<i>N,N,N</i>-trimethylanilinium
salts are known to display dual reactivity through both the aryl group and the <i>N</i>-methyl groups. These salts have thus
been widely applied in cross-coupling, aryl etherification, fluorine
radiolabelling, phase-transfer catalysis, supramolecular recognition, polymer
design, and (more recently) methylation. However, their application as electrophilic
methylating reagents remains somewhat underexplored, and an understanding of
their arylation versus methylation reactivities is lacking. This study presents
a mechanistic degradation analysis of <i>N,N,N</i>-trimethylanilinium
salts and highlights the implications for synthetic applications of this
important class of salts. Kinetic degradation studies, in both solid state and
solution phases, have delivered insights into the physical and chemical
parameters affecting anilinium salt stability. <sup>1</sup>H NMR kinetic
analysis of salt degradation has evidenced thermal degradation to methyl iodide
and the parent aniline, consistent with a closed-shell S<sub>N</sub>2-centred degradative
pathway, and methyl iodide being the key reactive species in applied
methylation procedures. Furthermore, the effect of halide and non-nucleophilic
counterions on salt degradation has been investigated, along with deuterium
isotope and solvent effects. Finally, new mechanistic insights have enabled the
investigation of the use of trimethylanilinium salts in O-methylation and in
improved cross-coupling strategies.
Front Cover: Pd
0
‐Mediated Cross‐Coupling of [
11
C]Methyl Iodide with Carboxysilane for Synthesis of [
11
C]Acetic Acid and its Active Esters:
11
C‐Acetylation of Small, Medium, and Large Molecules (Eur. J. Org. Chem. 29/2021)
