Carbon-Nitrogen Bond Formation Using Sodium Hexamethyldisilazide: Solvent-Dependent Reactivities and Mechanisms

The solvent-dependent reactivity of sodium hexamethyldisilazide (NaHMDS) toward carbon-centered electrophiles reveals reactions that are poorly represented or unrepresented in the literature, including direct aminolysis of aromatic methyl esters to give carboxamides, nitriles, or amidines, depending on the choice of solvent. SNAr substitutions of aryl halides and opening of terminal epoxides are also examined. A combination of H-1 and Si-29 nuclear magnetic resonance (NMR) spectroscopic studies using [N-15]NaHMDS, kinetic studies, and computational studies reveals the complex mechanistic basis of the preferences for simple aryl carboxamides in toluene and dimethylethylamine and arylnitriles or amidines in tetrahydrofuran (THF). A prevalence of dimer- and mixed dimer-based chemistry even starting from the observable NaHMDS monomer in THF solution is notable.

Automated summary

This study reveals the solvent-dependent reactivity of sodium hexamethyldisilazide (NaHMDS) towards carbon-centered electrophiles, including reactions that are not well-described in the literature. Using NMR spectroscopic studies, kinetic studies, and computational studies, the mechanistic preferences for simple aryl carboxamides in different solvents and the prevalence of dimer-based chemistry in THF solution are elucidated.