(21e) Impact of Sulfur Heteroatoms on the Activity of Quaternary Ammonium Salts As Phase Transfer Catalysts

Phase-transfer catalysis is a practice that enjoys widespread application in synthetic processes requiring reaction between reactants present in immiscible phases.  The most common class of phase transfer catalysts is quaternary ammonium salts.  In this work, the application of a new class of alkylammonium salts as phase-transfer catalysts is investigated.  These salts are tetra(4-thiaalkyl)ammonium bromides, which contain a sulfur atom in each of their alkyl chains as a result of a new synthesis method.  The versatile synthesis offers the opportunity to yield quat salts with a wide range of functionalization, and thus to tailor the salt to a specific application.  The key questions of the study focus on how the incorporation of a sulfur atom in the alkyl chains affects the efficacy of the salts as phase-transfer catalysts.  Employing the nucleophilic substitution of cyanide for bromide on 1-bromopentane as a model reaction, reaction rate constants and activation energies are evaluated.  The kinetic parameters obtained using the tetrathiaalkylammonium salts are compared to those obtained using their tetraalkylammonium analogs.  The general trend is that the presence of sulfur in the alkyl chains brings about slight reductions in reaction rates and increases in activation energies.  These effects are lessened by branching on carbons adjacent to the sulfur atoms.  The trends are analyzed both in terms of computational modeling and experimental distribution coefficients to determine the mechanistic cause of the slower reaction rates.  Thiaquats are shown to distribute more into the aqueous phase than traditional quat salts of similar chain lengths, resulting in lower organic phase concentrations.  Quantum calculations indicate stronger ion pairing for the thiaquats than for the traditional quats, with specific interactions existing between the anions and some of the protons in the thiaalkyl chains.   Based on the accepted reaction mechanism, the stronger pairing should increase activation energies and slow reaction rates, as observed.  Thus, differences in rate enhancements are attributable both to phase distribution and ion pairing effects.