organic compounds
2-(1,3-Dioxoisoindolin-2-yl)acetic acid–N′-[(E)-2-methoxybenzylidene]pyridine-4-carbohydrazide (1/1)
aChemistry and Environmental Division, Manchester Metropolitan University, Manchester M1 5GD, England, bDepartment of Chemistry, Government College University, Lahore 54000, Pakistan, cDepartment of Physics, Faculty of Sciences, Erciyes University, 38039 Kayseri, Turkey, and dChemistry Department, Tikrit University, Tikrit, Iraq
*Correspondence e-mail: akkurt@erciyes.edu.tr
In the title 1:1 cocrystal, C10H7NO4·C14H13N3O2, molecules are linked by intermolecular C—H⋯O, N—H⋯O and O—H⋯N hydrogen bonds, forming a three-dimensional network. In addition, π–π stacking interactions [with centroid–centroid distances of 3.5723 (19) and 3.6158 (18) Å] are observed.
Related literature
For the use of co-crystals in drug design and delivery, see: Vishweshwar et al. (2009); Peterson et al. (2006); McNamara et al. (2006). 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); Sriram et al. (2006).
Experimental
Crystal data
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Refinement
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Data collection: APEX2 (Bruker, 2009); cell SAINT (Bruker, 2009); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999) and PLATON (Spek, 2009).
Supporting information
https://doi.org/10.1107/S1600536812031388/qm2075sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536812031388/qm2075Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S1600536812031388/qm2075Isup3.cml
A mixture of 255 mg (1 mmol) N'-[(E)-(2-methoxyphenyl)methylidene]pyridine-4-carbohydrazide and 205 mg (1 mmol) (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid in 50 ml e thanol was refluxed at 351 K for six hours. The reaction mixture was poured onto crushed ice to afford a solid product which was filtered off, washed with ethanol dried under vacuum and recrystallized from ethanol in good yield (78%). Crystals (m.p. 449 K) suitable for X-ray diffraction were grown by slow evaporation from an ethanol solution at room temperature over 24 h.
H-atoms were placed in calculated positions [O—H = 0.82 Å, N—H = 0.86 Å, C–H = 0.93–0.97 Å] and were included in the
in the riding model approximation, with Uiso(H) = 1.2 or 1.5Ueq(C, N, O).The use of co-crystals in drug design and delivery and as functional materials with potential applications as pharmaceuticals has recently attracted considerable interest (Vishweshwar et al., 2009; Peterson et al., 2006; McNamara et al., 2006). Moreover, co-crystallization in particular is a reliable method for the modification of drug physical and technical properties such as solubility, dissolution rate, stability, hygroscopisity and compressibility without alternating the pharmacological behaviour of their ingredients (Schultheiss & Newman, 2009). 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; Shindikar & Viswanathan, 2005; Sinha et al., 2005; Sriram et al., 2006). In this context and on continuation of our interest in the synthesis of potentially biologically active molecules based on the core structure of isoniazid we decided to investigate the reaction of isoniazid-related
with phthalimido-acetic acid. The reaction showed the unexpected co-crystallized product (I) with its ingridients in a 1:1 ratio. In this study we report a new co-crystallization method for the anti-tubercular drug N'-[(E)-(4-methoxyphenyl)methylidene]pyridine-4-carbohydrazide with (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid and the of their cocrystal compound.Fig. 1 shows the molecules of a 1:1 cocrystal of (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid and N'-[(1E)-(2-methoxyphenyl)methylidene]pyridine-4-carbohydrazide. The bond lengths and bond angles are all within the expected ranges. In the molecule of (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid, the 2,3-dihydro-1H-isoindole ring (N1/C1–C8) is planar with a maimum deviation of 0.014 (3) Å for C2 atom. In the molecule of N'-[(1E)-(2-methoxyphenyl)methylidene]pyridine-4-carbohydrazide, the C11–C16 benzene and N4C19–C23 pyridine rings make a dihedral angle of 4.44 (15)° with each other.
The π-π stacking interactions [Cg3···Cg4(1 - x, -y, 1 - z) = 3.5723 (19) Å and Cg4···Cg4(1 - x, -y, -z) = 3.6158 (18) Å; where Cg3 and Cg4 are centroids of the N1/C1/C2/C7/C8 and C1–C6 rings, respectively] contribute to stabilize the crystal structure.
is stabilized by intermolecular C—H···O, N—H···O and O—H···N hydrogen bonds, forming a three dimensional network (Table 1, Fig. 2). Furthermore,For the use of co-crystals in drug design and delivery, see: Vishweshwar et al. (2009); Peterson et al. (2006); McNamara et al. (2006). 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); Sriram et al. (2006).
Data collection: APEX2 (Bruker, 2009); cell
SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999) and PLATON (Spek, 2009).C10H7NO4·C14H13N3O2 | F(000) = 960 |
Mr = 460.44 | Dx = 1.401 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2yn | Cell parameters from 410 reflections |
a = 7.0747 (10) Å | θ = 2.8–18.3° |
b = 43.511 (6) Å | µ = 0.10 mm−1 |
c = 7.5477 (9) Å | T = 296 K |
β = 110.015 (5)° | Prism, white |
V = 2183.1 (5) Å3 | 0.30 × 0.20 × 0.20 mm |
Z = 4 |
Bruker Kappa APEXII CCD diffractometer | 4304 independent reflections |
Radiation source: fine-focus sealed tube | 2345 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.061 |
ω scans | θmax = 26.0°, θmin = 1.9° |
Absorption correction: multi-scan (SADABS; Bruker, 2005) | h = −8→8 |
Tmin = 0.970, Tmax = 0.980 | k = −53→53 |
19892 measured reflections | l = −9→6 |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.055 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.135 | H-atom parameters constrained |
S = 1.02 | w = 1/[σ2(Fo2) + (0.0485P)2 + 0.2903P] where P = (Fo2 + 2Fc2)/3 |
4304 reflections | (Δ/σ)max < 0.001 |
309 parameters | Δρmax = 0.14 e Å−3 |
0 restraints | Δρmin = −0.18 e Å−3 |
C10H7NO4·C14H13N3O2 | V = 2183.1 (5) Å3 |
Mr = 460.44 | Z = 4 |
Monoclinic, P21/n | Mo Kα radiation |
a = 7.0747 (10) Å | µ = 0.10 mm−1 |
b = 43.511 (6) Å | T = 296 K |
c = 7.5477 (9) Å | 0.30 × 0.20 × 0.20 mm |
β = 110.015 (5)° |
Bruker Kappa APEXII CCD diffractometer | 4304 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2005) | 2345 reflections with I > 2σ(I) |
Tmin = 0.970, Tmax = 0.980 | Rint = 0.061 |
19892 measured reflections |
R[F2 > 2σ(F2)] = 0.055 | 0 restraints |
wR(F2) = 0.135 | H-atom parameters constrained |
S = 1.02 | Δρmax = 0.14 e Å−3 |
4304 reflections | Δρmin = −0.18 e Å−3 |
309 parameters |
Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles |
Refinement. Refinement on F2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The observed criterion of F2 > σ(F2) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger. |
x | y | z | Uiso*/Ueq | ||
O5 | 0.9659 (3) | 0.13677 (4) | 0.9365 (3) | 0.0713 (9) | |
O6 | 0.7705 (3) | 0.28342 (4) | 0.8630 (2) | 0.0491 (7) | |
N2 | 0.9227 (3) | 0.22710 (5) | 0.8728 (3) | 0.0448 (8) | |
N3 | 0.9636 (3) | 0.24511 (5) | 1.0332 (3) | 0.0431 (8) | |
N4 | 0.9687 (3) | 0.32666 (5) | 1.5100 (3) | 0.0475 (9) | |
C11 | 0.9448 (4) | 0.17874 (6) | 0.7399 (4) | 0.0426 (10) | |
C12 | 0.9519 (4) | 0.14724 (6) | 0.7626 (4) | 0.0527 (11) | |
C13 | 0.9412 (5) | 0.12788 (7) | 0.6119 (5) | 0.0733 (14) | |
C14 | 0.9201 (5) | 0.14100 (10) | 0.4399 (5) | 0.0838 (16) | |
C15 | 0.9080 (5) | 0.17224 (9) | 0.4141 (5) | 0.0780 (16) | |
C16 | 0.9193 (4) | 0.19068 (7) | 0.5638 (4) | 0.0574 (11) | |
C17 | 0.9700 (4) | 0.19899 (6) | 0.9011 (4) | 0.0425 (9) | |
C18 | 0.8817 (4) | 0.27317 (6) | 1.0142 (4) | 0.0383 (9) | |
C19 | 0.9250 (3) | 0.29134 (5) | 1.1918 (3) | 0.0345 (8) | |
C20 | 0.9321 (4) | 0.32285 (6) | 1.1838 (4) | 0.0425 (9) | |
C21 | 0.9562 (4) | 0.33942 (6) | 1.3457 (4) | 0.0478 (10) | |
C22 | 0.9617 (4) | 0.29627 (6) | 1.5154 (4) | 0.0474 (10) | |
C23 | 0.9432 (4) | 0.27773 (6) | 1.3624 (3) | 0.0432 (9) | |
C24 | 0.9578 (6) | 0.10465 (7) | 0.9630 (5) | 0.0989 (18) | |
O1 | 0.1383 (4) | 0.04421 (5) | 0.1887 (3) | 0.0801 (9) | |
O2 | 0.8106 (4) | 0.05255 (5) | 0.4959 (3) | 0.0820 (9) | |
O3 | 0.4269 (3) | 0.13691 (4) | 0.2806 (3) | 0.0563 (7) | |
O4 | 0.5019 (4) | 0.09977 (4) | 0.1147 (3) | 0.0768 (9) | |
N1 | 0.4681 (4) | 0.05545 (5) | 0.3577 (3) | 0.0530 (9) | |
C1 | 0.3116 (5) | 0.03656 (7) | 0.2495 (4) | 0.0554 (11) | |
C2 | 0.4075 (5) | 0.00722 (6) | 0.2291 (4) | 0.0524 (10) | |
C3 | 0.3233 (5) | −0.01899 (7) | 0.1349 (4) | 0.0665 (14) | |
C4 | 0.4514 (7) | −0.04291 (7) | 0.1340 (4) | 0.0748 (14) | |
C5 | 0.6539 (7) | −0.04044 (7) | 0.2267 (5) | 0.0771 (14) | |
C6 | 0.7384 (6) | −0.01406 (7) | 0.3214 (4) | 0.0711 (14) | |
C7 | 0.6119 (5) | 0.00973 (6) | 0.3213 (4) | 0.0528 (10) | |
C8 | 0.6528 (5) | 0.04091 (7) | 0.4045 (4) | 0.0562 (11) | |
C9 | 0.4417 (5) | 0.08717 (6) | 0.3977 (4) | 0.0571 (10) | |
C10 | 0.4610 (4) | 0.10833 (6) | 0.2468 (4) | 0.0495 (10) | |
H3B | 1.03930 | 0.23840 | 1.14160 | 0.0520* | |
H13 | 0.94820 | 0.10670 | 0.62710 | 0.0880* | |
H14 | 0.91390 | 0.12830 | 0.33880 | 0.1000* | |
H15 | 0.89240 | 0.18070 | 0.29680 | 0.0940* | |
H16 | 0.90950 | 0.21190 | 0.54670 | 0.0690* | |
H17 | 1.02040 | 0.19130 | 1.02330 | 0.0510* | |
H20 | 0.92090 | 0.33280 | 1.07150 | 0.0510* | |
H21 | 0.96430 | 0.36070 | 1.34000 | 0.0570* | |
H22 | 0.96960 | 0.28690 | 1.62860 | 0.0570* | |
H23 | 0.94310 | 0.25640 | 1.37370 | 0.0520* | |
H24A | 0.83290 | 0.09670 | 0.87840 | 0.1490* | |
H24B | 0.96730 | 0.10060 | 1.09080 | 0.1490* | |
H24C | 1.06770 | 0.09490 | 0.93790 | 0.1490* | |
H3 | 0.18520 | −0.02070 | 0.07370 | 0.0800* | |
H3A | 0.44340 | 0.14810 | 0.19960 | 0.0840* | |
H4 | 0.39910 | −0.06090 | 0.06940 | 0.0900* | |
H5 | 0.73670 | −0.05700 | 0.22570 | 0.0920* | |
H6 | 0.87640 | −0.01250 | 0.38320 | 0.0850* | |
H9A | 0.54170 | 0.09270 | 0.51780 | 0.0680* | |
H9B | 0.30990 | 0.08980 | 0.40850 | 0.0680* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O5 | 0.0945 (17) | 0.0458 (13) | 0.0698 (15) | 0.0059 (11) | 0.0233 (12) | 0.0036 (11) |
O6 | 0.0610 (13) | 0.0456 (11) | 0.0326 (10) | 0.0085 (9) | 0.0054 (9) | 0.0006 (8) |
N2 | 0.0474 (14) | 0.0426 (14) | 0.0398 (13) | 0.0021 (11) | 0.0089 (10) | −0.0081 (10) |
N3 | 0.0519 (14) | 0.0403 (13) | 0.0301 (12) | 0.0075 (11) | 0.0050 (10) | −0.0024 (10) |
N4 | 0.0560 (16) | 0.0456 (15) | 0.0419 (14) | −0.0016 (11) | 0.0179 (11) | −0.0047 (11) |
C11 | 0.0352 (16) | 0.0470 (17) | 0.0452 (17) | −0.0030 (12) | 0.0132 (12) | −0.0063 (13) |
C12 | 0.0480 (19) | 0.0502 (19) | 0.0577 (19) | −0.0030 (14) | 0.0154 (15) | −0.0086 (15) |
C13 | 0.064 (2) | 0.061 (2) | 0.092 (3) | −0.0124 (17) | 0.0228 (19) | −0.034 (2) |
C14 | 0.079 (3) | 0.108 (3) | 0.068 (2) | −0.026 (2) | 0.030 (2) | −0.044 (2) |
C15 | 0.079 (3) | 0.107 (3) | 0.053 (2) | −0.030 (2) | 0.0289 (18) | −0.019 (2) |
C16 | 0.059 (2) | 0.071 (2) | 0.0436 (18) | −0.0141 (15) | 0.0193 (15) | −0.0080 (15) |
C17 | 0.0410 (16) | 0.0442 (17) | 0.0432 (15) | 0.0010 (13) | 0.0157 (12) | −0.0013 (13) |
C18 | 0.0391 (16) | 0.0390 (16) | 0.0369 (15) | −0.0013 (12) | 0.0131 (12) | 0.0007 (12) |
C19 | 0.0288 (14) | 0.0390 (15) | 0.0340 (14) | 0.0002 (11) | 0.0084 (11) | 0.0010 (11) |
C20 | 0.0460 (17) | 0.0449 (17) | 0.0360 (15) | −0.0030 (13) | 0.0131 (12) | 0.0019 (12) |
C21 | 0.0545 (19) | 0.0391 (16) | 0.0489 (18) | −0.0064 (13) | 0.0166 (14) | −0.0018 (14) |
C22 | 0.0557 (19) | 0.0493 (18) | 0.0380 (15) | 0.0031 (14) | 0.0170 (13) | 0.0041 (13) |
C23 | 0.0527 (18) | 0.0374 (15) | 0.0407 (16) | 0.0046 (13) | 0.0177 (13) | 0.0039 (12) |
C24 | 0.125 (4) | 0.047 (2) | 0.114 (3) | 0.001 (2) | 0.027 (3) | 0.014 (2) |
O1 | 0.0718 (17) | 0.0643 (15) | 0.0895 (16) | 0.0049 (13) | 0.0088 (13) | 0.0052 (12) |
O2 | 0.0728 (17) | 0.0660 (15) | 0.0948 (17) | −0.0089 (13) | 0.0128 (14) | −0.0199 (13) |
O3 | 0.0881 (15) | 0.0373 (11) | 0.0495 (12) | 0.0022 (10) | 0.0312 (11) | 0.0029 (9) |
O4 | 0.136 (2) | 0.0485 (13) | 0.0652 (14) | 0.0040 (12) | 0.0592 (15) | −0.0054 (11) |
N1 | 0.0680 (18) | 0.0366 (13) | 0.0507 (14) | −0.0013 (12) | 0.0155 (13) | 0.0014 (11) |
C1 | 0.069 (2) | 0.0473 (18) | 0.0458 (17) | −0.0029 (17) | 0.0143 (16) | 0.0084 (14) |
C2 | 0.080 (2) | 0.0372 (17) | 0.0402 (16) | −0.0030 (15) | 0.0207 (16) | 0.0047 (13) |
C3 | 0.094 (3) | 0.050 (2) | 0.0545 (19) | −0.0154 (19) | 0.0243 (18) | −0.0047 (15) |
C4 | 0.127 (3) | 0.043 (2) | 0.062 (2) | −0.014 (2) | 0.042 (2) | −0.0098 (16) |
C5 | 0.119 (3) | 0.048 (2) | 0.075 (2) | 0.013 (2) | 0.047 (2) | 0.0021 (18) |
C6 | 0.087 (3) | 0.055 (2) | 0.071 (2) | 0.0114 (19) | 0.0266 (19) | −0.0008 (17) |
C7 | 0.072 (2) | 0.0431 (18) | 0.0423 (16) | −0.0014 (15) | 0.0181 (16) | 0.0025 (13) |
C8 | 0.071 (2) | 0.0447 (18) | 0.0505 (18) | −0.0034 (17) | 0.0178 (17) | −0.0006 (14) |
C9 | 0.083 (2) | 0.0366 (16) | 0.0546 (18) | −0.0009 (15) | 0.0275 (16) | 0.0006 (13) |
C10 | 0.063 (2) | 0.0380 (17) | 0.0460 (17) | −0.0006 (13) | 0.0168 (15) | −0.0031 (14) |
O5—C12 | 1.361 (4) | C22—C23 | 1.378 (4) |
O5—C24 | 1.416 (4) | C13—H13 | 0.9300 |
O6—C18 | 1.227 (3) | C14—H14 | 0.9300 |
O1—C1 | 1.200 (5) | C15—H15 | 0.9300 |
O2—C8 | 1.205 (4) | C16—H16 | 0.9300 |
O3—C10 | 1.308 (3) | C17—H17 | 0.9300 |
O4—C10 | 1.189 (4) | C20—H20 | 0.9300 |
O3—H3A | 0.8200 | C21—H21 | 0.9300 |
N2—N3 | 1.387 (3) | C22—H22 | 0.9300 |
N2—C17 | 1.267 (3) | C23—H23 | 0.9300 |
N3—C18 | 1.338 (3) | C24—H24A | 0.9600 |
N4—C21 | 1.334 (4) | C24—H24B | 0.9600 |
N4—C22 | 1.324 (3) | C24—H24C | 0.9600 |
N3—H3B | 0.8600 | C1—C2 | 1.478 (4) |
N1—C9 | 1.439 (3) | C2—C3 | 1.368 (4) |
N1—C8 | 1.384 (4) | C2—C7 | 1.378 (5) |
N1—C1 | 1.396 (4) | C3—C4 | 1.382 (5) |
C11—C17 | 1.463 (4) | C4—C5 | 1.367 (7) |
C11—C12 | 1.380 (4) | C5—C6 | 1.376 (5) |
C11—C16 | 1.380 (4) | C6—C7 | 1.368 (5) |
C12—C13 | 1.397 (4) | C7—C8 | 1.481 (4) |
C13—C14 | 1.379 (5) | C9—C10 | 1.507 (4) |
C14—C15 | 1.372 (6) | C3—H3 | 0.9300 |
C15—C16 | 1.366 (5) | C4—H4 | 0.9300 |
C18—C19 | 1.495 (4) | C5—H5 | 0.9300 |
C19—C23 | 1.383 (3) | C6—H6 | 0.9300 |
C19—C20 | 1.374 (3) | C9—H9A | 0.9700 |
C20—C21 | 1.378 (4) | C9—H9B | 0.9700 |
C12—O5—C24 | 118.3 (2) | N4—C21—H21 | 118.00 |
C10—O3—H3A | 110.00 | N4—C22—H22 | 118.00 |
N3—N2—C17 | 115.7 (2) | C23—C22—H22 | 118.00 |
N2—N3—C18 | 118.0 (2) | C22—C23—H23 | 121.00 |
C21—N4—C22 | 116.9 (2) | C19—C23—H23 | 121.00 |
C18—N3—H3B | 121.00 | O5—C24—H24C | 109.00 |
N2—N3—H3B | 121.00 | H24B—C24—H24C | 110.00 |
C1—N1—C9 | 123.6 (3) | H24A—C24—H24B | 110.00 |
C1—N1—C8 | 111.8 (2) | H24A—C24—H24C | 109.00 |
C8—N1—C9 | 124.3 (3) | O5—C24—H24B | 109.00 |
C12—C11—C16 | 118.7 (3) | O5—C24—H24A | 110.00 |
C16—C11—C17 | 120.9 (2) | O1—C1—N1 | 124.2 (3) |
C12—C11—C17 | 120.4 (3) | O1—C1—C2 | 130.2 (3) |
C11—C12—C13 | 120.6 (3) | N1—C1—C2 | 105.6 (3) |
O5—C12—C13 | 123.3 (2) | C1—C2—C3 | 129.8 (3) |
O5—C12—C11 | 116.1 (2) | C1—C2—C7 | 108.6 (3) |
C12—C13—C14 | 118.4 (3) | C3—C2—C7 | 121.6 (3) |
C13—C14—C15 | 121.7 (3) | C2—C3—C4 | 117.5 (3) |
C14—C15—C16 | 118.8 (3) | C3—C4—C5 | 120.9 (3) |
C11—C16—C15 | 121.8 (3) | C4—C5—C6 | 121.6 (4) |
N2—C17—C11 | 119.4 (3) | C5—C6—C7 | 117.6 (4) |
N3—C18—C19 | 116.0 (2) | C2—C7—C8 | 107.8 (3) |
O6—C18—C19 | 120.7 (2) | C6—C7—C8 | 131.3 (3) |
O6—C18—N3 | 123.2 (2) | C2—C7—C6 | 120.9 (3) |
C18—C19—C23 | 122.3 (2) | O2—C8—C7 | 129.5 (3) |
C20—C19—C23 | 118.4 (2) | N1—C8—C7 | 106.3 (3) |
C18—C19—C20 | 119.2 (2) | O2—C8—N1 | 124.2 (3) |
C19—C20—C21 | 118.6 (2) | N1—C9—C10 | 112.1 (2) |
N4—C21—C20 | 123.7 (2) | O3—C10—C9 | 111.3 (2) |
N4—C22—C23 | 123.6 (3) | O4—C10—C9 | 123.6 (2) |
C19—C23—C22 | 118.8 (2) | O3—C10—O4 | 125.1 (3) |
C12—C13—H13 | 121.00 | C2—C3—H3 | 121.00 |
C14—C13—H13 | 121.00 | C4—C3—H3 | 121.00 |
C15—C14—H14 | 119.00 | C3—C4—H4 | 120.00 |
C13—C14—H14 | 119.00 | C5—C4—H4 | 120.00 |
C16—C15—H15 | 121.00 | C4—C5—H5 | 119.00 |
C14—C15—H15 | 121.00 | C6—C5—H5 | 119.00 |
C11—C16—H16 | 119.00 | C5—C6—H6 | 121.00 |
C15—C16—H16 | 119.00 | C7—C6—H6 | 121.00 |
N2—C17—H17 | 120.00 | N1—C9—H9A | 109.00 |
C11—C17—H17 | 120.00 | N1—C9—H9B | 109.00 |
C21—C20—H20 | 121.00 | C10—C9—H9A | 109.00 |
C19—C20—H20 | 121.00 | C10—C9—H9B | 109.00 |
C20—C21—H21 | 118.00 | H9A—C9—H9B | 108.00 |
C24—O5—C12—C11 | 175.1 (3) | O6—C18—C19—C23 | 142.3 (3) |
C24—O5—C12—C13 | −3.7 (5) | O6—C18—C19—C20 | −32.7 (4) |
C17—N2—N3—C18 | −167.0 (3) | N3—C18—C19—C23 | −34.9 (4) |
N3—N2—C17—C11 | −175.9 (2) | N3—C18—C19—C20 | 150.1 (3) |
N2—N3—C18—O6 | 1.1 (4) | C18—C19—C23—C22 | −173.1 (3) |
N2—N3—C18—C19 | 178.2 (2) | C23—C19—C20—C21 | −0.3 (4) |
C22—N4—C21—C20 | 1.6 (4) | C18—C19—C20—C21 | 174.9 (3) |
C21—N4—C22—C23 | 0.2 (4) | C20—C19—C23—C22 | 1.9 (4) |
C1—N1—C9—C10 | −87.7 (4) | C19—C20—C21—N4 | −1.6 (5) |
C8—N1—C9—C10 | 85.4 (3) | N4—C22—C23—C19 | −1.9 (4) |
C8—N1—C1—C2 | 0.9 (3) | O1—C1—C2—C3 | 0.1 (6) |
C9—N1—C1—O1 | −4.7 (5) | O1—C1—C2—C7 | 178.7 (3) |
C9—N1—C1—C2 | 174.7 (3) | N1—C1—C2—C3 | −179.2 (3) |
C1—N1—C8—O2 | 179.4 (3) | N1—C1—C2—C7 | −0.7 (3) |
C1—N1—C8—C7 | −0.8 (3) | C1—C2—C3—C4 | 177.8 (3) |
C9—N1—C8—O2 | 5.7 (5) | C7—C2—C3—C4 | −0.6 (5) |
C8—N1—C1—O1 | −178.5 (3) | C1—C2—C7—C6 | −178.6 (3) |
C9—N1—C8—C7 | −174.5 (2) | C1—C2—C7—C8 | 0.2 (3) |
C17—C11—C12—C13 | −175.8 (3) | C3—C2—C7—C6 | 0.1 (5) |
C12—C11—C16—C15 | −2.3 (5) | C3—C2—C7—C8 | 178.9 (3) |
C17—C11—C12—O5 | 5.4 (4) | C2—C3—C4—C5 | 1.1 (5) |
C12—C11—C17—N2 | −165.6 (3) | C3—C4—C5—C6 | −1.1 (6) |
C16—C11—C17—N2 | 16.3 (4) | C4—C5—C6—C7 | 0.6 (5) |
C17—C11—C16—C15 | 175.9 (3) | C5—C6—C7—C2 | −0.1 (5) |
C16—C11—C12—O5 | −176.4 (3) | C5—C6—C7—C8 | −178.6 (3) |
C16—C11—C12—C13 | 2.4 (5) | C2—C7—C8—O2 | −179.9 (3) |
C11—C12—C13—C14 | −1.1 (5) | C2—C7—C8—N1 | 0.3 (3) |
O5—C12—C13—C14 | 177.7 (3) | C6—C7—C8—O2 | −1.3 (6) |
C12—C13—C14—C15 | −0.5 (6) | C6—C7—C8—N1 | 179.0 (3) |
C13—C14—C15—C16 | 0.7 (6) | N1—C9—C10—O3 | 176.9 (3) |
C14—C15—C16—C11 | 0.8 (5) | N1—C9—C10—O4 | −3.0 (5) |
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3A···N4i | 0.82 | 1.86 | 2.681 (3) | 177 |
N3—H3B···O6ii | 0.86 | 2.12 | 2.958 (3) | 164 |
C4—H4···O4iii | 0.93 | 2.44 | 3.190 (4) | 138 |
C20—H20···O3ii | 0.93 | 2.57 | 3.500 (4) | 174 |
Symmetry codes: (i) x−1/2, −y+1/2, z−3/2; (ii) x+1/2, −y+1/2, z+1/2; (iii) −x+1, −y, −z. |
Experimental details
Crystal data | |
Chemical formula | C10H7NO4·C14H13N3O2 |
Mr | 460.44 |
Crystal system, space group | Monoclinic, P21/n |
Temperature (K) | 296 |
a, b, c (Å) | 7.0747 (10), 43.511 (6), 7.5477 (9) |
β (°) | 110.015 (5) |
V (Å3) | 2183.1 (5) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.10 |
Crystal size (mm) | 0.30 × 0.20 × 0.20 |
Data collection | |
Diffractometer | Bruker Kappa APEXII CCD |
Absorption correction | Multi-scan (SADABS; Bruker, 2005) |
Tmin, Tmax | 0.970, 0.980 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 19892, 4304, 2345 |
Rint | 0.061 |
(sin θ/λ)max (Å−1) | 0.617 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.055, 0.135, 1.02 |
No. of reflections | 4304 |
No. of parameters | 309 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.14, −0.18 |
Computer programs: APEX2 (Bruker, 2009), SAINT (Bruker, 2009), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999) and PLATON (Spek, 2009).
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3A···N4i | 0.82 | 1.86 | 2.681 (3) | 177 |
N3—H3B···O6ii | 0.86 | 2.12 | 2.958 (3) | 164 |
C4—H4···O4iii | 0.93 | 2.44 | 3.190 (4) | 138 |
C20—H20···O3ii | 0.93 | 2.57 | 3.500 (4) | 174 |
Symmetry codes: (i) x−1/2, −y+1/2, z−3/2; (ii) x+1/2, −y+1/2, z+1/2; (iii) −x+1, −y, −z. |
Acknowledgements
The authors thank the Iraqi Higher Education Authority for their financial support. Manchester Metropolitan University is gratefully acknowledged for facilitating this study.
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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
The use of co-crystals in drug design and delivery and as functional materials with potential applications as pharmaceuticals has recently attracted considerable interest (Vishweshwar et al., 2009; Peterson et al., 2006; McNamara et al., 2006). Moreover, co-crystallization in particular is a reliable method for the modification of drug physical and technical properties such as solubility, dissolution rate, stability, hygroscopisity and compressibility without alternating the pharmacological behaviour of their ingredients (Schultheiss & Newman, 2009). 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; Shindikar & Viswanathan, 2005; Sinha et al., 2005; Sriram et al., 2006). In this context and on continuation of our interest in the synthesis of potentially biologically active molecules based on the core structure of isoniazid we decided to investigate the reaction of isoniazid-related hydrazones with phthalimido-acetic acid. The reaction showed the unexpected co-crystallized product (I) with its ingridients in a 1:1 ratio. In this study we report a new co-crystallization method for the anti-tubercular drug N'-[(E)-(4-methoxyphenyl)methylidene]pyridine-4-carbohydrazide with (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid and the crystal structure of their cocrystal compound.
Fig. 1 shows the molecules of a 1:1 cocrystal of (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid and N'-[(1E)-(2-methoxyphenyl)methylidene]pyridine-4-carbohydrazide. The bond lengths and bond angles are all within the expected ranges. In the molecule of (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid, the 2,3-dihydro-1H-isoindole ring (N1/C1–C8) is planar with a maimum deviation of 0.014 (3) Å for C2 atom. In the molecule of N'-[(1E)-(2-methoxyphenyl)methylidene]pyridine-4-carbohydrazide, the C11–C16 benzene and N4C19–C23 pyridine rings make a dihedral angle of 4.44 (15)° with each other.
The crystal structure is stabilized by intermolecular C—H···O, N—H···O and O—H···N hydrogen bonds, forming a three dimensional network (Table 1, Fig. 2). Furthermore, π-π stacking interactions [Cg3···Cg4(1 - x, -y, 1 - z) = 3.5723 (19) Å and Cg4···Cg4(1 - x, -y, -z) = 3.6158 (18) Å; where Cg3 and Cg4 are centroids of the N1/C1/C2/C7/C8 and C1–C6 rings, respectively] contribute to stabilize the crystal structure.