Scalability of Pharmaceutical Co-Crystal Formation by Mechanochemistry in Batch.

The development of mechanochemistry is considerably growing. Benign by design, this technology complies with several principles of green chemistry, contributing to the achievement of the United Nations Sustainable Development Goals (UN SDGs) and the European Green Deal objectives. Herein, we report the use of mechanochemical processes in batch to prepare kilogram-scale of the Active Pharmaceutical Ingredient (API): Ibuprofen-Nicotinamide (rac-IBP:NCT) co-crystal in an industrial eccentric vibration mill. This scenario shows a sustainable approach to the industrial up-scaling of pharmaceutical co-crystals by a solvent-free mechanochemical process in batch. The quantitative assessment of the greenness of the mechanochemical process against the Twelve Principles of Green Chemistry was performed using the DOZN 2.0 Green Chemistry Evaluator.

A Novel Electrode for Value-Generating Anode Reactions in Water Electrolyzers at Industrial Current Densities.

Hydrogen generated in electrolyzers is discussed as a key element in future energy scenarios, but oxygen evolution as the standard anode reaction is a complex multi-step reaction requiring a high overpotential. At the same time,it does not add value-the oxygen is typically released into the atmosphere. Alternative anode reactions which can proceed at similar current densities as the hydrogen evolution are, therefore, of highest interest. We have discovered a high-performance electrode based on earth-abundant elements synthesized in the presence of H2 O2 , which is able to sustain current densities of close to 1 A cm-2 for the oxidation of many organic molecules, which are partly needed at high production volumes. Such anode reactions could generate additional revenue streams, which help to solve one of the most important problems in the transition to renewable energy systems, i.e. the cost of hydrogen electrolysis.

Polymorphism of dimethylaminoborane N(CH3)2-BH2.

Dehydrocoupling of the adduct of dimethylamine and borane, NH(CH3)2-BH3 leads to dimethylaminoborane with formal composition N(CH3)2-BH2. The structure of this product depends on the conditions of the synthesis; it may crystallize either as a dimer in a triclinic space group forming a four-membered ring [N(CH3)2-BH2]2 or as a trimer forming a six-membered ring [N(CH3)2-BH2]3 in an orthorhombic space group. Due to the denser packing, the six-membered ring in the trimer structure should be energetically more stable than the four-membered ring. The triclinic structure is stable at low temperatures. Heating the triclinic phase above 290 K leads to a second-order phase transition to a new monoclinic polymorph. While the crystal structures of the triclinic and orthorhombic phases were already known in the literature, the monoclinic crystal structure was determined from powder diffraction data in this study. Monoclinic dimethylaminoborane crystallizes in space group C2/m with the boron and nitrogen atoms located on the mirror plane, Wyckoff position 4i, while the carbon and hydrogen atoms are on the general position 8j.

Group 13-derived radicals from α-diimines via hydro- and carboalumination reactions.

The mechanochemical synthesis of tertiary and secondary alanes AlR3 (R = Np 1 or Mes 2; HAlR2 R = Np 3 or Mes 4) is described. These species are reacted with several α-diimines to give a series of aluminium-derived radicals of the form [(diimine)AlR2]˙ (6-11). EPR and several crystallographic studies are reported. These species are thought to form via hydro- or carboalumination and subsequent elimination reactions. This view is supported by the structural data for minor products C12H7(NHDipp)(NDipp)AliBu25 and C13H8(C(iBu)[double bond, length as m-dash]N(m-Xy)(NH(m-Xy)))AliBu212. In addition, the characterization of (C6F5)2B(OC(C6F5)OC12H8) indicates that such a carboboration pathway also provides access to related boron-derived radicals.

Methane to Chloromethane by Mechanochemical Activation: A Selective Radical Pathway.

State-of-the-art processes to directly convert methane into CH3Cl are run under corrosive conditions and typically yield a mixture of chloromethanes requiring subsequent separation. We report a mechanochemical strategy to selectively convert methane to chloromethane under overall benign conditions, employing trichloroisocyanuric acid (TCCA) as a cheap and noncorrosive solid chlorinating agent. TCCA is shown to release active chlorine species upon milling with Lewis acids such as alumina and ceria to functionalize methane at moderate temperatures (<150 °C). A thorough parameter optimization led to a maximum methane chlorination rate of 0.8 µmol(CH4,conv) (g(catalyst) s)-1. Findings were compared to the thermal reaction of methane with TCCA and evidenced that mechanochemical activation permitted significantly lower reaction temperatures (90 vs 200 °C) at a drastically improved CH3Cl selectivity (95% vs 66% at 30% conversion). Considering the characterization of the interaction between TCCA and Lewis acids as well as the in-depth analysis of byproducts, we suggest a plausible reaction mechanism and a possible regeneration of the chlorinating agent.

Direct Hydrogenation of Aluminum via Stabilization with Triethylenediamine: A Mechanochemical Approach to Synthesize the Triethylenediamine ⋠AlH3 Adduct.

Two approaches for the synthesis of the triethylenediamine (TEDA) ⋅ AlH3 adduct have been discovered. Both, the mechanochemical procedure and the wet chemical method lead to crystalline products. Starting from metallic Al powder and TEDA, ball milling under a pressure of 100 bar H2 facilitates a direct hydrogenation of aluminum with conversions up to 90 %. Structure determination from X-ray powder diffraction data revealed an 1-D-coordination polymer of the type [TEDA-AlH3 ]n . Furthermore, solid-state NMR techniques have been applied to analyze composition and structure of the products. Due to the polymeric arrangement, an enhanced stability of the material occurred which was investigated by thermal analysis showing a decomposition located above 200 °C. Overall, the stabilization of AlH3 by TEDA holds promise for hydrogen storage applications.

Crystal structures of ordered and plastic-crystalline phases of iso-butyllithium by X-ray powder diffraction.

Donor-unsupported iso-butyllithium consists of hexamers with an ordered triclinic structure at -80 °C (α-phase). At ambient temperature, the compound exists as an orthorhombic, remarkably stable, plastic-crystalline γ-phase, which is built by disordered hexamers adopting a distorted face-centred cubic packing. Both structures were determined by X-ray powder diffraction. Additionally, an intermediate ß-phase is observed.

Syntheses and Crystal Structures of Phenyl-Lithium Derivatives.

Although organolithium compounds have been studied and applied for ∼100 years, only few crystal structures of pure, unsolvated organolithium compounds have been reported so far. Therefore, several phenyl-lithium derivatives were synthesized by lithium-halogen exchange reactions, yielding fairly soluble polymers in the cases of 4- and 2-methylphenyl-lithium ( p-TolLi and o-TolLi). Their crystal structures have been determined by X-ray powder diffraction. Remarkably, o-TolLi crystallizes in the noncentrosymmetric space group P212121 with two independent monomers, whereas the crystal structure of p-TolLi is described in spacegroup P21/ a. In contrast, no polymer of 5- m-XyLi (3,5-dimethyl-phenyl-lithium) could be observed, but single crystals of a [(5- m-XyLi)3(MTBE)3LiBr] adduct were isolated (MTBE = methyl- tert-butylether). This gives hints on the nature of lithium-halogen exchange reactions. Steric and electronic effects of the phenyl-lithium substitution are further discussed in conjunction with related compounds.