Kamlet-Taft parameters of solvents and their relationship with methylation of hydroxy group by Ag2O

We measured the effects of Kamlet-Taft parameters on methylation of hydroxy group of N-(2-hydroxyethyl) phthalimide by Ag2O. Optimization of methylation was done by tuning the solvents, mixtures of solvents, temperature, and concentrations of primary materials (methyl iodide, methyl-d3 iodide, Ag2O). Solvents had the most effective roles on methylation by Ag2O. Although methylation did not work in polar solvents such as DMF and acetonitrile, it was successful in non-polar solvents (n-heptane, n-hexane, n-pentane, and cyclohexane). Despite using hydrocarbons was favoured for methylation, adding chloroform as a co-solvent significantly improved the yield of the reaction while using less amount of Ag2O. Kamlet-Taft parameters showed the polarizability of the solvent was the most important parameter which controlled the methylation by Ag2O. As a minor goal, subsequently, this reaction was followed by hydrolysis of N-(deuterated 2-methoxyethyl) phthalimide to prepare deuterated 2-methoxyethylamine and the target urea derivative, MTU: N-{2-[(D3) methyloxy] ethyl}-N’-1,2,3-thiadiazol-5-ylurea. Deuterium-labelled MTU will be used for isotope tracing in plant cells to shed more light on MTU localization and mode of action in plants. NMR, UV–vis, IR spectroscopies, and mass spectrometry were used to confirm the structures. © 2024 Elsevier B.V.