Direct Mechanocatalysis: Using Milling Balls as Catalysts

Abstract Direct mechanocatalysis describes catalytic reactions under the involvement of mechanical energy with the distinct feature of milling equipment itself being the catalyst. This novel type of catalysis features no solubility challenges of the catalysts nor the substrate and on top offering most facile way of separation.


Introduction
Catalysis is indispensable in chemistry and society.M ost chemicals used in academia and industry have seen ac atalyst at least once during their production.Abig portion of the gross world product is relatedt og oods that have required catalysis. [1] Catalysis thus is rightfully one of the "Green Chemistry Principles" as it reduces the energy intensity of ar eaction and prevents waste accumulation during synthesis. [2] It is common to classify catalysis by the meanbywhich the activation barrier is overcome, that is, photonsf or photocatalysis, an electrical potentialf or electrocatalysis, or thermale nergy for conventional thermal catalysis. [3] Ag enerally overlooked energy source, however, is mechanical energy,w hich may also initiate chemical and catalytic reactions. [4] One way of transferring mechanical energy to the reactants is the collisiono fm illing balls inside of ball mills. [5] Reactions conducted this waya re called mechanochemical reactions, if ac atalyst is involved it is referred to as mechanocatalysis. [5] This solid-statet echnique has the great advantage of being solvent-free. Moreover, it has widely been demonstrated that mechanochemicalr eactions can proceed faster,m ore energy-a nd resource-efficient than conventional solution-based reactions, thus making this discipline immanently sustainable. [1] Additionally,f requently unexpected reactionp athways can be observed and sometimes even completely new products are accessible. [6] All of these perks led to the classification of mechanochemistrya so ne of the ten emerging future technologiesi nc hemistry by IUPAC in 2019. [7] Catalyticr eactions in ball mills range from CÀCc ross- [8] and homo-coupling [9] to Lewis acid and base chemistry [10] and CÀH activation. [8a, 11] In all these examples, however,t he catalysti s added as an additional powder,o ften simply adapted from the well-known solution-basedr eactiona nalogue or the reactions run autocatalytically. [12] We denote these types of reactions as indirectmechanocatalysis.
In the special case that the milling equipment( e.g. the milling ball) itself is the catalyst, we want to introduce the term "direct mechanocatalysis"f or this special concept. "Directm echanocatalysis" is conceptually different in the following sense: 1) While homogeneous catalysis requires the catalyst and the reactants to be soluble in the same solvent, solubility and advanced ligand development becomes entirely obsolete for direct mechanocatalysis.I tu ses the crude catalyst, in many cases ab all made out of the required metal. 2) While heterogeneous catalysis converts fluid reactants (gases or liquids) on the desirably high surface of solid catalysts, direct mechanocatalysis preferably uses solid reactants and convert them on the smallest geometrically possible surface;amilling ball. 3) In the idealized conception, it is neither photons, electrical potential nor thermale nergy that pushes the reaction above the activation barrier,b ut the mechanicale nergy of colliding milling items.
To dive into this topic, we want to exemplarily illustrate the first report on direct mechanocatalysis from 2009. Mack and co-workersp erformed am echanochemicalS onogashira reaction ( Figure 1A). In this pioneering work, palladium was still added as ac atalyst powder but the co-catalyst was Cu in the form of milling balls. This demonstrated that milling balls indeed participate in the reaction. They also conducted other Figure 1. CÀCcoupling reactions using either palladium or copper balls or vials as catalyst species. We proposet oc ombine the symbol for mechanochemical reactionsi ntroduced by Hanusa in addition with the catalytic element inside the milling balls as as ymbol for direct mechanocatalysis.A:Sonogashirar eaction with the replacement of the Copper co-catalyst by the Mack group. [11] B: Oxidative coupling catalyzed by copper balls by the Jiang group. [8a] C: Suzukip olymerization by Vogt et al. [9] reactions and consequently wrote af irst mini-review on this topic. [13] Considering the concept of involving the milling equipmenti nto ar eaction, one may even go back as far as the first-reported mechanochemical reaction at all. The famousr eaction of cinnabar to elemental mercury in ac opper mortar by Theophrastus of Eresos ca. 314 BC [14] while not being catalytic, it already made use of the milling equipmentd uring the reaction. On the following pages we want to introduce the concept of direct mechanocatalysis further,l ookinga t: 1) the reactions by summarizing which reactions have already been performed via direct mechanocatalysis and are potentially viable; 2) the catalyst,w hich is the millingb all, exhibiting ac ompletely differentc ompositiona nd requirements than conventional catalysts; 3) the milling process,including the role of the new reaction parameters that tend to be conceptually different than in solution-basedc hemistry;4 )a discussion on potential mechanisms,afield still being in its infancy.

The Reactions
At first, we want to present different reaction protocols using direct mechanocatalysis to introduce the scope of this technology.F or now,e xamples are still sparsea nd only as mallr ange of reaction types are represented in this field which will be summarized in this chapter.L ater on, we will also discuss other potentialreactionapplicable to this principle.

CÀCc oupling reactions
As the first reaction described to run via direct mechanocatalysis was the aforementioned Sonogashira reactionb yt he Mack group, we want to start this section with CÀCc oupling reactions. These reactions are commonly known for complex catalytic cycles, involving several reaction steps and often require co-catalysts. [15] At first glance,t hese reactions are thus not particularly suited for direct mechanocatalysis,s ince as imple ball or foil should hardly be capable to emulatet he whole catalytic cycle. Surprisingly however,i tw as these reactions which were first investigated in this regard.I nterestingly,t he mechano-chemicalS onogashirar eactionw as first established with the direct mechanocatalytic approach by the Mack group. [11] Later also palladium salts were used in the absence of copper to achieve astonishingy ields under solvent free conditions even withoutt he inert atmosphere,w hich is commonly required in homogeneous Palladium catalysis. [16] In their contribution the Mack group first developsaprotocol for the solvent-free Sonogashira reaction ( Figure 1A). [11] During the screeningo fr eactionp arameters, they noticed that the addition of ac opper iodide as co-catalyst is not required for the mechanochemical reaction. However, by omitting the co-catalyst the yield drops by more than 50 %. They then made the important step to replacet he usual stainless steel or tungstenc arbide milling ball with ac opper ball bearing in the hope that the leaching of catalytic amounts of metal due to abrasion is enough to co-catalyze the reaction. Since those experiments were successful, they went even further by producing their own copperm illing vial. With this setup the yields were comparable with their first experiments,w here copper iodide was used. They furthers tated that after each experiment, the ball and vessel were weighted and no significant change in weight, nor ad epreciation of the yield over time was noticed. They therefore concludet hat the co-catalysis is indeed happening on the surface of the reaction vial.
The Jiang group, while working on cross-dehydrogenativecoupling reactions with alkynes ( Figure 1B), came across the results of the Mack group. [8a] They had been screening the addition of coppers ourcest oe nhancet he reactivity and found that elemental copperl ed to good results. They also tried the use of copper balls andf ound that they could substitute the necessary copper,l eading to yields rivalling those of copper salt-catalyzed reactions. They further established that neither electron donating nor electron withdrawing groups had an influence on the yield under these reactionconditions, highlighting the advantages of the ballmillinga pproach further.
Followinghis Master studies with focus on Or-ganicC hemistry, Wilm started his PhD in 2019 at Ruhr-UniversitätB ochum. He is working on directm echanocatalysis,c onducting the established liquid phase reactions under direct mechanochemical conditions. Sven studied Chemistry and Chemical Engineering in Dresden and Strasbourg. He finished his PhD on the Mechanochemical Synthesis of Polymersi n2 018 at Technische Universi-tätD resden. Currently he is senior scientist at Ruhr-University Bochum working on mechanistic understanding of mechanochemical reactions as well as developing new synthesis concepts for porous polymers.
Lars did his PhD in 2013 at Technische Univer-sitätD resdeni nI norganic Chemistry. After postdoctoral stay at ETH Zürichw orking on heterogeneous catalysis, he became leader of aj unior research group working on mechanochemical synthesis of porous carbon materials for energy storage applications.I n2 019h e was appointed professor at Ruhr-University Bochum focusing on mechanochemistry entirely.
The Suzukic ross-coupling is another well-established andi nvestigated reaction in mechanochemistry. [17] Inspired by these results, our group hasr ecently shownt hat Suzuki cross-coupling reactions, can be conducted via direct mechanocatalysis as well. While the Mack group replaced the co-catalyst by active milling materials, we wanted to go one step further and completely eliminate the need for palladium salts in our reaction, since they are expensive and their reusability is limited. We chose as ystem on which we already established its benefits by transferring it from solution into the ballm ill, the synthesis of poly(p-phenylenes). [18] In our recentw ork ( Figure 1C) we first demonstrated that no ligands or salts are needed and pure palladium black was capable of catalyzing the reaction inside ab all mill. [9] In the next step we had palladium milling balls made and conducted the experiments inside az irconium vessel with said balls. By studying the conditions further, we made the following observations:1 .the reactioni sn ot proceeding in the absence of either palladium or base;2.the reaction is reaching completec onversion slower under directm echanocatalytic conditions compared to the palladium black or palladium salts. We, however,o bserved significant abrasion of palladium if the combination palladium balls and zirconia vessel was utilized. Softer vessel materials led to less abrasion withoutareduction in yield. Therefore, we also reached the conclusion that the reactioni tself has to happeno nt he palladium ball.

Cycloaddition reactions
From 2016 onwards,t he Mack group started to investigate cycloaddition reactions. While at first, they successfully utilized the known catalysts like Ni(PPh 3 ) 4 ,t hey quicklyc hanged to the direct mechanocatalytic system. They started with an ickel-catalyzed [2 + 2 + 2 + 2] cycloaddition reactiono fa na lkyne moiety ( Figure 2A). [6] Since they could not find nickel balls they utilized pellets instead. The reactionl ead to am ixture of variouss ubstituted cyclooctatetraenes and benzene derivatives, which was not expected according to solution-based results, where benzene derivate dominate. During this investigation, the Mack group established that the product mixture is tunable by interchanging the substitution pattern of ap henyl acetylene substrate. This approacho ffered the use of an inexpensive,a nd recyclable Ni 0 source and showedt hat direct mechanocatalysis can be conducted with readily available pellets insteado fb alls. Another,w ell investigated cycloaddition reaction was done by the Mack group as well. They established a coupling of ad iazo compound to an unsaturated hydrocarbon ( Figure 2B). They expanded the concept to silver but instead of balls they used as ilver-lined vial.
[8b] The established system was found to be reliable and robust in the synthesis of triazole derivatives. [19] Here, the used metal foil had ad irect influence on the obtained product. By switching between ac oppero r silver foil the positiono ft he cyclization could be changed. The Mack group also applied the acquired knowledget on ew reaction concepts.T hey developedacopper-mediated generation and cycloadditiono fo rganic azides ( Figure 2C)a nd successfully appliedt he direct mechanocatalysis of copper that they had observed earlier. [8c] The catalyst balls and foil-lined vials allowed for both reactions to be performed in ao ne pot synthesis.

Hydrogenationr eactions
Ac ompletely other type of reactions where direct mechanocatalysis has been successfully applied are hydrogenation reactions. While hydrogenation reactions themselves can be conducted via different methods inside the ball mill, [20] the Sawama group found au nique reaction pathway using a stainless-steel containing chromium and nickel.T hey were able to transfer hydrogen or deuterium from water or deuterium oxide,r espectively to as ubstrate ( Figure 3A). During this transfer,c hromium and nickel have distinct functions. Chromiumi s used to produce molecular hydrogen from water,w hile nickel is used to hydrogenatet he organic compound. [21] Further investigationso ft he same group showed how even organic molecules such as heptane can be used as ah ydrogen source ( Figure 3B).

Potential reactions
From thesef ew literature-known reactions we can already draw several conclusions on other reactions that might be accessible via direct mechanocatalysis.T he activation of terminal alkynes, as wella sc opper-catalyzed reactions are promising. Further,c ross-coupling reactionss eem to be feasible as well, even if they are palladium-catalyzed. Other reactions, which are in the focus of organic chemists are Ni 0 catalyzed conversions. Due to the abundance of nickel,i tw ould be ac heap and accessible catalyst, whereas the commonly used palladium is costly.Therefore, the application of nickel in the place of palladium in selectiveC ÀCc oupling under mild conditions would also be promising. Going even further it might be feasible to conductr hodium-catalyzed metatheses reactioni nt he same manner.
It also stands to reason that this approachi sn ot limitedt o organic synthesis alone. One shouldt ry to transfer common heterogeneously catalyzedr eactions like MTOo re ven the Fischer-Tropsch process into ad irectm echanocatalysis protocol. On the other hand, one is also not limited to molecular chemistry.A sw eh ave demonstrated this approachi sf easible for the synthesis of polymers. It stands to reason that other polymerization reactions especiallyt owards insoluble polymers can be conducted as well.

The Catalyst
After presenting the status quo, we want to discuss the reactions reported so far,r egarding the requirements towards the appliedc atalyst. Besides the distinct catalytic activity,t he catalyst has to be applicable in am illinge nvironment.A st he catalyst is the milling balli tself, it requires ac ertain breaking strength andh ardness. Screening typical milling materials, this usually leads to ceramics and metals being applied. It is therefore not astonishing that particularly transition metals such as Ag, Cr,C u, Ni and Pd have been in the focus of direct mechanocatalysis, demonstrating yields rivalling those from homogeneous reactions in solution. [13,21,22] The aforementionedm etals feature ac ommon property of being quite soft and thus, not very resistant towards abrasion. In consequence, during the re-action fine metal powder is created, which might also act as catalyst. Therefore, the abrasion resistancei sachallenge that needs to be tackled in order to elucidate mechanismsp resent in direct mechanocatalysis (Section 5). Ap otential method to circumvent the abrasion problem is to use alloys of the catalytic active metal.M etal alloys feature the advantage of being more resilient and can thus be used under milling conditions of higher energy.For severalofthe catalytically active materials there are harder and often cheaper alloys available(Ta ble1). To put the use of alloys into perspective:I fw ec onductacoppercatalyzed reactionv ia directm echanocatalysisa nd utilizes copperb alls in av ibratory ball mill we often observe abrasion in the order of severalh undred milligrams, or 10-20% of the ball mass. If, however brass is utilized instead, the reactionproceeds faster and the abrasion is barley measurable.W et hus postulate that one can substitute pure metals by alloys while keepingt heir catalytic activity comparable.I nt his context, the Sawamag roup recently published their resultso fadirect mechanocatalytic reaction. [21] SUS304 was used as ac atalyst material. This steel alloy consists mainly of three metals;i ron, nickel and chromium. In their work they then proceeded to use pure metal powders with inert millingballs to elucidate the function of each of the metals present. [21] This shows nicely,h ow a metal can be catalytically active under mechanochemical condition, even if the catalyst ball only contains 8-20 %o ft he catalytic active metal.M oreover,w ew ant to highlight the possibility of conducting tandemr eactions having two active metals within one alloy.T he shape of the catalyst also plays a role. Usually round millingb alls with polished surface are utilized in mechanochemistry.D ifferent materials, however,a re either nots old as balls or hard to shape into balls in the first place.F or those cases it has been shown that even pellets and more rough geometries can be utilized as "milling balls", as demonstrated nicely in the work of the Mack group on the nickel-catalyzed [2 + 2 + 2 + 2] cycloaddition reaction ( Fig-Figure 3. Dehydrogenation/hydrogenation reaction performedbyt he Sawama group. A: Water or deuterium oxide were dehydrated by the alloyed chromium.T he in situ formed hydrogenw as then used for ahydration of as ubstrate,u tilizing the nickel, which is also present in the alloy. [17] B: The described dehydrogenation/hydrogenation reaction using an alkane as hydrogens ource. ure 2A). [6] They went even further and utilized metal foils as a coating of the vessel to allow for ab road choice of milling items. [6,13] In those cases, the vessel andb all can then be chosen according to their density,h ardness or abrasion resistance. While both approaches feature their unique advantages, their distinct disadvantages have to be considered. The Mack group used silver and nickel foil lined vessels (Figure 4) for two differentc onversions.T he silver foil was used successfully in combination with as tainless-steel ball withoutm ajor losses of silver metal.I nt he case of the nickel foil, however,t he best conversion was achieved when the nickel foil was used in combination with at ungsten carbide ball. This combination lead to ad egradation of the foil, whichw as unusablea fter the reaction. [6] Switching to nickelp ellets leads to more impacts, but subsequently leads to microscopic particles, which are abraded during the reaction and need to be removed afterwards. [6, 8b] A commonlyu sed compromise between possible number of impacts, abrasion resistance, availability and uncomplicated recovery is the use of 10 mm balls out of the desired material. The ball shape, albeit having the lowest surface to volume ration, features the decisive advantages of being easy to produce and featuring the highest resistance against abrasion. [6, 8b, 9] These observations are also supported by computational calculations. Here it has been shown that oblique collisions in a milling vessel produce ah ighere ffective temperature than the impact of ab all and the vessel. [6,14] If this proves to be the case, am echanocatalytic setup should be designed in aw ay that generates the most oblique collisions duringt he milling process. [6,14] Possible approaches to this challenge are the use of smaller grinding equipmento rt he use of foils made out of the catalytic active metal to increase the probability of an oblique collision. [6, 8c, 13] The Milling After establishing the reactions and catalysts currently used in direct mechanocatalysis, it is important to take al ook at the milling conditions neededf or these types of reactions. Ag ood startingp oint can focus on the types of mills that are commonly utilized. While there is ap lethora of different mill types, only two of them are dominating mechanochemistry. These two types are the vibratory ball mills (also called mixer ball mills) and planetary ball mills. In vibratory ball mills the vessels are subjected to ah orizontal, vertical or elliptical arc. Due to sudden changes in the direction the balls inside the vessela re colliding with the wall and each other.I nt his type of mill usu-ally only af ew balls (one to four) and rather simple and small milling jars are utilized. To gether this makes for perfect systems for direct mechanocatalysiss ince even expensive materialsc an be manufactured into single balls and vessel geometriesa re simple and thusr eadily reproduced out of less common materials.
In planetary ball mills, vessels are moving on as un wheel arounda na ffixed point while rotating around their own axis simultaneously.T hese mills generally offer biggerr eactionv essels with the downside of requiring more balls. However,f or less expensive catalysts this millingg eometry can also be adaptedt owards direct mechanocatalysis.S ince no extensive studies on the importance of the mill type have been conducted ford irectly mechanocatalysis and the comparisons of different mill types has always been difficult for mechanochemical reactions, we can only extrapolate form the data pointsw e have to our disposal. One differenceb etween those two mill types is the ratio between sheer and impact forces during the milling.H ere, the data indicates that the sheer forces, dominant in planetary ball mills, are more effective in conducting these types of reactions. Planetary ball mills often show shorter reactiont imes comparedt om ixer mills. This might be caused by the more frequent creation of new surface by the sheering motion as comparedt ot he direct impact which rather compressest he powder present on the active surface. [23] It might also be the case that the highere nergy input in planetary ball mills is the sole reasonf or this apparent acceleration of reactions. The Sawama group could demonstrate that for their reactions higher rotational speeds are beneficial ( Figure 5A). [21b] Besides the mill geometries there exist several easy to control and reasonably well-understood parameters unique to mechanochemical reactions. As mentioned above,t he rotational speed (planetary ball mill) or millingf requency (vibrational ball mill) are an easy to adjust parameter to control the energy input in the milled powder.I nt he past it has been shown, that by increasing the speed, the grain size of the obtained powder can be reduced and in general reactions are proceedingf aster. ( Figure 5B)A dditionally,t he macroscopict emperature of the millingv essel is increasing since more energy is dissipated by heat. Therefore, it is hard to isolate the influence of the frequencyand temperature terms in amechanochemical reaction. Lately,M ack and co-workersd eveloped ac ooled mixer mill setup with which they could demonstrate that the milling frequencya lone can have an impacto nt he reaction. [24] On the different end of the temperatures pectrum the Group of Uzarevic hasl ately established ah eatablem illings etup. They observed drastic influenceso fm oderate increases in temperature on the selectivity and reaction rate of mechanochemicalr eactions. [25] For direct mechanocatalysis there is limitedd ata on the impact of temperature and millings peed since most of the reactionh ave only been studied at one frequency in vibratory ball mills. In planetary ball mills, where temperatures are generally higher than in vibratory ones, Sawama established that at higherr otational speeds the catalytic releaseo fh ydrogen is faster.Ac loser look on their data suggest that especially in the low rpm-range (400-800 rpm) this increase is mainly causedb y the faster rotation sincet he temperature stays in the same range. [21b] At this point, however,m ore studies of the effect of temperature on those reactions, have to be done in order to obtain ac onclusive answer.
The energy input can also be regulated by the density and size of the milling material. Since the millingm aterial is of crucial importance in direct mechanocatalysis, this parameter is hard to change, except by using alloys. The ball size, however, is easier to alter.I ng eneral, small millingb alls obtain as maller kinetic energy at ag iven speed than their biggerc ounterparts. The minimal achievable grain size, however,g ets smallerw ith smaller balls.A dditionally,i nn eat grinding experiments, smaller balls tend to agglomerate if the reaction mixturem elts during the millingp rocess.T aking all of this into consideration typicallym illing balls between 5mma nd 15 mm are used, this stays true for direct mechanocatalysis.
Another important but seldomly investigated parameter is the milling ball filling degree-thea mount of balls for ag iven vessel volume. Here, Kwade and co-workers established that approximately 30 %oft he vesselvolume needs to be occupied by the balls for an optimal energy input. In direct mechanocatalysis this rule is generally followed in planetary ball mills. [6, 21b, 26] The reactions in vibratory ball mills, however,u sually only use one or two balls. [13] Another interesting point is the combination/mixing of vessela nd ball materials. It is often unwise to produce the full vesselo ut of agiven catalytic material, be it due to cost or mechanicalp roperties of the metal in question. In those cases, either as tainless steel or zirconia milling vessel is used with the required catalysta sb all, shot, or foil. If the differences in hardness, however,i st oo sever,t he softer material is slowly being ground into powder by the hardero ne and massive abrasion has to be considered.T his leads to immensew ear [6] and ad rastic weightl oss duringr eaction and contaminationo f the sample with metal powder. Even with only slight differences in hardness, this can produce ac onsiderable amount of abrasion.I nt his case, it will be challenging to distinguish whether catalysis run on the surfaceo ftheb alls or at the abraded metal powder.A gain,a lloys can helpw ith this problem. For example, copper itselfi sasoft metal andn ot wellsuited fort he use as milling balls, brass shows almost no abrasion while still catalyzing the copper-catalyzed reactions.

The Mechanism
The mechanism of mechanochemical reactions in general is poorlyu nderstood.T his is causedb yt he unique reactione nvironment being as ealed and dense vessel that is rotatingo rv ibratingr apidly.C onventional spectroscopic characterization setupse stablished for solution-based chemistry is hardly viable.O nly in the last few years, in situ characterization setupsh ave been developed that allow to shed light into the mechanochemical reactor.N amely,i ns itu X-ray powder diffraction and in situ Raman spectroscopy have helped to identify reaction intermediates and propose mechanistic detail. [27] These techniques are indispensable for direct mechanocatalysis, but probably not sufficient. The keyq uestion is:W here does the catalytic reaction run at?I na ni dealized view,i ti st he surfaceo ft he milling ball and the millingv essel. Although, abrasion during millingc an be minimized due to wise selection of milling conditions, certain catalytic activity of the abraded species cannot be ruled out. [9] In ar ecent publication, our group conducted aP d-milling ball-catalyzedS uzukir eaction and exchanged the catalytically active milling balls against non-activeZ rO 2 balls after 4h of reaction. We observed that the rate of conversion decreaseda bruptly.T hat meanst hat Pd abrasion accumulating duringm illing is not the major active specie in this reaction and the Pd milling ball as well as their collisionsc ontributet ot he overall reaction. We want to take this cross-couplingr eaction as aconvenient example to discuss the challenge of mechanocatalytic reactionm echanism in more detail. Most cross-coupling reactions known from solution follow reaction cycles involving oxidation addition and reductive elimination steps. Transition states are stabilized by solvents, catalystl igandse nable solubility and direct product selectivities. Neither as olvent, nor al igand is present in direct mechanocatalysis, but the reactionp roceeds anyway. In con- trast, other conventionally used additives such as the base are still inevitable. Even more, many directm echanocatalytic reactions appear to be highly sensitive to the type of base used. The HSAB concept seems to be of utmost importance as beautifully demonstrated by the group of James Mack. [4b, 28] In this theory an atom, iono rm olecule is defined either as hard (low polarizability,for example, F À )orsoft (high polarizability,for example,C s + ). and ah ard-hard and soft-soft pairi se nergetically beneficial. [29] Thisc an be visualized by the fact that LiOH (hardhard) is not capable of enabling the mechanochemical enolate reactionb etween2 -methylcyclohexanone and bromobenzyl bromide,w hile NaOH (soft-hard) is leading to ah igh yield. [28] With this in mind, we strongly feel that direct mechanocatalytic reactions proceed differently to the well-known solutionbased analogues.R eaction intermediates need to be identified and the catalystitself needs to be investigated during reaction. This aims towards another fundamental question:I sd irect mechanocatalysis ah eterogeneousc atalysis?F rom the concept it should be. Although all components can be solid, the milling ball is obviously ad ifferent phase than the reactants. This macroscopically sized catalystc an easily be removed after reaction. However,t hat the catalytic transformation runs at the surface of the milling ball has never been shown. Direct mechanocatalysis has certainf eatures that are uncommon in established heterogeneous catalysis. Instead of fluid reactants (gases or liquids), solid reactants are preferably converted and instead of an ever-higher catalysts urface, the lowest possible one of a dense macroscopic milling balli sc hosen. Obviously,r eaction rates are not solely determined by parameters such as temperature or the number of active sites, but by new parameters such as the frequency of active-site-refreshment caused by various milling parameters, for example, milling speed, density of milling balls, size of balls. Only very little is knowna bout these types of reactions that is, catalysis on as urface under continuous mechanical impact.B ut how can we get ad eeper insight into direct mechanocatalysis?
In the last years two in situ characterization methods have been well established by the mechanochemical community. [27] The groups of Friscic, Uzarevic, Halasz and Emmerling in particular have done tremendous work on in situ powder X-ray diffraction (pXRD). [30] These techniquesa llowed for the trackingo f reactions involving crystalline reagents in general and the identification of intermediates in specific cases. [31] However, this technique is exclusively suitable for crystalline solids and long living intermediates since acquisition times of about 30 s are needed. Besides pXRD, in situ Ramans pectroscopy has been applied for similar reactions. [32] Here, no crystallinity is required but acquisitions times are still rather long ( % 1-10 s) and the technique suffers from fluorescence. With aw ise choice of laser parameters and reactants, however, it is possible to follow directm echanocatalysis reaction with both in situ techniques. [33] Both of these methods, however,c an only give indications towards the mechanismso fd irect mechanocatalytic reactions. To fully elucidate the mechanisms, one needs to closer investigate the milling balls urface in the moment of impact.T his on the other hand seems hardly feasible and thus ap roper investigation needs to heavily rely on ex-situd ata.
One important step would be to identify intermediates or immobilized materials on the millingb all surface itself. Possible characterization methods could be TEM/SEM of as liced of part of the milling ball, XPS of the milling ball surface before and after milling just to name two. As mentioned in the beginning, the field of direct mechanocatalysisisstill in its infancy and besides first hunches no clearm echanisms have been established. It is the job of the mechanochemical community to dig deeper into thiss ubject to uncover its full potential.

Conclusions
We propose to use the term "direct mechanocatalysis" for catalytic reactions where the reactants are exposed to mechanical forces and the source of force is catalytically activei tself. In general,t he milling ball or vessel is made from ac atalytically active component. This novel type of catalysis offerst he advantage of directly using solid eductst hat do not requirea ny solubility.C atalyst recycling and separation is most facile, as the macroscopic milling balls imply has to be taken out of the vessela fter the reaction. Until now,t his concept has been shownf or only af ew reactions, foremost transition metal-catalyzed cross-coupling reactions. However,i fa nd how it can be adaptedt oo ther catalytic reactions will strongly depend on a betteru nderstanding of the underlying reaction mechanisms, which are expected to differ significantly from solution-based reaction pathways. Since new reactiont ypes and product selectivities are very likely by this approach, direct mechanocatalysis may not only enable new products and reactions, but also pave the way towards sustainabler eactionalternatives.