Crystal structure of [4-(2-methoxyphenyl)-3-methyl-1-phenyl-6-trifluoromethyl-1H-pyrazolo[3,4-b]pyridin-5-yl](thiophen-2-yl)methanone

The title compound, C26H18F3N3O2S, a 2-methoxy-substituted derivative, is closely related to its 4-methyl- and 4-chloro-substituted analogues and yet displays no structural relationships with them. The thiophene ring is disorder free and the –CF3 group exhibits disorder, respectively, in contrast and similar to that observed in the 4-methyl- and 4-chloro-substituted derivatives. The torsion angle which defines the twist of the thiophene ring is −69.6 (2)° (gauche) in the title compound, whereas it is anticlinal in the 4-methyl- and 4-chloro-substituted derivatives, with respective values of 99.9 (2) and 99.3 (2)°. The absence of disorder in the thiophene ring facilitates one of its ring C atoms to participate in the lone intermolecular C—H⋯O hydrogen bond present in the crystal, leading to a characteristic C(5) chain graph-set motif linking molecules related through glides along [010]. An intramoleculr C—H⋯N hydrogen bond also occurs.

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT; program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL2013.  (Hardy, 1984;Chu & Lynch, 1975) and established as antimicrobial agents against bacterial and fungal strain (Ali, 2009 (Wilson et al., 2013). An evaluation of the cytotoxic activities of some thiophene derivatives have indicated that they could be considered promising compounds for the discovery of new antitumor agents (Souza et al., 2012). Also, in the background of coumarin dyes being successfully used as organic dye photo-sensitizers for Dye-Sensitized-Solar-Cells (DSSC), the design of new coumarin dyes through the introduction of thiophene moieties have shown to remarkably improve the solar cell performance (Hara et al., 2003).
The title compound, C 26 H 18 F 3 N 3 O 2 S, a 2-methoxy-substituted derivative, is closely related to its 4-methyl and 4-chloro analogues which have been earlier shown to obey the chloro-methyl exchange rule [Rajni Swamy et al., 2013] and yet displays no structural relationships. The title compound may be regarded as an example of a case where change in the nature and position of the substitution may affect intra and inter molecular interactions which in turn might alter the molecular geometry quite noticeably. Fig.1 shows the molecular structure of (I) showing the atom numbering scheme and displacement ellipsoids drawn at the 50% probability level.
The bond lengths and angles are comparable in all the three structures with deviations evident in the torsion angles related to the thiophene group which may be attributed to the absence of disorder in the ring, unlike in the methyl-and chloro-substituted derivatives. The torsion angle C3-C4-C7-C8 which defines the twist of the thiophene ring is -69.6 (2)° [gauche] in the title compound whereas it is anticlinal in 4-methyl and 4-chloro derivatives with respective values of 99.9 (2)° and 99.3 (2)° ( Figure 2). Correspondingly, the orientation of the carbonyl O with respect to the carbon to which the CF 3 group is attached, defined by the torsion angle C5-C4-C7-O1 is -70.8 (3)° in the present compound and 98.6 (2)° and 98.8 (2)°, respectively for 4-chloro and 4-methyl analogues.
The intramolecular distances H13···N3 and H17···N2, on either sides of the phenyl ring, involving the N3 and N2 atoms of the pyrazolo-pyridine rings are 2.416 (1)Å and 2.436 (2) Å respectively. The increased values observed for these distances in 4-methyl and 4-chloro counterparts are 2.483 (1)Å and 2.513( 1)Å which is due to the participation of the phenyl ring (atom C15) in an intermolecular C--H···.O hydrogen bond. The shortening of these distances in the present case is correlated to the non-participation of the phenyl ring in the hydrogen bond, which in turn has caused the associated phenyl and the fused pyrazolo-pyridine ring systems tend towards coplanarity. Thus, a C13-H13···N3 intramolecular hydrogen bond may well be regarded as present. The same argument is invalid for considering C17-H17···N2 as a hydrogen bond since its geometry is more of sterical consequence rather than a hydrogen bonded requirement.
The absence of disorder in the thiophene ring facilitates one of its ring C11 atom to participate in the lone intermolecular C-H···O hydrogen bond present in the crystal. As a consequene, the thiophene ring deviates significantly from being perpendicular to the central fused pyrazolo-pyridine ring. The C11-H11···O1 interaction gives rise to a characteristic C(5) chain graph-set motif [Bernstein et al.,1995] which links molecules related through glides extending along [010] ( Figure 3). Thus, the scheme of non-covalent interactions is entirely different compared to the 4-methyl and 4-chloro analogues and the significant C-H···π interaction observed in them is absent in the present case.

S2. Refinement
The structure displays disorder of the CF 3 group. The disorder was refined with the help of similarity restraints on 1-2 and 1-3 distances and displacement parameters as well as rigid bond restraints (aka Hirshfeld restraints) for anisotropic displacement parameters (Müller, 2009). The first approach to the CF 3 disorder was to refine the CF 3 group as freely rotating about the C5-C25 bond. The thermal ellipsoids of the six fluorine atoms form a circular toroid as expected for a pure rotation about the C-C bond, elongated in a direction approximately perpendicular to the aromatic ring plane to which the CF 3 group binds. The occupancy ratio of the two components was refined freely and converged at 0.956 (3).
All hydrogen atoms except the nitrogen bound hydrogens, were included into the model at geometrically calculated positions (C-H target distance 0.96Å for methyl hydrogen atoms, 0.93Å for all others) and refined using a riding model.
The torsion angle of the methyl groups were allowed to refine. The U iso values of all hydrogen atoms were constrained to 1.2 times U eq (1.5 times for methyl H atoms) of the respective atom to which the hydrogen atom binds.