Synthesis of Some New Benzimidazole Derivatives of Pharmaceutical Interest

Reaction of 2-(aminomethyl)benzimidazole dihydrochloride (1) with ethyl acetoacetate was studied to give diazepinone-benzimidazole derivative (2), while, treatment of 1 with phenylhydrazono ethylacetoacetate afforded phenylhydrazino diazepinone derivative (3). On the other hand, reaction of 1 with acetyl acetone resulted in the formation of diazepine derivative (4). The reaction of 1 with ethyl cyanoacetate was studied to give 3aminodiazepinone derivative (5). Also the reaction of 1 with acetophenone and/or benzophenone has been investigated to give the fused imidazolines 6 and 7 respectively, while the reaction of 1 with cyclopentanone gave benzimidazolyl derivative (8). Treatment of 1 with chloroacetyl chloride gave the fused pyrazinone (9). The treatment of 1 with benzoin gave the derivative (10). The structures of the hitherto unknown compounds have been confirmed from analytical and spectral data. The newly synthesized compounds were screened for antibacterial and antifungal activity


Introduction
Benzimidazole derivatives have been reported to have a wide range of pharmacological and biochemical activity; It consider to be CNS depressant, anti-Parkinson, antiviral activity, anti ulcerative, antihypertensive, antifungal, antitumor, antihistaminic, anti-bacterial and antihelminthes agents 1-4 .
Following the above findings and continuous to our previous work 5-8 directed towards the synthesis of fused heterocyclic compounds of potential biological activities the utilizing of 2-aminomethyl benzimidazole 9 as a title compound for the synthesis of some new benzimidazole derivatives was studied.
Due to the wide range of pharmacological activity and synthetic application of benzimidazoles in this study it was planned to synthesize benzimidazole derivatives using 2-aminomethyl benzimidazole 9 (1).Thus the reaction of 2-aminomethyl benzimidazole (1) with ethyl acetoacetate gave diazepinone derivative (2).IR spectrum revealed the disappearance of NH 2 absorption band at 3400-3550 cm -1 and the appearance of absorption band at 1680 cm -1 CO group.NMR spectra established the presence of a signals at δ 3.78(s, 2H, CH 2 ) and at δ 2.6 (s, 2H, CH 2 ) so it not present as tautomeric enaminone structure (2).Treatment of 1 with phenylhydrazeno ethyl acetoacetate afforded (1,4-diazepino [1,2-a] benzimidazole derivative (3), the structure of 3 was based on the analytical and spectral data, the 1 H NMR spectrum reveal the presence of a signal at δ 8.12 (s, 1H, NH) and δ 2.89 (s, 2H,CH 2 ).While the treatment of 1 with acetyl acetone in 1 N sodium hydroxide solution resulted in the formation of 3,5-dimethyl- [1,3]diazipene [1,2-a]benzimidazole derivative (4), the structure of 4 was inferred from the obtained analytical and spectral data.IR spectrum revealed the disappearance of NH 2 absorption band and the presence of absorption band at 1625 cm -1 for C=N.
As a further extension of the above studies, the reaction of 1 with cyclopentanone gave benzimidazole derivative (8).The structure of 8 was assigned from the analytical and spectral data. 1 H NMR spectrum displayed signal at δ 2.3 (s, 1H, NH).

Experimental
Melting points (uncorrected) were determined on Fisher-Johns melting point apparatus.Elemental analysis was performed in the microanalysis unit, Cairo University.IR spectra were recorded by means of pressed KBr on a Perkin-Elmer 883 infrared spectrophotometer. 1 H NMR spectra were recorded on a Varian 90 MHz in CDCl 3 .

Table 1 .
Characterization data of the compounds