Crystal structure, Hirshfeld surface analysis and computational study of the 1:2 co-crystal formed between N,N′-bis[(pyridin-4-yl)methyl]ethanediamide and 3-chlorobenzoic acid

In the title 1:2 co-crystal a three-molecule aggregate, i.e. 4 LH2.2(3-ClBA), is formed via carboxylic acid-O—H⋯N(pyridyl) hydrogen bonding. The three-molecule aggregates are connected into a supramolecular tape along [111] by amide-N—H⋯O(carbonyl) hydrogen bonding.


Chemical context
Herein, the X-ray crystal structure determination of the 1:2 cocrystal formed between bis(pyridin-4-ylmethyl)ethanediamide and 3-chlorobenzoic acid, (I), is described. The present crystallographic study continues recent studies into the structural chemistry of the isomeric bis(pyridin-n-ylmethyl)ethanediamide molecules, i.e. species with the general formula n-NC 5 H 4 CH 2 N(H)C( O)C( O)CH 2 C 5 H 4 N-n, for n = 2, 3 and 4, and hereafter, abbreviated as n LH 2 (Tiekink, 2017). These molecules have interest as co-crystal co-formers as they possess both hydrogen-bonding donating and accepting sites, i.e. amide and pyridyl functionalities. A particular focus of these studies has been upon co-crystals formed with carboxylic acids (Arman et al., 2012(Arman et al., , 2014Tan, Halcovitch et al., 2019;, directed by the reliability of the carboxylic acid-O-HÁ Á ÁN(pyridyl) synthon (Shattock et al., 2008). A common thread of recent investigations has been upon benzoic acid (Tan & Tiekink, 2020a) and derivatives (Syed et al., 2016), in particular halide-substituted species (Tan &

Structural commentary
The asymmetric unit of (I) comprises a molecule of 4-chlorobenzoic acid (3-ClBA) in a general position and onehalf molecule of 4 LH 2 , being disposed about a centre of inversion, Fig. 1. In the acid, 3-ClBA, there is a definitive disparity in the C8-O2 [1.225 (2) Å ] and C8-O3 [1.308 (2) Å ] bond lengths entirely consistent with the localization of the acidic proton on the O3 atom. This is also borne out in the angles subtended at the C8 atom with the widest angle involving the oxygen atoms [O2-C8-O3 = 123.38 (17) ] and the narrowest involving the atoms connected by a single bond [O3-C8-C9 = 114.23 (15) ]. A small twist in the molecule is evident as seen in the dihedral angle of 8.731 (12) formed between the CO 2 /C 6 residues; the O2-C8-C9-C10 torsion angle = 171.79 (19) Å .
The 4 LH 2 molecule is situated about a centre of inversion so the central C 2 N 2 O 2 chromophore is constrained to be planar. As is normal for n LH 2 molecules (Tiekink, 2017), the central C7-C7 i [1.539 (3) Å ; symmetry code: (i) 1 À x, À y, À z] bond length is considered long, an observation ascribed to the electronegative substituents bound to the sp 2 -C7 atom. The conformation of the 4 LH 2 molecule is (+)antiperiplanar so the 4-pyridyl residues lie to either side of the planar region of the molecule. The dihedral angle between the central core and the N1-pyridyl ring is 74.69 (11) . Owing to the anti-disposition of the amide groups intramolecular amide-N-HÁ Á ÁO(amide) hydrogen bonds are formed which complete S(5) loops, Table 1.

Supramolecular features
The most distinctive feature of the molecular packing is the association between 4 LH 2 and two symmetry-related 3-ClBA molecules via carboxylic acid-O-HÁ Á ÁN(pyridyl) hydrogen bonding, Table 1, to generate a three-molecule aggregate. These three-molecule aggregates are connected into a linear tape along [111] via amide-N-HÁ Á ÁO(carbonyl) hydrogen bonds Fig. 2 Table 1 Hydrogen-bond geometry (Å , ).

Figure 1
The molecular structures of the constituents of co-crystal (I) showing the atom-labelling scheme and displacement ellipsoids at the 50% probability level: (a) the 3-chlorobenzoic acid molecule and (b) the centrosymmetric N,N 0 -bis[(pyridin-4-yl)methyl]oxalamide molecule with the unlabelled atoms related by the symmetry operation (i) 1 À x, À y, À z. hydrogen-bonding arrangement is provided by supporting benzoic acid-C14-HÁ Á ÁO(amide) interaction which lead to non-symmetric 10-membered {Á Á ÁHC 3 OÁ Á ÁHNC 2 O} 2 synthons, which flank the larger 22-membered rings. Further, a complementary C-ClÁ Á Á(pyridyl) contact is noted, as detailed in Table 1. A survey of the literature (Imai et al., 2008) as well as the Cambridge Structural Database (Groom et al., 2016) shows that the average ClÁ Á Á distance is about 3.6 Å , which is shorter than the contact distance in (I). An end-on view of the tape is shown in Fig. 2(b). The tapes are connected into a supramolecular layer by relatively short pyridyl-C1-HÁ Á ÁO(amide) contacts, Fig. 2(c). A three-dimensional architecture results when benzoic acid-C12-HÁ Á ÁO(amide) and methylene-C-HÁ Á ÁO(carbonyl) interactions are taken into consideration, Fig. 2(d). In this scheme, the amide-O1 atom participates in three pivotal C-HÁ Á ÁO interactions.

Hirshfeld surface analysis
The Hirshfeld surface analysis was performed for the threemolecule aggregate of (I), i.e. that sustained by the carboxylic acid-O-HÁ Á ÁN(pyridyl) hydrogen bonds, and for the individual components, viz. the full molecule of 4 LH 2 and 3-ClBA, with the use of CrystalExplorer17 (Turner et al., 2017) and based on established methods (Tan, Jotani et al., 2019). As shown in the images of Fig. 3, the analysis reveals there are several red spots of variable intensity observed on the d norm maps calculated for 4 LH 2 and 3-ClBA. These are indicative of close contact distances shorter than the van der Waals radii (Spackman & Jayatilaka, 2009). Specifically, red spots with intensity in decreasing order are observed for hydroxyl-O3- benzene-C12-H12Á Á ÁO1(amide) and methylene-C6-H6A Á Á ÁO3(hydroxyl); the d norm distances for these short contacts are given in Table 2. While the identified close contacts are consistent with those obtained from PLATON analysis (Spek, 2020), additional red spots are noted for pyridyl-C4-H4Á Á ÁC11(benzene) as well as benzyl-C10Á Á ÁC10(benzene), albeit with relatively weaker intensity than the other inter-  Table 2 A summary of short interatomic contacts (Å ) for (I) a .
Contact Distance Symmetry operation 3.28 2 À x, 2 À y, 1 À z Notes: (a) The interatomic distances are calculated in Crystal Explorer 17 (Turner et al., 2017) whereby the X-H bond lengths are adjusted to their neutron values; (b) these interactions correspond to conventional hydrogen bonds.

Figure 3
The d   The electrostatic potential mapped onto the Hirshfeld surfaces within the isosurface value of À0.0481 to 0.0854 atomic units for (a) 3-ClBA and (b) actions mentioned above. As for the C13-Cl1Á Á Á(N1,C1-C5) contact, Table 2, the Hirshfeld surface analysis reveals only a faint-blue spot around the tip of Cl1 in Fig. 3(b) indicating the contact distance that is slightly less than the sum of the van der Waals radii (Spackman & Jayatilaka, 2009).
To verify the nature of the ClÁ Á Á contact in (I), the coformers were subjected to electrostatic potential mapping through DFT-B3LYP/6-31G(d,p), as available in Crystal-Explorer17. The analysis indicates that the ClÁ Á Á interaction is weak in nature as evidenced from the white spot around the -hole region about the Cl1 atom in Fig. 4(a) as well as the faint-red spot around the centre of the -ring centre, Fig. 4(b). A detailed study on the localized electrostatic charges shows that the -hole of Cl1 is about À0.0072 a.u. while the pyridyl -hole is about À0.1270 a.u. indicating that the interaction is rather dispersive in nature. This observation is in contrast with other charge complementary interactions as shown from the intense blue (i.e. electropositive) and red (i.e. electronegative) regions on the electrostatic surface map. For instance, the amide-N2-H2NÁ Á ÁO2(carbonyl) hydrogen bond has a pointto-point electrostatic charge of 0.1438 a.u. for H2N and À0.0622 a.u. for O2, suggestive of a strong interaction, while benzene-C14-H14Á Á ÁO1(amide) shows complementary charges of 0.0427 and À0.0486 a.u. for H14 and O1, respectively, being indicative of a relatively weaker interaction. Among all the identified close contacts, hydroxyl-O3-H3OÁ Á ÁN1(pyridyl) is considered to be the strongest exhibiting a marked difference in the electrostatic charge of 0.2919 a.u. for H3O and À0.0727 a.u. for N1.

Database survey
The aforementioned analogue of (I), 4 LH 2 Á2(4-ClBA) (Tan & Tiekink, 2020b), is the most closely related, and indeed, isomeric co-crystal available for comparison; this too has been subjected to a detailed analysis of the molecular packing. Cocrystals (I) and (II) are not isostructural, with the asymmetric unit of (II) comprising two half-molecules of 4 LH 2 , i.e. 4 LH 2 -IIa and 4 LH 2 -IIb, as each is disposed about a centre of inversion, and two symmetry-independent molecules of 4-ClBA, i.e. 4-ClBA-IIa and 4-ClBA-IIb. The common feature of the molecular packing of (I) and (II) is the formation of two three-molecule aggregates. The key difference in the molecular packing relates to the nature of the supramolecular tapes: in (II), the tapes are sustained by a sequence of tenmembered {Á Á ÁHNCCO} 2 synthons, as highlighted in Fig. 7.
A comparison of the percentage contributions by the most prominent contacts to the respective Hirshfeld surfaces of (I) and (II), and including their individual components has been made . The results are summarized in Fig. 8 and suggest that to a first approximation there are no dramatic variations between the contacts made to the Hirshfeld surfaces calculated for (I) and (II). Among the noticeable differences are due to the HÁ Á ÁO/OÁ Á ÁH contacts which are greater for 3-ClBA, by 5.8 and 5.6%, respectively than for 4-ClBA-IIa and IIb. This is compensated by a reduction in the HÁ Á ÁCl/ClÁ Á ÁH contacts by 4.9 and 5.6%. One possible reason for the increase in OÁ Á ÁH/HÁ Á ÁO contacts in (I) cf. (II) relates to the participation of the carbonyl-O atom in formal hydrogen bonding to the amide-N-H group and the prominent role of the amide-O1 atom in providing points of contact between molecules.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 4. The carbon-bound H atoms were placed in calculated positions (C-H = 0.95-0.99 Å ) and were included in the refinement in the riding-model approximation,  with U iso (H) set to 1.2U eq (C). The oxygen-and nitrogenbound H atoms were located from a difference-Fourier map and refined with O-H = 0.84AE0.01 Å and N-H = 0.86AE0.01 Å , respectively, and with U iso (H) set to 1.5U eq (O) or 1.2U eq (N).