A new heterogeneous Williamson synthesis of ethers using t-alkyl substrates

In general, the reactions of t-alkyl halides with alkali metal alkoxides and phenoxides in polar solvents give olefins (E) almost alone. However, we found a new method for the preparation of t-alkyl ethers (SN) in the reactions of t-alkyl substrates with metal alkoxides and aryl oxides in nonpolar solvents, Alkali metal phenoxides (PhO(-) M(+); M(+) = Li+, Na+ and K+) reacted With t-butyl bromide and iodide in hexane at 60 degrees C far few hours to give t-butyl phenyl ether in 41-59% yields. A similar S-N reaction of alkaline earth metal phenoxides also gave the ether in 54-60% yields. More hindered 1-adamantyl methanesulfonate, which is resistant to elimination compared with t-butyl halide, reacted with metal alkoxides in octane at 100-110 degrees C to give corresponding 1-adamantyl alkyl ethers in good yields. The comparable reaction of 1-adamantyl iodide was much slower than the case of 1-adamantyl methanesulfonate. Aprotic polar solvents (DMF, DMSO) were unfavorable for the SN reaction. On the ther hand, alkali metal alkoxides reacted with t-butyl halide in heptane to give X-methylpropene (E) exclusively, but strontium and barium alkoxides gave 15-50% of alkyl t-butyl ether (S-N) at 80-95 degrees C. The selectivity of S-N/E was governed by solvent, metal catian (Li+, Na+, K+, Mg2+, Ca2+, Sr2+, and Ba2+), nucleophile, and substrate. The nonpolar solvents were much more effective than polar solvents for the S-N reaction. The addition of crown ether to the system decreased markedly the S-N/E ratio. The addition effect of radical scavenger, galvinoxyl was not recognized.