Traceless solid-phase synthesis of 5-benzoylbenzimidazoles

Abstract

A traceless linker strategy for the solid-supported synthesis of 5-benzoylbenzimidazoles has been developed. A benzyl cyanide functional group was linked to 2% divinylbenzene cross-linked polystyrene through a dimethylsilyl linker. Coupling with 5-chloro-2-nitroaniline followed by oxidative decyanation gave benzophenone 11 as a key intermediate in an efficient one-pot reaction procedure. After reduction of the nitro group and oxidative cyclization with a variety of aldehydes in the presence of DDQ, a series of polymer-supported benzimidazoles was produced. Final traceless cleavage of the arylsilane linker with TBAF provided a small library of 5-benzoylbenzimidazoles.Key words: solid-support, traceless linker, arylsilane, 5-benzoylbenzimidazole.

Simple, Mild, and Highly Efficient Synthesis of 2-Substituted Benzimidazoles and Bisbenzimidazoles

“…Considering the reaction times, a significant effect of the substituents on either aldehydes or o-phenylenediamines were not observed. A methyl substitution on nitrogen atom of o-phenylenediamine decreased the rate, possibly because of steric hindrance (entries [25][26][27][28][29][30][31][32]. The reactions with N-methyl o-phenylenediamine were completed in longer times with lower yields compared with their unsubstituted analogues (entries 1, 4, 7, 10, 13, 16, 19, and 22).…”

“…The other method is condensation of o-phenylenediamines with aldehydes under oxidative conditions. 15,21 Various reagents such as I 2 /KI, 22 In(OTf) 3 , 23 nitrobenzene, 24 benzoquinone, 25 Oxone, 26 Fe(HSO 4 ) 3 27 and atmospheric air 28 are used for this purpose. Nevertheless, some of these reported methods have limitations such as low yields, high reaction temperatures, long reaction times, harsh reaction conditions, purification difficulties, and formation of by-products.…”

Highly Efficient and Facile Method for Synthesis of 2-Substituted Benzimidazoles via Reductive Cyclization of O-Nitroaniline and Aryl Aldehydes

“…The other way involves a two-step procedure that is oxidative cyclodehydrogenation of aniline schiff 's bases, which are often generated in situ from the condensation of o-phenylenediamines and aldehydes. Various oxidative reagents such as tetracyano ethylene [5], nitrobenzene [6], 1,4-benzoquinone [7], DDQ [8], benzofuroxan [9], NaHSO 3 [10], MnO 2 [11], oxone [12], DMP [13], Pb(OAc) 4 [14], and NH 4 VO 3 [15] have been employed. However, all of these methods have problems, including drastic reaction conditions, expensive catalyst, low yields, and severe side-reactions.…”

p-TsOH Catalyzed synthesis of 2-arylsubstituted benzimidazoles

“…The widespread interest in benzimidazole-containing structures has promoted extensive studies for their synthesis. While many strategies are available for benzimidazole synthesis, [7][8][9][10][11][12][13][14][15][16] there are two general methods for the synthesis of 2-substituted benzimidazoles. One is the coupling of phenylenediamines and carboxylic acids 4b or their derivatives (nitriles, imidates, or orthoesters), 5 which often requires strong acidic conditions, and sometimes combines with very high temperatures or microwave irradiation.…”