Synthesis and Single Crystal X-Ray Structure of New (2E)-2-[3-(1H-Imidazol-1-yl)-1-phenylpropylidene]-N- phenylhydrazinecarboxamide

Synthesis, spectroscopic characterization and X-ray crystal structure of a new (2E)-2-[3-(1H-imidazol-1-yl)-1-phenylpropylidene]N-phenylhydrazinecarboxamide (4) are reported.The stereochemistry of the title compound 4, C 19 H 19 N 5 O, about the imine bond [1.296 (4) Å] was assigned to have (E)-configuration. In the urea moiety, the N–H entities are trans to each other, and one of these forms is an intramolecular N–H⋅ ⋅ ⋅H hydrogen bond. The compound crystallizes in the monoclinic space group P2 1 /c with a = 5.8093 (2) Å, b = 20.5575 (6) Å, c = 14.0355 (5) Å, α = 90.00, β = 97.365 (2), γ = 90.00, V = 1662.36 (10) Å, and Z = 4. The molecules are packed in crystal structure by weak intermolecular hydrogen interactions.


Introduction
Epilepsy is the most prevalent neurological disorder, affecting nearly 50 million of mankind [1].Despite significant advances that have been made in epilepsy research, estimates suggest that convulsions in about 30% of epileptics are still inadequately controlled by the available antiepileptic medications [2].Additionally, the patients often suffer side effects from the currently used antiepileptics, such as nausea, headache, anorexia, hepatotoxicity, gingival hyperplasia, and hirsutism [3][4][5].Accordingly, there is a substantial demand for the development of more effective and safer antiepileptic therapies.
An evaluation of the literature exposed the emergence of structurally distinct anticonvulsants, namely, aralkylimidazoles.Nafimidone (I) and danzimol (II) (Figure 1) are two representatives of this class of anticonvulsants that are independently discovered.Moreover, compounds I and II displayed anticonvulsant profile similar to that of phenytoin or carbamazepine, but more distinguished than that of barbiturates and valproic acid [6][7][8][9].

Preparation of (2E)-2-[3-(1H-Imidazol-1-yl)-1-phenylpropylidene]-N-phenylhydrazinecarboxamide (4).
A solution of 2 (1.51 g, 10 mmol), ketone 3 (2.00 g, 10 mmol), and few drops of glacial acetic acid in ethanol (15 mL) was stirred at room temperature for 18 h.The reaction mixture was evaporated under reduced pressure, and the residue was crystallized from ethanol to give 2.3.Crystal Structure Determination.Slow evaporation of pure semicarbazone 4 in DMSO furnished the colorless single crystals.A colorless single crystal of suitable size, 0.42 mm × 0.11 mm × 0.09 mm, was selected for X-ray diffraction analysis.Data were collected on a Bruker APEX-II CCD area diffractometer equipped with graphite monochromatic Cu K radiation ( = 1.54178Å) at 296 K. Cell refinement and data reduction were done by Bruker SAINT [12]; program used to solve structure and refine structure is SHELXS-97 [13].The final refinement was performed by full-matrix least-squares techniques with anisotropic thermal data for nonhydrogen atoms on  2 .All the hydrogen atoms were placed in calculated positions and constrained to ride on their parent atoms.Multiscan absorption correction was applied by use of SADABS software [12].The crystallographic data and refinement information are summarized in Table 1.

Results and Discussion
3.1.Chemistry.The intermediate semicarbazide 2 was prepared according to our previously developed methodology [14] as outlined in Scheme 1.Thus, aniline was allowed to react with ethyl chloroformate to give the carbamate ester 1 which was subsequently reacted with hydrazine hydrate to furnish semicarbazide 2.
The imidazole-containing ketone 3 was synthesized from acetophenone in two steps according to the previously reported procedure as shown in Scheme 2 [15].Semicarbazide 2 was reacted with ketone 3 in ethanol in the presence of a catalytical amount of acetic acid at ambient temperature to yield the target semicabazone 4 in moderate yield (Scheme 2).The structure of compound 4 was confirmed via IR, 1 H NMR, 13 C NMR, and mass spectral data.X-ray crystallography is a decisive analytical tool which can confirm the configuration of the title semicarbazone 4. Fortunately, we have succeeded to get single crystals of compound 4 which were suitable for X-ray crystallography, and hence the assigned (E)-configuration of compound 4 was established via its single crystal X-ray structure.

Conclusion
The synthesis and spectroscopic characterization of a new imidazole-containing arylsemicarbazone, namely, (2E)-2-[3-(1H-imidazol-1-yl)-1-phenylpropylidene]-N-phenylhydrazinecarboxamide (4), have been successfully achieved.The assigned (E)-configuration of the title compound 4 was confirmed via its single crystal X-ray structure.Results and analysis of the X-ray crystal structure of compound 4 are also reported.Compound 4 can be screened for anticonvulsant potential as it is a hybrid structure containing both arylsemicarbazone and imidazole pharmacophoric moieties of anticonvulsants.

Table 1 :
Crystallographic data and refinement information.
bond angles, and bond torsion angles are listed in Table2.The hydrogen-bonded interactions are listed in Table3.