Crystal structures of three 3-chloro-3-methyl-2,6-diarylpiperidin-4-ones

The syntheses and crystal structures of 3-chloro-3-methyl-r-2,c-6-diphenylpiperidin-4-one and two of its derivatives are described. In each structure, the piperidine ring adopts a chair conformation. In the crystals, molecules are linked into C(6) chains by weak N—H⋯O hydrogen bonds and C—H⋯π interactions are also observed.


Chemical context
The piperidine ring is a ubiquitous structural feature of many alkaloid natural products and drug candidates: Watson et al. (2000) asserted that during a recent 10-year period there were thousands of piperidine compounds mentioned in clinical and preclinical studies. Piperidin-4-ones are reported to possess analgesic, anti-inflammatory, central nervous system (CNS), local anaesthetic, anticancer and antimicrobial activities (Perumal et al., 2001;Dimmock et al., 2001). As part of our ongoing structural studies of piperidin-4-ones (Arulraj et al., 2016), the syntheses and crystal structures of three 3-chloro-3methyl-2,6-diarylpiperidin-4-ones are now reported. ISSN 2056-9890

Structural commentary
The title compound containing the 2,6-diaryl-piperidin-4-one moiety, C 18 H 18 NOCl, (I), crystallizes in the triclinic space group P1 ( owing to the repulsion from a nearby oxygen atom. The phenyl rings bonded to the piperidine moiety occupy equatorial positions in all three compounds: the dihedral angles between the mean planes of the phenyl rings are 58.4 (2), 73.5 (5) and 78.6 (2) in (I), (II) and (III), respectively. The increase in the dihedral angles between the phenyl rings from (I) to (III) might be attributed to the steric repulsion resulting from the substituents on the phenyl rings. The sum of bond angles around N1 in each structure [333.1 (I), 332.0 (II), 337.3 (III)] is consistent with sp 3 hybridization (Beddoes et al., 1986). A view of the molecular structure of (I), showing displacement ellipsoids drawn at the 30% probability level.

Figure 2
A view of the molecular structure of (II), showing displacement ellipsoids drawn at the 30% probability level.

Figure 3
A view of the molecular structure of (III), showing displacement ellipsoids drawn at the 30% probability level. Table 1 Hydrogen-bond geometry (Å , ) for (I).

Supramolecular features
For each structure, the crystal packing is influenced by weak N1-H1Á Á ÁO1 hydrogen bonds, forming infinite chains along the a axis direction (Figs. 4,5 and 6). In (III), additional weak C10-H10Á Á ÁO1 interactions are observed. Weak C-HÁ Á Á interactions are observed in all three compounds (Tables 1, 2 and 3). In all three compounds,interactions must be extremely weak, with centroid-centroid separations greater than 4 Å .

Synthesis and crystallization
A mixture of ammonium acetate (0.1 mol, 7.71 g), the respective aldehyde (0.2 mol) (benzaldehyde/p-methylbenzaldehyde/p-chlorobenzaldehyde, 20.4 ml, 24.0 g and 28.1 ml) and 3-chloro-2-butanone (0.1 mol, 10.1 ml) in distilled ethanol was heated first to boiling. After cooling, the viscous liquid obtained was dissolved in diethyl ether (200 ml) and shaken with 100 ml concentrated hydrochloric acid. The precipitated hydrochloride of the 3-chloro, 3-methyl-r(6),c(6)diarylpiperidin-4-one was removed by filtration and washed first with a 40 ml mixture of ethanol and diethyl ether (1:1) and then with diethyl ether to remove most of the coloured impurities. The base was liberated from an alcoholic solution by adding aqueous ammonia and then diluted with water. Each compound was recrystallized twice from distilled ethanol solution: single crystals of (I), (II) and (III) were obtained after two days.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 4   located in a difference map and refined isotropically. Isotropic displacement parameters for all these atoms in (I), (II) and (III) were set to 1.2 (CH, CH 2 ) or 1.5 (CH 3 ) times U eq of the parent atom. Idealized methyl groups were refined as rotating groups. The refinement for (III) showed some parameter oscillation, and convergence was achieved with the use of a DAMP card. used to refine structure: SHELXL (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).  Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

(I) 3-Chloro-3-methyl-r-2,c-6-diphenylpiperidin-4-one
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 ) x y z U iso */U eq Cl1 0.84481 (9) 0.47065 (6) Hydrogen-bond geometry (Å, º) Cg2 and Cg3 are the centroids of the C6-C11 and C12-C17 rings, respectively.   Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.  (14) Geometric parameters (Å, º)