44ª Reunião Anual Virtual da SBQ

The preparation of 3-methylthio-4-arylmaleimides presents several synthetic drawbacks, such as the use of transition metals, the need of various reaction steps for its preparation and the formation of hazardous side-products. In this context, the development of a transition metal-free protocol for the preparation of 3-methylthio-4-arylmaleimides in a single step through the rearrangement of thiazolidine-2,4-diones is hereby described. After a careful optimization of the reaction conditions, we found a protocol that allowed the preparation of a broad scope of derivatives in up to 97% yield. The reaction tolerated several aryl-substituted groups, including challenging to prepare pyridyl-containing derivatives. The structure of derivative 1c was unambiguously confirmed by the X-ray crystallographic analysis. To demonstrate the synthetic utility of the prepared derivatives, the oxidation of the sulfide, as well as the N-alkylation of the imido group, were demonstrated affording the desired compounds in up to 97% yield.
A series of control experiments, including isotopic labelling and the use of selenated substrates, strongly suggested that the rearrangement involves a key isocyanate intermediate, as well as a further reaction with in situ generated methylthiomethyl acetate.
Moreover, some of the synthesized compounds proved to be fluorescent and had their photoproperties investigated. Since these derivatives presented promising emissive properties, their application in cell-imaging experiments was also carried out, revealing that some of these compounds are capable of selectively staining the perinuclear region of the cells.