A Variation of Favorskii Rearrangement Mechanism Under Weakly Acidic Conditions: The Case of Clobetasol Propionate Degradation in Solution

This paper describes our efforts in proposing a novel mechanism for the formation of the major degradant of clobetasol propionate under weakly acidic conditions through a comprehensive investigation. In the proposed mechanism, the key Favorskii intermediate plays a critical role. This variation of the original Favorskii rearrangement, which proceeds only under alkaline conditions, has not been reported before. This mechanism enriches the understanding of the degradation chemistry of corticosteroids containing the α-haloketone moiety on their 17-position.