Mechanochemical the synthesis of enaminones

Enaminones are important intermediates in the construction of N-heterocycles (Figure 1), so their synthesis has become the target of numerous studies over the years in order to develop more efficient methodologies to obtain them.1,2 The study of the reactivity of enaminones is favored by important aspects of this type of compound, such as the ease with which they are synthesized, isolated and stored, generally under atmospheric conditions and at room temperature. This is due to the carbonyl group that is conjugated to the enamine moiety, which confers a strong stability to this system.3 Over the years, several methodologies for the synthesis of enaminones have been developed and perfected from the original procedures. In addition to reducing reaction time, increasing yield and process efficiency, most methods are focused on Green Chemistry parameters.1 With the resurgence of mechanochemistry, a new frontier was established allowing the development of current methodologies, aiming for greater energy efficiency and an increase in the scale. In this work, different primary amines, secondary amines and diamines were used as the starting material for 1,3-dicarbonyl compounds to obtain β-enamino esters and ketones. The procedures were performed using the planetary ball mill, and the synthesis occurred without the presence of solvent or catalyst, and with simple and cleaner purification procedures, affording enaminones in reasonable to good yields around (Figure 2). In one example, we could prepare from 0.6 to 60.0 g of enaminone from ethanolamine and methyl acetoacetate, illustrating the scale up viability of the mechanochemical approach.