Crystal Structure and Theoretical Study of N,N-di[(5-chloro-2-oxo-2,3-dihydrobenzo[d]oxazole-3-yl) methyl]ethanamine

The aim of the present work is to explore crystal and electronic structure of N,N-di[(5-chloro-2-oxo-2,3-dihydrobenzo[d]oxazole-3-yl) methyl]ethanamine. In the title compound, C18H15Cl2N3O4, the two 2, 3-dihydro-1, 3-benzoxazole ring systems are almost planar and make a dihedral angle of 96.12(7) with each other. The ethyl group is disordered over two set of sites with a site-occupancy ratio of 0.766(12):0.234(12). The crystal structure contain intermolecular C—H...O hydrogen bonds which form a zigzag chains along the c-axis, C—H...π interactions and π-π stacking interactions [centroid-centroid distance = 3.5668(19) Å].


Introduction
A series N-substituted-5-chloro-2(3H)-benzoxazolone derivatives were synthesized and evaluated by [1] their acetylcholinesterase inhibitory activity. These compounds were synthesized by Mannich reaction of 5-chloro-2(3H)-benzoxazolone with the appropriated amines. The acetylcholinesterase inhibitory activity of the title compounds was determined by colorimetric Ellman\'s method. The preliminary screening results indicated that 5-chloro-2-(3H)-benzoxazolone scaffold demonstrated different inhibition range against acetylcholinesterase enzyme depending on the structural differences.
In this paper the title compound, C 18 H 15 Cl 2 N 3 O 4 was prepared and characterized using elemental analysis and FT-IR and 1 H-NMR spectroscopy studies. The crystal and molecular structure of the title compound was determined from single-crystal X-ray diffraction data. It crystallizes in the monoclinic space group P2 1 /c. Semi-emprical molecular orbital calculations were carried out using the AM1 method. 4-chloro-2-aminophenol (10 mmol), urea (50 mmol) and 37% HCl (2.5 ml) were irradiated (300 W, 413 K) for 15 min in a microwave oven. After completion of reaction (by monitoring with TLC), water (10 ml) was added to the reaction mixture and stirred at room temperature for 1 h. The resulting precipitate was filtered and washed with water.
This compound (2 mmol) was dissolved in methanol (5 ml). Ethylamine (2 mmol) and 37% formalin (2.5 mmol) were added to this solution. The mixture was stirred vigorously for 3h. The resulting precipitate was filtered and washed with cold methanol. The crude product was crystallized from methanol-water (1:1) (Figure 1

Crystal Structure Analysis
In this study, the crystal structure of the title compound, N,N-di[(5-chloro-2-oxo-2,3-dihydrobenzo[d]oxazole-3-yl) methyl]ethanamine, was determined by X-ray analysis. The crystal structure of the title compound was solved by direct methods and was refined by a full-matrix least-squares method on F 2 . A summary of the crystallographic data is given in Table 1.  A single crystal suitable for X-ray diffraction obtained in methanol-water was light yellow and prismatic. The data were collected using a STOE X-AREA [11], using graphite-monochromated MoKα radiation. Diffraction measurements were made at 296 K. The cell was refined on a X-AREA and the data were reducted on a X-RED32 [11]. The structure was solved by direct methods using SIR-97 [12] and refined by a full-matrix least-squares on F 2 and by using the program SHELXL-97 [13]. N-bound and C-bound H atoms were positioned geometrically [N-H = 0.86 Å, C-H = 0.93-0.97 Å] and refined using a riding model with U iso (H) =1.5 U eq (C) for methyl H atoms and U iso (H) = 1.2U eq (C, N) for the others. The software used to prepare material for publication: WinGX publication routines [14]. Empirical absorption corrections were applied by integration (XRED-32; [11]). Molecular graphics: ORTEP-3 for Windows [15]; PLATON [16] and PARST [17].

Spectral Studies
The synthesized compound was characterized IR and 1 H-NMR data. The 1 H-NMR data of the compound obtained in CDCl 3 solution were given in the experimental section and was consistent with the structural results. The significant absorption bands of the compound are given in Table 2. An ORTEP drawing of the title molecule with 30 % probability displacement thermal ellipsoids and atom-labeling scheme are shown in Figure. 2. Crystal data and details for the crystal structure determination of the compound are listed in Table 1, and selected bond lengths, bond and torsion angles are given in Table 3. As the C-O and C-C distances, and O-C-C angles, geometric parameters all lie in the expected ranges [18].

Theoretical Study
Semi-empirical molecular orbital calculations of the title compound were carried out using the AM1 method [21] with WinMopac7.2 software [22]. A spatial view of the single molecule of the title compound calculated in the gas phase is shown in Figure  4. The two planar 2,3-dihydro-1,3-benzoxazole ring systems of (I) make a dihedral angle of 68.83° with each other. The conformational analysis of the molecule as theoretically obtained (Figure 4) is in a good agreement with the X-ray structure. The calculated dipole moment of (I) is 5.430 Debye. The HOMO and LUMO energy levels are -9.35210 and -.48704 eV, respectively.

Conclusions
In conclusion, C 18 H 15 Cl 2 N 3 O 4 has been synthesized and structurally characterized. We summarize the results from synthesis and X-ray diffraction measurements for (I) single crystal. In the molecule, the ethyl group is disordered over two positions with occupancies of 0.766(12) (for atom labelled A) and 0.234(12) (for atom labelled B). The terminal C atoms of the disordered ethyl group were refined anisotropically with the U ij values restrained to behave isotropically, with the ISOR instruction [ISOR 0.010 C10A C10B].
In the crystal, molecules are linked by C-H...O hydrogen bonds forming a zigzag chains along the [001] direction. In addition, C-H... π interactions and π-π stacking interactions are observed.
According to the Semi-empirical molecular orbital calculations of the title compound with the AM1, the calculated dipole moment of (I) is 5.430 Debye. The HOMO and LUMO energy levels are -9.35210 and -.48704 eV, respectively.