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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 67| Part 10| October 2011| Pages o2714-o2715
https://doi.org/10.1107/S1600536811038128

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

Raoni S. B. Gonçalves,a Marcus V. N. de Souza,a Solange M. S. V. Wardell,b James L. Wardellc‡ and Edward R. T. Tiekinkd*

aFioCruz-Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far Manguinhos, Rua Sizenando Nabuco, 100, Manguinhos, 21041-250, Rio de Janeiro, RJ, Brazil, bCHEMSOL, 1 Harcourt Road, Aberdeen AB15 5NY, Scotland, cCentro de Desenvolvimento Tecnológico em Saúde (CDTS), Fundação Oswaldo Cruz (FIOCRUZ), Casa Amarela, Campus de Manguinhos, Av. Brasil 4365, 21040-900, Rio de Janeiro, RJ, Brazil, and dDepartment of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
*Correspondence e-mail: Edward.Tiekink@gmail.com

(Received 16 September 2011; accepted 18 September 2011; online 30 September 2011)

The title mefloquine derivative has been crystallized as its 1:1 methanol solvate, C19H18F6N2O2·CH3OH. Each of the meth­ine­hydroxyl 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 mol­ecule, enabling their participation in inter­molecular inter­actions. Thus, the hydroxyl and carbonyl groups of two centrosymmetrically related mol­ecules are bridged by two methanol mol­ecules via O—H⋯O hydrogen bonds, leading to a four-mol­ecule aggregate. These are linked into a supra­molecular chain along the a axis via C—H⋯O inter­actions involving the hydroxyl-O atom. The chains assemble into layers that inter­digitate along the c axis being connected by C—H⋯F inter­actions.

Related literature

For background to the use of quinoline derivatives, including mefloquine derivatives, for the treatment of tuberculosis, see: de Souza et al. (2009[Souza, M. V. N. de, Pais, K. C., Kaiser, C. R., Peralta, M. A., Ferreira, M. L. & Lourenço, M. C. S. (2009). Bioorg. Med. Chem. Lett. 17, 1474-1480.]); Candea et al. (2009[Candea, A. L. P., Ferreira, M. L., Pais, K. C., Cardoso, L. N. F., Kaiser, C. R., Henriques, M. G. M. O., Lourenco, M. C. S., Bezerra, F. A. F. M. & de Souza, M. V. N. (2009). Bioorg. Med. Chem. Lett. 19, 6272-6274.]); Danelishvili et al. (2005[Danelishvili, L., Wu, M., Young, L. S. & Bermudez, L. E. (2005). Antimicrob. Agents Chemother. 49, 3707-3714.]); Kunin & Ellis (2008[Kunin, C. M. & Ellis, W. Y. (2008). Antimicrob. Agents Chemother. 52, 2831-2835.]); Jayaprakash et al. (2006[Jayaprakash, S., Iso, Y., Wan, B., Franzblau, S. G. & Kozikowski, A. P. (2006). ChemMedChem, 1, 593-597.]); Bermudez et al. (2004[Bermudez, L. E., Kolonoski, P., Seitz, L. E., Petrofsky, M., Reynolds, R., Wu, M. & Young, L. E. (2004). Antimicrob. Agents Chemother. 48, 3556-3558.]). For related structural studies of mefloquine derivatives, see: Wardell et al. (2010[Wardell, J. L., Wardell, S. M. S. V., Tiekink, E. R. T. & de Lima, G. M. (2010). Acta Cryst. E66, m336-m337.], 2011[Wardell, S. M. S. V., Wardell, J. L., Skakle, J. M. S. & Tiekink, E. R. T. (2011). Z. Kristallogr. 226, 68-77.]).

[Scheme 1]

Experimental

Crystal data

  • C19H18F6N2O2·CH4O

  • Mr = 452.40

  • Triclinic, [P \overline 1]

  • 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[Sheldrick, G. M. (2007). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.883, Tmax = 1.000

  • 20055 measured reflections

  • 4602 independent reflections

  • 4038 reflections with I > 2σ(I)

  • Rint = 0.041
Refinement

  • R[F2 > 2σ(F2)] = 0.040

  • wR(F2) = 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

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) -x+1, -y+1, -z+1; (ii) x+1, y+1, z; (iii) x-1, y, z; (iv) -x, -y, -z+2.

Data collection: COLLECT (Hooft, 1998[Hooft, R. W. W. (1998). COLLECT. Nonius BV, Delft, The Netherlands.]); cell refinement: DENZO (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.]) and COLLECT; data reduction: DENZO and COLLECT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: ORTEP-3 (Farrugia, 1997[Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.]) and DIAMOND (Brandenburg, 2006[Brandenburg, K. (2006). DIAMOND. Crystal Impact GbR, Bonn, Germany.]); software used to prepare material for publication: publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536811038128/hb6409sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536811038128/hb6409Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S1600536811038128/hb6409Isup3.cml

checkCIF report


Comment top

Tuberculosis (TB) is considered a global health emergency by the World Health Organization (WHO). Quinoline derivatives have been reported to exhibit substantial anti-mycobacterial activities and can be considered a promising area for the discovery of new anti-TB agents (de Souza et al., 2009; Candea et al., 2009). The quinoline derivative, mefloquine, ((R*, S*)-(±)-α-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol, which has been used for a long time as an anti-malarial drug, has recently received considerable attention as an anti-mycobacterial drug. This substance has been found to possess substantial activities against Gram-positive bacteria (Kunin & Ellis, 2008) and Mycobacterium species (Danelishvili et al., 2005; Jayaprakash et al., 2006; Bermudez et al., 2004). However, there remains a need for more active and more resistant compounds. With this in mind, the acetoamido derivative of mefloquine, (R*, S*)-(±)-α-2-N-acetopiperidinyl-2,8-bis (trifluoromethyl)-4-quinolinemethanol, (I), has been prepared in continuation with biological and structural studies (Wardell et al., 2010; Wardell et al., 2011). Herein, we report its crystal structure.

In (I), Fig. 1, the asymmetric unit comprises a neutral mefloquine derivative and a methanol molecule of solvation. In the organic molecule, the methine-hydroxyl group is twisted out the least-squares plane through the quinolinyl ring (r.m.s. deviation = 0.008 Å) to which it is attached as seen in the value of the C2—C3—C12—O1 torsion angle of -16.35 (17) °. The piperidinyl group, with a distorted chair conformation, lies to one side and is directed away from the quinolinyl residue. Within the molecule, the hydroxyl and carbonyl groups are directed away from each other allowing for their participation in intermolecular hydrogen bonding interactions.

The formation of a centrosymmetric four molecule aggregate mediated by O—H···O hydrogen bonding, Table 1, is the most notable feature of the crystal packing. The hydroxyl group forms a donor O—H···O hydrogen bond with the solvent methanol molecule which in turn forms a O—H···O hydrogen bond with the carbonyl-O2 atom of a symmetry related molecule. In this way a centrosymmetric 18-membered {···OCNC2OH···OH···}2 synthon is formed. The four-molecule aggregates are linked into a linear supramolecular chain along the a-direction via C—H···O interactions where the acceptor atom is the mefloquine-hydroxyl group, Table 1 and Fig. 2. Chains assemble into layers in the ab plane and inter-digitate along the c axis, enabling the formation of C—H···F interactions, Table 1 and Fig. 3.

Related literature top

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 top

To a stirred solution of mefloquine (3.0 mmol) and triethylamine (7.5 mmol) in anhydrous THF (5 ml), acetyl chloride (6 mmol) was added drop wise at 273 K. The mixture stirred at room temperature for 2 h and after complete conversion of the starting material, as indicated by TLC, THF was evaporated under reduced pressure. The residue was dissolved in CH2Cl2 and washed with water (3 x 10 ml). The organic layer was separated, dried over anhydrous MgSO4, filtered, and solvent was evaporated under reduced pressure to give the desired product, which was recrystallized from MeOH as colourless blocks. M.pt. 458–460 K. IR νmax (cm-1; KBr pellets): 1682 (NC═O); 1189, 1150, 1115 (C—F).

Refinement top

The C-bound H atoms were geometrically placed (C–H = 0.95–1.00 Å) and refined as riding with Uiso(H) = 1.2–1.5Ueq(C). The O-bound H atoms were located from a difference map and their positions refined with O—H = 0.84±0.01 Å, and with Uiso(H) = 1.5Ueq(O).

Structure description top

Tuberculosis (TB) is considered a global health emergency by the World Health Organization (WHO). Quinoline derivatives have been reported to exhibit substantial anti-mycobacterial activities and can be considered a promising area for the discovery of new anti-TB agents (de Souza et al., 2009; Candea et al., 2009). The quinoline derivative, mefloquine, ((R*, S*)-(±)-α-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol, which has been used for a long time as an anti-malarial drug, has recently received considerable attention as an anti-mycobacterial drug. This substance has been found to possess substantial activities against Gram-positive bacteria (Kunin & Ellis, 2008) and Mycobacterium species (Danelishvili et al., 2005; Jayaprakash et al., 2006; Bermudez et al., 2004). However, there remains a need for more active and more resistant compounds. With this in mind, the acetoamido derivative of mefloquine, (R*, S*)-(±)-α-2-N-acetopiperidinyl-2,8-bis (trifluoromethyl)-4-quinolinemethanol, (I), has been prepared in continuation with biological and structural studies (Wardell et al., 2010; Wardell et al., 2011). Herein, we report its crystal structure.

In (I), Fig. 1, the asymmetric unit comprises a neutral mefloquine derivative and a methanol molecule of solvation. In the organic molecule, the methine-hydroxyl group is twisted out the least-squares plane through the quinolinyl ring (r.m.s. deviation = 0.008 Å) to which it is attached as seen in the value of the C2—C3—C12—O1 torsion angle of -16.35 (17) °. The piperidinyl group, with a distorted chair conformation, lies to one side and is directed away from the quinolinyl residue. Within the molecule, the hydroxyl and carbonyl groups are directed away from each other allowing for their participation in intermolecular hydrogen bonding interactions.

The formation of a centrosymmetric four molecule aggregate mediated by O—H···O hydrogen bonding, Table 1, is the most notable feature of the crystal packing. The hydroxyl group forms a donor O—H···O hydrogen bond with the solvent methanol molecule which in turn forms a O—H···O hydrogen bond with the carbonyl-O2 atom of a symmetry related molecule. In this way a centrosymmetric 18-membered {···OCNC2OH···OH···}2 synthon is formed. The four-molecule aggregates are linked into a linear supramolecular chain along the a-direction via C—H···O interactions where the acceptor atom is the mefloquine-hydroxyl group, Table 1 and Fig. 2. Chains assemble into layers in the ab plane and inter-digitate along the c axis, enabling the formation of C—H···F interactions, Table 1 and Fig. 3.

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).

Computing details top

Data collection: COLLECT (Hooft, 1998); cell refinement: DENZO (Otwinowski & Minor, 1997) and COLLECT (Hooft, 1998); data reduction: DENZO (Otwinowski & Minor, 1997) and COLLECT (Hooft, 1998); 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).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I) showing displacement ellipsoids at the 50% probability level.
[Figure 2] Fig. 2. A view of a supramolecular chain in (I) aligned along the a axis. The O—H···O and C—H···O interactions are shown as orange and blue dashed lines, respectively.
[Figure 3] Fig. 3. A view in projection down the a axis of the unit-cell contents in (I) highlighting the stacking of layers along c. The O—H···O, C—H···O and C—H···F interactions are shown as orange, blue and purple dashed lines, respectively.
(R*,S*)-(±)-1-(2-{[2,8-Bis(trifluoromethyl)quinolin- 4-yl](hydroxy)methyl}piperidin-1-yl)ethanone methanol monosolvate top
Crystal data top
C19H18F6N2O2·CH4OZ = 2
Mr = 452.40F(000) = 468
Triclinic, P1Dx = 1.491 Mg m−3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 9.4719 (2) ÅCell parameters from 16977 reflections
b = 10.1223 (3) Åθ = 2.9–27.5°
c = 11.9227 (3) ŵ = 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
Data collection top
Nonius KappaCCD
diffractometer		4602 independent reflections
Radiation source: Enraf Nonius FR591 rotating anode4038 reflections with I > 2σ(I)
10 cm confocal mirrors monochromatorRint = 0.041
Detector resolution: 9.091 pixels mm-1θmax = 27.5°, θmin = 3.1°
φ and ω scansh = −11→12
Absorption correction: multi-scan
(SADABS; Sheldrick, 2007)		k = −13→13
Tmin = 0.883, Tmax = 1.000l = −15→15
20055 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.040Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.110H 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 parametersΔρmax = 0.37 e Å−3
2 restraintsΔρmin = −0.33 e Å−3
Crystal data top
C19H18F6N2O2·CH4Oγ = 102.795 (2)°
Mr = 452.40V = 1007.61 (4) Å3
Triclinic, P1Z = 2
a = 9.4719 (2) ÅMo Kα radiation
b = 10.1223 (3) ŵ = 0.14 mm−1
c = 11.9227 (3) ÅT = 120 K
α = 114.567 (1)°0.20 × 0.08 × 0.08 mm
β = 90.343 (2)°
Data collection top
Nonius KappaCCD
diffractometer		4602 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 2007)		4038 reflections with I > 2σ(I)
Tmin = 0.883, Tmax = 1.000Rint = 0.041
20055 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0402 restraints
wR(F2) = 0.110H atoms treated by a mixture of independent and constrained refinement
S = 1.02Δρmax = 0.37 e Å−3
4602 reflectionsΔρmin = −0.33 e Å−3
288 parameters
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
F10.26612 (10)0.38078 (10)1.09873 (8)0.0321 (2)
F20.29759 (9)0.17772 (11)1.10061 (8)0.0292 (2)
F30.12314 (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)
O10.29182 (10)−0.01823 (11)0.64457 (9)0.0208 (2)
H1o0.315 (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)
N20.11869 (12)−0.30509 (13)0.44422 (11)0.0204 (2)
C10.09757 (14)0.15791 (15)0.96899 (12)0.0187 (3)
C20.15919 (14)0.08145 (15)0.86058 (13)0.0193 (3)
H20.25840.07800.86460.023*
C30.07291 (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)
H5−0.1441−0.10130.56200.026*
C6−0.31640 (16)−0.03461 (17)0.64485 (14)0.0256 (3)
H6−0.3819−0.08140.57090.031*
C7−0.36548 (15)0.04705 (17)0.75876 (14)0.0244 (3)
H7−0.46330.05580.76100.029*
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)
C100.19590 (14)0.24533 (16)1.09029 (13)0.0214 (3)
C11−0.32713 (16)0.20071 (18)0.98679 (14)0.0273 (3)
C120.13776 (14)−0.06447 (15)0.62862 (12)0.0181 (3)
H120.1016−0.03460.56580.022*
C130.09029 (15)−0.23709 (15)0.57593 (12)0.0193 (3)
H13−0.0178−0.26410.57640.023*
C140.26389 (16)−0.33204 (17)0.41659 (14)0.0250 (3)
H14A0.3357−0.23490.43990.030*
H14B0.2618−0.39240.32630.030*
C150.31159 (18)−0.41381 (18)0.48644 (15)0.0299 (3)
H15A0.2465−0.51570.45630.036*
H15B0.4119−0.42400.47020.036*
C160.30687 (17)−0.32879 (17)0.62526 (14)0.0274 (3)
H16A0.3781−0.23010.65700.033*
H16B0.3336−0.38580.66890.033*
C170.15401 (15)−0.30642 (16)0.65061 (13)0.0230 (3)
H17A0.1562−0.24150.74000.028*
H17B0.0876−0.40490.63290.028*
C180.01477 (15)−0.32362 (15)0.35744 (13)0.0225 (3)
C190.03672 (18)−0.39287 (17)0.22186 (13)0.0275 (3)
H19A0.0302−0.49990.19440.041*
H19B0.1329−0.34350.20980.041*
H19C−0.0387−0.38020.17320.041*
O30.63629 (12)0.72872 (12)0.32218 (11)0.0306 (3)
H3O0.7165 (15)0.711 (2)0.335 (2)0.046*
C200.56930 (19)0.61623 (19)0.20456 (17)0.0381 (4)
H20A0.47860.63670.18390.057*
H20B0.54770.51820.20690.057*
H20C0.63530.61600.14150.057*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0328 (5)0.0246 (4)0.0284 (5)−0.0055 (4)−0.0033 (4)0.0077 (4)
F20.0226 (4)0.0386 (5)0.0242 (4)0.0117 (4)−0.0019 (3)0.0092 (4)
F30.0241 (4)0.0398 (5)0.0185 (4)0.0074 (4)0.0042 (3)0.0090 (4)
F40.0211 (4)0.0556 (6)0.0317 (5)0.0187 (4)0.0061 (4)0.0130 (5)
F50.0297 (5)0.0309 (5)0.0469 (6)0.0096 (4)0.0068 (4)−0.0015 (4)
F60.0364 (5)0.0529 (6)0.0231 (5)0.0173 (5)0.0071 (4)0.0155 (4)
O10.0163 (5)0.0197 (5)0.0242 (5)0.0033 (4)0.0029 (4)0.0078 (4)
O20.0276 (5)0.0359 (6)0.0237 (5)0.0124 (5)−0.0031 (4)0.0064 (5)
N10.0170 (5)0.0196 (5)0.0210 (6)0.0038 (4)0.0015 (4)0.0077 (5)
N20.0205 (6)0.0193 (5)0.0187 (6)0.0046 (4)0.0010 (4)0.0056 (5)
C10.0185 (6)0.0175 (6)0.0194 (6)0.0027 (5)0.0010 (5)0.0080 (5)
C20.0148 (6)0.0200 (6)0.0222 (7)0.0038 (5)0.0017 (5)0.0084 (5)
C30.0180 (6)0.0156 (6)0.0201 (6)0.0038 (5)0.0024 (5)0.0080 (5)
C40.0173 (6)0.0180 (6)0.0217 (6)0.0033 (5)0.0012 (5)0.0099 (5)
C50.0207 (7)0.0246 (7)0.0200 (6)0.0057 (5)0.0014 (5)0.0095 (6)
C60.0204 (7)0.0316 (8)0.0226 (7)0.0046 (6)−0.0022 (5)0.0104 (6)
C70.0160 (6)0.0305 (7)0.0272 (7)0.0072 (5)0.0019 (5)0.0121 (6)
C80.0177 (6)0.0241 (7)0.0230 (7)0.0056 (5)0.0039 (5)0.0102 (6)
C90.0170 (6)0.0180 (6)0.0213 (6)0.0039 (5)0.0014 (5)0.0085 (5)
C100.0167 (6)0.0244 (7)0.0207 (7)0.0039 (5)0.0024 (5)0.0079 (6)
C110.0180 (7)0.0333 (8)0.0274 (7)0.0087 (6)0.0021 (5)0.0087 (6)
C120.0152 (6)0.0201 (6)0.0186 (6)0.0035 (5)0.0005 (5)0.0083 (5)
C130.0184 (6)0.0196 (6)0.0183 (6)0.0035 (5)0.0011 (5)0.0072 (5)
C140.0232 (7)0.0262 (7)0.0223 (7)0.0084 (5)0.0044 (5)0.0060 (6)
C150.0302 (8)0.0278 (8)0.0320 (8)0.0138 (6)0.0027 (6)0.0097 (6)
C160.0277 (7)0.0275 (7)0.0297 (8)0.0109 (6)−0.0002 (6)0.0128 (6)
C170.0256 (7)0.0207 (6)0.0234 (7)0.0050 (5)0.0012 (5)0.0103 (6)
C180.0257 (7)0.0172 (6)0.0227 (7)0.0034 (5)−0.0015 (5)0.0077 (5)
C190.0373 (8)0.0231 (7)0.0206 (7)0.0080 (6)0.0000 (6)0.0077 (6)
O30.0239 (5)0.0236 (5)0.0383 (6)0.0042 (4)−0.0052 (4)0.0085 (5)
C200.0317 (9)0.0300 (8)0.0434 (10)0.0044 (7)−0.0090 (7)0.0087 (7)
Geometric parameters (Å, º) top
F1—C101.3465 (17)C7—H70.9500
F2—C101.3311 (16)C8—C91.4257 (18)
F3—C101.3365 (16)C8—C111.506 (2)
F4—C111.3440 (17)C12—C131.5447 (18)
F5—C111.3376 (18)C12—H121.0000
F6—C111.3372 (19)C13—C171.5330 (19)
O1—C121.4159 (15)C13—H131.0000
O1—H1O0.841 (9)C14—C151.522 (2)
O2—C181.2389 (18)C14—H14A0.9900
N1—C11.3092 (18)C14—H14B0.9900
N1—C91.3676 (17)C15—C161.522 (2)
N2—C181.3489 (18)C15—H15A0.9900
N2—C141.4736 (18)C15—H15B0.9900
N2—C131.4833 (17)C16—C171.527 (2)
C1—C21.4099 (18)C16—H16A0.9900
C1—C101.5155 (19)C16—H16B0.9900
C2—C31.3731 (19)C17—H17A0.9900
C2—H20.9500C17—H17B0.9900
C3—C41.4277 (18)C18—C191.508 (2)
C3—C121.5284 (18)C19—H19A0.9800
C4—C51.4253 (18)C19—H19B0.9800
C4—C91.4233 (19)C19—H19C0.9800
C5—C61.365 (2)O3—C201.417 (2)
C5—H50.9500O3—H3O0.844 (10)
C6—C71.410 (2)C20—H20A0.9800
C6—H60.9500C20—H20B0.9800
C7—C81.369 (2)C20—H20C0.9800
C12—O1—H1O107.1 (13)C3—C12—H12107.9
C1—N1—C9116.47 (12)C13—C12—H12107.9
C18—N2—C14123.62 (12)N2—C13—C17111.09 (11)
C18—N2—C13117.51 (11)N2—C13—C12109.90 (11)
C14—N2—C13118.47 (11)C17—C13—C12115.71 (11)
N1—C1—C2125.94 (12)N2—C13—H13106.5
N1—C1—C10115.30 (12)C17—C13—H13106.5
C2—C1—C10118.58 (12)C12—C13—H13106.5
C3—C2—C1118.68 (12)N2—C14—C15111.64 (12)
C3—C2—H2120.7N2—C14—H14A109.3
C1—C2—H2120.7C15—C14—H14A109.3
C2—C3—C4117.93 (12)N2—C14—H14B109.3
C2—C3—C12120.24 (12)C15—C14—H14B109.3
C4—C3—C12121.76 (12)H14A—C14—H14B108.0
C5—C4—C9118.50 (12)C16—C15—C14110.70 (12)
C5—C4—C3123.12 (12)C16—C15—H15A109.5
C9—C4—C3118.37 (12)C14—C15—H15A109.5
C6—C5—C4120.85 (13)C16—C15—H15B109.5
C6—C5—H5119.6C14—C15—H15B109.5
C4—C5—H5119.6H15A—C15—H15B108.1
C5—C6—C7120.69 (13)C15—C16—C17109.83 (12)
C5—C6—H6119.7C15—C16—H16A109.7
C7—C6—H6119.7C17—C16—H16A109.7
C8—C7—C6120.23 (13)C15—C16—H16B109.7
C8—C7—H7119.9C17—C16—H16B109.7
C6—C7—H7119.9H16A—C16—H16B108.2
C7—C8—C9120.65 (13)C16—C17—C13115.50 (12)
C7—C8—C11119.37 (12)C16—C17—H17A108.4
C9—C8—C11119.98 (12)C13—C17—H17A108.4
N1—C9—C4122.62 (12)C16—C17—H17B108.4
N1—C9—C8118.31 (12)C13—C17—H17B108.4
C4—C9—C8119.07 (12)H17A—C17—H17B107.5
F2—C10—F3107.34 (11)O2—C18—N2120.45 (13)
F2—C10—F1106.85 (11)O2—C18—C19119.45 (13)
F3—C10—F1106.54 (11)N2—C18—C19120.07 (13)
F2—C10—C1112.72 (11)C18—C19—H19A109.5
F3—C10—C1113.03 (11)C18—C19—H19B109.5
F1—C10—C1109.98 (11)H19A—C19—H19B109.5
F6—C11—F5107.04 (13)C18—C19—H19C109.5
F6—C11—F4106.43 (12)H19A—C19—H19C109.5
F5—C11—F4106.05 (12)H19B—C19—H19C109.5
F6—C11—C8112.55 (12)C20—O3—H3O107.1 (15)
F5—C11—C8112.88 (12)O3—C20—H20A109.5
F4—C11—C8111.45 (12)O3—C20—H20B109.5
O1—C12—C3111.69 (10)H20A—C20—H20B109.5
O1—C12—C13109.10 (10)O3—C20—H20C109.5
C3—C12—C13112.24 (11)H20A—C20—H20C109.5
O1—C12—H12107.9H20B—C20—H20C109.5
C9—N1—C1—C20.4 (2)C2—C1—C10—F182.00 (15)
C9—N1—C1—C10175.34 (11)C7—C8—C11—F6114.64 (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—F555.94 (18)
C1—C2—C3—C12176.59 (12)C7—C8—C11—F4−4.8 (2)
C2—C3—C4—C5179.96 (13)C9—C8—C11—F4175.16 (13)
C12—C3—C4—C52.86 (19)C2—C3—C12—O1−16.35 (17)
C2—C3—C4—C90.88 (18)C4—C3—C12—O1160.69 (11)
C12—C3—C4—C9−176.22 (11)C2—C3—C12—C13106.55 (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—C17144.40 (12)
C4—C5—C6—C70.9 (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—C1286.79 (14)
C6—C7—C8—C11179.85 (14)O1—C12—C13—N2−72.10 (13)
C1—N1—C9—C40.01 (19)C3—C12—C13—N2163.56 (10)
C1—N1—C9—C8−179.10 (12)O1—C12—C13—C1754.71 (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—C1549.65 (16)
C3—C4—C9—C8178.48 (12)N2—C14—C15—C16−55.41 (17)
C7—C8—C9—N1179.97 (13)C14—C15—C16—C1756.65 (17)
C11—C8—C9—N10.0 (2)C15—C16—C17—C13−51.98 (16)
C7—C8—C9—C40.8 (2)N2—C13—C17—C1643.46 (16)
C11—C8—C9—C4−179.18 (12)C12—C13—C17—C16−82.74 (15)
N1—C1—C10—F2147.50 (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—F325.55 (17)C14—N2—C18—C197.7 (2)
C2—C1—C10—F3−159.07 (12)C13—N2—C18—C19−179.67 (12)
N1—C1—C10—F1−93.38 (14)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1o···O3i0.84 (2)1.87 (2)2.7121 (18)177 (2)
O3—H3o···O2ii0.85 (2)1.83 (2)2.6667 (17)168 (2)
C7—H7···O1iii0.952.493.3280 (18)147
C17—H17a···F6iv0.992.513.3123 (17)138
Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) x+1, y+1, z; (iii) x−1, y, z; (iv) −x, −y, −z+2.

Experimental details

Crystal data
Chemical formulaC19H18F6N2O2·CH4O
Mr452.40
Crystal system, space groupTriclinic, P1
Temperature (K)120
a, b, c (Å)9.4719 (2), 10.1223 (3), 11.9227 (3)
α, β, γ (°)114.567 (1), 90.343 (2), 102.795 (2)
V (Å3)1007.61 (4)
Z2
Radiation typeMo Kα
µ (mm−1)0.14
Crystal size (mm)0.20 × 0.08 × 0.08
Data collection
DiffractometerNonius KappaCCD
Absorption correctionMulti-scan
(SADABS; Sheldrick, 2007)
Tmin, Tmax0.883, 1.000
No. of measured, independent and
observed [I > 2σ(I)] reflections		20055, 4602, 4038
Rint0.041
(sin θ/λ)max (Å−1)0.650
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.040, 0.110, 1.02
No. of reflections4602
No. of parameters288
No. of restraints2
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)0.37, −0.33

Computer programs: DENZO (Otwinowski & Minor, 1997) and COLLECT (Hooft, 1998), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 1997) and DIAMOND (Brandenburg, 2006), publCIF (Westrip, 2010).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1o···O3i0.840 (15)1.873 (15)2.7121 (18)177 (2)
O3—H3o···O2ii0.845 (16)1.834 (16)2.6667 (17)168 (2)
C7—H7···O1iii0.952.493.3280 (18)147
C17—H17a···F6iv0.992.513.3123 (17)138
Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) x+1, y+1, z; (iii) x−1, y, z; (iv) −x, −y, −z+2.
 

Footnotes

‡Additional correspondence author, e-mail: j.wardell@abdn.ac.uk.

Acknowledgements

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

References

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ISSN: 2056-9890
Volume 67| Part 10| October 2011| Pages o2714-o2715
https://doi.org/10.1107/S1600536811038128
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