Different molecular conformations in the crystal structures of three 5-nitroimidazolyl derivatives

The title compounds show different conformations in the solid state.


Chemical context
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Computational calculations
The different conformations of (I) compared to (II) and (III) were investigated by computational means. All calculations were performed with the Orca software package version 4.0.0.2 (Neese, 2012). Geometry optimizations were performed at the spin-component-scaled MP2 (SCS-MP2) level (Grimme, 2003) using the Def2-TZVP (Hellweg et al., 2007) basis set. Optimized geometries were then subjected to single-point energy calculations at the SCS-MP2 level with the larger Def2-QZVPP basis set to obtain final relative conformational energies. Geometry optimizations and single point energies were repeated using the SMD method to model the methanol solvent environment (Marenich et al., 2009)   The molecular structure of (II) showing 50% displacement ellipsoids.

Figure 3
The molecular structure of (III) showing 50% displacement ellipsoids.

Figure 1
The molecular structure of (I) showing 50% displacement ellipsoids. the syn conformation [i.e. that found for (II) and (III)] is favoured for all substituents by roughly the same energy (with the energy of the syn conformer arbitrarily defined to be zero in each case) either in vacuo or in a methanol solvent environment, although the differences in the latter case are quite small.

Supramolecular features
In the crystal of (I), the molecules are linked by C-HÁ Á ÁN hydrogen bonds (Table 1) to generate [010] C(6) chains, with adjacent molecules related by the 2 1 screw axis (Fig. 4). The C5-H5Á Á ÁO3 contact is long and the angle is small, but if it is regarded as significant, it serves to cross-link the chains into (100) sheets. Weak aromaticstacking interactions arise between the sheets, such that each imidazole ring is sandwiched by two phenyl groups and vice versa [centroidcentroid separations = 3.7355 (10) and 4.1184 (10) Å ; corresponding slippages = 1.35 and 2.25 Å , respectively].
There are a number of intermolecular interactions in (II) ( Table 2) and (III) ( Table 3) and together they lead to threedimensional networks in each case. It is interesting that the C9-H9Á Á ÁN1 interaction in (II) is clearly a directional bond [HÁ Á ÁN = 2.58 Å compared to a van der Waals contact distance (Bondi, 1964) of 2.75 Å for these atoms] whereas the equivalent contact in (III), included in Table 3 for completeness, has an HÁ Á ÁN separation of 2.77 Å and, by itself, would be very doubtful as a bond, which shows that isostructural crystals can show distinct variations in their weak interactions. This is supported by the presence of a weak C4-H4CÁ Á ÁBr1 bond in (III) (HÁ Á ÁBr = 2.85 Å , van der Waals contact distance = 3.05 Å ) whilst the equivalent link in (II) has HÁ Á ÁF = 2.77 Å , significantly greater than the van der Waals contact distance of 2.67 Å and would not be regarded as a significant bond. As in (I),stacking appears to consolidate the crystals of (II) and (III), in which the imidazole rings and phenyl rings form alternating stacks, which propagate in [100]. In (II), the imidazole ring faces phenyl rings with centroid-centroid (slippage) distances of 3.7297 (7) (1.23) and 3.9323 (7) Å (1.64 Å ). Equivalent data for (III) are 3.7664 (18) (1.47) and 3.9698 (18) Å (1.82 Å ).
The two values refer to a vacuum and methanol solvation, respectively. The energy of the syn conformer is arbitrarily set to zero in each case.  Table 5) that as a percentage of surface interactions, HÁ Á ÁH contacts (i.e. van der Waals interactions) are the most significant in each structure, followed by OÁ Á ÁH/HÁ Á ÁO contacts. It is interesting the percentage of the latter for (I) is slightly higher than for (II), despite the fact that (I) features one weak C-HÁ Á ÁO bond at best whilst (II) features three such bonds. The CÁ Á ÁC contacts (associated with aromaticstacking) contribute a very small percentage in each structure, which is slightly surprising given the significantstacking interactions noted above. Finally, it may be noted that the CÁ Á ÁH/HÁ Á ÁC and NÁ Á ÁN/HÁ Á ÁN contributions for (I) and the CÁ Á ÁH/HÁ Á ÁC, NÁ Á ÁN/HÁ Á ÁN and X-H/HÁ Á ÁX contributions for (II) and (III) sum to approximately the same amount. Beyond a vague appeal to 'packing forces', we find it difficult to explain why (I) forms the energetically disfavoured anti conformation in the crystal: it allows the C5-H5 group to form a weak hydrogen bond (Table 1) to a nitro group oxygen atom but it should be noted that the same grouping forms a similar bond in the opposite direction (i.e. pointing away from C4) in both (II) and (III). The syn conformation for (II) and (III) seems to be favoured in terms of the occurrence of an intramolecular C-HÁ Á ÁN link and it is possible that weak C-HÁ Á ÁX (X = F, Br) interactions in the crystals of (II) and (III) provide some stabilization not possible in (I), although they are at the opposite end of the molecule. The Hirshfeld fingerprint data (Table 5) show that NÁ Á ÁH/HÁ Á ÁN and CÁ Á ÁH/ HÁ Á ÁC contacts are somewhat more significant in the crystal of (I) but the energetic consequences of these are not clear. We cannot rule out the posssibility that a polymorph of (I) may exist in which the N m -C-C N grouping has a syn conformation but with a different overall packing motif to (II) and (III).

Synthesis and crystallization
The syntheses and spectroscopic data of the title compounds have already been described (Carvalho et al., 2017). The crystals used for data collections in this study were recrystallized from methanol solution in each case as colourless plates of (I), orange blocks of (II) and yellow blocks of (III).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 6. The hydrogen atoms were geometrically placed (C-H = 0.95-0.99Å ) and refined as riding atoms. The constraint U iso (H) = 1.2U eq (carrier) or 1.5U eq (methyl carrier) was applied in all cases. The methyl groups were allowed to rotate, but not to tip, to best fit the electron density.

(E)-1-Methyl-5-nitro-1H-imidazole-2-carbaldehyde O-benzyloxime (I)
Crystal data 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq C1 −0.2026 (2) 0.18424 (17)   where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.29 e Å −3 Δρ min = −0.18 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.

(E)-1-Methyl-5-nitro-1H-imidazole-2-carbaldehyde O-(4-bromobenzyl) oxime (III)
Crystal data 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.