Acta Cryst. (2008). E64, o703 [ doi:10.1107/S1600536808006296 ]
The 3-methylbutanoyl group and the 5-fluorouracil unit of the title compound, C9H11FN2O3, are essentially coplanar, with the carbonyl group oriented towards the ring CH group and away from the nearer ring carbonyl group. The 3-methylbutanoyl (C=)C-N-C=O torsion angle of 9.6 (2)° is comparable to that in structurally related compounds. In the solid state, two inversion-related molecules form N-H
O hydrogen bonds to generate an intermolecular R22(8) ring. The crystal structure also diplays intra- and intermolecular C-HO interactions.
5-Fluoro-1-(1-oxo-3-methylbutyl)-2,4(1H,3H)-pyrimidinedione was synthesized by acylation of 5-fluorouracil with 3-methyl-butanoyl chloride and recrystallized from diethylether at -20°C (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: SHELX97 (Sheldrick, 2008) and local procedures.
![[Figure 1]](./om2217fig1thm.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 = 1.517 Mg m−3 |
| Hall symbol: -P 1 | Mo Kα radiation λ = 0.71073 Å |
| a = 5.4879 (3) Å | Cell parameters from 4363 reflections |
| b = 9.3702 (5) Å | θ = 1.0–27.5º |
| c = 9.9794 (5) Å | µ = 0.13 mm−1 |
| α = 103.470 (2)º | T = 90.0 (2) K |
| β = 100.204 (3)º | Irregular block, colourless |
| γ = 104.085 (3)º | 0.30 × 0.20 × 0.07 mm |
| V = 468.94 (4) Å3 |
| Nonius KappaCCD diffractometer | 2139 independent reflections |
| Radiation source: fine-focus sealed tube | 1629 reflections with I > 2σ(I) |
| Monochromator: graphite | Rint = 0.031 |
| Detector resolution: 18 pixels mm-1 | θmax = 27.5º |
| T = 88.0(2) K | θmin = 2.2º |
| ω scans at fixed χ = 55° | h = −7→7 |
| Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997) | k = −12→12 |
| Tmin = 0.963, Tmax = 0.991 | l = −12→12 |
| 4080 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)] = 0.049 | H-atom parameters constrained |
| wR(F2) = 0.112 | w = 1/[σ2(Fo2) + (0.0498P)2 + 0.0466P] where P = (Fo2 + 2Fc2)/3 |
| S = 1.07 | (Δ/σ)max = 0.001 |
| 2139 reflections | Δρmax = 0.27 e Å−3 |
| 138 parameters | Δρmin = −0.29 e Å−3 |
| Primary atom site location: structure-invariant direct methods | Extinction correction: none |
| C9H11FN2O3 | γ = 104.085 (3)º |
| Mr = 214.20 | V = 468.94 (4) Å3 |
| Triclinic, P1 | Z = 2 |
| a = 5.4879 (3) Å | Mo Kα |
| b = 9.3702 (5) Å | µ = 0.13 mm−1 |
| c = 9.9794 (5) Å | T = 90.0 (2) K |
| α = 103.470 (2)º | 0.30 × 0.20 × 0.07 mm |
| β = 100.204 (3)º |
| Nonius KappaCCD diffractometer | 2139 independent reflections |
| Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997) | 1629 reflections with I > 2σ(I) |
| Tmin = 0.963, Tmax = 0.991 | Rint = 0.031 |
| 4080 measured reflections |
| R[F2 > 2σ(F2)] = 0.049 | 138 parameters |
| wR(F2) = 0.112 | H-atom parameters constrained |
| S = 1.07 | Δρmax = 0.27 e Å−3 |
| 2139 reflections | Δρmin = −0.29 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 | 0.0774 (2) | 0.62396 (13) | 0.89316 (12) | 0.0141 (3) | |
| O2 | −0.2469 (2) | 0.74248 (12) | 0.89048 (11) | 0.0206 (3) | |
| C2 | −0.1490 (3) | 0.65330 (17) | 0.82969 (16) | 0.0152 (3) | |
| N3 | −0.2565 (2) | 0.56922 (13) | 0.68799 (12) | 0.0153 (3) | |
| H3 | −0.3906 | 0.5911 | 0.6444 | 0.018* | |
| O4 | −0.2928 (2) | 0.38819 (11) | 0.48195 (10) | 0.0189 (3) | |
| C4 | −0.1798 (3) | 0.45604 (16) | 0.60712 (15) | 0.0157 (4) | |
| F5 | 0.13171 (17) | 0.31908 (10) | 0.61287 (9) | 0.0218 (3) | |
| C5 | 0.0440 (3) | 0.42855 (17) | 0.68495 (16) | 0.0155 (3) | |
| C6 | 0.1651 (3) | 0.50812 (16) | 0.81867 (15) | 0.0152 (3) | |
| H6 | 0.3130 | 0.4864 | 0.8646 | 0.018* | |
| O7 | 0.3841 (2) | 0.64683 (11) | 1.08882 (11) | 0.0195 (3) | |
| C7 | 0.2244 (3) | 0.70161 (17) | 1.03933 (15) | 0.0157 (4) | |
| C8 | 0.1692 (3) | 0.84157 (17) | 1.12009 (15) | 0.0168 (4) | |
| H8A | 0.0015 | 0.8099 | 1.1450 | 0.020* | |
| H8B | 0.1534 | 0.9094 | 1.0584 | 0.020* | |
| C9 | 0.3816 (3) | 0.93148 (18) | 1.25622 (16) | 0.0210 (4) | |
| H9 | 0.4364 | 0.8564 | 1.3022 | 0.025* | |
| C10 | 0.6162 (3) | 1.02656 (19) | 1.22141 (19) | 0.0308 (4) | |
| H10A | 0.5657 | 1.1010 | 1.1765 | 0.046* | |
| H10B | 0.6817 | 0.9586 | 1.1561 | 0.046* | |
| H10C | 0.7522 | 1.0813 | 1.3092 | 0.046* | |
| C11 | 0.2765 (3) | 1.03360 (19) | 1.35944 (16) | 0.0255 (4) | |
| H11A | 0.4155 | 1.0936 | 1.4447 | 0.038* | |
| H11B | 0.1349 | 0.9693 | 1.3864 | 0.038* | |
| H11C | 0.2115 | 1.1034 | 1.3136 | 0.038* |
| U11 | U22 | U33 | U12 | U13 | U23 | |
| N1 | 0.0142 (7) | 0.0140 (6) | 0.0140 (7) | 0.0062 (5) | 0.0024 (5) | 0.0027 (5) |
| O2 | 0.0191 (6) | 0.0240 (6) | 0.0184 (6) | 0.0123 (5) | 0.0021 (5) | 0.0017 (5) |
| C2 | 0.0138 (8) | 0.0165 (8) | 0.0143 (8) | 0.0023 (6) | 0.0027 (6) | 0.0055 (6) |
| N3 | 0.0128 (7) | 0.0175 (7) | 0.0154 (7) | 0.0073 (6) | −0.0001 (5) | 0.0043 (5) |
| O4 | 0.0185 (6) | 0.0183 (6) | 0.0160 (6) | 0.0043 (5) | 0.0004 (5) | 0.0019 (5) |
| C4 | 0.0162 (9) | 0.0131 (8) | 0.0162 (8) | 0.0023 (6) | 0.0028 (6) | 0.0045 (6) |
| F5 | 0.0236 (6) | 0.0210 (5) | 0.0199 (5) | 0.0121 (4) | 0.0036 (4) | −0.0002 (4) |
| C5 | 0.0170 (8) | 0.0136 (7) | 0.0181 (8) | 0.0076 (6) | 0.0066 (6) | 0.0036 (6) |
| C6 | 0.0148 (8) | 0.0154 (8) | 0.0174 (8) | 0.0069 (6) | 0.0036 (6) | 0.0062 (6) |
| O7 | 0.0201 (6) | 0.0225 (6) | 0.0169 (6) | 0.0108 (5) | 0.0010 (5) | 0.0059 (5) |
| C7 | 0.0148 (9) | 0.0172 (8) | 0.0146 (8) | 0.0027 (7) | 0.0030 (6) | 0.0064 (6) |
| C8 | 0.0180 (9) | 0.0174 (8) | 0.0159 (8) | 0.0075 (7) | 0.0027 (6) | 0.0049 (6) |
| C9 | 0.0219 (9) | 0.0193 (8) | 0.0197 (9) | 0.0101 (7) | −0.0027 (7) | 0.0032 (7) |
| C10 | 0.0203 (10) | 0.0263 (10) | 0.0366 (11) | 0.0061 (8) | 0.0008 (8) | −0.0029 (8) |
| C11 | 0.0306 (10) | 0.0217 (9) | 0.0194 (9) | 0.0073 (8) | 0.0002 (7) | 0.0018 (7) |
| N1—C6 | 1.4026 (18) | C7—C8 | 1.499 (2) |
| N1—C2 | 1.4102 (19) | C8—C9 | 1.530 (2) |
| N1—C7 | 1.4529 (18) | C8—H8A | 0.9900 |
| O2—C2 | 1.2053 (17) | C8—H8B | 0.9900 |
| C2—N3 | 1.3884 (18) | C9—C10 | 1.522 (2) |
| N3—C4 | 1.3755 (19) | C9—C11 | 1.526 (2) |
| N3—H3 | 0.8800 | C9—H9 | 1.0000 |
| O4—C4 | 1.2300 (17) | C10—H10A | 0.9800 |
| C4—C5 | 1.445 (2) | C10—H10B | 0.9800 |
| F5—C5 | 1.3493 (16) | C10—H10C | 0.9800 |
| C5—C6 | 1.326 (2) | C11—H11A | 0.9800 |
| C6—H6 | 0.9500 | C11—H11B | 0.9800 |
| O7—C7 | 1.2079 (17) | C11—H11C | 0.9800 |
| C6—N1—C2 | 120.64 (12) | C9—C8—H8A | 109.1 |
| C6—N1—C7 | 115.63 (12) | C7—C8—H8B | 109.1 |
| C2—N1—C7 | 123.62 (12) | C9—C8—H8B | 109.1 |
| O2—C2—N3 | 121.20 (14) | H8A—C8—H8B | 107.9 |
| O2—C2—N1 | 124.36 (13) | C10—C9—C11 | 110.92 (13) |
| N3—C2—N1 | 114.44 (13) | C10—C9—C8 | 110.36 (13) |
| C4—N3—C2 | 128.19 (13) | C11—C9—C8 | 110.06 (13) |
| C4—N3—H3 | 115.9 | C10—C9—H9 | 108.5 |
| C2—N3—H3 | 115.9 | C11—C9—H9 | 108.5 |
| O4—C4—N3 | 122.26 (14) | C8—C9—H9 | 108.5 |
| O4—C4—C5 | 125.01 (14) | C9—C10—H10A | 109.5 |
| N3—C4—C5 | 112.73 (13) | C9—C10—H10B | 109.5 |
| C6—C5—F5 | 120.63 (13) | H10A—C10—H10B | 109.5 |
| C6—C5—C4 | 122.96 (14) | C9—C10—H10C | 109.5 |
| F5—C5—C4 | 116.38 (12) | H10A—C10—H10C | 109.5 |
| C5—C6—N1 | 120.82 (14) | H10B—C10—H10C | 109.5 |
| C5—C6—H6 | 119.6 | C9—C11—H11A | 109.5 |
| N1—C6—H6 | 119.6 | C9—C11—H11B | 109.5 |
| O7—C7—N1 | 116.87 (13) | H11A—C11—H11B | 109.5 |
| O7—C7—C8 | 123.93 (13) | C9—C11—H11C | 109.5 |
| N1—C7—C8 | 119.20 (12) | H11A—C11—H11C | 109.5 |
| C7—C8—C9 | 112.30 (13) | H11B—C11—H11C | 109.5 |
| C7—C8—H8A | 109.1 | ||
| C6—N1—C2—O2 | 174.10 (14) | F5—C5—C6—N1 | 178.82 (12) |
| C7—N1—C2—O2 | −1.8 (2) | C4—C5—C6—N1 | 0.9 (2) |
| C6—N1—C2—N3 | −5.5 (2) | C2—N1—C6—C5 | 3.1 (2) |
| C7—N1—C2—N3 | 178.58 (12) | C7—N1—C6—C5 | 179.32 (13) |
| O2—C2—N3—C4 | −174.94 (14) | C6—N1—C7—O7 | −9.6 (2) |
| N1—C2—N3—C4 | 4.7 (2) | C2—N1—C7—O7 | 166.53 (13) |
| C2—N3—C4—O4 | 179.30 (13) | C6—N1—C7—C8 | 171.17 (12) |
| C2—N3—C4—C5 | −1.1 (2) | C2—N1—C7—C8 | −12.7 (2) |
| O4—C4—C5—C6 | 177.69 (15) | O7—C7—C8—C9 | 15.1 (2) |
| N3—C4—C5—C6 | −1.9 (2) | N1—C7—C8—C9 | −165.67 (13) |
| O4—C4—C5—F5 | −0.3 (2) | C7—C8—C9—C10 | 78.01 (16) |
| N3—C4—C5—F5 | −179.92 (12) | C7—C8—C9—C11 | −159.23 (13) |
| D—H···A | D—H | H···A | D···A | D—H···A |
| N3—H3···O4i | 0.88 | 2.04 | 2.9091 (16) | 171 |
| Symmetry codes: (i) −x−1, −y+1, −z+1. |
| D—H···A | D—H | H···A | D···A | D—H···A |
| N3—H3···O4i | 0.88 | 2.04 | 2.9091 (16) | 171 |
| Symmetry codes: (i) −x−1, −y+1, −z+1. |
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Despite their potential pharmaceutical application, the crystal structures of only five 1-acyl-5-fluorouracil derivatives have been described in the literature (Beall et al., 1993; Jiang et al., 1988; Lehmler & Parkin, 2000; Lehmler & Parkin, 2008). We herein describe the crystal structure of a new 1-acyl-5-fluorouracil derivative, 5-fluoro-1-(1-oxo-3-methylbutyl)-2,4(1H,3H)-pyrimidinedione.
The molecular structures of 1-acyl-5-fluorouracil derivatives are similar. The 1-acyl group and the 5-fluorouracil moiety are essentially coplanar, with the C7=O7 carbonyl group oriented towards the C6—H group and away from the C2=O2 group. The C6—N1—C7—O7 dihedral angle of the title compound is 9.6 (2)°. The other 1-acyl-5-fluorouracil derivatives have comparable dihedral angles ranging from 1.6° to 17.3° (Beall et al., 1993; Jiang et al., 1988; Lehmler & Parkin, 2000; Lehmler & Parkin, 2008), which suggests that the carbonyl group of the 1-acyl group and the pyrimidine-2,4(1H,3H)-dione moiety are conjugated. The differences in the dihedral angles are most likely due to packing effects in the crystal.
Similar to the crystal structure of other 1-acyl-5-fluorouracil derivatives (Beall et al., 1993; Lehmler & Parkin, 2000; Lehmler & Parkin, 2008), the crystal structure of the title compound contains inversion related molecules that form dimers in which two N—H···O hydrogen bonds generate an intermolecular R22(8) ring. Furthermore, there are C—H···O type intra and intermolecular interactions.