Different hydrogen-bonded structures in the isomeric solvates 2-amino-6-anilino-4-methoxy-5-[(E)-4-nitro-benzylideneamino]pyrimidine dimethyl sulfoxide solvate and 2-amino-6-[methyl(phenyl)amino]-5-[(E)-4- nitrobenzylideneamino]-pyrimidin-4(3H)-one dimeth

Article abstract of DOI:10.1107/S0108270109004181

The title solvates, (I) and (II), both C18H16N6O3·C2H6OS, are isomeric. The conformations adopted by the 6-substituent are significantly different, with the 6-amino-phenyl unit remote from the nitro-phenyl ring in methoxy-pyrimidine (I) but adjacent to it

Full text of DOI:10.1107/S0108270109004181

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
[4,5-b][1,4]benzodiazepines using as the final key step a
Bischler–Napieralski cyclocondensation involving the reac-
tion of 2,5-diamino-4-anilino-6-methoxypyrimidine with acid
derivatives. We have now modified this procedure, replacing
the aromatic acid used previously (Cobo et al., 2008) with an
aromatic aldehyde, in the expectation of producing the
corresponding dihydropyrimidobenzo[4,5-b][1,4]diazepine
analogue. By the use of 4-nitrobenzaldehyde in the absence of
phosphoryl choride, so preventing the cyclization step, we
have isolated the intermediate Schiff bases 2-amino-6-anil-
ino-4-methoxy-5-[(E)-4-nitrobenzylideneamino]pyrimidine di-
methyl sulfoxide solvate, (I), and 2-amino-6-[methyl(phenyl)-
amino]-5-[(E)-4-nitrobenzylideneamino]pyrimidin-4(3H)-one
dimethyl sulfoxide solvate, (II), whose molecular and supra-
molecular structures we report here, both of them as stoi-
chiometric monosolvates with dimethyl sulfoxide. The Schiff
base components of the title solvates are isomeric, and they
were prepared by the acid-promoted condensation of
4-nitrobenzaldehyde with the isomeric heterocycles (A) for
the formation of (I) and (B) for the formation of (II).
ISSN 0108-2701
Different hydrogen-bonded structures
in the isomeric solvates 2-amino-
6-anilino-4-methoxy-5-[(E)-4-nitro-
benzylideneamino]pyrimidine
dimethyl sulfoxide solvate and
2-amino-6-[methyl(phenyl)amino]-
5-[(E)-4-nitrobenzylideneamino]-
pyrimidin-4(3H)-one dimethyl
sulfoxide solvate
a
a
a
´
Ricaurte Rodrıguez, ‡ Manuel Nogueras, Justo Cobo
and Christopher Glidewellb*
a
´
´
´
´
Departamento de Quımica Inorganica y Organica, Universidad de Jaen, 23071
Jaen, Spain, and bSchool of Chemistry, University of St Andrews, Fife KY16 9ST,
´
Scotland
Correspondence e-mail: cg@st-andrews.ac.uk
Received 3 February 2009
Accepted 4 February 2009
Online 25 February 2009
The title solvates, (I) and (II), both C18H16N6O3ꢀC2H6OS, are
isomeric. The conformations adopted by the 6-substituent are
significantly different, with the 6-aminophenyl unit remote
from the nitrophenyl ring in methoxypyrimidine (I) but
adjacent to it in pyrimidinone (II). Pairs of pyrimidine
molecules in (I) are linked by N—Hꢀ ꢀ ꢀN hydrogen bonds to
form cyclic centrosymmetric dimers from which the dimethyl
sulfoxide molecules are pendent, while in (II) a combination
of three independent N—Hꢀ ꢀ ꢀO hydrogen bonds links the
components into a chain containing both R22(8) and R24(8)
rings, in which the dimethyl sulfoxide component acts as a
double acceptor of hydrogen bonds. The significance of this
study lies in its observation of different conformations for
the pyrimidine components in (I) and (II), and different
hydrogen-bonded structures, apparently dominated by the
different roles adopted by the dimethyl sulfoxide components.
The molecular conformations can be defined in terms of a
rather small number of torsion angles (Table 1). These show
that the Schiff base backbone, running from amine atom N2 to
nitro atom N51, has the E configuration, and that it does not
deviate markedly from planarity. Similarly, the nitro group in
each compound deviates only a little from the plane of the
adjacent aryl ring, as does methoxy atom C41 in (I). On the
other hand, the substituent at N6 shows some differences
between (I) and (II), particularly in the location and orien-
tation of the C61–C66 aryl ring. The location of this ring
in (II) may be influenced both by the intramolecular
C—Hꢀ ꢀ ꢀꢀ(arene) interaction in the compound and, perhaps
Comment
Pyrimidodiazepines belong to the so-called bicyclic privileged
structures, which may be useful in the field of medicinal
chemistry (Horton et al., 2003). We have already reported the
´
preparations (Cobo et al., 2008) and structures (Rodrıguez et
al., 2008) of some 2-amino-6-aryl-4-methoxy-11H-pyrimido-
‡ Permanent address: Department of Chemistry, Universidad Nacional de
´
Colombia, Bogota, AA 14490, Colombia.
Acta Cryst. (2009). C65, o111–o114
doi:10.1107/S0108270109004181
# 2009 International Union of Crystallography o111

organic compounds
contrast, the structure of (II) contains
no N—Hꢀ ꢀ ꢀN hydrogen bonds, and sol-
vent atom O1 acts as a double acceptor
in N—Hꢀ ꢀ ꢀO hydrogen bonds (Table 2).
The reference atom O1 at (x, y, z)
accepts hydrogen bonds from atoms N2
at (x, y, z), via H21, and at (1 ꢁ x, 2 ꢁ y,
1 ꢁ z), via H22. The combined effect of
the three independent N—Hꢀ ꢀ ꢀO
hydrogen bonds is the formation of a
C33(12)[R22(8)][R24(8)] chain of rings
running parallel to the [010] direction,
in which the R22(8) rings formed by
paired amide units are centred at (12,
n + 12, 12 ), and the R24(8) rings are centred
at (12, n, 12 ) (in both cases, n represents an
integer; Fig. 3). There are no direction-
specific interactions between the four-
component aggregates in (I), or
between the chains in (II). The only
C—Hꢀ ꢀ ꢀꢀ interaction observed is the
intramolecular contact in (II) (Table 2).
The principal differences between the
hydrogen-bonded structures of (I) and
(II) arise from the nature of the
hydrogen bonds deployed and from the
role of the dimethyl sulfoxide compo-
Figure 1
The molecular components of (I), showing the atom-labelling scheme and the formation of a
centrosymmetric four-component aggregate containing pendent dimethyl sulfoxide units.
Displacement ellipsoids are drawn at the 30% probability level and atoms marked with A or B
are at the symmetry position (1 ꢁ x, 1 ꢁ y, 1 ꢁ z).
more significantly, by the necessity to locate the neighbouring
nents. The formation of an N—Hꢀ ꢀ ꢀN hydrogen bond with
pyrimidine ring atom N3, as found in (I), is not feasible in (II)
because N3 now carries a H atom; the alternative ring site N1
is very effectively shielded in (II) by the adjacent amine and
methyl substituents, while Schiff base atom N5 is shielded by
the C61–C66 aryl ring, so that formation of N—Hꢀ ꢀ ꢀN
hydrogen bonds is wholly impeded. On the other hand, in (II)
not only are there three N—H bonds readily available as
donors, but also atom O4 is available as a hydrogen-bond
acceptor. Finally, the dimethyl sulfoxide component acts only
as a single acceptor of hydrogen bonds in (I), and thus it plays
only a marginal role in the supramolecular aggregation,
possibly by simply filling space which would otherwise be
empty. In contrast, this component acts as a double acceptor in
(II), where it plays a key role in the chain formation, by acting
methyl group containing atom C67 away from the C51–C56
ring, in particular away from atom H56. The location of the
C61–C66 ring in (I) may be a consequence of the intra-
molecular N—Hꢀ ꢀ ꢀN interaction.
The Schiff base frameworks of (I) and (II) can be regarded
as chain-extended homologues of 4-nitroaniline, but, despite
the near planarity of these frameworks in both compounds,
the bond distances provide no evidence for any significant
polarization of the electronic structure, with its concomitant
development of quinonoid character in the nitroaryl ring, The
distances in both (I) and (II) show no significant deviations
from the expected values for unperturbed systems (Allen et
al., 1987). Although the development of such quinonoid
character is particularly marked in 4-nitroaniline itself (Qian
et al., 2006), it is scarcely apparent in the homologous 4-amino-
40-nitrobiphenyl, although more developed in the similarly
substituted biphenyl analogues where the two rings are
separated by acetylene spacer units (Graham et al., 1989).
In each compound, the two independent components are
linked within the selected asymmetric units (Figs. 1 and 2) by a
fairly short, and nearly linear, N—Hꢀ ꢀ ꢀO hydrogen bond
(Table 2). Despite this, the further linking of these bimolecular
aggregates differs significantly between the two compounds. In
(I), paired N—Hꢀ ꢀ ꢀN hydrogen bonds, having one of the
pyrimidine N atoms as the acceptor, form a centrosymmetric
R22(8) (Bernstein et al., 1995) motif, but there are no further
direction-specific intermolecular interactions. The hydrogen-
bonded structure thus consists of a four-component aggregate
(Fig. 1) whose overall graph-set descriptor is D33(9)[R22(8)]. By
Figure 2
The molecular components of (II), showing the atom-labelling scheme.
Displacement ellipsoids are drawn at the 30% probability level.
ꢂ
´
o112 Rodrıguez et al. C18H16N6O3ꢀC2H6OS
Acta Cryst. (2009). C65, o111–o114

organic compounds
Data collection
Bruker–Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.944, Tmax = 0.984
29080 measured reflections
4614 independent reflections
2569 reflections with I > 2ꢅ(I)
Rint = 0.089
Refinement
R[F2 > 2ꢅ(F2)] = 0.057
wR(F2) = 0.154
S = 1.05
283 parameters
H-atom parameteꢁrs3 constrained
˚
Áꢆmax = 0.38 e A
ꢁ3
˚
4614 reflections
Áꢆmin = ꢁ0.47 e A
Compound (II)
Crystal data
C18H16N6O3ꢀC2H6OS
ꢃ = 96.709 (8)ꢃ
3
˚
V = 992.0 (2) A
Z = 2
Mr = 442.50
Triclinic, P1
a = 10.2601 (8) A
Figure 3
˚
Mo Kꢁ radiation
ꢄ = 0.21 mmꢁ1
T = 120 (2) K
0.35 ꢄ 0.26 ꢄ 0.08 mm
A stereoview of part of the crystal structure of (II), showing the
formation of a hydrogen-bonded chain along [010] containing R22(8) and
R24(8) rings. For the sake of clarity, H atoms bonded to C atoms have been
omitted.
˚
b = 10.4555 (6) A
˚
c = 11.4537 (14) A
ꢁ = 113.230 (7)ꢃ
ꢂ = 112.295 (8)ꢃ
Data collection
as the sole link between R22(8) dimer units built from paired
N—Hꢀ ꢀ ꢀO C hydrogen bonds.
Bruker–Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.941, Tmax = 0.984
29046 measured reflections
4556 independent reflections
2896 reflections with I > 2ꢅ(I)
Rint = 0.074
Refinement
Experimental
R[F2 > 2ꢅ(F2)] = 0.057
wR(F2) = 0.161
S = 1.07
283 parameters
H-atom parameteꢁrs3 constrained
For the synthesis of (I), a mixture of 2,5-amino-6-anilino-4-meth-
oxypyrimidine (0.856 mmol) and 4-nitrobenzaldehyde (0.860 mmol)
was added to a mixture of methanol (10 ml) and acetic acid (0.5 ml),
and the resulting solution was stirred overnight (ca 12 h) at ambient
temperature. The resulting orange product, viz. 2-amino-6-anilino-4-
methoxy-5-[(E)-4-nitrobenzylideneamino]pyrimidine, was collected
by filtration, washed several times with water and then dried (yield
99%, m.p. 487–489 K). For the synthesis of (II), a mixture of 2,5-
diamino-6-[methyl(phenyl)amino]pyrimidin-4(3H)-one (0.822 mmol)
and 4-nitrobenzaldehyde (0.827 mmol) was added to a mixture of
methanol (10 ml) and acetic acid (0.5 ml), and the resulting solution
was stirred overnight (ca 12 h) at ambient temperature. The result-
ing dark-red product, viz. 2-amino-6-[methyl(phenyl)amino]-5-[(E)-
4-nitrobenzylideneamino]pyrimidin-4(3H)-one, was collected by
filtration, washed several times with water and then dried (yield 83%,
m.p. 510–512 K). Recrystallization of both compounds from dimethyl
sulfoxide gave crystals of the monosolvates suitable for single-crystal
X-ray diffraction.
˚
Áꢆmax = 0.40 e A
ꢁ3
˚
4556 reflections
Áꢆmin = ꢁ0.66 e A
Table 1
Selected torsion angles (ꢃ) for compounds (I) and (II).
(I)
(II)
N1—C6—N6—C61
C6—N6—C61—C62
C6—C5—N5—C57
C5—N5—C57—C51
N5—C57—C51—C52
C53—C54—N51—O51
N3—C4—O4—C41
5.2 (4)
179.6 (3)
176.2 (2)
178.7 (2)
172.1 (2)
5.1 (4)
ꢁ140.1
34.1 (4)
ꢁ178.0 (3)
176.8 (2)
165.6 (3)
3.4 (4)
ꢁ5.0 (4)
–
Table 2
Hydrogen bonds and short intramolecular contacts (A, ) for (I) and (II).
ꢃ
˚
Cg represents the centroid of the C61–C66 ring.
Compound (I)
Compound
(I)
D—Hꢀ ꢀ ꢀA
D—H
Hꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
D—Hꢀ ꢀ ꢀA
Crystal data
3
˚
N2—H21ꢀ ꢀ ꢀO1
N2—H22ꢀ ꢀ ꢀN3i
N6—H6ꢀ ꢀ ꢀN5
0.88
0.88
0.88
2.11
2.32
2.11
2.966 (3)
3.186 (3)
2.598 (3)
163
170
114
C18H16N6O3ꢀC2H6OS
V = 1005.9 (2) A
Z = 2
Mr = 442.50
Triclinic, P1
Mo Kꢁ radiation
ꢄ = 0.20 mmꢁ1
T = 120 (2) K
0.45 ꢄ 0.32 ꢄ 0.08 mm
˚
a = 8.0386 (8) A
b = 10.6862 (14) A
(II)
N2—H21ꢀ ꢀ ꢀO1
N2—H22ꢀ ꢀ ꢀO1ii
N3—H3ꢀ ꢀ ꢀO4i
C56—H56ꢀ ꢀ ꢀCg
0.88
0.88
0.88
0.95
2.07
2.15
1.86
2.46
2.949 (3)
2.935 (3)
2.739 (3)
3.397 (4)
175
148
176
168
˚
˚
c = 12.8856 (13) A
ꢁ = 71.007 (11)ꢃ
ꢂ = 74.463 (9)ꢃ
ꢃ = 88.672 (12)ꢃ
Symmetry codes: (i) ꢁx þ 1; ꢁy þ 1; ꢁz þ 1; (ii) ꢁx þ 1; ꢁy þ 2; ꢁz þ 1.
ꢂ
´
Acta Cryst. (2009). C65, o111–o114
Rodrıguez et al. C18H16N6O3ꢀC2H6OS o113

organic compounds
Crystals of (I) and (II) are triclinic; for each, the space group P1
was chose 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
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: SK3294). Services for accessing these data are
described at the back of the journal.
˚
(aromatic and methylidene) or 0.98 A (methyl) and N—H distances
˚
of 0.88 A, and with Uiso(H) = kUeq(carrier), where k = 1.5 for the
methyl groups and k = 1.2 for all other H atoms.
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The authors thank ‘Servicios Tecnicos de Investigacion of
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´
´
´
´
thanks the Consejerıa de Innovacion, Ciencia y Empresa
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´
´
reference UJA_07_16_33) and Ministerio de Ciencia e Inno-
´
vacion (project reference SAF2008-04685-C02-02) for finan-
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Nacional de Colombia for financial support, and Fundacion
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´
Universidad de Jaen.
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Acta Cryst. (2009). C65, o111–o114