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Acta Crystallogr Sect E Struct Rep Online. Sep 1, 2011; 67(Pt 9): o2331.
Published online Aug 11, 2011. doi:  10.1107/S1600536811031801
PMCID: PMC3200859
1-Isobutyl-4-meth­oxy-1H-imidazo[4,5-c]quinoline
Hoong-Kun Fun,a* Wan-Sin Loh,a§ Dinesha,b Reshma Kayarmar,c and G. K. Nagarajab
aX-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia
bDepartment of Chemistry, Mangalore University, Karnataka, India
cSequent Scientific Limited, Baikampady, New Mangalore, India
Correspondence e-mail: hkfun/at/usm.my
Thomson Reuters ResearcherID: A-3561-2009.
§Thomson Reuters ResearcherID: C-7581-2009.
Received August 5, 2011; Accepted August 5, 2011.
Abstract
In the title compound, C15H17N3O, the 1H-imidazo[4,5-c]quinoline ring system is approximately planar, with a maximum deviation of 0.036 (1) Å. The C—N—C—C torsion angles formed between this ring system and the isobutyl unit are −99.77 (16) and 79.71 (17)°. In the crystal, inter­molecular C—H(...)O hydrogen bonds link the mol­ecules into chains along the c axis.
Related literature
For background to quinolines and their microbial activity, see: Crozat & Beutler (2004 [triangle]); Stringfellow & Glasgow (1972 [triangle]); Miller et al. (1999 [triangle]); Hemmi et al. (2002 [triangle]). For related structures, see: Loh et al. (2011a [triangle],b [triangle]).
An external file that holds a picture, illustration, etc.
Object name is e-67-o2331-scheme1.jpg Object name is e-67-o2331-scheme1.jpg
Crystal data
  • C15H17N3O
  • M r = 255.32
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-67-o2331-efi1.jpg
  • a = 7.4196 (8) Å
  • b = 18.910 (2) Å
  • c = 10.4112 (14) Å
  • β = 110.568 (2)°
  • V = 1367.6 (3) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.08 mm−1
  • T = 297 K
  • 0.40 × 0.31 × 0.13 mm
Data collection
  • Bruker SMART APEXII DUO CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2009 [triangle]) T min = 0.969, T max = 0.989
  • 12741 measured reflections
  • 3463 independent reflections
  • 2386 reflections with I > 2σ(I)
  • R int = 0.023
Refinement
  • R[F 2 > 2σ(F 2)] = 0.042
  • wR(F 2) = 0.127
  • S = 1.04
  • 3463 reflections
  • 175 parameters
  • H-atom parameters constrained
  • Δρmax = 0.12 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
Table 1
Hydrogen-bond geometry (Å, °)
Supplementary Material
Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811031801/wn2444sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811031801/wn2444Isup2.hkl
Supplementary material file. DOI: 10.1107/S1600536811031801/wn2444Isup3.cml
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 thanks the Malaysian Government and USM for the award of a Research Fellowship.
supplementary crystallographic information
Comment
The quinoline scaffold is prevalent in a variety of pharmacologically active synthetic and natural products. Long before endosomal TLR7 was discovered to serve as the primary sensor for short, single-stranded, GU-rich RNA sequences (ssRNA), mainly of viral origin (Crozat & Beutler, 2004), a number of small molecules were synthesized and evaluated in the 1970's and 1980's for antiviral activities owing to their pronounced type I interferon (IFN-R and -β) inducing properties (Stringfellow & Glasgow, 1972). Although the mechanisms of innate immune stimulation of several of these compounds (such as tilorone14 and bromopirone16) remain yet to be formally elucidated, the members of the 1H-imidazo[4,5-c]quinolines were found to be good type I IFN inducers in human cell-derived assays and FDA approval was obtained in 1997 for imiquimod for the treatment of basal cell carcinoma and actinic keratosis (Miller et al., 1999). It was not until 2002, however, that the mechanistic basis of IFN induction by the imidazoquinolines was found to be a consequence of TLR7 engagement and activation (Hemmi et al., 2002). We have earlier reported the crystal structures of 1-isobutyl-N,N-dimethyl-1H-imidazo[4,5-c]quinolin- 4-amine and 4-hydrazinyl-1-isobutyl-1H-imidazo[4,5-c]quinoline (Loh et al., 2011a,b). Following on from these, we have synthesized 1-isobutyl-4-methoxy-1H-imidazo[4,5-c]quinoline.
In the title compound (Fig. 1), the 1H-imidazo[4,5-c]quinoline ring system (C1–C7/N3/C10/N2/C8/C9/N1) is approximately planar with a maximum deviation of 0.036 (1) Å at atom C8. The torsion angle, C10—N3—C11—C12, formed between this ring system and the isobutyl unit is -99.77 (16)°; the torsion angle C7—N3—C11—C12 is 79.71 (17)°. Bond lengths and angles are within the normal ranges and are comparable to those in the related crystal structures (Loh et al., 2011a,b).
In the crystal packing (Fig. 2), the intermolecular C10—H10A···O1 hydrogen bonds (Table 1) link the molecules into chains along the c axis.
Experimental
To a solution of 4-chloro-1-(2-methylpropyl)-1H-imidazo[4,5-c] quinoline (0.1 mol) in methanol (30 ml) was added a solution of sodium methoxide (0.01 mol) in methanol (10 ml) and the mixture was stirred for 1 h. The reaction mixture was heated under reflux for 12 h, concentrated and poured into crushed ice. The resultant solid was filtered, dried and recrystallized using a mixture of DMF and water (1:1). M. p. = 493–495 K.
Refinement
All H atoms were positioned geometrically and refined using a riding model; C—H = 0.93 to 0.98 Å; Uiso(H) = xUeq(C), where x = 1.5 for methyl H and 1.2 for all other H atoms. A rotating group model was applied to the methyl groups.
Figures
Fig. 1.
Fig. 1.
The molecular structure of the title compound, showing 30% probability displacement ellipsoids and the atom-numbering scheme. Hydrogen atoms are shown as spheres of arbitrary radius.
Fig. 2.
Fig. 2.
The crystal packing of the title compound, viewed along the a axis, showing the chains along the c axis. Hydrogen bonds are indicated by dashed lines.
Crystal data
C15H17N3OF(000) = 544
Mr = 255.32Dx = 1.240 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 3364 reflections
a = 7.4196 (8) Åθ = 2.9–28.4°
b = 18.910 (2) ŵ = 0.08 mm1
c = 10.4112 (14) ÅT = 297 K
β = 110.568 (2)°Plate, colourless
V = 1367.6 (3) Å30.40 × 0.31 × 0.13 mm
Z = 4
Data collection
Bruker SMART APEXII DUO CCD area-detector diffractometer3463 independent reflections
Radiation source: fine-focus sealed tube2386 reflections with I > 2σ(I)
graphiteRint = 0.023
[var phi] and ω scansθmax = 28.6°, θmin = 2.2°
Absorption correction: multi-scan (SADABS; Bruker, 2009)h = −7→9
Tmin = 0.969, Tmax = 0.989k = −25→25
12741 measured reflectionsl = −13→10
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)] = 0.042Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.127H-atom parameters constrained
S = 1.04w = 1/[σ2(Fo2) + (0.0619P)2 + 0.131P] where P = (Fo2 + 2Fc2)/3
3463 reflections(Δ/σ)max < 0.001
175 parametersΔρmax = 0.12 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
O10.48715 (15)0.63510 (5)0.85500 (9)0.0586 (3)
N10.37002 (15)0.53191 (5)0.73822 (10)0.0447 (3)
N20.44565 (18)0.70399 (5)0.59706 (12)0.0563 (3)
N30.33493 (16)0.64771 (5)0.39424 (11)0.0486 (3)
C10.29597 (16)0.49624 (6)0.61429 (12)0.0400 (3)
C20.24489 (19)0.42505 (6)0.61944 (13)0.0483 (3)
H2A0.26080.40450.70390.058*
C30.1725 (2)0.38552 (7)0.50312 (15)0.0549 (3)
H3A0.14000.33840.50890.066*
C40.1472 (2)0.41521 (7)0.37579 (14)0.0563 (4)
H4A0.09760.38790.29680.068*
C50.19492 (19)0.48452 (7)0.36623 (13)0.0491 (3)
H5A0.17760.50390.28060.059*
C60.26991 (16)0.52691 (6)0.48450 (12)0.0397 (3)
C70.32629 (17)0.59928 (6)0.49100 (12)0.0407 (3)
C80.39572 (18)0.63518 (6)0.61455 (13)0.0445 (3)
C90.41477 (18)0.59803 (6)0.73647 (12)0.0441 (3)
C100.4073 (2)0.70816 (7)0.46497 (16)0.0587 (4)
H10A0.42760.74910.42250.070*
C110.2801 (2)0.64045 (8)0.24607 (13)0.0545 (3)
H11A0.32240.59460.22580.065*
H11B0.34650.67630.21290.065*
C120.0645 (2)0.64739 (9)0.16888 (15)0.0639 (4)
H12A−0.00100.60970.20010.077*
C13−0.0102 (3)0.71824 (10)0.1988 (2)0.0988 (7)
H13A−0.14520.72210.14660.148*
H13B0.05780.75590.17370.148*
H13C0.00980.72140.29480.148*
C140.0257 (3)0.63667 (16)0.01661 (19)0.1156 (9)
H14A−0.10830.6447−0.03420.173*
H14B0.05910.58920.00120.173*
H14C0.10180.6694−0.01320.173*
C150.5158 (3)0.59705 (9)0.97911 (15)0.0718 (5)
H15A0.55860.62901.05550.108*
H15B0.61110.56100.99000.108*
H15C0.39680.57560.97530.108*
Atomic displacement parameters (Å2)
U11U22U33U12U13U23
O10.0849 (7)0.0443 (5)0.0409 (5)−0.0024 (4)0.0151 (5)−0.0067 (4)
N10.0532 (6)0.0404 (5)0.0403 (5)−0.0004 (4)0.0162 (4)−0.0010 (4)
N20.0727 (8)0.0350 (6)0.0589 (7)0.0006 (5)0.0202 (6)0.0013 (5)
N30.0575 (6)0.0416 (6)0.0460 (6)0.0052 (5)0.0174 (5)0.0094 (4)
C10.0401 (6)0.0382 (6)0.0419 (6)0.0013 (4)0.0147 (5)−0.0012 (5)
C20.0547 (7)0.0422 (7)0.0496 (7)−0.0038 (5)0.0205 (6)0.0020 (5)
C30.0614 (8)0.0403 (7)0.0622 (9)−0.0084 (6)0.0209 (6)−0.0056 (6)
C40.0642 (9)0.0483 (7)0.0514 (8)−0.0045 (6)0.0140 (6)−0.0134 (6)
C50.0561 (7)0.0476 (7)0.0405 (6)0.0040 (6)0.0130 (5)−0.0014 (5)
C60.0392 (6)0.0380 (6)0.0407 (6)0.0046 (5)0.0126 (5)0.0005 (5)
C70.0434 (6)0.0377 (6)0.0405 (6)0.0068 (5)0.0140 (5)0.0054 (5)
C80.0517 (7)0.0339 (6)0.0465 (7)0.0051 (5)0.0154 (5)0.0002 (5)
C90.0504 (7)0.0402 (6)0.0402 (6)0.0041 (5)0.0139 (5)−0.0038 (5)
C100.0725 (9)0.0381 (7)0.0644 (9)0.0021 (6)0.0229 (7)0.0091 (6)
C110.0586 (8)0.0614 (8)0.0447 (7)0.0030 (6)0.0196 (6)0.0128 (6)
C120.0580 (8)0.0774 (10)0.0539 (8)0.0034 (7)0.0167 (7)0.0247 (7)
C130.0755 (12)0.0790 (12)0.1277 (18)0.0253 (9)0.0180 (11)0.0352 (12)
C140.0779 (13)0.207 (3)0.0512 (10)−0.0164 (14)0.0093 (9)0.0234 (13)
C150.1055 (13)0.0641 (10)0.0429 (8)−0.0088 (8)0.0223 (8)−0.0056 (7)
Geometric parameters (Å, °)
O1—C91.3553 (14)C6—C71.4257 (16)
O1—C151.4281 (17)C7—C81.3839 (16)
N1—C91.2955 (15)C8—C91.4137 (17)
N1—C11.3870 (15)C10—H10A0.9300
N2—C101.3051 (19)C11—C121.523 (2)
N2—C81.3825 (15)C11—H11A0.9700
N3—C101.3635 (17)C11—H11B0.9700
N3—C71.3796 (15)C12—C141.522 (2)
N3—C111.4571 (17)C12—C131.523 (3)
C1—C21.4046 (17)C12—H12A0.9800
C1—C61.4199 (16)C13—H13A0.9600
C2—C31.3626 (18)C13—H13B0.9600
C2—H2A0.9300C13—H13C0.9600
C3—C41.3902 (19)C14—H14A0.9600
C3—H3A0.9300C14—H14B0.9600
C4—C51.3705 (18)C14—H14C0.9600
C4—H4A0.9300C15—H15A0.9600
C5—C61.4095 (16)C15—H15B0.9600
C5—H5A0.9300C15—H15C0.9600
C9—O1—C15116.66 (10)N2—C10—N3114.66 (12)
C9—N1—C1118.43 (10)N2—C10—H10A122.7
C10—N2—C8103.07 (11)N3—C10—H10A122.7
C10—N3—C7105.82 (11)N3—C11—C12113.66 (11)
C10—N3—C11124.15 (11)N3—C11—H11A108.8
C7—N3—C11130.03 (11)C12—C11—H11A108.8
N1—C1—C2117.04 (11)N3—C11—H11B108.8
N1—C1—C6124.31 (11)C12—C11—H11B108.8
C2—C1—C6118.65 (11)H11A—C11—H11B107.7
C3—C2—C1121.28 (12)C14—C12—C11108.51 (14)
C3—C2—H2A119.4C14—C12—C13112.37 (17)
C1—C2—H2A119.4C11—C12—C13110.99 (14)
C2—C3—C4120.33 (12)C14—C12—H12A108.3
C2—C3—H3A119.8C11—C12—H12A108.3
C4—C3—H3A119.8C13—C12—H12A108.3
C5—C4—C3120.24 (12)C12—C13—H13A109.5
C5—C4—H4A119.9C12—C13—H13B109.5
C3—C4—H4A119.9H13A—C13—H13B109.5
C4—C5—C6120.88 (12)C12—C13—H13C109.5
C4—C5—H5A119.6H13A—C13—H13C109.5
C6—C5—H5A119.6H13B—C13—H13C109.5
C5—C6—C1118.63 (11)C12—C14—H14A109.5
C5—C6—C7127.34 (11)C12—C14—H14B109.5
C1—C6—C7114.03 (10)H14A—C14—H14B109.5
N3—C7—C8104.80 (10)C12—C14—H14C109.5
N3—C7—C6133.69 (11)H14A—C14—H14C109.5
C8—C7—C6121.49 (11)H14B—C14—H14C109.5
N2—C8—C7111.65 (11)O1—C15—H15A109.5
N2—C8—C9129.72 (11)O1—C15—H15B109.5
C7—C8—C9118.55 (11)H15A—C15—H15B109.5
N1—C9—O1120.52 (11)O1—C15—H15C109.5
N1—C9—C8123.15 (11)H15A—C15—H15C109.5
O1—C9—C8116.31 (11)H15B—C15—H15C109.5
C9—N1—C1—C2−178.62 (11)C10—N2—C8—C7−0.46 (15)
C9—N1—C1—C61.65 (18)C10—N2—C8—C9176.13 (14)
N1—C1—C2—C3−179.42 (12)N3—C7—C8—N20.34 (14)
C6—C1—C2—C30.32 (18)C6—C7—C8—N2178.58 (11)
C1—C2—C3—C4−0.2 (2)N3—C7—C8—C9−176.68 (11)
C2—C3—C4—C50.1 (2)C6—C7—C8—C91.57 (18)
C3—C4—C5—C6−0.1 (2)C1—N1—C9—O1179.84 (11)
C4—C5—C6—C10.29 (19)C1—N1—C9—C8−1.44 (18)
C4—C5—C6—C7179.85 (12)C15—O1—C9—N11.81 (19)
N1—C1—C6—C5179.35 (11)C15—O1—C9—C8−177.00 (13)
C2—C1—C6—C5−0.37 (17)N2—C8—C9—N1−176.51 (13)
N1—C1—C6—C7−0.27 (16)C7—C8—C9—N1−0.11 (19)
C2—C1—C6—C7−179.99 (11)N2—C8—C9—O12.3 (2)
C10—N3—C7—C8−0.08 (14)C7—C8—C9—O1178.66 (11)
C11—N3—C7—C8−179.63 (12)C8—N2—C10—N30.41 (16)
C10—N3—C7—C6−178.01 (13)C7—N3—C10—N2−0.22 (17)
C11—N3—C7—C62.4 (2)C11—N3—C10—N2179.36 (12)
C5—C6—C7—N3−3.3 (2)C10—N3—C11—C12−99.77 (16)
C1—C6—C7—N3176.32 (12)C7—N3—C11—C1279.71 (17)
C5—C6—C7—C8179.09 (12)N3—C11—C12—C14−178.33 (15)
C1—C6—C7—C8−1.33 (16)N3—C11—C12—C1357.73 (17)
Hydrogen-bond geometry (Å, °)
D—H···AD—HH···AD···AD—H···A
C10—H10A···O1i0.932.393.3052 (16)169.
Symmetry codes: (i) x, −y+3/2, z−1/2.
Footnotes
Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: WN2444).
  • Bruker (2009). APEX2, SAINT and SADABS Bruker AXS Inc., Madison, Wisconsin, USA.
  • Crozat, K. & Beutler, B. (2004). Proc. Natl Acad. Sci. USA, 101, 6835–6836. [PubMed]
  • Hemmi, H., Kaisho, T., Takeuchi, O., Sato, S., Sanjo, H., Hoshino, K., Horiuchi, T., Tomizawa, H., Takeda, K. & Akira, S. (2002). Nat. Immunol. 3, 196–200. [PubMed]
  • Loh, W.-S., Fun, H.-K., Kayarmar, R., Viveka, S. & Nagaraja, G. K. (2011a). Acta Cryst. E67, o405. [PMC free article] [PubMed]
  • Loh, W.-S., Fun, H.-K., Kayarmar, R., Viveka, S. & Nagaraja, G. K. (2011b). Acta Cryst. E67, o406. [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]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]
  • Stringfellow, D. A. & Glasgow, L. A. (1972). Antimicrob. Agents Chemother. 2, 73–78. [PMC free article] [PubMed]
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