Crystal Structure and Hirshfeld Surface Analysis of 1,4-Pentadien-3-one, (1E,4E)-1,5-diphenyl-2-(2,4-dinitrophenyl)hydrazone

The compound 1,4-pentadien-3-one,(1E,4E)-1,5-diphenyl-2-(2,4-dinitrophenyl)hydrazone presents the molecular formula C23H18N4O4 and was prepared in an undergraduate laboratory. The hydrazone was synthesized from the condensation between dibenzalacetone and 2,4-dinitrophenylhydrazine (DNPH) and crystallized employing water/acetone liquid-liquid diffusion. The structure presents three aromatic rings connected by an unsaturated Y-shaped system. Dinitro substituted and one of the other aromatic rings are 15° out of a coplanarity, while the other phenyl group is almost orthogonal to the first (89°). The only observed classical hydrogen bonding is an intramolecular N-H···O. The supramolecular structure was analyzed employing the Hirshfeld surface and that is organized through C-H···O hydrogen bond and C-H···π, polar-π, and π-stacking. An interaction involving NO2···NO2 was also observed.


Introduction
Hydrazones are privileged structures in medicinal chemistry. They possess pharmacological activities like analgesic, anticonvulsant, antidepressant, antiinflammatory and antiplatelet, antimalarial, antimicrobial, antimycobacterial, anti-Schistosomiasis, antitumoral, antiviral, and vasodilator. 1,2 Hydrazone formation is a traditional identification and purification method (Brady's test) 3 for aldehydes and ketones, thus we have prepared the compound 1,4-pentadien-3-one,(1E,4E)-1,5-diphenyl-2-(2,4-dinitrophenyl)hydrazone (1) as part of an undergraduate laboratory course by an established method employing accessible reagents. 4 More recently, new applications of the hydrazone formation are the measurement of formaldehyde indoor or in cigarettes, 5,6 removal of acrolein from active pharmaceutical ingredients (APIs) 7 and finally the removal of aldehydes and ketones from essential oils by using a scavenger resin. 8 The hydrazone (1) is easily synthesized, and crystallization provides large single crystals employing different methods and solvent systems. Such aspects raise this hydrazone as an excellent example of crystallography teaching that can be extended to different aldehydes and ketones.

Synthesis
Acetone, absolute ethanol, sulfuric acid PA (Vetec, Rio de Janeiro, Brazil) and 2,4-dinitrophenylhydrazine (Merck KGaA, Darmstadt, Germany) were used without further purification. Dibenzalacetone was prepared as described in the literature. 4 The compound 1 (Scheme 1) was prepared from condensation between 2,4-dinitrophenylhydrazine (DNPH) and dibenzalacetone (1,5-diphenyl-1,4-pentadien-3-one): in an Erlenmeyer of 125 mL under magnetic stirring, 1.0 g of dibenzalacetone (4.3 mmol) was dissolved in absolute ethanol with gently heating (maximum of 60 °C). In another flask, 8.0 g of 2,4-DNPH were dissolved in 40 mL of H 2 SO 4 and added to a mixture of 60 mL of water and 200 mL of ethanol. Then, 30 mL of the 2,4-DNPH acid solution was added into the dibenzalacetone mixture while stirring at room temperature for 15 min. After the time, the reaction mixture was filtered over a Buchner filter to obtain a red powder, then washed with cold ethanol. The amorphous solid was transferred to another Erlenmeyer and recrystallized from a mixture of water and acetone to produce crystals of pure dibenzalacetone-2,4-dinitrophenylhydrazone. Single crystals as red prisms were obtained by slow diffusion of water through an acetone solution containing the compound 1.
2,4-Dinitrophenylhydrazine is sensitive to shock and friction and can be explosive when dry and it is a flammable solid. It is supplied damp or 'wetted', and it is important to keep it wet, so the current storage advice is to keep it in a sealed container, which is itself kept in an outer container filled with a small amount of water. 9 X-ray diffraction (XRD) single crystal analysis was conducted in a Bruker Venture II diffractometer employing Cu Kα radiation. Absorption was corrected by multi-scan method (SADABAS). 10 Data was collected until 0.83 Å of resolution, and it was indexed in the monoclinic crystalline system and in the P2 1 /c space group, with Z (formula unit per unit cell) = 4 and Z' (formula unit per asymmetric unit) = 1. Structure determination was done through directed methods with the software SHELXS inserted in the WinGX platform. 11,12 Refinement was realized with fullmatrix least-square method implemented in SHELXL. 13 Model convergence was attained with R-factor (residual factor for 3214 reflections or discrepancy index) of 0.046, R w (weighted R-factor) of 0.131, and S (goodness of fit) of 1.06. All non-hydrogen atoms were localized through the electron density map and anisotropically refined. N-H hydrogen was located from a difference-Fourier map and refined without constrains. Other H atoms were included in the final cycles of refinement using a riding model, with U iso (H) = 1.2U eq (C). Geometry data and figures were obtained with the software PLATON 14 and MERCURY. 15 Hirshfeld and electron density surfaces, and fingerprint plot were obtained with Crystal Explorer. 16,17 Crystallographic data for the structure in this work were deposited in the Cambridge Crystallographic Data Centre (CCDC) with number 2009611. Crystal data and refinement information are shown in Table 1 and in Supplementary Information section. The molecular structure of compound 1 can be seen in Figure 1a with thermal ellipsoids.

Results and Discussion
Dibenzalacetone was chosen as starting material as it is easily obtained after the aldol reaction between benzaldehyde and acetone, and it was already performed in the undergraduate laboratory. The compound 1 was easily and safely prepared in an undergraduate laboratory using quite non-expensive materials. Moreover, the easy Scheme 1. Synthesis of the compound 1. crystallization provided large single crystals employing different methods and solvent systems. The combination of synthesis and crystallization render this activity as an example of crystallography teaching, allows for improvement of the undergraduate curricula, and can be further extended to different aldehydes and ketones according to inventory availability.
The structure presents three aromatic rings, designated as A, B, and C (Figure 1b). A and B are almost orthogonal and their idealized least-square (LS) planes form an angle of 88.930(47)°. A and C are more coplanar and their ideal LS planes form an angle of 14.926(64)°. Dinitro substituted aromatic ring A is flat and exhibits the smallest HOMA (harmonic oscillator model of aromaticity) index (rms 0.0056 -deviation from the idealized least-square planes; HOMA A : 0.873). 18 The orthogonal B is the most aromatic one (rms 0.0049; HOMA B : 0.988), while the C ring presents slightly smaller local aromaticity when compared with B (rms 0.0053; HOMA C : 0.976). Coplanar part of the unsaturated Y-like system (between A and C) exhibits slightly more equalized bonds than the orthogonal side, denoting better electronic conjugation between A and C.
Here we observed some similar partial quinoidal behavior within A ring but is a less extend.  Hydrogen atoms of the dinitro-substituted A and nitro groups oxygens exhibit intermolecular self-assembly through C-H···O bonds giving rise to parallel linear polymeric tapes that grow along b axis (Figure 2). Distances in H···O contacts varies in the range 2.52-2.57 Å, shorter than the sum of van der Waals radii (2.72 Å). 24 Angles are in the range of 157-170°, indicating high directionality. They are organized by pairs of DD-AA interactions (D,A: hydrogen bond donator and acceptor) that give origin to rings with 11 (blue), 12 (orange), and 14 (yellow) members (Figure 2a). The overall graph set can be described as C 4 4 (6)[R 2 2 (11), R 3 3 (12), R 2 2 (14)]. 19 C-H···O hydrogen bonds connect linearly each molecule to the other three. Fingerprint plot in Figure 3 demonstrates that H···O/O···H contacts are responsible for 24.2% of the Hirshfeld surface, with the formation of two sharp features and a broad blue area in the Hirshfeld surface. 16 The polymeric tapes pile up with , but layering formation is prevented due to out of plane B-ring configuration, that establish CH···π and π-π interactions ( Figure 2b). Intermolecular hydrogen bonds geometry data can be found in Table 2.
Nitro function presents a higher electronic density over both oxygens, which enable this group to act as Lewis base accepting hydrogen bonds. In Figure 4a the electrostatic potential was plotted over an electron density surface and the red-colored oxygens emerged surrounded by hydrogen atoms. 16 This group, however, exhibit also a positive electrostatic portion described as a π-hole over the C-N bond. 25 This π-hole presents Lewis acid character and establishes an intermolecular interaction with oxygen from the nitro group, with N···O distance of 3.027 Å, slight smaller than the sum of the van der Waals radii (3.07 Å). 24 In the Figure 4a the complementary electrostatic character of the NO 2 ···NO 2 interaction is displayed. Each molecule of compound 1 is connected to the other two by the means of nitro contacts, giving origin to a zig-zag chain motif observed along b axis in Figure 4b.
A polar-π almost parallel offset interaction was observed between A and B rings, with centroids separation of 3.9601(9) Å and the horizontal displacement of 2.127 Å; (the angle formed between the planes was 4.25°). Two of these supramolecular interactions are intermediated by one A···A parallel offset with centroids distance of 4.4809(9) Å, with horizontal displacement of the planes of 3.106 Å. Orthogonal B rings show a parallel offset π-π interaction toluene-like with centroids distance of 3.7985(10) Å (horizontal displacement of 1.598 Å). In the fingerprint plot, 16 C···C interactions give origin to the light blue portion in the 1.8 vs. 1.8 π-stacking region ( Figure 3). B ring π···π contact is sandwiched between two C-H···π hydrogen bonds. These π interactions are summarized in Figure 5.
Despite exhibiting one basic nitrogen (from hydrazone group), the participation of N···H/H···N interactions are almost negligible in the supramolecular structure, probably because of steric effects.
The crystal packing view along b axis is displayed in Figure 6. It is possible to observe alternation between the A-ring hydrogen-bonded motif and B-ring with π interactions.
A search in the Cambridge Structural Database (CSD, version 5.41, 2020.0 CSD, last update November 2019) through the software CONQUEST with the keyword "hydrazone" returned 1661 hits. 26,27 Delimiting the search to dinitrophenyl hydrazone, a total of 191 hits were found. Most of the structures exhibit both nitro groups and the aromatic ring in a flat (or near flat) configuration. In the vast majority of these crystal structures, an intramolecular hydrogen bond was observed between hydrazone N-H and oxygen from nitro at the ortho position. Notable exceptions were the derivatives of 6-chloro-2,4-dinitrophenylhydrazine, an agent for the absolute structure determination. 28 Such hydrazones present both chlorine and nitro substituents in the ortho positions, but the ortho group adopts a different orientation, far from N-H and with about 60° of torsion.
Some examples are EDUJAO, EDUJES, EDUJOC, and GANQAO. 29 MOGUL 26 analysis revealed that most of the structural aspects of compound 1 find similarities with   related hydrazones. Some aspects concerned with C7 neighborhood, although are unusual. The angle formed by C7-N2-N1 fragment, of 116.17° (the average is 118.45° among 15 related hits). The torsion angle of 116.51° in the fragment C9-C8-C7-N2 is also unusual (common angle is closer to 180°). Such unusual aspects can be attributed to the presence of two phenylethene moieties bonded to C-7.

Conclusions
A combination of synthesis and crystallization was employed to obtain single crystals of a hydrazone. The red prisms obtained represents a crystallography demonstration to improve undergraduate curricula.

Supplementary Information
Crystallographic data (excluding structure factors) for the structures in this work were deposited in the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 2009611. Copies of the data can be obtained, free of charge, via https://www.ccdc.cam. ac.uk/structures/.