7-Amino-2,5-dimethylpyrazolo[1,5-a]-pyrimidine hemihydrate redetermined at 120 K: A three-dimensional hydrogen-bonded framework

Article abstract of DOI:10.1107/S0108270106005373

In the title compound, C₈H₁₀N₄·0. 5H₂O, where the water molecules lie on twofold rotation axes in the space group C2, the components are linked by three hydrogen bonds, one each of O-H...N, N-H...N and N-H...O types, into a complex three-dimensional framework structure.

Full text of DOI:10.1107/S0108270106005373

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
re®nement converged to R = 0.058 with a data/parameter ratio
of only 5.94, giving typiꢀcal s.u. values on the distances and
Ê
angles of 0.01 A and 1.5 , respectively. Although three inter-
ISSN 0108-2701
molecular hydrogen bonds were identi®ed, the authors gave
no analysis or discussion of their structural consequences.
We have now taken the opportunity to redetermine this
structure using diffraction data collected at 120 K, and the
resulting re®nement, which converged to R = 0.037 for a data/
parameter ratio of 9.62, gives much greater geometric preci-
7-Amino-2,5-dimethylpyrazolo[1,5-a]-
pyrimidine hemihydrate redetermined
at 120 K: a three-dimensional
Ê
sion, with typical s.u. values on distances and angles of 0.002 A
and 0.15ꢀ, respectively. We report here this redetermination,
with a detailed description of the supramolecular structure.
Within the heterocyclic component, the bond distances
(Table 1) show a number of deviations from the pattern
expected if the bond-localized form (I) (see scheme) is the
correct representation. In particular, the C3AÐN4 bond,
which is formally a single bond, is not very much longer than
the N1ÐC2 and N4ÐC5 bonds, both of which are formally
double bonds; similarly, the lengths of the C2ÐC3 and C5Ð
C6 bonds, which are formally single bonds, differ very little
from those of the C3ÐC3A and C6ÐC7 bonds, which are
formally double bonds. This pattern points to a considerable
degree of aromatic type 10-ꢀ electron delocalization. Also
noteworthy is the difference between the two exocyclic angles
at atom C7, a difference which has no obvious explanation. All
these metrical observations closely mimic those obtained, at
much lower precision, from the ambient-temperature deter-
mination (Mornon et al., 1975), although some of the
geometric and displacement parameters involving H atoms in
that report are clearly unreliable.
hydrogen-bonded framework
Jaime Portilla,a Jairo Quiroga,a Justo Cobo,b John N. Lowc
and Christopher Glidewelld*
a
Â
Â
Â
Grupo de Investigacion de Compuestos Heterocõclicos, Departamento de Quõmica,
b
Â
Universidad de Valle, AA 25360 Cali, Colombia, Departamento de Quõmica
Inorganica y Organica, Universidad de Jaen, 23071 Jaen, Spain, cDepartment of
Chemistry, University of Aberdeen, Meston Walk, Old Aberdeen AB24 3UE,
Scotland, and dSchool of Chemistry, University of St Andrews, Fife KY16 9ST,
Scotland
Â
Â
Â
Â
Correspondence e-mail: cg@st-andrews.ac.uk
Received 14 February 2006
Accepted 15 February 2006
Online 11 March 2006
In the title compound, C8H10N4Á0.5H2O, where the water
molecules lie on twofold rotation axes in the space group C2,
the components are linked by three hydrogen bonds, one each
of OÐHÁ Á ÁN, NÐHÁ Á ÁN and NÐHÁ Á ÁO types, into a complex
three-dimensional framework structure.
As reported previously, the water molecules lie on twofold
rotation axes in space group C2, with the heterocyclic
component in a general position. For the sake of convenience,
the reference water molecule has been selected as that lying
Comment
1
across the rotation axis along (12, y, ), with the two indepen-
Pyrazolo[1,5-a]pyrimidines are purine analogues which
exhibit a number of useful properties as antimetabolites in
purine biochemical reactions; they are of particular interest
because of their antitrypanosomal (Novinson et al., 1976) and
antischistosomal activities (Senga et al., 1981). Such interesting
biological properties have prompted the development of new
and ef®cient general procedures for the synthesis of pyra-
zolo[1,5-a]pyrimidine derivatives (Al-Shiekh et al., 2004;
Makarov et al., 2005). We present here the structure of 7-am-
ino-2,5-dimethylpyrazolo[1,5-a]pyrimidine, (I), prepared by
the solvent-free cyclocondensation reaction between 5-amino-
3-methyl-1H-pyrazole and 3-aminocrotononitrile induced by
microwave irradiation, and crystallized from ethanol as the
hemihydrate.
2
dent molecular components linked by an OÐHÁ Á ÁN hydrogen
Figure 1
The structure of (I) was determined many years ago using
diffraction data collected at ambient temperature (Mornon et
al., 1975). The coordinates and displacement parameters for
the H atoms bonded to C and O atoms were all re®ned and the
The independent molecular components of (I), showing the atom-
labelling scheme. Displacement ellipsoids are drawn at the 30%
probability level. Atom O1 lies on a twofold rotation axis (see
Comment).
o186 # 2006 International Union of Crystallography
DOI: 10.1107/S0108270106005373
Acta Cryst. (2006). C62, o186±o189

organic compounds
bond (Fig. 1 and Table 1). Three independent hydrogen bonds
(Table 2), one each of OÐHÁ Á ÁN, NÐHÁ Á ÁN and NÐHÁ Á ÁO
types, link the molecular components into a three-dimensional
framework of some complexity. However, descriptive analysis
of the formation of this framework is markedly simpli®ed by
the identi®cation of a number of simple substructures in zero,
one and two dimensions, whose combination generates the
overall framework structure.
A basic building block in the supramolecular structure is a
cyclic dimer containing only the heterocyclic component.
Amine atom N7 in the bicyclic molecule at (x, y, z) acts as a
Figure 2
Part of the crystal structure of (I), showing the formation of an R22(10)
dimer. For the sake of clarity, the unit-cell outline, the water molecule and
H atoms bonded to C atoms have all been omitted. Atoms marked with
an asterisk are at the symmetry position (2 x, y, 2 z).
Figure 4
Part of the crystal structure of (I), showing the formation of a [101] chain
of linked R22(10) dimers. For the sake of clarity, H atoms bonded to C
atoms have been omitted. Atoms marked with an asterisk (*), a hash (#)
or a dollar sign ($) are at the symmetry positions (2 x, y, 2 z), (1 x,
y, 1 z) and ( 1 + x, y, 1 + z), respectively.
Figure 3
Part of the crystal structure of (I), showing the formation of a [001] chain
of linked R22(10) dimers. For the sake of clarity, H atoms not involved in
the motif shown have been omitted. Atoms marked with an asterisk (*), a
hash (#), a dollar sign ($) or an ampersand (&) are at the symmetry
positions ( 21 +x, 12 + y, z), (23 x, 21 + y, 2 z), (32 x, 21 + y, 1 z) and ( 12 + x,
Figure 5
A stereoview of a part of the crystal structure of (I), showing the
formation of a (001) sheet of R88(32) rings. For the sake of clarity, H atoms
bonded to C atoms have been omitted.
(
12 + x, 12 + y, 1 + z), respectively. Atoms O1A and O1B are at (21, y, 32)
and (12, y, 12), respectively.
ꢁ
Acta Cryst. (2006). C62, o186±o189
Portilla et al. C8H10N4Á0.5H2O o187

organic compounds
Data collection
hydrogen-bond donor, via H7A, to ring atom N1 at (2 x, y,
z), so forming a cyclic R22(10) (Bernstein et al., 1995) dimer
2
Nonius KappaCCD diffractometer
' and ! scans
1032 re¯ections with I > 2ꢅ(I)
Rint = 0.024
(Fig. 2). The water molecules act as twofold donors in OÐ
HÁ Á ÁN hydrogen bonds and as twofold acceptors in NÐHÁ Á ÁO
hydrogen bonds (Table 2), and the resulting linking of the
water molecules and the heterocycles generates three inde-
pendent chains, whose combination leads to the formation of
the three-dimensional framework.
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.967, Tmax = 0.983
6163 measured re¯ections
1116 independent re¯ections
ꢃmax = 27.5ꢀ
h = 20 ! 20
k = 10 ! 10
l = 9 ! 10
Re®nement
Re®nement on F2
R[F2 > 2ꢅ(F2)] = 0.034
wR(F2) = 0.090
S = 1.06
1116 re¯ections
w = 1/[ꢅ2(F2o) + (0.0579P)2
+ 0.2034P]
The water O atom at (21, y, 12 ) accepts hydrogen bonds
from amine atoms N7 in the two heterocyclic molecules at
1
where P = (F2o + 2Fc2)/3
(Á/ꢅ)max < 0.001
1
1
(
+ x, + y, z) and (32 x, + y, 1 z). These molecules
2
2
2
are components of the R22(10) dimers lying across the
twofold rotation axes along (12, y, 1) and (21, y, 0), and these
dimers in turn also act as hydrogen-bond donors to the O
atoms at (12, y, 23 ) and (21, y, 32), respectively. In this
manner, a chain of linked dimers running parallel to the
[001] direction is generated by successive twofold rotations
(Fig. 3).
3
Ê
Áꢆmax = 0.17 e A
3
Ê
0.20 e A
116 parameters
H-atom parameters constrained
Áꢆmin
=
Table 1
Selected geometric parameters (A, ).
ꢀ
Ê
N1ÐC2
C2ÐC3
C3ÐC3A
C3AÐN4
N4ÐC5
C5ÐC6
1.342 (2)
1.401 (3)
1.392 (3)
1.355 (2)
1.332 (2)
1.393 (3)
C6ÐC7
1.390 (2)
1.371 (2)
1.368 (2)
1.384 (2)
1.333 (2)
C7ÐN7A
N7AÐN1
C3AÐN7A
C7ÐN7
The same water O atom at (12, y, 12 ) acts as a hydrogen-bond
donor to pyridine atoms N4 in the molecules at (x, y, z) and
(1 x, y, 1 z), respectively, which are themselves compo-
nents of the R22(10) dimers lying across the rotation axes along
(1, y, 1) and (0, y, 0). Propagation of these hydrogen bonds by
successive rotations then generates a second chain of linked
dimers, this time running parallel to the [101] direction (Fig. 4).
The combination of the [001] and [101] chains (Figs. 3 and 4)
generates the ®rst of the two-dimensional substructures in the
form of a (010) sheet.
N7ÐC7ÐN7A
117.38 (15)
N7ÐC7ÐC6
127.60 (16)
Table 2
Hydrogen-bond geometry (A, ).
ꢀ
Ê
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
In the ®nal substructure, which is also two-dimensional, the
reference water O atom at (12, y, ) acts as a hydrogen-bond
donor to the heterocyclic molecules at (x, y, z) and (1 x, y,
O1ÐH1Á Á ÁN4
0.96
0.88
0.88
1.81
2.21
2.01
2.763 (2)
2.971 (2)
2.877 (2)
172
144
168
1
2
N7ÐH7AÁ Á ÁN1i
N7ÐH7BÁ Á ÁO1ii
Symmetry codes: (i) x ‡ 2; y; z ‡ 2; (ii) x ‡ 12; y 21; z.
1
z), and as a hydrogen-bond acceptor from the corre-
sponding molecules at ( 12 + x, 21 + y, z) and (23 x, 12 + y, 1 z),
and propagation of these two hydrogen bonds in combination
generates a (001) sheet built from a single type of R88(32)
ring (Fig. 5). The combination of (010) and (001) sheets is
suf®cient to generate a single three-dimensional framework
structure.
The systematic absences permitted C2, Cm and C2/m as possible
space groups; C2 was selected and then con®rmed by the successful
structure analysis. All H atoms were located from difference maps
and then treated as riding atoms, with CÐH distances of 0.95
Ê
Ê
(aromatic) or 0.98 A (methyl), NÐH distances of 0.88 A, and Uiso(H)
values of 1.2Ueq(C,N), 1.5Ueq(O) or 1.5Ueq(methyl C). In the absence
of signi®cant anomalous scattering, the Flack (1983) parameter was
indeterminate (Flack & Bernardinelli, 2000), and the Friedel
equivalent re¯ections were merged prior to the ®nal re®nement.
Accordingly, it was not possible to establish the absolute con®gura-
tion of the asymmetric unit (Jones, 1986).
Experimental
An intimate mixture of 5-amino-3-methyl-1H-pyrazole (194 mg,
2 mmol) and 3-aminocrotononitrile (328 mg, 4 mmol) was placed in
an open Pyrex glass vessel and irradiated in a domestic microwave
oven for 2.5 min (at 600 W). The reaction mixture was then extracted
with ethanol and, after removal of the solvent, the product was
crystallized from ethanol as white crystals suitable for single-crystal
X-ray diffraction (yield 92%, m.p. 470±472 K). MS: (30 eV) m/z (%) =
162 (100, M+), 161 (24), 147 (5), 134 (11), 122 (26).
Data collection: COLLECT (Hooft, 1999); cell re®nement:
DENZO (Otwinowski & Minor, 1997) and COLLECT; data reduc-
tion: DENZO and COLLECT; program(s) used to solve structure:
OSCAIL (McArdle, 2003) and SHELXS97 (Sheldrick, 1997);
program(s) used to re®ne structure: OSCAIL and SHELXL97
(Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); soft-
ware used to prepare material for publication: SHELXL97 and
PRPKAPPA (Ferguson, 1999).
Crystal data
3
C8H10N4Á0.5H2O
Dx = 1.252 Mg m
Mo Kꢂ radiation
Cell parameters from 1116
re¯ections
Mr = 171.21
Monoclinic, C2
X-ray data were collected at the EPSRC X-ray Crystal-
lographic Service, University of Southampton, England. JC
Â
thanks the Consejerõa de Innovacion, Ciencia y Empresa
(Junta de Andalucõa, Spain) and the Universidad de Jaen for
Ê
a = 16.0851 (5) A
ꢃ = 4.5±27.5ꢀ
ꢄ = 0.09 mm
T = 120 (2) K
Ê
b = 7.9458 (3) A
1
Ê
c = 8.0003 (3) A
Â
ꢁ = 117.309 (2)ꢀ
3
Â
Â
Ê
V = 908.55 (6) A
Z = 4
Block, colourless
0.54 Â 0.36 Â 0.20 mm
®nancial support. JP and JQ thank COLCIENCIAS and
ꢁ
o188 Portilla et al. C8H10N4Á0.5H2O
Acta Cryst. (2006). C62, o186±o189

organic compounds
Jones, P. G. (1986). Acta Cryst. A42, 57.
McArdle, P. (2003). OSCAIL for Windows. Version 10. Crystallography
Centre, Chemistry Department, NUI Galway, Ireland.
UNIVALLE (Universidad del Valle, Colombia) for ®nancial
support.
Makarov, V., Riabova, O., Granik, V. G., Dahse, H.-M., Stelzner, A., Wutzler, P.
& Schmidtke, M. (2005). Bioorg. Med. Chem. Lett. 15, 37±39.
Â
Mornon, J.-P., Delettre, J. & Bally, R. (1975). Acta Cryst. B31, 2119±
2121.
Novinson, T., Bhooshan, B., Okabe, T., Revankar, G. R., Robins, R. K., Senga,
K. & Wilson, H. R. (1976). J. Med. Chem. 19, 512±516.
Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276,
Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M.
Sweet, pp. 307±326. New York: Academic Press.
Senga, K., Novinson, T., Wilson, H. R. & Robins, R. K. (1981). J. Med. Chem.
24, 610±613.
Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: SK3006). Services for accessing these data are
described at the back of the journal.
References
Al-Shiekh, M., Salah El-Din, A. M., Hafez, E. & Elnagdi, M. H. (2004). J.
Heterocycl. Chem. 41, 647±654.
Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem.
Int. Ed. Engl. 34, 1555±1573.
Ferguson, G. (1999). PRPKAPPA. University of Guelph, Canada.
Flack, H. D. (1983). Acta Cryst. A39, 876±881.
Flack, H. D. & Bernardinelli, G. (2000). J. Appl. Cryst. 33, 1143±1148.
Hooft, R. W. W. (1999). COLLECT. Nonius BV, Delft, The Netherlands.
È
Gottingen, Germany.
Sheldrick, G. M. (2003). SADABS. Version 2.10. University of GoÈttingen,
Germany.
Spek, A. L. (2003). J. Appl. Cryst. 36, 7±13.
ꢁ
Acta Cryst. (2006). C62, o186±o189
Portilla et al. C8H10N4Á0.5H2O o189