Synthesis of Quinone Metabolites by Electrochemical and Chemical Oxidation

Abstract

Electrochemical oxidation of polycyclic aromatic phenols (PAPs) has been developed in a microfluidic flow cell to synthesize polycyclic aromatic quinones. This method applies methanol as a nucleophile source while OH directs the oxidation to yield acetal quinones in either the ortho- or para-position. Transformation of PAPs into acetal quinones, new intermediate products, was successfully achieved through electrochemical oxidation, making it a valuable method. Hydroxy-PAHs are conveniently converted into their corresponding ortho-quinones using stabilized iodoxybenzoic acid (SIBX). SIBX provides a safer and commercially available alternative to IBX and displays the same selectivity with comparable or better yields for the oxidative dearomatization of phenols to ortho-quinones, including examples where para-quinone formation is feasible. The hydroxyl group was synthesized by either photochemical cyclization of stilbenes or Ptcatalyzed cycloisomerization. The later synthesis involved a four-step sequence where suitably substituted biphenyls were prepared by Suzuki-Miyaura cross-coupling, followed by the Corey–Fuchs alkynylation and cycloisomerization by a catalytic amount of PtCl2. 2- and 4-methyl phenanthrene were also prepared for the first time using this method. Hydroxylated polycyclic aromatic hydrocarbons (PAPs) are PAH metabolites that have been used widely as biomarkers for in-vivo oxidation products of PAH and for evaluating fish PAH exposure. This thesis presents the synthesis of quinone metabolites from PAPs that can be utilized for toxicology research. Pure compounds are also needed as standards to identify the same compounds in a more complex matrix in exposure studies.