Novel Synthesis and Characterization of 2-Aminobenzimidazole Derivative

Generally benzimidazole derivatives in numerous categories of therapeutic agent such as antimicrobial, antiviral, anti inflammatory, antioxidant, anticancer, anticoagulant, liquid level modulator, antidiabetics etc., various substituted around the benzimidazole nucleus have provided a wide biological activities. Important of this nucleus we are synthesized novel 2-aminobenzimidazole such as like N-((2-(1-(3-(trifluoromethyl) phenyl) ethylamino)-1H-benzo[d]imidazol-4-yl) methyl) methanesulfonamide. Aminobenzimidazoles are interesting heterocycles that are found in natural products as well as drugs and number of biologically active molecules [1]. The synthesis of 2-aminobenzimidazole involves the cyclodesulfurization of a pre-formed thiourea. The reported desulfurization agents was mercury(II) oxide [2], mercury(II) chloride [3], copper(I) chloride [4], methyl iodide [5], tosyl chloride [6], dicyclohexyl carbodiimide [7], PhI(OAc)2 [8] and polymer supported carbodiimide [9] etc., the reported method was frequently required heating and long reaction time. Furthermore formation of urea side product can pose significant challenges during purification. The variety of 2-aminobenzimidazole derivatives synthesized from diverse isothiocyanates (electron donating and electron withdrawing) groups was well tolerating the reaction.

We recognized that this process could be considerably simplified by using iodoaceic acid as a cyclodesulfurization agent and using ethanol solvent to provide desired product at 60°C, 3 hours without formation of side product with high yield.
FTIR spectra (KBr pellets) were measured using Alpha Bruker FTIR instrument scanning with the entire region of 4000 -400 cm -1 with typical resolution of 1.0 cm -1 .The NMR spectra of the compounds have been recorded on Bruker AV400 spectrometer operating at 400 MHz for recording 1 H NMR spectra in CDCl 3 as solvent using TMS as internal standard.Mass spectra have been recorded on SHIMADZU spectrometer using chemical ionization technique.

Synthesis Preparation of 7-(methanesulphonaminomethyl)-N-(1-(3-(trifluoromethyl)phenyl)ethyl)-1H-benzo[d]imidazol-2-amine:
) and iodoacetic acid (1.7g, 0.0139mmol, 1eq) in 30 mL of anhydrous ethanol was added at 0°C.The reaction mixture was heated at 60°C and stirred for 3 hrs.TLC was indicated absence of N-(2,3diaminobenzyl)methanesulfonamide.The residue was diluted with water and then extracted with Dichloro methane (30 ml* 3times).The combined organic layer washed with brine solution and dried with anhydrous sodium sulphate and filtered, concentrated in vacuum to afford crude product.The crude was purified by (60-120mesh silica gel) chromatography column using chloroform, ethanol as eluvent     FTIR spectra of compound 3 have been provided a preliminary idea for the formation of product.According to the FTIR, the presence of peak at 3480 cm -1 has clearly noticed the utilization of starting materials transforms into the product.Further, the corresponding peaks at 3332, 3365 and 2966 cm -  3) were synthesized successfully from the condensation between compound 1 and 2 in the presence of iodoacetic acid.Most of the researcher have been synthesized 2-aminobenzimidazole derivatives by using hazardous catalyst like mercury(II)oxide, mercury(II)chloride, copper(I) chloride, methyl iodide etc., which involves long time reaction and significant challenges during purification of the products.we have been synthesized the 2-aminobenzimidazole derivatives considerably simplified method used by iodoacetic acid as a cyclode sulfirization agent and using ethanol as solvent to provide desired product at 60°C, 3 hours without formation of side product with high yield.
In our scheme synthesis of compound 1 was involved 6 steps.The first step was protection of diamine followed by bromination and Di BOC amination, BOC deprotection, sulfonation using methane sulfonyl chloride and deprotection of diamine using raney nickel to get key intermediate 1 and 2 was synthesized using amine and thiophosgene.The chemical structures of compound 3 have been confirmed using various spectral techniques viz., FTIR, Mass, 1 H-NMR and 13 C spectra and were found to be in agreement with the chemical structures expected.
In literature survey variety of 2-aminobenzimidazole derivatives were reported using 3,4-substituted diamines and para trifluoro substituted isothiocynates as a key starting material.These derivatives show wide range of biological activity.So in our work we are synthesized various novel 2,3 substituted diamine derivative like compound (1) and various meta trifluoro substituted isothiocynates like compound (2).By using those key intermediates we are synthesized various substituted 2-aminobenzimidazole like N-((2-(1-(3-(trifluoromethyl) phenyl) ethylamino)-1Hbenzo[d]imidazol-4-yl)methyl)methanesulfonamide(3) which can possibly be further modified to research better potency than the reference drugs.

Figure 1 :
Figure 1: MASS Spectrum of the Compound.

Figure 2 :
Figure 2: 1 H NMR Spectrum of the Compound.