The crystal structure of 3-chloro-2-(4-methylphenyl)-2H-pyrazolo[3,4-b]quinoline

The crystal structure and supramolecular features of 3-chloro-2-(4-methylphenyl)-2H-pyrazolo[3,4-b]quinoline are reported.

In the molecule of 3-chloro-2-(4-methylphenyl)-2H-pyrazolo [3,4-b]quinoline, C 17 H 12 ClN 3 , (I), the dihedral angle between the planes of the pyrazole ring and the methylated phenyl ring is 54.25 (9) . The bond distances in the fused tricyclic system provide evidence for 10-delocalization in the pyrazolopyridine portion of the molecule, with diene character in the fused carbocyclic ring. In the crystal, molecules of (I) are linked by two independent C-HÁ Á ÁN hydrogen bonds, forming sheets containing centrosymmetric R 2 2 (16) and R 6 4 (28) rings, and these sheets are all linked together bystacking interactions with a ring-centroid separation of 3.5891 (9) Å .

Chemical context
Quinoline exhibits antimalarial, anti-bacterial, antifungal, anthelmintic, cardiotonic, anticonvulsant, anti-inflammatory and analgesic activity (Marella et al., 2013). Quinoline and its fused heterocyclic derivatives constitute an important class of compounds for new drug development (Kumar et al., 2009), and the medicinal applications of pyrazolo [3,4-b]quinolines have been summarized, along with an efficient synthetic method (Afghan et al., 2009). Recently, we have reported the synthesis of a number of novel pyrazolo [3,4-b]quinoline derivatives, including that of the title compound (I), and molecular docking studies of their binding affinity to the active sites of human telomerase (Sowmya et al., 2014). In a continuation of that study, we now report the crystal and molecular structure of one such example, the title compound 3-chloro-2p-tolyl-2H-pyrazolo[3,4-b]quinoline, (I).

Structural commentary
Within the molecule of compound (I) (Fig. 1), the pendent phenyl group is twisted out of the plane of the fused heterocyclic ring system, as indicated by the relevant torsional angles (Table 1): the dihedral angle between the mean planes of the pyrazole and the methylated phenyl rings is 54.25 (9) . The molecules of (I) exhibit no internal symmetry and thus they are conformationally chiral: however, the centrosymmetric ISSN 2056-9890 space group accommodates equal numbers of both of the conformational enantiomers. The non-planar character of the molecular skeleton may be plausibly ascribed to the combined effects of the intramolecular non-bonded repulsion between the Cl substituent and the nearest H atom of the methylated phenyl ring, and of the direction-specific intermolecular interactions, in particular the hydrogen bonds.
The bond distances in compound (I) ( Table 1) show some interesting features. Within the pyrazole ring, the bond distances N1-C9A and N2-C3 ( Fig. 1) are identical within experimental uncertainty, although these two bonds are formally double and single bonds, respectively. In the fused carbocyclic ring, the bonds C5-C6 and C7-C8 are much shorted than any other C-C bonds in the molecule. However, in the central pyridine ring, within each of the pairs of corresponding bonds C3A-C4 and C4-C4A, C8A-N9 and N9-C9A, and C3A-C9A and C4A-C8A, the two distances are very similar. These observations taken together are fully consistent with a 10-delocalized system in the pyrazolopyridine portion of the molecule, comparable to those found in naphthalene and azulene (Glidewell & Lloyd, 1984), while the fused carbocyclic ring has more the character of an isolated diene (cf. Glidewell & Lloyd, 1986).

Supramolecular features
The supramolecular assembly in compound (I) is determined by two independent C-HÁ Á ÁN hydrogen bonds (Table 2) and astacking interaction, which together link the molecules into a three-dimensional framework structure. The formation of this framework is readily analysed in terms of three simpler sub-structures (Ferguson et al., 1998a,b;Gregson et al., 2000). In the simplest sub-structure, the C-HÁ Á ÁN hydrogen bond having atom C23 as the donor links an inversion-related pair of molecules, forming a cyclic centrosymmetric dimer characterized by an R 2 2 (16) (Bernstein et al., 1995) motif (Fig. 2), and this dimeric unit can be regarded as the basic building block in the supramolecular assembly. The second C-HÁ Á ÁN hydrogen bond, having atom C26 as the donor, directly links the reference dimer, which is centred at (0, 1 2 , 1 2 ) to four symmetry-related dimers centred at (0, 0, 0), (0 1, 0), (0, 0, 1) and (0, 1, 1), thereby leading to the formation of a hydrogenbonded sheet lying parallel to (100), in which centrosymmetric R 2 2 (16) rings alternate with R 4 6 (28) rings (Fig. 3). Only one hydrogen-bonded sheet passes through each unit cell, but the sheets are linked by thestacking interaction which is associated with the extensive overlap between the tricyclic ring systems of inversion-related pairs of molecules in The molecular structure of compound (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. Table 1 Selected geometric parameters (Å , ).
Cg1 represents the centroid of the C21-C26 ring.

Figure 2
Part of the crystal structure of compound (I) showing the formation of a centrosymmetric hydrogen-bonded dimer. For the sake of clarity, the unit-cell outline and H atoms not involved in the motif shown have been omitted. Atoms marked with an asterisk (*) are at the symmetry position (Àx, 1 À y, 1 À z).
adjacent sheets (Fig. 4). The pyridine rings of the molecules at (x, y, z) and (1 À x, 1 À y, 1 À z), which lie in adjacent sheets, are strictly parallel with an interplanar spacing of 3.3819 (6) Å . The ring-centroid separation is 3.5891 (9) Å , corresponding to a ring-centroid offset of ca 1.202 Å (Fig. 4). The effect of this interaction is to link all of the hydrogen-bonded sheets into a single three-dimensional array.
Despite the large number of aromatic C-H bonds in the molecule of compound (I), the only short C-HÁ Á Á contact involves one of the C-H bonds of the methyl group. Not only are such bonds of low acidity but, perhaps more important, such a methyl group will be undergoing very rapid rotation about the adjacent C-C bond. When a group having local C 3 symmetry, such as a methyl group, is directly bonded to another group having local C 2 symmetry, such as a phenyl group, as in (I), the rotational barrier about the bond between them is very low, generally of the order of J mol À1 rather than the usual kJ mol À1 (Naylor & Wilson, 1957;Tannenbaum et al., 1956). Moreover, it has been shown that simple hydrocarbyl substituents undergo rapid rotation about C-C bonds in the solid state, even at reduced temperatures (Riddell & Rogerson, 1996, 1997. Therefore, while such a C-HÁ Á Á intermolecular interaction may not be regarded as structurally significant, we report it here for completeness (Table 2).

Database survey
Structural information on un-reduced pyrazolo[3,4-b]quinolines carrying a substituent at the N2 position but not at N1, is sparse. In a series of pyrazolo[3,4-b]quinolin-5-ones, each carrying a substituent at N2, the central heterocyclic ring is in reduced form, carrying H atoms at positions 4 and 8 (Cannon et al., 2001a,b,c,d). By contrast, in a series of less highly reduced pyrazolo[3,4-b]quinolin-5-ones which each carry a substituent at N1 but not at N2, the central fused ring is fully A stereoview of part of the crystal structure of compound (I) showing the formation of a hydrogen-bonded sheet lying parallel to (100) and containing alternating R 2 2 (16) and R 4 6 (28) rings. For the sake of clarity, H atoms not involved in the motifs shown have been omitted.

Figure 4
Part of the crystal structure of compound (I) showing the overlap of an inversion-related pair of molecules. For the sake of clarity, the unit-cell outline and all of the H atoms have been omitted. The molecules are viewed normal to the planes of the fused heterocyclic ring system and atoms marked with an asterisk (*) are at the symmetry position (1 À x, 1 À y, 1 À z).

Synthesis and crystallization
A sample of the title compound was prepared using the recently published procedure (Sowmya et al., 2014). Crystals suitable for single-crystal X-ray diffraction were obtained by slow evaporation, at ambient temperature and in the presence of air, of a solution in hexane-ethyl acetate (19:1, v/v).

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.