Metal‐Catalyzed Organic Reactions by Resonant Acoustic Mixing**

Abstract

We demonstrate catalytic organic synthesis by Resonant Acoustic Mixing (RAM): a mechanochemical methodology that does not require bulk solvent or milling media. Using as model reactions ruthenium‐catalyzed ring‐closing metathesis and copper‐catalyzed sulfonamide‐isocyanate coupling, RAM mechanosynthesis is shown to be faster, operationally simpler than conventional ball‐milling, while also providing the first example of a mechanochemical strategy for ruthenium‐catalyzed ene‐yne metathesis. Reactions by RAM are readily and directly scaled‐up without any significant changes in reaction conditions, as shown by the straightforward 200‐fold scaling‐up of the synthesis of the antidiabetic drug Tolbutamide, from hundreds of milligrams directly to 30 grams.

Spiers Memorial Lecture: Mechanochemistry, tribochemistry, mechanical alloying – retrospect, achievements and challenges

“…A large variety of reactions have been documented, which are highly selective, which have yields approaching 100%, or that are ecologically friendly and economically acceptable. 19–24,27,29–43 To date, a few examples of inorganic and organic reactions have been scaled up to levels suitable for practical applications. 9,15,39,43,122,123,131–140…”

“…Mechanical treatment can result in decomposition, 7,9,11,17,19,50,111,112 or synthesis of inorganic or organic compounds. 12,17,20–24,27,29–42,78,113,116–119,141–143 Quite often these compounds can be obtained as metastable polymorphs, 144 mesophases, quasicrystals, 145 or in amorphous states. 94,96,97,146 Mechanochemical processes can be used, in order to prepare product particles not only with target composition and structure, but also with a desirable shape, e.g .…”

“…- The jar and balls materials can be used as reactants, 264,265 or catalysts, 266–279 even for gas phase reactions like synthesis of NH 3 from elements. 280–284 The jar material can be modified by the sample during mechanical treatment, 38,285–289 and can have a pronounced effect on the mechanochemical transformations: on the rate, on the completion, on the products and on the very possibility of reactions, even if the material is not directly consumed as a reactant; covering the surface of the milling bodies and the reaction vessel with a catalyst is more efficient than simply adding the same catalyst to the sample, 290–292…”

“…Steel can act as a catalyst because its main component is iron, and this can be expected. 273,432 At the same time, different types of steel contain different transition metals as dopants, which may act as catalysts of the mechanochemical transformations, 38,287 yet remain unknown even to the experimentalists themselves, and thus not documented.…”

“…5–18 “Dry”, or liquid assisted mechanochemical organic synthesis by ball milling, grinding, extrusion, or resonant acoustic mixing (RAM) is becoming increasingly popular. 19–43 Based on what is observed today, it can be expected that more inorganic and organic syntheses will be soon conducted mechanochemically at the industrial level, alongside – and perhaps instead of – the long-standing “classical” solution thermal synthesis. However, scaling up practically relevant syntheses requires the community to achieve a better understanding of the processes that take place in a mechanoreactor during and after mechanical action.…”