Reactivity study of 4-hydroxythiocoumarin: a novel synthetic route to fused chromono-thiophene and -thiopyran derivatives through solvent-dependent thio-Claisen rearrangement

Abstract

The alkylation of 4-hydroxythiocoumarins (1a–f) was carried out with various allyl bromides as well as propargyl bromides using K₂CO₃ (2 equiv.) in anhydrous acetone at room temperature, and the corresponding regioselective S-alkylated products 4a–l and 5a–n were obtained in good yields. Then, the synthesis of a variety of new sulfur heterocycles is accomplished by employing thio-Claisen rearrangement from the corresponding S-allyl ethers (4a–l) and S-propargyl ethers (5a–n) to provide the cyclised products 7a–o and 8a–n in good yields. Interestingly, the S-propargyl ethers of the corresponding 4-hydroxythiocoumarins (1a–f) provided two different products depending on the solvent. Furthermore, various 4-hydroxythiocoumarins provided the cyclised products 10a–f directly upon reaction with 2-methylbut-3-yn-2-ol (9) in the presence of 10 mol% p-TSA as catalyst in nitromethane solvent at 80 °C. DFT calculations were performed to investigate the formation of different products, and the findings have been thoroughly discussed. The results demonstrate several notable attributes, including good to excellent yield, highly regioselective product formation, and high atom economy.