Table of Contents
Journal of Crystallography

Volume 2014, Article ID 862067, 9 pages

http://dx.doi.org/10.1155/2014/862067
Research Article

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

1Department of Studies in Physics, University of Mysore, Manasagangotri, Mysore 570006, India

2Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India

3Department of Studies in Microbiology, University of Mysore, Manasagangotri, Mysore 570006, India

Received 30 September 2013; Revised 8 December 2013; Accepted 14 February 2014; Published 19 May 2014

Academic Editor: Lígia R. Gomes

Copyright © 2014 Madan Kumar Shankar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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 in Pca21 space group, having cell parameters (18) Å, (18) Å, (13) Å, and and (3) Å3. And the compound 2 crystallizes in the orthorhombic crystal system and space group Pbca, with cell parameters (5) Å, (2) Å, (7) Å, and and (16) Å3. 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–Hπ 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 CH and HH intercontacts.

1. 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 M2 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-1-yl)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 5-methyl-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 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].

2. Material and Methods

2.1. Synthesis of 5-Methyl-5H-dibenzo[b,f]azepine (1)

5H-Dibenzo[b,f]azepine (0.0025 mol) was taken in dimethylformamide (DMF) solvent, and K2CO3 (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 (  mL), and the combined ethyl acetate layer was washed with 0.1 N hydrochloric acid (  mL), followed by brine solution (  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.

862067.sch.001
Scheme 1: The synthesis of compound 1.
2.2. Spectral Data

1H NMR (CDCl3, 400 MHz); δ 7.21 (q,  Hz, 2H), 7.01–6.91 (m, 6H), 6.66 (d,  Hz, 2H), and 3.30 (d, , 2H).Mass: Calc. 207.27 found: 208.27 (M++1).13C NMR (100 MHz, CDCl3): 152.28, 132.81, 132.42, 129.21, 128.90, 123.15, 118.82, and 39.30.MS: (calculated) [M+H]+ (found). Anal. Calcd. for C22H19N2: C, 86.92; H, 6.32; N, 6.76.

(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.)

2.3. Synthesis of 5-(4-Methylbenzyl)-5H-dibenzo[b,f]azepine (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)-4-methylbenzene (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 (  mL), and the combined ethyl acetate layer was washed with 0.1 N hydrochloric acid (  mL), followed by brine solution (  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, which yields colorless needle single crystals.

862067.sch.002
Scheme 2: The synthesis of compound 2.
2.4. Spectral Data

1H NMR (CDCl3, 400 MHz); δ 7.31 (d,  Hz, 2H), 7.15 (T,  Hz, 2H), 7.05–6.99 (m, 6H), 6.92 (T,  Hz, 2H), 6.79 (s, 2H), 4.91 (s, 2H), and 2.16 (s, 3H).Mass: Calc. 297.39 found: 298.39 (M++1).13C NMR (100 MHz, CDCl3):δ 150.52, 135.87, 134.51, 133.48, 131.92, 128.87, 128.70, 128.53, 128.28, 128.13, 127.50, 122.90, 120.15, 54.32, and 20.70.MS: (calculated) [M+H]+ (found). Anal. Calcd. for C22H19N: C, 88.85; H, 6.44; N, 4.71.

(We also performed DEPT (distortionless enhancement by polarization transfer), which will be given as supplementary data.)

2.5. 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 CuKα radiation (  Å) 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 using SHELXL [14]. Summary of crystal data, data collection procedures, structure determination methods, and refinement results are summarized in Table 1.

tab1
Table 1: Crystal data, data collection, and structure refinement.

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).

862067.fig.001
Figure 1: The molecular structure of compound 1 showing the atomic numbering system. Displacement ellipsoids are drawn at the 30% probability.
862067.fig.002
Figure 2: The crystal packing of compound 1 projected onto bc plane.
862067.fig.003
Figure 3: The molecular structure of compound 2 showing the atomic numbering system. Displacement ellipsoids are drawn at the 50% probability.
862067.fig.004
Figure 4: The crystal packing of compound 2 projected onto ac plane.
fig5
Figure 5: mapped on Hirshfeld surface (b) for visualizing the intercontacts of compound 1. Color scale in between −0.047 au (blue) and 1.152 au (red). Electrostatic potential mapped (c) on Hirshfeld surface (different orientation) with ±0.020 au. Blue region corresponds to positive electrostatic potential and red region to negative electrostatic potential. The ball and stick model represents the different orientations (front, back, top, and bottom) and correspondingly the Hirshfeld surfaces and their electrostatic potentials are oriented.
fig6
Figure 6: Fingerprint of compound 1: (a) CH, (b) NH, (c) CC, and (d) CH. The outline of the full fingerprint is shown in gray. di is the closest internal distance from a given point on the Hirshfeld surface and de is the closest external contacts.
fig7
Figure 7: mapped on Hirshfeld surface (b) for visualizing the intercontacts of compound 2. Color scale in between −0.075 au (blue) and 1.358 au (red). Electrostatic potential mapped (c) on Hirshfeld surface (different orientation) with ±0.020 au. Blue region corresponds to positive electrostatic potential and red region to negative electrostatic potential. The ball and stick model represents the different orientations (front, back, top, and bottom) and correspondingly the Hirshfeld surfaces and their electrostatic potentials are oriented.
fig8
Figure 8: Fingerprint of compound 2: (a) CH and (b) HH. The outline of the full fingerprint is shown in gray. di is the closest internal distance from a given point on the Hirshfeld surface and de is the closest external contacts.

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).

3. 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, respectively. The compounds 1 and 2 crystallize in the centrosymmetric and noncentrosymmetric space groups Pbca and Pca21, respectively. The structural analysis reveals that all geometric parameters agree well with the expected values reported in the literature, including the iminostilbene 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).

862067.fig.009
Figure 9: Hirshfeld surfaces percentage evaluation of short contacts for compound 1 and compound 2. The particular squared colour boxes on the right side represent the type of the intercontact visible at the percentage evaluation boxes.
3.1. Compound 1

The fused benzene ring (C1–C5/C15 and C9–C14) to the azepine motif makes a dihedral angle of 47.1(2)°. Seven-membered (azepine) ring adopts a boat conformation with nitrogen atom showing maximum deviations of 0.483 (2) Å, the puckering parameters  Å, ,  Å, and , and the total puckering amplitude  Å [20]. The ORTEP of compound 1 is shown in Figure 1. The packing (Figure 2) of the molecules is stabilized with the short contacts (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 0.930 Å.

tab2
Table 2: Intermolecular interactions geometry [Å, °].
3.2. 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 on the molecular Hirshfeld surfaces (Figure 5), where the red spot areas indicate intercontacts involved in the interactions. And the electrostatic potential (Figure 7) shows the distribution of positive and negative potential over the Hirshfeld surfaces.

3.3. Compound 2

The fused benzene rings (C1–C6 and C9–C14) to azepine motif make a dihedral angle of 52.59(6)°. The terminal benzene ring (C17–C22) makes dihedral angles of 26.66(6)° and 77.06(6)° with benzene rings C1–C6 and C9–C14, respectively. The ORTEP of the compound 2 is shown in Figure 3. Seven-membered (azepine) ring adopts a boat conformation with nitrogen atom showing maximum deviations of 0.5025 (10) Å, the puckering parameters  Å, ,  Å, and , and the total puckering amplitude  Å [20]. The packing (Figure 4) of the molecules is stabilized with the short contacts of the type (Table 2). These short contacts exist between C3 H3 Cg(1) with a distance 3.7513 (15) Å (angle ), C7 H7….Cg(2) with a distance of 3.7526 (14) Å (angle 156°), and C8 H8 Cg(1) with a distance 3.4987 (14) Å (angle 159°), with Cg(1): C1–C6; Cg(2): C9–C14.

3.4. Hirshfeld Surface Analysis

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

4. 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 (1H NMR, 13C 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.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Acknowledgment

The authors thank Institution of Excellence, University of Mysore, Mysore, for providing single crystal X-ray diffractometer and NMR facility for data collection.

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