2-Methyl-6-(trifluoro­meth­yl)imidazo[1,2-a]pyridine-3-carbonitrile

Hoong-Kun Fun; Mohd Mustaqim Rosli; D J Madhu Kumar; D Jagadeesh Prasad; G K Nagaraja

doi:10.1107/S1600536811003928

. 2011 Feb 5;67(Pt 3):o573. doi: 10.1107/S1600536811003928

2-Methyl-6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carbonitrile

Hoong-Kun Fun ^a,^*,^‡, Mohd Mustaqim Rosli ^a, D J Madhu Kumar ^b, D Jagadeesh Prasad ^b, G K Nagaraja ^b

PMCID: PMC3052008 PMID: 21522335

Abstract

In the title compound, C₁₀H₆F₃N₃, the imidazo[1,2-a]pyridine group is essentially planar with a maximum deviation of 0.021 (1) Å. The F atoms in the trifluoromethyl group and the methyl H atoms are each disordered over two sets of sites with refined site occupancies of 0.68 (1):0.32 (1). In the crystal, molecules are linked into infinite chains through two C—H⋯N interactions forming R ₂ ²(12) and R ₂ ²(8) hydrogen-bond ring motifs. These chains are stacked along the a axis.

Related literature

For the biological activity of imidazole derivatives, see: Biftu et al. (2006 ▶); Elhakmoui et al. (1994 ▶); Fisher & Lusi (1972 ▶); Gudmundsson & Johns (2003 ▶, 2007 ▶); Kaminski et al. (1989 ▶); Rewankar et al. (1975 ▶); Rupert et al. (2003 ▶). For graph-set descriptions of hydrogen-bond ring motifs, see: Bernstein et al. (1995 ▶).

Experimental

Crystal data

C₁₀H₆F₃N₃
M _r = 225.18
Monoclinic,
a = 5.6871 (3) Å
b = 8.5437 (5) Å
c = 20.5403 (13) Å
β = 96.653 (4)°
V = 991.31 (10) Å³
Z = 4
Mo Kα radiation
μ = 0.13 mm⁻¹
T = 297 K
0.43 × 0.22 × 0.07 mm

Data collection

Bruker APEXII DUO CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.945, T _max = 0.991
10175 measured reflections
2820 independent reflections
1720 reflections with I > 2σ(I)
R _int = 0.029

Refinement

R[F ² > 2σ(F ²)] = 0.049
wR(F ²) = 0.130
S = 1.03
2820 reflections
176 parameters
H-atom parameters constrained
Δρ_max = 0.13 e Å⁻³
Δρ_min = −0.22 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/S1600536811003928/fl2329sup1.cif

e-67-0o573-sup1.cif^{(17.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811003928/fl2329Isup2.hkl

e-67-0o573-Isup2.hkl^{(138.5KB, 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
C1—H1A⋯N3ⁱ	0.93	2.45	3.384 (2)	176
C4—H4A⋯N2ⁱⁱ	0.93	2.53	3.428 (2)	163

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

Acknowledgments

HKF and MMR thank USM for the Research University Grant (No. 1001/PFIZIK/ 811160).

supplementary crystallographic information

Comment

The imidazole nucleus is a widely used pharmacophore in medicinal compounds due to its broad spectrum of biological activities. Moreover imidazole derivatives are isosteres of naturally-occurring nucleotides which allow them to interact easily with the biopolymers of the living systems. It has been known that imidazo[1,2-a]pyridine derivatives exhibit diverse biological activities (Gudmundsson & Johns, 2003) and were used as antiviral (Elhakmoui et al., 1994), antiulcer (Kaminski et al., 1989), antibacterial (Rewankar et al., 1975), antifungal (Fisher & Lusi, 1972), antiprotozoal (Biftu et al., 2006), antiherpes (Gudmundsson & Johns, 2007) and anti-inflammatory (Rupert et al., 2003) compounds.

All bond lengths and angles in the compound are within normal range. The imidazo[1,2-a] pyridine group is planar with maximum deviation of -0.021 (1)Å for atom N1 (Fig. 1). The F atoms in the trifluoromethyl group and the methyl H atoms are disordered over two positions with refined site occupancies of 0.68 (1):0.32 (1).

In the crystal structure, the molecules form infinite chains through C1—H1A···N3ⁱ and C4—H4A···N2ⁱⁱ (Table 1) interactions. These interactions also form R²₂(12) and R²₂(8) hydrogen ring motifs, respectively (Bernstein et al., 1995). The chains are stacked along the a-axis (Fig. 2).

Experimental

A mixture of 5-(trifluoromethyl) pyridin-2-amine (0.01mol) and dimethylacetamide dimethyl acetal (0.03mol) was refluxed for 24 hr at 900 C. The resultant product was recrystallized from ethanol. The product so obtained (0.01mol) was refluxed with bromoacetonitrile (0.01mol) in toluene at 600 C. The product was then removed by evaporation of toluene under reduced pressure and it was isolated by column chromatography using ethyl acetate as an eluent. It was then recrystallized by slow evaporation from ethanol to give crystals suitable for x-ray analysis.