A methyl substitution on nitrogen atom of o phenylenediamine decreased the rate, possibly because of steric hindrance entries 2532. Various catalyzed synthesis of benzimidazole derivatives are known condensation of ophenylenediamine with ortho esters in the presence of various lewis acid. The synthesis and chemistry of certain anthelmintic. Benzimidazole is produced by condensation of ophenylenediamine with formic acid, or the equivalent trimethyl orthoformate. The product is applicable to aryl and heteroaryl aldehydes. The benzimidazole core was obtained by air oxidative cyclocondensation of o phenylenediamine with benzaldehyde under different conditions. It is isomeric with m phenylenediamine and p phenylenediamine. Journal of chemical and pharmaceutical research, 2015, 76. These metrics are regularly updated to reflect usage leading up to the last few days. Various catalysed synthesis of benzimidazole derivatives are known condensation of o. This ring system is present in numerous antiparasitic, fungicidal, antithelemintic and antiinflammatory agents 47. This aromatic diamine is an important precursor to many heterocyclic compounds.
This method provides a novel route for the synthesis of benzimidazoles in good yields with little catalyst loading. Dec 01, 2014 mechanism of synthesis of benzotriazole from o phenylenediamine click to continue biosynthesis of water soluble vitamins argumentative essay. The reaction mixture was cooled and basified by addition of sodium hydroxide solution. Ceric ammonium nitrate can efficiently catalysed the synthesis of benzimidazole derivatives from ophenylenediamine and aldehydes in peg. A green approach for the synthesis of nalkyl2thiomethyl benzimidazoles 2 rch 3, c 2 h 5, ch 2 ph under different conditions has been developed from nalkyl2chloromethyl benzimidazole i.
The benzimidazole core was obtained by air oxidative cyclocondensation of ophenylenediamine with benzaldehyde under different conditions. Benzimidazole has been prepared from o phenylenediamine by the action of chloroform and alcoholic potassium hydroxide 1 and of formic acid, 2 and by the reduction of o nitroformanilide. The reaction of o phenylenediamine with anthranillic acid yield compound 21hbenzodimidazol2yl aniline aop. Synthesis of benzimidazole 2 benzimidazole was prepared according to the reported literature. The hydroxyisoindolobenzimidazole derivatives 10 and 12 were synthesized from ophenylenediamine 1 and 3benzylidenephthalide 9 and with the 1,2di. The characterization data obtained for 2methyl1h benzimidazole. Synthetic routes to benzimidazolebased fused polyheterocycles kamal m. This reaction led to the formation of benzimidazoles new derivatives in good yields. Mechanism of synthesis of benzotriazole from ophenylenediamine click to continue biosynthesis of water soluble vitamins argumentative essay.
Supporting information cyclization of ophenylenediamines by. The compounds have been characterized by ir, nmr, mi. Jun 22, 2017 synthesis of benzimidazoles from o phenylenediamines and dmf. The reactor was sealed and maintained at 120 c in an oil bath, which was controlled by a haaked3 temperature controller. T s oh as a catalyst abdullah jawad kadhim1 and ali chazi kazim2 1,2university of alqadisiyah, college of education, chemistry department, iraq. Historically, the first benzimidazole was prepared in 1872 by hoebrecker, who obtained 2, 5 dimethyl benzimidazole 5 or 2, 6 dimethyl benzimidazole 6 by. In water and in the presence of erotf3, the diamine and benzaldehyde 1. Made the cooled reaction mixture distinctly basic by the gradual addition of the concentrated ammonia solution, the precipitated product was collected and recrystallised from 10% ethanol scheme. This protocol tolerates acidlabile functional groups. Synthesis of benzimidazoles from ophenylenediamines and. Various catalyzed synthesis of benzimidazole derivatives are known condensation of ophenylenediamine with ortho esters in the presence of. The reaction mixture was cooled and poured on to the crushed ice. Synthesis and characterization of benzimidazole by using o. Synthetic approaches to benzimidazoles from ophenylenediamine.
Ladenburg18 first prepared 2, 5 or 2, 6dimethylbenzimidazole by refluxing 4methylophenylenediamine in glacial acetic acid. Facile synthesis, characterization and antimicrobial. The results were also compared with results of synthesis by conventional heating under reflux. It is known that the reaction of ophenylenediamine opda with carbonyl compounds, under strong acidic conditions, gives benzimidazoles, whereas, opda in the presence of.
Synthesis and characterization of benzimidazole by using ophenylenediamine with different aldehydes and carboxylic acids in the presence of. One tablet, dissolved in 10 ml of water, gives a solution with a ph of 5. The reactions with nmethyl o phenylenediamine were completed in longer times with lower yields compared with their unsubstituted analogues entries 1, 4, 7, 10, 16, 19, and 22. Synthesis of benzimidazole from ophenylenediamine labmonk.
There are two general methods for the synthesis of 2substituted benzimidazoles 819. Various schiff bases are formed, named as 2methylbenzimidazole, 2benzylbenzimidazole, ethylacetate2methylbenzimidazole, 2substituted benzimidazole derivatives, 5nitro 2substituted benzimidazole derivatives. The benzimidazole nucleus has a significant importance in medicinal chemistry and many benzimidazolecontaining compounds exhibit important biological activities. Ophenylenediamine, benzimidazole, cyanoguanidine, acetophenone, chalcones. Benzimidazole has been prepared from ophenylenediamine by the action of chloroform and alcoholic potassium hydroxide 1 and of formic acid, 2 and by the reduction of onitroformanilide. It is isomeric with mphenylenediamine and pphenylenediamine. The benzimidazole nucleus has a significant importance in medicinal chemistry and many benzimidazole containing compounds exhibit important biological activities. This route provided moderate to high yields with a broad substrate scope.
The completion of the reaction was confirmed by tlc ethylacetate. Ladenburg18 first prepared 2, 5 or 2, 6dimethylbenzimidazole by refluxing 4methyl o phenylenediamine in glacial acetic acid. A concise synthesis of benzimidazoles via the microwaveassisted onepot batch reaction of amino acids up to a 10g scale. The synthesized benzimidazoles compounds were prepared from the condensation reaction between ophenylenediamine and various carbonyl compounds, in the presence of ammonium chloride as a catalyst. The bulky white precipitate obtained was stirred in cold water. This is a pdf file of an unedited manuscript that has been accepted for publication. The oxidation product of ophenylenediamine produced by horseradish peroxidase is 2,3diaminophenazine. Ammonium chloride is a commercial and environmentally benign catalyst. The two carbonnitrogen bonds in benzimidazole when disconnected give ophenylenediamine and formic acid. A new convenient method for preparation of 2substituted benzimidazoles and bisbenzimidazoles is presented.
Abstract the methods for the synthesis of benzimidazoles have become a. Synthetic approaches to benzimidazoles from o phenylenediamine. Benzimidazole and imidazole derivatives are very useful bioactive intermediates for the preparation of pharmalogical and biological active molecules 16. This product has been characterized by melting point, mass spectrometry, and nmr. It is a tautomer of a 4hbenzimidazole, a 2hbenzimidazole and a 3ahbenzimidazole. The compound aop was cadenced with aromatic acid chlorides in the presences of pyridine to get compound n21hbenzodimidazol2yl phenyl benzamide ab.
A simple approach to preparation of benzimidazoles from ophenylenediamines and dmf derivatives, only employing phsih 3 as promoter without any other additives, was reported. Evidence implicating the involvement of peroxidactic oxidation in nop activation has been obtained from plantcell suspension and isolated enzyme experiments. As a part of our research work in this area, a series of benzimidasole derivatives 3an were synthesized in good to high yields by reaction of o phenylenediamine and different aromatic aldehydes in the presence of sodium hexafluroaluminate, na 3 alf 6, as an efficient catalyst at 50 c. Selective and ecofriendly procedures for the synthesis of.
Also it can be used to synthesize various heterocycles. Original article synthetic approaches to benzimidazoles from o. A method for the preparation of nr amides of benzimidazole 2carboxylic acid on the basis of the reaction between o phenylenediamine and esters of nr oxamic acids was developed. An efficient and inexpensive synthesis of 2substituted. All the chemicals and reagents used were of analytical grade and were procured from nice chemicals. A method for the preparation of nr amides of benzimidazole2carboxylic acid on the basis of the reaction between ophenylenediamine and esters of nr oxamic acids was developed. Synthesis, characterization, and biological evaluation of. Molecular formula of ophenylenediamine c 6 h 8 n 2. Simple, mild, and highly efficient synthesis of 2substituted. Acetic acidpromoted condensation of ophenylenediamine. As one of the most effective polar solvents for various chemical reactions, n,n dimethylformamide has been employed as a widely utilized reactant in organic transformations such as formylation, amination, and cyanation reactions. This environmentally benign and practical method offers. Benzimidazole is a heterocyclic aromatic organic compound.
An improved and greener protocol for the synthesis of benzimidazole derivatives, starting from ophenylenediamine, with different aldehydes is reported. Synthesis of benzimidazole derivative 3a to a mixture of ophenylenediamine 0. The drawback in the phillips procedure is that diamine competes for the proton of the acid. The two carbonnitrogen bonds in benzimidazole when disconnected give o phenylenediamine and formic acid. Supporting information cyclization of ophenylenediamines. Procedure for the synthesis of byproduct from ophenylenediamine and co 2. Synthesis and antimicrobial studies of novel benzimidazole. Synthetic routes to benzimidazolebased fused polyheterocycles. The synthesis and chemistry of certain anthelmintic benzimidazoles lb. In the present study, synthesis, spectral studies and biological evaluation of nine novel benzimidazole derivatives were investigated. Synthesis, characterization and biological evaluation of some.
The reason that my hoffman rearrangement reaction failed was that i dissolved the amide in a naoh solution which hydrolyzed the amide bond. Various 2substituted benzimidazole derivatives in moderate to good yield have been prepared in a onepot reaction by condensation of ophenylenediamine. Synthesis and anthelmintic activity of benzimidazole derivatives. Generally, as far as synthesis is concerned, the alkanaminobenzimidazole derivatives 10ah were obtained in 83. A mild and efficient onepot synthesis enables the preparation of 2substituted benzimidazoles from 1,2phenylenediamines and triacyloxyborane intermediates generated in situ from carboxylic acids and boranethf. For instance, the reaction between ophenylenediamine and benzaldehyde readily affords benzimidazole derivatives scheme1. O phenylenediamine corboxylic acid nsubstituted2subsyituted benzimidazole rch 2ch 2cooh. The resulting solution was cooled and made alkaline to litmus with 10% sodium hydroxide solution. A plausible mechanism for the reaction is proposed based on the spectroscopic characterization e. The most prominent benzimidazole compound in nature is nribosyldimethyl benzimidazole, which serve as an axial ligand for cobalt in vitamin 1217,18,19. Synthesis of benzimidazoles from ophenylenediamines and dmf. The mixture was heated for about 10 h in oil bath, maintained at 150 0c.
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. Doublecondensation products were selectively obtained when erotf 3 was used as the catalyst in the presence of electronrich aldehydes. Formation of a mixture of an imino chloride and ophenylenediamine may be the ratedetermining step of the reaction. Monobmic carboxylic acids used in the synthesis of benzimidazoles.
The decomposition of unsymmetrically substituted benzimidazoline may lead to formation of two different benzimidazoles depending upon whether the. Synthesis of benzimidazoles has been developed by the o phenylenediamine with aldehydes using boric acid an efficient catalyst under mild reaction conditions in aqueous media. The reason for a special interest of researchers toward benzimidazole derivatives has been 5,6 dimethyl benzimidazole which is a constituent of naturally occur ring vitamin b12. It is a benzimidazole and a polycyclic heteroarene. Xxviii was synthesized in 95% yield by reacting ophenylenediamine hydrochloride xxvi with. Synthesis of 2substituted benzimidazoles by reaction of ophenylenediamine with aldehydes in the presence of scotf3 article in cheminform 3518 may 2004 with 128 reads how we measure reads. The latter approach has become more widely accepted, because of the easy access to a variety of substituted aldehydes. In water and in the presence of erotf 3, the diamine and benzaldehyde 1. Citations are the number of other articles citing this article, calculated by crossref and updated daily. Benzimidazole or diamide from a reaction of diamines and. The separated benzimidazole was filtered and washed with ice cold water.
Synthesis, characterization and antimicrobial activity of. Article views are the countercompliant sum of full text article downloads since november 2008 both pdf and html across all institutions and individuals. Ceric ammonium nitrate can efficiently catalysed the synthesis of benzimidazole derivatives from o phenylenediamine and aldehydes in peg. Further it to then treated with pcl 5 to get an intermediate. Mechanism of synthesis of benzotriazole from ophenylenediamine. Synthesis of 2substituted benzimidazoles by reaction of o. The reaction of ophenylenediamine with anthranillic acid yield compound 21hbenzodimidazol2yl aniline aop.
Synthesis and anthelmintic activity of benzimidazole. Jiatao yu, ming lu chemical engineering college, nanjing university of science and technology, nanjing 210094, china. At the outset, ophenylenediamine 1a and 4chlorobenzaldehyde 2a was chosen as model substrates and subjected to the condensation in the presence of tertbutyl nitrite tbn at room temperature. Simple synthesis and biological evaluation of some. It is a tautomer of a 4h benzimidazole, a 2h benzimidazole and a 3ah benzimidazole. Therefore, synthesis of benziemidazole is affected by simply heating the o phenylenediamine and formic acid together condensation type of reaction. Conversely, the formation of monocondensation products was the preferred path in absence of this catalyst.
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