Mechanochemistry continues to reveal new possibilities in chemistry including the opportunity for “greening” reactions. Nevertheless, a clear understanding of the energetic transformations within mechanochemical systems remains elusive. We employed a uniquely modified ball mill and strategically chosen Diels–Alder reactions to evaluate the role of several ball-milling variables. This revealed three different energetic regions that we believe are defining characteristics of most, if not all, mechanochemical reactors. Relative to the locations of a given ball mill's regions, activation energy determines whether a reaction is energetically easy (Region I), challenging (Region II), or unreasonable (Region III) in a given timeframe. It is in Region II, that great sensitivity to mechanochemical conditions such as vial material and oscillation frequency emerge. Our unique modifications granted control of reaction vessel temperature, which in turn allowed control of the locations of Regions I, II, and III for our mill. Taken together, these results suggest envisioning vibratory mills (and likely other mechanochemical methodologies) as molecular-collision facilitating devices that act upon molecules occupying a thermally-derived energy distribution. This unifies ball-milling energetics with solution-reaction energetics via a common tie to the Arrhenius equation, but gives mechanochemistry the unique opportunity to influence either half of the equation. In light of this, we discuss a strategy for translating solvent-based reaction conditions to ball milling conditions. Lastly, we posit that the extra control via frequency factor grants mechanochemistry the potential for greater selectivity than conventional solution reactions.

Mechanochemistry, more specifically high-speed ball milling, has garnered significant attention in several areas of chemistry, particularly for the synthesis of inorganic materials, cocrystals, organic compounds, discrete metal complexes and metal organic frameworks. This methodology is creating exciting research opportunities because, unlike traditional synthesis, a reaction carried out in a high-speed ball mill does not necessarily need a solvent, thus representing an environmentally friendly solution to the issue of solvent waste. This Chemistry Frontiers article delves into a unique area of ball milling that capitalizes on the solventless nature of the synthesis by using reaction vials, balls, foils, and pellets as both reaction medium and the catalyst. Several examples are highlighted, from nanoparticle synthesis and nanocatalysis to using transition metals in their metallic forms as catalysts. This article is aimed to show both the advantages and challenges present in the field, and to spark interest in further development of this research area.

Herein, we report on the dimerization of terminal alkynes using various palladium catalysts under solvent-free mechanochemical conditions. When tetrakis(triphenylphosphine)palladium(0) was employed as the catalyst, we observed the 1,3-butadiyne as the major product. However, when we employed bis(triphenylphosphine)palladium(II) dichloride as the catalyst, we observed the trans-enyne as the major product. When we used a polymer-supported bis(triphenylphosphine)palladium(II) dichloride catalyst under liquid-assisted grinding conditions, we discovered the ability to tune the catalyst to generate either the diyne or trans-enyne as the major product, depending on the grinding medium.Keywords: ball mill; catalysis; green chemistry; homocoupling; mechanochemistry; polymer support; solvent-free

A solvent-free, nickel-catalyzed [2 + 2+2 + 2] cycloaddition of alkynes to synthesize substituted cyclooctatetraene (COT) derivatives has been developed. This mechanochemical approach takes advantage of the frictional energy created by reusable nickel pellets, which also act as the catalyst. In contrast to solution chemistry, the major products are cyclooctatetraene isomers rather than substituted benzenes.Keywords: Cyclooctatetraene; Cyclotetramerization; Cyclotrimerization; Green chemistry; High speed ball mill; Mechanochemistry; Nickel catalysis;

Herein, we describe a copper-free, oxidant-free, solvent-free homocoupling reaction using a palladium catalyst under mechanochemical conditions. We extended the methodology to palladium catalyst on solid support which showed a different reactivity and different product ratios from the non-supported catalyst. We were able to recycle the polymer supported catalyst for 5 cycles.

Using a mechanically driven Diels–Alder reaction we were able to characterize the chemical energetics of a SPEX 8000M mixer/mill. Our results demonstrate that the conditions produced by this type of mill are similar to those produced when performing the same reaction at 90 °C in solution. Discrete element models and in situ temperature logging were used to analyse the energetics of this system. These models indicate that the yields obtained using a SPEX 8000M mill are best correlated to the velocity of the media and number of non-zero force collisions.

Herein we report the first copper vial catalysed CuAAC reaction. Under solvent-free mechanochemical conditions the reaction is complete in as little as 15 minutes and the triazole product isolated straight from the reaction vial with no further purification.

As regulations that restrict the use of organic solvents become more stringent, ball milling remains an attractive substitute for traditional organic synthesis. However, the mechanochemistry community does not have a purification pathway to complement the solvent-free, ball milling process. Functional resins have proven to be powerful synthetic tools that simplify purification, but traditional handling of these resins restricts their utility, as hazardous organic solvents are needed to swell the resin. Ball milling the functional resin exposes the functional groups as a function of surface area. This report details the use of ball milling and functional resins to perform an environmentally attractive version of the Wittig reaction.

Dry organic solvents are used for various organic reactions that employ moisture sensitive reagents. The processes to dry these solvents are hazardous and costly. Setting up reactions in an open atmosphere while using moisture sensitive reagents has little to no effect on the rate or yield of the reaction under mechanochemical conditions. We believe this is partly due to the gaseous nature of the water vapor in the air compared to the dissolved water and oxygen in solution.Dry organic solvents are used for various organic reactions that employ moisture sensitive reagents. The processes to dry these solvents are hazardous and costly. Setting up reactions in an open atmosphere while using moisture sensitive reagents has little to no effect on the rate or yield of the reaction under solvent-free mechanochemical conditions. We believe this is partly due to the gaseous nature of the water vapor in the air compared to the dissolved water and oxygen in solution.

We investigated the synthesis of dialkyl carbonates under solvent-free high speed ball milling conditions. We converted various metal carbonates with the assistance of metal complexing reagents into a variety of dialkyl carbonates. We also observed the increased reactivity of urea under similar reaction conditions.

Over the last decade, solvent-free methods have been gaining interest as replacements for traditional organic chemistry techniques. While solvent-free methods are well known for many processes, a simple, solvent-free purification procedure that supplements them does not exist. We report the solvent-free synthesis of α,β-unsaturated esters using a solvent-free Horner–Wadsworth–Emmons (HWE) reaction using high-speed ball milling (HSBM). We were able to perform the HWE reaction on a variety of aldehydes, and isolate their respective a,b-unsaturated esters in high yields, purities, and diastereoselectivities.

We investigated the ability to selectively form products arising from a kinetic or a thermodynamic enolate under solvent-free high speed ball milling conditions. Using 2-methylcyclohexanone as the substrate and sodium hydroxide or lithium hexamethyldisilazide as the base, we were able to trap the thermodynamic or kinetic enolate in high selectivity. Although all the reagents were ball milled simultaneously, we observed no products resulting from aldol condensation.

Herein, we report on the solvent-free Sonogashira reaction utilizing high speed ball milling. Sonogashira coupling of a variety of para substituted aryl halides were performed with trimethylsilylacetylene or phenylacetylene. We observed that iodo and bromo substituted aromatics successfully undergo Sonogashira coupling. However, chloro and fluoro substituted aryl compounds were unreactive. Conducting the coupling reaction in the absence of copper iodide led to low yields. Alternately, if the reaction is conducted with a copper ball in a copper vial in lieu of copper iodide, the coupling product is observed in high yields. This demonstrates the first report on the use of the vial and ball material as a catalyst in a ball milled chemical reaction.

Herein, we describe the solvent-free ball milling Tishchenko reaction. Using high speed ball milling and a sodium hydride catalyst, the Tishchenko reaction was performed for aryl aldehydes in high yields in 0.5 hours. The reaction is not affected by the type of ball bearing used and can be successful when conducted in a liquid nitrogen environment.

Utilizing the novel technique of high-speed ball milling, we herein report the first solvent-free reduction of esters.

Through the novel technique of high speed ball milling we were able to generate Baylis–Hillman products in as little as 0.5 hours. This represents one of the fastest methods of Baylis–Hillman reactions under neat conditions. Upon analysis of various catalysts we found 1,4-diazabicyclo[2.2.2]octane to be the catalyst that led to the highest product yields in the shortest reaction time.

Novel blue emitters were synthesized based on the fullerene fragment corannulene. 1,2- bis(corannulenylethynyl)benzene and 1,4-bis(corannulenylethynyl)benzene were designed, synthesized, and shown to exhibit significant red shifts in their absorption spectra as compared to that of the parent corannulene. Photoluminescence studies show both 1,2- bis(corannulenylethynyl)benzene and 1,4- bis(corannulenylethynyl)benzene gives enhanced blue luminescence compared to the parent corannulene structure. 1,4-bis(corannulenylethynyl)benzene was observed to give intense blue luminescence when excited at 400 nm. DFT and TD-DFT calculations were performed and shown to be consistent with the observed experimental results.

Novel blue emitters were synthesized based on the fullerene fragment corannulene. 1,2- bis(corannulenylethynyl)benzene and 1,4-bis(corannulenylethynyl)benzene were designed, synthesized, and shown to exhibit significant red shifts in their absorption spectra as compared to that of the parent corannulene. Photoluminescence studies show both 1,2- bis(corannulenylethynyl)benzene and 1,4- bis(corannulenylethynyl)benzene gives enhanced blue luminescence compared to the parent corannulene structure. 1,4-bis(corannulenylethynyl)benzene was observed to give intense blue luminescence when excited at 400 nm. DFT and TD-DFT calculations were performed and shown to be consistent with the observed experimental results.

Mechanochemistry continues to reveal new possibilities in chemistry including the opportunity for “greening” reactions. Nevertheless, a clear understanding of the energetic transformations within mechanochemical systems remains elusive. We employed a uniquely modified ball mill and strategically chosen Diels–Alder reactions to evaluate the role of several ball-milling variables. This revealed three different energetic regions that we believe are defining characteristics of most, if not all, mechanochemical reactors. Relative to the locations of a given ball mill's regions, activation energy determines whether a reaction is energetically easy (Region I), challenging (Region II), or unreasonable (Region III) in a given timeframe. It is in Region II, that great sensitivity to mechanochemical conditions such as vial material and oscillation frequency emerge. Our unique modifications granted control of reaction vessel temperature, which in turn allowed control of the locations of Regions I, II, and III for our mill. Taken together, these results suggest envisioning vibratory mills (and likely other mechanochemical methodologies) as molecular-collision facilitating devices that act upon molecules occupying a thermally-derived energy distribution. This unifies ball-milling energetics with solution-reaction energetics via a common tie to the Arrhenius equation, but gives mechanochemistry the unique opportunity to influence either half of the equation. In light of this, we discuss a strategy for translating solvent-based reaction conditions to ball milling conditions. Lastly, we posit that the extra control via frequency factor grants mechanochemistry the potential for greater selectivity than conventional solution reactions.

Mechanochemistry, more specifically high-speed ball milling, has garnered significant attention in several areas of chemistry, particularly for the synthesis of inorganic materials, cocrystals, organic compounds, discrete metal complexes and metal organic frameworks. This methodology is creating exciting research opportunities because, unlike traditional synthesis, a reaction carried out in a high-speed ball mill does not necessarily need a solvent, thus representing an environmentally friendly solution to the issue of solvent waste. This Chemistry Frontiers article delves into a unique area of ball milling that capitalizes on the solventless nature of the synthesis by using reaction vials, balls, foils, and pellets as both reaction medium and the catalyst. Several examples are highlighted, from nanoparticle synthesis and nanocatalysis to using transition metals in their metallic forms as catalysts. This article is aimed to show both the advantages and challenges present in the field, and to spark interest in further development of this research area.