(±)-3-Benzyloxy-1-(4-methoxybenzyl)piperidine-2-thione

The title molecule, C20H23NO2S, adopts a twisted conformation in which the two aromatic rings connected to the central piperidine ring are orientated trans to each other. An intramolecular C—H⋯S contact occurs. In the crystal, C—H⋯π and C—H⋯O interactions act to stabilize the structure in three dimensions.

The title molecule, C 20 H 23 NO 2 S, adopts a twisted conformation in which the two aromatic rings connected to the central piperidine ring are orientated trans to each other. An intramolecular C-HÁ Á ÁS contact occurs. In the crystal, C-HÁ Á Á and C-HÁ Á ÁO interactions act to stabilize the structure in three dimensions.

Related literature
For the use of related piperidinethiones in the synthesis of febrifugine analogues, see: Michael et al. (2006). For information on the biological activity of febrifugine, see: Murata et al. (1998).  Table 1 Hydrogen-bond geometry (Å , ).

Comment
The title piperidinethione was prepared as an intermediate for the total synthesis of febrifugine, a quinazoline alkaloid with potent antimalarial activity (Murata et al., 1998). Related thiolactam intermediates have been used in the synthesis of febrifugine analogues in ongoing investigations in our laboratories (Michael et al., 2006). It should be noted that, although an optically pure lactam was used in the synthesis of the title compound, racemization took place during the replacement of oxygen by sulfur with Lawesson's reagent.
The title organic compound ( Fig. 1) crystallizes in the space group Pbca. The molecule adopts a twisted conformation in which the two aromatic rings connected to the piperidine ring are orientated trans to each other. The aromatic rings are also rotated with respect to each other such that the angle between least squares planes defined by the two rings is 59.04 (6)°. The most significant weak interactions in this structure are listed in Table 1. Two C-H···π interactions involving the ring defined by C16-C21 are present in the structure while no such interactions exist for the aromatic ring defined by C8-C13. These two C-H···π interactions act to bring three molecules together which interact further through the C-H···O interaction as shown in Fig. 2. No significant π···π interactions are present in the structure.

Refinement
All H atoms attached to carbon were positioned geometrically, and allowed to ride on their parent atoms, with C-H bond lengths of 0.95 Å (CH), 0.99 Å (CH 2 ) or 0.98 Å (CH 3 ), and isotropic displacement parameters set to 1.2 (CH and CH 2 ) or 1.5 times (CH 3 ) the U eq of the parent atom.  The molecular structure of (I), showing the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.

Figure 2
C-H···π and C-H···O interactions in the structure of (I). Only the aromatic ring defined by C16-C21 is involved in C -H···π interactions but these act to bring three molecules together.

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