The crystal structures of three disordered 2-substituted benzimidazole esters

Three 2-substituted benzimidazole esters each exhibit different types of molecular disorder and different patterns of supramolecular assembly.

The structure of the related compound ethyl 1-methyl-2-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)-1H-benzimidazole-5-carboxylate (III) (Fig. 3) was reported recently (Manju et al., 2018), but the reported refinement was based on a rather unusual disorder model, in which only some of the atoms in the ester function, namely the methylene group and the H atoms of the methyl group, were described as disordered over two sets of atomic sites having occupancies 0.719 (14) and 0.281 (14), but with all other components of this substituent fully ordered. This model leads to some unexpected distances within the ethoxy unit, O-C =1.480 (4) and 1.618 (13) Å and C-C = 1.274 (6) and 1.295 (10) Å , which in turn cast doubt on the correctness of the disorder model. Accordingly, we have taken the opportunity to collect a new, and rather better data set for compound (III) [4250 reflections with R int = 0.0126 as against 4010 reflections with R int = 0.0418 (Manju et al., 2018)] and, using a more realistic disorder model, we have refined the structure of (III) to R 1 = 0.0395 as against a value of 0.0526 (Manju et al., 2018).
Compounds (I)-(III) were prepared from the commercially available precursor ethyl 4-chloro-3-nitrobenzoate (A) (Fig. 4), which readily undergoes nucleophilic substitution with primary amines to give the intermediates (B): subsequent reaction of (B) with sodium dithionite in the presence of the appropriate aldehyde leads to the products (I)-(III) in overall yields of 58-68%.

Figure 1
The molecular structure of compound (I) showing the atom-labelling scheme and the disorder. The major disorder form is drawn using full lines and the minor disorder component is drawn using broken lines. Displacement ellipsoids are drawn at the 30% probability level.

Figure 2
The molecular structure of compound (II) showing the atom-labelling scheme and the disorder. The major disorder form is drawn using full lines and the minor disorder component is drawn using broken lines. Displacement ellipsoids are drawn at the 30% probability level.

Figure 3
The molecular structure of compound (III) showing the atom-labelling scheme and the disorder. The major disorder form is drawn using full lines and the minor disorder component is drawn using broken lines. Displacement ellipsoids are drawn at the 30% probability level.

Structural commentary
The molecules of compounds (I)-(III) all exhibit disorder. In compound (I) (Fig. 1), the (prop-2-yn-1-oxy)phenyl unit is disordered over two sets of atomic sites having essentially equal occupancies, 0.506 (5) and 0.494 (5), such that the two orientations of the phenyl ring make almost identical dihedral angles with the adjacent imidazole ring, 27.8 (4) and 27.0 (4) respectively, and with a dihedral angle of 54.7 (3) between the planes of the two disorder components. The propyl group in compound (II) (Fig. 2) is disordered over two sets of atomic sites having occupancies 0.601 (8) and 0.399 (8), while in compound (III) (Fig. 3), the whole ester unit is disordered over two sets of atomic sites having occupancies 0.645 (7) and 0.355 (7); so, far from there being a single site for the methyl C atom in the ester unit (Manju et al., 2018), there are two such sites in the present disorder model, separated by 0.931 (11) Å .
Despite the fact that atom O51 acts as a hydrogen-bond acceptor in both (II) and (III), although not in (I), the conformation of the ester unit in (II) is different from that in (I) and (III) : the cause of this is unclear. The bond lengths in the pyrene fragment of compound (II) present some interesting features. While the distances in the rings containing atoms C22 and C27 are all typical of those in delocalized aromatic rings, those in the other two rings exhibit significant bond fixation (Glidewell & Lloyd, 1984). Thus the distances C24-C25 and C29-C210, 1.320 (3) and 1.342 (3) Å , are typical of double bonds (Allen et al., 1987), while those for the bonds C23A-C24, C23B-C25B, C25-C25A, C28A-C29 and C210-C20A are all closely grouped in the d range 1.424 (3)-1.436 (3) Å , typical of single bonds carrying alkenyl or aromatic substituents (Allen et al., 1987). Hence there can be no continuous peripheral delocalization in this unit.

Supramolecular features
The supramolecular assembly in compounds (II) and (III) is very simple, but that in compound (I) is less straightforward. In compound (II), molecules that are related by the 2 1 screw axis along (0.5, y, 0.25) are linked by a C-HÁ Á ÁO hydrogen bond (Table 1) to form a C(10) chain (Etter, 1990;Etter et al., 1990;Bernstein et al., 1995) running parallel to the [010] direction (Fig. 5). Two chains of this type, related to one another by inversion, pass through each unit cell, and these chains are linked by ainteraction involving the terminal aromatic ring, containing atom C27 (Fig. 2). The terminal aromatic rings in the molecules at (x, y, z) and (2 À x, 2 À y, 1 À z) are parallel with an interplanar spacing of 3.430 (2) Å : the ring-centroid separation is 3.727 (2) Å and the ringcentroid offset is 1.459 (2)  Part of the crystal structure of compound (II) showing the formation of a hydrogen-bonded C(10) chain parallel to [010]. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms not involved in the motif shown have been omitted.

Figure 6
A projection along [010] of part of the crystal structure of compound (II) showing the formation of a -stacked sheet of hydrogen-bonded chains. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms not involved in the hydrogen bonding have been omitted. hydrogen-bonded chain around the screw axis along (0.5, y, 0.25) (Fig. 5) with the corresponding chains along (1.5, y, 0.75) and (À0.5, y, À0.25), hence generating a -stacked sheet of hydrogen-bonded chains lying parallel to (102) (Fig. 6). There is also another short C-HÁ Á ÁO contact in the structure of (II), involving atom C11 (Table 1), but the C-HÁ Á ÁO angle is very small, such that the interaction energy here is likely to be negligibly small (Wood et al., 2009). Hence, it is probably better to regard this as an adventitious contact rather than as a structurally significant interaction: in any event, this contact would not influence the dimensionality of the supramolecular assembly.
There is just one C-HÁ Á ÁO hydrogen bond in the structure of compound (III), and its dimensions for the two disorder components are fairly similar, although the distances in the minor component are rather longer than those for the major form (Table 1); only the major disorder form needs to be considered. The hydrogen bond links molecules that are related by translation to form a C(13) chain running parallel to the [100] direction (Fig. 7).
The structure of compound (I) contains three C-HÁ Á Á(arene) hydrogen bonds, all involving the unfused aryl ring (Table 1), but the alkyne unit acts as neither donor nor acceptor. If all of the donors and acceptors were present with full occupancy, the effect of the hydrogen bonds would be to link the molecules of (I) into a complex ribbon running parallel to the [010] direction (Fig. 8). However, in each of these hydrogen bonds, the donor and the acceptor form parts of different disorder components, so that the ribbon cannot be continuous, but it is punctuated into a succession of short fragments. The punctuated ribbon containing the reference  Part of the crystal structure of compound (III) showing the formation of a hydrogen-bonded C(13) chain parallel to [100]. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms not involved in the motif shown have been omitted.

Synthesis and crystallization
All reagents were obtained commercially, and all were used as received. For the synthesis of the intermediates of type (B) (Fig. 4), ethyl 4-chloro-3-nitrobenzoate (2.29 g, 0.01 mol) was dissolved in tetrahydrofuran (20 ml) and 0.01 mol of the appropriate amine was added [0.80 ml of a 40% aqueous solution of methylamine when R = Me, or 0.059 g of propylamine when R = propyl], and these mixtures were then stirred at ambient temperature for 4 h. The resulting solid intermediates (B) were collected by filtration, dried in air and used without further purification. For the synthesis of the products (I)-(III), sodium dithionite (1.74 g, 0.01 mol) was added to a mixture of (B) (0.01 mol) and the appropriate aldehyde (0.01 mol) [1.61 g of 4-propynyloxybenzaldehyde for (I); 2.30 g of pyrene-1-carboxaldehyde for (II); 2.20 g of 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carboxaldehyde for (III)], in dimethylsulfoxide (30 ml). The reaction mixtures were then subjected to microwave irradiation (600 W) for 5 min for (I), 6.5 min for (II) and 6 min for (III). When the reactions were complete, as judged by thin-later chromatography, the resulting solid products were collected by filtration and dried in air.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. Two bad outlier reflections (2 2 9) and (1 1 19) were omitted from the final refinement of compound (I). All H atoms, apart from those in the minor disorder components, were located in difference maps. The H atoms were then all treated as riding atoms in geometrically idealized positions, with C-H distances of 0.93 Å (alkenyl, alkynyl and aromatic), 0.96 Å (CH 3 ) or 0.97 Å (CH 2 ), and with U iso (H) = kU eq (C), where k = 1.5 for the methyl groups, which were allowed to rotate but not to tilt, and 1.2 for all other H atoms. For the disorder components, the corresponding distances between bonding components and the 1,3 distances between non-bonding components were restrained to be equal, subject to s.u. values of 0.01 and 0.02 Å , respectively. In addition, for compound (I), similarity restraints were applied to the atoms of each orientation of the disordered aryl ring, while the anisotropic displacement parameters for corresponding pairs of atoms in the propynyloxy unit were constrained to be the same. Similarity restraints were applied to the displacement parameters of the terminal C atoms of the two disorder components of the propyl group in compound (II), and to those of corresponding pairs of atoms in the disordered ester unit of compound (III). Subject to these conditions, the site occupancies for the disordered fragments refined to 0.506 (5)   SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: PLATON (Spek, 2020); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015b) and PLATON (Spek, 2020). 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 Occ. (<1) N1 0.65691 (9) 0.7408 (2) 0.23708 (12) 0.0594 (5)  where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.32 e Å −3 Δρ min = −0.29 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.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )