Mechanochemistry: New Tools to Navigate the Uncharted Territory of “Impossible” Reactions

Abstract

Mechanochemical transformations have made chemists enter unknown territories, forcing a different chemistry perspective. While questioning or revisiting familiar concepts belonging to solution chemistry, mechanochemistry has broken new ground, especially in the panorama of organic synthesis. Not only does it foster new "thinking outside the box", but it also has opened new reaction paths, allowing to overcome the weaknesses of traditional chemistry exactly where the use of well-established solution-based methodologies rules out progress. In this Review, the reader is introduced to an intriguing research subject not yet fully explored and waiting for improved understanding. Indeed, the study is mainly focused on organic transformations that, although impossible in solution, become possible under mechanochemical processing conditions, simultaneously entailing innovation and expanding the chemical space.This publication is part of a joint Special Collection of Chemistry-Methods and ChemSusChem including invited contributions focusing on "Methods and Applications in Mechanochemistry". Please visit chemsuschem.org/ collections to view all contributions.

Disentangling the Effect of Pressure and Mixing on a Mechanochemical Bromination Reaction by Solid‐State NMR Spectroscopy**

“…The influence of mechanical forces on chemical reactions has attracted chemists for many decades, for instance, due to the possibility of opening alternative synthetic pathways otherwise unachievable using different means of energetic input, such as light and temperature. [1][2][3][4] The field of mechanochemistry 5 has experienced enormous advances in the past years, reflected in versatile chemical and biological applications (for selected reviews see [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] ), ranging from the solid-state synthesis of inorganic materials, [24][25][26][27] metal-organic [28][29][30][31][32] and organic compounds, [33][34][35][36] covalent organic frameworks, 37 and polymers [38][39][40][41][42][43] to enzymatic reactions 19,[44][45]…”

“…While studying halogen bonding of sulfoximines, 73 we also investigated co-crystallizations of cyclic scaffolds with brominating agents and found a fast bromination reaction when a cyclic sulfoximine (specifically, 2-methyl-3H-2λ 4 -benzo[c]isothiazole 2-oxide, 74 in the following denoted as sulfoximine) was treated with NBS. This result motivated us to investigate this halogenation in more detail.…”

“…This result motivated us to investigate this halogenation in more detail. We herein describe a bromination of 2-methyl-3H-2λ 4 benzo[c]isothiazole 2-oxide with N-bromosuccinimide (NBS) performed in a mixer mill and its detailed solid-state NMR spectroscopic investigation (for previous halogenation reactions of arenes, see [75][76][77][78][79][80] ). 13 C-detected solid-state MAS NMR has been used to study the reaction products ex situ.…”

From amines to (form)amides: a simple and successful mechanochemical approach

“…Mechanochemistry has been established as a powerful tool for the rapid, clean, and environmentally friendly synthesis of organic compounds, avoiding bulk solvent and restrictions of solvent-based chemistry [27][28][29][30][31][32][33][34]. In general, mechanochemistry refers to studying solid-state chemical changes promoted by external mechanical energy, such as grinding or milling.…”

N-Formylsaccharin: A Sweet(able) Formylating Agent in Mechanochemistry

“…Mechanochemistry [ 41 ], which IUPAC recently recognized as one of the ten chemical innovations that will change the world [ 42 ], has seriously contributed to overcoming these issues by greening many classical solvent-based procedures [ 43 , 44 , 45 , 46 , 47 , 48 , 49 ]. In addition, this technology has paved the way for preparing new compounds that are often challenging to synthesize due to solubility concerns [ 50 , 51 ].…”