Novel Mechanosynthesis for the 4-methyl-2H-chromen-2-one Molecules Via the Pechmann Condensation

Abstract

“Organic mechanosynthesis” involves chemical, organic transformations by applying mechanical energy to form consciously desired products. In this book chapter, such products are 4-methyl-2H-chromen-2-ones (4-methylcoumarin molecules), including 7-amino-4-methyl-2H-chromen-2-one (7-amino-4-methylcoumarin, coumarin 120), an important molecule and building block in biophysical research as a common fluorescent probe. The Pechmann condensation is one of the most straightforward methods for preparing substituted 4-methyl-2H-chromen-2-ones using a wide spectrum of reaction parameters, which generally suffer from harsh reaction conditions, e.g., stoichiometric amounts of strong acids or bases, no reusability of catalyst, production of large acidic wastes, elevated temperature, and prolonged reaction time. Considering the significance of green and sustainable protocols for obtaining such chromenone molecules, the mechanochemical Pechmann procedures allow for avoiding the use of such harsh reaction conditions This book chapter describes a simple and efficient method for the preparation of 4-methyl-2H-chromen-2-ones series through the acid-catalyzed Pechmann condensation under a rapid and environment-friendly protocol using a high-speed ball mill mixer at room temperature with short reaction times under solvent-free conditions. Substituted 4-methylcoumarins derived from phenols (or naphthols) and ethyl acetoacetate in the presence of 3 mol% InCl₃ were obtained in good yields (52-95%).