Synthesis of Annelated Imidazoles and Benzimidazoles

Abstract

A variety of fused ring imidazole or benzimidazole derivatives were prepared through two successive condensations of a dihalide with 4,5-diphenylimidazole or benzimidazole. The 2-methyl substituted derivatives of 4,5-diphenylimidazole or benzimidazole were also used. The size of the annelated ring, which is dependent on the dihalide used, can be varied from five to seven atoms. Initially, N-alkylhalo derivatives were prepared by condensation of the heterocyclic starting materials with a dihalide. Ring closure was then effected through intramolecular condensation of a carbanion derived from the 2-position or the 2-methyl group of the parent heterocyclic ring with the N-alkylhalo moiety.

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.…”