Heterocyclic compounds, aromatic benzimidazoles

Recently, a joint effort of material Laboratory at Wright Research and Development Center and Photonics Research Laboratory at SUNY at Buffalo has resulted in a comprehensive study of structure-nonlinear optical properties of a large number of systematically varied aromatic heterocyclic compounds involving fused ring benzimidazole and benzthiazole structures (10,30). 

The question of the rate-determining step in the Chichibabin reaction is still open. Clearly, it is difficult to expect that such a complex process can be controlled by any single parameter. On the basis of the rate of hydrogen gas evolution, the following sequence of the reactivity of aza-heterocyclic compounds has been established 1-R-benzimidazoles > isoquinoline > 1-R-perimidines > benzo[/]quinoline > pyridine acridine. Evidently, this raw indicates that sodamide amination depends on number of factors, involving electron deficiency of the substrate C(a)-atom, ease of the adduct aromatization, substrate basicity, etc. Evidently, acridine s position in this raw reflects the difficulty of the y-amination. 

Today, the application of the CS-NLC method is associated with more than 350 compounds as analytical objects, including a small number of inorganic compounds a large number of organic compounds such as aU essential amino acids, their salts, and amides a series of aliphatic and aromatic small homo- and heteropeptides, their salts, and metal complexes heterocyclic compounds, such as substituted pyridines, quinolines, benzimidazoles, benzotriazoles, and their salts and metal complexes aromatic amines pharmaceutical products alkaloids and organic dyes. The method has also been successfully employed for obtaining local information on the structures of tellurite, vanadate, and borate glasses. 

Additional work around the benzimidazole scaffold on compounds related to 29 [72,73] suggested that the dihedral angle between the heterocycle and the phenyl ring is a crucial determinant of binding affinity, leading to the design of tetracyclic compounds with the aromatic moieties linked [74], Thus, indole... 

Reactions of 5f/-2-methyl-l,2,4-triazepino[2,3- ]benzimidazol-4-one 71, prepared by reaction of 1,2-diaminobenz-imidazole 72 with acetoacetic ester 73, with different reagents was described, in the search of new heterocycles with biological activity <2002CHE598>. When lactam 71 was treated with aromatic aldehydes in boiling 1-BuOH with addition of piperidine 74, 577-3-arylidene-2-methyl-l,2,4-triazepino[2,3- ]benzimidazol-4-ones 75a-c were obtained (Scheme 7). Coupling lactam 71 with phenyldiazonium chloride 76 in dioxane afforded the 3-phenylazo-substituted tricycle 77. When 71 was treated with phosphorus pentasulfide 78 in boiling dioxane or pyridine, its thio analog 79 was obtained. The reaction proceeded most efficiently when lactam 71 was refluxed with twofold excess of 78 in dry dioxane. These thiones 79 react with ammonia and amines by nucleophilic substitution. When 79 was refluxed with ammonia, benzylamine, piperidine, or morpholine, the 4-amino-substituted tricycles 80a-d were obtained. All the described compounds were identified by NMR, mass spectrometry, and IR spectroscopy. 

There are some known unsuccessful attempts to carry out alkylation (Mel, Me2S04), halogenation (tert-butyl hypochloride) and nitration of aromatic dihydrobenzodiazepines [7, 105]. Such attempts only resulted in the destruction of the seven-membered heterocycle. As a rule, these destructive processes are typical of dihydrodiazepine systems and often manifest themselves during the synthesis and study of these compounds. Therefore, the results of the destruction of a seven-membered heterocycle are most widespread and include its decomposition into ortho-diamine and carbonyl compounds (Scheme 4.43, reactions A and B) [105, 106] and benzimidazole rearrangement accompanied by splitting out of a methyl aryl ketone molecule (Scheme 4.43, reaction C) [117]. 

The reaction between o-phenylenediamine and an equimolar amount of an aromatic or heterocyclic aldehyde has been shown to proceed by initial formation of a monoanil (74). In the presence of oxidizing agents (e.g. nitrobenzene, which also acts as the solvent) this can form the 2-substituted benzimidazole. With two moles of aldehyde the bis-anil (75) forms, giving rise to a 1,2-disubstituted benzimidazole (Scheme 42). This aldehyde route to benzimidazoles is particularly suited to the synthesis of compounds with a heterocyclic group (e.g. 2-thienyl-, 2-pyridyl-) at C-2. Reaction of 2,2,4,4-tetrakis(trifluoromethyl)-l,3-dithietane with o-phenylenediamine gives 2,2-bis(trifluoromethyl)benzimidazoline (7430785). 

Monocyclic and Bicyclic aromatic heterocycles such as imidazoles, thiazoles, thiadiazoles, oxazoles, oxadiazoles quinazolines, indoles, benzimidazoles, purines pyrido[43-d]pyri-midines, thiazolo[5,4-d]pyrimidines, thiazolo[4,5-d]pyrimidines, oxazolo[5,4-d]pyrimi-dines and thieno[2,3-d]pyrimidines are renowned pharmacophores in drug discovery. These special structures are well explained and exemplified in chemical compound libraries. In this chapter, several types of thiazole based heterocyclic scaffolds such as mono-cyclic or bicyclic systems synthesis and their biological activities studies are presented, which are not frequently present in books and reviews. We mention the first importance of synthetic route of various thiazole based compounds and their applications in medicinal chemistry in this chapter. 

This experiment illustrates the classic method of forming the benzimidazole ring system. This heterocycle is generally prepared from 1,2-diaminobenzene (o-phenylenediamine) derivatives by reaction with carboxylic acids, or their derivatives, under acidic conditions. The ring system is aromatic thus it is difficult to oxidize or reduce, and it is stable to both acids and bases. It is an important heterocyclic ring system that occurs in vitamin B12 and in many other biologically important compounds. Benzimidazole itself inhibits the growth of certain yeasts and bacteria. 

A second synthetic route to poly(aryl ethers) containing heterocyclic units involved the reaction of an aromatic dihydroxy heterocycle with conventional activated difluoro compounds. Bisphenols containing quinoxaline, phenylimidazole, oxadizaole, pyrazole, triazole, phenolphthalein, phenolphthalimidine, and phenolphthalein anilide heterocycles were prepared and polymerized to high molecular weight (84-95), However, the most noteworthy examples are the poly(aryl ether benzimidazoles), prepared from bis(4-hydroxyphenyl) bibenzimidazole, due to their unique combination of adhesive, thermal and mechanical properties (Scheme VIII) (93-95),... 

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