5-Fluoro-1-(3-metylbutano­yl)pyrimidine-2,4(1H,3H)-dione

Lehmler, H.-J.; Parkin, S.

doi:10.1107/S1600536808006296

organic compounds

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Volume 64| Part 4| April 2008| Page o703

doi:10.1107/S1600536808006296

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5-Fluoro-1-(3-metylbutanoyl)pyrimidine-2,4(1H,3H)-dione

Hans-Joachim Lehmler ^a ^* and Sean Parkin ^b

^aThe University of Iowa, Department of Occupational and Environmental Health, 100 Oakdale Campus, 124 IREH, Iowa City, IA 52242-5000, USA, and ^bUniversity of Kentucky, Department of Chemistry, Lexington, KY 40506-0055, USA
^*Correspondence e-mail: hans-joachim-lehmler@uiowa.edu

(Received 28 February 2008; accepted 6 March 2008; online 12 March 2008)

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—H⋯O interactions.

Related literature

For similar 5-fluoropyrimidine-2,4(1H,3H)-dione structures with N1-acyl substituents, see: Beall et al. (1993 ); Jiang et al. (1988 ); Lehmler & Parkin (2000 ); Lehmler & Parkin (2008 ). For related literature, see: Roberts & Sloan (1999 ).

Experimental

Crystal data

C₉H₁₁FN₂O₃
M_r = 214.20
Triclinic, $[P \overline 1]$
a = 5.4879 (3) Å
b = 9.3702 (5) Å
c = 9.9794 (5) Å
α = 103.470 (2)°
β = 100.204 (3)°
γ = 104.085 (3)°
V = 468.94 (4) Å³
Z = 2
Mo Kα radiation
μ = 0.13 mm⁻¹
T = 90.0 (2) K
0.30 × 0.20 × 0.07 mm

Data collection

Nonius KappaCCD diffractometer
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997 ) T_min = 0.963, T_max = 0.991
4080 measured reflections
2139 independent reflections
1629 reflections with I > 2σ(I)
R_int = 0.031

Refinement

R[F² > 2σ(F²)] = 0.049
wR(F²) = 0.112
S = 1.07
2139 reflections
138 parameters
H-atom parameters constrained
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.29 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3⋯O4ⁱ	0.88	2.04	2.9091 (16)	171
Symmetry code: (i) -x-1, -y+1, -z+1.

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 and local procedures.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808006296/om2217sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808006296/om2217Isup2.hkl

checkCIF report

Comment top

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.

Related literature top

For similar 5-fluoropyrimidine-2,4(1H,3H)-dione structures with N1-acyl substituents, see: Beall et al. (1993); Jiang et al. (1988); Lehmler & Parkin (2000); Lehmler & Parkin (2008). For related literature, see: Roberts & Sloan (1999).

Experimental top

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).

Computing details top

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.

Figures top

Fig. 1. View of the title compound showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.

5-Fluoro-1-(3-metylbutanoyl)pyrimidine-2,4(1H,3H)-dione top

Crystal data top

C₉H₁₁FN₂O₃	Z = 2
M_r = 214.20	F(000) = 224
Triclinic, P1	D_x = 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 = 1.0–27.5°
c = 9.9794 (5) Å	µ = 0.13 mm⁻¹
α = 103.470 (2)°	T = 90 K
β = 100.204 (3)°	Irregular block, colourless
γ = 104.085 (3)°	0.30 × 0.20 × 0.07 mm
V = 468.94 (4) Å³

Data collection top

Nonius KappaCCD diffractometer	2139 independent reflections
Radiation source: fine-focus sealed tube	1629 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.031
Detector resolution: 18 pixels mm^-1	θ_max = 27.5°, θ_min = 2.2°
ω scans at fixed χ = 55°	h = −7→7
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997)	k = −12→12
T_min = 0.963, T_max = 0.991	l = −12→12
4080 measured reflections

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: inferred from neighbouring sites
wR(F²) = 0.112	H-atom parameters constrained
S = 1.07	w = 1/[σ²(F_o²) + (0.0498P)² + 0.0466P] where P = (F_o² + 2F_c²)/3
2139 reflections	(Δ/σ)_max = 0.001
138 parameters	Δρ_max = 0.27 e Å⁻³
0 restraints	Δρ_min = −0.29 e Å⁻³

Crystal data top

C₉H₁₁FN₂O₃	γ = 104.085 (3)°
M_r = 214.20	V = 468.94 (4) Å³
Triclinic, P1	Z = 2
a = 5.4879 (3) Å	Mo Kα radiation
b = 9.3702 (5) Å	µ = 0.13 mm⁻¹
c = 9.9794 (5) Å	T = 90 K
α = 103.470 (2)°	0.30 × 0.20 × 0.07 mm
β = 100.204 (3)°

Data collection top

Nonius KappaCCD diffractometer	2139 independent reflections
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997)	1629 reflections with I > 2σ(I)
T_min = 0.963, T_max = 0.991	R_int = 0.031
4080 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.049	0 restraints
wR(F²) = 0.112	H-atom parameters constrained
S = 1.07	Δρ_max = 0.27 e Å⁻³
2139 reflections	Δρ_min = −0.29 e Å⁻³
138 parameters

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 > 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.

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

	x	y	z	U_iso*/U_eq
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*

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···O4ⁱ	0.88	2.04	2.9091 (16)	171

Symmetry code: (i) −x−1, −y+1, −z+1.

Experimental details

Crystal data
Chemical formula	C₉H₁₁FN₂O₃
M_r	214.20
Crystal system, space group	Triclinic, P1
Temperature (K)	90
a, b, c (Å)	5.4879 (3), 9.3702 (5), 9.9794 (5)
α, β, γ (°)	103.470 (2), 100.204 (3), 104.085 (3)
V (Å³)	468.94 (4)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.13
Crystal size (mm)	0.30 × 0.20 × 0.07

Data collection
Diffractometer	Nonius KappaCCD diffractometer
Absorption correction	Multi-scan (SCALEPACK; Otwinowski & Minor, 1997)
T_min, T_max	0.963, 0.991
No. of measured, independent and observed [I > 2σ(I)] reflections	4080, 2139, 1629
R_int	0.031
(sin θ/λ)_max (Å⁻¹)	0.649

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.049, 0.112, 1.07
No. of reflections	2139
No. of parameters	138
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.27, −0.29

Computer programs: COLLECT (Nonius, 1998), SCALEPACK (Otwinowski & Minor, 1997), DENZO-SMN (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), XP in SHELXTL (Sheldrick, 2008), SHELX97 (Sheldrick, 2008) and local procedures.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···O4ⁱ	0.88	2.04	2.9091 (16)	170.9

Symmetry code: (i) −x−1, −y+1, −z+1.

References

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doi:10.1107/S1600536808006296

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