The Mechanim of Formation of Grignard Reagents: Trapping of Free Alkyl Radical Intermediates by Reaction with Tetramethylpiperidine-N-oxyl

Article abstract of DOI:10.1021/ja00196a053

In the presence of the free radical scavenger 2,2,6,6-tetramethylpiperidine-N-oxyl (TMPO^., 0.50 M), cycloheptyl bromide (RBr, 0.001 M) reacts with magnesium metal in a solution containing tert-amyl alcohol (5.0 M), lithium bromide (0.05 M), and diethyl ether at 20 deg C and forms N-cycloheptoxy-2,2,6,6-tetramethylpiperidine (TMPOR) as the major product (>/=93percent yield, based on RBr).In the absence of TMPO^., cycloheptane (RH) is formed in >/=95percent yield.The dependence of the relative yields of TMPOR and RH on the initial concentration of TMPO^. suggests that bothproducts share a common precursor-free cycloheptyl radical-and that this radical has a median lifetime of ca. 1E-7 s.Cycloheptyl radicals appear to be intermediates on the major path to the Grignard reagent cycloheptylmagnesium bromide.TMPO^. is reduced by Mg(0) to the anion of the corresponding hydroxylamine, TMPO(1-), at a rate that is competitive with that of the reaction between RBr and Mg(0).Although the magnesium salts of TMPO(1-) are insoluble in diethyl ether, solutions containing TMPO(1-), Mg(2+), and Li(1+) remain homogeneous.For systems containing a high concentration of tert-amyl alcohol, a simple mathematical model attributes apparent zero-order kinetic behavior to the dependence of reactive surface area on the extent of reaction between alkyl halide and Mg.