Benzimidazoles. 2-amino-, condensation

The technical production of poly(benzimidazole) (PBI) is also carried out in two steps. In the first step an aromatic tetramine is condensed with the diphenyl ester of an aromatic dicarboxylic acid at 220-260 °C, yielding a poly(amino amid) with elimination of phenol. Ring closure with elimination of water occurs in the second step (solid-phase polycyclocondensation), conducted at 400 °C and yielding the polybenzimidazole (experimental procedure, see Table 2.3). 

Condensation reactions of aniline and of other bases with aromatic aldehydes to give Schiff s bases are accelerated by ultraviolet light in buffered media. For example, o-phenylenediamine reacts with formic acid to yield benzimidazole and acetylacetone reacts with guanidine to form 2-amino-4,6-dimethylpyrimidine.162 Similarly, lobelanine is formed by the photocondensation of glutaraldehyde, benzoylacetic acid, and methylamine hydrochloride.163... 

Crystalline benzimidazoles have been obtained from all aldonic acids so far tested with only one exception that is known to the writer. Lohmar and Link29 reported that the condensation of D-glucosaminic acid (= 2-amino-2-desoxy-D-gIuconic acid) with o-phenylenediamine under a variety of conditions failed to yield a crystalline product. The direct oxidative condensation of D-glucosamine hydrochloride with o-phenylenediamine in the presence of cupric acetate yielded only the known 2-(D-arofro-tetrahydroxybutyl)quinoxaline (III) and not the desired benzimidazole. 

Amino-6-nitro-Fischer s base (36, R = N02) was reduced to the 5,6-diamino compound (36, R = NH2) in 80% yield, which (as its hexachlorostannate salt) was condensed with benzoic acid and with benzil to give, respectively, a 68% yield of 5,7,7-trimethyl-6-methylene-6,7-dihydro-5 7/-pyrrolo[2,3-/]-benzimidazole (37) and a 62% yield of 6,8,8-trimethyl-7-methylene-2,3-diphenyl-7,8-dihydro-6 7/-pyrrolo[2,3-g]quinoxaline (38).42 Spiropyrans from these linearly annellated Fischer s bases were not reported they likely would color upon irradiation with blue light. 

By condensation of 2-amino-1,3,4-thiadiazoles with p-benzoquinone the 6-hydroxy[l,3,4]-thiadiazolo[3,2-a]benzimidazoles (356) are prepared (Equation (117)) <86IJC(B)1266>. 

Although the first benzimidazole was prepared by Hobrecker in 1872, it was Ladenburg who extensively explored the preparation of benzimidazole derivatives by the condensation between ort/to-amino aniline and carbonyl compounds (aldehydes and ketones) in 1875. Subsequently, Phillips further extended Ladenburg s preparation to the condensation between ort/io-amino aniline and acetic acid to produce different kinds of carboxylic acids in the presence of dilute mineral acid. Therefore, the preparation of benzimidazole from ort/io-amino aniline is referred to as the Ladenburg method," Phillips method, Phillips modification, or the Phillips-Ladenburg reaction. It has been proposed that the condensation between ortho-dxaim aniline and carbonyl compounds involves the formation of a Schiff base intermediate," whereas the condensation between ort/io-amino aniline and acid proceeds via the A,lV -diacyl and monoacyl intermediated This condensation generally works for aliphatic acids and is feasible for aromatic acids if the condensations are carried out above 180°C in sealed reaction vessels. ... 

In one of their patents (13WO018928), Sumitomo chemists described the preparation of S-SFs-benzimidazole 70 and its use as an active pest-control agent. In their method, SFs-nitroaniHne 60, obtained in two steps from 4-SFs-anihne (11) by N-acetylation and subsequent nitration, was first converted into JV-methyl nitroaniline 71, the nitro group of which was then reduced to amino and coupled with 3-chloropyridine-2-carboxyUc acid to give amide 72. One-pot nucleophihc substitution of chlorine in 72 with sodium ethanethiolate and further condensation furnished 2-substituted 5-SFs-benzimidazole 73, the sulfide function of which was later oxidized to sulfone using 3-chloroperoxyhenzoic acid (MCPBA), thus providing the desired insecticide 70 (Scheme 18). 

Saleh et al. (2012) have developed a novel and efficient three-component condensation reaction of an aldehyde, amino azoles, and p-keto sulfone for the synthesis of pyrimido[l,2-a]benzimidazoles (143) and pyrazolo[3,4-b]pyridines (146) under ultrasonic irradiation via utilization of P-keto sulfone as an important synthon (Schemes 8.47 and 8.48). 

The corresponding ligands may be produced via condensation of phthalonitrile or iminoisoindolinone with appropriate N- and C-nucleophiles, namely 2-amino-benzimidazole and 2-cyanomethylene benzimidazole. 

Methylbenzimidazole (492 R = Me) yields the benzimidazoline (506) in the Vilsmeier-Haack reaction with DMF-phosphorus oxychloride. Treatment of 2-amino-l-benzhydryl-benzimidazole with sodium in liquid ammonia affords a mixture of 2-nitrobenzimidazole and the azo-compound (507) by an autoxidation process. " The benzimidazole derivative (508), prepared by the action of diphenylamine-2,2 -dicarbonyl chloride on benzimidazole, is dearomatized on heating to give the condensed heterocycle (509). ... 

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