Crystal Structure, Spectral Studies, and Hirshfeld Surfaces Analysis of 5-Methyl-5H-dibenzo[b,f ]azepine and 5-(4-Methylbenzyl)-5H-dibenzo[b,f ]azepine

The compounds, 5-methyl-5H-dibenzo[b,f ]azepine (1) and 5-(4-methylbenzyl)-5H-dibenzo[b,f ]azepine (2), were synthesized and characterized by spectral studies, and finally confirmed by single crystal X-ray diffraction method. The compound 1 crystallizes in the orthorhombic crystal system inPca2 1 space group, having cell parameters a = 11.5681 (18) Å, b = 11.8958 (18) Å, c = 8.0342 (13) Å, and Z = 4 and V = 1105.6 (3) Å. And the compound 2 crystallizes in the orthorhombic crystal system and space group Pbca, with cell parameters a = 16.5858 (5) Å, b = 8.4947 (2) Å, c = 23.1733 (7) Å, andZ = 8 andV = 3264.92 (16) Å.The azepine ring of both molecules 1 and 2 adopts boat conformation with nitrogen atom showing maximum deviations of 0.483 (2) Å and 0.5025 (10) Å, respectively. The C–H⋅ ⋅ ⋅ π short contacts were observed. The dihedral angle between fused benzene rings to the azepine motif is 47.1 (2) for compound 1 and 52.59 (6) for compound 2, respectively. The short contacts were analyzed and Hirshfeld surfaces computational method for both molecules revealed that the major contribution is from C⋅ ⋅ ⋅H and H⋅ ⋅ ⋅H intercontacts.


Introduction
Azepine derivatives have showed to be associated with different pharmacological activities such as antiviral, anticancer, anti-insecticidal, and vasopressin antagonist. Iminostilbene derivatives are found in montainine, coccinine, manthine, and pancracine alkaloids present in Haemanthus and Rhodophiala species [1]. They are the derivatives of drugs, such as carbamazepine [2], opipramol [3], and oxcarbazepine [4], which are used as anticonvulsants and antidepressants and in the treatment of epilepsy and trigeminal neuralgia [5]. Another compound, G32883, an iminostilbene derivative, shows effect on peripheral nerves [6]. Recently, it is reported that carbamazepine with magnesium oxide is used to treat anticonvulsant in albino rats [7]. Lateral dibenzazepine moieties are known to have potential to act as substituents for the binding site of the acetylcholine M 2 receptor [8]. The 11-phenyl-[b,e]-dibenzazepine compounds are proved to be novel antitumor compounds [9].
Synthesis and crystal structures of other iminostilbene derivatives, 5-(prop-2-yn-1-yl)-5H-dibenzo[b,f ]-azepine, orthorhombic polymorph, and 5-[(4-Benzyl-1H-1,2,3-triazol-1yl)methyl]-5H-dibenzo[b,f]azepine have been reported [10,11]. As a part of our ongoing research on the synthesis and crystal structures and their importance of iminostilbene derivatives, we report here the synthesis and characterization by spectral studies and crystal structure using single crystal X-ray crystal diffraction of compounds 5methyl-5H-dibenzo[b,f ]azepine (1) and 5-(4-methylbenzyl)-5H-dibenzo[b,f]azepine (2). Here, we investigate the role of the main intermolecular interactions on stabilization of the 2 Journal of Crystallography  solid state architecture of the iminostilbene derivatives. And, Hirshfeld surface analysis and fingerprint plots analyzing intermolecular interactions were presented in the same procedure as we reported [12]. (1). 5H-Dibenzo[b,f ]azepine (0.0025 mol) was taken in dimethylformamide (DMF) solvent, and K 2 CO 3 (0.0038 mol) was added at room temperature and stirred for 5 minutes. The reaction mixture was cooled to 0 ∘ C, then iodomethane was added (0.0038 mol). After 15 minutes, the resulting reaction mixture was heated at 60 ∘ C for 7 hours (Scheme 1). After completion of reaction (monitored by TLC), the reaction mixture was diluted with water (50 mL). The aqueous layer was extracted with ethyl acetate (3 * 20 mL), and the combined ethyl acetate layer was washed with 0.1 N hydrochloric acid (2 * 25 mL), followed by brine solution (2 * 25 mL). Then, the organic layer was dried over anhydrous sodium sulfate and filtered and concentrated under reduced pressure to afford crude product, which was purified by column chromatography over silica gel (60-120 mesh) using hexane : ethyl acetate mixture in 9.5 : 0.5 ratios as eluent. The pure compound was crystallized in ethyl acetate and hexane to obtain yellow hexagonal shaped single crystals. (We also performed DEPT (distortionless enhancement by polarization transfer), which will be given as supplementary data in Supplementary Material available online at http://dx.doi.org/10.1155/2014/862067.) (2). 5H-Dibenzo[b,f ]azepine (0.0025 mol) was taken in a mixture of toluene and water in the ratio of 1 : 1, and sodium hydroxide (0.029 mol) was added followed by tetra-n-butylammonium bromide (TBAB) (0.00029 mol) at room temperature. After 15 minutes, 1-(chloromethyl)-4methylbenzene (0.0031 mol) was added to the reaction mixture at room temperature. Then, the resulting reaction mixture was heated at 60 ∘ C for 5 hours (Scheme 2). After completion of reaction (monitored by TLC), the reaction mixture was diluted with water (50 mL). The aqueous layer was extracted with ethyl acetate (3 * 20 mL), and the combined ethyl acetate layer was washed with 0.1 N hydrochloric acid (2 * 25 mL), followed by brine solution (2 * 25 mL). Then, the organic layer was dried over anhydrous sodium sulfate and filtered and concentrated under reduced pressure to afford crude product, which was purified by column chromatography over silica gel (60-120 mesh) using hexane: ethyl acetate mixture in 9.5 : 0.5 ratios as eluent. The pure (We also performed DEPT (distortionless enhancement by polarization transfer), which will be given as supplementary data.)

Single Crystal X-Ray Diffraction
Studies. X-ray intensity data were collected for 1 (hexagonal shaped) and 2 (needle shaped) using Bruker X8 Proteum diffractometer at 296 K and 100 K, respectively. Data were collected using CuK radiation ( = 1.54178Å) with the and scan method [13]. The final unit cell parameters were based on all reflections. Data collections, integration, and scaling of the reflections were performed using the APEX2 program [13].
The structures were solved by direct methods using SHELXS [14] and all of the nonhydrogen atoms were refined anisotropically by full-matrix least-squares on 2 using SHELXL [14]. Summary of crystal data, data collection procedures, structure determination methods, and refinement results are summarized in Table 1.
ORTEP (Figures 1 and 2) and packing diagrams ( Figures  3 and 4) were generated using MERCURY [15]. And the program Crystal Explorer 3.0 [16] was used to perform Hirshfeld surfaces computational analysis and to quantify the intermolecular interactions in terms of surface contribution and generating graphical representations ( Figure 5), plotting 2D fingerprint plots (Figures 6 and 8) [17], and generating electrostatic potential ( Figure 5) [18] with TONTO [19]. The electrostatic potential is mapped on Hirshfeld surfaces using Hartree-Fock (STO-3G basis set) theory over the range of −0.020 a.u. to +0.020 a.u. (Figures 5 and 7). The electrostatic potential surfaces are plotted with red region which is a negative electrostatic potential (hydrogen acceptors) and blue region which is a positive electrostatic potential (hydrogen donor). Crystallographic data (excluding structure factors) for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Center as supplementary publications numbers 959827 (1) and 958853 (2).

Results and Discussion
The X-ray crystallographic analysis of 1 and 2 was performed, confirming the structures previously established by the NMR data. The crystal structure of each compound presents only one molecule in the asymmetric unit. The ORTEP diagrams of 1 and 2 including the atoms labeled are shown in Figures  1 and 3  derivatives previously published by us [10,11]. Overall, both the molecules adopt butterfly shape and the percentage of intercontacts of 1 and 2 to the Hirshfeld surface is compared (Figure 9).  Figure 1. The packing (Figure 2) of the molecules is stabilized with the short contacts C-H ⋅ ⋅ ⋅ (Table 2), which exist between C12-H12 and the centroid (Cg(1): C1-C5/C15) of the ring of the neighboring molecules with a distance of 0.930Å.

Hirshfeld Surface Analysis.
Here, we estimated the intermolecular intercontacts contributing to the Hirshfeld surfaces shown in Figures 5 and 9. It shows that the major contribution is from C-H (39%) (Figures 6(d) and 9) and H-H (57%) (Figures 6(a) and 9). This is evidence that van der Waals forces exert an important influence on the stabilization of the packing in 1. And other intercontacts C-C (2%) (Figures 6(c) and 9) and N-H (2%) (Figures 6(b) and 9) contribute less to the Hirshfeld surfaces. The mentioned intercontacts are highlighted by conventional mapping norm

Hirshfeld Surface Analysis.
The major contribution is from C-H (39%) (Figures 8(b) and 9) and H-H (61%) (Figures 8(a) and 9) intercontacts. The mentioned intercontacts are highlighted by conventional mapping norm on the molecular Hirshfeld surfaces (Figure 7). In Figure 7, the red spot areas indicate intercontacts involved in the C-H⋅ ⋅ ⋅ interactions. And the electrostatic potential (Figure 7) shows the distribution of positive and negative potential over the Hirshfeld surfaces.

Conclusions
Two derivatives, called 5-methyl-5H-dibenzo[b,f ]azepine (1) and 5-(4-methylbenzyl)-5H-dibenzo[b,f ]azepine (2), were synthesized, charactrized by spectral studies ( 1 H NMR, 13 C NMR and DEPT) and finally, structural elucidation by   single crystal X-ray diffraction studies. The azepine rings of compounds 1 and 2 adopt the boat conformation, and, as a whole, molecule assumes butterfly shape. The fused benzene ring to azepine motif makes a dihedral angle of 47.1 (2) ∘ for compound 1 and 52.59 (6) ∘ for compound 2, respectively. Hirshfeld surface analysis of 1 and 2 reveals that H⋅ ⋅ ⋅ H and C⋅ ⋅ ⋅ H are the most abundant intercontacts. This is evidence that van der Waals forces exert an important influence on the stabilization of the packing in 1 and 2.