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Acta Crystallogr C. Mar 15, 2010; 66(Pt 3): o137–o140.
Published online Feb 24, 2010. doi:  10.1107/S0108270110004026
PMCID: PMC2855570
(E)-N-{[6-Chloro-4-(4-chloro­phen­yl)-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl­ene}benzene-1,2-diamine: a three-dimensional framework structure built from only two hydrogen bonds
Yurina Díaz,a Jairo Quiroga,a Justo Cobo,b and Christopher Glidewellc*
aDepartamento de Química, Universidad de Valle, AA 25360 Cali, Colombia
bDepartamento de Química Inorgánica y Orgánica, Universidad de Jaén, 23071 Jaén, Spain
cSchool of Chemistry, University of St Andrews, Fife KY16 9ST, Scotland
Correspondence e-mail: cg/at/st-andrews.ac.uk
Received February 1, 2010; Accepted February 1, 2010.
Abstract
The mol­ecules of the title compound, C26H19Cl2N5, are conformationally chiral, with none of the aryl groups coplanar with the pyrazolo[3,4-b]pyridine core of the mol­ecule. A single unique N—H(...)N hydrogen bond links the mol­ecules into two symmetry-related sets of C(11) chains running parallel to the [011] and [01An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi1.jpg] directions, respectively, and these two sets of chains are linked into a continuous three-dimensional framework structure by a single unique C—H(...)N hydrogen bond which forms a chain parallel to the [100] direction.
Simple nitro­gen heterocycles, such as pyridines, pyrazoles, pyrimidines or pyrroles, are of inter­est in chemical biology or medicinal chemistry, and also for the preparation of new fused pyrazolo heterocyclic derivatives. We are currently exploring the use of 6-chloro-4-(4-chloro­phen­yl)-3-methyl-1-phenyl-1H- pyrazolo[3,4-b]pyridine-5-carbaldehyde, itself readily pre­pared under Vilsmeier–Haack formyl­ation conditions from 4-(4-chloro­phen­yl)-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazolo[3,4-b]pyridin-6(7H)-one, as a building block for the synthesis of polyannellated heterocyclic systems (Verdecía et al., 1996 [triangle]; Girreser et al., 2004 [triangle]; Quiroga et al., 1998 [triangle], 2005 [triangle]). It was hoped that the reaction of this carbaldehyde with benz­ene-1,2-­diamine would lead to a cyclization, forming a dihydro­pyrazolo[4′,3′:5,6]pyrido[2,3-b][1,5]benzodiazepine system, but instead this reaction led to the formation and isolation of the inter­mediate title compound, (I) (Fig. 1 [triangle]). In the formation of (I), condensation has occurred between the aldehyde function and one of the amino groups in the benz­ene­­diamine reactant (see reaction scheme below), but the cyclization step, involving nucleophilic displacement of the 6-chloro atom on the pyridine ring by the second amino group, has not occurred. We report here the structure of (I), which proves to be of inter­est as the mol­ecules are linked into a single three-dimensional framework structure by the action of just two symmetry-independent hydrogen bonds.
An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-scheme1.jpg Object name is c-66-0o137-scheme1.jpg
Figure 1
Figure 1
The mol­ecular structure of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
The mol­ecular conformation of (I) can be readily defined in terms of five torsion angles (Fig. 1 [triangle] and Table 1 [triangle]), which show that while the Schiff base-type spacer unit comprising atoms C57, N57 and C51 is almost coplanar with the pyrazolopyri­dine unit, the three pendent aryl rings are all markedly rotated out of this plane. The dihedral angles made between the plane of the pyrazolopyridine unit and the planes of the C11–C16, C41–C46 and C51–C56 aryl rings are 21.4 (2), 75.3 (2) and 29.9 (2)°, respectively. It is reasonable to associate the much larger dihedral angle involving ring C41–C46 with the greater steric congestion in the vicinity of this ring. In particular, a small dihedral angle between this ring and the heterocyclic unit is almost certainly prevented by the presence of both the methyl group containing atom C31 and the C—H bond at atom C57 (Fig. 1 [triangle]). Consistent with this idea, the smallest dihedral angle is found for ring C11–C16, where the intra­molecular steric constraints are the least for any of the rings. This conformation means that the mol­ecule of (I) exhibits no inter­nal symmetry and so is conformationally chiral. However, the space group accommodates equal numbers of the two conformational enanti­omers, and the choice of the selected asymmetric unit has no chemical significance. The bond distances (Table 1 [triangle]) in the heterocyclic fragment of the mol­ecule, which show the same pattern as found in similar pyrazolo[3,4-b]pyridines (Low et al., 2002 [triangle], 2007 [triangle]; Abonia et al., 2005 [triangle]; Quiroga et al., 2009 [triangle]), having due regard to the differences between the peripheral substituents, are consistent with the occurrence of aromatic-type electronic delocalization within the pyridine ring and strong bond fixation in the pyrazole ring. Likewise, there is strong bond fixation, as expected, in the spacer unit between the pyridine and the amino­phenyl rings.
Table 1
Table 1
Selected geometric parameters (Å, °)
The mol­ecules of (I) are linked into a continuous three-dimensional framework structure by just two symmetry-independent hydrogen bonds, one each of the N—H(...)N and C—H(...)N types (Table 2 [triangle]), and the formation of the framework structure is readily analysed in terms of two simple one-dimensional substructures, each of which depends on only one type of hydrogen bond. The N—H(...)N hydrogen bond links mol­ecules related by an n-glide plane. Amino atom N52 in the mol­ecule at (x, y, z) acts as hydrogen-bond donor to pyrazole atom N2 in the mol­ecule at (An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi2.jpg − x, An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi2.jpg + y, −An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi2.jpg + z), so linking mol­ecules related by the n-glide plane at x = An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi5.jpg into a C(11) [see Bernstein et al. (1995 [triangle]) for graph-set notation] chain running parallel to the [01An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi1.jpg] direction (Fig. 2 [triangle]). A similar chain is formed by mol­ecules related by the n-glide plane at x = An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi7.jpg, and this second chain is related to the first by the action of the 21 screw axes parallel to [001]. Hence, the chain based on the n-glide plane at x = An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi7.jpg runs parallel to [011] (Fig. 2 [triangle]), so that the structure consists of alternating layers of C(11) chains along [011] and [01An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi1.jpg], stacked in the [100] direction. Within each layer, the chains are related to one another by unit translations along [010] or [001].
Table 2
Table 2
Hydrogen-bond geometry (Å, °)
Figure 2
Figure 2
Part of the crystal structure of (I), showing symmetry-related hydrogen-bonded C(11) chains running parallel to the [011] and [01An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi1.jpg] directions, and linked by the C—H(...)N hydrogen bond. For the sake of clarity, H atoms bonded to C atoms not (more ...)
The second substructure is simpler and consists of just a simple chain. Aryl atom C46 in the mol­ecule at (x, y, z) acts as hydrogen-bond donor to pyridine atom N7 in the mol­ecule at (An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi2.jpg + x, An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi11.jpg − y, z), so forming a C(7) chain running parallel to the [100] direction and containing mol­ecules related by the a-glide plane at y = An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi7.jpg (Fig. 3 [triangle]). Within this chain, adjacent mol­ecules, for example those at (x, y, z) and (An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi2.jpg + x, An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi11.jpg − y, z), are components of C(11) chains along [01An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi1.jpg] and [011], respectively. Hence, the overall action of all the chains parallel to [100] is to link each chain along [01An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi1.jpg] to each chain along [011], so linking all of the mol­ecules into a single three-dimensional framework. There are neither C—H(...)π(arene) nor C—H(...)π(pyridine) hydrogen bonds nor any π–π stack­ing inter­actions in the structure of (I).
Figure 3
Figure 3
Part of the crystal structure of (I), showing a hydrogen-bonded C(7) chain running parallel to the [100] direction, in which alternate mol­ecules lie in C(11) chains along [011] and [01An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi1.jpg]. Hydrogen bonds are shown as dashed lines. For the sake (more ...)
It is of inter­est briefly to compare the crystal structure of (I) reported here with those of some close analogues, compounds (II)–(VI) (see scheme below). The crystallization characteristics of (II)-(VI) differ markedly from those of (I). Firstly, (IV) and (V) both crystallize as stoichiometric monosolvates with dimethyl­formamide (Low et al., 2007 [triangle]). Secondly, unlike (I), which crystallizes in the Sohnke space group Pna21, com­pounds (II)–(VI) all crystallize in the centrosymmetric space groups P An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi1.jpg [for (II) (Low et al., 2002 [triangle]), (III) (Abonia et al., 2005 [triangle]) and (IV) (Low et al., 2007 [triangle])] or C2/c [for (V) (Low et al., 2007 [triangle]) and (VI) (Quiroga et al., 2009 [triangle])]. In addition, the crystal structures of (II)–(VI) all contain C—H(...)π(arene) hydrogen bonds, whereas such inter­actions are absent from the structure of (I).
An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-scheme2.jpg Object name is c-66-0o137-scheme2.jpg
In the structure of (II), there are two independent C—H(...)π(arene) hydrogen bonds, each using a different arene ring as acceptor, and their action is to link the mol­ecules into chains of centrosymmetric rings. These chains are linked into sheets by a π–π stacking inter­action between pairs of pyridine rings, giving a two-dimensional supra­molecular structure. In (III), the supra­molecular structure is one-dimensional and consists of two types of centrosymmetric ring built alternately from pairs of C—H(...)π(arene) hydrogen bonds and pairs of C—H(...)O hydrogen bonds. Symmetry-related pairs of C—H(...)π(arene) hydrogen bonds in the structure of (IV) link pairs of mol­ecules into centrosymmetric dimers, i.e. a finite zero-dimensional hydrogen-bonded structure, while in (V), C—H(...)π(arene) and C—H(...)N hydrogen bonds once again generate a chain in which two types of centrosymmetric ring alternate. Finally, in the structure of (VI), the mol­ecules are linked into rather complex double chains by a combination of N—H(...)N, C—H(...)N and C—H(...)π(arene) hydrogen bonds. Thus, overall, the supra­molecular structures generated by direction-specific inter­actions are zero-dimensional in (IV), one-dimensional in (III), (V) and (VI), two-dimensional in (II) and three-dimensional in (I). However, in terms just of hydrogen bonds, as opposed to π–π stacking inter­actions, the hydrogen-bonded structures in (II), (III), (V) and (VI) are one-dimensional. The sharp contrast between this behaviour and that of (I) can be traced directly to the space group for (I), viz. Pna21, where the combination of two hydrogen bonds connecting mol­ecules related by a glide plane and a screw axis, respectively, generates a three-dimensional array. But this simply raises the question of why (I) crystallizes in the relatively uncommon space group Pna21, representing only ca 1.4% of the entries in the Cambridge Strcutural Database (release 5.31, November 2009; Allen, 2002 [triangle]), rather than P An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi1.jpg (23.0% of entries) or C2/c (8.0% of entries).
Glacial acetic acid (3 drops) was added to a solution of 6-chloro-4-(4-chloro­phen­yl)-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbaldehyde (0.64 mmol) and benzene-1,2-­diamine (0.64 mmol) in ethanol (5 ml) and the mixture was heated under reflux for 1 h. The mixture was then cooled to ambient temperature and the resulting precipitate was collected by filtration, washed with cold ethanol and recrystallized from ethanol to afford yellow crystals of (I) suitable for single-crystal X-ray diffraction (yield 80%, m.p. 474–476 K). MS (EI, 70 eV) m/z (%): 475/473/471 (M +, 2/5/10), 359 (5), 119 (100), 77 (11). Analysis found: C 66.3, H 4.0, N 14.6%; C26H19Cl2N5 requires: C 66.1, H 4.1, N 14.8%.
Crystal data
  • C26H19Cl2N5
  • M r = 472.36
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is c-66-0o137-efi19.jpg
  • a = 10.013 (2) Å
  • b = 12.3487 (12) Å
  • c = 17.666 (4) Å
  • V = 2184.4 (7) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.32 mm−1
  • T = 120 K
  • 0.37 × 0.06 × 0.04 mm
Data collection
  • Bruker–Nonius KappaCCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 2003 [triangle]) T min = 0.899, T max = 0.987
  • 15595 measured reflections
  • 3777 independent reflections
  • 2630 reflections with I > 2σ(I)
  • R int = 0.104
Refinement
  • R[F 2 > 2σ(F 2)] = 0.057
  • wR(F 2) = 0.127
  • S = 1.10
  • 3777 reflections
  • 306 parameters
  • 1 restraint
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.39 e Å−3
  • Δρmin = −0.34 e Å−3
  • Absolute structure: Flack (1983 [triangle]), with 1792 pairs
  • Flack parameter: 0.12 (10)
All H atoms were located in difference maps. H atoms bonded to C atoms were then treated as riding atoms in geometrically idealized positions, with C—H = 0.95 (aromatic and alken­yl) or 0.98 Å (meth­yl), and with U iso(H) = kU eq(C), where k = 1.5 for the methyl group, which was permitted to rotate but not to tilt, and 1.2 for all other H atoms bonded to C atoms. The coordinates of the H atoms bonded to N52 were refined with U iso(H) = 1.2U eq(N), giving N—H distances of 1.00 (6) and 1.02 (6) Å. The correct orientation of the structure with respect to the polar-axis direction was established by means of the Flack x parameter (Flack, 1983 [triangle]), x = 0.12 (10), and the Hooft y parameter (Hooft et al., 2008 [triangle]), y = 0.15 (8), both calculated with 1792 Bijvoet pairs (96.4% coverage).
Data collection: COLLECT (Nonius, 1999 [triangle]); cell refinement: DIRAX/LSQ (Duisenberg et al., 2000 [triangle]); data reduction: EVALCCD (Duisenberg et al., 2003 [triangle]); program(s) used to solve structure: SIR2004 (Burla et al., 2005 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: PLATON (Spek, 2009 [triangle]); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008 [triangle]) and PLATON (Spek, 2009 [triangle]).
Supplementary Material
Crystal structure: contains datablocks global, I. DOI: 10.1107/S0108270110004026/sk3364sup1.cif
Structure factors: contains datablocks I. DOI: 10.1107/S0108270110004026/sk3364Isup2.hkl
Acknowledgments
The authors thank the Servicios Técnicos de Investigación of the Universidad de Jaén and the staff for the data collection. JQ and YD thank COLCIENCIAS and Universidad del Valle for financial support. JC thanks the Consejería de Innovación, Ciencia y Empresa (Junta de Andalucía, Spain), the Universidad de Jaén (project reference UJA_07_16_33) and the Ministerio de Ciencia e Innovación (project reference SAF2008-04685-C02-02) for financial support.
Footnotes
Supplementary data for this paper are available from the IUCr electronic archives (Reference: SK3364). Services for accessing these data are described at the back of the journal.
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