Three 4,7-diaryl-2-ethylsulfanyl-pyrazolo[1,5-a][1,3,5]triazines

Article abstract of DOI:10.1107/S0108270107064074

The molecular dimensions of 2-ethylsulfanyl-7-(4-methylphenyl)-4- phenylpyrazolo[1,5-a][1,3,5]triazine, C₂₀H₁₈N ₄S, (I), 7-(4-chlorophenyl)-2-ethylsulfanyl-4-phenylpyrazolo[1,5-a] [1,3,5]triazine, C₁₉H₁₅ClN₄S, (II), and 4,7-bis(4-chlorophenyl)-2-(ethylsulfanyl)pyrazolo[1,5-a][1,3,5]triazine, C ₁₉H₁₄Cl₂-N₄S, (III), show evidence for some aromatic delocalization in the pyrazole rings. The conformations adopted by the ethylsulfanyl substituents are different in all three compounds. There are no hydrogen bonds in any of the crystal structures, but pairs of molecules in (II) and (III) are linked into centrosymmetric dimers by π-stacking interactions.

Full text of DOI:10.1107/S0108270107064074

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
phenyl substituents are often isomorphous and isostructural,
no such similarities are apparent when compounds (I) and
(II) are compared. These two compounds crystallize in
ISSN 0108-2701
Three 4,7-diaryl-2-ethylsulfanyl-
pyrazolo[1,5-a][1,3,5]triazines
Henry Insuasty,a Paola Mier,a Gina Suarez,a John N. Low,b
Justo Coboc and Christopher Glidewelld*
a
Â
Departamento de Quõmica, Universidad de Narino, Cuidad Universitaria Torobajo,
Ä
AA 1175 Pasto, Colombia, bDepartment of Chemistry, University of Aberdeen,
c
Â
Meston Walk, Old Aberdeen AB24 3UE, Scotland, Departamento de Quõmica
Inorganica y Organica, Universidad de Jaen, 23071 Jaen, Spain, and dSchool of
Chemistry, University of St Andrews, Fife KY16 9ST, Scotland
Correspondence e-mail: cg@st-andrews.ac.uk
Â
Â
Â
Â
Received 27 November 2007
Accepted 28 November 2007
Online 22 December 2007
The molecular dimensions of 2-ethylsulfanyl-7-(4-methyl-
phenyl)-4-phenylpyrazolo[1,5-a][1,3,5]triazine,
C20H18N4S,
(I), 7-(4-chlorophenyl)-2-ethylsulfanyl-4-phenylpyrazolo[1,5-
a][1,3,5]triazine, C19H15ClN4S, (II), and 4,7-bis(4-chlorophen-
yl)-2-(ethylsulfanyl)pyrazolo[1,5-a][1,3,5]triazine, C19H14Cl2-
N4S, (III), show evidence for some aromatic delocalization
in the pyrazole rings. The conformations adopted by the
ethylsulfanyl substituents are different in all three compounds.
There are no hydrogen bonds in any of the crystal structures,
but pairs of molecules in (II) and (III) are linked into
centrosymmetric dimers by ꢀ-stacking interactions.
different crystal systems with markedly different cell dimen-
sions; in addition, compound (I) exhibits orientational
disorder in the unsubstituted phenyl ring, while compound
(II) is fully ordered; furthermore, the structure of (II)
contains a ꢀ±ꢀ stacking interaction which is absent from the
structure of (I).
The bond distances within the heterocyclic portions of
compounds (I)±(III) do not differ signi®cantly from one
compound to another (Table 1); however, the values them-
selves show some interesting features. In each compound, the
Comment
Compounds having a pyrazolo[1,5-a][1,3,5]triazine residue are
of great interest in the treatment and prevention of central
È
nervous system disorders (Bos et al., 1999), metabolic and
peripheral disorders (Darrow et al., 2001), and Parkinson's and
È
Alzheimer's diseases (Bos et al., 1999). Recently, a pyrazolo-
triazine derivative has been reported to be a powerful corti-
cotrophin releasing factor type 1 (CFR1) receptor antagonist
(He et al., 2000), playing an important role in modulating the
endocrinal, autonomic and immune responses to stress
(Kumar et al., 2004).
Pyrazolo[1,5-a][1,3,5]triazines can be readily synthesized
from 5-aminopyrazoles and an appropriate biselectrophilic
reagent (Insuasty et al., 2006). We report here the structure of
three 4,7-diaryl-2-ethylsulfanylpyrazolo[1,5-a][1,3,5] triazines
(Figs. 1±3), which were all obtained in good yields from the
reactions of S,S-diethyl aroyliminodithiocarbonates with the
appropriate 5-amino-3-arylpyrazoles (see scheme) using
microwave irradiation under solvent-free conditions.
Compounds (I)±(III) are all very similar in composition and
constitution, but they show some marked differences in both
molecular conformation and crystal packing. Although analo-
gous compounds containing 4-methylphenyl and 4-chloro-
Figure 1
A molecule of (I), showing the atom-labelling scheme. For clarity, only
one orientation of the disordered phenyl ring is shown. Displacement
ellipsoids are drawn at the 30% probability level.
Acta Cryst. (2008). C64, o27±o30
DOI: 10.1107/S0108270107064074
# 2008 International Union of Crystallography o27

organic compounds
N1ÐC2 and N3ÐC4 bonds are signi®cantly shorter than any
of the other CÐN bonds, and the differences between the
displaced signi®cantly further from the plane of the hetero-
cyclic component than in either of (II) and (III).
Ê
C7ÐC8 and C8ÐC8A bond distances [0.034 (4)±0.037 (4) A]
Ê
are much less than the difference (ca 0.15 A) between typical
There are no hydrogen bonds of any kind in the structures
of compounds (I) and (II); however, in compounds (II) and
(III), pairs of molecules are linked into centrosymmetric
single and double bonds of this type (Allen et al., 1987). These
observations are consistent with a measure of aromatic delo-
calization within the pyrazole ring, allied to strong bond
®xation in the triazine ring, as opposed to the fully localized
form A (see scheme). In compounds (I)±(III), the conforma-
tions of the ethylsulfanyl substituents are all different, as
shown by the relevant torsion angles (Table 1); only in (I) are
the non-H atoms of this substituent effectively coplanar with
the adjacent triazine ring. The ring components in compounds
(II) and (III) are almost coplanar, as shown by the dihedral
angles (Table 1), but in compound (I) both of the aryl rings are
Figure 4
Part of the crystal structure of (II), showing the formation of a
centrosymmetric ꢀ-stacked dimer. For clarity, H atoms have been
omitted. Atoms marked with an asterisk (*) are at the symmetry position
(1 x, 1 y, 1 z).
Figure 2
A molecule of (II), showing the atom-labelling scheme. Displacement
ellipsoids are drawn at the 30% probability level.
Figure 5
Part of the crystal structure of (III), showing the formation of a
centrosymmetric ꢀ-stacked dimer. For clarity, H atoms have been
omitted. Atoms marked with an asterisk (*) are at the symmetry position
(1 x, 1 y, 1 z).
Figure 3
A molecule of (III), showing the atom-labelling scheme. Displacement
ellipsoids are drawn at the 30% probability level.
ꢀ
o28 Insuasty et al.
C20H18N4S, C19H15ClN4S and C19H14Cl2N4S
Acta Cryst. (2008). C64, o27±o30

organic compounds
Re®nement
dimers by means of ꢀ±ꢀ stacking interactions. In compound
(II), the triazine and unsubstituted phenyl rings in a pair of
molecules related by inversion make a dihedral angle of
R[F2 > 2ꢅ(F2)] = 0.036
wR(F2) = 0.092
S = 1.10
227 parameters
H-atom parameters constrained
3
Ê
Áꢆmax = 0.29 e A
ꢁ
Ê
4.8 (2) . The interplanar spacing is ca 3.39 A, and the corre-
3
Ê
0.34 e A
3822 re¯ections
Áꢆmin
=
Ê
sponding centroid separation is 3.551 (2) A (Fig. 4). In
compound (III), the two independent chlorophenyl rings of a
centrosymmetrically related pair of molecules make a dihedral
Ê
angle of 5.6 (2) ; here, the interplanar spacing is ca 3.53 A,
Compound (III)
ꢁ
Crystal data
3
Ê
Ê
with a ring-centroid separation of 3.711 (2) A (Fig. 5). In
neither orientation of the molecule of compound (I) are there
any stacking interactions.
C19H14Cl2N4S
Mr = 401.30
V = 1770.5 (3) A
Z = 4
Monoclinic, P21=n
Mo Kꢁ radiation
1
Ê
a = 7.7117 (4) A
ꢄ = 0.50 mm
T = 120 (2) K
Ê
b = 8.3261 (10) A
Ê
c = 27.678 (3) A
0.47 Â 0.24 Â 0.14 mm
Experimental
ꢂ = 94.978 (5)ꢁ
Equimolar quantities (2 mmol of each component) of an S,S-diethyl
aroyliminodithiocarbonate and the appropriate 5-amino-3-aryl-
pyrazole (see scheme) were placed in open Pyrex glass vessels and
irradiated in a domestic microwave oven for 10±15 min to give the
products (I)±(III). The compounds were puri®ed by column chro-
matography on silica gel, using a mixture of hexanes and ethyl acetate
(4:1 v/v) as eluant. After removal of the solvent, crystallization from
ethyl acetate solutions provided crystals of (I)±(III) suitable for
single-crystal X-ray diffraction [(I): yield 60%, m.p. 397 K; (II): yield
63%, m.p. 407 K; (III): yield 71%, m.p. 431 K].
Data collection
Bruker±Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.801, Tmax = 0.934
39992 measured re¯ections
4039 independent re¯ections
2513 re¯ections with I > 2ꢅ(I)
Rint = 0.074
Re®nement
R[F2 > 2ꢅ(F2)] = 0.055
wR(F2) = 0.155
S = 1.06
236 parameters
H-atom parameters constrained
3
Ê
Áꢆmax = 0.49 e A
3
Ê
0.50 e A
4039 re¯ections
Áꢆmin
=
Compound (I)
Table 1
Selected geometric parameters (A, ) for compounds (I)±(III).
ꢁ
Ê
Crystal data
C20H18N4S
Mr = 346.45
Triclinic, P1
ꢃ = 100.087 (4)ꢁ
3
(I)
(II)
(III)
Ê
V = 847.56 (8) A
Z = 2
N1ÐC2
C2ÐN3
N3ÐC4
C4ÐN5
N5ÐN6
N6ÐC7
C7ÐC8
C8ÐC8A
C8AÐN1
N5ÐC8A
1.309 (2)
1.368 (2)
1.312 (2)
1.368 (2)
1.366 (2)
1.342 (2)
1.404 (3)
1.367 (2)
1.361 (2)
1.402 (2)
1.305 (2)
1.364 (2)
1.314 (2)
1.374 (2)
1.3636 (19)
1.339 (2)
1.406 (2)
1.370 (2)
1.354 (2)
1.399 (2)
1.318 (4)
1.358 (4)
1.310 (4)
1.366 (4)
1.366 (3)
1.333 (4)
1.405 (4)
1.371 (4)
1.353 (4)
1.403 (4)
Ê
a = 4.8076 (3) A
Mo Kꢁ radiation
1
Ê
b = 11.6397 (5) A
ꢄ = 0.20 mm
T = 120 (2) K
Ê
c = 15.5010 (7) A
ꢁ = 92.164 (4)ꢁ
ꢂ = 96.217 (5)ꢁ
0.62 Â 0.42 Â 0.05 mm
Data collection
Bruker±Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.886, Tmax = 0.990
13384 measured re¯ections
3861 independent re¯ections
2858 re¯ections with I > 2ꢅ(I)
Rint = 0.036
N1ÐC2ÐS2ÐC21
C2ÐS2ÐC21ÐC22
0.74 (16)
177.01 (12)
15.00 (16)
74.19 (14)
179.6 (2)
80.3 (3)
Triazine/C41±C46
Pyrazole/C71±C76
20.77 (13)/25.99 (13)a
10.20 (10)
4.78 (8)
2.63 (9)
7.58 (15)(9)
2.52 (16)
Re®nement
R[F2 > 2ꢅ(F2)] = 0.042
wR(F2) = 0.106
S = 1.07
264 parameters
H-atom parameters constrained
Note: (a) values are given for both orientations of the disordered phenyl ring.
3
Ê
Áꢆmax = 0.32 e A
3
Ê
0.31 e A
3861 re¯ections
Áꢆmin
=
Crystals of (I) are triclinic; the space group P1 was selected and
con®rmed by the structure analysis. For (II) and (III), the space
groups P21/c and P21/n, respectively, were uniquely assigned from the
systematic absences. All H atoms were located in difference maps and
then treated as riding atoms in geometrically idealized positions, with
CÐH distances of 0.95 (aromatic and heteroaromatic), 0.98 (CH3) or
Compound (II)
Crystal data
3
Ê
C19H15ClN4S
Mr = 366.86
V = 1670.61 (18) A
Z = 4
Ê
0.99 A (CH2), and with Uiso(H) = kUeq(C), where k = 1.5 for the
Monoclinic, P21=c
Mo Kꢁ radiation
ꢄ = 0.36 mm
T = 120 (2) K
0.56 Â 0.34 Â 0.05 mm
1
Ê
a = 11.8290 (10) A
methyl groups and k = 1.2 for all other H atoms. In (I), the unsub-
stituted phenyl ring was found to exhibit orientational disorder; this
was modelled using two sets of sites, labelled A and B, for atoms C42,
C42, C45 and C46. Re®nement of the site-occupancy factors for these
two sets of atoms gave values that were identical within experimental
uncertainly, and so these occupancies were ®xed at 0.5 during the ®nal
re®nements.
Ê
b = 7.5703 (5) A
Ê
c = 19.5297 (5) A
ꢂ = 107.200 (3)ꢁ
Data collection
Bruker±Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.822, Tmax = 0.982
37866 measured re¯ections
3822 independent re¯ections
2968 re¯ections with I > 2ꢅ(I)
Rint = 0.039
For all compounds, data collection: COLLECT (Hooft, 1999); cell
re®nement: DIRAX/LSQ (Duisenberg et al., 2000); data reduction:
ꢀ
Acta Cryst. (2008). C64, o27±o30
Insuasty et al.
C20H18N4S, C19H15ClN4S and C19H14Cl2N4S o29

organic compounds
È
Bos, M., Riemer, C. & Stadler, H. (1999). EU Patent 941 994 A1.
EVALCCD (Duisenberg et al., 2003); program(s) used to solve
structure: SIR2004 (Burla et al., 2005); program(s) used to re®ne
structure: OSCAIL (McArdle, 2003) and SHELXL97 (Sheldrick,
1997); molecular graphics: PLATON (Spek, 2003); software used to
prepare material for publication: SHELXL97 and PRPKAPPA
(Ferguson, 1999).
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.
Darrow, J. W., Lombaert, S., Blum, C., Tran, J., Giangiordano, M., Grif®th,
D. A. & Carpino, P. A. (2001). WO Patent 023388 A2.
Duisenberg, A. J. M., Hooft, R. W. W., Schreurs, A. M. M. & Kroon, J. (2000).
J. Appl. Cryst. 33, 893±898.
Duisenberg, A. J. M., Kroon-Batenburg, L. M. J. & Schreurs, A. M. M. (2003).
J. Appl. Cryst. 36, 220±229.
Ferguson, G. (1999). PRPKAPPA. University of Guelph, Canada.
He, L., Gilligan, P. J., Zaczek, R., Fitzgerald, L. W., McElroy, J., Shen, H.-S. L.,
Saye, J. A., Kalin, N. H., Shelton, S., Christ, D., Trainor, G. & Hartig, P.
(2000). J. Med. Chem. 43, 449±456.
Â
The authors thank Servicios Tecnicos de Investigacion of
Universidad de Jaen and the staff for data collection. JC
Â
Â
Â
Â
thanks the Consejerõa de Innovacion, Ciencia y Empresa
Â
Â
(Junta de Andalucõa, Spain) and the Universidad de Jaen for
®nancial support. HI, PM and GS thank COLCIENCIAS and
Universidad de NarinÄo, Colombia, for ®nancial support.
Hooft, R. W. W. (1999). COLLECT. Nonius BV, Delft, The Netherlands.
Â
Â
Insuasty, H., Estrada, M., Cortes, E., Quiroga, J., Insuasty, B., Abonõa, R.,
Nogueras, M. & Cobo, J. (2006). Tetrahedron Lett. 47, 5441±5443.
Kumar, J. S. D., Majo, V. J., Simpson, N. R., Prabhakaran, J., Van
Heertum, R. L. & Mann, J. J. (2004). J. Labelled Compd Radiopharm. 47,
971±976.
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: GG3133). Services for accessing these data are
described at the back of the journal.
McArdle, P. (2003). OSCAIL for Windows. Version 10. Crystallography
Centre, Chemistry Department, NUI Galway, Ireland.
Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of
È
Gottingen, Germany.
Sheldrick, G. M. (2003). SADABS. Version 2.10. University of Gottingen,
References
È
Germany.
Spek, A. L. (2003). J. Appl. Cryst. 36, 7±13.
Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor,
R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1±19.
ꢀ
o30 Insuasty et al.
C20H18N4S, C19H15ClN4S and C19H14Cl2N4S
Acta Cryst. (2008). C64, o27±o30