REGIOSELECTIVE REDUCTIVE ELECTROPHILIC SUBSTITUTION OF 1,2,3-TRIMETHOXYBENZENE AND ITS 5-ALKYL-SUBSTITUTED HOMOLOGS

The methoxy group in the 2-position of 1,2,3-trimethoxybenzene (1) can be regioselectively removed by electron transfer from alkali metals and replaced with a variety of electrophiles in a one-pot procedure, affording 2-substituted resorcinol dimethyl ethers. The usefulness of this synthetic method is illustrated by numerous examples. This reaction procedure has been successfully extended to the 5-methyl-substituted homologue (2), but limitations occur with the higher homologue l-pentyl-3,4,5-trimethoxybenzene (3). Investigations on the mechanism of demethoxylation, with the aid of labeling experiments, provided clear evidence for the intermediacy of aryl radicals and explained the low yields obtained in the reductive electrophilic substitutions of compound 3. © 1990, American Chemical Society. All rights reserved.