Aromatic heterocycle synthesis benzimidazoles

Significant attention has been paid to the synthesis of polynaphthoylene-benzimidazoles based on bis(naphthalic anhydrides) containing various aromatic heterocycles. 

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. 

Abstract This review covers the recent recyclable protocols for the C-N bond forming reactions between aromatic, heterocyclic and aliphatic amines such as imidazoles, benzimidazoles, benzylamines, piperidine, pyrrole, imides, anilines, hexyl, cyclohexyl amines, and amides as coupling partners with aryl iodides, bromides, chlorides, and arylboronic acids employing copper-mediated systems. The physical properties and characterization of the catalysts and their use in organic synthesis will be outlined. Most importantly, these recyclable versions developed by many groups in the recent years are potential candidates for commercial exploitation. The effect of additives, solvents, temperature, base, the nature of aryl halides on reactivity, and recycle studies of the heterogeneous catalysts are included in this... 

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). 

The catalytic oxidative system H/oxidant has also been applied for the synthesis of the following heterocyclic systems 2-imidazolines 134 by the oxidative coupling of benzaldehydes with ethylenediamines [113], benzimidazoles 135 by a similar oxidative coupling reaction of phenylenediamines with aromatic or aliphatic aldehydes [109] and oxazole derivatives 136 by the oxidative coupling of p-ketoesters with benzylamines (Scheme 4.70) [114]. 

A new method has been developed for the synthesis of aromatic diamines containing A-phenyl benzimidazole rings. The polymers softened in the region of 320—450 °C. Poly(p-phenylene terephthalamide) from the vapour phase apparently produces coatings with exceptionally good oxygen barrier properties. Chelate-forming heterocyclic polyamides, poly(amino)benzoxazoles have also been synthesized. ... 

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