(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, 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.

The title mefloquine derivative has been crystallized as its 1:1 methanol solvate, C 19 H 18 F 6 N 2 O 2 ÁCH 3 OH. Each of the methinehydroxyl residue [the C-C-C-O torsion angle is À16. 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-HÁ Á ÁO hydrogen bonds, leading to a four-molecule aggregate. These are linked into a supramolecular chain along the a axis via C-HÁ Á ÁO interactions involving the hydroxyl-O atom. The chains assemble into layers that interdigitate along the c axis being connected by C-HÁ Á ÁF interactions.
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). 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 {···OCNC 2 OH···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.

Experimental
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 CH 2 Cl 2 and washed with water (3 x 10 ml). The organic layer was separated, dried over anhydrous MgSO 4 , filtered, and solvent was evaporated under reduced pressure to give the desired product, which was recrystallized from MeOH as colourless blocks. The C-bound H atoms were geometrically placed (C-H = 0.95-1.00 Å) and refined as riding with U iso (H) = 1.2-1.5U eq (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 U iso (H) = 1.5U eq (O). Fig. 1. The molecular structure of (I) showing displacement ellipsoids at the 50% probability level.  Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2σ(F 2 ) is used only for calculating Rfactors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.