Ring synthesis benzimidazole

In the synthesis of 47, 4-methoxysalicylaldehyde is condensed with 2-chloro-methyl-l-methyl-5-methylsulfonylbenzimidazole, ring closure is effected, and the product is quatemized with dimethyl sulfate [83], To enhance water solubility, the methyl sulfate anion is converted to the acetate anion the benzimidazole ring is... 

Syntheses of various types of quaternary salts 2 containing a 2-benzimidazole ring are summarized in Table IV the best results have been achieved using the modified protocol of Hein s benzimidazole synthesis. 

Although it is frequently more convenient to make imidazole and benzimidazole sulfones (and sometimes sulfoxides) by direct oxidation of the thioethers, 4-tosyl groups can also be introduced quite conveniently by a ring synthesis based on the reagent TOSMIC (see Section 4.2 and Scheme 4.2.1). 

The hypothesized binding pose places the C-5 and C-6 atoms of the benzimidazole ring proximal to Asp200, precipitating the hypothesis that the introduction of basic or polar substituents at these sites of the heterocycle may establish additional productive interactions with the acid moiety. The model also predicts that substituents at C-7 of the benzimidazole ring would be poorly tolerated while C-4 would be more accommodating of substitution but, nevertheless, restricted in size since these sites are in close proximity with the protein. These hypotheses were explored experimentally with the synthesis and evaluation of the series of compounds compiled in Table 4, which systematically survey common substituents at the C-4, C-5, C-6 and C-7 sites of the benzimidazole heterocycle. It is clear from... 

Many reactions in heterocyclic multistep syntheses involve thermal condensations. Among these, the Niementowski reaction is the most common method for synthesis of the 31-f-quinazolin-4-one ring. It involves the fusion of anthranilic acid (or a derivative, e.g. 2-aminobenzonitrile) vith formamides or thioamides (or their S-methyl derivatives) and usually needs high temperatures and requires lengthy and tedious conditions. Recently, Besson and coworkers studied the possibilities offered by this reaction and explored the preparation of novel bioactive heterocycles (e.g. 38, 39, and 40 in Scheme 9.11) in which the quinazoline skeleton is fused with thiazole, indole or benzimidazole rings [50a-c]. 

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. 

Benzimidazole ring-bearing heterocyclic compounds are important in pharmacology and medicinal chemistry. The synthesis of benzimidazoles from o-phenylenediamines and carboxylic acids or nitriles needs harsh conditions. Hence, the synthesis of benzimidazoles can be accomplished with < -phenylenediamines and aldehydes. Benzimidazole derivatives were synthesized by the reaction of o-phenylenediamine with either aldehydes or nitriles in the presence of SSA as a cheap and readily available heterogeneous catalyst in refluxing ethanol (Sadeghi and Nejad, 2013) (Scheme 5.16). The protocol is beneficial in terms of short reaction time, high yield, and operational simplicity. Salehi et al. (2006) synthesized... 

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. ... 

As in the case of benzimidazole, a parallel synthesis of benzoxazoles was described. The authors report that mixing directly differently substituted o-amino phenols 193 with acylating agents 194 and heating at 200 °C for 10-15 min under microwave irradiation, a collection of benzoxazoles 195 was obtained (Scheme 70). With this reaction, a 48-member library of benzoxazoles with different substituents on the aromatic rings was obtained [125]. 

With S-vinylsulfilimines. A novel synthesis of the dihydro-thiazolo [3,2- ]benzimidazole 414 was achieved by the ring closure of 2-mercaptobenzoimidazole 412 using d -ethenylsulfilimine 413 and basic conditions (Equation 188)... 

Two approaches have been applied for the synthesis of imidazo[2,l + thia/,ole ring systems. Reaction of 2-mercapto-benzimidazole with perfluoro-2-methylpent-2-ene in the presence of triethylamine gave compound 419 (Equation 192), and cyclocondensation of 2-imidazolidinethione with the alkynyl(phenyl)iodonium salt 420 afforded product 421 (Equation 193) <2001RCB1446, 2003JCM715>. 

Finally, single bead FT-IR has been further exploited in many applications, such as the study of the tetrapropylammonium perrutherate (TPAP)-catalyzed oxidation of supported alcohols [167], the ring opening of a supported oxazolidinone [173], and the solid-phase synthesis of a benzimidazole [174]. 

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. 

---