2-tert-Butyl-5-methyl-7,8-dihydro-6H-cyclo-penta-[e]pyrazolo[1,5-a] pyrimi-dine: Molecular stacks built from C - H...π(pyrazole) hydrogen bonds and π-π Stacking interactions

Article abstract of DOI:10.1107/S010827010802266X

In the title compound, C₁₄H₁₉N₃, the bond distances within the heterocyclic portion of the mol-ecule indicate incomplete π delocalization. The mol-ecules are linked into stacks by a combination of two C - H...π(pyrazole) hydrogen bonds and two independent π-π stacking inter-actions between inversion-related pyrimidine rings. The significance of this study lies in its observation of significant differences in both mol-ecular conformation and supra-molecular aggregation between the title compound, an example of a 2-alkyl-pyrazolo[1,5-a]pyrimidine, and some analogous 2-aryl-pyrazolo[1,5-a]pyrimidines.

Full text of DOI:10.1107/S010827010802266X

organic compounds
Acta Crystallographica Section C
Crystal Structure
maximum deviation from the mean plane of the ring atoms in
˚
(I) is only 0.024 (3) A, for atom C7. There is no obvious
Communications
interpretation of this difference. While the tricyclic skeleton in
(I) is effectively planar, the tert-butyl group is rotated by ca 10ꢁ
from the conformation that corresponds to an approximate
ISSN 0108-2701
2-tert-Butyl-5-methyl-7,8-dihydro-6H-
cyclopenta[e]pyrazolo[1,5-a]pyrimi-
dine: molecular stacks built from
C—Hꢀ ꢀ ꢀp(pyrazole) hydrogen bonds
and p–p stacking interactions
Jaime Portilla,a Jairo Quiroga,a Justo Cobob and
Christopher Glidewellc*
a
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Grupo de Investigacion de Compuestos Heterocıclicos, Departamento de Quımica,
b
´
Universidad de Valle, AA 25360 Cali, 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
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´
´
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Received 18 July 2008
Accepted 18 July 2008
Online 9 August 2008
In the title compound, C14H19N3, the bond distances within the
heterocyclic portion of the molecule indicate incomplete ꢀ
delocalization. The molecules are linked into stacks by a
combination of two C—Hꢀ ꢀ ꢀꢀ(pyrazole) hydrogen bonds and
two independent ꢀ–ꢀ stacking interactions between inversion-
related pyrimidine rings. The significance of this study lies in
its observation of significant differences in both molecular
conformation and supramolecular aggregation between the
title compound, an example of a 2-alkylpyrazolo[1,5-a]pyrimi-
dine, and some analogous 2-arylpyrazolo[1,5-a]pyrimidines.
mirror symmetry, as shown by the key torsion angles (Table 1).
However, the pattern of the bond distances within the
heterocyclic system in (I) (Table 1) shows a close similarity
with those in (II)–(V), and, as before, this suggests a naph-
thalene-type arrangement of the ten ꢀ electrons in this system
rather than full delocalization.
Comment
Pyrazolo[1,5-a]pyrimidines are purine analogues and their
pharmacological activity (Novinson et al., 1976; Senga et al.,
1981) has prompted interest in the development of efficient
general procedures for their synthesis. One attractive route
(Portilla et al., 2005) to such compounds involves the
condensation of a substituted 5-amino-1H-pyrazole (A) with a
2-acylcyclopentanone (B) to give the 2,5-disubstituted product
(C). We report here the molecular and supramolecular
structure of the title compound, (I) (Fig. 1), which was
prepared using a simple fusion-induced condensation reaction
between 5-amino-3-tert-butyl-1H-pyrazole and 2-acetylcyclo-
pentanone under solvent-free conditions. We compare the
structure of (I) with those of the aryl-substituted analogues
(II)–(V) (see scheme), which were all prepared using similar
condensation reactions under solvent-free conditions but
induced by microwave irradiation (Portilla et al., 2005).
In contrast to the conformations found for compounds (II)–
(V), where the carbocyclic rings all adopt envelope confor-
mations, the corresponding ring in (I) is effectively planar; the
Despite the presence of two ring N atoms, N1 and N4, each
carrying an in-plane lone pair of electrons potentially avail-
able for hydrogen-bond formation, there are, in fact, no C—
Hꢀ ꢀ ꢀN hydrogen bonds in the structure of (I). In this respect,
Figure 1
The molecular structure of (I), showing the atom-labelling scheme.
Displacement ellipsoids are drawn at the 30% probability level.
Acta Cryst. (2008). C64, o471–o473
doi:10.1107/S010827010802266X
# 2008 International Union of Crystallography o471

organic compounds
(I) resembles compounds (II)–(IV), although a single C—
Hꢀ ꢀ ꢀN interaction is present in (V). The molecules of (I) are
linked by a combination of C—Hꢀ ꢀ ꢀꢀ(pyrazone) hydrogen
bonds (Table 2) and ꢀ–ꢀ stacking interactions. Atom C6 in the
molecule at (x, y, z) acts as hydrogen-bond donor, via atoms
H6A and H6B, respectively, to the pyrazole rings in the mol-
ecules at (ꢂx + 1, ꢂy + 1, ꢂz + 1) and (ꢂx + 2, ꢂy + 1, ꢂz + 1),
respectively. Thus, the pyrazole ring accepts a C—H bond onto
each face, such that the angle H6Aꢀ ꢀ ꢀCg1iꢀ ꢀ ꢀH6Biii [Cg1
represents the centroid of the pyrazole ring; symmetry codes:
(i) ꢂx + 1, ꢂy + 1, ꢂz + 1; (iii) x ꢂ 1, y, z] is 150ꢁ. In addition,
the pyrimidine rings of the molecules at (x, y, z) and (ꢂx + 1,
ꢂy + 1, z), which are strictly parallel because they are related
bond, while (I) is the sole member in which the pyrazole ring
acts as a double acceptor of hydrogen bonds.
Only in (V) does the substituent at atom C2 play any direct
role in the hydrogen bonding. Nonetheless, the pattern of
supramolecular aggregation in (I) is different from that in the
isomorphous series (II)–(IV); likewise, the conformational
difference between (I) and (II)–(V) involves the carbocyclic
ring remote from the substituent at C2. Very subtle factors
appear to connect the nature of the substituent at C2 with both
the overall molecular conformation and the direction-specific
intermolecular forces, making structure predictions extremely
uncertain.
˚
by inversion, have an interplanar spacing of 3.422 (2) A and a
˚
ring-centroid separation of 3.611 (2) A, corresponding to a
˚
ring centroid offset of 1.152 (2) A. Similarly, for the pyrimi-
Experimental
Equimolar quantities (2 mmol of each component) of 5-amino-3-tert-
butyl-1H-pyrazole and 2-acetylcyclopentanone were mixed thor-
oughly at room temperature. The mixture was heated in an oil bath at
393 K for 1.5 min. It was then stirred and allowed to cool to room
temperature, at which point it solidified. The solid material was
extracted with ethanol; after removal of this solvent, the product, (I),
was recrystallized from dimethylformamide to give yellow crystals
suitable for single-crystal X-ray diffraction (yield 93%, m.p. 459–
461 K). MS (70 eV) m/z (%): 229 (64, M+), 214 (100), 187 (87),
106 (19), 53 (20), 41 (527), 39 (40).
dine rings of the molecules at (x, y, z) and (ꢂx + 2, ꢂy + 1,
˚
ꢂz + 1), the interplanar separation is 3.443 (2) A and the ring-
˚
centroid separation is 3.674 (2) A, corresponding in this case
˚
to a ring-centroid offset of 1.282 (2) A. The combined and co-
operative effect of the C—Hꢀ ꢀ ꢀꢀ hydrogen bonds and the ꢀ–ꢀ
stacking interaction is to link the molecules into a stack
running parallel to the [100] direction, in which alternate
molecules are related by inversion (Fig. 2).
In the isostructural compounds (II)–(IV) (Portilla et al.,
2005), the molecules are linked into chains by a single C—
Hꢀ ꢀ ꢀꢀ(pyrazole) hydrogen bond, again involving atom C6 as
the donor. In these hydrogen bonds, the Hꢀ ꢀ ꢀA and Dꢀ ꢀ ꢀA
distances are all significantly greater than the corresponding
distances in (I), while the organization of the molecules within
the chains in (II)–(IV) effectively precludes the formation of a
second C—Hꢀ ꢀ ꢀꢀ hydrogen bond, as found in (I). There is a
single C—Hꢀ ꢀ ꢀN hydrogen bond in (V), with one of the C—H
bonds in the pendent aryl group providing the donor and the
pyrimidine ring atom N4 as the acceptor. The resulting C(7)
(Bernstein et al., 1995) chains are then linked into a sheet by
means of a ꢀ–ꢀ stacking interaction between inversion-related
heterocyclic rings. Compound (V) is thus the only member of
this series so far observed to exhibit a C—Hꢀ ꢀ ꢀN hydrogen
Crystal data
C14H19N3
ꢃ = 111.097 (12)ꢁ
3
˚
Mr = 229.32
Triclinic, P1
a = 6.8665 (6) A
V = 632.22 (18) A
Z = 2
˚
Mo Kꢁ radiation
ꢄ = 0.07 mmꢂ1
T = 120 (2) K
0.38 ꢃ 0.37 ꢃ 0.25 mm
˚
b = 9.4084 (14) A
˚
c = 11.147 (2) A
ꢁ = 91.611 (14)ꢁ
ꢂ = 107.728 (14)ꢁ
Data collection
Bruker–Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.966, Tmax = 0.982
15695 measured reflections
2898 independent reflections
1804 reflections with I > 2ꢅ(I)
Rint = 0.049
Refinement
R[F2 > 2ꢅ(F2)] = 0.062
wR(F2) = 0.180
S = 1.11
158 parameters
H-atom parameteꢂrs3 constrained
˚
Áꢆmax = 0.29 e A
ꢂ3
˚
2898 reflections
Áꢆmin = ꢂ0.29 e A
Table 1
Selected geometric parameters (A, ).
ꢁ
˚
N1—C2
C2—C3
C3—C3a
C3a—N4
N4—C5
1.353 (3)
1.397 (3)
1.387 (3)
1.355 (3)
1.329 (3)
C5—C5a
C8a—N9
N9—N1
C3a—N9
C5a—C8a
1.409 (3)
1.354 (3)
1.356 (3)
1.389 (3)
1.360 (3)
Figure 2
A stereoview of part of the crystal structure of (I), showing the formation
of a stack of molecules along [100] built from a combination of C—
Hꢀ ꢀ ꢀꢀ(pyrazole) hydrogen bonds and ꢀ–ꢀ stacking interactions. For the
sake of clarity, H atoms not involved in the motifs shown have been
omitted.
N1—C2—C21—C22
N1—C2—C21—C23
N1—C2—C21—C24
170.4 (2)
ꢂ69.1 (3)
49.8 (3)
C3—C2—C21—C22
C3—C2—C21—C23
C3—C2—C21—C24
ꢂ10.1 (4)
110.4 (3)
ꢂ130.7 (3)
ꢄ
o472 Portilla et al. C14H19N3
Acta Cryst. (2008). C64, o471–o473

organic compounds
Table 2
Hydrogen-bond geometry (A, ).
´
´
thanks the Consejerıa de Innovacion, Ciencia y Empresa
ꢁ
˚
´
´
(Junta de Andalucıa, Spain) and the Universidad de Jaen for
financial support. JP and JQ thank COLCIENCIAS and
UNIVALLE (Universidad del Valle, Colombia) for financial
support.
Cg1 is the centroid of the pyrazole ring (atoms N1/C2/C3/C3a/N9).
D—Hꢀ ꢀ ꢀA
D—H
Hꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
D—Hꢀ ꢀ ꢀA
C6—H6Aꢀ ꢀ ꢀCg1i
0.99
0.99
2.76
2.70
3.602 (3)
3.581 (3)
144
148
C6—H6Bꢀ ꢀ ꢀCg1ii
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: SK3259). Services for accessing these data are
described at the back of the journal.
Symmetry codes: (i) ꢂx þ 1; ꢂy þ 1; ꢂz þ 1; (ii) ꢂx þ 2; ꢂy þ 1; ꢂz þ 1.
Crystals of (I) are triclinic; the space group P1 was selected and
confirmed by the structure analysis. 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 (pyrazole), 0.98
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The authors thank ‘Servicios Tecnicos de Investigacion of
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Acta Cryst. (2008). C64, o471–o473
Portilla et al. C14H19N3 o473