A Versatile One-pot Strategy for Thiazolylazo Extensions: Visible Light-Driven Photoswitches

Among various azoheteroarenes, thiazolylazo derivatives have recently emerged as bidirectional visible-light switches. However, their widespread application as molecular photoswitches remains limited due to synthetic challenges like robust reaction conditions, lack of commercial availability of starting material, and low reaction yield. This work presents a straightforward one-pot methodology for synthesizing thiazolylazo derivatives by reacting 2-trimethylsilylthiazole with various diazonium salts. This approach offers mild reaction conditions, short reaction times, and moderate to good yields for different derivatives. Using this de novo synthesis strategy, we developed several new phenylazothiazole derivatives and asymmetric bis-heteroaryl azo compounds. The resulting thiazolylazo derivatives exhibit excellent E-to-Z isomerization under visible light, with a tunable thermal back-isomerization half-life ranging from seconds to days in acetonitrile. The prolonged thermal stability of the metastable isomers of these visible-light switches is attributed to specific noncovalent interactions in the transition state. Our method provides a versatile platform for late-stage thiazolylazo functionalization of complex ligands and drug molecules, paving the way for visible light switchable ligands in photopharmacological applications.