Crystal structure of 4-bromo-2-[(E)-N-(2,2,6,6-tetramethylpiperidin-4-yl)carboximidoyl]phenol dihydrate

In the title hydrate, C16H23BrN2O·2H2O, the organic molecule features a strong intramolecular O—H⋯N hydrogen bond. The piperidine ring, in addition, adopts a chair conformation with the exocyclic C—N bond in an equatorial orientation. The water molecules of crystallization are disordered (each over two sets of sites with half occupancy. In the crystal, they associate into corrugated (100) sheets of (H2O)4 tetramers linked by O—H⋯O hydrogen bonds. The organic molecules, in turn, are arranged at both sides of these sheets, linked by water–piperidine O—H⋯N hydrogen bonds.


S1. Comment
Piperidine-bearing compounds have diverse applications in commercial and medicinal fields. The piperidine nucleus is an ubiquitous structural feature of biologically active compounds and numerous secondary metabolites, for example (S)pipecolic acid a non-proteinogenic amino acid associated with epilepsy (Sánchez-Sancho & Herrandón, 1998;Nithiya et al., 2011;Adger et al., 1996). Moreover, piperidine-containing compounds were evaluated for their effect on plasma glucose level (Kozikowski et al., 1998), insulin normalization and treatment of cocaine abuse (Brau et al., 2000). In this vein and following our strategy for synthesis of bio-active heterocyclic compounds, we report the synthesis and crystal structure of the title compound.
The conformation of the title molecule is determined in part by the strong O1-H1a···N1 hydrogen bond. The substituted piperidine ring adopts a chair conformation with puckering parameters Q = 0.503 (2) Å, θ = 12.0 (2) Å and φ = 176 (1)°. In the crystal, hydrogen bonding between the lattice water molecules generates corrugated layers approximately parallel to (100) with the piperidine nitrogen atoms (N2) hydrogen bonded to both sides (Table 1 and

S2. Experimental
A mixture of 1 mmol (156 mg) of 2,2,6,6-tetramethylpiperidin-4-amine and 1 mmol (201 mg) of 5-bromo-2-hydroxybenzaldehyde in 30 ml ethanol was heated under reflux for 5 h. The solid product was obtained on cooling, filtered off, dried under vacuum and recrystallized from ethanol to afford pale yellow columns which were suitable for X-ray diffraction. Mp. 361 K.

S3. Refinement
H-atoms attached to carbon were placed in calculated positions (C-H = 0.95 -0.98 Å) while those attached to nitrogen and oxygen were placed in locations derived from a difference map and their parameters adjusted to give N-H = 0.91 Å and O-H = 0.84 Å. All were included as riding contributions with isotropic displacement parameters 1.2 -1.5 times those of the attached atoms. Each lattice water molecule is disordered over two sites with the oxygen and one hydrogen in common. Based on peak heights for the disordered H atoms, the two sites for these atoms were judged to be equally occupied.

Figure 1
The the asymmetric unit showing the intra-and intermolecular O-H···N hydrogen bonds as dotted lines. Only one set of the disordered hydrogen atoms is shown.

Figure 2
Packing viewed down the b axis with intermolecular O-H···N and O-H···O hydrogen bonds shown, respectively, as purple and red dotted lines. Only one set of the disordered hydrogen atoms is shown.

Figure 3
A portion of the layer of lattice water molecules. Only one set of the disordered hydrogen atoms is shown.  Special details Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 > σ(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. H-atoms attached to carbon were placed in calculated positions (C-H = 0.95 -0.98 Å) while those attached to nitrogen and oxygen were placed in locations derived from a difference map and their parameters adjusted to give N-H = 0.91 Å and O-H = 0.84 Å. All were included as riding contributions with isotropic displacement parameters 1.2 -1.5 times those of the attached atoms. Each lattice water molecule is disordered over two sites with the oxygen and one hydrogen in common. Based on peak heights for the disordered H atoms, the two sites for these atoms were judged to be equally occupied.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq Occ. (