3 Methyl 5 nitro­uracil

organic papers

Acta Cryst.(2006). E62, o1257–o1259 doi:10.1107/S1600536806007033 Wagner and Kubicki _C

5H5N3O4

o1257

Acta Crystallographica Section E

Structure Reports Online

ISSN 1600-5368

3-Methyl-5-nitrouracil

Paweł Wagneraand Maciej Kubickib*

a

Nanomaterials Research Centre and MacDiarmid Institute for Advanced Materials, and Nanotechnology, Massey University, Private Bag 11 222, Palmerston North, New Zealand, andb_{Department of Chemistry, Adam} Mickiewicz University, Grunwaldzka 6, 60-780 Poznan´, Poland

Correspondence e-mail: [email protected]

Key indicators

Single-crystal X-ray study

T= 295 K

Mean(C–C) = 0.002 A˚

Rfactor = 0.045

wRfactor = 0.128

Data-to-parameter ratio = 10.1

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

Received 23 February 2006 Accepted 27 February 2006

#2006 International Union of Crystallography All rights reserved

The molecules of the title compound, C5H5N3O4, are

approximately planar. The nitro group makes a dihedral angle

of 1.3 (4) _{with the plane of the six-membered ring. This}

coplanar disposition is a reason for the changes in valence angles in the vicinity of the nitro group. Molecules are

connected into dimers by means of N—H O hydrogen

bonds, and these dimers make larger structures with the help

of relatively short C—H O hydrogen bonds.

Comment

Synthetic analogues of natural biopolymers, such as nucleic acids and peptides, are promising candidates as antisense and antigene drugs, and as diagnostic and biological tools. The improved hybridization properties exhibited by oligonucleo-tides containing LNAs (locked nucleic acids; Petersen &

Wengel, 2003) and PNAs (peptide nucleic acids; Larsenet al.,

1999) are particularly interesting for such purposes. The pyrimidine nucleosides and their analogues exhibit extremely diverse physiological activities. For example, 5-fluorouracil is an important anticancer agent widely used in oncology

(Longley et al., 2003),

1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) is applied as a non-nucleoside reverse transcriptase inhibitor in HIV-infection therapy

(Tanaka et al., 1992), and

5-nitro-1-[3-(5-nitro-2-furan-2-yl)acryloyl]uracil exhibits antitumour activity on leukaemia P388 cells (Trusuleet al., 1991).

5-Nitrouracil derivatives, besides their biological impor-tance, have also become more interesting for their application in non-linear optics (e.g.Puccetti et al., 1993). Knowledge of the factors influencing the crystal packing modes of these compounds is therefore very important and there is a need for more data regarding these modes. For 5-nitrouracil itself, the crystal structures of three polymorphic modifications have been reported, one monoclinic (P21/n; Kennedy et al., 1998)

and two orthorhombic [centrosymmetric Pbca reported by

Pierce & Wing (1986) and re-examined by Gopalan et al.

(2000), together with the non-centrosymmetricP212121form].

It should be noted, however, that for the orthorhombic structures there are no data in the Cambridge Structural Database (CSD; Version 5.27, January 2006 update; Allen, 2002). There are also two different solvates: a hydrate

(Craven, 1967) and a dimethyl sulfoxide solvate (Kennedyet

al., 1998). Interestingly, in the CSD there are many more

available, error-free). Therefore, new data on simple 3-methyluracils might be of interest. We report here the crystal structure of 3-methyl-5-nitrouracil, (I).

The pyrimidine ring is almost planar (Fig. 1), the largest

deviation from the least-squares plane being 0.024 (1) A˚ .

Carbonyl atom O2 lies in this plane [insignificant deviation of 0.007 (3) A˚ ], while the other three substituents deviate more significantly, although slightly, from the ring plane. Owing to the steric stress, the directions of deviations are opposite for

neighbouring atoms:0.019 (3) A˚ for C31, 0.092 (2) A˚ for O4

and 0.042 (3) A˚ for N5. Overall, the whole molecule is

almost planar; the dihedral angle between the ring plane and the nitro group is as small as 1.3 (4)_{. Bond lengths and angles}

are typical and similar to those of related compounds. There is an asymmetry in C—N—O angles caused by steric factors; the angle on the side of the C4/O4 group, C5—N5—O52, of 120.6 (2)_{, is significantly larger than the angle on the other}

side, C5—N5—O51 [117.8 (2)_{]. The same asymmetry is}

observed for C—C—N angles; the C4—C5—N5 angle of

121.6 (2) _{is more than 3 larger than C6—C5—N5, of}

117.3 (2)_{. This proves that, in order to gain the advantage of}

being coplanar with the-electron system and in the absence

of the steric hindrance, the nitro group has to accommodate the more flexible geometrical parameters, valence angles.

In the crystal structure the molecules are linked into centrosymmetric pairs by means of relatively strong and linear

N1—H1 O2 hydrogen bonds. Using graph-set notation

(Etter et al., 1990; Bernstein et al., 1995) the appropriate

symbol is R2

2(8). The tendency towards creating

hydrogen-bonded pairs in uracil derivatives is so strong that, even in the

case of 1,3-dimethyluracil, the C(methyl)—H O hydrogen

bonds can take the pattern-determining role (Banerjeeet al.,

1977). Only in the case of the non-centrosymmetric structure

of 5-nitrouracil (Gopalanet al., 2000) and, what is even more

surprising, in the centrosymmetric structure of 3-methyluracil

(Portaloneet al., 2002), are no dimers formed. Weaker C—

H O bonds are also involved in the determination of crystal

packing (cf. Table 2 and Fig. 2). These bonds connect

mol-ecules into C(5) chains which are interconnected by ring

organic papers

o1258

Wagner and Kubicki _C

[image:2.610.45.297.69.260.2] [image:2.610.315.562.74.294.2]

5H5N3O4 Acta Cryst.(2006). E62, o1257–o1259

Figure 1

[image:2.610.49.292.317.510.2]

A view of the molecular structure of (I) (Siemens, 1989). Displacement ellipsoids are drawn at the 50% probability level; H atoms are depicted as spheres of arbitrary radii.

Figure 2

A fragment of the hydrogen-bond pattern (Siemens, 1989); the ring graph symbols are shown. Hydrogen bonds are depicted as dashed lines.

Figure 3

[image:2.610.133.212.617.710.2]

structures of R2

2(10); all these patterns make larger rings,

R4

3(15). These interactions, together with other weak hydrogen

bonds (cf. Table 2) and van der Waals interactions, create a

grid-like structure of molecules (Fig. 3).

Experimental

Direct alkylation by methyl iodide of 5-nitrouracil in dimethylform-amide in the presence of Bu4NOH gave 3-methyl-5-nitrouracil in

moderate yield (Blank & Fox, 1970). Crystals for X-ray data collec-tion were grown from a methanol solucollec-tion.

Crystal data

C5H5N3O4

Mr= 171.12

Monoclinic,P2₁=c a= 5.7510 (12) A˚

b= 10.176 (2) A˚

c= 11.775 (2) A˚

= 100.69 (3) V= 677.1 (2) A˚3

Z= 4

Dx= 1.679 Mg m 3 MoKradiation Cell parameters from 50

reflections

= 4–32 = 0.15 mm1

T= 295 (1) K Block, colourless 0.40.20.1 mm

Data collection

Kuma KM-4 diffractometer

!–2scans

Absorption correction: none 1256 measured reflections 1196 independent reflections 926 reflections withI> 2(I)

Rint= 0.066

max= 25.1

h=6!6

k= 0!12

l= 0!14

2 standard reflections every 100 reflections intensity decay: 0.3%

Refinement

Refinement onF2

R[F2> 2(F2)] = 0.045

wR(F2_{) = 0.128}

S= 1.04 1196 reflections 119 parameters

H atoms treated by a mixture of independent and constrained refinement

w= 1/[2_(F

o2) + (0.0911P)2 + 0.05P]

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

max= 0.22 e A˚

3

min=0.27 e A˚

3

Extinction correction:SHELXL97

Extinction coefficient: 0.067 (11)

Table 1

Selected geometric parameters (A˚ ,_).

N1—C6 1.329 (2) N1—C2 1.376 (2) C2—O2 1.220 (2) C2—N3 1.371 (2) N3—C4 1.404 (2) N3—C31 1.470 (2)

C4—O4 1.209 (2) C4—C5 1.449 (3) C5—C6 1.356 (2) C5—N5 1.440 (2) N5—O52 1.212 (2) N5—O51 1.216 (2)

C6—N1—C2 123.3 (2) N3—C2—N1 115.9 (2) C2—N3—C4 125.4 (2) N3—C4—C5 113.3 (1) C6—C5—N5 117.3 (2) C6—C5—C4 121.1 (2)

[image:3.610.312.568.111.183.2]

N5—C5—C4 121.6 (2) O52—N5—O51 121.7 (2) O52—N5—C5 120.6 (2) O51—N5—C5 117.8 (2) N1—C6—C5 120.9 (2)

Table 2

Hydrogen-bond geometry (A˚ ,_).

D—H A D—H H A D A D—H A

N1—H1 O2i

0.82 (2) 2.05 (2) 2.859 (2) 169 (2) C31—H31A O51ii

0.95 2.55 3.260 (3) 132 C31—H31A O4iii

0.95 2.57 3.330 (2) 138 C31—H31B O51iv

0.97 2.58 3.474 (3) 155 C6—H6 O52v 0.96 (2) 2.48 (2) 3.281 (3) 141 (2) C6—H6 O4v

0.96 (2) 2.59 (2) 2.958 (2) 103 (1)

Symmetry codes: (i)xþ1;y;zþ1; (ii)x;y1 2;zþ

3

2; (iii)xþ1;y;zþ2;

(iv)xþ1;yþ1 2;zþ

1

2; (v)x;yþ 1 2;z

1 2.

The H atoms of the methyl group were found in a difference Fourier map and then refined as a rigid body (AFIX 3); theirUiso(H)

values were refined as a common FVAR.

Data collection: KM-4 Software (Kuma Diffraction, 1991); cell refinement: KM-4 Software; data reduction: KM-4 Software; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure:SHELXL97(Sheldrick, 1997); molecular graphics:Stereochemical Workstation Operation Manual (Siemens, 1989); software used to prepare material for publication: SHELXL97.

References

Allen, F. H. (2002).Acta Cryst.B58, 380–388.

Banerjee, A., Dattagupta, J. K., Saenger, W. & Rabczenko, A. (1977).Acta Cryst.B33, 90–94.

Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995).Angew. Chem. Int. Ed. Engl.34, 1555–1573.

Blank, H., U. & Fox, J. J. (1970).J. Heterocycl. Chem.7, 735–737. Craven, B. M. (1967).Acta Cryst.23, 376–383.

Etter, M. C., MacDonald, J. C. & Bernstein, J. (1990).Acta Cryst.B46, 256–262. Gopalan, R. S., Kulkarni, G. U. & Rao, C. N. R. (2000).ChemPhysChem,1,

127–135.

Kennedy, A. R., Okoth, M. O., Sheen, D. B., Sherwood, J. N. & Vrcelj, R. M. (1998).Acta Cryst.C54, 547–550.

Kuma Diffraction, (1991).KM-4 Software. User’s Guide, Version 5.0. Kuma Diffraction, Wrocław, Poland.

Larsen, H. J., Bentin, T. & Nielsen, P. E. (1999).Biochim. Biophys. Acta,1489, 159–166.

Longley, D. B., Harkin, D. P. & Johnston, P. G. (2003).Nat. Rev.3, 330–338. Petersen, M. & Wengel, J. (2003).Trends Biotechnol.21, 74–81.

Pierce, B. P. & Wing, R. M. (1986).Molecular and Polymeric Optoelectronic Materials: Fundamentals and Applications. Proc. Soc. Photo-Opt. Instrum. Eng.682, 27–35.

Portalone, G., Ballirano, P. & Maras, A. (2002).J. Mol. Struct.608, 35–39. Puccetti, G., Perigaud, A., Badan, J., Ledoux, I. & Zyss, J. (1993).J. Opt. Soc.

Am. B,10, 733–744.

Sheldrick, G. M. (1990).Acta Cryst.A46, 467–473.

Sheldrick, G. M. (1997).SHELXL97. University of Go¨ttingen, Germany. Siemens (1989).Stereochemical Workstation Operation Manual.Release 3.4.

Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA. Tanaka, H., Takashima, H., Ubasawa, M., Sekiya, K., Nitta, I., Baba, M.,

Shigeta, S., Walker, R. T., De Clercq, E. & Miyasaka, T. (1992).J. Med. Chem.35, 337–345.

Trusule, M., Kupce, E., Augustane, I., Verovskii, N. V., Lukevics, E., Baumane, L., Gavars, R. & Stradins, J. (1991).Khim. Geterotsikl. Soedin.12, 1687– 1694. (In Russian.)

organic papers

Acta Cryst.(2006). E62, o1257–o1259 Wagner and Kubicki _C

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sup-1 Acta Cryst. (2006). E62, o1257–o1259

supporting information

Acta Cryst. (2006). E62, o1257–o1259 [https://doi.org/10.1107/S1600536806007033]

3-Methyl-5-nitrouracil

Pawe

ł

Wagner and Maciej Kubicki

3-Methyl-5-nitrouracil

Crystal data

C5H5N3O4 Mr = 171.12 Monoclinic, P21/c Hall symbol: -P 2ybc a = 5.7510 (12) Å b = 10.176 (2) Å c = 11.775 (2) Å β = 100.69 (3)° V = 677.1 (2) Å3 Z = 4

F(000) = 352 Dx = 1.679 Mg m−3

Mo Kα radiation, λ = 0.71073 Å Cell parameters from 50 reflections θ = 4–32°

µ = 0.15 mm−1 T = 295 K Block, colourless 0.4 × 0.2 × 0.1 mm

Data collection

Kuma KM-4 diffractometer

Radiation source: fine-focus sealed tube Graphite monochromator

ω–2θ scans

1256 measured reflections 1196 independent reflections 926 reflections with I > 2σ(I)

Rint = 0.066

θmax = 25.1°, θmin = 2.7° h = −6→6

k = 0→12 l = 0→14

2 standard reflections every 100 reflections intensity decay: 0.3%

Refinement

Refinement on F2 Least-squares matrix: full R[F2 _{> 2σ(F}2_{)] = 0.045} wR(F2_{) = 0.128} S = 1.04 1196 reflections 119 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_{) + (0.0911P)}2 _{+ 0.05P]} where P = (Fo2 _{+ 2Fc}2_)/3

(Δ/σ)max < 0.001 Δρmax = 0.22 e Å−3 Δρmin = −0.27 e Å−3

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sup-2 Acta Cryst. (2006). E62, o1257–o1259

Special details

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 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

N1 0.3041 (3) 0.10318 (16) 0.58178 (12) 0.0400 (5) H1 0.305 (4) 0.085 (2) 0.514 (2) 0.052 (6)* C2 0.4814 (3) 0.05458 (18) 0.66604 (14) 0.0374 (5) O2 0.6399 (3) −0.01339 (15) 0.64165 (11) 0.0545 (5) N3 0.4690 (3) 0.08839 (14) 0.77744 (11) 0.0339 (4) C31 0.6539 (3) 0.0368 (2) 0.86989 (15) 0.0439 (5)

H31A 0.6011 −0.0405 0.9018 0.082 (5)*

H31B 0.6728 0.0990 0.9328 0.082 (5)*

H31C 0.8032 0.0313 0.8459 0.082 (5)*

C4 0.2863 (3) 0.16141 (16) 0.81129 (14) 0.0347 (5) O4 0.2850 (3) 0.17753 (14) 0.91292 (10) 0.0532 (5) C5 0.1152 (3) 0.21061 (17) 0.71467 (14) 0.0357 (5) N5 −0.0782 (3) 0.29368 (16) 0.73154 (13) 0.0436 (5) O51 −0.2155 (3) 0.3304 (2) 0.64614 (14) 0.0964 (8) O52 −0.1018 (3) 0.32526 (15) 0.82795 (12) 0.0563 (5) C6 0.1302 (3) 0.17918 (18) 0.60439 (15) 0.0380 (5) H6 0.019 (4) 0.210 (2) 0.5393 (16) 0.044 (5)*

Atomic displacement parameters (Å2₎

U11 _U22 _U33 _U12 _U13 _U23

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sup-3 Acta Cryst. (2006). E62, o1257–o1259

Geometric parameters (Å, º)

N1—C6 1.329 (2) C31—H31C 0.95

N1—C2 1.376 (2) C4—O4 1.209 (2)

N1—H1 0.82 (2) C4—C5 1.449 (3)

C2—O2 1.220 (2) C5—C6 1.356 (2)

C2—N3 1.371 (2) C5—N5 1.440 (2)

N3—C4 1.404 (2) N5—O52 1.212 (2)

N3—C31 1.470 (2) N5—O51 1.216 (2)

C31—H31A 0.94 C6—H6 0.96 (2)

C31—H31B 0.96

C6—N1—C2 123.3 (2) H31B—C31—H31C 107

C6—N1—H1 118 (2) O4—C4—N3 119.7 (2)

C2—N1—H1 118.7 (2) O4—C4—C5 127.0 (2)

O2—C2—N3 122.8 (2) N3—C4—C5 113.3 (1)

O2—C2—N1 121.3 (2) C6—C5—N5 117.3 (2)

N3—C2—N1 115.9 (2) C6—C5—C4 121.1 (2)

C2—N3—C4 125.4 (2) N5—C5—C4 121.6 (2)

C2—N3—C31 117.4 (2) O52—N5—O51 121.7 (2)

C4—N3—C31 117.1 (1) O52—N5—C5 120.6 (2)

N3—C31—H31A 111 O51—N5—C5 117.8 (2)

N3—C31—H31B 107 N1—C6—C5 120.9 (2)

H31A—C31—H31B 104 N1—C6—H6 117 (1)

N3—C31—H31C 112 C5—C6—H6 123 (1)

H31A—C31—H31C 116

C6—N1—C2—O2 −178.9 (2) N3—C4—C5—C6 3.9 (3)

C6—N1—C2—N3 0.5 (3) O4—C4—C5—N5 3.2 (3)

O2—C2—N3—C4 −177.1 (2) N3—C4—C5—N5 −176.6 (2) N1—C2—N3—C4 3.5 (3) C6—C5—N5—O52 179.9 (2) O2—C2—N3—C31 −1.4 (3) C4—C5—N5—O52 0.4 (3) N1—C2—N3—C31 179.2 (2) C6—C5—N5—O51 0.0 (3) C2—N3—C4—O4 174.7 (2) C4—C5—N5—O51 −179.5 (2) C31—N3—C4—O4 −1.0 (3) C2—N1—C6—C5 −1.8 (3) C2—N3—C4—C5 −5.5 (3) N5—C5—C6—N1 179.8 (2) C31—N3—C4—C5 178.8 (2) C4—C5—C6—N1 −0.6 (3) O4—C4—C5—C6 −176.3 (2)

Hydrogen-bond geometry (Å, º)

D—H···A D—H H···A D···A D—H···A

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sup-4 Acta Cryst. (2006). E62, o1257–o1259

C6—H6···O52v _{0.96 (2) 2.48 (2) 3.281 (3) 141 (2)} C6—H6···O4v _{0.96 (2) 2.59 (2) 2.958 (2) 103 (1)}