2-(1,3-Dioxoisoindolin-2-yl)acetic acid–N′-[(E)-4-methoxybenzylidene]pyridine-4-carbohydrazide (2/1)

In the crystal structure of the title compound, 2C10H7NO4·C14H13N3O2, the two independent acid molecules are connected through strong O—H⋯N and O—H⋯O hydrogen bonds to the central molecule of the antitubercular drug N′-[(E)-4-methoxybenzylidene]pyridine-4-carbohydrazide. Two such trimolecular units related by an inversion centre interact through a pair of N—H⋯O hydrogen bonds, forming a 3 + 3 molecular aggregate. The dihedral angle between the aromatic rings of the hydrazone molecule is 1.99 (12)°. The crystal packing features weak C—H⋯O and π–π stacking interactions, with centroid–centroid distances of 3.8460 (19) and 3.8703 (13) Å.


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Besides the different engagement in the strongest interactions, the important difference between molecules A and B concerns their conformation. Thus the O1 carbonyl atom adopts trans and cis orientation relating to N1 atom in A and B.
In addition, the O1-C1-C2-N1 torsion angle is 161.2 (2) and 1.4 (2)°, in molecules A and B respectively. It is worth mentioning that in a previously reported cocrystal (Mohamed et al., 2012) as well as in the crystal structures of 2-(1,3dioxoisoindolin-2-yl)acetic acid containing one molecule in the asymmetric unit (Feeder & Jones, 1996), two independent molecules (Barooah et al., 2006) or the same molecule as monohydrate (Feeder & Jones, 1994), the value of the corresponding torsion angle O1-C1-C2-N1 is below 15.8° indicating the preferred conformation is similar to that of molecule B.
The above described trimer with strongly intermolecular hydrogen-bonded components ( Fig. 1 Apart from this classical N-H···O hydrogen bond, the arrangement of the molecules in the cocrystal is further based on weak C-H···O (Table 1) and π-π interactions. Figure 2 displays the three-dimensional crystal packing as viewed down the a axis. The molecules of hydrazone are stacked in the ac plane with the perpendicular interplanar distances of 3.44 [for molecule at (-x, -y + 2, -z + 1)] and 3.46 Å [for molecule at (-x + 1, -y + 2, -z + 1)]. On the other hand, the acid molecules arrange along the c axis in an AABBAABB sequence, with the perpendicular distances between the rings ranging from 3.31 to 3.43 Å. Considering only the six membered aromatic rings one can observe only a modest overlap: Cg1···Cg2 (-x, -y + 2, -z + 1) = 3.8460 (10) Å, where Cg1 and Cg2 are the centroids of the N1-C5 and C8-C13 rings, respectively and Cg4···Cg4 (x + 1/2, -y + 1, -z) 3.8703 (13) Å where Cg4 is the centroid of the C4a-C9a ring.

Experimental
The cocrystallized solid (I) was obtained unintentionally from a reaction of 0.01 mol (2.55 g) of N′-[(E)-(4-methoxyphenyl)methylidene]pyridine-4-carbohydrazide with 0.02 mol (4.10 g) of (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid in 50 ml ethanol. The reaction mixture was heated for 6 h at 351 K, then poured on crushed ice (50 g). The resulting solid was filtered off, washed with cold ethanol and recrystallized from ethanol. Yellow crystals suitable for X-ray diffraction analysis were grown up in a diluted ethanolic solution over two days. M.p. 472-474 K. Crystals of the title compound can also be obtained by a simple crystallization of two components dissolved in ethanol.

N′-[(E)-(4-methoxyphenyl)methylidene]pyridine-4-carbohydrazide was prepared by the reaction of an equimolar solution
of isoniazid (0.01 mol; 1.37 g) and p-methoxybenzaldehyde (0.01 mol; 1.21 g) in ethanol. The reaction mixture was heated at 351 K and monitored by TLC until completed after 4 h, then left at fume cupboard where the solvent evaporated. The resulting solid was recrystallized from ethanol in a very good yield (87%); m.p. 435-437 K.

Refinement
H atoms bonded to C atoms were placed at calculated positions, with C-H distances fixed at 0.93 Å for aromatic C(sp 2 ) atoms and at 0.96 and 0.97 Å for methyl and methylene C(sp 3 ) atoms, respectively. The corresponding isotropic displacement parameters of the H atoms were set equal to 1.2U eq or 1.5U eq of the parent C(sp 2 ) or C(sp 3 ) atoms, respectively. A rotating model was employed for the methyl group. The H atoms attached to N and O atoms were located in a difference Fourier map and refined isotropically. The molecular structure of the title compound with displacement ellipsoids drawn at the 35% probability level.