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organic papers

o1504

Quet al. C

6H5FN2O4 doi:10.1107/S1600536806009676 Acta Cryst.(2006). E62, o1504–o1506

Acta Crystallographica Section E Structure Reports Online

ISSN 1600-5368

5-Fluorouracil-1-acetic acid

Jian-Qiang Qu,a* Ling Quband Xiao-Fei Jiaa

a

Department of Chemistry, Tianjin University, Tianjin 300072, People’s Republic of China, andbNingxia Academy of Agriculture and Forestry Sciences, Yinchuan 750002, People’s Republic of China

Correspondence e-mail: jqqu@tju.edu.cn

Key indicators

Single-crystal X-ray study

T= 294 K

Mean(C–C) = 0.003 A˚

Rfactor = 0.041

wRfactor = 0.121

Data-to-parameter ratio = 12.0

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

Received 4 March 2006 Accepted 15 March 2006

#2006 International Union of Crystallography

All rights reserved

In the title compound, C6H5FN2O4, the acetic acid group lies

out of the pyrimidine plane. In the crystal structure, molecules are connected by intermolecular N—H O, O—H O and C—H O hydrogen bonds, forming a three-dimensional network.

Comment

The cycle-specific schedule-dependent antimetabolite 5-fluorouracil has been used in clinics for 40 years and has evolved as an important agent in the treatment of a large spectrum of tumours, including breast cancer, gastric carci-noma and bladder cancer (Duschinsky et al., 1957; Heidel-bergeret al., 1957; Correale et al., 2005). However, its slight harmfulness to the liver, kidney and digestive system limits its wider applicability (Wasterack & Bettina, 1987). For these reasons, many derivatives of 5-fluorouracil have been synthesized and some compounds have better biological activity. 5-Fluorouracil-1-acetic acid, (I), is a member of the family (Tada, 1975). Its metal complexes have been reported to have biological activity (Wanget al., 1993; Quet al., 2001; Huanget al., 2005).

The acetic acid group lies out of the pyrimidine plane (Fig. 1). The C—F, C—O and C—N bond distances are given in Table 1. In (I), there are intermolecular N—H O, O— H O and C—H O hydrogen bonds (Table 2), forming a three-dimensional network (Fig. 2).

Experimental

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Crystal data

C6H5FN2O4

Mr= 188.12

Monoclinic,P21=n

a= 4.9730 (10) A˚

b= 17.093 (3) A˚

c= 8.7485 (17) A˚

= 97.424 (3)

V= 737.4 (2) A˚3

Z= 4

Dx= 1.694 Mg m

3 MoKradiation Cell parameters from 1757

reflections

= 2.6–26.2

= 0.16 mm1

T= 294 (2) K Block, colourless 0.240.200.18 mm

Data collection

Bruker SMART CCD area-detector diffractometer

’and!scans

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

Tmin= 0.963,Tmax= 0.972 4104 measured reflections

1507 independent reflections 1139 reflections withI> 2(I)

Rint= 0.023

max= 26.4

h=6!6

k=11!21

l=10!10

Refinement

Refinement onF2

R[F2> 2(F2)] = 0.041

wR(F2) = 0.121

S= 1.03 1507 reflections 126 parameters

H atoms treated by a mixture of independent and constrained refinement

w= 1/[2(F

o2) + (0.0616P)2 + 0.3397P]

whereP= (Fo2+ 2Fc2)/3 (/)max< 0.001

max= 0.38 e A˚

3

min=0.19 e A˚

3

Table 1

Selected bond lengths (A˚ ).

F1—C3 1.422 (2)

O1—C2 1.232 (2)

O2—C1 1.213 (2)

O3—C6 1.200 (2)

O4—C6 1.322 (2)

N1—C2 1.370 (3)

N1—C1 1.385 (3)

N2—C1 1.374 (2)

N2—C4 1.376 (3)

[image:2.610.316.563.341.523.2]

N2—C5 1.461 (2)

Table 2

Hydrogen-bond geometry (A˚ ,).

D—H A D—H H A D A D—H A

O4—H4 O1i 0.98 (3) 1.81 (3) 2.696 (2) 148 (3) N1—H1 O1ii

0.91 (3) 2.00 (3) 2.904 (2) 171 (2) C4—H4A O2iii

0.93 2.53 3.284 (3) 139

C5—H5A O3iv 0.97 2.56 3.368 (2) 141 C5—H5B O3v

0.97 2.50 3.459 (3) 172

Symmetry codes: (i) xþ1 2;y

1 2;zþ

1

2; (ii) xþ1;yþ1;z; (iii)

x1 2;yþ

1 2;zþ

1 2; (iv)xþ

1 2;yþ

1 2;zþ

1

2; (v)xþ1;y;z.

The H atoms attached to O and N atoms were located in a difference map and refined freely. Other H atoms were placed in geometrically calculated positions, with C—H = 0.93 or 0.97 A˚ , and refined as riding atoms, withUiso(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 5.501) and

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

Huang, J., Qu, J.-Q., Wang, L.-F., Liu, Y.-Q., Wang, Y.-Y., Song, Y.-M., Zhang, C.-J. & Zhan, R. (2005).Chem. Pap.59, 267–270.

Qu, J.-Q., Huang, J., Wang, L.-F. & Sun, G.-C. (2001).Chem. Pap.55, 319–322.

organic papers

Acta Cryst.(2006). E62, o1504–o1506 Quet al. C

6H5FN2O4

o1505

Figure 1

The molecular structure of (I), showing the atom-labelling scheme. Displacement ellipsolids are drawn at the 30% probability level.

Figure 2

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

Go¨ttingen, Germany.

Tada, M. (1975).Bull. Chem. Soc. Jpn,48, 3427–3428.

Wang, L.-F., Yang, Z.-Y., Peng, Z.-R., Cheng, G.-Q., Guo, H.-Y., Sun, A.-L., Wang, Q. & He, F.-Y. (1993).J. Coord. Chem.28, 167–172.

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

organic papers

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Quet al. C

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supporting information

sup-1 Acta Cryst. (2006). E62, o1504–o1506

supporting information

Acta Cryst. (2006). E62, o1504–o1506 [https://doi.org/10.1107/S1600536806009676]

5-Fluorouracil-1-acetic acid

Jian-Qiang Qu, Ling Qu and Xiao-Fei Jia

5-Fluorouracil-1-acetic acid

Crystal data

C6H5FN2O4 Mr = 188.12 Monoclinic, P21/n a = 4.973 (1) Å

b = 17.093 (3) Å

c = 8.7485 (17) Å

β = 97.424 (3)°

V = 737.4 (2) Å3 Z = 4

F(000) = 384

Dx = 1.694 Mg m−3

Melting point: 549 K

Mo radiation, λ = 0.71073 Å Cell parameters from 1757 reflections

θ = 2.6–26.2°

µ = 0.16 mm−1 T = 294 K Block, colorless 0.24 × 0.20 × 0.18 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 = 0.963, Tmax = 0.972

4104 measured reflections 1507 independent reflections 1139 reflections with I > 2σ(I)

Rint = 0.023

θmax = 26.4°, θmin = 2.4°

h = −6→6

k = −11→21

l = −10→10

Refinement

Refinement on F2

Least-squares matrix: full

R[F2 > 2σ(F2)] = 0.041 wR(F2) = 0.121 S = 1.03 1507 reflections 126 parameters 0 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(Fo2) + (0.0616P)2 + 0.3397P]

where P = (Fo2 + 2Fc2)/3

(Δ/σ)max < 0.001

Δρmax = 0.38 e Å−3

Δρmin = −0.19 e Å−3

Special details

Experimental. IR (KBr, ν cm-1): 3191, 1705, 1668, 1242; 1H NMR (d

6DMSO): δ 11.85 (s, 1H), 11.80 (s, 1H), 8.18 (d,

1H, J = 7.0 Hz), 4.50 (s, 2H); analysis calculated for C6H5FN2O4: C 38.29, H 2.68, N 14.90%; found: C 38.20, H 2.75, N

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supporting information

sup-2 Acta Cryst. (2006). E62, o1504–o1506

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)

x y z Uiso*/Ueq

F1 0.1657 (3) 0.44882 (8) 0.43020 (17) 0.0553 (4)

O1 0.2805 (3) 0.50870 (9) 0.14724 (18) 0.0439 (4)

O2 0.8668 (3) 0.31106 (9) 0.08864 (18) 0.0462 (4)

O3 0.3581 (3) 0.18579 (9) 0.20437 (19) 0.0467 (4)

O4 0.6516 (3) 0.10093 (9) 0.3280 (2) 0.0434 (4)

H4 0.504 (7) 0.064 (2) 0.298 (4) 0.084 (10)*

N1 0.5887 (4) 0.41255 (10) 0.1279 (2) 0.0340 (4)

H1 0.625 (5) 0.4325 (16) 0.036 (3) 0.056 (7)*

N2 0.6630 (3) 0.31179 (9) 0.30709 (18) 0.0304 (4)

C1 0.7176 (4) 0.34248 (12) 0.1693 (2) 0.0306 (5)

C2 0.3980 (4) 0.44955 (11) 0.2018 (2) 0.0319 (5)

C3 0.3542 (4) 0.41234 (12) 0.3438 (2) 0.0373 (5)

C4 0.4805 (4) 0.34640 (12) 0.3916 (2) 0.0355 (5)

H4A 0.4449 0.3234 0.4832 0.043*

C5 0.7651 (4) 0.23365 (11) 0.3501 (2) 0.0317 (5)

H5A 0.7944 0.2291 0.4615 0.038*

H5B 0.9377 0.2257 0.3119 0.038*

C6 0.5671 (4) 0.17181 (12) 0.2844 (2) 0.0310 (5)

Atomic displacement parameters (Å2)

U11 U22 U33 U12 U13 U23

F1 0.0655 (9) 0.0500 (9) 0.0564 (9) 0.0226 (7) 0.0302 (7) 0.0137 (6)

O1 0.0514 (9) 0.0316 (8) 0.0502 (9) 0.0127 (7) 0.0126 (7) 0.0095 (7)

O2 0.0558 (10) 0.0443 (10) 0.0415 (9) 0.0172 (8) 0.0182 (8) 0.0074 (7)

O3 0.0431 (9) 0.0425 (10) 0.0500 (10) 0.0013 (7) −0.0113 (7) 0.0041 (7)

O4 0.0417 (9) 0.0251 (8) 0.0620 (11) 0.0023 (7) 0.0010 (7) 0.0061 (7)

N1 0.0424 (10) 0.0284 (9) 0.0321 (9) 0.0055 (7) 0.0084 (8) 0.0076 (7)

N2 0.0348 (9) 0.0259 (9) 0.0307 (9) 0.0015 (7) 0.0050 (7) 0.0048 (6)

C1 0.0327 (10) 0.0281 (10) 0.0308 (10) 0.0012 (8) 0.0033 (8) 0.0004 (8)

C2 0.0341 (10) 0.0242 (10) 0.0373 (11) 0.0015 (8) 0.0042 (8) 0.0002 (8)

C3 0.0431 (12) 0.0344 (12) 0.0366 (11) 0.0056 (9) 0.0131 (9) −0.0006 (9)

C4 0.0418 (12) 0.0353 (12) 0.0306 (11) 0.0010 (9) 0.0095 (9) 0.0049 (9)

C5 0.0322 (10) 0.0280 (11) 0.0345 (11) 0.0028 (8) 0.0028 (8) 0.0072 (8)

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supporting information

sup-3 Acta Cryst. (2006). E62, o1504–o1506

Geometric parameters (Å, º)

F1—C3 1.422 (2) N2—C1 1.374 (2)

O1—C2 1.232 (2) N2—C4 1.376 (3)

O2—C1 1.213 (2) N2—C5 1.461 (2)

O3—C6 1.200 (2) C2—C3 1.437 (3)

O4—C6 1.322 (2) C3—C4 1.331 (3)

O4—H4 0.98 (3) C4—H4A 0.9300

N1—C2 1.370 (3) C5—C6 1.507 (3)

N1—C1 1.385 (3) C5—H5A 0.9700

N1—H1 0.91 (3) C5—H5B 0.9700

C6—O4—H4 109 (2) C4—C3—C2 121.91 (19)

C2—N1—C1 126.97 (18) F1—C3—C2 116.70 (17)

C2—N1—H1 118.0 (17) C3—C4—N2 120.81 (19)

C1—N1—H1 114.7 (17) C3—C4—H4A 119.6

C1—N2—C4 121.75 (17) N2—C4—H4A 119.6

C1—N2—C5 118.27 (16) N2—C5—C6 110.77 (16)

C4—N2—C5 119.09 (16) N2—C5—H5A 109.5

O2—C1—N2 123.12 (19) C6—C5—H5A 109.5

O2—C1—N1 121.89 (19) N2—C5—H5B 109.5

N2—C1—N1 115.00 (17) C6—C5—H5B 109.5

O1—C2—N1 121.22 (19) H5A—C5—H5B 108.1

O1—C2—C3 125.51 (19) O3—C6—O4 124.76 (19)

N1—C2—C3 113.27 (18) O3—C6—C5 123.85 (18)

C4—C3—F1 121.38 (19) O4—C6—C5 111.38 (17)

C4—N2—C1—O2 −176.1 (2) O1—C2—C3—F1 −2.2 (3)

C5—N2—C1—O2 −7.0 (3) N1—C2—C3—F1 177.90 (17)

C4—N2—C1—N1 3.8 (3) F1—C3—C4—N2 −179.83 (18)

C5—N2—C1—N1 172.85 (16) C2—C3—C4—N2 1.1 (3)

C2—N1—C1—O2 173.5 (2) C1—N2—C4—C3 −1.5 (3)

C2—N1—C1—N2 −6.3 (3) C5—N2—C4—C3 −170.5 (2)

C1—N1—C2—O1 −174.0 (2) C1—N2—C5—C6 −87.1 (2)

C1—N1—C2—C3 5.9 (3) C4—N2—C5—C6 82.3 (2)

O1—C2—C3—C4 176.9 (2) N2—C5—C6—O3 1.8 (3)

N1—C2—C3—C4 −3.0 (3) N2—C5—C6—O4 −177.26 (16)

Hydrogen-bond geometry (Å, º)

D—H···A D—H H···A D···A D—H···A

O4—H4···O1i 0.98 (3) 1.81 (3) 2.696 (2) 148 (3)

N1—H1···O1ii 0.91 (3) 2.00 (3) 2.904 (2) 171 (2)

C4—H4A···O2iii 0.93 2.53 3.284 (3) 139

C5—H5A···O3iv 0.97 2.56 3.368 (2) 141

C5—H5B···O3v 0.97 2.50 3.459 (3) 172

Figure

Table 2

References

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