Synthesis of 5-Trifluoromethyl-1,2,4-Triazoles via Metal-Free Annulation of Trifluoroacetimidohydrazides and Methyl Ketones

A metal-free approach for the synthesis of 5-trifluoromethyl-1,2,4-triazoles via I-2-mediated [4+1] annulation of readily available trifluoroacetimidohydrazides and methyl ketones has been achieved. The transformation involves iodination/Kornblum oxidation, intermolecular dehydration condensation and an iodine-mediated intramolecular cyclization/aromatization sequence. The developed protocol can be easily scaled up to 3 mmol scale without obvious efficiency decrease and be implemented by a consecutive one-pot manner.

Automated summary

A metal-free approach for the synthesis of 5-trifluoromethyl-1,2,4-triazoles has been developed via I2-mediated [4+1] annulation, allowing for easy scalability and consecutive one-pot operation. The transformation involves iodination/Kornblum oxidation, intermolecular dehydration condensation, and an iodine-mediated intramolecular cyclization/aromatization sequence.