Effect of Reaction Parameters on the Synthesis of 5-Arylidene Barbituric Acid Derivatives in Ball Mills

The influence of crucial reaction parameters on Knoevenagel condensation in planetary ball mills was investigated. Rotation frequency ( ν rot ), milling ball diameter ( d MB ), milling ball filling degree ( Φ MB ), and beaker size had obvious influences on yield. It was found that higher ν rot, lower d MB, milling beakers with larger diameter, and a Φ MB of ∼0.3 are advantageous for the reaction. Furthermore, the influence of the type of mill was investigated, including reactions performed in different planetary and mixer ball mills, in a stirred media mill, and with a mortar mill. Comparisons with the other solvent-free synthetic routes showed that ball milling is an effective way of performing the reaction with low energy intensity.