240.054*
C120.7563 (2)0.17189 (10)0.2307 (2)0.0466 (4)
H12A0.79800.16690.34500.056*
C130.8672 (2)0.14245 (12)0.1367 (3)0.0684 (6)
H13A0.88400.09230.16090.103*
H13B0.95790.16840.16570.103*
H13C0.82980.14810.02420.103*
C140.7246 (3)0.25132 (11)0.1958 (3)0.0689 (6)
H14A0.81370.27850.22540.103*
H14B0.65390.26800.25640.103*
H14C0.68620.25760.08370.103*
C150.1048 (2)0.17851 (13)0.5909 (3)0.0690 (6)
H15A0.12120.18070.48300.103*
H15B0.10020.22650.63180.103*
H15C0.01390.15400.59230.103*
C160.1954 (2)0.11825 (15)0.8435 (3)0.0716 (7)
H16A0.28650.11750.91930.107*
H16B0.15270.07090.83550.107*
H16C0.12920.15170.87840.107*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N10.0436 (8)0.0471 (8)0.0387 (8)0.0035 (7)0.0084 (6)−0.0017 (7)
N30.0483 (8)0.0502 (9)0.0556 (10)0.0094 (7)0.0110 (7)0.0128 (8)
N20.0434 (8)0.0424 (8)0.0401 (8)−0.0001 (6)0.0093 (6)0.0054 (7)
N40.0468 (8)0.0622 (10)0.0497 (10)0.0129 (8)0.0161 (7)0.0038 (8)
C70.0396 (9)0.0384 (9)0.0425 (10)−0.0003 (7)0.0089 (7)−0.0055 (8)
C60.0388 (8)0.0368 (9)0.0395 (9)−0.0017 (7)0.0058 (7)−0.0033 (7)
C50.0525 (11)0.0512 (11)0.0354 (10)0.0042 (9)0.0062 (8)0.0028 (8)
C40.0479 (10)0.0540 (11)0.0456 (11)0.0095 (9)0.0023 (8)0.0075 (9)
C30.0428 (10)0.0512 (11)0.0568 (12)0.0086 (8)0.0126 (8)0.0068 (9)
C20.0446 (9)0.0405 (9)0.0453 (10)0.0015 (8)0.0137 (8)0.0049 (8)
C10.0376 (8)0.0309 (8)0.0385 (9)−0.0022 (7)0.0064 (7)−0.0010 (7)
C90.0410 (9)0.0311 (8)0.0367 (9)−0.0036 (7)0.0069 (7)0.0000 (7)
C80.0400 (9)0.0342 (8)0.0432 (10)0.0001 (7)0.0052 (7)0.0016 (8)
C100.0502 (10)0.0514 (11)0.0508 (11)0.0071 (9)0.0080 (9)0.0145 (9)
C110.0500 (10)0.0485 (10)0.0368 (10)0.0018 (8)0.0100 (8)0.0018 (8)
C120.0483 (10)0.0483 (10)0.0449 (10)0.0000 (8)0.0132 (8)0.0083 (8)
C130.0610 (13)0.0689 (14)0.0824 (16)0.0028 (11)0.0312 (12)0.0030 (13)
C140.0788 (15)0.0514 (12)0.0844 (17)−0.0004 (11)0.0352 (13)0.0129 (12)
C150.0460 (11)0.0844 (16)0.0790 (16)0.0166 (11)0.0183 (10)0.0156 (13)
C160.0606 (13)0.1034 (19)0.0566 (13)0.0146 (12)0.0256 (11)0.0048 (13)

Geometric parameters (Å, °)

N1—C71.325 (2)C1—C91.425 (2)
N1—C61.376 (2)C9—C81.385 (2)
N3—C101.305 (2)C10—H10A0.9300
N3—C81.388 (2)C11—C121.519 (3)
N2—C101.365 (2)C11—H11A0.9700
N2—C91.384 (2)C11—H11B0.9700
N2—C111.461 (2)C12—C141.521 (3)
N4—C71.361 (2)C12—C131.521 (3)
N4—C151.427 (2)C12—H12A0.9800
N4—C161.450 (2)C13—H13A0.9600
C7—C81.439 (2)C13—H13B0.9600
C6—C51.406 (2)C13—H13C0.9600
C6—C11.426 (2)C14—H14A0.9600
C5—C41.368 (2)C14—H14B0.9600
C5—H5A0.9300C14—H14C0.9600
C4—C31.393 (3)C15—H15A0.9600
C4—H4A0.9300C15—H15B0.9600
C3—C21.368 (2)C15—H15C0.9600
C3—H3A0.9300C16—H16A0.9600
C2—C11.405 (2)C16—H16B0.9600
C2—H2A0.9300C16—H16C0.9600
C7—N1—C6120.37 (15)N2—C10—H10A122.9
C10—N3—C8103.93 (14)N2—C11—C12113.65 (15)
C10—N2—C9105.91 (14)N2—C11—H11A108.8
C10—N2—C11125.01 (15)C12—C11—H11A108.8
C9—N2—C11129.00 (14)N2—C11—H11B108.8
C7—N4—C15125.46 (16)C12—C11—H11B108.8
C7—N4—C16119.42 (16)H11A—C11—H11B107.7
C15—N4—C16115.06 (16)C11—C12—C14111.44 (16)
N1—C7—N4117.22 (16)C11—C12—C13109.34 (16)
N1—C7—C8119.85 (15)C14—C12—C13111.73 (17)
N4—C7—C8122.93 (16)C11—C12—H12A108.1
N1—C6—C5117.17 (15)C14—C12—H12A108.1
N1—C6—C1124.58 (15)C13—C12—H12A108.1
C5—C6—C1118.24 (15)C12—C13—H13A109.5
C4—C5—C6121.37 (17)C12—C13—H13B109.5
C4—C5—H5A119.3H13A—C13—H13B109.5
C6—C5—H5A119.3C12—C13—H13C109.5
C5—C4—C3120.26 (17)H13A—C13—H13C109.5
C5—C4—H4A119.9H13B—C13—H13C109.5
C3—C4—H4A119.9C12—C14—H14A109.5
C2—C3—C4120.10 (17)C12—C14—H14B109.5
C2—C3—H3A119.9H14A—C14—H14B109.5
C4—C3—H3A119.9C12—C14—H14C109.5
C3—C2—C1121.20 (16)H14A—C14—H14C109.5
C3—C2—H2A119.4H14B—C14—H14C109.5
C1—C2—H2A119.4N4—C15—H15A109.5
C2—C1—C9127.93 (15)N4—C15—H15B109.5
C2—C1—C6118.81 (15)H15A—C15—H15B109.5
C9—C1—C6113.24 (14)N4—C15—H15C109.5
N2—C9—C8105.21 (14)H15A—C15—H15C109.5
N2—C9—C1132.15 (15)H15B—C15—H15C109.5
C8—C9—C1122.60 (15)N4—C16—H16A109.5
C9—C8—N3110.77 (15)N4—C16—H16B109.5
C9—C8—C7119.13 (15)H16A—C16—H16B109.5
N3—C8—C7130.09 (15)N4—C16—H16C109.5
N3—C10—N2114.14 (16)H16A—C16—H16C109.5
N3—C10—H10A122.9H16B—C16—H16C109.5
C6—N1—C7—N4177.51 (15)C11—N2—C9—C16.5 (3)
C6—N1—C7—C8−2.0 (2)C2—C1—C9—N2−0.3 (3)
C15—N4—C7—N1−175.07 (19)C6—C1—C9—N2178.26 (16)
C16—N4—C7—N11.9 (3)C2—C1—C9—C8−177.77 (16)
C15—N4—C7—C84.4 (3)C6—C1—C9—C80.8 (2)
C16—N4—C7—C8−178.62 (18)N2—C9—C8—N3−1.55 (19)
C7—N1—C6—C5179.12 (15)C1—C9—C8—N3176.52 (15)
C7—N1—C6—C1−2.1 (3)N2—C9—C8—C7177.37 (14)
N1—C6—C5—C4179.43 (17)C1—C9—C8—C7−4.6 (2)
C1—C6—C5—C40.5 (3)C10—N3—C8—C91.2 (2)
C6—C5—C4—C3−0.6 (3)C10—N3—C8—C7−177.58 (18)
C5—C4—C3—C2−0.1 (3)N1—C7—C8—C95.2 (2)
C4—C3—C2—C10.8 (3)N4—C7—C8—C9−174.26 (16)
C3—C2—C1—C9177.63 (17)N1—C7—C8—N3−176.11 (17)
C3—C2—C1—C6−0.8 (3)N4—C7—C8—N34.4 (3)
N1—C6—C1—C2−178.65 (15)C8—N3—C10—N2−0.4 (2)
C5—C6—C1—C20.1 (2)C9—N2—C10—N3−0.6 (2)
N1—C6—C1—C92.7 (2)C11—N2—C10—N3176.48 (16)
C5—C6—C1—C9−178.54 (15)C10—N2—C11—C12100.8 (2)
C10—N2—C9—C81.26 (18)C9—N2—C11—C12−82.9 (2)
C11—N2—C9—C8−175.65 (16)N2—C11—C12—C14−67.1 (2)
C10—N2—C9—C1−176.54 (18)N2—C11—C12—C13168.91 (16)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C15—H15A···N30.962.162.918 (3)135

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: IS2656).

References

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