A π-stacked chain of hydrogen-bonded dimers in 3-tert-butyl-1-(4-chloro- phen-yl)-4-phenyl-indeno-[1,2-b]pyrazolo-[4,3-e]pyridin-5(1H)-one and a π-stacked sheet of hydrogen-bonded chains in 3-tert-butyl-1-(4-chloro-phen- yl)-4-(4-meth-oxy-phen-yl)indeno-[

Article abstract of DOI:10.1107/S0108270111045082

In 3-tert-butyl-1-(4-chloro-phen-yl)-4-phenyl-indeno-[1,2-b]pyra-zolo-[4,3- e]pyridin-5(1H)-one, C₂₉H₂₂ClN₃O, (I), inversion-related pairs of mol-ecules are linked by C - H...O hydrogen bonds to form R ²₂

Full text of DOI:10.1107/S0108270111045082

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
fused ring systems, we report here the structure of 3-tert-butyl-
1-(4-chlorophenyl)-4-phenylindeno[1,2-b]pyrazolo[4,3-e]pyri-
din-5(1H)-one, (I), and the 4-(4-methoxyphenyl) derivative,
(II) (Figs. 1 and 2), which were prepared in good yield by
means of a tricomponent reaction between indan-1,3-dione,
the corresponding substituted benzaldehyde and 5-amino-
3-tert-butyl-1-(4-chlorophenyl)-1H-pyrazole (see Scheme),
which was induced by smooth microwave irradiation using
water as solvent and triethylamine as catalyst.
ISSN 0108-2701
A p-stacked chain of hydrogen-bonded
dimers in 3-tert-butyl-1-(4-chloro-
phenyl)-4-phenylindeno[1,2-b]-
pyrazolo[4,3-e]pyridin-5(1H)-one and
a p-stacked sheet of hydrogen-bonded
chains in 3-tert-butyl-1-(4-chloro-
phenyl)-4-(4-methoxyphenyl)-
indeno[1,2-b]pyrazolo[4,3-e]pyridin-
5(1H)-one
Jaime Portilla,a Carolina Lizarazo,a Justo Cobob and
Christopher Glidewellc*
a
´
´
´
Grupo de Investigacion en Compuestos Bio-organicos, Departamento de Quımica,
´
Universidad de los Andes, Cra. 1E No. 18A-10, Edificio H, A.A. 4976, Bogota D.C.,
b
´
´
´
´
Colombia, Departamento de Quımica Inorganica y Organica, Universidad de Jaen,
23071 Jaen, Spain, and cSchool of Chemistry, University of St Andrews, Fife
´
KY16 9ST, Scotland
Correspondence e-mail: cg@st-andrews.ac.uk
Received 24 October 2011
Accepted 27 October 2011
Online 5 November 2011
In 3-tert-butyl-1-(4-chlorophenyl)-4-phenylindeno[1,2-b]pyra-
zolo[4,3-e]pyridin-5(1H)-one, C29H22ClN3O, (I), inversion-
related pairs of molecules are linked by C—Hꢀ ꢀ ꢀO hydrogen
bonds to form R22(18) dimers, which are themselves linked into
a chain by a ꢀ–ꢀ stacking interaction between inversion-
related pairs of molecules. In 3-tert-butyl-1-(4-chlorophenyl)-
4-(4-methoxyphenyl)indeno[1,2-b]pyrazolo[4,3-e]pyridin-5(1H)-
one, C30H24ClN3O2, (II), which crystallizes in the space group
P1, with Z0 = 2 and with different orientations for the methoxy
groups in the two independent molecules, a combination of
C—Hꢀ ꢀ ꢀO and C—Hꢀ ꢀ ꢀꢀ(arene) hydrogen bonds links the
molecules into chains of rings, which are further linked into
sheets by a ꢀ–ꢀ stacking interaction.
Compounds (I) and (II) both crystallize in the space group
P1, but with Z0 values of 1 and 2, respectively (Figs. 1 and 2); in
(II) it will be convenient to refer to the molecules having x = 1
and 2 as type 1 and type 2 molecules, respectively. For each of
the independent molecules, the conformations can be defined
in terms of the orientations of the tert-butyl group and of the
two pendent aryl substituents relative to the fused ring system,
along with the orientation of the methoxy groups in (II).
None of the molecules exhibits any internal symmetry and
hence they are all conformationally chiral; however, in each
compound the centrosymmetric space group accommodates
equal numbers of both conformational enantiomers. In each of
the independent molecules, the fused ring system is essentially
planar. In compound (I), the maximum deviations from the
Comment
Pyrazolo[3,4-b]pyridines are fused heterocyclic compounds of
considerable interest for drug development because of the
wide range of biological activities that they exhibit (Quiroga et
al., 2005, 2007). Independently, indenopyridine compounds
have shown potential activity as antioxidant, antihistamine
and antidepressant agents (de Almeida et al., 1976; Strunz &
Findlay, 1985; Earl et al., 1998; Padwa et al., 2000; Peters et al.,
2004; Evdokimov et al., 2011). As part of a programme to
prepare new heterocyclic derivatives combining both these
˚
mean plane through the fused ring system are 0.060 (2) A for
˚
atom C3 and 0.045 (2) A for atom C5A, displaced to opposite
sides of the plane; for the type 1 molecule in compound (II),
Acta Cryst. (2011). C67, o479–o483
doi:10.1107/S0108270111045082
# 2011 International Union of Crystallography o479

organic compounds
Figure 1
The molecular structure of compound (I), showing the atom-labelling
scheme. Displacement ellipsoids are drawn at the 30% probability level.
˚
the maximum deviations are 0.118 (2) A for atom C17 and
˚
0.086 (2) A for atom C19B, again displaced to opposite sides
of the plane; and in the type 2 molecule of compound (II), the
˚
maximum deviations are 0.086 (2) A for atom C23 and
˚
0.057 (2) A for atom C28, this time with both displaced to the
same side of the mean plane. Amongst the three independent
molecules, no obvious pattern for these displacements can be
recognized, so that the displacements are not regarded as
chemically or structurally significant.
The corresponding bond distances within the fused ring
systems are very similar, and they are consistent with aromatic
delocalization in the fused aryl ring, and with delocalization in
the pyridine ring accompanied by strong bond fixation in the
pyrazole ring, as typically observed in pyrazolopyridine deri-
vatives (Low et al., 2007; Quiroga et al., 2009, 2010; Insuasty et
al., 2010).
The key torsion angles (Table 1) confirm that the two
independent molecules within the selected asymmetric unit of
compound (II) have the same conformation, which is the same
as that for the selected asymmetric unit in compound (I). The
corresponding values for each of the torsion angles amongst
the three independent molecular species are remarkably
similar. In each case, one of the methyl C atoms of the tert-
butyl group, designated C32 in compound (I) and C132 and
C232 in the two independent molecules of compound (II)
(Figs. 1 and 2), lies close to, but not exactly in, the plane of the
adjacent pyrazole ring. The deviations of this atom from the
Figure 2
The structures of the two independent molecules of compound (II),
showing the atom-labelling scheme for (a) a type 1 molecule and (b) a
type 2 molecule. Displacement ellipsoids are drawn at the 30%
probability level.
Despite their close similarity in both constitution and
conformation, the molecules of compounds (I) and (II) show
different patterns of supramolecular aggregation, leading to
arrays which are one- and two-dimensional, respectively.
In the crystal structure of (I), inversion-related pairs of
molecules are linked by rather long and weak C—Hꢀ ꢀ ꢀO
hydrogen bonds (Table 2) into centrosymmetric R22(18)
(Bernstein et al., 1995) dimers, and these hydrogen-bonded
˚
pyrazole plane are 0.388 (2) A for atom C32 in compound (I),
˚
and 0.210 (2) and 0.386 (2) A for atoms C132 and C232,
respectively, in compound (II). Curiously, however, the two
independent molecules in compound (II) exhibit different
orientations for their methoxy groups (Table 1 and Fig. 2), and
this alone suffices to preclude the possibility of any additional
crystallographic symmetry.
ꢁ
o480 Portilla et al. C29H22ClN3O and C30H24ClN3O2
Acta Cryst. (2011). C67, o479–o483

organic compounds
Figure 4
A stereoview of part of the crystal structure of compound (II), showing
the formation of one of the hydrogen-bonded C22(14) chains along [110].
For the sake of clarity, H atoms not involved in the motifs shown have
been omitted.
Figure 3
A stereoview of part of the crystal structure of compound (I), showing the
formation of a ꢀ-stacked chain of hydrogen-bonded dimers along [001].
For the sake of clarity, H atoms not involved in the motif shown have
been omitted.
dimers are linked into chains by a single ꢀ–ꢀ stacking inter-
action. The planes of the pyridine ring in the molecule at (x, y,
z) and the fused aryl ring in the molecule at (ꢂx + 1, ꢂy + 1,
ꢂz + 1) make a dihedral angle of only 1.2 (2)ꢃ; the corre-
˚
sponding ring-centroid separation is 3.573 (2) A and the
˚
interplanar spacing is ca 3.36 A, giving a ring-centroid offset of
˚
ca 1.22 A. The effect of this ꢀ-stacking interaction is to link the
hydrogen-bonded dimers into a chain running parallel to the
[001] direction, with the hydrogen-bonded rings centred at
(12, 12, n), where n represents an integer, alternating with the ꢀ-
1
2
1
2
stacking interactions across (12, , n + ), where n again repre-
sents an integer (Fig. 3). It is notable that neither of the
pendent aryl rings, viz. C11–C16 and C41–C46, participates in
any ꢀ–ꢀ stacking interactions and that, despite the number of
aromatic rings present, there are no C—Hꢀ ꢀ ꢀꢀ hydrogen
bonds in the structure of (I).
The direction-specific intermolecular interactions in the
crystal structure of compound (II) differ from those in the
structure of compound (I) in several respects: firstly, Z0 = 2 in
compound (II); secondly, there is a C—Hꢀ ꢀ ꢀꢀ(arene)
hydrogen bond present; and thirdly, this hydrogen bond
involves both types of pendent aryl ring, with the 4-methoxy-
phenyl ring in the type 1 molecule providing the donor and the
4-chlorophenyl ring in the type 2 molecule acting as the
acceptor.
The single, fairly short, C—Hꢀ ꢀ ꢀꢀ(arene) hydrogen bond
(Table 2) links the two independent molecules in the selected
asymmetric unit. Two independent C—Hꢀ ꢀ ꢀO hydrogen
bonds, each linking inversion-related pairs of molecules into
R22(14) rings, thus generate, in combination with the C—
Hꢀ ꢀ ꢀꢀ(arene) hydrogen bond, a chain of rings running parallel
to the [110] direction (Fig. 4). There are two independent ꢀ–ꢀ
stacking interactions present in the structure of compound
(II). The first of these occurs within the selected asymmetric
Figure 5
Part of the crystal structure of compound (II), showing the ꢀ–ꢀ stacking
interaction between pairs of type 2 molecules. For the sake of clarity, all H
atoms have been omitted. Atoms marked with an asterisk (*) are at the
symmetry position (ꢂx + 1, ꢂy + 1, ꢂz + 1).
unit, where the fused aryl ring of the type 1 molecule and the
pyridine ring of the type 2 molecule make a dihedral angle of
ꢃ
˚
2.5 (2) ; the ring-centroid separation is 3.701 (2) A and the
˚
interplanar separation is ca 3.53 A, corresponding to a ring-
˚
centroid offset of ca 1.11 A. Hence this interaction provides
some modest reinforcement to the action of the C—Hꢀ ꢀ ꢀ
ꢀ(arene) hydrogen bond.
Only type 2 molecules of compound (II) are involved in the
second type of stacking interaction. The pyridine ring of the
type 2 molecule at (x, y, z) and the fused aryl ring of the type 2
molecule at (ꢂx + 1, ꢂy + 1, ꢂz + 1) make a dihedral angle of
ꢃ
˚
2.2 (2) , with a ring-centroid separation of 3.743 (2) A, an
ꢁ
Acta Cryst. (2011). C67, o479–o483
Portilla et al.
C29H22ClN3O and C30H24ClN3O2 o481

organic compounds
˚
interplanar spacing of ca 3.56 A, and a ring-centroid offset of
˚
ca 1.16 A (Fig. 5). The effect of this interaction is to link the
Table 2
Hydrogen-bond parameters (A, ) for compounds (I) and (II).
ꢃ
˚
Cg represents the centroid of the C211–C216 ring.
hydrogen-bonded chains into a sheet parallel to (001). It may
be noted here that the overall behaviour of this ꢀ-stacking
interaction of the type 2 molecules of compound (II) closely
corresponds to the ꢀ-stacking interaction in compound (I),
although the metrics of the two interactions differ somewhat,
not surprisingly in view of the presence of an additional
molecular type in compound (II).
Compound D—Hꢀ ꢀ ꢀA
D—H Hꢀ ꢀ ꢀA Dꢀ ꢀ ꢀA
D—Hꢀ ꢀ ꢀA
(I)
C44—H44ꢀ ꢀ ꢀO5i
0.95
2.59
3.232 (2) 125
(II)
C146—H146ꢀ ꢀ ꢀCg
C18—H18ꢀ ꢀ ꢀO25ii
C28—H28ꢀ ꢀ ꢀO15iii
0.95
0.95
0.95
2.71
2.50
2.46
3.655 (2) 172
3.151 (3) 126
3.226 (3) 138
Symmetry codes: (i) ꢂx + 1, ꢂy + 1, ꢂz + 2; (ii) ꢂx + 2, ꢂy + 1, ꢂz + 1; (iii) ꢂx + 1, ꢂy,
ꢂz + 1.
Experimental
Refinement
For the synthesis of compounds (I) and (II), equimolar quantities
(1 mmol of each component) of indan-1,3-dione, 4-R-benzaldehyde,
where R = H for compound (I) and R = OMe for compound (II), and
5-amino-3-tert-butyl-1-(4-chlorophenyl)-1H-pyrazole were added to
a mixture of water and triethylamine (3 ml, 15:1 v/v), and then
subjected to microwave irradiation at 353 K with a maximum power
of 80 W for 10 min. The reaction mixture was allowed to cool to
ambient temperature and it was then extracted with dichloromethane
(3 ꢄ 15 ml). The combined extracts were dried over sodium sulfate,
filtered and concentrated to give a red solid. The products were
recrystallized from ethanol, at ambient temperature and in air, to give
light-yellow crystals suitable for single-crystal X-ray diffraction.
Compound (I) (R = H): yield 77%, m.p. 510–511 K; MS (70 eV) m/z
(%) 465/463 (25/71, M + 2/M), 450/448 (36/100), 435/433 (9/26),
422/420 (7/20); HRMS m/z found 463.1469, C29H22ClN3O requires
m/z = 463.1451. Compound (II) (R = OMe), yield 75%, m.p. 503–
504 K; MS (70 eV) m/z (%) 495/493 (28/80, M + 2/M), 480/478 (30/
100), 465/463 (11/37), 452/450 (10/29); HRMS m/z found 493.1544,
C30H24ClN3O2 requires m/z = 493.1557.
R[F2 > 2ꢅ(F2)] = 0.043
wR(F2) = 0.098
S = 1.06
310 parameters
H-atom parameteꢂrs3 constrained
˚
Áꢆmax = 0.22 e A
Áꢆmin = ꢂ0.39 e A
ꢂ3
˚
5310 reflections
Compound (II)
Crystal data
C30H24ClN3O2
Mr = 493.97
Triclinic, P1
ꢃ = 107.635 (6)ꢃ
˚
V = 2415.7 (4) A
Z = 4
3
˚
a = 11.1911 (9) A
Mo Kꢁ radiation
ꢄ = 0.19 mmꢂ1
T = 120 K
0.42 ꢄ 0.30 ꢄ 0.29 mm
˚
b = 11.4258 (8) A
˚
c = 20.095 (2) A
ꢁ = 97.411 (6)ꢃ
ꢂ = 93.272 (7)ꢃ
Data collection
Bruker–Nonius KappaCCD
diffractometer
63410 measured reflections
11085 independent reflections
7328 reflections with I > 2ꢅ(I)
Rint = 0.061
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.924, Tmax = 0.946
Compound (I)
Crystal data
Refinement
C29H22ClN3O
Mr = 463.95
Triclinic, P1
a = 8.1014 (5) A
b = 11.3554 (10) A
˚
c = 13.5762 (11) A
ꢁ = 102.755 (7)ꢃ
ꢂ = 90.013 (8)ꢃ
ꢃ = 108.268 (7)ꢃ
V = 1153.47 (16) A
Z = 2
Mo Kꢁ radiation
ꢄ = 0.19 mmꢂ1
T = 120 K
0.43 ꢄ 0.22 ꢄ 0.16 mm
R[F2 > 2ꢅ(F2)] = 0.048
wR(F2) = 0.115
S = 1.06
657 parameters
H-atom parameteꢂrs3 constrained
3
˚
˚
Áꢆmax = 0.34 e A
˚
ꢂ3
˚
11085 reflections
Áꢆmin = ꢂ0.37 e A
˚
All H atoms were located in difference maps and then treated as
riding atoms in geometrically idealized positions, with C—H
˚
distances of 0.95 (aromatic) or 0.98 A (methyl), and with Uiso(H) =
Data collection
kUeq(C), where k = 1.5 for the methyl groups, which were permitted
to rotate but not to tilt, and 1.2 otherwise.
Bruker–Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.921, Tmax = 0.970
29371 measured reflections
5310 independent reflections
4065 reflections with I > 2ꢅ(I)
Rint = 0.045
For both compounds, data collection: COLLECT (Hooft, 1999);
cell refinement: DIRAX/LSQ (Duisenberg et al., 2000); data reduc-
tion: EVALCCD (Duisenberg et al., 2003); program(s) used to solve
structure: SIR2004 (Burla et al., 2005); program(s) used to refine
structure: SHELXL97 (Sheldrick, 2008); molecular graphics:
PLATON (Spek, 2009); software used to prepare material for
publication: SHELXL97 and PLATON.
Table 1
Selected torsion angles (ꢃ) for compounds (I) and (II).
(I)
x = null
(II)
x = 1
(II)
x = 2
´
The authors thank ‘Centro de Instrumentacion Cientıfico-
Tecnica of Universidad de Jaen’ and the staff for data collec-
tion. JP and CL thank COLCIENCIAS and Universidad de
´
´
´
Nx2—Nx1—Cx11—Cx12
Nx2—Cx3—Cx31—Cx32
Nx2—Cx3—Cx31—Cx33
Nx2—Cx3—Cx31—Cx34
Cx3A—Cx4—Cx41—Cx42
Cx43—Cx44—Ox44—Cx47
ꢂ170.54 (14)
ꢂ12.9 (2)
ꢂ156.56 (19)
ꢂ10.7 (2)
108.3 (2)
ꢂ155.80 (18)
ꢂ12.8 (2)
105.68 (17)
ꢂ131.81 (16)
78.8 (2)
106.2 (2)
ꢂ131.46 (19)
´
los Andes for financial support. JC thanks the Consejerıa de
Innovacion, Ciencia y Empresa (Junta de Andalucıa, Spain)
ꢂ129.98 (19)
84.6 (3)
10.7 (3)
76.8 (3)
ꢂ177.08 (19)
´
´
´
and the Universidad de Jaen for financial support.
ꢁ
o482 Portilla et al. C29H22ClN3O and C30H24ClN3O2
Acta Cryst. (2011). C67, o479–o483

organic compounds
Hooft, R. W. W. (1999). COLLECT. Nonius BV, Delft, The Netherlands.
´
Insuasty, H., Castro, E., Sanchez, E., Cobo, J. & Glidewell, C. (2010). Acta
Cryst. C66, o141–o146.
´
Low, J. N., Cobo, J., Sanchez, A., Trilleras, J. & Glidewell, C. (2007). Acta Cryst.
C63, o287–o291.
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: FG3236). Services for accessing these data are
described at the back of the journal.
Padwa, A., Heidelbaugh, T. M. & Kuethe, J. T. (2000). J. Org. Chem. 65, 2368–2378.
Peters, J.-U., Weber, S., Kritter, S., Weiss, P., Wallier, A., Zimmerli, D.,
Boehringer, M., Steger, M. & Loeffler, B.-M. (2004). Bioorg. Med. Chem.
Lett. 14, 3579–3580.
References
Almeida, M. E. L. de, Braz, F. R., von Bulow, M. V., Gottlieb, O. R. & Maia,
J. G. S. (1976). Phytochemistry, 1976, 1186–1187.
Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem.
Int. Ed. Engl. 34, 1555–1573.
Burla, M. C., Caliandro, R., Camalli, M., Carrozzini, B., Cascarano, G. L., De
Caro, L., Giacovazzo, C., Polidori, G. & Spagna, R. (2005). J. Appl. Cryst. 38,
381–388.
´
Quiroga, J., Portilla, J., Insuasty, B., Abonıa, R., Nogueras, M., Sortino, M. &
Zacchino, S. (2005). J. Heterocycl. Chem. 42, 61–66.
´
Quiroga, J., Portilla, J., Serrano, H., Abonıa, R., Insuasty, B., Nogueras, M. &
Cobo, J. (2007). Tetrahedron Lett. 48, 1987–1990.
´
Quiroga, J., Sanchez, A., Cobo, J. & Glidewell, C. (2009). Acta Cryst. C65,
o374–o376.
Duisenberg, A. J. M., Hooft, R. W. W., Schreurs, A. M. M. & Kroon, J. (2000).
J. Appl. Cryst. 33, 893–898.
Quiroga, J., Trilleras, J., Hursthouse, M. B., Cobo, J. & Glidewell, C. (2010).
Acta Cryst. C66, o163–o167.
Duisenberg, A. J. M., Kroon-Batenburg, L. M. J. & Schreurs, A. M. M. (2003).
J. Appl. Cryst. 36, 220–229.
Sheldrick, G. M. (2003). SADABS. Version 2.10. University of Go¨ttingen,
Germany.
Earl, R. A., Zaczek, R., Teleha, C. A., Fisher, B. N., Maciag, C. M.,
Marynowski, M. E., Logue, A. R., Tam, S. W., Tinker, W. J., Huang, S.-M. &
Chorvat, R. J. (1998). J. Med. Chem. 41, 4615–4622.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.
Spek, A. L. (2009). Acta Cryst. D65, 148–155.
Strunz, G. M. & Findlay, J. A. (1985). The Alkaloids, Vol. 26. New York:
Academic Press.
Evdokimov, N. M. et al. (2011). J. Med. Chem. 54, 2012–2021.
ꢁ
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C29H22ClN3O and C30H24ClN3O2 o483