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Acta Crystallogr C. 2009 September 15; 65(Pt 9): o441–o443.
Published online 2009 August 8. doi:  10.1107/S010827010902887X
PMCID: PMC2737423

2-Amino-3-methyl-6-[meth­yl­(phen­yl)­amino]-5-nitro­pyrimidin-4(3H)-one: polarized mol­ecules within hydrogen-bonded sheets

Abstract

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 mol­ecules are linked into sheets by a combination of N—H(...)O and N—H(...)π(arene) hydrogen bonds. Comparisons are made with the mol­ecular and supra­molecular structures of the precursor compound 2-amino-6-[meth­yl(phen­yl)amino]-5-nitro­pyrimidin-4(3H)-one.

Comment

We report here the structure of the title compound, (I) (Fig. 1 [triangle]), which was prepared by methyl­ation under basic conditions of the precursor (II), whose structure we reported previously (Rodríguez et al., 2007 [triangle]). 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 [triangle]), and have been regarded as candidates for anti-HIV-1 inhibitors (Di Braccio et al., 2001 [triangle]).

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Figure 1
The mol­ecular structure of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.

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) Å (for atom C4). Significant distortion from planarity is quite commonly observed in highly substituted pyrimidines (Low et al., 2007 [triangle]; Melguizo et al., 2003 [triangle]; Quesada et al., 2003 [triangle], 2004 [triangle]; Trilleras et al., 2007 [triangle], 2009 [triangle]; Cobo et al., 2008 [triangle]). The conformation of the mol­ecular skeleton can be defined in terms of just four torsion angles (Table 1 [triangle]), 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 [triangle], are −49.4 (5), 161.7 (4), −6.1 (5) and −51.5 (5)° (Rodríguez et al., 2007 [triangle]).

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Table 1
Selected geometric parameters (Å, °)

The bond distances within the substituted pyrimidine part of the mol­ecule show a number of unusual values (Table 1 [triangle]). 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 [triangle]) = 1.468 Å; lower quartile value = 1.460 Å], while the N—O distances are both somewhat long for their type (mean value = 1.210 Å; upper quartile value = 1.218 Å). 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).

The mol­ecules of compound (I) are linked into sheets by a combination of one N—H(...)π(arene) hydrogen bond and one N—H(...)O hydrogen bond (Table 2 [triangle]). Pairs of mol­ecules related by inversion are linked by the N—H(...)π(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, An external file that holds a picture, illustration, etc.
Object name is c-65-0o441-efi1.jpg, An external file that holds a picture, illustration, etc.
Object name is c-65-0o441-efi1.jpg), is directly linked by N—H(...)O hydrogen bonds to four further dimers, viz. those centred at (−An external file that holds a picture, illustration, etc.
Object name is c-65-0o441-efi1.jpg, 0, 0), (−An external file that holds a picture, illustration, etc.
Object name is c-65-0o441-efi1.jpg, 1, 0), (An external file that holds a picture, illustration, etc.
Object name is c-65-0o441-efi1.jpg, 0, 1) and (An external file that holds a picture, illustration, etc.
Object name is c-65-0o441-efi1.jpg, 1, 1), so that propagation by the space group of the two hydrogen bonds generates a thick sheet lying parallel to (10An external file that holds a picture, illustration, etc.
Object name is c-65-0o441-efi7.jpg) (Fig. 2 [triangle]). There are no direction-specific inter­actions between adjacent sheets; in particular, aromatic π–π stacking inter­actions are absent from the structure of (I).

Figure 2
A stereoview of part of the crystal structure of (I), showing the formation of a hydrogen-bonded sheet lying parallel to (10An external file that holds a picture, illustration, etc.
Object name is c-65-0o441-efi7.jpg). For the sake of clarity, H atoms bonded to C atoms have been omitted.
Table 2
Hydrogen-bond geometry (Å, °)

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 present in each crystal (Rodríguez et al., 2007 [triangle]). Although the mol­ecule of (II) contains three N—H bonds, only two of them are involved in hydrogen-bond formation. The supra­molecular aggregation of (II) in fact depends upon two independent three-centre N—H(...)(O)2 systems, which link mol­ecules related by a 21 screw axis into a ribbon of edge-fused rings containing rings of An external file that holds a picture, illustration, etc.
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Object name is c-65-0o441-efi9.jpg(6) and An external file that holds a picture, illustration, etc.
Object name is c-65-0o441-efi10.jpg(6) (Bernstein et al., 1995 [triangle]) 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).

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) 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 × 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 solution in dimethyl ­sulfoxide.

Crystal data

  • C12H13N5O3
  • M r = 275.27
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is c-65-0o441-efi11.jpg
  • a = 9.158 (2) Å
  • b = 12.178 (3) Å
  • c = 11.103 (2) Å
  • β = 105.207 (18)°
  • V = 1194.9 (5) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.11 mm−1
  • T = 120 K
  • 0.46 × 0.22 × 0.21 mm

Data collection

  • Bruker–Nonius KappaCCD diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 2003 [triangle]) T min = 0.942, T max = 0.976
  • 29059 measured reflections
  • 2743 independent reflections
  • 1816 reflections with I > 2σ(I)
  • R int = 0.057

Refinement

  • R[F 2 > 2σ(F 2)] = 0.050
  • wR(F 2) = 0.154
  • S = 1.08
  • 2743 reflections
  • 183 parameters
  • H-atom parameters constrained
  • Δρmax = 0.41 e Å−3
  • Δρmin = −0.37 e Å−3

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 Å (meth­yl) and N—H distances of 0.88 Å, and with U iso(H) = kU eq(carrier), where k = 1.5 for the methyl groups, which were permitted to rotate but not to tilt, and k = 1.2 for all other H atoms.

Data collection: COLLECT (Hooft, 1999 [triangle]); cell refinement: DIRAX/LSQ (Duisenberg et al., 2000 [triangle]); data reduction: EVALCCD (Duisenberg et al., 2003 [triangle]); program(s) used to solve structure: SIR2004 (Burla et al., 2005 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: PLATON (Spek, 2009 [triangle]); software used to prepare material for publication: SHELXL97 and PLATON.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S010827010902887X/dn3119sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S010827010902887X/dn3119Isup2.hkl

Acknowledgments

The authors thank ‘Servicios Técnicos de Investigación of Universidad de Jaén’ and the staff for the data collection. JC and MN thank the Consejería de Innovación, Ciencia y Empresa (Junta de Andalucía, Spain), the Universidad de Jaén (project reference UJA_07_16_33), and Ministerio de Ciencia e Innovación (project reference SAF2008-04685-C02-02) for financial support. RR thanks COLCIENCIAS and Universidad Nacional for financial support, and Fundación Carolina for a fellowship to carry out postgraduate studies at Universidad de Jaén.

Footnotes

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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Articles from Acta Crystallographica Section C: Crystal Structure Communications are provided here courtesy of International Union of Crystallography