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6-Methyl­uracil: a redetermination of polymorph (II)

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aChemistry Department, "Sapienza" University of Rome, P.le A. Moro, 5, I-00185 Rome, Italy
*Correspondence e-mail: gustavo.portalone@uniroma1.it

Edited by C. Rizzoli, Universita degli Studi di Parma, Italy (Received 28 May 2019; accepted 17 June 2019; online 21 June 2019)

6-Methyluracil, C5H6N2O2, exists in two crystalline phases: form (I), monoclinic, space group P21/c [Reck et al. (1988[Reck, G., Kretschmer, R.-G., Kutschabsky, L. & Pritzkow, W. (1988). Acta Cryst. A44, 417-421.]). Acta Cryst. A44, 417–421] and form (II), monoclinic, space group C2/c [Leonidov et al. (1993[Leonidov, N. B., Zorkij, P. M., Masunov, A. E., Gladkikh, O. P., Bel'skii, V. K., Dzyabchenko, A. V. & Ivanov, S. A. (1993). Russ. J. Phys. Chem. 67, 2220-2223.]). Russ. J. Phys. Chem. 67, 2220–2223]. The structure of polymorph (II) has been redetermined providing a significant increase in the precision of the derived geometric parameters. In the crystal, mol­ecules form ribbons approximately running parallel to the c-axis direction through N—H⋯O hydrogen bonds. The radical differences observed between the crystal packing of the two polymorphs may be responsible in form (II) for an increase in the contribution of the polar canonical forms C—(O)=N—H+ relative to the neutral canonical form C(=O)—N—H induced by hydrogen-bonding inter­actions.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

As a result of the fundamental role of nucleic acids in genetic processes of living systems, much attention has been devoted to determining the structure of methyl­ated derivatives of uracil, because methyl­ation of DNA is probably involved in various genetic alterations and in the initiation of carcinogenic processes. In previous theoretical and experimental studies of uracil derivatives from this laboratory (Portalone et al., 1999[Portalone, G., Bencivenni, L., Colapietro, M., Pieretti, A. & Ramondo, F. (1999). Acta Chem. Scand. 53, 57-68.], 2002[Portalone, G., Ballirano, P. & Maras, A. (2002). J. Mol. Struct. 608, 35-39.]; Brunetti et al., 2002[Brunetti, B., Portalone, G. & Piacente, V. (2002). J. Chem. Eng. Data, 47, 17-19.]; Portalone & Colapietro, 2004[Portalone, G. & Colapietro, M. (2004). J. Chem. Crystallogr. 34, 609-612.]; Portalone, 2010[Portalone, G. (2010). Acta Cryst. C66, o295-o301.]), it has been shown that the hydrogen bonding can change the electronic properties of similar pyrimidine bases experiencing different crystal environments, i.e. showing different sites available for hydrogen-bond inter­actions.

In this context, 6-methyl­uracil (6Mura) is particularly attractive, as it exists in two crystalline forms characterized by completely different hydrogen-bonding schemes. A search for crystal structures of the title compound with the Cambridge Structural Database (CSD, version 5.40 updated to May 2019: Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) gave two hits, as crystalline polymorphs. Form (I), monoclinic space group P21/c, was determined by XRPD at R = 0.040 (Reck et al., 1988[Reck, G., Kretschmer, R.-G., Kutschabsky, L. & Pritzkow, W. (1988). Acta Cryst. A44, 417-421.]). Form (II), monoclinic space group C2/c, was determined by RT single-crystal diffraction performed on a Syntex P1 diffractometer at R = 0.085 (Leonidov et al., 1993[Leonidov, N. B., Zorkij, P. M., Masunov, A. E., Gladkikh, O. P., Bel'skii, V. K., Dzyabchenko, A. V. & Ivanov, S. A. (1993). Russ. J. Phys. Chem. 67, 2220-2223.]). Inter­estingly, Leonidov and coworkers analysed the differences in the mol­ecular geometries of 6Mura in form (I) and (II), and came to the conclusion that the observed discrepancies in the corresponding bond distances and bond angles were insignificant. Therefore, to verify this assumption, it was considered worthwhile and of significant chemical inter­est to redetermine the crystal structure of form (II) to a better precision. The present determination (R = 0.048), although based on RT data collection, decreases the s.u.s on the bond distances and bond angles to about one third to one fourth of those in the original determination.

In the asymmetric unit, 6Mura is present as the diketo tautomer (Fig. 1[link]). As previously mentioned, the crystal structures of the two polymorphs are radically different. In form (II), infinite ribbons approximately running parallel to the c-axis direction are connected by N—H⋯O hydrogen bonds (Fig. 2[link]). Within a ribbon, each mol­ecule is linked to two adjacent mol­ecules via centrosymmetric, pairwise N1—H1⋯O1 and N3—H3⋯O2 hydrogen bonds (Table 1[link]). In form (I), centrosymmetric dimers are formed by N3⋯O2 hydrogen bonds. These dimers are then connected through N1⋯O2 hydrogen bonds to form layers approximately parallel to the bc plane, leaving the O1 atom free from hydrogen-bonding inter­actions (Fig. 3[link]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N1—H1⋯O1i 0.91 (2) 1.95 (2) 2.8594 (17) 174.0 (16)
N3—H3⋯O2ii 0.93 (2) 1.90 (2) 2.8246 (18) 171.5 (18)
Symmetry codes: (i) [-x, -y+1, -z]; (ii) [-x+{\script{1\over 2}}, -y+{\script{1\over 2}}, -z].
[Figure 1]
Figure 1
The asymmetric unit of 6Mura in form (II), showing the atom-labelling scheme. Displacements ellipsoids are at the 50% probability level. H atoms are shown as small spheres of arbitrary radii.
[Figure 2]
Figure 2
Crystal packing diagram for 6Mura in form (II), viewed approximately down b. All atoms are shown as small spheres of arbitrary radii. Hydrogen bonding is indicated by red dashed lines.
[Figure 3]
Figure 3
Crystal packing diagram for 6Mura in form (I), viewed approximately down a. All atoms are shown as small spheres of arbitrary radii. Hydrogen bonding is indicated by red dashed lines.

The effect of the different crystal environments on the mol­ecular geometry of the two polymorphs can be appreciated in particular in the region involved in the hydrogen bonding, and mainly consists in a concerted distortion of the C=O and C—N bond distances. Indeed, by comparing the mol­ecular geometry of the almost planar O1=C2—N3—C4=O2 fragment in the two polymorphs, in passing from form (I) to form (II):

(i) the two carbonyl bond distances are longer by 0.008–0.035 (2) Å;

(ii) the N3—C2 and N3—C4 bond distances are shorter by 0.031–0.035 (2) Å.

Therefore, the observed structural changes in form (II) can be inter­preted, in terms of VB theory, as an increase in the contribution of the polar canonical forms C—(O)=N+—H [(Ia) and (Ib) in Fig. 4[link]], which are better proton donors and acceptors than the neutral canonical form C(=O)—N—H to form hydrogen-bonding inter­actions.

[Figure 4]
Figure 4
Polar canonical forms of 6Mura in form (II).

Synthesis and crystallization

6-Methyl­uracil (Sigma Aldrich, 97%) was subjected to further purification by successive sublimation under reduced pressure. 1 mmol was dissolved in DMF (3 ml) and stirred for 8 h at 50°C. The solution was then cooled to room temperature and allowed to slowly evaporate to give, after two weeks, colourless crystals of polymorph (II) suitable for X-ray analysis. Several trials of data collection at LT using a crystal of polymorph (II) mounted under paraffin oil in a nylon loop failed, as the sample cracked when slowly cooled in liquid nitro­gen.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link].

Table 2
Experimental details

Crystal data
Chemical formula C5H6N2O2
Mr 126.12
Crystal system, space group Monoclinic, C2/c
Temperature (K) 298
a, b, c (Å) 20.572 (3), 3.9052 (5), 14.811 (3)
β (°) 110.95 (2)
V3) 1111.2 (4)
Z 8
Radiation type Mo Kα
μ (mm−1) 0.12
Crystal size (mm) 0.14 × 0.11 × 0.08
 
Data collection
Diffractometer Agilent Xcalibur Sapphire3
Absorption correction Multi-scan (CrysAlis PRO; Agilent, 2014[Agilent (2014). CrysAlis PRO. Agilent Technologies Ltd, Yarnton, England.])
Tmin, Tmax 0.770, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections 8110, 1400, 1154
Rint 0.044
(sin θ/λ)max−1) 0.671
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.048, 0.133, 1.11
No. of reflections 1400
No. of parameters 91
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.27, −0.17
Computer programs: CrysAlis PRO (Agilent, 2014[Agilent (2014). CrysAlis PRO. Agilent Technologies Ltd, Yarnton, England.]), SIR2004 (Burla et al., 2005[Burla, M. C., Caliandro, R., Camalli, M., Carrozzini, B., Cascarano, G. L., De Caro, L., Giacovazzo, C., Polidori, G. & Spagna, R. (2005). J. Appl. Cryst. 38, 381-388.]), SHELXL2014 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]) and WinGX (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]).

Structural data


Computing details top

Data collection: CrysAlis PRO (Agilent, 2014); cell refinement: CrysAlis PRO (Agilent, 2014); data reduction: CrysAlis PRO (Agilent, 2014); program(s) used to solve structure: SIR2004 (Burla et al., 2005); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: WinGX (Farrugia, 2012); software used to prepare material for publication: WinGX (Farrugia, 2012).

6-Methyluracil top
Crystal data top
C5H6N2O2F(000) = 528
Mr = 126.12Dx = 1.508 Mg m3
Monoclinic, C2/cMo Kα radiation, λ = 0.710689 Å
a = 20.572 (3) ÅCell parameters from 2315 reflections
b = 3.9052 (5) Åθ = 2.9–30.6°
c = 14.811 (3) ŵ = 0.12 mm1
β = 110.95 (2)°T = 298 K
V = 1111.2 (4) Å3Tablets, colourless
Z = 80.14 × 0.11 × 0.08 mm
Data collection top
Agilent Xcalibur Sapphire3
diffractometer
1400 independent reflections
Radiation source: fine-focus sealed X-ray tube, Enhance (Mo) X-ray Source1154 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.044
Detector resolution: 16.0696 pixels mm-1θmax = 28.5°, θmin = 3.0°
ω and φ scansh = 2727
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2014)
k = 55
Tmin = 0.770, Tmax = 1.000l = 1919
8110 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.048Hydrogen site location: mixed
wR(F2) = 0.133H atoms treated by a mixture of independent and constrained refinement
S = 1.11 w = 1/[σ2(Fo2) + (0.0609P)2 + 0.4161P]
where P = (Fo2 + 2Fc2)/3
1400 reflections(Δ/σ)max < 0.001
91 parametersΔρmax = 0.27 e Å3
0 restraintsΔρmin = 0.17 e Å3
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. The N-bound H atoms were located in a difference Fourier map and refined freely. All other H atoms were placed geometrically and refined using a riding atom approximation, with C–H = 0.97 Å, and with Uiso(H) = 1.2Ueq(C) or 1.5Ueq(C) for methyl H atoms. A rotating model was used for the methyl groups.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.06097 (6)0.5147 (3)0.06247 (9)0.0486 (4)
O20.26885 (6)0.0108 (3)0.10454 (9)0.0468 (3)
N10.07366 (7)0.2401 (3)0.07840 (9)0.0380 (3)
H10.0293 (10)0.304 (5)0.0715 (13)0.049 (5)*
C20.09750 (8)0.3466 (4)0.00759 (11)0.0366 (4)
N30.16426 (6)0.2545 (3)0.02038 (9)0.0361 (3)
H30.1820 (10)0.333 (5)0.0258 (15)0.057 (5)*
C40.20846 (7)0.0710 (4)0.09840 (11)0.0357 (4)
C50.17907 (7)0.0298 (4)0.16844 (11)0.0372 (4)
H50.20660.16410.22400.045*
C60.11357 (8)0.0595 (4)0.15811 (11)0.0359 (4)
C70.08038 (9)0.0227 (5)0.23014 (13)0.0488 (5)
H7A0.11000.17900.27830.073*
H7B0.03540.12890.19750.073*
H7C0.07420.18640.26150.073*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0372 (6)0.0662 (8)0.0451 (7)0.0128 (5)0.0178 (5)0.0152 (5)
O20.0319 (6)0.0639 (8)0.0475 (7)0.0091 (5)0.0178 (5)0.0105 (5)
N10.0300 (7)0.0451 (7)0.0423 (7)0.0023 (5)0.0171 (5)0.0025 (6)
C20.0312 (7)0.0414 (8)0.0387 (8)0.0008 (6)0.0142 (6)0.0007 (6)
N30.0308 (6)0.0435 (7)0.0365 (7)0.0021 (5)0.0150 (5)0.0031 (5)
C40.0304 (7)0.0389 (7)0.0383 (8)0.0006 (6)0.0130 (6)0.0022 (6)
C50.0344 (8)0.0416 (8)0.0359 (8)0.0005 (6)0.0129 (6)0.0038 (6)
C60.0369 (8)0.0356 (7)0.0385 (8)0.0035 (6)0.0174 (6)0.0016 (6)
C70.0496 (10)0.0552 (10)0.0519 (11)0.0006 (7)0.0308 (8)0.0042 (7)
Geometric parameters (Å, º) top
O1—C21.2308 (19)C4—C51.430 (2)
O2—C41.2352 (18)C5—C61.347 (2)
N1—C61.368 (2)C5—H50.9700
N1—C21.372 (2)C6—C71.493 (2)
N1—H10.91 (2)C7—H7A0.9701
C2—N31.3657 (19)C7—H7B0.9701
N3—C41.3872 (19)C7—H7C0.9701
N3—H30.93 (2)
C6—N1—C2123.21 (13)C6—C5—C4120.79 (14)
C6—N1—H1120.2 (12)C6—C5—H5119.6
C2—N1—H1116.6 (12)C5—C6—N1119.92 (14)
O1—C2—N3122.54 (14)C5—C6—C7123.91 (15)
O1—C2—N1121.93 (14)N1—C6—C7116.16 (13)
N3—C2—N1115.53 (14)C6—C7—H7A109.5
C2—N3—C4125.36 (13)C6—C7—H7B109.5
C2—N3—H3116.6 (12)H7A—C7—H7B109.5
C4—N3—H3117.9 (12)C6—C7—H7C109.5
O2—C4—N3120.14 (14)H7A—C7—H7C109.5
O2—C4—C5124.69 (14)H7B—C7—H7C109.5
N3—C4—C5115.16 (13)
C6—N1—C2—O1178.53 (14)O2—C4—C5—C6177.08 (14)
C6—N1—C2—N31.3 (2)N3—C4—C5—C61.6 (2)
O1—C2—N3—C4178.78 (14)C4—C5—C6—N11.9 (2)
N1—C2—N3—C41.0 (2)C4—C5—C6—C7177.22 (14)
C2—N3—C4—O2177.57 (14)C2—N1—C6—C51.8 (2)
C2—N3—C4—C51.2 (2)C2—N1—C6—C7177.42 (14)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.91 (2)1.95 (2)2.8594 (17)174.0 (16)
N3—H3···O2ii0.93 (2)1.90 (2)2.8246 (18)171.5 (18)
Symmetry codes: (i) x, y+1, z; (ii) x+1/2, y+1/2, z.
 

References

First citationAgilent (2014). CrysAlis PRO. Agilent Technologies Ltd, Yarnton, England.  Google Scholar
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First citationSheldrick, G. M. (2015). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar

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