Crystal structure and Hirshfeld surface analysis of 3-(hydroxymethyl)-3-methyl-2,6-diphenylpiperidin-4-one

3-(Hydroxymethyl)-3-methyl-2,6-diphenylpiperidin-4-one was synthesized by condensing 4-hydroxy-3-methyl-2-butanone with the benzaldehyde and ammonium acetate. In the crystal, the molecules are linked by O—H⋯O and C—H⋯O hydrogen bonds into double ribbons.


Chemical context
Many piperidine derivatives are found to possess pharmacological activity and are constituents of important drugs. Numerous biological effects including antiviral, antitumor, bactericidal, fungicidal and anti-inflammatory activities have been reported for these compounds (Kappe, 2000;Rameshkumar et al., 2003;Sasitha & John, 2021). In this work, a new protocol for the synthesis of diphenylpiperidin-4-one from 4-hydroxy-3-methyl-2-butanone, benzaldehyde and ammonium acetate under mild reaction conditions was developed. In addition, 3-(hydroxymethyl)-3-methyl-2,6-diphenylpiperidin-4-one was characterized by single crystal X-ray diffraction and studied by Hirshfeld surface analysis.

Structural commentary
The title compound, C 19 H 21 NO 2 , crystallizes in the space group Pna2 1 with one molecule in the asymmetric unit of the ISSN 2056-9890 cell. As shown in Fig. 1, it involves two terminal aromatic rings (C1-C6 and C14-C19) and a central piperidinone fragment (N1/C7-C10/Cl3/O1). The piperidine ring adopts a chair conformation, with the carbonyl O1 and the N-bound H1 atoms being in the equatorial positions. The least-squares basal plane of the piperidine ring (C7, C8, C10, C13) makes dihedral angles of 85.71 (11) and 77.27 (11) , respectively, with the planes of the C1-C6 and C14-C19 aromatic rings.

Supramolecular features
In the crystal, molecules of the title compound are linked by strong O-HÁ Á ÁO and weak C-HÁ Á ÁO hydrogen bonds (Table 1) into double ribbons stretched along the c-axis direction (Fig. 2). Neighbouring molecules in the ribbon are related by the 2 1 screw axis. Besides this, the molecules are connected by N1-H1Á Á ÁC3 contacts into chains along the baxis direction, thus layers perpendicular to the a axis are formed. Noor C-HÁ Á Á interactions are present in this structure.

Figure 2
View of the hydrogen-bonded double ribbon in the title structure showing C8-H8AÁ Á ÁO2 hydrogen bonds as green dashed lines and O2-H2Á Á ÁO1 hydrogen bonds as blue dashed lines.

Figure 3
The red spots on the d norm surface of the title structure represent the O-HÁ Á ÁO and C-HÁ Á ÁO intermolecular interactions.

Synthesis and crystallization
The title compound was prepared ( Fig. 5) according to the procedure reported in the literature for preparation of diphenylpiperidin-4-one (Kim & Tulemisova, 1997). To a mixture of 3.03 g (0.03 mol) of 4-hydroxy-3-methyl-2-butanone and 6.04 g (0.06 mol) of benzaldehyde in glacial acetic acid as a solvent, kept at 293-298 K until the initial keto alcohol disappears as indicated by TLC (1.5 h), 2.3 g (0.03 mol) of ammonium acetate was added. Then the mixture was stirred at the same temperature for 6-7 h. The formed white precipitate was separated and after acidification of the solution with 5% hydrochloric acid to pH 4, the hydrochlorides were converted to bases by neutralization with K 2 CO 3 in a strongly basic reaction. After the extraction with diethyl ether of the by-product base (control of the completeness of extraction by TLC), the title compound was extracted with chloroform. After drying the chloroform extracts and distilling off the solvent, a white crystalline compound was obtained (5.95 g, 70%), readily soluble in chloroform, acetone, and hot ethanol (Fig. 5).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The N-bound H atom was refined freely. The O-bound H atom was located in a difference-Fourier map and refined with O-H = 0.82 Å , and with U iso (H) = 1.5U eq (O). The C-bound H atoms were positioned geometrically (C-H = 0.93, 0.96, 0.97 and 0.98 Å for sp 2hybridized, methyl, methylene and methine C atoms, respectively) and refined using a riding model, with U iso (H) = 1.5U eq (C) and 1.2U eq (C) for methyl and other H atoms, 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.