Crystal structure of 2,6-bis(2,5-dimethoxyphenyl)-3,5-dimethylpiperidin-4-one

In the title molecule, C23H29NO5, the central piperidine ring has a chair conformation. The planes of the two benzene rings are inclined each to other at 61.7 (1)°. The crystal packing exhibits no directional interactions only van der Waals contacts.


S1. Comment
The piperidin-4-one pharmacophore is responsible for numerous biological actions such as antibacterial, antimycobacterial, antifungal, anticancer, antioxidant, antiinflammatory, neuronal nicotinistinic, and CNS stimulant and depressant. Its activity is further increased by the incorporation of aryl groups on both sides of the hetero atom along with/without the introduction of functionalities on the hetero atom itself. Interestingly, the amino group of the piperidone that is flanked by aryl groups are responsible not only for the increment in activity, but also in suppressing the toxicity (Sahu et al. 2013;Parthiban et al. 2011). Generally, the piperidin-4-one moiety exists in different stereochemistries upon the modifications in their structure. Since the stereochemistry of the molecule is an important key for its biological response, it is of curious to explore the stereochemistry. Hence the present study is caried out to explore the stereochemistry of the title compound (I) (Fig. 1).
The crystallographic parameters viz., torsion angles, asymmetry parameters and ring puckering parameters calculated for (I) show that the piperidone ring adopts a chair conformation. According to Cremer & Pople and Nardelli, the total puckering amplitude, Q T is 0.5875 (8) Å, the phase angle θ is 0.94 (8)° and phi is 34 (4)°. The smallest displacement asymmetry parameters q 2 and q 3 are 0.0114 (8) and -0.5874 Å, respectively. On the whole, the complete crystallographic analysis of the title compound, C 23 H 29 NO 5 , exhibits a chair conformation with equatorial orientations of all the aryl and alkyl substituents.

S2. Experimental
The 2,6-bis(2,5-dimethoxyphenyl)-3,5-dimethylpiperidin-4-one was synthesized by a modified and an optimized Mannich condensation in one-pot, using 2,5-dimethoxybenzaldehyde (0.1 mol, 16.618 g), 2-pentanone (0.05 mol) and ammonium acetate (0.075 mol, 5.78 g) in a 50 ml of absolute ethanol (Parthiban et al., 2011). The mixture was gently warmed on a hot plate at 303-308 K (30-35° C) with moderate stirring till the complete consumption of the starting materials, which was monitored by TLC. At the end, the crude azabicyclic ketone was separated by filtration and gently washed with 1:5 cold ethanol-ether mixture. X-ray diffraction quality crystals of the title compound were obtained by slow evaporation from ethanol.

S3. Refinement
All hydrogen atoms were fixed geometrically and allowed to ride on the parent carbon atoms with aromatic C-H = 0.93 Å, aliphatic C-H = 0.98 Å, methylene C-H = 0.97 Å. The displacement parameters were set for phenyl, methylene and supporting information aliphatic H atoms at U iso (H) = 1.2U eq (C), methyl H atoms at U iso (H) = 1.5U eq (C) and the hydrogen atoms were fixed geometrically and allowed to ride on the parent nitrogen atom with N-H = 0.86 Å and the displacement parameter was set at U iso (H)= 1.2U eq (N).

Figure 1
View of (I) showing the atomic numbering and 30% probability displacement ellipsoids.