5-Fluoro­uracil–di­methyl­form­amide (2/1)

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

doi:10.1107/S1600536804022263

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 60| Part 10| October 2004| Pages o1783-o1785

https://doi.org/10.1107/S1600536804022263

5-Fluorouracil–dimethylformamide (2/1)

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 dimethylformamide (DMF), 2C₄H₃FN₂O₂·C₃H₇NO, is reported. It crystallizes in the monoclinic space group P2₁/n, with two molecules of 5-fluorouracil and one molecule of DMF in the asymmetric unit. This solvate exhibits a sheet structure, with the DMF molecules present on both surfaces of the sheet and 5-fluorouracil molecules within the sheath of DMF molecules.

Comment

In the course of a polymorph screen performed on 5-fluorouracil, three solvates were discovered. One of the solvate structures, (I), containing two independent molecules of 5-fluorouracil and one molecule of dimethyl formamide (DMF) in the asymmetric unit (Fig. 1), and crystallizing in the space group P2₁/n, is reported here.

The two 5-fluorouracil molecules in the asymmetric unit are linked to one another via N11—H11⋯O7 [N⋯O = 2.7962 (18) Å] hydrogen bonds. The DMF molecule forms a hydrogen bond to one of the 5-fluorouracil molecules in the asymmetric unit [N3—H3⋯O20, 2.7518 (19) Å]. A further two N—H⋯O hydrogen bonds link 5-fluorouracil molecules in the crystal structure; these bonds are N1—H1⋯O17ⁱ [N⋯O = 2.8205 (19) Å], and N13—H13^...O18ⁱⁱ [N⋯O = 2.8203 (18) Å]. The N13—H13⋯O18ⁱⁱ hydrogen bonds link the 5-fluorouracil molecules into a centrosymmetric hydrogen-bonded dimer.

This solvate exhibits a sheet structure, in which the sheet has a discrete thickness of approximately 13.9 Å in the direction perpendicular to the plane of the sheet, and stacks parallel to the (10 $[\overline 1]$ ) planes. The DMF molecules are present on both surfaces of the sheet with 5-fluorouracil molecules within this sheath of DMF molecules. The parallel sheets approach each other closely, though there are no short intermolecular contacts between DMF molecules in adjacent sheets. Within the sheets the 5-fluorouracil molecules do not lie parallel to each other, but form a series of smaller blocks of parallel ribbons, as shown in Fig. 2. These ribbons are finite in length and are terminated by surface DMF molecules. Each of these ribbons is ca 26.8 Å long (Fig. 3).

Figure 1
View (Watkin et al., 1996

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

Figure 2
View parallel to the plane of two sheets of the structure. 5-Fluorouracil molecules are coloured blue, while the DMF molecules are red. Dashed lines indicate hydrogen bonds.

Figure 3
Three adjacent ribbons of a larger sheet, showing an alternating crossed orientation. Other ribbons stack parallel to each of the ribbons in the diagram. Dashed lines indicate hydrogen bonds.

Experimental

5-Fluorouracil was obtained from the Aldrich Chemical Company Inc. The crystals were grown by vapour diffusion of diethyl ether into a saturated solution of 5-fluorouracil in dimethylformamide.

Crystal data

2C₄H₃FN₂O₂·C₃H₇NO
M_r = 333.26
Monoclinic, P2₁/n
a = 14.7361 (18) Å
b = 5.8693 (7) Å
c = 16.397 (2) Å
β = 100.524 (2)°
V = 1394.3 (3) Å³
Z = 4
D_x = 1.588 Mg m⁻³
Mo Kα radiation
Cell parameters from 2752 reflections
θ = 2.5–27.7°
μ = 0.14 mm⁻¹
T = 150 (2) K
Block, colourless
0.42 × 0.21 × 0.11 mm

Data collection

Bruker SMART APEX diffractometer
Narrow-frame ω scans
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ) T_min = 0.942, T_max = 0.984
11 701 measured reflections
3331 independent reflections
2768 reflections with I > 2σ(I)
R_int = 0.032
θ_max = 28.3°
h = −19 → 19
k = −7 → 7
l = −21 → 20

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.049
wR(F²) = 0.108
S = 1.10
3331 reflections
238 parameters
H atoms treated by a mixture of independent and constrained refinement
w = 1/[σ²(F_o²) + (0.043P)² + 0.5804P] where P = (F_o² + 2F_c²)/3
(Δ/σ)_max < 0.001
Δρ_max = 0.29 e Å⁻³
Δρ_min = −0.22 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 (2)	2.01 (2)	2.8205 (19)	167 (2)
N3—H3⋯O20	0.85 (2)	1.90 (2)	2.7518 (19)	176 (2)
N11—H11⋯O7	0.86 (2)	1.97 (2)	2.7962 (18)	160 (2)
N13—H13⋯O18ⁱⁱ	0.86 (2)	1.96 (2)	2.8203 (18)	175 (2)
Symmetry codes: (i) $[{\script{1\over 2}}-x,y-{\script{1\over 2}},{\script{1\over 2}}-z]$ ; (ii) -x,-y,-z.

The methyl H atoms were placed in geometrically idealized positions (C—H = 0.98 Å) and allowed to ride on their parent atoms with U_iso(H) = 1.5U_eq(C). All other H atoms were located in a difference map and were refined isotropically; N—H and C—H distances were in the range 0.83 (2)–0.86 (2) and 0.94 (2)–0.97 (2) Å, respectively.

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, str0210. DOI: https://doi.org/10.1107/S1600536804022263/ci6441sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536804022263/ci6441Isup2.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 Dimethylformamide (2/1) top

Crystal data top

2C₄H₃FN₂O₂·C₃H₇NO	F(000) = 688
M_r = 333.26	D_x = 1.588 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 2752 reflections
a = 14.7361 (18) Å	θ = 2.5–27.7°
b = 5.8693 (7) Å	µ = 0.14 mm⁻¹
c = 16.397 (2) Å	T = 150 K
β = 100.524 (2)°	Block, colourless
V = 1394.3 (3) Å³	0.42 × 0.21 × 0.11 mm
Z = 4

Data collection top

Bruker SMART APEX diffractometer	3331 independent reflections
Radiation source: fine-focus sealed tube	2768 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.032
ω rotation with narrow frames scans	θ_max = 28.3°, θ_min = 1.7°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −19→19
T_min = 0.942, T_max = 0.984	k = −7→7
11701 measured reflections	l = −21→20

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)] = 0.049	Hydrogen site location: found from delta F, methyl hydrogens placed using rigid rotor model
wR(F²) = 0.108	H atoms treated by a mixture of independent and constrained refinement
S = 1.10	w = 1/[σ²(F_o²) + (0.043P)² + 0.5804P] where P = (F_o² + 2F_c²)/3
3331 reflections	(Δ/σ)_max < 0.001
238 parameters	Δρ_max = 0.29 e Å⁻³
0 restraints	Δρ_min = −0.22 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	0.74489 (8)	0.3172 (2)	0.40798 (8)	0.0457 (3)
O7	0.39619 (8)	0.3532 (2)	0.24355 (8)	0.0250 (3)
O8	0.68162 (9)	0.6691 (2)	0.29920 (10)	0.0418 (4)
N1	0.50826 (10)	0.1673 (3)	0.33347 (9)	0.0226 (3)
H1	0.4706 (15)	0.067 (4)	0.3390 (13)	0.035 (6)*
N3	0.53929 (10)	0.5079 (2)	0.27412 (9)	0.0217 (3)
H3	0.5228 (14)	0.610 (4)	0.2378 (13)	0.032 (6)*
C2	0.47601 (11)	0.3415 (3)	0.28135 (10)	0.0193 (3)
C4	0.63096 (12)	0.5142 (3)	0.31233 (11)	0.0259 (4)
C5	0.65670 (12)	0.3215 (3)	0.36632 (11)	0.0280 (4)
C6	0.59742 (13)	0.1573 (3)	0.37572 (11)	0.0257 (4)
H6	0.6136 (13)	0.031 (4)	0.4103 (12)	0.031 (5)*
F19	0.24134 (7)	−0.42399 (17)	0.04386 (6)	0.0274 (3)
O17	0.13892 (8)	0.3590 (2)	0.16837 (7)	0.0242 (3)
O18	0.07207 (8)	−0.2263 (2)	−0.01531 (7)	0.0260 (3)
N11	0.24840 (9)	0.0874 (2)	0.16475 (9)	0.0209 (3)
H11	0.2885 (13)	0.162 (3)	0.1997 (12)	0.024 (5)*
N13	0.10821 (9)	0.0668 (2)	0.07569 (9)	0.0198 (3)
H13	0.0542 (15)	0.124 (3)	0.0582 (13)	0.032 (6)*
C12	0.16439 (11)	0.1830 (3)	0.13902 (10)	0.0193 (3)
C14	0.12779 (11)	−0.1352 (3)	0.04047 (10)	0.0196 (3)
C15	0.21743 (11)	−0.2249 (3)	0.07521 (10)	0.0196 (3)
C16	0.27456 (11)	−0.1152 (3)	0.13482 (10)	0.0222 (4)
H16	0.3353 (13)	−0.167 (3)	0.1594 (12)	0.026 (5)*
O20	0.49362 (8)	0.8486 (2)	0.15864 (8)	0.0279 (3)
N20	0.54350 (10)	1.1737 (2)	0.10675 (9)	0.0232 (3)
C20	0.61968 (13)	1.3266 (3)	0.10100 (13)	0.0342 (4)
H20A	0.6758	1.2713	0.1370	0.051*
H20B	0.6051	1.4797	0.1186	0.051*
H20C	0.6295	1.3318	0.0435	0.051*
C21	0.45396 (12)	1.2308 (3)	0.05755 (11)	0.0304 (4)
H21A	0.4120	1.1010	0.0569	0.046*
H21B	0.4611	1.2666	0.0007	0.046*
H21C	0.4285	1.3633	0.0819	0.046*
C22	0.55522 (12)	0.9873 (3)	0.15346 (10)	0.0224 (4)
H22	0.6169 (13)	0.966 (3)	0.1847 (12)	0.028 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F9	0.0267 (6)	0.0442 (7)	0.0568 (8)	−0.0046 (5)	−0.0171 (5)	0.0188 (6)
O7	0.0196 (6)	0.0247 (6)	0.0289 (6)	−0.0033 (5)	−0.0005 (5)	−0.0026 (5)
O8	0.0291 (7)	0.0347 (8)	0.0558 (9)	−0.0127 (6)	−0.0073 (6)	0.0173 (7)
N1	0.0245 (7)	0.0172 (7)	0.0256 (8)	−0.0045 (6)	0.0033 (6)	0.0015 (6)
N3	0.0222 (7)	0.0170 (7)	0.0240 (7)	−0.0026 (6)	−0.0010 (6)	0.0058 (6)
C2	0.0220 (8)	0.0180 (8)	0.0182 (8)	−0.0018 (6)	0.0045 (6)	−0.0038 (6)
C4	0.0227 (9)	0.0225 (9)	0.0302 (9)	−0.0047 (7)	−0.0011 (7)	0.0025 (7)
C5	0.0225 (9)	0.0279 (9)	0.0298 (9)	−0.0010 (7)	−0.0050 (7)	0.0054 (8)
C6	0.0305 (9)	0.0201 (9)	0.0246 (9)	0.0019 (7)	0.0003 (7)	0.0047 (7)
F19	0.0264 (5)	0.0233 (5)	0.0315 (6)	0.0062 (4)	0.0028 (4)	−0.0078 (4)
O17	0.0244 (6)	0.0196 (6)	0.0265 (6)	0.0022 (5)	−0.0005 (5)	−0.0063 (5)
O18	0.0218 (6)	0.0260 (7)	0.0266 (6)	0.0025 (5)	−0.0048 (5)	−0.0097 (5)
N11	0.0173 (7)	0.0211 (7)	0.0223 (7)	−0.0017 (6)	−0.0015 (6)	−0.0051 (6)
N13	0.0164 (7)	0.0201 (7)	0.0210 (7)	0.0032 (5)	−0.0015 (5)	−0.0022 (6)
C12	0.0198 (8)	0.0183 (8)	0.0187 (8)	−0.0017 (6)	0.0008 (6)	−0.0005 (6)
C14	0.0200 (8)	0.0204 (8)	0.0183 (8)	−0.0010 (6)	0.0031 (6)	−0.0023 (6)
C15	0.0216 (8)	0.0165 (8)	0.0212 (8)	0.0015 (6)	0.0052 (6)	−0.0020 (6)
C16	0.0178 (8)	0.0244 (9)	0.0239 (8)	0.0027 (6)	0.0025 (7)	0.0012 (7)
O20	0.0271 (6)	0.0235 (6)	0.0321 (7)	0.0006 (5)	0.0025 (5)	0.0098 (5)
N20	0.0231 (7)	0.0218 (7)	0.0247 (7)	0.0044 (6)	0.0046 (6)	0.0064 (6)
C20	0.0280 (10)	0.0291 (10)	0.0459 (12)	0.0015 (8)	0.0080 (8)	0.0141 (9)
C21	0.0285 (9)	0.0316 (10)	0.0291 (10)	0.0062 (8)	0.0002 (8)	0.0117 (8)
C22	0.0236 (9)	0.0214 (9)	0.0224 (8)	0.0057 (7)	0.0048 (7)	0.0029 (7)

Geometric parameters (Å, º) top

F9—C5	1.353 (2)	N13—C14	1.372 (2)
O7—C2	1.227 (2)	N13—C12	1.384 (2)
O8—C4	1.220 (2)	N13—H13	0.86 (2)
N1—C2	1.361 (2)	C14—C15	1.439 (2)
N1—C6	1.370 (2)	C15—C16	1.333 (2)
N1—H1	0.83 (2)	C16—H16	0.963 (19)
N3—C2	1.370 (2)	O20—C22	1.234 (2)
N3—C4	1.382 (2)	N20—C22	1.328 (2)
N3—H3	0.85 (2)	N20—C20	1.454 (2)
C4—C5	1.444 (2)	N20—C21	1.454 (2)
C5—C6	1.329 (3)	C20—H20A	0.98
C6—H6	0.94 (2)	C20—H20B	0.98
F19—C15	1.3491 (19)	C20—H20C	0.98
O17—C12	1.227 (2)	C21—H21A	0.98
O18—C14	1.2340 (19)	C21—H21B	0.98
N11—C12	1.354 (2)	C21—H21C	0.98
N11—C16	1.369 (2)	C22—H22	0.967 (19)
N11—H11	0.86 (2)

C2—N1—C6	122.85 (15)	O18—C14—N13	121.60 (15)
C2—N1—H1	116.2 (15)	O18—C14—C15	124.96 (15)
C6—N1—H1	120.9 (15)	N13—C14—C15	113.45 (14)
C2—N3—C4	127.17 (15)	C16—C15—F19	121.59 (15)
C2—N3—H3	116.8 (14)	C16—C15—C14	121.62 (15)
C4—N3—H3	115.5 (14)	F19—C15—C14	116.79 (14)
O7—C2—N1	123.49 (15)	C15—C16—N11	120.07 (15)
O7—C2—N3	121.39 (15)	C15—C16—H16	124.6 (11)
N1—C2—N3	115.12 (14)	N11—C16—H16	115.3 (11)
O8—C4—N3	121.27 (16)	C22—N20—C20	121.68 (15)
O8—C4—C5	126.24 (16)	C22—N20—C21	121.25 (15)
N3—C4—C5	112.49 (15)	C20—N20—C21	117.06 (14)
C6—C5—F9	121.25 (16)	N20—C20—H20A	109.5
C6—C5—C4	122.34 (16)	N20—C20—H20B	109.5
F9—C5—C4	116.41 (15)	H20A—C20—H20B	109.5
C5—C6—N1	120.00 (16)	N20—C20—H20C	109.5
C5—C6—H6	123.0 (12)	H20A—C20—H20C	109.5
N1—C6—H6	117.0 (12)	H20B—C20—H20C	109.5
C12—N11—C16	123.32 (14)	N20—C21—H21A	109.5
C12—N11—H11	118.2 (13)	N20—C21—H21B	109.5
C16—N11—H11	118.4 (13)	H21A—C21—H21B	109.5
C14—N13—C12	126.76 (14)	N20—C21—H21C	109.5
C14—N13—H13	116.6 (14)	H21A—C21—H21C	109.5
C12—N13—H13	116.6 (14)	H21B—C21—H21C	109.5
O17—C12—N11	123.64 (15)	O20—C22—N20	124.28 (16)
O17—C12—N13	121.68 (15)	O20—C22—H22	120.6 (12)
N11—C12—N13	114.68 (14)	N20—C22—H22	115.1 (12)

C6—N1—C2—O7	−179.53 (16)	C16—N11—C12—N13	−3.9 (2)
C6—N1—C2—N3	−0.2 (2)	C14—N13—C12—O17	−177.25 (16)
C4—N3—C2—O7	−179.27 (16)	C14—N13—C12—N11	3.1 (2)
C4—N3—C2—N1	1.3 (3)	C12—N13—C14—O18	179.08 (16)
C2—N3—C4—O8	177.84 (18)	C12—N13—C14—C15	−0.7 (2)
C2—N3—C4—C5	−1.7 (3)	O18—C14—C15—C16	179.13 (17)
O8—C4—C5—C6	−178.5 (2)	N13—C14—C15—C16	−1.1 (2)
N3—C4—C5—C6	1.1 (3)	O18—C14—C15—F19	−0.1 (3)
O8—C4—C5—F9	2.1 (3)	N13—C14—C15—F19	179.71 (13)
N3—C4—C5—F9	−178.35 (16)	F19—C15—C16—N11	179.46 (14)
F9—C5—C6—N1	179.27 (17)	C14—C15—C16—N11	0.3 (3)
C4—C5—C6—N1	−0.1 (3)	C12—N11—C16—C15	2.4 (3)
C2—N1—C6—C5	−0.4 (3)	C20—N20—C22—O20	−177.80 (17)
C16—N11—C12—O17	176.43 (16)	C21—N20—C22—O20	0.8 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O17ⁱ	0.83 (2)	2.01 (2)	2.8205 (19)	167 (2)
N3—H3···O20	0.85 (2)	1.90 (2)	2.7518 (19)	176 (2)
N11—H11···O7	0.86 (2)	1.97 (2)	2.7962 (18)	160 (2)
N13—H13···O18ⁱⁱ	0.86 (2)	1.96 (2)	2.8203 (18)	175 (2)

Symmetry codes: (i) −x+1/2, y−1/2, −z+1/2; (ii) −x, −y, −z.

Acknowledgements

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

References

Bruker (1998). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
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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