Use of fluoroform as a source of difluorocarbene in the synthesis of N-CF2H heterocycles and difluoromethoxypyridines

• Preparation of N-difluoromethylimidazoles and benzimidazoles.
• Use of fluoroform as a source of difluorocarbene.
• Preparation of difluoromethoxypyridines.

Fluoroform is used as a source of difluorocarbene to convert various N-, O-, and C-nucleophiles to their difluoromethylated derivatives. Imidazole, benzimidazole, benztriazole, hydroxypyridines, and their derivatives underwent reaction at moderate temperatures and atmospheric pressure, using potassium hydroxide as base in a two-phase (water/acetonitrile) process to provide moderate to good yields of the respective products. Nitrophenols required addition of a co-solvent (methanol) to obtain good yields of products.

Difluorocarbene source, CHF3, can be used as a diverse difluoromethylating agent.Figure optionsDownload as PowerPoint slide