Synthesis of seven- and eight-membered [1,2-a] alicyclic ring-fused benzimidazoles and 3-aziridinylazepino[1,2-a]benzimidazolequinone as a potential antitumour agent

Greener synthesis using hydrogen peroxide in ethyl acetate of alicyclic ring-fused benzimidazoles and anti-tumour benzimidazolequinones

“…22 The most convenient protocol remains the traditional oxidative cyclization of o-cyclic amine substituted anilines, which was first reported in the early 1960s using hydrogen peroxide in the presence of trifluoroacetic acid. 23 Variations include converting o-tert-aminoacetanilide to benzimidazole using H 2 O 2 in formic acid 24,25 and ring-fused benzimidazole and imidazobenzimidazole were precipitated without the requirement for chromatography using Oxone in formic acid. 26 Most recently, H 2 O 2 in combination with hydrochloric or hydrobromic acid mediated the cyclization of ocyclic amine substituted anilines to give respectively dichlorinated and dibrominated ring-fused benzimidazoles in high yields of >80%.…”

“…30 It was envisaged that the weak acidic property of H 2 O 2 would negate the requirement for carrying out the cyclization in organic and mineral acids, as described in literature procedures. 3,[23][24][25][26][27][28] Recently the preparation of alicyclic ring-fused benzimidazoles in formic acid was reported at high temperatures using an iodinemediated cyclization of o-nitro-t-anilines, where corrosive HI was generated in situ. 28 Ethyl acetate is classified as a preferred solvent by Pfizer, 31 while GSK give ethyl acetate high ratings for environmental impact, health and reactivity / stability.…”

Advances in the Synthesis of Ring-Fused Benzimidazoles and Imidazobenzimidazoles

“…Mechanisms were proposed for benzimidazole formation from anilide, via an amine- N -oxide rather than the nitroso intermediate (see Section 2.1.2 ). Later the use of anilide derivatives as substrates for preparation of ring-fused benzimidazoles would become commonplace ( Scheme 3 ) [ 13 , 15 , 27 , 37 , 38 , 39 , 40 ].…”

“…Significant amounts of seven- and eight-membered ring-fused [1,2- a ]benzimidazoles 9a and 9b were formed from nitrobenzenes 7a and 7b during the one-pot catalytic hydrogenation and acetylation to give acetamides 8a and 8b ( Scheme 3 a) [ 39 ]. It seemed that the conformation of these large alicyclic rings favored advantageous cyclization of nitroso intermediates formed during the hydrogenation process.…”

Synthesis of a Spirocyclic Oxetane-Fused Benzimidazole

“…In order to fuse the spirocyclic oxetane of 8a and 8b, the well-established oxidative cyclization reaction of acetamide onto the neighbouring cyclic amine was used [11][12][13]. Oxone ® in formic acid is as an expedient means of converting o-cycloalkylaminoacetanilides into [1,2-a] alicyclic ring-fused benzimidazoles and double annulated imidazobenzimidazoles in high yields [13].…”