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

Abstract

In recent years it is 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 elucidated 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.

Keywords: ball milling; mechanochemistry; organic chemistry; pressure; solid-state NMR.