2-{1-[2,8-Bis(trifluoro­meth­yl)quinolin-4-yl]-3,5,6,7,8,8a-hexa­hydro-1H-1,3-oxazolo[3,4-a]pyridin-3-yl}phenol

Raoni S B Gonçalves; Carlos R Kaiser; Marcus V N de Souza; James L Wardell; Solange M S V Wardell; Edward R T Tiekink

doi:10.1107/S1600536811022379

. 2011 Jun 18;67(Pt 7):o1656–o1657. doi: 10.1107/S1600536811022379

2-{1-[2,8-Bis(trifluoromethyl)quinolin-4-yl]-3,5,6,7,8,8a-hexahydro-1H-1,3-oxazolo[3,4-a]pyridin-3-yl}phenol

Raoni S B Gonçalves ^a,^b, Carlos R Kaiser ^b, Marcus V N de Souza ^a, James L Wardell ^c,^‡, Solange M S V Wardell ^d, Edward R T Tiekink ^e,^*

PMCID: PMC3151884 PMID: 21837057

Abstract

In the title mefloquine–oxazolidine derivative, C₂₄H₂₀F₆N₂O₂, the oxazoline ring adopts an envelope conformation (the flap atom is N) and the piperidine ring has a chair conformation. The oxazoline and benzene residues lie away from the C₆ ring of the quinoline group and, to a first approximation, to one side of the plane through the ten atoms (r.m.s. deviation = 0.025 Å). An intramolecular O—H⋯N(piperidine) hydrogen bond is present. The crystal packing features C—H⋯O, C—H⋯F and C—H⋯π(hydroxybenzene) interactions.

Related literature

For background to the anti-mycobacterial activities of quinoline derivatives related to mefloquine, see: Gonçalves et al. (2010 ▶). For additional geometric analysis, see: Cremer & Pople (1975 ▶); Spek (2009 ▶).

Experimental

Crystal data

C₂₄H₂₀F₆N₂O₂
M _r = 482.42
Orthorhombic,
a = 27.2766 (11) Å
b = 34.1005 (9) Å
c = 9.4431 (2) Å
V = 8783.5 (5) Å³
Z = 16
Mo Kα radiation
μ = 0.13 mm⁻¹
T = 120 K
0.40 × 0.20 × 0.16 mm

Data collection

Enraf–Nonius KappaCCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2007 ▶) T _min = 0.799, T _max = 1.000
13970 measured reflections
2660 independent reflections
2519 reflections with I > 2σ(I)
R _int = 0.043

Refinement

R[F ² > 2σ(F ²)] = 0.035
wR(F ²) = 0.082
S = 1.10
2660 reflections
308 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.24 e Å⁻³

Data collection: COLLECT (Hooft, 1998 ▶); cell refinement: DENZO (Otwinowski & Minor, 1997 ▶) and COLLECT; data reduction: DENZO and COLLECT; 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 DIAMOND (Brandenburg, 2006 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶) and publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811022379/hb5905sup1.cif

e-67-o1656-sup1.cif^{(24.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811022379/hb5905Isup2.hkl

e-67-o1656-Isup2.hkl^{(128.2KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

Cg1 is the centroid of the benzene ring C19–C24.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2o⋯N2	0.84	1.93	2.672 (3)	146
C6—H6⋯O1ⁱ	0.95	2.52	3.384 (3)	152
C16—H16B⋯F4ⁱⁱ	0.99	2.47	3.043 (3)	116
C18—H18B⋯F1ⁱⁱ	0.99	2.54	3.275 (3)	131
C15—H15B⋯Cg1ⁱⁱⁱ	0.99	2.93	3.792 (3)	146

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

Acknowledgments

The use of the EPSRC X-ray crystallographic service at the University of Southampton, England, and the valuable assistance of the staff there are gratefully acknowledged. JLW acknowledges support from CAPES (Brazil).

supplementary crystallographic information

Comment

A recent publication reported the synthesis and anti-tubercular activity of mefloquine-oxazolidine derivatives (Gonçalves et al., 2010). Subsequently, crystals became available for one of the derivatives, the title compound (I), allowing full characterization by X-ray crystallography.

In (I), Fig. 1, the oxazoline ring adopts an envelope conformation with the flap atom being N2 as seen in the puckering parameters Q(2) = 0.409 (2) Å and φ₂ = 100.6 (3) ° (Cremer & Pople, 1975). The piperidinyl ring is close to a chair conformation with puckering parameters: Q(2) = 0.060 (3) Å and Q(3) = -0.596 (3) Å, and amplitudes: Q = 0.599 (3) Å, θ = 174.6 (3) ° and φ = 214 (3) ° (Cremer & Pople, 1975). The 10 non-hydrogen atom comprising the quinoline residue are co-planar with the r.m.s. deviation being 0.025 Å. With reference to this plane, the oxazolidine residue, with the exception of the O1 atom, lies to one side of the plane. By contrast, the benzene ring is somewhat splayed [forming a dihedral angle of 50.34 (11) °] with half the ring above and the other half below the plane through the quinoline atoms. The oxazolidine and benzene ring are directed away from the C₆ ring of the quinoline residue, and the hydroxyl group is orientated to allow the formation of a O—H···N hydrogen bond, Table 1.

Molecules are stabilized in the crystal structure by a combination of C—H···O, C—H···F and C—H···π(hydroxybenzene) interactions, Table 1 and Fig. 2.

Experimental

The compound was prepared as reported in the literature (Gonçalves et al., 2010) and was recrystallized from its ethanol solution for the structural study.