Crystal structures of two new 3-(2-chloroethyl)-r(2),c(6)-diarylpiperidin-4-ones

The syntheses and crystal structures of 3-(2-chloroethyl)-r-2,c-6-diphenylpiperidin-4-one C19H20ClNO and 3-(2-chloroethyl)-r-2,c-6- bis(p-fluorophenyl)piperidin-4-one C19H18ClF2NO are described.


Chemical context
Piperidone molecules exhibit a wide spectrum of biological activities ranging from anti-bacterial to anti-cancer (Parthiban et al., 2005(Parthiban et al., , 2009(Parthiban et al., , 2011. Most of the 2,6-diaryl-substituted piperidones and their derivatives are of significant pharmacological importance (Aridoss et al., 2007). Some novel 3,5dichloro-2,6-diarylpiperidin-4-ones are also reported to possess antimicrobial activity (Bhakiaraj et al., 2014). Piperidones also display analgesic, anti-inflammatory, central nervous system (CNS), local anaesthetic, anticancer and antimicrobial activity (Perumal et al., 2001). In view of the relevance of piperidone derivatives to a variety of ongoing health and pharmalogical issues, we have synthesized the title compounds and report their crystal structures here. Arulraj et al. (2017) has reported the crystal structure of three related 3-chloro-3-methyl-2,6-diarylpiperidin-4-ones. In each of these structures, the piperidine rings adopt chair conformations similar to what we have observed in the title compounds. ISSN 2056-9890
The substituents on the piperidine ring in both (I) and (

Supramolecular features
The crystal packing features very weak N1-H1Á Á ÁO1 hydrogen bonds in (I), forming infinite C(6) chains along the b-axis direction, with the molecules rotating in a 180 spiral motif along the axis (Table 1, Fig. 3). In addition, a weak C-HÁ Á Á interaction between the piperdine ring and a diaryl group in (I) also occurs.

Figure 1
A view of the molecular structure of (I), showing displacement ellipsoids drawn at the 30% probability level.

Figure 3
A partial view along the a axis of the crystal packing for ( acceptor of weak hydrogen bonds involving atom N1 from a piperdine ring in the same plane and with atom C12 from one of the diaryl groups of a molecule in an adjacent plane along the a axis. An unusual weak C1-O1Á Á Á [O1Á Á Á = 3.8263 (19) Å , C1Á Á Á = 4.377 (2) Å , C1-O1Á Á Á = 109 ; x, 1 2 À y, À 1 2 + z; centroid of the C8-C13 ring] interaction also between the piperidine ring and a diaryl group is observed.

Database survey
A search in the Cambridge Crystallographic Database (CSD version 5.38 of Nov, 2016, updates May, 2017Groom et al., 2016) for the 2,6-diphenylpiperidin-4-one skeleton resulted in 229 hits, which was further refined to 50 hits by removing those structures in which the title skeleton substructure was combined with larger molecules. The two most closely related remaining structures based on the pendant arms of the 2,6diphenylpiperidine-4-one central substructure, viz. 2,6diphenyl-3-isopropylpiperidin-4-one (ACEZUD; Nilofar Nissa et al., 2001) and t-3-pentyl-r-2,c-6-diphenylpiperidin-4one (RUGLOV; Gayathri et al., 2009) were then compared with the two reported here. The piperidone ring in compounds (I) and (II) reported here adopt chair or distorted chair conformations, unlike in ACEZUD and RUGLOV. The crystal packing is stabilized by N-HÁ Á ÁO intermolecular hydrogen bonds in both (I) and (II), as well as in ACEZUD. In contrast, the crystal packing in RUGLOV is influenced only by weak C-HÁ Á ÁO and C-HÁ Á Á intermolecular interactions.

Synthesis and crystallization
A mixture of ammonium acetate (0.1 mol, 7.71 g), the respective aldehyde (0.2 mol), benzaldehyde/p-fluorobenzaldehyde (20.4 ml/21.0 ml) and 5-chloro-2-pentanone (0.1 mol, 11.4 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 of concentrated hydrochloric acid. The precipitated hydrochlorides of the 3-(2-chloroethyl)-r-2,c-6-diarylpiperidin-4ones were 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 a distilled ethanol solution: single crystals of (I) and (II) were obtained after two days. The yield of the isolated product was 3.0 g (I) and 2.5 g (II).

Refinement
Crystal data, data collection and structure refinement details are summarized in A partial view along the a axis of the crystal packing for (II), showing infinite chains formed along [001] by weak N1-H1Á Á ÁO1 and C12-H12Á Á ÁO1 hydrogen-bonding interactions. The keto oxygen, O1, forms a weak hydrogen bond with N1 from a piperdine ring in the same plane and with C12 from one of the diaryl groups of a molecule in an adjacent plane along the a axis. H atoms not involved in these interactions have been omitted for clarity. Table 2 Hydrogen-bond geometry (Å , ) for (II). (2) 3.189 (2) 165 (2) molecules were located in a difference-Fourier map and their coordinates and displacement parameters freely refined. All C-bound H atoms were refined using a riding model with d(C-H) = 0.93 Å for aromatic, 0.97 Å for methylene and 0.98 Å for methine H atoms, all with U iso = 1.2U eq (C)

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.