Synthesis and Characterization of Some New Benzimidazole Derivatives

In this paper the new starting material 2-(5-chloro-1H-benzo[d]imidazole-2-yl) aniline (1) was synthesized by the condensation reaction of 4-chloro-o-phenylenediamine and anthranilic acid .The new Mannich base derivatives were synthesized using formaldehyde and different secondary amines to synthesize a new set of benzimidazole derivatives(2-5). Also, the new Schiff-base derivatives (6-10) were synthesized from the reaction of compound (1) with various aromatic aldehydes and the closure-ring was done successfully using mercapto acetic acid to get the new thiazolidine derivatives(11-12).These new compounds were characterized using some physical techniques like:FT-IR Spectra and 1 HNMR Spectra.


Introduction:
Benzimidazole is a heterocyclic aromatic organic compound.It is a Bicyclic compound composed of the fusion of benzene and imidazole.The most noticeable benzimidazole compound in nature is N-ribosyldimethyl benzimidazole, which used as an axial ligand for cobalt in vitamin B 12 [1].Benzimidazole derivatives have important functions in medical field with many pharmacological activities such as antimicrobial, antiviral, antidiabetic and anticancer activity.It is an important pharmacophore in drug field due to being a good bio activity of naturally forming nucleotides [2][3][4][5].Mannich reactions have become important tools for the synthesis of new compounds.Mannich bases can either be directly used as intermediate chemical synthesis [6].They are organic compounds with the general formula R-CH 2 -N< [7] [8].Also,Schiff's bases are condensation products of primary amines with carbonyl compounds and they were first known by Schiff in 1864 [9].A broad variety of benzimidazole derivatives have been well-known for their chemotherapeutic importance.for example: the presence of mannich side chains in a drug may fight the water bacteria through the formation of hydrochlorides [10] ,schiff᾽s bases have anti cancer activity in animal inspection [11].

Materials and Methods:
Melting points were recorded with Sturat Melting point apparatus and were un corrected.Infra red spectra (FT-IR) were recorded on Shimadzu FT-IR-8300 spectrophotometer in Ibn Sina State Company(ISSC). 1 H-NMR spectra were carried out in Al-al Bayt University (Jordan) operating at 300 MHz in (DMSO -d 6 ) on Fourier transform Varian spectrometer.

2) Synthesis of Mannich Bases (2-5)
Compound ( 1) , (2.435 g,0.01 mol) was dissolved in hot methanol (25ml) and the compounds having secondary amine such as indole , isatine , 4-chloro acetanilide, benzanilide were added slowly to this hot solution, then formaldehyde (0.01 mol) was added all at once and refluxed for (4 hours) .The contents were kept overnight in the freezer.The corresponding crystals of mannich bases obtained were recrystallized from ethanol.

Nomenclature and
(3)drops of glacial acetic acid were refluxed for (6 hours).The mixture was cooled , collected by filtration and recrystallized from methanol.A mixture of the compounds (9or10) (0.01 mmole), 10 ml absolute ethanol were refluxed for 15 minutes.Then mercapto acetic acid (0.01 mmole) was added drop wise during 15 minutes while the mixture is hot.After that the mixture was refluxed for 10 hr, evaporated and treated with saturated solution of sodium bicarbonate filtered off and set aside at R.T up to dryness and recrystallized from ethanol to give the thiazolidine compounds.

Fig
Fig.(1): 1 H-NMR Spectrum of compound (1) Scheme (1 ( : The reactions sequence for the synthesis of some new benzimidazole derivatives