A 2:1 co-crystal of 2-methyl­benzoic acid and N,N′-bis­­(pyridin-4-ylmeth­yl)ethanedi­amide: crystal structure and Hirshfeld surface analysis

The asymmetric unit of the title 2:1 co-crystal, 2C₈H₈O₂·C₁₄H₁₄N₄O₂, comprises an acid mol­ecule in a general position and half a di­amide mol­ecule, the latter being located about a centre of inversion. In the acid, the carb­oxy­lic acid group is twisted out of the plane of the benzene ring to which it is attached [dihedral angle = 28.51 (8)°] and the carbonyl O atom and methyl group lie approximately to the same side of the mol­ecule [hy­droxy-O—C—C—C(H) torsion angle = −27.92 (17)°]. In the di­amide, the central C₄N₂O₂ core is almost planar (r.m.s. deviation = 0.031 Å), and the pyridyl rings are perpendicular, lying to either side of the central plane [central residue/pyridyl dihedral angle = 88.60 (5)°]. In the mol­ecular packing, three-mol­ecule aggregates are formed via hy­droxy-O—H⋯N(pyrid­yl) hydrogen bonds. These are connected into a supra­molecular layer parallel to (12) via amide-N—H⋯O(carbon­yl) hydrogen bonds, as well as methyl­ene-C—H⋯O(amide) inter­actions. Significant π–π inter­actions occur between benzene/benzene, pyrid­yl/benzene and pyrid­yl/pyridyl rings within and between layers to consolidate the three-dimensional packing.

1. Chemical context

Multi-component crystals, incorporating co-crystals, salts and co-crystal salts, attract continuing inter­est for a wide variety of applications as this technology may be employed, for example, to provide additives to promote the growth of crystals, to stabilize unusual and unstable coformers, to generate new luminescent materials, to separate enanti­omers, to facilitate absolute structure determination where the mol­ecule of concern does not have a significant anomalous scatterer, etc. (Aakeröy, 2015; Tiekink, 2012). Arguably, the areas attracting most inter­est in this context are the applications of multi-component crystals in the pharmaceutical industry (Duggirala et al., 2016). Controlled/designed crystallization of multi-component crystals requires reliable synthon formation between the various components and that, of course, is the challenge of crystal engineering, let alone engineering small aggregates within crystals (Tiekink, 2014).

Systematic work on synthon propensities in multi-component crystals have revealed that carb­oxy­lic acids have a great likelihood of forming hy­droxy-O—H⋯N hydrogen bonds when co-crystallized with mol­ecules with pyridyl residues (Shattock et al., 2008). A plausible explanation for this reliability is the formation of a supporting carbonyl-O⋯H inter­action involving the hydrogen atom adjacent to the pyridyl-nitro­gen atom. Indeed, in the absence of competing hydrogen-bonding functionality, the resulting seven-membered {⋯HOCO⋯HCN} heterosynthon is formed in more than 98% of relevant crystal structures (Shattock et al., 2008). Recent systematic work in this phenomenon relates to mol­ecules shown in Scheme 1, where isomeric mol­ecules with two pyridyl rings separated by a di­amide residue have been co-crystallized with various carb­oxy­lic acids (Arman, Miller et al., 2012; Arman et al., 2013, Syed et al., 2016; Jotani et al., 2016). As a continuation of these studies, the title 2:1 co-crystal was isolated and characterized crystallographically and by Hirshfeld surface analysis.

2. Structural commentary

The title co-crystal, Fig. 1, was formed from the 1:1 co-crystallization of 2-methyl­benzoic acid (hereafter, the acid) and N,N′-bis­(pyridin-4-ylmeth­yl)ethanedi­amide (hereafter, the di­amide) conducted in ethanol solution. The asymmetric unit comprises a full acid mol­ecule in a general position and half a di­amide mol­ecule, located about a centre of inversion, so the co-crystal is formulated as a 2:1 acid:di­amide co-crystal.

Figure 1 The mol­ecular structures of the mol­ecules comprising the title co-crystal showing the atom-labelling scheme and displacement ellipsoids at the 50% probability level: (a) 2-methyl­benzoic acid and (b) N,N′-bis­(pyridin-4-ylmeth­yl)ethanedi­amide; unlabelled atoms in the di­amide are generated by the symmetry operation (−1 − x, 2 − y, 1 − z).

In the acid, the carb­oxy­lic acid group is twisted out of the plane of the benzene ring to which it is attached with the O3—C8—C9—C10 torsion angle being 150.23 (14)°, and, to a first approximation, with the carbonyl-O3 atom and methyl group lying to the same side of the mol­ecule as indicated in the O2—C8—C9—C10 torsion angle of −27.92 (17)°. The structure of the parent acid and several co-crystals featuring coformers shown in Scheme 2 are available for comparison; data are collected in Table 1. The common feature of all structures is the relative orientation of the carbonyl-O and methyl groups. Twists in the acid mol­ecules vary from almost co-planar to the situation found in the title co-crystal, with an even split of conformations amongst the six known co-crystal structures.

Table 1
Dihedral and torsion angles (°) for 2-methyl­benzoic acid in the title co-crystal and in literature precedents

Compound	CH—C—C—OH	C6/CO2	CSD Refcode^b	Reference
Parent compound	1.7 (2)	1.5 (5)	OTOLIC02	Thakur & Desiraju (2008)
1:1 Co-crystal with CF_1	7.5 (2)	8.04 (9)	WICZUF	Day et al. (2009)
1:1 Co-crystal with CF_2	4.25 (19)	4.02 (12)	EXIBOD	Ebenezer et al. (2011)
1:1 Co-crystal with CF_3	27.4 (3)	27.8 (2)	EXIZIR	Ebenezer et al. (2011)
1:1 Co-crystal with CF_4	23.0 (2)	23.86 (8)	CEKLEL	Wales et al. (2012)
Title co-crystal	−27.92 (18)	28.51 (8)	–	This work
Notes: (a) Refer to Scheme 2 for the chemical structures of coformers CF_1–CF_4. (b) Groom & Allen (2014).

In the centrosymmetric di­amide, the central C₄N₂O₂ core is essentially planar with an r.m.s. deviation (O1, N2, C6, C7 and symmetry equivalents) = 0.031 Å. This arrangement facilitates the formation of an intra­molecular amide-N—H⋯O(amide) hydrogen bond, Table 2. The pyridyl rings occupy positions on opposite sides of the central residue and project almost prime to this with the central residue/pyridyl dihedral angle being 88.60 (5)°. The aforementioned structural features match literature precedents, i.e. the two polymorphic forms of the parent di­amide and the di­amide in co-crystals with carb­oxy­lic acids and in a salt with a carboxyl­ate, Table 3. Finally, the central C—C bond length, considered long for a Csp²—Csp² bond (Spek, 2009), matches the structural data included in Table 3; see Scheme 3 for chemical diagrams of coformers.

Table 2
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2N⋯O1^i	0.87 (1)	2.31 (1)	2.7100 (16)	108 (1)
O2—H2O⋯N1	0.85 (2)	1.79 (2)	2.6378 (16)	178 (2)
N2—H2N⋯O3^ii	0.87 (1)	2.17 (1)	2.8933 (15)	140 (1)
C6—H3B⋯O1^iii	0.99	2.48	3.3461 (18)	146
Symmetry codes: (i) -x-1, -y+2, -z+1; (ii) -x, -y+1, -z+1; (iii) -x, -y+2, -z+1.

Table 3
Selected geometric details (Å, °) for N,N′-bis­(pyridin-4-ylmeth­yl)ethanedi­amide mol­ecules and protonated forms^a

Coformer	C4N2O2/N-ring	C(=O)—C(=O)	Refcode^b	Ref.
–^c,d	74.90 (4)	1.532 (2)	CICYOD01	Lee (2010)
–^e	68.83 (4); 70.89 (5)	1.541 (3)	CICYOD	Lee & Wang (2007)
	80.46 (5); 83.35 (6)	1.541 (3)
CF_5^c,f	87.37 (4)	1.534 (2)	NAXMEG	Arman, Kaulgud et al. (2012)
CF_6^c,f	79.86 (4)	1.542 (2)	AJEZEV	Arman et al. (2009)
CF_7^g	70.50 (4); 76.89 (4)	1.52 (2)	CAJRAH	Nguyen et al. (2001)
CF_8^c,g,h	73.38 (11)	1.523 (7)	SEPSIP	Nguyen et al. (1998)
CF_8^c,g,i	72.87 (9)	1.514 (5)	SEPSIP01	Nguyen et al. (2001)
CF_9^c,f	75.83 (5)	1.543 (3)	TIPGUW	Arman et al. (2013)
2-Methyl­benzoic acid	88.66 (4)	1.5356 (19)	–	This work
Notes: (a) Refer to Scheme 3 for the chemical structures of coformers, CF_5–CF_9; (b) Groom & Allen (2014); (c) mol­ecule/dianion is centrosymmetric; (d) form I; (e) form II (two independent mol­ecules); (f) 2:1 carb­oxy­lic acid/carboxyl­ate di­amide co-crystal/salt; (g) 1:1 di­carb­oxy­lic acid di­amide co-crystal; (h) form I; (i) form II.

3. Supra­molecular features

The mol­ecular packing of the title co-crystal is dominated by hydrogen bonding, detailed in Table 2. The acid is connected to the di­amide via hy­droxy-O—H⋯N(pyrid­yl) hydrogen bonds to form a three-mol­ecule aggregate, Fig. 2a. The inter­acting residues are not co-planar with the dihedral angle between the pyridyl and three CO₂ groups being 25.67 (8)° so that the carbonyl-O3⋯H3 distance is 2.60 Å. This suggests only a minor role for the putative seven-membered heterosynthon {⋯OCOH⋯NCH} mentioned in the Chemical context and is consistent with the significant hydrogen-bonding inter­action involving the carbonyl-O3 atom to another residue. Indeed, the three-mol­ecule aggregates are connected into a supra­molecular layer parallel to (12) via amide-N—H⋯O(carbon­yl) hydrogen bonds as well as methyl­ene-C—H⋯O(amide) inter­actions, Fig. 2b. Within layers, π–π inter­actions occur between pyridyl rings, and between layers additional π–π inter­actions occur between pyrid­yl/benzene and benzene/benzene rings to consolidate the three-dimensional packing, Table 4 and Fig. 2c. Globally, the packing may be described as comprising alternating layers of aromatic rings and non-aromatic residues.

Table 4
π–π Inter­actions (Å, °)

Ring 1	Ring 2	Inter-centroid distance	Dihedral angle	Symmetry
N1,C1–C5	N1,C1–C5	3.5980 (8)	0	−x, 1 − y, 1 − z
N1,C1–C5	C9–C14	3.7833 (9)	4.63 (7)	1 − x, 1 − y, −z
C9–C14	C9–C14	3.8473 (8)	0	−1 − x, −y, −z

Figure 2 Mol­ecular packing in the title co-crystal: (a) three-mol­ecule aggregate sustained by hy­droxy-O—H⋯N(pyrid­yl) hydrogen bonds, (b) supra­molecular layers whereby the aggregates in (a) are connected by amide-N—H⋯O(carbon­yl) and methyl­ene-C—H⋯O(amide) inter­actions, and (c) a view of the unit-cell contents shown in projection down the a axis, highlighting the intra- and inter-layer π–π inter­actions to consolidate a three-dimensional architecture. The O—H⋯N, N—H⋯O, C—H⋯O and π–π inter­actions are shown as orange, blue, green and purple dashed lines, respectively.

4. Analysis of the Hirshfeld surfaces

Crystal Explorer 3.1 (Wolff et al., 2012) was used to generate Hirshfeld surfaces mapped over d_norm, d_e, electrostatic potential, shape-index and curvedness for the title 2:1 co-crystal. The electrostatic potentials were calculated using TONTO (Spackman et al., 2008; Jayatilaka et al., 2005) integrated with Crystal Explorer, using the experimentally determined geometry as the input. Further, the electrostatic potentials were mapped on Hirshfeld surfaces using the STO-3G basis set at Hartree–Fock theory over a range ±0.15 au. The contact distances d_i and d_e from the Hirshfeld surface to the nearest atom inside and outside, respectively, enabled the analysis of the inter­molecular inter­actions through the mapping of d_norm. The combination of d_i and d_e in the form of a two-dimensional fingerprint plot (Rohl et al., 2008) provides a summary of the inter­molecular contacts.

The strong hy­droxy-O—H⋯N(pyrid­yl) and amide-N—H⋯O(carbon­yl) inter­actions between the acid and di­amide mol­ecules are visualized as bright-red spots at the respective donor and acceptor atoms on the Hirshfeld surfaces mapped over d_norm, and labelled as 1 and 2 in Fig. 3. The inter­molecular methyl­ene-C—H⋯O(amide) inter­actions appears as faint-red spots in Fig. 3b, marked with a `3'. The immediate environment about each mol­ecule highlighting close contacts to the Hirshfeld surface by neighbouring mol­ecules is shown in Fig. 4. The full fingerprint (FP) plots showing various crystal packing inter­actions in the acid, di­amide and 2:1 co-crystal are shown in Fig. 5; the contributions from various contacts are listed in Table 5.

Table 5
Major percentage contribution of the different inter­molecular inter­actions to the Hirshfeld surfaces for the acid, di­amide and 2:1 co-crystal

Contact	Acid	Di­amide	Co-crystal
H⋯H	48.7	45.2	49.9
O⋯H/H⋯O	20.6	25.6	21.3
C⋯H/H⋯C	16.7	12.0	15.9
N⋯H/H⋯N	3.8	8.9	2.7
C⋯C	5.9	6.4	6.6

Figure 3 Views of the Hirshfeld surfaces mapped over dnorm: (a) acid and (b) di­amide in the title 2:1 co-crystal. The contact points (red) are labelled to indicate the atoms participating in the inter­molecular inter­actions.

Figure 4 Hirshfeld surfaces mapped over dnorm showing hydrogen bonds with neighbouring mol­ecules with the reference mol­ecule being the (a) acid and (b) di­amide.

Figure 5 The two-dimensional fingerprint plots for the (a) acid, (b) di­amide, and (c) overall 2:1 co-crystal.

The prominent long spike at d_e + d_i ∼1.8 Å in the upper left (donor) region for the FP plot of the acid corresponds to H⋯N contacts and the spike at the same distance in the lower right (acceptor) region of the FP plot for the di­amide are the result of hy­droxy-O—H⋯N(pyrid­yl) inter­actions, Fig. 5a and b, respectively. However, these spikes are not apparent in the overall FP for the 2:1 co-crystal as they no longer contribute to the surface of the resultant aggregate, Fig. 5c. Pairs of somewhat blunted spikes corresponding to N⋯H/H⋯N contacts at d_e + d_i ∼ 2.9 Å result from amide-N—H⋯O(carbon­yl) inter­actions between the acid and di­amide mol­ecules are evident in the overall FP, Fig. 5c.

The O⋯H/H⋯O contacts, which make a significant contribution to the mol­ecular packing, show different characteristic features in the respective delineated FP plots of the acid and di­amide. For the acid, Fig. 5a, a long prominent spike at d_e + d_i ∼ 2.5 Å in the acceptor region corresponds to a 6.6% contribution from H⋯O contacts to the Hirshfeld surface, and a short spike at d_e + d_i ∼ 2.15 Å in the donor region with a 14.0% contribution. The reverse situation is observed for the di­amide mol­ecule wherein the FP plot, Fig. 5b, contains a long prominent spike in the donor region and the short spike in the acceptor at the same d_e + d_i distance, and with 10.7 and 14.9% contributions from O⋯H and H⋯O contacts, respectively.

FP plots for the co-crystal delineated into H⋯H, O⋯H/H⋯O, C⋯H/H⋯C, N⋯H/H⋯N and C⋯C are shown in Fig. 6a–e, respectively. The H⋯H contacts appear as asymmetrically scattered points covering a large region of the FP plot with a single broad peak at d_e = d_i ∼ 1.2 Å for each of the co-crystal constituents, with percentage contributions of 48.7 and 45.7% for the acid and di­amide mol­ecules, respectively. The overall 49.9% contribution to Hirshfeld surface of the co-crystal results in nearly symmetric through the superimposition of individual fingerprint plots, Fig. 6a.

Figure 6 The two-dimensional fingerprint plot for the title 2:1 co-crystal showing contributions from different contacts: (a) H⋯H, (b) O⋯H/H⋯O, (c) C⋯H/H⋯C, (d) N⋯H/H⋯N, and (e) C⋯C.

The FP plot for O⋯H/H⋯O contacts, Fig. 6b, has two pairs of spikes superimposed in the (d_e, d_i) region with minimum d_e + d_i distances ∼ 2.2 and 2.5 Å. These correspond to a 21.3% contribution to the Hirshfeld surface, and reflect the presence of inter­molecular N—H⋯O and C—H⋯O inter­actions, identified with labels 1 and 2 in Fig. 6b. The 15.9% contribution from the C⋯H/H⋯C contacts to the Hirshfeld surface results in a symmetric pair of wings, Fig. 6c. The FP plot corresponding to C⋯C contacts, Fig. 6e, in the (d_e, d_i) region between 1.7 to 2.2 Å appears as the two distinct, overlapping triangles identified with red and yellow boundaries in Fig. 6e, and shows two types of π–π stacking inter­actions: one between dissimilar rings (pyridyl and benzene) and the other between symmetry-related rings (benzene and benzene, and pyridyl and pyrid­yl). The presence of these π–π stacking inter­actions is also indicated by the appearance of red and blue triangles on the shape-indexed surfaces identified with arrows in the images of Fig. 7, and in the flat regions on the Hirshfeld surfaces mapped with curvedness in Fig. 8.

Figure 7 Hirshfeld surfaces mapped over the shape index for (a) the acid and (b) the di­amide, highlighting the regions involved in π–π stacking inter­actions.

Figure 8 Hirshfeld surfaces mapped over curvedness for (a) the acid and (b) the di­amide, highlighting the regions involved in π–π stacking inter­actions.

The inter­molecular inter­actions were further assessed by using the enrichment ratio, ER (Jelsch et al., 2014). This is a relatively new descriptor and is based on Hirshfeld surface analysis. The ER for the co-crystal together with those for the acid and di­amide mol­ecules are listed in Table 6. The largest contribution to the Hirshfeld surfaces are from H⋯H contacts, Table 5, and their respective ER values are close to unity. This shows that the contribution from dispersive forces are significant in the mol­ecule packing of the title 2:1 co-crystal, in contrast to that observed in a related, recently published structure, namely, the salt [2-({[(pyridin-1-ium-2-yl­meth­yl)carbamo­yl]formamido}­meth­yl)-pyridin-1-ium][3,5-di­carb­oxy­benzoate], i.e. containing the diprotonated form of the isomeric 2-pyridyl-containing di­amide (Syed et al., 2016). In the latter, O⋯H/H⋯O contacts make the greatest contribution to the crystal packing. It is the presence of different substituents in the benzene ring in the acid mol­ecule in the co-crystal, i.e. methyl, as opposed to carb­oxy­lic acid/carboxyl­ate groups in the salt, that provides an explanation for this difference. The ER value for O⋯H/H⋯O contacts, i.e. 1.30, shows the propensity to form hy­droxy-O—H⋯N(pyrid­yl) and amide-N—H⋯O(carbon­yl) hydrogen bonds as well as methyl­ene-C—H⋯O(amide) inter­actions. The formation of extensive π–π inter­actions is reflected in the relatively high ER values corresponding/related to C⋯C contacts, Table 6. The absence of C—H⋯π and related inter­actions is reflected in low ER values, i.e. < 0.8. Conversely, the N⋯H/H⋯N contacts in a crystal having ER values equal to greater than or equal to unity for the acid/di­amide mol­ecules reduces to 0.84 in the 2:1 co-crystal, indicating a reduced likelihood of formation once the co-crystal is stabil­ized by other inter­actions. The enrichment ratios for other contacts are of low significance as they are derived from less important inter­actions which have small contributions to Hirshfeld surfaces.

Table 6
Enrichment ratios (ER) for the acid, di­amide and co-crystal

Inter­action	Acid	Di­amide	Co-crystal
H⋯H	1.02	0.97	1.02
O⋯H/H⋯O	1.22	1.46	1.30
C⋯C	2.30	3.60	2.55
C⋯H/H⋯C	0.75	0.66	0.71
N⋯H/H⋯N	1.06	1.20	0.84

5. Database survey

As mentioned in the Chemical context, the di­amide in the title 2:1 co-crystal and isomeric forms have attracted considerable inter­est in the crystal engineering community no doubt owing to the variable functional groups and conformational flexibility. Indeed, the di­amide in the title co-crystal featured in early studies of halogen I⋯N halogen bonding (Goroff et al., 2005). Over and above these investigations, the role of the di­amide in coordination chemistry has also been studied. Bidentate bridging is the prominent coordination mode observed in both neutral, e.g. [HgI₂(di­amide)]_n (Zeng et al., 2008) and charged, e.g. polymeric [Ag(di­amide)NO₃]_n (Schauer et al., 1998) and oligiomeric {[Ph₂PCH₂PPh₂Au₂(di­amide)]₂(ClO₄)₄(EtOEt)₄} (Tzeng et al., 2006), species.

6. Synthesis and crystallization

The di­amide (0.2 g), prepared in accord with the literature procedure (Schauer et al., 1997), in ethanol (10 ml) was added to a ethanol solution (10 ml) of 2-methyl­benzoic acid (Merck, 0.1 g). The mixture was stirred for 1 h at room temperature after which a white precipitate was deposited. The solution was filtered by vacuum suction, and the filtrate was then left to stand under ambient conditions, yielding colourless prisms after 2 weeks.

7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 7. 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 nitro­gen-bound H-atoms were located in a difference Fourier map but were refined with distance restraints of O—H = 0.84±0.01 Å and N—H = 0.88±0.01 Å, and with U_iso(H) set to 1.5U_eq(O) and 1.2U_eq(N).

Table 7
Experimental details

Crystal data
Chemical formula	C14H14N4O2·2C8H8O2
Mr	542.58
Crystal system, space group	Triclinic, P
Temperature (K)	100
a, b, c (Å)	6.8948 (5), 9.7219 (5), 9.9621 (7)
α, β, γ (°)	82.971 (5), 81.638 (6), 85.686 (5)
V (Å^3)	654.58 (8)
Z	1
Radiation type	Mo Kα
μ (mm^−1)	0.10
Crystal size (mm)	0.21 × 0.15 × 0.10
Data collection
Diffractometer	Agilent Technologies SuperNova Dual diffractometer with an Atlas detector
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2014)
Tmin, Tmax	0.580, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	15067, 2993, 2358
Rint	0.044
(sin θ/λ)max (Å^−1)	0.650
Refinement
R[F^2 > 2σ(F^2)], wR(F^2), S	0.041, 0.106, 1.06
No. of reflections	2993
No. of parameters	188
No. of restraints	2
Δρmax, Δρmin (e Å^−3)	0.34, −0.23
Computer programs: CrysAlis PRO (Agilent, 2014), SHELXS97 (Sheldrick, 2008), SHELXL2014 (Sheldrick, 2015), ORTEP-3 for Windows (Farrugia, 2012), DIAMOND (Brandenburg, 2006) and publCIF (Westrip, 2010).

Supporting information

S1. Chemical context

Multi-component crystals, incorporating co-crystals, salts and co-crystal salts, attract continuing inter­est for a wide variety of applications as this technology may be employed, for example, to provide additives to promote the growth of crystals, to stabilize unusual and unstable coformers, to generate new luminescent materials, to separate enanti­omers, to facilitate absolute structure determination where the molecule of concern does not have a significant anomalous scatterer, etc (Aakeröy, 2015; Tiekink, 2012). Arguably, the area attracting most inter­est in this context is the applications of multi-component crystals in the pharmaceutical industry (Duggirala et al., 2016). Controlled/designed crystallization of multi-component crystals requires reliable synthon formation between the various components and that, of course, is the challenge of crystal engineering, let alone engineering small aggregates within crystals (Tiekink, 2014).

Systematic work on synthon propensities in multi-component crystals have revealed that carb­oxy­lic acids have a great likelihood of forming hy­droxy-O—H···N hydrogen bonds when co-crystallized with molecules with pyridyl residues (Shattock et al., 2008). A plausible explanation for this reliability is the formation of a supporting carbonyl-O···H inter­action involving the hydrogen atom adjacent to the pyridyl-nitro­gen atom. Indeed, in the absence of competing hydrogen-bonding functionality, the resulting seven-membered {···HOCO···HCN} heterosynthon is formed in more than 98% of relevant crystal structures (Shattock et al., 2008). Recent systematic work in this phenomenon relates to molecules shown in Scheme 1, where isomeric molecules with two pyridyl rings separated by a di­amide residue have been co-crystallized with various carb­oxy­lic acids (Arman, Miller et al., 2012; Arman et al., 2013, Syed et al., 2016; Jotani et al., 2016). As a continuation of these studies, the title 2:1 co-crystal was isolated and characterized crystallographically and by Hirshfeld surface analysis.

S2. Structural commentary

The title co-crystal, Fig. 1, was formed from the 1:1 co-crystallization of 2-methyl­benzoic acid and N,N'-bis­(pyridin-4-yl­methyl)­ethanedi­amide (hereafter, the di­amide) conducted in ethanol solution. The asymmetric unit comprises a full acid molecule in a general position and half a di­amide molecule, located about a centre of inversion, so the co-crystal is formulated as a 2:1 acid:di­amide co-crystal.

In the acid, the carb­oxy­lic acid group is twisted out of the plane of the benzene ring to which it is attached with the O3—C8—C9—C10 torsion angle being 150.23 (14)°, and, to a first approximation, with the carbonyl-O3 atom and methyl group lying to the same side of the molecule as indicated in the hy­droxy-O2—C8—C9—C10(H) torsion angle of -27.92 (17)°. The structure of the parent acid and several co-crystals featuring coformers shown in Scheme 2 are available for comparison; data are collected in Table 1. The common feature of all structures is the relative orientation of the carbonyl-O and methyl groups. Twists in the acid molecules vary from almost co-planar to the situation found in the title co-crystal, with an even split of conformations amongst the six known co-crystal structures.

In the centrosymmetric di­amide, the central C₄N₂O₂ core is essentially planar with an r.m.s. deviation (O1, N2, C6, C7 and symmetry equivalents) = 0.031 Å. This arrangement facilitates the formation of an intra­molecular amide-N—H···O(amide) hydrogen bond, Table 2. The pyridyl rings occupy positions on opposite sides of the central residue and project almost prime to this with the central residue/pyridyl dihedral angle being 88.60 (5)°. The aforementioned structural features match literature precedents, i.e. the two polymorphic forms of the parent di­amide and the di­amide in co-crystals with carb­oxy­lic acids and in a salt with a carboxyl­ate, Table 3. Finally, the central C—C bond length, considered long for a Csp²—Csp² bond (Spek, 2009), matches the structural data included in Table 3; see Scheme 3 for chemical diagrams of coformers.

S3. Supra­molecular features

The molecular packing of the title co-crystal is dominated by hydrogen bonding, detailed in Table 2. The carb­oxy­lic acid is connected to the di­amide via hy­droxy-O—H···N(pyridyl) hydrogen bonds to form a three-molecule aggregate, Fig. 2a. The inter­acting residues are not co-planar with the dihedral angle between the pyridyl and three CO₂ groups being 25.67 (8)° so that the carbonyl-O3···H3 distance is 2.60 Å. This suggests only a minor role for the putative seven-membered heterosynthon {···OCOH···NCH} mentioned in the Chemical context and is consistent with the significant hydrogen-bonding inter­action involving the carbonyl-O3 atom to another residue. Indeed, the three-molecule aggregates are connected into a supra­molecular layer parallel to (122) via amide-N—H···O(carbonyl) hydrogen bonds as well as methyl­ene-C—H···O(amide) inter­actions, Fig. 2b. Within layers, π–π inter­actions occur between pyridyl rings, and between layers additional π–π inter­actions occur between pyridyl/benzene and benzene/benzene rings to consolidate the three-dimensional packing, Table 4 and Fig. 2c. Globally, the packing may be described as comprising alternating layers of aromatic rings and non-aromatic residues.

S4. Analysis of the Hirshfeld surfaces

Crystal Explorer 3.1 (Wolff et al., 2012) was used to generate Hirshfeld surfaces mapped over d_norm, d_e, electrostatic potential, shape-index and curvedness for the title 2:1 co-crystal. The electrostatic potentials were calculated using TONTO (Spackman et al., 2008; Jayatilaka et al., 2005) integrated with Crystal Explorer, using the experimentally determined geometry as the input. Further, the electrostatic potentials were mapped on Hirshfeld surfaces using the STO-3G basis set at Hartree–Fock theory over a range ±0.15 au. The contact distances d_i and d_e from the Hirshfeld surface to the nearest atom inside and outside, respectively, enabled the analysis of the inter­molecular inter­actions through the mapping of d_norm. The combination of d_i and d_e in the form of a two-dimensional fingerprint plot (Rohl et al., 2008) provides a summary of the inter­molecular contacts.

The strong hy­droxy-O—H···N(pyridyl) and amide-N—H···O(carbonyl) inter­actions between the acid and di­amide molecules are visualized as bright-red spots at the respective donor and acceptor atoms on the Hirshfeld surfaces mapped over d_norm, and labelled as 1 and 2 in Fig. 3. The inter­molecular methyl­ene-C—H···O(amide) inter­actions appears as faint-red spots in Fig. 3b, marked with a `3'. The immediate environment about each molecule highlighting close contacts to the Hirshfeld surface by neighbouring molecules is shown in Fig. 4. The full fingerprint (FP) plots showing various crystal packing inter­actions in the acid, di­amide and 2:1 co-crystal are shown in Fig. 5; the contributions from various contacts are listed in Table 5.

The prominent long spike at d_e + d_i ~1.8 Å in the upper left (donor) region for the FP plot of the acid corresponds to H···N contacts and the spike at the same distance in the lower right (acceptor) region of the FP plot for the di­amide are the result of hy­droxy-O—H···N(pyridyl) inter­actions, Figs 5a and b, respectively. However, these spikes are not apparent in the overall FP for the 2:1 co-crystal as they no longer contribute to the surface of the resultant aggregate, Fig. 5c. Pairs of somewhat blunted spikes corresponding to N···H/H···N contacts at d_e + d_i ~2.9 Å result from amide-N—H···O(carbonyl) inter­actions between the acid and di­amide molecules are evident in the overall FP, Fig. 5c.

The O···H/H···O contacts, which make a significant contribution to the molecular packing, show different characteristic features in the respective delineated FP plots of the acid and di­amide. For the acid, Fig. 5a, a long prominent spike at d_e + d_i ~2.5 Å in the acceptor region corresponds to a 6.6% contribution from H···O contacts to the Hirshfeld surface, and a short spike at d_e + d_i ~2.15 Å in the donor region with a 14.0% contribution from O···H contacts. The reverse situation is observed for the di­amide molecule wherein the FP plot, Fig. 5b, contains a long prominent spike in the donor region and the short spike in the acceptor at the same d_e + d_i distance, and with 10.7 and 14.9% contributions from O···H and H···O contacts, respectively.

FP plots for the co-crystal delineated into H···H, O···H/H···O, C···H/H···C, N···H/H···N and C···C are shown in Figs 6a–e, respectively. The H···H contacts appear as asymmetrically scattered points covering a large region of the FP plot with a single broad peak at d_e = d_i ~1.2 Å for each of the co-crystal constituents, with percentage contributions of 48.7 and 45.2% for the acid and di­amide molecules, respectively. The overall 49.9% contribution to Hirshfeld surface of the co-crystal results in nearly symmetric through the superimposition of individual fingerprint plots, Fig. 6a.

The FP plot for O···H/H···O contacts, Fig. 6b, has two pairs of spikes superimposed in the (d_e, d_i) region with minimum d_e + d_i distances ~2.15 and 2.5 Å. These correspond to a 21.3% contribution to the Hirshfeld surface, and reflect the presence of inter­molecular N—H···O and C—H···O inter­actions, identified with labels 1 and 2 in Fig. 6b. The 15.9 % contribution from the C···H/H···C contacts to the Hirshfeld surface results in a symmetric pair of wings, Fig. 6c. The FP plot corresponding to C···C contacts, Fig. 6e, in the (d_e, d_i ) region between 1.7 to 2.2 Å appears as the two distinct, overlapping triangles identified with red and yellow boundaries in Fig. 6e, and shows two types of π–π stacking inter­actions: one between dissimilar rings (pyridyl and benzene) and the other between symmetry-related rings (benzene and benzene, and pyridyl and pyridyl). The presence of these π–π stacking inter­actions is also indicated by the appearance of red and blue triangles on the shape-indexed surfaces identified with arrows in the images of Fig. 7, and in the flat regions on the Hirshfeld surfaces mapped with curvedness in Fig. 8.

The inter­molecular inter­actions were further assessed by using the enrichment ratio, ER (Jelsch et al., 2014). This is a relatively new descriptor and is based on Hirshfeld surface analysis. The ER for the co-crystal together with those for the acid and di­amide molecules are listed in Table 6. The largest contribution to the Hirshfeld surfaces are from H···H contacts, Table 5, and their respective ER values are close to unity. This shows that the contribution from dispersive forces are significant in the molecule packing of the title 2:1 co-crystal, in contrast to that observed in a related, recently published structure, namely, the salt [2-({[(pyridin-1-ium-2-yl­methyl)­carbamoyl]formamido}­methyl)-pyridin-1-ium][3,5-di­carb­oxy­benzoate], i.e. containing the diprotonated form of the isomeric 2-pyridyl-containing di­amide (Syed et al., 2016). In the latter, O···H/H···O contacts make the greatest contribution to the crystal packing. It is the presence of different substituents in the benzene ring in the acid molecule in the co-crystal, i.e. methyl, as opposed to carb­oxy­lic acid/carboxyl­ate groups in the salt, that provides an explanation for this difference. The ER value for O···H/H···O contacts, i.e. 1.30, shows the propensity to form hy­droxy-O—H···N(pyridyl) and amide-N—H···O(carbonyl) hydrogen bonds as well as methyl­ene-C—H···O(amide) inter­actions. The formation of extensive π–π inter­actions is reflected in the relatively high ER values, Table 6. The absence of C—H···π and related inter­actions is reflected in low ER values, i. e. < 0.8. The N···H/H···N contacts in a crystal having ER values equal to greater than or equal to unity for the acid/di­amide molecules reduces to 0.84 in the 2:1 co-crystals, indicating a reduced likelihood of formation once the co-crystal is stabilized by other inter­actions. The enrichment ratios for other contacts are of low significance as they are derived from less important inter­actions which have small contributions to Hirshfeld surfaces.

S5. Database survey

As mentioned in the Chemical context, the di­amide in the title 2:1 co-crystal and isomeric forms have attracted considerable inter­est in the crystal engineering community no doubt owing to the variable functional groups and conformational flexibility. Indeed, the di­amide in the title co-crystal featured in early studies of halogen I···N halogen bonding (Goroff et al., 2005). Over and above these investigations, the role of the di­amide in coordination chemistry has also been studied. Bidentate bridging is the prominent coordination mode observed in both neutral, e.g. [HgI₂(di­amide)]_n (Zeng et al., 2008) and charged, e.g. polymeric [Ag(di­amide)NO₃]_n (Schauer et al., 1998) and oligiomeric {[Ph₂PCH₂PPh₂Au₂(di­amide)]₂(ClO₄)₄(EtOEt)₄} (Tzeng et al., 2006), species.

S6. Synthesis and crystallization

The di­amide (0.2 g), prepared in accord with the literature procedure (Schauer et al., 1997), in ethanol (10 ml) was added to a ethanol solution (10 ml) of 2-methyl­benzoic acid (Merck, 0.1 g). The mixture was stirred for 1 h at room temperature after which a white precipitate was deposited. The solution was filtered by vacuum suction, and the filtrate was then left to stand under ambient conditions, yielding colourless prisms after 2 weeks.

S7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 7. 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 nitro­gen-bound H-atoms were located in a difference Fourier map but were refined with distance restraints of O—H = 0.84±0.01 Å and N—H = 0.88±0.01 Å, and with U_iso(H) set to 1.5U_eq(O) and 1.2U_eq(N).

Related literature

For related literature, see: Aakeröy (2015); Arman, Kaulgud et al. (2012); Arman et al. (2013); Arman et al. (2009); Arman, Miller et al. (2012); Day et al. (2009); Duggirala et al. (2016); Ebenezer et al. (2011); Goroff et al. (2005); Groom & Allen (2014); Jelsch et al. (2014); Jotani et al. (2016); Lee (2010); Lee & Wang (2007); Nguyen et al. (2001); Nguyen et al. (1998); Rohl et al. (2008); Schauer et al. (1997); Schauer et al. (1998); Shattock et al. (2008); Spackman et al. (2008) Syed et al. (2016); Thakur & Desiraju (2008); Tiekink (2012); Tiekink (2014); Tzeng et al. (2006); Wales et al. (2012); Zeng et al. (2008).

Structure description

Multi-component crystals, incorporating co-crystals, salts and co-crystal salts, attract continuing inter­est for a wide variety of applications as this technology may be employed, for example, to provide additives to promote the growth of crystals, to stabilize unusual and unstable coformers, to generate new luminescent materials, to separate enanti­omers, to facilitate absolute structure determination where the molecule of concern does not have a significant anomalous scatterer, etc (Aakeröy, 2015; Tiekink, 2012). Arguably, the area attracting most inter­est in this context is the applications of multi-component crystals in the pharmaceutical industry (Duggirala et al., 2016). Controlled/designed crystallization of multi-component crystals requires reliable synthon formation between the various components and that, of course, is the challenge of crystal engineering, let alone engineering small aggregates within crystals (Tiekink, 2014).

Systematic work on synthon propensities in multi-component crystals have revealed that carb­oxy­lic acids have a great likelihood of forming hy­droxy-O—H···N hydrogen bonds when co-crystallized with molecules with pyridyl residues (Shattock et al., 2008). A plausible explanation for this reliability is the formation of a supporting carbonyl-O···H inter­action involving the hydrogen atom adjacent to the pyridyl-nitro­gen atom. Indeed, in the absence of competing hydrogen-bonding functionality, the resulting seven-membered {···HOCO···HCN} heterosynthon is formed in more than 98% of relevant crystal structures (Shattock et al., 2008). Recent systematic work in this phenomenon relates to molecules shown in Scheme 1, where isomeric molecules with two pyridyl rings separated by a di­amide residue have been co-crystallized with various carb­oxy­lic acids (Arman, Miller et al., 2012; Arman et al., 2013, Syed et al., 2016; Jotani et al., 2016). As a continuation of these studies, the title 2:1 co-crystal was isolated and characterized crystallographically and by Hirshfeld surface analysis.

The title co-crystal, Fig. 1, was formed from the 1:1 co-crystallization of 2-methyl­benzoic acid and N,N'-bis­(pyridin-4-yl­methyl)­ethanedi­amide (hereafter, the di­amide) conducted in ethanol solution. The asymmetric unit comprises a full acid molecule in a general position and half a di­amide molecule, located about a centre of inversion, so the co-crystal is formulated as a 2:1 acid:di­amide co-crystal.

In the acid, the carb­oxy­lic acid group is twisted out of the plane of the benzene ring to which it is attached with the O3—C8—C9—C10 torsion angle being 150.23 (14)°, and, to a first approximation, with the carbonyl-O3 atom and methyl group lying to the same side of the molecule as indicated in the hy­droxy-O2—C8—C9—C10(H) torsion angle of -27.92 (17)°. The structure of the parent acid and several co-crystals featuring coformers shown in Scheme 2 are available for comparison; data are collected in Table 1. The common feature of all structures is the relative orientation of the carbonyl-O and methyl groups. Twists in the acid molecules vary from almost co-planar to the situation found in the title co-crystal, with an even split of conformations amongst the six known co-crystal structures.

In the centrosymmetric di­amide, the central C₄N₂O₂ core is essentially planar with an r.m.s. deviation (O1, N2, C6, C7 and symmetry equivalents) = 0.031 Å. This arrangement facilitates the formation of an intra­molecular amide-N—H···O(amide) hydrogen bond, Table 2. The pyridyl rings occupy positions on opposite sides of the central residue and project almost prime to this with the central residue/pyridyl dihedral angle being 88.60 (5)°. The aforementioned structural features match literature precedents, i.e. the two polymorphic forms of the parent di­amide and the di­amide in co-crystals with carb­oxy­lic acids and in a salt with a carboxyl­ate, Table 3. Finally, the central C—C bond length, considered long for a Csp²—Csp² bond (Spek, 2009), matches the structural data included in Table 3; see Scheme 3 for chemical diagrams of coformers.

The molecular packing of the title co-crystal is dominated by hydrogen bonding, detailed in Table 2. The carb­oxy­lic acid is connected to the di­amide via hy­droxy-O—H···N(pyridyl) hydrogen bonds to form a three-molecule aggregate, Fig. 2a. The inter­acting residues are not co-planar with the dihedral angle between the pyridyl and three CO₂ groups being 25.67 (8)° so that the carbonyl-O3···H3 distance is 2.60 Å. This suggests only a minor role for the putative seven-membered heterosynthon {···OCOH···NCH} mentioned in the Chemical context and is consistent with the significant hydrogen-bonding inter­action involving the carbonyl-O3 atom to another residue. Indeed, the three-molecule aggregates are connected into a supra­molecular layer parallel to (122) via amide-N—H···O(carbonyl) hydrogen bonds as well as methyl­ene-C—H···O(amide) inter­actions, Fig. 2b. Within layers, π–π inter­actions occur between pyridyl rings, and between layers additional π–π inter­actions occur between pyridyl/benzene and benzene/benzene rings to consolidate the three-dimensional packing, Table 4 and Fig. 2c. Globally, the packing may be described as comprising alternating layers of aromatic rings and non-aromatic residues.

Crystal Explorer 3.1 (Wolff et al., 2012) was used to generate Hirshfeld surfaces mapped over d_norm, d_e, electrostatic potential, shape-index and curvedness for the title 2:1 co-crystal. The electrostatic potentials were calculated using TONTO (Spackman et al., 2008; Jayatilaka et al., 2005) integrated with Crystal Explorer, using the experimentally determined geometry as the input. Further, the electrostatic potentials were mapped on Hirshfeld surfaces using the STO-3G basis set at Hartree–Fock theory over a range ±0.15 au. The contact distances d_i and d_e from the Hirshfeld surface to the nearest atom inside and outside, respectively, enabled the analysis of the inter­molecular inter­actions through the mapping of d_norm. The combination of d_i and d_e in the form of a two-dimensional fingerprint plot (Rohl et al., 2008) provides a summary of the inter­molecular contacts.

The strong hy­droxy-O—H···N(pyridyl) and amide-N—H···O(carbonyl) inter­actions between the acid and di­amide molecules are visualized as bright-red spots at the respective donor and acceptor atoms on the Hirshfeld surfaces mapped over d_norm, and labelled as 1 and 2 in Fig. 3. The inter­molecular methyl­ene-C—H···O(amide) inter­actions appears as faint-red spots in Fig. 3b, marked with a `3'. The immediate environment about each molecule highlighting close contacts to the Hirshfeld surface by neighbouring molecules is shown in Fig. 4. The full fingerprint (FP) plots showing various crystal packing inter­actions in the acid, di­amide and 2:1 co-crystal are shown in Fig. 5; the contributions from various contacts are listed in Table 5.

The prominent long spike at d_e + d_i ~1.8 Å in the upper left (donor) region for the FP plot of the acid corresponds to H···N contacts and the spike at the same distance in the lower right (acceptor) region of the FP plot for the di­amide are the result of hy­droxy-O—H···N(pyridyl) inter­actions, Figs 5a and b, respectively. However, these spikes are not apparent in the overall FP for the 2:1 co-crystal as they no longer contribute to the surface of the resultant aggregate, Fig. 5c. Pairs of somewhat blunted spikes corresponding to N···H/H···N contacts at d_e + d_i ~2.9 Å result from amide-N—H···O(carbonyl) inter­actions between the acid and di­amide molecules are evident in the overall FP, Fig. 5c.

The O···H/H···O contacts, which make a significant contribution to the molecular packing, show different characteristic features in the respective delineated FP plots of the acid and di­amide. For the acid, Fig. 5a, a long prominent spike at d_e + d_i ~2.5 Å in the acceptor region corresponds to a 6.6% contribution from H···O contacts to the Hirshfeld surface, and a short spike at d_e + d_i ~2.15 Å in the donor region with a 14.0% contribution from O···H contacts. The reverse situation is observed for the di­amide molecule wherein the FP plot, Fig. 5b, contains a long prominent spike in the donor region and the short spike in the acceptor at the same d_e + d_i distance, and with 10.7 and 14.9% contributions from O···H and H···O contacts, respectively.

FP plots for the co-crystal delineated into H···H, O···H/H···O, C···H/H···C, N···H/H···N and C···C are shown in Figs 6a–e, respectively. The H···H contacts appear as asymmetrically scattered points covering a large region of the FP plot with a single broad peak at d_e = d_i ~1.2 Å for each of the co-crystal constituents, with percentage contributions of 48.7 and 45.2% for the acid and di­amide molecules, respectively. The overall 49.9% contribution to Hirshfeld surface of the co-crystal results in nearly symmetric through the superimposition of individual fingerprint plots, Fig. 6a.

The FP plot for O···H/H···O contacts, Fig. 6b, has two pairs of spikes superimposed in the (d_e, d_i) region with minimum d_e + d_i distances ~2.15 and 2.5 Å. These correspond to a 21.3% contribution to the Hirshfeld surface, and reflect the presence of inter­molecular N—H···O and C—H···O inter­actions, identified with labels 1 and 2 in Fig. 6b. The 15.9 % contribution from the C···H/H···C contacts to the Hirshfeld surface results in a symmetric pair of wings, Fig. 6c. The FP plot corresponding to C···C contacts, Fig. 6e, in the (d_e, d_i ) region between 1.7 to 2.2 Å appears as the two distinct, overlapping triangles identified with red and yellow boundaries in Fig. 6e, and shows two types of π–π stacking inter­actions: one between dissimilar rings (pyridyl and benzene) and the other between symmetry-related rings (benzene and benzene, and pyridyl and pyridyl). The presence of these π–π stacking inter­actions is also indicated by the appearance of red and blue triangles on the shape-indexed surfaces identified with arrows in the images of Fig. 7, and in the flat regions on the Hirshfeld surfaces mapped with curvedness in Fig. 8.

The inter­molecular inter­actions were further assessed by using the enrichment ratio, ER (Jelsch et al., 2014). This is a relatively new descriptor and is based on Hirshfeld surface analysis. The ER for the co-crystal together with those for the acid and di­amide molecules are listed in Table 6. The largest contribution to the Hirshfeld surfaces are from H···H contacts, Table 5, and their respective ER values are close to unity. This shows that the contribution from dispersive forces are significant in the molecule packing of the title 2:1 co-crystal, in contrast to that observed in a related, recently published structure, namely, the salt [2-({[(pyridin-1-ium-2-yl­methyl)­carbamoyl]formamido}­methyl)-pyridin-1-ium][3,5-di­carb­oxy­benzoate], i.e. containing the diprotonated form of the isomeric 2-pyridyl-containing di­amide (Syed et al., 2016). In the latter, O···H/H···O contacts make the greatest contribution to the crystal packing. It is the presence of different substituents in the benzene ring in the acid molecule in the co-crystal, i.e. methyl, as opposed to carb­oxy­lic acid/carboxyl­ate groups in the salt, that provides an explanation for this difference. The ER value for O···H/H···O contacts, i.e. 1.30, shows the propensity to form hy­droxy-O—H···N(pyridyl) and amide-N—H···O(carbonyl) hydrogen bonds as well as methyl­ene-C—H···O(amide) inter­actions. The formation of extensive π–π inter­actions is reflected in the relatively high ER values, Table 6. The absence of C—H···π and related inter­actions is reflected in low ER values, i. e. < 0.8. The N···H/H···N contacts in a crystal having ER values equal to greater than or equal to unity for the acid/di­amide molecules reduces to 0.84 in the 2:1 co-crystals, indicating a reduced likelihood of formation once the co-crystal is stabilized by other inter­actions. The enrichment ratios for other contacts are of low significance as they are derived from less important inter­actions which have small contributions to Hirshfeld surfaces.

As mentioned in the Chemical context, the di­amide in the title 2:1 co-crystal and isomeric forms have attracted considerable inter­est in the crystal engineering community no doubt owing to the variable functional groups and conformational flexibility. Indeed, the di­amide in the title co-crystal featured in early studies of halogen I···N halogen bonding (Goroff et al., 2005). Over and above these investigations, the role of the di­amide in coordination chemistry has also been studied. Bidentate bridging is the prominent coordination mode observed in both neutral, e.g. [HgI₂(di­amide)]_n (Zeng et al., 2008) and charged, e.g. polymeric [Ag(di­amide)NO₃]_n (Schauer et al., 1998) and oligiomeric {[Ph₂PCH₂PPh₂Au₂(di­amide)]₂(ClO₄)₄(EtOEt)₄} (Tzeng et al., 2006), species.

For related literature, see: Aakeröy (2015); Arman, Kaulgud et al. (2012); Arman et al. (2013); Arman et al. (2009); Arman, Miller et al. (2012); Day et al. (2009); Duggirala et al. (2016); Ebenezer et al. (2011); Goroff et al. (2005); Groom & Allen (2014); Jelsch et al. (2014); Jotani et al. (2016); Lee (2010); Lee & Wang (2007); Nguyen et al. (2001); Nguyen et al. (1998); Rohl et al. (2008); Schauer et al. (1997); Schauer et al. (1998); Shattock et al. (2008); Spackman et al. (2008) Syed et al. (2016); Thakur & Desiraju (2008); Tiekink (2012); Tiekink (2014); Tzeng et al. (2006); Wales et al. (2012); Zeng et al. (2008).

Synthesis and crystallization

The di­amide (0.2 g), prepared in accord with the literature procedure (Schauer et al., 1997), in ethanol (10 ml) was added to a ethanol solution (10 ml) of 2-methyl­benzoic acid (Merck, 0.1 g). The mixture was stirred for 1 h at room temperature after which a white precipitate was deposited. The solution was filtered by vacuum suction, and the filtrate was then left to stand under ambient conditions, yielding colourless prisms after 2 weeks.

Refinement details

Crystal data, data collection and structure refinement details are summarized in Table 7. 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 nitro­gen-bound H-atoms were located in a difference Fourier map but were refined with distance restraints of O—H = 0.84±0.01 Å and N—H = 0.88±0.01 Å, and with U_iso(H) set to 1.5U_eq(O) and 1.2U_eq(N).

Computing details

Data collection: CrysAlis PRO (Agilent, 2014); cell refinement: CrysAlis PRO (Agilent, 2014); data reduction: CrysAlis PRO (Agilent, 2014); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and DIAMOND (Brandenburg, 2006); software used to prepare material for publication: publCIF (Westrip, 2010).

Figures

	Fig. 1. The molecular structures of the molecules comprising the title co-crystal showing the atom-labelling scheme and displacement ellipsoids at the 50% probability level: (a) 2-methylbenzoic acid and (b) N,N'-bis(pyridin-4-ylmethyl)ethanediamide; unlabelled atoms in the diamide are generated by the symmetry operation (-1 - x, 2 - y, 1 - z).
	Fig. 2. Molecular packing in the title co-crystal: (a) three-molecule aggregate sustained by hydroxy-O—H···N(pyridyl) hydrogen bonds, (b) supramolecular layers whereby the aggregates in (a) are connected by amide-N—H···O(carbonyl) and methylene-C—H···O(amide) interactions, and (c) a view of the unit-cell contents shown in projection down the a axis, highlighting the intra- and inter-layer π–π interactions to consolidate a three-dimensional architecture. The O—H···N, N—H···O,C—H···O and π–π interactions are shown as orange, blue, green and purple dashed lines, respectively.
	Fig. 3. Views of the Hirshfeld surfaces mapped over dnorm: (a) acid and (b) diamide in the title 2:1 co-crystal. The contact points (red) are labelled to indicate the atoms participating in the intermolecular interactions.
	Fig. 4. Hirshfeld surfaces mapped over electrostatic potential showing hydrogen bonds with neighbouring molecules with the reference molecule being the (a) acid and (b) diamide.
	Fig. 5. The two-dimensional fingerprint plots for the (a) acid, (b) diamide and (c) overall 2:1 co-crystal.
	Fig. 6. The two-dimensional fingerprint plot for the title 2:1 co-crystal showing contributions from different contacts: (a) H···H, (b) O···H/H···O, (c) C···H/H···C, (d) N···H/H···N and (e) C···C.
	Fig. 7. Hirshfeld surfaces mapped over the shape index for (a) the acid and (b) the diamide, highlighting the regions involved in π–π stacking interactions.
	Fig. 8. Hirshfeld surfaces mapped over curvedness for (a) the acid and (b) the diamide, highlighting the regions involved in π–π stacking interactions.

2-Methylbenzoic acid–\ N,N'-bis(pyridin-4-ylmethyl)ethanediamide (2/1)

Crystal data

C14H14N4O2·2C8H8O2	Z = 1
Mr = 542.58	F(000) = 286
Triclinic, P1	Dx = 1.376 Mg m^−3
a = 6.8948 (5) Å	Mo Kα radiation, λ = 0.71073 Å
b = 9.7219 (5) Å	Cell parameters from 3840 reflections
c = 9.9621 (7) Å	θ = 3.5–30.0°
α = 82.971 (5)°	µ = 0.10 mm^−1
β = 81.638 (6)°	T = 100 K
γ = 85.686 (5)°	Prism, colourless
V = 654.58 (8) Å^3	0.21 × 0.15 × 0.10 mm

Data collection

Agilent Technologies SuperNova Dual diffractometer with an Atlas detector	2993 independent reflections
Radiation source: SuperNova (Mo) X-ray Source	2358 reflections with I > 2σ(I)
Mirror monochromator	Rint = 0.044
Detector resolution: 10.4041 pixels mm^-1	θmax = 27.5°, θmin = 3.0°
ω scan	h = −8→8
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2014)	k = −12→12
Tmin = 0.580, Tmax = 1.000	l = −12→12
15067 measured reflections

Refinement

Refinement on F^2	2 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.041	w = 1/[σ^2(Fo^2) + (0.0434P)^2 + 0.2225P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.106	(Δ/σ)max < 0.001
S = 1.06	Δρmax = 0.34 e Å^−3
2993 reflections	Δρmin = −0.23 e Å^−3
188 parameters

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 (Ų)

	x	y	z	Uiso*/Ueq
O1	−0.26845 (15)	1.04906 (10)	0.41903 (10)	0.0202 (2)
N1	0.10595 (19)	0.54943 (12)	0.25502 (12)	0.0194 (3)
N2	−0.34990 (18)	0.85635 (11)	0.56442 (12)	0.0157 (3)
H2N	−0.4483 (18)	0.8165 (15)	0.6161 (14)	0.019*
C1	−0.0650 (2)	0.71369 (13)	0.45691 (14)	0.0159 (3)
C2	0.1324 (2)	0.66915 (14)	0.44690 (15)	0.0183 (3)
H2	0.2123	0.6945	0.5089	0.022*
C3	0.2113 (2)	0.58766 (14)	0.34574 (15)	0.0197 (3)
H3	0.3461	0.5574	0.3403	0.024*
C4	−0.0837 (2)	0.59250 (14)	0.26467 (15)	0.0205 (3)
H4	−0.1600	0.5661	0.2009	0.025*
C5	−0.1746 (2)	0.67411 (14)	0.36357 (15)	0.0182 (3)
H5	−0.3100	0.7024	0.3672	0.022*
C6	−0.1494 (2)	0.80107 (14)	0.57005 (14)	0.0165 (3)
H3A	−0.1442	0.7438	0.6589	0.020*
H3B	−0.0648	0.8796	0.5668	0.020*
C7	−0.3901 (2)	0.97768 (13)	0.49211 (14)	0.0154 (3)
O2	0.30435 (15)	0.41238 (10)	0.06130 (11)	0.0200 (2)
H2O	0.242 (2)	0.4581 (16)	0.1233 (15)	0.030*
O3	0.50558 (15)	0.34690 (10)	0.21737 (10)	0.0210 (2)
C8	0.4571 (2)	0.33987 (13)	0.10547 (14)	0.0160 (3)
C9	0.5600 (2)	0.24530 (13)	0.00615 (14)	0.0157 (3)
C10	0.4507 (2)	0.19550 (14)	−0.08313 (15)	0.0183 (3)
H10	0.3160	0.2250	−0.0817	0.022*
C11	0.5355 (2)	0.10374 (14)	−0.17385 (15)	0.0222 (3)
H11	0.4586	0.0672	−0.2314	0.027*
C12	0.7337 (2)	0.06622 (14)	−0.17932 (15)	0.0220 (3)
H12	0.7947	0.0059	−0.2432	0.026*
C13	0.8436 (2)	0.11621 (14)	−0.09211 (15)	0.0195 (3)
H13	0.9800	0.0904	−0.0983	0.023*
C14	0.7595 (2)	0.20349 (13)	0.00468 (14)	0.0166 (3)
C15	0.8858 (2)	0.24942 (15)	0.09983 (16)	0.0225 (3)
H15A	0.8762	0.3510	0.0945	0.034*
H15B	1.0226	0.2173	0.0735	0.034*
H15C	0.8409	0.2100	0.1935	0.034*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0158 (5)	0.0209 (5)	0.0229 (6)	−0.0017 (4)	−0.0010 (4)	−0.0004 (4)
N1	0.0224 (7)	0.0166 (6)	0.0179 (6)	0.0030 (5)	0.0001 (5)	−0.0027 (5)
N2	0.0132 (6)	0.0170 (6)	0.0166 (6)	0.0005 (4)	−0.0005 (5)	−0.0031 (4)
C1	0.0179 (7)	0.0129 (6)	0.0155 (7)	−0.0004 (5)	0.0001 (6)	0.0004 (5)
C2	0.0170 (7)	0.0173 (6)	0.0208 (7)	−0.0004 (5)	−0.0025 (6)	−0.0029 (5)
C3	0.0170 (7)	0.0164 (6)	0.0243 (8)	0.0011 (5)	0.0006 (6)	−0.0018 (6)
C4	0.0238 (8)	0.0190 (7)	0.0190 (7)	0.0025 (6)	−0.0048 (6)	−0.0037 (6)
C5	0.0160 (7)	0.0185 (7)	0.0199 (7)	0.0031 (5)	−0.0028 (6)	−0.0039 (5)
C6	0.0150 (7)	0.0176 (6)	0.0170 (7)	0.0011 (5)	−0.0021 (6)	−0.0035 (5)
C7	0.0176 (8)	0.0158 (6)	0.0137 (7)	−0.0006 (5)	−0.0019 (6)	−0.0058 (5)
O2	0.0177 (6)	0.0225 (5)	0.0196 (5)	0.0044 (4)	−0.0008 (4)	−0.0067 (4)
O3	0.0239 (6)	0.0232 (5)	0.0156 (5)	0.0019 (4)	−0.0012 (4)	−0.0042 (4)
C8	0.0154 (7)	0.0151 (6)	0.0163 (7)	−0.0020 (5)	0.0015 (6)	−0.0005 (5)
C9	0.0174 (7)	0.0144 (6)	0.0140 (7)	−0.0017 (5)	0.0009 (6)	0.0001 (5)
C10	0.0166 (7)	0.0197 (7)	0.0180 (7)	0.0005 (5)	−0.0023 (6)	−0.0008 (5)
C11	0.0283 (9)	0.0211 (7)	0.0185 (8)	−0.0015 (6)	−0.0062 (6)	−0.0039 (6)
C12	0.0296 (9)	0.0182 (7)	0.0172 (7)	0.0046 (6)	−0.0005 (6)	−0.0045 (6)
C13	0.0198 (8)	0.0186 (7)	0.0183 (7)	0.0028 (6)	0.0004 (6)	−0.0008 (5)
C14	0.0185 (7)	0.0140 (6)	0.0163 (7)	−0.0021 (5)	0.0000 (6)	0.0001 (5)
C15	0.0173 (8)	0.0259 (7)	0.0251 (8)	−0.0003 (6)	−0.0024 (6)	−0.0075 (6)

Geometric parameters (Å, º)

O1—C7	1.2252 (17)	O2—C8	1.3217 (17)
N1—C4	1.3364 (19)	O2—H2O	0.853 (9)
N1—C3	1.3401 (19)	O3—C8	1.2205 (17)
N2—C7	1.3371 (17)	C8—C9	1.4994 (18)
N2—C6	1.4510 (18)	C9—C10	1.396 (2)
N2—H2N	0.874 (9)	C9—C14	1.403 (2)
C1—C5	1.385 (2)	C10—C11	1.385 (2)
C1—C2	1.390 (2)	C10—H10	0.9500
C1—C6	1.5166 (18)	C11—C12	1.383 (2)
C2—C3	1.3820 (19)	C11—H11	0.9500
C2—H2	0.9500	C12—C13	1.384 (2)
C3—H3	0.9500	C12—H12	0.9500
C4—C5	1.3892 (19)	C13—C14	1.3964 (19)
C4—H4	0.9500	C13—H13	0.9500
C5—H5	0.9500	C14—C15	1.503 (2)
C6—H3A	0.9900	C15—H15A	0.9800
C6—H3B	0.9900	C15—H15B	0.9800
C7—C7^i	1.536 (3)	C15—H15C	0.9800
C4—N1—C3	117.67 (12)	C8—O2—H2O	110.8 (13)
C7—N2—C6	121.54 (12)	O3—C8—O2	123.13 (12)
C7—N2—H2N	117.2 (11)	O3—C8—C9	123.68 (13)
C6—N2—H2N	120.9 (11)	O2—C8—C9	113.16 (12)
C5—C1—C2	117.97 (13)	C10—C9—C14	120.20 (12)
C5—C1—C6	123.56 (13)	C10—C9—C8	118.28 (13)
C2—C1—C6	118.47 (13)	C14—C9—C8	121.48 (12)
C3—C2—C1	119.31 (14)	C11—C10—C9	121.07 (14)
C3—C2—H2	120.3	C11—C10—H10	119.5
C1—C2—H2	120.3	C9—C10—H10	119.5
N1—C3—C2	122.93 (14)	C12—C11—C10	118.97 (14)
N1—C3—H3	118.5	C12—C11—H11	120.5
C2—C3—H3	118.5	C10—C11—H11	120.5
N1—C4—C5	123.05 (14)	C11—C12—C13	120.28 (13)
N1—C4—H4	118.5	C11—C12—H12	119.9
C5—C4—H4	118.5	C13—C12—H12	119.9
C1—C5—C4	119.07 (13)	C12—C13—C14	121.79 (14)
C1—C5—H5	120.5	C12—C13—H13	119.1
C4—C5—H5	120.5	C14—C13—H13	119.1
N2—C6—C1	115.06 (12)	C13—C14—C9	117.56 (13)
N2—C6—H3A	108.5	C13—C14—C15	119.00 (13)
C1—C6—H3A	108.5	C9—C14—C15	123.43 (12)
N2—C6—H3B	108.5	C14—C15—H15A	109.5
C1—C6—H3B	108.5	C14—C15—H15B	109.5
H3A—C6—H3B	107.5	H15A—C15—H15B	109.5
O1—C7—N2	125.26 (13)	C14—C15—H15C	109.5
O1—C7—C7^i	121.45 (15)	H15A—C15—H15C	109.5
N2—C7—C7^i	113.29 (15)	H15B—C15—H15C	109.5
C5—C1—C2—C3	−0.2 (2)	O2—C8—C9—C10	−27.92 (17)
C6—C1—C2—C3	179.02 (12)	O3—C8—C9—C14	−27.8 (2)
C4—N1—C3—C2	−0.3 (2)	O2—C8—C9—C14	154.08 (12)
C1—C2—C3—N1	0.4 (2)	C14—C9—C10—C11	0.4 (2)
C3—N1—C4—C5	0.0 (2)	C8—C9—C10—C11	−177.60 (12)
C2—C1—C5—C4	−0.1 (2)	C9—C10—C11—C12	−2.8 (2)
C6—C1—C5—C4	−179.24 (12)	C10—C11—C12—C13	2.1 (2)
N1—C4—C5—C1	0.2 (2)	C11—C12—C13—C14	0.9 (2)
C7—N2—C6—C1	−87.65 (15)	C12—C13—C14—C9	−3.3 (2)
C5—C1—C6—N2	−7.47 (19)	C12—C13—C14—C15	177.62 (13)
C2—C1—C6—N2	173.38 (12)	C10—C9—C14—C13	2.56 (19)
C6—N2—C7—O1	4.4 (2)	C8—C9—C14—C13	−179.48 (12)
C6—N2—C7—C7^i	−175.86 (13)	C10—C9—C14—C15	−178.36 (13)
O3—C8—C9—C10	150.23 (14)	C8—C9—C14—C15	−0.4 (2)

Symmetry code: (i) −x−1, −y+2, −z+1.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2N···O1^i	0.87 (1)	2.31 (1)	2.7100 (16)	108 (1)
O2—H2O···N1	0.85 (2)	1.79 (2)	2.6378 (16)	178 (2)
N2—H2N···O3^ii	0.87 (1)	2.17 (1)	2.8933 (15)	140 (1)
C6—H3B···O1^iii	0.99	2.48	3.3461 (18)	146

Symmetry codes: (i) −x−1, −y+2, −z+1; (ii) −x, −y+1, −z+1; (iii) −x, −y+2, −z+1.

 

Footnotes

‡Additional correspondence author, e-mail: [e-mail].