Synthesis, Single Crystal X-ray, Hirshfeld and DFT Studies of 1,8-Dichloro-9,10-dihydro-9,10-ethanoanthracene-11-carboxylicAcid

: In this paper, synthesis, single-crystal X-ray structure, Hirshfeld and DFT studies of 1,8-dichloro-9,10-dihydro-9,10-ethanoanthracene-11-carboxylic acid are discussed. Different intermolecular contacts affecting the crystal stability are studied using Hirshfeld calculations. The H . . . Cl and O . . . H contacts are the most signiﬁcant, showing corresponding interaction distances of 2.731 Å (Cl2 . . . H10) and 1.681Å (H1 . . . O1), 2.328 Å (O1 . . . H13), 2.510 Å (O1 . . . H12) based on Hirshfeld calculations. DFT calculations are carried out to study the electronic behavior, as well as the 1 H- and 13 C-NMR spectra of the synthesized compound. The computed NMR chemical shifts show excellent correlation with the experimental data (R 2 = 0.9884–0.9705).

In constructing this ethano-bridge of the anthracene-privileged structure, one of the most efficient and powerful protocols is the Diels-Alder reaction. Several representative examples have been reported in the literature regarding their synthesis and applications in different areas. Barton and his team reported on the selectivity of the host behavior of the roof-shaped compounds based on the ethanoanthracene dicarboxylic acids and their derivatives using mixed solvent systems such as ethylbenezene and xylene as guest solutions. The study revealed that these compounds worked selectively as roof-shaped compounds [19].
A recent review reported the development of highly efficient materials for fluid separation in between these studies on anthracene derivatives [20]. Li et al. reported on the synthesis and application of europium metal complexes containing an ethanoanthracene derivative as the binding ligand, which proved to have excellent water-quenching-resistant capability [21]. Another reperesntitive example reported by Lane and Capuano involved subsitituted ethanoanthracene, which worked effectively as an allosteric modulator of the dopamine D1 receptor [22].
The synthesis of new molecules and the elucidation of their molecular and supramolecular structures via single-crystal X-ray diffraction analysis are topics of great interest. We have previously studied ethanoanthracenes and published several articles in this field, which have been shown the biological importance of these compounds [23][24][25][26][27]. In this paper, we syntheize and elucidate the molecular and supramolecular structures of 1,8-dichloro-9,10-dihydro-9,10-ethanoanthracene-11-carboxylic acid. DFT calculations are performed to predict the spectral (NMR) and electronic properties of the synthesized compound.
aration in between these studies on anthracene derivatives [20]. Li et al. reported on the synthesis and application of europium metal complexes containing an ethanoanthracene derivative as the binding ligand, which proved to have excellent water-quenching-resistant capability [21]. Another reperesntitive example reported by Lane and Capuano involved subsitituted ethanoanthracene, which worked effectively as an allosteric modulator of the dopamine D1 receptor [22].
The synthesis of new molecules and the elucidation of their molecular and supramolecular structures via single-crystal X-ray diffraction analysis are topics of great interest. We have previously studied ethanoanthracenes and published several articles in this field, which have been shown the biological importance of these compounds [23][24][25][26][27]. In this paper, we syntheize and elucidate the molecular and supramolecular structures of 1,8dichloro-9,10-dihydro-9,10-ethanoanthracene-11-carboxylic acid. DFT calculations are performed to predict the spectral (NMR) and electronic properties of the synthesized compound.

Single-Crystal X-Ray Measurements of 5
The full analysis, data collection and refinement protocol is provided in the Supplementary Materials and summary of these details are listed in Table 1

Single-Crystal X-ray Measurements of 5
The full analysis, data collection and refinement protocol is provided in the Supplementary Materials and summary of these details are listed in Table 1.

Hirshfeld Surface Analysis and Computational Methods
"Hirshfeld surface analysis was carried out using Crystal Explorer 17.5 [28]. Calculations were performed using the Gaussian 09 software package [29,30] utilizing the B3LYP/6-31G(d,p) method. Natural charges were calculated using the NBO 3.1 program as implemented in the Gaussian 09W package [31]. The self-consistent reaction-filed (SCRF) method [32,33] was used to calculate the optimized structure of 5 considering the solvent effects (DMSO). Then, the NMR chemical shifts for the protons and carbons were computed using the GIAO method [34]".

Chemistry
According to the literature [18], cycloadducts 3 and 4 were obtained as a result of the BF 3 -OEt 2 -catalyzed Diels-Alder reaction of 1,8-dichloroanthracene 1 with acrolein 2 at room temperature. This step was considered to be the most important in the total synthesis of pharmaceutical agents such as maprotiline and benzoctamine [35,36]. The purified carbaldehyde 3 was air-oxidized into its corresponding carboxylic acid 5.

Analysis of Molecular Packing
In the solid-state crystalline structure, the molecular units are held together by intermolecular contacts, which have great impact on the crystal stability. In this study, the crystal stability was affected by different intermolecular contacts, which was analysed using Hirshfeld surface analysis (Figure 3). In the dnorm map, the short significant contacts appeared as red spots, while the less important intermolecular interactions appeared as blue or white areas. The percentage contributions of each contact were determined based on the decomposition of the fingerprint plot ( Figure 4). A summary of the intermolecular contacts is depicted in Figure 5.

Analysis of Molecular Packing
In the solid-state crystalline structure, the molecular units are held together by intermolecular contacts, which have great impact on the crystal stability. In this study, the crystal stability was affected by different intermolecular contacts, which was analysed using Hirshfeld surface analysis (Figure 3). In the d norm map, the short significant contacts appeared as red spots, while the less important intermolecular interactions appeared as blue or white areas. The percentage contributions of each contact were determined based on the decomposition of the fingerprint plot ( Figure 4). A summary of the intermolecular contacts is depicted in Figure 5.          In the dnorm Hirshfeld surface of 5, several significant contacts appeared as red regions. These interactions were due to O…H and H…Cl, as shown in Figure 6. The percentages of these interactions were 23.3 and 15.0%, respectively. In addition, these interactions revealed intense staples in the decomposed fingerprint plots, which could be considered another feature of short, significant contacts. The corresponding interaction distances based on the Hirshfeld analysis were 1.681Å (H1…O1), 2.328 Å (O1…H13), 2.510 Å (O1…H12), and 2.731 Å (Cl2…H10).

DFT Studies
The structure of 5 is shown in Figure 7A. The structure is overlaid with the results obtained from the single-crystal X-ray analysis, as shown in Figure 7B. Table S1 (Supplementary Materials) shows that the geometric parameters of the studied compound are in harmony between the computed and experimental data. The presence of slight differences may be due to the crystal packing effects. In addition, the relation between the computed and experimental geometric parameters clearly shows the high correlation coefficients for the bond distances (R 2 = 0.9947; Figure 7C) and angles (R 2 = 0.9644; Figure 7D).

DFT Studies
The structure of 5 is shown in Figure 7A. The structure is overlaid with the results obtained from the single-crystal X-ray analysis, as shown in Figure 7B. Table S1 (Supplementary Materials) shows that the geometric parameters of the studied compound are in harmony between the computed and experimental data. The presence of slight differences may be due to the crystal packing effects. In addition, the relation between the computed and experimental geometric parameters clearly shows the high correlation coefficients for the bond distances (R 2 = 0.9947; Figure 7C) and angles (R 2 = 0.9644; Figure 7D).  The natural population analysis was used to calculate the atomic charges at the different atomic sites. The results are presented graphically in Figure 8. The figure shows two slightly negative chlorine atoms with very close natural charges (−0.0067 and −0.0073 e). On the other hand, the oxygen atoms of the -CO 2 H group are strongly electronegative, with natural charges of −0.5915 and −0.7223 e for the carbonyl and hydroxyl oxygen atoms, respectively. The carboxylic group has the most electronegative atom and the most electropositive atomic sites, which are the oxygen of the OH group and carbon atom of the carbonyl group, respectively. The latter has a natural charge of 0.8463 e, while the rest of the carbon atoms are electronegative. In contrast, the OH proton is the most positive hydrogen site, with a natural charge of 0.5059 e. The molecular electrostatic potential (MEP) map shown in Figure 9 reveals the high negative charge density related to the carbonyl oxygen and the high positive charge related to the OH proton. Additionally, the presence of an intense red region close to the carbonyl oxygen atom and a blue region close to the OH proton shed light on the most probable hydrogen bond acceptor and donor sites, respectively. These results are in agreement with the observed X-ray structure of the studied system. The calculated dipole moment is 4.2782 Debye, indicating a highly polar molecule, while the direction of the dipole moment vector is presented in the left part of Figure 9.  The natural population analysis was used to calculate the atomic charges at the different atomic sites. The results are presented graphically in Figure 8. The figure shows two slightly negative chlorine atoms with very close natural charges (−0.0067 and −0.0073 e). On the other hand, the oxygen atoms of the -CO2H group are strongly electronegative, with natural charges of −0.5915 and −0.7223 e for the carbonyl and hydroxyl oxygen atoms, respectively. The carboxylic group has the most electronegative atom and the most electropositive atomic sites, which are the oxygen of the OH group and carbon atom of the carbonyl group, respectively. The latter has a natural charge of 0.8463 e, while the rest of the carbon atoms are electronegative. In contrast, the OH proton is the most positive hydrogen site, with a natural charge of 0.5059 e. The molecular electrostatic potential (MEP) map shown in Figure 9 reveals the high negative charge density related to the carbonyl oxygen and the high positive charge related to the OH proton. Additionally, the presence of an intense red region close to the carbonyl oxygen atom and a blue region close to the OH proton shed light on the most probable hydrogen bond acceptor and donor sites, respectively. These results are in agreement with the observed X-ray structure of the studied system. The calculated dipole moment is 4.2782 Debye, indicating a highly polar molecule, while the direction of the dipole moment vector is presented in the left part of Figure 9.   Figure 9 presents the HOMO and LUMO levels of the studied compound 5. The πsystem exists mainly in the studied compound; hence, the HOMO-LUMO intramolecular charge transfer could be portrayed as mainly π-π* excitation. The following indices were calculated, namely I = −EHOMO (ionization potential), A = −ELUMO (electron affinity), μ = − (I + A)/2 (chemical potential), η = (I-A)/2) (hardness), and ω = μ 2 /2η (electrophilicity) [40][41][42][43][44][45],  charge transfer could be portrayed as mainly π-π* excitation. The following indices were calculated, namely I = −E HOMO (ionization potential), A = −E LUMO (electron affinity), µ = − (I + A)/2 (chemical potential), η = (I-A)/2) (hardness), and ω = µ 2 /2η (electrophilicity) [40][41][42][43][44][45], giving values of 6.635, 0.687, −3.661, 5.948, and 1.127 eV, respectively. It was believed that these electronic parameters play important roles in the biomolecular reactivity.

NMR Spectra
DFT calculations were also used to calculate the NMR spectra of 5 (Table S3, Supplementary Data). Indeed, the chemical shifts in the NMR spectra were computed and compared with the values obtained experimentally. The resulting straight line plots were found to have high correlation coefficients (R 2 ). The R 2 values were 0.9884 and 0.9705 for the bond angles and distances, respectively, indicating harmony between the computed and experimental results ( Figure 10). giving values of 6.635, 0.687, −3.661, 5.948, and 1.127 eV, respectively. It was believed that these electronic parameters play important roles in the biomolecular reactivity.

NMR Spectra
DFT calculations were also used to calculate the NMR spectra of 5 (Table S3, Supplementary Data). Indeed, the chemical shifts in the NMR spectra were computed and compared with the values obtained experimentally. The resulting straight line plots were found to have high correlation coefficients (R 2 ). The R 2 values were 0.9884 and 0.9705 for the bond angles and distances, respectively, indicating harmony between the computed and experimental results ( Figure 10).

Conclusions
In summary, the synthesis and single-crystal X-ray structure of 1,8-dichloro-9,10-dihydro-9,10-ethanoanthracene-11-carboxylic acid were reported. The molecular structure of the studied compound was elcuidated via single-crystal X-ray diffraction analysis. Additionally, Hirshfeld calculations were computed and the electronic properties were assessed, such as the dipole moment, atomic charge, HOMO and LUMO levels and NMR spectra. The calculated NMR chemical shifts revealed a high level of harmony in the experimentally obtained results.
Supplementary Materials: The following are available online at www.mdpi.com/xxx/s1: Table S1-S3: The calculated geometric parameters, natural charges and nuclear magnetic resonance chemical shifts ( 1 H-and 13 C-NMR) of the studied compound 5.

Conclusions
In summary, the synthesis and single-crystal X-ray structure of 1,8-dichloro-9,10dihydro-9,10-ethanoanthracene-11-carboxylic acid were reported. The molecular structure of the studied compound was elcuidated via single-crystal X-ray diffraction analysis. Additionally, Hirshfeld calculations were computed and the electronic properties were assessed, such as the dipole moment, atomic charge, HOMO and LUMO levels and NMR spectra. The calculated NMR chemical shifts revealed a high level of harmony in the experimentally obtained results.