organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890

6-Ethyl-5-fluoro-2-meth­oxy­pyrimidin-4(3H)-one

aSchool of Life Science and Pharmaceutical and Chemical Engineering, Taizhou University, Linhai 317000, People's Republic of China, and bCollege of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China
*Correspondence e-mail: yeyuyuan@163.com

(Received 23 August 2009; accepted 2 September 2009; online 30 September 2009)

In the title compound, C7H9FN2O2, the meth­oxy and ethyl groups form dihedral angles of 1.4 (2) and 73.5 (3)°, respectively, with the mean plane of the pyrimidine ring. In the crystal structure, two mol­ecules are linked by a pair of N—H⋯O hydrogen bonds, forming a centrosymmetric dimer.

Related literature

For fluoro-containing pyrimidines as inter­mediates for the synthesis of some anti­cancer and anti­fungal drugs, see: Bergmann et al. (1959[Bergmann, E. D., Cohen, S. & Shahak, I. (1959). J. Chem. Soc. 11, 3278-3285.]); Butters et al. (2001[Butters, M., Ebbs, J., Green, S. P., MacRae, J., Morland, M. C., Murtiashaw, C. W. & Pettman, A. J. (2001). Org. Process Res. Dev. 5, 28-36.]).

[Scheme 1]

Experimental

Crystal data
  • C7H9FN2O2

  • Mr = 172.16

  • Triclinic, [P \overline 1]

  • a = 4.5711 (4) Å

  • b = 8.4985 (8) Å

  • c = 10.8546 (11) Å

  • α = 88.043 (2)°

  • β = 79.737 (3)°

  • γ = 79.616 (2)°

  • V = 408.13 (7) Å3

  • Z = 2

  • Mo Kα radiation

  • μ = 0.12 mm−1

  • T = 296 K

  • 0.40 × 0.28 × 0.18 mm

Data collection
  • Rigaku R-AXIS RAPID diffractometer

  • Absorption correction: multi-scan (ABSCOR; Higashi, 1995[Higashi, T. (1995). ABSCOR. Rigaku Corporation, Tokyo, Japan.]) Tmin = 0.948, Tmax = 0.979

  • 4010 measured reflections

  • 1842 independent reflections

  • 945 reflections with I > 2σ(I)

  • Rint = 0.019

Refinement
  • R[F2 > 2σ(F2)] = 0.047

  • wR(F2) = 0.106

  • S = 1.00

  • 1842 reflections

  • 111 parameters

  • H-atom parameters constrained

  • Δρmax = 0.39 e Å−3

  • Δρmin = −0.37 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N1—H1⋯O2i 0.86 1.91 2.763 (2) 174
Symmetry code: (i) -x+1, -y+1, -z+1.

Data collection: PROCESS-AUTO (Rigaku/MSC, 2004[Rigaku/MSC (2004). PROCESS-AUTO and CrystalStructure. Rigaku/MSC, The Woodlands, Texas, USA.]); cell refinement: PROCESS-AUTO; data reduction: CrystalStructure (Rigaku/MSC, 2004[Rigaku/MSC (2004). PROCESS-AUTO and CrystalStructure. Rigaku/MSC, The Woodlands, Texas, USA.]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: ORTEP-3 (Farrugia, 1997[Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.]); software used to prepare material for publication: CrystalStructure (Rigaku/MSC, 2004[Rigaku/MSC (2004). PROCESS-AUTO and CrystalStructure. Rigaku/MSC, The Woodlands, Texas, USA.]).

Supporting information


Comment top

The fluoro-containing pyrimidines have been used as a kind of important intermediates for the synthesis of some anticancer drugs and antifungal drugs (Bergmann et al., 1959; Butters et al., 2001). In the synthesis of the novel antifungal drug-Voriconazole, we have prepared the title compound 6-ethyl-5-fluoro-2-methoxypyrimidin-4(3H)-one as an intermediate, which was synthesized by reacting methyl 2-fluoro-3-oxopentanoate with o-methylisourea sulfate in a solution of sodium methylate in methanol.

The molecular structure of the title compound, (I), is illustrated in Fig. 1. The bond lenghth of C4—O2 and C1—O1 are 1.238 (3) and 1.321 (2) Å, respectively, corresponding to a double C=O bond and a Csp2—O single bond. In the six-membered pyrimidine ring, the even bond lengths of C—N and C—C are 1.361 (3) and 1.380 (3) Å, respectively, indicating these bond forming a conjugating system. The atoms in the pyrimidine ring (C1–C4/N1/N2) form a good plane with a mean deviation of 0.006 Å. An intermolecular N—H···O hydrogen bond was found to link two molecules as a pair (Fig. 2 and Table 1).

Related literature top

For fluoro-containing pyrimidines as intermediates for the synthesis of some anticancer and antifungal drugs, see: Bergmann et al. (1959); Butters et al. (2001).

Experimental top

To a 250 ml flask was added a 80 ml solution of 25% sodium methylate in methanol. The solution was cooled to 278 K, and then 40 g o-methylisourea sulfate and 20 g methyl 2-fluoro-3-oxopentanoate were added. After the addition, the mixture were stirred at 298 K for half an hour and refluxed for three hours. The mixture was concentrated under reduced pressure, and the residue was dissolved with 200 ml water. The aqueous solution was treated with 6M hydrochloric acid to pH3 and cooled in refrigerator for three hours. The resulted precipitate was filtered, to give 12.5 g product as white powder (yield 53.8%; m.p. 447–449 K). Since the product was not found to be suitable for X-ray diffraction studies, a few samples were dissolved in absolute ethanol, which was allowed to evaporate slowly to give colourless crystals of (I) suitable for X-ray diffraction studies.

Refinement top

H atoms were placed in calculated positions (C—H = 0.96–0.97 Å and N—H = 0.86 Å) and refined using a riding model, with Uiso(H) = 1.2Ueq(C, N) or 1.5Ueq(methyl C).

Computing details top

Data collection: PROCESS-AUTO (Rigaku/MSC, 2004); cell refinement: PROCESS-AUTO (Rigaku/MSC, 2004); data reduction: CrystalStructure (Rigaku/MSC, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: CrystalStructure (Rigaku/MSC, 2004).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I) with 30% probability displacement ellipsoids.
[Figure 2] Fig. 2. Packing diagram of (I), showing hydrogen bonds as dashed lines.
6-Ethyl-5-fluoro-2-methoxypyrimidin-4(3H)-one top
Crystal data top
C7H9FN2O2Z = 2
Mr = 172.16F(000) = 180.00
Triclinic, P1Dx = 1.401 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71075 Å
a = 4.5711 (4) ÅCell parameters from 2411 reflections
b = 8.4985 (8) Åθ = 3.1–27.4°
c = 10.8546 (11) ŵ = 0.12 mm1
α = 88.043 (2)°T = 296 K
β = 79.737 (3)°Chunk, colorless
γ = 79.616 (2)°0.40 × 0.28 × 0.18 mm
V = 408.13 (7) Å3
Data collection top
Rigaku R-AXIS RAPID
diffractometer
945 reflections with I > 2σ(I)
Detector resolution: 10.00 pixels mm-1Rint = 0.019
ω scansθmax = 27.4°
Absorption correction: multi-scan
(ABSCOR; Higashi, 1995)
h = 55
Tmin = 0.948, Tmax = 0.979k = 1011
4010 measured reflectionsl = 1414
1842 independent reflections
Refinement top
Refinement on F2 w = 1/[σ2(Fo2) + (0.P)2 + 0.345P]
where P = (Fo2 + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.047(Δ/σ)max < 0.001
wR(F2) = 0.106Δρmax = 0.39 e Å3
S = 1.00Δρmin = 0.37 e Å3
1842 reflectionsExtinction correction: SHELXL97 (Sheldrick, 2008)
111 parametersExtinction coefficient: 0.025 (2)
H-atom parameters constrained
Crystal data top
C7H9FN2O2γ = 79.616 (2)°
Mr = 172.16V = 408.13 (7) Å3
Triclinic, P1Z = 2
a = 4.5711 (4) ÅMo Kα radiation
b = 8.4985 (8) ŵ = 0.12 mm1
c = 10.8546 (11) ÅT = 296 K
α = 88.043 (2)°0.40 × 0.28 × 0.18 mm
β = 79.737 (3)°
Data collection top
Rigaku R-AXIS RAPID
diffractometer
1842 independent reflections
Absorption correction: multi-scan
(ABSCOR; Higashi, 1995)
945 reflections with I > 2σ(I)
Tmin = 0.948, Tmax = 0.979Rint = 0.019
4010 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.047111 parameters
wR(F2) = 0.106H-atom parameters constrained
S = 1.00Δρmax = 0.39 e Å3
1842 reflectionsΔρmin = 0.37 e Å3
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 using all reflections. The weighted R-factor (wR) and goodness of fit (S) are based on F2. R-factor (gt) are based on F. The threshold expression of F2 > 2.0 σ(F2) is used only for calculating R-factor (gt).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
F10.2750 (3)0.5521 (2)0.78974 (17)0.0840 (5)
O10.6346 (4)0.0891 (2)0.60826 (17)0.0674 (5)
O20.1625 (4)0.6002 (2)0.58950 (19)0.0754 (6)
N10.3901 (4)0.3399 (2)0.6042 (2)0.0577 (5)
N20.2058 (4)0.1623 (2)0.7615 (2)0.0587 (5)
C10.4039 (5)0.1970 (2)0.6603 (2)0.0558 (6)
C20.0212 (5)0.2877 (3)0.8040 (2)0.0579 (6)
C30.0446 (5)0.4310 (3)0.7475 (2)0.0590 (7)
C40.1656 (6)0.4689 (3)0.6427 (2)0.0603 (7)
C50.6683 (7)0.0711 (2)0.6608 (2)0.0788 (9)
C60.2321 (6)0.2513 (3)0.9191 (2)0.0753 (8)
C70.0903 (8)0.2402 (4)1.0339 (2)0.0997 (11)
H10.52760.35200.54120.069*
H510.70010.06700.74570.095*
H520.83840.13800.61220.095*
H530.48860.11420.65950.095*
H610.29300.15000.90750.090*
H620.40850.33550.93110.090*
H710.08510.15731.02310.120*
H720.23280.21561.10500.120*
H730.03240.34051.04730.120*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0660 (10)0.0684 (10)0.1026 (13)0.0173 (8)0.0007 (9)0.0156 (9)
O10.0774 (13)0.0441 (9)0.0690 (12)0.0153 (9)0.0074 (10)0.0028 (8)
O20.0822 (14)0.0447 (10)0.0864 (14)0.0146 (9)0.0062 (11)0.0003 (9)
N10.0625 (13)0.0437 (11)0.0595 (13)0.0091 (10)0.0095 (10)0.0023 (10)
N20.0594 (13)0.0517 (12)0.0629 (14)0.0013 (10)0.0131 (11)0.0034 (10)
C10.0606 (16)0.0431 (13)0.0625 (16)0.0074 (11)0.0230 (13)0.0094 (12)
C20.0502 (15)0.0603 (16)0.0623 (16)0.0031 (12)0.0122 (12)0.0101 (13)
C30.0499 (15)0.0520 (15)0.0694 (17)0.0079 (12)0.0097 (13)0.0117 (13)
C40.0620 (17)0.0456 (14)0.0698 (17)0.0082 (12)0.0187 (14)0.0083 (13)
C50.102 (2)0.0428 (14)0.082 (2)0.0155 (15)0.0193 (18)0.0009 (14)
C60.0602 (18)0.077 (2)0.085 (2)0.0112 (15)0.0033 (16)0.0051 (17)
C70.091 (2)0.136 (3)0.069 (2)0.029 (2)0.0017 (18)0.004 (2)
Geometric parameters (Å, º) top
F1—C31.359 (2)C6—C71.496 (4)
O1—C11.321 (2)N1—H10.860
O1—C51.451 (3)C5—H510.960
O2—C41.238 (3)C5—H520.960
N1—C11.336 (3)C5—H530.960
N1—C41.379 (3)C6—H610.970
N2—C11.354 (3)C6—H620.970
N2—C21.375 (3)C7—H710.960
C2—C31.340 (3)C7—H720.960
C2—C61.496 (3)C7—H730.960
C3—C41.420 (3)
C1—O1—C5118.15 (19)O1—C5—H51109.5
C1—N1—C4123.1 (2)O1—C5—H52109.5
C1—N2—C2114.5 (2)O1—C5—H53109.5
O1—C1—N1113.63 (19)H51—C5—H52109.5
O1—C1—N2121.8 (2)H51—C5—H53109.5
N1—C1—N2124.6 (2)H52—C5—H53109.5
N2—C2—C3122.1 (2)C2—C6—H61108.7
N2—C2—C6114.4 (2)C2—C6—H62108.7
C3—C2—C6123.5 (2)C7—C6—H61108.7
F1—C3—C2121.0 (2)C7—C6—H62108.7
F1—C3—C4115.4 (2)H61—C6—H62109.5
C2—C3—C4123.6 (2)C6—C7—H71109.5
O2—C4—N1121.3 (2)C6—C7—H72109.5
O2—C4—C3126.6 (2)C6—C7—H73109.5
N1—C4—C3112.1 (2)H71—C7—H72109.5
C2—C6—C7112.5 (2)H71—C7—H73109.5
C1—N1—H1118.5H72—C7—H73109.5
C4—N1—H1118.5
C5—O1—C1—N1179.1 (2)N2—C2—C3—F1178.6 (2)
C5—O1—C1—N21.4 (3)N2—C2—C3—C42.4 (4)
C1—N1—C4—O2179.0 (2)N2—C2—C6—C772.7 (3)
C1—N1—C4—C30.0 (3)C3—C2—C6—C7105.8 (3)
C4—N1—C1—O1179.3 (2)C6—C2—C3—F13.0 (4)
C4—N1—C1—N21.2 (4)C6—C2—C3—C4176.0 (3)
C1—N2—C2—C31.1 (4)F1—C3—C4—O21.9 (4)
C1—N2—C2—C6177.5 (2)F1—C3—C4—N1179.2 (2)
C2—N2—C1—O1179.9 (2)C2—C3—C4—O2177.2 (3)
C2—N2—C1—N10.6 (4)C2—C3—C4—N11.8 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O2i0.861.912.763 (2)174
Symmetry code: (i) x+1, y+1, z+1.

Experimental details

Crystal data
Chemical formulaC7H9FN2O2
Mr172.16
Crystal system, space groupTriclinic, P1
Temperature (K)296
a, b, c (Å)4.5711 (4), 8.4985 (8), 10.8546 (11)
α, β, γ (°)88.043 (2), 79.737 (3), 79.616 (2)
V3)408.13 (7)
Z2
Radiation typeMo Kα
µ (mm1)0.12
Crystal size (mm)0.40 × 0.28 × 0.18
Data collection
DiffractometerRigaku R-AXIS RAPID
diffractometer
Absorption correctionMulti-scan
(ABSCOR; Higashi, 1995)
Tmin, Tmax0.948, 0.979
No. of measured, independent and
observed [I > 2σ(I)] reflections
4010, 1842, 945
Rint0.019
(sin θ/λ)max1)0.648
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.047, 0.106, 1.00
No. of reflections1842
No. of parameters111
No. of restraints?
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.39, 0.37

Computer programs: PROCESS-AUTO (Rigaku/MSC, 2004), CrystalStructure (Rigaku/MSC, 2004), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 1997).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O2i0.861.9072.763 (2)174
Symmetry code: (i) x+1, y+1, z+1.
 

Acknowledgements

The authors acknowledge support from the Educational Commission of Zhejiang Province (200803289).

References

First citationBergmann, E. D., Cohen, S. & Shahak, I. (1959). J. Chem. Soc. 11, 3278–3285.  CrossRef Web of Science Google Scholar
First citationButters, M., Ebbs, J., Green, S. P., MacRae, J., Morland, M. C., Murtiashaw, C. W. & Pettman, A. J. (2001). Org. Process Res. Dev. 5, 28–36.  Web of Science CrossRef CAS Google Scholar
First citationFarrugia, L. J. (1997). J. Appl. Cryst. 30, 565.  CrossRef IUCr Journals Google Scholar
First citationHigashi, T. (1995). ABSCOR. Rigaku Corporation, Tokyo, Japan.  Google Scholar
First citationRigaku/MSC (2004). PROCESS-AUTO and CrystalStructure. Rigaku/MSC, The Woodlands, Texas, USA.  Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar

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