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

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.

S1. 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 several years ago (Rodríguez 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).

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; Melguizo et al., 2003; Quesada et al., 2003, 2004; Trilleras et al., 2007, 2009; Cobo et al., 2008). The conformation of the molecular 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 the un-methylated compound (II), where the corresponding values of the key torsion angles, listed in the same order as given in Table 1, are -49.4 (5), 161.7 (4), -6.1 (5) and -51.5 (5)° (Rodríguez et al., 2007).

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 formally are 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 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; Cg represents the centroid of the C61–C66 ring). 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, 1/2, 1/2), is directly linked by N—H···O hydrogen bonds to four further dimers, those centred at (-1/2, 0, 0), (-1/2, 1, 0), (1/2, 0, 1) and (1/2, 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 π–π 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 present in each crystal (Rodríguez et al., 2007). 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 R¹₂(6), R²₁(6) and R²₂(6) (Bernstein 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).

Related literature

For related literature, see: Allen et al. (1987); Bernstein et al. (1995); Cobo et al. (2008); Di Braccio, Grossi, Roma, Vargiu, Mura & Marongiu (2001); Dlugosz & Machon (1990); Low et al. (2007); Melguizo et al. (2003); Quesada et al. (2003, 2004); Rodríguez et al. (2007); Trilleras et al. (2007, 2009).

S2. Experimental

Solid sodium hydroxide (2.85 mmol) was added to a solution of 2-amino-6-(N-methylanilino)-5-nitro-4(3H)-pyrimidinone (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 dimethylsulfate was added dropwise, following which the entire mixture was stirred overnight. The reaction mixture was poured onto 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 dimethylsulfoxide.

S3. Refinement

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 Å (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.

Computing details

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

Figures

	Fig. 1. The molecular structure of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. 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.

2-Amino-3-methyl-6-[methyl(phenyl)amino]-5-nitropyrimidin-4(3H)-one

Crystal data

C12H13N5O3	F(000) = 576
Mr = 275.27	Dx = 1.530 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 2743 reflections
a = 9.158 (2) Å	θ = 3.1–27.5°
b = 12.178 (3) Å	µ = 0.11 mm^−1
c = 11.103 (2) Å	T = 120 K
β = 105.207 (18)°	Block, colourless
V = 1194.9 (5) Å^3	0.46 × 0.22 × 0.21 mm
Z = 4

Data collection

Bruker–Nonius KappaCCD diffractometer	2743 independent reflections
Radiation source: Bruker-Nonius FR591 rotating anode	1816 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.057
Detector resolution: 9.091 pixels mm^-1	θmax = 27.5°, θmin = 3.1°
ϕ and ω scans	h = −11→11
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	k = −15→15
Tmin = 0.942, Tmax = 0.976	l = −14→14
29059 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.050	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.154	H-atom parameters constrained
S = 1.08	w = 1/[σ^2(Fo^2) + (0.0765P)^2 + 0.6383P] where P = (Fo^2 + 2Fc^2)/3
2743 reflections	(Δ/σ)max = 0.001
183 parameters	Δρmax = 0.41 e Å^−3
0 restraints	Δρmin = −0.37 e Å^−3

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
N1	0.1759 (2)	0.47934 (14)	0.40280 (16)	0.0228 (4)
C2	0.1998 (2)	0.40033 (17)	0.32896 (19)	0.0223 (5)
N3	0.3054 (2)	0.32090 (15)	0.36588 (16)	0.0237 (4)
C4	0.4036 (2)	0.32139 (17)	0.48588 (19)	0.0220 (5)
C5	0.3709 (2)	0.40218 (17)	0.56549 (18)	0.0218 (5)
C6	0.2581 (2)	0.48040 (17)	0.52184 (19)	0.0211 (5)
N21	0.1148 (2)	0.39955 (15)	0.21103 (16)	0.0259 (4)
H21	0.0457	0.4506	0.1851	0.031*
H22	0.1279	0.3480	0.1593	0.031*
C31	0.3418 (3)	0.2459 (2)	0.2744 (2)	0.0357 (6)
H31A	0.2530	0.2009	0.2364	0.053*
H31B	0.4260	0.1982	0.3164	0.053*
H31C	0.3707	0.2886	0.2095	0.053*
O41	0.51071 (17)	0.25681 (13)	0.51191 (14)	0.0287 (4)
N51	0.4768 (2)	0.41103 (15)	0.68542 (17)	0.0251 (4)
O51	0.5049 (2)	0.32873 (13)	0.75131 (15)	0.0352 (4)
O52	0.53541 (18)	0.50020 (13)	0.71759 (14)	0.0302 (4)
N61	0.2209 (2)	0.55972 (14)	0.59422 (16)	0.0228 (4)
C61	0.2429 (2)	0.54730 (18)	0.72536 (19)	0.0217 (5)
C62	0.1980 (2)	0.45233 (18)	0.7732 (2)	0.0249 (5)
H62	0.1554	0.3937	0.7189	0.030*
C63	0.2151 (3)	0.44235 (19)	0.9004 (2)	0.0298 (5)
H63	0.1841	0.3768	0.9330	0.036*
C64	0.2765 (3)	0.5267 (2)	0.9796 (2)	0.0317 (6)
H64	0.2890	0.5196	1.0669	0.038*
C65	0.3199 (3)	0.6215 (2)	0.9313 (2)	0.0324 (5)
H65	0.3618	0.6802	0.9857	0.039*
C66	0.3034 (3)	0.63213 (18)	0.8051 (2)	0.0278 (5)
H66	0.3338	0.6981	0.7728	0.033*
C67	0.1278 (3)	0.65095 (18)	0.5342 (2)	0.0273 (5)
H67A	0.1758	0.6866	0.4753	0.041*
H67B	0.1171	0.7041	0.5976	0.041*
H67C	0.0277	0.6237	0.4892	0.041*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0234 (9)	0.0252 (10)	0.0195 (9)	−0.0007 (7)	0.0050 (7)	0.0003 (7)
C2	0.0216 (10)	0.0255 (11)	0.0197 (10)	−0.0038 (9)	0.0056 (8)	0.0016 (9)
N3	0.0272 (10)	0.0240 (10)	0.0195 (9)	0.0007 (8)	0.0055 (8)	−0.0020 (7)
C4	0.0236 (11)	0.0234 (11)	0.0185 (10)	−0.0016 (9)	0.0046 (8)	0.0010 (8)
C5	0.0236 (11)	0.0237 (11)	0.0166 (10)	−0.0001 (9)	0.0024 (8)	0.0004 (8)
C6	0.0213 (10)	0.0218 (11)	0.0202 (10)	−0.0034 (8)	0.0055 (8)	0.0014 (8)
N21	0.0274 (10)	0.0290 (10)	0.0192 (9)	0.0022 (8)	0.0022 (8)	−0.0008 (8)
C31	0.0355 (14)	0.0411 (15)	0.0292 (12)	0.0027 (11)	0.0065 (11)	−0.0077 (11)
O41	0.0318 (9)	0.0302 (9)	0.0239 (8)	0.0088 (7)	0.0070 (7)	0.0008 (6)
N51	0.0255 (9)	0.0280 (10)	0.0210 (9)	0.0014 (8)	0.0050 (8)	−0.0017 (8)
O51	0.0445 (10)	0.0321 (9)	0.0248 (8)	0.0091 (8)	0.0012 (7)	0.0033 (7)
O52	0.0268 (8)	0.0348 (9)	0.0271 (9)	−0.0060 (7)	0.0036 (7)	−0.0049 (7)
N61	0.0279 (10)	0.0217 (9)	0.0185 (9)	0.0021 (7)	0.0055 (7)	0.0017 (7)
C61	0.0208 (10)	0.0250 (11)	0.0190 (10)	0.0012 (9)	0.0045 (8)	−0.0011 (8)
C62	0.0263 (11)	0.0244 (11)	0.0227 (11)	0.0002 (9)	0.0040 (9)	−0.0009 (9)
C63	0.0336 (12)	0.0299 (12)	0.0258 (12)	0.0044 (10)	0.0079 (10)	0.0049 (10)
C64	0.0317 (13)	0.0423 (14)	0.0204 (11)	0.0070 (11)	0.0053 (10)	0.0002 (10)
C65	0.0301 (12)	0.0383 (14)	0.0276 (12)	−0.0012 (11)	0.0051 (10)	−0.0113 (10)
C66	0.0296 (12)	0.0236 (11)	0.0305 (12)	−0.0038 (9)	0.0080 (10)	−0.0041 (9)
C67	0.0314 (12)	0.0246 (11)	0.0248 (11)	0.0035 (9)	0.0051 (9)	0.0025 (9)

Geometric parameters (Å, º)

N1—C2	1.319 (3)	C31—H31C	0.9800
C2—N3	1.353 (3)	N61—C61	1.425 (3)
N3—C4	1.398 (3)	N61—C67	1.452 (3)
C4—C5	1.406 (3)	C61—C66	1.379 (3)
C5—C6	1.395 (3)	C61—C62	1.380 (3)
C6—N1	1.339 (3)	C62—C63	1.385 (3)
C2—N21	1.336 (3)	C62—H62	0.9500
N3—C31	1.467 (3)	C63—C64	1.373 (3)
C4—O41	1.231 (3)	C63—H63	0.9500
C5—N51	1.431 (3)	C64—C65	1.375 (4)
N51—O51	1.228 (2)	C64—H64	0.9500
N51—O52	1.222 (2)	C65—C66	1.375 (3)
C6—N61	1.356 (3)	C65—H65	0.9500
N21—H21	0.8800	C66—H66	0.9500
N21—H22	0.8800	C67—H67A	0.9800
C31—H31A	0.9800	C67—H67B	0.9800
C31—H31B	0.9800	C67—H67C	0.9800
C2—N1—C6	118.58 (18)	C6—N61—C61	122.69 (17)
N1—C2—N21	117.72 (19)	C6—N61—C67	118.81 (17)
N1—C2—N3	123.72 (19)	C61—N61—C67	117.29 (17)
N21—C2—N3	118.56 (19)	C66—C61—C62	119.40 (19)
C2—N3—C4	121.03 (18)	C66—C61—N61	120.11 (19)
C2—N3—C31	120.61 (18)	C62—C61—N61	120.43 (19)
C4—N3—C31	117.13 (18)	C61—C62—C63	120.1 (2)
O41—C4—N3	119.64 (18)	C61—C62—H62	120.0
O41—C4—C5	126.0 (2)	C63—C62—H62	120.0
N3—C4—C5	114.33 (18)	C64—C63—C62	120.3 (2)
C6—C5—C4	121.31 (19)	C64—C63—H63	119.8
C6—C5—N51	122.09 (18)	C62—C63—H63	119.8
C4—C5—N51	115.67 (18)	C63—C64—C65	119.4 (2)
N1—C6—N61	115.35 (18)	C63—C64—H64	120.3
N1—C6—C5	120.67 (19)	C65—C64—H64	120.3
N61—C6—C5	123.96 (19)	C64—C65—C66	120.7 (2)
C2—N21—H21	120.0	C64—C65—H65	119.6
C2—N21—H22	120.0	C66—C65—H65	119.6
H21—N21—H22	120.0	C65—C66—C61	120.1 (2)
N3—C31—H31A	109.5	C65—C66—H66	119.9
N3—C31—H31B	109.5	C61—C66—H66	119.9
H31A—C31—H31B	109.5	N61—C67—H67A	109.5
N3—C31—H31C	109.5	N61—C67—H67B	109.5
H31A—C31—H31C	109.5	H67A—C67—H67B	109.5
H31B—C31—H31C	109.5	N61—C67—H67C	109.5
O52—N51—O51	122.95 (19)	H67A—C67—H67C	109.5
O52—N51—C5	118.51 (18)	H67B—C67—H67C	109.5
O51—N51—C5	118.54 (18)
C6—N1—C2—N21	178.88 (18)	C6—C5—N51—O52	−44.5 (3)
C6—N1—C2—N3	−1.4 (3)	C4—C5—N51—O52	124.5 (2)
N1—C2—N3—C4	−3.6 (3)	C6—C5—N51—O51	135.5 (2)
N21—C2—N3—C4	176.15 (18)	C4—C5—N51—O51	−55.4 (3)
N1—C2—N3—C31	−170.5 (2)	N1—C6—N61—C61	151.52 (19)
N21—C2—N3—C31	9.2 (3)	C5—C6—N61—C61	−26.9 (3)
C2—N3—C4—O41	−170.72 (19)	N1—C6—N61—C67	−15.6 (3)
C31—N3—C4—O41	−3.3 (3)	C5—C6—N61—C67	166.0 (2)
C2—N3—C4—C5	6.8 (3)	C6—N61—C61—C66	135.8 (2)
C31—N3—C4—C5	174.21 (19)	C67—N61—C61—C66	−56.9 (3)
O41—C4—C5—C6	171.7 (2)	C6—N61—C61—C62	−46.9 (3)
N3—C4—C5—C6	−5.7 (3)	C67—N61—C61—C62	120.4 (2)
O41—C4—C5—N51	2.5 (3)	C66—C61—C62—C63	−0.5 (3)
N3—C4—C5—N51	−174.84 (17)	N61—C61—C62—C63	−177.8 (2)
C2—N1—C6—N61	−175.99 (18)	C61—C62—C63—C64	0.0 (3)
C2—N1—C6—C5	2.5 (3)	C62—C63—C64—C65	0.5 (4)
C4—C5—C6—N1	1.2 (3)	C63—C64—C65—C66	−0.5 (4)
N51—C5—C6—N1	169.67 (19)	C64—C65—C66—C61	0.0 (4)
C4—C5—C6—N61	179.6 (2)	C62—C61—C66—C65	0.5 (3)
N51—C5—C6—N61	−12.0 (3)	N61—C61—C66—C65	177.9 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N21—H21···Cg^i	0.88	2.72	3.401 (2)	135
N21—H22···O41^ii	0.88	2.13	2.884 (2)	143

Symmetry codes: (i) −x, −y+1, −z+1; (ii) x−1/2, −y+1/2, z−1/2.