Solvent‐Less Organic Synthesis

Abstract

Solvent‐less reactions realize 100% yield of one product without involvement of any added solvent for reaction and workup. They occur in virtually all reaction types by proper choice of the states of aggregation and reaction technique. This article is subdivided into melting, kneading, dry milling, gas–solid reactions, and gas–liquid reactions. The choice depends on the crystal packing, melting points, and eutectic temperatures during a reaction. Temperature control is essential for achieving the full benefit of crystal packing or the maximal concentration in the absence of deactivating solvation. The reaction temperatures are decreased as a result of the most favorable kinetics that lead to complete conversions and mostly avoid catalysis. An additional advantage is the direct and perfect exclusion of moisture. A decreased reaction temperature often enables staying below the eutectic temperature, or allows for obtaining otherwise nonaccessible new products that directly crystallize without involving a liquid phase. If the yield is also quantitative with the product directly crystallizing from the melt, it may be easier to perform melt reactions with slight heating. The so‐called “solvent‐free” (rather than solvent‐less) reactions are mostly not quantitative and often not free of auxiliaries, which requires solvent‐consuming chromatography and separation of the auxiliary with usually difficult recovery (eg, catalysts or supports). The hype surrounding catalysis from “green chemistry” to perform reactions in “green‐solvents” or “solvent‐free” is counterproductive. Solvent‐less reactions without catalyst and with 100% yield of pure product are the better choice. It is therefore necessary to report the broad application and variability of solvent‐less techniques, for the sake of sustainability.

Elucidation of the Diels–Alder Reaction Kinetics between Diphenylfulvene and Maleimide by Mechanochemistry and in Solution

“…7 The organic mechanochemistry has remained undeveloped until the pioneering work reported by Toda in the 1980s 8 and Kaupp. 9 Due to several advantages, the mechanochemistry area has received significant attention over solution-based chemical methods and process developments. The mechanochemical formation of the carbon−carbon bond (aldol reaction, Michael addition, Morita−Baylis−Hillman, Wittig, Suzuki, cycloaddition reactions), heterocyclic synthesis, carbon−heteroatom formation, multicomponent reactions, and C−H functionalization are popularly known in literature.…”

Synthesis of Biologically Relevant 1,2,3- and 1,3,4-Triazoles: From Classical Pathway to Green Chemistry

“…In the two last decades, this green chemistry approach has been developed considerably in areas related to inorganic compounds and metal complexes synthesis and related mechanistic aspects [ 34 , 35 , 36 ] while less interest was focused on organic mechanochemistry, even after the pioneering work reported by Toda in the 1980s [ 37 ] and Kaupp [ 38 ]. This is actually changing since the last decade’s focus was essentially on the green chemistry and green processes approach [ 39 ].…”

Mechanochemical synthesis of small organic molecules

“…In mechanomilling methods generally, the reactions are carried out in sealed vessels or jars of materials like stainless steel, tungsten carbide, zirconia, agate, etc. [ 24 ].…”

“…are well documented in seminal reviews and will not be discussed here. The organic mechanochemistry has remained undeveloped until the pioneering work reported by Toda in the 1980s [ 38 ] and Kaupp [ 24 ]. Due to several advantages, the area mechanochemistry has received significant attention over solution-based chemical methods and process developments [ 12 , 27 , 29 ].…”