Abstract
Ionic liquids have been exploited to assist dissolution of poorly soluble (and poorly bioavailable) drugs, enhancing permeation through physiological barriers to deliver drugs to target sites. Herein, the solubility of 6-methyl-2-thiouracil – a common antithyroid drug, with low solubility in water and common organic solvents – was studied by employing six different imidazolium-based ionic liquids with variable anions. We demonstrate facile, regiospecific S-alkylation of 2-thiouracil with various lipophilic side chains in high yields (91–94%) and in the absence of catalysts. The reaction yields are correlated with the H-bond formation ability between the ILs' anions and the solute, indicating that the hydrogen bond is perhaps responsible for the high solubility of 2-thiouracil in [C2mim][OAc] and [C2mim][Cl].