Crystal structures and hydrogen-bonding analysis of a series of benzamide complexes of zinc(II) chloride

Five new bis(arylamide)dichloridozinc(II) complexes have been prepared and characterized. All of the complexes contain hydrogen bonds between the amide N—H group and the amide carbonyl oxygen atoms or the chlorine atoms, forming extended networks.


Chemical context
Ionic co-crystals, formed from the combination of inorganic salts and organic molecules, are of interest for their ability to promote or stabilize crystal forms of organic or pharmaceutical molecules (Braga et al., 2011. The chloride salts of magnesium, calcium, and strontium have been shown to form an extensive range of structure types when co-crystallized with drug molecules such as piracetam (Braga et al., 2011;, etiracetam and levitiracetam (Song et al., 2019, and nicotinamide and isonicotinamide (Braga et al., 2011;Song et al., 2020). Sodium bromide and sodium iodide form ionic co-crystals with carbamazepine (Buist & Kennedy, 2014). More recently, it has been shown that co-crystallization with ionic salts can produce chirally resolved forms when combining lithium halides with l-and dl-histidine (Braga et al., 2016), magnesium chloride with RS-oxiracetam (Shemchuk et al., 2020), and zinc chloride with RS-etiracetam . Co-crystallization of nefiracetam with zinc chloride produced products with improved solubility and dissolution rates (Buol et al., 2020). ISSN 2056-9890 The current study was undertaken to explore the preparation of ionic co-crystals (alternatively termed co-crystal salts; Grothe, et al., 2016) using zinc chloride combined with various organic amides (specifically benzamide, 4-hydroxybenzamide, and toluamide) that can serve as models of pharmaceutical molecules.

Structural commentary
Five new zinc complexes, (1) through (5), have been prepared and structurally characterized. All five complexes are 2:1 Obonded aryl amide:ZnCl 2 complexes with approximately tetrahedral zinc(II) centers. The complexes crystallize in five different space groups and form hydrogen-bonding interactions between the amide N-H groups and either an amide oxygen or a zinc-bound chlorido ligand.

Figure 1
Displacement ellipsoid (50%) diagram and atom-numbering scheme of the two independent molecules in (1). N-HÁ Á ÁO contacts are shown in red and N-HÁ Á ÁCl contacts are shown in green.
A comparison of selected bond lengths and bond angles for all five complexes is given in Table 6. The average zincchlorine distance of 2.224 (13) Å compares well with the average of 2.22 (2) Å observed for 27 similar four-coordinate ZnCl 2 L 2 complexes (with L = carbonyl oxygen donating ligand) found in a search of the CSD (Version 5.42, May 2021; Groom et al., 2016). A similar agreement is found for the zincoxygen distance with both averages at 1.98 (2) Å . The bond angles in the complexes in this study display an average Cl-Zn-Cl angle of 117 (5) and an average O-Zn-O angle of 101 (3) , again quite close to the average angles of 119 (4) and 100 (7) for the set of comparable molecules.

Supramolecular features
Each compound displays a unique hydrogen-bonding network, consisting primarily of N-HÁ Á ÁO and N-HÁ Á ÁCl interactions, summarized in Table 1 through 5. In addition to four intramolecular hydrogen bonds, compound (1) forms four N-HÁ Á ÁCl intermolecular hydrogen bonds (two from each independent molecule), forming an extended network as shown in Fig. 6 and summarized in Table 1. Compound (2) also utilizes N-H bonds in hydrogen-bonding interactions, two intramolecular and two intermolecular, to form layers within the structure (see Fig. 7 and Table 2). Only intermolecular N-HÁ Á ÁCl hydrogen bonds are found in compound (3) (shown in Fig. 8, two interactions per asymmetric unit, four per molecule, see Table 3) and they combine to form chains that run parallel to the c axis. Compound (4) forms two N-HÁ Á ÁCl intermolecular contacts in addition to the two intramolecular Displacement ellipsoid (50%) diagram and atom-numbering scheme for (4). The N-HÁ Á ÁO contact is shown in red and the N-HÁ Á ÁCl contact is shown in green.

Figure 8
Packing diagram of (3) (viewed along [101]) showing N-HÁ Á ÁCl contacts (green). The minor component of the disordered methyl group is not shown for clarity.
is the dihedral angle between planes. Cg is the centroid of the benzene ring of the benzamide or toluamide molecule.
addition of the 4-hydroxy group in compound (5) results in the greatest number of hydrogen bonds among this set of complexes, as shown in Fig. 10 and summarized in Table 5, with two N-HÁ Á ÁCl and three O-HÁ Á ÁCl intermolecular interactions per molecule. Compounds (1), (3), and (5) forminteractions between the benzene rings of the benzamide or toluamide groups as summarized in Table 7. No significantinteractions were found for compounds (2) or (4).
Three structural studies have prepared zinc(II)chloride complexes with pharmaceutically relevant molecules. Sultana et al. (2016) prepared bis(4 0 -methoxyacetanilide)dichloridozinc(II) (EQIGOC). Dichloridobis(nicotinamide)zinc(II) has also been studied (WUKZAD; İde et al., 2002) but differs from the structures in this report in that the two nicotinamide ligands are N-bonded through the ring nitrogen instead of the amide oxygen. Buol et al. (2020) describe the preparation and crystal structures of co-crystals obtained from the co-crystallization of nefiracetam with zinc(II)chloride, producing two different structures. In one form (CCDC 2010272), the fourcoordinate zinc atom binds to one nefiracetam molecule (via the -lactam carbonyl), one water molecule, and two chlorido ligands. In the second form (CCDC 2010264), the zinc bonds to one nefiracetam molecule through the -lactam and to a second via the amide carbonyl, forming a cyclic zinc dimer.

Synthesis and crystallization
All reagents were used as received from the manufacturer. Compounds (1) through (5) were prepared by dissolution of the respective components in various solvents [50:50 v:v ratio of water and ethanol (benzamide, 4-hydroxybenzamide), ethanol (o,m,p-toluamide)] followed by slow evaporation. In a typical preparation, a 1:1 stoichiometric ratio of benzamide (0.1352 g) and zinc(II) chloride (0.1336 g) was dissolved in approximately 5 mL of a 50:50 v:v ratio of water and ethanol. Slow evaporation of the resulting solution produced single crystals of compound (1).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 8. All hydrogen atoms were located in difference maps.
The methyl group in compound (3) was modeled as a disordered methyl group with each set of hydrogen atoms Packing diagram of (5) (viewed along a) showing N-HÁ Á ÁO contacts (red) and N-HÁ Á ÁCl contacts (green). rotated by 60 (AFIX 127). The disorder was identified from multiple peaks near C8 in the difference map. The refined occupancies of the two hydrogen atom sets were 0.54 (2):0.46 (2).

Funding information
Funding for this research was provided by: National Science Foundation, Directorate for Education and Human Resources (grant No. 0942850 to DHJ).

Dichloridobis(2-methylbenzamide-κO)zinc(II) (2)
Crystal data where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.31 e Å −3 Δρ min = −0.24 e Å −3 Absolute structure: Refined as an inversion twin. Absolute structure parameter: 0.016 (6) 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.

Dichloridobis(3-methylbenzamide-κO)zinc(II) (3)
Crystal data where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.39 e Å −3 Δρ min = −0.26 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 )
x y z U iso */U eq Occ. (

Dichloridobis(4-methylbenzamide-κO)zinc(II) (4)
Crystal data where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.46 e Å −3 Δρ min = −0.32 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 )
x y z U iso */U eq where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.46 e Å −3 Δρ min = −0.29 e Å −3 Absolute structure: Refined as an inversion twin Absolute structure parameter: 0.024 (13) 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. Refinement. Refined as a 2-component inversion twin.