The synthesis of benzimidazoles derivative involves subsequent synthesis of 42chloroethoxybenzaldehyde, 4 methyl benzaldehyde followed by benzimidazoles derivative by reaction between amines. Yi fang, can liu, weidong rao, shunyi wang, shunjun ji. Synthesis of benzimidazole from ophenylenediamine labmonk. Benzimidazole nucleus plays a very important role as a therapeutic. Here in we report a green and efficient synthesis of benzimidazoles and its derivatives, by the condensation of 1,2phenylendiamine and orthoesters in presence of ionic liquid, 1butylimidazolium bisulphate hbimhso 4 as a catalyst and water as solvent. This reaction proceeds smoothly in an unmodified household microwave oven, even though scaleup is to 10 g. A detailed study of the structureactivity relationship of these derivatives will pave the road to. The synthesis of benzimidazole fused iminosugars through a tandem. Anxiety is a psychological and physiological state characterized by cognitive, somatic, emotional, and behavioral components. Synthesis of chiral polyhydroxylated benzimidazoles by a. Microwaveassisted solidphase synthesis of benzimidazoles. Cobaltcatalyzed sustainable synthesis of benzimidazoles by redoxeconomical coupling of onitroanilines and alcohols. Benzimidazole is not readily metabolized by isolated soil microbial strains that metabolize benzimidazole based fungicides, and is inhibitory to some microbes at concentrations ranging from 500 to ugg.
General procedure for the synthesis of 2substituted benzimidazoles 4. Synthesis and evaluation of selected benzimidazole. View enhanced pdf access article on wiley online library html view download pdf for offline viewing. The mixture was stirred for 8 h and allowed to stand at room temperature for 3 days. Although unedited, the content has been subjected to preliminary formatting. The invention is directed to physiologically active compounds of the general formula ix and compositions containing such compounds, and their prodrugs, and pharmaceutically acceptable salts and solvates of such compounds and their prodrugs, as well as to novel compounds within the scope of formula ix, and to processes for their preparation.
Direct synthesis of benzimidazoles by dehydrogenative. Synthesis and medicinal applications of benzimidazoles. The widespread interest in benzimidazole containing structures has prompted extensive studies for their synthesis. Generally, benzimidazoles can be synthesized from a variety of starting materials and a few of them are listed below in detail. Synthesis of benzimidazoles virtually starts with benzene derivatives having nitrogencontaining functions ortho to each other like ophenylenediamines 7 opd and reacting with different carboxylic acids 8 to give 2substituted benzimidazole derivatives 9, generally in good yield. The reaction is catalyzed by pincer complexes of earthabundant cobalt under basefree conditions. Synthesis of 41h benzimidazole 2ylphenyl3chloro4phenylazetidine2one chloroacetyl chloride 0. In this paper, we report on the synthesis of a series of benzimidazole derivatives and their antimicrobial activity. The reaction is carried out by heating the reactants. All products are known compounds and structures of them were confirmed by comparison with their known physical and spectral nmr and ir data 1116. Imidazole and benzimidazole synthesis sciencedirect.
Generally, the synthesis of 2substituted benzimidazoles involves the treatment of. Synthesis of 2substituted benzimidazoles and bis benzimidazoles by microwave in the presence of aluminamethanesulfonic acid. The use of the benzimidazole ring as the internal nucleophile and the use of phenyliodosophthalate phiphth, a new metalfree and low toxic hypervalent iodine reagent, are the most remarkable novelties of this synthetic strategy. Synthesis of benzimidazole 2 benzimidazole was prepared according to the reported literature. Benzimidazole is a bicyclic heteroaromatic compound of fused benzene and imidazole. Coppermediated synthesis of druglike bicyclopentanes xiaheng zhang, russell t. As antihypertensive agents article pdf available in ejournal of chemistry 34 january 2006 with 861 reads how we measure reads. The compounds were tested for their ability to inhibit isolates amongst. Synthesis, characterization and antimicrobial activity of. The synthesized derivatives were screened for analgesic and antiinflammatory activities. Synthesis and antimicrobial activity of some novel n. However, owing to fast developing benzimidazole containing new drugs numerous reports have appeared on the synthesis of this privileged scaffold. A convenient method for the synthesis of 2substituted benzimidazoles and benzothizoles offers short reaction times, largescale synthesis, easy and quick isolation of the products, excellent chemoselectivity, and excellent yields as main advantages. The journal of organic chemistry 2019, article asap.
The two carbonnitrogen bonds in benzimidazole when disconnected give ophenylenediamine and formic acid. An efficient coppercatalyzed threecomponent reaction of 2haloaniline, ammonia and aldehyde for the synthesis of benzimidazoles with 1,10phenanthroline as the ligand has been developed. Benzimidazoles are weakly basic in nature, slightly less basic than imidazoles, therefore they are generally soluble in dilute acids. With hydroxy3methylbutyl benzimidazole carboxaldehyde 6 in hand, next, we turned our attention to the synthesis of 2aryliminomethylbenzimidazol1ylbutan2ols. It indicated that silica supported sodium hydrogen sulphate catalyzed reaction has a favorable selectivity for the synthesis of 2substituted benzimidazoles. Benzimidazole derivatives have shown hopeful activity in the treatment of several diseases, for this reason, the synthesis of novel benzimidazole remains a main focus for researchers. A thick wall test tube 25 ml was charged sequentially with resinbound ester 2300mg, 15% ppa in 1methyl2pyrrolidinone nmp, 3 ml, and 1,2phenylendiamine 3a4 equiv the test tube was then sealed with the teflon septum and aluminum crimp and stirred. When the mole ratio of ophenylenediamine and aldehyde are taken in 1.
Synthesis general procedure for the synthesis of 2aryl1h benzimidazoles equimolar amounts of ophenylenediamine 0. The reaction mixture was stirred on magnetic stirrer for four hrs. All the compounds were characterized by uv, ir, 1 h nmr, mass spectral data and chn elemental analysis. A novel series of 2substituted benzimidazole derivatives 3a3j were synthesized by the reaction of 2chloro methyl benzimidazole with substituted primary aromatic amines. Synthesis, in vitro and in vivo antitumor and antiviral. There are two broad based and general methods for the synthesis of 2substitutedbenzimidazoles.
Imidazole and benzimidazole synthesis is a comprehensive survey of the known methods of syntheses and ring modification. An efficient and inexpensive synthesis 169 were effective substrates to successfully execute couplings by boric acid. An efficient and inexpensive synthesis of 2substituted. Abstract an organocatalytic method for the modular synthesis of diverse n.
A desirable method for the quick synthesis of benzimidazoles, which are used as a kind of important. Therefore, synthesis of benziemidazole is affected by simply heating the ophenylenediamine and formic acid together condensation type of. Wise a basis for interest in the benzimidazole ring system as a nucleus from which to develop potential chemotherapeutic agents was established in the i95os when it was found that 5,6dimethyl i. Recent trends in the synthesis of benzimidazoles from o. Nahso sio promoted synthesis of benzimidazole derivatives. Iodine is a commercial and environmentally benign catalyst. General procedure for the synthesis of benzimidazole series series a a solution of 590 mg benzimidazole 5 mmol, 0. The synthesis and chemistry of certain anthelmintic. Pdf synthesis of 2substituted benzimidazoles and bis. Synthesis and antifungal activity of benzimidazole. It brings together the multitude of synthesis of the imidazole ring in a systemic way interms of specific bond formation, and recommends the most attractive synthetic approaches.
Hydrolysis of benzimidazole is not expected to occur due to the lack of hydrolyzable functional groups. Synthesis of 2substituted benzimidazoles in the presence of boric acid. Herein, we present the basemetalcatalyzed dehydrogenative coupling of primary alcohols and aromatic diamines to selectively form functionalized 2substituted benzimidazoles, liberating water and hydrogen gas as the sole byproducts. Substituted benzimidazoles have found applications in diverse therapeutic areas19. Phenylenediamine via nanoparticles and green strategies using transition metal catalysts sugandha singhal. The synthesis and chemistry of certain anthelmintic benzimidazoles lb.
This method is simple, convenient, environmental friendly, reusable, efficient and practical. The resulting solution was cooled and made alkaline to litmus with 10% sodium hydroxide solution. Synthesis, spectroscopic, xray diffraction and dft. An efficient method for the synthesis of aminomethyl benzimidazoles is developed by using a onepot batch reaction between amino acids and ophenylenediamines.
The synthesis highlights a comparative study of conventional, ultrasound and. Facile route for the synthesis of benzothiazoles and benzimidazoles 205 figure 2 xrd patterns of a zrp and b 40 wt% htpzrp, dried at 110 c. Pdf green chemistry is the new and rapidly emerging field of chemistry. Journal of chemical and pharmaceutical research, 2017, 98. Benzimidazole is a heterocyclic aromatic organic compound. Synthesis, characterization, and biological evaluation of. Molecules 2015, 20 15208 designing more potent compounds. Synthesis and biological evaluation of 2substituted. The use of microwave irradiation is an important development for the synthesis of benzimidazoles in the 21st century, and in recent years, microwaveassisted heterocyclic synthesis has gained significant attention in modern drug discovery studies. The methods for the synthesis of benzimidazoles have become a focus of synthetic organic chemists, as they are useful building blocks for the development of important therapeutic compounds in medicine. The pk value of benzimidazole was deduced a while ago and found to be pk a1 5. The synthesis of the title compounds involves simple cyclization reaction between substituted ophenylene diamine and corresponding carboxylic acid derivatives and was reacted with the substituted benzoyl chloride derivatives to form the corresponding benzoyl substituted benzimidazoles. The standard synthesis for benzimidazoles is the cyclocondensation of ophenylenediamine or substituted ophenylenediamines with carboxylic acids or their derivatives. Microwaveassisted synthesis of benzimidazoles and their.
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