REACTIVITY OF 3,6-DIMETHOXY-3,6-DIMETHYLCYCLOHEXA-1,4-DIENE - NUCLEAR VERSUS BENZYLIC NUCLEOPHILIC-SUBSTITUTION

The treatment of cis/trans-3,6-dimethoxy-3,6-dimethylcyclo-hexa-1, 4-diene (ca. 1/1 mixture; easily prepared electrochemically in multigram scale from p-xylene) under acidic conditions (acetic, trifluoroacetic, sulfuric, or a Lewis acid) yields almost exclusively 2-methoxy-1,4-dimethylbenzene 4, through a transposition reaction. The use of aqueous hydrochloric or hydrofluoric acid gives 2,5-di-methylphenol 12, and with hydrogen chloride a mixture of 2- and α- chloro-P-xylene (13, 14) is isolated. Different oxygen-, nitrogen-, and sulfur-containing nucleophiles (alcohols, thiols, or hydrazoic acid) react with 3 under acid catalysis giving the corresponding products resulting from a nuclear or/and benzylic substitution on P-xylene (15-20). The reaction of compound 3 with organolithium reagents affords exclusively benzylic products 21 in a regiospecific manner. In all cases the mixtures of isomers are separated by column chromatography. The lithiation of compound 3 with lithium powder or lithium naphthalenide fails, giving P-xylene. A probable mechanism is proposed for the studied reactions. © 1990.