The 1:1 co-crystal N′-[(2-methylphenyl)methylidene]pyridine-4-carbohydrazide–benzoic acid (1/1) formed unexpectedly after autoxidation of benzaldehyde during the slow evaporation process of a solution of isoniazid in benzaldehyde. The original intent of the synthesis was to modify isoniazid with benzaldehyde and crystallize the product in order to improve efficacy against Mycobacteria species, but benzoic acid formed spontaneously and co-crystallized with the intended product, N′-benzylidenepyridine-4-carbohydrazide.
Keywords: crystal structure, autoxidation, benzoic acid, isoniazid
Abstract
The 1:1 co-crystal N′-[(2-methylphenyl)methylidene]pyridine-4-carbohydrazide–benzoic acid (1/1), C13H11N3O·C7H6O2, formed unexpectedly after autoxidation of benzaldehyde during the slow evaporation process of a solution of isoniazid in benzaldehyde. The original intent of the synthesis was to modify isoniazid with benzaldehyde and crystallize the product in order to improve efficacy against Mycobacteria species, but benzoic acid formed spontaneously and co-crystallized with the intended product, N′-benzylidenepyridine-4-carbohydrazide.
1. Chemical context
Mycobacterial infections are a historic tribulation to mankind, and are managed with an array of drugs ranging from natural to synthetic derivatives that possess antimicrobial properties. However, these strategies have failed over time due to the emergence of resistant mycobacteria (Cully, 2014 ▸). A number of constituents such as isoniazid (INH) have been modified to try and curb the scourge of tuberculosis (Cully, 2014 ▸). Some of the resulting modified INH derivatives have been shown to render the active pharmaceutical ingredients (API) a lot more active to the circulating resistant strains of TB (Hearn & Cynamon, 2004 ▸; Suarez et al., 2009 ▸). It was for this reason that the covalent modification of API’s was adopted to synthesize new analogues by modifying the NH2 group of the hydrazide moiety of INH (Smith et al., 2015 ▸), believed to assist in the evasion of the N-arylaminoacetyl transferases, an enzyme capable of reducing the efficacy of INH in particular, by acetylating the NH2 position, thus ultimately preventing its reaction with nicotinamide adenine dinucleotide (NADH) (Vishweshwar et al., 2006 ▸; Smith et al., 2015 ▸).
Benzaldehyde is known to undergo autoxidation resulting in the formation of benzoic acid. The formation of benzoic acid occurs when benzaldehyde is exposed to air at room temperature (293 K) where the rate of the reaction is increased by the presence of a catalyst. However, this phenomenon can occur spontaneously without a catalyst over a prolonged period (Sankar et al., 2014 ▸). The synthesis of this co-crystal was interesting as there were three separate processes that took place within the reaction mixture to create the final product. Firstly, benzaldehyde reacted with isoniazid to form N′-benzylidenepyridine-4-carbohydrazide. Secondly, excess benzaldehyde spontaneously autoxidized to form benzoic acid as described above (no benzoic acid was added to the reaction mixture). Lastly, the carbohydrazide moiety co-crystallized with the benzoic acid (as shown in Fig. 1 ▸) to form the product, N′-[(2-methylphenyl)methylidene]pyridine-4-carbohydrazide–benzoic acid (1/1).
Figure 1.
Modification and autoxidative co-crystallization.
2. Structural commentary
The asymmetric unit contains one molecule of N′-benzylidenepyridine-4-carbohydrazide (C13H11N3O1·C7H6O2) and one molecule of benzoic acid (as shown in Fig. 2 ▸). This co-crystal crystallizes in the Pbca space group. The benzoic acid molecule lies in the plane of the pyridine ring of the benzylidene derivative. All bond lengths and angles are normal.
Figure 2.
Asymmetric unit of N′-[(2-methylphenyl)methylidene]pyridine-4-carbohydrazide–benzoic acid (1/1).
3. Supramolecular features
Each carbohydrazide moiety is hydrogen bonded by a strong O2—H2⋯N2 hydrogen bond (Table 1 ▸) to a benzoic acid molecule to form a co-crystal. This interaction is supported by a weaker C—H⋯O hydrogen bond that stabilizes the co-planar arrangement of the carboxylic acid moiety and the pyridine ring. The graph-set notation for this would be
(7) (Bernstein et al., 1995 ▸), and is observed in other isoniazid co-crystals (Lemmerer et al., 2010 ▸) (Fig. 2 ▸). This co-crystal is another example of the robust carboxylic acid⋯pyridine heterosynthon (Shattock et al., 2008 ▸; Aakeröy et al., 2007 ▸). Each carbohydrazide moiety is also hydrogen bonded via its N1—H1 donor to the carbonyl oxygen (O1) acceptor of an adjacent carbohydrazide moiety. This results in a mono-periodic hydrogen-bonded chain along the b-axis direction, with graph-set notation C(4). Overall, the combined carbohydrazide moiety with the benzoic acid forms a ribbon motif (as shown in Fig. 3 ▸
a). Viewed along the b-axis, the ribbons forms a X-shaped motif seen in other carbohydrazide moieties (Hean et al. 2018 ▸) (Fig. 3 ▸
b).
Table 1. Hydrogen-bond geometry (Å, °).
| D—H⋯A | D—H | H⋯A | D⋯A | D—H⋯A |
|---|---|---|---|---|
| N1—H1⋯O1i | 0.89 (2) | 2.02 (2) | 2.8981 (17) | 171 (2) |
| O2—H2⋯N2 | 0.95 (2) | 1.72 (3) | 2.6693 (17) | 176 (2) |
| C3—H3⋯O3 | 0.95 | 2.53 | 3.236 (2) | 131 |
Symmetry code: (i)
.
Figure 3.
(a) View of the strong hydrogen bonds that link the carbohydrazide molecules in a chain, and the benzoic acid molecules to the carbohydrazide forming a ribbon. (b) Packing diagram along the b axis.
4. Database survey
ConQuest (Bruno et al., 2002 ▸), Version 2022.1.0 of the CSD (Groom et al., 2016 ▸) was used for the database survey, where only one similar structure was found. The survey consisted of structures consisting of isoniazid that had been modified with benzaldehyde and may have either a co-former or solvent molecule in the crystal structure. The structure of the anhydrous benzylidene derivative, N′-[(2-methylphenyl)methylidene]pyridine-4-carbohydrazide (as shown in Fig. 4 ▸), formed from the reaction of isoniazid and benzaldehyde, was reported by Wardell et al., (2007 ▸) (YIQDEI). Several structures have been reported where substituted benzaldehyde reacted with isoniazid, for example, three polymorphs of the 4-methylbenzylidene derivative (WOGGOR, WOGGOR01 and WOGGUX) were reported by Purushothaman et al. (2019 ▸) and in 2016, Almeida and colleagues published the structure of a hydrate of the same 4-methylbenzylidene derivative (OLECOZ; Pereira Almeida et al., 2016 ▸). However, there has not been any co-crystal of the benzylidene derivative (Fig. 4 ▸) reported in the literature to date.
Figure 4.
Benzylidene derivative of isoniazid.
5. Synthesis and crystallization
All reagents were commercially sourced and used without further purification. 1.00 g of isonicotinic acid hydrazide (isoniazid) (7.29 mmol) were dissolved in 15 ml of benzaldehyde in a 50 ml amber Schott bottle. The mixture was placed on a stirring heating block and heated to 333 K while stirring with a magnetic stirrer bar. Once the isoniazid had completely dissolved, the lid was tightly sealed. The solution was then allowed to react for 24 h. To maintain the temperature throughout the duration of the experiment, the amber Schott bottle was covered with an inverted round glass evaporation dish. After 24 h, the solution was allowed to cool to ambient temperature. The stirrer bar was retrieved and the sample was left to evaporate slowly for 6 weeks at ambient temperature without a lid. Over the 6 weeks, the temperature in the laboratory fluctuated between 298 and 300 K. Due to the fact that benzaldehyde evaporates extremely slowly, the Schott bottle was placed in the laminar flow biohazard safety level 2 cabinet to facilitate evaporation. Crystals (colourless blocks) started forming on the rim on the outside of the bottle as the benzaldehyde evaporated. One of these crystals was sampled for XRD analysis.
6. Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. C-bound H atoms were first located in the difference map, then positioned geometrically and allowed to ride on their respective parent atoms, with thermal displacement parameters 1.2 times of the parent C atom. The coordinates and isotropic displacement parameters of the O and N-bound H atoms involved in hydrogen-bonding interactions (H1 and H2) were allowed to refine freely.
Table 2. Experimental details.
| Crystal data | |
| Chemical formula | C13H11N3O·C7H6O2 |
| M r | 347.36 |
| Crystal system, space group | Orthorhombic, P b c a |
| Temperature (K) | 173 |
| a, b, c (Å) | 11.7044 (17), 7.8531 (10), 38.253 (5) |
| V (Å3) | 3516.1 (8) |
| Z | 8 |
| Radiation type | Mo Kα |
| μ (mm−1) | 0.09 |
| Crystal size (mm) | 0.30 × 0.22 × 0.16 |
| Data collection | |
| Diffractometer | Bruker D8 Venture Microfocus with Photon III CCD area-detector |
| Absorption correction | Multi-scan (SADABS; Krause et al., 2015 ▸) |
| T min, T max | 0.709, 0.746 |
| No. of measured, independent and observed [I > 2σ(I)] reflections | 73794, 4239, 3902 |
| R int | 0.036 |
| (sin θ/λ)max (Å−1) | 0.660 |
| Refinement | |
| R[F 2 > 2σ(F 2)], wR(F 2), S | 0.054, 0.112, 1.18 |
| No. of reflections | 4239 |
| No. of parameters | 243 |
| H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
| Δρmax, Δρmin (e Å−3) | 0.33, −0.21 |
Supplementary Material
Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989023005698/ex2072sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989023005698/ex2072Isup3.hkl
Supporting information file. DOI: 10.1107/S2056989023005698/ex2072Isup5.mol
Supporting information file. DOI: 10.1107/S2056989023005698/ex2072Isup4.cml
CCDC reference: 2250754
Additional supporting information: crystallographic information; 3D view; checkCIF report
Acknowledgments
The authors would like to acknowledge the University of South Africa for the Masters and Doctoral Grant award.
supplementary crystallographic information
Crystal data
| C13H11N3O·C7H6O2 | Dx = 1.312 Mg m−3 |
| Mr = 347.36 | Mo Kα radiation, λ = 0.71073 Å |
| Orthorhombic, Pbca | Cell parameters from 9857 reflections |
| a = 11.7044 (17) Å | θ = 2.8–28.1° |
| b = 7.8531 (10) Å | µ = 0.09 mm−1 |
| c = 38.253 (5) Å | T = 173 K |
| V = 3516.1 (8) Å3 | Block, colourless |
| Z = 8 | 0.30 × 0.22 × 0.16 mm |
| F(000) = 1456 |
Data collection
| Bruker D8 Venture Microfocus with Photon III CCD area-detector diffractometer | 3902 reflections with I > 2σ(I) |
| Graphite monochromator | Rint = 0.036 |
| ω scans | θmax = 28.0°, θmin = 3.2° |
| Absorption correction: multi-scan (SADABS; Krause et al., 2015) | h = −15→15 |
| Tmin = 0.709, Tmax = 0.746 | k = −8→10 |
| 73794 measured reflections | l = −49→50 |
| 4239 independent reflections |
Refinement
| 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) = 0.112 | H atoms treated by a mixture of independent and constrained refinement |
| S = 1.18 | w = 1/[σ2(Fo2) + (0.0274P)2 + 2.3245P] where P = (Fo2 + 2Fc2)/3 |
| 4239 reflections | (Δ/σ)max = 0.001 |
| 243 parameters | Δρmax = 0.33 e Å−3 |
| 0 restraints | Δρmin = −0.21 e Å−3 |
| 0 constraints |
Special details
| Experimental. Absorption corrections were made using the program SADABS (Sheldrick, 1996) |
| Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
| Refinement. The crystal structure was solved through direct methods using SHELXT. Non-hydrogen atoms were first refined isotropically followed by anisotropic refinement by full matrix least-squares calculations based on F2 using SHELXL. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
| x | y | z | Uiso*/Ueq | ||
| C1 | 0.63979 (12) | 0.05245 (18) | 0.40684 (4) | 0.0224 (3) | |
| C2 | 0.71809 (13) | 0.15589 (19) | 0.42397 (4) | 0.0252 (3) | |
| H2A | 0.79074 | 0.178612 | 0.413922 | 0.03* | |
| C3 | 0.68809 (13) | 0.2256 (2) | 0.45612 (4) | 0.0278 (3) | |
| H3 | 0.742184 | 0.295037 | 0.467926 | 0.033* | |
| C4 | 0.51195 (13) | 0.0976 (2) | 0.45471 (4) | 0.0294 (3) | |
| H4 | 0.439948 | 0.077268 | 0.465382 | 0.035* | |
| C5 | 0.53502 (13) | 0.0207 (2) | 0.42278 (4) | 0.0273 (3) | |
| H5 | 0.48046 | −0.052042 | 0.412045 | 0.033* | |
| C6 | 0.66282 (12) | −0.03373 (18) | 0.37245 (4) | 0.0217 (3) | |
| C7 | 0.83497 (12) | 0.04298 (19) | 0.29981 (4) | 0.0241 (3) | |
| H7 | 0.875011 | 0.138628 | 0.308817 | 0.029* | |
| C8 | 0.85942 (12) | −0.01869 (18) | 0.26424 (4) | 0.0225 (3) | |
| C9 | 0.78697 (13) | −0.13366 (19) | 0.24744 (4) | 0.0275 (3) | |
| H9 | 0.72116 | −0.175227 | 0.259209 | 0.033* | |
| C10 | 0.81045 (14) | −0.1876 (2) | 0.21367 (4) | 0.0325 (3) | |
| H10 | 0.761097 | −0.266749 | 0.202491 | 0.039* | |
| C11 | 0.90585 (15) | −0.1264 (2) | 0.19618 (4) | 0.0329 (4) | |
| H11 | 0.921511 | −0.16284 | 0.17299 | 0.039* | |
| C12 | 0.97809 (14) | −0.0121 (2) | 0.21258 (4) | 0.0330 (4) | |
| H12 | 1.043564 | 0.029452 | 0.200633 | 0.04* | |
| C13 | 0.95532 (13) | 0.0423 (2) | 0.24649 (4) | 0.0288 (3) | |
| H13 | 1.005101 | 0.121063 | 0.257586 | 0.035* | |
| N1 | 0.73940 (11) | 0.04239 (16) | 0.35104 (3) | 0.0243 (3) | |
| N2 | 0.58653 (11) | 0.19911 (17) | 0.47113 (3) | 0.0284 (3) | |
| N3 | 0.75993 (11) | −0.03198 (16) | 0.31860 (3) | 0.0235 (3) | |
| O1 | 0.61404 (9) | −0.16790 (13) | 0.36487 (3) | 0.0264 (2) | |
| H1 | 0.7778 (16) | 0.136 (3) | 0.3562 (5) | 0.035 (5)* | |
| C14 | 0.62773 (13) | 0.54692 (19) | 0.57434 (4) | 0.0255 (3) | |
| C15 | 0.71251 (13) | 0.6581 (2) | 0.58553 (4) | 0.0296 (3) | |
| H15 | 0.776244 | 0.680985 | 0.570885 | 0.036* | |
| C16 | 0.70449 (15) | 0.7358 (2) | 0.61798 (4) | 0.0359 (4) | |
| H16 | 0.762819 | 0.81133 | 0.625584 | 0.043* | |
| C17 | 0.61171 (16) | 0.7034 (3) | 0.63923 (4) | 0.0415 (4) | |
| H17 | 0.605726 | 0.757686 | 0.661344 | 0.05* | |
| C18 | 0.52751 (16) | 0.5920 (3) | 0.62834 (5) | 0.0463 (5) | |
| H18 | 0.463906 | 0.569504 | 0.643068 | 0.056* | |
| C19 | 0.53547 (14) | 0.5127 (2) | 0.59597 (4) | 0.0365 (4) | |
| H19 | 0.477851 | 0.435326 | 0.588664 | 0.044* | |
| C20 | 0.63940 (13) | 0.4638 (2) | 0.53921 (4) | 0.0281 (3) | |
| O2 | 0.55589 (10) | 0.35567 (16) | 0.53235 (3) | 0.0357 (3) | |
| O3 | 0.71911 (11) | 0.49208 (17) | 0.51992 (3) | 0.0428 (3) | |
| H2 | 0.565 (2) | 0.303 (3) | 0.5101 (6) | 0.070 (7)* |
Atomic displacement parameters (Å2)
| U11 | U22 | U33 | U12 | U13 | U23 | |
| C1 | 0.0269 (7) | 0.0212 (6) | 0.0192 (6) | 0.0038 (6) | −0.0001 (5) | 0.0006 (5) |
| C2 | 0.0264 (7) | 0.0278 (7) | 0.0212 (6) | −0.0004 (6) | 0.0014 (5) | 0.0009 (6) |
| C3 | 0.0313 (8) | 0.0302 (8) | 0.0220 (7) | −0.0009 (6) | −0.0012 (6) | −0.0021 (6) |
| C4 | 0.0280 (7) | 0.0339 (8) | 0.0261 (7) | 0.0010 (6) | 0.0051 (6) | 0.0002 (6) |
| C5 | 0.0266 (7) | 0.0280 (7) | 0.0273 (7) | −0.0013 (6) | 0.0017 (6) | −0.0017 (6) |
| C6 | 0.0229 (7) | 0.0218 (6) | 0.0205 (6) | 0.0042 (5) | −0.0018 (5) | −0.0001 (5) |
| C7 | 0.0262 (7) | 0.0235 (7) | 0.0226 (7) | −0.0011 (6) | −0.0010 (5) | −0.0012 (5) |
| C8 | 0.0258 (7) | 0.0214 (6) | 0.0203 (6) | 0.0027 (6) | 0.0007 (5) | 0.0017 (5) |
| C9 | 0.0296 (7) | 0.0304 (7) | 0.0226 (7) | −0.0043 (6) | 0.0001 (6) | 0.0015 (6) |
| C10 | 0.0383 (8) | 0.0353 (8) | 0.0240 (7) | −0.0029 (7) | −0.0047 (6) | −0.0032 (6) |
| C11 | 0.0403 (9) | 0.0392 (9) | 0.0192 (7) | 0.0088 (7) | 0.0023 (6) | −0.0003 (6) |
| C12 | 0.0298 (8) | 0.0415 (9) | 0.0276 (8) | 0.0025 (7) | 0.0075 (6) | 0.0043 (7) |
| C13 | 0.0267 (7) | 0.0317 (8) | 0.0279 (7) | −0.0022 (6) | 0.0018 (6) | −0.0009 (6) |
| N1 | 0.0289 (6) | 0.0238 (6) | 0.0201 (5) | −0.0027 (5) | 0.0019 (5) | −0.0051 (5) |
| N2 | 0.0340 (7) | 0.0300 (7) | 0.0212 (6) | 0.0026 (5) | 0.0023 (5) | −0.0012 (5) |
| N3 | 0.0266 (6) | 0.0254 (6) | 0.0185 (5) | 0.0017 (5) | 0.0003 (5) | −0.0031 (5) |
| O1 | 0.0295 (5) | 0.0244 (5) | 0.0252 (5) | −0.0022 (4) | 0.0007 (4) | −0.0028 (4) |
| C14 | 0.0261 (7) | 0.0264 (7) | 0.0240 (7) | 0.0016 (6) | −0.0001 (6) | 0.0018 (6) |
| C15 | 0.0294 (7) | 0.0300 (8) | 0.0294 (7) | −0.0038 (6) | 0.0006 (6) | 0.0032 (6) |
| C16 | 0.0382 (9) | 0.0349 (8) | 0.0348 (8) | −0.0053 (7) | −0.0086 (7) | −0.0029 (7) |
| C17 | 0.0439 (10) | 0.0542 (11) | 0.0263 (8) | 0.0004 (9) | −0.0018 (7) | −0.0125 (8) |
| C18 | 0.0338 (9) | 0.0726 (14) | 0.0324 (9) | −0.0093 (9) | 0.0096 (7) | −0.0118 (9) |
| C19 | 0.0277 (8) | 0.0499 (10) | 0.0318 (8) | −0.0110 (7) | 0.0037 (6) | −0.0070 (7) |
| C20 | 0.0312 (7) | 0.0282 (7) | 0.0250 (7) | −0.0002 (6) | 0.0023 (6) | 0.0016 (6) |
| O2 | 0.0366 (6) | 0.0436 (7) | 0.0271 (6) | −0.0091 (5) | 0.0055 (5) | −0.0098 (5) |
| O3 | 0.0474 (8) | 0.0493 (7) | 0.0316 (6) | −0.0129 (6) | 0.0156 (5) | −0.0054 (6) |
Geometric parameters (Å, º)
| C1—C2 | 1.389 (2) | C11—C12 | 1.384 (2) |
| C1—C5 | 1.392 (2) | C11—H11 | 0.95 |
| C1—C6 | 1.5039 (19) | C12—C13 | 1.391 (2) |
| C2—C3 | 1.391 (2) | C12—H12 | 0.95 |
| C2—H2A | 0.95 | C13—H13 | 0.95 |
| C3—N2 | 1.336 (2) | N1—N3 | 1.3922 (16) |
| C3—H3 | 0.95 | N1—H1 | 0.89 (2) |
| C4—N2 | 1.338 (2) | C14—C19 | 1.387 (2) |
| C4—C5 | 1.389 (2) | C14—C15 | 1.389 (2) |
| C4—H4 | 0.95 | C14—C20 | 1.500 (2) |
| C5—H5 | 0.95 | C15—C16 | 1.386 (2) |
| C6—O1 | 1.2328 (17) | C15—H15 | 0.95 |
| C6—N1 | 1.3533 (19) | C16—C17 | 1.380 (2) |
| C7—N3 | 1.2784 (19) | C16—H16 | 0.95 |
| C7—C8 | 1.4725 (19) | C17—C18 | 1.382 (3) |
| C7—H7 | 0.95 | C17—H17 | 0.95 |
| C8—C9 | 1.395 (2) | C18—C19 | 1.389 (2) |
| C8—C13 | 1.397 (2) | C18—H18 | 0.95 |
| C9—C10 | 1.387 (2) | C19—H19 | 0.95 |
| C9—H9 | 0.95 | C20—O3 | 1.2101 (19) |
| C10—C11 | 1.388 (2) | C20—O2 | 1.3210 (19) |
| C10—H10 | 0.95 | O2—H2 | 0.95 (2) |
| C2—C1—C5 | 118.66 (13) | C11—C12—C13 | 120.31 (15) |
| C2—C1—C6 | 123.89 (13) | C11—C12—H12 | 119.8 |
| C5—C1—C6 | 117.41 (13) | C13—C12—H12 | 119.8 |
| C3—C2—C1 | 118.72 (14) | C12—C13—C8 | 120.14 (15) |
| C3—C2—H2A | 120.6 | C12—C13—H13 | 119.9 |
| C1—C2—H2A | 120.6 | C8—C13—H13 | 119.9 |
| N2—C3—C2 | 122.90 (14) | C6—N1—N3 | 117.93 (12) |
| N2—C3—H3 | 118.6 | C6—N1—H1 | 124.6 (12) |
| C2—C3—H3 | 118.6 | N3—N1—H1 | 117.5 (12) |
| N2—C4—C5 | 123.01 (14) | C3—N2—C4 | 118.11 (13) |
| N2—C4—H4 | 118.5 | C7—N3—N1 | 115.24 (12) |
| C5—C4—H4 | 118.5 | C19—C14—C15 | 119.61 (14) |
| C4—C5—C1 | 118.57 (14) | C19—C14—C20 | 121.40 (14) |
| C4—C5—H5 | 120.7 | C15—C14—C20 | 118.98 (14) |
| C1—C5—H5 | 120.7 | C16—C15—C14 | 120.27 (15) |
| O1—C6—N1 | 122.82 (13) | C16—C15—H15 | 119.9 |
| O1—C6—C1 | 120.47 (13) | C14—C15—H15 | 119.9 |
| N1—C6—C1 | 116.70 (12) | C17—C16—C15 | 119.97 (16) |
| N3—C7—C8 | 120.11 (13) | C17—C16—H16 | 120 |
| N3—C7—H7 | 119.9 | C15—C16—H16 | 120 |
| C8—C7—H7 | 119.9 | C16—C17—C18 | 120.03 (16) |
| C9—C8—C13 | 119.10 (13) | C16—C17—H17 | 120 |
| C9—C8—C7 | 121.35 (13) | C18—C17—H17 | 120 |
| C13—C8—C7 | 119.53 (13) | C17—C18—C19 | 120.28 (16) |
| C10—C9—C8 | 120.42 (14) | C17—C18—H18 | 119.9 |
| C10—C9—H9 | 119.8 | C19—C18—H18 | 119.9 |
| C8—C9—H9 | 119.8 | C14—C19—C18 | 119.84 (16) |
| C9—C10—C11 | 120.16 (15) | C14—C19—H19 | 120.1 |
| C9—C10—H10 | 119.9 | C18—C19—H19 | 120.1 |
| C11—C10—H10 | 119.9 | O3—C20—O2 | 124.57 (15) |
| C12—C11—C10 | 119.87 (14) | O3—C20—C14 | 122.44 (15) |
| C12—C11—H11 | 120.1 | O2—C20—C14 | 112.98 (13) |
| C10—C11—H11 | 120.1 | C20—O2—H2 | 112.0 (15) |
| C5—C1—C2—C3 | −0.9 (2) | C7—C8—C13—C12 | −178.61 (14) |
| C6—C1—C2—C3 | −178.49 (13) | O1—C6—N1—N3 | 2.5 (2) |
| C1—C2—C3—N2 | −0.8 (2) | C1—C6—N1—N3 | −178.20 (11) |
| N2—C4—C5—C1 | −1.0 (2) | C2—C3—N2—C4 | 1.6 (2) |
| C2—C1—C5—C4 | 1.7 (2) | C5—C4—N2—C3 | −0.7 (2) |
| C6—C1—C5—C4 | 179.49 (13) | C8—C7—N3—N1 | −176.72 (12) |
| C2—C1—C6—O1 | 152.30 (14) | C6—N1—N3—C7 | −178.41 (13) |
| C5—C1—C6—O1 | −25.3 (2) | C19—C14—C15—C16 | −0.6 (2) |
| C2—C1—C6—N1 | −27.0 (2) | C20—C14—C15—C16 | −179.49 (15) |
| C5—C1—C6—N1 | 155.35 (13) | C14—C15—C16—C17 | −0.3 (3) |
| N3—C7—C8—C9 | 13.8 (2) | C15—C16—C17—C18 | 0.8 (3) |
| N3—C7—C8—C13 | −167.96 (14) | C16—C17—C18—C19 | −0.3 (3) |
| C13—C8—C9—C10 | 0.5 (2) | C15—C14—C19—C18 | 1.1 (3) |
| C7—C8—C9—C10 | 178.77 (14) | C20—C14—C19—C18 | 179.94 (17) |
| C8—C9—C10—C11 | −0.6 (2) | C17—C18—C19—C14 | −0.7 (3) |
| C9—C10—C11—C12 | 0.5 (3) | C19—C14—C20—O3 | 179.85 (17) |
| C10—C11—C12—C13 | −0.3 (3) | C15—C14—C20—O3 | −1.3 (2) |
| C11—C12—C13—C8 | 0.2 (2) | C19—C14—C20—O2 | −1.6 (2) |
| C9—C8—C13—C12 | −0.3 (2) | C15—C14—C20—O2 | 177.25 (14) |
Hydrogen-bond geometry (Å, º)
| D—H···A | D—H | H···A | D···A | D—H···A |
| N1—H1···O1i | 0.89 (2) | 2.02 (2) | 2.8981 (17) | 171 (2) |
| O2—H2···N2 | 0.95 (2) | 1.72 (3) | 2.6693 (17) | 176 (2) |
| C3—H3···O3 | 0.95 | 2.53 | 3.236 (2) | 131 |
Symmetry code: (i) −x+3/2, y+1/2, z.
Funding Statement
Funding for this research was provided by: National Research Foundation (grant No. 118127; grant No. 117850).
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989023005698/ex2072sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989023005698/ex2072Isup3.hkl
Supporting information file. DOI: 10.1107/S2056989023005698/ex2072Isup5.mol
Supporting information file. DOI: 10.1107/S2056989023005698/ex2072Isup4.cml
CCDC reference: 2250754
Additional supporting information: crystallographic information; 3D view; checkCIF report