Kinetics of Nucleophilic Substitution of Compounds Containing Multiple Leaving Groups Bound to a Neopentyl Skeleton.

Ammonium salt derivatives with a neopentyl moiety are remarkably stable against Hofmann elimination, but the neopentyl moiety slows nucleophilic substitution, complicating their synthesis. To identify the best leaving group for the synthesis of the ammonium salts, we prepared six 1,1,1-tris(X-methyl)ethane derivatives, where X is chloride, bromide, iodide, methanesulfonate, p -toluenesulfonate, and trifluoromethanesulfonate (triflate), and studied the kinetics of their reactions with sodium, cesium, or tetramethylammonium azide in deuterated dimethylsulfoxide (DMSO) at 100 °C by NMR spectroscopy. Iodide and bromide were found to be more reactive than p -toluenesulfonate and methanesulfonate. As expected, the best leaving group for nucleophilic substitution was triflate. Despite the usual high reactivity and instability of primary alkyl triflates, neopentyl triflate can be used as a stable but sufficiently reactive reactant for nucleophilic substitution on neopentyl skeletons.