4-Methoxy-N-(pyridin-4-ylmethyl)-3-(trifluoromethyl)benzamide monohydrate

In the title compound, C15H13F3N2O2·H2O, the dihedral angle between the benzene and pyridine rings is 74.97 (1)°. The –CF3 group attached to the benzene ring is syn to the C=O bond in the adjacent side chain. In the crystal, molecules are linked to one another through the water molecules by strong N—H⋯O, O—H⋯O and O—H⋯N hydrogen bonds, forming a ladder-type network. The benzamide molecules are also linked to one another through C—H⋯F interactions, forming C(6) chains parallel to the b-axis direction. Aromatic π–π stacking interactions [centroid–centroid separations = 3.7150 (1) and 3.7857 (1) Å] between adjacent pairs of pyridine and benzene rings are also observed, resulting in a three-dimensional architecture are also observed.

In the title compound, C 15 H 13 F 3 N 2 O 2 ÁH 2 O, the dihedral angle between the benzene and pyridine rings is 74.97 (1) . The -CF 3 group attached to the benzene ring is syn to the C O bond in the adjacent side chain. In the crystal, molecules are linked to one another through the water molecules by strong N-HÁ Á ÁO, O-HÁ Á ÁO and O-HÁ Á ÁN hydrogen bonds, forming a ladder-type network. The benzamide molecules are also linked to one another through C-HÁ Á ÁF interactions, forming C(6) chains parallel to the b-axis direction. Aromatic stacking interactions [centroid-centroid separations = 3.7150 (1) and 3.7857 (1) Å ] between adjacent pairs of pyridine and benzene rings are also observed, resulting in a three-dimensional architecture are also observed.

Comment
Amides containing trifluoromethyl substituents have been considered as important pharmacophores ). Amide groups are very common in nature, form easily and provide structural rigidity to molecules (Sreenivasa et al. 2013b). Amides show a broad spectrum of pharmacological properties, including antibacterial ), anti-inflammatory, antioxidant, analgesic and antiviral activity (Manojkumar et al. 2013b, Sreenivasa et al. 2013c. Keeping this in mind, the crystal structure of the title compound was determined. In the title compound, C 15 H 13 F 3 N 2 O 2 ·H 2 O, the dihedral angle between the benzene ring and the pyridine ring is 74.97 (1)°. The -CF 3 group attached to the benzene ring is syn to the C=O bond in the adjacent side chain. Further, the conformation of the N-H bond in the chain is anti with respect to the C=O bond. In the crystal structure, the molecules are linked to one another via water molecules through strong N1-HN1···O3, O3-H2O···O2 and O3-H1O···N2 hydrogen bonds, forming a ladder type network. The benzamide molecules are also linked to one another forming C (6) chains (Bernstein et al., 1995) parallel to the b axis through intermolecular C6-H6···F3 interactions. Further, aromatic π-π stacking interactions [centroid-centroid separations Cg1···Cg1 = 3.7150 (1) Å and Cg2···Cg2 = 3.7857 (1) Å] are also observed in the crystal structure. Cg1 and Cg2 are the centroids of the C11···C13,N2,C14,C15 and C1···C6 rings respectively.

Experimental
3-Tri-fluoromethyl-4-methoxy benzoic acid (1 mmol) and 1,1-carbonyldiimidazole (1.5 mmol) were dissolved in dichloroethane (5 ml) and heated to 45 o C for 30 min. 4-Aminomethyl pyridine (1.5 mmol) was added and the heating was continued for 4 h. The reaction was monitored by TLC. The organic layer was washed with sodium bicarbonate, dried using sodium sulfate and concentrated to yield the crude compound. This was further purified by column chromatography using petroleum ether / ethyl acetate (7:3) as eluent. Fine colorless crystals were grown by slow evaporation of the solvent system: petroleum ether / ethyl acetate (4:1) at room temperature.

Refinement
The hydrogen atoms attached to O3 were located in difference maps and refined in a rigid group. The remaining H atoms were positioned with idealized geometry using a riding model with N-H = 0.86 and C-H = 0.93 -0.97 Å. The isotropic displacement parameters for all H atoms were set to 1.2 times U eq of the parent atom or 1.5 times that of the parent atom for CH 3 .

Figure 4
Aromatic π-π stacking interactions observed in the crystal structure. Special details Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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.