6-Methyluracil: a redetermination of polymorph (II)

(C) for A was for methyl groups.


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., 1999Brunetti et al., 2002;Portalone & Colapietro, 2004;Portalone, 2010), 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) gave two hits, as crystalline polymorphs. Form (I), monoclinic space group P2 1 /c, was determined by data reports XRPD at R = 0.040 (Reck et al., 1988). 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). 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). 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-HÁ Á ÁO hydrogen bonds (Fig. 2). Within a ribbon, each molecule is linked to two adjacent molecules via centrosymmetric, pairwise N1-H1Á Á ÁO1 and N3-H3Á Á ÁO2 hydrogen bonds (Table 1). In form (I), centrosymmetric dimers are formed by N3Á Á ÁO2 hydrogen bonds. These dimers are then connected through N1Á Á ÁO2 hydrogen bonds to form layers approximately parallel to the bc plane, leaving the O1 atom free from hydrogen-bonding interactions (Fig. 3).
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 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. Table 1 Hydrogen-bond geometry (Å , ). Symmetry codes: (i) Àx; Ày þ 1; Àz; (ii) Àx þ 1 2 ; Ày þ 1 2 ; Àz.

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.

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.
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 À ) N + -H [(Ia) and (Ib) in Fig. 4], which are better proton donors and acceptors than the neutral canonical form C( O)-N-H to form hydrogen-bonding interactions.

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.   where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.27 e Å −3 Δρ min = −0.17 e Å −3 Special details 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.

data-2
IUCrData (2019). 4, x190861 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 U iso (H) = 1.2U eq (C) or 1.5U eq (C) for methyl H atoms. A rotating model was used for the methyl groups.