2-(5,6-Diphenyl-1,2,4-triazin-3-yl)aniline

The title compound, C21H16N4, obtained under standard Suzuki cross-coupling conditions, is a model compound in the synthesis and biological activity evaluation of new aza-analogues of sildenafil containing a pyrazolo[4,3-e][1,2,4]triazine system. An N—H⋯N intramolecular hydrogen bond involving the aminobenzene system and the 1,2,4-triazine moiety helps to establish a near coplanar orientation of the rings with a dihedral angle of 12.04 (4)°, which is believed to be necessary for the biological activity of sildenafil analogues. The 1,2,4-triazine ring is slightly distorted from planarity [r.m.s deviation = 0.0299 (11) Å] and forms dihedral angles of 58.60 (4) and 36.35 (3)° with the pendant phenyl rings. The crystal packing features bifurcated N—H⋯(N,N) hydrogen bonds linking screw-axis-related molecules into chains parallel to the [010] direction and π–π interactions, with a centroid–centroid separation of 3.8722 (7) Å and a slippage of 1.412 (3) Å. The crystal studied was a nonmerohedral twin with a ratio of 0.707 (2):0293 (2).

The title compound, C 21 H 16 N 4 , obtained under standard Suzuki cross-coupling conditions, is a model compound in the synthesis and biological activity evaluation of new azaanalogues of sildenafil containing a pyrazolo [4,3-e][1,2,4]triazine system. An N-HÁ Á ÁN intramolecular hydrogen bond involving the aminobenzene system and the 1,2,4-triazine moiety helps to establish a near coplanar orientation of the rings with a dihedral angle of 12.04 (4) , which is believed to be necessary for the biological activity of sildenafil analogues. The 1,2,4-triazine ring is slightly distorted from planarity [r.m.s deviation = 0.0299 (11) Å ] and forms dihedral angles of 58.60 (4) and 36.35 (3) Table 1 Hydrogen-bond geometry (Å , ). Nowadays, sildenafil citrate (Viagra) is the first orally effective phosphodiesterase type 5 (PDE5) inhibitor available for the treatment of common and important medical problem e.g. male erectile dysfunction (MED) (Terrett et al., 1996). The earlier work on crystal structures of the catalytic domains of PDEs with different inhibitors have revealed two common features of inhibitor binding to PDEs: a planar ring structure of the inhibitor and hydrogen bond iteractions with an invariant glutamine residue (Card et al., 2004). With this in mind we have planned a new series of sildenafil analogues with pyrazolo[4,3-e][1,2,4]triazine system in which triazine ring nitrogen N1 plays a role of C=O group present in pyrimidinone moiety of sildenafil and ethylamino group in the position 2′ of phenyl ring allowed to form intramolecular hydrogen bond between aminophenyl ring and pyrazolotriazine ring system. To clearly define the possibility and the place of intramolecular hydrogen bond formation in the new sildenafil analogues the synthesis and the crystal structure determination of an appropriate model 2-(5,6-diphenyl-1,2,4-triazin-3-yl)aniline, (I), were undertaken.
A search of the Cambridge Structural Database (CSD version 5.33, November 2011;Allen, 2002;Bruno et al., 2002) did not reveal any crystal structures containing the 3-(2-aminophenyl)-1,2,4-triazine structural unit. The structure of the molecule (I) is shown in Fig. 1. One can see that the 3-aminophenyl-1,2,4-triazine system exists in the crystal in the conformation with the torsion angle N2-C3-C31-C32 of -6.86 (17)°. This conformation is forced by the strong N7-H72···N2 intramolecular hydrogen bond (Table 1). The conformation of the 5-and 6-phenyl substituents of the 1,2,4triazine system in relation to the triazine ring described by the torsion angles N4-C5-C51-C52 of -120.48 (13)° and N1-C6-C61-C62 of 35.44 (15)°, respectively, is forced by the steric effect of these bulky groups in adjacent positions of the heterocyclic system. This strong steric interaction causing the appearance of the strains in the triazine ring results in the distortion of its planarity with the displacements of the triazine atoms from the best plane within 0.0299 (11) Å.
In the crystal structure, the screw-related molecules are linked into chains along the [010] direction by bifurcated N7-H71···N1 and N7-H71···N2 intermolecular hydrogen bonds (Fig. 2) and the methine groups C53-H53 of the inversionrelated molecules interact with π-electron system of the aminophenyl ring via C-H···π interaction (Table 1). Moreover, nearly coplanar mutual position of the triazine and aminophenyl rings is stabilized by the π-π interaction of these rings in the crystal structure. The π-electron systems of the pairs of triazine and aminophenyl rings belonging to the translationrelated molecules overlap each other, with centroid-to-centroid separation of 3.8722 (7) Å between the triazine ring at (x, y, z) and aminophenyl ring at (x, -1 + y, z) and aminophenyl ring at (x, y, z) and triazine ring at (x, 1 + y, z). The π-π distances are 3.2886 (4) and 3.6055 (6) Å, respectively, the angle between overlapping planes is 12.13 (6)° and the slippage is 1.412 (3) Å.
In conclusion, the X-ray investigations of molecule (I) confirmed the assumed possibility of forming the N7-H···N2 intramolecular hydrogen bond stabilizing its cis conformation in the crystalline state, analogous to active conformation of sildenafil molecule.
Crystals suitable for X-ray diffraction analysis were grown by slow evaporation of an ethanol solution.

Refinement
The structure of (I) was refined as a nonmerohedral twin using 4591 reflections in the HKLF 5 file format and a BASF parameter of 0.70752 in SHELXL97 (Sheldrick, 2008). All H atoms were located from difference electron-density maps and their coordinates were refined with isotropic displacement parameters taken as 1.5 times those of the respective parent atoms.    167.68, 164.37, 162.95, 155.22, 153.98, 147.70, 135.91, 135.47, 132.71, 130.89, 130.77, 130.71, 129.82, 129.51, 129.36, 128.81, 128.61, 128.55, 117.98. 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq N1 0.18725 (9