(R*,S*)-(±)-1-(2-{[2,8-Bis(trifluoromethyl)quinolin-4-yl](hydroxy)methyl}piperidin-1-yl)ethanone methanol monosolvate.

The title mefloquine derivative has been crystallized as its 1:1 methanol solvate, C(19)H(18)F(6)N(2)O(2)·CH(3)OH. Each of the meth-ine-hydroxyl residue [the C-C-C-O torsion angle is -16.35 (17) °] and the piperidinyl group [distorted chair conformation] lies to one side of the quinolinyl ring system. The hydroxyl and carbonyl groups lie to either side of the mol-ecule, enabling their participation in inter-molecular inter-actions. Thus, the hydroxyl and carbonyl groups of two centrosymmetrically related mol-ecules are bridged by two methanol mol-ecules via O-H⋯O hydrogen bonds, leading to a four-mol-ecule aggregate. These are linked into a supra-molecular chain along the a axis via C-H⋯O inter-actions involving the hydroxyl-O atom. The chains assemble into layers that inter-digitate along the c axis being connected by C-H⋯F inter-actions.

Related literature

For background to the use of quinoline derivatives, including mefloquine derivatives, for the treatment of tuberculosis, see: de Souza et al. (2009 ▶); Candea et al. (2009 ▶); Danelishvili et al. (2005 ▶); Kunin & Ellis (2008 ▶); Jayaprakash et al. (2006 ▶); Bermudez et al. (2004 ▶). For related structural studies of mefloquine derivatives, see: Wardell et al. (2010 ▶, 2011 ▶).

Experimental

Crystal data

C19H18F6N2O2·CH4O

M = 452.40

Triclinic,

a = 9.4719 (2) Å

b = 10.1223 (3) Å

c = 11.9227 (3) Å

α = 114.567 (1)°

β = 90.343 (2)°

γ = 102.795 (2)°

V = 1007.61 (4) Å3

Z = 2

Mo Kα radiation

μ = 0.14 mm−1

T = 120 K

0.20 × 0.08 × 0.08 mm

Data collection

Nonius KappaCCD diffractometer

Absorption correction: multi-scan (SADABS; Sheldrick, 2007 ▶) T min = 0.883, T max = 1.000

20055 measured reflections

4602 independent reflections

4038 reflections with I > 2σ(I)

R int = 0.041

Refinement

R[F 2 > 2σ(F 2)] = 0.040

wR(F 2) = 0.110

S = 1.02

4602 reflections

288 parameters

2 restraints

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.37 e Å−3

Δρmin = −0.33 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: publCIF (Westrip, 2010 ▶).

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811038128/hb6409sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811038128/hb6409Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536811038128/hb6409Isup3.cml

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

C19H18F6N2O2·CH4O	Z = 2
Mr = 452.40	F(000) = 468
Triclinic, P1	Dx = 1.491 Mg m−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 9.4719 (2) Å	Cell parameters from 16977 reflections
b = 10.1223 (3) Å	θ = 2.9–27.5°
c = 11.9227 (3) Å	µ = 0.14 mm−1
α = 114.567 (1)°	T = 120 K
β = 90.343 (2)°	Block, colourless
γ = 102.795 (2)°	0.20 × 0.08 × 0.08 mm
V = 1007.61 (4) Å3

Nonius KappaCCD diffractometer	4602 independent reflections
Radiation source: Enraf Nonius FR591 rotating anode	4038 reflections with I > 2σ(I)
10 cm confocal mirrors	Rint = 0.041
Detector resolution: 9.091 pixels mm-1	θmax = 27.5°, θmin = 3.1°
φ and ω scans	h = −11→12
Absorption correction: multi-scan (SADABS; Sheldrick, 2007)	k = −13→13
Tmin = 0.883, Tmax = 1.000	l = −15→15
20055 measured reflections

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)] = 0.040	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.110	H atoms treated by a mixture of independent and constrained refinement
S = 1.02	w = 1/[σ2(Fo2) + (0.0544P)2 + 0.5339P] where P = (Fo2 + 2Fc2)/3
4602 reflections	(Δ/σ)max = 0.001
288 parameters	Δρmax = 0.37 e Å−3
2 restraints	Δρmin = −0.33 e Å−3

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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.

	x	y	z	Uiso*/Ueq
F1	0.26612 (10)	0.38078 (10)	1.09873 (8)	0.0321 (2)
F2	0.29759 (9)	0.17772 (11)	1.10061 (8)	0.0292 (2)
F3	0.12314 (9)	0.27028 (11)	1.18989 (8)	0.0287 (2)
F4	−0.46418 (10)	0.20984 (12)	0.96873 (9)	0.0365 (2)
F5	−0.24743 (11)	0.34198 (11)	1.04600 (10)	0.0418 (3)
F6	−0.32894 (11)	0.13779 (12)	1.06582 (8)	0.0366 (2)
O1	0.29182 (10)	−0.01823 (11)	0.64457 (9)	0.0208 (2)
H1o	0.315 (2)	0.0724 (12)	0.6576 (18)	0.031*
O2	−0.10074 (12)	−0.28747 (13)	0.38799 (10)	0.0305 (3)
N1	−0.03724 (12)	0.17012 (13)	0.97451 (11)	0.0197 (2)
N2	0.11869 (12)	−0.30509 (13)	0.44422 (11)	0.0204 (2)
C1	0.09757 (14)	0.15791 (15)	0.96899 (12)	0.0187 (3)
C2	0.15919 (14)	0.08145 (15)	0.86058 (13)	0.0193 (3)
H2	0.2584	0.0780	0.8646	0.023*
C3	0.07291 (14)	0.01209 (14)	0.74906 (12)	0.0178 (3)
C4	−0.07565 (14)	0.02027 (15)	0.74941 (13)	0.0187 (3)
C5	−0.17571 (15)	−0.04706 (16)	0.63970 (13)	0.0218 (3)
H5	−0.1441	−0.1013	0.5620	0.026*
C6	−0.31640 (16)	−0.03461 (17)	0.64485 (14)	0.0256 (3)
H6	−0.3819	−0.0814	0.5709	0.031*
C7	−0.36548 (15)	0.04705 (17)	0.75876 (14)	0.0244 (3)
H7	−0.4633	0.0558	0.7610	0.029*
C8	−0.27259 (15)	0.11371 (16)	0.86618 (13)	0.0215 (3)
C9	−0.12550 (14)	0.10137 (15)	0.86463 (12)	0.0188 (3)
C10	0.19590 (14)	0.24533 (16)	1.09029 (13)	0.0214 (3)
C11	−0.32713 (16)	0.20071 (18)	0.98679 (14)	0.0273 (3)
C12	0.13776 (14)	−0.06447 (15)	0.62862 (12)	0.0181 (3)
H12	0.1016	−0.0346	0.5658	0.022*
C13	0.09029 (15)	−0.23709 (15)	0.57593 (12)	0.0193 (3)
H13	−0.0178	−0.2641	0.5764	0.023*
C14	0.26389 (16)	−0.33204 (17)	0.41659 (14)	0.0250 (3)
H14A	0.3357	−0.2349	0.4399	0.030*
H14B	0.2618	−0.3924	0.3263	0.030*
C15	0.31159 (18)	−0.41381 (18)	0.48644 (15)	0.0299 (3)
H15A	0.2465	−0.5157	0.4563	0.036*
H15B	0.4119	−0.4240	0.4702	0.036*
C16	0.30687 (17)	−0.32879 (17)	0.62526 (14)	0.0274 (3)
H16A	0.3781	−0.2301	0.6570	0.033*
H16B	0.3336	−0.3858	0.6689	0.033*
C17	0.15401 (15)	−0.30642 (16)	0.65061 (13)	0.0230 (3)
H17A	0.1562	−0.2415	0.7400	0.028*
H17B	0.0876	−0.4049	0.6329	0.028*
C18	0.01477 (15)	−0.32362 (15)	0.35744 (13)	0.0225 (3)
C19	0.03672 (18)	−0.39287 (17)	0.22186 (13)	0.0275 (3)
H19A	0.0302	−0.4999	0.1944	0.041*
H19B	0.1329	−0.3435	0.2098	0.041*
H19C	−0.0387	−0.3802	0.1732	0.041*
O3	0.63629 (12)	0.72872 (12)	0.32218 (11)	0.0306 (3)
H3O	0.7165 (15)	0.711 (2)	0.335 (2)	0.046*
C20	0.56930 (19)	0.61623 (19)	0.20456 (17)	0.0381 (4)
H20A	0.4786	0.6367	0.1839	0.057*
H20B	0.5477	0.5182	0.2069	0.057*
H20C	0.6353	0.6160	0.1415	0.057*

	U11	U22	U33	U12	U13	U23
F1	0.0328 (5)	0.0246 (4)	0.0284 (5)	−0.0055 (4)	−0.0033 (4)	0.0077 (4)
F2	0.0226 (4)	0.0386 (5)	0.0242 (4)	0.0117 (4)	−0.0019 (3)	0.0092 (4)
F3	0.0241 (4)	0.0398 (5)	0.0185 (4)	0.0074 (4)	0.0042 (3)	0.0090 (4)
F4	0.0211 (4)	0.0556 (6)	0.0317 (5)	0.0187 (4)	0.0061 (4)	0.0130 (5)
F5	0.0297 (5)	0.0309 (5)	0.0469 (6)	0.0096 (4)	0.0068 (4)	−0.0015 (4)
F6	0.0364 (5)	0.0529 (6)	0.0231 (5)	0.0173 (5)	0.0071 (4)	0.0155 (4)
O1	0.0163 (5)	0.0197 (5)	0.0242 (5)	0.0033 (4)	0.0029 (4)	0.0078 (4)
O2	0.0276 (5)	0.0359 (6)	0.0237 (5)	0.0124 (5)	−0.0031 (4)	0.0064 (5)
N1	0.0170 (5)	0.0196 (5)	0.0210 (6)	0.0038 (4)	0.0015 (4)	0.0077 (5)
N2	0.0205 (6)	0.0193 (5)	0.0187 (6)	0.0046 (4)	0.0010 (4)	0.0056 (5)
C1	0.0185 (6)	0.0175 (6)	0.0194 (6)	0.0027 (5)	0.0010 (5)	0.0080 (5)
C2	0.0148 (6)	0.0200 (6)	0.0222 (7)	0.0038 (5)	0.0017 (5)	0.0084 (5)
C3	0.0180 (6)	0.0156 (6)	0.0201 (6)	0.0038 (5)	0.0024 (5)	0.0080 (5)
C4	0.0173 (6)	0.0180 (6)	0.0217 (6)	0.0033 (5)	0.0012 (5)	0.0099 (5)
C5	0.0207 (7)	0.0246 (7)	0.0200 (6)	0.0057 (5)	0.0014 (5)	0.0095 (6)
C6	0.0204 (7)	0.0316 (8)	0.0226 (7)	0.0046 (6)	−0.0022 (5)	0.0104 (6)
C7	0.0160 (6)	0.0305 (7)	0.0272 (7)	0.0072 (5)	0.0019 (5)	0.0121 (6)
C8	0.0177 (6)	0.0241 (7)	0.0230 (7)	0.0056 (5)	0.0039 (5)	0.0102 (6)
C9	0.0170 (6)	0.0180 (6)	0.0213 (6)	0.0039 (5)	0.0014 (5)	0.0085 (5)
C10	0.0167 (6)	0.0244 (7)	0.0207 (7)	0.0039 (5)	0.0024 (5)	0.0079 (6)
C11	0.0180 (7)	0.0333 (8)	0.0274 (7)	0.0087 (6)	0.0021 (5)	0.0087 (6)
C12	0.0152 (6)	0.0201 (6)	0.0186 (6)	0.0035 (5)	0.0005 (5)	0.0083 (5)
C13	0.0184 (6)	0.0196 (6)	0.0183 (6)	0.0035 (5)	0.0011 (5)	0.0072 (5)
C14	0.0232 (7)	0.0262 (7)	0.0223 (7)	0.0084 (5)	0.0044 (5)	0.0060 (6)
C15	0.0302 (8)	0.0278 (8)	0.0320 (8)	0.0138 (6)	0.0027 (6)	0.0097 (6)
C16	0.0277 (7)	0.0275 (7)	0.0297 (8)	0.0109 (6)	−0.0002 (6)	0.0128 (6)
C17	0.0256 (7)	0.0207 (6)	0.0234 (7)	0.0050 (5)	0.0012 (5)	0.0103 (6)
C18	0.0257 (7)	0.0172 (6)	0.0227 (7)	0.0034 (5)	−0.0015 (5)	0.0077 (5)
C19	0.0373 (8)	0.0231 (7)	0.0206 (7)	0.0080 (6)	0.0000 (6)	0.0077 (6)
O3	0.0239 (5)	0.0236 (5)	0.0383 (6)	0.0042 (4)	−0.0052 (4)	0.0085 (5)
C20	0.0317 (9)	0.0300 (8)	0.0434 (10)	0.0044 (7)	−0.0090 (7)	0.0087 (7)

F1—C10	1.3465 (17)	C7—H7	0.9500
F2—C10	1.3311 (16)	C8—C9	1.4257 (18)
F3—C10	1.3365 (16)	C8—C11	1.506 (2)
F4—C11	1.3440 (17)	C12—C13	1.5447 (18)
F5—C11	1.3376 (18)	C12—H12	1.0000
F6—C11	1.3372 (19)	C13—C17	1.5330 (19)
O1—C12	1.4159 (15)	C13—H13	1.0000
O1—H1O	0.841 (9)	C14—C15	1.522 (2)
O2—C18	1.2389 (18)	C14—H14A	0.9900
N1—C1	1.3092 (18)	C14—H14B	0.9900
N1—C9	1.3676 (17)	C15—C16	1.522 (2)
N2—C18	1.3489 (18)	C15—H15A	0.9900
N2—C14	1.4736 (18)	C15—H15B	0.9900
N2—C13	1.4833 (17)	C16—C17	1.527 (2)
C1—C2	1.4099 (18)	C16—H16A	0.9900
C1—C10	1.5155 (19)	C16—H16B	0.9900
C2—C3	1.3731 (19)	C17—H17A	0.9900
C2—H2	0.9500	C17—H17B	0.9900
C3—C4	1.4277 (18)	C18—C19	1.508 (2)
C3—C12	1.5284 (18)	C19—H19A	0.9800
C4—C5	1.4253 (18)	C19—H19B	0.9800
C4—C9	1.4233 (19)	C19—H19C	0.9800
C5—C6	1.365 (2)	O3—C20	1.417 (2)
C5—H5	0.9500	O3—H3O	0.844 (10)
C6—C7	1.410 (2)	C20—H20A	0.9800
C6—H6	0.9500	C20—H20B	0.9800
C7—C8	1.369 (2)	C20—H20C	0.9800
C12—O1—H1O	107.1 (13)	C3—C12—H12	107.9
C1—N1—C9	116.47 (12)	C13—C12—H12	107.9
C18—N2—C14	123.62 (12)	N2—C13—C17	111.09 (11)
C18—N2—C13	117.51 (11)	N2—C13—C12	109.90 (11)
C14—N2—C13	118.47 (11)	C17—C13—C12	115.71 (11)
N1—C1—C2	125.94 (12)	N2—C13—H13	106.5
N1—C1—C10	115.30 (12)	C17—C13—H13	106.5
C2—C1—C10	118.58 (12)	C12—C13—H13	106.5
C3—C2—C1	118.68 (12)	N2—C14—C15	111.64 (12)
C3—C2—H2	120.7	N2—C14—H14A	109.3
C1—C2—H2	120.7	C15—C14—H14A	109.3
C2—C3—C4	117.93 (12)	N2—C14—H14B	109.3
C2—C3—C12	120.24 (12)	C15—C14—H14B	109.3
C4—C3—C12	121.76 (12)	H14A—C14—H14B	108.0
C5—C4—C9	118.50 (12)	C16—C15—C14	110.70 (12)
C5—C4—C3	123.12 (12)	C16—C15—H15A	109.5
C9—C4—C3	118.37 (12)	C14—C15—H15A	109.5
C6—C5—C4	120.85 (13)	C16—C15—H15B	109.5
C6—C5—H5	119.6	C14—C15—H15B	109.5
C4—C5—H5	119.6	H15A—C15—H15B	108.1
C5—C6—C7	120.69 (13)	C15—C16—C17	109.83 (12)
C5—C6—H6	119.7	C15—C16—H16A	109.7
C7—C6—H6	119.7	C17—C16—H16A	109.7
C8—C7—C6	120.23 (13)	C15—C16—H16B	109.7
C8—C7—H7	119.9	C17—C16—H16B	109.7
C6—C7—H7	119.9	H16A—C16—H16B	108.2
C7—C8—C9	120.65 (13)	C16—C17—C13	115.50 (12)
C7—C8—C11	119.37 (12)	C16—C17—H17A	108.4
C9—C8—C11	119.98 (12)	C13—C17—H17A	108.4
N1—C9—C4	122.62 (12)	C16—C17—H17B	108.4
N1—C9—C8	118.31 (12)	C13—C17—H17B	108.4
C4—C9—C8	119.07 (12)	H17A—C17—H17B	107.5
F2—C10—F3	107.34 (11)	O2—C18—N2	120.45 (13)
F2—C10—F1	106.85 (11)	O2—C18—C19	119.45 (13)
F3—C10—F1	106.54 (11)	N2—C18—C19	120.07 (13)
F2—C10—C1	112.72 (11)	C18—C19—H19A	109.5
F3—C10—C1	113.03 (11)	C18—C19—H19B	109.5
F1—C10—C1	109.98 (11)	H19A—C19—H19B	109.5
F6—C11—F5	107.04 (13)	C18—C19—H19C	109.5
F6—C11—F4	106.43 (12)	H19A—C19—H19C	109.5
F5—C11—F4	106.05 (12)	H19B—C19—H19C	109.5
F6—C11—C8	112.55 (12)	C20—O3—H3O	107.1 (15)
F5—C11—C8	112.88 (12)	O3—C20—H20A	109.5
F4—C11—C8	111.45 (12)	O3—C20—H20B	109.5
O1—C12—C3	111.69 (10)	H20A—C20—H20B	109.5
O1—C12—C13	109.10 (10)	O3—C20—H20C	109.5
C3—C12—C13	112.24 (11)	H20A—C20—H20C	109.5
O1—C12—H12	107.9	H20B—C20—H20C	109.5
C9—N1—C1—C2	0.4 (2)	C2—C1—C10—F1	82.00 (15)
C9—N1—C1—C10	175.34 (11)	C7—C8—C11—F6	114.64 (15)
N1—C1—C2—C3	−0.1 (2)	C9—C8—C11—F6	−65.36 (17)
C10—C1—C2—C3	−174.91 (12)	C7—C8—C11—F5	−124.06 (15)
C1—C2—C3—C4	−0.56 (19)	C9—C8—C11—F5	55.94 (18)
C1—C2—C3—C12	176.59 (12)	C7—C8—C11—F4	−4.8 (2)
C2—C3—C4—C5	179.96 (13)	C9—C8—C11—F4	175.16 (13)
C12—C3—C4—C5	2.86 (19)	C2—C3—C12—O1	−16.35 (17)
C2—C3—C4—C9	0.88 (18)	C4—C3—C12—O1	160.69 (11)
C12—C3—C4—C9	−176.22 (11)	C2—C3—C12—C13	106.55 (14)
C9—C4—C5—C6	−0.2 (2)	C4—C3—C12—C13	−76.41 (15)
C3—C4—C5—C6	−179.28 (13)	C18—N2—C13—C17	144.40 (12)
C4—C5—C6—C7	0.9 (2)	C14—N2—C13—C17	−42.57 (16)
C5—C6—C7—C8	−0.7 (2)	C18—N2—C13—C12	−86.24 (14)
C6—C7—C8—C9	−0.2 (2)	C14—N2—C13—C12	86.79 (14)
C6—C7—C8—C11	179.85 (14)	O1—C12—C13—N2	−72.10 (13)
C1—N1—C9—C4	0.01 (19)	C3—C12—C13—N2	163.56 (10)
C1—N1—C9—C8	−179.10 (12)	O1—C12—C13—C17	54.71 (15)
C5—C4—C9—N1	−179.75 (12)	C3—C12—C13—C17	−69.64 (15)
C3—C4—C9—N1	−0.63 (19)	C18—N2—C14—C15	−137.78 (14)
C5—C4—C9—C8	−0.65 (19)	C13—N2—C14—C15	49.65 (16)
C3—C4—C9—C8	178.48 (12)	N2—C14—C15—C16	−55.41 (17)
C7—C8—C9—N1	179.97 (13)	C14—C15—C16—C17	56.65 (17)
C11—C8—C9—N1	0.0 (2)	C15—C16—C17—C13	−51.98 (16)
C7—C8—C9—C4	0.8 (2)	N2—C13—C17—C16	43.46 (16)
C11—C8—C9—C4	−179.18 (12)	C12—C13—C17—C16	−82.74 (15)
N1—C1—C10—F2	147.50 (12)	C14—N2—C18—O2	−174.09 (13)
C2—C1—C10—F2	−37.12 (17)	C13—N2—C18—O2	−1.46 (19)
N1—C1—C10—F3	25.55 (17)	C14—N2—C18—C19	7.7 (2)
C2—C1—C10—F3	−159.07 (12)	C13—N2—C18—C19	−179.67 (12)
N1—C1—C10—F1	−93.38 (14)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1o···O3i	0.84 (2)	1.87 (2)	2.7121 (18)	177 (2)
O3—H3o···O2ii	0.845 (16)	1.834 (16)	2.6667 (17)	168 (2)
C7—H7···O1iii	0.95	2.49	3.3280 (18)	147
C17—H17a···F6iv	0.99	2.51	3.3123 (17)	138

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1o⋯O3i	0.84 (2)	1.87 (2)	2.7121 (18)	177 (2)
O3—H3o⋯O2ii	0.85 (2)	1.83 (2)	2.6667 (17)	168 (2)
C7—H7⋯O1iii	0.95	2.49	3.3280 (18)	147
C17—H17a⋯F6iv	0.99	2.51	3.3123 (17)	138

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .