Ball Milling: A Green Tool in Synthetic Organic Chemistry

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Background: Activation of covalent bonds for the initiation of chemical reactions can be achieved by all kinds of energy including light, thermal heating, microwave heating, electrical, sonochemical and mechanical energy. Among these, ball milling is an attractive alternative source of energy for the activation of bonds leading to chemical reactions due to its simplicity, ease of purification of products, mild reaction conditions and greenness of the process. Methods: Mechano-chemical reaction is defined as "a chemical reaction that is induced by the direct absorption of mechanical energy." Simply, mechanical energy can be generated by grinding using a mortar and a pestle and the process of milling is carried out in ball mills. The process of milling is more reproducible due to the regulation of parameters like time and energy entry. Results: The ball milling is mainly applicable in the industry for particle refinement processes, disagglomeration, the cracking of bacteria, etc. However, recently, ball milling has attracted considerable attention in organic synthesis due to its operational simplicity, economy, environment friendliness, and its potential to produce very good yields of products, and as a consequence, several research articles, review papers and book chapters have been published in recent time. The literature studies revealed that various carbon-carbon, carbon-heteroatom bond formation, condensation reactions, coupling reactions and oxidation-reduction reactions have been performed in a ball mill under mild and environmental-friendly reaction conditions. Conclusion: The aim of this review is to highlight the recent breakthrough of ball milling in organic transformation leading to the synthesis of bioactive molecules in the context of Green Chemistry.