Benzimidazoles benzimidazol-2-ones

Randall and Alberly (136) have studied the binding of various ligands to aquocobalamin using stopped flow techniques. This work suffers from the fact that it is not clear if the added ligand is displacing coordinated water or coordinated benzimidazole. One might be led to believe that the reaction studied in this work is in fact displacement of benzimidazole because the kinetics are at least inconsistent with a mechanism in which unimolecular dissociation of coordinated water is the rate limiting step. 

When faced with the challenge of writing a monograph on the synthesis of imidazoles and benzimidazoles, one is immediately aware that although there are general methods available for the bicyclic compounds, the contrary is true for imidazoles themselves. Indeed, it is necessary to consider a number of widely divergent processes each time a synthesis is contemplated. For this reason I have divided the synthetic approaches arbitrarily into methods which make specific bonds in the imidazole product, those which transform another heterocycle, and those which start with the preformed imidazole ring. 

Benzimidazoles. Further modification of the benzimidazol-one-moiety of oxatomide has led to the synthesis of a large number of benzimidazoles, which are summarized in Table II. These compounds were synthesized as outlined in Scheme 4. Cyclization of IX with the appropriate carboxylic acids or with the bisulphite complexes of the aldehydes gave benzimidazoles XI (9). Successive chlorination with thionylchloride and coupling with l-(a, a -diaryl-methyl)-piperazines (II) afforded the benzimidazoles XIII (R = H, alkyl, aryl, cycloalkyl, aralkyl). 

Recognition of the mechanism of acid secretion then led to the development of a new class of antiulcer drugs, the substituted pyridyl methylsulfinyl benzimidazoles, one of which is shown in the figure above. These are now the mainstay for treatment of most add related diseases. Both the sodium pump and the acid pump remain specific drug targets, digoxin for the former, proton pump inhibitors for the latter. 

Cobalt is tightly encircled into the corrin cycle. Corrin is a more or less substituted cycle. It is coplanar and possesses a hydrogen atom that can be substituted. The last two bonds we must mention are the Co-CN and Co-benzimidazole ones. 

Firefly lucifenn is an example of an azole that contains a benzene ring fused to the five membered ring Such structures are fairly common Another example is benzimidazole present as a structural unit m vitamin B12 Some compounds related to benzimidazole include purine and its ammo substituted derivative adenine one of the so called het erocychc bases found m DNA and RNA (Chapter 28)... 

The photorearrangement of pyrazoles to imidazoles is probably analogous, proceeding via iminoylazirines (82AHC(30)239) indazoles similarly rearrange to benzimidazoles (67HCA2244). 3-Pyrazolin-5-ones (56) are photochemically converted into imidazolones (57) and open-chain products (58) (70AHC(ll)l). The 1,2- and 1,4-disubstituted imidazoles are interconverted photochemically. 

The photolysis of 1,2-benzisoxazole in the absence of air in acetonitrile gave salicylonitrile and benzoxazole (67AHC(8)277). When air-saturated acetonitrile was employed, 2,2 -dimeriz-ation to (38) occurred, accompanied by benzoxazole. Photolysis of the 2,2 -dimer (38) and benzoxazole did not alter the ratio, thus indicating that neither one arose from the other. Selective excitation also ruled out dimer formation from benzoxazole under the reaction conditions (Scheme 9). This dimerization is similar to that observed for benzimidazole, except that in that series no 2,2 -dimerization was observed (74TL375). 

H-Pyrido[3,2-c]azepine, 7-methoxy-nucleophilic displacement reactions, 7, 514 Pyridoazepines synthesis, 7, 535, 540 Pyridoazepinones synthesis, 7, 531 Py rido[2,1-a]benzazepin-6-one physiological properties, 7, 546 Py rido[ 1,2-a]benzimidazoles reactions, 6, 1041... 

If one amino group in o-phenylenediamine is converted to an amide group by formic acid, the intermediate benzimidazole is formed. This reaction, conducted with a wide range of reactants, produces resins (polybenzimidazoles) used as high-temperature adhesives for laminates in the aerospace industry. Heat insulation is made by including tiny bubbles of silica and all... 

Other advances in the use of IR spectroscopy are (1) The substitution of sulfur by selenium, for comparison with the spectra of benzimidazole-, benzoxazole-, and benzothiazole-2-thiones 72 (80AJC279). (2) The use of IR, as a quantitative tool to determine the association (homo- and heterodimers) of thia- and oxa-diazolin-5-thiones and -5-ones 73 (80NJC527). 

By using basicity data, Ridd and Smith- showed that 5-nitro- and 5-chloro-benzimidazole and their 2-methyl analogs exist essentially as mixtures of equivalent amounts of 29 and 30, and, in agreement with this ratio, 5-substituted benzimidazoles form comparable amounts of 1- and 3-derivatives on alkylation,- showing earlier alkylation ratios- to be erroneous. There are, however, other factors which can lead to the predominance of one tautomeric form. Basicity measurements indicate that 31 is preferred to the alternative non-hydro-... 

Chemical Name 5-Chloro-1-[1-[3-(2,3-dihydro-2-oxo-1 H-benzimidazol-1-yl)-propyll -4-pi-peridinyl] -1,3-dihydro-2H-benzimidazol-2-one... 

A mixture of 2.3 parts of 1-(3-chloropropyl)-1 -dihydro-2H-benzimidazol-2-one, 2.5 parts of 5-chloro-1 -dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one, 3.2 parts of sodium carbonate,... 

The reaction of 4-phenylbut-3-yn-2-one and TV-alkylated benzimidazoles 9 leads to benzo[b [l,4]diazocine derivatives 10 in very low yields.32... 

Only one example in this category has been described in recent years (as of 2003). Treatment of o-phenylenediamine (396) with 3,4,5,6-tetrachloropyridazine (397) in A-methylpyrrolidine at 115°C for 17 h gave a separable mixture of products, one of which was 2,3-bis(benzimidazol-2-yl)quinoxaline (398) (unstated yield). The structure (398) was confirmed by X-ray analysis,and a mechanism for its formation was suggested. ... 

Phenylsulfonyl-1,3-dihydrospiro[2//-benzimidazole-2, l -cyclohexan]-5-amine (601) gave 7-phenylsulfonyl-6-quinoxalinamine (602) [Me0H-H20, 60°C, 20 min then (CH0)2-NaHS02i, 95°C, 5 min 55% clearly a two-stage one-pot synthesis via the unisolated intermediate shown] 7-morpholino-6-... 

The one-pot synthesis of thiazolo[3,4-a]benzimidazoles has been reported using a microwave-assisted condensation-cyclization (see Scheme 17) of a substituted 1,2-diamine, substituted benzaldehyde and mercaptoacetic acid [74]. Heating the mixture at reflux for 12 min using a single-mode microwave reactor for the most part gave the fused benzimidazoles in improved yield and dramatically shorter times, when compared to classical conditions of heating at reflux in benzene for 24-48 h (Scheme 29). 

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