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.