Regioselectivity evaluation of the (Z)-5-(4-hydroxybenzylidene)-thiazolidine-2,4-dione alkylation in alkaline environment

Thiazolidine-2,4-dione represents a key heterocyclic core in medicinal chemistry because it has the ability to bind to a wide variety of protein targets and has been intensively studied for developing bioactive multitargeting agents. The N-alkylation of imides and O-alkylation of phenols are important reactions frequently used in the synthesis of biologically active compounds, like the thiazolidine-2,4-dione derivatives. Based on literature data, by treating (Z)-5-(4-hydroxybenzylidene)-thiazolidine-2,4-dione with alkyl halides in a 1:1 molar ratio, either O-alkylation or N-alkylation reactions can take place. Six (Z)-5-(4-hydroxybenzylidene)-thiazolidine-2,4-dione derivatives were synthesized by alkylating (Z)-5-(4-hydroxybenzylidene)-thiazolidine-2,4-dione with aliphatic halogenated derivatives in alkaline environment, using a 1:1 molar ratio and then were physically and spectrally analyzed. The spectral data and the results obtained from the theoretical evaluation of the parent compound's acidity support the formation of N-alkylated derivatives in the reaction conditions. (C) 2021 Elsevier B.V. All rights reserved.