Crystal structure of 1H-imidazol-3-ium 2-(1,3-dioxoisoindolin-2-yl)acetate

Shaaban K Mohamed; Mehmet Akkurt; Herman Potgieter; Muizz Ali

doi:10.1107/S1600536814017619

. 2014 Aug 6;70(Pt 9):o979–o980. doi: 10.1107/S1600536814017619

Crystal structure of 1H-imidazol-3-ium 2-(1,3-dioxoisoindolin-2-yl)acetate

Shaaban K Mohamed ^a,^b, Mehmet Akkurt ^c,^*, Herman Potgieter ^d, Muizz Ali ^a

PMCID: PMC4186205 PMID: 25309291

Abstract

The title salt, C₃H₅N₂ ⁺·C₁₀H₆NO₄ ⁻, was obtained during a study of the co-crystallization of N′-[bis(1H-imidazol-1-yl)methylene]isonicotinohydrazide with (1,3-dioxoisoindolin-2-yl)acetic acid under aqueous conditions. The 1,3-dioxoisoindolinyl ring system of the anion is essentially planar [maximum deviation = 0.023 (2) Å]. In the crystal, cations and anions are linked via classical N—H⋯O hydrogen bonds and weak C—H⋯O hydrogen bonds, forming a three-dimensional network. Weak C—H⋯π interactions and π–π stacking interactions [centroid–centroid distances = 3.4728 (13) and 3.7339 (13) Å] also occur in the crystal.

Keywords: crystal structure; 1H-imidazol-3-ium salt; 2-(1,3-dioxoisoindolin-2-yl)acetate salt; hydrogen bonding; π–π stacking interactions; co-crystallization; pharmaceuticals

Related literature

For the use of co-crystals in drug design, see: Babu & Nangia (2011 ▶); Sekhon (2013 ▶); Frantz (2006 ▶); Pan et al. (2008 ▶); Vermeire et al. (2001 ▶).

Experimental

Crystal data

C₃H₅N₂ ⁺·C₁₀H₆NO₄ ⁻
M _r = 273.25
Monoclinic,
a = 9.8750 (7) Å
b = 18.0543 (15) Å
c = 7.0942 (5) Å
β = 100.955 (7)°
V = 1241.75 (16) Å³
Z = 4
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 150 K
0.09 × 0.02 × 0.02 mm

Data collection

Agilent SuperNova, Single source at offset, Eos diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2013 ▶) T _min = 0.859, T _max = 1.000
4781 measured reflections
2756 independent reflections
1993 reflections with I > 2σ(I)
R _int = 0.028

Refinement

R[F ² > 2σ(F ²)] = 0.053
wR(F ²) = 0.118
S = 1.06
2756 reflections
189 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.26 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2013 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▶) and PLATON (Spek, 2009 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536814017619/xu5807sup1.cif

e-70-0o979-sup1.cif^{(22.6KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814017619/xu5807Isup2.hkl

e-70-0o979-Isup2.hkl^{(151.5KB, hkl)}

Click here for additional data file.^{(5.1KB, cml)}

Supporting information file. DOI: 10.1107/S1600536814017619/xu5807Isup3.cml

Click here for additional data file.^{(1.2MB, tif)}

. DOI: 10.1107/S1600536814017619/xu5807fig1.tif

Perspective view of the title compound (I). Displacement ellipsoids are drawn at the 50% probability level.

Click here for additional data file.^{(1.5MB, tif)}

a . DOI: 10.1107/S1600536814017619/xu5807fig2.tif

Packing viewed down the a axis showing the intermolecular interactions as dotted lines.

CCDC reference: 1017262

Additional supporting information: crystallographic information; 3D view; checkCIF report

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

Cg4 is the centroid of the N2/N3/C11–C13 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2N⋯O4ⁱ	0.99 (3)	1.69 (3)	2.6846 (19)	178 (4)
N3—H3N⋯O4ⁱⁱ	0.97 (2)	1.71 (2)	2.680 (2)	175 (2)
C3—H3⋯O4ⁱⁱⁱ	0.95	2.45	3.321 (3)	153
C5—H5⋯O3^iv	0.95	2.48	3.266 (3)	141
C9—H9B⋯O2ⁱ	0.99	2.41	3.397 (3)	172
C11—H11⋯O3ⁱⁱ	0.95	2.40	2.987 (3)	120
C13—H13⋯O1^v	0.95	2.54	3.352 (2)	143
C2—H2⋯Cg4	0.95	2.87	3.805 (2)	166

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

Acknowledgments

The authors express their thanks to Dr Robin Pritchard, The University of Manchester, for providing the X-ray diffraction data.

supplementary crystallographic information

S1. Comment

The use of co-crystals in drug design see and delivery and as functional materials with potential applications as pharmaceuticals has recently attracted a significant amount of interest in the pharmaceutical industry (Babu & Nangia, 2011). Co-crystallization in particular is a reliable technique for the modification of the physical properties of a drug as it enables the control of physical properties of Active Pharmaceutical Ingredient (API) molecules such as dissolution, stability, solubility, bioavailability, hygroscopisity and compressibility without changing the chemical composition of the API (Sekhon, 2013). Multi-API co-crystals are also possible solid forms for the delivery of combination drugs that can be tested to overcome problems related with traditional combination drugs (Frantz, 2006). Another benefit of multi-API co-crystal is the ability to reduce the number of pills being taken by a patient due to the improvement of patients long-term medication compliance in long-term drug therapy, since fewer pills need to be taken (Pan et al., 2008; Vermeire et al., 2001). The title compound was obtained during our study on co-crystallization reaction of N'-(di-1H-imidazol-1-ylmethylene)isonicotinohydrazide with (1,3-dioxoisoindolin-2-yl)acetic acid under aqouse condition.

Fig. 1 shows one 1H-imidazol-3-ium cation and one (1,3-dioxoisoindolin-2-yl)acetate anion in the asymmetric unit of the title compound (I).

The five-membered ring (N2/N3/C11—C13) of the 1H-imidazol-3-ium cation is essentially planar [maximum deviation = 0.003 (2) Å for C12]. The nine-membered ring system (N1/C1–C8) of the (1,3-dioxoisoindolin-2-yl)acetate anion is also essentially planar [maximum deviation = -0.023 (2) Å for C8].

In the crystal structure, the anions and cations of (I) are linked via N—H···O and C—H···O hydrogen bonds (Table 1, Fig. 2), forming three dimensional network. Further C—H···π interactions (Table 1) and face-to-face π-π stacking interactions [Cg1···Cg2 (x, 1/2 - y, -1/2 + z) = 3.4728 (13) Å, Cg2···Cg2 (x, 1/2-y, 1/2+z) = 3.7339 (13) Å, where Cg1 and Cg2 are the centroids of the N1/C1/C6–C8 and C1–C6 rings, respectively] presents in the three-dimensional framework.

S2. Experimental

A mixture of 1 mmol (281 mg) of N'-(di-1H-imidazol-1-ylmethylene)isonicotinohydrazide and 1 mmol (205 mg) of (1,3-dioxoisoindolin-2-yl)acetic acid was stirred in 30 ml ethanol at room temperature. Few drops of glacial acetic acid as a catalyst was added to the reaction mixture and allowed to reflux at 351 K for 5 h. The reaction progress was monitored by TLC using a mixture of cyclohexane and ethyl acetate (1:1) as an eluent. On completion, the reaction mixture was poured on crushed ice (50 g). The resulting solid was filtered off, washed with cold ethanol dried under vacuum and recrystallized from ethanol to yield colourless blocks of the title compound (74% yield).