2-Amino-4,6-bis(benzyloxy)-5-nitrosopyrimidine: chains built from three-centre N-H...(N,O) and N-H...[pi](arene) hydrogen bonds

The molecules of the title compound, C₁₈H₁₆N₄O₃, exhibit a very polarized molecular-electronic structure. The mol­ecules are linked into chains by a combination of an asymmetric three-centre N-H...(N,O) hydrogen bond [H...N 2.19, H...O 2.54, N...N 3.041 (4) and N...O 2.977 (4) Å, and N-H...N 168, N-H...O 112 and N...H...O 67°] and an N-H...[pi](arene) interaction [H...Cg 2.67 Å, N...Cg 3.496 (4) Å and N-H...Cg 163°; Cg is a benzyl ring centroid].

S1. Comment

We recently reported the molecular and supramolecular structures of a number of 2-amino-benzyloxy-5-nitrosopyrimidines (Quesada et al., 2002). The majority of the compounds in that study contained a 4-amino substituent, derived either from a simple primary amine or from an amino-acid ester. Here, we report the structure of the title compound, (I), an example containing an unsubstituted 2-amino group and a 4-benzyloxy substituent, and we compare the conformation, molecular dimensions and supramolecular aggregation of (I) with those of the related compounds, (II) and (III) (Quesada et al., 2002). \sch

In compound (I) (Fig. 1), the N—C—O—C and C—O—C—C torsion angles (Table 1) defining the orientation of the benzyloxy groups are very similar for the two independent substituents, and indicate that atoms C41, C47, C61 and C67 all lie close to the plane defined by the pyrimidine ring, with both benzyl groups oriented remote from the nitrosyl substituent. The torsion angles around the C41—C47 and C61—C67 bonds are, however, entirely different. In compound (II), for comparison, the two independent N—C—O—C torsion angles indicate a different conformation, which does not even approximately manifest the potential twofold rotation symmetry available to molecules of (II), although atoms C41, C47, C61 and C67 are again close to the plane of the pyrimidine. In (III), the N—C—O—C angles resemble those in (I), but the C6—O6—C67—C61 torsion angle is unlike any of the other analogous angles in this series. In this connection, it is interesting to note that, in compound (IV) (Low et al., 2002), the conformation of the alkoxy substituents is similar to that in (II).

The C2—N2, N3—C4 and C6—N1 bond distances (Table 2) in (I) are all short for their types (Allen et al., 1987). These distances and those in the C-nitroso fragment point to the charge-separated form, (Ia), as an important contributor to the overall molecular-electronic structure, as generally found for substituted 2-amino-5-nitrosopyrimidines (Low et al., 2000; Quesada et al., 2002). By contrast, when the 5-nitroso group is absent, as in (II) and (IV), there is no geometric evidence for any significant polarization of the electronic structure.

The supramolecular aggregation in (I) (Table 3) involves both conventional hydrogen bonds and an N—H···π(arene) hydrogen bond, now a well recognized intermolecular interaction (Malone et al., 1997; Braga et al., 1998). The amino atom N2 in the molecule at (x, y, z) acts as a hydrogen-bond donor, via atom H2A, to nitrosyl atom N5 in the molecule at (x, y - 1, z), so generating by translation a C(7) chain parallel to [010] (Fig. 2). Both the donor atom, N2, and the acceptor atom, N5, in this hydrogen bond carry significant partial charges, and hence this interaction is an example of a resonance-assisted hydrogen bond (Gilli et al., 1994). The same atom H2A at (x, y, z) also makes a rather long contact with atom O4 in the molecule at (x, y - 1, z), so forming a very asymmetric three-centre N—H···(N, O) hydrogen bond, but the H···O contact may well be more adventitious than significant. The other H atom of the amino group, H2B, does not form a conventional hard (Braga et al., 1995) hydrogen bond, but instead forms a nearly linear N—H···π(arene) contact with the centroid, Cg2, of the C41—C46 phenyl ring in the molecule at (x, y - 1, z) (Fig. 2), so that all three contacts may be mutually cooperative.

In view of the N—H···π(arene) interaction found in (I), we have reviewed the supramolecular structures of other substituted 2-amino-6-benzyloxy-5-nitrosopyrimidines (Quesada et al., 2002), and we have now, indeed, identified N—H···π(arene) interactions in three such compounds, (V)-(VII) (Figs. 3–5). In compound (V) (Fig. 3), the amino groups in both independent molecules participate in exactly the same type of asymmetric three-centre N—H···(N,O) hydrogen bond as found in (I), together with an N—H···π(arene) interaction with the centroids Cg1 and Cg2 of the adjacent O6-benzyl rings [for type 1 molecules, H···Cg1ⁱⁱ 2.61 Å, N···Cg1ⁱⁱ 3.418 (2) Å and N—H···Cg1ⁱⁱ 153°; for type 2 molecules, H···Cg2ⁱⁱⁱ 2.50 Å, N···Cgⁱⁱⁱ 3.318 (2) Å and N—H···Cg2ⁱⁱⁱ 156°; symmetry codes: (ii) -3/2 - x, y - 1/2, 1/2 - z Query initial minus; (iii) 5/2 - x, 1/2 + y, 1/2 - z].

In the P₁ polymorph (Quesada et al., 2002) of compound (VI) (Fig. 4), while the hard intermolecular hydrogen bonds formed by each of the two independent molecules are of the two-centre N—H···N type, there are again N—H···π(arene) interactions with the ring centroids, Cg3 and Cg4, in the adjacent benzyl groups [for type 1 molecules, H···Cg3^iv 2.79 Å, N···Cg3^iv 3.621 (4) Å and N—H···Cg3^iv 158°; for type 2 molecules, H···Cg4^v 2.68 Å, N···Cg4^v 3.546 (4) Å and N—H···Cg4^v 170°; symmetry codes: (iv) 1 + x, y, z; (v) x - 1, y, z].

Compound (VII), where Z' = 1, exhibits the same type of asymmetric three-centre N—H···(N,O) hydrogen bonds as found in both (I) and (V), but here the corresponding N—H···Cg5 contact (Fig. 5) is long, although still close to linear [H···Cg5^iv 2.91 Å, N···Cg5^iv 3.748 (3) Å and N—H···Cg5^iv 161°; symmetry code: (iv) 1 + x, y, z].

In all of these examples, the multiple intermolecular contacts appear to be mutually cooperative. However, it is clear that the distinction between genuine attractive interactions and adventitious contacts, or near contacts, is not easy to judge. Nonetheless, the conformation of the benzyloxy group involved in each such putative interaction, which effectively prevents access of any other acceptor to the NH bond in question, is suggestive.

S2. Experimental

A sample of (I) was synthesized following the published method of Quesada et al. (2000) and Marchal et al. (2002). Compound (IV) (ex Aldrich) was converted to (II) by reaction of sodium benzylate in toluene, and (II) was then nitrosated with isoamyl nitrite in dimethylsulfoxide solution at room temperature. Crystals of (I) for single-crystal X-ray diffraction were grown by slow evaporation of a solution in acetone.

S3. Refinement

Compound (I) crystallized in the monoclinic system; space group P2₁/c was uniquely assigned from the systematic absences. H atoms were treated as riding atoms, with C—H = 0.93–0.97 Å and N—H = 0.86 Å. The data were collected at 298 (2) K, where the proportion of data labelled observed is only 0.31, because all attempts to cool the crystals caused irreversible damage; this may underlie the high R_int value and the comparatively low precision in the refined structure.

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, 2002); software used to prepare material for publication: SHELXL97 and PRPKAPPA (Ferguson, 1999).

Figures

	Fig. 1. A view of the molecule of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. Part of the crystal structure of (I), showing formation of a chain along [010]. For the sake of clarity, the unit-cell box has been omitted. The atoms marked with an asterisk (*) or a hash sign (#) are at the symmetry positions (x, y - 1, z) and (x, 1 + y, z), respectively.
	Fig. 3. Part of the crystal structure of (V), showing the hard hydrogen bonds and the N—H···π(arene) interaction formed by type 1 molecules. The atoms marked with an asterisk (*) or a hash sign (#) are at the symmetry positions (3/2 - x, y - 1/2, 1/2 - z) and (x, y - 1, z), respectively.
	Fig. 4. Part of the crystal structure of (VI), showing the N—H···N hydrogen bond and the N—H···π(arene) interaction formed by type 1 molecules. The atoms marked with an asterisk (*) or a hash sign (#) are at the symmetry positions (1 + x, y, z) and (x - 1, y, z), respectively.
	Fig. 5. Part of the crystal structure of (VII), showing the hard hydrogen bonds and the long N—H···π(arene) contact. The atoms marked with an asterisk (*) or a hash sign (#) are at the symmetry positions (1 + x, y, z) and (x - 1, y, z), respectively.

2-Amino-4,6-bis(benzyloxy)-5-nitrosopyrimidine

Crystal data

C18H16N4O3	F(000) = 704
Mr = 336.35	Dx = 1.285 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 3895 reflections
a = 11.0731 (5) Å	θ = 2.9–27.6°
b = 7.3642 (3) Å	µ = 0.09 mm^−1
c = 22.9129 (11) Å	T = 298 K
β = 111.456 (2)°	Needle, blue
V = 1738.94 (13) Å^3	0.25 × 0.10 × 0.08 mm
Z = 4

Data collection

Nonius KappaCCD area-detector diffractometer	3895 independent reflections
Radiation source: fine-focus sealed X-ray tube	1203 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.014
ϕ scans, and ω scans with κ offsets	θmax = 27.6°, θmin = 2.9°
Absorption correction: multi-scan (DENZO-SMN; Otwinowski & Minor, 1997)	h = −14→12
Tmin = 0.975, Tmax = 0.993	k = −8→9
13067 measured reflections	l = −25→29

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)] = 0.063	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.169	H-atom parameters constrained
S = 0.90	w = 1/[σ^2(Fo^2) + (0.0536P)^2] where P = (Fo^2 + 2Fc^2)/3
3895 reflections	(Δ/σ)max < 0.001
226 parameters	Δρmax = 0.14 e Å^−3
0 restraints	Δρmin = −0.19 e Å^−3

Special details

Experimental. Data collection was carried out at room temperature because the crystals flaked on cooling.

The program DENZO-SMN (Otwinowski & Minor, 1997) uses a scaling algorithm [Fox, G. C. & Holmes, K. C. (1966). Acta Cryst. 20, 886–891] which effectively corrects for absorption effects. High-redundancy data were used in the scaling program, hence the 'multi-scan' code word was used.

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

	x	y	z	Uiso*/Ueq
N1	0.2250 (3)	−0.1634 (3)	0.00421 (13)	0.0586 (8)
C2	0.1619 (3)	−0.1771 (5)	0.04435 (17)	0.0597 (9)
N2	0.1348 (3)	−0.3428 (4)	0.05732 (14)	0.0861 (11)
N3	0.1232 (3)	−0.0393 (3)	0.07247 (12)	0.0591 (8)
C4	0.1563 (3)	0.1226 (4)	0.05998 (15)	0.0531 (9)
O4	0.1272 (2)	0.2660 (3)	0.08853 (10)	0.0641 (7)
C47	0.0702 (4)	0.2280 (4)	0.13540 (17)	0.0708 (11)
C41	0.0557 (4)	0.4087 (4)	0.16239 (17)	0.0555 (9)
C42	−0.0578 (4)	0.5044 (5)	0.13773 (17)	0.0667 (10)
C43	−0.0697 (4)	0.6740 (5)	0.1610 (2)	0.0800 (12)
C44	0.0316 (6)	0.7469 (6)	0.2091 (2)	0.0868 (14)
C45	0.1440 (5)	0.6533 (6)	0.2343 (2)	0.0903 (13)
C46	0.1576 (4)	0.4845 (5)	0.21121 (18)	0.0746 (11)
C5	0.2240 (3)	0.1590 (4)	0.01983 (14)	0.0496 (8)
N5	0.2524 (3)	0.3375 (4)	0.01281 (13)	0.0610 (8)
O5	0.3201 (2)	0.3712 (3)	−0.01890 (12)	0.0758 (8)
C6	0.2565 (3)	0.0008 (4)	−0.00656 (15)	0.0525 (9)
O6	0.3226 (2)	0.0224 (3)	−0.04448 (11)	0.0660 (7)
C67	0.3601 (4)	−0.1411 (5)	−0.06850 (19)	0.0815 (12)
C61	0.4320 (4)	−0.0870 (6)	−0.10946 (18)	0.0732 (11)
C62	0.4577 (4)	0.0886 (7)	−0.11957 (18)	0.0896 (13)
C63	0.5258 (5)	0.1308 (9)	−0.1582 (2)	0.1207 (19)
C64	0.5695 (6)	−0.0060 (13)	−0.1862 (3)	0.149 (3)
C65	0.5435 (6)	−0.1804 (12)	−0.1766 (3)	0.139 (3)
C66	0.4765 (4)	−0.2256 (7)	−0.1381 (2)	0.0962 (14)
H2A	0.1572	−0.4346	0.0404	0.103*
H2B	0.0946	−0.3592	0.0827	0.103*
H47A	0.1263	0.1490	0.1679	0.085*
H47B	−0.0137	0.1697	0.1162	0.085*
H42	−0.1274	0.4550	0.1051	0.080*
H43	−0.1469	0.7383	0.1438	0.096*
H44	0.0235	0.8610	0.2246	0.104*
H45	0.2126	0.7031	0.2673	0.108*
H46	0.2354	0.4215	0.2286	0.090*
H67A	0.2837	−0.2109	−0.0924	0.098*
H67B	0.4149	−0.2156	−0.0341	0.098*
H62	0.4293	0.1818	−0.1004	0.108*
H63	0.5417	0.2514	−0.1650	0.145*
H64	0.6164	0.0212	−0.2115	0.179*
H65	0.5714	−0.2726	−0.1964	0.166*
H66	0.4612	−0.3466	−0.1315	0.115*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.075 (2)	0.0408 (17)	0.071 (2)	−0.0046 (13)	0.0408 (18)	−0.0039 (13)
C2	0.070 (3)	0.046 (2)	0.070 (3)	−0.0027 (18)	0.035 (2)	−0.0011 (18)
N2	0.133 (3)	0.044 (2)	0.114 (3)	−0.0095 (17)	0.084 (2)	−0.0049 (16)
N3	0.075 (2)	0.0406 (16)	0.073 (2)	−0.0020 (13)	0.0397 (17)	−0.0021 (13)
C4	0.064 (3)	0.046 (2)	0.054 (2)	0.0024 (16)	0.026 (2)	−0.0040 (16)
O4	0.090 (2)	0.0469 (13)	0.0749 (17)	0.0027 (11)	0.0532 (15)	0.0015 (11)
C47	0.093 (3)	0.060 (2)	0.080 (3)	0.0021 (18)	0.056 (2)	0.0045 (18)
C41	0.067 (3)	0.056 (2)	0.052 (2)	0.002 (2)	0.032 (2)	0.0024 (17)
C42	0.066 (3)	0.065 (2)	0.071 (3)	−0.004 (2)	0.027 (2)	0.0012 (19)
C43	0.081 (3)	0.069 (3)	0.102 (4)	0.016 (2)	0.048 (3)	0.003 (2)
C44	0.117 (4)	0.075 (3)	0.087 (3)	−0.002 (3)	0.060 (3)	−0.015 (3)
C45	0.096 (4)	0.103 (3)	0.075 (3)	−0.019 (3)	0.035 (3)	−0.026 (3)
C46	0.069 (3)	0.090 (3)	0.069 (3)	0.014 (2)	0.030 (2)	−0.002 (2)
C5	0.059 (2)	0.043 (2)	0.053 (2)	−0.0006 (15)	0.0271 (19)	−0.0001 (15)
N5	0.073 (2)	0.0544 (18)	0.064 (2)	−0.0029 (15)	0.0345 (18)	0.0058 (14)
O5	0.093 (2)	0.0624 (16)	0.092 (2)	−0.0045 (13)	0.0575 (18)	0.0109 (13)
C6	0.056 (3)	0.056 (2)	0.052 (2)	−0.0023 (17)	0.027 (2)	−0.0036 (17)
O6	0.0816 (19)	0.0577 (15)	0.0770 (17)	−0.0058 (12)	0.0507 (15)	−0.0087 (12)
C67	0.092 (3)	0.077 (3)	0.098 (3)	−0.005 (2)	0.061 (3)	−0.024 (2)
C61	0.061 (3)	0.102 (3)	0.060 (3)	0.002 (2)	0.026 (2)	−0.014 (2)
C62	0.076 (3)	0.133 (4)	0.068 (3)	0.004 (3)	0.037 (3)	0.009 (3)
C63	0.095 (4)	0.191 (6)	0.089 (4)	0.006 (4)	0.048 (3)	0.037 (4)
C64	0.082 (4)	0.299 (11)	0.081 (4)	0.033 (6)	0.045 (3)	0.036 (6)
C65	0.082 (4)	0.272 (9)	0.069 (4)	0.030 (5)	0.037 (3)	−0.037 (5)
C66	0.071 (3)	0.142 (4)	0.077 (3)	0.007 (3)	0.029 (3)	−0.036 (3)

Geometric parameters (Å, º)

C6—N1	1.306 (4)	C43—H43	0.9300
N1—C2	1.347 (4)	C44—C45	1.353 (6)
C2—N3	1.353 (4)	C44—H44	0.9300
N3—C4	1.310 (4)	C45—C46	1.380 (5)
C4—C5	1.408 (4)	C45—H45	0.9300
C5—C6	1.419 (4)	C46—H46	0.9300
C2—N2	1.316 (4)	O6—C67	1.446 (4)
C4—O4	1.342 (3)	C67—C61	1.490 (5)
C6—O6	1.334 (4)	C67—H67A	0.9700
C5—N5	1.374 (4)	C67—H67B	0.9700
N5—O5	1.245 (3)	C61—C62	1.363 (5)
N2—H2A	0.8600	C61—C66	1.397 (5)
N2—H2B	0.8600	C62—C63	1.392 (6)
O4—C47	1.458 (4)	C62—H62	0.9300
C47—C41	1.500 (4)	C63—C64	1.374 (8)
C47—H47A	0.9700	C63—H63	0.9300
C47—H47B	0.9700	C64—C65	1.352 (8)
C41—C42	1.369 (5)	C64—H64	0.9300
C41—C46	1.383 (5)	C65—C66	1.385 (7)
C42—C43	1.383 (5)	C65—H65	0.9300
C42—H42	0.9300	C66—H66	0.9300
C43—C44	1.362 (5)
C6—N1—C2	116.1 (3)	C45—C46—H46	119.9
N2—C2—N1	116.2 (3)	C41—C46—H46	119.9
N2—C2—N3	116.7 (3)	N5—C5—C4	117.3 (3)
N1—C2—N3	127.1 (3)	N5—C5—C6	129.1 (3)
C2—N2—H2A	120.0	C4—C5—C6	113.6 (3)
C2—N2—H2B	120.0	O5—N5—C5	118.2 (3)
H2A—N2—H2B	120.0	N1—C6—O6	118.8 (3)
C4—N3—C2	114.6 (3)	N1—C6—C5	123.5 (3)
N3—C4—O4	118.2 (3)	O6—C6—C5	117.7 (3)
N3—C4—C5	125.1 (3)	C6—O6—C67	116.8 (3)
O4—C4—C5	116.6 (3)	O6—C67—C61	108.1 (3)
C4—O4—C47	117.0 (2)	O6—C67—H67A	110.1
O4—C47—C41	105.9 (2)	C61—C67—H67A	110.1
O4—C47—H47A	110.6	O6—C67—H67B	110.1
C41—C47—H47A	110.6	C61—C67—H67B	110.1
O4—C47—H47B	110.6	H67A—C67—H67B	108.4
C41—C47—H47B	110.6	C62—C61—C66	118.8 (4)
H47A—C47—H47B	108.7	C62—C61—C67	123.6 (4)
C42—C41—C46	118.7 (3)	C66—C61—C67	117.6 (4)
C42—C41—C47	120.4 (4)	C61—C62—C63	121.0 (5)
C46—C41—C47	120.9 (4)	C61—C62—H62	119.5
C41—C42—C43	120.5 (4)	C63—C62—H62	119.5
C41—C42—H42	119.7	C64—C63—C62	120.0 (6)
C43—C42—H42	119.7	C64—C63—H63	120.0
C44—C43—C42	120.1 (4)	C62—C63—H63	120.0
C44—C43—H43	120.0	C65—C64—C63	119.2 (7)
C42—C43—H43	120.0	C65—C64—H64	120.4
C45—C44—C43	120.0 (4)	C63—C64—H64	120.4
C45—C44—H44	120.0	C64—C65—C66	121.8 (7)
C43—C44—H44	120.0	C64—C65—H65	119.1
C44—C45—C46	120.5 (4)	C66—C65—H65	119.1
C44—C45—H45	119.7	C65—C66—C61	119.2 (5)
C46—C45—H45	119.7	C65—C66—H66	120.4
C45—C46—C41	120.1 (4)	C61—C66—H66	120.4
C6—N1—C2—N2	−177.3 (3)	O4—C4—C5—C6	177.4 (3)
C6—N1—C2—N3	3.0 (5)	C4—C5—N5—O5	175.0 (3)
N2—C2—N3—C4	177.6 (3)	C6—C5—N5—O5	−3.0 (5)
N1—C2—N3—C4	−2.6 (5)	C2—N1—C6—O6	178.0 (3)
C2—N3—C4—O4	−176.7 (3)	C2—N1—C6—C5	−2.1 (5)
C2—N3—C4—C5	1.5 (5)	N5—C5—C6—N1	179.2 (3)
N3—C4—O4—C47	4.9 (4)	C4—C5—C6—N1	1.2 (5)
C5—C4—O4—C47	−173.4 (3)	N5—C5—C6—O6	−1.0 (5)
C4—O4—C47—C41	176.4 (3)	C4—C5—C6—O6	−179.0 (3)
O4—C47—C41—C42	92.6 (4)	N1—C6—O6—C67	−3.0 (4)
O4—C47—C41—C46	−85.3 (4)	C5—C6—O6—C67	177.1 (3)
C46—C41—C42—C43	0.4 (5)	C6—O6—C67—C61	179.9 (3)
C47—C41—C42—C43	−177.6 (3)	O6—C67—C61—C62	1.4 (5)
C41—C42—C43—C44	−0.4 (6)	O6—C67—C61—C66	−179.5 (3)
C42—C43—C44—C45	−0.1 (6)	C66—C61—C62—C63	0.7 (7)
C43—C44—C45—C46	0.6 (7)	C67—C61—C62—C63	179.7 (4)
C44—C45—C46—C41	−0.5 (6)	C61—C62—C63—C64	−0.7 (8)
C42—C41—C46—C45	0.0 (6)	C62—C63—C64—C65	1.1 (9)
C47—C41—C46—C45	178.0 (3)	C63—C64—C65—C66	−1.5 (10)
N3—C4—C5—N5	−179.1 (3)	C64—C65—C66—C61	1.4 (8)
O4—C4—C5—N5	−0.9 (4)	C62—C61—C66—C65	−1.0 (6)
N3—C4—C5—C6	−0.8 (5)	C67—C61—C66—C65	179.9 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···O4^i	0.86	2.54	2.977 (4)	112
N2—H2A···N5^i	0.86	2.19	3.041 (4)	168
N2—H2B···Cg2^i	0.86	2.67	3.496 (4)	163

Symmetry code: (i) x, y−1, z.