Synthesis of N-alkoxy-substituted 2H-benzimidazoles

Abstract

Treatment of 2-nitro-N-(2-methyl-1-propen-1-yl)benzenamines with potassium tert-butoxide in tert-butanol followed by the addition of an electrophile affords N-alkoxy-2H-benzimidazoles. Electrophiles including methyl iodide, allylic bromides, propargylic bromides, benzyl bromide, and acetyl chloride gave good to excellent yields of product while 1-iodo- and 2-iodo-butane afforded very low yields.

Recent achievements in the synthesis of benzimidazole derivatives

“…Ansari et al obtained N -alkoxy-2 H -benzimidazoles from 2-nitro- N -(2-methyl-1-propen-1-yl)benzenamines by treatment with potassium tert -butoxide followed by the addition of MeI. 203 Various products were produced in moderate to excellent yields under mild reaction conditions. A reaction pathway was also proposed ( Scheme 134 ).…”

2-(3,4-Dimethoxyphenyl)-N-(4-methoxyphenyl)-1-propyl-1H-benzo[d]imidazole-5-carboxamide

“…Thus, benzimidazole derivatives have found a very strong application in the medicine filed. The synthesis and application of benzimidazole and its derivatives is discussed in several articles [4,5]. Optimization of substituents around the benzimidazole nucleus has resulted in many drugs like Albendazole, Mebendazole, Triclabendazole, Fenbendazole, Oxfendazole, Thiabendazole, Omeprazole, Lansoprazole, and Pantoprazole [6].…”

Base-mediated formation of N-hydroxy- and N-alkoxyindoles, synthesis of dilemmaones A and B, and novel efforts in indole methodology and total synthesis

“…Ansari of the Söderberg lab recently described a related cyclization of 2-nitroimine derivatives to yield N-methoxybenzimidazoles (Scheme 4). 18 Based on the observation that 2-(2-nitroaryl)butenoates esters can be transformed into N-alkoxyindoles, we sought to expand on this transformation. Herein is described the scope and limitations of the direct and facile base-mediated synthesis of N-hydroxy-and N-alkoxyindoles.…”