Synthesis of thiophenes in a deep eutectic solvent: heterocyclodehydration and iodocyclization of 1-mercapto-3-yn-2-ols in a choline chloride/glycerol medium

The heterocyclodehydration and iodocyclization of readily available 1-mercapto-3-yn-2-ols has been performed in a deep eutectic solvent (DES), that is, ChCl/Gly (1:2 molar ratio; ChCl=choline chloride, Gly=glycerol), as a non-conventional green solvent. The processes, carried out at 50 °C for 8 h in the presence of the PdI2/KI catalytic system or at room temperature for 5 h with 1.2 equiv of I2, led to the formation of the corresponding thiophenes and 3-iodothiophenes in good to high yields. The DES/catalytic system could be easily recycled several times without appreciable loss of activity, after extraction of the thiophene product with hexane or Et2O. The alkynylation reaction of α-mercapto ketones, necessary for the preparation of the alkynylthiol substrates, was also successfully accomplished in the above protic eutectic mixture competitively with protonolysis.