Organic Synthesis without Conventional Solvents

Abstract

Organic synthesis without an organic solvent is still the exception. In this microreview, we discuss and compare different synthetic methods that proceed in the absence of conventional organic solvents. This includes solvent‐free methods in solids (mechanochemistry and solid‐state photochemistry), and in neat liquids (thermal and photocatalytic), as well as the application of unconventional solvents, such as ionic liquids and deep‐eutectic solvents. The different approaches are briefly introduced and examples illustrate their specific advantages, followed by a critical discussion of their limitations. Some methods have the intrinsic benefits of solvent‐free operation, such as avoiding solubility problems and side‐reactions with the solvent. However, every method has specific advantages and the demand of the synthetic application is crucial for selecting the best technique.

Mechanochemistry for Synthesis

“…Photocatalysis in the solid-state was reported by the Kçnig group [84] in 2016, who used arod mill reactor in which at hin layer of as olid reaction mixture is sheared under irradiation. To achieve photocatalysis while ball milling, Hernµndez used ap oly(methylmethacrylate) jar wrapped by as trip of blue-or green-emitting light-emitting diodes to perform borylation of diazonium salts mediated by Eosin Y.…”

Challenges and Directions for Green Chemical Engineering—Role of Nanoscale Materials

“…deep eutectic solvents (DES) 71 and Natural Deep Eutectic Solvents (NADES) 72 , prepared from natural products with fewer EHS issues is increasing, and these solvents are showing some surprising reactivity. 73,74 The application of chemo-and biocatalysis is aligned to green chemistry principles 75 and can be more compatible with the "greener" solvent classes. The use of nano-particulate metal catalysts is emerging in the field of chemo-catalysis and applied to reactions commonly used in API synthesis.…”

Systematic evaluation of hydrophobic deep-melting eutectics as alternative solvents for the extraction of organic solutes from aqueous solution

“…24,25 Finally, while the practical utility of ionic liquids is sometimes limited by their expense (uorinated anions being particularly problematic in this context), 26,27 numerous DESs can be prepared from inexpensive, commodity chemicals. 28 These favorable characteristics have led to a range of applications in a variety of elds, including synthesis, 29,30 catalysis, 31 and chemical analysis, 32 among others. While the vast majority of deep eutectic solvents described to date are hydrophilic, 33,34 recent work has shown that a hydrophobic DES (designated hereaer as an HDES) can be readily obtained by combining menthol [35][36][37][38] or an appropriate quaternary ammonium halide [39][40][41] with a longchain carboxylic acid.…”