1-Benzyl-3,5-bis(2-thienylmethylene)-4-piperidone

In the title compound, C22H19NOS2, the thiophene rings form angles of 69.74 (18) and 65.56 (16)° with the benzene ring. The piperidone ring adopts a half-chair conformation due to the presence of the conjugated ketone systems. Both thiophene rings are disordered over two orientations [occupancies of 0.758 (2)/0.242 (2) and 0.588 (2)/0.412 (2)] at 180° from one another. In the crystal, weak intermolecular C—H⋯O hydrogen bonds, C—H⋯π and aromatic π–π stacking interactions [shortest centroid–centroid separation = 3.865 (3) Å] help to stabilize the packing.


S1. Comment
At present, a series of 3,5-bis(arylidene)-4-piperidone derivatives have been synthesized and proved to display cytotoxic and anticancer properties (El-Subbagh, et al. 2000;Dimmock, et al. 2003). These compounds possess marked affinities for thiols but with little or no affinities for amino or hydroxyl groups found in nucleic acids (Baluja, et al. 1964;Dimmock, et al. 1983). Thus development of these compounds as candidate cytotoxics may lead to the obtention od drugs which lack the undesirable genotoxic properties present in various antineoplastic agents (Benvenuto et al. 1993).
Here, we report the title compound (I), which is a combination of cyclic α, β-unsaturated ketone (chalcone) and β-amino ketone, which could be used as a basic unit to prepare antineoplastic compounds.
The molecular structure of the title compound (I) is shown in Fig. 1. The thiophene rings determine angles of 69.74 (18)° and 65.56 (16)° with the benzene ring. The piperidone ring adopts a half-chair conformation due to the presence of conjugated ketone systems,and both of the thiophene rings were found disordered over two orientations, respectively. In the crystal, weak intermolecular C-H···O hydrogen bonds and aromatic π-π stacking interactions [shortest centroid-centroid separation = 3.865 (3) Å] help stabilizing the packing.

S2. Experimental
The title compound was synthesized according to the literature (Pati et al. 2009). Dry hydrogen chloride was continuously bubbled into a solution of N-benzyl-4-piperidone (0.01 mol) and 2-thieneylaldehyde (0.02 mol) in acetic acid (25 ml) at room temperature. Then the mixture was stirred at room temperature for 8 h., when the precipitate obtained was collected and washed with acetone (20 ml) and added to an aqueous potassium carbonate solution (5%, w/v). The desired product was obtained after the solid was crystallized in a mixture of ethanol and chloroform (1:1, V/V), in a yield of 75.6%. Suitable crystals for X-ray analysis were obtained by slow evaporation of the solution of title compound in a mixture of chloroform and methanol.

S3. Refinement
All H atoms were positioned geometrically and refined in the riding model approximation with C-H = 0.95 and 0.99 Å.

Figure 2
The packing diagram of (I). Dashed lines indicate C-H···O hydrogen bonds.

1-Benzyl-3,5-bis(2-thienylmethylene)-4-piperidone
where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.002 Δρ max = 0.33 e Å −3 Δρ min = −0.23 e Å −3 Extinction correction: SHELXL97 (Sheldrick, 2008), Fc * =kFc[1+0.001xFc 2 λ 3 /sin(2θ)] -1/4 Extinction coefficient: 0.062 (7) 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.