6-Amino-2-(3,4-di­methoxy­benzyl­amino)-3-methyl-5-nitro­so­pyrimidin-4(3H)-one: hydrogen-bonded sheets form interdigitated bilayers

Molecules of the title compound, C₁₄H₁₇N₅O₄, exhibit a highly polarized molecular-electronic structure. The mol­ecules are linked into sheets by two N-H...O hydrogen bonds [H...O = 2.03 and 2.02 Å, N...O = 2.836 (2) and 2.887 (2) Å, and N-H...O = 153 and 168°], augmented by a single C-H...O hydrogen bond [H...O = 2.47 Å, C...O = 3.403 (2) Å and C-H...O = 166°]. Pairs of sheets, related by inversion, form bilayers with interdigitated di­methoxy­benzyl substituents, weakly linked by a further C-H...O interaction [H...O = 2.50 Å, C...O = 3.350 (2) Å and C-H...O = 146°].

S1. Comment

The title compound, (I) (Fig. 1), has been prepared for use as an intermediate in the preparation of new heterocycles containing the pyrimidine nucleus. The bond distances in (I) (Table 1) show the pattern now familiar for compounds containing this type of substituted oxopyrimidinyl ring (Low et al., 2000; Low, Moreno et al., 2001; Low, Cannon et al., 2001; Low, Arranz, Cobo, Fontecha, Godino, López & Glidewell, 2001; Low, Arranz, Cobo, Fontecha, Godino, López, Cannon et al., 2001; Glidewell et al., 2002; Low et al., 2002). In particular, the sequence of four N—C bonds between atoms N2 and N4 all have similar lengths, so that it is not possible to describe the individual bonds in this sequence as being either single or double bonds; moreover, both of the exocyclic bonds in this sequence are much shorter than typical C(aryl)—NH₂ or C(aryl)—NHR distances (Allen et al., 1987). On the other hand, the distances C5—N5 and N5—O5 differ by less than 0.05 Å, whereas in simple neutral compounds where there is no possibility of significant electronic delocalization, these distances normally differ by at least 0.20 Å (Talberg, 1977; Schlemper et al., 1986) and the N—O distance rarely exceeds 1.25 Å (Davis et al., 1965; Bauer & Andreassen, 1972; Talberg, 1977; Schlemper et al., 1986). Finally, the C4—C5 and C5—C6 distances are very similar, with again no possibility of distinguishing here between single and double bonds. These observations, taken together. indicate the polarized form (Ia) as the dominant contributor to the overall molecular–electronic structure, at the expense of the classically localized form (I).

Within the dimethoxyphenyl fragment, the exocyclic C—C—O angles show the usual pattern observed for methoxyaryl compounds (Seip & Seip, 1973; Ferguson et al., 1996; Patterson et al., 1998), in which the C—C—O angles cisoid to the substituents are much larger than 120°, while those transoid are very much smaller. At the same time, the C—O—C angles are well in excess of tetrahedral values, consistent with the occurrence of repulsive interactions between the methyl groups and the neighbouring aryl C—H units.

The nitroso substituent is essentially coplanar with the pyrimidine ring, and the two methoxy groups are nearly coplanar with the aryl ring, while methylene atom C27 is also nearly coplanar with the pyrimidine ring; however, the torsion angles C2—N2—C27—C21 and N2—C27—C21—C22 (Table 1) indicate that the two ring systems are very far from being coplanar. Thus, while the molecule as a whole could adopt a conformation having mirror symmetry, it does not do so, and this may be a consequence of direction-specific intermolecular forces, in particular the hydrogen bonds.

Within the molecule of (I) there is an N—H···O hydrogen bond (Table 2), with the nitroso O atom acting as acceptor in the formation of an S(6) motif (Bernstein et al., 1995). The molecules are linked into sheets by two hard (Desiraju & Steiner, 1999) hydrogen bonds, both of the N—H···O type, augmented by a soft C—H···O hydrogen bond. Amino atom N4 in the molecule at (x, y, z) acts as hydrogen-bond donor, via H4A, to amide atom O6 in the molecule at (x, 1 + y, z), so generating by translation a C(6) chain running arallel to the [010] direction. In addition, amino atom N2 in the molecule at (x, y, z) acts as hydrogen-bond donor to nitroso atom O5 in the molecule at (x, 0.5 − y, 0.5 + z), while N2 at (x, 0.5 − y, 0.5 + z), in turn, acts as donor to O5 at (x, y, 1 + z), so producing a C(8) chain running parallel to the [001] direction and generated by the c-glide plane at y = 0.25. The formation of this [001] chain is reinforced by a C—H···O hydrogen bond, in which atom C26 at (x, y, z) acts as donor to amide atom O6 at (x, 0.5 − y, 0.5 + z). Hence, the [001] motif is better represented as a C(8) C(9)[R²₂(11)] chain of rings (Bernstein et al., 1995). The combination of the [010] and [001] chains generates a sheet parallel to (100), containing S(6), R²₂(11) and R³₅(21) rings, in the latter of which there are double acceptors (Fig. 2).

In the formation of the reference (100) sheet, the network formed by the hard hydrogen bonds is almost planar, lying in the domain 0.35 < x < 0.39, while the pendent dimethoxybenzyl substituents all lie on the same side of the sheet (Fig. 2). A second hydrogen-bonded network, related to the first by inversion, lies in the domain −0.39 < x < −0.35, with its dimethoxybenzyl substituents lying on the opposite side of this sheet. There is thus close interdigitation of the aryl substituents of these two sheets (Fig. 3), and a further C—H···O interaction (Table 2) may provide a weak link between the paired sheets. Atom C241 at (x, y, z) lies in a substituent pendent from the reference network in the domain 0.35 < x < 0.39, and it acts as hydrogen-bond donor to nitroso atom O5 in the molecule at (-x, 0.5 + y, 0.5 − z), which forms part of the hydrogen-bonded network in the domain −0.39 < x < −0.35. Hence, pairs of (100) sheets form interdigitated and weakly linked bilayers, but with no direction-specific interactions between adjacent bilayers (Fig. 3). There are no aromatic π–π-stacking interactions either within or between adjacent sheets.

It is of interest to note that while the nitroso atom O5 acts as a threefold acceptor of hydrogen bonds (Table 2), consistent with its highly anionic nature, and the amide atom O6 acts as a double acceptor. The two O atoms in the methoxy groups play no role whatsoever in the intermolecular aggregation.

S2. Experimental

A suspension of 6-amino-2-methoxy-3-methyl-5-nitrosopyrimidin-4(3H)-one (0.10 g, 0.543 mmol), 3,4-dimethoxybenzylamine (0.364 g, 2.18 mmol) and methanol (4 ml) was stirred at room temperature for 30 min. The pink solid formed was collected by filtration and washed with methanol (89% yield; m.p. 496 K). NMR: δ(H) (300 MHz, DMSO-d₆) 3.36 (3H, s), 3.71 (3H, s), 3.73 (3H, s), 4.55 (2H, s), 6.87 (1H, d, J = 9.0 Hz), 6.91 (1H, d, J = 9.0 Hz), 7.02 (1H, s), 8.31 (1H, d, J = 4.5 Hz, NH), 8.49 (1H, br s, NH), 10.89 (1H, d, J = 4.5 Hz, NH); δ(C) (75 MHz, DMSO-d₆) 27.4 (CH₂), 44.4 (CH₃—N), 55.5 and 55.6 (2 × CH₃—O), 111.6, 111.8, 119.8, 130.8, 142.1, 148.0, 148.6, 149.9, 154.5 and 161.6 (aromatic and heterocyclic). IR (cm⁻¹, KBr): 3335 (NH), 3200 (NH), 3180 (NH), 1681 (C═O), 1458 (N═O). MS (70 eV CI): m/e (%) 303 (92), 302 (87), 275 (32), 191 (21), 151 (100), 43 (40), 42 (41). Compound (I) could also be obtained in comparable yield from 6-amino-3-methyl-5-nitroso-2-methylthiopyrimidin-4(3H)-one, under similar reaction conditions. Crystals suitable for single-crystal X-ray diffraction were grown from a solution in DMSO.

S3. Refinement

Crystals of (I) are monoclinic and the space group P2₁/c was uniquely assigned from the systematic absences. All H atoms were treated as riding atoms, with C—H = 0.95 (aromatic), 0.98 (CH₃) or 0.99 Å (CH₂), and N—H = 0.88 Å.

Computing details

Data collection: KappaCCD Server Software (Nonius, 1997); cell refinement: DENZO–SMN (Otwinowski & Minor, 1997); data reduction: DENZO–SMN; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 and PRPKAPPA (Ferguson, 1999).

Figures

	Fig. 1. The molecule of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. Stereoview of part of the crystal structure of (I), showing the formation of a (100) sheet. For the sake of clarity, H atoms in methyl groups have been omitted.
	Fig. 3. Stereoview of part of the crystal structure of (I), showing the formation of interdigitated (100) bilayers.

6-Amino-2-(3,4-dimethoxybenzylamino)-3-methyl-5-nitroso-pyrimidin-4(3H)-one

Crystal data

C14H17N5O4	F(000) = 672
Mr = 319.33	Dx = 1.429 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 3378 reflections
a = 12.8488 (10) Å	θ = 3.0–27.4°
b = 7.4416 (10) Å	µ = 0.11 mm^−1
c = 16.962 (2) Å	T = 120 K
β = 113.728 (8)°	Block, pink
V = 1484.7 (3) Å^3	0.60 × 0.30 × 0.20 mm
Z = 4

Data collection

Nonius KappaCCD diffractometer	3378 independent reflections
Radiation source: rotating anode	2545 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.074
ϕ scans, and ω scans with κ offsets	θmax = 27.4°, θmin = 3.0°
Absorption correction: multi-scan (DENZO–SMN; Otwinowski & Minor, 1997)	h = −16→16
Tmin = 0.942, Tmax = 0.979	k = −9→8
22739 measured reflections	l = −21→21

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)] = 0.045	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.117	H-atom parameters constrained
S = 1.04	w = 1/[σ^2(Fo^2) + (0.0612P)^2 + 0.397P] where P = (Fo^2 + 2Fc^2)/3
3378 reflections	(Δ/σ)max < 0.001
211 parameters	Δρmax = 0.29 e Å^−3
0 restraints	Δρmin = −0.30 e Å^−3

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

	x	y	z	Uiso*/Ueq
O5	0.38137 (9)	0.34968 (14)	0.67339 (7)	0.0214 (2)
O6	0.37787 (10)	−0.04153 (14)	0.51094 (7)	0.0249 (3)
O23	−0.03951 (11)	0.74513 (18)	0.20514 (8)	0.0364 (3)
O24	−0.07906 (10)	0.80129 (16)	0.04642 (8)	0.0304 (3)
N1	0.36011 (11)	0.15896 (16)	0.40592 (8)	0.0188 (3)
N2	0.35439 (11)	0.36436 (16)	0.30223 (8)	0.0185 (3)
N3	0.35778 (10)	0.47540 (16)	0.42846 (8)	0.0178 (3)
N4	0.36632 (11)	0.58658 (16)	0.55531 (8)	0.0215 (3)
N5	0.38368 (11)	0.22268 (16)	0.62241 (8)	0.0194 (3)
C2	0.35747 (12)	0.33502 (18)	0.38003 (9)	0.0164 (3)
C4	0.36534 (12)	0.44606 (19)	0.50815 (9)	0.0176 (3)
C5	0.37418 (12)	0.26720 (19)	0.54363 (9)	0.0176 (3)
C6	0.37152 (12)	0.11596 (19)	0.48890 (9)	0.0187 (3)
C11	0.35491 (15)	0.0122 (2)	0.34696 (10)	0.0262 (4)
C21	0.23825 (13)	0.60791 (19)	0.20803 (10)	0.0191 (3)
C22	0.15443 (14)	0.6461 (2)	0.23842 (10)	0.0237 (3)
C23	0.04918 (14)	0.7062 (2)	0.18298 (11)	0.0252 (4)
C24	0.02595 (13)	0.7319 (2)	0.09518 (10)	0.0234 (3)
C25	0.10768 (14)	0.6908 (2)	0.06532 (10)	0.0239 (3)
C26	0.21395 (13)	0.6282 (2)	0.12188 (10)	0.0207 (3)
C27	0.35466 (13)	0.54514 (19)	0.26832 (10)	0.0198 (3)
C231	−0.02022 (18)	0.7212 (3)	0.29277 (13)	0.0422 (5)
C241	−0.10504 (15)	0.8221 (2)	−0.04285 (11)	0.0287 (4)
H2	0.3521	0.2714	0.2695	0.022*
H4A	0.3621	0.6955	0.5340	0.026*
H4B	0.3712	0.5718	0.6082	0.026*
H11A	0.2878	0.0274	0.2929	0.039*
H11B	0.3499	−0.1029	0.3733	0.039*
H11C	0.4235	0.0138	0.3351	0.039*
H22	0.1703	0.6304	0.2977	0.028*
H23A	0.0022	0.5965	0.3097	0.063*
H23B	−0.0901	0.7486	0.3006	0.063*
H23C	0.0406	0.8021	0.3286	0.063*
H24A	−0.1786	0.8825	−0.0708	0.043*
H24B	−0.1085	0.7036	−0.0690	0.043*
H24C	−0.0458	0.8945	−0.0502	0.043*
H25	0.0919	0.7049	0.0059	0.029*
H26	0.2700	0.5994	0.1006	0.025*
H27A	0.4056	0.5466	0.2374	0.024*
H27B	0.3857	0.6304	0.3171	0.024*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O5	0.0279 (6)	0.0190 (5)	0.0189 (5)	−0.0021 (4)	0.0112 (5)	−0.0023 (4)
O6	0.0372 (7)	0.0135 (5)	0.0277 (6)	0.0016 (4)	0.0170 (5)	0.0031 (4)
O23	0.0345 (7)	0.0488 (8)	0.0344 (7)	0.0158 (6)	0.0226 (6)	0.0145 (6)
O24	0.0253 (6)	0.0380 (7)	0.0270 (6)	0.0069 (5)	0.0094 (5)	0.0099 (5)
N1	0.0261 (7)	0.0127 (6)	0.0181 (6)	0.0011 (5)	0.0095 (5)	−0.0007 (5)
N2	0.0262 (7)	0.0129 (6)	0.0161 (6)	0.0019 (5)	0.0084 (5)	−0.0004 (4)
N3	0.0232 (7)	0.0139 (6)	0.0170 (6)	0.0011 (5)	0.0089 (5)	0.0007 (4)
N4	0.0343 (8)	0.0143 (6)	0.0195 (7)	0.0010 (5)	0.0145 (6)	0.0005 (5)
N5	0.0206 (7)	0.0194 (6)	0.0193 (7)	−0.0010 (5)	0.0093 (5)	−0.0001 (5)
C2	0.0154 (7)	0.0158 (7)	0.0171 (7)	0.0018 (5)	0.0055 (6)	0.0008 (5)
C4	0.0182 (7)	0.0157 (7)	0.0192 (7)	0.0000 (5)	0.0077 (6)	0.0001 (5)
C5	0.0190 (7)	0.0162 (7)	0.0177 (7)	0.0004 (5)	0.0074 (6)	0.0015 (5)
C6	0.0197 (7)	0.0163 (7)	0.0205 (8)	0.0003 (5)	0.0085 (6)	0.0021 (5)
C11	0.0421 (10)	0.0151 (7)	0.0228 (8)	0.0005 (6)	0.0145 (7)	−0.0033 (6)
C21	0.0242 (8)	0.0131 (7)	0.0205 (8)	−0.0009 (5)	0.0096 (6)	0.0005 (5)
C22	0.0307 (9)	0.0227 (8)	0.0207 (8)	0.0025 (6)	0.0133 (7)	0.0032 (6)
C23	0.0286 (9)	0.0241 (8)	0.0279 (9)	0.0037 (6)	0.0168 (7)	0.0049 (6)
C24	0.0227 (8)	0.0198 (8)	0.0252 (8)	0.0018 (6)	0.0071 (7)	0.0045 (6)
C25	0.0309 (9)	0.0218 (8)	0.0191 (8)	0.0020 (6)	0.0103 (7)	0.0029 (6)
C26	0.0273 (8)	0.0159 (7)	0.0226 (8)	0.0007 (6)	0.0139 (7)	0.0011 (6)
C27	0.0248 (8)	0.0167 (7)	0.0184 (7)	−0.0010 (6)	0.0092 (6)	0.0009 (5)
C231	0.0481 (12)	0.0526 (12)	0.0404 (11)	0.0216 (9)	0.0329 (10)	0.0183 (9)
C241	0.0261 (9)	0.0298 (9)	0.0250 (9)	−0.0014 (6)	0.0048 (7)	0.0053 (7)

Geometric parameters (Å, º)

N1—C2	1.378 (2)	C21—C22	1.397 (2)
C2—N3	1.328 (2)	C22—C23	1.375 (2)
N3—C4	1.334 (2)	C22—H22	0.95
C4—C5	1.446 (2)	C23—O23	1.367 (2)
C5—C6	1.451 (2)	C23—C24	1.409 (2)
C6—N1	1.392 (2)	O23—C231	1.416 (2)
N1—C11	1.464 (2)	C231—H23A	0.98
C2—N2	1.323 (2)	C231—H23B	0.98
C4—N4	1.314 (2)	C231—H23C	0.98
C5—N5	1.334 (2)	C24—O24	1.369 (2)
N5—O5	1.290 (2)	C24—C25	1.372 (2)
C6—O6	1.223 (2)	O24—C241	1.422 (2)
C11—H11A	0.98	C241—H24A	0.98
C11—H11B	0.98	C241—H24B	0.98
C11—H11C	0.98	C241—H24C	0.98
N2—C27	1.4636 (18)	C25—C26	1.396 (2)
N2—H2	0.88	C25—H25	0.95
C27—C21	1.507 (2)	C26—H26	0.95
C27—H27A	0.99	N4—H4A	0.88
C27—H27B	0.99	N4—H4B	0.88
C21—C26	1.374 (2)
C2—N1—C6	121.32 (12)	O23—C231—H23C	109.5
C2—N1—C11	120.21 (12)	H23A—C231—H23C	109.5
C6—N1—C11	118.44 (12)	H23B—C231—H23C	109.5
N1—C11—H11A	109.5	O24—C24—C23	115.33 (14)
N1—C11—H11B	109.5	O24—C24—C25	125.18 (15)
H11A—C11—H11B	109.5	C25—C24—C23	119.47 (14)
N1—C11—H11C	109.5	C24—O24—C241	115.88 (13)
H11A—C11—H11C	109.5	O24—C241—H24A	109.5
H11B—C11—H11C	109.5	O24—C241—H24B	109.5
N2—C2—N3	118.61 (13)	H24A—C241—H24B	109.5
N2—C2—N1	117.52 (13)	O24—C241—H24C	109.5
N3—C2—N1	123.87 (13)	H24A—C241—H24C	109.5
C2—N2—C27	122.69 (12)	H24B—C241—H24C	109.5
C2—N2—H2	118.7	C24—C25—C26	120.22 (14)
C27—N2—H2	118.7	C24—C25—H25	119.9
N2—C27—C21	113.14 (12)	C26—C25—H25	119.9
N2—C27—H27A	109.0	C21—C26—C25	120.56 (14)
C21—C27—H27A	109.0	C21—C26—H26	119.7
N2—C27—H27B	109.0	C25—C26—H26	119.7
C21—C27—H27B	109.0	C2—N3—C4	118.62 (12)
H27A—C27—H27B	107.8	N4—C4—N3	117.76 (13)
C26—C21—C22	119.39 (14)	N4—C4—C5	119.95 (13)
C26—C21—C27	119.63 (13)	N3—C4—C5	122.27 (13)
C22—C21—C27	120.98 (13)	C4—N4—H4A	120.0
C23—C22—C21	120.39 (14)	C4—N4—H4B	120.0
C23—C22—H22	119.8	H4A—N4—H4B	120.0
C21—C22—H22	119.8	N5—C5—C4	127.28 (13)
O23—C23—C22	125.47 (15)	N5—C5—C6	114.68 (12)
O23—C23—C24	114.61 (14)	C4—C5—C6	118.04 (13)
C22—C23—C24	119.92 (14)	O5—N5—C5	118.19 (12)
C23—O23—C231	116.67 (14)	O6—C6—N1	119.75 (13)
O23—C231—H23A	109.5	O6—C6—C5	124.50 (14)
O23—C231—H23B	109.5	N1—C6—C5	115.75 (12)
H23A—C231—H23B	109.5
C6—N1—C2—N2	175.41 (13)	C23—C24—C25—C26	−1.6 (2)
C11—N1—C2—N2	−2.4 (2)	C22—C21—C26—C25	1.7 (2)
C6—N1—C2—N3	−4.6 (2)	C27—C21—C26—C25	−178.27 (13)
C11—N1—C2—N3	177.53 (14)	C24—C25—C26—C21	−0.3 (2)
N3—C2—N2—C27	1.8 (2)	N2—C2—N3—C4	−177.43 (13)
N1—C2—N2—C27	−178.2 (2)	N1—C2—N3—C4	2.6 (2)
C2—N2—C27—C21	−100.4 (2)	C2—N3—C4—N4	179.54 (13)
N2—C27—C21—C26	−111.20 (15)	C2—N3—C4—C5	0.5 (2)
N2—C27—C21—C22	68.9 (2)	N4—C4—C5—N5	0.1 (2)
C26—C21—C22—C23	−1.1 (2)	N3—C4—C5—N5	179.02 (14)
C27—C21—C22—C23	178.88 (14)	N4—C4—C5—C6	179.36 (13)
C21—C22—C23—O23	178.99 (15)	N3—C4—C5—C6	−1.7 (2)
C21—C22—C23—C24	−0.8 (2)	C4—C5—N5—O5	2.4 (2)
C22—C23—O23—C231	0.1 (3)	C6—C5—N5—O5	−176.88 (12)
C24—C23—O23—C231	179.96 (16)	C2—N1—C6—O6	−177.27 (13)
O23—C23—C24—O24	3.6 (2)	C11—N1—C6—O6	0.6 (2)
C22—C23—C24—O24	−176.59 (14)	C2—N1—C6—C5	3.1 (2)
O23—C23—C24—C25	−177.69 (15)	C11—N1—C6—C5	−178.97 (13)
C22—C23—C24—C25	2.2 (2)	N5—C5—C6—O6	−0.4 (2)
C25—C24—O24—C241	3.4 (2)	C4—C5—C6—O6	−179.77 (14)
C23—C24—O24—C241	−177.92 (14)	N5—C5—C6—N1	179.18 (12)
O24—C24—C25—C26	177.05 (14)	C4—C5—C6—N1	−0.21 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O5^i	0.88	2.03	2.836 (2)	153
N4—H4A···O6^ii	0.88	2.02	2.887 (2)	168
N4—H4B···O5	0.88	1.96	2.616 (2)	130
C26—H26···O6^i	0.95	2.47	3.403 (2)	166
C241—H24A···O5^iii	0.98	2.50	3.350 (2)	146

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