Lithium Hexamethyldisilazane Transformation of Transiently Protected 4-Aza/Benzimidazole Nitriles to Amidines and their Dimethyl Sulfoxide Mediated Imidazole Ring Formation

• DOI: 10.1021/acs.orglett.6b02359
• Publication Date: 2016-09-08T14:07:26Z
• Authors: Reham A. I. Abou-...; Abdalla E. A. Hassan; David W. Boykin; W. David Wilson
• Keywords: Benzimidazole; Imidazole; Sulfoxide

Trimethylsilyl-transient protection successfully allowed the use of lithium hexamethyldisilazane to prepare benzimidazole (BI) and 4-azabenzimidazole (azaBI) amidines from nitriles in 58–88% yields. This strategy offers a much better choice BI/azaBI than lengthy, low-yielding Pinner reaction. Synthesis aza/benzimidazole rings aromatic diamines aldehydes was affected dimethyl sulfoxide 10–15 min, while known procedures require long time purification. These methods are important for BI/azaBI-based drug industry developing specific DNA binders expanded therapeutic applications.