Benzimidazole rings formation

The fate of the dinitroaniline herbicides in soil is extremely complex and many metabolites have been identified. Golab and Althaus reported 28 metabolites identified in a degradation study of trifluralin in soil. Major degradation products of dinitroaniline herbicides were formed by nitro reduction, A-dealkylation (mono-dealkylated and completely dealkylated) and the ring formation of benzimidazole. 

Omeprazole 5 -Methoxy-2- [(4 -methoxy-3,5-dimethyl-2-pyridinyl) methyl] sulfinylj -17/-benzimidazol O-methylation, imidazole ring formation using thiourea, A-oxidation, nucleophilic displacement, A-methylation, S -oxidation... 

Examples of five-membered heterocyclic systems having more than one heteroatom, the derivatives of which have been selected to illustrate some important methods of ring formation, are pyrazole (36), pyrazolone (37), hydan-toin (38), oxazolone (39), thiazole (40), benzimidazole (41) and benzotriazole (42). 

Prevailing formation of the 7-nitro derivative was observed in the nitration of 4-fluoro- [95] and 4-ferf-butylbenzimidazole [96, 97], When the benzimidazole ring has its 4 and 6 positions substituted, the nitration proceeds across the C-4 or C-7 atom [98-101],... 

In the formation of the l,l -bibenzimidazole (16) the second benzimidazole ring is formed by cyclization of a monoacylated o-phenylenediamine (8UCS(Pl)403), while thermolysis of the anils (17) derived from 2-azidoaniline also gives good yields of 2-aryl-substituted... 

The evolution of the formation constants of the binuclear triple-stranded helicates [1 2(L11)3] (NNN-S-NNN donor sets) and [R2(L13 )3] " " (ONN-S-NNO donor sets) along the lanthanide series mimics the size-discriminating effects previously established with the mononuclear precursors (Figure 31). When NNN donor sites are used in Lll, the stability constants drops for the smaller R , a trend removed when the terminal benzimidazole rings are replaced with carboxamide units in (Table 8). The connection of electron-withdrawing halo-... 

Ring formation via cycloaddition reactions has been illustrated by the [1 + 2 + 2] cycloaddition of 5-aryl-3-methylimidazo[5,l-Z>]thiazoles (426) with dialkyl ethynedicarboxylates. In an aprotic solvent, the reaction afforded several products, including the epimeric thiazolo[3,2-c]benzimidazoles (427) (Equation (16)) <82BCJ2464>. 

Numerous syntheses have been reported of the AT i receptor antagonist telmisartan, which contains two benzimidazoles/ Although typical reductive cyclization conditions are used in most of the reported syntheses, one patent describes unique cyclization conditions for formation of the second benzimidazole ring system/ In this one-pot protocol, the 2-propyl-4-methyl-l//-benzimidazole-6-carboxylic acid is first activated with 2-chloro-4,6-dimethoxy-l,3,5-triazine in A-methyl morpholine (NMM) and methanol, then treated with A-methyl-o-phenylenediamine and heated to reflux to provide the cyclized product. This protocol allow for synthesis of the benzimidazole system under nonacidic conditions and moderate temperatures. 

They have further studied the nitration reaction of 5(6)-(l-adamantyl)benzimidazole [95, 96]. The positive inductive effect of the adamantyl radical leads to an increase in electron density in the corresponding ortho positions, i.e. in positions 4 and 6 of the benzimidazole ring. This explains the formation of a mixture of isomers 153 and 154 as a result of the nitration reaction. 

A variety of methods have been developed for the preparation of substituted benzimidazoles. Of these, one of the most traditional methods involves the condensation of an o-phenylenediamine with carboxylic acid or its derivatives. Subsequently, several improved protocols have been developed for the synthesis of benzimidazoles via the condensation of o-phenylenediamines with aldehydes in the presence of acid catalysts under various reaction conditions. However, many of these methods suffer from certain drawbacks, including longer reaction times, unsatisfactory yields, harsh reaction conditions, expensive reagents, tedious work-up procedures, co-occurrence of several side reactions, and poor selectivity. Bismuth triflate provides a handy alternative to the conventional methods. It catalyzes the reaction of mono- and disubstituted aryl 1,2-diamines with aromatic aldehydes bearing either electron-rich or electron-deficient substituents on the aromatic ring in the presence of Bi(OTf)3 (10 mol%) in water, resulting in the formation of benzimidazole [119] (Fig. 29). Furthermore, the reaction also works well with heteroaromatic aldehydes. 

Benzimidazoles substituted with an alkylamine at position 2 have a venerable history as Hi antihistaminic agents. The standard starting material for many benzimidazoles consists of phenylenediamine (40-1), or its derivatives. Reaction of that compound with chloroacetic acid can be rationalized by invoking initial formation of the chloromethyl amide (40-2). Imide formation with the remaining free amino group closes the ring to afford the 2-chloromethyl benzimidazole (40-3). Displacement of... 

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