Electrochemical Study of Propofol (2,6-diisopropylphenol): A Novel Insight into the Dimerization of Propofol

Abstract

Electrochemical oxidation of propofol (2,6-diisopropylphenol) (PPF) has been studied in a water/acetonitrile (50/50, v/v) mixture by cyclic voltammetry, differential pulse voltammetry and galvanostatic coulometry. The results show that PPF can be electrochemically oxidized in a chemically irreversible one-electron/one-proton process to form the corresponding radical (PPF • ) which couples to yield propofol dimer (PD). Due to the easier oxidation of PD compared to PPF, the PD is oxidized in a reversible two-electron/two-proton process to form 3,3′,5,5′-tetraisopropyl-[1,1′-bi(cyclohexylidene)]-2,2′,5,5′-tetraene-4,4′-dione (PDQ). We call this mechanism EDE for simplicity, where E represents an electron transfer at an electrode surface and D represents a homogeneous dimerization step. We also investigated the catalytic effect of sulfite ions on the oxidation of PPF and found strong evidence to support it. The electrochemical synthesis of PDQ was successfully carried out directly using drug samples or by using commercial samples of PPF in the presence of sodium sulfite as a catalyst. The electrochemical dimerization of PPF is carried out under mild conditions at room temperature and atmospheric pressure in an undivided cell using carbon anode and stainless steel cathode, using the electrode as an electron source instead of toxic oxidants, under greener conditions.