Acta Cryst. (2008). E64, o617 [ doi:10.1107/S1600536808004418 ]
The pentanoyl group and the 5-fluorouracil moiety of the title compound, C9H11FN2O3, are essentially coplanar, with the pentanoyl carbonyl group oriented towards the ring CH group and away from the nearer ring carbonyl group. In the crystal structure, two inversion-related molecules form a dimer structure, in which two N-H
O hydrogen bonds generate an intermolecular R22(8) ring. In addition, there are intra- and intermolecular C-HO interactions.
5-Fluoro-1-(1-oxopentyl)-2,4(1H,3H)-pyrimidinedione was synthesized by acylation of 5-fluorouracil with pentanoyl chloride and recrystallized from diethylether at 253 K (Beall et al., 1997; Lehmler & Parkin, 2000; Roberts & Sloan, 1999).
H atoms were found in difference Fourier maps and subsequently placed in idealized positions with constrained C—H distances of 0.98 Å (RCH3), 0.99 Å (R2CH2), 0.95 Å (CArH) and 0.88 Å (NH) with Uiso(H) values set to either 1.2Ueq or 1.5Ueq (RCH3 only) of the attached atom.
Data collection: COLLECT (Nonius, 1998); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO-SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and local procedures.
![[Figure 1]](./at2544fig1thm.gif)
| Fig. 1. View of the title compound showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. |
| C9H11FN2O3 | Z = 2 |
| Mr = 214.20 | F000 = 224 |
| Triclinic, P1 | Dx = 1.497 Mg m−3 |
| Hall symbol: -P 1 | Mo Kα radiation λ = 0.71073 Å |
| a = 5.3165 (2) Å | Cell parameters from 6994 reflections |
| b = 9.3986 (4) Å | θ = 1.0–27.5º |
| c = 10.1895 (5) Å | µ = 0.13 mm−1 |
| α = 96.000 (3)º | T = 87.8 (2) K |
| β = 100.957 (3)º | Irregular plate, colourless |
| γ = 105.539 (3)º | 0.30 × 0.30 × 0.03 mm |
| V = 475.04 (4) Å3 |
| Nonius KappaCCD diffractometer | 2167 independent reflections |
| Radiation source: fine-focus sealed tube | 1727 reflections with I > 2σ(I) |
| Monochromator: graphite | Rint = 0.037 |
| Detector resolution: 18 pixels mm-1 | θmax = 27.5º |
| T = 87.8(2) K | θmin = 2.1º |
| ω scans at fixed χ = 55° | h = −6→6 |
| Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997) | k = −12→12 |
| Tmin = 0.963, Tmax = 0.996 | l = −13→13 |
| 12409 measured reflections |
| Refinement on F2 | Secondary atom site location: difference Fourier map |
| Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
| R[F2 > 2σ(F2)] = 0.047 | H-atom parameters constrained |
| wR(F2) = 0.092 | w = 1/[σ2(Fo2) + (0.0269P)2 + 0.2309P] where P = (Fo2 + 2Fc2)/3 |
| S = 1.02 | (Δ/σ)max < 0.001 |
| 2167 reflections | Δρmax = 0.23 e Å−3 |
| 137 parameters | Δρmin = −0.24 e Å−3 |
| Primary atom site location: structure-invariant direct methods | Extinction correction: none |
| C9H11FN2O3 | γ = 105.539 (3)º |
| Mr = 214.20 | V = 475.04 (4) Å3 |
| Triclinic, P1 | Z = 2 |
| a = 5.3165 (2) Å | Mo Kα |
| b = 9.3986 (4) Å | µ = 0.13 mm−1 |
| c = 10.1895 (5) Å | T = 87.8 (2) K |
| α = 96.000 (3)º | 0.30 × 0.30 × 0.03 mm |
| β = 100.957 (3)º |
| Nonius KappaCCD diffractometer | 2167 independent reflections |
| Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997) | 1727 reflections with I > 2σ(I) |
| Tmin = 0.963, Tmax = 0.996 | Rint = 0.037 |
| 12409 measured reflections |
| R[F2 > 2σ(F2)] = 0.047 | 137 parameters |
| wR(F2) = 0.092 | H-atom parameters constrained |
| S = 1.02 | Δρmax = 0.23 e Å−3 |
| 2167 reflections | Δρmin = −0.24 e Å−3 |
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. |
| x | y | z | Uiso*/Ueq | ||
| N1 | 0.4196 (2) | 0.37039 (13) | 0.62262 (12) | 0.0131 (3) | |
| O2 | 0.7435 (2) | 0.24634 (12) | 0.65488 (10) | 0.0208 (3) | |
| C2 | 0.6455 (3) | 0.33911 (17) | 0.69638 (15) | 0.0146 (3) | |
| N3 | 0.7532 (2) | 0.42493 (13) | 0.82378 (12) | 0.0149 (3) | |
| H3 | 0.8913 | 0.4049 | 0.8723 | 0.018* | |
| O4 | 0.7890 (2) | 0.60838 (12) | 0.99779 (10) | 0.0176 (3) | |
| C4 | 0.6725 (3) | 0.53737 (16) | 0.88432 (15) | 0.0148 (3) | |
| F5 | 0.34305 (17) | 0.66618 (10) | 0.85412 (8) | 0.0198 (2) | |
| C5 | 0.4391 (3) | 0.56025 (16) | 0.80080 (15) | 0.0142 (3) | |
| C6 | 0.3224 (3) | 0.48168 (16) | 0.67833 (14) | 0.0135 (3) | |
| H6 | 0.1698 | 0.5013 | 0.6273 | 0.016* | |
| O7 | 0.1183 (2) | 0.35259 (12) | 0.42664 (10) | 0.0189 (3) | |
| C7 | 0.2850 (3) | 0.30070 (16) | 0.48388 (15) | 0.0139 (3) | |
| C8 | 0.3615 (3) | 0.17280 (17) | 0.41877 (15) | 0.0162 (3) | |
| H8A | 0.3494 | 0.0949 | 0.4775 | 0.019* | |
| H8B | 0.5500 | 0.2088 | 0.4108 | 0.019* | |
| C9 | 0.1823 (3) | 0.10375 (17) | 0.27854 (15) | 0.0170 (3) | |
| H9A | 0.1644 | 0.1853 | 0.2267 | 0.020* | |
| H9B | 0.2710 | 0.0418 | 0.2302 | 0.020* | |
| C10 | −0.0962 (3) | 0.00735 (17) | 0.28048 (16) | 0.0192 (4) | |
| H10A | −0.1828 | 0.0668 | 0.3330 | 0.023* | |
| H10B | −0.0809 | −0.0788 | 0.3262 | 0.023* | |
| C11 | −0.2706 (3) | −0.0500 (2) | 0.13778 (17) | 0.0266 (4) | |
| H11A | −0.2890 | 0.0351 | 0.0929 | 0.040* | |
| H11B | −0.4482 | −0.1117 | 0.1427 | 0.040* | |
| H11C | −0.1868 | −0.1103 | 0.0860 | 0.040* |
| U11 | U22 | U33 | U12 | U13 | U23 | |
| N1 | 0.0116 (6) | 0.0140 (6) | 0.0139 (6) | 0.0054 (5) | 0.0013 (5) | 0.0013 (5) |
| O2 | 0.0197 (6) | 0.0233 (6) | 0.0206 (6) | 0.0133 (5) | −0.0006 (5) | −0.0007 (5) |
| C2 | 0.0119 (7) | 0.0156 (8) | 0.0167 (8) | 0.0044 (6) | 0.0029 (6) | 0.0047 (6) |
| N3 | 0.0117 (6) | 0.0165 (7) | 0.0155 (7) | 0.0060 (5) | −0.0016 (5) | 0.0023 (5) |
| O4 | 0.0164 (6) | 0.0196 (6) | 0.0153 (6) | 0.0061 (5) | 0.0002 (4) | 0.0007 (5) |
| C4 | 0.0141 (8) | 0.0139 (8) | 0.0170 (8) | 0.0031 (6) | 0.0050 (6) | 0.0047 (6) |
| F5 | 0.0199 (5) | 0.0208 (5) | 0.0193 (5) | 0.0116 (4) | 0.0009 (4) | −0.0027 (4) |
| C5 | 0.0142 (7) | 0.0139 (8) | 0.0170 (8) | 0.0069 (6) | 0.0049 (6) | 0.0033 (6) |
| C6 | 0.0106 (7) | 0.0152 (8) | 0.0166 (8) | 0.0062 (6) | 0.0037 (6) | 0.0043 (6) |
| O7 | 0.0197 (6) | 0.0210 (6) | 0.0163 (6) | 0.0108 (5) | −0.0009 (5) | 0.0011 (5) |
| C7 | 0.0115 (7) | 0.0153 (8) | 0.0149 (7) | 0.0030 (6) | 0.0035 (6) | 0.0036 (6) |
| C8 | 0.0159 (8) | 0.0166 (8) | 0.0172 (8) | 0.0066 (6) | 0.0035 (6) | 0.0037 (6) |
| C9 | 0.0175 (8) | 0.0176 (8) | 0.0156 (8) | 0.0064 (7) | 0.0026 (6) | −0.0006 (6) |
| C10 | 0.0189 (8) | 0.0175 (8) | 0.0219 (8) | 0.0066 (7) | 0.0051 (7) | 0.0029 (7) |
| C11 | 0.0242 (9) | 0.0236 (9) | 0.0270 (9) | 0.0045 (7) | 0.0013 (7) | −0.0024 (7) |
| N1—C6 | 1.3999 (18) | C7—C8 | 1.499 (2) |
| N1—C2 | 1.4093 (19) | C8—C9 | 1.526 (2) |
| N1—C7 | 1.4526 (18) | C8—H8A | 0.9900 |
| O2—C2 | 1.2084 (17) | C8—H8B | 0.9900 |
| C2—N3 | 1.3837 (18) | C9—C10 | 1.520 (2) |
| N3—C4 | 1.3743 (19) | C9—H9A | 0.9900 |
| N3—H3 | 0.8800 | C9—H9B | 0.9900 |
| O4—C4 | 1.2291 (17) | C10—C11 | 1.523 (2) |
| C4—C5 | 1.446 (2) | C10—H10A | 0.9900 |
| F5—C5 | 1.3462 (16) | C10—H10B | 0.9900 |
| C5—C6 | 1.325 (2) | C11—H11A | 0.9800 |
| C6—H6 | 0.9500 | C11—H11B | 0.9800 |
| O7—C7 | 1.2077 (17) | C11—H11C | 0.9800 |
| C6—N1—C2 | 120.42 (12) | C9—C8—H8A | 109.1 |
| C6—N1—C7 | 115.53 (12) | C7—C8—H8B | 109.1 |
| C2—N1—C7 | 123.89 (12) | C9—C8—H8B | 109.1 |
| O2—C2—N3 | 121.00 (13) | H8A—C8—H8B | 107.9 |
| O2—C2—N1 | 124.45 (13) | C10—C9—C8 | 114.16 (12) |
| N3—C2—N1 | 114.55 (13) | C10—C9—H9A | 108.7 |
| C4—N3—C2 | 128.41 (13) | C8—C9—H9A | 108.7 |
| C4—N3—H3 | 115.8 | C10—C9—H9B | 108.7 |
| C2—N3—H3 | 115.8 | C8—C9—H9B | 108.7 |
| O4—C4—N3 | 122.41 (13) | H9A—C9—H9B | 107.6 |
| O4—C4—C5 | 124.89 (14) | C9—C10—C11 | 111.57 (13) |
| N3—C4—C5 | 112.70 (13) | C9—C10—H10A | 109.3 |
| C6—C5—F5 | 120.95 (13) | C11—C10—H10A | 109.3 |
| C6—C5—C4 | 122.57 (14) | C9—C10—H10B | 109.3 |
| F5—C5—C4 | 116.48 (13) | C11—C10—H10B | 109.3 |
| C5—C6—N1 | 121.32 (13) | H10A—C10—H10B | 108.0 |
| C5—C6—H6 | 119.3 | C10—C11—H11A | 109.5 |
| N1—C6—H6 | 119.3 | C10—C11—H11B | 109.5 |
| O7—C7—N1 | 116.83 (13) | H11A—C11—H11B | 109.5 |
| O7—C7—C8 | 123.69 (13) | C10—C11—H11C | 109.5 |
| N1—C7—C8 | 119.47 (12) | H11A—C11—H11C | 109.5 |
| C7—C8—C9 | 112.37 (12) | H11B—C11—H11C | 109.5 |
| C7—C8—H8A | 109.1 | ||
| C6—N1—C2—O2 | −179.04 (14) | F5—C5—C6—N1 | −179.41 (12) |
| C7—N1—C2—O2 | −3.7 (2) | C4—C5—C6—N1 | 0.2 (2) |
| C6—N1—C2—N3 | 0.63 (19) | C2—N1—C6—C5 | 0.1 (2) |
| C7—N1—C2—N3 | 175.95 (12) | C7—N1—C6—C5 | −175.62 (13) |
| O2—C2—N3—C4 | 177.79 (14) | C6—N1—C7—O7 | 5.59 (19) |
| N1—C2—N3—C4 | −1.9 (2) | C2—N1—C7—O7 | −169.94 (13) |
| C2—N3—C4—O4 | −178.30 (14) | C6—N1—C7—C8 | −175.64 (12) |
| C2—N3—C4—C5 | 2.1 (2) | C2—N1—C7—C8 | 8.8 (2) |
| O4—C4—C5—C6 | 179.25 (14) | O7—C7—C8—C9 | −6.9 (2) |
| N3—C4—C5—C6 | −1.2 (2) | N1—C7—C8—C9 | 174.46 (12) |
| O4—C4—C5—F5 | −1.1 (2) | C7—C8—C9—C10 | −74.69 (17) |
| N3—C4—C5—F5 | 178.46 (12) | C8—C9—C10—C11 | 176.35 (13) |
| D—H···A | D—H | H···A | D···A | D—H···A |
| N3—H3···O4i | 0.88 | 1.99 | 2.8588 (16) | 170 |
| C6—H6···O7 | 0.95 | 2.28 | 2.6102 (17) | 100 |
| C6—H6···O7ii | 0.95 | 2.34 | 3.2266 (19) | 154 |
| Symmetry codes: (i) −x+2, −y+1, −z+2; (ii) −x, −y+1, −z+1. |
| D—H···A | D—H | H···A | D···A | D—H···A |
| N3—H3···O4i | 0.88 | 1.99 | 2.8588 (16) | 170 |
| C6—H6···O7 | 0.95 | 2.28 | 2.6102 (17) | 100 |
| C6—H6···O7ii | 0.95 | 2.34 | 3.2266 (19) | 154 |
| Symmetry codes: (i) −x+2, −y+1, −z+2; (ii) −x, −y+1, −z+1. |
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Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.
Despite the potential pharmaceutical application of acyl-5-fluorouracil prodrugs, the crystal structures of only three acyl derivatives have been reported (Beall et al., 1997; Jiang et al., 1988; Lehmler & Parkin, 2000). We herein describe the crystal structures of another acyl-5-fluorouracil prodrug, 5-fluoro-1-(1-oxopentyl)-2,4(1H,3H)-pyrimidinedione.
The molecular structures of the title compound and the other 1-acyl-5-fluorouracil derivatives are very similar. Specifically, the 1-acyl group and the 5-fluorouracil moiety are almost coplanar, with the C7?O7 carbonyl group oriented towards the C6—H group and away from the C2?O2 group in all four crystal structures. The C6—N1—C7—O7 dihedral angle of all 1-acyl-5-fluorouracil derivatives is comparable and ranges from 1.6 to 17.3° (Beall et al., 1997; Jiang et al., 1988; Lehmler & Parkin, 2000). In the crystal structure, two inversion-related molecules form a dimer structure, in which two N—H···O hydrogen bonds generate an intermolecular R22(8) ring. In addition, there are C—H···O type-intra and intermolecular interactions.