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

• Published in: Organic letters Vol. 18; no. 18; pp. 4714 - 4717
• Main Authors: Abou-Elkhair, Reham A. I, Hassan, Abdalla E. A, Boykin, David W, Wilson, W. David
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 16-09-2016
• Subjects: Amidines - chemical synthesis; Amidines - chemistry; Aza Compounds - chemical synthesis; Aza Compounds - chemistry; Benzimidazoles - chemical synthesis; Benzimidazoles - chemistry; Dimethyl Sulfoxide - chemistry; Imidazoles - chemical synthesis; Imidazoles - chemistry; Lithium Compounds - chemistry; Molecular Structure; Nitriles - chemical synthesis; Nitriles - chemistry; Silanes - chemistry
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/acs.orglett.6b02359

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 to prepare BI/azaBI amidines than the lengthy, low-yielding Pinner reaction. Synthesis of aza/benzimidazole rings from aromatic diamines and aldehydes was affected in dimethyl sulfoxide in 10–15 min, while known procedures require long time and purification. These methods are important for the BI/azaBI-based drug industry and for developing specific DNA binders for expanded therapeutic applications.