Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270102010387/na1579sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270102010387/na1579Isup2.hkl |
CCDC reference: 192996
A sample of (I) was prepared by reaction of 2-amino-4,6-bis(benzyloxy)-5-nitrosopyrimidine (Quesada, Low et al., 2002) with allylamine in ethanol at ambient temperature. Crystals suitable for single-crystal X-ray diffraction analysis were grown from a water–ethanol mixture (1:1 v/v).
H atoms were treated as riding atoms, with C—H distances of 0.95 (aromatic) or 0.99 Å (CH2) and N—H distances of 0.84 (for N4—H4) or 0.88 Å (NH2). An initial data set was collected at 120 (2) on a KappaCCD diffractometer using Mo Kα radiation. While it was possible to achieve a satisfactory description of the molecular and supramolecular structures from these data, from a refinement to R = 0.059 (wR = 0.153), the proportion of data labelled observed, even at 120 K, was only 0.48, and the average value of σ(C—C) was 0.012 Å. We therefore collected a second data set, at 150 (2) K, at the Daresbury synchrotron radiation source station 9.8 (Cernik et al., 1997; Clegg et al., 1998), and the proportion of data labelled observed rose to 0.69 and the refinement gave a mean σ(C—C) of only 0.003 Å. The greatly enhanced quality of the synchrotron data set may be significant for compounds of this type; as noted earlier (Quesada, Marchal et al., 2002), it is not always a straightforward matter to obtain crystals of substituted 5-nitrosopyrimidines suitable for single-crystal X-ray diffraction analysis and, indeed, some compounds of this type cannot be obtained in crystalline form at all. It seems clear that for some compounds of this series conventional diffactometry at ambient temperature would be fruitless and even CCD data at 120 K can lead to structural refinements of, at best, questionable acceptability.
Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 1998); program(s) used to refine structure: SHELXTL and SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2002); software used to prepare material for publication: SHELXL97 and PRPKAPPA (Ferguson, 1999).
C14H15N5O2 | F(000) = 600 |
Mr = 285.31 | Dx = 1.351 Mg m−3 |
Monoclinic, P21/c | Synchrotron radiation, λ = 0.6867 Å |
Hall symbol: -P 2ybc | Cell parameters from 2791 reflections |
a = 8.0338 (6) Å | θ = 2.6–25.4° |
b = 24.627 (2) Å | µ = 0.10 mm−1 |
c = 7.4087 (5) Å | T = 150 K |
β = 106.872 (2)° | Plate, purple |
V = 1402.7 (2) Å3 | 0.08 × 0.04 × 0.01 mm |
Z = 4 |
Bruker SMART 1K CCD diffractometer | 2791 independent reflections |
Radiation source: Daresbury SRS station 9.8 | 1931 reflections with I > 2σ(I) |
Silicon 111 monochromator | Rint = 0.038 |
ω rotation scans with narrow frames | θmax = 25.4°, θmin = 2.6° |
Absorption correction: multi-scan (SADABS; Bruker, 2000) | h = −10→9 |
Tmin = 0.992, Tmax = 0.999 | k = −28→30 |
7631 measured reflections | l = −9→9 |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.047 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.125 | H-atom parameters constrained |
S = 1.03 | w = 1/[σ2(Fo2) + (0.0633P)2 + 0.1705P] where P = (Fo2 + 2Fc2)/3 |
2791 reflections | (Δ/σ)max < 0.001 |
190 parameters | Δρmax = 0.17 e Å−3 |
0 restraints | Δρmin = −0.27 e Å−3 |
C14H15N5O2 | V = 1402.7 (2) Å3 |
Mr = 285.31 | Z = 4 |
Monoclinic, P21/c | Synchrotron radiation, λ = 0.6867 Å |
a = 8.0338 (6) Å | µ = 0.10 mm−1 |
b = 24.627 (2) Å | T = 150 K |
c = 7.4087 (5) Å | 0.08 × 0.04 × 0.01 mm |
β = 106.872 (2)° |
Bruker SMART 1K CCD diffractometer | 2791 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2000) | 1931 reflections with I > 2σ(I) |
Tmin = 0.992, Tmax = 0.999 | Rint = 0.038 |
7631 measured reflections |
R[F2 > 2σ(F2)] = 0.047 | 0 restraints |
wR(F2) = 0.125 | H-atom parameters constrained |
S = 1.03 | Δρmax = 0.17 e Å−3 |
2791 reflections | Δρmin = −0.27 e Å−3 |
190 parameters |
x | y | z | Uiso*/Ueq | ||
N1 | 0.3161 (2) | 0.46034 (7) | 0.5285 (2) | 0.0309 (4) | |
N2 | 0.2980 (2) | 0.47602 (7) | 0.8268 (2) | 0.0389 (4) | |
C2 | 0.2614 (3) | 0.49352 (8) | 0.6499 (2) | 0.0306 (4) | |
N3 | 0.1769 (2) | 0.54067 (6) | 0.6094 (2) | 0.0304 (4) | |
N4 | 0.0524 (2) | 0.60415 (7) | 0.3854 (2) | 0.0345 (4) | |
C4 | 0.1377 (2) | 0.55755 (8) | 0.4302 (2) | 0.0280 (4) | |
C5 | 0.1880 (2) | 0.52673 (7) | 0.2880 (2) | 0.0276 (4) | |
N5 | 0.1612 (2) | 0.53997 (7) | 0.1038 (2) | 0.0325 (4) | |
O5 | 0.07881 (19) | 0.58396 (6) | 0.04541 (18) | 0.0381 (4) | |
O6 | 0.32262 (18) | 0.44649 (5) | 0.22616 (17) | 0.0317 (3) | |
C6 | 0.2778 (2) | 0.47725 (7) | 0.3543 (2) | 0.0278 (4) | |
C7 | −0.0030 (3) | 0.63751 (9) | 0.5207 (3) | 0.0410 (5) | |
C8 | 0.0868 (3) | 0.69082 (10) | 0.5583 (3) | 0.0498 (6) | |
C9 | 0.2027 (4) | 0.70983 (11) | 0.4840 (4) | 0.0651 (7) | |
C67 | 0.4035 (3) | 0.39442 (8) | 0.2922 (3) | 0.0344 (5) | |
C61 | 0.4135 (3) | 0.36349 (8) | 0.1208 (3) | 0.0308 (4) | |
C62 | 0.5526 (3) | 0.37115 (8) | 0.0485 (3) | 0.0352 (5) | |
C63 | 0.5595 (3) | 0.34374 (9) | −0.1137 (3) | 0.0414 (5) | |
C64 | 0.4301 (3) | 0.30761 (9) | −0.2002 (3) | 0.0455 (6) | |
C65 | 0.2915 (3) | 0.29946 (9) | −0.1286 (3) | 0.0460 (6) | |
C66 | 0.2818 (3) | 0.32760 (9) | 0.0314 (3) | 0.0388 (5) | |
H2A | 0.2667 | 0.4953 | 0.9114 | 0.058* | |
H2B | 0.3537 | 0.4451 | 0.8593 | 0.058* | |
H4 | 0.0289 | 0.6122 | 0.2706 | 0.041* | |
H7A | 0.0193 | 0.6173 | 0.6410 | 0.061* | |
H7B | −0.1299 | 0.6438 | 0.4720 | 0.061* | |
H8 | 0.0559 | 0.7136 | 0.6468 | 0.075* | |
H9A | 0.2387 | 0.6888 | 0.3946 | 0.098* | |
H9B | 0.2514 | 0.7448 | 0.5192 | 0.098* | |
H67A | 0.3330 | 0.3742 | 0.3593 | 0.052* | |
H67B | 0.5215 | 0.4000 | 0.3798 | 0.052* | |
H62 | 0.6438 | 0.3952 | 0.1098 | 0.042* | |
H63 | 0.6536 | 0.3500 | −0.1646 | 0.050* | |
H64 | 0.4362 | 0.2883 | −0.3091 | 0.055* | |
H65 | 0.2023 | 0.2746 | −0.1886 | 0.055* | |
H66 | 0.1854 | 0.3222 | 0.0792 | 0.047* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0421 (9) | 0.0335 (9) | 0.0188 (8) | −0.0002 (7) | 0.0116 (7) | 0.0006 (6) |
N2 | 0.0601 (11) | 0.0406 (10) | 0.0179 (8) | 0.0053 (8) | 0.0143 (8) | 0.0025 (7) |
C2 | 0.0391 (11) | 0.0364 (11) | 0.0177 (9) | −0.0062 (9) | 0.0106 (8) | −0.0014 (8) |
N3 | 0.0401 (9) | 0.0328 (9) | 0.0201 (8) | −0.0030 (7) | 0.0117 (7) | −0.0017 (6) |
N4 | 0.0484 (10) | 0.0350 (9) | 0.0236 (8) | 0.0032 (8) | 0.0160 (7) | 0.0006 (7) |
C4 | 0.0342 (10) | 0.0296 (10) | 0.0222 (9) | −0.0058 (8) | 0.0111 (8) | −0.0016 (7) |
C5 | 0.0342 (10) | 0.0304 (10) | 0.0197 (9) | −0.0046 (8) | 0.0101 (8) | −0.0015 (7) |
N5 | 0.0421 (9) | 0.0347 (9) | 0.0221 (8) | −0.0020 (8) | 0.0116 (7) | 0.0031 (7) |
O5 | 0.0514 (9) | 0.0386 (8) | 0.0255 (7) | 0.0045 (7) | 0.0128 (6) | 0.0070 (6) |
O6 | 0.0482 (8) | 0.0304 (7) | 0.0197 (6) | 0.0045 (6) | 0.0148 (6) | 0.0014 (5) |
C6 | 0.0357 (10) | 0.0316 (10) | 0.0182 (9) | −0.0040 (8) | 0.0113 (8) | −0.0024 (7) |
C7 | 0.0509 (13) | 0.0438 (12) | 0.0333 (11) | 0.0101 (10) | 0.0202 (10) | −0.0014 (9) |
C8 | 0.0579 (15) | 0.0463 (13) | 0.0459 (13) | 0.0059 (11) | 0.0163 (12) | −0.0142 (11) |
C9 | 0.0787 (19) | 0.0516 (16) | 0.0684 (18) | −0.0173 (14) | 0.0269 (15) | −0.0173 (13) |
C67 | 0.0463 (12) | 0.0348 (11) | 0.0259 (10) | 0.0066 (9) | 0.0163 (9) | 0.0041 (8) |
C61 | 0.0392 (11) | 0.0301 (10) | 0.0231 (9) | 0.0047 (8) | 0.0092 (8) | 0.0028 (7) |
C62 | 0.0397 (11) | 0.0369 (11) | 0.0302 (11) | −0.0005 (9) | 0.0119 (9) | −0.0060 (8) |
C63 | 0.0471 (13) | 0.0457 (13) | 0.0354 (12) | 0.0035 (10) | 0.0181 (10) | −0.0079 (10) |
C64 | 0.0614 (15) | 0.0426 (13) | 0.0297 (11) | 0.0043 (11) | 0.0088 (10) | −0.0091 (9) |
C65 | 0.0537 (14) | 0.0404 (13) | 0.0373 (12) | −0.0058 (10) | 0.0029 (11) | −0.0063 (10) |
C66 | 0.0417 (12) | 0.0395 (11) | 0.0345 (11) | −0.0008 (9) | 0.0100 (9) | 0.0044 (9) |
N1—C2 | 1.378 (2) | C7—H7B | 0.990 |
C2—N3 | 1.335 (2) | C8—H8 | 0.9500 |
N3—C4 | 1.339 (2) | C9—H9A | 0.9500 |
C4—C5 | 1.448 (2) | C9—H9B | 0.9500 |
C5—C6 | 1.429 (3) | C67—C61 | 1.503 (3) |
C6—N1 | 1.305 (2) | C67—H67A | 0.990 |
C2—N2 | 1.329 (2) | C67—H67B | 0.990 |
C4—N4 | 1.329 (2) | C61—C62 | 1.385 (3) |
N4—C7 | 1.462 (2) | C61—C66 | 1.390 (3) |
C7—C8 | 1.485 (3) | C62—C63 | 1.393 (3) |
C8—C9 | 1.298 (3) | C62—H62 | 0.950 |
C5—N5 | 1.358 (2) | C63—C64 | 1.377 (3) |
N5—O5 | 1.278 (2) | C63—H63 | 0.950 |
O6—C6 | 1.343 (2) | C64—C65 | 1.380 (3) |
O6—C67 | 1.457 (2) | C64—H64 | 0.950 |
N2—H2A | 0.880 | C65—C66 | 1.395 (3) |
N2—H2B | 0.880 | C65—H65 | 0.950 |
N4—H4 | 0.840 | C66—H66 | 0.950 |
C7—H7A | 0.990 | ||
C6—N1—C2 | 115.32 (16) | C9—C8—H8 | 116.2 |
C2—N2—H2A | 120.0 | C7—C8—H8 | 116.2 |
C2—N2—H2B | 120.0 | C8—C9—H9A | 120.0 |
H2A—N2—H2B | 120.0 | C8—C9—H9B | 120.0 |
N2—C2—N3 | 117.15 (17) | H9A—C9—H9B | 120.0 |
N2—C2—N1 | 115.46 (18) | O6—C67—C61 | 106.87 (15) |
N3—C2—N1 | 127.38 (16) | O6—C67—H67A | 110.3 |
C2—N3—C4 | 116.80 (15) | C61—C67—H67A | 110.3 |
C4—N4—C7 | 123.50 (16) | O6—C67—H67B | 110.3 |
C4—N4—H4 | 114.0 | C61—C67—H67B | 110.3 |
C7—N4—H4 | 122.5 | H67A—C67—H67B | 108.6 |
N4—C4—N3 | 118.14 (16) | C62—C61—C66 | 119.34 (18) |
N4—C4—C5 | 120.26 (16) | C62—C61—C67 | 120.31 (18) |
N3—C4—C5 | 121.60 (17) | C66—C61—C67 | 120.34 (18) |
N5—C5—C6 | 117.88 (16) | C61—C62—C63 | 120.41 (19) |
N5—C5—C4 | 127.51 (17) | C61—C62—H62 | 119.8 |
C6—C5—C4 | 114.61 (15) | C63—C62—H62 | 119.8 |
O5—N5—C5 | 117.33 (15) | C64—C63—C62 | 120.0 (2) |
C6—O6—C67 | 116.36 (13) | C64—C63—H63 | 120.0 |
N1—C6—O6 | 118.98 (17) | C62—C63—H63 | 120.0 |
N1—C6—C5 | 124.27 (16) | C63—C64—C65 | 120.0 (2) |
O6—C6—C5 | 116.74 (15) | C63—C64—H64 | 120.0 |
N4—C7—C8 | 113.42 (18) | C65—C64—H64 | 120.0 |
N4—C7—H7A | 108.9 | C64—C65—C66 | 120.3 (2) |
C8—C7—H7A | 108.9 | C64—C65—H65 | 119.8 |
N4—C7—H7B | 108.9 | C66—C65—H65 | 119.8 |
C8—C7—H7B | 108.9 | C61—C66—C65 | 119.9 (2) |
H7A—C7—H7B | 107.7 | C61—C66—H66 | 120.0 |
C9—C8—C7 | 127.5 (2) | C65—C66—H66 | 120.0 |
C4—C5—N5—O5 | −1.7 (3) | N1—C6—O6—C67 | 3.3 (2) |
N3—C4—N4—C7 | −0.9 (3) | C6—O6—C67—C61 | 170.4 (2) |
C4—N4—C7—C8 | 113.9 (2) | O6—C67—C61—C62 | 85.5 (2) |
N4—C7—C8—C9 | 0.9 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
N4—H4···O5 | 0.84 | 1.95 | 2.636 (2) | 138 |
N2—H2A···N5i | 0.88 | 2.16 | 3.035 (2) | 174 |
N2—H2A···O6i | 0.88 | 2.54 | 2.997 (2) | 113 |
N2—H2B···Cg2i | 0.88 | 2.81 | 3.655 (2) | 161 |
Symmetry code: (i) x, y, z+1. |
Experimental details
Crystal data | |
Chemical formula | C14H15N5O2 |
Mr | 285.31 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 150 |
a, b, c (Å) | 8.0338 (6), 24.627 (2), 7.4087 (5) |
β (°) | 106.872 (2) |
V (Å3) | 1402.7 (2) |
Z | 4 |
Radiation type | Synchrotron, λ = 0.6867 Å |
µ (mm−1) | 0.10 |
Crystal size (mm) | 0.08 × 0.04 × 0.01 |
Data collection | |
Diffractometer | Bruker SMART 1K CCD diffractometer |
Absorption correction | Multi-scan (SADABS; Bruker, 2000) |
Tmin, Tmax | 0.992, 0.999 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 7631, 2791, 1931 |
Rint | 0.038 |
(sin θ/λ)max (Å−1) | 0.625 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.047, 0.125, 1.03 |
No. of reflections | 2791 |
No. of parameters | 190 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.17, −0.27 |
Computer programs: SMART (Bruker, 1998), SAINT (Bruker, 2000), SAINT, SHELXTL (Sheldrick, 1998), SHELXTL and SHELXL97 (Sheldrick, 1997), PLATON (Spek, 2002), SHELXL97 and PRPKAPPA (Ferguson, 1999).
N1—C2 | 1.378 (2) | N4—C7 | 1.462 (2) |
C2—N3 | 1.335 (2) | C7—C8 | 1.485 (3) |
N3—C4 | 1.339 (2) | C8—C9 | 1.298 (3) |
C4—C5 | 1.448 (2) | C5—N5 | 1.358 (2) |
C5—C6 | 1.429 (3) | N5—O5 | 1.278 (2) |
C6—N1 | 1.305 (2) | O6—C6 | 1.343 (2) |
C2—N2 | 1.329 (2) | O6—C67 | 1.457 (2) |
C4—N4 | 1.329 (2) | ||
C4—C5—N5—O5 | −1.7 (3) | N1—C6—O6—C67 | 3.3 (2) |
N3—C4—N4—C7 | −0.9 (3) | C6—O6—C67—C61 | 170.4 (2) |
C4—N4—C7—C8 | 113.9 (2) | O6—C67—C61—C62 | 85.5 (2) |
N4—C7—C8—C9 | 0.9 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
N4—H4···O5 | 0.84 | 1.95 | 2.636 (2) | 138 |
N2—H2A···N5i | 0.88 | 2.16 | 3.035 (2) | 174 |
N2—H2A···O6i | 0.88 | 2.54 | 2.997 (2) | 113 |
N2—H2B···Cg2i | 0.88 | 2.81 | 3.655 (2) | 161 |
Symmetry code: (i) x, y, z+1. |
Alkoxy- and amino-substituted O6-benzyloxy-5-nitrosopyrimidines (Marchal et al., 2000, 2002) are important as potential, or proven, in vitro inhibitors of the human DNA repair protein O6-alkylguanine-DNA-transferase (Chae et al., 1995; Quesada, Marchal et al., 2002). We report here the molecular and supramolecular structure of an analogue, 4-(allylamino)-2-amino-6-benzyloxy-5-nitrosopyrimidine, (I), containing an N-allyl substituent.
The intramolecular dimensions of (I) (Table 1) show a number of features typical of substituted 5-nitrosopyrimidines (Low et al., 2000; Quesada, Marchal et al., 2002); in particular, the sequence of four C—N bonds between N2 and N4 (Fig. 1) spans only a very small range of distances, 1.329 (2)–1.339 (2) Å, while the bond C6—N1 is significantly shorter and C2—N1 is significantly longer; the distances C4—C5 and C5—C6 are rather similar; and, in addition, the C—N and N—O distances in each C-nitroso fragment differ by only ca 0.11 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 NO distance rarely exceeds 1.25 Å (Davis et al., 1965; Bauer & Andreassen, 1972; Talberg, 1977; Schlemper et al., 1986). These observations all point to the charge-separated form (Ia) as an important contributor to the overall electronic structure, at the expense of classically bond-fixed forms, such as (Ib) and (Ic).
The nitrosyl O atom is almost coplanar with the pyrimidine ring (Table 2). This is associated both with the electronic delocalization and with the intramolecular hydrogen bond (see below). Similarly, the torsion angles indicate that atom C7 of the allylamino substituent, and both C67 and C61 of the benzyloxy substituent, are also nearly coplanar with the pyrimidine ring; however, there are substantial twists away from planarity around the N4—C7 and C61—C67 bonds.
There is an intramolecular N—H···O hydrogen bond (Table 2) generating an S(6) motif (Bernstein et al., 1995); the N—H···O angle is small, constrained both by the ring size and shape and by the near coplanarity of the nitroso group and the pyrimidine ring, but both donor and acceptor in this interaction carry partial charges [cf. structure (Ia)], and hence this interaction is an example of a resonance-assisted hydrogen bond (Gilli et al., 1994). The molecules are linked by further hydrogen bonds into chains running parallel to the [001] direction. Amino atom N2 acts as hydrogen-bond donor, via H2A, to both N5i and O6i [symmetry code: (i) x, y, 1 + z], so generating by translation a C(6) C(7)[R21(5)] chain of rings (Fig. 2). This three-centre N—H···(N,O) hydrogen bond has a sum of the angles at H2A of 355°, but the H···O distance is long and the N—H···O angle is small (Table 2); hence, it may be that the H···O contact is more adventitious than significant. The conventional chain-forming hydrogen bonds are augmented by an N—H···π(arene) interaction; amino atom N2 also acts as donor, via H2B, which is not involved in any conventional hydrogen bonds, to the centroid (Cg2i) of arene ring C61–C66 (Table 2 and Fig. 2).
Four [001] chains run through each unit cell, two in the domain 0.29 < y < 0.71 and two in the domain 0.79 < y < 1.21. Within each domain, the [001] chains are pairwise linked by π–π-stacking interactions; the parallel pyrimidine rings in the molecules at (x, y, z) and (-x, 1 - y, 1 - z) have an interplanar spacing of 3.310 (2) Å and a centroid separation of 3.779 (2) Å (Fig. 3). While the ring-centroid offset, ca 1.82 Å, is quite large, the offset direction is such that cationic and anionic regions of the adjacent molecules [cf. structure (Ia)] are reasonably close (Fig. 3), thus enhancing this attractive interaction.
All three independent N—H bonds in (I) are thus involved in the overall hydrogen bonding, with each forming a different type of interaction. Although the hard (Braga et al., 1995) hydrogen-bond donors are all utilized, unusually (Low et al., 2000; Quesada, Marchal et al. 2002) there are neither hard intermolecular hydrogen bonds involving the nitrosyl atom O5 nor any soft hydrogen bonds involving atom O5.