6-Chloro-2-cyclo­propyl-4-(trifluoro­meth­yl)quinoline

H C Devarajegowda; H K Arunkashi; Suresh Babu Vepuri; N Chidananda; V D Jagadeesh Prasad

doi:10.1107/S1600536811003746

. 2011 Feb 5;67(Pt 3):o564. doi: 10.1107/S1600536811003746

6-Chloro-2-cyclopropyl-4-(trifluoromethyl)quinoline

H C Devarajegowda ^a,^*, H K Arunkashi ^a, Suresh Babu Vepuri ^b, N Chidananda ^c, V D Jagadeesh Prasad ^c

PMCID: PMC3051946 PMID: 21522327

Abstract

In the title compound, C₁₃H₉ClF₃N, the quinoline ring system makes a dihedral angle of 88.8 (2)° with the cyclopropyl ring.

Related literature

For general background to quinolines see: Kayser & Novak (1987 ▶); Rudin et al. (1984 ▶); Mao et al. (2009 ▶); Bermudez et al. (2004 ▶); Jayaprakash et al. (2006 ▶); Andries et al. (2005 ▶). For related structures, see: Skörska et al. (2005 ▶); Devarajegowda et al. (2010 ▶); Li et al. (2005 ▶).

Experimental

Crystal data

C₁₃H₉ClF₃N
M _r = 271.66
Monoclinic,
a = 13.8482 (19) Å
b = 5.0534 (8) Å
c = 18.048 (3) Å
β = 107.503 (17)°
V = 1204.5 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.33 mm⁻¹
T = 293 K
0.22 × 0.15 × 0.12 mm

Data collection

Oxford Diffraction Xcalibur diffractometer
Absorption correction: multi-scan (CrysAlis PRO RED; Oxford Diffraction, 2010 ▶) T _min = 0.942, T _max = 0.961
11631 measured reflections
2105 independent reflections
946 reflections with I > 2σ(I)
R _int = 0.092

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.081
S = 0.78
2105 reflections
164 parameters
H-atom parameters constrained
Δρ_max = 0.13 e Å⁻³
Δρ_min = −0.17 e Å⁻³

Data collection: CrysAlis PRO CCD (Oxford Diffraction, 2010 ▶); cell refinement: CrysAlis PRO CCD; data reduction: CrysAlis PRO RED (Oxford Diffraction, 2010 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and CAMERON (Watkin et al., 1993) ▶; software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811003746/wn2420sup1.cif

e-67-0o564-sup1.cif^{(17.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811003746/wn2420Isup2.hkl

e-67-0o564-Isup2.hkl^{(101.4KB, hkl)}

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

Acknowledgments

The authors thank Professor T. N. Guru Row and Mr Venkatesha R. Hathwar, Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore, for their help with the data collection.

supplementary crystallographic information

Comment

1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)- 3-quinolinecarboxylic acid (ciprofloxacin) is a widely used broad-spectrum antibiotic, which is active against both Gram-positive and Gram-negative bacteria (Kayser & Novak, 1987; Rudin et al., 1984). 2,8-Bis(trifluoromethyl)quinolin-4-yl]-(2-piperidyl)methanol (mefloquin) is another popular quinoline derivative used in the treatment of malaria. Furthermore, studies have reported that it also possesses important structural features required for antimicrobial activity (Mao et al., 2009; Bermudez et al., 2004; Jayaprakash et al., 2006). Quinoline is the essential structural feature found in these drugs and recently developed antimycobacterial drugs (Andries et al., 2005). Thus, quinoline derivatives are good lead molecules to further develop drug candidates against mycobacterium tuberculosis and as antibacterial agents. On the basis of these observations, we have synthesized a quinoline derivative, with a cyclopropyl group and a trifluoromethyl group as substituents, expecting that the newly designed hybrid molecule would exhibit some antibacterial activity. In this paper we report the crystal structure of 6-chloro-2-cyclopropyl-4-(trifluoromethyl)quinoline.

The asymmetric unit of the 6-chloro-2-cyclopropyl-4-(trifluoromethyl) quinoline contains one molecule (Fig. 1). The quinoline ring system makes a dihedral angle of 88.8 (2)° with the cyclopropyl ring. Bond distances and bond angles in the quinoline ring system are in good agreement with those observed in related crystal structures (Skörska et al., 2005; Devarajegowda et al., 2010; Li et al., 2005). The packing of the molecules, when viewed along the b axis, is shown in Fig. 2.

Experimental

A mixture of cyclopropyl acetylene (0.012 mol), anhydrous zinc(II) (0.012 mol), triethylamine (1.67 ml, 0.012 mol), and toluene (25 ml) was stirred at 50°C for 2 h and cooled to 25°C. 4-Chloro- 2-trifluoroacetylaniline (0.01 mol) was added and the reaction mixture was stirred at 25°C for 4 h, then at 50°C for 4 h. After cooling to room temperature, the mixture was added to water (10 ml) and extracted three times with ethyl acetate (20 ml). The combined organic phase was washed with brine and dried over anhydrous sodium sulfate. After removal of solvent, the residue was purified by column chromatography on silica gel (hexane/ethyl acetate; 20:1). M.p. 335 K.