Benzimidazole Syntheses by Oxidative Cyclization with Peroxytrifluoroacetic Acid

o‐Amine‐Assisted Cannizzaro Reaction of Glyoxal with New 2,6‐Diaminoanilines

“…The precipitate was filtered and dried to yield 3a as a white solid (yield 3.55 g, 88 %). The synthetic method for 3g [5] and 3h [24] was similar to that for 3a-3d.…”

“…A series of o-monoamine-substituted anilines have already been reported. [5] However, although some primary anilines having amines at the 2-and 6-positions have been synthesized until now, [6] difficulties in the synthesis are unknown to prepare various new 2,6-diaminoanilines. This prompted us to prepare several new 2,6-substituted anilines having secondary or primary amino substituents.…”

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.…”

Copper-catalyzed ortho-C–H amination of protected anilines with secondary amines

“…The resulting 2-morpholinoaniline was next derivatized into the corresponding benzimidazol 59 via an oxidative cyclization reaction. 17 Although the mechanism is unclear at this point, the lack of reactivity of 1 in the presence of radical scavengers such as TEMPO or Galvinoxyl suggests that a SET pathway might operate 18 (see the ESI † for intramolecular kinetic isotope effect and competition studies).…”