Abstract A straightforward strategy for the synthesis of pharmaceutically active 2‐aminobenzoxazoles and 2‐aminobenzothiazoles is described by using 2‐aminophenols, 2‐aminothiophenols, and functionalized phenylisothiocyanates as the model substrates. The developed method proceeds through the HFIP‐promoted cyclodesulfurization process which allows for the efficient synthesis of these scaffolds at 60 °C of reaction temperature without the addition of a transition metal‐catalyst or hazardous solvents with excellent yields (up to 92 %) of product formation. This process involves HFIP‐mediated hydrogen bonding interactions with the hydroxyl and thiol moieties, leading to bond breaking and formation during the reaction, resulting in the compounds of interest and the in situ release of H 2 S gas.

HFIP‐Mediated Cyclodesulfurization Approach for the Synthesis of 2‐Aminobenzoxazole and 2‐Aminobenzothiazole Derivatives