Liquids with High Compressibility.

Compressibility is a fundamental property of all materials. For fluids, that is, gases and liquids, compressibility forms the basis of technologies such as pneumatics and hydraulics and determines basic phenomena such as the propagation of sound and shock waves. In contrast to gases, liquids are almost incompressible. If the compressibility of liquids could be increased and controlled, new applications in hydraulics and shock absorption could result. Here, it is shown that dispersing hydrophobic porous particles into water gives aqueous suspensions with much greater compressibilities than any normal liquids such as water (specifically, up to 20 times greater over certain pressure ranges). The increased compressibility results from water molecules being forced into the hydrophobic pores of the particles under applied pressure. The degree of compression can be controlled by varying the amount of porous particles added. Also, the pressure range of compression can be reduced by adding methanol or increased by adding salt. In all cases, the liquids expand back to their original volume when the applied pressure is released. The approach shown here is simple and economical and could potentially be scaled up to give large amounts of highly compressible liquids.

Noria and its derivatives as hosts for chemically and thermally robust Type II porous liquids.

Porous Liquids (PLs) are a new class of material that possess both fluidity and permanent porosity. As such they can act as enhanced, selective solvents and may ultimately find applications which are not possible for porous solids, such as continuous flow separation processes. Type II PLs consist of empty molecular hosts dissolved in size-excluded solvents and to date have mainly been based on hosts that have limited chemical and thermal stability. Here we identify Noria, a rigid cyclic oligomer as a new host for the synthesis of more robust Type II PLs. Although the structure of Noria is well-documented, we find that literature has overlooked the true composition of bulk Noria samples. We find that bulk samples typically consist of Noria (ca. 40%), a Noria isomer, specifically a resorcinarene trimer, "R3" (ca. 30%) and other unidentified oligomers (ca. 30%). Noria has been characterised crystallographically as a diethyl ether solvate and its 1H NMR spectrum fully assigned for the first time. The previously postulated but unreported R3 has also been characterised crystallographically as a dimethyl sulfoxide solvate, which confirms its alternative connectivity to Noria. Noria and R3 have low solubility which precludes their use in Type II PLs, however, the partially ethylated derivative Noria-OEt dissolves in the size-excluded solvent 15-crown-5 to give a new Type II PL. This PL exhibits enhanced uptake of methane (CH4) gas supporting the presence of empty pores in the liquid. Detailed molecular dynamics simulations support the existence of pores in the liquid and show that occupation of the pores by CH4 is favoured. Overall, this work revises the general accepted composition of bulk Noria samples and shows that Noria derivatives are appropriate for the synthesis of more robust Type II PLs.

Mechanochemical synthesis of mononuclear gold(I) halide complexes of diphosphine ligands with tuneable luminescent properties.

A mechanochemical method is reported for the synthesis of Au(diphos)X complexes of diphosphine (diphos = XantPhos and N-XantPhos) ligands and halide ions (X = Cl and I). The Au(XantPhos)X (1: X = Cl; 2: X = I) and Au(N-XantPhos)Cl (3) complexes exhibited either yellowish green (1) or bluish green (2) emission, whereas 3 was seemingly non-emissive in the solid state at room temperature. Blue- (2B) and bluish green (2G) luminescent concomitant solvates of 2 were obtained by recrystallization. Luminescent colour changes from blue (2B) or bluish green (2G) to yellow were observed when these forms were subjected to mechanical stimulus, while the original emission colour can be recovered in the presence of solvent vapours. Moreover, the luminescence of 2B can be reversibly altered between blue and yellow by heating/cooling-cycles. These results demonstrate the power of mechanochemistry in the rapid (4 min reaction time), efficient (up to 98% yield) and greener synthesis of luminescent and stimuli-responsive gold(I) complexes.

Continuous and scalable synthesis of a porous organic cage by twin screw extrusion (TSE).

The continuous and scalable synthesis of a porous organic cage (CC3), obtained through a 10-component imine polycondensation between triformylbenzene and a vicinal diamine, was achieved using twin screw extrusion (TSE). Compared to both batch and flow syntheses, the use of TSE enabled the large scale synthesis of CC3 using minimal solvent and in short reaction times, with liquid-assisted grinding (LAG) also promoting window-to-window crystal packing to form a 3-D diamondoid pore network in the solid state. A new kinetically trapped [3+5] product was also observed alongside the formation of the targeted [4+6] cage species. Post-synthetic purification by Soxhlet extraction of the as-extruded 'technical grade' mixture of CC3 and [3+5] species rendered the material porous.

Greener Dye Synthesis: Continuous, Solvent-Free Synthesis of Commodity Perylene Diimides by Twin-Screw Extrusion.

A continuous, scalable, and solvent-free method for the synthesis of various naphthalic imides and perylene diimides (PDIs) using twin-screw extrusion (TSE) is reported. Using TSE, naphthalic imides were obtained quantitatively without the need for excess amine reactant or product purification. With good functional-group tolerance, alkyl and benzyl amine derived PDIs (incl. commercial dyes) were obtained in 50-99 % yield. Use of K2 CO3 , enabled synthesis of more difficult aniline-derived PDIs. Furthermore, an automated continuous TSE process for Pigments Black 31 and 32 is demonstrated, with a throughput rate of about 1500 g day-1 , corresponding to a space time yield of about 30×103  kg m-3  day-1 , which is 1-2 orders of magnitude greater than for solvent-based batch methods. These methods provide substantial waste reductions and improved efficiency compared to conventional solvent-based methods.

Insights into mechanochemical reactions at the molecular level: simulated indentations of aspirin and meloxicam crystals.

Although solvent-free mechanochemical synthesis continues to gain ever greater importance, the molecular scale processes that occur during such reactions remain largely uncharacterised. Here, we apply computational modelling to indentations between particles of crystals of aspirin and meloxicam under a variety of conditions to mimic the early stages of their mechanochemical cocrystallisation reaction. The study also extends to the effects of the presence of small amounts of solvent. It is found that, despite the solid crystalline nature of the reactants and the presence of little or no solvent, mixing occurs readily at the molecular level even during relatively low-energy collisions. When indented crystals are subsequently drawn apart, a connective neck formed by a mixture of the reactant molecules is observed, suggesting plastic-like behaviour of the reacting materials. Overall the work reveals some striking new insights including (i) relatively facile mixing of crystals under solvent-free conditions, (ii) no appreciable local temperature increases, (iii) localised amorphisation at the contact region and neck of the reacting crystals, and (iv) small amounts of solvent have relatively little effect during this early stage of the reaction, suggesting that their accelerating effect on the reaction may be exerted at later stages.

Solvent-free sonochemistry as a route to pharmaceutical co-crystals.

We describe the synthesis of pharmaceutically relevant co-crystals by solvent-free sonochemistry starting from solid reagents. Employing a standard ultrasonic cleaning bath, quantitative conversions occurred within 20-60 minutes to give co-crystals of paracetamol and aspirin with a range of co-formers. As well as the utility of the method, the work raises interesting mechanistic questions regarding acoustic cavitation with no liquid phase being present.

Mechanochemical dehydrocoupling of dimethylamine borane and hydrogenation reactions using Wilkinson's catalyst.

Mechanochemistry enabled the selective synthesis of the recherché orange polymorph of Wilkinson's catalyst [RhCl(PPh3)3]. The mechanochemically prepared Rh-complex catalysed the solvent-free dehydrogenation of Me2NH·BH3 in a ball mill. The in situ-generated hydrogen (H2) could be utilised for Rh-catalysed hydrogenation reactions by ball milling.

Continuous multi-step synthesis by extrusion - telescoping solvent-free reactions for greater efficiency.

Chemical manufacturing typically requires more than one step, involving multiple batch processes, which makes synthesis at scale laborious and wasteful. Herein, we demonstrate that several reactions can be telescoped into a single continuous process and/or be carried out as a continuous multi-component reaction (MCR), by twin screw extrusion (TSE), in the complete absence of solvent.

Solvent-free sonochemistry: Sonochemical organic synthesis in the absence of a liquid medium.

Sonochemistry, i.e., the application of mechanical energy in the form of sound waves, has recently been recognised for its similarity to mechanochemistry and is now included under the umbrella term of mechanochemistry. Typically, due to the hypothesised cavitation mechanism, a liquid medium is considered as a necessity for a process to take place as a result of ultrasonic irradiation. In view of this, condensation reactions between solid reagents in the complete absence of solvent were carried out successfully by ultrasonic irradiation with the importance of particle size being highlighted. This work increases the potential of sonochemistry in the drive towards a sustainable future.

Feedback Kinetics in Mechanochemistry: The Importance of Cohesive States.

Although mechanochemical synthesis is becoming more widely applied and even commercialised, greater basic understanding is needed if the field is to progress on less of a trial-and-error basis. We report that a mechanochemical reaction in a ball mill exhibits unusual sigmoidal feedback kinetics that differ dramatically from the simple first-order kinetics for the same reaction in solution. An induction period is followed by a rapid increase in reaction rate before the rate decreases again as the reaction goes to completion. The origin of these unusual kinetics is found to be a feedback cycle involving both chemical and mechanical factors. During the reaction the physical form of the reaction mixture changes from a powder to a cohesive rubber-like state, and this results in the observed reaction rate increase. The study reveals that non-obvious and dynamic rheological changes in the reaction mixture must be appreciated to understand how mechanochemical reactions progress.

Extrusion - back to the future: Using an established technique to reform automated chemical synthesis.

Herein, the benefits which extrusion can provide for the automated continuous synthesis of organic compounds are highlighted. Extrusion is a well-established technique that has a vital role in the manufacturing processes of polymers, pharmaceuticals and food products. Furthermore, this technique has recently been applied to the solvent-free continuous synthesis of co-crystals and coordination compounds including metal-organic frameworks (MOFs). To date, a vast amount of research has already been conducted into reactive extrusion (REX), particularly in the polymer industry, which in many cases has involved organic transformations, however, it has not received significant recognition for this. This review highlights these transformations and discusses how this previous research can be applied to the future of organic compound manufacture.

Recent Developments in Mechanochemical Materials Synthesis by Extrusion.

Mechanochemical synthesis, i.e., reactions conducted by grinding solid reactants together with no or minimal solvent, has been demonstrated as an excellent technique for the formation of both organic and inorganic compounds. Mechanochemistry is viewed as an alternative approach to chemical synthesis and is not always considered when developing manufacturing processes of fine chemicals. Here, recent advances are highlighted regarding mechanochemical synthesis, by utilizing a well-developed continuous technique - extrusion, and the advantages it offers to further support its use in the manufacturing of these chemicals. To put this work into context, it is shown how extrusion plays a vital role for manufacturing in the food, polymer, and pharmaceutical industries, and how the research carried out by these respective industrialists provides great insight and understanding of the technique, with the results being applicable in the chemical industry. The synthesis of metal-organic frameworks (MOFs) is highlighted herein as an excellent example showcasing the advantages that extrusion provides to the manufacture of these materials, one advantage being the exceptional space time yields (STYs) reported for these processes, at three orders of magnitude greater than conventional (solvothermal) synthesis.