5-Fluoro­uracil–1,4-dioxane (4/1)

Hulme, A.T.; Tocher, D.A.

doi:10.1107/S1600536804022251

organic compounds

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ISSN: 2056-9890

Volume 60| Part 10| October 2004| Pages o1781-o1782

https://doi.org/10.1107/S1600536804022251

5-Fluorouracil–1,4-dioxane (4/1)

Ashley T. Hulme ^a ^* and Derek A. Tocher ^a

^aChristopher Ingold Laboratory, Department of Chemistry, 20 Gordon Street, London WC1H 0AJ, England
^*Correspondence e-mail: a.hulme@ucl.ac.uk

(Received 1 September 2004; accepted 8 September 2004; online 18 September 2004)

A solvate of 5-fluorouracil with 1,4-dioxane, 4C₄H₃FN₂O₂·C₄H₈O₂, is reported. It crystallizes in the triclinic space group P $[\overline 1]$ . Two molecules of 5-fluorouracil are present in the asymmetric unit, together with one-half molecule of 1,4-dioxane, which lies on a centre of symmetry. In the crystal structure, ribbons of 5-fluorouracil molecules are joined by 1,4-dioxane-mediated interactions, forming sheets parallel to the (2 $[\overline 1]$ 1) planes.

Comment

In the course of a polymorph screen performed on 5-fluorouracil, three solvates were discovered; the crystal structure of one of these solvates is reported here.

The title compound, (I), crystallizes in the space group P $[\overline 1]$ with two molecules of 5-fluorouracil and one-half molecule of 1,4-dioxane in the asymmetric unit (Fig. 1). The 1,4-dioxane molecule is located on a crystallographic centre of symmetry.

Four distinct N—H⋯O hydrogen bonds occur in the crystal structure (Table 1). Both the crystallographically independent 5-fluorouracil molecules are present as centrosymmetric hydrogen-bonded dimers. One dimer contains the hydrogen bond N3—H3⋯O7ⁱⁱ (symmetry codes are given in Table 1), with a donor–acceptor distance of 2.857 (2) Å, while the other dimer contains the hydrogen bond N13—H13⋯O18ⁱⁱⁱ [2.824 (2) Å]. These dimers are linked, forming ribbon-like structures, by N1—H1⋯O17ⁱ hydrogen bonds. Adjacent ribbons of 5-fluorouracil molecules are linked, forming sheets parallel to the (2 $[\overline1]$ 1) planes via 1,4-dioxane molecules which act as N11—H11⋯O21 [N⋯O = 2.746 (2) Å] hydrogen-bond bridges (Fig. 2).

Figure 1
View (Watkin et al., 1996

) of the asymmetric unit of the title compound and the other half of the dioxane molecule, with atomic numbering. Displacement ellipsoids are drawn at the 50% probability level.

Figure 2
The hydrogen-bonded sheet structure, viewed along the a axis. Ribbons of 5-fluorouracil molecules are joined by 1,4-dioxane-mediated interactions, forming the sheet structure. Dashed lines indicate hydrogen bonds.

Experimental

5-Fluorouracil was obtained from the Aldrich Chemical Company Inc. The crystals were grown by solvent evaporation of a saturated solution of 5-fluorouracil in 1,4-dioxane.

Crystal data

4C₄H₃FN₂O₂·C₄H₈O₂
M_r = 608.44
Triclinic, $[P\overline 1]$
a = 7.0847 (11) Å
b = 8.4733 (13) Å
c = 10.2291 (15) Å
α = 98.128 (3)°
β = 96.913 (3)°
γ = 99.785 (3)°
V = 592.45 (16) Å³
Z = 1
D_x = 1.705 Mg m⁻³
Mo Kα radiation
Cell parameters from 1082 reflections
θ = 2.5–26.7°
μ = 0.16 mm⁻¹
T = 150 (2) K
Plate, colourless
0.35 × 0.24 × 0.03 mm

Data collection

Bruker SMART APEX diffractometer
Narrow-frame ω scans
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ) T_min = 0.947, T_max = 0.995
5320 measured reflections
2741 independent reflections
2131 reflections with I > 2σ(I)
R_int = 0.029
θ_max = 28.3°
h = −9 → 9
k = −11 → 11
l = −13 → 13

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.052
wR(F²) = 0.114
S = 1.08
2741 reflections
230 parameters
All H-atom parameters refined
w = 1/[σ²(F_o²) + (0.0457P)² + 0.1655P] where P = (F_o² + 2F_c²)/3
(Δ/σ)_max < 0.001
Δρ_max = 0.33 e Å⁻³
Δρ_min = −0.33 e Å⁻³

Table 1
Hydrogen-bonding geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O17ⁱ	0.83 (3)	1.98 (3)	2.798 (2)	167 (2)
N3—H3⋯O7ⁱⁱ	0.91 (2)	1.95 (2)	2.857 (2)	176 (2)
N11—H11⋯O21	0.91 (2)	1.84 (2)	2.746 (2)	171 (2)
N13—H13⋯O18ⁱⁱⁱ	0.85 (2)	1.98 (2)	2.824 (2)	175 (2)
Symmetry codes: (i) x,1+y,z; (ii) -x,1-y,1-z; (iii) 1-x,1-y,1-z.

All H atoms were located in a difference map and were refined isotropically. C—H distances were in the range 0.93 (2)–1.00 (2) Å and N—H distances were in the range 0.83 (3)–0.91 (2) Å.

Data collection: SMART (Bruker, 1998 ); cell refinement: SAINT (Bruker, 1998); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: CAMERON (Watkin et al., 1996 ); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks I, str0223. DOI: https://doi.org/10.1107/S1600536804022251/ci6440sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536804022251/ci6440Isup2.hkl

Computing details top

Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1998); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: CAMERON (Watkin et al., 1996); software used to prepare material for publication: SHELXL97.

5-Fluorouracil 1,4-dioxane (4/1) top

Crystal data top

C₄H₈O₂·4C₄H₃FN₂O₂	Z = 1
M_r = 608.44	F(000) = 312
Triclinic, P1	D_x = 1.705 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.0847 (11) Å	Cell parameters from 1082 reflections
b = 8.4733 (13) Å	θ = 2.5–26.7°
c = 10.2291 (15) Å	µ = 0.16 mm⁻¹
α = 98.128 (3)°	T = 150 K
β = 96.913 (3)°	Plate, colourless
γ = 99.785 (3)°	0.35 × 0.24 × 0.03 mm
V = 592.45 (16) Å³

Data collection top

Bruker SMART APEX diffractometer	2741 independent reflections
Radiation source: fine-focus sealed tube	2131 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.029
ω rotation with narrow frames scans	θ_max = 28.3°, θ_min = 2.0°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −9→9
T_min = 0.947, T_max = 0.995	k = −11→11
5320 measured reflections	l = −13→13

Refinement top

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)] = 0.052	Hydrogen site location: found from delta F
wR(F²) = 0.114	All H-atom parameters refined
S = 1.08	w = 1/[σ²(F_o²) + (0.0457P)² + 0.1655P] where P = (F_o² + 2F_c²)/3
2741 reflections	(Δ/σ)_max < 0.001
230 parameters	Δρ_max = 0.33 e Å⁻³
0 restraints	Δρ_min = −0.33 e Å⁻³

Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
F9	0.37304 (19)	0.84841 (15)	0.16434 (12)	0.0278 (3)
O7	0.0566 (2)	0.69895 (17)	0.59096 (14)	0.0232 (4)
O8	0.1991 (2)	0.53627 (17)	0.17616 (14)	0.0234 (4)
N1	0.2094 (3)	0.8886 (2)	0.48334 (18)	0.0196 (4)
H1	0.207 (4)	0.966 (3)	0.543 (3)	0.035 (7)*
N3	0.1319 (2)	0.6192 (2)	0.38430 (16)	0.0172 (4)
H3	0.075 (3)	0.515 (3)	0.389 (2)	0.025 (6)*
C2	0.1276 (3)	0.7343 (2)	0.4933 (2)	0.0175 (4)
C4	0.2065 (3)	0.6469 (2)	0.2685 (2)	0.0172 (4)
C5	0.2912 (3)	0.8144 (2)	0.2720 (2)	0.0182 (4)
C6	0.2897 (3)	0.9295 (3)	0.3745 (2)	0.0206 (5)
H6	0.341 (3)	1.040 (3)	0.377 (2)	0.016 (5)*
F19	0.47754 (18)	0.80432 (14)	0.86893 (12)	0.0258 (3)
O17	0.2285 (2)	0.17889 (17)	0.65744 (14)	0.0222 (4)
O18	0.5329 (2)	0.68229 (17)	0.61498 (14)	0.0214 (3)
N11	0.2653 (2)	0.3825 (2)	0.83458 (16)	0.0162 (4)
H11	0.203 (3)	0.311 (3)	0.881 (2)	0.026 (6)*
N13	0.3790 (3)	0.4320 (2)	0.63923 (17)	0.0167 (4)
H13	0.399 (3)	0.398 (3)	0.561 (2)	0.021 (6)*
C12	0.2873 (3)	0.3209 (2)	0.70817 (19)	0.0158 (4)
C14	0.4501 (3)	0.5943 (2)	0.6848 (2)	0.0161 (4)
C15	0.4153 (3)	0.6458 (2)	0.8187 (2)	0.0169 (4)
C16	0.3266 (3)	0.5434 (2)	0.8892 (2)	0.0171 (4)
H16	0.304 (3)	0.576 (3)	0.976 (2)	0.020 (6)*
O21	0.0777 (2)	0.14345 (17)	0.95410 (15)	0.0241 (4)
C21	0.1347 (3)	−0.0087 (3)	0.9117 (2)	0.0230 (5)
H21A	0.162 (3)	−0.009 (3)	0.819 (2)	0.021 (6)*
H21B	0.255 (3)	−0.013 (3)	0.973 (2)	0.021 (6)*
C22	0.0271 (4)	0.1472 (3)	1.0864 (2)	0.0237 (5)
H22A	0.143 (3)	0.138 (3)	1.150 (2)	0.031 (7)*
H22B	−0.012 (3)	0.249 (3)	1.109 (2)	0.019 (6)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F9	0.0363 (8)	0.0252 (7)	0.0238 (7)	0.0018 (6)	0.0137 (6)	0.0079 (6)
O7	0.0332 (9)	0.0184 (8)	0.0172 (8)	0.0007 (6)	0.0091 (7)	0.0006 (6)
O8	0.0327 (9)	0.0190 (8)	0.0178 (8)	0.0029 (6)	0.0092 (7)	−0.0015 (6)
N1	0.0261 (10)	0.0149 (9)	0.0155 (9)	0.0021 (7)	0.0035 (8)	−0.0032 (7)
N3	0.0236 (10)	0.0126 (9)	0.0150 (9)	0.0014 (7)	0.0056 (7)	0.0010 (7)
C2	0.0201 (11)	0.0174 (10)	0.0141 (10)	0.0034 (8)	0.0020 (8)	0.0009 (8)
C4	0.0176 (10)	0.0194 (10)	0.0149 (10)	0.0055 (8)	0.0022 (8)	0.0018 (8)
C5	0.0208 (11)	0.0190 (11)	0.0160 (10)	0.0021 (8)	0.0060 (8)	0.0059 (8)
C6	0.0242 (12)	0.0141 (10)	0.0231 (11)	0.0001 (8)	0.0030 (9)	0.0062 (9)
F19	0.0354 (8)	0.0137 (6)	0.0255 (7)	−0.0024 (5)	0.0111 (6)	−0.0034 (5)
O17	0.0314 (9)	0.0136 (7)	0.0202 (8)	0.0001 (6)	0.0071 (7)	0.0006 (6)
O18	0.0297 (8)	0.0166 (8)	0.0183 (7)	0.0001 (6)	0.0109 (6)	0.0031 (6)
N11	0.0221 (9)	0.0147 (9)	0.0132 (8)	0.0016 (7)	0.0077 (7)	0.0047 (7)
N13	0.0233 (9)	0.0150 (9)	0.0116 (8)	0.0022 (7)	0.0064 (7)	0.0002 (7)
C12	0.0171 (10)	0.0150 (10)	0.0162 (10)	0.0025 (8)	0.0060 (8)	0.0034 (8)
C14	0.0173 (10)	0.0161 (10)	0.0157 (10)	0.0032 (8)	0.0041 (8)	0.0036 (8)
C15	0.0200 (11)	0.0130 (10)	0.0166 (10)	0.0020 (8)	0.0039 (8)	−0.0005 (8)
C16	0.0194 (11)	0.0197 (11)	0.0123 (10)	0.0052 (8)	0.0038 (8)	0.0004 (8)
O21	0.0348 (9)	0.0160 (8)	0.0251 (8)	0.0031 (6)	0.0163 (7)	0.0078 (6)
C21	0.0301 (13)	0.0190 (11)	0.0232 (12)	0.0046 (9)	0.0138 (10)	0.0058 (9)
C22	0.0344 (13)	0.0158 (11)	0.0214 (12)	0.0023 (9)	0.0109 (10)	0.0017 (9)

Geometric parameters (Å, º) top

F9—C5	1.349 (2)	N11—C16	1.372 (3)
O7—C2	1.223 (2)	N11—H11	0.91 (2)
O8—C4	1.223 (2)	N13—C14	1.374 (3)
N1—C2	1.360 (3)	N13—C12	1.376 (3)
N1—C6	1.371 (3)	N13—H13	0.85 (2)
N1—H1	0.83 (3)	C14—C15	1.441 (3)
N3—C2	1.380 (3)	C15—C16	1.330 (3)
N3—C4	1.387 (3)	C16—H16	0.93 (2)
N3—H3	0.91 (2)	O21—C22	1.439 (2)
C4—C5	1.437 (3)	O21—C21	1.440 (3)
C5—C6	1.330 (3)	C21—C22ⁱ	1.499 (3)
C6—H6	0.94 (2)	C21—H21A	0.99 (2)
F19—C15	1.346 (2)	C21—H21B	1.00 (2)
O17—C12	1.222 (2)	C22—C21ⁱ	1.499 (3)
O18—C14	1.230 (2)	C22—H22A	1.00 (2)
N11—C12	1.362 (2)	C22—H22B	0.96 (2)

C2—N1—C6	123.56 (18)	O17—C12—N13	121.69 (18)
C2—N1—H1	120.8 (18)	N11—C12—N13	114.89 (17)
C6—N1—H1	115.6 (18)	O18—C14—N13	121.64 (18)
C2—N3—C4	126.62 (18)	O18—C14—C15	125.45 (18)
C2—N3—H3	115.6 (15)	N13—C14—C15	112.90 (17)
C4—N3—H3	117.7 (15)	C16—C15—F19	121.57 (18)
O7—C2—N1	123.09 (19)	C16—C15—C14	122.27 (19)
O7—C2—N3	122.19 (19)	F19—C15—C14	116.16 (17)
N1—C2—N3	114.72 (18)	C15—C16—N11	119.84 (19)
O8—C4—N3	121.43 (19)	C15—C16—H16	122.7 (14)
O8—C4—C5	125.64 (19)	N11—C16—H16	117.5 (14)
N3—C4—C5	112.93 (17)	C22—O21—C21	109.42 (16)
C6—C5—F9	121.62 (18)	O21—C21—C22ⁱ	110.12 (18)
C6—C5—C4	122.52 (19)	O21—C21—H21A	107.1 (13)
F9—C5—C4	115.86 (17)	C22ⁱ—C21—H21A	109.0 (13)
C5—C6—N1	119.60 (19)	O21—C21—H21B	107.8 (12)
C5—C6—H6	123.6 (13)	C22ⁱ—C21—H21B	112.2 (12)
N1—C6—H6	116.8 (13)	H21A—C21—H21B	110.5 (17)
C12—N11—C16	122.96 (17)	O21—C22—C21ⁱ	110.23 (18)
C12—N11—H11	116.2 (15)	O21—C22—H22A	109.5 (14)
C16—N11—H11	120.8 (14)	C21ⁱ—C22—H22A	109.2 (14)
C14—N13—C12	127.10 (18)	O21—C22—H22B	106.3 (13)
C14—N13—H13	115.1 (15)	C21ⁱ—C22—H22B	110.9 (13)
C12—N13—H13	117.7 (15)	H22A—C22—H22B	110.6 (19)
O17—C12—N11	123.41 (18)

C6—N1—C2—O7	179.8 (2)	C16—N11—C12—N13	1.0 (3)
C6—N1—C2—N3	0.3 (3)	C14—N13—C12—O17	179.6 (2)
C4—N3—C2—O7	179.2 (2)	C14—N13—C12—N11	0.7 (3)
C4—N3—C2—N1	−1.3 (3)	C12—N13—C14—O18	178.74 (19)
C2—N3—C4—O8	−178.30 (19)	C12—N13—C14—C15	−1.7 (3)
C2—N3—C4—C5	2.3 (3)	O18—C14—C15—C16	−179.2 (2)
O8—C4—C5—C6	178.1 (2)	N13—C14—C15—C16	1.3 (3)
N3—C4—C5—C6	−2.4 (3)	O18—C14—C15—F19	0.9 (3)
O8—C4—C5—F9	−1.8 (3)	N13—C14—C15—F19	−178.66 (17)
N3—C4—C5—F9	177.60 (17)	F19—C15—C16—N11	−179.98 (18)
F9—C5—C6—N1	−178.30 (19)	C14—C15—C16—N11	0.1 (3)
C4—C5—C6—N1	1.7 (3)	C12—N11—C16—C15	−1.3 (3)
C2—N1—C6—C5	−0.6 (3)	C22—O21—C21—C22ⁱ	58.7 (3)
C16—N11—C12—O17	−178.0 (2)	C21—O21—C22—C21ⁱ	−58.8 (3)

Symmetry code: (i) −x, −y, −z+2.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O17ⁱⁱ	0.83 (3)	1.98 (3)	2.798 (2)	167 (2)
N3—H3···O7ⁱⁱⁱ	0.91 (2)	1.95 (2)	2.857 (2)	176 (2)
N11—H11···O21	0.91 (2)	1.84 (2)	2.746 (2)	171 (2)
N13—H13···O18^iv	0.85 (2)	1.98 (2)	2.824 (2)	175 (2)

Symmetry codes: (ii) x, y+1, z; (iii) −x, −y+1, −z+1; (iv) −x+1, −y+1, −z+1.

Acknowledgements

The authors acknowledge the Research Councils UK Basic Technology Programme for supporting `Control and Prediction of the Organic Solid State'.

References

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Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Göttingen, Germany. Google Scholar
Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany. Google Scholar
Watkin, D. J., Prout, C. K. & Pearce, L. J. (1996). CAMERON. Chemical Crystallography Laboratory, Oxford, England. Google Scholar

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