A facile base-mediated synthesis of N-alkoxy-substituted benzimidazoles

Synthesis of N-alkoxy-substituted 2H-benzimidazoles

“…7 The base-mediated transformation of enamines to afford N -alkoxy-2 H -benzimidazoles is limited by the availability of the starting material. It should be noted that we were unable to prepare enamines in synthetically useful yields from 3- or 6-substituted 2-nitroanilines even under more forced reaction conditions.…”

“…stirred for 24 h then treated with MeI (5 equiv.) as described in reference 7. d Benzophenone was also isolated in 97% yield. …”

“…7 By simply changing the amount of base and electrophile used, either a hydroxy or an alkoxy substituent could be introduced on the side chain. For example, treatment of enamine 1 with 2.0 equivalents of sodium hydride (NaH) in DMSO at ambient temperature followed by addition of 1.05 equivalents of methyl iodide (MeI) gave after purification N -methoxybenzimidazole 2 (Scheme 2).…”

N-Hydroxybenzimidazole as a structurally modifiable platform forN-oxyl radicals for direct C–H functionalization reactions

“…N -Hydroxybenzimidazoles, which are planar and stable heterocycles bearing an N -hydroxy moiety, have recently attracted interest in the field of biological and pharmaceutical sciences as anti-virulence or anti-cancer agents. 9 , 10 However, they have rarely been used in synthetic organic chemistry and, to the best of our knowledge, studies on the potential of NHBIs to generate the corresponding N -oxyl radicals have not yet been conducted. 11 In this context, we became interested in the potential of NHBIs as novel organoradical precursors based on the following features: (1) NHBIs can be readily prepared from 2-nitroaniline derivatives in a few steps (see the ESI † ); (2) substituents can be easily introduced at both the aromatic ring and the 2-position of the benzimidazole moiety; (3) NHBIs contain additional modification sites such as the nitrogen atom at the 3-position of the benzimidazole moiety and the counteranion of the resulting benzimidazolium species, which may potentially be exploited for further functionalization.…”