Benzimidazole is prepared from ophenylenediamine which is treated with formic acid in presence of alkali. Synthesis of benzimidazoles the synthesis of benzimidazole. It is an antimetabolite and inhibitor of histamine and is used as an insecticide. We report the synthesis of benzimidazoles using lanthanum chloride as an efficient catalyst. Transitionmetalfree synthesis of benzimidazoles mediated by kohdmso. Benzimidazoles heterocyclic building blocks sigmaaldrich. Benzimidazoles and paragonimiasis five patients, aged 738 years, with paragonimus skrjabini infections, were treated with oral triclabendazole 10 mgkg bd for 3 consecutive days, an antihelminthic benzimidazole derivative used in the treatment of fascioliasis in sheep 1 c.
It is a tautomer of a 4hbenzimidazole, a 2hbenzimidazole and a 3ahbenzimidazole. The first chapter provides an introduction to benzimidazoles and nheterocyclic carbenes, a unique class of molecules derived from benzimidazoles. Substituted ophenylenediamine for benzimidazoles, 2 mmol. As such, benzimidazoles are a versatile structural motif seen in a multitude of biologically active molecules and interestingly several recent articles have described alternate, yet longer methods for their preparation via other mcrs 1417. Benzimidazoles pharmacology merck veterinary manual.
Benzimidazole and imidazole derivatives are very useful bioactive intermediates for the preparation of pharmalogical and biological active molecules 16. Benzimidazoles eg, fenbendazole, flubendazole show high efficacy against both adult and immature stages of ascaris suum. Files available from the acs website may be downloaded for. The objective of this research was to conduct constructive organic chemistry in water and to achieve yields that were comparable to, or better than, those in conventional media.
Thore 301 as a part of our continued work to develop organic reactions in aqueous media,20 we have tried to develop synthesis of 2 aryl benzimidazole in aqueous media, here we report a simple. Jul 17, 2014 an efficient method for the synthesis of aminomethyl benzimidazoles is developed by using a onepot batch reaction between amino acids and ophenylenediamines. Us3406178a us42916165a us3406178a us 3406178 a us3406178 a us 3406178a us 42916165 a us42916165 a us 42916165a us 3406178 a us3406178 a us 3406178a authority us united states prior art keywords aldehyde nitroaniline catalyst reaction carboxylic acid prior art date 19640204 legal status the legal status is an assumption and is not a legal conclusion. Benzimidazoles are an important class of heterocyclic compounds, several derivatives of which were found to beuseful intermediatessubunits for the development of molecules of pharmaceutical or biological. An efficient oxidative protocol enables the synthesis of multisubstituted or fused tetracyclic benzimidazoles via a metal free oxidative cn coupling between the sp 3 ch and free nh of readily available n 1benzylalkyl1,2phenylenediamines in the presence of oxygen and tempo. Simple, mild, and highly efficient synthesis of 2substituted. The synthesis of 2phenylbenzimidazole from 1,2phenylenediamine and benzoic acid was chosen as a benchmark reaction. Simple synthesis and biological evaluation of some. Metal free synthesis of ncarboselenoate benzimidazolones by cascade cyclization of orthodiisocyanoarenes and selenosulfonates. However, the reactions were performed in solventfree and the catalyst could be reused for several runs.
Facile, novel twostep syntheses of benzimidazoles, bis. Microwaveassisted synthesis of benzimidazoles dergipark. Whereas most metal salts hydrolyze very readily in aqueous media, they can be. A desirable method for the quick synthesis of benzimidazoles, which are used as a kind of important. Udc multicomponent reactions mcrs benzimidazoles bisbenzimidazoles bisbenzimidazoledihydroquinoxalines electronic supplementary material the online version of this article doi. Imidazole and benzimidazole synthesis best synthetic. Many anthelmintic drugs albendazole, mebendazole, triclabendazole etc. Stephen w page, in small animal clinical pharmacology second edition, 2008.
Benzimidazoles exhibit significant activity as potential antitumor agents, antimicrobial agents, smooth muscle cell proliferation inhibitors, a treatment for intestinal cystitis, and in diverse area of chemistry ansari et al. Synthesis and antioxidant properties of novel benzimidazoles. Benzimidazole, a heterocyclic aromatic organic compound consisting of a fusion of benzene and imidazole, in an extension of the wellelaborated imidazole system, has been used as a carbon skeleton for n heterocyclic carbenes, usually used as ligand for transition metal complexes. Other than for strictly personal use, it is not permitted to download or to forwarddistribute the text or. The most prominent benzimidazole compound in nature is nribosyldimethylbenzimidazole, which serves as an. Compound 8 was also obtained by similar reaction of compounds 4 and 7. Antimicrobial activity of benzimidazole authorstream presentation. Synthesis of benzimidazoles the synthesis of benzimidazole derivatives starts with the benzene derivatives having nitrogen at ortho position to each other. A class of drugs known as the benzimidazole family is one such therapy. Benzimidazoles definition of benzimidazoles by medical. Ir kbr, 30003600 benzimidazole nh, 1720 and 1710 imide co. Novel preparation of benzimidazoles from narylamidines.
Coordination behavior of benzimidazole, 2substituted. The early 1950s was an important period regarding discovery of the biological significance of benzimidazolecontaining structures and the closelyrelated purines. The conditions are mild, and a wide range of functional groups can be tolerated. Files are available under licenses specified on their description page. Synthesis and biological activity of novel 2, 5disubstituted. Benzimidazole definition of benzimidazole by the free. The method described has the benefits of operational simplicity, excellent yields, and high chemoselectivity. As antihypertensive agents article pdf available in ejournal of chemistry 34. Benzimidazoles have also been prepared on a solid phase. This ring system is present in numerous antiparasitic, fungicidal, antithelemintic and antiinflammatory agents 47. Mass spectroscopy ms the mass spectrum of benzimidazoles exhibits molecular ion as a base peak12. Boric acid catalyzed convenient synthesis of benzimidazoles. The full text of this article hosted at is unavailable due to technical difficulties.
Importance of microwave reactions in the synthesis of. Chemistry benzimidazole is a heterocyclic aromatic organic compound. Organic chemistry arkivoc an electronic journal completely free to authors and readers at. A class of antihelmintic, often used to treat nematodes and cestodes. Substituted benzimidazoles inhibit gastric acid secretion.
Pages in category benzimidazoles the following 89 pages are in this category, out of 89 total. We have examined the effect of different solvents using the same reaction conditions. Use it for writing poetry, composing lyrics for your song or coming up with rap verses. Generally, benzimidazoles can be synthesized from a variety of starting materials and a few of them are listed below in detail. Benzimidazole, a heterocyclic aromatic organic compound consisting of a fusion of benzene and imidazole, in an extension of the wellelaborated imidazole system, has been used as a carbon skeleton for nheterocyclic carbenes, usually used as ligand for transition metal complexes. The research presented in this thesis is centered on the design and synthesis of molecules which are derived from benzimidazoles and their applications. Benzimidazoles are also highly effective against most other swine nematodes.
Pharmacological compounds of benzimidazole derivatives are potent inhibitors for a variety of enzymes. The synthesis and chemistry of certain anthelmintic. Prosenjit daw, yehoshoa bendavid, and david milstein. This page is about the various possible words that rhymes or sounds like benzimidazoles. Preparation of 2substituted benzimidazoles download pdf info publication number us3406178a. Purchase imidazole and benzimidazole synthesis 1st edition. A practical and convenient synthetic method has been developed for the facile synthesis of 1,2disubstituted benzimidazoles, 2substituted benzimidazoles and 2substituted benzothiazoles. It also collects nonringsynthetic approaches to classes of compounds such as nitro, halogeno.
This reaction proceeds smoothly in an unmodified household microwave oven, even though scaleup is to 10 g. It is considered as an alternative treatment for hydatid disease and is often indicated for patients who do not respond to surgery or benzimidazole. Direct synthesis of benzimidazoles by dehydrogenative coupling of aromatic diamines and alcohols catalyzed by cobalt. The synthesis and chemistry of certain anthelmintic benzimidazoles lb. Benzimidazoles are a class of heterocyclic, aromatic compounds which share a fundamental structural. It will be interesting to observe that these modifications can be utilized as potent therapeutic agents in future. A ring system composed of a benzene ring fused with an imidazole ring. Due to the important biological activity of benzimidazoles and in line with our research works in synthesis of this ring system 2024 we wish to report a simple procedure for preparation of 2arylbenzimidazoles through a condensation reaction of ophenylenediamine and aromatic aldehydes in the presence of na 3 alf 6 as a catalyst. Benzimidazole is a heterocyclic aromatic organic compound. Benzimidazole definition is a crystalline base c7h6n2 that is composed of a benzene ring fused with an imidazole ring and is structurally similar to purine. Onepot synthesis of 2substituted benzimidazole derivatives from ophenylenediamine and a variety of aldehydes were developed under mild reaction conditions. General procedure for the synthesis of 2substituted benzimidazoles and bis benzimidazoles.
Benzimidazoles and triazoles are useful structures for research and development of new pharmaceutical molecules and have received much attention in the last decade because of their highly potent medicinal activities. A simple, rapid and environmentally benign synthesis of n. Download fulltext pdf download fulltext pdf synthesis of benzimidazole derivatives. Benzimidazole moieties are a very important class of heterocyclic compounds that have many applications in pharmaceutical chemistry. Alkylative coupling of enaminones and benzimidazole milena staykova, stela statkovaabeghe, plamen angelov, and iliyan ivanov department of organic chemistry, university of plovdiv, 24 tzar asen str. 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. They act by binding to the fungal microtubules and stopping hyphal growth. This bicyclic compound consists of the fusion of benzene and imidazole. Recently saberi has reported synthesis of 2 benzimidazoles under microwave irradiation and solvent free conditions which is catalyzed by alumina, silica gel and zeolite hy as shown in scheme 6, ophenylenediamine 2 mmol with aromatic, aliphatic and heterocyclic carboxylic 2 mmol and 50 mg of alumina or silica gel or zeolite were mixed. In conclusion, we have demonstrated a very simple, efficient, and practical method for the synthesis of benzimidazoles with boric acid as catalyst in aqueous media, from readily available ophenylenediamines and aromatic aldehydes, under simple and convenient conditions. Studies both in vivo1,2 and in vitro15 have shown that substituted benzimidazoles inhibit the stimulation of acid secretion produced by dibutyryl cyclic amp and histamine. Introduction to benzimidazoles and coumarins karnatak science college, dharwad 68 substituents is due to the magnetic anisotropy of the unsaturated nitrogen lone pair11, which is removed when protonation occurs at this nitrogen. All structured data from the file and property namespaces is available under the creative commons cc0 license. This worm medicine is not usually used with humans, but is instead sometimes given as a treatment to.
Benzimidazole definition of benzimidazole by medical dictionary. Synthesis of benzimidazole substituted pyridone azo. It is a benzimidazole and a polycyclic heteroarene. Some 6fluoro5substitutedbenzimidazole derivatives in which indole and 1,1,4. Benzimidazoles and benzothiazoles from styrenes and n.
Benzimidazole definition of benzimidazole by merriamwebster. The structures of the synthesized compounds were confirmed by ir, 1h. Antimicrobial activity of benzimidazole authorstream. Facile and efficient onepot synthesis of benzimidazoles. The pmr spectrum of 8 could not be run due to its poor solubility in the common organic solvents. Alkylative coupling of enaminones and benzimidazole. Synthesis and biological evaluation of benzimidazole. 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. Introduction of substituent in to 1 st position lowers the melting point benzimidazoles with the imide nitrogen in the 1positionmore soluble in polar solvents and less soluble in organic solvents. Similarly, the general synthesis of benzimidazoles is by the condensation reaction of 1,2phenylenediamine with carboxaldehydes, carboxylic acids,6,7 or their derivatives8,9 such as, chlorides, nitriles, and orthoesters, under strong acidic conditions, with high temperatures. A new series of 2, 5 disubstituted benzimidazole derivatives have been synthesized. Synthesis and biological activities of novel bisheterocyclic pyrrodiazole derivatives.
Synthesis of benzimidazoles organic chemistry portal. Though rareearth metal catalysts give better yields, the prohibitive cost of the catalysts make them unsuitable for industrial application. Ligandfree coppercatalyzed synthesis of substituted. The most commonly used starting material is orthophenylenediamine opda. Benzimidazoles find several applications in different areas of chemistry. This compound is bicyclic in nature which consists of the fusion of benzene and imidazole. Benzimidazoles article about benzimidazoles by the free. A desirable method for the quick synthesis of benzimidazoles, which are used as a kind of important intermediates in drug. Mild and efficient synthesis of 2aryl benzimidazoles in water using sds s.
Mild and efficient synthesis of 2aryl benzimidazoles in. Apr 02, 2020 infections from relatively large organisms such as worms can often require treatment with special pharmaceutical drugs. Imidazoles and benzimidazoles with a free nh group are weak acids, but sufficiently acidic to be able to form anions in the presence of strong bases. Dribofuranosylbenzimidazole ring system was discovered in 1948 as an integral part of the structure of vitamin b12. Synthesis of benzimidazoles in hightemperature water. The standard synthesis for benzimidazoles is the cyclocondensation of ophenylenediamine or substituted ophenylenediamines with carboxylic acids or their derivatives. Synthesis of 1,2disubstituted benzimidazoles, 2substituted. Benzimidazole article about benzimidazole by the free.
Synthesis, characterization, and biological evaluation of. Srimani and coworkers reported the synthesis of 2substituted and 1,2disubstituted benzimidazoles by coupling of diamine with alcohols. Historically, hydrazones were considered to have more chemotherapeutic value in the development of novel anti. The high boiling point of nitrobenzene as solvent increases safety risks at high temperature and difficulties in removal from the product. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. Imidazole and benzimidazole synthesis 1st edition elsevier. A heterocyclic compound, c7h6n2, that is used in organic synthesis and inhibits the growth of certain fungi. Synthesis and antimicrobial studies of novel benzimidazole. There are two general methods for the synthesis of 2substituted benzimidazoles 819.
In this chapter, i will report the development of a new, additivefree method for the. In dogs and cats, mebendazole, fenbendazole, febantel, oxfendazole, oxibendazole, and flubendazole are used for treatment of roundworms, hookworms. Us3406178a preparation of 2substituted benzimidazoles. It is an important pharmacophore and privileged structure in medicinal chemistry. The position and type of substituents on the benzimidazole ring are responsible for a variety of biological activity.
A simple and efficient synthesis of triazole was carried out by treatment of 24azidophenyl1hbenzodimidazole 6 with different types of terminal alkynes in tbuohh2o. Synthesis of substituted benzimidazoles via tosylation of naryl amidoxime. Synthesis and pharmacological profile of benzimidazoles. Importance of microwave reactions in the synthesis of novel benzimidazole derivatives. Imidazole and benzimidazole synthesis is a comprehensive survey of the known methods of syntheses and ring modification. Historically, hydrazones were considered to have more chemotherapeutic value in the development of.