Crystal structure of (4-hydroxypiperidin-1-yl)(4-methylphenyl)methanone

In the title compound, C13H17NO2, the dihedral angle between the planes of the piperidine and benzene rings is 51.7 (2)°. The bond-angle sum around the N atom [359.8 (3)°] indicates sp 2 hybridization of the atom. In the crystal, O—H⋯O hydrogen bonds link the molecules, forming chains along [001].


S1. Comment
The piperidine ring is one of the most recognizable structural entities among heterocyclic molecules (Katritzky, 1995). A piperidine series of gamma-secretase inhibitors have been evaluated for treatment of Alzheimer's disease (AD) (Pissamitski et al., 2007). Some piperidines were found to possess high profile biological activities, including cytotoxic and anticancer properties (Dimmock et al., 2001). The piperidine ring is a feature of oral anaesthetics and narcotic analgesics (Watson et al., 2000); Thomas et al., 1998). Piperidine derivatives are used clinically to prevent post-operative vomiting, to speed up gastric emptying before anaesthesia, to facilitate radiological investigations and to correct a variety of disturbances of gastrointestinal functions (Sambath et al., 2004).

S2. Experimental
The title compound was synthesized using a published procedure . In a 250 ml round-bottomed flask, 120 mL of ethyl methyl ketone was added to 4-hydroxypiperdine (0.02 mol) and stirred at room temperature. After 5 min, triethylamine (0.04 mol) was added and the mixture was stirred for 15 min. 4-Methyl benzoyl chloride (0.04 mol) was then added and the reaction mixture was stirred at room temperature for ca. 2 h. A white precipitate of triethylammonium chloride was formed, which was removed by filtration and the filtrate was evaporated to give the crude product. This was recrystallized twice from ethyl methyl ketone giving colourless block-like crystals of the title compound (yield: 82%).  (Flack, 1983), although not of particular relevance but meaningless in this structure, was determined as 0(3) for 1610 Friedel pairs.

Figure 1
The molecular structure and atom numbering scheme for the title compound, with displacement ellipsoids drawn at the 30% probability level.

Figure 2
The crystal packing in the unit cell viewed along b. The dashed lines indicate hydrogen bonds.
(4-Hydroxypiperidin-1-yl)(4-methylphenyl)methanone where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.28 e Å −3 Δρ min = −0.22 e Å −3 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. 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 > 2sigma(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.