Sodium Alkyl(trimethylsilyl)amides: Substituent- and Solvent-dependent Solution Structures and Reactivities

The preparation of sodium isopropyl(trimethylsilyl)amide (NaPTA), sodium (1-phenylethyl)(trimethylsilyl)amide (NaPETA), sodium <i>tert</i>-butyl(trimethylsilyl)amide (NaBTA), and isotopologues [¹⁵N]NaPTA and [¹⁵N]NaBTA are described. Solution structural studies using a combination of ²⁹Si NMR spectroscopy, the Method of Continuous Variations, and density functional theory computations provided insights into aggregation and solvation in a range of solvents including toluene, <i>N</i>,<i>N</i>-dimethylethylamine, triethylamine, MTBE, THF, 1,2-dimethoxyethane (DME), diglyme, <i>N</i>,<i>N</i>,<i>N</i>',<i>N</i>'-tetramethylethylenediamine (TMEDA), <i>N</i>,<i>N</i>,<i>N</i>',<i>N</i>'-tetramethylcyclohexanediamine (TMCDA), <i>N</i>,<i>N</i>,<i>N</i>',<i>N</i>″,<i>N</i>″-pentamethyldiethylenetriamine (PMDTA). 12-crown-4, 15-crown-5, and 18-crown-6 revealed solvent- and substituent-dependent dimer-monomer mixtures with affiliated solvation numbers. Complexation of the three crown ethers documented both crown and substituent dependencies. Qualitative studies of reactivity showed a variety of reactions of NaPETA. Aminolysis of methyl benzoate with dialkylamines mediated by NaPTA afforded high yields of benzamides. Quantitative rate studies of aminolysis of methyl benzoate by NaPTA revealed a 47,000-fold range of rates. Detailed rate studies in toluene and THF showed dimer-based mechanisms. The role of primary- and secondary-shell solvation by THF is discussed, including nuances of methods used to separate the two contributions. PMDTA-solvated NaPTA monomer reacts as a monomer whereas bis-diglyme solvated monomer reacts as a dimer. Rate studies exploring the structure-reactivity correlations of the three crown ethers show mono- and bis-crown-based pathways in which 15-crown-5─the crown ether often said to be of choice for sodium─was decidedly inferior as an accelerant.