Methylation of alcohols with diazomethane

Abstract

Alcoholic hydroxyl groups were methylated by diazomethane in the presence of catalytic amounts of fluoboric acid (FBA). Primary aliphatic and unhindered secondary alcohols gave 84–98% yields of methyl ethers, while tertiary and moderately hindered secondary alcohols afforded lower yields. The order of reactivity in the methylation of the isomeric butyl alcohols, as determined in competition experiments, was n > s > t, and of the epimeric cholestanols, 3β (e) > 3 α(a). The highly hindered alcoholic hydroxyl groups of isoborneol was not methylated by the new reagent. The methylation of weakly acidic phenols was catalyzed by FBA. The new methylation reaction was used to prepare directly methyl ethers of desoxycorticosterone and of testosterone, and to convert ascorbic acid selectively to its 2:3:6-trimethyl ether.