A Simple and Effective Protocol for the Pechmann Reaction to Obtain 4-Methylcoumarin Derivatives Using a High-Speed Mixer Ball Mill Process

We hereby report a simple and efficient method for the preparation of 4-methylcoumarins series, including Coumarin 120 (7-amino-4-methylcoumarin) from phenols (or naphthols) and ethyl acetoacetate in the presence of 3 mol% InCl3. Coumarins were obtained in good yields (52-92%) through Pechmann condensation, under a rapid and environmentally friendly protocol using a high-speed ball mill mixer at room temperature, with short reaction times, under solvent-free conditions.

Automated summary

We report a simple and efficient method for the synthesis of 4-methylcoumarins series, including Coumarin 120 (7-amino-4-methylcoumarin), from phenols (or naphthols) and ethyl acetoacetate in the presence of 3 mol% InCl3. Coumarins were obtained with good yields (52-92%) through Pechmann condensation, using a high-speed ball mill mixer at room temperature, under solvent-free conditions with short reaction times.