research papers\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoSTRUCTURAL
CHEMISTRY
ISSN: 2053-2296

The synthesis and characterization of a series of cocrystals of an isoniazid derivative with butan-2-one and propan-2-one

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aMolecular Sciences Institute, School of Chemistry, University of the Witwatersrand, Private Bag 3, Johannesburg, Gauteng 2050, South Africa
*Correspondence e-mail: andreas.lemmerer@wits.ac.za

Edited by L. Dawe, Wilfrid Laurier University, Waterloo, Ontario, Canada (Received 22 May 2023; accepted 15 August 2023; online 21 August 2023)

This article is part of a collection of articles to commemorate the founding of the African Crystallographic Association and the 75th anniversary of the IUCr.

Four cocrystals containing N′-(butan-2-yl­idene)pyridine-4-carbohydrazide (izbt) and one cocrystal containing N′-iso­propyl­ideneisonicotinohydrazide (izact) were synthesized by reacting isoniazid with either butan-2-one (for the former) or acetone (for the latter). The coformers used to synthesize the izbt cocrystals were 2,4-di­hydroxy­benzoic acid, 2,5-di­hydroxy­benzoic acid, 2-chloro-4-nitro­benzoic acid and 1-naphthoic acid. 1-Naphthoic acid was also used with izact to form a cocrystal. The 1:1 cocrystals are: N′-(butan-2-yl­idene)pyridine-4-car­bohydrazide–1-naphthoic acid (izbt1nta), C10H13N3O·C11H8O2, N′-(butan-2-yl­idene)pyridine-4-carbohydrazide–2,4-di­hydroxy­benzoic acid (izbt2,4-dhba), C10H13N3O·C7H6O4, N′-(propan-2-yl­idene)pyridine-4-carbohydrazide–1-naphthoic acid (izact1nta), C9H11N3O·C11H8O2, N′-(butan-2-yl­idene)pyridine-4-carbohydrazide–2-chloro-4-nitro­benzoic acid (izbt2c4n), C10H13N3O·C7H4ClNO4, and N′-(butan-2-yl­idene)pyridine-4-carbohydrazide–2,5-di­hy­droxy­benzoic acid (izbt2,5-dhba), C10H13N3O·C7H6O4. The cocrystals con­taining izbt were com­pared to those containing the same (or similar) coformers with izact that have been reported either here or in the Cambridge Structural Database (CSD). Most of the cocrystals showed different packing despite having the same hydrogen-bonding motifs. The cocrystals were characterized by single-crystal X-ray diffraction (SC-XRD), powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC).

1. Introduction

In the pharmaceutical industry, it is often typical for new and existing drugs to have poor physicochemical properties. The poor performance from these drugs can hamper their success on the market. The modification of an existing drug can yield a new product with possibly improved properties compared to the original drug mol­ecule. Although this would require new clinical trials, it could prove to be advantageous for long-term success. From a crystal engineering perspective, this could prove to be an opportunity to explore new solid-state structural landscapes.

One approach of crystal engineering with repsect to changing the solid-state form of active pharmaceutical ingredients (APIs) is to use cocrystals. Although no universal definition of a cocrystal exists, several different definitions have been proposed by different authors. The definition proposed by Aitipamula et al. (2012[Aitipamula, S., Banerjee, R., Bansal, A. K., Biradha, K., Cheney, M. L., Choudhury, A. R., Desiraju, G. R., Dikundwar, A. G., Dubey, R., Duggirala, N., Ghogale, P. P., Ghosh, S., Goswami, P. K., Goud, N. R., Jetti, R. R. K. R., Karpinski, P., Kaushik, P., Kumar, D., Kumar, V., Moulton, B., Mukherjee, A., Mukherjee, G., Myerson, A. S., Puri, V., Ramanan, A., Rajamannar, T., Reddy, C. M., Rodriguez-Hornedo, N., Rogers, R. D., Row, T. N. G., Sanphui, P., Shan, N., Shete, G., Singh, A., Sun, C. C., Swift, J. A., Thaimattam, R., Thakur, T. S., Kumar Thaper, R., Thomas, S. P., Tothadi, S., Vangala, V. R., Variankaval, N., Vishweshwar, P., Weyna, D. R. & Zaworotko, M. J. (2012). Cryst. Growth Des. 12, 2147-2152.]) is as follows: `cocrystals are solids that are crystalline single phase materials com­posed of two or more different mol­ecular and/or ionic com­pounds generally in a stoichiometric ratio.' Grothe defines a cocrystal as `a crystal with a coformer mol­ecule plus either another coformer or at least two ions,' with further classifications depending on whether the crystal also contains ions, solvate mol­ecules or water (Grothe et al., 2016[Grothe, E., Meekes, H., Vlieg, E., ter Horst, J. H. & de Gelder, R. (2016). Cryst. Growth Des. 16, 3237-3243.]). Cocrystals have been proven to have new properties, such as having a different solubility or bioavailability over the starting material (Karimi-Jafari et al., 2018[Karimi-Jafari, M., Padrela, L., Walker, G. M. & Croker, D. M. (2018). Cryst. Growth Des. 18, 6370-6387.]). It can even lead to the possibility of having multiple drugs in one crystal form (Wang et al., 2021[Wang, X., Du, S., Zhang, R., Jia, X., Yang, T. & Zhang, X. (2021). Asia. J. Pharm. Sci. 16, 307-317.]). Unfortunately, cocrystal design and synthesis is not straightforward; it is possible to fail creating a cocrystal despite using a reasonable cocrystal design methodology (Bučar et al., 2013[Bučar, D. K., Day, G. M., Halasz, I., Zhang, G. G. Z., Sander, J. R. G., Reid, D. G., MacGillivray, L. R., Duer, M. J. & Jones, W. (2013). Chem. Sci. 4, 4417-4425.]).

[Scheme 1]

Isoniazid (inh) is an anti­bacterial drug used to treat Mycobacterium tuberculosis bacteria (TB). It is often combined with several different drugs in a fixed-dose combination (FDC) as part of the treatment for this disease (Murray et al., 2015[Murray, J. F., Schraufnagel, D. E. & Hopewell, P. C. (2015). Ann. Am. Thorac. Soc. 12, 1749-1759.]). However, inh has been known to undergo degradation in the presence of other drugs (Bhutani et al., 2005[Bhutani, H., Singh, S., Jindal, K. C. & Chakraborti, A. K. (2005). J. Pharm. Biomed. Anal. 39, 892-899.]). Inh is a fairly simple drug mol­ecule, consisting of a pyridine ring, an amide group and a hydrazine group. One way to modify inh is to employ a Schiff base reaction using inh and either an aldehyde or a ketone. In previous work, we modified isoniazid with acetone, butan-2-one, 4-hy­droxy-4-methyl­pentan-2-one and benzo­phenone, and explored a different number of cocrystal and mol­ecular salt crystal structures (Lemmerer et al., 2010[Lemmerer, A., Bernstein, J. & Kahlenberg, V. (2010). Cryst­EngComm, 12, 2856-2864.]; Madeley et al., 2019[Madeley, L. G., Levendis, D. C. & Lemmerer, A. (2019). Acta Cryst. C75, 200-207.]; Scheepers & Lem­merer, 2022[Scheepers, M. C. & Lemmerer, A. (2022). Acta Cryst. B78, 857-867.]; Lemmerer, 2012[Lemmerer, A. (2012). CrystEngComm, 14, 2465-2478.]). In particular, a decent number of cocrystals and mol­ecular salts with isoniazid derived from acetone and butan-2-one have been reported, with seven crystal structures containing N′-(butan-2-yl­idene)pyridine-4-carbohydrazide (butan-2-one-based derivative, izbt) and 15 containing N′-iso­propyl­idene­iso­nico­tino­hy­dra­zide (acetone-based derivative, izact). Out of these, only five pairs share the same coformer, of which, three pairs are isostructural (Table 1[link]). It should not be too surprising to find crystal structures becoming isostructural when certain functional groups are exchanged with a similar one, for example, changing a chlorine to a bromine or methyl to an amino group (Clarke et al., 2012[Clarke, H. D., Hickey, M. B., Moulton, B., Perman, J. A., Peterson, M. L., Wojtas, Ł., Almarsson, Ö. & Zaworotko, M. J. (2012). Cryst. Growth Des. 12, 4194-4201.]). However, it is still possible that exchanging one functional group for another can yield a com­pletely different structure. In the case of izact and izbt, the difference is the presence or absence of the methyl­ene group in the alkyl group. In three of the cases, this had no effect, but in the case of the anyhydrous forms of izact– and izbt–3-hy­droxy­benzoic acid, and izact– and izbt–2-hydro­benzoic acid, there was a significant difference in the packing. Based on the structures listed in Table 1[link], we would expect that the methyl­ene group would very likely have a small or even insignificant effect on the overall packing of the mol­ecules in the crystal structure; however, with a small sample size it is difficult to assess if this is a reasonable assertion. Therefore, the aim of this work is to expand the number of multi­com­ponent crystal structure pairs and com­pare them, in order to confirm whether the addition of the methyl­ene group can have a significant impact of the packing of these structures. The simplest way to achieve this is to expand the number of izbt cocrystals using coformers that worked for izact; the coformers used include: 2,4-di­hydroxy­benzoic acid (2,4-dhba), 2,5-di­hydroxy­benzoic acid (2,5-dhba) and 2-chloro-4-nitro­benzoic acid (2c4n). In addition, cocrystals containing 1-naphthoic acid (1nta) with izact and izbt, respectively, were synthesized and characterized. 1nta was used to observe the effect of using a bulky double ring as opposed to using coformers consisting of a single ring. The structures of these com­pounds are represented in Scheme 1[link].

Table 1
Cocrystals of izact and izbt that share the same coformer

The Crystal Structure Similarity tool of Mercury (Macrae et al., 2020[Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226-235.]) was used to help determine if related structures were isostructural.

Coformer izact refcode izbt refcode Isostructural
4-tert-Butyl­benzoic acid GIYMAF GIYMEJ Yes
2-Hy­droxy­benzoic acid (salicylic acid)* LATLAV UBILAW No
3-Hy­droxy­benzoic acid (anhydrous) FADHUP FADHOJ No
3-Hy­droxy­benzoic acid hydrate SAYPIT SAYPOZ Yes
4-Nitro­benzoic acid XOPYEJ XOPYUZ Yes
Note: (*) it should be noted that the unit-cell parameters of both structures are similar but the orientations of the mol­ecules with respect to the unit cells differ significantly.

2. Experimental

2.1. Materials

All materials were purchased from Sigma–Aldrich and were used without further purification.

2.2. General procedure for the synthesis of izbt and izact cocrystals

The general procedure for synthesizing cocrystals featuring either izbt or izact is as follows: stoichiometric ratios of inh and the respective coformer (1:1 ratio) were dissolved in absolute ethanol (5 ml) in a small vial. The deriving ketone (acetone or butan-2-one) (1 ml) was added. This vial was closed and the mixture stirred for 4 h. Afterwards, the lid on the vial was replaced with a lid with a hole in it and the vial kept in a dark cupboard. After several days, crystals remained after the solvent evaporated.

2.3. Powder X-ray diffraction (PXRD)

PXRD was used to determine the bulk phase purity of each sample. PXRD data for all forms were measured at 293 K on a Bruker D2 Phaser diffractometer which employs a sealed tube Co X-ray source (λ = 1.78896 Å), operating at 30 kV and 10 mA, and a LynxEye PSD detector in Bragg–Brentano geometry. The powder patterns for the cocrystals are pre­sented in the supporting information, where the experimentally measured pattern is com­pared to the calculated patterns obtained from the single-crystal X-ray diffraction (SC-XRD) data, as well as the calculated patterns of its com­ponents using data from the Cambridge Structural Database (CSD, Version 2022.1.0; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]).

2.4. Single-crystal X-ray diffraction (SC-XRD) and refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. All carbon-bound H atoms were placed in idealized positions and refined as riding atoms, with Uiso(H) parameters 1.2 or 1.5 times those of the parent atoms. Most nitro­gen- and oxygen-bound H atoms were located in difference Fourier maps, and their coordinates and isotropic displacement parameters were refined freely.

Table 2
Experimental details

For all structures: Z = 4. Experiments were carried out with Mo Kα radiation using a Bruker D8 VENTURE PHOTON CMOS 100 area-detector diffractometer.

  izbt1nta izbt2,4-dhba izact1nta
Crystal data
Chemical formula C10H13N3O·C11H8O2 C10H13N3O·C7H6O4 C9H11N3O·C11H8O2
Mr 363.41 345.35 349.38
Crystal system, space group Monoclinic, P21/n Monoclinic, P21/n Monoclinic, Cc
Temperature (K) 173 173 173
a, b, c (Å) 7.4355 (13), 34.195 (6), 7.7242 (14) 11.0834 (6), 13.8364 (8), 12.0014 (7) 7.6312 (3), 33.5293 (12), 7.3493 (3)
α, β, γ (°) 90, 112.512 (4), 90 90, 115.710 (3), 90 90, 114.298 (1), 90
V3) 1814.3 (6) 1658.26 (17) 1713.88 (12)
μ (mm−1) 0.09 0.10 0.09
Crystal size (mm) 0.34 × 0.28 × 0.12 0.32 × 0.25 × 0.21 0.72 × 0.33 × 0.08
 
Data collection
Absorption correction Multi-scan (SADABS; Sheldrick, 2001[Sheldrick, G. M. (2001). SADABS. University of Göttingen, Ger­many.]; Krause et al., 2015[Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3-10.])
Tmin, Tmax 0.684, 0.747
No. of measured, independent and observed [I > 2σ(I)] reflections 35501, 4511, 3552 25708, 4008, 1946 39441, 6819, 6145
Rint 0.033 0.092 0.056
(sin θ/λ)max−1) 0.668 0.660 0.782
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.054, 0.142, 1.03 0.061, 0.219, 1.02 0.043, 0.122, 1.08
No. of reflections 4511 4008 6819
No. of parameters 254 248 238
No. of restraints 0 39 2
H-atom treatment H atoms treated by a mixture of independent and constrained refinement H-atom parameters constrained H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.54, −0.34 0.70, −0.27 0.33, −0.17
Absolute structure Flack x determined using 2626 quotients [(I+) − (I)]/[(I+) + (I)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.])
Absolute structure parameter 0.0 (3)
  izbt2c4n izbt2,5-dhba
Crystal data
Chemical formula C7H4ClNO4·C10H13N3O C10H13N3O·C7H6O4
Mr 392.79 345.35
Crystal system, space group Monoclinic, P21/n Triclinic, P[\overline{1}]
Temperature (K) 173 123
a, b, c (Å) 7.2682 (3), 34.0775 (15), 7.6124 (3) 9.2054 (3), 11.5589 (4), 15.6268 (6)
α, β, γ (°) 90, 111.081 (2), 90 92.383 (2), 93.092 (2), 90.666 (2)
V3) 1759.27 (13) 1658.74 (10)
μ (mm−1) 0.26 0.10
Crystal size (mm) 0.46 × 0.26 × 0.11 0.45 × 0.38 × 0.13
 
Data collection
No. of measured, independent and observed [I > 2σ(I)] reflections 111394, 5624, 5056 73254, 8026, 5972
Rint 0.081 0.079
(sin θ/λ)max−1) 0.726 0.661
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.047, 0.129, 1.07 0.068, 0.191, 1.04
No. of reflections 5624 8026
No. of parameters 250 506
No. of restraints 0 21
H-atom treatment H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.41, −0.28 1.33, −0.68
Computer programs: APEX2 (Bruker, 2012[Bruker (2012). APEX2, SAINT-Plus and XPREP. Bruker AXS Inc., Madison, Wisconsin, USA.]), SAINT-Plus (Bruker, 2012[Bruker (2012). APEX2, SAINT-Plus and XPREP. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT2018 (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2018 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), Mercury (Macrae et al., 2020[Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226-235.]), ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]), XPREP (Bruker, 2012[Bruker (2012). APEX2, SAINT-Plus and XPREP. Bruker AXS Inc., Madison, Wisconsin, USA.]) and WinGX (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]).

2.5. The Cambridge Structural Database (CSD)

The CSD (Version 2022.1.0; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) was used to com­pare the cocrystals presented in this work with the cocrystals of izact. The only restriction was that entries must be classified as being organic. Mercury (Macrae et al., 2020[Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226-235.]) was used to inspect the crystal structures. The Crystal Structure Similarity tool was used to com­pare the structural similarity of selected structures.

2.6. Differential scanning calorimetry (DSC)

DSC data were collected using a Mettler Toledo DSC 3 with aluminium pans under nitro­gen gas (flow rate = 10 ml min−1). Exothermic events were shown as peaks. Samples were heated and cooled to determine the melting points, as well as any additional phase transitions. The tem­per­ature and energy cali­brations were performed using pure indium (purity 99.99%, m.p. 156.6 °C, heat of fusion: 28.45 J g−1) and pure zinc (purity 99.99%, m.p. 479.5 °C, heat of fusion: 107.5 J g−1). Samples were heated to 250 °C from 25 °C before being cooled back down to 25 °C at a heating or cooling rate of 10 °C min−1.

3. Results and discussion

3.1. Synthesis of cocrystals

In this work, six cocrystals were synthesized and characterized. Five of these cocrystals contained izbt and one contained izact. The four coformers chosen were: 2,4-di­hydroxy­benzoic acid (2,4-dhba), 2,5-di­hydroxy­benzoic acid (gentisic acid, abbreviated as 2,5-dhba), 2-chloro-4-nitro­benzoic acid (2c4n) and 1-naphthoic acid (1nta). The first three coformers were chosen because previous cocrystals containing said coformers with izact had been synthesized and characterized previously, and it would be a good reference to com­pare the respective corystals. 1nta was chosen due to its naphthalene ring, as it would be inter­esting to see if its bulky nature had an effect on the overall packing. These cocrystals are described below, together with that of izbt com­pared to its izact counterpart, as well as any other notable cocrystal of izact. The crystal structure data are given in Table 2[link], while the displacement ellipsoid plots are shown in Fig. 1[link]. Hydrogen-bond tables can be found in the supporting information.

[Figure 1]
Figure 1
The mol­ecular structures of (a) izbt2c4n, (b) izact1nta, (c) izbt2,4-dhba, (d) izbt1nta and (e) izbt2,5-dhba. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.

Powder patterns were collected for each sample and were com­pared to the powder patterns calculated from the single-crystal structural data. These powder patterns are also com­pared to the powder patterns of each of the com­ponents, including the polymorphic forms of the com­ponents which are polymorphic. It should be noted that we are com­paring the hydrated form of izbt to the powder patterns of the cocrystals presented here. This was done because it was the closest form to a `pure' com­ponent we can get, and in our own investigations, we have obtained the hydrated form of izbt exclusively when using the same crystallizing conditions we used to obtain the cocrystals presented here, which indicates that izbt is most likely highly hygroscopic, obtaining the water from either the waters of reaction or atmospheric moisture, or both. This com­parison between the experimental and calculated patterns was made to confirm the bulk phase purity. These patterns are presented in the supporting information.

3.2. Crystal structure of izbt–2,4-dhba

Izbt formed a cocrystal with 2,4-dhba which crystallized as colourless blocks in the space group P21/n, with the asymmetric unit consisting of one mol­ecule each of izbt and 2,4-dhba. A disorder model is present, where two C atoms (C9 and C10) of the alkyl portion of izbt were split over two different positions, respectively. The pyridine ring of izbt forms a hydrogen bond with the carb­oxy­lic acid group of 2,4-dhba, while the hy­droxy group at the 4-position of the 2,4-dhba mol­ecule (O5—H5) forms two different hydrogen bonds with the amide group of izbt, one where the hy­droxy group is the hydrogen-bond donor, forming a hydrogen bond with the O atom of the amide group [O5—H5⋯O1i; symmetry code: (i) x + [{3\over 2}], −y + [{1\over 2}], z + [{1\over 2}]], and one where the hy­droxy group is the hydrogen-bond acceptor, forming a hydrogen bond with the amine portion of the amide group [N1—H1⋯O5ii; symmetry code: (ii) −x + [{3\over 2}], y + [{1\over 2}], −z + [{1\over 2}]] [Fig. 2[link](a)]. This hydrogen-bond arrangement ultimately forms a tetra­mer with an R44(12) ring hydrogen-bond motif. The hy­droxy group at the 2-position of 2,4-dhba does not form any strong hydrogen bonds other than the typical intra­molecular hydrogen bond with the carb­oxy­lic acid group. The overall packing of the structure resembles a herringbone-type structure [Fig. 2[link](b)].

[Figure 2]
Figure 2
The crystal structure of izbt2,4-dhba, showing (a) the hydrogen bonding present in the structure, (b) the packing of the structure (with H atoms omitted) and (c) an overlay of izbt2,4-dhba with izact4hba, showing their isostructurality.

Although there is no equivalent cocrystal featuring 2,4-dhba and izact, the crystal structure of izbt2,4-dhba may be com­pared to that of izact4hba (CSD refcode LATKOI). Fig. 2[link](c) shows the overlay of these two structures using the Crystal Structure Similarity tool of Mercury (Macrae et al., 2020[Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226-235.]). The crystal structure parameters of izact4hba match closely with those of izbt2,4-dhba, and when the Crystal Structure Similarity tool of Mercury was used, it showed that the respective mol­ecules matched up well, indicating that they were isostructural. This implies that, in this case, the hy­droxy group at the 2-position and the extra methyl group on the alkyl chain did not have any significant effect on the overall packing on the structure.

3.3. Crystal structure of izbt–2,5-dhba

Izbt formed a cocrystal with 2,5-dhba which crystallized as colourless blocks in the space group P[\overline 1], with the asymmetric unit consisting of two molecules each of izbt and 2,5-dhba. A disorder model exists where the methylene group of one of the izbt molecules has been split into two different sites (C26A and C26B). Like izbt2,4-dhba, the corystals of izbt2,5-dhba exhibit a similar hydrogen-bonding trend: a hydrogen bond is formed between the pyridine ring of izbt and the carboxylic acid group of 2,5-dhba, while the hydroxy group at the 5-position of 2,5-dhba forms a C22(11) chain–ring hydrogen-bond motif with the O and H atom of the amide group of adjacent izbt molecules [Fig. 3[link](a)]. The overall packing is a layered-type structure, with the alkyl group separating the ring layers [Fig. 3[link](b)]. In comparison, the structure of izact2,5-dhba (refcode NAKYOQ; Oruganti et al., 2016[Oruganti, M., Khade, P., Das, U. K. & Trivedi, D. R. (2016). RSC Adv. 6, 15868-15876.]) is very similar to its izbt counterpart. Both exhibit the same hydrogen-bond pattern, as well as the overall packing pattern, and the reduced unit-cell lengths of NAKYOQ are comparable (a = 9.119, b = 11.581 and c = 15.273 Å) [Fig. 3[link](c)].

[Figure 3]
Figure 3
The crystal structure of izbt2,5-dhba, showing (a) the hydrogen bonding present, (b) the packing (with H atoms omitted, izbt in blue and green, and 2,5-dhba in red and yellow) and (c) the overlay of izact2,5-dhba and izbt2,5-dhba.

3.4. Crystal structure of izbt–2c4n

Izbt and 2c4n formed a cocrystal, crystallizing as yellow plates. The asymmetric unit consists of one mol­ecule each of izbt and 2c4n, crystallizing in the space group P21/n. The hydrogen bonding observed in izact2c4n consists of the typical scheme observed for these types of structures: the carb­oxy­lic acid group of 2c4n forms a hydrogen bond with the pyridine ring of izbt, while the amide group of izbt forms a C(4) chain hydrogen-bond motif between the H atom of the amide group and the O atom of the amide group of another izbt mol­ecule [Fig. 4[link](a)]. This chain hydrogen-bond motif causes the mol­ecules of izbt to lie almost perpendicular with respect to each other in an alternating pattern, and extends along the a and c axes. This ultimately forms a series of ribbons which pack together to form the crystal structure observed in Fig. 4[link](c).

[Figure 4]
Figure 4
The crystal structure of izbt2c4n and izact2c4n (CSD refcode LATLID), showing (a) the hydrogen bonding present in izbt2c4n, (b) the asymmetric unit of izact2c4n, (c) the packing of izbt2c4n (with H atoms omitted for clarity) and (d) the packing of izact2c4n (with H atoms omitted for clarity).

The izact2c4n cocrystal (refcode LATLID) is much different in com­parison. According to Grothe et al. (2016[Grothe, E., Meekes, H., Vlieg, E., ter Horst, J. H. & de Gelder, R. (2016). Cryst. Growth Des. 16, 3237-3243.]), this crystal system can be defined as a `cocrystal salt', since its asymmetric unit consists of three neutral mol­ecules of 2c4n and one ion of 2c4n, with three neutral mol­ecules of izact and one protonated ion of izact [Fig. 4[link](b)]. This crystal structure crystallizes in the chiral space group P21. Like the structure of izbt2c4n, mol­ecules and ions of izact are connected to each other via a series of C44(16) chain hydrogen-bond motifs involving the H atom of the amide group forming a hydrogen bond with the O atom of the amide group from another izact mol­ecule. The carb­oxy­lic acid group of 2c4n also forms a hydrogen bond with the pyridine ring of izact (charge-assisted for the cation–anion pair). The overall packing of izact2c4n also consists of ribbons, but these differ from the structure of izbt2c4n [Fig. 4[link](d)]. Unlike in the crystal structure of izbt2c4n, the arrangement of the izbt2c4n bonded pairs lie almost parallel to each other, instead of the rotation of almost 90° seen in izbt2c4n.

3.5. Crystal structures of izact–1nta and izbt–1nta

Izact and izbt each formed a cocrystal with 1nta, both crystallizing as colourless plates. Despite sharing similar unit-cell parameters, the structures are not isostructural, as the crystal structure of izact1nta crystallizes in the space group Cc, while the crystal structure of izbt1nta crystallizes in the space group P21/n. These structures are also not isostructural with izbt2c4n, despite sharing similar unit-cell parameters, as can be seen in Fig. 5[link](d). Both crystal structures share the same hydrogen-bonding patterns. 1nta forms a hydrogen bond with the isoniazid derivative, while the isoniazid derivative forms a C(4) chain hydrogen-bond motif involving the H atom of the amide group and the O atom of the amide group from a neighbouring mol­ecule of the isoniazid derivative [Fig. 5[link](a)], which expands generally in the direction of the a axis as ribbons. The key difference between the two structures lies in the packing, where the difference between the P21/n and Cc space groups is that the inversion centres in P21/n [Fig. 5[link](b)] are replaced by glide planes in Cc [Fig. 5[link](c)]. This changes the orientation of the mol­ecules existing in both structures with respect to the unit cell. Overall, the packing of both structures may be described as herringbone.

[Figure 5]
Figure 5
(a) The hydrogen bonding present in izact1nta, showing the typical hydrogen bonding in the structures of izact1nta and izbt1nta. The packing present in the crystal structure of (b) izact1nta and (c) izbt1nta, with the H atoms omitted for clarity. In parts (b) and (c), the respective isoniazid derivative is presented in green, 1nta in blue, glide planes as magenta lines and inversion centres as orange spheres. (d) The overlap of izbt1nta and izbt2c4n (mol­ecules in green), showing that the structures are not isostructural.

3.6. Thermal analysis

DSC curves were collected for all ten cocrystals. The DSC curve of izbt1nta is presented in Fig. 6[link] as a representative curve, while the remaining DSC curves can be found in the supporting information. The onset and enthalpy values are presented in Table 3[link]. The melting points and enthalpies of some of the cocrystals related to the cocrystals presented in this work are also included. In each of the curves, only one large distinct peak was observed on the heating stage, which correlates to the melting/decom­position of the sample. No peaks were observed on the cooling stage of the DSC curves, indicating that no recrystallization occurred. A common feature between the cocrystals is that their melting points are much lower than the melting points of the acid coformers. This makes sense since the R22(8) hydrogen-bond ring motif formed between the carb­oxy­lic acid pairs is expected to be stronger than that formed by carb­oxy­lic acid–pyridine. From a pharmaceutical point of view, a lower melting point is usually indicative of a product that has a better drug solubility, which indicates the possibility of having better pharmaceutical properties compared to their individual com­ponents (Chu & Yalkowsky, 2009[Chu, K. A. & Yalkowsky, S. H. (2009). Int. J. Pharm. 373, 24-40.]). A comparison of the melting/decom­position points and enthalpies of the izact cocrystals with those of their izbt counterparts indicates that the values tend to be similar to each other, which would make sense considering their overall similar hydrogen-bond schemes.

Table 3
Onset temperatures and associated enthalpies for the DSC curves of the cocrystals presented in this work, as well as the melting points and enthalpies of some of the com­parison cocrystals

Thermal event Onset (°C) Enthalpy (J g−1) Enthalpy (kJ mol−1)
Izact1nta melting/decom­position 106.1 ± 0.5 170.9 ± 5.2 59.7 ± 2
Izbt1nta melting/decom­position 89.5± 0.1 167.8 ± 2.5 61.0 ± 1
Izbt2c4n melting/decom­position 102.1 ± 0.2 100.6 ± 2.3 39.5 ± 1
Izbt2,4-dhba melting/decom­position 174.8± 0.2 226.3 ± 4.3 78.2 ± 1
Izbt2,5-dhba melting/decom­position 151.2 ± 0.2 132.5 ± 3.2 45.8 ± 1
Izact m.p. (Lemmerer, 2012[Lemmerer, A. (2012). CrystEngComm, 14, 2465-2478.]) 160.0 29.7
Izact2c4n m.p. (Lemmerer, 2012[Lemmerer, A. (2012). CrystEngComm, 14, 2465-2478.]) 93.4 33.4
[Figure 6]
Figure 6
DSC curve for izbt1nta, representing the typical DSC curve observed for each of the cocrystals.

4. Conclusions

Four cocrystals containing izbt and one cocrystal containing izact were synthesized and characterized. The structures of the cocrystals containing izbt were com­pared to their izact counterparts, except for izbt2,4-dhba, which was instead com­pared to izact4hba. Most of the structures of the cocrystals of izbt were different com­pared to their izact counterparts in terms of packing, despite sharing similar hydrogen-bond patterns. This would imply that the presence or absence of a methylene group can have a significant impact on the overall crystal structure packing, contrary to our initial assumption that the methyl­ene group has a small or even insignificant effect on the packing of mol­ecules in the crystal structure. The melting/decom­position points were found to be much lower than those of the coformers. The overall result shows that many crystal systems are temperamental: small differences between mol­ecules can lead to big changes in the overall packing.

Supporting information


Computing details top

Data collection: APEX2 (Bruker, 2012) for izbt1nta, izbt24dhba, izact1nta, izbt2c4n. Cell refinement: SAINT-Plus (Bruker, 2012) for izbt1nta, izbt24dhba, izact1nta, izbt2c4n. Data reduction: SAINT-Plus (Bruker, 2012) for izbt1nta, izbt24dhba, izact1nta, izbt2c4n. For all structures, program(s) used to solve structure: SHELXT2018 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b). Molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and Mercury (Macrae et al., 2020) for izbt1nta, izbt24dhba, izact1nta, izbt2c4n; ORTEP-3 for Windows (Farrugia, 2012) for izbt25dhba. Software used to prepare material for publication: WinGX (Farrugia, 2012) and XPREP (Bruker, 2012) for izbt1nta, izbt24dhba, izact1nta, izbt2c4n; WinGX (Farrugia, 2012) for izbt25dhba.

N'-(Butan-2-ylidene)pyridine-4-carbohydrazide; 1-naphthoic acid (izbt1nta) top
Crystal data top
C10H13N3O·C11H8O2F(000) = 768
Mr = 363.41Dx = 1.33 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 9890 reflections
a = 7.4355 (13) Åθ = 2.9–28.3°
b = 34.195 (6) ŵ = 0.09 mm1
c = 7.7242 (14) ÅT = 173 K
β = 112.512 (4)°Block, colourless
V = 1814.3 (6) Å30.34 × 0.28 × 0.12 mm
Z = 4
Data collection top
Bruker APEXII CCD
diffractometer
Rint = 0.033
φ and ω scansθmax = 28.3°, θmin = 3.4°
35501 measured reflectionsh = 99
4511 independent reflectionsk = 4545
3552 reflections with I > 2σ(I)l = 1010
Refinement top
Refinement on F20 constraints
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.054H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.142 w = 1/[σ2(Fo2) + (0.0637P)2 + 1.0375P]
where P = (Fo2 + 2Fc2)/3
S = 1.03(Δ/σ)max = 0.001
4511 reflectionsΔρmax = 0.54 e Å3
254 parametersΔρmin = 0.34 e Å3
0 restraints
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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.4865 (3)0.64234 (5)0.5961 (2)0.0289 (4)
H10.4793460.6146250.5995410.035*
C20.5137 (2)0.66303 (4)0.7582 (2)0.0244 (3)
H2A0.5285770.6497640.8709610.029*
C30.5189 (2)0.70353 (4)0.7527 (2)0.0208 (3)
C40.5009 (2)0.72157 (5)0.5857 (2)0.0264 (3)
H40.5041980.7492570.5774210.032*
C50.4780 (3)0.69843 (5)0.4313 (2)0.0300 (4)
H50.4676330.7108990.3179440.036*
C60.5592 (2)0.72591 (4)0.9309 (2)0.0219 (3)
C70.4945 (2)0.82004 (5)1.0579 (2)0.0269 (3)
C80.4585 (3)0.84331 (5)0.8828 (2)0.0367 (4)
H8A0.5148580.8295820.8041710.055*
H8B0.5190330.869130.9164330.055*
H8C0.3179670.8463920.8136470.055*
C90.5210 (3)0.84343 (5)1.2308 (2)0.0312 (4)
H9A0.6303370.8618631.2535230.037*
H9B0.4020590.8591911.206230.037*
C100.5606 (3)0.82005 (6)1.4061 (2)0.0376 (4)
H10A0.4483830.8032781.3899220.056*
H10B0.5828750.8378241.5118220.056*
H10C0.6762820.803771.4309320.056*
C110.3204 (2)0.54602 (4)0.0208 (2)0.0218 (3)
C120.3179 (2)0.55966 (4)0.1480 (2)0.0241 (3)
H120.3545230.5859920.1564680.029*
C130.2629 (2)0.53579 (5)0.3079 (2)0.0281 (3)
H130.262640.5458840.422590.034*
C140.2099 (2)0.49802 (5)0.2971 (2)0.0289 (4)
H140.1724040.4818520.4051590.035*
C150.2097 (2)0.48253 (5)0.1277 (2)0.0253 (3)
C160.2665 (2)0.50632 (4)0.0363 (2)0.0221 (3)
C170.2661 (2)0.48883 (5)0.2031 (2)0.0282 (3)
H170.3042480.5038620.3148770.034*
C180.2117 (3)0.45067 (5)0.2051 (3)0.0346 (4)
H180.2127440.4395980.3182940.042*
C190.1544 (3)0.42767 (5)0.0429 (3)0.0374 (4)
H190.1160510.4012690.0460690.045*
C200.1539 (3)0.44330 (5)0.1191 (3)0.0334 (4)
H200.1152880.4275420.228660.04*
C210.3808 (2)0.57384 (5)0.1818 (2)0.0273 (3)
N10.4697 (2)0.65943 (4)0.43437 (19)0.0295 (3)
N20.4799 (2)0.76157 (4)0.91231 (18)0.0261 (3)
N30.5099 (2)0.78278 (4)1.07692 (18)0.0273 (3)
O10.66638 (17)0.71153 (3)1.08121 (15)0.0301 (3)
O20.3999 (2)0.61035 (4)0.13403 (18)0.0412 (3)
O30.4134 (3)0.56528 (4)0.34138 (18)0.0645 (5)
H20.385 (3)0.7684 (6)0.805 (3)0.039 (5)*
H2B0.432 (4)0.6256 (8)0.232 (4)0.063 (7)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0369 (9)0.0208 (8)0.0284 (8)0.0006 (6)0.0117 (7)0.0033 (6)
C20.0285 (8)0.0207 (7)0.0221 (7)0.0009 (6)0.0077 (6)0.0003 (6)
C30.0202 (7)0.0208 (7)0.0193 (7)0.0001 (5)0.0051 (5)0.0027 (5)
C40.0349 (9)0.0202 (7)0.0246 (7)0.0004 (6)0.0119 (6)0.0001 (6)
C50.0404 (9)0.0287 (8)0.0232 (7)0.0007 (7)0.0148 (7)0.0006 (6)
C60.0232 (7)0.0210 (7)0.0199 (7)0.0030 (6)0.0064 (6)0.0028 (5)
C70.0236 (8)0.0261 (8)0.0295 (8)0.0014 (6)0.0085 (6)0.0070 (6)
C80.0486 (11)0.0262 (9)0.0314 (9)0.0017 (7)0.0113 (8)0.0017 (7)
C90.0349 (9)0.0269 (8)0.0332 (9)0.0017 (7)0.0145 (7)0.0080 (7)
C100.0428 (10)0.0366 (10)0.0337 (9)0.0006 (8)0.0150 (8)0.0074 (7)
C110.0234 (7)0.0218 (7)0.0201 (7)0.0016 (6)0.0083 (6)0.0012 (5)
C120.0283 (8)0.0216 (7)0.0230 (7)0.0012 (6)0.0103 (6)0.0006 (6)
C130.0335 (9)0.0307 (8)0.0205 (7)0.0028 (7)0.0106 (6)0.0001 (6)
C140.0295 (8)0.0321 (8)0.0224 (7)0.0021 (7)0.0069 (6)0.0077 (6)
C150.0219 (7)0.0239 (7)0.0285 (8)0.0016 (6)0.0081 (6)0.0028 (6)
C160.0209 (7)0.0216 (7)0.0241 (7)0.0033 (6)0.0090 (6)0.0007 (6)
C170.0320 (9)0.0267 (8)0.0294 (8)0.0029 (6)0.0156 (7)0.0021 (6)
C180.0378 (10)0.0298 (9)0.0424 (10)0.0037 (7)0.0224 (8)0.0095 (7)
C190.0381 (10)0.0232 (8)0.0527 (11)0.0032 (7)0.0195 (9)0.0022 (8)
C200.0318 (9)0.0254 (8)0.0408 (10)0.0019 (7)0.0114 (7)0.0065 (7)
C210.0344 (9)0.0241 (8)0.0229 (7)0.0005 (6)0.0105 (6)0.0019 (6)
N10.0368 (8)0.0279 (7)0.0250 (7)0.0007 (6)0.0130 (6)0.0058 (5)
N20.0306 (7)0.0231 (7)0.0194 (6)0.0020 (5)0.0037 (5)0.0051 (5)
N30.0294 (7)0.0270 (7)0.0231 (6)0.0010 (5)0.0075 (5)0.0077 (5)
O10.0364 (6)0.0266 (6)0.0193 (5)0.0020 (5)0.0017 (5)0.0001 (4)
O20.0758 (10)0.0223 (6)0.0276 (6)0.0044 (6)0.0222 (7)0.0052 (5)
O30.1335 (16)0.0346 (8)0.0231 (7)0.0192 (9)0.0272 (8)0.0066 (5)
Geometric parameters (Å, º) top
C1—N11.341 (2)C11—C121.378 (2)
C1—C21.384 (2)C11—C161.433 (2)
C1—H10.95C11—C211.492 (2)
C2—C31.387 (2)C12—C131.404 (2)
C2—H2A0.95C12—H120.95
C3—C41.389 (2)C13—C141.362 (2)
C3—C61.5016 (19)C13—H130.95
C4—C51.386 (2)C14—C151.412 (2)
C4—H40.95C14—H140.95
C5—N11.335 (2)C15—C201.413 (2)
C5—H50.95C15—C161.427 (2)
C6—O11.2311 (18)C16—C171.422 (2)
C6—N21.338 (2)C17—C181.368 (2)
C7—N31.283 (2)C17—H170.95
C7—C81.502 (2)C18—C191.400 (3)
C7—C91.504 (2)C18—H180.95
C8—H8A0.98C19—C201.359 (3)
C8—H8B0.98C19—H190.95
C8—H8C0.98C20—H200.95
C9—C101.501 (2)C21—O31.198 (2)
C9—H9A0.99C21—O21.325 (2)
C9—H9B0.99N2—N31.4054 (17)
C10—H10A0.98N2—H20.89 (2)
C10—H10B0.98O2—H2B0.87 (3)
C10—H10C0.98
N1—C1—C2123.30 (15)C12—C11—C16119.79 (13)
N1—C1—H1118.3C12—C11—C21117.61 (14)
C2—C1—H1118.3C16—C11—C21122.60 (13)
C1—C2—C3118.61 (14)C11—C12—C13121.94 (14)
C1—C2—H2A120.7C11—C12—H12119
C3—C2—H2A120.7C13—C12—H12119
C2—C3—C4118.55 (13)C14—C13—C12119.39 (14)
C2—C3—C6118.61 (13)C14—C13—H13120.3
C4—C3—C6122.66 (13)C12—C13—H13120.3
C5—C4—C3118.82 (14)C13—C14—C15121.05 (14)
C5—C4—H4120.6C13—C14—H14119.5
C3—C4—H4120.6C15—C14—H14119.5
N1—C5—C4123.08 (15)C14—C15—C20120.28 (15)
N1—C5—H5118.5C14—C15—C16120.26 (14)
C4—C5—H5118.5C20—C15—C16119.46 (15)
O1—C6—N2124.39 (14)C17—C16—C15117.54 (14)
O1—C6—C3119.40 (13)C17—C16—C11124.88 (14)
N2—C6—C3116.15 (12)C15—C16—C11117.57 (13)
N3—C7—C8127.34 (14)C18—C17—C16120.98 (15)
N3—C7—C9116.82 (15)C18—C17—H17119.5
C8—C7—C9115.82 (14)C16—C17—H17119.5
C7—C8—H8A109.5C17—C18—C19121.03 (16)
C7—C8—H8B109.5C17—C18—H18119.5
H8A—C8—H8B109.5C19—C18—H18119.5
C7—C8—H8C109.5C20—C19—C18119.72 (16)
H8A—C8—H8C109.5C20—C19—H19120.1
H8B—C8—H8C109.5C18—C19—H19120.1
C10—C9—C7115.56 (14)C19—C20—C15121.26 (16)
C10—C9—H9A108.4C19—C20—H20119.4
C7—C9—H9A108.4C15—C20—H20119.4
C10—C9—H9B108.4O3—C21—O2121.05 (15)
C7—C9—H9B108.4O3—C21—C11125.43 (15)
H9A—C9—H9B107.5O2—C21—C11113.50 (13)
C9—C10—H10A109.5C5—N1—C1117.61 (14)
C9—C10—H10B109.5C6—N2—N3117.53 (12)
H10A—C10—H10B109.5C6—N2—H2119.9 (13)
C9—C10—H10C109.5N3—N2—H2120.1 (14)
H10A—C10—H10C109.5C7—N3—N2115.64 (13)
H10B—C10—H10C109.5C21—O2—H2B110.2 (17)
N1—C1—C2—C31.8 (3)C12—C11—C16—C17179.06 (15)
C1—C2—C3—C41.4 (2)C21—C11—C16—C170.8 (2)
C1—C2—C3—C6176.73 (14)C12—C11—C16—C150.7 (2)
C2—C3—C4—C50.2 (2)C21—C11—C16—C15179.46 (14)
C6—C3—C4—C5175.28 (15)C15—C16—C17—C180.5 (2)
C3—C4—C5—N10.9 (3)C11—C16—C17—C18179.73 (16)
C2—C3—C6—O132.2 (2)C16—C17—C18—C190.1 (3)
C4—C3—C6—O1142.93 (16)C17—C18—C19—C200.4 (3)
C2—C3—C6—N2150.56 (15)C18—C19—C20—C150.2 (3)
C4—C3—C6—N234.3 (2)C14—C15—C20—C19179.39 (16)
N3—C7—C9—C100.6 (2)C16—C15—C20—C190.4 (2)
C8—C7—C9—C10178.93 (16)C12—C11—C21—O3170.22 (19)
C16—C11—C12—C130.3 (2)C16—C11—C21—O39.6 (3)
C21—C11—C12—C13179.86 (14)C12—C11—C21—O28.6 (2)
C11—C12—C13—C140.1 (2)C16—C11—C21—O2171.56 (15)
C12—C13—C14—C150.1 (2)C4—C5—N1—C10.7 (3)
C13—C14—C15—C20179.88 (16)C2—C1—N1—C50.7 (3)
C13—C14—C15—C160.3 (2)O1—C6—N2—N34.8 (2)
C14—C15—C16—C17179.06 (14)C3—C6—N2—N3178.06 (13)
C20—C15—C16—C170.7 (2)C8—C7—N3—N23.4 (2)
C14—C15—C16—C110.7 (2)C9—C7—N3—N2178.55 (14)
C20—C15—C16—C11179.47 (14)C6—N2—N3—C7156.63 (15)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C1—H1···O30.952.513.208 (2)130
C8—H8C···O1i0.982.623.128 (2)112
N2—H2···O1i0.89 (2)1.98 (2)2.8732 (17)174 (2)
O2—H2B···N10.87 (3)1.88 (3)2.7472 (18)173 (2)
Symmetry code: (i) x1/2, y+3/2, z1/2.
N'-(Butan-2-ylidene)pyridine-4-carbohydrazide; 2,4-dihydroxybenzoic acid (izbt24dhba) top
Crystal data top
C10H13N3O·C7H6O4F(000) = 728
Mr = 345.35Dx = 1.383 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 2614 reflections
a = 11.0834 (6) Åθ = 2.4–21.7°
b = 13.8364 (8) ŵ = 0.10 mm1
c = 12.0014 (7) ÅT = 173 K
β = 115.710 (3)°Block, colourless
V = 1658.26 (17) Å30.32 × 0.25 × 0.21 mm
Z = 4
Data collection top
Bruker APEXII CCD
diffractometer
Rint = 0.092
φ and ω scansθmax = 28.0°, θmin = 2.1°
25708 measured reflectionsh = 1414
4008 independent reflectionsk = 1418
1946 reflections with I > 2σ(I)l = 1515
Refinement top
Refinement on F20 constraints
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.061H-atom parameters constrained
wR(F2) = 0.219 w = 1/[σ2(Fo2) + (0.1075P)2 + 0.2167P]
where P = (Fo2 + 2Fc2)/3
S = 1.02(Δ/σ)max < 0.001
4008 reflectionsΔρmax = 0.70 e Å3
248 parametersΔρmin = 0.27 e Å3
39 restraints
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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
C10.2256 (3)0.3307 (2)0.1115 (2)0.0462 (7)
C20.3201 (3)0.3638 (2)0.2233 (3)0.0517 (7)
H2A0.2946480.402670.2748820.062*
C30.4529 (3)0.3395 (2)0.2596 (3)0.0565 (8)
H30.5174550.3633070.3366710.068*
C40.4034 (3)0.2515 (3)0.0874 (3)0.0656 (9)
H4A0.4315380.2110080.0392420.079*
C50.2688 (3)0.2722 (2)0.0432 (3)0.0611 (8)
H5A0.206510.2463470.0336610.073*
C60.0790 (3)0.3539 (2)0.0579 (3)0.0486 (7)
C70.0363 (4)0.4971 (3)0.2909 (4)0.0926 (13)
H7A0.0859590.5310160.3296090.139*
H7B0.003220.4353340.3332190.139*
H7C0.039540.5368360.2972370.139*
C80.1270 (3)0.4788 (2)0.1576 (4)0.0669 (9)
C9A0.2718 (8)0.5139 (7)0.0969 (7)0.068 (2)0.681 (9)
H9A10.2737610.5845950.1090210.082*0.681 (9)
H9A20.3103080.5012780.0069090.082*0.681 (9)
C10A0.3526 (6)0.4664 (5)0.1481 (7)0.093 (2)0.681 (9)
H10A0.4446450.4906660.1071510.14*0.681 (9)
H10B0.3521830.3965410.1349130.14*0.681 (9)
H10C0.3156580.4798090.2369630.14*0.681 (9)
C9B0.2550 (16)0.5059 (17)0.1534 (14)0.086 (5)0.319 (9)
H9B10.2668170.4765160.2231580.104*0.319 (9)
H9B20.2615270.5770590.1580460.104*0.319 (9)
C10B0.3542 (15)0.4705 (11)0.0377 (13)0.095 (4)0.319 (9)
H10D0.4435480.4869290.0297380.143*0.319 (9)
H10E0.3407530.5001080.0302430.143*0.319 (9)
H10F0.3460150.4001110.0345160.143*0.319 (9)
N10.0399 (2)0.40980 (18)0.1262 (2)0.0549 (7)
H10.0983130.4299030.1993950.066*
N20.4951 (2)0.28521 (19)0.1933 (2)0.0582 (7)
N30.0929 (2)0.43602 (19)0.0816 (3)0.0626 (7)
O10.00257 (19)0.32187 (16)0.0423 (2)0.0651 (6)
C110.9062 (2)0.17767 (19)0.1967 (2)0.0437 (6)
C120.9337 (3)0.1210 (2)0.1135 (3)0.0462 (7)
C131.0644 (3)0.0963 (2)0.1403 (3)0.0483 (7)
H131.0828470.0582640.0836280.058*
C141.1674 (2)0.1266 (2)0.2486 (3)0.0461 (7)
C151.1424 (3)0.1830 (2)0.3328 (3)0.0518 (7)
H151.2138190.203930.4077840.062*
C161.0126 (3)0.2074 (2)0.3052 (3)0.0497 (7)
H160.9949890.2459320.3620020.06*
C170.7666 (3)0.2014 (2)0.1685 (3)0.0473 (7)
O20.74959 (18)0.25109 (16)0.25335 (18)0.0598 (6)
H20.6673490.2591160.2318090.09*
O30.67159 (18)0.17496 (15)0.07253 (18)0.0559 (6)
O40.83565 (18)0.08837 (17)0.00710 (18)0.0614 (6)
H40.7609840.1056580.0025230.092*
O51.29304 (18)0.09825 (15)0.27164 (19)0.0567 (6)
H51.3483080.1249580.3366230.085*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0322 (13)0.0605 (18)0.0483 (17)0.0021 (12)0.0197 (13)0.0023 (13)
C20.0377 (15)0.069 (2)0.0518 (18)0.0077 (13)0.0226 (14)0.0001 (15)
C30.0337 (14)0.078 (2)0.0557 (18)0.0036 (14)0.0172 (14)0.0056 (16)
C40.0418 (16)0.097 (3)0.066 (2)0.0071 (16)0.0309 (17)0.0140 (18)
C50.0379 (15)0.088 (2)0.0595 (19)0.0001 (15)0.0230 (15)0.0129 (17)
C60.0323 (14)0.0587 (18)0.0574 (19)0.0000 (12)0.0218 (15)0.0013 (14)
C70.080 (3)0.106 (3)0.125 (4)0.013 (2)0.076 (3)0.028 (3)
C80.0505 (18)0.064 (2)0.105 (3)0.0021 (15)0.050 (2)0.0004 (19)
C9A0.056 (4)0.088 (4)0.071 (5)0.016 (3)0.037 (4)0.006 (4)
C10A0.064 (4)0.103 (5)0.135 (6)0.010 (3)0.064 (4)0.018 (4)
C9B0.063 (8)0.110 (10)0.113 (11)0.027 (7)0.063 (8)0.018 (10)
C10B0.098 (9)0.086 (9)0.132 (10)0.009 (7)0.079 (8)0.007 (8)
N10.0325 (12)0.0766 (17)0.0606 (16)0.0031 (11)0.0250 (12)0.0011 (13)
N20.0351 (12)0.0826 (19)0.0602 (16)0.0074 (12)0.0237 (13)0.0070 (14)
N30.0336 (12)0.0738 (18)0.0819 (19)0.0088 (11)0.0265 (13)0.0040 (14)
O10.0379 (11)0.0789 (15)0.0678 (15)0.0051 (10)0.0129 (11)0.0127 (12)
C110.0340 (13)0.0511 (17)0.0505 (16)0.0028 (11)0.0226 (13)0.0028 (13)
C120.0325 (13)0.0589 (18)0.0467 (17)0.0021 (12)0.0168 (13)0.0012 (13)
C130.0383 (14)0.0592 (18)0.0535 (17)0.0019 (12)0.0257 (14)0.0057 (14)
C140.0311 (13)0.0525 (17)0.0561 (18)0.0036 (11)0.0201 (14)0.0002 (13)
C150.0346 (14)0.0643 (19)0.0531 (18)0.0004 (12)0.0158 (13)0.0096 (14)
C160.0364 (14)0.0598 (18)0.0549 (18)0.0042 (12)0.0216 (14)0.0067 (14)
C170.0352 (14)0.0590 (18)0.0507 (17)0.0041 (12)0.0215 (14)0.0058 (14)
O20.0373 (10)0.0837 (15)0.0614 (13)0.0108 (10)0.0242 (10)0.0097 (11)
O30.0325 (10)0.0817 (15)0.0535 (13)0.0023 (9)0.0187 (10)0.0035 (10)
O40.0361 (10)0.0921 (16)0.0542 (13)0.0026 (10)0.0179 (10)0.0153 (11)
O50.0316 (10)0.0738 (14)0.0651 (14)0.0044 (9)0.0212 (10)0.0110 (10)
Geometric parameters (Å, º) top
C1—C21.374 (4)C9B—C10B1.432 (10)
C1—C51.378 (4)C9B—H9B10.99
C1—C61.500 (4)C9B—H9B20.99
C2—C31.383 (4)C10B—H10D0.98
C2—H2A0.95C10B—H10E0.98
C3—N21.319 (4)C10B—H10F0.98
C3—H30.95N1—N31.379 (3)
C4—N21.321 (4)N1—H10.88
C4—C51.379 (4)C11—C161.386 (4)
C4—H4A0.95C11—C121.403 (4)
C5—H5A0.95C11—C171.471 (3)
C6—O11.215 (3)C12—O41.346 (3)
C6—N11.329 (4)C12—C131.384 (3)
C7—C81.496 (5)C13—C141.371 (4)
C7—H7A0.98C13—H130.95
C7—H7B0.98C14—O51.355 (3)
C7—H7C0.98C14—C151.397 (4)
C8—N31.273 (4)C15—C161.371 (3)
C8—C9B1.447 (18)C15—H150.95
C8—C9A1.526 (9)C16—H160.95
C9A—C10A1.445 (7)C17—O31.232 (3)
C9A—H9A10.99C17—O21.308 (3)
C9A—H9A20.99O2—H20.84
C10A—H10A0.98O4—H40.84
C10A—H10B0.98O5—H50.84
C10A—H10C0.98
C2—C1—C5117.6 (2)C10B—C9B—C8105.9 (13)
C2—C1—C6124.9 (2)C10B—C9B—H9B1110.6
C5—C1—C6117.5 (3)C8—C9B—H9B1110.6
C1—C2—C3118.8 (3)C10B—C9B—H9B2110.6
C1—C2—H2A120.6C8—C9B—H9B2110.6
C3—C2—H2A120.6H9B1—C9B—H9B2108.7
N2—C3—C2123.8 (3)C9B—C10B—H10D109.5
N2—C3—H3118.1C9B—C10B—H10E109.5
C2—C3—H3118.1H10D—C10B—H10E109.5
N2—C4—C5123.4 (3)C9B—C10B—H10F109.5
N2—C4—H4A118.3H10D—C10B—H10F109.5
C5—C4—H4A118.3H10E—C10B—H10F109.5
C1—C5—C4119.4 (3)C6—N1—N3119.5 (3)
C1—C5—H5A120.3C6—N1—H1120.2
C4—C5—H5A120.3N3—N1—H1120.2
O1—C6—N1123.3 (2)C3—N2—C4117.0 (2)
O1—C6—C1120.5 (2)C8—N3—N1116.2 (3)
N1—C6—C1116.3 (3)C16—C11—C12118.4 (2)
C8—C7—H7A109.5C16—C11—C17122.1 (2)
C8—C7—H7B109.5C12—C11—C17119.5 (2)
H7A—C7—H7B109.5O4—C12—C13118.1 (2)
C8—C7—H7C109.5O4—C12—C11121.9 (2)
H7A—C7—H7C109.5C13—C12—C11120.1 (3)
H7B—C7—H7C109.5C14—C13—C12120.1 (2)
N3—C8—C9B133.3 (7)C14—C13—H13119.9
N3—C8—C7125.0 (3)C12—C13—H13119.9
C9B—C8—C7100.8 (6)O5—C14—C13117.7 (2)
N3—C8—C9A112.6 (4)O5—C14—C15121.5 (2)
C7—C8—C9A122.4 (4)C13—C14—C15120.8 (2)
C10A—C9A—C8111.7 (6)C16—C15—C14118.7 (3)
C10A—C9A—H9A1109.3C16—C15—H15120.7
C8—C9A—H9A1109.3C14—C15—H15120.7
C10A—C9A—H9A2109.3C15—C16—C11122.0 (3)
C8—C9A—H9A2109.3C15—C16—H16119
H9A1—C9A—H9A2107.9C11—C16—H16119
C9A—C10A—H10A109.5O3—C17—O2122.1 (2)
C9A—C10A—H10B109.5O3—C17—C11122.4 (3)
H10A—C10A—H10B109.5O2—C17—C11115.5 (3)
C9A—C10A—H10C109.5C17—O2—H2109.5
H10A—C10A—H10C109.5C12—O4—H4109.5
H10B—C10A—H10C109.5C14—O5—H5109.5
C5—C1—C2—C32.0 (4)C9A—C8—N3—N1174.3 (4)
C6—C1—C2—C3177.7 (3)C6—N1—N3—C8171.1 (3)
C1—C2—C3—N20.6 (5)C16—C11—C12—O4179.1 (3)
C2—C1—C5—C41.7 (5)C17—C11—C12—O40.8 (4)
C6—C1—C5—C4178.1 (3)C16—C11—C12—C130.1 (4)
N2—C4—C5—C10.1 (5)C17—C11—C12—C13178.5 (2)
C2—C1—C6—O1179.6 (3)O4—C12—C13—C14178.9 (3)
C5—C1—C6—O10.2 (4)C11—C12—C13—C140.4 (4)
C2—C1—C6—N10.9 (4)C12—C13—C14—O5178.4 (3)
C5—C1—C6—N1179.4 (3)C12—C13—C14—C150.3 (4)
N3—C8—C9A—C10A116.4 (6)O5—C14—C15—C16178.6 (3)
C7—C8—C9A—C10A65.7 (8)C13—C14—C15—C160.1 (4)
N3—C8—C9B—C10B2 (2)C14—C15—C16—C110.2 (5)
C7—C8—C9B—C10B166.8 (13)C12—C11—C16—C150.1 (4)
O1—C6—N1—N32.0 (4)C17—C11—C16—C15178.2 (3)
C1—C6—N1—N3178.5 (2)C16—C11—C17—O3179.7 (3)
C2—C3—N2—C41.1 (5)C12—C11—C17—O31.4 (4)
C5—C4—N2—C31.5 (5)C16—C11—C17—O21.0 (4)
C9B—C8—N3—N1170.6 (12)C12—C11—C17—O2177.3 (2)
C7—C8—N3—N13.6 (5)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O5i0.882.583.124 (3)121
O2—H2···N20.841.82.633 (3)175
C4—H4A···O30.952.563.233 (3)128
O4—H4···O30.841.822.568 (3)147
O5—H5···O1ii0.841.852.665 (3)163
Symmetry codes: (i) x+3/2, y+1/2, z+1/2; (ii) x+3/2, y+1/2, z+1/2.
N'-(Propan-2-ylidene)pyridine-4-carbohydrazide; 1-naphthoic acid (izact1nta) top
Crystal data top
C9H11N3O·C11H8O2F(000) = 736
Mr = 349.38Dx = 1.354 Mg m3
Monoclinic, CcMo Kα radiation, λ = 0.71073 Å
Hall symbol: C -2ycCell parameters from 9944 reflections
a = 7.6312 (3) Åθ = 2.4–32.0°
b = 33.5293 (12) ŵ = 0.09 mm1
c = 7.3493 (3) ÅT = 173 K
β = 114.298 (1)°Plate, colourless
V = 1713.88 (12) Å30.72 × 0.33 × 0.08 mm
Z = 4
Data collection top
Bruker APEXII CCD
diffractometer
6145 reflections with I > 2σ(I)
φ and ω scansRint = 0.056
Absorption correction: multi-scan
(SADABS; Sheldrick, 2001; Krause et al., 2015)
θmax = 33.7°, θmin = 2.4°
Tmin = 0.684, Tmax = 0.747h = 1111
39441 measured reflectionsk = 5252
6819 independent reflectionsl = 1111
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.043 w = 1/[σ2(Fo2) + (0.0746P)2 + 0.0558P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.122(Δ/σ)max = 0.001
S = 1.08Δρmax = 0.33 e Å3
6819 reflectionsΔρmin = 0.17 e Å3
238 parametersAbsolute structure: Flack x determined using 2626 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
2 restraintsAbsolute structure parameter: 0.0 (3)
0 constraints
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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.4245 (2)0.64077 (4)0.5306 (3)0.0271 (3)
H10.4273940.6124950.53990.033*
C20.2532 (2)0.66022 (4)0.4942 (2)0.0245 (3)
H20.1408060.6455370.4763330.029*
C30.2488 (2)0.70167 (4)0.4844 (2)0.0213 (2)
C40.4160 (2)0.72176 (4)0.5094 (2)0.0268 (3)
H40.4179230.7500660.5045390.032*
C50.5808 (2)0.69982 (5)0.5418 (3)0.0294 (3)
H50.6942210.7137390.5564490.035*
C60.0586 (2)0.72170 (4)0.4316 (2)0.0231 (2)
C70.1291 (2)0.81130 (4)0.4976 (2)0.0270 (3)
C80.0322 (3)0.84017 (5)0.5454 (3)0.0378 (4)
H8A0.0994180.8431030.6905920.057*
H8B0.0188150.8661020.4855230.057*
H8C0.1221640.8302940.4916530.057*
C90.3242 (3)0.82752 (6)0.4609 (3)0.0387 (4)
H9A0.3253170.8362750.5876830.058*
H9B0.4211650.8066540.4020730.058*
H9C0.3535390.8502120.3690820.058*
C100.98959 (19)0.54175 (4)0.6266 (2)0.0229 (3)
C111.1694 (2)0.55617 (5)0.6594 (2)0.0275 (3)
H111.189280.5841750.6624430.033*
C121.3245 (2)0.53034 (5)0.6887 (3)0.0330 (3)
H121.447020.540940.7108340.04*
C131.2980 (2)0.49021 (5)0.6851 (3)0.0321 (3)
H131.4026650.4728830.7041240.039*
C141.1176 (2)0.47396 (5)0.6536 (2)0.0263 (3)
C150.9586 (2)0.49954 (4)0.6251 (2)0.0228 (2)
C160.7820 (2)0.48134 (5)0.5987 (3)0.0307 (3)
H160.6741840.4975540.5813320.037*
C170.7649 (3)0.44058 (5)0.5979 (3)0.0362 (4)
H170.6453410.4291030.5808910.043*
C180.9200 (3)0.41547 (5)0.6216 (3)0.0375 (4)
H180.9050310.387320.6184880.045*
C191.0922 (3)0.43199 (5)0.6491 (3)0.0340 (3)
H191.1974490.4150570.6655930.041*
C200.8321 (2)0.57131 (4)0.5883 (2)0.0249 (3)
N10.58678 (19)0.65991 (4)0.5534 (2)0.0284 (3)
N20.06057 (18)0.75731 (4)0.5167 (2)0.0249 (2)
H2A0.1682760.769590.5911970.03*
N30.12045 (19)0.77355 (4)0.4788 (2)0.0270 (3)
O10.08842 (17)0.70564 (3)0.3110 (2)0.0312 (3)
O20.89085 (18)0.60918 (3)0.6040 (2)0.0338 (3)
H2B0.7979580.624430.586660.051*
O30.66461 (19)0.56323 (4)0.5423 (3)0.0446 (4)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0247 (6)0.0208 (5)0.0370 (7)0.0017 (5)0.0138 (6)0.0004 (5)
C20.0205 (6)0.0196 (5)0.0317 (7)0.0001 (4)0.0090 (5)0.0007 (5)
C30.0190 (5)0.0195 (5)0.0236 (6)0.0011 (4)0.0069 (5)0.0001 (5)
C40.0251 (6)0.0204 (5)0.0359 (8)0.0021 (5)0.0137 (6)0.0015 (5)
C50.0240 (7)0.0260 (6)0.0415 (8)0.0031 (5)0.0169 (6)0.0027 (6)
C60.0199 (6)0.0187 (5)0.0274 (6)0.0004 (4)0.0064 (5)0.0021 (5)
C70.0292 (7)0.0231 (6)0.0262 (6)0.0057 (5)0.0088 (6)0.0027 (5)
C80.0355 (9)0.0235 (7)0.0441 (10)0.0003 (6)0.0062 (7)0.0027 (6)
C90.0390 (9)0.0343 (8)0.0450 (10)0.0149 (7)0.0195 (8)0.0070 (7)
C100.0184 (6)0.0237 (6)0.0272 (6)0.0007 (4)0.0100 (5)0.0006 (5)
C110.0196 (6)0.0282 (7)0.0352 (7)0.0008 (5)0.0117 (6)0.0042 (6)
C120.0199 (6)0.0389 (8)0.0415 (9)0.0038 (6)0.0138 (6)0.0094 (7)
C130.0246 (7)0.0364 (8)0.0373 (8)0.0094 (6)0.0147 (6)0.0083 (6)
C140.0266 (7)0.0263 (6)0.0263 (6)0.0056 (5)0.0113 (6)0.0037 (5)
C150.0211 (6)0.0223 (6)0.0247 (6)0.0008 (5)0.0091 (5)0.0005 (5)
C160.0252 (7)0.0242 (6)0.0422 (9)0.0023 (5)0.0133 (6)0.0025 (6)
C170.0316 (8)0.0253 (7)0.0475 (10)0.0054 (6)0.0121 (7)0.0022 (6)
C180.0416 (9)0.0223 (7)0.0428 (9)0.0002 (6)0.0115 (8)0.0022 (6)
C190.0377 (9)0.0255 (7)0.0368 (8)0.0089 (6)0.0134 (7)0.0025 (6)
C200.0212 (6)0.0213 (6)0.0338 (7)0.0011 (5)0.0129 (5)0.0033 (5)
N10.0233 (6)0.0260 (6)0.0386 (7)0.0013 (5)0.0155 (5)0.0018 (5)
N20.0189 (5)0.0204 (5)0.0307 (6)0.0019 (4)0.0054 (5)0.0012 (4)
N30.0214 (5)0.0241 (6)0.0337 (7)0.0038 (4)0.0095 (5)0.0017 (4)
O10.0211 (5)0.0240 (5)0.0382 (6)0.0005 (4)0.0017 (4)0.0036 (4)
O20.0219 (5)0.0207 (5)0.0578 (8)0.0017 (4)0.0152 (5)0.0047 (5)
O30.0235 (6)0.0256 (5)0.0863 (12)0.0018 (4)0.0242 (6)0.0063 (6)
Geometric parameters (Å, º) top
C1—N11.342 (2)C10—C151.4344 (19)
C1—C21.385 (2)C10—C201.4923 (19)
C1—H10.95C11—C121.409 (2)
C2—C31.3914 (18)C11—H110.95
C2—H20.95C12—C131.359 (2)
C3—C41.386 (2)C12—H120.95
C3—C61.4987 (19)C13—C141.409 (2)
C4—C51.390 (2)C13—H130.95
C4—H40.95C14—C191.419 (2)
C5—N11.340 (2)C14—C151.4293 (19)
C5—H50.95C15—C161.418 (2)
C6—O11.2311 (18)C16—C171.372 (2)
C6—N21.3450 (18)C16—H160.95
C7—N31.2778 (19)C17—C181.403 (3)
C7—C81.490 (2)C17—H170.95
C7—C91.501 (2)C18—C191.362 (3)
C8—H8A0.98C18—H180.95
C8—H8B0.98C19—H190.95
C8—H8C0.98C20—O31.2109 (18)
C9—H9A0.98C20—O21.3357 (17)
C9—H9B0.98N2—N31.4021 (17)
C9—H9C0.98N2—H2A0.88
C10—C111.3794 (19)O2—H2B0.84
N1—C1—C2123.21 (13)C10—C11—C12121.57 (14)
N1—C1—H1118.4C10—C11—H11119.2
C2—C1—H1118.4C12—C11—H11119.2
C1—C2—C3118.74 (13)C13—C12—C11119.80 (15)
C1—C2—H2120.6C13—C12—H12120.1
C3—C2—H2120.6C11—C12—H12120.1
C4—C3—C2118.52 (12)C12—C13—C14120.87 (14)
C4—C3—C6123.86 (12)C12—C13—H13119.6
C2—C3—C6117.45 (12)C14—C13—H13119.6
C3—C4—C5118.92 (12)C13—C14—C19120.15 (14)
C3—C4—H4120.5C13—C14—C15120.38 (14)
C5—C4—H4120.5C19—C14—C15119.47 (14)
N1—C5—C4122.97 (13)C16—C15—C14117.61 (13)
N1—C5—H5118.5C16—C15—C10124.78 (13)
C4—C5—H5118.5C14—C15—C10117.61 (13)
O1—C6—N2123.76 (14)C17—C16—C15120.83 (15)
O1—C6—C3119.27 (13)C17—C16—H16119.6
N2—C6—C3116.95 (12)C15—C16—H16119.6
N3—C7—C8126.46 (15)C16—C17—C18121.53 (16)
N3—C7—C9115.53 (15)C16—C17—H17119.2
C8—C7—C9117.98 (14)C18—C17—H17119.2
C7—C8—H8A109.5C19—C18—C17119.15 (15)
C7—C8—H8B109.5C19—C18—H18120.4
H8A—C8—H8B109.5C17—C18—H18120.4
C7—C8—H8C109.5C18—C19—C14121.39 (15)
H8A—C8—H8C109.5C18—C19—H19119.3
H8B—C8—H8C109.5C14—C19—H19119.3
C7—C9—H9A109.5O3—C20—O2120.99 (13)
C7—C9—H9B109.5O3—C20—C10125.43 (13)
H9A—C9—H9B109.5O2—C20—C10113.56 (12)
C7—C9—H9C109.5C5—N1—C1117.63 (13)
H9A—C9—H9C109.5C6—N2—N3115.52 (12)
H9B—C9—H9C109.5C6—N2—H2A122.2
C11—C10—C15119.76 (12)N3—N2—H2A122.2
C11—C10—C20117.79 (13)C7—N3—N2117.00 (13)
C15—C10—C20122.43 (12)C20—O2—H2B109.5
N1—C1—C2—C31.3 (3)C20—C10—C15—C163.5 (2)
C1—C2—C3—C40.6 (2)C11—C10—C15—C141.5 (2)
C1—C2—C3—C6176.11 (14)C20—C10—C15—C14176.86 (13)
C2—C3—C4—C50.5 (2)C14—C15—C16—C170.9 (2)
C6—C3—C4—C5174.67 (14)C10—C15—C16—C17179.51 (16)
C3—C4—C5—N11.1 (3)C15—C16—C17—C180.5 (3)
C4—C3—C6—O1139.64 (16)C16—C17—C18—C191.0 (3)
C2—C3—C6—O135.6 (2)C17—C18—C19—C140.2 (3)
C4—C3—C6—N238.5 (2)C13—C14—C19—C18179.09 (18)
C2—C3—C6—N2146.30 (14)C15—C14—C19—C181.1 (3)
C15—C10—C11—C121.1 (2)C11—C10—C20—O3174.12 (18)
C20—C10—C11—C12177.37 (15)C15—C10—C20—O34.3 (2)
C10—C11—C12—C130.1 (3)C11—C10—C20—O24.2 (2)
C11—C12—C13—C140.4 (3)C15—C10—C20—O2177.43 (14)
C12—C13—C14—C19179.62 (17)C4—C5—N1—C10.6 (3)
C12—C13—C14—C150.1 (2)C2—C1—N1—C50.6 (3)
C13—C14—C15—C16178.58 (15)O1—C6—N2—N37.5 (2)
C19—C14—C15—C161.7 (2)C3—C6—N2—N3174.42 (12)
C13—C14—C15—C101.1 (2)C8—C7—N3—N23.5 (2)
C19—C14—C15—C10178.71 (15)C9—C7—N3—N2178.53 (14)
C11—C10—C15—C16178.10 (15)C6—N2—N3—C7157.47 (14)
N'-(Butan-2-ylidene)pyridine-4-carbohydrazide; 2-chloro-4-nitrobenzoic acid (izbt2c4n) top
Crystal data top
C7H4ClNO4·C10H13N3OF(000) = 816
Mr = 392.79Dx = 1.483 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 9966 reflections
a = 7.2682 (3) Åθ = 2.4–30.8°
b = 34.0775 (15) ŵ = 0.26 mm1
c = 7.6124 (3) ÅT = 173 K
β = 111.081 (2)°Plate, colourless
V = 1759.27 (13) Å30.46 × 0.26 × 0.11 mm
Z = 4
Data collection top
Bruker APEXII CCD
diffractometer
Rint = 0.081
φ and ω scansθmax = 31.1°, θmin = 2.4°
111394 measured reflectionsh = 1010
5624 independent reflectionsk = 4949
5056 reflections with I > 2σ(I)l = 1111
Refinement top
Refinement on F2Primary atom site location: dual
Least-squares matrix: fullSecondary atom site location: dual
R[F2 > 2σ(F2)] = 0.047Hydrogen site location: mixed
wR(F2) = 0.129H atoms treated by a mixture of independent and constrained refinement
S = 1.07 w = 1/[σ2(Fo2) + (0.0581P)2 + 0.7134P]
where P = (Fo2 + 2Fc2)/3
5624 reflections(Δ/σ)max = 0.002
250 parametersΔρmax = 0.41 e Å3
0 restraintsΔρmin = 0.28 e Å3
0 constraints
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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.34552 (19)0.70488 (4)0.34294 (16)0.0265 (2)
H10.3381960.7183390.2313430.032*
C20.36445 (17)0.72661 (3)0.50281 (16)0.0236 (2)
H2A0.3683920.7544610.5001260.028*
C30.37753 (15)0.70697 (3)0.66653 (14)0.01940 (19)
C40.37152 (18)0.66621 (3)0.66495 (16)0.0239 (2)
H40.3825890.6519680.775590.029*
C50.34909 (19)0.64679 (4)0.49885 (18)0.0281 (2)
H50.3417890.618950.4968360.034*
C60.41408 (16)0.72790 (3)0.84962 (14)0.01968 (19)
C70.35850 (16)0.82289 (3)0.97889 (16)0.0224 (2)
C80.3268 (2)0.84432 (4)0.79821 (18)0.0308 (3)
H8A0.3985130.8309270.7285250.046*
H8B0.3754390.8712880.8260950.046*
H8C0.1857140.8447550.7219550.046*
C90.38785 (18)0.84802 (3)1.14869 (17)0.0252 (2)
H9A0.2708120.8651161.1221330.03*
H9B0.5029540.8652781.1674950.03*
C100.4201 (2)0.82623 (4)1.33066 (18)0.0306 (3)
H10A0.3036470.810271.3172690.046*
H10B0.4417880.845141.433140.046*
H10C0.5357490.8091591.359370.046*
C110.2577 (2)0.55646 (4)0.06804 (19)0.0329 (3)
C120.4153 (2)0.55063 (4)0.12851 (19)0.0359 (3)
C130.4172 (3)0.51828 (4)0.2402 (2)0.0497 (5)
H130.5245220.5139350.2812110.06*
C140.2596 (4)0.49280 (4)0.2897 (2)0.0552 (5)
C150.1001 (3)0.49746 (5)0.2356 (2)0.0532 (5)
H150.0063690.4793480.2727870.064*
C160.1008 (3)0.52969 (4)0.1245 (2)0.0429 (4)
H160.0080830.5337640.0854490.051*
C170.2412 (2)0.58813 (4)0.0638 (2)0.0339 (3)
Cl010.62203 (6)0.58034 (2)0.06254 (6)0.04457 (12)
N10.33722 (16)0.66570 (3)0.34045 (15)0.0273 (2)
N20.33516 (15)0.76384 (3)0.83540 (13)0.02305 (19)
H20.2648670.7737030.7247110.028*
N30.36705 (15)0.78542 (3)1.00102 (13)0.02341 (19)
N40.2662 (4)0.45802 (4)0.4029 (2)0.0803 (8)
O10.51772 (13)0.71240 (2)0.99850 (11)0.02553 (18)
O20.33658 (16)0.62034 (3)0.06437 (13)0.0320 (2)
O30.1408 (3)0.58288 (4)0.1583 (3)0.0712 (5)
O40.4196 (5)0.45158 (5)0.4308 (3)0.1193 (10)
O50.1146 (4)0.43750 (4)0.4613 (2)0.0987 (8)
H2B0.326 (4)0.6369 (7)0.163 (4)0.075 (7)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0313 (6)0.0300 (6)0.0208 (5)0.0006 (4)0.0124 (4)0.0006 (4)
C20.0288 (5)0.0221 (5)0.0216 (5)0.0003 (4)0.0111 (4)0.0005 (4)
C30.0186 (4)0.0216 (5)0.0174 (4)0.0007 (3)0.0058 (4)0.0007 (3)
C40.0277 (5)0.0213 (5)0.0217 (5)0.0014 (4)0.0077 (4)0.0004 (4)
C50.0338 (6)0.0226 (5)0.0280 (6)0.0006 (4)0.0111 (5)0.0040 (4)
C60.0202 (4)0.0208 (5)0.0171 (4)0.0010 (4)0.0055 (4)0.0004 (3)
C70.0212 (5)0.0239 (5)0.0210 (5)0.0006 (4)0.0063 (4)0.0018 (4)
C80.0407 (7)0.0259 (5)0.0234 (5)0.0039 (5)0.0085 (5)0.0009 (4)
C90.0292 (5)0.0228 (5)0.0243 (5)0.0011 (4)0.0107 (4)0.0033 (4)
C100.0371 (6)0.0318 (6)0.0242 (5)0.0035 (5)0.0127 (5)0.0014 (4)
C110.0482 (8)0.0233 (5)0.0264 (6)0.0043 (5)0.0123 (5)0.0024 (4)
C120.0565 (9)0.0266 (6)0.0269 (6)0.0121 (6)0.0178 (6)0.0037 (5)
C130.0922 (14)0.0308 (7)0.0333 (7)0.0233 (8)0.0313 (8)0.0064 (6)
C140.1142 (17)0.0216 (6)0.0247 (6)0.0129 (8)0.0189 (8)0.0011 (5)
C150.0877 (14)0.0268 (7)0.0341 (8)0.0060 (8)0.0087 (8)0.0048 (6)
C160.0588 (10)0.0281 (6)0.0367 (7)0.0036 (6)0.0111 (7)0.0052 (5)
C170.0411 (7)0.0288 (6)0.0351 (7)0.0022 (5)0.0176 (6)0.0086 (5)
Cl010.0506 (2)0.0406 (2)0.0516 (2)0.01217 (15)0.02936 (18)0.00589 (15)
N10.0296 (5)0.0295 (5)0.0239 (5)0.0001 (4)0.0109 (4)0.0059 (4)
N20.0280 (5)0.0215 (4)0.0159 (4)0.0033 (3)0.0035 (3)0.0019 (3)
N30.0259 (5)0.0242 (4)0.0180 (4)0.0014 (3)0.0053 (3)0.0039 (3)
N40.180 (2)0.0260 (7)0.0347 (7)0.0174 (10)0.0383 (11)0.0012 (6)
O10.0293 (4)0.0247 (4)0.0179 (4)0.0024 (3)0.0028 (3)0.0015 (3)
O20.0455 (5)0.0255 (4)0.0291 (4)0.0021 (4)0.0184 (4)0.0069 (3)
O30.0978 (12)0.0514 (8)0.0994 (12)0.0357 (8)0.0777 (11)0.0389 (8)
O40.243 (3)0.0530 (10)0.0986 (15)0.0310 (14)0.1064 (19)0.0144 (9)
O50.199 (2)0.0292 (6)0.0447 (8)0.0000 (10)0.0163 (11)0.0110 (6)
Geometric parameters (Å, º) top
C1—N11.3361 (16)C10—H10A0.98
C1—C21.3885 (16)C10—H10B0.98
C1—H10.95C10—H10C0.98
C2—C31.3874 (15)C11—C121.394 (2)
C2—H2A0.95C11—C161.402 (2)
C3—C41.3897 (15)C11—C171.5076 (18)
C3—C61.5019 (14)C12—C131.396 (2)
C4—C51.3838 (16)C12—Cl011.7297 (17)
C4—H40.95C13—C141.377 (3)
C5—N11.3423 (16)C13—H130.95
C5—H50.95C14—C151.372 (3)
C6—O11.2316 (13)C14—N41.476 (2)
C6—N21.3400 (14)C15—C161.385 (2)
C7—N31.2865 (15)C15—H150.95
C7—C81.5001 (16)C16—H160.95
C7—C91.5004 (16)C17—O31.2077 (19)
C8—H8A0.98C17—O21.2974 (17)
C8—H8B0.98N2—N31.4051 (13)
C8—H8C0.98N2—H20.88
C9—C101.5139 (17)N4—O41.228 (4)
C9—H9A0.99N4—O51.244 (3)
C9—H9B0.99O2—H2B0.96 (3)
N1—C1—C2122.35 (11)H10A—C10—H10B109.5
N1—C1—H1118.8C9—C10—H10C109.5
C2—C1—H1118.8H10A—C10—H10C109.5
C3—C2—C1118.89 (11)H10B—C10—H10C109.5
C3—C2—H2A120.6C12—C11—C16118.74 (13)
C1—C2—H2A120.6C12—C11—C17126.39 (13)
C2—C3—C4118.86 (10)C16—C11—C17114.78 (14)
C2—C3—C6122.45 (10)C11—C12—C13120.22 (16)
C4—C3—C6118.51 (9)C11—C12—Cl01123.50 (11)
C5—C4—C3118.61 (11)C13—C12—Cl01116.19 (14)
C5—C4—H4120.7C14—C13—C12118.36 (18)
C3—C4—H4120.7C14—C13—H13120.8
N1—C5—C4122.66 (11)C12—C13—H13120.8
N1—C5—H5118.7C15—C14—C13123.66 (14)
C4—C5—H5118.7C15—C14—N4118.4 (2)
O1—C6—N2124.65 (10)C13—C14—N4117.9 (2)
O1—C6—C3119.72 (10)C14—C15—C16117.22 (18)
N2—C6—C3115.56 (9)C14—C15—H15121.4
N3—C7—C8125.98 (10)C16—C15—H15121.4
N3—C7—C9117.93 (10)C15—C16—C11121.79 (18)
C8—C7—C9116.07 (10)C15—C16—H16119.1
C7—C8—H8A109.5C11—C16—H16119.1
C7—C8—H8B109.5O3—C17—O2124.04 (13)
H8A—C8—H8B109.5O3—C17—C11120.00 (13)
C7—C8—H8C109.5O2—C17—C11115.95 (12)
H8A—C8—H8C109.5C1—N1—C5118.62 (10)
H8B—C8—H8C109.5C6—N2—N3118.58 (9)
C7—C9—C10115.82 (10)C6—N2—H2120.7
C7—C9—H9A108.3N3—N2—H2120.7
C10—C9—H9A108.3C7—N3—N2114.68 (10)
C7—C9—H9B108.3O4—N4—O5125.48 (19)
C10—C9—H9B108.3O4—N4—C14117.8 (2)
H9A—C9—H9B107.4O5—N4—C14116.7 (2)
C9—C10—H10A109.5C17—O2—H2B107.9 (15)
C9—C10—H10B109.5
N1—C1—C2—C30.76 (18)C13—C14—C15—C160.3 (3)
C1—C2—C3—C40.10 (17)N4—C14—C15—C16178.00 (15)
C1—C2—C3—C6175.11 (10)C14—C15—C16—C110.4 (2)
C2—C3—C4—C51.16 (17)C12—C11—C16—C151.1 (2)
C6—C3—C4—C5176.37 (11)C17—C11—C16—C15175.78 (14)
C3—C4—C5—N11.49 (19)C12—C11—C17—O3153.35 (18)
C2—C3—C6—O1143.50 (12)C16—C11—C17—O323.2 (2)
C4—C3—C6—O131.53 (15)C12—C11—C17—O227.9 (2)
C2—C3—C6—N233.63 (15)C16—C11—C17—O2155.51 (13)
C4—C3—C6—N2151.34 (11)C2—C1—N1—C50.49 (19)
N3—C7—C9—C101.45 (16)C4—C5—N1—C10.66 (19)
C8—C7—C9—C10179.90 (11)O1—C6—N2—N31.73 (17)
C16—C11—C12—C131.1 (2)C3—C6—N2—N3178.70 (9)
C17—C11—C12—C13175.29 (14)C8—C7—N3—N22.66 (17)
C16—C11—C12—Cl01177.59 (11)C9—C7—N3—N2179.06 (10)
C17—C11—C12—Cl011.2 (2)C6—N2—N3—C7153.96 (11)
C11—C12—C13—C140.6 (2)C15—C14—N4—O4171.23 (19)
Cl01—C12—C13—C14177.25 (11)C13—C14—N4—O47.1 (3)
C12—C13—C14—C150.2 (2)C15—C14—N4—O58.4 (2)
C12—C13—C14—N4178.11 (13)C13—C14—N4—O5173.23 (15)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2···O1i0.882.052.8809 (13)158
C4—H4···O2ii0.952.583.5082 (15)167
C1—H1···O1iii0.952.563.2966 (15)135
C8—H8B···O5iv0.982.473.380 (2)154
C8—H8C···O1i0.982.593.2095 (15)122
C13—H13···O4v0.952.643.297 (3)126
C15—H15···O3vi0.952.613.413 (2)142
O2—H2B···N10.96 (3)1.65 (3)2.6076 (13)173 (2)
N2—H2···O1i0.882.052.8809 (13)158
C4—H4···O2ii0.952.583.5082 (15)167
C1—H1···O1iii0.952.563.2966 (15)135
C8—H8B···O5iv0.982.473.380 (2)154
C8—H8C···O1i0.982.593.2095 (15)122
C13—H13···O4v0.952.643.297 (3)126
C15—H15···O3vi0.952.613.413 (2)142
O2—H2B···N10.96 (3)1.65 (3)2.6076 (13)173 (2)
Symmetry codes: (i) x1/2, y+3/2, z1/2; (ii) x, y, z+1; (iii) x, y, z1; (iv) x+1/2, y+1/2, z+1/2; (v) x+1, y+1, z1; (vi) x, y+1, z.
N'-(Butan-2-ylidene)pyridine-4-carbohydrazide; 2,5-dihydroxybenzoic acid (izbt25dhba) top
Crystal data top
C10H13N3O·C7H6O4Z = 4
Mr = 345.35F(000) = 728
Triclinic, P1Dx = 1.383 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 9.2054 (3) ÅCell parameters from 9903 reflections
b = 11.5589 (4) Åθ = 2.2–27.3°
c = 15.6268 (6) ŵ = 0.10 mm1
α = 92.383 (2)°T = 123 K
β = 93.092 (2)°Plate, colourless
γ = 90.666 (2)°0.45 × 0.38 × 0.13 mm
V = 1658.74 (10) Å3
Data collection top
Bruker APEXII CCD
diffractometer
Rint = 0.079
φ and ω scansθmax = 28°, θmin = 1.8°
73254 measured reflectionsh = 1212
8026 independent reflectionsk = 1515
5972 reflections with I > 2σ(I)l = 2020
Refinement top
Refinement on F2Primary atom site location: dual
Least-squares matrix: fullSecondary atom site location: dual
R[F2 > 2σ(F2)] = 0.068Hydrogen site location: mixed
wR(F2) = 0.191H atoms treated by a mixture of independent and constrained refinement
S = 1.04 w = 1/[σ2(Fo2) + (0.0779P)2 + 1.3095P]
where P = (Fo2 + 2Fc2)/3
8026 reflections(Δ/σ)max < 0.001
506 parametersΔρmax = 1.33 e Å3
21 restraintsΔρmin = 0.68 e Å3
0 constraints
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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
C10.2112 (3)0.59980 (18)0.42485 (14)0.0394 (5)
H10.2289480.5240650.4440160.047*
C20.1065 (2)0.61362 (17)0.36000 (14)0.0350 (4)
H20.053370.5486250.3350130.042*
C30.0796 (2)0.72412 (16)0.33160 (13)0.0302 (4)
C40.1587 (2)0.81679 (16)0.37099 (13)0.0315 (4)
H40.1415960.8936510.3540460.038*
C50.2624 (2)0.79498 (17)0.43507 (14)0.0332 (4)
H50.3173520.8582360.4612660.04*
C60.0350 (2)0.75020 (17)0.26420 (15)0.0349 (4)
C70.2250 (4)0.5985 (2)0.0953 (2)0.0687 (9)
C80.1519 (4)0.4878 (2)0.0876 (2)0.0647 (8)
H8A0.049540.5011060.0761890.097*
H8B0.1990550.4406530.040150.097*
H8C0.1580240.4471990.1410790.097*
C90.3335 (6)0.6135 (4)0.0212 (3)0.0541 (16)0.625 (10)
H9A0.2888220.5872170.0323320.065*0.625 (10)
H9B0.4187170.5625310.0284340.065*0.625 (10)
C100.3857 (7)0.7345 (6)0.0110 (4)0.074 (2)0.625 (10)
H10A0.4616490.7349970.0353980.111*0.625 (10)
H10B0.3042340.7843780.0028770.111*0.625 (10)
H10C0.4254970.7633120.0646520.111*0.625 (10)
C110.6568 (2)0.73609 (16)0.68602 (14)0.0332 (4)
C120.7330 (2)0.83240 (17)0.72385 (17)0.0407 (5)
C130.8377 (3)0.81677 (18)0.78881 (18)0.0451 (6)
H130.891990.8815480.8131750.054*
C140.8644 (3)0.70739 (19)0.81880 (17)0.0423 (5)
H140.9364310.6977520.8636810.051*
C150.7863 (2)0.61188 (16)0.78356 (14)0.0337 (4)
C160.6847 (2)0.62589 (16)0.71685 (13)0.0318 (4)
H160.6331090.5603250.691550.038*
C170.5472 (3)0.75068 (18)0.61543 (14)0.0375 (5)
C180.2402 (2)0.30223 (17)0.56766 (15)0.0378 (5)
H180.1848740.3615750.5417480.045*
C190.3424 (2)0.33290 (17)0.63206 (15)0.0373 (5)
H190.3582760.4118270.6498880.045*
C200.4225 (2)0.24569 (17)0.67075 (16)0.0365 (5)
C210.3967 (2)0.13173 (17)0.64134 (17)0.0411 (5)
H210.4502130.0704070.6659010.049*
C220.2930 (3)0.10924 (18)0.57636 (16)0.0430 (5)
H220.2759250.0312030.5565430.052*
C230.5371 (2)0.28117 (18)0.73810 (17)0.0405 (5)
C240.7335 (3)0.1562 (2)0.9060 (2)0.0587 (7)
C250.6514 (4)0.0440 (2)0.9189 (2)0.0685 (9)
H25A0.6987970.003690.9665350.103*
H25B0.5508610.0612860.9319740.103*
H25C0.6516950.0054470.8663720.103*
C260.8651 (4)0.1869 (3)0.9665 (3)0.0792 (10)
H26A0.8961880.2675190.9573940.095*
H26B0.8361780.1832451.0264260.095*
C27A0.9875 (6)0.1110 (6)0.9547 (4)0.108 (2)0.773 (9)
H27A1.0682480.1351480.9951750.161*0.773 (9)
H27B0.9584890.0311880.9649480.161*0.773 (9)
H27C1.0185480.115530.8958610.161*0.773 (9)
C27B0.988 (2)0.239 (3)0.932 (2)0.164 (10)0.227 (9)
H27D1.0637970.2542990.9774890.246*0.227 (9)
H27E1.0252030.1875170.8872170.246*0.227 (9)
H27F0.9592340.3127070.9069150.246*0.227 (9)
C280.1528 (2)0.21103 (17)0.31637 (15)0.0359 (5)
C290.2306 (3)0.30216 (18)0.28099 (18)0.0444 (6)
C300.3371 (3)0.2784 (2)0.2164 (2)0.0506 (6)
H300.3931050.3397040.1938440.061*
C310.3626 (3)0.1658 (2)0.18448 (19)0.0472 (6)
H310.4351070.1505530.1397090.057*
C320.2823 (2)0.07531 (17)0.21785 (15)0.0374 (5)
C330.1794 (2)0.09764 (17)0.28375 (14)0.0342 (4)
H330.1258510.0356390.3073250.041*
C340.0415 (3)0.23411 (18)0.38673 (15)0.0394 (5)
N10.2889 (2)0.68817 (15)0.46199 (11)0.0370 (4)
N20.0756 (2)0.66280 (16)0.20764 (14)0.0439 (5)
N30.1888 (3)0.6817 (2)0.1479 (2)0.0776 (9)
N40.2149 (2)0.19217 (15)0.53972 (13)0.0401 (4)
N50.5822 (2)0.20013 (16)0.79252 (15)0.0432 (5)
N60.7001 (2)0.22903 (18)0.84909 (16)0.0526 (6)
O10.08959 (17)0.84598 (13)0.26287 (12)0.0440 (4)
O20.49050 (19)0.65507 (13)0.58071 (10)0.0423 (4)
H2B0.4234950.6708140.5445970.063*
O30.51263 (19)0.84794 (13)0.59033 (11)0.0456 (4)
O40.7059 (2)0.94157 (13)0.69790 (14)0.0548 (5)
H4A0.6440750.9385170.6562750.082*
O50.81552 (18)0.50542 (12)0.81722 (10)0.0380 (4)
O60.58774 (19)0.37970 (14)0.74097 (14)0.0543 (5)
O70.0166 (2)0.14267 (13)0.41965 (10)0.0448 (4)
H70.0801140.1631810.4580940.067*
O80.0078 (2)0.33425 (13)0.41276 (11)0.0479 (4)
O90.2047 (2)0.41438 (14)0.30888 (16)0.0575 (5)
O100.31118 (18)0.03452 (13)0.18240 (12)0.0434 (4)
C9A0.4007 (9)0.6164 (8)0.0684 (6)0.061 (3)0.375 (10)
H9AA0.4562090.5426740.0693610.074*0.375 (10)
H9AB0.4444970.6749630.1068750.074*0.375 (10)
C10A0.3944 (13)0.6563 (13)0.0178 (11)0.099 (5)0.375 (10)
H10D0.3553350.5950550.0548620.149*0.375 (10)
H10E0.3312150.7251780.0172860.149*0.375 (10)
H10F0.4924910.675740.0397290.149*0.375 (10)
H2A0.020 (3)0.600 (2)0.2030 (16)0.044 (7)*
H5B0.742 (3)0.460 (3)0.7997 (19)0.061 (9)*
H5A0.526 (4)0.137 (3)0.798 (2)0.075 (10)*
H90.134 (5)0.409 (4)0.349 (3)0.127 (19)*
H100.239 (4)0.082 (3)0.207 (2)0.088 (12)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0562 (14)0.0226 (9)0.0405 (11)0.0040 (9)0.0094 (10)0.0040 (8)
C20.0423 (11)0.0194 (9)0.0440 (11)0.0030 (8)0.0112 (9)0.0006 (8)
C30.0279 (9)0.0205 (8)0.0426 (11)0.0002 (7)0.0084 (8)0.0016 (7)
C40.0312 (10)0.0189 (8)0.0445 (11)0.0001 (7)0.0042 (8)0.0002 (7)
C50.0351 (10)0.0232 (9)0.0413 (11)0.0015 (7)0.0046 (8)0.0025 (8)
C60.0260 (9)0.0240 (9)0.0542 (12)0.0000 (7)0.0027 (8)0.0049 (8)
C70.079 (2)0.0343 (13)0.088 (2)0.0137 (13)0.0413 (17)0.0059 (13)
C80.082 (2)0.0470 (15)0.0618 (17)0.0132 (14)0.0140 (15)0.0107 (13)
C90.061 (3)0.050 (3)0.049 (3)0.003 (2)0.015 (2)0.002 (2)
C100.084 (4)0.072 (4)0.061 (3)0.034 (3)0.028 (3)0.019 (3)
C110.0362 (10)0.0217 (9)0.0433 (11)0.0021 (7)0.0127 (9)0.0043 (8)
C120.0391 (11)0.0177 (9)0.0670 (15)0.0003 (8)0.0160 (10)0.0042 (9)
C130.0375 (12)0.0206 (9)0.0765 (17)0.0053 (8)0.0063 (11)0.0077 (10)
C140.0366 (11)0.0285 (10)0.0609 (14)0.0004 (8)0.0001 (10)0.0061 (9)
C150.0353 (10)0.0207 (9)0.0454 (11)0.0022 (7)0.0065 (9)0.0010 (8)
C160.0363 (10)0.0188 (8)0.0409 (10)0.0005 (7)0.0085 (8)0.0002 (7)
C170.0461 (12)0.0264 (10)0.0420 (11)0.0065 (8)0.0156 (9)0.0077 (8)
C180.0384 (11)0.0240 (9)0.0521 (13)0.0012 (8)0.0112 (9)0.0034 (8)
C190.0325 (10)0.0203 (9)0.0599 (13)0.0018 (7)0.0092 (9)0.0025 (8)
C200.0283 (10)0.0203 (9)0.0622 (14)0.0010 (7)0.0111 (9)0.0056 (8)
C210.0371 (11)0.0210 (9)0.0670 (15)0.0033 (8)0.0162 (10)0.0031 (9)
C220.0515 (14)0.0219 (9)0.0568 (14)0.0028 (9)0.0186 (11)0.0025 (9)
C230.0272 (10)0.0242 (10)0.0710 (15)0.0001 (8)0.0059 (10)0.0094 (9)
C240.0481 (15)0.0388 (13)0.090 (2)0.0071 (11)0.0034 (14)0.0163 (13)
C250.070 (2)0.0406 (14)0.095 (2)0.0018 (13)0.0085 (17)0.0245 (15)
C260.0548 (18)0.0601 (19)0.121 (3)0.0008 (14)0.0222 (18)0.0203 (19)
C27A0.073 (3)0.102 (5)0.141 (5)0.020 (3)0.035 (3)0.012 (4)
C27B0.123 (16)0.15 (2)0.23 (2)0.035 (14)0.033 (15)0.029 (18)
C280.0381 (11)0.0217 (9)0.0493 (12)0.0007 (8)0.0181 (9)0.0002 (8)
C290.0423 (12)0.0195 (9)0.0737 (16)0.0003 (8)0.0236 (11)0.0043 (9)
C300.0376 (12)0.0274 (11)0.0890 (19)0.0049 (9)0.0128 (12)0.0173 (11)
C310.0340 (11)0.0331 (11)0.0755 (17)0.0022 (9)0.0033 (11)0.0152 (11)
C320.0324 (10)0.0243 (9)0.0562 (13)0.0017 (8)0.0072 (9)0.0035 (9)
C330.0339 (10)0.0210 (9)0.0488 (12)0.0001 (7)0.0114 (9)0.0022 (8)
C340.0510 (13)0.0240 (9)0.0446 (12)0.0058 (9)0.0204 (10)0.0036 (8)
N10.0463 (10)0.0283 (9)0.0368 (9)0.0069 (7)0.0054 (8)0.0010 (7)
N20.0381 (10)0.0248 (9)0.0662 (13)0.0025 (7)0.0114 (9)0.0091 (8)
N30.0660 (16)0.0400 (12)0.119 (2)0.0099 (11)0.0517 (16)0.0155 (13)
N40.0460 (11)0.0268 (9)0.0483 (10)0.0054 (7)0.0136 (8)0.0004 (7)
N50.0358 (10)0.0251 (9)0.0693 (13)0.0005 (7)0.0021 (9)0.0120 (8)
N60.0353 (10)0.0390 (11)0.0839 (16)0.0011 (8)0.0041 (10)0.0178 (10)
O10.0360 (8)0.0258 (7)0.0684 (11)0.0074 (6)0.0066 (7)0.0091 (7)
O20.0569 (10)0.0297 (8)0.0402 (8)0.0081 (7)0.0009 (7)0.0035 (6)
O30.0568 (10)0.0285 (8)0.0539 (10)0.0121 (7)0.0133 (8)0.0144 (7)
O40.0524 (11)0.0180 (7)0.0956 (15)0.0001 (7)0.0130 (10)0.0095 (8)
O50.0407 (8)0.0225 (7)0.0498 (9)0.0005 (6)0.0052 (7)0.0021 (6)
O60.0416 (9)0.0256 (8)0.0951 (14)0.0106 (7)0.0117 (9)0.0181 (8)
O70.0642 (11)0.0259 (7)0.0438 (9)0.0065 (7)0.0033 (8)0.0013 (6)
O80.0626 (11)0.0245 (7)0.0569 (10)0.0098 (7)0.0181 (8)0.0092 (7)
O90.0582 (12)0.0171 (7)0.0991 (16)0.0008 (7)0.0220 (11)0.0012 (8)
O100.0389 (9)0.0258 (7)0.0644 (11)0.0019 (6)0.0071 (8)0.0010 (7)
C9A0.052 (5)0.080 (6)0.050 (5)0.005 (4)0.005 (4)0.025 (4)
C10A0.073 (7)0.097 (10)0.131 (12)0.001 (6)0.001 (7)0.059 (9)
Geometric parameters (Å, º) top
C1—N11.334 (3)C22—H220.95
C1—C21.376 (3)C23—O61.224 (3)
C1—H10.95C23—N51.345 (3)
C2—C31.390 (3)C24—N61.278 (3)
C2—H20.95C24—C251.519 (4)
C3—C41.391 (3)C24—C261.526 (4)
C3—C61.492 (3)C25—H25A0.98
C4—C51.379 (3)C25—H25B0.98
C4—H40.95C25—H25C0.98
C5—N11.342 (3)C26—C27B1.419 (11)
C5—H50.95C26—C27A1.450 (6)
C6—O11.222 (2)C26—H26A0.99
C6—N21.350 (3)C26—H26B0.99
C7—N31.268 (4)C27A—H27A0.98
C7—C81.456 (4)C27A—H27B0.98
C7—C91.506 (5)C27A—H27C0.98
C7—C9A1.667 (9)C27B—H27D0.98
C8—H8A0.98C27B—H27E0.98
C8—H8B0.98C27B—H27F0.98
C8—H8C0.98C28—C291.397 (3)
C9—C101.496 (8)C28—C331.400 (3)
C9—H9A0.99C28—C341.475 (3)
C9—H9B0.99C29—O91.365 (3)
C10—H10A0.98C29—C301.385 (4)
C10—H10B0.98C30—C311.387 (3)
C10—H10C0.98C30—H300.95
C11—C121.401 (3)C31—C321.391 (3)
C11—C161.402 (3)C31—H310.95
C11—C171.471 (3)C32—C331.376 (3)
C12—O41.363 (2)C32—O101.381 (3)
C12—C131.381 (4)C33—H330.95
C13—C141.387 (3)C34—O81.241 (2)
C13—H130.95C34—O71.303 (3)
C14—C151.388 (3)N2—N31.386 (3)
C14—H140.95N2—H2A0.89 (3)
C15—C161.378 (3)N5—N61.391 (3)
C15—O51.382 (2)N5—H5A0.90 (4)
C16—H160.95O2—H2B0.84
C17—O31.245 (2)O4—H4A0.84
C17—O21.302 (3)O5—H5B0.88 (3)
C18—N41.341 (3)O7—H70.84
C18—C191.373 (3)O9—H90.88 (5)
C18—H180.95O10—H100.95 (4)
C19—C201.395 (3)C9A—C10A1.446 (18)
C19—H190.95C9A—H9AA0.99
C20—C211.390 (3)C9A—H9AB0.99
C20—C231.491 (3)C10A—H10D0.98
C21—C221.371 (4)C10A—H10E0.98
C21—H210.95C10A—H10F0.98
C22—N41.334 (3)
N1—C1—C2122.84 (19)N5—C23—C20117.07 (19)
N1—C1—H1118.6N6—C24—C25125.4 (3)
C2—C1—H1118.6N6—C24—C26116.5 (3)
C1—C2—C3119.01 (19)C25—C24—C26118.1 (3)
C1—C2—H2120.5C24—C25—H25A109.5
C3—C2—H2120.5C24—C25—H25B109.5
C2—C3—C4118.4 (2)H25A—C25—H25B109.5
C2—C3—C6123.74 (18)C24—C25—H25C109.5
C4—C3—C6117.78 (17)H25A—C25—H25C109.5
C5—C4—C3118.75 (18)H25B—C25—H25C109.5
C5—C4—H4120.6C27B—C26—C24118.2 (14)
C3—C4—H4120.6C27A—C26—C24113.4 (4)
N1—C5—C4122.76 (19)C27A—C26—H26A108.9
N1—C5—H5118.6C24—C26—H26A108.9
C4—C5—H5118.6C27A—C26—H26B108.9
O1—C6—N2123.0 (2)C24—C26—H26B108.9
O1—C6—C3120.31 (19)H26A—C26—H26B107.7
N2—C6—C3116.69 (18)C26—C27A—H27A109.5
N3—C7—C8126.1 (3)C26—C27A—H27B109.5
N3—C7—C9121.6 (3)H27A—C27A—H27B109.5
C8—C7—C9111.3 (3)C26—C27A—H27C109.5
N3—C7—C9A105.9 (4)H27A—C27A—H27C109.5
C8—C7—C9A123.6 (4)H27B—C27A—H27C109.5
C7—C8—H8A109.5C26—C27B—H27D109.5
C7—C8—H8B109.5C26—C27B—H27E109.5
H8A—C8—H8B109.5H27D—C27B—H27E109.5
C7—C8—H8C109.5C26—C27B—H27F109.5
H8A—C8—H8C109.5H27D—C27B—H27F109.5
H8B—C8—H8C109.5H27E—C27B—H27F109.5
C10—C9—C7115.1 (4)C29—C28—C33119.6 (2)
C10—C9—H9A108.5C29—C28—C34120.31 (19)
C7—C9—H9A108.5C33—C28—C34120.1 (2)
C10—C9—H9B108.5O9—C29—C30119.1 (2)
C7—C9—H9B108.5O9—C29—C28121.5 (2)
H9A—C9—H9B107.5C30—C29—C28119.4 (2)
C9—C10—H10A109.5C29—C30—C31120.6 (2)
C9—C10—H10B109.5C29—C30—H30119.7
H10A—C10—H10B109.5C31—C30—H30119.7
C9—C10—H10C109.5C30—C31—C32120.1 (2)
H10A—C10—H10C109.5C30—C31—H31119.9
H10B—C10—H10C109.5C32—C31—H31119.9
C12—C11—C16119.4 (2)C33—C32—O10122.89 (19)
C12—C11—C17120.30 (18)C33—C32—C31119.7 (2)
C16—C11—C17120.32 (19)O10—C32—C31117.4 (2)
O4—C12—C13119.1 (2)C32—C33—C28120.5 (2)
O4—C12—C11121.4 (2)C32—C33—H33119.7
C13—C12—C11119.49 (19)C28—C33—H33119.7
C12—C13—C14120.6 (2)O8—C34—O7122.9 (2)
C12—C13—H13119.7O8—C34—C28121.6 (2)
C14—C13—H13119.7O7—C34—C28115.43 (18)
C13—C14—C15120.3 (2)C1—N1—C5118.24 (19)
C13—C14—H14119.8C6—N2—N3118.15 (19)
C15—C14—H14119.8C6—N2—H2A119.9 (17)
C16—C15—O5122.69 (18)N3—N2—H2A121.0 (17)
C16—C15—C14119.58 (19)C7—N3—N2117.1 (2)
O5—C15—C14117.7 (2)C22—N4—C18118.3 (2)
C15—C16—C11120.56 (19)C23—N5—N6117.11 (19)
C15—C16—H16119.7C23—N5—H5A120 (2)
C11—C16—H16119.7N6—N5—H5A122 (2)
O3—C17—O2122.6 (2)C24—N6—N5116.7 (2)
O3—C17—C11122.0 (2)C17—O2—H2B109.5
O2—C17—C11115.34 (17)C12—O4—H4A109.5
N4—C18—C19122.9 (2)C15—O5—H5B106 (2)
N4—C18—H18118.6C34—O7—H7109.5
C19—C18—H18118.6C29—O9—H9103 (3)
C18—C19—C20118.57 (19)C32—O10—H10106 (2)
C18—C19—H19120.7C10A—C9A—C7101.5 (8)
C20—C19—H19120.7C10A—C9A—H9AA111.5
C21—C20—C19118.4 (2)C7—C9A—H9AA111.5
C21—C20—C23123.8 (2)C10A—C9A—H9AB111.5
C19—C20—C23117.71 (18)C7—C9A—H9AB111.5
C22—C21—C20119.0 (2)H9AA—C9A—H9AB109.3
C22—C21—H21120.5C9A—C10A—H10D109.5
C20—C21—H21120.5C9A—C10A—H10E109.5
N4—C22—C21122.9 (2)H10D—C10A—H10E109.5
N4—C22—H22118.6C9A—C10A—H10F109.5
C21—C22—H22118.6H10D—C10A—H10F109.5
O6—C23—N5123.0 (2)H10E—C10A—H10F109.5
O6—C23—C20119.9 (2)
N1—C1—C2—C30.1 (3)N6—C24—C26—C27B39.4 (16)
C1—C2—C3—C40.9 (3)C25—C24—C26—C27B141.7 (16)
C1—C2—C3—C6177.54 (19)N6—C24—C26—C27A112.4 (5)
C2—C3—C4—C51.4 (3)C25—C24—C26—C27A68.7 (5)
C6—C3—C4—C5178.25 (18)C33—C28—C29—O9177.8 (2)
C3—C4—C5—N11.0 (3)C34—C28—C29—O91.3 (3)
C2—C3—C6—O1153.6 (2)C33—C28—C29—C302.5 (3)
C4—C3—C6—O123.1 (3)C34—C28—C29—C30178.4 (2)
C2—C3—C6—N225.0 (3)O9—C29—C30—C31177.7 (2)
C4—C3—C6—N2158.3 (2)C28—C29—C30—C312.6 (4)
N3—C7—C9—C104.3 (7)C29—C30—C31—C320.8 (4)
C8—C7—C9—C10164.9 (5)C30—C31—C32—C331.2 (4)
C16—C11—C12—O4177.7 (2)C30—C31—C32—O10179.0 (2)
C17—C11—C12—O41.4 (3)O10—C32—C33—C28178.92 (19)
C16—C11—C12—C132.2 (3)C31—C32—C33—C281.2 (3)
C17—C11—C12—C13178.6 (2)C29—C28—C33—C320.6 (3)
O4—C12—C13—C14177.7 (2)C34—C28—C33—C32179.67 (19)
C11—C12—C13—C142.3 (4)C29—C28—C34—O84.4 (3)
C12—C13—C14—C150.2 (4)C33—C28—C34—O8174.6 (2)
C13—C14—C15—C161.8 (3)C29—C28—C34—O7174.84 (19)
C13—C14—C15—O5178.7 (2)C33—C28—C34—O76.1 (3)
O5—C15—C16—C11178.74 (18)C2—C1—N1—C50.5 (3)
C14—C15—C16—C111.8 (3)C4—C5—N1—C10.0 (3)
C12—C11—C16—C150.2 (3)O1—C6—N2—N32.9 (4)
C17—C11—C16—C15179.35 (19)C3—C6—N2—N3175.6 (2)
C12—C11—C17—O34.1 (3)C8—C7—N3—N24.9 (6)
C16—C11—C17—O3175.05 (19)C9—C7—N3—N2172.5 (4)
C12—C11—C17—O2175.17 (19)C9A—C7—N3—N2152.1 (5)
C16—C11—C17—O25.7 (3)C6—N2—N3—C7179.9 (3)
N4—C18—C19—C200.7 (3)C21—C22—N4—C180.4 (3)
C18—C19—C20—C211.0 (3)C19—C18—N4—C220.0 (3)
C18—C19—C20—C23177.6 (2)O6—C23—N5—N65.6 (4)
C19—C20—C21—C220.7 (3)C20—C23—N5—N6173.0 (2)
C23—C20—C21—C22177.1 (2)C25—C24—N6—N52.7 (5)
C20—C21—C22—N40.0 (3)C26—C24—N6—N5178.5 (3)
C21—C20—C23—O6155.2 (2)C23—N5—N6—C24173.4 (3)
C19—C20—C23—O621.2 (3)N3—C7—C9A—C10A106.4 (9)
C21—C20—C23—N523.4 (3)C8—C7—C9A—C10A95.9 (9)
C19—C20—C23—N5160.2 (2)
Cocrystals of izact and izbt that share the same coformer. The crystal structure similarity tool of Mercury (Macrae et al., 2020) was used to help determine if related structures were isostructural top
Coformerizact refcodeizbt refcodeIsostructural
4-tert-Butylbenzoic acidGIYMAFGIYMEJYes
2-Hydroxybenzoic acid (salicylic acid)*LATLAVUBILAWNo
3-Hydroxybenzoic acid (anhydrous)FADHUPFADHOJNo
3-Hydroxybenzoic acid hydrateSAYPITSAYPOZYes
4-Nitrobenzoic acidXOPYEJXOPYUZYes
Note: (*) it should be noted that the unit-cell parameters of both structures are similar but the orientation of the molecules with respect to the unit cells differ significantly.
Onset temperatures and associated enthalpies for the DSC curves of the cocrystals presented in this work, as well as the melting points and entahlpies of some of the comparison cocrystals top
Thermal eventOnset (°C)Enthalpy (J g-1)Enthalpy (kJ mol-1)
izact1-nta melting/decomposition106.1 ± 0.5170.9 ± 5.259.7 ± 2
izbt1-nta melting/decomposition89.5± 0.1167.8± 2.561.0 ± 1
izbt2c4n melting/decomposition102.1 ± 0.2100.6 ± 2.339.5 ± 1
izbt2,4-dhba melting/decomposition174.8± 0.2226.3 ± 4.378.2 ± 1
izbt2,5-dhba melting/decomposition151.2 ± 0.2132.5 ± 3.245.8 ± 1
izact m.p. (Lemmerer, 2012)160.029.7
izact2c4n m.p. (Lemmerer, 2012)93.433.4
 

Acknowledgements

The authors acknowledge and thank the DSI/NRF Centre of Excellence in Strong Materials, as well as the NRF, for funding the Bruker D2 Phaser diffractometer.

References

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