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

Sladjana B Novaković; Goran A Bogdanović; Shaaban K Mohamed; Mustafa R Albayati; Ayad S Hameed

doi:10.1107/S1600536812038032

. 2012 Sep 8;68(Pt 10):o2897–o2898. doi: 10.1107/S1600536812038032

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

Sladjana B Novaković ^a,^*, Goran A Bogdanović ^a, Shaaban K Mohamed ^b, Mustafa R Albayati ^c, Ayad S Hameed ^d

PMCID: PMC3470249 PMID: 23125693

Abstract

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.

Related literature

For anti-tuberculosis drugs containing the isoniazid core structure, see: Bijev (2006 ▶); Imramovský et al. (2007 ▶); Maccari et al. (2005 ▶); Schultheiss & Newman (2009 ▶); Shindikar & Viswanathan (2005 ▶); Sinha et al. (2005 ▶). For crystal structures with N′-[(E)-(4-methoxyphenyl)methylidene]pyridine-4-carbohydrazide, see: Jing et al. (2005 ▶); Lin & Liu (2007 ▶); Shanmuga Sundara Raj et al. (1999 ▶); Wardell et al. (2007 ▶). For crystal structures with 2-(1,3-dioxoisoindolin-2-yl)acetic acid, see: Barooah et al. (2006 ▶); Feeder & Jones (1994 ▶, 1996 ▶). For a related co-crystal, see: Mohamed et al. (2012 ▶). For the synthesis of 2-(1,3-dioxoisoindolin-2-yl)acetic acid, see: Rajpurohit & Sah (2005 ▶).

Experimental

Crystal data

2C₁₀H₇NO₄·C₁₄H₁₃N₃O₂
M _r = 665.61
Triclinic,
a = 8.1238 (4) Å
b = 12.7963 (7) Å
c = 15.9191 (11) Å
α = 105.590 (5)°
β = 101.160 (5)°
γ = 97.535 (4)°
V = 1534.19 (17) Å³
Z = 2
Cu Kα radiation
μ = 0.91 mm⁻¹
T = 293 K
0.16 × 0.10 × 0.08 mm

Data collection

Oxford Diffraction Xcalibur (Sapphire3, Gemini) diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009 ▶) T _min = 0.963, T _max = 1.000
10334 measured reflections
5912 independent reflections
4836 reflections with I > 2σ(I)
R _int = 0.022

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.116
S = 1.06
5912 reflections
456 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.28 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: CrysAlis PRO (Oxford Diffraction, 2009 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶), PLATON (Spek, 2009 ▶) and PARST (Nardelli, 1995 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812038032/rz2799sup1.cif

e-68-o2897-sup1.cif^{(37.3KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812038032/rz2799Isup2.hkl

e-68-o2897-Isup2.hkl^{(283.5KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812038032/rz2799Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2A—H1OA⋯N1	1.00 (3)	1.60 (3)	2.5997 (19)	177 (2)
O2B—H1OB⋯O1	0.93 (2)	1.75 (2)	2.6736 (16)	170 (2)
N2—H1N2⋯O4B ⁱ	0.87 (2)	2.22 (2)	3.0549 (18)	161 (2)
C2A—H2A2⋯O3B ⁱⁱ	0.97	2.57	3.477 (2)	156
C5B—H5B⋯O1ⁱⁱⁱ	0.93	2.51	3.158 (2)	126
C7B—H7B⋯O3B ^iv	0.93	2.55	3.275 (2)	135
C5—H5⋯O3A ^v	0.93	2.48	3.341 (2)	154

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) .

Acknowledgments

The authors are grateful to the Higher Education Authority of Iraq for sponsoring this project. Our gratitude is also extended to the Manchester Metropolitan University for facilitating and supporting this study. SBN and GAB thank the Ministry of Education, Science and Technological Development of the Republic of Serbia for the financial support (projects 172014 and 172035).

supplementary crystallographic information

Comment

Compounds incorporating the isoniazid (INH) core structure have shown high inhibitory activity in vitro (Bijev, 2006; Imramovský et al., 2007) and in mice towards M. tuberculosis H37Rv, ATCC 27294, M. tuberculosis clinical isolates and isoniazid-resistant M. tuberculosis (Maccari et al., 2005; Schultheiss & Newman 2009; Shindikar & Viswanathan, 2005; Sinha et al., 2005). In the present study we report the crystal structure of a novel, tricomponent cocrystal (I) containing the isoniazid-related hydrazone N'-[(E)-(4-methoxyphenyl)methylidene]pyridine-4-carbohydrazide and 2-(1,3-dioxoisoindolin-2-yl)acetic acid in a 1:2 molar ratio.

The asymmetric unit of (I) contains one hydrazone molecule and two crystallographically independent molecules of the acid denoted as A and B in Fig. 1. The A and B molecules tightly connect to the hydrazone via short and directional O2a—H1Oa···N1 and O2b— H1Ob···O1 hydrogen bond, respectively (Table 1). The interactions of A and B molecules significantly differ as their carboxyl acid groups, serving as proton donors, find different acceptors within the hydrazone molecule i.e. pyridinyl N1 and carboxyl O1 (Fig. 1). The interaction O2a—H1Oa···N1 which directly involves the acidic –COOH group and the most basic pyridinyl N1 atom causes the noticeable elongation of O2—H1Oa bond in molecule A (Table 1), yet no proton transfer occurs and all components remain neutral.

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-(1,3-dioxoisoindolin-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.

There are several crystal structures of hydrazone N'-[(E)-(4-methoxyphenyl)methylidene]pyridine-4-carbohydrazide describing this compound as monohydrate crystallizing in two forms, monoclinic (Jing et al., 2005; Shanmuga Sundara Raj et al., 1999; Wardell et al., 2007) and orthorhombic (Lin & Liu, 2007). The present form of the molecule shows no particular difference in bond lengths and angles in comparison to the previous ones.

The above described trimer with strongly intermolecular hydrogen-bonded components (Fig. 1), undergoes further arrangement via much weaker interamolecular interactions. Two such trimolecular units related by an inversion centre interact through a pair of N2—H1N2···O4b hydrogen bonds (Table 1) forming a 3 + 3 molecular aggregate.

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.

2-(1,3-Dioxoisoindolin-2-yl)acetic acid was prepared according to the literature procedure (Rajpurohit & Sah, 2005). 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.