Mechanochemical organic synthesis

Abstract

Recently, mechanical milling using a mixer mill or planetary mill has been fruitfully utilized in organic synthesis under solvent-free conditions. This review article provides a comprehensive overview of various solvent-free mechanochemical organic reactions, including metal-mediated or -catalyzed reactions, condensation reactions, nucleophilic additions, cascade reactions, Diels-Alder reactions, oxidations, reductions, halogenation/aminohalogenation, etc. The ball milling technique has also been applied to the synthesis of calixarenes, rotaxanes and cage compounds, asymmetric synthesis as well as the transformation of biologically active compounds.

Organic synthesis by Twin Screw Extrusion (TSE): continuous, scalable and solvent-free

“…4 Along with an increasing interest in the formation of inorganic and coordination compounds by mechanochemical means, there has also been a keen interest in carrying out organic synthesis this way, and a diverse range of organic reactions has been demonstrated, mainly through ball milling. 12 In particular, several successful mechanochemical condensation reactions have been reported, including the Knoevenagel condensation and Aldol reaction. 8,9 , 17 , 10 Other examples of organic reactions performed mechanochemically include the Wittig reaction, Diels-Alder, click and Suzuki reactions, some of which usually require quite stringent conditions in their conventional solution-based synthesis such as the use of dry solvents and inert atmospheres.…”

“…5 A variety of materials and compounds have been prepared mechanochemically including metal alloys, 6 metal organic frameworks (MOFs), 7 and organic compounds from reactions such as the Knoevenagel condensation [8][9][10] and Wittig reaction, 11 amongst others. 12 However, two main drawbacks of mechanochemical synthesis are the general lack of both temperature control and scalability. 1 Generally, ball milling or grinding in a mortar and pestle do not allow control of the temperature.…”

Temperature progression in a mixer ball mill

“…Mechanochemistry using ball mills is a promising technique with applications in organic and inorganic chemistry as well as material sciences [1][2][3][4]. During ball milling, up to 80 % of the energy that is generated in the mill is dissipated as heat [5].…”

Radical-radical rotaxanes with tetracationic cyclophane ring, and quaternary azaaromatic rotaxanes with cage macrocycles

“…Another class is the calixarene-based rotaxanes. [96][97][98][99] One should note the large variety of calixarenes…”