Cinnamic acid hydrogen bonds to isoniazid and N′-(propan-2-yl­idene)isonicotinohydrazide, an in situ reaction product of isoniazid and acetone

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.

S1. Introduction

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···N_py 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.

S2. Experimental

S2.1. Synthesis and crystallization

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, λ_max, cm^-1): 1636 (C═O), 1671 (C═O), 2990–3040 (COOH group bands), 3236 (N—H).

S2.2. Refinement

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 U_iso(H) = 1.5U_eq(C) for methyl H atoms and 1.2U_eq(C) otherwise. The 001 reflection was omitted from the refinement of (1). The floating-origin restraint was generated for (2).

S3. Results and discussion

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 π–π 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 π–π 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 π–π 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

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

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

	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.
	Fig. 2. The arrangement of hydrogen-bonded (dashed lines) four-molecule synthons in polymorphs I, II and III.
	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.
	Fig. 4. Hydrogen-bonding (dashed lines) motifs in the crystal structure of (II). Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 5. A packing diagram for (2). Displacement ellipsoids are drawn at the 50% probability level.

(1) Cinnamic acid–pyridine-4-carbohydrazide (1/1)

Crystal data

C6H7N3O·C9H8O2	Z = 2
Mr = 285.30	F(000) = 300
Triclinic, P1	Dx = 1.373 Mg m^−3
Hall symbol: -P 1	Melting point: 399 K
a = 6.4872 (2) Å	Mo Kα radiation, λ = 0.71073 Å
b = 8.1478 (4) Å	Cell parameters from 8000 reflections
c = 13.56030 (11) Å	θ = 1.0–27.5°
α = 95.1691 (11)°	µ = 0.10 mm^−1
β = 101.1111 (11)°	T = 173 K
γ = 98.6376 (17)°	Plate, colourless
V = 690.08 (4) Å^3	0.5 × 0.4 × 0.4 mm

Data collection

Bruker Nonius KappaCCD area-detector diffractometer	2430 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.023
Horizonally mounted graphite crystal monochromator	θmax = 27.5°, θmin = 3.1°
Detector resolution: 9 pixels mm^-1	h = −8→8
ϕ and ω scans	k = −10→9
4637 measured reflections	l = −17→17
3145 independent reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.045	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.123	H atoms treated by a mixture of independent and constrained refinement
S = 1.05	w = 1/[σ^2(Fo^2) + (0.0537P)^2 + 0.1682P] where P = (Fo^2 + 2Fc^2)/3
3145 reflections	(Δ/σ)max < 0.001
204 parameters	Δρmax = 0.35 e Å^−3
0 restraints	Δρmin = −0.20 e Å^−3

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
N1	0.69034 (18)	0.56375 (15)	0.79286 (9)	0.0270 (3)
C2	0.4774 (2)	0.53573 (19)	0.76533 (11)	0.0284 (3)
H2	0.4135	0.5896	0.7130	0.034*
C3	0.3481 (2)	0.43007 (18)	0.81138 (10)	0.0267 (3)
H3	0.2006	0.4147	0.7904	0.032*
C4	0.4394 (2)	0.34763 (16)	0.88859 (10)	0.0220 (3)
C5	0.6608 (2)	0.37391 (17)	0.91641 (11)	0.0260 (3)
H5	0.7288	0.3193	0.9672	0.031*
C6	0.7780 (2)	0.48296 (18)	0.86703 (11)	0.0277 (3)
H6	0.9258	0.5009	0.8866	0.033*
C7	0.2918 (2)	0.23682 (16)	0.93853 (10)	0.0223 (3)
O8	0.09778 (15)	0.21558 (13)	0.90755 (8)	0.0326 (3)
N9	0.38371 (18)	0.16741 (15)	1.01730 (9)	0.0243 (3)
H9	0.519 (3)	0.185 (2)	1.0433 (13)	0.033 (4)*
N10	0.26216 (19)	0.06591 (17)	1.07273 (10)	0.0291 (3)
H10A	0.163 (3)	0.125 (3)	1.0915 (14)	0.049 (5)*
H10B	0.186 (3)	−0.026 (2)	1.0273 (14)	0.041 (5)*
O11	0.95518 (17)	0.77111 (15)	0.71545 (8)	0.0388 (3)
H11	0.8749	0.7073	0.7403	0.080 (8)*
O12	1.16107 (15)	0.79207 (13)	0.86998 (8)	0.0309 (3)
C13	1.1330 (2)	0.82833 (18)	0.78323 (11)	0.0272 (3)
C14	1.2994 (2)	0.93732 (18)	0.74799 (11)	0.0292 (3)
H14	1.4340	0.9658	0.7901	0.035*
C15	1.2681 (2)	0.99692 (18)	0.65973 (11)	0.0288 (3)
H15	1.1330	0.9667	0.6183	0.035*
C16	1.4284 (2)	1.10700 (18)	0.62148 (11)	0.0290 (3)
C17	1.3616 (3)	1.1835 (2)	0.53647 (12)	0.0357 (4)
H17	1.2176	1.1653	0.5058	0.043*
C18	1.5056 (3)	1.2866 (2)	0.49655 (13)	0.0443 (4)
H18	1.4579	1.3376	0.4398	0.053*
C19	1.7189 (3)	1.3136 (2)	0.54044 (14)	0.0481 (5)
H19	1.8156	1.3831	0.5136	0.058*
C20	1.7898 (3)	1.2373 (2)	0.62477 (13)	0.0428 (4)
H20	1.9344	1.2547	0.6541	0.051*
C21	1.6455 (3)	1.1347 (2)	0.66566 (12)	0.0348 (4)
H21	1.6937	1.0843	0.7226	0.042*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0284 (6)	0.0258 (6)	0.0276 (6)	0.0016 (5)	0.0095 (5)	0.0043 (5)
C2	0.0284 (7)	0.0317 (8)	0.0255 (7)	0.0035 (6)	0.0056 (5)	0.0084 (6)
C3	0.0219 (6)	0.0315 (8)	0.0254 (7)	0.0022 (5)	0.0034 (5)	0.0034 (6)
C4	0.0219 (6)	0.0190 (7)	0.0249 (7)	0.0011 (5)	0.0075 (5)	0.0004 (5)
C5	0.0230 (7)	0.0244 (7)	0.0317 (8)	0.0042 (5)	0.0060 (5)	0.0084 (6)
C6	0.0212 (7)	0.0277 (7)	0.0355 (8)	0.0021 (5)	0.0093 (5)	0.0067 (6)
C7	0.0197 (6)	0.0196 (6)	0.0275 (7)	0.0018 (5)	0.0062 (5)	0.0024 (5)
O8	0.0188 (5)	0.0377 (6)	0.0415 (6)	0.0008 (4)	0.0046 (4)	0.0153 (5)
N9	0.0176 (6)	0.0271 (6)	0.0279 (6)	−0.0008 (5)	0.0055 (5)	0.0085 (5)
N10	0.0219 (6)	0.0319 (7)	0.0341 (7)	−0.0016 (5)	0.0081 (5)	0.0124 (6)
O11	0.0305 (6)	0.0502 (7)	0.0313 (6)	−0.0095 (5)	0.0038 (4)	0.0157 (5)
O12	0.0280 (5)	0.0347 (6)	0.0297 (6)	0.0012 (4)	0.0056 (4)	0.0100 (4)
C13	0.0245 (7)	0.0260 (7)	0.0321 (8)	0.0032 (5)	0.0091 (6)	0.0045 (6)
C14	0.0260 (7)	0.0294 (8)	0.0314 (8)	−0.0004 (6)	0.0071 (6)	0.0050 (6)
C15	0.0270 (7)	0.0302 (8)	0.0287 (8)	0.0031 (6)	0.0056 (6)	0.0043 (6)
C16	0.0357 (8)	0.0245 (7)	0.0279 (8)	0.0015 (6)	0.0126 (6)	0.0021 (6)
C17	0.0397 (8)	0.0354 (9)	0.0309 (8)	−0.0003 (7)	0.0097 (6)	0.0048 (7)
C18	0.0613 (12)	0.0387 (10)	0.0337 (9)	−0.0017 (8)	0.0167 (8)	0.0104 (7)
C19	0.0594 (12)	0.0367 (10)	0.0479 (11)	−0.0139 (8)	0.0290 (9)	0.0022 (8)
C20	0.0355 (9)	0.0413 (10)	0.0463 (10)	−0.0077 (7)	0.0123 (7)	−0.0067 (8)
C21	0.0370 (8)	0.0338 (8)	0.0326 (8)	0.0020 (6)	0.0093 (6)	0.0022 (6)

Geometric parameters (Å, º)

N1—C6	1.3340 (19)	O11—H11	0.8200
N1—C2	1.3382 (18)	O12—C13	1.2250 (17)
C2—C3	1.3843 (19)	C13—C14	1.4729 (19)
C2—H2	0.9300	C14—C15	1.323 (2)
C3—C4	1.380 (2)	C14—H14	0.9300
C3—H3	0.9300	C15—C16	1.472 (2)
C4—C5	1.3910 (18)	C15—H15	0.9300
C4—C7	1.5137 (18)	C16—C17	1.387 (2)
C5—C6	1.3842 (19)	C16—C21	1.396 (2)
C5—H5	0.9300	C17—C18	1.383 (2)
C6—H6	0.9300	C17—H17	0.9300
C7—O8	1.2279 (16)	C18—C19	1.373 (3)
C7—N9	1.3346 (18)	C18—H18	0.9300
N9—N10	1.4196 (16)	C19—C20	1.385 (3)
N9—H9	0.866 (18)	C19—H19	0.9300
N10—H10A	0.92 (2)	C20—C21	1.390 (2)
N10—H10B	0.94 (2)	C20—H20	0.9300
O11—C13	1.3213 (18)	C21—H21	0.9300
C6—N1—C2	117.35 (12)	O12—C13—C14	121.37 (13)
N1—C2—C3	122.83 (13)	O11—C13—C14	115.98 (13)
N1—C2—H2	118.6	C15—C14—C13	123.62 (14)
C3—C2—H2	118.6	C15—C14—H14	118.2
C4—C3—C2	119.62 (13)	C13—C14—H14	118.2
C4—C3—H3	120.2	C14—C15—C16	125.66 (14)
C2—C3—H3	120.2	C14—C15—H15	117.2
C3—C4—C5	117.86 (12)	C16—C15—H15	117.2
C3—C4—C7	117.79 (12)	C17—C16—C21	118.56 (14)
C5—C4—C7	124.34 (13)	C17—C16—C15	118.59 (14)
C6—C5—C4	118.75 (13)	C21—C16—C15	122.84 (14)
C6—C5—H5	120.6	C18—C17—C16	121.05 (16)
C4—C5—H5	120.6	C18—C17—H17	119.5
N1—C6—C5	123.57 (13)	C16—C17—H17	119.5
N1—C6—H6	118.2	C19—C18—C17	120.15 (17)
C5—C6—H6	118.2	C19—C18—H18	119.9
O8—C7—N9	122.90 (12)	C17—C18—H18	119.9
O8—C7—C4	120.54 (12)	C18—C19—C20	119.86 (15)
N9—C7—C4	116.55 (11)	C18—C19—H19	120.1
C7—N9—N10	121.90 (11)	C20—C19—H19	120.1
C7—N9—H9	125.2 (11)	C19—C20—C21	120.21 (16)
N10—N9—H9	112.7 (11)	C19—C20—H20	119.9
N9—N10—H10A	107.6 (12)	C21—C20—H20	119.9
N9—N10—H10B	106.6 (11)	C20—C21—C16	120.16 (16)
H10A—N10—H10B	106.5 (17)	C20—C21—H21	119.9
C13—O11—H11	109.5	C16—C21—H21	119.9
O12—C13—O11	122.64 (12)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N9—H9···O12^i	0.866 (18)	2.151 (19)	3.0071 (15)	169.9 (15)
O11—H11···N1	0.82	1.84	2.6554 (15)	179
N10—H10A···O12^ii	0.92 (2)	2.44 (2)	3.3309 (17)	164.5 (16)
N10—H10B···O12^iii	0.94 (2)	2.449 (19)	3.2753 (18)	147.3 (15)
N10—H10B···O8^iv	0.94 (2)	2.563 (18)	3.0865 (15)	115.7 (13)
C6—H6···O12	0.93	2.67	3.2535 (16)	121

Symmetry codes: (i) −x+2, −y+1, −z+2; (ii) −x+1, −y+1, −z+2; (iii) x−1, y−1, z; (iv) −x, −y, −z+2.

(2) Cinnamic acid–N'-(propan-2-ylidene)pyridine-4-carbohydrazide (1/1)

Crystal data

C9H11N3O·C9H8O2	Dx = 1.274 Mg m^−3
Mr = 325.36	Melting point: 377 K
Orthorhombic, Pca21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P -2a -2ab	Cell parameters from 18975 reflections
a = 8.8818 (1) Å	θ = 1.0–27.5°
b = 21.0445 (4) Å	µ = 0.09 mm^−1
c = 9.0764 (1) Å	T = 173 K
V = 1696.50 (4) Å^3	Prism, colourless
Z = 4	0.4 × 0.3 × 0.2 mm
F(000) = 688.0

Data collection

Nonius KappaCCD area-detector diffractometer	1791 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.023
Horizonally mounted graphite crystal monochromator	θmax = 27.5°, θmin = 2.5°
Detector resolution: 9 pixels mm^-1	h = −11→11
ϕ and ω scans	k = −27→27
3694 measured reflections	l = −11→11
2058 independent reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.037	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.088	H atoms treated by a mixture of independent and constrained refinement
S = 1.05	w = 1/[σ^2(Fo^2) + (0.0412P)^2 + 0.2535P] where P = (Fo^2 + 2Fc^2)/3
2058 reflections	(Δ/σ)max < 0.001
225 parameters	Δρmax = 0.25 e Å^−3
1 restraint	Δρmin = −0.14 e Å^−3

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
N1	0.9050 (2)	0.16280 (8)	0.3969 (2)	0.0365 (4)
C2	0.9888 (3)	0.11412 (10)	0.3498 (2)	0.0327 (5)
H2	1.0693	0.1226	0.2873	0.039*
C3	0.9615 (2)	0.05154 (9)	0.3896 (2)	0.0289 (4)
H3	1.0220	0.0189	0.3542	0.035*
C4	0.8415 (2)	0.03878 (9)	0.4836 (2)	0.0267 (4)
C5	0.7550 (3)	0.08914 (9)	0.5332 (2)	0.0340 (5)
H5	0.6745	0.0821	0.5967	0.041*
C6	0.7896 (3)	0.14979 (10)	0.4874 (3)	0.0394 (5)
H6	0.7303	0.1833	0.5206	0.047*
C7	0.8091 (2)	−0.02658 (9)	0.5420 (2)	0.0274 (4)
O8	0.7528 (2)	−0.03385 (6)	0.66400 (17)	0.0380 (4)
N9	0.8529 (2)	−0.07475 (8)	0.45257 (18)	0.0287 (4)
H9	0.859 (2)	−0.0660 (10)	0.357 (3)	0.028 (6)*
N10	0.8372 (2)	−0.13715 (8)	0.50252 (19)	0.0321 (4)
C11	0.8835 (2)	−0.18048 (10)	0.4137 (2)	0.0325 (5)
C12	0.9508 (3)	−0.17017 (11)	0.2650 (3)	0.0412 (5)
H12A	0.8725	−0.1607	0.1955	0.062*
H12B	1.0031	−0.2079	0.2346	0.062*
H12C	1.0203	−0.1353	0.2691	0.062*
C13	0.8648 (3)	−0.24761 (11)	0.4648 (3)	0.0487 (6)
H13A	0.8263	−0.2478	0.5636	0.073*
H13B	0.9606	−0.2688	0.4626	0.073*
H13C	0.7957	−0.2693	0.4010	0.073*
O14	0.9817 (2)	0.28333 (8)	0.3413 (2)	0.0521 (5)
H14	0.9562	0.2459	0.3452	0.087 (12)*
O15	0.7904 (2)	0.28889 (8)	0.1846 (3)	0.0713 (6)
C16	0.8914 (3)	0.31398 (11)	0.2545 (3)	0.0453 (6)
C17	0.9244 (3)	0.38341 (11)	0.2513 (3)	0.0466 (6)
H17	0.9992	0.3994	0.3128	0.056*
C18	0.8519 (3)	0.42263 (11)	0.1651 (3)	0.0424 (5)
H18	0.7819	0.4048	0.1011	0.051*
C19	0.8696 (3)	0.49226 (10)	0.1588 (3)	0.0378 (5)
C20	0.9695 (3)	0.52573 (11)	0.2481 (3)	0.0419 (5)
H20	1.0298	0.5039	0.3149	0.050*
C21	0.9798 (3)	0.59133 (11)	0.2383 (3)	0.0473 (6)
H21	1.0465	0.6134	0.2985	0.057*
C22	0.8905 (3)	0.62406 (11)	0.1388 (3)	0.0490 (6)
H22	0.8983	0.6680	0.1313	0.059*
C23	0.7906 (3)	0.59175 (11)	0.0514 (3)	0.0501 (6)
H23	0.7299	0.6138	−0.0146	0.060*
C24	0.7801 (3)	0.52611 (11)	0.0615 (3)	0.0448 (6)
H24	0.7118	0.5045	0.0021	0.054*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0398 (10)	0.0313 (9)	0.0383 (10)	−0.0013 (8)	−0.0076 (9)	0.0003 (8)
C2	0.0352 (11)	0.0345 (11)	0.0285 (10)	−0.0069 (9)	−0.0026 (9)	0.0008 (9)
C3	0.0319 (10)	0.0285 (10)	0.0263 (9)	0.0004 (8)	−0.0019 (9)	−0.0017 (8)
C4	0.0285 (9)	0.0312 (10)	0.0205 (9)	0.0003 (8)	−0.0042 (8)	0.0008 (8)
C5	0.0312 (9)	0.0374 (11)	0.0333 (11)	0.0048 (10)	0.0009 (9)	−0.0009 (9)
C6	0.0404 (12)	0.0330 (11)	0.0447 (13)	0.0053 (9)	−0.0042 (11)	−0.0028 (10)
C7	0.0286 (9)	0.0311 (10)	0.0225 (10)	0.0006 (8)	−0.0048 (8)	0.0011 (8)
O8	0.0510 (8)	0.0390 (8)	0.0240 (7)	0.0019 (8)	0.0067 (7)	0.0030 (7)
N9	0.0360 (9)	0.0281 (9)	0.0222 (8)	−0.0010 (7)	0.0009 (7)	0.0047 (7)
N10	0.0407 (10)	0.0280 (9)	0.0276 (8)	−0.0016 (7)	−0.0029 (8)	0.0051 (7)
C11	0.0350 (11)	0.0313 (11)	0.0312 (10)	−0.0005 (9)	−0.0047 (10)	0.0041 (9)
C12	0.0535 (14)	0.0357 (12)	0.0345 (11)	0.0073 (10)	0.0030 (11)	−0.0002 (10)
C13	0.0694 (17)	0.0306 (12)	0.0460 (14)	−0.0012 (11)	−0.0023 (12)	0.0034 (10)
O14	0.0616 (11)	0.0300 (8)	0.0648 (12)	−0.0080 (8)	−0.0123 (10)	0.0065 (9)
O15	0.0756 (15)	0.0452 (10)	0.0932 (15)	0.0001 (10)	−0.0329 (13)	0.0041 (11)
C16	0.0482 (14)	0.0336 (12)	0.0541 (14)	−0.0007 (11)	0.0020 (12)	−0.0035 (12)
C17	0.0463 (13)	0.0419 (13)	0.0517 (14)	−0.0021 (11)	−0.0065 (13)	0.0034 (12)
C18	0.0407 (12)	0.0425 (13)	0.0439 (13)	0.0017 (10)	0.0044 (11)	0.0004 (11)
C19	0.0395 (11)	0.0337 (11)	0.0404 (11)	0.0038 (10)	0.0128 (10)	0.0023 (10)
C20	0.0387 (12)	0.0390 (12)	0.0482 (13)	0.0062 (10)	0.0038 (11)	0.0087 (11)
C21	0.0458 (13)	0.0403 (14)	0.0559 (16)	−0.0017 (11)	0.0061 (12)	−0.0012 (11)
C22	0.0617 (16)	0.0309 (12)	0.0544 (16)	0.0051 (11)	0.0139 (13)	0.0072 (11)
C23	0.0605 (16)	0.0434 (14)	0.0464 (14)	0.0103 (12)	0.0043 (14)	0.0123 (12)
C24	0.0483 (14)	0.0471 (13)	0.0391 (13)	0.0012 (11)	0.0032 (12)	0.0046 (11)

Geometric parameters (Å, º)

N1—C2	1.337 (3)	C13—H13B	0.9600
N1—C6	1.341 (3)	C13—H13C	0.9600
C2—C3	1.387 (3)	O14—C16	1.296 (3)
C2—H2	0.9300	O14—H14	0.8200
C3—C4	1.392 (3)	O15—C16	1.219 (3)
C3—H3	0.9300	C16—C17	1.491 (3)
C4—C5	1.384 (3)	C17—C18	1.307 (3)
C4—C7	1.502 (3)	C17—H17	0.9300
C5—C6	1.377 (3)	C18—C19	1.475 (3)
C5—H5	0.9300	C18—H18	0.9300
C6—H6	0.9300	C19—C24	1.385 (3)
C7—O8	1.225 (3)	C19—C20	1.393 (3)
C7—N9	1.356 (3)	C20—C21	1.387 (3)
N9—N10	1.396 (2)	C20—H20	0.9300
N9—H9	0.89 (2)	C21—C22	1.385 (4)
N10—C11	1.284 (3)	C21—H21	0.9300
C11—C12	1.493 (3)	C22—C23	1.371 (4)
C11—C13	1.496 (3)	C22—H22	0.9300
C12—H12A	0.9600	C23—C24	1.387 (3)
C12—H12B	0.9600	C23—H23	0.9300
C12—H12C	0.9600	C24—H24	0.9300
C13—H13A	0.9600
C2—N1—C6	117.71 (18)	C11—C13—H13B	109.5
N1—C2—C3	123.2 (2)	H13A—C13—H13B	109.5
N1—C2—H2	118.4	C11—C13—H13C	109.5
C3—C2—H2	118.4	H13A—C13—H13C	109.5
C2—C3—C4	118.49 (19)	H13B—C13—H13C	109.5
C2—C3—H3	120.8	C16—O14—H14	109.5
C4—C3—H3	120.8	O15—C16—O14	123.8 (2)
C5—C4—C3	118.47 (18)	O15—C16—C17	124.0 (2)
C5—C4—C7	118.72 (18)	O14—C16—C17	112.2 (2)
C3—C4—C7	122.66 (17)	C18—C17—C16	122.2 (2)
C6—C5—C4	119.2 (2)	C18—C17—H17	118.9
C6—C5—H5	120.4	C16—C17—H17	118.9
C4—C5—H5	120.4	C17—C18—C19	126.7 (2)
N1—C6—C5	123.0 (2)	C17—C18—H18	116.6
N1—C6—H6	118.5	C19—C18—H18	116.6
C5—C6—H6	118.5	C24—C19—C20	118.5 (2)
O8—C7—N9	124.41 (19)	C24—C19—C18	118.3 (2)
O8—C7—C4	120.77 (18)	C20—C19—C18	123.2 (2)
N9—C7—C4	114.77 (17)	C21—C20—C19	120.5 (2)
C7—N9—N10	118.72 (17)	C21—C20—H20	119.7
C7—N9—H9	116.6 (14)	C19—C20—H20	119.7
N10—N9—H9	121.2 (14)	C22—C21—C20	120.0 (2)
C11—N10—N9	115.61 (17)	C22—C21—H21	120.0
N10—C11—C12	126.34 (19)	C20—C21—H21	120.0
N10—C11—C13	116.1 (2)	C23—C22—C21	120.1 (2)
C12—C11—C13	117.5 (2)	C23—C22—H22	120.0
C11—C12—H12A	109.5	C21—C22—H22	120.0
C11—C12—H12B	109.5	C22—C23—C24	119.9 (2)
H12A—C12—H12B	109.5	C22—C23—H23	120.0
C11—C12—H12C	109.5	C24—C23—H23	120.0
H12A—C12—H12C	109.5	C19—C24—C23	121.0 (2)
H12B—C12—H12C	109.5	C19—C24—H24	119.5
C11—C13—H13A	109.5	C23—C24—H24	119.5

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N9—H9···O8^i	0.89 (2)	2.12 (2)	2.912 (2)	147 (2)
O14—H14···N1	0.82 (1)	1.87 (1)	2.675 (2)	168 (1)

Symmetry code: (i) −x+3/2, y+1/2, z−1.