Light-driven method simplifies synthesis of complex heterocycles

A new photochemical method enables precise rearrangement of thiazoles and isothiazoles, providing new synthetic routes for complex azole derivatives.

Typically, thiazole and isothiazole derivatives are generated using multi-step synthetic strategies that require extensive preparation of functionalised precursors. These methods often struggle to access certain structural isomers, produce low yields and involve complex reaction conditions.

Researchers led by Alessandro Ruffoni and Daniele Leonori at RWTH-Aachen University, Germany, addressed these limitations using controlled photochemical irradiation. The thiazole and isothiazole compounds were excited using specific wavelengths of light and this was enough to initiate a cascade of structural rearrangements through high-energy intermediates.

To achieve precise control over these arrangements, the researchers explored two strategies. Initially, they considered using different wavelengths to selectively activate specific derivatives based on their light absorption properties. However, because the absorption ranges of the compounds largely overlapped, they focused instead on manipulating reaction conditions, such as solvents and additives, to influence molecular stability during photoexcitation. By exploiting differences in photostability they accumulated desired products selectively. Preliminary work indicates this method may extend to other azoles, potentially increasing accessible derivatives for drug discovery libraries and offering broad utility in heterocyclic chemistry.