Crystal structure of [4-(chloromethyl)phenyl](4-hydroxypiperidin-1-yl)methanone

The title compound, C13H16ClNO2, crystallized with two independent molecules in the asymmetric unit (A and B). The piperidinol ring in molecule B is disordered over two positions with a site occupancy ratio of 0.667 (5):0.333 (5). In both molecules these rings have a chair conformation, including the minor component in molecule B. Their mean planes are inclined to the benzene ring by 45.57 (13)° in molecule A, and by 50.5 (4)° for the major component of the piperidine ring in molecule B. In the crystal, the individual molecules are linked by O—H⋯O hydrogen bonds, forming chains of A and B molecules along the [100] direction. The chains are interlinked by C—H⋯O hydrogen bonds, forming ribbons.


S1. Comment
Many piperidine containing compounds possess remarkable biological and medicinal properties (Daly et al., (1986);Fodor et al., (1985)). Among their remarkable properties, they show appreciable effect on plasma glucose level (Campfield et al., (1995)), insulin normalization, therapeutics on cocaine abuse (Kozikowski et al., (1998)). Piperidine also participates in amny local anesthetics, such as mepivacaine, ropivacaine, and bupivacaine, extensively used in clinical practice (Brau et al., (2000); Bolzani et al., (1995)). Piperidine derivatives are found to exhibit pharmacological activity and form a vital part of the molecular structures of important drugs such as raloxifene and minoxidil. Selective inhibition of a number of enzymes has rendered piperidine alkaloids as important paraphernalia in the study of biochemical pathways (Gulluoglu et al., (2007). In the crystal packing the molecules form chains running along the diagonal of ′bc′ plane through O-H···O type hydrogen bonds. These chains are further inter linked through C-H···O type hydrogen bonds to form molecular ribbons ( Fig. 2).

S2. Experimental
The title compound was synthesized following a publish procedure ). In a 250 ml roundbottomed flask 120 ml of ethylmethylketone 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. Then 4-chloromethyl benzoylchloride(0.04 mol) was added and the reaction mixture was stirred at room temperature for ca 2 h. A white precipitate of triethylammoniumchloride was formed. It was filtered and the filtrate was evaporated to give the crude product. It was recrystallized twice from ethylmethylketone (yield: 82%) giving colourless block-like crystals of the title compound.
supporting information

S3. Refinement
H atoms were positioned geometrically and treated as riding on their parent atoms and refined with, C-H distance of 0.93-0.98 Å, O-H distance of 0.82 Å with U iso (H)= 1.5 U eq (c-methyl),U iso (H)= 1.5 U eq (O) and U iso (H)= 1.2Ueq(C) for other H atom. The piperidinol ring in one of the molecules is disordered over two positions with site occupancies in the ratio 67:33. The disorder was resolved by successive Fourier electron density maps and least squares refinements. Sum of the occupancies of the disordered components were restrained as 1 during refinement. The bond distances in the disordered groups were restrained using SADI or DFIX with an effective standard deviation of 0.01 Å and 0.02 Å respectively, wherever necessary. Rigid group restraint(RIGU) with e.s.d.'s 0.002 Å and 0.004 Å was also applied to get satisfactory model of the disorder.

Figure 1
The molecular structure of the title compound (left: molecula A; right: molecule B), with displacement ellipsoids drawn at the 30% probability level.

Figure 2
The packing of the molecules in the crystal structure. The dashed lines indicate the hydrogen bonds.