Design of a series of cocrystals featuring isoniazid modified with diacetone alcohol

Scheepers, M.C.; Lemmerer, A.

doi:10.1107/S2052520622009532

research papers

STRUCTURAL SCIENCE
CRYSTAL ENGINEERING
MATERIALS

ISSN: 2052-5206

Volume 78| Part 6| December 2022| Pages 857-867

https://doi.org/10.1107/S2052520622009532

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Design of a series of cocrystals featuring isoniazid modified with diacetone alcohol

Matthew Clarke Scheepers ^a and Andreas Lemmerer ^a ^*

^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 A. Nangia, CSIR–National Chemical Laboratory, India (Received 25 July 2022; accepted 27 September 2022; online 8 November 2022)

Eight cocrystals containing an isoniazid derivative derivatized with diacetone alcohol [N′-[(2E)-4-hydroxy-4-methylpentan-2-ylidene]pyridine-4-carbohydrazide, iz4h4m2p] were synthesized and characterized. All coformers used in this work feature at least one carboxylic acid functional group. These coformers include: succinic acid, 3,5-dinitrobenzoic acid, 4-nitrobenzoic acid, 2-chloro-4-nitrobenzoic acid, 2,5-dihydroxybenzoic acid, 3-hydroxybenzoic acid, 4-hydroxybenzoic acid and cinammic acid. Crystal structures were obtained using single crystal X-ray diffraction, which shows that cocrystals containing iz4h4m2p feature a similar chain hydrogen bond between molecules of iz4h4m2p in addition to the expected carboxylic acid⋯pyridine hydrogen-bond interaction. Differences between the structures arise when additional hydroxyl group(s) are present, such as the case featuring the hydroxybenzoic acids. These structures are compared to their isoniazid counterparts presented previously in the literature. All cocrystals were also characterized with differential scanning calorimetry and Fourier transform infrared spectroscopy.

Keywords: isoniazid; cocrystal; covalent-assisted supramolecular synthesis; crystal structure; pharmaceutical.

CCDC references: 2177244; 2177245; 2177246; 2177247; 2177248; 2177249; 2177250; 2177251

1. Introduction

Isoniazid or isonicotinic acid hydrazide (inh) is an antibacterial prodrug, often used together with a combination of other drugs as part of an effective treatment for tuberculosis (TB). Originally it was combined with p-aminosalicylic acid and streptomycin (Iseman, 2002 ). inh itself is a fairly simple prodrug molecule consisting of primarily a pyridine ring and a hydrazine group. It is converted into the active isonicotinic acyl radical form by the catalase–peroxidase enzyme KatG present in Mycobacterium tuberculosis (de Faria et al., 2021 ). When treating TB, a single oral dose which contains all the necessary active pharmaceutical ingredients (APIs) in a fixed-dose combination (FDC) is preferred. However, it is known that inh can degrade in the presence of other APIs (Bhutani et al., 2004 ; Diniz et al., 2018 ). As such, this proves to be problematic. Several different strategies can be used to solve this problem.

One of these potential solutions is to use cocrystals. Although no universal agreement of the exact definition of a cocrystal exists, several proposed definitions are available. The definition of a cocrystal proposed by the FDA is: `Solids that are crystalline materials composed of two or more molecules in the same crystal lattice.' (Aitipamula et al., 2012 ). Aitipamula et al. (2012) proposed several different definitions that included the presence of ions to avoid separating cocrystals and salts from falling under different regulations. Grothe et al. (2016 ) proposed that a cocrystal is a `crystal with a coformer molecule plus either another coformer or at least two ions' with further classifications into different classes. Cocrystals offer the advantage in that the intermolecular interactions between API and coformer can be planned, in addition to the opportunity to patent new intellectual properties (Oruganti et al., 2016 ). Cocrystals can potentially offer the advantage of improved properties such as solubility, bioavailability and dissolution rates over the pure material (Blagden et al., 2007 ; Ganie et al., 2022 ). For pharmaceutical cocrystals the ideal strategy is to use a Generally Regarded As Safe (GRAS) or a pharmaceutically-accepted compound which can form complementary hydrogen bonds with the targeted API (Trask, 2007 ). However, in practise, this strategy may prove difficult, as the number of suitable GRAS or pharmaceutically acceptable compounds that could be used is limited. Even if a potentially suitable conformer is found, cocrystallization may not occur due to unknown factors such as kinetic and/or thermodynamic barriers (Bučar et al., 2013 ). Therefore, it becomes imperative to explore the structural landscape of new and already existing APIs.

One approach to finding a product with improved properties is to modify an already existing API. Although modifying an API would involve starting clinical trials from scratch, it may prove worthwhile in the long term if the modified API is better than the original form. From a crystal engineering perspective, the modification is a crystal engineering opportunity that can either simplify complex intermolecular interactions or introduce functional groups that can become involved in new intermolecular interactions. For inh the hydrazine group is targeted because it can be easily modified (Hearn & Cynamon, 2004 ). One of these modifications involves a Schiff-base condensation reaction between inh and a ketone or aldehyde of choice. In particular, derivatives using 2-propanone (Wang et al., 2008 ; Lemmerer, 2012 ; Oruganti et al., 2016; Boles et al., 2021 ) or 2-butanone (Lemmerer et al., 2011 ; Madeley et al., 2019 ; Setshedi & Smith, 2021 ) as the ketones and aldehydes (Ganie et al., 2022) including salinazid (Surov et al., 2016 ) have been reported in the literature in crystal engineering studies. This changes the hydrazide group to an amide and an imine group. From a crystal engineering perspective, these modified inh can have a reduced number of hydrogen bond donors. Although this may reduce the chances of forming a cocrystal since the only hydrogen pair donor remaining will be the amide and hydrogen bond acceptors will be the oxygen from the amide and the pyridine ring; however, this should not be a big problem, as carboxylic acids have been shown to form a robust interaction with pyridines (either a hydrogen bond or a proton transfer) very easily (Shattock et al., 2008 ).

In a previous work (Scheepers et al., 2022 ), we presented N′-[(2E)-4-hydroxy-4-methylpentan-2-ylidene]pyridine-4-carbohydrazide (iz4h4m2p), which is inh derivatized using diacetone alcohol (4-hydroxy-4-methyl-2-pentanone) via a Schiff-base condensation reaction. This ketone consists of a five carbon length alkyl chain with an extra methyl group and a hydroxyl group. This compound was determined to be polymorphic in our previous study (Scheepers et al., 2022), consisting of a metastable form, form I and a stable form, form II (Scheepers et al., 2022). The major difference between the two forms is the different hydrogen bonding present in each form: form I forms a chain hydrogen-bond motif between the hydroxyl group to the oxygen atom from the amide group from a neighbouring iz4h4m2p molecule, while form II forms a ring hydrogen-bond motif where the hydroxyl group forms a hydrogen bond to the pyridine ring, which subsequently combines to form dimers (Fig. 1). Like the other hydrazone derivatives of inh mentioned, iz4h4m2p still features a bulky alkyl chain backbone. However, the newly introduced hydroxyl group should allow for some variation from the previously observed cocrystals of the hydrazone derivatives of inh. Since iz4h4m2p contains a pyridine, it should readily interact with molecules containing a carboxylic acid group. This interaction can potentially reduce the supramolecular assembly from 2D sheets to a 1D ribbon (Lemmerer et al., 2011). This increases the chances of forming cocrystals with more predictable supramolecular assemblies.

Figure 1
The structures of iz4h4m2p and the different hydrogen-bonding schemes between (a) form I and (b) form II.

So far, only one cocrystal containing iz4h4m2p has been reported (Madeley et al., 2019) and it contained 4-tert-butylbenzoic acid. This cocrystal consists of a hydrogen bond formed between the pyridine ring of iz4h4m2p and the carboxylic acid group, while a chain hydrogen-bond motif exists between the hydroxyl group of the iz4h4m2p molecule to the oxygen of the amide group from a neighbouring iz4h4m2p molecule. Based on this, would other iz4h4m2p cocrystals with carboxylic acid coformers form similar structures with similar hydrogen-bond motifs? Will additional hydrogen-bond donors/acceptors from the coformers have a considerable effect on the structure of these cocrystals? Hence, the objective for this work is to explore the multicomponent crystal landscape of iz4h4m2p. This involves designing and synthesizing cocrystals of iz4h4m2p with coformers containing the carboxylic acid group.

2. Experimental

2.1. Materials

All materials were purchased from Sigma-Aldrich and were used as is without further purification.

2.2. General procedure for synthesis of iz4h4m2p and its cocrystals

iz4h4m2p was synthesized using a previously described method. inh and diacetone alcohol were dissolved in absolute ethanol (5 ml) in a small glass vial containing a magnetic stirrer bar. This vial was closed and stirred for 24 h at room temperature (∼295–300 K). After which, the lid of the vial was replaced with another lid with a small hole in it to allow solvent to evaporate out. After several days crystals of iz4h4m2p were obtained. These crystals were of form II.

The general procedure for the synthesizing cocrystals was as follows: stoichiometric amounts of iz4h4m2p and the respective coformer were dissolved in an appropriate solvent/solvent combination in a small glass vial at room temperature. The vial is closed using a lid with a small hole in it to allow solvent to evaporate out. Crystals are obtained after several days.

2.3. Powder X-ray diffraction

Powder X-ray diffraction (PXRD) is 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 LynxEye PSD detector in Bragg–Brentano geometry. 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 SC-XRD data.

2.4. Single crystal X-ray diffraction

A Bruker D8 Venture Photon CMOS 100 area detector diffractometer, equipped with a graphite-monochromated Mo Kα₁ (λ = 0.71073 Å) sealed tube (50 kV, 30 mA), was used to collect all the intensity data. Crystal structures were determined at 173 K. The program SAINT+ (version 6.02) (Bruker, 2012 ) was used to integrate the data and the program SADABS (Krause et al., 2015 ) was used to make empirical absorption corrections. Space group assignments were made using XPREP (Bruker, 2012) for all compounds. In all cases except for the case of iz4h4m2p + 4hba, the structures were solved in the WinGX suite of programs (Farrugia, 1999 ) by intrinsic phasing using SHELXT (Sheldrick, 2015 ) and refined using full-matrix least-squares/difference Fourier techniques on F² using SHELXL (Sheldrick, 2018 ). All non-hydrogen atoms were refined anisotropically. All carbon-bound hydrogen atoms were placed at idealized positions and refined as riding atoms with the U_iso parameter 1.2 or 1.5 times that of their parent atoms. Nitrogen-bound and oxygen-bound hydrogen atoms were located in a difference Fourier map and their coordinates and isotropic displacement parameters refined freely. Olex2 (version 1.3) (Dolomanov et al., 2009 ) was used to solve the disordered system of iz4h4m2p + 4hba. Diagrams and publication material were generated using ORTEP-3 (Farrugia, 2012 ) and MERCURY (Macrae et al., 2020 ). The crystallographic information can be found in Table 1.

Table 1
Coformers, molar ratios and solvent systems used to synthesize cocrystals presented in this work

3hba: 3-hydroxybenzoic acid, 4hba: 4-hydroxybenzoic acid, 2,5hba: 2,5-dihydroxybenzoic acid, 2c4n: 2-chloro-4-nitrobenzoic acid, 4nba: 4-nitrobenzoic acid, dnba: 3,5-dinitrobenzoic acid, ca: cinammic acid, sa: succinic acid.

Coformer	Molar ratio (iz4h4m2p:coformer)	Solvent system
3hba	1:1	Ethanol
4hba	1:1	Ethanol
2,5-dhba	1:1	Methanol or 1:1 v/v methanol : acetonitrile
2c4n	1:1	Ethanol
4nba	1:1	Ethanol
dnba	1:1	Ethanol
ca	1:1	Methanol
sa	2:1	Ethanol

2.5. The Cambridge Structural Database

The Cambridge Structural Database (CSD version 2022.1.0) (Groom et al., 2016 ) was used to compare the cocrystals presented in this work with the cocrystals of inh, as well as the cocrystals of any notable inh derivative. The only restriction was that entries must be classified as being organic. MERCURY (Macrae et al., 2020) was used to inspect the crystal structures. The aromatic analyser tool of MERCURY was used to inspect the aromatic interactions of the aryl rings. The crystal structure similarity tool was used to compare the structural similarity of selected structures.

2.6. Differential scanning calorimetry

Differential scanning calorimetry (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 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 at 25°C at a heating or cooling rate of 10°C min⁻¹.

2.7. Fourier transform infrared analysis

FTIR spectra were collected using the Bruker Alpha II spectrometer equipped with an Eco-ATR sampling module. Background noise was subtracted and a small amount of the sample of interest was placed onto the ATR crystal. Spectra were measured in the 600 to 4000 cm⁻¹ range, resolution was 4 cm⁻¹ with 24 scans per sample. Spectra were collected in a room with air conditioning set at 295 K. After spectral acquisition the ATR crystal was cleaned using isopropanol.

3. Results and discussion

3.1. Obtaining cocrystals

In order to obtain cocrystals containing iz4h4m2p with molecules containing at least one carboxylic acid, several coformers were used. Most of these consist of Generally Regarded As Safe (GRAS) compounds, such as succinic acid (sa) and gentisic acid (2,5-dihydroxybenzoic acid, 2,5-dhba). These coformers include ones which have either one or two carboxylic acid groups. A full list of all the coformers used is included in the supporting information. For this work, we used various stoichiometric ratios such as 1:1, 2:1 and 1:2 of iz4h4m2p: coformer with different solvents (methanol, ethanol, acetonitrile, water) and solvent mixtures (1:1 ratios of solvent 1:solvent 2). It should be noted that we avoided heating the solution, as iz4h4m2p can decompose in a hot solution, resulting in an oil. Thus we relied on stirring the solution for 10–20 min at room temperature to ensure complete dissolution. Out of a list of 28 coformers used, only eight formed cocrystals. The reasons why we did not obtain more were due to the possibility that some of the acids still produced oils as opposed to crystals, while in other cases the coformers precipitated out separately without forming a cocrystal. The eight cocrystals that were synthesized used the following coformers: 3,5-dinitrobenzoic acid (dnba), succinic acid, 2,5-dhba, 3-hydroxybenzoic acid (3hba), 4-hydroxybenzoic acid (4hba), 4-nitrobenzoic acid (4nba), 2-chloro-4-nitrobenzoic acid (2c4n) and cinammic acid. The molar ratios and solvents used to synthesize these are presented in Table 1. The results are presented below in four separate sections because of some similarities and major differences between certain crystal structures and/or coformers. These sections are: (i) iz4h4m2p + sa and iz4h4m2p + ca, (ii) iz4h4m2p + dnba, iz4h4m2p + 2c4n and iz4h4m2p + 4nba, (iii) iz4h4m2p + 4hba, (iv) iz4h4m2p + 2,5-dhba and iz4h4m2p + 3hba. The reasoning for splitting these cocrystals into these sections is as follows: (i) it was suspected that iz4h4m2p + ca and iz4h4m2p + sa to have a similar hydrogen-bonding patterns due to the absence of additional hydrogen bond donors/acceptors, (ii)) in iz4h4m2p + dnba, iz4h4m2p + 2c4n, and iz4h4m2p + 4nba the coformers all feature a nitro group, which may or may not have had a significant impact on the crystal structure formation while (iii) and (iv) the additional hydrogen bond donors had a significant impact in the overall hydrogen bond interactions observed that made the structures unique in comparison to the structures described in (i) and (ii). The crystal structure information is presented in Table 2, while ORTEP diagrams are presented in Fig. 2. Graph sets have been used to describe some of the hydrogen bonding observed in the crystal structures (Etter et al., 1990 ).

Table 2
Crystallographic information for cocrystals presented in this work

For all structures: Mo Kα radiation, Bruker APEX-II CCD diffractometer, multi-scan absorption correction using SADABS (Krause et al., 2015). H atoms treated by a mixture of independent and constrained refinement.

	iz4h4m2p + 2c4n	iz4h4m2p + 3hba	iz4h4m2p + ca	iz4h4m2p + dnba
Crystal data
Chemical formula	C₁₂H₁₇N₃O₂·C₇H₄NO₄Cl	C₇H₆O₃·C₁₂H₁₇N₃O₂	C₁₂H₁₇N₃O₂·C₉H₈O₂	C₁₂H₁₇N₃O₂·C₇H₄N₂O₆
M_r	436.85	373.4	383.44	447.41
Crystal system, space group	Triclinic, $[P {\bar 1}]$	Monoclinic, P2₁/n	Triclinic, $[P{\bar 1}]$	Monoclinic, P2₁/n
Temperature (K)	173	173	173	173
a, b, c (Å)	7.0381 (1), 12.2643 (2), 12.4636 (2)	8.7472 (3), 16.9734 (5), 13.2480 (4)	6.9734 (3), 11.2540 (5), 13.4029 (6)	6.9538 (3), 18.9491 (8), 15.9042 (7)
α, β, γ (°)	103.215 (1), 97.797 (1), 93.497 (1)	90, 94.886 (1), 90	89.949 (2), 82.689 (2), 74.261 (2)	90, 99.261 (2), 90
V (Å³)	1032.92 (3)	1959.78 (11)	1003.55 (8)	2068.35 (15)
Z	2	4	2	4
μ (mm⁻¹)	0.23	0.09	0.09	0.11
Crystal size (mm)	0.52 × 0.25 × 0.21	0.59 × 0.48 × 0.22	0.37 × 0.18 × 0.10	0.39 × 0.29 × 0.13

Data collection
T_min, T_max	0.674, 0.746	0.686, 0.747	0.631, 0.746	0.699, 0.747
No. of measured, independent and observed I > 2σ(I)] reflections	49833, 7362, 4908	78332, 8649, 7062	47711, 4995, 4111	196011, 11136, 9039
R_int	0.039	0.033	0.078	0.082
(sin θ/λ)_max (Å⁻¹)	0.753	0.809	0.668	0.864

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.044, 0.117, 1.06	0.051, 0.145, 1.06	0.039, 0.107, 1.03	0.054, 0.140, 1.07
No. of reflections	7362	8649	4995	11136
No. of parameters	286	263	268	304
Δρ_max, Δρ_min (e Å⁻³)	0.42, −0.35	0.50, −0.20	0.25, −0.20	0.54, −0.30

	iz4h4m2p + sa	iz4h4m2p + 4nba	iz4h4m2p + 25dhba	iz4h4m2p + 4hba
Crystal data
Chemical formula	C₁₂H₁₇N₃O₂·C₂H₃O₂	C₁₂H₁₇N₃O₂·C₇H₅NO₄	C₁₂H₁₇N₃O₂·C₇H₆O₄	C₁₂H₁₆N₃O₂·2(C₇H₆O₃)
M_r	294.33	402.4	389.4	884.92
Crystal system, space group	Monoclinic, P2₁/c	Triclinic, $[P{\bar 1}]$	Monoclinic, P2₁/n	Monoclinic, C2/c
Temperature (K)	173	173	133	173
a, b, c (Å)	6.9773 (4), 20.6482 (11), 10.5035 (5)	6.8701 (3), 12.1647 (6), 12.1779 (6)	8.5777 (5), 17.5407 (9), 13.2200 (8)	41.700 (2), 8.2992 (4), 12.9536 (8)
α, β, γ (°)	90, 98.764 (2), 90	101.130 (2), 92.818 (2), 105.005 (2)	90, 96.605 (2), 90	90, 97.033 (2), 90
V (Å³)	1495.56 (14)	959.26 (8)	1975.86 (19)	4449.2 (4)
Z	4	2	4	4
μ (mm⁻¹)	0.10	0.11	0.10	0.09
Crystal size (mm)	0.52 × 0.23 × 0.07	0.57 × 0.42 × 0.11	0.58 × 0.49 × 0.27	0.55 × 0.26 × 0.14

Data collection
T_min, T_max	0.676, 0.746	0.642, 0.746	0.689, 0.746	0.600, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections	45682, 3733, 3131	42678, 5857, 4742	41489, 4917, 4391	54732, 5529, 5529
R_int	0.089	0.047	0.028	0.088
(sin θ/λ)_max (Å⁻¹)	0.668	0.715	0.668	0.667

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.044, 0.113, 1.03	0.045, 0.136, 1.07	0.038, 0.105, 0.99	0.056, 0.150, 1.04
No. of reflections	3733	5857	4917	5529
No. of parameters	205	277	273	352
Δρ_max, Δρ_min (e Å⁻³)	0.33, −0.21	0.34, −0.27	0.30, −0.21	0.29, −0.27
Computer programs: SAINT (v. 8.40B) (Bruker, 2016), SHELXT-2018/2 (Sheldrick, 2015), SHELXL2018/3 (Sheldrick, 2018), ORTEP for Windows (Farrugia, 2012), Olex2 (v. 1.3) (Dolomanov et al., 2009), WinGX publication routines (Farrugia, 2012).

Figure 2
ORTEP diagrams of (a) iz4h4m2p + 2c4n, (b) iz4h4m2p + 3hba, (c) iz4h4m2p + 4hba, (d) iz4h4m2p + 4nba, (e) iz4h4m2p + ca, (f) iz4h4m2p + dnba, (g) iz4h4m2p + sa and (h) iz4h4m2p + 2,5-dhba.

3.2. Crystal structures of iz4h4m2p + sa and iz4h4m2p + ca

iz4h4m2p formed cocrystals with succinic acid and cinammic acid, forming colourless needles and colourless plates, respectively. The asymmetric unit of iz4h4m2p + ca consists of one molecule each of iz4h4m2p and ca and crystallizes in space group $[P\overline 1]$ , while the asymmetric unit of iz4h4m2p + sa consists of one molecule of iz4h4m2p and half a molecule of succinic acid (which sits on a special crystallographic site), and crystallizes in space group P2₁/c. In each case the respective carboxylic acid forms a hydrogen bond with the pyridyl nitrogen of iz4h4m2p. Furthermore, this results in the hydroxyl group of iz4h4m2p forming a hydrogen bond with the oxygen of the amide from a neighbouring iz4h4m2p molecule, which forms a C₂²(6) chain hydrogen-bond motif similar to the one observed in form I of iz4h4m2p. Additionally, for iz4h4m2p + ca, π⋯π stacking exists between the rings of adjacent ca molecules and pyridine rings of iz4h4m2p (Cg⋯Cg = 4.01 Å). Although both crystal structures form 1D ribbons (Fig. 3), the packing between the two are different. The ribbons in iz4h4m2p + ca feature a more stacked or layered structure, with cinammic acid and iz4h4m2p separated by alternating layers [Figs. 4(a) and 4(b)], while the ribbons from the cocrystal of iz4h4m2p + sa form a zigzag pattern [Fig. 4(c)].

Figure 3
Hydrogen bonding in iz4h4m2p + ca which is the standard hydrogen-bonding scheme in most of the structures presented.

Figure 4
Crystal structure packing of (a) iz4h4m2p + ca (down the b-axis), (b) iz4h4m2p + ca (down the a-axis) and (c) iz4h4m2p + sa (down the a-axis). Iz4h4m2p molecules are presented in green while the respective coformers are in blue.

3.3. Crystal structures of iz4h4m2p + dnba, iz4h4m2p + 2c4n and iz4h4m2p + 4nba

iz4h4m2p formed cocrystals with dnba, 2c4n and 4nba, yielding colourless plates, colourless blocks and colourless plates, respectively. Each cocrystal contains one molecule of iz4h4m2p and one molecule of the respective coformer in the asymmetric unit. Both iz4h4m2p + 2c4n and iz4h4m2p + 4nba crystallize in space group $[P\overline 1]$ , while iz4h4m2p + dnba crystallizes in the space group P2₁/n. It should be noted that the cocrystals of iz4h4m2p + 2c4n and iz4h4m2p + 4nba share similar unit-cell parameters and the same space group, which would imply the structures may be isostructural. Using the crystal structure similarity tool and restricting the size of the cluster to 30 molecules, there is a strong correlation that shows that the two structures may be isostructural to a degree, as seen in Fig. 5(d), despite some deviations observed (such as, for example, some of the pyridine ring having different torsion angles). This slight difference is due to the presence of the chlorine atom in 2c4n. The major hydrogen bonding for all three structures is the same as the one described in the previously discussed structures: the carboxylic acid⋯pyridine ring hydrogen bond and the amide⋯hydroxyl⋯amide chain hydrogen bond. Nitro groups in all structures do not participate in any hydrogen bonding. π⋯π stacking exists between 2c4n molecules to 2c4n molecules and iz4h4m2p molecules to iz4h4m2p molecules in the structure of iz4h4m2p + 2c4n (2c4n⋯2c4n: Cg⋯Cg = 3.58 Å and iz4h4m2p⋯iz4h4m2p: Cg⋯Cg = 3.74 Å). A similar pattern of π⋯π stacking was observed for the structure of iz4h4m2p + 4nba (4nba⋯4nba: Cg⋯Cg = 3.66 Å and iz4h4m2p⋯iz4h4m2p: Cg⋯Cg = 3.81 Å). For iz4h4m2p + dnba, the only π⋯π stacking observed was between adjacent dnba molecules (Cg⋯Cg = 3.90 Å). The packing of iz4h4m2p + dnba, iz4h4m2p + 2c4n and iz4h4m2p + 4nba is similar: alternating rows of 1D ribbons formed from the chain hydrogen-bond motif [Figs. 5(a)–5(c)].

Figure 5
Crystal structure packing of (a) iz4h4m2p + 2c4n (viewed down the a-axis), (b) iz4h4m2p + 4nba (viewed down the a-axis), (c) iz4h4m2p + dnba (viewed down the a-axis). In (a)–(c) iz4h4m2p molecules are presented in green while the respective coformer is shown in blue. (d) The overlay of molecules from iz4h4m2p + 4nba (represented as green molecules) and iz4h4m2p + 2c4n (using standard colours).

3.4. Crystal structure of iz4h4m2p + 4hba

iz4h4m2p and 4hba formed a cocrystal, forming colourless plates. This cocrystal contains one molecule of iz4h4m2p and two molecules 4hba in the asymmetric unit and crystallizes in space group C2/c. One of the two molecules of 4hba, the one located at a special crystallographic site, is disordered. This causes the disordered 4hba molecule to exist in one of two possible orientations at these sites. To distinguish between the two 4hba molecules, they will be referred to as either the disordered or non-disordered 4hba molecule. Not all the hydrogens attached to an oxygen atom could be found precisely and were placed geometrically with respect to the oxygen atom. These hydrogen atoms are H3, H6 and H8. Like the previous structures, the hydroxyl group of iz4h4m2p forms a hydrogen bond to the oxygen of the amide group from a neighbouring iz4h4m2p molecule (O2—H2⋯O1), while the carboxylic acid group of the non-disordered 4hba molecule forms a hydrogen bond with the pyridine ring of iz4h2m2p. The hydroxyl group of the non-disordered 4hba molecule forms a hydrogen bond with one of the oxygen atoms of the carboxylic acid group from a neighbouring 4hba molecule (O5—H5A⋯O4) [Fig. 6(a)]. A π⋯π stacking interaction between the pyridine ring of iz4h4m2p and the aromatic ring of the non-disordered 4hba molecule is present (Cg⋯Cg = 3.695 Å). Due to the nature of the varied orientation of the disordered 4hba molecule and it sitting on an inversion site, two sets of almost identical hydrogen bonding are present. The hydrogen atoms from the carboxylic acid group (O6—H6) and the hydroxyl group (O8—H8) to the one nitrogen atom of the hydrazine group (N3) and the oxygen atom of the amide (O1). The packing is made up of a series of alternating layers of the disordered 4hba molecules, iz4h4m2p molecules and non-disordered 4hba molecules.

Figure 6
The crystal structure of iz4h4m2p + 4hba showing (a) the hydrogen bonding between the non-disordered 4hba molecules and iz4h4m2p (excluding the disordered 4hba molecule), (b) the hydrogen bonding between the disordered 4hba molecules and iz4h4m2p and (c) the packing of the structure down the c-axis [with hydrogens omitted for clarity; the molecules are colour-coded as follows: green: iz4h4m2p, blue: 4hba (non-disordered) and red: 4hba (disordered)].

3.5. Crystal structures of iz4h4m2p + 2,5-dhba and iz4h4m2p + 3hba

iz4h4m2p formed cocrystals with 2,5-dhba and 3hba, forming colourless blocks and colourless plates, respectively. The asymmetric unit for both structures consists of one molecule of each iz4h4m2p and the respective coformer, forming in space group P2₁/n. In our initial refinement of the crystal structure for iz4h4m2p + 2,5-dhba we observed some electron density that located around one of the inversion sites. It is plausible that this electron density could correlate to some methanol molecules partially occupying these sites. However, this electron density was determined to be too weak to be refined as proper atoms, therefore we used the SQUEEZE program of PLATON to remove it (Spek, 2020 ). In addition, the hydrogen atom H3 in iz4h4m2p + 2,5-dhba could not be found precisely, and was placed geometrically with respect to the O3 atom. Due to both structures having similar unit-cell parameters, the crystal structure similarity tool in MERCURY was used to confirm whether both structures are isostructural. The search was restricted to a cluster of 15 molecules and molecular differences were allowed. From Fig. 7(a) it can be seen that all 15 molecules matched, which is indicative of both structures being isostructural. This should not be too surprising, since the difference between 3hba and 2,5-dhba is simply the additional hydroxyl group on 2,5-dhba, which ultimately forms an intramolecular hydrogen bond with the carboxylic acid group. Both structures are also unusual with respect to most of the other cocrystals presented here, as the amide⋯hydroxyl⋯amide (iz4h4m2p) chain hydrogen-bond motif does not exist. Instead, the hydroxyl group of the carboxylic acid forms a bifurcated hydrogen bond with the amide and imine group's nitrogen (O5—H5A⋯O1 and O5—H5A⋯N3 for iz4h4m2p + 3hba and O6—H6⋯N3 and O6—H6⋯O1 for iz4h4m2p + 2,5-dhba). The hydroxyl group of iz4h4m2p then forms a hydrogen bond to the phenol of the benzoic acid (in place of the amide group from a neighbouring iz4h4m2p molecule). This, in turn, forms a new chain hydrogen-bond motif C₃³(7), which alternates between iz4h4m2p and the respective benzoic acid molecules [Fig. 7(b)]. Due to this chain hydrogen-bond motif, the packing of iz4h4m2p + 2,5-dhba forms a series of zigzag ribbons [Fig. 7(c)].

Figure 7
The crystal structure of iz4h4m2p + 2,5-dhba showing (a) the overlap of iz4h4m2p + 3hba and iz4h4m2p + 2,5-dhba using the crystal structure similarity tool in MERCURY (iz4h4m2p + 3hba in standard colours while the carbon atoms in iz4h4m2p + 2,5-dhba are in green), (b) the hydrogen bonding present and (c) the packing diagram (iz4h4m2p is presented in green while 2,5-dhba is presented in blue).

3.6. Comparison of cocrystals with literature examples

The CSD was used to evaluate and compare the cocrystals presented in this work with other cocrystals containing inh (or a Schiff-based derivative of inh). A complete list of CSD entries with their refcodes used to make these comparisons is included in the supporting information. First, for cocrystals and molecular salts containing inh, 78 results were obtained after removing duplicate entries, alkali or alkali metal salts, inorganic acids and other derivatives of inh. Almost all cocrystals of inh were formed using a coformer with a carboxylic acid functional group, forming either a carboxylic acid⋯pyridine ring hydrogen bond or a proton transfer if the result was a molecular salt. Nine cocrystals containing a coformer without a carboxylic were found which include the following: hydrochlorothiazide (CSD refcode: DADLUS), cyanuric acid (CSD refcode: MOXNAR), 2,4,6-trinitrophenolate (CSD refcode: PEZVAU), 5-fluorocytosine, (CSD refcode: PINJII), 5,7-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydro-4H-1-benzopyran-4-one (CSD refcode: UDUJIP), 1,5-naphthalenedisulfonic acid (CSD refcode: VEGHUN), resveratrol (CSD refcode: VOPQEZ), naphthalene-2,7-diol (CSD refcode: KEBLUC) and nitrofurantoin monohydrate (CSD refcode: KEFXOM). The CSD contains 433 hits of Schiff-based inh derivatives with the imine functional group, of which 227 contain more than one chemical entity (molecules, ions etc.), of which 131 were hydrates. After removing inorganic salts and solvates, only 53 cocrystals and molecular salts containing a Schiff-based inh-derivative remained. Like inh, most of the coformers used to synthesize these cocrystals and molecular salts contains a carboxylic acid functional group. Exceptions include 2,4,6-trinitrophenolate (CSD refcodes: CETWEF, EPISAY, LIGXEG and ZECXEN), saccharin (CSD refcodes: ZUVWUK and ZUVXAR) and acesulfame (CSD refcode: OKAVUT).

Similar to the cocrystals of iz4h4m2p presented here, cocrystals featuring a carboxylic acid will form a carboxylic acid⋯pyridine ring hydrogen-bond motif. A large degree of variability in hydrogen bonding exists in cocrystals containing inh. Cocrystals featuring an isoniazid derivative have a limited degree of variability in the hydrogen bonding, most of which stems from the nature of the coformer chosen. The variability of hydrogen bonding in inh cocrystals can include forming the following hydrogen-bond motifs: homodimers between the hydrazide groups, tetramers and chains. The packing can vary drastically in crystals containing inh molecules, which can range from 1D ribbons to 3D networks, which is due to the different combinations of hydrogen-bond pairing. For the cocrystals containing an isoniazid derivative with a reduced number of hydrogen pair donors, most packing is reduced to 1D ribbons, which can stack either parallel (such as iz4h4m2p + dnba, iz4h4m2p + 2c4n and iz4h4m2p + 4nba) or zigzag (such as iz4h4m2p + 2,5-dhba and iz4h4m2p + sa).

Some exceptional cases arise. For example, in the cocrystal of the isoniazid derivative derivatized using acetone [N′-(propan-2-ylidene)isonicotinohydrazide] and 2c4n (CSD refcode: LATLID) (Lemmerer, 2012) contains both neutral and ionized species in the same asymmetric unit. Not only is this crystal structure chiral, the pyridine rings alternate in alignment along the chain hydrogen-bond motif at different points, which has not been observed in any of the cocrystals of iz4h4m2p. Polymorphism exists for the case of inh and cinammic acid, where three different forms exist (CSD refcodes: SETSAN01, SETSAN02, SETSAN03) (Sarcevica et al., 2013 , 2014 ). All three polymorphs featured forming an R₄⁴(16) ring-based tetramer, connected using the carboxylic acid⋯pyridine hydrogen pair as well as one of the hydrazide hydrogens forming a hydrogen pair to the oxygen of the carboxylic acid, similar to the one reported for inh + dnba. Form I and form II exhibit the same hydrogen bonding pattern, which forms tetramers. The difference between form I and form II is the orientation in which the tetramers exist in relation to each other: the tetramers in form I are parallel while in form II some of the tetramers lie at an angle. Form III has different hydrogen bonding compared to the form I and form II, which features a bifurcated hydrogen bond between the one oxygen of the carboxylic acid to two hydrogens from the hydrazide group from different inh molecules. The packing of form III is similar to form I, a layered packing. In comparison, iz4h4m2p + ca forms a zigzag packing. This is a clear example that derivatizing inh using a Schiff-base reaction and reducing the number of hydrogen bond donors can reduce the complexity of a structure to a simpler one.

3.7. FTIR spectra

FTIR spectroscopy is a useful technique to identify the different functional groups present in a solid, as well as to measure the strength of the intermolecular interactions between the different functional groups. For cocrystals, it is expected that FTIR spectra will differ to the spectra of the individual components, not just due to the addition of potential new functional groups but also due to the different intermolecular interactions occurring (i.e. new hydrogen bonds etc.). In particular, hydrogen bonds will cause a shift of significant FTIR peaks, which will be dependent on the strength or degree of the hydrogen bond in question. The FTIR spectra are represented together in Fig. 8, while each spectra is presented separately in the supporting information. The spectral assignments for the carboxylic acid functional group (or for iz4h4m2p the hydroxyl and carbonyl groups) for the cocrystals and both forms of iz4h4m2p have been included in Table 3. Another important use of FTIR here is to determine whether proton transfer occurred or not in the cocrystal of iz4h4m2p + 2,5-dhba. As noted before, the acidic protons from 2,5-dhba could not be located precisely in the difference Fourier maps, which were assigned geometrically with respect to the carboxylic acid. FTIR can be used to determine whether proton transfer has occurred or not. To determine whether a proton transfer has occurred, one could check to see if stretching band of either the carbonyl group (C=O) or the hydroxyl group (O—H) is present or absent. If these characteristic peaks are absent, a salt would be present. Unfortunately iz4h4m2p has both a carbonyl (associated with the amide) and hydroxyl groups present, making identification of a salt using this method difficult. However, a carboxylate group can also be identified by strong peaks associated with the symmetric and asymmetric stretching of the CO₂⁻ group in the 1450–1360 cm⁻¹ and 1650–1540 cm⁻¹ ranges, respectively. With the exception of iz4h4m2p + dnba these peaks are absent in each spectrum, indicating that no proton transfer occurs. For the case of iz4h4m2p + dnba, the asymmetric stretching of the nitro groups occurs in the same range of the asymmetric stretching of the CO₂⁻ group, making this identification elusive. However, based on the absent strong CO₂⁻ group symmetric stretching band, it is more likely iz4h4m2p + dnba is a cocrystal as opposed to a salt.

Table 3
IR spectral assignments of the wavenumbers for iz4h4m2p and its cocrystals to the carboxylic acid functional and/or the hydroxyl and carbonyl functional groups

Sample	C=O stretch (cm^{− 1})	O—H stretch (cm⁻¹)	C—O stretch (cm⁻¹)	O—H bend in-plane (cm⁻¹)	O—H bend out-plane (cm⁻¹)
i4h4m2p (form I)	1660	2969	1273	1407	932
i4h4m2p (form II)	1673	2971	1271	1404	919
iz4h4m2p + 2c4n	1662	2980	1309	1408	924
iz4h4m2p + 3hba	1674	2964	1292	1412	924
iz4h4m2p + 4nba	1662	2982	1285	1410	925
iz4h4m2p + ca	1667	2975	1281	1409	927
iz4h4m2p + sa	1662	2968	1309	1407	925
iz4h4m2p + dnba	1655	2976	1286	1412	912
iz4h4m2p + 4hba	1651	2962	1271	1415	926
iz4h4m2p + 2,5-dhba	1673	2972	1305	1413	928

Figure 8
FTIR spectra of iz4h4m2p (form II) and its cocrystals.

3.8. Thermal analysis

DSC curves were collected for all eight cocrystals. Two of the DSC curves are presented in Fig. 9, with the curve of iz4h4m2p + 4hba being a representative DSC curve for all the cocrystals. The DSCs of the other cocrystals are presented in the supporting information. The associated onset temperatures and enthalpies are represented in Table 4. For most of the samples, a single large endothermic peak was observed (corresponding to the melting/decomposition point of the sample) on the heating cycle, while no thermal events were observed on the cooling cycle which corresponds closely to the behaviour of form II of iz4h4m2p. It should be noted that only one large endothermic peak was observed for iz4h4m2p + 4hba, which indicates that desolvation does not occur before melting.

Table 4
Onset temperatures and associated enthalpies for thermal events observed in DSC curves for the cocrystals presented in this work

The melting/decomposition points of both polymorphic forms of iz4h4m2p are also given for comparison purposes (Scheepers et al., 2022).

Thermal event	Onset (°C)	Enthalpy (J g⁻¹)
iz4h4m2p (form I) melting/decomposition	139.7 ± 0.1	137.2 ± 2.3
iz4h4m2p (form II) melting/decomposition	142.1 ± 0.1	144.2 ± 2.4
iz4h4m2p + 2c4n melting/decomposition	117.1 ± 0.2	237.7 ± 2.3
iz4h4m2p + 3hba melting/decomposition	145.6 ± 0.2	276.8 ± 4.3
iz4h4m2p + 4nba melting/decomposition	155.8 ± 0.2	279.9 ± 5.2
iz4h4m2p + ca melting/decomposition	103.4 ± 0.1	102.3 ± 6.6
iz4h4m2p + dnba melting/decomposition	130.5 ± 0.2	263.2 ± 2.8
iz4h4m2p + sa melting/decomposition	119.8 ± 0.1	102.2 ± 1.3
iz4h4m2p + 4hba melting/decomposition	153.2 ± 0.2	233.9 ± 3.2
iz4h4m2p + 2,5-dhba melting/decomposition	149.4 ± 0.2	300.6 ± 2.4

Figure 9
DSC diagrams of iz4h4m2p + 4hba representing the typical behaviour of DSC curves of all cocrystals of iz4h4m2p.

4. Conclusions

Eight cocrystals containing iz4h4m2p were synthesized and characterized. Most of the cocrystals were uniform with regard to their hydrogen bonding, with two major hydrogen-bonding motifs observed: the carboxylic acid⋯pyridine hydrogen bond and the chain hydrogen-bond motif formed between the amide and hydroxyl groups, which is the same hydrogen-bond motif observed in form I. Exceptions to this arose when the carboxylic acid coformer had additional hydrogen bond donors (the hydroxybenzoic acids), which caused the overall hydrogen-bonding patterns to deviate from the expected hydrogen-bonding motifs. Packing of the structures featured either a zigzag or a layered formation, which indicates a greater degree of predicting the supramolecular assimilation. Most cocrystals did not feature any additional thermal events in their DSC curves. The derivatization of inh with diacetone alcohol made the cocrystals of iz4h4m2p more predictable than the cocrystals formed with inh. This could potentially prove useful in the design and synthesis of new FDC drugs. As such it would prove useful to evaluate the biological activity of iz4h4m2p and its cocrystals with GRAS compounds, as well as stability studies in the presence of these other drugs.

Supporting information

CCDC references: 2177244; 2177245; 2177246; 2177247; 2177248; 2177249; 2177250; 2177251

Crystal structure: contains datablocks iz4h4m2p2c4n, iz4h4m2p3hba, iz4h4m2pca, iz4h4m2pdnba, iz4h4m2psa, iz4h4m2p4nba, iz4h4m2p25dhba, 22mcsiz4h4m2p4hba. DOI: https://doi.org/10.1107/S2052520622009532/aw5075sup1.cif

iz4h4m2p + 2c4n cocrystal. DOI: https://doi.org/10.1107/S2052520622009532/aw5075iz4h4m2p2c4nsup2.hkl

iz4h4m2p3 + hba cocrystal. DOI: https://doi.org/10.1107/S2052520622009532/aw5075iz4h4m2p3hbasup3.hkl

iz4h4m2p + ca cocrystal. DOI: https://doi.org/10.1107/S2052520622009532/aw5075iz4h4m2pcasup4.hkl

iz4h4m2p + dnba cocrystal. DOI: https://doi.org/10.1107/S2052520622009532/aw5075iz4h4m2pdnbasup5.hkl

iz4h4m2p + sa cocrystal. DOI: https://doi.org/10.1107/S2052520622009532/aw5075iz4h4m2psasup6.hkl

iz4h4m2p + 4nba cocrystal. DOI: https://doi.org/10.1107/S2052520622009532/aw5075iz4h4m2p4nbasup7.hkl

iz4h4m2p + 25dhba cocrystal. DOI: https://doi.org/10.1107/S2052520622009532/aw5075iz4h4m2p25dhbasup8.hkl

iz4h4m2p + 4hba cocrystal. DOI: https://doi.org/10.1107/S2052520622009532/aw507522mcsiz4h4m2p4hbasup9.hkl

Tables S1 and S2, Figs S1-S23. DOI: https://doi.org/10.1107/S2052520622009532/aw5075sup10.pdf

Computing details top

Cell refinement: SAINT V8.40B (?, 2016) for iz4h4m2pdnba, 22mcsiz4h4m2p4hba. Data reduction: SAINT V8.40B (?, 2016) for iz4h4m2pdnba, 22mcsiz4h4m2p4hba. Program(s) used to solve structure: SHELXT-2018/2 (Sheldrick, 2015) for iz4h4m2p2c4n, iz4h4m2p3hba, iz4h4m2pca, iz4h4m2pdnba, iz4h4m2psa, iz4h4m2p4nba; SHELXT (Sheldrick, 2015) for 22mcsiz4h4m2p4hba. Program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2018) for iz4h4m2p2c4n, iz4h4m2p3hba, iz4h4m2pca, iz4h4m2psa, iz4h4m2p4nba, iz4h4m2p25dhba; SHELXL 2018/3 (Sheldrick, 2015) for iz4h4m2pdnba, 22mcsiz4h4m2p4hba. Molecular graphics: ORTEP for Windows (Farrugia, 2012) for iz4h4m2p2c4n, iz4h4m2p3hba, iz4h4m2pca, iz4h4m2psa, iz4h4m2p4nba, iz4h4m2p25dhba; Olex2 1.3 (Dolomanov et al., 2009) for iz4h4m2pdnba; Olex2 1.5 (Dolomanov et al., 2009) for 22mcsiz4h4m2p4hba. Software used to prepare material for publication: WinGX publication routines (Farrugia, 2012) for iz4h4m2p2c4n, iz4h4m2p3hba, iz4h4m2pca, iz4h4m2psa, iz4h4m2p4nba, iz4h4m2p25dhba; Olex2 1.3 (Dolomanov et al., 2009) for iz4h4m2pdnba; Olex2 1.5 (Dolomanov et al., 2009) for 22mcsiz4h4m2p4hba.

(iz4h4m2p2c4n) top

Crystal data top

C₁₂H₁₇N₃O₂·C₇H₄NO₄Cl	Z = 2
M_r = 436.85	F(000) = 456
Triclinic, P1	D_x = 1.405 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.0381 (1) Å	Cell parameters from 9933 reflections
b = 12.2643 (2) Å	θ = 2.7–25.2°
c = 12.4636 (2) Å	µ = 0.23 mm⁻¹
α = 103.215 (1)°	T = 173 K
β = 97.797 (1)°	Block, colourless
γ = 93.497 (1)°	0.52 × 0.25 × 0.21 mm
V = 1032.92 (3) Å³

Data collection top

Bruker APEX-II CCD diffractometer	R_int = 0.039
φ and ω scans	θ_max = 32.4°, θ_min = 1.7°
49833 measured reflections	h = −10→10
7362 independent reflections	k = −18→18
4908 reflections with I > 2σ(I)	l = −18→18

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Secondary atom site location: dual
R[F² > 2σ(F²)] = 0.044	Hydrogen site location: mixed
wR(F²) = 0.117	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ²(F_o²) + (0.0518P)² + 0.1163P] where P = (F_o² + 2F_c²)/3
7362 reflections	(Δ/σ)_max = 0.001
286 parameters	Δρ_max = 0.42 e Å⁻³
0 restraints	Δρ_min = −0.35 e Å⁻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

	x	y	z	U_iso*/U_eq
C1	1.03126 (19)	0.37903 (11)	0.37027 (11)	0.0300 (3)
H1	1.107444	0.322189	0.387511	0.036*
C2	1.10327 (18)	0.45202 (10)	0.31219 (10)	0.0274 (3)
H2	1.227246	0.445601	0.290577	0.033*
C3	0.99150 (16)	0.53473 (9)	0.28602 (9)	0.0221 (2)
C4	0.81231 (17)	0.54285 (10)	0.32108 (9)	0.0243 (2)
H4	0.733295	0.59914	0.305471	0.029*
C5	0.75182 (17)	0.46681 (10)	0.37936 (10)	0.0260 (2)
H5	0.629738	0.472445	0.40361	0.031*
C6	1.07473 (17)	0.61287 (10)	0.22319 (9)	0.0242 (2)
C7	0.89322 (18)	0.75741 (11)	0.03021 (11)	0.0323 (3)
C8	0.9548 (2)	0.85086 (15)	−0.02108 (17)	0.0562 (5)
H8A	1.068284	0.895851	0.026304	0.084*
H8B	0.849578	0.898848	−0.027719	0.084*
H8C	0.986674	0.818816	−0.095252	0.084*
C9	0.71353 (18)	0.68304 (10)	−0.02818 (10)	0.0278 (3)
H9A	0.738997	0.603964	−0.031245	0.033*
H9B	0.689112	0.69101	−0.106	0.033*
C10	0.52834 (17)	0.70466 (10)	0.02324 (10)	0.0261 (2)
C11	0.3583 (2)	0.63429 (12)	−0.05535 (11)	0.0361 (3)
H11A	0.386624	0.555551	−0.074828	0.054*
H11B	0.335257	0.662082	−0.123259	0.054*
H11C	0.243427	0.639809	−0.018681	0.054*
C12	0.4944 (2)	0.82883 (11)	0.04973 (11)	0.0352 (3)
H12A	0.379029	0.839181	0.085582	0.053*
H12B	0.476347	0.854608	−0.019499	0.053*
H12C	0.606045	0.872579	0.100137	0.053*
C13	0.52507 (16)	0.15155 (9)	0.59221 (9)	0.0214 (2)
C14	0.33681 (17)	0.11071 (10)	0.59639 (10)	0.0247 (2)
C15	0.30182 (19)	0.02325 (10)	0.64708 (10)	0.0291 (3)
H15	0.173736	−0.003826	0.650071	0.035*
C16	0.4562 (2)	−0.02327 (10)	0.69279 (10)	0.0291 (3)
C17	0.6448 (2)	0.01397 (11)	0.69107 (10)	0.0307 (3)
H17	0.74916	−0.019682	0.723169	0.037*
C18	0.67693 (18)	0.10197 (10)	0.64105 (10)	0.0258 (2)
H18	0.805669	0.129344	0.639906	0.031*
C19	0.57215 (16)	0.24531 (9)	0.53680 (10)	0.0229 (2)
N1	0.85735 (15)	0.38605 (8)	0.40294 (8)	0.0267 (2)
N2	0.94383 (16)	0.66115 (9)	0.16497 (9)	0.0284 (2)
N3	1.00631 (15)	0.74647 (9)	0.11621 (10)	0.0339 (3)
N4	0.4174 (2)	−0.11651 (10)	0.74559 (9)	0.0423 (3)
O1	1.24980 (12)	0.62644 (8)	0.22519 (8)	0.0334 (2)
O2	0.55739 (14)	0.66816 (9)	0.12589 (8)	0.0353 (2)
O3	0.74190 (12)	0.23927 (7)	0.50456 (8)	0.0301 (2)
O4	0.46521 (13)	0.31639 (8)	0.52352 (9)	0.0374 (2)
O5	0.5497 (2)	−0.17307 (10)	0.76468 (11)	0.0630 (3)
O6	0.25526 (19)	−0.13293 (10)	0.76753 (10)	0.0582 (3)
Cl1	0.13536 (4)	0.16095 (3)	0.53595 (3)	0.03766 (10)
H2A	0.819 (2)	0.6508 (13)	0.1620 (13)	0.042 (4)*
H2B	0.459 (3)	0.6614 (15)	0.1488 (15)	0.056 (5)*
H3A	0.774 (3)	0.2990 (19)	0.4693 (18)	0.086 (7)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0298 (7)	0.0309 (6)	0.0340 (7)	0.0049 (5)	0.0085 (5)	0.0151 (5)
C2	0.0229 (6)	0.0334 (6)	0.0300 (6)	0.0030 (5)	0.0084 (5)	0.0134 (5)
C3	0.0223 (6)	0.0249 (5)	0.0194 (5)	−0.0033 (4)	0.0026 (4)	0.0075 (4)
C4	0.0239 (6)	0.0262 (6)	0.0248 (6)	0.0016 (4)	0.0057 (4)	0.0092 (5)
C5	0.0233 (6)	0.0299 (6)	0.0272 (6)	−0.0010 (5)	0.0077 (5)	0.0103 (5)
C6	0.0237 (6)	0.0276 (6)	0.0230 (6)	−0.0027 (4)	0.0039 (4)	0.0104 (5)
C7	0.0262 (6)	0.0373 (7)	0.0429 (7)	0.0054 (5)	0.0117 (5)	0.0248 (6)
C8	0.0355 (8)	0.0645 (10)	0.0878 (13)	−0.0005 (7)	0.0065 (8)	0.0603 (10)
C9	0.0310 (6)	0.0315 (6)	0.0256 (6)	0.0064 (5)	0.0093 (5)	0.0130 (5)
C10	0.0262 (6)	0.0315 (6)	0.0224 (6)	0.0023 (5)	0.0034 (5)	0.0103 (5)
C11	0.0328 (7)	0.0371 (7)	0.0359 (7)	−0.0016 (6)	−0.0010 (6)	0.0087 (6)
C12	0.0357 (7)	0.0331 (7)	0.0342 (7)	0.0070 (6)	0.0045 (6)	0.0022 (6)
C13	0.0209 (5)	0.0225 (5)	0.0227 (5)	0.0015 (4)	0.0072 (4)	0.0072 (4)
C14	0.0225 (6)	0.0252 (6)	0.0266 (6)	0.0013 (4)	0.0058 (5)	0.0058 (5)
C15	0.0292 (6)	0.0301 (6)	0.0280 (6)	−0.0061 (5)	0.0102 (5)	0.0060 (5)
C16	0.0434 (8)	0.0258 (6)	0.0197 (6)	−0.0036 (5)	0.0077 (5)	0.0091 (5)
C17	0.0354 (7)	0.0330 (6)	0.0268 (6)	0.0050 (5)	0.0033 (5)	0.0136 (5)
C18	0.0233 (6)	0.0285 (6)	0.0285 (6)	0.0029 (5)	0.0058 (5)	0.0115 (5)
C19	0.0199 (5)	0.0233 (5)	0.0277 (6)	0.0019 (4)	0.0059 (4)	0.0092 (4)
N1	0.0281 (5)	0.0270 (5)	0.0278 (5)	−0.0015 (4)	0.0073 (4)	0.0115 (4)
N2	0.0215 (5)	0.0350 (6)	0.0345 (6)	−0.0024 (4)	0.0048 (4)	0.0211 (5)
N3	0.0271 (6)	0.0343 (6)	0.0487 (7)	−0.0002 (4)	0.0079 (5)	0.0268 (5)
N4	0.0633 (9)	0.0373 (6)	0.0278 (6)	−0.0092 (6)	0.0045 (6)	0.0156 (5)
O1	0.0210 (4)	0.0453 (5)	0.0402 (5)	−0.0018 (4)	0.0066 (4)	0.0235 (4)
O2	0.0230 (5)	0.0607 (6)	0.0311 (5)	0.0055 (4)	0.0086 (4)	0.0258 (4)
O3	0.0232 (4)	0.0319 (5)	0.0450 (5)	0.0060 (3)	0.0161 (4)	0.0217 (4)
O4	0.0278 (5)	0.0348 (5)	0.0601 (6)	0.0112 (4)	0.0142 (4)	0.0261 (5)
O5	0.0804 (9)	0.0552 (7)	0.0655 (8)	0.0056 (6)	0.0045 (7)	0.0436 (6)
O6	0.0726 (9)	0.0572 (7)	0.0521 (7)	−0.0177 (6)	0.0200 (6)	0.0279 (6)
Cl1	0.01885 (15)	0.03771 (18)	0.0594 (2)	0.00232 (12)	0.00464 (14)	0.01860 (16)

Geometric parameters (Å, º) top

C1—N1	1.3429 (16)	C10—C12	1.5235 (17)
C1—C2	1.3866 (16)	C13—C18	1.3981 (16)
C2—C3	1.3904 (16)	C13—C14	1.3996 (16)
C3—C4	1.3916 (16)	C13—C19	1.5125 (15)
C3—C6	1.5080 (15)	C14—C15	1.3894 (17)
C4—C5	1.3871 (16)	C14—Cl1	1.7281 (12)
C5—N1	1.3352 (16)	C15—C16	1.3734 (19)
C6—O1	1.2294 (14)	C16—C17	1.3821 (18)
C6—N2	1.3444 (16)	C16—N4	1.4729 (16)
C7—N3	1.2836 (17)	C17—C18	1.3859 (17)
C7—C8	1.5033 (18)	C19—O4	1.2108 (14)
C7—C9	1.5057 (19)	C19—O3	1.3121 (14)
C9—C10	1.5398 (17)	N2—N3	1.4017 (13)
C10—O2	1.4425 (14)	N4—O5	1.2239 (18)
C10—C11	1.5183 (18)	N4—O6	1.2249 (17)

N1—C1—C2	122.16 (11)	C18—C13—C19	118.57 (10)
C1—C2—C3	119.07 (11)	C14—C13—C19	123.46 (10)
C2—C3—C4	118.74 (10)	C15—C14—C13	121.04 (11)
C2—C3—C6	117.62 (10)	C15—C14—Cl1	115.90 (9)
C4—C3—C6	123.62 (10)	C13—C14—Cl1	123.03 (9)
C5—C4—C3	118.41 (11)	C16—C15—C14	118.65 (11)
N1—C5—C4	122.99 (11)	C15—C16—C17	122.63 (11)
O1—C6—N2	124.72 (11)	C15—C16—N4	118.22 (12)
O1—C6—C3	120.36 (11)	C17—C16—N4	119.15 (12)
N2—C6—C3	114.90 (10)	C16—C17—C18	117.89 (12)
N3—C7—C8	115.82 (12)	C17—C18—C13	121.81 (11)
N3—C7—C9	127.13 (11)	O4—C19—O3	124.55 (11)
C8—C7—C9	116.93 (12)	O4—C19—C13	123.87 (10)
C7—C9—C10	116.85 (10)	O3—C19—C13	111.58 (9)
O2—C10—C11	109.93 (10)	C5—N1—C1	118.60 (10)
O2—C10—C12	108.93 (10)	C6—N2—N3	119.27 (10)
C11—C10—C12	110.91 (11)	C7—N3—N2	115.07 (10)
O2—C10—C9	105.46 (10)	O5—N4—O6	123.97 (13)
C11—C10—C9	109.24 (10)	O5—N4—C16	117.84 (13)
C12—C10—C9	112.23 (10)	O6—N4—C16	118.18 (13)
C18—C13—C14	117.97 (10)

N1—C1—C2—C3	−0.52 (19)	C14—C15—C16—N4	−179.55 (11)
C1—C2—C3—C4	1.28 (18)	C15—C16—C17—C18	0.10 (19)
C1—C2—C3—C6	179.77 (11)	N4—C16—C17—C18	−179.87 (11)
C2—C3—C4—C5	−0.91 (17)	C16—C17—C18—C13	−0.80 (18)
C6—C3—C4—C5	−179.32 (11)	C14—C13—C18—C17	0.88 (17)
C3—C4—C5—N1	−0.25 (18)	C19—C13—C18—C17	−178.51 (11)
C2—C3—C6—O1	−21.78 (17)	C18—C13—C19—O4	−155.92 (12)
C4—C3—C6—O1	156.64 (12)	C14—C13—C19—O4	24.72 (18)
C2—C3—C6—N2	156.41 (11)	C18—C13—C19—O3	24.50 (15)
C4—C3—C6—N2	−25.17 (16)	C14—C13—C19—O3	−154.86 (11)
N3—C7—C9—C10	81.65 (17)	C4—C5—N1—C1	1.02 (18)
C8—C7—C9—C10	−102.32 (14)	C2—C1—N1—C5	−0.63 (18)
C7—C9—C10—O2	−70.15 (13)	O1—C6—N2—N3	−10.50 (19)
C7—C9—C10—C11	171.75 (11)	C3—C6—N2—N3	171.40 (10)
C7—C9—C10—C12	48.32 (14)	C8—C7—N3—N2	178.16 (13)
C18—C13—C14—C15	−0.27 (17)	C9—C7—N3—N2	−5.8 (2)
C19—C13—C14—C15	179.09 (11)	C6—N2—N3—C7	153.87 (12)
C18—C13—C14—Cl1	−177.98 (9)	C15—C16—N4—O5	164.78 (13)
C19—C13—C14—Cl1	1.38 (16)	C17—C16—N4—O5	−15.26 (18)
C13—C14—C15—C16	−0.38 (18)	C15—C16—N4—O6	−15.09 (17)
Cl1—C14—C15—C16	177.48 (9)	C17—C16—N4—O6	164.88 (12)
C14—C15—C16—C17	0.48 (19)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···O2	0.874 (17)	1.873 (17)	2.7074 (14)	159.2 (15)
O2—H2B···O1ⁱ	0.792 (19)	1.935 (19)	2.7133 (12)	167.3 (19)
O3—H3A···N1	0.97 (2)	1.62 (2)	2.5784 (12)	170 (2)

Symmetry code: (i) x−1, y, z.

(iz4h4m2p3hba) top

Crystal data top

C₇H₆O₃·C₁₂H₁₇N₃O₂	F(000) = 792
M_r = 373.4	D_x = 1.266 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 9131 reflections
a = 8.7472 (3) Å	θ = 2.4–35.0°
b = 16.9734 (5) Å	µ = 0.09 mm⁻¹
c = 13.2480 (4) Å	T = 173 K
β = 94.886 (1)°	Plate, colourless
V = 1959.78 (11) Å³	0.59 × 0.48 × 0.22 mm
Z = 4

Data collection top

Bruker APEX-II CCD diffractometer	R_int = 0.033
φ and ω scans	θ_max = 35.1°, θ_min = 2.7°
78332 measured reflections	h = −14→14
8649 independent reflections	k = −27→27
7062 reflections with I > 2σ(I)	l = −20→21

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Secondary atom site location: dual
R[F² > 2σ(F²)] = 0.051	Hydrogen site location: mixed
wR(F²) = 0.145	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ²(F_o²) + (0.0745P)² + 0.3644P] where P = (F_o² + 2F_c²)/3
8649 reflections	(Δ/σ)_max = 0.001
263 parameters	Δρ_max = 0.50 e Å⁻³
0 restraints	Δρ_min = −0.20 e Å⁻³
0 constraints

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.60251 (11)	0.47803 (5)	0.36054 (7)	0.02617 (16)
H1	0.615361	0.47169	0.43201	0.031*
C2	0.49289 (10)	0.43238 (5)	0.30558 (6)	0.02434 (15)
H2	0.431229	0.396224	0.338874	0.029*
C3	0.47537 (9)	0.44074 (5)	0.20081 (6)	0.02156 (14)
C4	0.56740 (10)	0.49541 (5)	0.15586 (7)	0.02620 (16)
H4	0.55803	0.50269	0.084497	0.031*
C5	0.67262 (10)	0.53891 (5)	0.21679 (7)	0.02642 (16)
H5	0.734517	0.576298	0.185792	0.032*
C6	0.36335 (11)	0.39388 (5)	0.13273 (7)	0.02704 (17)
C7	0.15910 (9)	0.21835 (5)	0.15384 (6)	0.02298 (15)
C8	0.07087 (14)	0.16252 (7)	0.08309 (8)	0.0371 (2)
H8A	0.077985	0.179692	0.013016	0.056*
H8B	−0.036968	0.16196	0.097968	0.056*
H8C	0.113928	0.109428	0.092038	0.056*
C9	0.15905 (9)	0.20277 (5)	0.26628 (6)	0.02308 (15)
H9A	0.074314	0.16566	0.276214	0.028*
H9B	0.134417	0.252923	0.299443	0.028*
C10	0.30602 (10)	0.16941 (5)	0.32273 (7)	0.02441 (15)
C11	0.36971 (14)	0.09981 (7)	0.26792 (10)	0.0402 (2)
H11A	0.398776	0.116883	0.201526	0.06*
H11B	0.291349	0.058568	0.258853	0.06*
H11C	0.460157	0.079041	0.307987	0.06*
C12	0.27345 (16)	0.14662 (9)	0.43018 (9)	0.0445 (3)
H12A	0.369241	0.130605	0.468418	0.067*
H12B	0.200402	0.102745	0.427607	0.067*
H12C	0.229764	0.191884	0.463552	0.067*
C13	1.00800 (10)	0.63115 (5)	0.60239 (6)	0.02262 (14)
C14	1.09324 (9)	0.69338 (5)	0.56737 (6)	0.02148 (14)
H14	1.080521	0.708451	0.498101	0.026*
C15	1.19724 (9)	0.73333 (5)	0.63468 (6)	0.02146 (14)
C16	1.21527 (10)	0.71152 (6)	0.73652 (6)	0.02651 (16)
H16	1.285417	0.739067	0.782506	0.032*
C17	1.12999 (12)	0.64926 (6)	0.77025 (7)	0.03011 (18)
H17	1.142685	0.634197	0.83952	0.036*
C18	1.02632 (11)	0.60873 (6)	0.70394 (7)	0.02826 (17)
H18	0.968521	0.566162	0.727569	0.034*
C19	0.89316 (11)	0.58861 (5)	0.53211 (7)	0.02675 (16)
N1	0.69075 (9)	0.53048 (4)	0.31751 (6)	0.02510 (14)
N2	0.30892 (8)	0.32818 (4)	0.17505 (5)	0.02246 (13)
N3	0.22138 (8)	0.27730 (4)	0.11168 (5)	0.02315 (13)
O1	0.32665 (12)	0.41450 (6)	0.04532 (6)	0.0530 (3)
O2	0.41339 (9)	0.23369 (4)	0.32903 (7)	0.03578 (17)
O3	0.88672 (9)	0.61437 (5)	0.43773 (5)	0.03435 (17)
O4	0.81213 (11)	0.53619 (6)	0.56027 (7)	0.0464 (2)
O5	1.28439 (8)	0.79455 (4)	0.60442 (5)	0.02714 (13)
H2A	0.3513 (17)	0.3060 (8)	0.2323 (12)	0.039 (4)*
H2B	0.504 (2)	0.2182 (10)	0.3524 (13)	0.050 (4)*
H3	0.814 (2)	0.5806 (12)	0.3944 (15)	0.074 (6)*
H5A	1.268 (2)	0.8017 (10)	0.5415 (14)	0.054 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0336 (4)	0.0236 (3)	0.0211 (3)	−0.0052 (3)	0.0007 (3)	−0.0034 (3)
C2	0.0302 (4)	0.0220 (3)	0.0209 (3)	−0.0065 (3)	0.0026 (3)	−0.0009 (3)
C3	0.0232 (3)	0.0197 (3)	0.0213 (3)	−0.0036 (2)	−0.0010 (3)	0.0016 (3)
C4	0.0282 (4)	0.0264 (4)	0.0232 (4)	−0.0071 (3)	−0.0024 (3)	0.0058 (3)
C5	0.0261 (4)	0.0238 (3)	0.0287 (4)	−0.0067 (3)	−0.0011 (3)	0.0039 (3)
C6	0.0290 (4)	0.0300 (4)	0.0214 (4)	−0.0102 (3)	−0.0023 (3)	0.0026 (3)
C7	0.0214 (3)	0.0250 (3)	0.0224 (3)	−0.0048 (3)	0.0010 (3)	−0.0032 (3)
C8	0.0450 (6)	0.0373 (5)	0.0279 (4)	−0.0218 (4)	−0.0029 (4)	−0.0033 (4)
C9	0.0209 (3)	0.0267 (3)	0.0220 (3)	−0.0020 (3)	0.0039 (3)	−0.0020 (3)
C10	0.0252 (4)	0.0223 (3)	0.0256 (4)	−0.0021 (3)	0.0013 (3)	0.0006 (3)
C11	0.0392 (5)	0.0325 (5)	0.0489 (6)	0.0099 (4)	0.0029 (5)	−0.0059 (4)
C12	0.0491 (6)	0.0559 (7)	0.0284 (5)	−0.0017 (5)	0.0023 (4)	0.0107 (5)
C13	0.0240 (3)	0.0234 (3)	0.0208 (3)	0.0004 (3)	0.0041 (3)	−0.0027 (3)
C14	0.0214 (3)	0.0253 (3)	0.0176 (3)	−0.0005 (3)	0.0006 (2)	−0.0019 (3)
C15	0.0208 (3)	0.0237 (3)	0.0193 (3)	0.0029 (3)	−0.0017 (2)	−0.0015 (3)
C16	0.0266 (4)	0.0330 (4)	0.0189 (3)	0.0051 (3)	−0.0039 (3)	−0.0014 (3)
C17	0.0351 (4)	0.0361 (4)	0.0189 (3)	0.0063 (4)	0.0010 (3)	0.0044 (3)
C18	0.0333 (4)	0.0278 (4)	0.0242 (4)	0.0017 (3)	0.0057 (3)	0.0039 (3)
C19	0.0283 (4)	0.0274 (4)	0.0251 (4)	−0.0044 (3)	0.0052 (3)	−0.0042 (3)
N1	0.0269 (3)	0.0210 (3)	0.0269 (3)	−0.0036 (2)	−0.0004 (3)	−0.0026 (2)
N2	0.0244 (3)	0.0226 (3)	0.0198 (3)	−0.0064 (2)	−0.0017 (2)	−0.0006 (2)
N3	0.0234 (3)	0.0252 (3)	0.0204 (3)	−0.0063 (2)	−0.0003 (2)	−0.0035 (2)
O1	0.0672 (6)	0.0612 (6)	0.0268 (4)	−0.0379 (5)	−0.0180 (4)	0.0171 (4)
O2	0.0284 (3)	0.0279 (3)	0.0482 (4)	−0.0069 (3)	−0.0135 (3)	0.0090 (3)
O3	0.0389 (4)	0.0396 (4)	0.0240 (3)	−0.0178 (3)	−0.0004 (3)	−0.0027 (3)
O4	0.0546 (5)	0.0489 (5)	0.0357 (4)	−0.0287 (4)	0.0032 (4)	0.0023 (3)
O5	0.0268 (3)	0.0292 (3)	0.0239 (3)	−0.0049 (2)	−0.0069 (2)	0.0017 (2)

Geometric parameters (Å, º) top

C1—N1	1.3372 (11)	C11—H11A	0.98
C1—C2	1.3897 (12)	C11—H11B	0.98
C1—H1	0.95	C11—H11C	0.98
C2—C3	1.3907 (11)	C12—H12A	0.98
C2—H2	0.95	C12—H12B	0.98
C3—C4	1.3948 (11)	C12—H12C	0.98
C3—C6	1.5018 (11)	C13—C18	1.3941 (12)
C4—C5	1.3847 (12)	C13—C14	1.3950 (12)
C4—H4	0.95	C13—C19	1.4961 (12)
C5—N1	1.3378 (12)	C14—C15	1.3944 (11)
C5—H5	0.95	C14—H14	0.95
C6—O1	1.2260 (11)	C15—O5	1.3688 (11)
C6—N2	1.3528 (11)	C15—C16	1.3950 (12)
C7—N3	1.2892 (11)	C16—C17	1.3892 (14)
C7—C8	1.4996 (12)	C16—H16	0.95
C7—C9	1.5129 (12)	C17—C18	1.3899 (14)
C8—H8A	0.98	C17—H17	0.95
C8—H8B	0.98	C18—H18	0.95
C8—H8C	0.98	C19—O4	1.2159 (11)
C9—C10	1.5392 (12)	C19—O3	1.3212 (12)
C9—H9A	0.99	N2—N3	1.3884 (9)
C9—H9B	0.99	N2—H2A	0.898 (15)
C10—O2	1.4375 (11)	O2—H2B	0.863 (18)
C10—C11	1.5172 (14)	O3—H3	1.00 (2)
C10—C12	1.5251 (14)	O5—H5A	0.842 (19)

N1—C1—C2	123.05 (8)	C10—C11—H11B	109.5
N1—C1—H1	118.5	H11A—C11—H11B	109.5
C2—C1—H1	118.5	C10—C11—H11C	109.5
C1—C2—C3	118.59 (8)	H11A—C11—H11C	109.5
C1—C2—H2	120.7	H11B—C11—H11C	109.5
C3—C2—H2	120.7	C10—C12—H12A	109.5
C2—C3—C4	118.39 (7)	C10—C12—H12B	109.5
C2—C3—C6	123.79 (7)	H12A—C12—H12B	109.5
C4—C3—C6	117.81 (7)	C10—C12—H12C	109.5
C5—C4—C3	119.01 (8)	H12A—C12—H12C	109.5
C5—C4—H4	120.5	H12B—C12—H12C	109.5
C3—C4—H4	120.5	C18—C13—C14	120.46 (8)
N1—C5—C4	122.74 (8)	C18—C13—C19	118.99 (8)
N1—C5—H5	118.6	C14—C13—C19	120.54 (8)
C4—C5—H5	118.6	C15—C14—C13	119.58 (8)
O1—C6—N2	123.62 (8)	C15—C14—H14	120.2
O1—C6—C3	121.40 (8)	C13—C14—H14	120.2
N2—C6—C3	114.97 (7)	O5—C15—C14	122.08 (7)
N3—C7—C8	115.70 (8)	O5—C15—C16	117.70 (7)
N3—C7—C9	126.71 (7)	C14—C15—C16	120.22 (8)
C8—C7—C9	117.50 (7)	C17—C16—C15	119.56 (8)
C7—C8—H8A	109.5	C17—C16—H16	120.2
C7—C8—H8B	109.5	C15—C16—H16	120.2
H8A—C8—H8B	109.5	C16—C17—C18	120.84 (8)
C7—C8—H8C	109.5	C16—C17—H17	119.6
H8A—C8—H8C	109.5	C18—C17—H17	119.6
H8B—C8—H8C	109.5	C17—C18—C13	119.34 (8)
C7—C9—C10	118.19 (7)	C17—C18—H18	120.3
C7—C9—H9A	107.8	C13—C18—H18	120.3
C10—C9—H9A	107.8	O4—C19—O3	123.62 (9)
C7—C9—H9B	107.8	O4—C19—C13	122.70 (9)
C10—C9—H9B	107.8	O3—C19—C13	113.67 (8)
H9A—C9—H9B	107.1	C1—N1—C5	118.21 (7)
O2—C10—C11	110.73 (8)	C6—N2—N3	117.23 (7)
O2—C10—C12	108.14 (8)	C6—N2—H2A	124.1 (9)
C11—C10—C12	110.78 (9)	N3—N2—H2A	114.6 (9)
O2—C10—C9	105.28 (7)	C7—N3—N2	116.90 (7)
C11—C10—C9	112.30 (8)	C10—O2—H2B	111.3 (11)
C12—C10—C9	109.40 (8)	C19—O3—H3	109.1 (11)
C10—C11—H11A	109.5	C15—O5—H5A	110.3 (12)

N1—C1—C2—C3	0.91 (14)	C13—C14—C15—C16	−0.38 (12)
C1—C2—C3—C4	−0.84 (13)	O5—C15—C16—C17	−179.46 (8)
C1—C2—C3—C6	178.80 (9)	C14—C15—C16—C17	0.60 (13)
C2—C3—C4—C5	0.23 (13)	C15—C16—C17—C18	−0.37 (14)
C6—C3—C4—C5	−179.44 (9)	C16—C17—C18—C13	−0.09 (14)
C3—C4—C5—N1	0.40 (15)	C14—C13—C18—C17	0.31 (13)
C2—C3—C6—O1	163.39 (11)	C19—C13—C18—C17	−178.39 (8)
C4—C3—C6—O1	−16.96 (15)	C18—C13—C19—O4	1.71 (14)
C2—C3—C6—N2	−17.14 (13)	C14—C13—C19—O4	−176.99 (10)
C4—C3—C6—N2	162.50 (8)	C18—C13—C19—O3	−179.41 (8)
N3—C7—C9—C10	−77.53 (11)	C14—C13—C19—O3	1.89 (12)
C8—C7—C9—C10	106.13 (10)	C2—C1—N1—C5	−0.29 (14)
C7—C9—C10—O2	72.55 (9)	C4—C5—N1—C1	−0.38 (14)
C7—C9—C10—C11	−48.02 (11)	O1—C6—N2—N3	7.85 (15)
C7—C9—C10—C12	−171.45 (9)	C3—C6—N2—N3	−171.60 (7)
C18—C13—C14—C15	−0.08 (12)	C8—C7—N3—N2	−177.48 (8)
C19—C13—C14—C15	178.60 (8)	C9—C7—N3—N2	6.12 (13)
C13—C14—C15—O5	179.68 (7)	C6—N2—N3—C7	−174.30 (8)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1···O4	0.95	2.56	3.2421 (12)	129
C4—H4···O1ⁱ	0.95	2.5	3.2744 (12)	139
C5—H5···O5ⁱⁱ	0.95	2.5	3.3781 (11)	154
C14—H14···N3ⁱⁱⁱ	0.95	2.63	3.3075 (11)	129
N2—H2A···O2	0.898 (15)	1.824 (15)	2.6928 (11)	162.2 (14)
O2—H2B···O5^iv	0.863 (18)	1.906 (18)	2.7565 (10)	168.0 (16)
O3—H3···N1	1.00 (2)	1.65 (2)	2.6529 (10)	175.8 (18)
O5—H5A···N3ⁱⁱⁱ	0.842 (19)	2.081 (18)	2.8739 (10)	156.7 (16)
O5—H5A···O1ⁱⁱⁱ	0.842 (19)	2.349 (18)	2.9489 (11)	128.7 (15)

Symmetry codes: (i) −x+1, −y+1, −z; (ii) x−1/2, −y+3/2, z−1/2; (iii) −x+3/2, y+1/2, −z+1/2; (iv) −x+2, −y+1, −z+1.

(iz4h4m2pca) top

Crystal data top

C₁₂H₁₇N₃O₂·C₉H₈O₂	Z = 2
M_r = 383.44	F(000) = 408
Triclinic, P1	D_x = 1.269 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 6.9734 (3) Å	Cell parameters from 8523 reflections
b = 11.2540 (5) Å	θ = 2.4–28.1°
c = 13.4029 (6) Å	µ = 0.09 mm⁻¹
α = 89.949 (2)°	T = 173 K
β = 82.689 (2)°	Plate, colourless
γ = 74.261 (2)°	0.37 × 0.18 × 0.10 mm
V = 1003.55 (8) Å³

Data collection top

Bruker APEX-II CCD diffractometer	R_int = 0.078
φ and ω scans	θ_max = 28.4°, θ_min = 1.9°
47711 measured reflections	h = −9→9
4995 independent reflections	k = −14→14
4111 reflections with I > 2σ(I)	l = −17→17

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Secondary atom site location: dual
R[F² > 2σ(F²)] = 0.039	Hydrogen site location: mixed
wR(F²) = 0.107	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ²(F_o²) + (0.0438P)² + 0.2367P] where P = (F_o² + 2F_c²)/3
4995 reflections	(Δ/σ)_max < 0.001
268 parameters	Δρ_max = 0.25 e Å⁻³
0 restraints	Δρ_min = −0.20 e Å⁻³
0 constraints

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.42910 (18)	0.70594 (11)	0.77301 (10)	0.0328 (3)
H1	0.304009	0.689644	0.767658	0.039*
C2	0.42746 (17)	0.81636 (10)	0.81877 (9)	0.0300 (2)
H2	0.304092	0.87453	0.843767	0.036*
C3	0.60986 (16)	0.84053 (10)	0.82744 (8)	0.0242 (2)
C4	0.78506 (16)	0.75118 (10)	0.79152 (9)	0.0275 (2)
H4	0.912333	0.763547	0.798248	0.033*
C5	0.77285 (17)	0.64387 (11)	0.74580 (9)	0.0302 (2)
H5	0.893903	0.583902	0.720334	0.036*
C6	0.63073 (16)	0.95851 (10)	0.87162 (8)	0.0245 (2)
C7	0.33289 (17)	1.26100 (10)	0.90521 (9)	0.0286 (2)
C8	0.3278 (2)	1.37815 (11)	0.96018 (11)	0.0397 (3)
H8A	0.428227	1.3604	1.007024	0.06*
H8B	0.193916	1.412673	0.997787	0.06*
H8C	0.357912	1.437874	0.911627	0.06*
C9	0.19080 (17)	1.27061 (11)	0.82765 (9)	0.0303 (2)
H9A	0.267623	1.22372	0.766143	0.036*
H9B	0.14566	1.358359	0.810022	0.036*
C10	0.00267 (16)	1.22479 (10)	0.85622 (9)	0.0270 (2)
C11	−0.14558 (19)	1.27321 (12)	0.78190 (10)	0.0376 (3)
H11A	−0.076974	1.253378	0.713042	0.056*
H11B	−0.199114	1.36298	0.791658	0.056*
H11C	−0.256183	1.234458	0.793099	0.056*
C12	−0.09428 (18)	1.26077 (12)	0.96387 (9)	0.0342 (3)
H12A	−0.211706	1.228538	0.97837	0.051*
H12B	−0.136564	1.350995	0.972505	0.051*
H12C	0.002875	1.226002	1.010193	0.051*
C13	0.15366 (18)	0.21864 (11)	0.47968 (9)	0.0296 (2)
C14	0.3059 (2)	0.11306 (11)	0.44413 (9)	0.0338 (3)
H14	0.439485	0.104259	0.457581	0.041*
C15	0.2633 (2)	0.02134 (12)	0.38949 (10)	0.0400 (3)
H15	0.367625	−0.050309	0.365953	0.048*
C16	0.0695 (2)	0.03342 (13)	0.36894 (9)	0.0426 (3)
H16	0.040883	−0.029452	0.330989	0.051*
C17	−0.0817 (2)	0.13707 (14)	0.40380 (10)	0.0412 (3)
H17	−0.214758	0.145566	0.389706	0.049*
C18	−0.04076 (19)	0.22885 (13)	0.45922 (9)	0.0355 (3)
H18	−0.146402	0.299489	0.483534	0.043*
C19	0.19098 (18)	0.31837 (11)	0.53788 (9)	0.0304 (2)
H19	0.075822	0.380149	0.56752	0.036*
C20	0.36794 (18)	0.33177 (11)	0.55369 (9)	0.0319 (3)
H20	0.487071	0.273613	0.523457	0.038*
C21	0.38448 (17)	0.43480 (10)	0.61709 (9)	0.0290 (2)
N1	0.59765 (15)	0.62105 (9)	0.73597 (8)	0.0309 (2)
N2	0.46567 (14)	1.05494 (8)	0.87685 (7)	0.0261 (2)
N3	0.46591 (14)	1.16406 (8)	0.92599 (7)	0.0278 (2)
O1	0.79188 (12)	0.96396 (7)	0.89609 (7)	0.03126 (19)
O2	0.07164 (12)	1.09213 (7)	0.84521 (7)	0.03019 (19)
O3	0.57291 (13)	0.43698 (9)	0.61793 (7)	0.0385 (2)
O4	0.24295 (13)	0.50838 (9)	0.66455 (8)	0.0424 (2)
H2A	0.346 (2)	1.0478 (13)	0.8608 (11)	0.037 (4)*
H2B	−0.030 (3)	1.0596 (16)	0.8684 (12)	0.053 (5)*
H3A	0.577 (3)	0.5051 (19)	0.6622 (15)	0.072 (6)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0260 (5)	0.0288 (6)	0.0444 (7)	−0.0088 (4)	−0.0047 (5)	−0.0060 (5)
C2	0.0221 (5)	0.0251 (5)	0.0408 (6)	−0.0048 (4)	−0.0005 (4)	−0.0056 (5)
C3	0.0241 (5)	0.0225 (5)	0.0256 (5)	−0.0064 (4)	−0.0014 (4)	−0.0005 (4)
C4	0.0222 (5)	0.0277 (5)	0.0320 (6)	−0.0069 (4)	−0.0010 (4)	−0.0007 (4)
C5	0.0258 (5)	0.0270 (5)	0.0343 (6)	−0.0032 (4)	0.0000 (4)	−0.0045 (4)
C6	0.0237 (5)	0.0235 (5)	0.0271 (5)	−0.0084 (4)	−0.0015 (4)	0.0002 (4)
C7	0.0259 (5)	0.0240 (5)	0.0364 (6)	−0.0098 (4)	0.0004 (4)	−0.0021 (4)
C8	0.0352 (6)	0.0254 (6)	0.0582 (8)	−0.0082 (5)	−0.0048 (6)	−0.0095 (5)
C9	0.0299 (6)	0.0259 (5)	0.0355 (6)	−0.0088 (4)	−0.0028 (5)	0.0039 (4)
C10	0.0253 (5)	0.0226 (5)	0.0325 (6)	−0.0057 (4)	−0.0036 (4)	0.0002 (4)
C11	0.0333 (6)	0.0387 (7)	0.0416 (7)	−0.0086 (5)	−0.0111 (5)	0.0079 (5)
C12	0.0288 (6)	0.0368 (6)	0.0357 (6)	−0.0086 (5)	−0.0006 (5)	−0.0044 (5)
C13	0.0335 (6)	0.0305 (6)	0.0269 (5)	−0.0123 (5)	−0.0037 (4)	0.0021 (4)
C14	0.0375 (6)	0.0315 (6)	0.0333 (6)	−0.0103 (5)	−0.0059 (5)	0.0013 (5)
C15	0.0547 (8)	0.0313 (6)	0.0333 (6)	−0.0126 (6)	−0.0016 (6)	−0.0026 (5)
C16	0.0642 (9)	0.0449 (8)	0.0284 (6)	−0.0315 (7)	−0.0065 (6)	−0.0005 (5)
C17	0.0433 (7)	0.0552 (8)	0.0335 (6)	−0.0268 (6)	−0.0074 (5)	0.0033 (6)
C18	0.0341 (6)	0.0409 (7)	0.0332 (6)	−0.0137 (5)	−0.0023 (5)	0.0009 (5)
C19	0.0315 (6)	0.0282 (6)	0.0309 (6)	−0.0083 (5)	−0.0016 (4)	−0.0007 (4)
C20	0.0313 (6)	0.0297 (6)	0.0335 (6)	−0.0077 (5)	−0.0015 (5)	−0.0060 (5)
C21	0.0295 (6)	0.0263 (5)	0.0307 (6)	−0.0073 (4)	−0.0029 (4)	−0.0002 (4)
N1	0.0299 (5)	0.0260 (5)	0.0359 (5)	−0.0064 (4)	−0.0037 (4)	−0.0058 (4)
N2	0.0237 (4)	0.0218 (4)	0.0334 (5)	−0.0072 (4)	−0.0038 (4)	−0.0050 (4)
N3	0.0266 (5)	0.0228 (4)	0.0348 (5)	−0.0091 (4)	−0.0017 (4)	−0.0058 (4)
O1	0.0253 (4)	0.0276 (4)	0.0428 (5)	−0.0094 (3)	−0.0068 (3)	−0.0006 (3)
O2	0.0246 (4)	0.0233 (4)	0.0433 (5)	−0.0079 (3)	−0.0039 (3)	−0.0020 (3)
O3	0.0276 (4)	0.0371 (5)	0.0494 (5)	−0.0061 (4)	−0.0054 (4)	−0.0171 (4)
O4	0.0302 (4)	0.0363 (5)	0.0576 (6)	−0.0081 (4)	0.0034 (4)	−0.0172 (4)

Geometric parameters (Å, º) top

C1—N1	1.3356 (15)	C10—C12	1.5189 (16)
C1—C2	1.3828 (16)	C10—C11	1.5210 (16)
C2—C3	1.3895 (15)	C13—C18	1.3916 (17)
C3—C4	1.3857 (15)	C13—C14	1.3978 (17)
C3—C6	1.5043 (15)	C13—C19	1.4655 (16)
C4—C5	1.3827 (16)	C14—C15	1.3831 (18)
C5—N1	1.3369 (15)	C15—C16	1.384 (2)
C6—O1	1.2270 (13)	C16—C17	1.378 (2)
C6—N2	1.3451 (14)	C17—C18	1.3839 (18)
C7—N3	1.2823 (15)	C19—C20	1.3259 (17)
C7—C8	1.5006 (16)	C20—C21	1.4762 (16)
C7—C9	1.5092 (16)	C21—O4	1.2092 (14)
C9—C10	1.5403 (16)	C21—O3	1.3223 (14)
C10—O2	1.4404 (13)	N2—N3	1.3945 (12)

N1—C1—C2	123.32 (11)	C12—C10—C9	112.80 (10)
C1—C2—C3	118.68 (10)	C11—C10—C9	108.96 (10)
C4—C3—C2	118.13 (10)	C18—C13—C14	118.56 (11)
C4—C3—C6	117.42 (10)	C18—C13—C19	118.92 (11)
C2—C3—C6	124.44 (10)	C14—C13—C19	122.52 (11)
C5—C4—C3	119.36 (10)	C15—C14—C13	120.41 (12)
N1—C5—C4	122.68 (10)	C14—C15—C16	120.33 (13)
O1—C6—N2	124.30 (10)	C17—C16—C15	119.69 (12)
O1—C6—C3	120.53 (10)	C16—C17—C18	120.38 (13)
N2—C6—C3	115.10 (9)	C17—C18—C13	120.62 (12)
N3—C7—C8	115.83 (11)	C20—C19—C13	127.09 (11)
N3—C7—C9	126.93 (10)	C19—C20—C21	121.65 (11)
C8—C7—C9	117.13 (10)	O4—C21—O3	123.21 (11)
C7—C9—C10	117.46 (10)	O4—C21—C20	124.32 (11)
O2—C10—C12	109.13 (9)	O3—C21—C20	112.47 (10)
O2—C10—C11	109.03 (9)	C1—N1—C5	117.80 (10)
C12—C10—C11	111.19 (10)	C6—N2—N3	118.61 (9)
O2—C10—C9	105.53 (9)	C7—N3—N2	115.47 (10)

N1—C1—C2—C3	−0.4 (2)	C14—C15—C16—C17	−0.5 (2)
C1—C2—C3—C4	−1.34 (17)	C15—C16—C17—C18	−0.1 (2)
C1—C2—C3—C6	177.48 (11)	C16—C17—C18—C13	0.70 (19)
C2—C3—C4—C5	2.07 (17)	C14—C13—C18—C17	−0.79 (18)
C6—C3—C4—C5	−176.83 (10)	C19—C13—C18—C17	179.47 (11)
C3—C4—C5—N1	−1.15 (18)	C18—C13—C19—C20	−170.97 (12)
C4—C3—C6—O1	−16.46 (16)	C14—C13—C19—C20	9.3 (2)
C2—C3—C6—O1	164.72 (11)	C13—C19—C20—C21	−177.83 (11)
C4—C3—C6—N2	160.53 (10)	C19—C20—C21—O4	5.5 (2)
C2—C3—C6—N2	−18.29 (16)	C19—C20—C21—O3	−175.60 (11)
N3—C7—C9—C10	79.46 (15)	C2—C1—N1—C5	1.36 (19)
C8—C7—C9—C10	−104.40 (12)	C4—C5—N1—C1	−0.57 (18)
C7—C9—C10—O2	−78.16 (12)	O1—C6—N2—N3	−9.49 (16)
C7—C9—C10—C12	40.90 (14)	C3—C6—N2—N3	173.65 (9)
C7—C9—C10—C11	164.89 (10)	C8—C7—N3—N2	178.15 (10)
C18—C13—C14—C15	0.27 (18)	C9—C7—N3—N2	−5.66 (17)
C19—C13—C14—C15	179.99 (11)	C6—N2—N3—C7	161.38 (10)
C13—C14—C15—C16	0.35 (19)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5···O4ⁱ	0.95	2.37	3.2619 (15)	156
C2—H2···O2	0.95	2.54	3.3934 (14)	149
C1—H1···O4	0.95	2.62	3.2853 (15)	127
C12—H12C···O1ⁱⁱ	0.98	2.64	3.5315 (16)	151
N2—H2A···O2	0.913 (15)	1.879 (15)	2.7527 (12)	159.4 (13)
O2—H2B···O1ⁱⁱⁱ	0.901 (18)	1.859 (18)	2.7455 (12)	167.3 (15)
O3—H3A···N1	0.98 (2)	1.69 (2)	2.6633 (13)	176.7 (18)

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

(iz4h4m2pdnba) top

Crystal data top

C₁₂H₁₇N₃O₂·C₇H₄N₂O₆	F(000) = 936
M_r = 447.41	D_x = 1.437 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 9806 reflections
a = 6.9538 (3) Å	θ = 3.0–33.2°
b = 18.9491 (8) Å	µ = 0.11 mm⁻¹
c = 15.9042 (7) Å	T = 173 K
β = 99.261 (2)°	Plate, colourless
V = 2068.35 (15) Å³	0.39 × 0.29 × 0.13 mm
Z = 4

Data collection top

Bruker APEX-II CCD diffractometer	R_int = 0.082
φ and ω scans	θ_max = 37.9°, θ_min = 2.2°
196011 measured reflections	h = −12→12
11136 independent reflections	k = −32→32
9039 reflections with I > 2σ(I)	l = −27→27

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Secondary atom site location: dual
R[F² > 2σ(F²)] = 0.054	Hydrogen site location: mixed
wR(F²) = 0.140	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ²(F_o²) + (0.063P)² + 0.3866P] where P = (F_o² + 2F_c²)/3
11136 reflections	(Δ/σ)_max = 0.001
304 parameters	Δρ_max = 0.54 e Å⁻³
0 restraints	Δρ_min = −0.30 e Å⁻³
0 constraints

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.75023 (12)	0.79305 (4)	0.37655 (6)	0.02685 (16)
H1	0.620056	0.785049	0.385332	0.032*
C2	0.80882 (12)	0.86173 (4)	0.36493 (6)	0.02502 (15)
H2	0.721035	0.899982	0.366196	0.03*
C3	0.99891 (11)	0.87353 (3)	0.35136 (5)	0.01802 (12)
C4	1.12072 (11)	0.81555 (4)	0.34983 (6)	0.02293 (14)
H4	1.25075	0.821707	0.339865	0.028*
C5	1.05070 (12)	0.74873 (4)	0.36298 (6)	0.02489 (15)
H5	1.135422	0.709432	0.362735	0.03*
C6	1.08384 (11)	0.94510 (4)	0.33945 (5)	0.01863 (12)
C7	0.94740 (11)	1.11908 (4)	0.35685 (5)	0.02163 (13)
C8	1.00008 (14)	1.19146 (4)	0.33061 (7)	0.03136 (19)
H8A	1.079146	1.187817	0.285047	0.047*
H8B	1.074625	1.215897	0.379607	0.047*
H8C	0.880971	1.218069	0.309991	0.047*
C9	0.81736 (11)	1.11407 (4)	0.42407 (5)	0.02171 (13)
H9A	0.823097	1.159772	0.454536	0.026*
H9B	0.872309	1.07781	0.465971	0.026*
C10	0.60157 (11)	1.09601 (4)	0.39340 (5)	0.02058 (13)
C11	0.48520 (14)	1.11251 (5)	0.46426 (6)	0.02943 (17)
H11A	0.350751	1.096165	0.447658	0.044*
H11B	0.485621	1.163566	0.474142	0.044*
H11C	0.544314	1.088436	0.516625	0.044*
C12	0.51860 (13)	1.13425 (5)	0.31174 (6)	0.02751 (16)
H12A	0.592938	1.121279	0.26668	0.041*
H12B	0.527493	1.185327	0.321271	0.041*
H12C	0.381814	1.120851	0.294537	0.041*
C13	0.50422 (12)	0.52598 (4)	0.38858 (5)	0.02120 (13)
C14	0.64086 (12)	0.47440 (4)	0.41780 (5)	0.02264 (13)
H14	0.7727	0.486708	0.437857	0.027*
C15	0.58071 (13)	0.40461 (4)	0.41704 (5)	0.02386 (14)
C16	0.39212 (13)	0.38386 (4)	0.38674 (6)	0.02573 (15)
H16	0.354264	0.335647	0.385426	0.031*
C17	0.26133 (12)	0.43682 (4)	0.35845 (5)	0.02404 (14)
C18	0.31133 (12)	0.50765 (4)	0.35975 (5)	0.02292 (14)
H18	0.216274	0.542758	0.341426	0.028*
C19	0.56384 (12)	0.60195 (4)	0.38677 (5)	0.02299 (14)
N1	0.86819 (11)	0.73764 (3)	0.37599 (5)	0.02401 (13)
N2	0.96641 (10)	1.00026 (3)	0.34532 (5)	0.02225 (12)
N3	1.02608 (10)	1.06712 (3)	0.32286 (5)	0.02345 (13)
N4	0.06215 (12)	0.41643 (4)	0.32138 (5)	0.03026 (15)
N5	0.72474 (13)	0.35010 (4)	0.44851 (6)	0.03100 (16)
O1	1.25363 (9)	0.95028 (3)	0.32695 (4)	0.02453 (12)
O2	0.59720 (9)	1.02117 (3)	0.37826 (5)	0.02669 (13)
O3	0.75146 (10)	0.60968 (3)	0.39297 (6)	0.03384 (16)
O4	0.44527 (10)	0.64953 (3)	0.38067 (5)	0.03307 (15)
O5	−0.05911 (11)	0.46311 (4)	0.30469 (5)	0.03650 (16)
O6	0.02945 (14)	0.35353 (4)	0.30823 (7)	0.0490 (2)
O7	0.67404 (14)	0.28836 (4)	0.44060 (7)	0.0463 (2)
O8	0.88692 (13)	0.36924 (4)	0.48066 (6)	0.0446 (2)
H2A	0.844 (2)	0.9946 (8)	0.3511 (10)	0.041 (4)*
H2B	0.481 (2)	1.0091 (9)	0.3595 (11)	0.050 (4)*
H3	0.789 (3)	0.6602 (11)	0.3894 (12)	0.070 (6)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0217 (3)	0.0168 (3)	0.0432 (5)	−0.0020 (2)	0.0088 (3)	0.0015 (3)
C2	0.0203 (3)	0.0151 (3)	0.0407 (4)	0.0001 (2)	0.0081 (3)	0.0012 (3)
C3	0.0188 (3)	0.0139 (2)	0.0214 (3)	−0.0010 (2)	0.0031 (2)	−0.0005 (2)
C4	0.0194 (3)	0.0161 (3)	0.0338 (4)	0.0001 (2)	0.0060 (3)	−0.0008 (3)
C5	0.0228 (3)	0.0153 (3)	0.0366 (4)	0.0016 (2)	0.0046 (3)	0.0003 (3)
C6	0.0189 (3)	0.0145 (2)	0.0229 (3)	−0.0014 (2)	0.0045 (2)	−0.0008 (2)
C7	0.0192 (3)	0.0146 (3)	0.0312 (4)	−0.0021 (2)	0.0043 (3)	0.0005 (2)
C8	0.0304 (4)	0.0151 (3)	0.0510 (5)	−0.0020 (3)	0.0138 (4)	0.0034 (3)
C9	0.0213 (3)	0.0183 (3)	0.0252 (3)	−0.0011 (2)	0.0027 (3)	−0.0017 (2)
C10	0.0201 (3)	0.0176 (3)	0.0247 (3)	−0.0003 (2)	0.0055 (2)	−0.0004 (2)
C11	0.0284 (4)	0.0330 (4)	0.0290 (4)	0.0025 (3)	0.0111 (3)	−0.0004 (3)
C12	0.0249 (4)	0.0303 (4)	0.0268 (4)	0.0007 (3)	0.0024 (3)	0.0037 (3)
C13	0.0244 (3)	0.0153 (3)	0.0249 (3)	−0.0009 (2)	0.0067 (3)	0.0014 (2)
C14	0.0251 (3)	0.0171 (3)	0.0262 (3)	0.0001 (2)	0.0057 (3)	0.0010 (2)
C15	0.0291 (4)	0.0162 (3)	0.0267 (3)	0.0017 (2)	0.0056 (3)	0.0023 (2)
C16	0.0321 (4)	0.0174 (3)	0.0282 (4)	−0.0035 (3)	0.0062 (3)	0.0014 (3)
C17	0.0260 (3)	0.0210 (3)	0.0252 (3)	−0.0048 (3)	0.0046 (3)	0.0016 (2)
C18	0.0249 (3)	0.0186 (3)	0.0259 (3)	−0.0009 (2)	0.0059 (3)	0.0026 (2)
C19	0.0255 (3)	0.0158 (3)	0.0285 (3)	−0.0007 (2)	0.0068 (3)	0.0011 (2)
N1	0.0236 (3)	0.0147 (2)	0.0337 (3)	−0.0014 (2)	0.0045 (3)	0.0007 (2)
N2	0.0201 (3)	0.0130 (2)	0.0353 (3)	−0.0014 (2)	0.0094 (2)	0.0008 (2)
N3	0.0220 (3)	0.0140 (2)	0.0356 (3)	−0.0021 (2)	0.0086 (3)	0.0019 (2)
N4	0.0290 (4)	0.0297 (3)	0.0318 (4)	−0.0095 (3)	0.0041 (3)	0.0042 (3)
N5	0.0366 (4)	0.0201 (3)	0.0363 (4)	0.0050 (3)	0.0060 (3)	0.0043 (3)
O1	0.0190 (2)	0.0197 (2)	0.0363 (3)	−0.00242 (19)	0.0086 (2)	−0.0007 (2)
O2	0.0197 (3)	0.0181 (2)	0.0428 (4)	−0.00306 (19)	0.0066 (2)	−0.0038 (2)
O3	0.0240 (3)	0.0164 (2)	0.0610 (5)	−0.0024 (2)	0.0065 (3)	0.0029 (3)
O4	0.0302 (3)	0.0178 (2)	0.0532 (4)	0.0035 (2)	0.0124 (3)	0.0018 (3)
O5	0.0252 (3)	0.0413 (4)	0.0431 (4)	−0.0021 (3)	0.0058 (3)	0.0021 (3)
O6	0.0479 (5)	0.0298 (4)	0.0634 (6)	−0.0189 (3)	−0.0091 (4)	0.0063 (3)
O7	0.0548 (5)	0.0166 (3)	0.0657 (6)	0.0065 (3)	0.0043 (4)	0.0005 (3)
O8	0.0354 (4)	0.0339 (4)	0.0607 (5)	0.0049 (3)	−0.0036 (4)	0.0136 (4)

Geometric parameters (Å, º) top

C1—H1	0.95	C11—H11C	0.98
C1—C2	1.3849 (11)	C12—H12A	0.98
C1—N1	1.3333 (11)	C12—H12B	0.98
C2—H2	0.95	C12—H12C	0.98
C2—C3	1.3913 (11)	C13—C14	1.3899 (11)
C3—C4	1.3899 (10)	C13—C18	1.3899 (11)
C3—C6	1.5034 (10)	C13—C19	1.4996 (10)
C4—H4	0.95	C14—H14	0.95
C4—C5	1.3844 (11)	C14—C15	1.3865 (11)
C5—H5	0.95	C15—C16	1.3796 (12)
C5—N1	1.3349 (11)	C15—N5	1.4694 (11)
C6—N2	1.3389 (9)	C16—H16	0.95
C6—O1	1.2324 (9)	C16—C17	1.3803 (12)
C7—C8	1.4962 (11)	C17—C18	1.3858 (11)
C7—C9	1.5104 (11)	C17—N4	1.4671 (12)
C7—N3	1.2869 (10)	C18—H18	0.95
C8—H8A	0.98	C19—O3	1.3008 (10)
C8—H8B	0.98	C19—O4	1.2151 (10)
C8—H8C	0.98	N2—N3	1.3972 (9)
C9—H9A	0.99	N2—H2A	0.881 (16)
C9—H9B	0.99	N4—O5	1.2214 (12)
C9—C10	1.5399 (11)	N4—O6	1.2251 (11)
C10—C11	1.5220 (11)	N5—O7	1.2226 (11)
C10—C12	1.5178 (12)	N5—O8	1.2162 (12)
C10—O2	1.4379 (9)	O2—H2B	0.846 (17)
C11—H11A	0.98	O3—H3	1.00 (2)
C11—H11B	0.98

C2—C1—H1	118.5	H11A—C11—H11C	109.5
N1—C1—H1	118.5	H11B—C11—H11C	109.5
N1—C1—C2	122.99 (8)	C10—C12—H12A	109.5
C1—C2—H2	120.7	C10—C12—H12B	109.5
C1—C2—C3	118.62 (7)	C10—C12—H12C	109.5
C3—C2—H2	120.7	H12A—C12—H12B	109.5
C2—C3—C6	124.53 (6)	H12A—C12—H12C	109.5
C4—C3—C2	118.20 (6)	H12B—C12—H12C	109.5
C4—C3—C6	117.26 (6)	C14—C13—C18	120.40 (7)
C3—C4—H4	120.3	C14—C13—C19	120.34 (7)
C5—C4—C3	119.35 (7)	C18—C13—C19	119.25 (7)
C5—C4—H4	120.3	C13—C14—H14	120.7
C4—C5—H5	118.9	C15—C14—C13	118.60 (8)
N1—C5—C4	122.25 (7)	C15—C14—H14	120.7
N1—C5—H5	118.9	C14—C15—N5	118.64 (8)
N2—C6—C3	116.05 (6)	C16—C15—C14	122.92 (8)
O1—C6—C3	119.88 (6)	C16—C15—N5	118.43 (7)
O1—C6—N2	124.06 (7)	C15—C16—H16	121.8
C8—C7—C9	117.15 (7)	C15—C16—C17	116.49 (7)
N3—C7—C8	116.39 (7)	C17—C16—H16	121.8
N3—C7—C9	126.35 (7)	C16—C17—C18	123.28 (8)
C7—C8—H8A	109.5	C16—C17—N4	118.00 (7)
C7—C8—H8B	109.5	C18—C17—N4	118.65 (8)
C7—C8—H8C	109.5	C13—C18—H18	120.9
H8A—C8—H8B	109.5	C17—C18—C13	118.26 (7)
H8A—C8—H8C	109.5	C17—C18—H18	120.9
H8B—C8—H8C	109.5	O3—C19—C13	112.57 (7)
C7—C9—H9A	108.1	O4—C19—C13	121.85 (8)
C7—C9—H9B	108.1	O4—C19—O3	125.58 (8)
C7—C9—C10	116.98 (7)	C1—N1—C5	118.58 (7)
H9A—C9—H9B	107.3	C6—N2—N3	118.71 (6)
C10—C9—H9A	108.1	C6—N2—H2A	121.6 (10)
C10—C9—H9B	108.1	N3—N2—H2A	118.1 (10)
C11—C10—C9	109.08 (7)	C7—N3—N2	114.99 (7)
C12—C10—C9	112.45 (6)	O5—N4—C17	118.09 (8)
C12—C10—C11	111.19 (7)	O5—N4—O6	124.39 (9)
O2—C10—C9	105.39 (6)	O6—N4—C17	117.52 (9)
O2—C10—C11	109.10 (7)	O7—N5—C15	117.92 (9)
O2—C10—C12	109.44 (7)	O8—N5—C15	117.95 (8)
C10—C11—H11A	109.5	O8—N5—O7	124.14 (9)
C10—C11—H11B	109.5	C10—O2—H2B	108.5 (11)
C10—C11—H11C	109.5	C19—O3—H3	111.7 (11)
H11A—C11—H11B	109.5

C1—C2—C3—C4	0.24 (13)	C14—C13—C19—O4	−162.85 (9)
C1—C2—C3—C6	−178.79 (8)	C14—C15—C16—C17	−1.57 (13)
C2—C1—N1—C5	−0.53 (14)	C14—C15—N5—O7	−173.72 (9)
C2—C3—C4—C5	−0.95 (12)	C14—C15—N5—O8	6.17 (13)
C2—C3—C6—N2	2.16 (12)	C15—C16—C17—C18	−0.26 (13)
C2—C3—C6—O1	−179.31 (8)	C15—C16—C17—N4	176.65 (8)
C3—C4—C5—N1	0.98 (14)	C16—C15—N5—O7	5.25 (13)
C3—C6—N2—N3	−170.90 (7)	C16—C15—N5—O8	−174.86 (9)
C4—C3—C6—N2	−176.87 (7)	C16—C17—C18—C13	2.04 (13)
C4—C3—C6—O1	1.66 (11)	C16—C17—N4—O5	172.34 (8)
C4—C5—N1—C1	−0.23 (14)	C16—C17—N4—O6	−8.59 (13)
C6—C3—C4—C5	178.15 (7)	C18—C13—C14—C15	0.35 (12)
C6—N2—N3—C7	−156.49 (8)	C18—C13—C19—O3	−162.53 (8)
C7—C9—C10—C11	−164.94 (7)	C18—C13—C19—O4	17.93 (13)
C7—C9—C10—C12	−41.12 (9)	C18—C17—N4—O5	−10.60 (12)
C7—C9—C10—O2	78.04 (8)	C18—C17—N4—O6	168.47 (9)
C8—C7—C9—C10	102.98 (9)	C19—C13—C14—C15	−178.85 (7)
C8—C7—N3—N2	−176.90 (8)	C19—C13—C18—C17	177.17 (7)
C9—C7—N3—N2	6.96 (12)	N1—C1—C2—C3	0.52 (15)
C13—C14—C15—C16	1.54 (13)	N3—C7—C9—C10	−80.91 (11)
C13—C14—C15—N5	−179.54 (8)	N4—C17—C18—C13	−174.86 (7)
C14—C13—C18—C17	−2.05 (12)	N5—C15—C16—C17	179.50 (8)
C14—C13—C19—O3	16.69 (11)	O1—C6—N2—N3	10.65 (12)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2···O2	0.95	2.47	3.3822 (10)	161
C5—H5···O4ⁱ	0.95	2.41	3.3004 (11)	156
C9—H9A···O7ⁱⁱ	0.99	2.64	3.4719 (11)	141
N2—H2A···O2	0.881 (16)	1.901 (16)	2.7305 (9)	156.4 (14)
O2—H2B···O1ⁱⁱⁱ	0.846 (17)	1.936 (17)	2.7479 (9)	160.4 (16)
O3—H3···N1	1.00 (2)	1.59 (2)	2.5849 (9)	172.5 (18)

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

(iz4h4m2psa) top

Crystal data top

C₁₂H₁₇N₃O₂·C₂H₃O₂	F(000) = 628
M_r = 294.33	D_x = 1.307 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 5313 reflections
a = 6.9773 (4) Å	θ = 2.2–27.9°
b = 20.6482 (11) Å	µ = 0.10 mm⁻¹
c = 10.5035 (5) Å	T = 173 K
β = 98.764 (2)°	Needle, colourless
V = 1495.56 (14) Å³	0.52 × 0.23 × 0.07 mm
Z = 4

Data collection top

Bruker APEX-II CCD diffractometer	R_int = 0.089
φ and ω scans	θ_max = 28.4°, θ_min = 2.2°
45682 measured reflections	h = −9→9
3733 independent reflections	k = −27→27
3131 reflections with I > 2σ(I)	l = −14→14

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Secondary atom site location: dual
R[F² > 2σ(F²)] = 0.044	Hydrogen site location: mixed
wR(F²) = 0.113	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ²(F_o²) + (0.0392P)² + 0.535P] where P = (F_o² + 2F_c²)/3
3733 reflections	(Δ/σ)_max < 0.001
205 parameters	Δρ_max = 0.33 e Å⁻³
0 restraints	Δρ_min = −0.21 e Å⁻³
0 constraints

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.52226 (18)	0.57047 (6)	0.44293 (12)	0.0300 (3)
H1	0.384809	0.567409	0.429973	0.036*
C2	0.61528 (18)	0.59085 (6)	0.56188 (12)	0.0285 (3)
H2	0.543232	0.600767	0.629178	0.034*
C3	0.81585 (17)	0.59654 (6)	0.58116 (12)	0.0253 (2)
C4	0.9128 (2)	0.58140 (8)	0.47972 (14)	0.0381 (3)
H4	1.049871	0.585332	0.488833	0.046*
C5	0.8076 (2)	0.56043 (9)	0.36467 (14)	0.0423 (4)
H5	0.87581	0.54945	0.296013	0.051*
C6	0.93522 (18)	0.61718 (6)	0.70627 (12)	0.0271 (3)
C7	0.85002 (18)	0.69442 (7)	0.98589 (13)	0.0305 (3)
C8	0.9455 (2)	0.70029 (9)	1.12325 (14)	0.0453 (4)
H8A	1.045501	0.666863	1.14185	0.068*
H8B	0.848147	0.694676	1.180498	0.068*
H8C	1.0051	0.743184	1.137199	0.068*
C9	0.68010 (18)	0.73834 (6)	0.94142 (14)	0.0310 (3)
H9A	0.699849	0.757522	0.858011	0.037*
H9B	0.683813	0.774323	1.004043	0.037*
C10	0.47549 (18)	0.70887 (6)	0.92409 (13)	0.0290 (3)
C11	0.4490 (2)	0.66207 (8)	1.03095 (15)	0.0408 (3)
H11A	0.316533	0.644886	1.016283	0.061*
H11B	0.47173	0.684693	1.113897	0.061*
H11C	0.541577	0.626315	1.031853	0.061*
C12	0.3266 (2)	0.76336 (7)	0.91431 (16)	0.0384 (3)
H12A	0.351928	0.79424	0.848004	0.058*
H12B	0.336029	0.785603	0.997447	0.058*
H12C	0.196083	0.745262	0.891178	0.058*
C13	0.22651 (18)	0.51680 (6)	0.12596 (12)	0.0289 (3)
C14	0.10831 (18)	0.49903 (7)	−0.00143 (12)	0.0290 (3)
H14A	0.144832	0.454908	−0.025756	0.035*
H14B	0.139657	0.52936	−0.068293	0.035*
N1	0.61526 (16)	0.55494 (6)	0.34579 (11)	0.0327 (3)
N2	0.83557 (16)	0.64498 (5)	0.79153 (10)	0.0276 (2)
N3	0.92959 (15)	0.65410 (6)	0.91728 (10)	0.0297 (2)
O1	1.11160 (13)	0.60926 (5)	0.72428 (10)	0.0381 (2)
O2	0.45415 (14)	0.67502 (5)	0.80286 (10)	0.0383 (3)
O3	0.41009 (14)	0.50102 (5)	0.13342 (10)	0.0378 (2)
O4	0.16127 (15)	0.54358 (6)	0.21215 (10)	0.0479 (3)
H2A	0.705 (3)	0.6495 (8)	0.7760 (15)	0.036 (4)*
H3A	0.477 (3)	0.5206 (10)	0.211 (2)	0.063 (6)*
H3B	0.345 (3)	0.6556 (9)	0.7882 (18)	0.052 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0214 (6)	0.0365 (7)	0.0312 (6)	−0.0007 (5)	0.0015 (5)	−0.0051 (5)
C2	0.0233 (6)	0.0330 (6)	0.0292 (6)	−0.0023 (5)	0.0040 (5)	−0.0067 (5)
C3	0.0238 (6)	0.0254 (6)	0.0259 (6)	−0.0012 (4)	0.0011 (4)	−0.0024 (4)
C4	0.0217 (6)	0.0580 (9)	0.0344 (7)	−0.0013 (6)	0.0041 (5)	−0.0103 (6)
C5	0.0289 (7)	0.0691 (10)	0.0294 (7)	0.0005 (7)	0.0062 (5)	−0.0117 (7)
C6	0.0226 (6)	0.0292 (6)	0.0285 (6)	−0.0029 (5)	0.0013 (5)	−0.0045 (5)
C7	0.0229 (6)	0.0374 (7)	0.0306 (6)	−0.0047 (5)	0.0024 (5)	−0.0081 (5)
C8	0.0331 (8)	0.0673 (10)	0.0336 (7)	0.0056 (7)	−0.0009 (6)	−0.0187 (7)
C9	0.0258 (6)	0.0306 (6)	0.0364 (7)	−0.0033 (5)	0.0044 (5)	−0.0079 (5)
C10	0.0230 (6)	0.0324 (6)	0.0315 (6)	−0.0028 (5)	0.0038 (5)	−0.0065 (5)
C11	0.0308 (7)	0.0459 (8)	0.0465 (8)	−0.0024 (6)	0.0087 (6)	0.0076 (7)
C12	0.0270 (7)	0.0384 (7)	0.0497 (9)	0.0014 (5)	0.0052 (6)	−0.0023 (6)
C13	0.0274 (6)	0.0344 (6)	0.0244 (6)	−0.0021 (5)	0.0027 (5)	−0.0003 (5)
C14	0.0282 (7)	0.0349 (6)	0.0232 (6)	−0.0020 (5)	0.0014 (5)	−0.0039 (5)
N1	0.0269 (5)	0.0436 (6)	0.0267 (5)	0.0011 (5)	0.0010 (4)	−0.0045 (5)
N2	0.0210 (5)	0.0340 (6)	0.0268 (5)	−0.0021 (4)	0.0000 (4)	−0.0065 (4)
N3	0.0228 (5)	0.0381 (6)	0.0269 (5)	−0.0028 (4)	−0.0003 (4)	−0.0076 (4)
O1	0.0209 (4)	0.0536 (6)	0.0385 (5)	−0.0007 (4)	0.0005 (4)	−0.0158 (5)
O2	0.0237 (5)	0.0508 (6)	0.0400 (6)	−0.0075 (4)	0.0042 (4)	−0.0187 (5)
O3	0.0273 (5)	0.0546 (6)	0.0300 (5)	0.0034 (4)	−0.0003 (4)	−0.0112 (4)
O4	0.0292 (5)	0.0827 (9)	0.0314 (5)	0.0010 (5)	0.0034 (4)	−0.0213 (5)

Geometric parameters (Å, º) top

C1—N1	1.3291 (17)	C7—C9	1.5092 (19)
C1—C2	1.3828 (17)	C9—C10	1.5371 (17)
C2—C3	1.3881 (17)	C10—O2	1.4402 (16)
C3—C4	1.3821 (18)	C10—C11	1.514 (2)
C3—C6	1.5061 (17)	C10—C12	1.5242 (19)
C4—C5	1.3843 (19)	C13—O4	1.2075 (16)
C5—N1	1.3312 (18)	C13—O3	1.3124 (16)
C6—O1	1.2272 (15)	C13—C14	1.5062 (17)
C6—N2	1.3434 (16)	C14—C14ⁱ	1.517 (3)
C7—N3	1.2815 (17)	N2—N3	1.3951 (14)
C7—C8	1.4990 (19)

N1—C1—C2	123.38 (12)	O2—C10—C11	109.75 (11)
C1—C2—C3	118.78 (12)	O2—C10—C12	108.72 (11)
C4—C3—C2	117.99 (11)	C11—C10—C12	111.24 (11)
C4—C3—C6	117.78 (11)	O2—C10—C9	105.42 (10)
C2—C3—C6	124.22 (11)	C11—C10—C9	112.40 (11)
C3—C4—C5	119.14 (12)	C12—C10—C9	109.09 (11)
N1—C5—C4	123.03 (13)	O4—C13—O3	123.02 (12)
O1—C6—N2	124.25 (11)	O4—C13—C14	124.03 (12)
O1—C6—C3	120.34 (11)	O3—C13—C14	112.95 (11)
N2—C6—C3	115.40 (11)	C13—C14—C14ⁱ	112.86 (13)
N3—C7—C8	115.27 (12)	C1—N1—C5	117.65 (11)
N3—C7—C9	127.12 (12)	C6—N2—N3	118.19 (10)
C8—C7—C9	117.52 (12)	C7—N3—N2	116.02 (11)
C7—C9—C10	118.06 (11)

N1—C1—C2—C3	1.1 (2)	C7—C9—C10—O2	−78.30 (14)
C1—C2—C3—C4	−0.04 (19)	C7—C9—C10—C11	41.23 (16)
C1—C2—C3—C6	−179.03 (12)	C7—C9—C10—C12	165.10 (12)
C2—C3—C4—C5	−1.0 (2)	O4—C13—C14—C14ⁱ	−15.8 (2)
C6—C3—C4—C5	178.10 (14)	O3—C13—C14—C14ⁱ	165.18 (14)
C3—C4—C5—N1	1.0 (3)	C2—C1—N1—C5	−1.0 (2)
C4—C3—C6—O1	−13.09 (19)	C4—C5—N1—C1	−0.1 (2)
C2—C3—C6—O1	165.90 (13)	O1—C6—N2—N3	−13.1 (2)
C4—C3—C6—N2	165.71 (12)	C3—C6—N2—N3	168.19 (11)
C2—C3—C6—N2	−15.30 (18)	C8—C7—N3—N2	176.08 (12)
N3—C7—C9—C10	79.06 (18)	C9—C7—N3—N2	−7.5 (2)
C8—C7—C9—C10	−104.58 (15)	C6—N2—N3—C7	163.07 (12)

Symmetry code: (i) −x, −y+1, −z.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1···O4	0.95	2.61	3.2662 (16)	126
C2—H2···O2	0.95	2.53	3.3998 (16)	152
C5—H5···O4ⁱⁱ	0.95	2.3	3.1594 (18)	150
C12—H12C···N3ⁱⁱⁱ	0.98	2.69	3.5762 (18)	151
C14—H14A···N3^iv	0.99	2.61	3.3046 (18)	127
N2—H2A···O2	0.904 (17)	1.892 (17)	2.7529 (15)	158.6 (15)
O3—H3A···N1	0.96 (2)	1.74 (2)	2.7003 (15)	175.4 (19)
O2—H3B···O1ⁱⁱⁱ	0.85 (2)	1.92 (2)	2.7634 (14)	169.4 (18)

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

(iz4h4m2p4nba) top

Crystal data top

C₁₂H₁₇N₃O₂·C₇H₅NO₄	Z = 2
M_r = 402.4	F(000) = 424
Triclinic, P1	D_x = 1.393 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 6.8701 (3) Å	Cell parameters from 9953 reflections
b = 12.1647 (6) Å	θ = 2.7–30.4°
c = 12.1779 (6) Å	µ = 0.11 mm⁻¹
α = 101.130 (2)°	T = 173 K
β = 92.818 (2)°	Plate, colourless
γ = 105.005 (2)°	0.57 × 0.42 × 0.11 mm
V = 959.26 (8) Å³

Data collection top

Bruker APEX-II CCD diffractometer	R_int = 0.047
φ and ω scans	θ_max = 30.5°, θ_min = 1.7°
42678 measured reflections	h = −9→9
5857 independent reflections	k = −17→17
4742 reflections with I > 2σ(I)	l = −17→17

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Secondary atom site location: dual
R[F² > 2σ(F²)] = 0.045	Hydrogen site location: mixed
wR(F²) = 0.136	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ²(F_o²) + (0.0594P)² + 0.2865P] where P = (F_o² + 2F_c²)/3
5857 reflections	(Δ/σ)_max < 0.001
277 parameters	Δρ_max = 0.34 e Å⁻³
0 restraints	Δρ_min = −0.27 e Å⁻³
0 constraints

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	−0.1541 (2)	0.38928 (12)	0.39749 (11)	0.0352 (3)
H1	−0.258859	0.350927	0.436237	0.042*
C2	−0.18684 (19)	0.47540 (12)	0.34533 (11)	0.0330 (3)
H2	−0.310744	0.496247	0.34955	0.04*
C3	−0.03734 (17)	0.53074 (11)	0.28704 (9)	0.0282 (2)
C4	0.1434 (2)	0.49881 (13)	0.28520 (12)	0.0358 (3)
H4	0.2504	0.535459	0.246799	0.043*
C5	0.1635 (2)	0.41250 (14)	0.34057 (13)	0.0397 (3)
H5	0.286955	0.391043	0.339298	0.048*
C6	−0.08285 (18)	0.62108 (11)	0.22847 (10)	0.0284 (2)
C7	0.12358 (18)	0.76898 (11)	0.02733 (11)	0.0311 (2)
C8	0.1066 (2)	0.87056 (14)	−0.02139 (16)	0.0459 (4)
H8A	0.017029	0.842469	−0.091994	0.069*
H8B	0.241178	0.913328	−0.036073	0.069*
H8C	0.050525	0.922347	0.032008	0.069*
C9	0.23639 (18)	0.68911 (10)	−0.03456 (10)	0.0294 (2)
H9A	0.240627	0.700134	−0.112945	0.035*
H9B	0.158325	0.60762	−0.03764	0.035*
C10	0.45432 (17)	0.70603 (10)	0.01601 (10)	0.0275 (2)
C11	0.57501 (19)	0.83345 (11)	0.04678 (12)	0.0343 (3)
H11A	0.503002	0.877538	0.098032	0.051*
H11B	0.591037	0.864717	−0.02162	0.051*
H11C	0.708818	0.840248	0.083784	0.051*
C12	0.5590 (2)	0.63557 (11)	−0.06631 (11)	0.0351 (3)
H12A	0.692034	0.638627	−0.030878	0.053*
H12B	0.576211	0.668254	−0.133871	0.053*
H12C	0.476164	0.554451	−0.087218	0.053*
C13	0.36829 (19)	0.14586 (11)	0.58877 (10)	0.0310 (2)
C14	0.5757 (2)	0.16108 (12)	0.60918 (11)	0.0353 (3)
H14	0.668564	0.225786	0.590452	0.042*
C15	0.6475 (2)	0.08268 (13)	0.65652 (12)	0.0373 (3)
H15	0.788872	0.092412	0.67056	0.045*
C16	0.5082 (2)	−0.00987 (12)	0.68269 (11)	0.0351 (3)
C17	0.3013 (2)	−0.02690 (12)	0.66533 (11)	0.0370 (3)
H17	0.209226	−0.091023	0.685514	0.044*
C18	0.2320 (2)	0.05244 (12)	0.61755 (11)	0.0351 (3)
H18	0.090472	0.04278	0.604448	0.042*
C19	0.3010 (2)	0.23056 (12)	0.53185 (11)	0.0336 (3)
N1	0.01815 (17)	0.35778 (10)	0.39572 (10)	0.0360 (2)
N2	0.05309 (16)	0.66254 (9)	0.16110 (9)	0.0297 (2)
N3	0.03172 (16)	0.75593 (9)	0.11481 (10)	0.0326 (2)
N4	0.5837 (2)	−0.09489 (12)	0.73115 (11)	0.0451 (3)
O1	−0.24155 (14)	0.64889 (9)	0.24079 (8)	0.0372 (2)
O2	0.43284 (14)	0.66011 (9)	0.11625 (8)	0.0346 (2)
O3	0.10264 (14)	0.20816 (9)	0.51162 (9)	0.0385 (2)
O4	0.42121 (16)	0.31012 (10)	0.50445 (10)	0.0479 (3)
O5	0.4607 (2)	−0.17109 (12)	0.76304 (12)	0.0632 (4)
O6	0.7659 (2)	−0.08548 (13)	0.73687 (14)	0.0671 (4)
H2A	0.170 (3)	0.6461 (14)	0.1561 (14)	0.037 (4)*
H2B	0.549 (3)	0.6666 (17)	0.1477 (16)	0.052 (5)*
H3A	0.079 (4)	0.264 (2)	0.4718 (19)	0.071 (6)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0293 (6)	0.0416 (7)	0.0347 (6)	0.0052 (5)	0.0044 (5)	0.0138 (5)
C2	0.0250 (5)	0.0409 (6)	0.0339 (6)	0.0087 (5)	0.0035 (4)	0.0107 (5)
C3	0.0257 (5)	0.0333 (6)	0.0261 (5)	0.0089 (4)	0.0007 (4)	0.0072 (4)
C4	0.0295 (6)	0.0471 (7)	0.0406 (6)	0.0164 (5)	0.0110 (5)	0.0228 (6)
C5	0.0334 (6)	0.0508 (8)	0.0466 (7)	0.0192 (6)	0.0115 (5)	0.0260 (6)
C6	0.0255 (5)	0.0334 (6)	0.0274 (5)	0.0103 (4)	0.0003 (4)	0.0067 (4)
C7	0.0234 (5)	0.0295 (5)	0.0440 (6)	0.0089 (4)	0.0006 (5)	0.0151 (5)
C8	0.0382 (7)	0.0435 (7)	0.0720 (10)	0.0206 (6)	0.0144 (7)	0.0354 (7)
C9	0.0277 (5)	0.0280 (5)	0.0330 (5)	0.0067 (4)	0.0001 (4)	0.0099 (4)
C10	0.0266 (5)	0.0275 (5)	0.0315 (5)	0.0108 (4)	0.0035 (4)	0.0091 (4)
C11	0.0279 (6)	0.0298 (6)	0.0431 (7)	0.0073 (5)	0.0030 (5)	0.0040 (5)
C12	0.0366 (6)	0.0327 (6)	0.0397 (6)	0.0154 (5)	0.0070 (5)	0.0074 (5)
C13	0.0309 (6)	0.0344 (6)	0.0279 (5)	0.0087 (5)	0.0054 (4)	0.0065 (4)
C14	0.0311 (6)	0.0372 (6)	0.0366 (6)	0.0074 (5)	0.0056 (5)	0.0079 (5)
C15	0.0331 (6)	0.0421 (7)	0.0373 (6)	0.0138 (5)	0.0039 (5)	0.0050 (5)
C16	0.0424 (7)	0.0362 (6)	0.0291 (6)	0.0167 (5)	0.0027 (5)	0.0048 (5)
C17	0.0392 (7)	0.0366 (6)	0.0352 (6)	0.0077 (5)	0.0053 (5)	0.0108 (5)
C18	0.0314 (6)	0.0399 (7)	0.0348 (6)	0.0089 (5)	0.0051 (5)	0.0107 (5)
C19	0.0308 (6)	0.0386 (6)	0.0325 (6)	0.0085 (5)	0.0072 (5)	0.0110 (5)
N1	0.0340 (6)	0.0406 (6)	0.0364 (5)	0.0099 (5)	0.0043 (4)	0.0159 (5)
N2	0.0258 (5)	0.0317 (5)	0.0375 (5)	0.0127 (4)	0.0056 (4)	0.0140 (4)
N3	0.0274 (5)	0.0308 (5)	0.0454 (6)	0.0124 (4)	0.0044 (4)	0.0158 (4)
N4	0.0558 (8)	0.0444 (7)	0.0386 (6)	0.0213 (6)	0.0004 (5)	0.0081 (5)
O1	0.0294 (4)	0.0540 (6)	0.0364 (5)	0.0209 (4)	0.0056 (4)	0.0157 (4)
O2	0.0263 (4)	0.0479 (5)	0.0374 (5)	0.0156 (4)	0.0043 (4)	0.0200 (4)
O3	0.0306 (5)	0.0424 (5)	0.0440 (5)	0.0060 (4)	−0.0006 (4)	0.0191 (4)
O4	0.0347 (5)	0.0553 (6)	0.0622 (7)	0.0100 (5)	0.0136 (5)	0.0341 (5)
O5	0.0715 (9)	0.0620 (8)	0.0673 (8)	0.0210 (7)	0.0074 (7)	0.0370 (7)
O6	0.0546 (7)	0.0658 (8)	0.0918 (10)	0.0308 (7)	−0.0014 (7)	0.0254 (7)

Geometric parameters (Å, º) top

C1—N1	1.3352 (17)	C10—C12	1.5216 (17)
C1—C2	1.3843 (18)	C13—C18	1.3879 (19)
C2—C3	1.3821 (18)	C13—C14	1.3916 (18)
C3—C4	1.3937 (16)	C13—C19	1.4987 (18)
C3—C6	1.5076 (16)	C14—C15	1.3834 (19)
C4—C5	1.3839 (18)	C15—C16	1.377 (2)
C5—N1	1.3361 (18)	C16—C17	1.382 (2)
C6—O1	1.2300 (14)	C16—N4	1.4734 (18)
C6—N2	1.3383 (16)	C17—C18	1.3872 (19)
C7—N3	1.2798 (17)	C19—O4	1.2115 (17)
C7—C8	1.4978 (17)	C19—O3	1.3197 (16)
C7—C9	1.5091 (17)	N2—N3	1.3983 (14)
C9—C10	1.5376 (16)	N4—O5	1.2204 (19)
C10—O2	1.4360 (14)	N4—O6	1.2244 (19)
C10—C11	1.5200 (17)

N1—C1—C2	122.87 (12)	C18—C13—C14	119.96 (12)
C3—C2—C1	119.30 (12)	C18—C13—C19	122.35 (11)
C2—C3—C4	118.22 (11)	C14—C13—C19	117.66 (12)
C2—C3—C6	117.30 (11)	C15—C14—C13	120.50 (13)
C4—C3—C6	124.48 (11)	C16—C15—C14	118.05 (12)
C5—C4—C3	118.50 (12)	C15—C16—C17	123.14 (12)
N1—C5—C4	123.40 (12)	C15—C16—N4	118.32 (13)
O1—C6—N2	124.07 (11)	C17—C16—N4	118.54 (13)
O1—C6—C3	119.82 (11)	C16—C17—C18	118.00 (13)
N2—C6—C3	116.05 (10)	C17—C18—C13	120.34 (12)
N3—C7—C8	116.07 (12)	O4—C19—O3	123.87 (12)
N3—C7—C9	126.61 (11)	O4—C19—C13	121.89 (12)
C8—C7—C9	117.23 (12)	O3—C19—C13	114.21 (11)
C7—C9—C10	115.77 (10)	C1—N1—C5	117.70 (11)
O2—C10—C11	109.36 (10)	C6—N2—N3	118.66 (10)
O2—C10—C12	109.70 (9)	C7—N3—N2	115.47 (10)
C11—C10—C12	110.84 (10)	O5—N4—O6	123.67 (14)
O2—C10—C9	105.04 (9)	O5—N4—C16	118.05 (14)
C11—C10—C9	112.50 (10)	O6—N4—C16	118.28 (14)
C12—C10—C9	109.23 (10)

N1—C1—C2—C3	1.1 (2)	C15—C16—C17—C18	1.1 (2)
C1—C2—C3—C4	−1.30 (19)	N4—C16—C17—C18	−178.72 (12)
C1—C2—C3—C6	178.02 (11)	C16—C17—C18—C13	−0.2 (2)
C2—C3—C4—C5	0.7 (2)	C14—C13—C18—C17	−0.8 (2)
C6—C3—C4—C5	−178.53 (13)	C19—C13—C18—C17	176.94 (12)
C3—C4—C5—N1	0.1 (2)	C18—C13—C19—O4	−178.07 (13)
C2—C3—C6—O1	5.39 (17)	C14—C13—C19—O4	−0.26 (19)
C4—C3—C6—O1	−175.34 (13)	C18—C13—C19—O3	−0.16 (18)
C2—C3—C6—N2	−171.79 (11)	C14—C13—C19—O3	177.65 (12)
C4—C3—C6—N2	7.49 (18)	C2—C1—N1—C5	−0.2 (2)
N3—C7—C9—C10	−81.86 (16)	C4—C5—N1—C1	−0.4 (2)
C8—C7—C9—C10	101.78 (14)	O1—C6—N2—N3	10.29 (18)
C7—C9—C10—O2	72.54 (12)	C3—C6—N2—N3	−172.67 (10)
C7—C9—C10—C11	−46.33 (14)	C8—C7—N3—N2	−178.43 (11)
C7—C9—C10—C12	−169.86 (10)	C9—C7—N3—N2	5.17 (18)
C18—C13—C14—C15	1.0 (2)	C6—N2—N3—C7	−159.73 (11)
C19—C13—C14—C15	−176.89 (12)	C15—C16—N4—O5	173.89 (14)
C13—C14—C15—C16	−0.1 (2)	C17—C16—N4—O5	−6.31 (19)
C14—C15—C16—C17	−0.9 (2)	C15—C16—N4—O6	−6.4 (2)
C14—C15—C16—N4	178.87 (12)	C17—C16—N4—O6	173.45 (14)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1···O4ⁱ	0.95	2.35	3.2462 (17)	156
C4—H4···O2	0.95	2.56	3.4609 (16)	159
C5—H5···O4	0.95	2.63	3.2285 (17)	121
C9—H9A···O5ⁱⁱ	0.99	2.63	3.4608 (18)	141
C11—H11B···O5ⁱⁱ	0.98	2.64	3.492 (2)	145
N2—H2A···O2	0.876 (17)	1.869 (17)	2.6981 (14)	157.2 (16)
O2—H2B···O1ⁱⁱⁱ	0.84 (2)	1.87 (2)	2.6884 (12)	162.6 (19)
O3—H3A···N1	0.94 (2)	1.72 (2)	2.6646 (15)	176 (2)

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

(iz4h4m2p25dhba) top

Crystal data top

C₁₂H₁₇N₃O₂·C₇H₆O₄	F(000) = 824
M_r = 389.4	D_x = 1.309 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 9975 reflections
a = 8.5777 (5) Å	θ = 2.7–28.3°
b = 17.5407 (9) Å	µ = 0.10 mm⁻¹
c = 13.2200 (8) Å	T = 133 K
β = 96.605 (2)°	Block, colourless
V = 1975.86 (19) Å³	0.58 × 0.49 × 0.27 mm
Z = 4

Data collection top

Bruker APEX-II CCD diffractometer	4391 reflections with I > 2σ(I)
φ and ω scans	R_int = 0.028
Absorption correction: multi-scan SADABS (Sheldrick, 1996)	θ_max = 28.3°, θ_min = 2.7°
T_min = 0.689, T_max = 0.746	h = −11→11
41489 measured reflections	k = −23→23
4917 independent reflections	l = −17→17

Refinement top

Refinement on F²	0 constraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.038	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.105	w = 1/[σ²(F_o²) + (0.0563P)² + 0.6282P] where P = (F_o² + 2F_c²)/3
S = 0.99	(Δ/σ)_max = 0.002
4917 reflections	Δρ_max = 0.30 e Å⁻³
273 parameters	Δρ_min = −0.21 e Å⁻³
0 restraints

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.33567 (13)	0.40959 (6)	0.04190 (7)	0.0499 (3)
O2	0.40462 (10)	0.24120 (4)	0.33566 (7)	0.02967 (18)
N1	0.68923 (11)	0.53186 (5)	0.32259 (7)	0.02567 (19)
N2	0.30640 (10)	0.33146 (5)	0.17506 (7)	0.02280 (18)
N3	0.21850 (10)	0.28094 (5)	0.11044 (7)	0.02453 (19)
C1	0.60091 (13)	0.48059 (6)	0.36485 (8)	0.0258 (2)
H1	0.613773	0.475257	0.436842	0.031*
C2	0.49146 (12)	0.43490 (6)	0.30814 (8)	0.0239 (2)
H2B	0.429437	0.39967	0.340676	0.029*
C3	0.47442 (12)	0.44176 (6)	0.20255 (8)	0.0229 (2)
C4	0.56594 (13)	0.49526 (6)	0.15887 (8)	0.0269 (2)
H4	0.556356	0.501552	0.087044	0.032*
C5	0.67109 (13)	0.53924 (6)	0.22113 (9)	0.0272 (2)
H5	0.732578	0.575962	0.19079	0.033*
C6	0.36534 (13)	0.39331 (7)	0.13209 (8)	0.0275 (2)
C7	0.14981 (12)	0.22632 (6)	0.15249 (8)	0.0245 (2)
C8	0.05999 (15)	0.17101 (7)	0.08130 (9)	0.0358 (3)
H8A	0.070467	0.185411	0.010773	0.054*
H8B	−0.051054	0.171989	0.09227	0.054*
H8C	0.101933	0.119532	0.094376	0.054*
C9	0.14366 (12)	0.21453 (6)	0.26539 (8)	0.0242 (2)
H9A	0.053693	0.180655	0.273676	0.029*
H9B	0.121159	0.264427	0.295566	0.029*
C10	0.28947 (13)	0.18092 (6)	0.32794 (8)	0.0249 (2)
C11	0.35211 (16)	0.11144 (7)	0.27760 (11)	0.0365 (3)
H11A	0.386561	0.126165	0.212202	0.055*
H11B	0.26912	0.072954	0.266204	0.055*
H11C	0.441125	0.090285	0.321872	0.055*
C12	0.25117 (17)	0.16232 (9)	0.43508 (10)	0.0405 (3)
H12A	0.345854	0.143724	0.476232	0.061*
H12B	0.169713	0.122917	0.431415	0.061*
H12C	0.213329	0.208373	0.466415	0.061*
O3	0.89122 (10)	0.61477 (5)	0.43598 (6)	0.02935 (18)
H3	0.826706	0.587005	0.400326	0.044*
O4	0.83848 (11)	0.53331 (5)	0.55747 (7)	0.0353 (2)
O5	0.98052 (12)	0.54740 (5)	0.73987 (7)	0.0358 (2)
O6	1.28808 (9)	0.79900 (4)	0.60852 (6)	0.02509 (17)
C13	1.02636 (12)	0.63101 (6)	0.60061 (8)	0.0221 (2)
C14	1.05291 (13)	0.60839 (6)	0.70296 (8)	0.0259 (2)
C15	1.15658 (13)	0.65005 (7)	0.77055 (8)	0.0279 (2)
H15	1.174578	0.635025	0.839951	0.033*
C16	1.23346 (12)	0.71295 (6)	0.73772 (8)	0.0248 (2)
H16	1.303786	0.740933	0.784571	0.03*
C17	1.20814 (11)	0.73559 (5)	0.63579 (8)	0.0208 (2)
C18	1.10520 (12)	0.69496 (6)	0.56782 (7)	0.02070 (19)
H18	1.087739	0.710403	0.498569	0.025*
C19	0.91146 (13)	0.58868 (6)	0.52912 (8)	0.0257 (2)
H2	0.497 (2)	0.2229 (10)	0.3592 (13)	0.053 (5)*
H2A	0.3499 (18)	0.3128 (8)	0.2338 (12)	0.035 (4)*
H5A	0.917 (2)	0.5296 (12)	0.6823 (17)	0.070 (6)*
H6	1.268 (2)	0.8085 (11)	0.5438 (15)	0.060 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0572 (6)	0.0634 (7)	0.0256 (4)	−0.0326 (5)	−0.0106 (4)	0.0136 (4)
O2	0.0254 (4)	0.0235 (4)	0.0380 (5)	−0.0024 (3)	−0.0055 (3)	0.0037 (3)
N1	0.0278 (4)	0.0192 (4)	0.0300 (5)	−0.0019 (3)	0.0029 (4)	−0.0034 (3)
N2	0.0249 (4)	0.0230 (4)	0.0197 (4)	−0.0044 (3)	−0.0005 (3)	−0.0027 (3)
N3	0.0230 (4)	0.0285 (4)	0.0216 (4)	−0.0052 (3)	0.0005 (3)	−0.0054 (3)
C1	0.0305 (5)	0.0227 (5)	0.0244 (5)	−0.0023 (4)	0.0042 (4)	−0.0038 (4)
C2	0.0270 (5)	0.0205 (5)	0.0246 (5)	−0.0031 (4)	0.0045 (4)	−0.0013 (4)
C3	0.0234 (5)	0.0198 (5)	0.0249 (5)	−0.0005 (4)	0.0000 (4)	0.0007 (4)
C4	0.0297 (5)	0.0254 (5)	0.0247 (5)	−0.0028 (4)	−0.0006 (4)	0.0056 (4)
C5	0.0287 (5)	0.0207 (5)	0.0320 (6)	−0.0040 (4)	0.0025 (4)	0.0040 (4)
C6	0.0271 (5)	0.0312 (5)	0.0234 (5)	−0.0069 (4)	0.0000 (4)	0.0011 (4)
C7	0.0205 (5)	0.0289 (5)	0.0241 (5)	−0.0035 (4)	0.0028 (4)	−0.0050 (4)
C8	0.0392 (6)	0.0402 (7)	0.0274 (6)	−0.0185 (5)	0.0012 (5)	−0.0047 (5)
C9	0.0217 (5)	0.0278 (5)	0.0239 (5)	−0.0013 (4)	0.0061 (4)	−0.0039 (4)
C10	0.0255 (5)	0.0223 (5)	0.0271 (5)	−0.0017 (4)	0.0042 (4)	−0.0008 (4)
C11	0.0387 (6)	0.0246 (5)	0.0466 (7)	0.0047 (5)	0.0067 (5)	−0.0053 (5)
C12	0.0440 (7)	0.0493 (8)	0.0285 (6)	−0.0029 (6)	0.0051 (5)	0.0063 (5)
O3	0.0334 (4)	0.0281 (4)	0.0261 (4)	−0.0109 (3)	0.0016 (3)	−0.0040 (3)
O4	0.0407 (5)	0.0288 (4)	0.0375 (5)	−0.0132 (3)	0.0098 (4)	−0.0016 (3)
O5	0.0463 (5)	0.0283 (4)	0.0346 (5)	−0.0043 (4)	0.0119 (4)	0.0091 (3)
O6	0.0260 (4)	0.0229 (4)	0.0245 (4)	−0.0036 (3)	−0.0051 (3)	0.0030 (3)
C13	0.0244 (5)	0.0194 (4)	0.0234 (5)	0.0015 (4)	0.0065 (4)	−0.0020 (4)
C14	0.0310 (5)	0.0212 (5)	0.0269 (5)	0.0038 (4)	0.0102 (4)	0.0034 (4)
C15	0.0333 (5)	0.0303 (5)	0.0204 (5)	0.0082 (4)	0.0046 (4)	0.0043 (4)
C16	0.0253 (5)	0.0274 (5)	0.0207 (5)	0.0051 (4)	−0.0008 (4)	−0.0013 (4)
C17	0.0206 (4)	0.0194 (4)	0.0223 (5)	0.0033 (3)	0.0017 (4)	0.0007 (3)
C18	0.0222 (5)	0.0218 (5)	0.0184 (4)	0.0014 (4)	0.0036 (4)	−0.0008 (3)
C19	0.0270 (5)	0.0217 (5)	0.0298 (5)	−0.0016 (4)	0.0092 (4)	−0.0043 (4)

Geometric parameters (Å, º) top

O1—C6	1.2239 (14)	C10—C11	1.5163 (15)
O2—C10	1.4425 (13)	C10—C12	1.5257 (16)
O2—H2	0.882 (19)	C11—H11A	0.98
N1—C5	1.3388 (15)	C11—H11B	0.98
N1—C1	1.3388 (14)	C11—H11C	0.98
N2—C6	1.3496 (14)	C12—H12A	0.98
N2—N3	1.3911 (12)	C12—H12B	0.98
N2—H2A	0.884 (16)	C12—H12C	0.98
N3—C7	1.2844 (14)	O3—C19	1.3064 (14)
C1—C2	1.3870 (15)	O3—H3	0.84
C1—H1	0.95	O4—C19	1.2368 (13)
C2—C3	1.3919 (14)	O5—C14	1.3558 (13)
C2—H2B	0.95	O5—H5A	0.94 (2)
C3—C4	1.3910 (14)	O6—C17	1.3763 (12)
C3—C6	1.5050 (14)	O6—H6	0.87 (2)
C4—C5	1.3839 (15)	C13—C18	1.4039 (14)
C4—H4	0.95	C13—C14	1.4032 (15)
C5—H5	0.95	C13—C19	1.4838 (15)
C7—C8	1.5012 (15)	C14—C15	1.3930 (17)
C7—C9	1.5137 (14)	C15—C16	1.3807 (16)
C8—H8A	0.98	C15—H15	0.95
C8—H8B	0.98	C16—C17	1.3977 (14)
C8—H8C	0.98	C16—H16	0.95
C9—C10	1.5354 (15)	C17—C18	1.3829 (14)
C9—H9A	0.99	C18—H18	0.95
C9—H9B	0.99

C10—O2—H2	110.0 (12)	C11—C10—C12	111.13 (10)
C5—N1—C1	118.49 (9)	O2—C10—C9	105.39 (8)
C6—N2—N3	117.15 (9)	C11—C10—C9	112.34 (9)
C6—N2—H2A	121.8 (10)	C12—C10—C9	109.45 (9)
N3—N2—H2A	116.5 (10)	C10—C11—H11A	109.5
C7—N3—N2	116.91 (9)	C10—C11—H11B	109.5
N1—C1—C2	122.88 (10)	H11A—C11—H11B	109.5
N1—C1—H1	118.6	C10—C11—H11C	109.5
C2—C1—H1	118.6	H11A—C11—H11C	109.5
C1—C2—C3	118.59 (10)	H11B—C11—H11C	109.5
C1—C2—H2B	120.7	C10—C12—H12A	109.5
C3—C2—H2B	120.7	C10—C12—H12B	109.5
C4—C3—C2	118.39 (9)	H12A—C12—H12B	109.5
C4—C3—C6	117.67 (9)	C10—C12—H12C	109.5
C2—C3—C6	123.92 (9)	H12A—C12—H12C	109.5
C5—C4—C3	119.31 (10)	H12B—C12—H12C	109.5
C5—C4—H4	120.3	C19—O3—H3	109.5
C3—C4—H4	120.3	C14—O5—H5A	102.6 (12)
N1—C5—C4	122.32 (10)	C17—O6—H6	111.3 (12)
N1—C5—H5	118.8	C18—C13—C14	119.54 (10)
C4—C5—H5	118.8	C18—C13—C19	120.76 (9)
O1—C6—N2	123.48 (10)	C14—C13—C19	119.66 (9)
O1—C6—C3	121.07 (10)	O5—C14—C15	117.91 (10)
N2—C6—C3	115.45 (9)	O5—C14—C13	122.68 (10)
N3—C7—C8	116.02 (10)	C15—C14—C13	119.41 (10)
N3—C7—C9	126.76 (9)	C16—C15—C14	120.68 (10)
C8—C7—C9	117.15 (9)	C16—C15—H15	119.7
C7—C8—H8A	109.5	C14—C15—H15	119.7
C7—C8—H8B	109.5	C15—C16—C17	120.21 (10)
H8A—C8—H8B	109.5	C15—C16—H16	119.9
C7—C8—H8C	109.5	C17—C16—H16	119.9
H8A—C8—H8C	109.5	O6—C17—C18	123.12 (9)
H8B—C8—H8C	109.5	O6—C17—C16	117.09 (9)
C7—C9—C10	117.70 (8)	C18—C17—C16	119.79 (9)
C7—C9—H9A	107.9	C17—C18—C13	120.36 (9)
C10—C9—H9A	107.9	C17—C18—H18	119.8
C7—C9—H9B	107.9	C13—C18—H18	119.8
C10—C9—H9B	107.9	O4—C19—O3	122.94 (10)
H9A—C9—H9B	107.2	O4—C19—C13	121.48 (10)
O2—C10—C11	110.24 (9)	O3—C19—C13	115.57 (9)
O2—C10—C12	108.05 (9)

C6—N2—N3—C7	−173.32 (10)	C7—C9—C10—C11	−47.44 (13)
C5—N1—C1—C2	−0.08 (16)	C7—C9—C10—C12	−171.40 (10)
N1—C1—C2—C3	1.07 (16)	C18—C13—C14—O5	179.81 (9)
C1—C2—C3—C4	−1.24 (15)	C19—C13—C14—O5	1.84 (15)
C1—C2—C3—C6	177.20 (10)	C18—C13—C14—C15	0.33 (15)
C2—C3—C4—C5	0.50 (16)	C19—C13—C14—C15	−177.64 (9)
C6—C3—C4—C5	−178.05 (10)	O5—C14—C15—C16	−179.73 (10)
C1—N1—C5—C4	−0.73 (16)	C13—C14—C15—C16	−0.22 (16)
C3—C4—C5—N1	0.52 (17)	C14—C15—C16—C17	−0.08 (16)
N3—N2—C6—O1	5.63 (17)	C15—C16—C17—O6	179.69 (9)
N3—N2—C6—C3	−173.41 (9)	C15—C16—C17—C18	0.28 (15)
C4—C3—C6—O1	−13.57 (17)	O6—C17—C18—C13	−179.55 (9)
C2—C3—C6—O1	167.98 (12)	C16—C17—C18—C13	−0.17 (15)
C4—C3—C6—N2	165.50 (10)	C14—C13—C18—C17	−0.13 (15)
C2—C3—C6—N2	−12.96 (16)	C19—C13—C18—C17	177.82 (9)
N2—N3—C7—C8	−178.06 (10)	C18—C13—C19—O4	−178.33 (10)
N2—N3—C7—C9	5.23 (16)	C14—C13—C19—O4	−0.38 (15)
N3—C7—C9—C10	−78.25 (14)	C18—C13—C19—O3	0.41 (14)
C8—C7—C9—C10	105.07 (12)	C14—C13—C19—O3	178.36 (9)
C7—C9—C10—O2	72.63 (11)

(22mcsiz4h4m2p4hba) top

Crystal data top

2(C₁₂H₁₇N₃O₂)·3(C₇H₆O₃)	F(000) = 1872
M_r = 884.92	D_x = 1.321 Mg m⁻³
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 41.700 (2) Å	Cell parameters from 5820 reflections
b = 8.2992 (4) Å	θ = 2.9–27.4°
c = 12.9536 (8) Å	µ = 0.10 mm⁻¹
β = 97.033 (2)°	T = 173 K
V = 4449.2 (4) Å³	Plate, colourless
Z = 4	0.55 × 0.26 × 0.14 mm

Data collection top

Bruker APEX-II CCD diffractometer	4386 reflections with I > 2σ(I)
φ and ω scans	R_int = 0.088
Absorption correction: multi-scan SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.1671 before and 0.0738 after correction. The Ratio of minimum to maximum transmission is 0.8051. The λ/2 correction factor is Not present.	θ_max = 28.3°, θ_min = 2.0°
T_min = 0.600, T_max = 0.746	h = −55→55
54732 measured reflections	k = −11→11
5529 independent reflections	l = −17→17

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.056	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.150	w = 1/[σ²(F_o²) + (0.0649P)² + 2.5863P] where P = (F_o² + 2F_c²)/3
S = 1.04	(Δ/σ)_max = 0.001
5529 reflections	Δρ_max = 0.29 e Å⁻³
352 parameters	Δρ_min = −0.27 e Å⁻³
23 restraints

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
O1	0.59773 (4)	0.5103 (2)	0.80887 (11)	0.0731 (5)
O2	0.60714 (4)	0.71726 (16)	0.46192 (9)	0.0529 (3)
N1	0.68301 (3)	0.23585 (16)	0.63031 (11)	0.0415 (3)
N2	0.59888 (3)	0.6522 (2)	0.66087 (11)	0.0473 (4)
N3	0.57176 (3)	0.7417 (2)	0.67707 (11)	0.0470 (4)
C1	0.68152 (4)	0.2702 (2)	0.73021 (14)	0.0528 (4)
H1	0.697733	0.227914	0.780891	0.063*
C2	0.65751 (4)	0.3641 (3)	0.76317 (13)	0.0531 (5)
H2B	0.657141	0.385009	0.835120	0.064*
C3	0.63411 (4)	0.4273 (2)	0.69052 (13)	0.0434 (4)
C4	0.63502 (4)	0.3891 (2)	0.58675 (13)	0.0482 (4)
H4	0.618810	0.427679	0.534701	0.058*
C5	0.65993 (4)	0.2939 (2)	0.56047 (13)	0.0456 (4)
H5	0.660589	0.268835	0.489207	0.055*
C6	0.60840 (4)	0.5329 (2)	0.72558 (14)	0.0512 (4)
C7	0.56749 (4)	0.8710 (2)	0.62264 (13)	0.0472 (4)
C8	0.53618 (5)	0.9574 (3)	0.63147 (17)	0.0629 (5)
H8A	0.522744	0.956211	0.563892	0.094*
H8B	0.540726	1.069180	0.652979	0.094*
H8C	0.524715	0.903223	0.683289	0.094*
C9	0.59100 (4)	0.9439 (2)	0.55526 (14)	0.0486 (4)
H9A	0.613011	0.935013	0.593348	0.058*
H9B	0.586005	1.060095	0.546947	0.058*
C10	0.59165 (5)	0.8715 (2)	0.44660 (14)	0.0516 (4)
C11	0.55732 (6)	0.8509 (3)	0.39017 (17)	0.0771 (7)
H11A	0.558389	0.801239	0.322024	0.116*
H11B	0.546882	0.956543	0.380822	0.116*
H11C	0.544784	0.781673	0.431625	0.116*
C12	0.61198 (6)	0.9754 (3)	0.38334 (18)	0.0720 (6)
H12A	0.634083	0.981998	0.418865	0.108*
H12B	0.602667	1.083863	0.376005	0.108*
H12C	0.612311	0.927584	0.314321	0.108*
O3	0.76927 (3)	0.41682 (14)	0.44204 (8)	0.0422 (3)
H3	0.785353	0.368939	0.423430	0.063*
O4	0.79807 (3)	0.39390 (14)	0.59784 (8)	0.0396 (3)
O5	0.67767 (3)	0.80957 (15)	0.69937 (10)	0.0463 (3)
C13	0.74719 (3)	0.52828 (16)	0.58360 (10)	0.0311 (3)
C14	0.72224 (4)	0.59938 (19)	0.51751 (11)	0.0386 (3)
H14	0.721259	0.584496	0.444477	0.046*
C15	0.69893 (4)	0.6912 (2)	0.55699 (12)	0.0413 (4)
H15	0.681971	0.738634	0.511319	0.050*
C16	0.70036 (3)	0.71379 (17)	0.66328 (11)	0.0346 (3)
C17	0.72440 (4)	0.63954 (17)	0.73056 (11)	0.0349 (3)
H17	0.724845	0.651487	0.803658	0.042*
C18	0.74764 (3)	0.54832 (17)	0.69050 (11)	0.0327 (3)
H18	0.764189	0.498453	0.736542	0.039*
C19	0.77377 (3)	0.43995 (17)	0.54302 (11)	0.0322 (3)
O6	0.53413 (7)	0.6244 (4)	0.8323 (2)	0.0684 (8)	0.5
H6	0.549917	0.675956	0.814628	0.103*	0.5
O7	0.55849 (8)	0.6787 (4)	0.9921 (3)	0.0699 (9)	0.5
O8	0.43237 (8)	0.2945 (4)	1.0771 (3)	0.0684 (9)	0.5
H8	0.428951	0.331193	1.135197	0.103*	0.5
C20	0.50842 (7)	0.5377 (4)	0.9722 (3)	0.0354 (6)	0.5
C21	0.48442 (14)	0.4655 (13)	0.9040 (4)	0.0419 (13)	0.5
H21	0.485453	0.471910	0.831275	0.050*	0.5
C22	0.45913 (7)	0.3846 (4)	0.9397 (2)	0.0448 (7)	0.5
H22	0.442470	0.339007	0.892032	0.054*	0.5
C23	0.4582 (4)	0.371 (3)	1.0451 (4)	0.0450 (15)	0.5
C24	0.48108 (10)	0.4477 (5)	1.1149 (3)	0.0558 (9)	0.5
H24	0.479293	0.446048	1.187338	0.067*	0.5
C25	0.50641 (16)	0.5267 (13)	1.0779 (4)	0.0481 (15)	0.5
H25	0.522773	0.574402	1.125732	0.058*	0.5
C26	0.5368 (3)	0.615 (3)	0.9345 (4)	0.0453 (15)	0.5
H5A	0.6842 (5)	0.837 (3)	0.7655 (19)	0.065 (6)*
H2A	0.6061 (5)	0.662 (3)	0.5967 (19)	0.068 (6)*
H2	0.6021 (6)	0.655 (3)	0.407 (2)	0.079 (8)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0736 (9)	0.1053 (12)	0.0475 (8)	0.0445 (8)	0.0358 (7)	0.0376 (8)
O2	0.0821 (9)	0.0481 (7)	0.0288 (6)	0.0026 (6)	0.0077 (6)	−0.0013 (5)
N1	0.0440 (7)	0.0424 (7)	0.0396 (7)	0.0013 (6)	0.0113 (6)	−0.0005 (6)
N2	0.0438 (7)	0.0660 (9)	0.0347 (7)	0.0166 (7)	0.0149 (6)	0.0137 (7)
N3	0.0401 (7)	0.0659 (9)	0.0363 (7)	0.0139 (6)	0.0095 (6)	0.0090 (6)
C1	0.0509 (9)	0.0698 (12)	0.0376 (9)	0.0190 (9)	0.0052 (7)	0.0027 (8)
C2	0.0544 (10)	0.0754 (12)	0.0311 (8)	0.0213 (9)	0.0124 (7)	0.0075 (8)
C3	0.0397 (8)	0.0559 (9)	0.0371 (8)	0.0074 (7)	0.0143 (6)	0.0133 (7)
C4	0.0482 (9)	0.0606 (10)	0.0360 (9)	0.0088 (8)	0.0065 (7)	0.0081 (7)
C5	0.0538 (9)	0.0489 (9)	0.0352 (8)	0.0022 (7)	0.0095 (7)	−0.0001 (7)
C6	0.0470 (9)	0.0731 (12)	0.0363 (9)	0.0169 (8)	0.0163 (7)	0.0178 (8)
C7	0.0471 (9)	0.0601 (10)	0.0339 (8)	0.0093 (8)	0.0032 (7)	0.0014 (7)
C8	0.0558 (11)	0.0800 (14)	0.0531 (12)	0.0249 (10)	0.0076 (9)	0.0058 (10)
C9	0.0553 (10)	0.0503 (9)	0.0401 (9)	0.0041 (8)	0.0055 (7)	0.0027 (7)
C10	0.0644 (11)	0.0559 (10)	0.0346 (9)	0.0038 (8)	0.0066 (8)	0.0069 (7)
C11	0.0793 (15)	0.1042 (18)	0.0434 (12)	0.0044 (13)	−0.0098 (10)	−0.0005 (12)
C12	0.0963 (16)	0.0684 (13)	0.0570 (13)	0.0122 (12)	0.0327 (12)	0.0192 (10)
O3	0.0467 (6)	0.0538 (7)	0.0264 (5)	0.0085 (5)	0.0051 (4)	−0.0067 (5)
O4	0.0398 (5)	0.0512 (6)	0.0284 (5)	0.0017 (5)	0.0059 (4)	0.0023 (5)
O5	0.0447 (6)	0.0572 (7)	0.0364 (6)	0.0109 (5)	0.0029 (5)	−0.0103 (5)
C13	0.0365 (7)	0.0314 (6)	0.0256 (7)	−0.0059 (5)	0.0052 (5)	−0.0012 (5)
C14	0.0443 (8)	0.0457 (8)	0.0249 (7)	−0.0028 (6)	0.0008 (6)	−0.0055 (6)
C15	0.0393 (8)	0.0505 (9)	0.0321 (8)	0.0044 (7)	−0.0043 (6)	−0.0053 (7)
C16	0.0348 (7)	0.0365 (7)	0.0328 (7)	−0.0030 (6)	0.0054 (6)	−0.0048 (6)
C17	0.0447 (8)	0.0364 (7)	0.0243 (7)	−0.0007 (6)	0.0068 (6)	0.0003 (5)
C18	0.0391 (7)	0.0332 (7)	0.0258 (7)	−0.0018 (5)	0.0038 (5)	0.0027 (5)
C19	0.0390 (7)	0.0337 (7)	0.0248 (6)	−0.0062 (6)	0.0071 (5)	−0.0010 (5)
O6	0.0542 (15)	0.098 (2)	0.0592 (18)	−0.0204 (15)	0.0320 (13)	0.0001 (16)
O7	0.0511 (17)	0.079 (2)	0.084 (2)	−0.0290 (15)	0.0262 (16)	−0.0323 (18)
O8	0.0726 (18)	0.0736 (19)	0.0667 (19)	−0.0376 (15)	0.0394 (16)	−0.0168 (15)
C20	0.0298 (13)	0.0378 (15)	0.0391 (16)	0.0011 (12)	0.0069 (12)	−0.0034 (13)
C21	0.037 (3)	0.059 (3)	0.032 (2)	−0.004 (3)	0.009 (2)	−0.004 (2)
C22	0.0352 (15)	0.059 (2)	0.0407 (18)	−0.0073 (14)	0.0052 (13)	−0.0136 (15)
C23	0.048 (4)	0.043 (4)	0.049 (3)	−0.016 (2)	0.022 (3)	−0.016 (4)
C24	0.068 (2)	0.067 (2)	0.0342 (18)	−0.021 (2)	0.0135 (17)	−0.0011 (17)
C25	0.044 (4)	0.062 (3)	0.038 (3)	−0.010 (3)	0.006 (2)	−0.008 (3)
C26	0.050 (4)	0.037 (4)	0.054 (3)	−0.010 (3)	0.026 (3)	−0.015 (4)

Geometric parameters (Å, º) top

O1—C6	1.231 (2)	C12—H12C	0.9800
O2—C10	1.437 (2)	O3—H3	0.8400
O2—H2	0.89 (3)	O3—C19	1.3126 (17)
N1—C1	1.334 (2)	O4—C19	1.2250 (17)
N1—C5	1.328 (2)	O5—C16	1.3615 (18)
N2—N3	1.3903 (19)	O5—H5A	0.90 (2)
N2—C6	1.326 (2)	C13—C14	1.395 (2)
N2—H2A	0.92 (2)	C13—C18	1.3926 (19)
N3—C7	1.284 (2)	C13—C19	1.4781 (19)
C1—H1	0.9500	C14—H14	0.9500
C1—C2	1.377 (2)	C14—C15	1.382 (2)
C2—H2B	0.9500	C15—H15	0.9500
C2—C3	1.374 (2)	C15—C16	1.384 (2)
C3—C4	1.386 (2)	C16—C17	1.389 (2)
C3—C6	1.498 (2)	C17—H17	0.9500
C4—H4	0.9500	C17—C18	1.380 (2)
C4—C5	1.380 (2)	C18—H18	0.9500
C5—H5	0.9500	O6—H6	0.8400
C7—C8	1.506 (2)	O6—C26	1.318 (4)
C7—C9	1.516 (3)	O7—C26	1.222 (4)
C8—H8A	0.9800	O8—H8	0.8400
C8—H8B	0.9800	O8—C23	1.357 (4)
C8—H8C	0.9800	C20—C21	1.387 (4)
C9—H9A	0.9900	C20—C25	1.385 (4)
C9—H9B	0.9900	C20—C26	1.478 (4)
C9—C10	1.534 (3)	C21—H21	0.9500
C10—C11	1.535 (3)	C21—C22	1.377 (4)
C10—C12	1.518 (3)	C22—H22	0.9500
C11—H11A	0.9800	C22—C23	1.375 (4)
C11—H11B	0.9800	C23—C24	1.387 (4)
C11—H11C	0.9800	C24—H24	0.9500
C12—H12A	0.9800	C24—C25	1.378 (4)
C12—H12B	0.9800	C25—H25	0.9500

C10—O2—H2	110.6 (16)	C10—C12—H12B	109.5
C5—N1—C1	117.85 (14)	C10—C12—H12C	109.5
N3—N2—H2A	116.6 (14)	H12A—C12—H12B	109.5
C6—N2—N3	119.33 (14)	H12A—C12—H12C	109.5
C6—N2—H2A	122.2 (14)	H12B—C12—H12C	109.5
C7—N3—N2	115.13 (14)	C19—O3—H3	109.5
N1—C1—H1	118.5	C16—O5—H5A	109.4 (14)
N1—C1—C2	122.93 (16)	C14—C13—C19	121.81 (13)
C2—C1—H1	118.5	C18—C13—C14	118.55 (13)
C1—C2—H2B	120.5	C18—C13—C19	119.57 (13)
C3—C2—C1	119.07 (16)	C13—C14—H14	119.6
C3—C2—H2B	120.5	C15—C14—C13	120.79 (14)
C2—C3—C4	118.40 (15)	C15—C14—H14	119.6
C2—C3—C6	119.36 (15)	C14—C15—H15	120.1
C4—C3—C6	122.24 (15)	C14—C15—C16	119.77 (14)
C3—C4—H4	120.6	C16—C15—H15	120.1
C5—C4—C3	118.74 (16)	O5—C16—C15	118.27 (13)
C5—C4—H4	120.6	O5—C16—C17	121.47 (13)
N1—C5—C4	122.97 (16)	C15—C16—C17	120.26 (14)
N1—C5—H5	118.5	C16—C17—H17	120.2
C4—C5—H5	118.5	C18—C17—C16	119.57 (13)
O1—C6—N2	123.75 (16)	C18—C17—H17	120.2
O1—C6—C3	121.70 (16)	C13—C18—H18	119.5
N2—C6—C3	114.54 (14)	C17—C18—C13	120.99 (13)
N3—C7—C8	114.82 (17)	C17—C18—H18	119.5
N3—C7—C9	126.38 (15)	O3—C19—C13	113.88 (12)
C8—C7—C9	118.77 (16)	O4—C19—O3	122.64 (13)
C7—C8—H8A	109.5	O4—C19—C13	123.47 (13)
C7—C8—H8B	109.5	C26—O6—H6	109.5
C7—C8—H8C	109.5	C23—O8—H8	109.5
H8A—C8—H8B	109.5	C21—C20—C26	121.3 (3)
H8A—C8—H8C	109.5	C25—C20—C21	118.4 (4)
H8B—C8—H8C	109.5	C25—C20—C26	120.2 (3)
C7—C9—H9A	108.0	C20—C21—H21	119.4
C7—C9—H9B	108.0	C22—C21—C20	121.3 (4)
C7—C9—C10	117.22 (16)	C22—C21—H21	119.4
H9A—C9—H9B	107.2	C21—C22—H22	120.3
C10—C9—H9A	108.0	C23—C22—C21	119.4 (4)
C10—C9—H9B	108.0	C23—C22—H22	120.3
O2—C10—C9	106.28 (14)	O8—C23—C22	117.5 (4)
O2—C10—C11	110.10 (18)	O8—C23—C24	121.6 (4)
O2—C10—C12	108.04 (16)	C22—C23—C24	120.5 (4)
C9—C10—C11	111.13 (17)	C23—C24—H24	120.4
C12—C10—C9	110.28 (17)	C25—C24—C23	119.2 (4)
C12—C10—C11	110.86 (18)	C25—C24—H24	120.4
C10—C11—H11A	109.5	C20—C25—H25	119.4
C10—C11—H11B	109.5	C24—C25—C20	121.1 (4)
C10—C11—H11C	109.5	C24—C25—H25	119.4
H11A—C11—H11B	109.5	O6—C26—C20	112.8 (4)
H11A—C11—H11C	109.5	O7—C26—O6	123.4 (4)
H11B—C11—H11C	109.5	O7—C26—C20	123.4 (4)
C10—C12—H12A	109.5

N1—C1—C2—C3	−0.7 (3)	C14—C13—C19—O3	−8.71 (19)
N2—N3—C7—C8	173.40 (16)	C14—C13—C19—O4	170.39 (14)
N2—N3—C7—C9	−8.6 (3)	C14—C15—C16—O5	177.72 (14)
N3—N2—C6—O1	−11.3 (3)	C14—C15—C16—C17	−2.5 (2)
N3—N2—C6—C3	169.91 (16)	C15—C16—C17—C18	2.6 (2)
N3—C7—C9—C10	81.1 (2)	C16—C17—C18—C13	−0.6 (2)
C1—N1—C5—C4	0.9 (3)	C18—C13—C14—C15	1.7 (2)
C1—C2—C3—C4	2.2 (3)	C18—C13—C19—O3	174.39 (13)
C1—C2—C3—C6	−178.51 (18)	C18—C13—C19—O4	−6.5 (2)
C2—C3—C4—C5	−2.1 (3)	C19—C13—C14—C15	−175.28 (14)
C2—C3—C6—O1	−34.2 (3)	C19—C13—C18—C17	175.49 (13)
C2—C3—C6—N2	144.66 (19)	O8—C23—C24—C25	−178.3 (15)
C3—C4—C5—N1	0.6 (3)	C20—C21—C22—C23	−2.2 (17)
C4—C3—C6—O1	145.2 (2)	C21—C20—C25—C24	−0.7 (17)
C4—C3—C6—N2	−36.0 (3)	C21—C20—C26—O6	8 (2)
C5—N1—C1—C2	−0.9 (3)	C21—C20—C26—O7	−179.6 (16)
C6—N2—N3—C7	168.45 (18)	C21—C22—C23—O8	178.0 (14)
C6—C3—C4—C5	178.56 (17)	C21—C22—C23—C24	5 (3)
C7—C9—C10—O2	−72.9 (2)	C22—C23—C24—C25	−6 (3)
C7—C9—C10—C11	46.9 (2)	C23—C24—C25—C20	3.5 (18)
C7—C9—C10—C12	170.29 (17)	C25—C20—C21—C22	0.0 (16)
C8—C7—C9—C10	−101.0 (2)	C25—C20—C26—O6	−176.1 (12)
O5—C16—C17—C18	−177.58 (13)	C25—C20—C26—O7	−4 (3)
C13—C14—C15—C16	0.3 (2)	C26—C20—C21—C22	175.7 (13)
C14—C13—C18—C17	−1.5 (2)	C26—C20—C25—C24	−176.4 (13)

Acknowledgements

We would like to acknowledge and thank the DSI/NRF Centre of Excellence in Strong Materials as well as the NRF for funding the Bruker D2 Phaser diffractometer. We would also like to thank Professor Manuel Fernandes for his assistance with the solution of the iz4h4m2p + 4hba crystal structure.

References

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., Thaper, R. K., 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. Google Scholar
Bhutani, H., Mariappan, T. T. & Singh, S. (2004). Drug Dev. Ind. Pharm. 30, 667–672. Google Scholar
Blagden, N., de Matas, M., Gavan, P. T. & York, P. (2007). Adv. Drug Deliv. Rev. 59, 617–630. Web of Science CrossRef PubMed CAS Google Scholar
Boles, J. E., Ellaby, R. J., Shepherd, H. J. & Hiscock, J. R. (2021). RSC Adv. 11, 9550–9556. Google Scholar
Bruker (2012). SAINT+ (version 6.02), SAINT (version 8.40B) and XREP. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
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. Google Scholar
Diniz, L. F., Souza, M. S., Carvalho, P. S., da Silva, C. C. P., D'Vries, R. F. & Ellena, J. (2018). J. Mol. Struct. 1153, 58–68. Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Etter, M. C., MacDonald, J. C. & Bernstein, J. (1990). Acta Cryst. B46, 256–262. CrossRef ICSD CAS Web of Science IUCr Journals Google Scholar
Faria, C. F. de, Moreira, T., Lopes, P., Costa, H., Krewall, J. R., Barton, C. M., Santos, S., Goodwin, D., Machado, D., Viveiros, M., Machuqueiro, M. & Martins, F. (2021). Biomed. Pharmacother. 144, 112362. Google Scholar
Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838. CrossRef CAS IUCr Journals Google Scholar
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854. Web of Science CrossRef CAS IUCr Journals Google Scholar
Ganie, A. A., Marimuthu, R., Islam, S. T., Narang, S. & Dar, A. A. (2022). J. Solid State Chem. 307, 122762. Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CrossRef IUCr Journals Google Scholar
Grothe, E., Meekes, H., Vlieg, E., ter Horst, J. H. & de Gelder, R. (2016). Cryst. Growth Des. 16, 3237–3243. Web of Science CrossRef CAS Google Scholar
Hearn, M. J. & Cynamon, M. H. (2004). J. Antimicrob. Chemother. 53, 185–191. Web of Science CrossRef PubMed CAS Google Scholar
Iseman, M. D. (2002). Eur. Respir. J. Suppl. 20, 87S–94S. Google Scholar
Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3–10. Web of Science CSD CrossRef ICSD CAS IUCr Journals Google Scholar
Lemmerer, A. (2012). CrystEngComm, 14, 2465–2478. Web of Science CrossRef CAS Google Scholar
Lemmerer, A., Bernstein, J. & Kahlenberg, V. (2011). CrystEngComm, 13, 5692–5708. Web of Science CrossRef CAS Google Scholar
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. Web of Science CrossRef CAS IUCr Journals Google Scholar
Madeley, L. G., Levendis, D. C. & Lemmerer, A. (2019). Acta Cryst. C75, 200–207. Google Scholar
Oruganti, M., Khade, P., Das, U. K. & Trivedi, D. R. (2016). RSC Adv. 6, 15868–15876. Google Scholar
Sarcevica, I., Orola, L., Veidis, M. V. & Belyakov, S. (2014). Acta Cryst. C70, 392–395. CrossRef IUCr Journals Google Scholar
Sarcevica, I., Orola, L., Veidis, M. V., Podjava, A. & Belyakov, S. (2013). Cryst. Growth Des. 13, 1082–1090. Web of Science CrossRef CAS Google Scholar
Scheepers, M. C., Fernandes, M. A. & Lemmerer, A. (2022). RSC Adv. 12, 11658–11664. Google Scholar
Setshedi, I. B. & Smith, M. G. (2021). Z. Kristallogr. New Cryst. Struct. 236, 1093–1095. Google Scholar
Shattock, T. R., Arora, K. K., Vishweshwar, P. & Zaworotko, M. J. (2008). Cryst. Growth Des. 8, 4533–4545. Web of Science CSD CrossRef CAS Google Scholar
Sheldrick, G. M. (2015). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015). Acta Cryst. C71, 3–9. CrossRef IUCr Journals Google Scholar
Spek, A. L. (2020). Acta Cryst. E76, 1–11. Web of Science CrossRef IUCr Journals Google Scholar
Surov, A. O., Voronin, A. P., Simagina, A. A., Churakov, A. V. & Perlovich, G. L. (2016). Cryst. Growth Des. 16, 2605–2617. Web of Science CrossRef Google Scholar
Trask, A. V. (2007). Mol. Pharm. 4, 301–309. Web of Science CrossRef PubMed CAS Google Scholar
Wang, S. Y., Song, X. M. & Duan, L. X. (2008). Acta Cryst. E64, o1880. Google Scholar

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STRUCTURAL SCIENCE
CRYSTAL ENGINEERING
MATERIALS

ISSN: 2052-5206

Volume 78| Part 6| December 2022| Pages 857-867

https://doi.org/10.1107/S2052520622009532

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

Design of a series of cocrystals featuring isoniazid modified with diacetone alcohol

1. Introduction

2. Experimental

2.1. Materials

2.2. General procedure for synthesis of iz4h4m2p and its cocrystals

2.3. Powder X-ray diffraction

2.4. Single crystal X-ray diffraction

2.5. The Cambridge Structural Database

2.6. Differential scanning calorimetry

2.7. Fourier transform infrared analysis

3. Results and discussion

3.1. Obtaining cocrystals

3.2. Crystal structures of iz4h4m2p + sa and iz4h4m2p + ca

3.3. Crystal structures of iz4h4m2p + dnba, iz4h4m2p + 2c4n and iz4h4m2p + 4nba

3.4. Crystal structure of iz4h4m2p + 4hba

3.5. Crystal structures of iz4h4m2p + 2,5-dhba and iz4h4m2p + 3hba

3.6. Comparison of cocrystals with literature examples

3.7. FTIR spectra

3.8. Thermal analysis

4. Conclusions

Supporting information

Acknowledgements

References

research papers