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A new polymorph of the cinnamic acid–isoniazid cocrystal has been prepared by slow evaporation, namely cinnamic acid–pyridine-4-carbohydrazide (1/1), C9H8O2·C6H7N3O. The crys­tal structure is characterized by a hydrogen-bonded tetra­meric arrangement of two mol­ecules of isoniazid and two of cinnamic acid. Possible modification of the hydrogen bonding was investigated by changing the hydrazide group of isoniazid via an in situ reaction with acetone and cocrystallization with cinnamic acid. In the structure of cinnamic acid–N′-(propan-2-yl­idene)isonicotinohydrazide (1/1), C9H8O2·C9H11N3O, car­box­ylic acid–pyridine O—H...N and hydrazide–hydrazide N—H...O hydrogen bonds are formed.

Supporting information

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Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229614003684/cu3047sup1.cif
Contains datablocks 1, 2, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S2053229614003684/cu30471sup2.hkl
Contains datablock 1

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S2053229614003684/cu30472sup3.hkl
Contains datablock 2

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Chemical Markup Language (CML) file https://doi.org/10.1107/S2053229614003684/cu30471sup4.cml
Supplementary material

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Chemical Markup Language (CML) file https://doi.org/10.1107/S2053229614003684/cu30472sup5.cml
Supplementary material

CCDC references: 987640; 987641

Introduction top

Isoniazid (pyridine-4-carbohydrazide) is a pharmaceutically active compound widely used in the treatment of tuberculosis (LoBue & Moser, 2003). It is known to have synergistic activity with cinnamic acid (Rastogi et al., 1998; Chen et al., 2011).

Recently, we have reported two polymorphs of the cinnamic acid–isoniazid cocrystal (Sarcevica et al., 2013). Polymorph I crystallizes in the triclinic P1 space group and polymorph II crystallizes in the monoclinic P21/c space group. In this study, a third polymorph, denoted polymorph III, has been isolated and its structure determined.

Isoniazid shows a propensity to form O—H···Npy hydrogen bonds (py is pyridine) in cocrystals with carb­oxy­lic acids. Homomeric hydrazide–hydrazide inter­actions are also characteristic of such cocrystals (Lemmerer et al., 2010; Lemmerer & Bernstein, 2011). It is possible to change the hydrogen-bonding preferences in a crystal structure by modifying the functional groups. The ability to influence the hydrogen-bonding preferences by modifying the hydrazide group of isoniazid has been investigated (Lemmerer et al., 2010, 2011; Lemmerer, 2012).

In this study, the in situ modification of isoniazid with acetone and cocrystallization with cinnamic acid have been performed. The differences between the hydrogen-bonding motifs in cinnamic acid cocrystals with isoniazid [cinnamic acid–pyridine-4-carbohydrazide (1/1), (1)] and its reaction product with acetone [cinnamic acid–N'-(propan-2-yl­idene)isonicotinohydrazide (1/1), (2)] are identified.

Experimental top

Synthesis and crystallization top

All chemicals were purchased from commercial suppliers and were used without further purification. For the preparation of the cinnamic acid–isoniazid cocrystal polymorph III, (1), isoniazid (68.6 mg, 0.500 mmol) and cinnamic acid (74.1 mg, 0.500 mmol) were dissolved in a hot (343 K) ethyl acetate–aceto­nitrile solution (5 ml, 1:1 v/v). Slow evaporation of the solvent under ambient conditions produced single crystals of (1) (m.p. 399 K).

The cinnamic acid–N'-(propan-2-yl­idene)isonicotinohydrazide (1/1)cocrystal, (2), was prepared by adapting the crystallization method described in the literature (Lemmerer et al., 2010, 2011; Lemmerer, 2012). The product was obtained by cocrystallization of isoniazid (68.6 mg, 0.500 mmol) and cinnamic acid (74.1 mg, 0.500 mmol) from acetone (5.0 ml) at room temperature. Slow evaporation of the solvent under ambient conditions produced single crystals of (2) (yield 60%; m.p. 377 K). Elemental analysis, calculated: C 66.45, H 5.89, N 12.91, O 14.75%; found: C 65.88, H 5.65, N 12.98, O 15.49%. Spectroscopic analysis: 1H NMR (300 MHz, CDCl3, δ, p.p.m.): 9.59 (1H, m, N9—H9), 8.75–8.78 (2H, m, C2—H2, C6—H6), 7.76 (1H, d, J = 16.1 Hz, C18—H18), 7.68–7.70 (2H, m, C3—H3, C5—H5), 7.54–7.56 (2H, m, C20—H20, C24—H24), 7.38–7.40 (3H, m, C21—H21, C22—H22, C23—H23), 6.46 (1H, d, J = 16.1 Hz, C17—H17), 2.15–2.19 (6H, m, C12—H12A, C12—H12B, C12—H12C, C13—H13A, C13—H13B, C13—H13C); IR (KBr, λmax, cm-1): 1636 (CO), 1671 (CO), 2990–3040 (COOH group bands), 3236 (N—H).

Refinement top

Crystal data, data collection and structure refinement details are summarized in Table 1. The O- and N-bound H atoms of (1) and (2) were located in Fourier difference maps. Subsequently, the O-bound H atoms were positioned geometrically with O—H = 0.82 Å, while the positions of the N-bound H atoms were freely refined. The displacement parameters of O- and N-bound H atoms were refined isotropically. C-bound H atoms were refined in riding positions, with C—H = 0.93–0.96 Å, and Uiso(H) = 1.5Ueq(C) for methyl H atoms and 1.2Ueq(C) otherwise. The 001 reflection was omitted from the refinement of (1). The floating-origin restraint was generated for (2).

Results and discussion top

Cocrystal (1) crystallizes in the triclinic P1 space group with one isoniazid and one cinnamic acid molecule in the asymmetric unit. The molecular structure and atom-numbering scheme of (1) are presented in Fig. 1.

The carb­oxy­lic acid group of cinnamic acid is connected to the pyridine N atom by an O—H···N hydrogen bond (Table 2). An additional weak C—H···O inter­action prompts the formation of a cyclic hydrogen-bonded R22(7) graph-set motif (Bernstein et al., 1995) between the pyridine ring and the carb­oxy­lic acid group. The carbonyl O atom of the cinnamic acid molecule is also connected to the hydrazide group of isoniazid to form an N—H···O hydrogen bond. These motifs combine to form a hydrogen-bonded acid–base–acid–base cyclic synthon with the R44(16) graph set (Fig. 2). Such synthons are also observed in the crystal structures of cinnamic acid–isoniazid cocrystal polymorphs I and II. Four-molecule synthons in (1) are connected by weak N—H···O inter­actions (N···O = 3.09 Å) between the hydrazide groups of isoniazid. Such inter­actions are not present in cinnamic acid–isoniazid cocrystal polymorphs I and II. The packing of the synthons in polymorphs I, II and III is shown in Fig. 2.

The torsion angles C5—C4—C7—N9, C4—C7—N9—N10 and C21—C16—C15—C14 of the three polymorphs express the conformational differences between the isoniazid and cinnamic acid molecules. The dihedral angles between the planes of the carb­oxy­lic acid group and the pyridine ring characterize the planarity of the four-molecule assembly. The values of the torsion and dihedral angles of each polymorph are listed in Table 3.

In the crystal structures of all three cinnamic acid–isoniazid cocrystal polymorphs, hydrogen-bonded acid–base–acid–base rings tend to order with anti­parallel cinnamic acid molecules next to each other (Fig. 2). A coplanar arrangement of the cinnamic acid–isoniazid hydrogen-bonded rings in polymorphs I and III results in planar sheets. These sheets in the crystal structure of polymorph III are then arranged in layers to allow an offset face-to-face ππ stacking between the aromatic rings of cinnamic acid and the pyridine rings of isoniazid [symmetry operation (x + 1, y + 1, z); angle between ring planes = 6.92°, distance between centroids = 3.90 Å and shift = 1.69 Å] and between symmetry-related cinnamic acid molecules [symmetry code (-x + 3, -y + 2, -z + 1); angle between ring planes = 0.00°, distance between centroids = 3.78 Å and shift = 1.43 Å]. For comparison, in the crystal structure of polymorph I the aromatic ring of the cinnamic acid forms ππ inter­actions with the pyridine ring of isoniazid. The centroid-to-centroid distances between the aromatic rings of cinnamic acid and isoniazid [symmetry codes (x - 1, y - 1, z) and (x, y - 1, z)] are 3.66 and 3.80 Å, respectively. The correspondig shifts in polymorph I are 1.32 and 1.62 Å. The angle between the plane of the cinnamic acid aromatic ring and that of isoniazid [symmetry codes (x - 1, y - 1, z) and (x, y - 1, z) [what do these symmetry codes relate to?]] pyridine ring is 0.85°. In the crystal structure of polymorph II, the isoniazid and cinnamic acid molecules are located above each other. Offset ππ inter­actions are observed between the cinnamic acid molecules and between the isoniazid molecules (distance between centroids of aromatic rings = 3.75 Å, shift = 1.26 Å and angle between ring planes = 0.00°).

The cinnamic acid–N'-(propan-2-yl­idene)isonicotinohydrazide (1/1) cocrystal, (2), crystallizes in the orthorhombic Pb21a space group. The asymmetric unit contains one isonicotinohydrazide and one cinnamic acid molecule (Fig. 3).

The characteristic carb­oxy­lic acid–pyridine heterosynthon forms between the cinnamic acid and N'-(propan-2-yl­idene)isonicotinohydrazide molecules in (2) (Table 4 and Fig. 3). The angle between the plane of the carb­oxy­lic acid group of cinnamic acid and the plane of the pyridine ring of isoniazid is 76.2° and, in the absence of weak C—H···O hydrogen bonding, a simple D graph set forms. The carb­oxy­lic acid–pyridine synthon forms in all known N'-(propan-2-yl­idene)isonicotinohydrazide–carb­oxy­lic acid cocrystal structures (Lemmerer et al., 2010, 2011; Lemmerer, 2012).

The propan-2-yl­idene substituent hinders the formation of an N—H···O hydrogen bond between the hydrazide and carb­oxy­lic acid groups. However, an N—H···O hydrogen bond to a symmetry-related [Symmetry code?] N'-(propan-2-yl­idene)isonicotinohydrazide molecule is formed and the isonicotinohydrazide molecules in (2) are linked into linear chains that extend along the crystallographic b axis (Fig. 4). Such chains have been observed in N'-(propan-2-yl­idene)isonicotinohydrazide cocrystals with other carb­oxy­lic acids, for example succinic acid, salicylic acid and 3-hy­droxy­benzoic acid (Lemmerer et al., 2010, 2011; Lemmerer, 2012). Alternating layers of N'-(propan-2-yl­idene)isonicotinohydrazide and cinnamic acid are stacked to form a sandwich-type packing (Fig. 5).

In conclusion, isoniazid tends to form a hydrogen-bonded R44(16) synthon with cinnamic acid. These synthon-based assemblies have different spatial arrangements, giving rise to polymorphism of the cinnamic acid–isoniazid cocrystal. Modification of the isoniazid hydrazide group by replacing the –NH2 functional group can be utilized to hinder the formation of the cyclic cinnamic acid–isoniazid hydrogen-bonded R44(16) synthon.

Related literature top

For related literature, see: Bernstein et al. (1995); Chen et al. (2011); Lemmerer (2012); Lemmerer & Bernstein (2011); Lemmerer et al. (2010); Lemmerer, Bernstein & Kahlenberg (2011); LoBue & Moser (2003); Rastogi et al. (1998); Sarcevica et al. (2013).

Computing details top

For both compounds, data collection: COLLECT (Nonius, 1998); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO and SCALEPACK (Otwinowski & Minor, 1997); 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, 2012). Software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009) for (1); SHELXL97 (Sheldrick, 2008) for (2).

Figures top
[Figure 1] Fig. 1. The molecular structure and numbering scheme of cinnamic acid–isoniazid cocrystal polymorph III, (1). Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate hydrogen bonds.
[Figure 2] Fig. 2. The arrangement of hydrogen-bonded (dashed lines) four-molecule synthons in polymorphs I, II and III.
[Figure 3] Fig. 3. The molecular structure and numbering scheme of the cinnamic acid–N'-(propan-2-ylidene)isonicotinohydrazide (1/1) cocrystal, (2). Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate hydrogen bonds.
[Figure 4] Fig. 4. Hydrogen-bonding (dashed lines) motifs in the crystal structure of (II). Displacement ellipsoids are drawn at the 50% probability level.
[Figure 5] Fig. 5. A packing diagram for (2). Displacement ellipsoids are drawn at the 50% probability level.
(1) Cinnamic acid–pyridine-4-carbohydrazide (1/1) top
Crystal data top
C6H7N3O·C9H8O2Z = 2
Mr = 285.30F(000) = 300
Triclinic, P1Dx = 1.373 Mg m3
Hall symbol: -P 1Melting point: 399 K
a = 6.4872 (2) ÅMo Kα radiation, λ = 0.71073 Å
b = 8.1478 (4) ÅCell parameters from 8000 reflections
c = 13.56030 (11) Åθ = 1.0–27.5°
α = 95.1691 (11)°µ = 0.10 mm1
β = 101.1111 (11)°T = 173 K
γ = 98.6376 (17)°Plate, colourless
V = 690.08 (4) Å30.5 × 0.4 × 0.4 mm
Data collection top
Bruker Nonius KappaCCD area-detector
diffractometer
2430 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.023
Horizonally mounted graphite crystal monochromatorθmax = 27.5°, θmin = 3.1°
Detector resolution: 9 pixels mm-1h = 88
ϕ and ω scansk = 109
4637 measured reflectionsl = 1717
3145 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.045Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.123H atoms treated by a mixture of independent and constrained refinement
S = 1.05 w = 1/[σ2(Fo2) + (0.0537P)2 + 0.1682P]
where P = (Fo2 + 2Fc2)/3
3145 reflections(Δ/σ)max < 0.001
204 parametersΔρmax = 0.35 e Å3
0 restraintsΔρmin = 0.20 e Å3
Crystal data top
C6H7N3O·C9H8O2γ = 98.6376 (17)°
Mr = 285.30V = 690.08 (4) Å3
Triclinic, P1Z = 2
a = 6.4872 (2) ÅMo Kα radiation
b = 8.1478 (4) ŵ = 0.10 mm1
c = 13.56030 (11) ÅT = 173 K
α = 95.1691 (11)°0.5 × 0.4 × 0.4 mm
β = 101.1111 (11)°
Data collection top
Bruker Nonius KappaCCD area-detector
diffractometer
2430 reflections with I > 2σ(I)
4637 measured reflectionsRint = 0.023
3145 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0450 restraints
wR(F2) = 0.123H atoms treated by a mixture of independent and constrained refinement
S = 1.05Δρmax = 0.35 e Å3
3145 reflectionsΔρmin = 0.20 e Å3
204 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
N10.69034 (18)0.56375 (15)0.79286 (9)0.0270 (3)
C20.4774 (2)0.53573 (19)0.76533 (11)0.0284 (3)
H20.41350.58960.71300.034*
C30.3481 (2)0.43007 (18)0.81138 (10)0.0267 (3)
H30.20060.41470.79040.032*
C40.4394 (2)0.34763 (16)0.88859 (10)0.0220 (3)
C50.6608 (2)0.37391 (17)0.91641 (11)0.0260 (3)
H50.72880.31930.96720.031*
C60.7780 (2)0.48296 (18)0.86703 (11)0.0277 (3)
H60.92580.50090.88660.033*
C70.2918 (2)0.23682 (16)0.93853 (10)0.0223 (3)
O80.09778 (15)0.21558 (13)0.90755 (8)0.0326 (3)
N90.38371 (18)0.16741 (15)1.01730 (9)0.0243 (3)
H90.519 (3)0.185 (2)1.0433 (13)0.033 (4)*
N100.26216 (19)0.06591 (17)1.07273 (10)0.0291 (3)
H10A0.163 (3)0.125 (3)1.0915 (14)0.049 (5)*
H10B0.186 (3)0.026 (2)1.0273 (14)0.041 (5)*
O110.95518 (17)0.77111 (15)0.71545 (8)0.0388 (3)
H110.87490.70730.74030.080 (8)*
O121.16107 (15)0.79207 (13)0.86998 (8)0.0309 (3)
C131.1330 (2)0.82833 (18)0.78323 (11)0.0272 (3)
C141.2994 (2)0.93732 (18)0.74799 (11)0.0292 (3)
H141.43400.96580.79010.035*
C151.2681 (2)0.99692 (18)0.65973 (11)0.0288 (3)
H151.13300.96670.61830.035*
C161.4284 (2)1.10700 (18)0.62148 (11)0.0290 (3)
C171.3616 (3)1.1835 (2)0.53647 (12)0.0357 (4)
H171.21761.16530.50580.043*
C181.5056 (3)1.2866 (2)0.49655 (13)0.0443 (4)
H181.45791.33760.43980.053*
C191.7189 (3)1.3136 (2)0.54044 (14)0.0481 (5)
H191.81561.38310.51360.058*
C201.7898 (3)1.2373 (2)0.62477 (13)0.0428 (4)
H201.93441.25470.65410.051*
C211.6455 (3)1.1347 (2)0.66566 (12)0.0348 (4)
H211.69371.08430.72260.042*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0284 (6)0.0258 (6)0.0276 (6)0.0016 (5)0.0095 (5)0.0043 (5)
C20.0284 (7)0.0317 (8)0.0255 (7)0.0035 (6)0.0056 (5)0.0084 (6)
C30.0219 (6)0.0315 (8)0.0254 (7)0.0022 (5)0.0034 (5)0.0034 (6)
C40.0219 (6)0.0190 (7)0.0249 (7)0.0011 (5)0.0075 (5)0.0004 (5)
C50.0230 (7)0.0244 (7)0.0317 (8)0.0042 (5)0.0060 (5)0.0084 (6)
C60.0212 (7)0.0277 (7)0.0355 (8)0.0021 (5)0.0093 (5)0.0067 (6)
C70.0197 (6)0.0196 (6)0.0275 (7)0.0018 (5)0.0062 (5)0.0024 (5)
O80.0188 (5)0.0377 (6)0.0415 (6)0.0008 (4)0.0046 (4)0.0153 (5)
N90.0176 (6)0.0271 (6)0.0279 (6)0.0008 (5)0.0055 (5)0.0085 (5)
N100.0219 (6)0.0319 (7)0.0341 (7)0.0016 (5)0.0081 (5)0.0124 (6)
O110.0305 (6)0.0502 (7)0.0313 (6)0.0095 (5)0.0038 (4)0.0157 (5)
O120.0280 (5)0.0347 (6)0.0297 (6)0.0012 (4)0.0056 (4)0.0100 (4)
C130.0245 (7)0.0260 (7)0.0321 (8)0.0032 (5)0.0091 (6)0.0045 (6)
C140.0260 (7)0.0294 (8)0.0314 (8)0.0004 (6)0.0071 (6)0.0050 (6)
C150.0270 (7)0.0302 (8)0.0287 (8)0.0031 (6)0.0056 (6)0.0043 (6)
C160.0357 (8)0.0245 (7)0.0279 (8)0.0015 (6)0.0126 (6)0.0021 (6)
C170.0397 (8)0.0354 (9)0.0309 (8)0.0003 (7)0.0097 (6)0.0048 (7)
C180.0613 (12)0.0387 (10)0.0337 (9)0.0017 (8)0.0167 (8)0.0104 (7)
C190.0594 (12)0.0367 (10)0.0479 (11)0.0139 (8)0.0290 (9)0.0022 (8)
C200.0355 (9)0.0413 (10)0.0463 (10)0.0077 (7)0.0123 (7)0.0067 (8)
C210.0370 (8)0.0338 (8)0.0326 (8)0.0020 (6)0.0093 (6)0.0022 (6)
Geometric parameters (Å, º) top
N1—C61.3340 (19)O11—H110.8200
N1—C21.3382 (18)O12—C131.2250 (17)
C2—C31.3843 (19)C13—C141.4729 (19)
C2—H20.9300C14—C151.323 (2)
C3—C41.380 (2)C14—H140.9300
C3—H30.9300C15—C161.472 (2)
C4—C51.3910 (18)C15—H150.9300
C4—C71.5137 (18)C16—C171.387 (2)
C5—C61.3842 (19)C16—C211.396 (2)
C5—H50.9300C17—C181.383 (2)
C6—H60.9300C17—H170.9300
C7—O81.2279 (16)C18—C191.373 (3)
C7—N91.3346 (18)C18—H180.9300
N9—N101.4196 (16)C19—C201.385 (3)
N9—H90.866 (18)C19—H190.9300
N10—H10A0.92 (2)C20—C211.390 (2)
N10—H10B0.94 (2)C20—H200.9300
O11—C131.3213 (18)C21—H210.9300
C6—N1—C2117.35 (12)O12—C13—C14121.37 (13)
N1—C2—C3122.83 (13)O11—C13—C14115.98 (13)
N1—C2—H2118.6C15—C14—C13123.62 (14)
C3—C2—H2118.6C15—C14—H14118.2
C4—C3—C2119.62 (13)C13—C14—H14118.2
C4—C3—H3120.2C14—C15—C16125.66 (14)
C2—C3—H3120.2C14—C15—H15117.2
C3—C4—C5117.86 (12)C16—C15—H15117.2
C3—C4—C7117.79 (12)C17—C16—C21118.56 (14)
C5—C4—C7124.34 (13)C17—C16—C15118.59 (14)
C6—C5—C4118.75 (13)C21—C16—C15122.84 (14)
C6—C5—H5120.6C18—C17—C16121.05 (16)
C4—C5—H5120.6C18—C17—H17119.5
N1—C6—C5123.57 (13)C16—C17—H17119.5
N1—C6—H6118.2C19—C18—C17120.15 (17)
C5—C6—H6118.2C19—C18—H18119.9
O8—C7—N9122.90 (12)C17—C18—H18119.9
O8—C7—C4120.54 (12)C18—C19—C20119.86 (15)
N9—C7—C4116.55 (11)C18—C19—H19120.1
C7—N9—N10121.90 (11)C20—C19—H19120.1
C7—N9—H9125.2 (11)C19—C20—C21120.21 (16)
N10—N9—H9112.7 (11)C19—C20—H20119.9
N9—N10—H10A107.6 (12)C21—C20—H20119.9
N9—N10—H10B106.6 (11)C20—C21—C16120.16 (16)
H10A—N10—H10B106.5 (17)C20—C21—H21119.9
C13—O11—H11109.5C16—C21—H21119.9
O12—C13—O11122.64 (12)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N9—H9···O12i0.866 (18)2.151 (19)3.0071 (15)169.9 (15)
O11—H11···N10.821.842.6554 (15)179
N10—H10A···O12ii0.92 (2)2.44 (2)3.3309 (17)164.5 (16)
N10—H10B···O12iii0.94 (2)2.449 (19)3.2753 (18)147.3 (15)
N10—H10B···O8iv0.94 (2)2.563 (18)3.0865 (15)115.7 (13)
C6—H6···O120.932.673.2535 (16)121
Symmetry codes: (i) x+2, y+1, z+2; (ii) x+1, y+1, z+2; (iii) x1, y1, z; (iv) x, y, z+2.
(2) Cinnamic acid–N'-(propan-2-ylidene)pyridine-4-carbohydrazide (1/1) top
Crystal data top
C9H11N3O·C9H8O2Dx = 1.274 Mg m3
Mr = 325.36Melting point: 377 K
Orthorhombic, Pca21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P -2a -2abCell parameters from 18975 reflections
a = 8.8818 (1) Åθ = 1.0–27.5°
b = 21.0445 (4) ŵ = 0.09 mm1
c = 9.0764 (1) ÅT = 173 K
V = 1696.50 (4) Å3Prism, colourless
Z = 40.4 × 0.3 × 0.2 mm
F(000) = 688.0
Data collection top
Nonius KappaCCD area-detector
diffractometer
1791 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.023
Horizonally mounted graphite crystal monochromatorθmax = 27.5°, θmin = 2.5°
Detector resolution: 9 pixels mm-1h = 1111
ϕ and ω scansk = 2727
3694 measured reflectionsl = 1111
2058 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.037Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.088H atoms treated by a mixture of independent and constrained refinement
S = 1.05 w = 1/[σ2(Fo2) + (0.0412P)2 + 0.2535P]
where P = (Fo2 + 2Fc2)/3
2058 reflections(Δ/σ)max < 0.001
225 parametersΔρmax = 0.25 e Å3
1 restraintΔρmin = 0.14 e Å3
Crystal data top
C9H11N3O·C9H8O2V = 1696.50 (4) Å3
Mr = 325.36Z = 4
Orthorhombic, Pca21Mo Kα radiation
a = 8.8818 (1) ŵ = 0.09 mm1
b = 21.0445 (4) ÅT = 173 K
c = 9.0764 (1) Å0.4 × 0.3 × 0.2 mm
Data collection top
Nonius KappaCCD area-detector
diffractometer
1791 reflections with I > 2σ(I)
3694 measured reflectionsRint = 0.023
2058 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0371 restraint
wR(F2) = 0.088H atoms treated by a mixture of independent and constrained refinement
S = 1.05Δρmax = 0.25 e Å3
2058 reflectionsΔρmin = 0.14 e Å3
225 parameters
Special details top

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.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
N10.9050 (2)0.16280 (8)0.3969 (2)0.0365 (4)
C20.9888 (3)0.11412 (10)0.3498 (2)0.0327 (5)
H21.06930.12260.28730.039*
C30.9615 (2)0.05154 (9)0.3896 (2)0.0289 (4)
H31.02200.01890.35420.035*
C40.8415 (2)0.03878 (9)0.4836 (2)0.0267 (4)
C50.7550 (3)0.08914 (9)0.5332 (2)0.0340 (5)
H50.67450.08210.59670.041*
C60.7896 (3)0.14979 (10)0.4874 (3)0.0394 (5)
H60.73030.18330.52060.047*
C70.8091 (2)0.02658 (9)0.5420 (2)0.0274 (4)
O80.7528 (2)0.03385 (6)0.66400 (17)0.0380 (4)
N90.8529 (2)0.07475 (8)0.45257 (18)0.0287 (4)
H90.859 (2)0.0660 (10)0.357 (3)0.028 (6)*
N100.8372 (2)0.13715 (8)0.50252 (19)0.0321 (4)
C110.8835 (2)0.18048 (10)0.4137 (2)0.0325 (5)
C120.9508 (3)0.17017 (11)0.2650 (3)0.0412 (5)
H12A0.87250.16070.19550.062*
H12B1.00310.20790.23460.062*
H12C1.02030.13530.26910.062*
C130.8648 (3)0.24761 (11)0.4648 (3)0.0487 (6)
H13A0.82630.24780.56360.073*
H13B0.96060.26880.46260.073*
H13C0.79570.26930.40100.073*
O140.9817 (2)0.28333 (8)0.3413 (2)0.0521 (5)
H140.95620.24590.34520.087 (12)*
O150.7904 (2)0.28889 (8)0.1846 (3)0.0713 (6)
C160.8914 (3)0.31398 (11)0.2545 (3)0.0453 (6)
C170.9244 (3)0.38341 (11)0.2513 (3)0.0466 (6)
H170.99920.39940.31280.056*
C180.8519 (3)0.42263 (11)0.1651 (3)0.0424 (5)
H180.78190.40480.10110.051*
C190.8696 (3)0.49226 (10)0.1588 (3)0.0378 (5)
C200.9695 (3)0.52573 (11)0.2481 (3)0.0419 (5)
H201.02980.50390.31490.050*
C210.9798 (3)0.59133 (11)0.2383 (3)0.0473 (6)
H211.04650.61340.29850.057*
C220.8905 (3)0.62406 (11)0.1388 (3)0.0490 (6)
H220.89830.66800.13130.059*
C230.7906 (3)0.59175 (11)0.0514 (3)0.0501 (6)
H230.72990.61380.01460.060*
C240.7801 (3)0.52611 (11)0.0615 (3)0.0448 (6)
H240.71180.50450.00210.054*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0398 (10)0.0313 (9)0.0383 (10)0.0013 (8)0.0076 (9)0.0003 (8)
C20.0352 (11)0.0345 (11)0.0285 (10)0.0069 (9)0.0026 (9)0.0008 (9)
C30.0319 (10)0.0285 (10)0.0263 (9)0.0004 (8)0.0019 (9)0.0017 (8)
C40.0285 (9)0.0312 (10)0.0205 (9)0.0003 (8)0.0042 (8)0.0008 (8)
C50.0312 (9)0.0374 (11)0.0333 (11)0.0048 (10)0.0009 (9)0.0009 (9)
C60.0404 (12)0.0330 (11)0.0447 (13)0.0053 (9)0.0042 (11)0.0028 (10)
C70.0286 (9)0.0311 (10)0.0225 (10)0.0006 (8)0.0048 (8)0.0011 (8)
O80.0510 (8)0.0390 (8)0.0240 (7)0.0019 (8)0.0067 (7)0.0030 (7)
N90.0360 (9)0.0281 (9)0.0222 (8)0.0010 (7)0.0009 (7)0.0047 (7)
N100.0407 (10)0.0280 (9)0.0276 (8)0.0016 (7)0.0029 (8)0.0051 (7)
C110.0350 (11)0.0313 (11)0.0312 (10)0.0005 (9)0.0047 (10)0.0041 (9)
C120.0535 (14)0.0357 (12)0.0345 (11)0.0073 (10)0.0030 (11)0.0002 (10)
C130.0694 (17)0.0306 (12)0.0460 (14)0.0012 (11)0.0023 (12)0.0034 (10)
O140.0616 (11)0.0300 (8)0.0648 (12)0.0080 (8)0.0123 (10)0.0065 (9)
O150.0756 (15)0.0452 (10)0.0932 (15)0.0001 (10)0.0329 (13)0.0041 (11)
C160.0482 (14)0.0336 (12)0.0541 (14)0.0007 (11)0.0020 (12)0.0035 (12)
C170.0463 (13)0.0419 (13)0.0517 (14)0.0021 (11)0.0065 (13)0.0034 (12)
C180.0407 (12)0.0425 (13)0.0439 (13)0.0017 (10)0.0044 (11)0.0004 (11)
C190.0395 (11)0.0337 (11)0.0404 (11)0.0038 (10)0.0128 (10)0.0023 (10)
C200.0387 (12)0.0390 (12)0.0482 (13)0.0062 (10)0.0038 (11)0.0087 (11)
C210.0458 (13)0.0403 (14)0.0559 (16)0.0017 (11)0.0061 (12)0.0012 (11)
C220.0617 (16)0.0309 (12)0.0544 (16)0.0051 (11)0.0139 (13)0.0072 (11)
C230.0605 (16)0.0434 (14)0.0464 (14)0.0103 (12)0.0043 (14)0.0123 (12)
C240.0483 (14)0.0471 (13)0.0391 (13)0.0012 (11)0.0032 (12)0.0046 (11)
Geometric parameters (Å, º) top
N1—C21.337 (3)C13—H13B0.9600
N1—C61.341 (3)C13—H13C0.9600
C2—C31.387 (3)O14—C161.296 (3)
C2—H20.9300O14—H140.8200
C3—C41.392 (3)O15—C161.219 (3)
C3—H30.9300C16—C171.491 (3)
C4—C51.384 (3)C17—C181.307 (3)
C4—C71.502 (3)C17—H170.9300
C5—C61.377 (3)C18—C191.475 (3)
C5—H50.9300C18—H180.9300
C6—H60.9300C19—C241.385 (3)
C7—O81.225 (3)C19—C201.393 (3)
C7—N91.356 (3)C20—C211.387 (3)
N9—N101.396 (2)C20—H200.9300
N9—H90.89 (2)C21—C221.385 (4)
N10—C111.284 (3)C21—H210.9300
C11—C121.493 (3)C22—C231.371 (4)
C11—C131.496 (3)C22—H220.9300
C12—H12A0.9600C23—C241.387 (3)
C12—H12B0.9600C23—H230.9300
C12—H12C0.9600C24—H240.9300
C13—H13A0.9600
C2—N1—C6117.71 (18)C11—C13—H13B109.5
N1—C2—C3123.2 (2)H13A—C13—H13B109.5
N1—C2—H2118.4C11—C13—H13C109.5
C3—C2—H2118.4H13A—C13—H13C109.5
C2—C3—C4118.49 (19)H13B—C13—H13C109.5
C2—C3—H3120.8C16—O14—H14109.5
C4—C3—H3120.8O15—C16—O14123.8 (2)
C5—C4—C3118.47 (18)O15—C16—C17124.0 (2)
C5—C4—C7118.72 (18)O14—C16—C17112.2 (2)
C3—C4—C7122.66 (17)C18—C17—C16122.2 (2)
C6—C5—C4119.2 (2)C18—C17—H17118.9
C6—C5—H5120.4C16—C17—H17118.9
C4—C5—H5120.4C17—C18—C19126.7 (2)
N1—C6—C5123.0 (2)C17—C18—H18116.6
N1—C6—H6118.5C19—C18—H18116.6
C5—C6—H6118.5C24—C19—C20118.5 (2)
O8—C7—N9124.41 (19)C24—C19—C18118.3 (2)
O8—C7—C4120.77 (18)C20—C19—C18123.2 (2)
N9—C7—C4114.77 (17)C21—C20—C19120.5 (2)
C7—N9—N10118.72 (17)C21—C20—H20119.7
C7—N9—H9116.6 (14)C19—C20—H20119.7
N10—N9—H9121.2 (14)C22—C21—C20120.0 (2)
C11—N10—N9115.61 (17)C22—C21—H21120.0
N10—C11—C12126.34 (19)C20—C21—H21120.0
N10—C11—C13116.1 (2)C23—C22—C21120.1 (2)
C12—C11—C13117.5 (2)C23—C22—H22120.0
C11—C12—H12A109.5C21—C22—H22120.0
C11—C12—H12B109.5C22—C23—C24119.9 (2)
H12A—C12—H12B109.5C22—C23—H23120.0
C11—C12—H12C109.5C24—C23—H23120.0
H12A—C12—H12C109.5C19—C24—C23121.0 (2)
H12B—C12—H12C109.5C19—C24—H24119.5
C11—C13—H13A109.5C23—C24—H24119.5
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N9—H9···O8i0.89 (2)2.12 (2)2.912 (2)147 (2)
O14—H14···N10.82 (1)1.87 (1)2.675 (2)168 (1)
Symmetry code: (i) x+3/2, y+1/2, z1.

Experimental details

(1)(2)
Crystal data
Chemical formulaC6H7N3O·C9H8O2C9H11N3O·C9H8O2
Mr285.30325.36
Crystal system, space groupTriclinic, P1Orthorhombic, Pca21
Temperature (K)173173
a, b, c (Å)6.4872 (2), 8.1478 (4), 13.56030 (11)8.8818 (1), 21.0445 (4), 9.0764 (1)
α, β, γ (°)95.1691 (11), 101.1111 (11), 98.6376 (17)90, 90, 90
V3)690.08 (4)1696.50 (4)
Z24
Radiation typeMo KαMo Kα
µ (mm1)0.100.09
Crystal size (mm)0.5 × 0.4 × 0.40.4 × 0.3 × 0.2
Data collection
DiffractometerBruker Nonius KappaCCD area-detector
diffractometer
Nonius KappaCCD area-detector
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
4637, 3145, 2430 3694, 2058, 1791
Rint0.0230.023
(sin θ/λ)max1)0.6490.649
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.045, 0.123, 1.05 0.037, 0.088, 1.05
No. of reflections31452058
No. of parameters204225
No. of restraints01
H-atom treatmentH atoms treated by a mixture of independent and constrained refinementH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.35, 0.200.25, 0.14

Computer programs: COLLECT (Nonius, 1998), DENZO and SCALEPACK (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 2012), OLEX2 (Dolomanov et al., 2009).

Hydrogen-bond geometry (Å, º) for (1) top
D—H···AD—HH···AD···AD—H···A
N9—H9···O12i0.866 (18)2.151 (19)3.0071 (15)169.9 (15)
O11—H11···N10.821.842.6554 (15)178.6
N10—H10A···O12ii0.92 (2)2.44 (2)3.3309 (17)164.5 (16)
N10—H10B···O12iii0.94 (2)2.449 (19)3.2753 (18)147.3 (15)
N10—H10B···O8iv0.94 (2)2.563 (18)3.0865 (15)115.7 (13)
C6—H6···O120.932.673.2535 (16)121.1
Symmetry codes: (i) x+2, y+1, z+2; (ii) x+1, y+1, z+2; (iii) x1, y1, z; (iv) x, y, z+2.
Torsion and dihedral angles (°) in cinnamic acid–isoniazid polymorphs top
The dihedral angle is between the planes of the carboxylic acid group and the pyridine ring.
PolymorphIIIIII
Dihedral angle*17.658.9128.76
C5—C4—C7—N90.3 (2)12.9 (6)3.3 (2)
C4—C7–N9—N10-179.9 (1)174.2 (3)177.7 (1)
C21(17)—C16—C15—C14-6.6 (2)7.0 (7)13.2 (2)
Hydrogen-bond geometry (Å, º) for (2) top
D—H···AD—HH···AD···AD—H···A
N9—H9···O8i0.89 (2)2.12 (2)2.912 (2)147 (2)
O14—H14···N10.820 (2)1.867 (2)2.675 (2)167.75 (14)
Symmetry code: (i) x+3/2, y+1/2, z1.
 

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