The pattern of medicative chemical science is concerned with the find and development of new agents or drugs for handling diseases at molecular degree. Medicative chemical science is besides called every bit Pharmaceutical, Therapeutic and Pharmacochemistry.
Most of the activities in the subject of medicative chemical science is direct to formation of new man-made or natural organic compounds.
Pharmacological activities shown by the organic compounds are really specific so they are prevailing over the natural compounds. The resent progresss in computing machine scientific discipline and molecular biological science dramas of import function in drug design, development and production.
The procedure of drug development is really complex. It requires endowments of people from assorted subjects like chemical science ( organic chemical science, chemical science of natural compounds, biochemistry etc. ) , physiology, pharmacological medicine, pharmaceuticals and medical specialty. Medicative chemical science links between chemical construction and biological activity and besides pharmacokinetic and pharmacodynamic behaviour of drug to the physicochemical belongingss of curative agents. There is considerable convergence between medicative chemical science and pharmacological medicine.
While seeking in front on a new drug development or research on presymptomatic drugs status, medicative chemist and life scientist have ruling activity of happening the biochemical tracts by which drug shows good activities.
The other countries which are collaborated with medicative chemical science are biological science, computing machine aided drug design ( CAD ) , x-ray crystallography, metamorphosis and pharmacokinetics besides legal and regulative personal businesss, clinical test directions, pharmacies and process research activity.
Together all these squads utilizations sophisticated analytical techniques for development of new drug merchandises and most effectual ecofriendly production processs.
Majority of pharmacological active compounds in medicative chemical science has the heterocyclic ring system. Benzimidazole is besides one among them which is holding pronounce Biological activities.
The benzimidazole is a heterocyclic compound. In its construction six membered benzine ring is fused with five membered iminazole ring.
First benzimidazole discovered as a portion of Vit.B12 construction. It is in the signifier of 5,6-dimethyl benzimidazole. It has two N atoms at 1 and 3 place.
In general benzimidazole are crystalline compounds holding reasonably high runing points, permutation at 1 place lowers the thaw point.
Benzimidazoles are holding really less solubility in H2O. Sometimes they may be recrystallised with hot H2O besides. Many of benzimidazole holding good solubility in aqueous base and besides in aqueous acids.
Benzimidazole possess both features i.e. acidic and basic. The aa‚¬ ” NH- group nowadays in it is holding strongly acidic and comparatively really decrepit basic features. Due to itaa‚¬a„?s acidic nature they form N-metallic compounds when dissolved in acids. As Benzimidazole are decrepit basic, it is holding pka value of 5-3 to 12-3. Under suited benzimidazoles may be protonated at pka 5-6 and it may be deprotonated at pka12.
SYNTHESIS OF BENZIMIDAZOLES
The benzimidazole synthesis starts with Benzene derived functions, which is holding nitrogen incorporating maps at ortho place to each other.
FROM CARBOXYLIC ACIDS.
2-substituted benzimidazole normally in really good output is obtained by responding o-phenylenediamines with most carboxylic acids.
Phillips1 reported the synthesis of 2-substituted benzimidazoles. He introduced an of import alteration in this reaction, when o-phenylenediamines reacts with organic acids in presence dilute mineral acid ( normally about 4N Hydrochloric Acid ) , it gives substituted benzimidazoles. The output obtained with aliphatic acids and aromatic acids are good.
After analyzing reaction mechanism Phillips concluded that, for the reaction to continue monoacyl derived function was the necessary intermediate. On heating dilute mineral acid with the monoacyl derived functions, Monoacyl derivatives readily passed into the corresponding benzimidazoles. At similar reaction conditions diacyl-orthophenylenediamine besides give benzimidazoles, but it was concluded that due to the hydrolysis of acyl derivative to the monoacyl derived functions better reaction involved as the first measure.
Hydrochloric acid shows the catalytic activity in the reaction. It activates the carboxyl group by add-on of a proton to oxygen which leads to formation of a carbonium ion, with electron lack at C atom. Due to the entry of unshared negatron brace nowadays on one of N to the carbonium ion of the acerb group, the intermediate formed in the reaction is the extra merchandise.
Dibasic acids are besides reacted with o-phenylenediamine to organize substituted benzimidazole derived functions. The merchandise formed in this reaction is depends upon the mole ratio of the reactants and besides on the experimental conditions. When one mole of dibasic acid heated with the two or more moles of o-phenylenediamine, merchandise formed in most of the instances are benzimidazoles2.
By utilizing microwave irradiations
Synthesis of 2-substituted benzimidazole by utilizing microwave irradiation requires less clip and less solvent. The output obtained by this method is besides more.
K. Niknam et Al ; 3 synthesized substituted benzimidazole by utilizing microwave irradiations. In this o-phenylenediamine reacted with different aromatic and aliphatic carboxylic acids in presence of alumina-methanesulfonic acid at microwave power of 20 % for 4-10 mins.
By utilizing high temperature and supercritical H2O as dissolver
The application of the green chemical science is the chief challenge for research workers. Above 3740C and 221bar ( 22.1mPa ) H2O is become supercritical fluid. At this point the physicochemical belongingss such as H bonding, grade of ionisation, dielectric invariable and besides denseness can be eventually tuned by utilizing temperature and force per unit area. This means without altering the solvent chemical environment can besides be changed.
In some of the instances H2O besides plays function of dissolver, reactant and accelerator.
Joan Fragra-Dubreuil et Al ; 4 synthesized 2-substituted benzimidazole in high temperature H2O ( HTW ) by utilizing high force per unit area mini sterilizer. He synthesized these compounds by utilizing o-phenylenediamine and different carboxylic acids.
The compounds formed by the dual desiccation and intramolecular cyclization.
The best output was obtained at 3500C and 20 MPa ( 90 % ) .