5 Fluoro­uracil 1 propionic acid

organic papers

o586

7H7FN2O4 doi:10.1107/S1600536806000584 Acta Cryst.(2006). E62, o586–o588

Acta Crystallographica Section E Structure Reports Online

ISSN 1600-5368

5-Fluorouracil-1-propionic acid

Jian-Qiang Qu,a* Xiao-Fei Jia,a Jian-Zhong Cui,aHong Zhanga and Liu-Fang Wangb

a_{Department of Chemistry, Tianjin University,}

Tianjin 300072, People’s Republic of China, andb_{State Key Laboratory of Applied Organic}

Chemistry, Lanzhou University, Lanzhou 730000, People’s Republic of China

Correspondence e-mail: [email protected]

Key indicators

Single-crystal X-ray study

T= 294 K

Mean(C–C) = 0.004 A˚ Disorder in main residue

Rfactor = 0.047

wRfactor = 0.145

Data-to-parameter ratio = 12.8

For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.

Received 12 December 2005 Accepted 5 January 2006

#2006 International Union of Crystallography All rights reserved

In the title compound, C7H7FN2O4, the propionic acid group is

twisted out of the pyrimidine plane. In the crystal structure, molecules are connected by intermolecular N—H O and O—H O hydrogen bonds, forming columns.

Comment

5-Fluorouracil is a normal antitumor medicine which has been used in clinics for 40 years; it can be used to treat breast cancer, gastric carcinoma and bladder cancer (Duschinsky et al., 1957; Heidelberger et al., 1957; Correale et al., 2005). However, the toxic side effects, such as marrow inhibition and a little harmful to liver, kidney and digestive system, limit its wider applicability (Wasterack & Bettina, 1987). Searching for compounds with high antitumor activity and low toxicity is an urgent task for scientists. In order to reduce the side effects, many derivatives of 5-fluorouracil have been synthesized and some of these compounds have better biological activity (Zhuo et al., 1986). 5-Fluorouracil-1-propionic acid, (I), is a member of the family. Its rare earth metal complexes have been reported to have prooxidative and antitumor activity (Liuet al., 2000).

The propionic acid group is twisted out of the pyrimidine plane [torsion angles C7—N1—C3—C2 and C4—N1—C3— C2 are 88.0 (3) and 94.4 (2), respectively] (Fig. 1). C—F, C—O and C—N bond distances are given in Table 1.

Inter-molecular N—H O and O—H O hydrogen bonds

(Table 2) form columns along thebaxis (Fig. 2).

Experimental

obtained by slow evaporation of an ethanol solution. IR (KBr,

cm1_{): 3284, 1694, 1416;}1_{H NMR (d}

6-DMSO,, p.p.m.): 11.70 (s, 1H),

12.65 (b, 1H), 7.85 (d, 1H), 3.72 (t, 2H), 2.54 (t, 2H); analysis calcu-lated for C7H7FN2O4: C 41.58, H 3.49, N 13.86%; found: C 41.50,

H 3.62, N 13.77%.

Crystal data

C7H7FN2O4 Mr= 202.15

Monoclinic,C2=c a= 20.279 (6) A˚

b= 8.137 (2) A˚

c= 13.222 (4) A˚

= 128.673 (4)

V= 1703.3 (8) A˚3 Z= 8

Dx= 1.577 Mg m

3

MoKradiation Cell parameters from 1663

reflections

= 2.8–26.3

= 0.14 mm1 T= 294 (2) K Block, colourless 0.260.240.20 mm

Data collection

Bruker SMART CCD area-detector diffractometer

’and!scans

Absorption correction: multi-scan (SADABS; Sheldrick, 1996)

Tmin= 0.958,Tmax= 0.972

4556 measured reflections

1747 independent reflections 1245 reflections withI> 2(I)

Rint= 0.035

max= 26.5 h=20!25

k=7!10

l=16!16

Refinement

Refinement onF2 R[F2_{> 2(F}2_{)] = 0.047} wR(F2) = 0.145

S= 1.05 1747 reflections 137 parameters

H atoms treated by a mixture of independent and constrained refinement

w= 1/[2_(F

o2) + (0.0679P)2

+ 1.9948P]

whereP= (Fo2+ 2Fc2)/3

(/)max= 0.002 max= 0.30 e A˚

3 min=0.41 e A˚

3

Table 1

Selected bond lengths (A˚ ).

F1—C6 1.352 (3) O1—C1 1.229 (3) O2—C1 1.324 (3) O3—C4 1.217 (3) O4—C5 1.222 (3)

N1—C3 1.473 (3) N1—C4 1.380 (3) N1—C7 1.370 (3) N2—C4 1.377 (3) N2—C5 1.376 (3)

Table 2

Hydrogen-bond geometry (A˚ ,_).

D—H A D—H H A D A D—H A

N2—H2E O1i

0.81 (3) 2.00 (3) 2.797 (3) 171 (3) O2—H2C O4ii

0.839 (10) 2.06 (2) 2.887 (3) 167 (8) O2—H2D O3iii 0.839 (10) 2.154 (14) 2.990 (3) 174 (8)

Symmetry codes: (i)x;yþ1;z; (ii)x;y1;zþ1

2; (iii)xþ12;yþ32;zþ1.

H atoms attached to O and N atoms were located in a difference map. The OH group is disordered over two positions with an occu-pancy ratio of 0.5:0.5 and the H atom was refined with a restraint of O—H = 0.82 (2) A˚ . The H atom of the NH group was refined freely. All other H atoms were placed in geometrically calculated positions (C—H = 0.93 or 0.97 A˚ ) and refined as riding atoms [Uiso(H) =

1.2Ueq(C)].

Data collection:SMART(Bruker, 1997); cell refinement:SAINT

(Bruker, 1997); data reduction: SAINT; program(s) used to solve structure: SHELXS97(Sheldrick, 1997); program(s) used to refine

structure: SHELXL97 (Sheldrick, 1997); molecular graphics:

SHELXTL (Bruker, 1997); software used to prepare material for publication:SHELXTL.

This work was supported by the Scientific Research Foun-dation of Tianjin University.

References

Bruker (1997). SMART (Version 5.06a), SAINT (Version 5.051) and

SHELXTL(Version 5.10). Bruker AXS Inc., Madison, Wiscosin, USA.

organic papers

Acta Cryst.(2006). E62, o586–o588 Quet al. _C

7H7FN2O4

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Figure 1

The molecular structure of (I), showing the atom-labelling scheme. Displacement ellipsolids are drawn at the 35% probability level. Both disorder components of the OH group are shown.

Figure 2

Correale, P., Fulfaro, F., Marsili, S., Cicero, G., Bajardi, E., Intrivici, C., Vuolo, G., Carli, A. F., Caraglia, M., Prete, S. D., Greco, E., Gebbia, N. & Francini, G. (2005).Cancer Chemother. Pharmacol.56, 563–568.

Duschinsky, R., Pleven, E. & Heidelberger, C. (1957).J. Am. Chem. Soc.79, 4559–4560.

Heidelberger, C., Chaudhuri, M. S., Danneberg, P., Mooren, D., Duschinsky, R., Schnitzer, R. J., Pleven, E. & Scheiner, J. (1957).Nature (London),179, 663–666.

Liu, Y.-M., Kang, J.-H., Wang, Z.-P., Wang, L.-F., Gao, L., Xia, C.-G. & Cui, J.-R. (2000).J. Coord. Chem.52, 1–13.

Sheldrick, G. M. (1996).SADABS. University of Go¨ttingen, Germany. Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of

Go¨ttingen, Germany.

Wasterack, C. & Bettina, H. (1987).Pharmazie,12, 73–75.

Zhuo, R.-X., Fan, C.-L. & Zhou, R.-L. (1986).Chem. J. Chin. Univ.7, 508– 510.

organic papers

o588

supporting information

sup-1 Acta Cryst. (2006). E62, o586–o588

supporting information

Acta Cryst. (2006). E62, o586–o588 [https://doi.org/10.1107/S1600536806000584]

5-Fluorouracil-1-propionic acid

Jian-Qiang Qu, Xiao-Fei Jia, Jian-Zhong Cui, Hong Zhang and Liu-Fang Wang

5-Fluorouracil-1-propionic acid

Crystal data

C7H7FN2O4

Mr = 202.15 Monoclinic, C2/c a = 20.279 (6) Å

b = 8.137 (2) Å

c = 13.222 (4) Å

β = 128.673 (4)°

V = 1703.3 (8) Å3

Z = 8

F(000) = 832

Dx = 1.577 Mg m−3

Melting point: 457 K

Mo Kα radiation, λ = 0.71073 Å Cell parameters from 1663 reflections

θ = 2.8–26.3°

µ = 0.14 mm−1

T = 294 K Block, colourless 0.26 × 0.24 × 0.20 mm

Data collection

Bruker SMART CCD area-detector diffractometer

Radiation source: fine-focus sealed tube Graphite monochromator

φ and ω scans

Absorption correction: multi-scan (SADABS; Sheldrick, 1996)

Tmin = 0.958, Tmax = 0.972

4556 measured reflections 1747 independent reflections 1245 reflections with I > 2σ(I)

Rint = 0.035

θmax = 26.5°, θmin = 2.6°

h = −20→25

k = −7→10

l = −16→16

Refinement

Refinement on F2

Least-squares matrix: full

R[F2 _{> 2σ(F}2_{)] = 0.047}

wR(F2_{) = 0.145}

S = 1.05 1747 reflections 137 parameters 14 restraints

Primary atom site location: structure-invariant direct methods

Secondary atom site location: difference Fourier map

Hydrogen site location: inferred from neighbouring sites

H atoms treated by a mixture of independent and constrained refinement

w = 1/[σ2_(F

o2) + (0.0679P)2 + 1.9948P]

where P = (Fo2 + 2Fc2)/3

(Δ/σ)max = 0.002

Δρmax = 0.30 e Å−3

Δρmin = −0.41 e Å−3

Special details

supporting information

sup-2 Acta Cryst. (2006). E62, o586–o588

Refinement. Refinement of F2 _{against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F}2_,

conventional R-factors R are based on F, with F set to zero for negative F2_{. The threshold expression of F}2 _{> σ(F}2_{) 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₎

x y z Uiso*/Ueq Occ. (<1)

F1 −0.11918 (9) 0.74550 (19) −0.00859 (18) 0.0595 (5) O1 0.09860 (12) 0.3482 (2) 0.23697 (17) 0.0488 (5) O2 0.16000 (17) 0.3696 (3) 0.4480 (3) 0.0767 (7)

H2C 0.130 (4) 0.291 (6) 0.439 (8) 0.092* 0.50 H2D 0.199 (3) 0.411 (10) 0.520 (4) 0.092* 0.50 O3 0.19940 (10) 0.9631 (2) 0.30681 (17) 0.0455 (5)

O4 −0.08222 (10) 1.0748 (2) 0.04855 (17) 0.0453 (5) N1 0.10767 (11) 0.7502 (2) 0.19657 (18) 0.0301 (5) N2 0.05845 (12) 1.0148 (2) 0.18074 (19) 0.0315 (5) H2E 0.0676 (17) 1.110 (4) 0.201 (3) 0.042 (8)* C1 0.15073 (15) 0.4128 (3) 0.3432 (2) 0.0348 (6) C2 0.20949 (14) 0.5458 (3) 0.3625 (2) 0.0391 (6)

H2A 0.2185 0.6243 0.4252 0.047*

H2B 0.2637 0.4969 0.3982 0.047*

C3 0.17716 (14) 0.6360 (3) 0.2399 (2) 0.0360 (6)

H3A 0.2233 0.6972 0.2539 0.043*

H3B 0.1577 0.5564 0.1718 0.043*

C4 0.12708 (14) 0.9128 (3) 0.2337 (2) 0.0300 (5) C5 −0.02572 (14) 0.9731 (3) 0.0961 (2) 0.0302 (5) C6 −0.03845 (14) 0.7997 (3) 0.0698 (2) 0.0345 (6) C7 0.02560 (14) 0.6967 (3) 0.1174 (2) 0.0351 (6)

H7 0.0145 0.5857 0.0965 0.042*

Atomic displacement parameters (Å2₎

U11 _U22 _U33 _U12 _U13 _U23

supporting information

sup-3 Acta Cryst. (2006). E62, o586–o588

Geometric parameters (Å, º)

F1—C6 1.352 (3) N2—C5 1.376 (3)

O1—C1 1.229 (3) N2—H2E 0.81 (3)

O2—C1 1.324 (3) C1—C2 1.509 (3)

O2—H2C 0.839 (10) C2—C3 1.506 (3)

O2—H2D 0.839 (10) C2—H2A 0.9700

O3—C4 1.217 (3) C2—H2B 0.9700

O4—C5 1.222 (3) C3—H3A 0.9700

N1—C3 1.473 (3) C3—H3B 0.9700

N1—C4 1.380 (3) C5—C6 1.437 (3)

N1—C7 1.370 (3) C6—C7 1.328 (3)

N2—C4 1.377 (3) C7—H7 0.9300

C1—O2—H2C 116 (6) N1—C3—C2 113.14 (19)

C1—O2—H2D 119 (6) N1—C3—H3A 109.0

H2C—O2—H2D 124 (8) C2—C3—H3A 109.0

C7—N1—C4 121.10 (19) N1—C3—H3B 109.0

C7—N1—C3 120.44 (18) C2—C3—H3B 109.0

C4—N1—C3 118.42 (18) H3A—C3—H3B 107.8

C5—N2—C4 127.6 (2) O3—C4—N2 122.3 (2)

C5—N2—H2E 114.8 (19) O3—C4—N1 122.6 (2)

C4—N2—H2E 118 (2) N2—C4—N1 115.05 (19)

O1—C1—O2 122.7 (2) O4—C5—N2 122.6 (2)

O1—C1—C2 121.6 (2) O4—C5—C6 124.9 (2)

O2—C1—C2 115.7 (2) N2—C5—C6 112.51 (19)

C3—C2—C1 113.6 (2) C7—C6—F1 121.0 (2)

C3—C2—H2A 108.8 C7—C6—C5 122.0 (2)

C1—C2—H2A 108.8 F1—C6—C5 117.01 (19)

C3—C2—H2B 108.8 C6—C7—N1 121.5 (2)

C1—C2—H2B 108.8 C6—C7—H7 119.2

H2A—C2—H2B 107.7 N1—C7—H7 119.2

O1—C1—C2—C3 23.2 (3) C4—N2—C5—O4 −175.6 (2) O2—C1—C2—C3 −157.7 (2) C4—N2—C5—C6 3.5 (3) C7—N1—C3—C2 −88.0 (3) O4—C5—C6—C7 175.1 (2) C4—N1—C3—C2 94.4 (2) N2—C5—C6—C7 −3.9 (3) C1—C2—C3—N1 73.9 (3) O4—C5—C6—F1 −3.4 (4) C5—N2—C4—O3 179.1 (2) N2—C5—C6—F1 177.6 (2) C5—N2—C4—N1 −0.3 (3) F1—C6—C7—N1 179.8 (2) C7—N1—C4—O3 177.8 (2) C5—C6—C7—N1 1.3 (4)

C3—N1—C4—O3 −4.6 (3) C4—N1—C7—C6 2.3 (3)

supporting information

sup-4 Acta Cryst. (2006). E62, o586–o588

Hydrogen-bond geometry (Å, º)

D—H···A D—H H···A D···A D—H···A

N2—H2E···O1i _{0.81 (3) 2.00 (3) 2.797 (3) 171 (3)}

O2—H2C···O4ii _{0.84 (1) 2.06 (2) 2.887 (3) 167 (8)}

O2—H2D···O3iii _{0.84 (1) 2.15 (1) 2.990 (3) 174 (8)}