Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807046454/cf2143sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807046454/cf2143Isup2.hkl |
CCDC reference: 667278
Key indicators
- Single-crystal X-ray study
- T = 298 K
- Mean (C-C) = 0.010 Å
- R factor = 0.067
- wR factor = 0.203
- Data-to-parameter ratio = 8.8
checkCIF/PLATON results
No syntax errors found
Alert level C PLAT222_ALERT_3_C Large Non-Solvent H Ueq(max)/Ueq(min) ... 3.45 Ratio PLAT230_ALERT_2_C Hirshfeld Test Diff for O4 - C6 .. 5.20 su PLAT242_ALERT_2_C Check Low Ueq as Compared to Neighbors for C6 PLAT340_ALERT_3_C Low Bond Precision on C-C Bonds (x 1000) Ang ... 10
Alert level G REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is correct. If it is not, please give the correct count in the _publ_section_exptl_refinement section of the submitted CIF. From the CIF: _diffrn_reflns_theta_max 25.02 From the CIF: _reflns_number_total 686 Count of symmetry unique reflns 690 Completeness (_total/calc) 99.42% TEST3: Check Friedels for noncentro structure Estimate of Friedel pairs measured 0 Fraction of Friedel pairs measured 0.000 Are heavy atom types Z>Si present no PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints ....... 2
0 ALERT level A = In general: serious problem 0 ALERT level B = Potentially serious problem 4 ALERT level C = Check and explain 2 ALERT level G = General alerts; check 0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 2 ALERT type 2 Indicator that the structure model may be wrong or deficient 3 ALERT type 3 Indicator that the structure quality may be low 1 ALERT type 4 Improvement, methodology, query or suggestion 0 ALERT type 5 Informative message, check
For related literature, see: Akalin et al. (2007); Hulme et al. (2005); Maeda et al. (1997). For the first polymorph, see Zhang et al. (2006).
The title compound was synthesized according to the method of Zhang et al. (2006) and single crystals were obtained by slow evaporation of an acetone solution.
All of the H atoms were placed in calculated positions and allowed to ride on their parent atoms at distances of 0.82 (hydroxyl), 0.93 (aromatic) and 0.96 Å (methyl), with Uiso(H) = 1.2–1.5Ueq(C,O). In the absence of significant anomalous scattering effects, Friedel pairs were merged.
Because of the poor tumor selectivity and high incidence of toxicity of 5-fluorouracil (5FU), which was frequently used as an antitumor agent, many derivatives of 5FU have been developed to improve its topical delivery and reduce the side effects (Akalin et al., 2007; Hulme et al., 2005; Maeda et al., 1997). In this work, the title compound (I) was synthesized in our laboratory.
The structure of compound (I) was first determined by Zhang et al. (2006) [space group P21/c, cell constants a = 4.9363 (5), b = 17.056 (2), c = 9.4940 (8) Å and β = 114.466 (4)°]. Now we have discovered a new polymorph of (I), which crystallized in space group Pc and with different unit-cell parameters. The molecule of (I) is shown in Fig. 1. Most of the geometric parameters are similar in both polymorphs. The dihedral angle between the carboxyl group and uracil ring is 82.1 (8)°, which is essentially the same as that of the previous polymorph (Zhang et al., 2006); these two planes are almost perpendicular.
The molecular packing in the present case is completely different from that of the first polymorph (Fig. 2). The molecules are linked by O—H···O and N—H···O hydrogen bonds to form a zigzag chain. These zigzag chains are cross-linked by C—H···O hydrogen bonds to form layers parallel to the (100) plane.
For related literature, see: Akalin et al. (2007); Hulme et al. (2005); Maeda et al. (1997). For the first polymorph, see Zhang et al. (2006).
Data collection: SMART (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT (Bruker, 2002); program(s) used to solve structure: SHELXTL (Bruker, 2002); program(s) used to refine structure: SHELXTL (Bruker, 2002); molecular graphics: SHELXTL (Bruker, 2002); software used to prepare material for publication: SHELXTL (Bruker, 2002).
Fig. 1. The molecular structure of (I) with atom labels, showing 50% probability displacement ellipsoids. | |
Fig. 2. A packing diagram viewed along the a axis. Hydrogen bonds are shown as dashed lines. |
C6H5FN2O4 | F(000) = 192 |
Mr = 188.12 | Dx = 1.588 Mg m−3 |
Monoclinic, Pc | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P -2yc | Cell parameters from 792 reflections |
a = 6.809 (4) Å | θ = 3.0–24.9° |
b = 4.840 (3) Å | µ = 0.15 mm−1 |
c = 11.946 (7) Å | T = 298 K |
β = 92.218 (9)° | Prism, colorless |
V = 393.4 (4) Å3 | 0.24 × 0.15 × 0.06 mm |
Z = 2 |
Bruker APEX area-detector diffractometer | 686 independent reflections |
Radiation source: fine-focus sealed tube | 651 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.050 |
φ and ω scans | θmax = 25.0°, θmin = 3.0° |
Absorption correction: multi-scan (SADABS; Bruker, 2002) | h = −8→8 |
Tmin = 0.965, Tmax = 0.984 | k = −5→5 |
1810 measured reflections | l = −14→10 |
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)] = 0.067 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.203 | H-atom parameters constrained |
S = 1.01 | w = 1/[σ2(Fo2) + (0.1506P)2 + 0.4386P] where P = (Fo2 + 2Fc2)/3 |
686 reflections | (Δ/σ)max < 0.001 |
78 parameters | Δρmax = 0.31 e Å−3 |
2 restraints | Δρmin = −0.25 e Å−3 |
C6H5FN2O4 | V = 393.4 (4) Å3 |
Mr = 188.12 | Z = 2 |
Monoclinic, Pc | Mo Kα radiation |
a = 6.809 (4) Å | µ = 0.15 mm−1 |
b = 4.840 (3) Å | T = 298 K |
c = 11.946 (7) Å | 0.24 × 0.15 × 0.06 mm |
β = 92.218 (9)° |
Bruker APEX area-detector diffractometer | 686 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2002) | 651 reflections with I > 2σ(I) |
Tmin = 0.965, Tmax = 0.984 | Rint = 0.050 |
1810 measured reflections |
R[F2 > 2σ(F2)] = 0.067 | 2 restraints |
wR(F2) = 0.203 | H-atom parameters constrained |
S = 1.01 | Δρmax = 0.31 e Å−3 |
686 reflections | Δρmin = −0.25 e Å−3 |
78 parameters |
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 > σ(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 | ||
F1 | −0.0373 (7) | −0.2785 (12) | 0.8215 (5) | 0.0534 (15) | |
O1 | 0.5896 (8) | 0.3756 (13) | 0.8203 (5) | 0.0409 (15) | |
O2 | 0.0272 (8) | 0.1213 (12) | 0.9853 (4) | 0.0406 (15) | |
O3 | 0.3896 (7) | 0.3555 (11) | 0.5663 (4) | 0.0336 (14) | |
O4 | 0.6827 (13) | 0.2288 (18) | 0.5011 (8) | 0.076 (2) | |
H4 | 0.6498 | 0.3303 | 0.4488 | 0.114* | |
N1 | 0.4205 (8) | 0.0178 (12) | 0.7466 (5) | 0.0251 (14) | |
N2 | 0.3075 (8) | 0.2427 (15) | 0.9007 (5) | 0.0272 (14) | |
H2 | 0.3254 | 0.3686 | 0.9508 | 0.033* | |
C1 | 0.4518 (11) | 0.2258 (15) | 0.8224 (6) | 0.0277 (17) | |
C2 | 0.1388 (10) | 0.0870 (15) | 0.9099 (6) | 0.0300 (18) | |
C3 | 0.1195 (10) | −0.1137 (16) | 0.8207 (5) | 0.0286 (17) | |
C4 | 0.2555 (12) | −0.1477 (16) | 0.7452 (6) | 0.0350 (19) | |
H4A | 0.2393 | −0.2841 | 0.6908 | 0.042* | |
C5 | 0.5662 (11) | −0.0101 (16) | 0.6602 (6) | 0.0324 (19) | |
H5A | 0.5543 | −0.1913 | 0.6259 | 0.039* | |
H5B | 0.6973 | 0.0056 | 0.6945 | 0.039* | |
C6 | 0.5375 (10) | 0.2102 (15) | 0.5711 (5) | 0.0240 (16) |
U11 | U22 | U33 | U12 | U13 | U23 | |
F1 | 0.048 (3) | 0.054 (3) | 0.060 (3) | −0.027 (3) | 0.017 (2) | −0.020 (3) |
O1 | 0.040 (3) | 0.039 (3) | 0.044 (3) | −0.018 (3) | 0.010 (3) | −0.007 (3) |
O2 | 0.038 (3) | 0.045 (3) | 0.041 (3) | −0.012 (3) | 0.021 (3) | −0.012 (3) |
O3 | 0.033 (3) | 0.031 (3) | 0.037 (3) | 0.010 (3) | 0.011 (2) | 0.009 (2) |
O4 | 0.089 (6) | 0.071 (5) | 0.072 (5) | 0.012 (5) | 0.033 (4) | 0.023 (4) |
N1 | 0.027 (3) | 0.026 (3) | 0.024 (3) | 0.000 (3) | 0.005 (2) | −0.001 (3) |
N2 | 0.034 (3) | 0.027 (3) | 0.022 (3) | −0.009 (3) | 0.007 (2) | −0.006 (2) |
C1 | 0.035 (4) | 0.023 (4) | 0.026 (4) | −0.001 (4) | 0.004 (3) | −0.001 (3) |
C2 | 0.024 (4) | 0.031 (4) | 0.036 (4) | −0.004 (4) | 0.005 (3) | 0.006 (3) |
C3 | 0.034 (4) | 0.030 (4) | 0.021 (3) | −0.008 (3) | 0.003 (3) | −0.002 (3) |
C4 | 0.055 (5) | 0.022 (4) | 0.028 (4) | −0.007 (4) | 0.000 (4) | −0.001 (3) |
C5 | 0.044 (5) | 0.020 (4) | 0.034 (4) | 0.002 (3) | 0.005 (3) | 0.003 (3) |
C6 | 0.028 (4) | 0.025 (3) | 0.020 (3) | 0.006 (4) | 0.009 (3) | −0.007 (3) |
F1—C3 | 1.333 (9) | N2—C2 | 1.382 (10) |
O1—C1 | 1.187 (9) | N2—C1 | 1.385 (10) |
O2—C2 | 1.212 (9) | N2—H2 | 0.860 |
O3—C6 | 1.227 (8) | C2—C3 | 1.445 (10) |
O4—C6 | 1.322 (11) | C3—C4 | 1.328 (11) |
O4—H4 | 0.820 | C4—H4A | 0.930 |
N1—C1 | 1.365 (10) | C5—C6 | 1.515 (10) |
N1—C4 | 1.379 (10) | C5—H5A | 0.970 |
N1—C5 | 1.465 (8) | C5—H5B | 0.970 |
C6—O4—H4 | 109.5 | C4—C3—C2 | 122.6 (7) |
C1—N1—C4 | 122.9 (6) | F1—C3—C2 | 116.5 (6) |
C1—N1—C5 | 116.3 (6) | C3—C4—N1 | 120.6 (7) |
C4—N1—C5 | 120.7 (6) | C3—C4—H4A | 119.7 |
C2—N2—C1 | 129.5 (7) | N1—C4—H4A | 119.7 |
C2—N2—H2 | 115.3 | N1—C5—C6 | 111.0 (6) |
C1—N2—H2 | 115.3 | N1—C5—H5A | 109.4 |
O1—C1—N1 | 122.7 (7) | C6—C5—H5A | 109.4 |
O1—C1—N2 | 124.1 (7) | N1—C5—H5B | 109.4 |
N1—C1—N2 | 113.2 (6) | C6—C5—H5B | 109.4 |
O2—C2—N2 | 122.1 (7) | H5A—C5—H5B | 108.0 |
O2—C2—C3 | 126.8 (6) | O3—C6—O4 | 124.3 (7) |
N2—C2—C3 | 111.1 (6) | O3—C6—C5 | 121.3 (6) |
C4—C3—F1 | 120.7 (6) | O4—C6—C5 | 114.4 (7) |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2···O3i | 0.86 | 1.96 | 2.815 (8) | 175 |
O4—H4···O1ii | 0.82 | 2.12 | 2.938 (10) | 174 |
C5—H5A···O3iii | 0.97 | 2.55 | 3.468 (7) | 158 |
C4—H4A···O3iii | 0.93 | 2.53 | 3.367 (7) | 149 |
Symmetry codes: (i) x, −y+1, z+1/2; (ii) x, −y+1, z−1/2; (iii) x, y−1, z. |
Experimental details
Crystal data | |
Chemical formula | C6H5FN2O4 |
Mr | 188.12 |
Crystal system, space group | Monoclinic, Pc |
Temperature (K) | 298 |
a, b, c (Å) | 6.809 (4), 4.840 (3), 11.946 (7) |
β (°) | 92.218 (9) |
V (Å3) | 393.4 (4) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.15 |
Crystal size (mm) | 0.24 × 0.15 × 0.06 |
Data collection | |
Diffractometer | Bruker APEX area-detector |
Absorption correction | Multi-scan (SADABS; Bruker, 2002) |
Tmin, Tmax | 0.965, 0.984 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 1810, 686, 651 |
Rint | 0.050 |
(sin θ/λ)max (Å−1) | 0.595 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.067, 0.203, 1.01 |
No. of reflections | 686 |
No. of parameters | 78 |
No. of restraints | 2 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.31, −0.25 |
Computer programs: SMART (Bruker, 2002), SAINT (Bruker, 2002), SHELXTL (Bruker, 2002).
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2···O3i | 0.86 | 1.96 | 2.815 (8) | 175.1 |
O4—H4···O1ii | 0.82 | 2.12 | 2.938 (10) | 173.5 |
C5—H5A···O3iii | 0.97 | 2.55 | 3.468 (7) | 157.5 |
C4—H4A···O3iii | 0.93 | 2.53 | 3.367 (7) | 149.2 |
Symmetry codes: (i) x, −y+1, z+1/2; (ii) x, −y+1, z−1/2; (iii) x, y−1, z. |
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Because of the poor tumor selectivity and high incidence of toxicity of 5-fluorouracil (5FU), which was frequently used as an antitumor agent, many derivatives of 5FU have been developed to improve its topical delivery and reduce the side effects (Akalin et al., 2007; Hulme et al., 2005; Maeda et al., 1997). In this work, the title compound (I) was synthesized in our laboratory.
The structure of compound (I) was first determined by Zhang et al. (2006) [space group P21/c, cell constants a = 4.9363 (5), b = 17.056 (2), c = 9.4940 (8) Å and β = 114.466 (4)°]. Now we have discovered a new polymorph of (I), which crystallized in space group Pc and with different unit-cell parameters. The molecule of (I) is shown in Fig. 1. Most of the geometric parameters are similar in both polymorphs. The dihedral angle between the carboxyl group and uracil ring is 82.1 (8)°, which is essentially the same as that of the previous polymorph (Zhang et al., 2006); these two planes are almost perpendicular.
The molecular packing in the present case is completely different from that of the first polymorph (Fig. 2). The molecules are linked by O—H···O and N—H···O hydrogen bonds to form a zigzag chain. These zigzag chains are cross-linked by C—H···O hydrogen bonds to form layers parallel to the (100) plane.