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

doi:10.1107/S160053681100153X

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

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

^aX-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia

^bDepartment of Chemistry, Mangalore University, Karnataka, India

Correspondence e-mail: hkfun/at/usm.my

^‡Thomson Reuters ResearcherID: C-7581-2009.

^§Thomson Reuters ResearcherID: A-3561-2009.

Received December 27, 2010; Accepted January 11, 2011.

This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

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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

); Gershon et al. (2004

); Dardari et al. (2004

). For the syntheses of 1H-imidazo[4,5-c]quinolin-4-amines, see: Gabriel (1918

); Izumi et al. (2003

). For bond-length data, see: Allen et al. (1987

). For hydrogen-bond motifs, see: Bernstein et al. (1995

An external file that holds a picture, illustration, etc.
Object name is e-67-0o405-scheme1.jpg Object name is e-67-0o405-scheme1.jpg

Experimental

Crystal data

C₁₆H₂₀N₄
M _r = 268.36
Monoclinic,
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 ) 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
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.18 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

Table 1

Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053681100153X/is2656sup1.cif

Click here to view.^{(19K, cif)}

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

Click here to view.^{(170K, 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.

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

C₁₆H₂₀N₄	F(000) = 576
M_r = 268.36	D_x = 1.239 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 3031 reflections
a = 9.2804 (2) Å	θ = 2.2–27.4°
b = 18.5492 (6) Å	µ = 0.08 mm⁻¹
c = 8.5147 (2) Å	T = 296 K
β = 101.051 (2)°	Block, colourless
V = 1438.57 (7) Å³	0.39 × 0.29 × 0.14 mm
Z = 4

Data collection

Bruker SMART APEXII CCD area-detector diffractometer	3456 independent reflections
Radiation source: fine-focus sealed tube	2271 reflections with I > 2σ(I)
graphite	R_int = 0.037
and ω scans	θ_max = 28.0°, θ_min = 2.2°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −12→12
T_min = 0.971, T_max = 0.989	k = −19→24
13134 measured reflections	l = −10→11

Refinement

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.055	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.146	H-atom parameters constrained
S = 1.02	w = 1/[σ²(F_o²) + (0.0604P)² + 0.3608P] where P = (F_o² + 2F_c²)/3
3456 reflections	(Δ/σ)_max = 0.001
185 parameters	Δρ_max = 0.26 e Å⁻³
0 restraints	Δρ_min = −0.18 e Å⁻³

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)

	x	y	z	U_iso*/U_eq
N1	0.44302 (15)	0.08084 (8)	0.74563 (17)	0.0430 (4)
N3	0.31258 (17)	0.18631 (8)	0.3740 (2)	0.0512 (4)
N2	0.51431 (15)	0.14182 (8)	0.30069 (17)	0.0418 (4)
N4	0.22238 (16)	0.14021 (9)	0.68830 (19)	0.0520 (4)
C7	0.35046 (18)	0.12102 (9)	0.6440 (2)	0.0400 (4)
C6	0.57198 (17)	0.05715 (9)	0.7062 (2)	0.0386 (4)
C5	0.66567 (19)	0.01562 (10)	0.8208 (2)	0.0467 (5)
H5A	0.6387	0.0059	0.9184	0.056*
C4	0.7957 (2)	−0.01084 (11)	0.7918 (2)	0.0500 (5)
H4A	0.8563	−0.0378	0.8698	0.060*
C3	0.8376 (2)	0.00247 (10)	0.6460 (2)	0.0499 (5)
H3A	0.9262	−0.0155	0.6269	0.060*
C2	0.74870 (18)	0.04200 (9)	0.5307 (2)	0.0428 (4)
H2A	0.7771	0.0500	0.4333	0.051*
C1	0.61517 (17)	0.07070 (8)	0.55699 (19)	0.0358 (4)
C9	0.51360 (17)	0.11474 (8)	0.45202 (19)	0.0363 (4)
C8	0.38711 (18)	0.14192 (9)	0.4938 (2)	0.0395 (4)
C10	0.3921 (2)	0.18403 (10)	0.2632 (2)	0.0510 (5)
H10A	0.3677	0.2090	0.1670	0.061*
C11	0.61699 (19)	0.12704 (10)	0.1942 (2)	0.0449 (4)
H11A	0.5682	0.1362	0.0848	0.054*
H11B	0.6434	0.0764	0.2024	0.054*
C12	0.7563 (2)	0.17189 (10)	0.2307 (2)	0.0466 (4)
H12A	0.7980	0.1669	0.3450	0.056*
C13	0.8672 (2)	0.14245 (12)	0.1367 (3)	0.0684 (6)
H13A	0.8840	0.0923	0.1609	0.103*
H13B	0.9579	0.1684	0.1657	0.103*
H13C	0.8298	0.1481	0.0242	0.103*
C14	0.7246 (3)	0.25132 (11)	0.1958 (3)	0.0689 (6)
H14A	0.8137	0.2785	0.2254	0.103*
H14B	0.6539	0.2680	0.2564	0.103*
H14C	0.6862	0.2576	0.0837	0.103*
C15	0.1048 (2)	0.17851 (13)	0.5909 (3)	0.0690 (6)
H15A	0.1212	0.1807	0.4830	0.103*
H15B	0.1002	0.2265	0.6318	0.103*
H15C	0.0139	0.1540	0.5923	0.103*
C16	0.1954 (2)	0.11825 (15)	0.8435 (3)	0.0716 (7)
H16A	0.2865	0.1175	0.9193	0.107*
H16B	0.1527	0.0709	0.8355	0.107*
H16C	0.1292	0.1517	0.8784	0.107*

Atomic displacement parameters (Å²)

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0436 (8)	0.0471 (8)	0.0387 (8)	0.0035 (7)	0.0084 (6)	−0.0017 (7)
N3	0.0483 (8)	0.0502 (9)	0.0556 (10)	0.0094 (7)	0.0110 (7)	0.0128 (8)
N2	0.0434 (8)	0.0424 (8)	0.0401 (8)	−0.0001 (6)	0.0093 (6)	0.0054 (7)
N4	0.0468 (8)	0.0622 (10)	0.0497 (10)	0.0129 (8)	0.0161 (7)	0.0038 (8)
C7	0.0396 (9)	0.0384 (9)	0.0425 (10)	−0.0003 (7)	0.0089 (7)	−0.0055 (8)
C6	0.0388 (8)	0.0368 (9)	0.0395 (9)	−0.0017 (7)	0.0058 (7)	−0.0033 (7)
C5	0.0525 (11)	0.0512 (11)	0.0354 (10)	0.0042 (9)	0.0062 (8)	0.0028 (8)
C4	0.0479 (10)	0.0540 (11)	0.0456 (11)	0.0095 (9)	0.0023 (8)	0.0075 (9)
C3	0.0428 (10)	0.0512 (11)	0.0568 (12)	0.0086 (8)	0.0126 (8)	0.0068 (9)
C2	0.0446 (9)	0.0405 (9)	0.0453 (10)	0.0015 (8)	0.0137 (8)	0.0049 (8)
C1	0.0376 (8)	0.0309 (8)	0.0385 (9)	−0.0022 (7)	0.0064 (7)	−0.0010 (7)
C9	0.0410 (9)	0.0311 (8)	0.0367 (9)	−0.0036 (7)	0.0069 (7)	0.0000 (7)
C8	0.0400 (9)	0.0342 (8)	0.0432 (10)	0.0001 (7)	0.0052 (7)	0.0016 (8)
C10	0.0502 (10)	0.0514 (11)	0.0508 (11)	0.0071 (9)	0.0080 (9)	0.0145 (9)
C11	0.0500 (10)	0.0485 (10)	0.0368 (10)	0.0018 (8)	0.0100 (8)	0.0018 (8)
C12	0.0483 (10)	0.0483 (10)	0.0449 (10)	0.0000 (8)	0.0132 (8)	0.0083 (8)
C13	0.0610 (13)	0.0689 (14)	0.0824 (16)	0.0028 (11)	0.0312 (12)	0.0030 (13)
C14	0.0788 (15)	0.0514 (12)	0.0844 (17)	−0.0004 (11)	0.0352 (13)	0.0129 (12)
C15	0.0460 (11)	0.0844 (16)	0.0790 (16)	0.0166 (11)	0.0183 (10)	0.0156 (13)
C16	0.0606 (13)	0.1034 (19)	0.0566 (13)	0.0146 (12)	0.0256 (11)	0.0048 (13)

Geometric parameters (Å, °)

N1—C7	1.325 (2)	C1—C9	1.425 (2)
N1—C6	1.376 (2)	C9—C8	1.385 (2)
N3—C10	1.305 (2)	C10—H10A	0.9300
N3—C8	1.388 (2)	C11—C12	1.519 (3)
N2—C10	1.365 (2)	C11—H11A	0.9700
N2—C9	1.384 (2)	C11—H11B	0.9700
N2—C11	1.461 (2)	C12—C14	1.521 (3)
N4—C7	1.361 (2)	C12—C13	1.521 (3)
N4—C15	1.427 (2)	C12—H12A	0.9800
N4—C16	1.450 (2)	C13—H13A	0.9600
C7—C8	1.439 (2)	C13—H13B	0.9600
C6—C5	1.406 (2)	C13—H13C	0.9600
C6—C1	1.426 (2)	C14—H14A	0.9600
C5—C4	1.368 (2)	C14—H14B	0.9600
C5—H5A	0.9300	C14—H14C	0.9600
C4—C3	1.393 (3)	C15—H15A	0.9600
C4—H4A	0.9300	C15—H15B	0.9600
C3—C2	1.368 (2)	C15—H15C	0.9600
C3—H3A	0.9300	C16—H16A	0.9600
C2—C1	1.405 (2)	C16—H16B	0.9600
C2—H2A	0.9300	C16—H16C	0.9600

C7—N1—C6	120.37 (15)	N2—C10—H10A	122.9
C10—N3—C8	103.93 (14)	N2—C11—C12	113.65 (15)
C10—N2—C9	105.91 (14)	N2—C11—H11A	108.8
C10—N2—C11	125.01 (15)	C12—C11—H11A	108.8
C9—N2—C11	129.00 (14)	N2—C11—H11B	108.8
C7—N4—C15	125.46 (16)	C12—C11—H11B	108.8
C7—N4—C16	119.42 (16)	H11A—C11—H11B	107.7
C15—N4—C16	115.06 (16)	C11—C12—C14	111.44 (16)
N1—C7—N4	117.22 (16)	C11—C12—C13	109.34 (16)
N1—C7—C8	119.85 (15)	C14—C12—C13	111.73 (17)
N4—C7—C8	122.93 (16)	C11—C12—H12A	108.1
N1—C6—C5	117.17 (15)	C14—C12—H12A	108.1
N1—C6—C1	124.58 (15)	C13—C12—H12A	108.1
C5—C6—C1	118.24 (15)	C12—C13—H13A	109.5
C4—C5—C6	121.37 (17)	C12—C13—H13B	109.5
C4—C5—H5A	119.3	H13A—C13—H13B	109.5
C6—C5—H5A	119.3	C12—C13—H13C	109.5
C5—C4—C3	120.26 (17)	H13A—C13—H13C	109.5
C5—C4—H4A	119.9	H13B—C13—H13C	109.5
C3—C4—H4A	119.9	C12—C14—H14A	109.5
C2—C3—C4	120.10 (17)	C12—C14—H14B	109.5
C2—C3—H3A	119.9	H14A—C14—H14B	109.5
C4—C3—H3A	119.9	C12—C14—H14C	109.5
C3—C2—C1	121.20 (16)	H14A—C14—H14C	109.5
C3—C2—H2A	119.4	H14B—C14—H14C	109.5
C1—C2—H2A	119.4	N4—C15—H15A	109.5
C2—C1—C9	127.93 (15)	N4—C15—H15B	109.5
C2—C1—C6	118.81 (15)	H15A—C15—H15B	109.5
C9—C1—C6	113.24 (14)	N4—C15—H15C	109.5
N2—C9—C8	105.21 (14)	H15A—C15—H15C	109.5
N2—C9—C1	132.15 (15)	H15B—C15—H15C	109.5
C8—C9—C1	122.60 (15)	N4—C16—H16A	109.5
C9—C8—N3	110.77 (15)	N4—C16—H16B	109.5
C9—C8—C7	119.13 (15)	H16A—C16—H16B	109.5
N3—C8—C7	130.09 (15)	N4—C16—H16C	109.5
N3—C10—N2	114.14 (16)	H16A—C16—H16C	109.5
N3—C10—H10A	122.9	H16B—C16—H16C	109.5

C6—N1—C7—N4	177.51 (15)	C11—N2—C9—C1	6.5 (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—N2	178.26 (16)
C16—N4—C7—N1	1.9 (3)	C2—C1—C9—C8	−177.77 (16)
C15—N4—C7—C8	4.4 (3)	C6—C1—C9—C8	0.8 (2)
C16—N4—C7—C8	−178.62 (18)	N2—C9—C8—N3	−1.55 (19)
C7—N1—C6—C5	179.12 (15)	C1—C9—C8—N3	176.52 (15)
C7—N1—C6—C1	−2.1 (3)	N2—C9—C8—C7	177.37 (14)
N1—C6—C5—C4	179.43 (17)	C1—C9—C8—C7	−4.6 (2)
C1—C6—C5—C4	0.5 (3)	C10—N3—C8—C9	1.2 (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—C9	5.2 (2)
C4—C3—C2—C1	0.8 (3)	N4—C7—C8—C9	−174.26 (16)
C3—C2—C1—C9	177.63 (17)	N1—C7—C8—N3	−176.11 (17)
C3—C2—C1—C6	−0.8 (3)	N4—C7—C8—N3	4.4 (3)
N1—C6—C1—C2	−178.65 (15)	C8—N3—C10—N2	−0.4 (2)
C5—C6—C1—C2	0.1 (2)	C9—N2—C10—N3	−0.6 (2)
N1—C6—C1—C9	2.7 (2)	C11—N2—C10—N3	176.48 (16)
C5—C6—C1—C9	−178.54 (15)	C10—N2—C11—C12	100.8 (2)
C10—N2—C9—C8	1.26 (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—C13	168.91 (16)

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
C15—H15A···N3	0.96	2.16	2.918 (3)	135

Footnotes

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

References

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