Eight 7-benzyl-3-tert-butyl-1-phenyl-pyrazolo[3,4-d]oxazines, encompassing structures containing no inter-molecular hydrogen bonds, and hydrogen-bonded structures in one, two or three dimensions

Article abstract of DOI:10.1107/S0108270109028017

7-Benzyl-3-tert-butyl-1-phenyl-6,7-dihydro-1H,4H-pyrazolo[3,4-d][1,3] oxazine, C₂₂H₂₅N₃O, (I), and 3-tert-butyl-7-(4-methyl-benz-yl)-1-phenyl-6,7-dihydro-1H,4H-pyrazolo[3,4-d][1, 3]oxazine, C₂₃H₂₇N

Full text of DOI:10.1107/S0108270109028017

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
Comment
In connection with our wider study of new synthetic routes to
fused pyrazole derivatives having potential applications in
fields such as drug precursors, pesticides and new materials
(Elguero, 1984, 1996), we report here the structures of eight
substituted pyrazolo[3,4-d]oxazines. These derivatives have
been prepared following a synthetic sequence based on the
condensation of a substituted 5-aminopyrazole with the
appropriate aldehyde to provide (E)-3-tert-butyl-5-arylidene-
amino-1-phenyl-1H-pyrazole derivatives, followed by re-
duction of these intermediates to the corresponding 5-aryl-
methylamino-3-tert-butyl-1-phenyl-1H-pyrazoles (Castillo et
al., 2009), and finally reaction with formaldehyde under acid
catalysis.
ISSN 0108-2701
Eight 7-benzyl-3-tert-butyl-1-phenyl-
pyrazolo[3,4-d]oxazines, encompassing
structures containing no intermolecular
hydrogen bonds, and hydrogen-bonded
structures in one, two or three
dimensions
a
a
b
´
Juan C. Castillo, Rodrigo Abonıa, Justo Cobo and
Christopher Glidewellc*
a
´
´
´
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
´
´
´
´
Received 6 July 2009
Accepted 16 July 2009
Online 30 July 2009
7-Benzyl-3-tert-butyl-1-phenyl-6,7-dihydro-1H,4H-pyrazolo-
[3,4-d][1,3]oxazine, C22H25N3O, (I), and 3-tert-butyl-7-(4-
methylbenzyl)-1-phenyl-6,7-dihydro-1H,4H-pyrazolo[3,4-d]-
[1,3]oxazine, C23H27N3O, (II), are isomorphous in the space
group P21, and molecules are linked into chains by C—Hꢀ ꢀ ꢀO
hydrogen bonds. In each of 3-tert-butyl-7-(4-methoxybenzyl)-
1-phenyl-6,7-dihydro-1H,4H-pyrazolo[3,4-d][1,3]oxazine, C23-
H27N3O2, (III), which has cell dimensions rather similar to
those of (I) and (II), also in P21, and 3-tert-butyl-1-phenyl-7-
[4-(trifluoromethyl)benzyl]-6,7-dihydro-1H,4H-pyrazolo[3,4-d]-
[1,3]oxazine, C23H24F3N3O, (IV), there are no direction-
specific interactions between the molecules. In 3-tert-butyl-7-
(4-nitrobenzyl)-1-phenyl-6,7-dihydro-1H,4H-pyrazolo[3,4-d]-
[1,3]oxazine, C22H24N4O3, (V), a combination of C—Hꢀ ꢀ ꢀO
and C—Hꢀ ꢀ ꢀN hydrogen bonds links the molecules into
complex sheets. There are no direction-specific interactions
between the molecules of 3-tert-butyl-7-(2,3-dimethoxybenz-
yl)-1-phenyl-6,7-dihydro-1H,4H-pyrazolo[3,4-d][1,3]oxazine,
C24H29N3O3, (VI), but a three-dimensional framework
is formed in 3-tert-butyl-7-(3,4-methylenedioxybenzyl)-1-
phenyl-6,7-dihydro-1H,4H-pyrazolo[3,4-d][1,3]oxazine, C23-
H25N3O3, (VII), by a combination of C—Hꢀ ꢀ ꢀO, C—Hꢀ ꢀ ꢀN
and C—Hꢀ ꢀ ꢀꢀ(arene) hydrogen bonds, while a combination
of C—Hꢀ ꢀ ꢀO and C—Hꢀ ꢀ ꢀꢀ(arene) hydrogen bonds links the
molecules of 3-tert-butyl-1-phenyl-7-(3,4,5-trimethoxybenzyl)-
6,7-dihydro-1H,4H-pyrazolo[3,4-d][1,3]oxazine, C25H31N3O4,
(VIII), into complex sheets. In each compound, the oxazine
ring adopts a half-chair conformation, while the orientations
of the pendent phenyl and tert-butyl substituents relative to
the pyrazolo[3,4-d]oxazine unit are all very similar.
Thus, we now report the structures of 7-benzyl-3-tert-butyl-
1-phenyl-6,7-dihydro-1H,4H-pyrazolo[3,4-d][1,3]oxazine, (I),
and seven derivatives, (II)–(VIII) (see scheme and Figs. 1 and
2), bearing a range of simple substituents in the aromatic ring
of the benzyl unit. Compounds (I) and (II) are isomorphous in
the space group P21. While compound (III) also crystallizes in
P21 with cell dimensions and atomic coordinates similar to
those in (I) and (II), it cannot be regarded as either isomor-
phous or isostructural with (I) and (II). Thus, while the unit-
cell vectors a and b both differ by less than 0.8% between
compounds (I) and (II), the corresponding difference between
(II) and (III) are both >2%; similarly, for the unit-cell vector c,
the values for (I) and (II) differ by ca 1.3%, while those for
(II) and (III) differ by ca 3.5%. Corresponding differences are
Acta Cryst. (2009). C65, o423–o430
doi:10.1107/S0108270109028017
# 2009 International Union of Crystallography o423

organic compounds
Figure 1
The molecular structures of compounds (I)–(IV), showing the atom-labelling schemes. Displacement ellipsoids are drawn at the 30% probability level.
also found for the cell angle ꢁ and the unit-cell volume. In
addition, the intermolecular interactions in (III) differ signif-
icantly from those in (I) and (II) (see below). Compound (VI)
also crystallizes in P21, but with cell dimensions significantly
different from those in compounds (I)–(III).
while the methoxy substituents exhibit different patterns of
orientation in compounds (VI) and (VIII). In compound (VI),
the methoxy atoms C721 and C731 are displaced from the
˚
plane of the ring (C71–C76) by 1.168 (4) and 0.009 (3) A,
respectively, while the displacements of atoms C731, C741 and
C751 in compound (VIII) are 0.407 (2), 1.309 (2) and
In each compound, the ring-puckering parameters (Cremer
& Pople, 1975) show that the oxazine ring adopts an almost
perfect half-chair conformation (Table 1): for this conforma-
tion, the idealized values of the puckering angles (calculated
assuming equal bond distances throughout the ring) are ꢂ =
129.2ꢁ and ’ = (60n + 30)ꢁ, where n represents an integer. The
rest of the skeletal conformation, defining the orientation of
the pendent substituents relative to the pyrazolo[3,4-d]-
oxazine unit, can be defined in terms of just four torsion angles
(Table 1). These data show the following: (i) the aromatic ring
(C11–C16) adopts a very similar orientation in every
compound; (ii) the orientation of the tert-butyl group is always
such that one atom, C32, is close to the plane of the pyrazole
ring, but always displaced from it, with a maximum displace-
˚
0.262 (2) A, respectively. In each compound, there is a short
intramolecular C—Hꢀ ꢀ ꢀN contact (Table 2) involving aryl
atom C12 and ring atom N7; in every case, the C—Hꢀ ꢀ ꢀN
angle is narrow at 120ꢁ or less, suggesting that the interaction
energy is likely to be small. This contact is probably adventi-
tious, rather than a significant influence on the molecular
conformation.
In each of compounds (I)–(VIII), the molecules have no
internal symmetry and hence they are all chiral. While
compounds (IV), (V), (VII) and (VIII) all crystallize as
racemic mixtures of enantiomorphs, the crystals of compounds
(I)–(III) and (VI) all contain a single enantiomorph. However,
in the absence of significant resonant scattering, the enanti-
omorphs present in the crystals of compounds (I)–(III) and
(VI) which had been selected for data collection cannot be
identified. The synthesis of these compounds utilizes no
reagents capable of imparting enantiomeric bias, and all are
therefore expected to be formed as racemic mixtures, crys-
tallizing as racemates for compounds (IV), (V), (VII) and
˚
ment of 0.413 (3) A in compound (VII) and a minimum
˚
displacement of 0.186 (2) A in compound (V), respectively;
the orientation of the aromatic ring of the benzyl substituent
shows by far the widest range, although with no obvious
systematic variation. In compound (V), the dihedral angle
between the nitro group and the adjacent aryl ring is 11.2 (2)ꢁ,
ꢂ
o424 Castillo et al. Eight pyrazolo[3,4-d]oxazines
Acta Cryst. (2009). C65, o423–o430

organic compounds
Figure 2
The molecular structures of compounds (V)–(VIII), showing the atom-labelling schemes. Displacement ellipsoids are drawn at the 30% probability level.
(VIII), and as conglomerates for compounds (I)–(III) and
(VI).
one-dimensional substructures. In the simpler of these two
substructures, molecules related by the 21 screw axis along
1
4
Despite their close similarities in both constitution and
conformation, compounds (I)–(VIII) nonetheless show some
interesting variations in their supramolecular aggregation,
which is dominated by C—Hꢀ ꢀ ꢀO and C—Hꢀ ꢀ ꢀN hydrogen
bonds, along with a single C—Hꢀ ꢀ ꢀꢀ(arene) hydrogen bond in
each of compounds (II), (VII) and (VIII) (Table 2).
In both (I) and (II), molecules related by translation are
linked into simple C(9) (Bernstein et al., 1995) chains running
parallel to the [001] direction (Fig. 3). In addition, there is a
rather long C—Hꢀ ꢀ ꢀꢀ(arene) hydrogen bond in (II), the effect
of which is to form a weak link between the chains along [001],
so forming a sheet parallel to (010). No interaction of this kind
can be identified in the structure of (I), so that while
compounds (I) and (II) are isomorphous, they are not strictly
isostructural (Acosta et al., 2009). In contrast, there are no
direction-specific intermolecular interactions in the structures
of compounds (III), (IV) or (VI), despite the presence of
additional potential hydrogen-bond acceptor atoms in
compounds (III) and (VI) (Figs. 1 and 2).
(12, y, ) are linked by a single C—Hꢀ ꢀ ꢀO hydrogen bond
(Table 2) into a simple C(6) chain running parallel to the [010]
direction (Fig. 4). In the second substructure, molecules
related by the c-glide plane at y = 0.75 are linked by one C—
Hꢀ ꢀ ꢀN hydrogen bond and one C—Hꢀ ꢀ ꢀO hydrogen bond to
form a C(6)C(8)[R22(17)] chain of rings running parallel to the
[001] direction (Fig. 5). The combination of these two chain
motifs generates a sheet parallel to (100).
There are five independent hydrogen bonds in the structure
of compound (VII), which together generate a three-dimen-
sional framework structure, the formation of which can,
however, be readily analysed in terms of three one-dimen-
sional substructures, which involve, respectively, the three C—
Hꢀ ꢀ ꢀO hydrogen bonds, the C—Hꢀ ꢀ ꢀN hydrogen bond and the
C—Hꢀ ꢀ ꢀꢀ(arene) hydrogen bond. In the first substructure
(Fig. 6), pairs of molecules related by inversion are linked by
two independent C—Hꢀ ꢀ ꢀO hydrogen bonds to form a dimeric
unit containing three edge-fused hydrogen-bonded rings, with
1
1
a centrosymmetric R22(14) ring centred at (12, , ) flanked by
2
2
The supramolecular aggregation in compound (V) is two-
dimensional, in the form of deeply puckered sheets, and the
formation of these sheets is readily analysed in terms of two
two noncentrosymmetric but symmetry-related R22(7) rings. In
addition, these units are linked by the third C—Hꢀ ꢀ ꢀO
hydrogen bond, forming a further R22(8) ring motif, this time
ꢂ
Acta Cryst. (2009). C65, o423–o430
Castillo et al.
Eight pyrazolo[3,4-d]oxazines o425

organic compounds
Figure 5
A stereoview of part of the crystal structure of compound (V), showing
the formation of a hydrogen-bonded C(6)C(8)[R22(17)] chain of rings
along [001]. For the sake of clarity, H atoms not involved in the motif
shown have been omitted.
Figure 3
A stereoview of part of the crystal structure of compound (I), showing the
formation of a hydrogen-bonded C(9) chain along [001]. For the sake of
clarity, H atoms not involved in the motif shown have been omitted. An
entirely similar chain is formed by compound (II).
Figure 4
A stereoview of part of the crystal structure of compound (V), showing
the formation of a hydrogen-bonded C(6) chain along [010]. For the sake
of clarity, H atoms not involved in the motif shown have been omitted.
Figure 6
A stereoview of part of the crystal structure of compound (VII), showing
the formation of a hydrogen-bonded ribbon running along [110], and
containing three types of ring. For the sake of clarity, H atoms not
involved in the motif shown have been omitted. A symmetry-related
chain runs parallel to the [110] direction.
1
2
centrosymmetric and centred at (0, 1, ). Propagation by
inversion of these hydrogen bonds then generates a ribbon
running parallel to the [110] direction, in which R22(8) rings
centred at (n, 1 ꢃ n, ) alternate with R22(14) rings centred at
1
2
(12 + n, ꢃ n, ), where n represents an integer (Fig. 6). A
shares with compound (VII) the formation of a ribbon
containing three types of ring (two of them centrosymmetric,
built from three independent C—Hꢀ ꢀ ꢀO hydrogen bonds),
even though the details of the ribbon construction for the two
compounds are different (Table 2). Pairs of molecules related
by inversion are again linked by two C—Hꢀ ꢀ ꢀO hydrogen
bonds to form a dimer containing three edge-fused rings, but
now with a centrosymmetric R22(24) ring flanked by two non-
centrosymmetric R22(8) rings (Fig. 8). The third C—Hꢀ ꢀ ꢀO
hydrogen bond here generates a centrosymmetric R22(6) ring,
and the combination of the these motifs generates a ribbon
running parallel to the [210] direction, with R22(6) rings centred
1
1
2
2
symmetry-related chain runs in the [110] direction.
In the second substructure in (VII), a single C—Hꢀ ꢀ ꢀN
hydrogen bond links molecules related by the c-glide plane at
y = 0.75 into a simple C(11) chain running parallel to the [201]
direction (Fig. 7). Finally, a rather weak C—Hꢀ ꢀ ꢀꢀ(arene)
hydrogen bond links molecules related by translation into a
chain running along [100]. The combination of the one-
dimensional substructures parallel to [100], [110], [110] and
[201] is sufficient to link the molecules into a single three-
dimensional framework.
Although the hydrogen-bonded supramolecular structure
of compound (VIII) is only two-dimensional, as opposed to
the three-dimensional structure found in compound (VII), it
1
1
at (2n, ꢃ n, ), alternating with R22(24) rings centred at
2
2
1
(ꢃ1 + 2n, 1 ꢃ n, ), where n represents an integer (Fig. 8).
2
ꢂ
o426 Castillo et al. Eight pyrazolo[3,4-d]oxazines
Acta Cryst. (2009). C65, o423–o430

organic compounds
Figure 7
A stereoview of part of the crystal structure of compound (VII), showing
the formation of a simple hydrogen-bonded C(11) chain along [201]. For
the sake of clarity, H atoms not involved in the motif shown have been
omitted.
Figure 9
A stereoview of part of the crystal structure of compound (VIII), showing
the formation of a hydrogen-bonded chain of rings running along [100].
For the sake of clarity, H atoms bonded to C atoms not involved in the
motif shown have been omitted.
there are no intermolecular hydrogen bonds, the conforma-
tions adopted by the benzyl unit are very similar. Similarly, in
the isomorphous pair of compounds (I) and (II), where the
chain-forming C—Hꢀ ꢀ ꢀO hydrogen bond does not involve the
benzyl unit, the overall conformations are very similar; the
C—Hꢀ ꢀ ꢀꢀ(arene) unit in compound (II), which is to be
regarded on geometric grounds as weak, appears to have little
influence on the molecular conformation. The structures of
compounds (VII) and (VIII) both contain a number of
hydrogen bonds which involve the benzyl unit, providing both
donors and acceptors in compound (VII) but only acceptors in
compound (VIII). While this gives rise to a distinct benzyl ring
orientation in compound (VIII), the conformation of
compound (VII) is not significantly different from those of
compounds (III) and (IV), where there are no direction-
specific interactions of any kind between the molecules.
Figure 8
A stereoview of part of the crystal structure of compound (VIII), showing
the formation of a hydrogen-bonded ribbon running along [210], and
containing three types of ring. For the sake of clarity, H atoms not
involved in the motif shown have been omitted.
Experimental
A mixture of the corresponding 5-arylmethylamino-3-tert-butyl-1-
phenyl-1H-pyrazole (0.29 mmol), ethanol (0.5 ml), acetic acid
(0.5 ml) and formaldehyde (0.9 mmol, as an aqueous solution) was
heated at 328 K for 10–16 h. After each reaction was complete, the
solvent was reduced to one-third of the initial volume, and the
resulting solid was collected by filtration and washed with cold
ethanol. The products thus obtained were crystallized from ethanol
except for (I) which was crystallized from hexane, to give colourless
crystals suitable for single-crystal X-ray diffraction. For (I): yield
81%, m.p. 405–406 K; MS (70 eV) m/z (%) = 347 (100) [M+],
316 (11), 302 (12), 256 (29), 228 (9), 91 (16), 77 (9) [Ph]; analysis
found: C 75.8, H 7.5, N 12.3%; C22H25N3O requires C 76.0, H 7.3, N
12.1%. For (II): yield 86%, m.p. 403–404 K; MS (70 eV) m/z (%) =
361 (51) [M+], 256 (16), 105 (100) [C8H9]; analysis found: C 76.2, H
7.5, N 11.5%; C23H27N3O requires C 76.4, H 7.5, N 11.6%. For (III):
yield 83%, m.p. 436–437 K; MS (70 eV) m/z (%) = 377 (10) [M+],
121 (100) [C8H9O]; analysis found: C 72.9, H 7.1, N 10.9%;
C23H27N3O2 requires C 73.2, H 7.2, N 11.1%. For (IV): yield 87%,
In the second substructure of compound (VIII), a combi-
nation of C—Hꢀ ꢀ ꢀO and C—Hꢀ ꢀ ꢀꢀ(arene) hydrogen bonds
generates a chain of edge-fused rings parallel to the [100]
direction, where centrosymmetric R22(6) rings centred at (n, 21,
12), where n represents an integer, formed by paired C—Hꢀ ꢀ ꢀO
hydrogen bonds alternate with centrosymmetric rings at (12 + n,
1
2
,
12) formed by paired C—Hꢀ ꢀ ꢀꢀ(arene) hydrogen bonds
(Fig. 9). The combination of the chains along [100] and the
ribbons along [210] generates a sheet parallel to (001).
The structures reported here illustrate the subtle and often
unpredictable interplay between intra- and intermolecular
forces, particularly the interplay between intermolecular
hydrogen bonding and molecular conformation, manifested
here in the orientation of the aryl ring in the benzyl unit
(Table 1). Thus, in compounds (III), (IV) and (VI), where
ꢂ
Acta Cryst. (2009). C65, o423–o430
Castillo et al.
Eight pyrazolo[3,4-d]oxazines o427

organic compounds
m.p. 425–426 K; MS (70 eV) m/z (%) = 415 (100) [M+], 370 (24),
170 (31), 159 (24) [C8H6F3]; analysis found: C 66.6, H 5.9, N 9.9%;
C23H24F3N3O requires C 66.5, H 5.8, N 10.1%. For (V): yield 79%,
m.p. 408–409 K; MS (70 eV) m/z (%) = 392 (100) [M+], 256 (41),
228 (24), 170 (25); analysis found: C 67.1, H 6.3, N 14.1%;
C22H24N4O3 requires C 67.3, H 6.2, N 14.3%. For (VI): yield 83%,
m.p. 385–386 K; MS (70 eV) m/z (%) = 407 (34) [M+], 151 (100)
[C9H11O2], 136 (81), 91 (21), 77 (10) [Ph]; analysis found: C 70.5, H
7.3, N 10.2%; C24H29N3O3 requires C 70.7, H 7.2, N 10.3%. For (VII):
yield 88%, m.p. 436–437 K; MS: (70 eV) m/z (%) = 391 (11) [M+],
135 (100) [C8H7O2]; analysis found: C 70.8, H 6.4, N 10.9%;
C23H25N3O3 requires C 70.6, H 6.4, N 10.7%. For (VIII): yield 79%,
m.p. 439–440 K; MS (70 eV) m/z (%) = 437 (5) [M+], 181 (100)
[C10H13O3]; analysis found: C 68.5, H 7.1, N 9.3%; C25H31N3O4
requires C 68.6, H 7.1, N 9.6%.
Compound (III)
Crystal data
3
˚
V = 1000.93 (4) A
Z = 2
Mo Kꢃ radiation
ꢄ = 0.08 mmꢃ1
T = 120 K
C23H27N3O2
Mr = 377.48
Monoclinic, P21
˚
a = 9.1888 (2) A
˚
b = 11.4499 (3) A
˚
c = 9.7210 (2) A
0.15 ꢄ 0.12 ꢄ 0.05 mm
ꢁ = 101.857 (1)ꢁ
Data collection
Bruker–Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.980, Tmax = 0.996
12855 measured reflections
2411 independent reflections
2237 reflections with I > 2ꢅ(I)
Rint = 0.036
Refinement
R[F2 > 2ꢅ(F2)] = 0.038
wR(F2) = 0.085
S = 1.19
2411 reflections
257 parameters
1 restraint
H-atom parameteꢃrs3 constrained
Compound (I)
˚
Crystal data
Áꢆmax = 0.17 e A
ꢃ3
˚
3
Áꢆmin = ꢃ0.20 e A
˚
C22H25N3O
V = 951.11 (18) A
Z = 2
Mr = 347.45
Monoclinic, P21
a = 8.8930 (10) A
b = 11.1321 (12) A
˚
c = 10.2078 (9) A
ꢁ = 109.749 (7)ꢁ
Mo Kꢃ radiation
ꢄ = 0.08 mmꢃ1
T = 120 K
˚
˚
Compound (IV)
0.41 ꢄ 0.25 ꢄ 0.22 mm
Crystal data
C23H24F3N3O
Mr = 415.45
Triclinic, P1
ꢇ = 67.162 (9)ꢁ
V = 1000.6 (2) A
Z = 2
Mo Kꢃ radiation
ꢄ = 0.11 mmꢃ1
T = 120 K
Data collection
3
˚
Bruker–Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.885, Tmax = 0.975
15738 measured reflections
2303 independent reflections
1768 reflections with I > 2ꢅ(I)
Rint = 0.057
˚
a = 9.0277 (11) A
˚
b = 9.8597 (12) A
˚
c = 12.6835 (18) A
ꢃ = 85.531 (11)ꢁ
ꢁ = 74.180 (11)ꢁ
0.27 ꢄ 0.17 ꢄ 0.14 mm
Refinement
R[F2 > 2ꢅ(F2)] = 0.043
wR(F2) = 0.103
S = 1.10
2303 reflections
239 parameters
1 restraint
H-atom parameteꢃrs3 constrained
Data collection
Bruker–Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.922, Tmax = 0.986
24473 measured reflections
4601 independent reflections
2336 reflections with I > 2ꢅ(I)
Rint = 0.099
˚
Áꢆmax = 0.20 e A
ꢃ3
˚
Áꢆmin = ꢃ0.26 e A
Refinement
Compound (II)
R[F2 > 2ꢅ(F2)] = 0.061
wR(F2) = 0.183
S = 1.04
274 parameters
H-atom parameteꢃrs3 constrained
Crystal data
˚
Áꢆmax = 0.33 e A
Áꢆmin = ꢃ0.37 e A
3
˚
V = 964.22 (15) A
Z = 2
Mo Kꢃ radiation
ꢄ = 0.08 mmꢃ1
T = 120 K
C23H27N3O
Mr = 361.48
Monoclinic, P21
ꢃ3
˚
4601 reflections
˚
a = 8.9500 (7) A
˚
b = 11.2146 (10) A
Compound (V)
˚
c = 10.0768 (9) A
0.32 ꢄ 0.22 ꢄ 0.15 mm
ꢁ = 107.572 (5)ꢁ
Crystal data
3
˚
V = 1930.3 (3) A
Z = 4
C22H24N4O3
Mr = 392.45
Data collection
Bruker–Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.957, Tmax = 0.989
15494 measured reflections
2323 independent reflections
1443 reflections with I > 2ꢅ(I)
Rint = 0.096
Monoclinic, P21=c
Mo Kꢃ radiation
ꢄ = 0.09 mmꢃ1
T = 120 K
0.33 ꢄ 0.22 ꢄ 0.18 mm
˚
a = 19.164 (2) A
˚
b = 8.7781 (7) A
˚
c = 11.7188 (12) A
ꢁ = 101.717 (10)ꢁ
Refinement
Data collection
R[F2 > 2ꢅ(F2)] = 0.052
wR(F2) = 0.149
S = 1.07
2323 reflections
249 parameters
1 restraint
H-atom parameteꢃrs3 constrained
Bruker–Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.917, Tmax = 0.984
27769 measured reflections
4417 independent reflections
2821 reflections with I > 2ꢅ(I)
Rint = 0.066
˚
Áꢆmax = 0.27 e A
ꢃ3
˚
Áꢆmin = ꢃ0.30 e A
ꢂ
o428 Castillo et al. Eight pyrazolo[3,4-d]oxazines
Acta Cryst. (2009). C65, o423–o430

organic compounds
Table 1
Conformational parameters (A, ) for compounds (I)–(VIII).
Refinement
ꢁ
˚
R[F2 > 2ꢅ(F2)] = 0.050
wR(F2) = 0.116
S = 1.09
265 parameters
H-atom parameteꢃrs3 constrained
Ring-puckering parameters
˚
Áꢆmax = 0.24 e A
ꢃ3
˚
4417 reflections
Áꢆmin = ꢃ0.29 e A
Q
ꢂ
’
(I)
(II)
(III)
(IV)
(V)
(VI)
(VII)
(VIII)
0.496 (3)
0.491 (4)
0.501 (2)
0.499 (3)
0.475 (2)
0.498 (3)
0.488 (3)
0.498 (2)
128.3 (3)
128.8 (5)
128.6 (2)
127.6 (3)
132.3 (2)
127.7 (3)
130.1 (4)
128.6 (2)
146.7 (4)
143.9 (7)
146.1 (3)
150.1 (4)
145.3 (3)
151.3 (4)
149.6 (4)
148.1 (2)
Compound (VI)
Crystal data
3
˚
V = 1065.63 (17) A
Z = 2
Mo Kꢃ radiation
ꢄ = 0.09 mmꢃ1
T = 120 K
C24H29N3O3
Mr = 407.50
Monoclinic, P21
a = 8.8268 (10) A
b = 11.6521 (10) A
˚
c = 10.3831 (7) A
ꢁ = 93.747 (9)ꢁ
˚
˚
Selected torsion angles
0.25 ꢄ 0.20 ꢄ 0.19 mm
A
B
C
D
(I)
(II)
(III)
(IV)
(V)
(VI)
(VII)
(VIII)
145.5 (2)
143.5 (4)
142.89 (19)
150.6 (2)
140.79 (17)
151.1 (2)
142.7 (2)
ꢃ14.8 (4)
ꢃ13.7 (5)
ꢃ19.9 (3)
ꢃ11.1 (4)
ꢃ11.8 (2)
ꢃ11.7 (4)
ꢃ21.5 (3)
ꢃ19.1 (2)
ꢃ67.5 (3)
ꢃ69.2 (5)
ꢃ71.6 (2)
ꢃ70.9 (3)
ꢃ75.3 (2)
ꢃ68.5 (3)
ꢃ71.8 (3)
ꢃ83.53 (16)
117.1 (3)
122.1 (4)
143.1 (2)
147.0 (3)
138.65 (18)
148.5 (3)
146.8 (2)
84.69 (18)
Data collection
Bruker–Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.972, Tmax = 0.984
17934 measured reflections
2560 independent reflections
2132 reflections with I > 2ꢅ(I)
Rint = 0.049
142.14 (15)
Notes: puckering parameters are calculated for the atom sequence O5—C4—C3a—
C7a—N7—C6. Torsion angles: A = N2—N1—C11—C12; B = N2—C3—C31—C32; C =
C6—N7—C77—C71; D = N7—C77—C71—C72.
Refinement
R[F2 > 2ꢅ(F2)] = 0.044
wR(F2) = 0.112
S = 1.13
2560 reflections
276 parameters
1 restraint
H-atom parameteꢃrs3 constrained
˚
Áꢆmax = 0.32 e A
ꢃ3
˚
Áꢆmin = ꢃ0.27 e A
Table 2
Hydrogen bonds and short intramolecular contacts (A, ) for compounds
(I)–(VIII).
ꢁ
˚
Cg1 represents the centroid of the C71–C76 ring.
Compound (VII)
Compound D—Hꢀ ꢀ ꢀA
D—H Hꢀ ꢀ ꢀA Dꢀ ꢀ ꢀA
D—Hꢀ ꢀ ꢀA
Crystal data
3
˚
V = 2004.7 (5) A
Z = 4
(I)
C12—H12ꢀ ꢀ ꢀN7
0.95
0.95
0.95
0.95
0.99
0.95
0.95
0.95
0.95
0.95
0.95
0.95
0.99
0.95
0.99
0.95
0.95
0.99
0.99
0.95
0.99
0.95
0.95
0.99
2.55
2.42
2.60
2.61
2.96
2.62
2.48
2.55
2.55
2.37
2.50
2.45
2.40
2.55
2.41
2.52
2.55
2.48
2.91
2.53
2.47
2.57
2.46
2.76
3.079 (4) 115
C23H25N3O3
Mr = 391.46
C15—H15ꢀ ꢀ ꢀO5i
C12—H12ꢀ ꢀ ꢀN7
C15—H15ꢀ ꢀ ꢀO5i
C4—H41ꢀ ꢀ ꢀCg1ii
C12—H12ꢀ ꢀ ꢀN7
C12—H12ꢀ ꢀ ꢀN7
C12—H12ꢀ ꢀ ꢀN7
C13—H13ꢀ ꢀ ꢀN2iii
C72—H72ꢀ ꢀ ꢀO41iv
C75—H75ꢀ ꢀ ꢀO5iii
C12—H12ꢀ ꢀ ꢀN7
C77—H772ꢀ ꢀ ꢀO72
C12—H12ꢀ ꢀ ꢀN7
C4—H42ꢀ ꢀ ꢀO73v
C72—H72ꢀ ꢀ ꢀO5v
C75—H75ꢀ ꢀ ꢀO74vi
C78—H781ꢀ ꢀ ꢀN2vii
C4—H41ꢀ ꢀ ꢀCg1viii
C12—H12ꢀ ꢀ ꢀN7
C4—H42ꢀ ꢀ ꢀO5ix
C13—H13ꢀ ꢀ ꢀO75x
C14—H14ꢀ ꢀ ꢀO74x
C6—H62ꢀ ꢀ ꢀCg1v
3.210 (3) 140
3.103 (5) 113
3.258 (5) 126
3.872 (5) 154
3.108 (3) 113
3.040 (4) 118
3.062 (3) 114
3.399 (2) 148
3.293 (3) 163
3.409 (2) 161
3.043 (4) 120
2.776 (4) 102
3.078 (3) 115
3.381 (4) 167
3.413 (3) 156
3.456 (4) 160
3.338 (4) 145
3.799 (3) 150
3.071 (2) 116
3.354 (2) 148
3.466 (2) 157
3.247 (2) 140
3.737 (2) 167
(II)
Monoclinic, P21=c
Mo Kꢃ radiation
ꢄ = 0.09 mmꢃ1
T = 120 K
0.38 ꢄ 0.12 ꢄ 0.08 mm
˚
a = 9.1164 (14) A
˚
b = 11.3303 (18) A
(III)
(IV)
(V)
˚
c = 19.694 (2) A
ꢁ = 99.775 (13)ꢁ
Data collection
Bruker–Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.977, Tmax = 0.993
28641 measured reflections
4592 independent reflections
2768 reflections with I > 2ꢅ(I)
Rint = 0.098
(VI)
(VII)
Refinement
R[F2 > 2ꢅ(F2)] = 0.069
wR(F2) = 0.165
S = 1.16
265 parameters
H-atom parameteꢃrs3 constrained
(VIII)
˚
Áꢆmax = 0.32 e A
ꢃ3
˚
4592 reflections
Áꢆmin = ꢃ0.49 e A
Symmetry codes: (i) x; y; ꢃ1 þ z; (ii) ꢃ1 þ x; y; z; (iii) x; 32 ꢃ y; 21 þ z; (iv) 1 ꢃ x; ꢃ þ y,
1
2
1
2
1
2
ꢃ z; (v) 1 ꢃ x; 1 ꢃ y; 1 ꢃ z; (vi) ꢃx; 2 ꢃ y; 1 ꢃ z; (vii) ꢃ1 þ x; 32 ꢃ y; ꢃ þ z; (viii)
Compound (VIII)
1 þ x; y; z; (ix) ꢃx; 1 ꢃ y; 1 ꢃ z; (x) 2 ꢃ x; ꢃy; 1 ꢃ z.
Crystal data
C25H31N3O4
Mr = 437.53
Triclinic, P1
ꢇ = 70.982 (8)ꢁ
V = 1089.8 (2) A
Z = 2
Mo Kꢃ radiation
ꢄ = 0.09 mmꢃ1
T = 120 K
3
˚
Data collection
˚
a = 9.8189 (10) A
Bruker–Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.958, Tmax = 0.987
30046 measured reflections
˚
b = 10.0499 (8) A
4970 independent reflections
3754 reflections with I > 2ꢅ(I)
Rint = 0.050
˚
c = 12.8130 (14) A
ꢃ = 68.710 (9)ꢁ
ꢁ = 72.537 (8)ꢁ
0.36 ꢄ 0.25 ꢄ 0.15 mm
ꢂ
Acta Cryst. (2009). C65, o423–o430
Castillo et al.
Eight pyrazolo[3,4-d]oxazines o429

organic compounds
´
(Junta de Andalucıa, Spain), the Universidad de Jaen (project
reference UJA_07_16_33), and Ministerio de Ciencia e Inno-
´
vacion (project reference SAF2008–04685-C02–02) for finan-
cial support.
´
Refinement
R[F2 > 2ꢅ(F2)] = 0.047
wR(F2) = 0.120
S = 1.07
295 parameters
H-atom parameteꢃrs3 constrained
˚
Áꢆmax = 0.24 e A
ꢃ3
˚
4970 reflections
Áꢆmin = ꢃ0.32 e A
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: FA3197). Services for accessing these data are
described at the back of the journal.
All H atoms were located in difference maps and then treated as
riding atoms in geometrically idealized positions, with C—H = 0.95
˚
(aromatic), 0.98 (CH3) or 0.99 A (CH2) and Uiso(H) = kUeq(C), where
k = 1.5 for methyl groups and 1.2 for all other H atoms. The methyl
groups were permitted to rotate about the adjacent C—X (X = C or
O) bonds but not to tilt. In the absence of significant resonant scat-
tering, the Flack x parameters (Flack, 1983) for compounds (I)–(III)
and (VI) were indeterminate; accordingly, the Friedel-equivalent
reflections were merged, and for these compounds it is not possible to
establish the absolute configurations of the molecules in the crystals
which were selected for data collection. For all compounds, the
reference molecules were selected to have the same absolute
configuration (see Figs. 1 and 2).
References
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EVALCCD (Duisenberg et al., 2003); program(s) used to solve
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publication: SHELXL97 and PLATON.
´
The authors thank Servicios Tecnicos de Investigacion of
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´
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´
¨
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CIAS and Universidad del Valle for financial support. JC
´ ´
thanks the Consejerıa de Innovacion, Ciencia y Empresa
ꢂ
o430 Castillo et al. Eight pyrazolo[3,4-d]oxazines
Acta Cryst. (2009). C65, o423–o430