A Switchable Oxidation Process Leading to Two Various Versatile Pharmaceutical Intermediates

An efficient high-yielding and environmentally benign switchable oxidation process that can selectively produce two different versatile synthetic intermediates is disclosed. One of the two intermediates, 2,3-dimethoxy-5-methylcyclohexa-2,5-diene-1,4-dione (coenzyme Q0), is obtained by means of a telescoped two-step synthetic protocol that in the first step involves treatment of the substrate (1,2,3-trimethoxy-5-methylbenzene) with hydrogen peroxide in acetic acid with p-toluene sulphonic acid present as a Bronsted acid catalyst, succeeded by a telescoped second step that entails treatment with fuming nitric acid to achieve the target molecule in an excellent isolated yield (88%). If the substrate is treated directly with nitric acid (65%) in glacial acetic acid two different products can be obtained, namely acetic acid 3,4,5-trimethoxybenzyl ester in a superb isolated yield (93%) or, under slightly altered reaction conditions, 1,2,3-trimethoxy-5-(nitromethyl)benzene in a moderate to low yield (35%) and lo...