Opportunities and Challenges in Applying Solid‐State NMR Spectroscopy in Organic Mechanochemistry

Abstract

In recent years it was shown that mechanochemical strategies can be beneficial in directed conversions of organic compounds. Finding new reactions proved difficult, and due to the lack of mechanistic understanding of mechanochemical reaction events, respective efforts have mostly remained empirical. Spectroscopic techniques are crucial in shedding light on these questions. In this overview, the opportunities and challenges of solid‐state nuclear magnetic resonance (NMR) spectroscopy in the field of organic mechanochemistry are discussed. After a brief discussion of the basics of high‐resolution solid‐state NMR under magic‐angle spinning (MAS) conditions, seven opportunities for solid‐state NMR in the field of organic mechanochemistry are presented, ranging from ex‐situ approaches to structurally elucidate reaction products obtained by milling to the potential and limitations of in‐situ solid‐state NMR approaches. Particular strengths of solid‐state NMR, for instance in differentiating polymorphs, in NMR‐crystallographic structure‐determination protocols, or in detecting weak noncovalent interactions in molecular‐recognition events employing proton‐detected solid‐state NMR experiments at fast MAS frequencies, are discussed.This article is protected by copyright. All rights reserved

Initial Primer Synthesis of a DNA Primase Monitored by Real-Time NMR Spectroscopy

“…This allows measurement of reaction kinetics by both, solution- and solid-state NMR . Chemical reactions occurring in the magic-angle spinning (MAS) NMR rotor and followed by real-time NMR have been reported, for instance for battery materials (for a review see ref ), or for mechanochemical transformations (for selected examples see refs − ). Biochemical reactions have also been studied in real time in the MAS rotor, such as for instance amyloid-β self-assembly processes, , the enzymatic degradation of polyethylene terephthalate, drug binding, cellular processes or structural transitions of silk proteins .…”

Charge Redistribution in Mechanochemical Reactions for Solid Interfaces

“…As the fourth strategy for activating reactions − different from the well-known thermochemistry, photochemistry, and electrochemistry, mechanochemistry refers to chemical processes initiated by mechanical stress. − Being a widely applicable scheme for a range of tribological, biological, and geophysical systems, , mechanochemical reactions have attracted much interest but remain poorly understood at the electronic level. , Lea first proposed the transformation of mechanical energy into chemical energy . Subsequently, Eyring, − Zhurkov, and Bell et al pioneered the foundational model of mechanochemistry, from diverse perspectives .…”

Molecular Recognition in Mechanochemistry: Insights from Solid-State NMR Spectroscopy

“…When monitoring the reaction progress by in operando solution-state NMR spectroscopy, [3] we realized the immense opportunities that solid-state NMR techniques offer to organic mechanochemistry. [4] With respect to chiral compounds, the behaviour and interactions of both structurally identical (as object and mirror image) or chemically different entities can be studied. Consequently, we decided to apply solidstate NMR spectroscopy for investigating fundamental solid state molecular-recognition processes in mechanochemically-induced reactions in more detail, and the first results are summarized here.Solid-state NMR is of particular importance in studying mechanochemical transformations since the material taken from the milling jar can be analysed without any further post-modification (for recent articles, see [4,5] ).…”

“…[4] With respect to chiral compounds, the behaviour and interactions of both structurally identical (as object and mirror image) or chemically different entities can be studied. Consequently, we decided to apply solidstate NMR spectroscopy for investigating fundamental solid state molecular-recognition processes in mechanochemically-induced reactions in more detail, and the first results are summarized here.Solid-state NMR is of particular importance in studying mechanochemical transformations since the material taken from the milling jar can be analysed without any further post-modification (for recent articles, see [4,5] ). NMR observables, such as chemical-shift values, are extremely indicative probes for molecular recognition due to their sensitivity to noncovalent interactions, such as hydrogen bonds or dispersion interactions.…”

“…Solid-state NMR is of particular importance in studying mechanochemical transformations since the material taken from the milling jar can be analysed without any further post-modification (for recent articles, see [4,5] ). NMR observables, such as chemical-shift values, are extremely indicative probes for molecular recognition due to their sensitivity to noncovalent interactions, such as hydrogen bonds or dispersion interactions.…”