2-[(Adamantan-1-yl)aminomethyl]-4-chlorophenol hemihydrate

In the title compound, C17H22ClNO·0.5H2O, the water molecule O atom resides on a twofold rotation axis. In the organic molecule, the phenol group forms an intramolecular O—H⋯N hydrogen bond. In the crystal, pairs of organic molecules are hydrogen bonded through bridging solvent water molecules, forming chains along the b-axis direction.


2-[(Adamantan-1-yl)aminomethyl]-4-chlorophenol hemihydrate
Xu-Dong Jin, Xue-Yue Yin, Lu-Sha Xu, Chun-Hua Ge and Xiao-Hong Chang Comment Amantadine and its derivatives attract interest because of their biological activity and many potential applications (Camps et al., 2008). As an extension of our previous work on the compounds containing an adamantane group, we synthesized the title compound by reduction of the corresponding Schiff base. It crystallizes with solvent water. Asymmetric unit contains one molecule of the title compound and one half of solvent water (Fig. 1). In the organic molecule, all bond lengths and angles are normal and comparable with another reported compound, N-(2-Hydroxybenzyl)adamantan-1amine (Wang et al., 2012). The hydroxyl O atom is involved in hydrogen bond (Table 1) with amino N atom with the OH···N distance of 2.611 (5) Å. This intra-molecular hydrogen bond formally results in a chiral center at the nitrogen atom, but the centrosymmetric crystal represents a racemate. The intramolecular hydrogen bond forms a R 2 1 (6) ring which stabilizes the molecular conformation (Table 1)

Experimental
Amantadine hydrochloride (0.376 g, 2.0 mmol) and KOH (0.112 g, 2.0 mmol) were stirred in 10 ml of anhydrous alcohol for 2 h. The produced white precipitate was filtered out and the transparent filtrate was added dropwise to 5-chloro-2-hydroxybenzaldehyde (0.312 g, 2.0 mmol) in 10 ml of anhydrous alcohol under constant stirring. The resulting solution was refluxed for ca. 3 h, concentrated to about 5 ml through reduced pressure distillation and then left at room temperature. A yellow Schiff base precipitate was obtained after one week under slow solvent evaporation. NaBH 4 (0.303 g, 8 mmol) was added into solution of the Schiff base (0.580 g, 2 mmol) in anhydrous methanol (10 ml).
After 1 h stirring, a light-yellow solid, 4-chloro-2-((adamantan-1-ylamino)methyl)phenol was filtered and dried. A crystal of the title compound suitable for X-ray analysis has developed from a solution in H 2 O/EtOH mixture (1:2 v/v) after 5 days of slow solvent evaporation.

Refinement
The C-bound H atoms were positioned geometrically with C-H = 0.93-0.98 Å, and treated as riding with U iso (H) = 1.2 U eq (C). H atoms bonded to N and O atoms were located in difference Fourier series and refined isotropically.  Molecular structure of the title compound with displacement ellipsoids drawn at 30% probability level.

Figure 2
Packing diagram showing the H-bonded chains parallel to b axis. H atoms are omitted for clarity. 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.