A Novel Approach to the Synthesis of [1,2-a]Fused Polymethylenebenzimidazoles

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

“…3,16,29 There are drawbacks to reported syntheses of alicyclic ring-fused benzimidazoles such as requirements for transition metals, [1][2][3][4][5][6][7][8][9] prior synthesis of cyclization precursors, [10][11][12][13][14][15][16][17] full equivalents of strong base, [17][18][19][20] high molar mass hypervalent iodine reagents, 21 and the formation of mixtures of isomeric products. 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.…”

Chemistry of heterocyclic compounds at the Institute of Organic Chemistry, National Academy of Sciences of Ukraine (Review)

“…One of them is thermal cyclization, involving the heating of the initial compounds above 150°C. The method is suitable for the synthesis of 1,2-polymethylenebenzimidazoles with accepting substituents (K. G. Nazarenko, T. I. Shirokaya) [95], and also derivatives of 1,2-polymethylene-4-quinazolone [96].…”

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

“…[1][2][3][4]6,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] The procedures can be categorized into the following cyclization protocols: (i) metalcatalyzed reduction of aromatic nitro groups to amines (or nitroso), which undergo acid-catalyzed cyclization onto adjacent azacycloalkanes; [1][2][3][4]9,11,13,14 (ii) nucleophilic displacement by the N-1 benzimidazole anion of halo substituents in 2-(x-haloalkyl)benzimidazoles or generation of the benzimidazol-2-yl anion to undergo the inverse displacement reaction; 10,12,17,19 (iii) Rh-catalyzed reaction of N-alkenyl-1,2-diaminobenzene with H 2 and CO followed by annulation; 16 (v) N-nucleophilic anionic aromatic substitution using activated aromatic amidine analogues. 8,15,20 However, none of these synthetic approaches have thus far been reported to give eight-membered [1,2-a] alicyclic ring-fused benzimidazoles (e.g., 4). Thus, we now report the efficient use of the annulation protocol in category (i) to give azepino and azocino [1,2-a]benzimidazoles.…”