2-Amino-3-methyl-6-[meth-yl-(phen-yl)-amino]-5-nitro-pyrimidin-4(3H)-one: Polarized mol-ecules within hydrogen-bonded sheets

Article abstract of DOI:10.1107/S010827010902887X

The pyrimidinone ring in the title compound, C12H13N5O3, is effectively planar, despite the presence of five substituents. The bond distances provide evidence for significant polarization of the electronic structure, with charge separation, and the mol-ec

Full text of DOI:10.1107/S010827010902887X

organic compounds
Acta Crystallographica Section C
Crystal Structure
Despite the high degree of substitution of the pyrimidine
ring in (I), this ring is effectively planar, with a maximum
˚
deviation from the mean plane of only 0.038 (2) A (for atom
Communications
ISSN 0108-2701
C4). Significant distortion from planarity is quite commonly
observed in highly substituted pyrimidines (Low et al., 2007;
Melguizo et al., 2003; Quesada et al., 2003, 2004; Trilleras et al.,
2007, 2009; Cobo et al., 2008). The conformation of the mol-
ecular skeleton can be defined in terms of just four torsion
angles (Table 1), which show that both the nitro group and
the phenyl ring deviate significantly from the plane of the
pyrimidine ring; the dihedral angles between the pyrimidine
ring and the nitro and phenyl groups are, respectively, 49.8 (2)
and 64.0 (2)ꢁ. The molecules of (I) thus have no internal
symmetry so that, as crystallized, they are conformationally
chiral; the centrosymmetric space group accommodates equal
numbers of the two conformational enantiomers. The overall
conformation of (I) is remarkably similar to that of un-
methylated compound (II), where the corresponding values of
the key torsion angles, listed in the same order as given in
Table 1, are ꢂ49.4 (5), 161.7 (4), ꢂ6.1 (5) and ꢂ51.5 (5)ꢁ
2-Amino-3-methyl-6-[methyl(phenyl)-
amino]-5-nitropyrimidin-4(3H)-one:
polarized molecules within hydrogen-
bonded sheets
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 13 July 2009
Accepted 21 July 2009
Online 8 August 2009
´
(Rodrıguez et al., 2007).
The pyrimidinone ring in the title compound, C12H13N5O3, is
effectively planar, despite the presence of five substituents.
The bond distances provide evidence for significant polariza-
tion of the electronic structure, with charge separation, and
the molecules are linked into sheets by a combination of
N—Hꢀ ꢀ ꢀO and N—Hꢀ ꢀ ꢀꢀ(arene) hydrogen bonds. Compar-
isons are made with the molecular and supramolecular
structures of the precursor compound 2-amino-6-[methyl-
(phenyl)amino]-5-nitropyrimidin-4(3H)-one.
The bond distances within the substituted pyrimidine part
of the molecule show a number of unusual values (Table 1).
Firstly, the C4—C5 and C5—C6 bonds, which are formally
single and double bonds, respectively, have almost identical
lengths. Secondly, the C5—N51 distance is short for its type
˚
[mean value (Allen et al., 1987) = 1.468 A; lower quartile
˚
value = 1.460 A], while the N—O distances are both somewhat
˚
long for their type (mean value = 1.210 A; upper quartile value
˚
= 1.218 A). Thirdly, the four C—N distances between atoms
N21 and N61 span a fairly small range, despite one of them
being formally a double bond and the rest of them single
bonds. These observations taken together indicate that the
polarized forms (Ia) and (Ib) (see scheme) are both significant
contributors to the overall electronic structure, in addition to
the localized form (I).
Comment
We report here the structure of the title compound, (I) (Fig. 1),
which was prepared by methylation under basic conditions of
the precursor (II), whose structure we reported previously
´
(Rodrıguez et al., 2007). Compounds (I) and (II) have both
been prepared as potential intermediates for the synthesis of
benzo-fused pyrimidine derivatives which resemble the well
known benzodiazepines, and which have also shown related
pharmacological properties, as anti-anxiety or antidepressive
agents (Dlugosz & Machon, 1990), and have been regarded as
candidates for anti-HIV-1 inhibitors (Di Braccio et al., 2001).
Figure 1
The molecular structure of (I), showing the atom-labelling scheme.
Displacement ellipsoids are drawn at the 30% probability level.
‡ Permanent address: Department of Chemistry, Universidad Nacional de
´
Colombia, Bogota AA 14490, Colombia.
Acta Cryst. (2009). C65, o441–o443
doi:10.1107/S010827010902887X
# 2009 International Union of Crystallography o441

organic compounds
in dimethylformamide (25 ml). This mixture was heated at 363 K for a
period of 1 h and then held at 333 K while one equivalent of dimethyl
sulfate was added dropwise, following which the entire mixture was
stirred overnight. The reaction mixture was poured on to ice–water
(100 ml) and neutralized with 20% aqueous hydrochloric acid. The
resulting solution was extracted with ethyl acetate (4 ꢃ 20 ml), and
the combined organic extracts were dried over anhydrous sodium
sulfate. Subsequent removal of the solvent under reduced pressure
gave the title compound (yield 97%, m.p. 549–551 K). Crystals
suitable for single-crystal X-ray diffraction were grown from a solu-
tion in dimethyl sulfoxide.
Crystal data
3
˚
C12H13N5O3
Mr = 275.27
V = 1194.9 (5) A
Z = 4
Monoclinic, P21=n
Mo Kꢂ radiation
ꢃ = 0.11 mmꢂ1
T = 120 K
0.46 ꢃ 0.22 ꢃ 0.21 mm
˚
a = 9.158 (2) A
˚
Figure 2
b = 12.178 (3) A
˚
A stereoview of part of the crystal structure of (I), showing the formation
of a hydrogen-bonded sheet lying parallel to (101). For the sake of clarity,
H atoms bonded to C atoms have been omitted.
c = 11.103 (2) A
ꢁ = 105.207 (18)ꢁ
Data collection
Bruker–Nonius KappaCCD
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.942, Tmax = 0.976
29059 measured reflections
2743 independent reflections
1816 reflections with I > 2ꢄ(I)
Rint = 0.057
The molecules of compound (I) are linked into sheets by a
combination of one N—Hꢀ ꢀ ꢀꢀ(arene) hydrogen bond and one
N—Hꢀ ꢀ ꢀO hydrogen bond (Table 2). Pairs of molecules
related by inversion are linked by the N—Hꢀ ꢀ ꢀꢀ(arene)
hydrogen bond to form a centrosymmetric dimer unit and this
dimer can conveniently be regarded as the basic building
block from which the hydrogen-bonded sheet is constructed.
This reference dimer unit, centred at (0, 12, 21 ), is directly linked
by N—Hꢀ ꢀ ꢀO hydrogen bonds to four further dimers, viz.
Refinement
R[F2 > 2ꢄ(F2)] = 0.050
wR(F2) = 0.154
S = 1.08
183 parameters
H-atom parameteꢂrs3 constrained
˚
Áꢅmax = 0.41 e A
Áꢅmin = ꢂ0.37 e A
ꢂ3
˚
2743 reflections
1
2
1
2
those centred at (ꢂ , 0, 0), (ꢂ , 1, 0), (12, 0, 1) and (21, 1, 1), so
that propagation by the space group of the two hydrogen
bonds generates a thick sheet lying parallel to (101) (Fig. 2).
There are no direction-specific interactions between adjacent
sheets; in particular, aromatic ꢀ–ꢀ stacking interactions are
absent from the structure of (I).
Despite the close similarities between the conformations of
(I) and (II) and thus the overall molecular shapes, these
compounds have different crystallization properties. While (I)
crystallizes in the centrosymmetric space group P21/n with
both conformational enantiomers present, (II) crystallizes in
the Sohnke space group P212121 with just a single enantiomer
Table 1
Selected geometric parameters (A, ).
ꢁ
˚
N1—C2
C2—N3
N3—C4
C4—C5
C5—C6
C6—N1
1.319 (3)
1.353 (3)
1.398 (3)
1.406 (3)
1.395 (3)
1.339 (3)
C2—N21
C4—O41
C5—N51
N51—O51
N51—O52
C6—N61
1.336 (3)
1.231 (3)
1.431 (3)
1.228 (2)
1.222 (2)
1.356 (3)
C4—C5—N51—O51
N1—C6—N61—C61
ꢂ55.4 (3)
N1—C6—N61—C67
C6—N61—C61—C62
ꢂ15.6 (3)
ꢂ46.9 (3)
151.52 (19)
´
present in each crystal (Rodrıguez et al., 2007). Although the
Table 2
Hydrogen-bond geometry (A, ).
molecule of (II) contains three N—H bonds, only two of them
are involved in hydrogen-bond formation. The supra-
molecular aggregation of (II) in fact depends upon two
independent three-centre N—Hꢀ ꢀ ꢀ(O)2 systems, which link
molecules related by a 21 screw axis into a ribbon of edge-
fused rings containing rings of R12(6), R12(6) and R22(6) (Bern-
stein et al., 1995) types. Thus, although the molecule of (II)
participates in more N—H bonds than that of (I), the
hydrogen-bonded aggregation in (II) is one-dimensional, as
opposed to two-dimensional in compound (I).
ꢁ
˚
Cg represents the centroid of the C61–C66 ring.
D—Hꢀ ꢀ ꢀA
D—H
Hꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
D—Hꢀ ꢀ ꢀA
N21—H21ꢀ ꢀ ꢀCgi
0.88
0.88
2.72
2.13
3.401 (2)
2.884 (2)
135
143
N21—H22ꢀ ꢀ ꢀO41ii
1
2
1
2
1
2
Symmetry codes: (i) ꢂx; ꢂy þ 1; ꢂz þ 1; (ii) x ꢂ ; ꢂy þ ; z ꢂ .
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 (aromatic) 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
Experimental
Solid sodium hydroxide (2.85 mmol) was added to a solution of
2-amino-6-(N-methylanilino)-5-nitropyrimidin-4(3H)-one (2.37 mmol)
methyl groups, which were permitted to rotate but not to tilt, and k =
1.2 for all other H atoms.
ꢄ
´
o442 Rodrıguez et al. C12H13N5O3
Acta Cryst. (2009). C65, o441–o443

organic compounds
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´
The authors thank ‘Servicios Tecnicos de Investigacion of
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´
´
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and MN thank the Consejerıa de Innovacion, Ciencia y
Empresa (Junta de Andalucıa, Spain), the Universidad de
´
´
´
Jaen (project reference UJA_07_16_33), and Ministerio de
Ciencia e Innovacion (project reference SAF2008-04685-C02-
´
02) for financial support. RR thanks COLCIENCIAS and
´
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Supplementary data for this paper are available from the IUCr electronic
archives (Reference: DN3119). Services for accessing these data are
described at the back of the journal.
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Acta Cryst. (2009). C65, o441–o443
Rodrıguez et al. C12H13N5O3 o443