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A further example of using a covalent-bond-forming reaction to alter supra­molecular assembly by modification of hydrogen-bonding possibilities is presented. This concept was introduced by Lemmerer, Bernstein & Kahlenberg [CrystEngComm (2011), 13, 55-59]. The title structure, C9H11N3O·C7H6O4, which consists of a reacted niazid mol­ecule, viz. N'-(propan-2-yl­idene)nicotinohydrazide, and 2,4-di­hy­droxy­benzoic acid, was solved from powder diffraction data using simulated annealing. The results further demonstrate the relevance and utility of powder diffraction as an analytical tool in the study of cocrystals and their hydrogen-bond inter­actions.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270112029022/fa3277sup1.cif
Contains datablocks global, I

rtv

Rietveld powder data file (CIF format) https://doi.org/10.1107/S0108270112029022/fa3277Isup2.rtv
Contains datablock I

mol

MDL mol file https://doi.org/10.1107/S0108270112029022/fa3277Isup3.mol
Supplementary material

cml

Chemical Markup Language (CML) file https://doi.org/10.1107/S0108270112029022/fa3277Isup4.cml
Supplementary material

CCDC reference: 908130

Comment top

The two molecules, isonicotinic acid hydrazide (isoniazid) and nicotinic acid hydrazide (niazid), are ideal supramolecular reagents that readily cocrystallize with a number of carboxylic acid coformer molecules (Lemmerer et al., 2010). Interest in these two molecules, especially the former, which is widely used as an antituberculosis agent, comes about due to a recently introduced strategy called covalent assistance to supramolecular synthesis (Lemmerer et al., 2011a,b). This approach enables the crystal engineer to control the supramolecular assembly of either molecule by altering its hydrogen-bonding functionality through a covalent reaction with a ketone molecule that transforms the amine functional group to an alkylidene group in a Schiff base condensation reaction. Specifically, the use of propan-2-one (acetone) replaces the two H atoms with hydrogen-bonding inert methyl groups. Under this concept, the acetone molecule is termed a `modifier'. This `modifying' reaction occurs within the crystallization vessel using acetone as the crystallization solvent in a solution containing niazid and a molecule with carboxylic acid functionality, in this case 2,4-dihydroxybenzoic acid. Such a one-pot covalent and supramolecular reaction to form a cocrystal occasionally results in a powder sample rather than single crystals. In this case, crystals of the title cocrystal, (I), suitable for single-crystal analysis were not obtained, so the structure was determined by powder diffraction. The structure solution of (I) from X-ray (synchrotron) powder diffraction data and Rietveld refinement (Figs. 1 and 2) is reported here.

The asymmetric unit of (I) consists of one modified niazid molecule, N'-(propan-2-ylidene)nicotinohydrazide (p-niazid), and one molecule of 2,4-dihydroxybenzoic acid, both on general positions. In terms of forming a cocrystal, the essential features are the hydrogen-bond interactions between unlike [dissimilar?] but complementary functional groups on the two molecules. The carboxy–pyridine hydrogen bond (COO—H···N) is often observed in cocrystals involving pyridine and carboxylic acids (Aakeröy et al., 2002), and it appears in the majority of cocrystals of unreacted and reacted niazid and isoniazid. As the covalent reaction does not alter any of the latter two functional groups, we expect this hydrogen bond to be present in (I), as is indeed observed (Fig. 1). In addition, the hydroxy group in the para position also participates in a hydrogen bond to a lone pair on an N atom [O4—H4···N3i; symmetry code: (i) -x + 2, -y + 1, -z + 1], in this case on the now altered propanylidene functional group, providing a further link between the two molecules in the cocrystal. The combination of these two different O—H···N hydrogen bonds forms a four-molecule hydrogen-bonded ring, with graph-set notation R44(30) (Bernstein et al., 1995) (Fig. 3). The second hydroxy group, in the 2-position, forms an intramolecular S(6) hydrogen bond, in agreement with Etter's rules (Etter, 1990). The p-niazid molecules themselves are hydrogen-bonded to each other using the unreacted amide functional group, to form C(4) chains using N1—H1···O1ii [symmetry code: (ii) x, -y + 3/2, z + 1/2] hydrogen bonds along the crystallographic c axis (Fig. 4). These chains connect the rings to form a two-dimensional layer in the bc plane.

Cocrystal (I) presents a third example in which niazid has been reacted with acetone to form a cocrystal with a suitable carboxylic acid coformer. The previous two examples involved alkyldicarboxylic acids, namely adipic and sebacic acid, and presented one-dimensional ribbons (Lemmerer et al., 2011a). Nonetheless, the C(4) chain is observed in all three cocrystals, as well as the carboxy–pyridine hydrogen bond. The two-dimensional assembly of (I) results from the para hydroxy group hydrogen-bonding to the p-niazid molecule, in addition to the carboxy–pyridine hydrogen bond, whereas the first two cocrystals both have carboxy functional groups hydrogen-bonding to two crystallographically related p-niazid molecules.

The present results further demonstrate that structure solution from powder diffraction data is a relevant and useful analytical tool in the study of cocrystals and their hydrogen-bond interactions (Lapidus et al., 2010).

Related literature top

For related literature, see: Aakeröy et al. (2002); Bernstein et al. (1995); Coelho (2003); Efron & Tibshirani (1986); Etter (1990); Lapidus et al. (2010); Lemmerer et al. (2010, 2011a, 2011b).

Experimental top

The title cocrystal, (I), was synthesized according to previously reported methods, in which an acetone solution (10 ml) of niazid (0.150 g, 1.09 mmol) and 2,4-dihydroxybenzoic acid (0.169 g, 1.09 mmol) is heated for a few hours, followed by cooling and crystallization over a period of a few days by slow evaporation.

High-resolution synchrotron X-ray powder diffraction data were collected on the X16C beamline at the National Synchrotron Light Source at Brookhaven National Laboratory. X-rays of wavelength 0.6999 Å were selected using an Si(111) channel-cut monochromator. The diffracted beam was analysed with a Ge(111) crystal and detected by an NaI scintillation counter. The wavelength and diffractometer zero were calibrated using a sample of NIST Standard Reference Material 1976, a sintered plate of Al2O3. The sample was loaded into a nominal 1.5 mm glass capillary and spun during data collection to improve powder averaging.

Refinement top

Indexing of the powder pattern was performed using TOPAS-Academic (Coelho, 2003). This indexing revealed a monoclinic unit cell, and from systematic absences a tentative space group of P21/c was assigned. From the volume of the unit cell, the contents of the asymmetric unit were hypothesized to be one of each molecule. These molecules were then defined as z matrices and simulated annealing was performed in TOPAS-Academic. This structure solution was confirmed by a successful refinement, in which bond lengths and angles of similar chemical character (e.g. aromatic, O—C bonds, N—C bonds etc.) were refined to a single joint value. Aromatic rings were restricted to be regular planar hexagons. The C9—C8—N3—N1 and C7—C8—N3—N1 torsion angles were restricted to being planar, as the double bond between atoms N3 and C8 would not allow a rotation about that bond. This strategy of refining bond lengths has been shown to result in values comparable with a single-crystal measurement (Lapidus et al., 2010).

H atoms were placed by idealized geometry with reference to the other atoms. Hydrogen bonds were inferred from donor–acceptor distances.

Errors in atomic positions were estimated by the bootstrap method of error determination (Efron & Tibshirani, 1986), as implemented in TOPAS-Academic. This error estimation is performed by modifying a fraction of the data within its statistical uncertainty and observing the change in each refined atomic position. This process is repeated many times and an uncertainty in each atomic position is estimated from the overall motion of each atom over these cycles.

Computing details top

Data collection: SPEC (Reference needed); cell refinement: TOPAS-Academic (Coelho, 2003); data reduction: TOPAS-Academic (Coelho, 2007); program(s) used to solve structure: TOPAS-Academic (Coelho, 2007); program(s) used to refine structure: TOPAS-Academic (Coelho, 2007); molecular graphics: DIAMOND (Brandenburg, 1999); software used to prepare material for publication: publCIF (Westrip, 2010).

Figures top
[Figure 1] Fig. 1. A view of the components of cocrystal (I), showing the atom-labelling scheme. Dashed lines indicate hydrogen bonds.
[Figure 2] Fig. 2. High-resolution synchrotron powder diffraction data for (I) (dots) and the Rietveld fit to the data (solid line). The lower trace is the difference, i.e. measured minus calculated, plotted on the same vertical scale.
[Figure 3] Fig. 3. A view of the R44(30) rings in the structure of (I). Dashed lines indicate hydrogen bonds.
[Figure 4] Fig. 4. A view of the C(4) synthon formed by the N1—H1···O1 hydrogen bond. Dashed lines indicate hydrogen bonds.
2,4-dihydroxybenzoic acid–N'-(propan-2-ylidene)nicotinohydrazide (1/1) top
Crystal data top
C9H11N3O·C7H6O4V = 1717.16 (9) Å3
Mr = 331.33Z = 4
Monoclinic, P21/cDx = 1.282 Mg m3
Hall symbol: -P 2ybcSynchrotron radiation, λ = 0.6999 Å
a = 8.5813 (3) ŵ = 0.09 mm1
b = 22.7241 (7) ÅT = 295 K
c = 8.8506 (3) Åwhite
β = 95.760 (3)°cylinder, 8 × 1.5 mm
Data collection top
Huber [Model?]
diffractometer
Data collection mode: transmission
Radiation source: synchrotronScan method: step
Si(111) channel cut monochromator2θmin = 3.0°, 2θmax = 35.0°, 2θstep = 0.005°
Specimen mounting: capillary
Refinement top
Rp = 0.03867 parameters
Rwp = 0.045H-atom parameters constrained
Rexp = 0.031Weighting scheme based on measured s.u.'s 1/σ2
RBragg = 0.026(Δ/σ)max = 0.001
χ2 = 2.176Background function: two Pearson–Voight peaks and Chebyshev polynomial with eight coefficients
6401 data pointsPreferred orientation correction: none
Profile function: Simple axial model function with Rp = 9999, Rs = 330 in TOPAS-Academic
Crystal data top
C9H11N3O·C7H6O4V = 1717.16 (9) Å3
Mr = 331.33Z = 4
Monoclinic, P21/cSynchrotron radiation, λ = 0.6999 Å
a = 8.5813 (3) ŵ = 0.09 mm1
b = 22.7241 (7) ÅT = 295 K
c = 8.8506 (3) Åcylinder, 8 × 1.5 mm
β = 95.760 (3)°
Data collection top
Huber [Model?]
diffractometer
Scan method: step
Specimen mounting: capillary2θmin = 3.0°, 2θmax = 35.0°, 2θstep = 0.005°
Data collection mode: transmission
Refinement top
Rp = 0.038χ2 = 2.176
Rwp = 0.0456401 data points
Rexp = 0.03167 parameters
RBragg = 0.026H-atom parameters constrained
Special details top

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.7415 (5)0.70461 (17)0.2383 (7)0.0536 (7)*
N10.7505 (5)0.78157 (12)0.4156 (5)0.0536 (7)*
N20.5864 (5)0.59285 (12)0.5666 (3)0.0536 (7)*
N30.8521 (4)0.8122 (3)0.3279 (7)0.0536 (7)*
C10.63152 (5)0.68879 (7)0.4629 (18)0.0536 (7)*
C20.6644 (5)0.62883 (15)0.4714 (3)0.0536 (7)*
C30.4755 (4)0.61686 (16)0.6534 (3)0.0536 (7)*
C40.4426 (4)0.67682 (11)0.6449 (4)0.0536 (7)*
C50.5206 (3)0.71278 (7)0.5498 (5)0.0536 (7)*
C60.7095 (4)0.72476 (10)0.3678 (3)0.0536 (7)*
C70.9891 (6)0.90319 (19)0.2737 (6)0.0536 (7)*
C80.8839 (2)0.8674 (2)0.3612 (4)0.0536 (7)*
C90.8169 (7)0.898 (2)0.4886 (6)0.0536 (7)*
O20.6892 (5)0.4881 (3)0.5974 (5)0.0645 (5)*
O30.5693 (5)0.4852 (3)0.8131 (5)0.0645 (5)*
O40.9391 (4)0.24385 (11)0.8496 (4)0.0645 (5)*
O50.6268 (5)0.39759 (19)0.997 (2)0.0645 (5)*
C100.7317 (2)0.40453 (12)0.7582 (2)0.0645 (5)*
C110.7114 (3)0.37562 (13)0.8935 (3)0.0645 (5)*
C120.7817 (3)0.32116 (13)0.9245 (3)0.0645 (5)*
C130.8723 (3)0.29561 (13)0.8202 (3)0.0645 (5)*
C140.8926 (3)0.32452 (10)0.6849 (3)0.0645 (5)*
C150.8223 (2)0.37898 (8)0.6539 (3)0.0645 (5)*
C160.6565 (4)0.4628 (2)0.725 (3)0.0645 (5)*
H10.71250.796690.49840.0536 (7)*
H2A0.73610.613320.41530.0536 (7)*
H30.42510.593610.71490.0536 (7)*
H4A0.3710.692340.7010.0536 (7)*
H5A0.49930.751550.54440.0536 (7)*
H7A0.9410.93710.2450.0536 (7)*
H7B1.0780.91080.33310.0536 (7)*
H7C1.0110.88280.1910.0536 (7)*
H9A0.8090.87220.5650.0536 (7)*
H9B0.880.92790.5210.0536 (7)*
H9C0.7210.9120.45550.0536 (7)*
H20.63950.5230.58580.0645 (5)*
H40.99350.232990.77240.0645 (5)*
H50.58680.432680.9660.0645 (5)*
H120.76860.302461.01190.0645 (5)*
H140.95110.3080.61740.0645 (5)*
H150.83540.397670.56640.0645 (5)*
Geometric parameters (Å, º) top
O1—C61.289 (6)C2—H2A0.9000
O2—C161.32 (2)C3—H30.9000
O3—C161.243 (17)C4—H4A0.9000
O4—C131.323 (4)C5—H5A0.9000
O5—C111.323 (13)C7—H7B0.9000
O2—H20.9000C7—H7A0.9000
O4—H40.9000C7—H7C0.9000
O5—H50.9000C9—H9C0.9000
N1—N31.408 (7)C9—H9A0.9000
N1—C61.393 (4)C9—H9B0.9000
N2—C21.393 (5)C10—C161.489 (7)
N2—C31.393 (5)C10—C111.392 (3)
N3—C81.311 (8)C10—C151.392 (3)
N1—H10.9000C11—C121.392 (4)
C1—C61.392 (10)C12—C131.392 (4)
C1—C21.392 (4)C13—C141.392 (4)
C1—C51.393 (9)C14—C151.392 (3)
C3—C41.392 (4)C12—H120.9000
C4—C51.392 (4)C14—H140.9000
C7—C81.489 (6)C15—H150.9000
C8—C91.49 (2)
C16—O2—H2110.00C8—C7—H7C109.00
C13—O4—H4110.00H7A—C7—H7B110.00
C11—O5—H5110.00C8—C7—H7A109.00
N3—N1—C6116.3 (4)H7B—C7—H7C110.00
C2—N2—C3120.0 (3)C8—C9—H9C109.00
N1—N3—C8118.4 (5)H9A—C9—H9C110.00
C6—N1—H1120.00H9B—C9—H9C110.00
N3—N1—H1124.00H9A—C9—H9B110.00
C5—C1—C6120.0 (2)C8—C9—H9A109.00
C2—C1—C6120.0 (7)C8—C9—H9B109.00
C2—C1—C5119.9 (7)C15—C10—C16120.0 (9)
N2—C2—C1120.0 (5)C11—C10—C15120.0 (2)
N2—C3—C4120.0 (3)C11—C10—C16120.0 (9)
C3—C4—C5120.0 (3)O5—C11—C12117.2 (5)
C1—C5—C4120.1 (3)O5—C11—C10122.9 (5)
N1—C6—C1118.9 (5)C10—C11—C12120.0 (2)
O1—C6—C1119.2 (5)C11—C12—C13120.0 (3)
O1—C6—N1122.0 (3)O4—C13—C12120.0 (3)
N3—C8—C7122.0 (4)O4—C13—C14120.0 (3)
C7—C8—C9116.1 (15)C12—C13—C14120.0 (3)
N3—C8—C9122.0 (15)C13—C14—C15120.0 (2)
N2—C2—H2A120.00C10—C15—C14120.0 (2)
C1—C2—H2A120.00O2—C16—O3123.4 (8)
N2—C3—H3120.00O2—C16—C10115.5 (11)
C4—C3—H3120.00O3—C16—C10121.1 (16)
C5—C4—H4A120.00C11—C12—H12120.00
C3—C4—H4A120.00C13—C12—H12120.00
C1—C5—H5A120.00C13—C14—H14120.00
C4—C5—H5A120.00C15—C14—H14120.00
C8—C7—H7B109.00C10—C15—H15120.00
H7A—C7—H7C110.00C14—C15—H15120.00
C6—N1—N3—C8174.6 (4)C15—C10—C11—O5180.0 (5)
N3—N1—C6—O110.7 (6)C15—C10—C11—C120.0 (4)
N3—N1—C6—C1169.4 (5)C16—C10—C11—O50.0 (8)
C3—N2—C2—C10.0 (7)C16—C10—C11—C12180.0 (6)
C2—N2—C3—C40.0 (5)C11—C10—C15—C140.0 (3)
N1—N3—C8—C7179.5 (4)C16—C10—C15—C14180.0 (6)
N1—N3—C8—C90.4 (9)C11—C10—C16—O2176.7 (7)
C5—C1—C2—N20.0 (12)C11—C10—C16—O33.4 (14)
C6—C1—C2—N2180.0 (6)C15—C10—C16—O23.3 (12)
C2—C1—C5—C40.1 (12)C15—C10—C16—O3176.7 (9)
C6—C1—C5—C4180.0 (6)O5—C11—C12—C13180.0 (5)
C2—C1—C6—O137.0 (11)C10—C11—C12—C130.0 (4)
C2—C1—C6—N1143.0 (7)C11—C12—C13—O4180.0 (3)
C5—C1—C6—O1143.0 (8)C11—C12—C13—C140.0 (4)
C5—C1—C6—N136.9 (11)O4—C13—C14—C15180.0 (3)
N2—C3—C4—C50.1 (5)C12—C13—C14—C150.0 (4)
C3—C4—C5—C10.1 (8)C13—C14—C15—C100.0 (3)

Experimental details

Crystal data
Chemical formulaC9H11N3O·C7H6O4
Mr331.33
Crystal system, space groupMonoclinic, P21/c
Temperature (K)295
a, b, c (Å)8.5813 (3), 22.7241 (7), 8.8506 (3)
β (°) 95.760 (3)
V3)1717.16 (9)
Z4
Radiation typeSynchrotron, λ = 0.6999 Å
µ (mm1)0.09
Specimen shape, size (mm)Cylinder, 8 × 1.5
Data collection
DiffractometerHuber [Model?]
diffractometer
Specimen mountingCapillary
Data collection modeTransmission
Scan methodStep
2θ values (°)2θmin = 3.0 2θmax = 35.0 2θstep = 0.005
Refinement
R factors and goodness of fitRp = 0.038, Rwp = 0.045, Rexp = 0.031, RBragg = 0.026, χ2 = 2.176
No. of data points6401
No. of parameters67
No. of restraints?
H-atom treatmentH-atom parameters constrained

Computer programs: SPEC (Reference needed), TOPAS-Academic (Coelho, 2003), TOPAS-Academic (Coelho, 2007), DIAMOND (Brandenburg, 1999), publCIF (Westrip, 2010).

Selected geometric parameters (Å, º) top
O1—C61.289 (6)N1—N31.408 (7)
O2—C161.32 (2)N1—C61.393 (4)
O3—C161.243 (17)N2—C21.393 (5)
O4—C131.323 (4)N2—C31.393 (5)
O5—C111.323 (13)N3—C81.311 (8)
N3—N1—C6116.3 (4)N3—C8—C9122.0 (15)
C2—N2—C3120.0 (3)O5—C11—C12117.2 (5)
N1—N3—C8118.4 (5)O5—C11—C10122.9 (5)
N2—C2—C1120.0 (5)O4—C13—C12120.0 (3)
N2—C3—C4120.0 (3)O4—C13—C14120.0 (3)
N1—C6—C1118.9 (5)O2—C16—O3123.4 (8)
O1—C6—C1119.2 (5)O2—C16—C10115.5 (11)
O1—C6—N1122.0 (3)O3—C16—C10121.1 (16)
N3—C8—C7122.0 (4)
 

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